UEMURA Hirotsugu

    Department of Medicine Professor/Senior Staff
Last Updated :2024/02/02

Researcher Information

Degree

  • Ph.D(1996/11 Nara Medical University)
  • Ph.D.(1995/11 University of Nijmegen)

J-Global ID

Research Interests

  • 分子標的治療   免疫療法   泌尿器癌   癌ワクチン療法   

Research Areas

  • Life sciences / Urology

Published Papers

  • Yasunori Akashi; Yutaka Yamamoto; Mamoru Hashimoto; Shogo Adomi; Kazutoshi Fujita; Keisuke Kiba; Takafumi Minami; Kazuhiro Yoshimura; Akihide Hirayama; Hirotsugu Uemura
    Cancers 15 (24) 2023/12 
    INTRODUCTION: Immune checkpoint inhibitor (ICI) therapy has significantly improved the prognosis of some patients with advanced urothelial carcinoma (UC), but it does not provide high therapeutic efficacy in all patients. Therefore, identifying predictive biomarkers is crucial in determining which patients are candidates for ICI treatment. This study aimed to identify the predictors of ICI treatment response in patients with platinum-refractory advanced UC treated with pembrolizumab. METHODS: Patients with platinum-refractory advanced UC who had received pembrolizumab at two hospitals in Japan were included. Univariate and multivariate analyses were performed to identify biomarkers for progression-free survival (PFS) and overall survival (OS). RESULTS: Forty-one patients were evaluable for this analysis. Their median age was 75 years, and the vast majority of the patients were male (85.4%). The objective response rate was 29.3%, with a median overall survival (OS) of 17.8 months. On multivariate analysis, an Eastern Cooperative Oncology Group performance status (ECOG-PS) ≥ 2 (HR = 6.33, p = 0.03) and a baseline neutrophil-to-lymphocyte ratio (NLR) > 3 (HR = 2.79, p = 0.04) were significantly associated with poor OS. Antibiotic exposure did not have a significant impact on either PFS or OS. CONCLUSIONS: ECOG-PS ≥ 2 and baseline NLR > 3 were independent risk factors for OS in patients with platinum-refractory advanced UC treated with pembrolizumab. Antibiotic exposure was not a predictor of ICI treatment response.
  • Eisuke Tomiyama; Kazutoshi Fujita; Mamoru Hashimoto; Hirotsugu Uemura; Norio Nonomura
    International journal of urology : official journal of the Japanese Urological Association 2023/11 
    Bladder cancer is a common urological cancer with a high recurrence rate that requires long-term follow-up, and early detection positively affects prognosis. To date, the initial diagnosis and follow-up for bladder cancer rely on cystoscopy, which is an invasive and expensive procedure. Therefore, urinary markers for the detection of bladder cancer have attracted research attention for decades to reduce unnecessary cystoscopies. Urine, which is in continuous contact with bladder cancer, is considered a suitable fluid for providing tumor information. Urinary cytology is the only widely used urinary marker in clinical practice; however, it has poor sensitivity for low-grade tumors; indicating the need for novel urinary markers. Considerable research has been conducted on this topic over the years, resulting in a complex landscape with a wide range of urinary markers, including protein-, exfoliated cell-, RNA-, DNA-, and extracellular vesicle-based markers. Although some of these markers have been approved by the U.S. Food and Drug Administration and are commercially available, their use in clinical practice is limited. To facilitate clinical application, potential urinary markers must withstand prospective clinical trials and be easy for patients and clinicians to understand and utilize in a clinical context. This review provides a comprehensive overview of currently available and recently reported promising urinary markers for bladder cancer. Additionally, the challenges and the prospects of these urinary markers for clinical implementation in bladder cancer treatment were discussed.
  • Mamoru Hashimoto; Sergei Karnup; Stephanie L Daugherty; Kang Jun Cho; Eri Banno; Nobutaka Shimizu; Kazutoshi Fujita; Akihide Hirayama; Hirotsugu Uemura; William C de Groat; Jonathan M Beckel; Naoki Yoshimura
    Neurourology and urodynamics 2023/11 
    OBJECTIVES: We examined sex differences of lower urinary tract function and molecular mechanisms in mice with and without spinal cord injury (SCI). METHODS: SCI was induced by Th8-9 spinal cord transection in male and female mice. We evaluated cystometrograms (CMG) and electromyography (EMG) of external urethral sphincter (EUS) at 6 weeks after SCI in spinal intact (SI) and SCI mice. The mRNA levels of Piezo2 and TRPV1 were measured in L6-S1 dorsal root ganglia (DRG). Protein levels of nerve growth factor (NGF) in the bladder mucosa was evaluated using an enzyme-linked immunosorbent assay. RESULTS: Sex differences were found in the EUS behavior during voiding as voiding events in female mice with or without SCI occurred during EUS relaxation periods without EUS bursting activity whereas male mice with or without SCI urinated during EUS bursting activity in EMG recordings. In both sexes, SCI decreased voiding efficiency along with increased tonic EUS activities evident as reduced EUS relaxation time in females and longer active periods of EUS bursting activity in males. mRNA levels of Piezo2 and TRPV1 of DRG in male and female SCI mice were significantly upregulated compared with SI mice. NGF in the bladder mucosa showed a significant increase in male and female SCI mice compared with SI mice. However, there were no significant differences in Piezo2 or TRPV1 levels in DRG or NGF protein levels in the bladder mucosa between male and female SCI mice. CONCLUSIONS: We demonstrated that female and male mice voided during EUS relaxation and EUS bursting activity, respectively. Also, upregulation of TRPV1 and Piezo2 in L6-S1 DRG and NGF in the bladder could be involved in SCI-induced lower urinary tract dysfunction in both sexes of mice.
  • Kojiro Ohba; Keisuke Monji; Takahiro Osawa; Kazutoshi Yamana; Yosuke Yasuda; Hajime Tanaka; Yuki Nakagawa; Tamaki Fukuyama; Nobuaki Matsubara; Hirotsugu Uemura; Hideki Sakai; Masatoshi Eto
    International journal of urology : official journal of the Japanese Urological Association 2023/07 
    OBJECTIVES: Current prognostic models for metastatic renal cell carcinoma (mRCC) are likely inaccurate due to recent treatment advances and improved survival outcomes. The JEWEL study used a data set from patients who received tyrosine kinase inhibitors (TKIs) to explore the prognostic impact of the tumor immune environment in the absence of immune checkpoint inhibitor intervention. METHODS: The primary analysis population comprised 569 of the 770 Japanese patients enrolled in the ARCHERY study who received first-line TKIs. Multivariable Cox proportional hazard models were used to identify factors associated with the primary (overall survival [OS]) and secondary outcomes (treatment duration) using 34 candidate explanatory variables. RESULTS: Median OS was 34.1 months (95% CI, 30.4-37.6) in the primary analysis population. A considerable negative prognostic impact (descriptive p ≤ 0.0005) on OS was seen with lactate dehydrogenase (LDH) >1.5 × upper limit of normal (adjusted HR [aHR], 3.30; 95% CI, 2.19-4.98), Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 (aHR, 2.14; 95% CI, 1.56-2.94), World Health Organization (WHO)/International Society of Urological Pathology (ISUP) Grade 4 (aHR, 1.89; 95% CI, 1.43-2.51), C-reactive protein (CRP) level ≥0.3 (aHR, 1.78; 95% CI, 1.40-2.26), and age ≥75 years (aHR, 1.65; 95% CI, 1.24-2.18) in the multivariable analysis. PD-L1 and immunophenotype affected OS in univariable analyses but were not selected in the multivariable model as explanatory variables. CONCLUSIONS: JEWEL identified sex, age, ECOG PS, liver and bone metastases, CRP levels, WHO/ISUP grade, LDH, and albumin levels as key prognostic factors for OS after first-line TKI therapy for mRCC.
  • Junji Yonese; Nobuyuki Hinata; Satoru Masui; Yasutomo Nakai; Suguru Shirotake; Ario Takeuchi; Teruo Inamoto; Masahiro Nozawa; Kosuke Ueda; Toru Etsunaga; Takahiro Osawa; Motohide Uemura; Go Kimura; Kazuyuki Numakura; Kazutoshi Yamana; Hideaki Miyake; Satoshi Fukasawa; Naoto Morishima; Hiroaki Ito; Hirotsugu Uemura
    International journal of urology : official journal of the Japanese Urological Association 2023/05 
    OBJECTIVES: To examine the long-term effectiveness of nivolumab monotherapy and following subsequent therapies for metastatic renal cell carcinoma (mRCC) in Japanese real-world settings. METHODS: This was a multicenter, retrospective, observational study, with a 36-month follow-up, and conducted in Japanese patients with mRCC who initiated nivolumab monotherapy between 1 Feb 2017 and 31 Oct 2017. Endpoints included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). RESULTS: Of the 208 patients, 36.5% received nivolumab monotherapy as second-line, 30.8% as third-line, and 31.7% as fourth- or later-line therapy. By 36 months, 12.0% of patients continued nivolumab monotherapy; 88.0% discontinued, mainly because of disease progression (66.7%). The median (m) OS was not reached irrespective of treatment line, with a 36-month OS rate of 54.3% (second-line, 57.4%; third-line, 52.6%; fourth- or later-line, 52.9%). The ORR was 24.2% and five patients achieved complete response. The OS from first-line therapy was 8.9 years. In the 95 patients receiving therapy after nivolumab, 87.4% received vascular endothelial growth factor receptor-tyrosine kinase inhibitors, with mOS and mPFS of 27.4 and 8.1 months, respectively. Irrespective of treatment line, the mOS was not reached in patients with International Metastatic RCC Database Consortium (IMDC) favorable or intermediate risk at mRCC diagnosis. CONCLUSIONS: This 36-month real-world follow-up analysis showed a survival benefit of nivolumab monotherapy for patients with mRCC. The long-term effectiveness of sequential therapy from first-line therapy to therapy after nivolumab was also demonstrated. Additionally, nivolumab monotherapy was beneficial for patients with favorable IMDC risk at the time of mRCC diagnosis.
  • Takafumi Minami; Kazutoshi Fujita; Mamoru Hashimoto; Mitsuhisa Nishimoto; Shogo Adomi; Eri Banno; Masahiro Nozawa; Kazuhiro Nose; Kazuhiro Yoshimura; Masahiro Inada; Masaki Yokokawa; Kiyoshi Nakamatsu; Hirotsugu Uemura
    World journal of urology 2023/04 
    PURPOSE: To investigate the risk of bladder cancer (BCa) in patients treated with brachytherapy for prostate cancer (PCa). METHODS: We retrospectively analyzed 583 patients with PCa who underwent brachytherapy with or without external beam radiotherapy (EBRT). We analyzed the disease-free survival (DFS) of BCa in patients with PCa who underwent brachytherapy with or without EBRT. We performed multivariate Cox regression analyses of DFS using age, EBRT, and Brinkman index (BI) score (number of cigarettes smoked per day × number of years smoking) ≥ 200 as variables for BCa after brachytherapy. RESULTS: Fourteen patients (2.4%) developed BCa after brachytherapy with or without EBRT. The percentage of high-grade urothelial carcinoma (UC) was 63.6%. A total of 85.7% of patients had non-muscle invasive BCa, and 14.3% of patients had muscle invasive BCa. DFS was longer in brachytherapy monotherapy than in combination therapy (brachytherapy + EBRT). Multivariate Cox regression analysis showed that a BI score ≥ 200 (Hazard Ratio (HR 8.61; 95% Confidence Interval (CI) 1.12-65.98) and EBRT combination (HR 3.29; 95% CI 1.03-10.52) were significantly associated with BCa development in patients with PCa treated with brachytherapy. Furthermore, patients with BI score ≥ 200 and EBRT combination had a significantly higher risk of BCa compared with patients with BI score < 200 (HR Log-rank test P = 0.010). CONCLUSION: Most cases of BCa after brachytherapy with or without EBRT are high grade and invasive. We hypothesized that the EBRT combination might be a risk factor for BCa in patients with PCa who underwent brachytherapy.
  • 日本人未治療転移性腎細胞癌を対象としたニボルマブ+イピリムマブの有効性・安全性の他施設共同前向き観察研究(J-ENCORE) 第3回中間解析結果(Japanese prospective registry of nivolumab plus ipilimumab for patients in first-line metastatic renal cell carcinoma(J-ENCORE): 3rd interim analysis results)
    溝上 敦; 木村 剛; 西本 紘嗣郎; 佐塚 智和; 濱本 周造; 野澤 昌弘; 沼倉 一幸; 近藤 恒徳; 内藤 整; 小野寺 俊太; 伊藤 寛明; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 110回 OP22 - 01 2023/04
  • ニボルマブ+イピリムマブにより早期増悪がみられた転移性腎細胞癌症例の患者背景および予後 J-ENCORE試験サブグループ解析(Characteristics and prognosis of metastatic RCC patients with early progression treated with nivolumab and ipilimumab: subgroup analysis of J-ENCORE study)
    安部 崇重; 玉田 聡; 西本 紘嗣郎; 佐塚 智和; 濱本 周造; 野澤 昌弘; 沼倉 一幸; 溝上 敦; 近藤 恒徳; 田嶋 洋平; 山口 勝己; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 110回 OP22 - 02 2023/04
  • Makoto Matsushita; Kazutoshi Fujita; Koji Hatano; Marco A De Velasco; Akira Tsujimura; Hirotsugu Uemura; Norio Nonomura
    The world journal of men's health 2023/02 
    The human gut microbiota changes under the influence of environmental and genetic factors, affecting human health. Extensive studies have revealed that the gut microbiome is closely associated with many non-intestinal diseases. Among these, the influence of the gut microbiome on cancer biology and the efficacy of cancer therapy has attracted much attention. Prostate cancer cells are affected by direct contact with the microbiota of local tissues and urine, and a relationship between prostate cancer cells and the gut microbiota has been suggested. In the human gut microbiota, bacterial composition differs depending on prostate cancer characteristics, such as histological grade and castration resistance. Moreover, the involvement of several intestinal bacteria in testosterone metabolism has been demonstrated, suggesting that they may affect prostate cancer progression and treatment through this mechanism. Basic research indicates that the gut microbiome also plays an important role in the underlying biology of prostate cancer through multiple mechanisms owing to the activity of microbial-derived metabolites and components. In this review, we describe the evidence surrounding the emerging relationship between the gut microbiome and prostate cancer, termed the "gut-prostate axis."
  • Kazutoshi Fujita; Makoto Matsushita; Marco A De Velasco; Koji Hatano; Takafumi Minami; Norio Nonomura; Hirotsugu Uemura
    Cancers 15 (5) 2023/02 
    Obesity and a high-fat diet are risk factors associated with prostate cancer, and lifestyle, especially diet, impacts the gut microbiome. The gut microbiome plays important roles in the development of several diseases, such as Alzheimer's disease, rheumatoid arthritis, and colon cancer. The analysis of feces from patients with prostate cancer by 16S rRNA sequencing has uncovered various associations between altered gut microbiomes and prostate cancer. Gut dysbiosis caused by the leakage of gut bacterial metabolites, such as short-chain fatty acids and lipopolysaccharide results in prostate cancer growth. Gut microbiota also play a role in the metabolism of androgen which could affect castration-resistant prostate cancer. Moreover, men with high-risk prostate cancer share a specific gut microbiome and treatments such as androgen-deprivation therapy alter the gut microbiome in a manner that favors prostate cancer growth. Thus, implementing interventions aiming to modify lifestyle or altering the gut microbiome with prebiotics or probiotics may curtail the development of prostate cancer. From this perspective, the "Gut-Prostate Axis" plays a fundamental bidirectional role in prostate cancer biology and should be considered when screening and treating prostate cancer patients.
  • Shogo Adomi; Kazutoshi Fujita; Hiroyuki Kita; Ken Kuwahara; Yasunori Akashi; Mitsuhisa Nishimoto; Naoki Matsumura; Koichi Sugimoto; Takafumi Minami; Masahiro Nozawa; Kazuhiro Yoshimura; Hideo Tahara; Akihide Hirayama; Tsukasa Nishioka; Atsunobu Esa; Hirotsugu Uemura
    Cancer diagnosis & prognosis 3 (4) 484 - 490 2023 
    BACKGROUND/AIM: The treatment strategy for metastatic upper tract urothelial carcinoma (mUTUC) is currently based on the evidence from metastatic urinary bladder cancer (mUBC). However, some reports have shown that the outcomes of UTUC differ from those of UBC. Therefore, we retrospectively analyzed the prognosis of patients with mUBC and mUTUC treated with first-line platinum-based chemotherapy. PATIENTS AND METHODS: Patients who underwent platinum-based chemotherapy at the Kindai University Hospital and affiliated hospitals between January 2010 and December 2021 were included in the study. There were 56 patients with mUBC and 73 with mUTUC. Kaplan-Meier curves were used to estimate progression-free (PFS) and overall (OS) survival. Multivariate analyses were performed using Cox proportional hazards model to predict prognostic factors. RESULTS: The median PFS was 4.5 and 4.0 months for the mUBC and mUTUC groups, respectively (p=0.094). The median OS was 17.0 months for both groups (p=0.821). The multivariate analysis showed no prognostic factor for PFS. The multivariate analysis for OS showed that younger age at the initiation of chemotherapy and immune checkpoint inhibitor use after first-line therapy were significantly associated with better OS. CONCLUSION: Platinum-based chemotherapy had a similar effect on patients with mUTUC and mUBC.
  • Mamoru Hashimoto; Kazutoshi Fujita; Eisuke Tomiyama; Saizo Fujimoto; Shogo Adomi; Eri Banno; Takafumi Minami; Tetsuya Takao; Masahiro Nozawa; Hiroaki Fushimi; Kazuhiro Yoshimura; Norio Nonomura; Hirotsugu Uemura
    Anticancer research 43 (1) 167 - 174 2023/01 
    BACKGROUND/AIM: Upper urinary tract urothelial carcinoma (UTUC) is a rare disease, often discovered at an advanced stage at diagnosis. Nectin-4 is expressed in a broad range of patients with UTUC and is associated with poor progression-free survival. The receptors of the erythroblastosis oncogene B (ErbB) family are potential therapeutic targets for urothelial carcinoma. Herein, we aimed to investigate the relationship of nectin-4 and ErbB family receptors, namely epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) in patients with UTUC. Targeted therapies for these receptors could be used in sequence or in combination for increasing treatment efficiency. PATIENTS AND METHODS: We performed immunohisto-chemical analysis for HER2, EGFR, and nectin-4 using tissue microarrays. A total of 98 UTUC patients were included in the study. We investigated the impact of EGFR and HER2 expression status on recurrence-free survival (RFS) and cancer-specific survival (CSS) of all patients. RESULTS: The percentages of patients positive for HER2, EGFR, and nectin-4 were 97%, 70%, and 65%, respectively. The co-expression rates of HER2-EGFR, HER2-nectin-4, and EGFR-nectin-4 were 69%, 64%, and 47%, respectively. The number of patients positive for all three receptors was 47%. Higher HER2 levels were significantly associated with worse CSS and RFS. Higher EGFR levels were associated with a worse CSS. CONCLUSION: HER2, EGFR, and nectin-4 were highly expressed in UTUC. Combination of HER2-, EGFR-, and nectin-4-targeted therapy may be an effective option for the treatment of patients with UTUC.
  • 非セミノーマ精巣腫瘍の晩期再発を疑ったEpidermoid cystの1例
    中山 尭仁; 藤本 西蔵; 井之口 舜亮; 橋本 士; 菊池 尭; 西本 光寿; 安富 正悟; 坂野 恵里; 齋藤 允孝; 清水 信貴; 森 康範; 南 高文; 藤田 和利; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 植村 天受
    泌尿器科紀要 泌尿器科紀要刊行会 68 (12) 401 - 401 0018-1994 2022/12
  • Takashi Ueda; Kazutoshi Fujita; Mitsuhisa Nishimoto; Takumi Shiraishi; Masatsugu Miyashita; Naruhiro Kayukawa; Yuichi Nakamura; Satoshi Sako; Ryota Ogura; Atsuko Fujihara; Takafumi Minami; Fumiya Hongo; Koji Okihara; Kazuhiro Yoshimura; Hirotsugu Uemura; Osamu Ukimura
    World journal of urology 2022/11 [Refereed]
     
    PURPOSE: There is a discrepancy in the efficacy of abiraterone acetate for overall survival (OS) in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC). This study aimed to identify predictive factors for the efficacy of abiraterone acetate for OS in high-risk mHSPC patients by analyzing them over a longer observation period. METHODS: Five hundred high-risk mHSPC patients were retrospectively identified at our hospital and affiliated hospitals in the Kindai Oncology Study Group and Kyoto Prefectural University of Medicine Oncology Study Group between December 2013 and March 2022. Two hundred patients were treated with abiraterone acetate (1000 mg/day) plus prednisolone (5 mg/day) combined with androgen deprivation therapy (ADT). A total of 300 patients were treated with bicalutamide (80 mg/day) in combination with ADT. RESULTS: OS was not significantly different between the two treatments in the overall cohort (p = 0.1643). In the subgroup without Gleason pattern 5 at the primary lesion, OS was significantly better in patients treated with abiraterone acetate than in those treated with bicalutamide (p = 0.0192). In the subgroup with Gleason pattern 5 at the primary lesion, no significant difference was found between the two treatments (p = 0.1799). Univariate and multivariate analyses in the subgroup without Gleason pattern 5 at the primary lesion suggested that abiraterone therapy may be an important and independent predictor of OS in high-risk mHSPC patients. CONCLUSION: The presence of Gleason pattern 5 at the primary lesion may be a predictor for high-risk mHSPC patients who could benefit from abiraterone acetate treatment.
  • 馬蹄腎ドナーからGraftをHALSにて抽出した生体腎移植術の1例
    齋藤 允孝; 菊池 尭; 安富 正悟; 森 康範; 南 高文; 藤田 和利; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 植村 天受
    日本泌尿器内視鏡・ロボティクス学会総会 (一社)日本泌尿器内視鏡・ロボティクス学会 36回 V - 1 2022/11
  • Yoshihiko Tomita; Ko Kobayashi; Go Kimura; Mototsugu Oya; Hirotsugu Uemura; Hiroyuki Nishiyama; Matthew D Galsky; Federico Nasroulah; Sandra Collette; Edward Broughton; Keziban Ünsal-Kaçmaz; Yukinori Kamisuki; Dean F Bajorin
    Japanese journal of clinical oncology 2022/10 
    BACKGROUND: The phase 3 CheckMate 274 trial demonstrated superiority of adjuvant nivolumab over placebo after radical surgery in patients with high-risk muscle-invasive urothelial carcinoma. However, the efficacy and safety of adjuvant nivolumab in Japanese patients with muscle-invasive urothelial carcinoma have not been clarified. METHODS: Patients with muscle-invasive urothelial carcinoma were randomized to adjuvant nivolumab 240 mg or placebo (every 2 weeks via intravenous infusion) up to 120 days after radical surgery in CheckMate 274. RESULTS: Of 49 patients in the Japanese subgroup, 27 and 22 patients were randomized to nivolumab and placebo, respectively. Eleven and 8 patients, respectively, had tumor PD-L1 expression level of 1% or more. The median disease-free survival times in the nivolumab and placebo groups were 29.67 months (95% confidence interval 7.79-not reached) and 9.72 months (95% confidence interval 4.73-not reached), respectively (hazard ratio 0.77, 95% confidence interval 0.35-1.69). The corresponding values in patients with tumor PD-L1 expression level of 1% or more were 29.67 months (95% confidence interval 2.63-not reached) and 25.95 months (95% confidence interval 5.59-not reached) (hazard ratio 1.10, 95% confidence interval 0.31-3.92), respectively. Treatment-related adverse events of Grade 3-4 occurred in 25.9 and 13.6% of patients in the nivolumab and placebo groups, respectively. The most common treatment-related adverse events in the nivolumab group were lipase increased, amylase increased and diarrhea. The changes in quality of life scores from baseline over time were similar in both groups. CONCLUSIONS: The efficacy and safety results in the Japanese subgroup were consistent with the overall population of CheckMate 274.
  • Kazutoshi Fujita; Go Kimura; Toyonori Tsuzuki; Taigo Kato; Eri Banno; Akira Kazama; Ryo Yamashita; Yuto Matsushita; Daisuke Ishii; Tomoya Fukawa; Yuki Nakagawa; Tamaki Fukuyama; Fumikazu Sano; Yukihiro Kondo; Hirotsugu Uemura
    Cancers 14 (21) 2022/10 
    Biological or immunological differences in primary lesions between synchronous and metachronous metastatic renal cell carcinoma (mRCC) have been reported. However, the association between the tumor immune microenvironment (TIME) of primary lesions and time to metastasis remains unknown. We investigated the differences in the TIME of primary lesions based on time intervals to metastasis, mainly between the synchronous group (SG; metastasis within 3 months) and metachronous group (MG; metastasis after 3 months), and its association with clinicopathological parameters in patients with mRCC. Overall, 568 patients treated first-line with vascular endothelial growth factor receptor inhibitors comprised the analysis population (SG: N = 307 [54.0%]; MG: N = 261 [46.0%]). SG had a higher proportion of patients with poor prognostic pathological feature tumors: WHO/ISUP grade 4, necrosis, lymphovascular invasion, infiltrative growth pattern, and sarcomatoid differentiation. Regarding the TIME, more immunogenic features were seen in SG than MG, with a higher PD-L1 positivity and a lower proportion of the desert phenotype. This is the first study to examine the differences in the TIME of primary lesions in patients with mRCC based on the time intervals to metastasis. The TIME of primary lesions could affect the time to metastasis.
  • Yujiro Hayashi; Kazutoshi Fujita; Kazuko Sakai; Shogo Adomi; Eri Banno; Satoshi Nojima; Eisuke Tomiyama; Makoto Matsushita; Taigo Kato; Koji Hatano; Atsunari Kawashima; Takafumi Minami; Eiichi Morii; Hirotsugu Uemura; Kazuto Nishio; Norio Nonomura
    Scientific reports 12 (1) 16642 - 16642 2022/10 
    During tumorigenesis, certain tissues are colonized by mutant clones with oncogenic driver mutations as precancer lesions. These mutations can facilitate clonal expansion and may contribute to malignant transformation. The molecular features of low-grade non-muscle invasive bladder cancer (NMIBC) and high-grade bladder cancer are so distinct that they are thought to follow different evolutionary tumorigenesis pathways. Although NMIBC accounts for most bladder tumors, the somatic mutation patterns in "precancer" urothelium of patients with NMIBC remain unclear. Here, we analyzed specimens of normal urothelium and bladder tumors from patients with low-grade and high-grade NMIBC and investigated the genomic evolution of the cancer. Somatic mutations were analyzed using 50 oncogene-targeted sequences and droplet digital polymerase chain reaction for TERT promoter mutations. Somatic mutations in TERT promoter, FGFR3, and CDKN2A were characteristically identified in the normal urothelium of patients with NMIBC. These mutations, consistently identified in both tumor and normal specimens, likely affect clonal expansion during the malignant transformation of NMIBC. Though larger samples and comprehensive study are warranted to confirm our results, the difference in mutational landscape of the precancerous urothelium of patients with bladder cancer could offer deeper understandings of genomic evolution in bladder tumorigenesis.
  • 菊池 尭; 齋藤 允孝; 森 康範; 藤田 和利; 能勢 和宏; 吉村 一宏; 植村 天受; 林 泰司; 西岡 伯; 玉井 健太郎; 今西 正昭; 秋山 隆弘
    移植 (一社)日本移植学会 57 (総会臨時) 265 - 265 0578-7947 2022/10
  • mRCCに対する1L NIVO+IPIの有効性・安全性 J-ENCORE試験第2回中間解析結果
    野澤 昌弘; 水野 隆一; 西本 紘嗣郎; 佐塚 智和; 濱本 周造; 沼倉 一幸; 溝上 敦; 近藤 恒徳; 内藤 整; 安部 崇重; 大庭 康司郎; 木村 剛; 田嶋 洋平; 伊藤 寛明; 植村 天受
    日本癌治療学会学術集会抄録集 (一社)日本癌治療学会 60回 優秀O9 - 1 2022/10
  • Mamoru Hashimoto; Nobutaka Shimizu; Saizo Fujimoto; Ken Kuwahara; Mitsuhisa Nishimoto; Shogo Adomi; Eri Banno; Takafumi Minami; Kazutoshi Fujita; Kazuhiro Yoshimura; Akihide Hirayama; Hirotsugu Uemura
    International urology and nephrology 2022/09 
    PURPOSE: In this study, we aimed to elucidate the pathophysiology of post-micturition dribble (PMD) through analyzing several variables including pressure flow study (PFS) findings and symptoms questionnaire. METHODS: We retrospectively analyzed male patients who visited our department between 2010 and 2020. We used modified international prostate symptom score (m-IPSS), which consists of eight sub-score related to lower urinary tract symptoms (Incomplete Emptying, Frequency, Intermittency, Urgency, Weak Stream, Straining, Nocturia, and PMD) and one question related to quality of life (QOL). Multivariate regression analysis was conducted to evaluate the relationship between PMD and the variables, including age, prostate volume (PV), body mass index, bladder outlet obstruction index (BOOI), bladder contractility index, and bladder voiding efficiency, which were obtained by PFS. RESULTS: A total of 143 male patients were analyzed. The patients with PMD showed significantly larger PV and higher BOOI, and worse IPSS total and QOL score than those without PMD. Multivariate regression analysis showed that large PV and BOOI were significantly associated with PMD. In Spearman's correlation analysis, PMD and each m-IPSS sub-score except nocturia had significant positive correlation. Furthermore, Spearman's correlation analysis showed that PMD and QOL had significant strong positive correlation. CONCLUSION: PMD was significantly associated with large PV and BOO evaluated by PFS. Furthermore, PMD significantly exacerbated QOL. The severity of PMD and the other m-IPSS sub-score except nocturia could have intercorrelation with each other.
  • Oguma Y; Hosono M; Okajima K; Inoue E; Nakamatsu K; Doi H; Matsuura T; Inada M; Uehara T; Wada Y; Ri A; Yamamoto Y; Yoshimura Y; Uemura H; Nishimura Y
    Radiation 2 (3) 273 - 284 2022/09 [Refereed]
  • Hirotsugu Uemura; Rikiya Matsumoto; Atsushi Mizokami; Hideaki Miyake; Hiroji Uemura; Hideyasu Matsuyama; Kazuyoshi Nakamura; Kazutaka Saito; Mutsushi Kawakita; Hideki Takeshita; Yosuke Koroki; Shintaro Ono; Maiko Murota; Miku Ito; Toshiyuki Kamoto; Kiyohide Fujimoto
    International journal of urology : official journal of the Japanese Urological Association 29 (9) 1061 - 1070 2022/09 
    OBJECTIVE: The prognosis of high-risk metastatic hormone-naïve prostate cancer is poor, and real-world evidence of therapeutic options and sequences is lacking. The J-ROCK study aimed to evaluate the outcomes in a real-world setting in Japan. METHODS: Patients with high-risk metastatic hormone-naïve prostate cancer diagnosed after May 2019 were eligible. Based on their treatment within 3 months after diagnosis, patients were allocated to either cohort 1 (androgen deprivation therapy alone or combined androgen blockade with bicalutamide) or cohort 2 (androgen deprivation therapy with abiraterone acetate+prednisolone, docetaxel, enzalutamide, or apalutamide). RESULTS: In this first interim analysis (cut-off January 2021), 410 patients were enrolled, including 163 patients in cohort 1 and 247 in cohort 2. The median follow-up period was 7.6 (range 0.1-20.5) months. A higher proportion of patients in cohort 2 (42.5%) achieved nadir prostate-specific antigen levels ≤0.2 ng/ml within a year, compared with cohort 1 (22.1%). Prostate-specific antigen-progression-free survival was also more favorable in cohort 2 (adjusted hazard ratio 0.629 [95% confidence interval 0.345-1.147]). CONCLUSIONS: The higher proportion of cohort 2 suggest a paradigm shift has occurred in the real-world treatment of high-risk metastatic hormone-naïve prostate cancer in Japan. Some factors including prostate-specific antigen may affect treatment selection but need further observation. Most patients in cohort 2 received abiraterone acetate+prednisolone. The proportion of patients in cohort 1 receiving combined androgen blockade was lower than previously reported in Japan. This analysis suggest that more intensive therapy tends to prolong prostate-specific antigen-progression-free survival in patients with high-risk metastatic hormone-naïve prostate cancer.
  • マウス前立腺癌におけるアンドロゲン除去による腸内細菌叢の一時的変化について(Temporal changes in gut microbial composition in response to androgen deprivation in mouse prostate cancer)
    若森 千怜; デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 藤田 和利; 坂野 恵里; 橋本 士; 西本 光寿; 野澤 昌弘; 吉村 一宏; 西尾 和人; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 81回 J - 1001 0546-0476 2022/09
  • PTENノックアウトマウス前立腺癌におけるCD73およびアデノシン2a受容体阻害による細胞外アデノシンの制御について(Targeting extracellular adenosine with combined anti-CD73 and A2aR blockade in mouse PTEN-deficient prostate cancer)
    橋本 士; デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 藤田 和利; 坂野 恵里; 西本 光寿; 野澤 昌弘; 吉村 一宏; 西尾 和人; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 81回 E - 1056 0546-0476 2022/09
  • クルクミンモノグルクロニドのPten欠損前立腺癌マウスに対する化学予防の可能性(Chemopreventive potential of curcumin monoglucuronide in mouse Pten-null prostate cancer)
    倉 由吏恵; デベラスコ・マルコ; 坂井 和子; 藤田 和利; 坂野 恵里; 藤田 至彦; 橋本 士; 西本 光寿; 野澤 昌弘; 吉村 一宏; 掛谷 秀昭; 植村 天受; 西尾 和人
    日本癌学会総会記事 (一社)日本癌学会 81回 P - 2387 0546-0476 2022/09
  • 細胞外アデノシンを標的とした治療は前立腺癌の抗腫瘍免疫を高める(Targeting extracellular adenosine to enhance antitumor immunity in prostate cancer)
    デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 藤田 和利; 坂野 恵里; 橋本 士; 西本 光寿; 野澤 昌弘; 吉村 一宏; 西尾 和人; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 81回 E - 3011 0546-0476 2022/09
  • PTEN KOマウス前立腺癌におけるabiraterone+capivasertib併用治療による抗腫瘍効果および免疫反応についての検討(Profiling antitumor and immune responses of abiraterone plus capivasertib in mouse Pten-deficient prostate cancer)
    植村 天受; 倉 由吏恵; 坂井 和子; 藤田 和利; 坂野 恵里; 西本 光寿; 橋本 士; 野澤 昌弘; 吉村 一宏; 西尾 和人; デベラスコ・マルコ
    日本癌学会総会記事 (一社)日本癌学会 81回 P - 3286 0546-0476 2022/09
  • Toyonori Tsuzuki; Chisato Ohe; Takahiro Osawa; Yosuke Yasuda; Toshiaki Tanaka; Satoshi Anai; Go Kimura; Kazutoshi Yamana; Shingo Hatakeyama; Takuya Yoshimoto; Yuki Nakagawa; Tamaki Fukuyama; Nobuaki Matsubara; Hirotsugu Uemura
    Pathology 55 (1) 31 - 39 2022/09 [Refereed]
     
    Studies have reported the relevance of immune phenotype, or presence of cluster of differentiation 8 (CD8)-positive tumour-infiltrating lymphocytes, to the anti-tumour efficacy of checkpoint inhibitors and to prognosis. The multicentre, retrospective ARCHERY study (UMIN000034131) collected tissue samples from Japanese patients with recurrent or metastatic renal cell carcinoma (RCC) who received systemic therapy between 2010 and 2015. In this exploratory analysis, the prognostic impact of immune phenotype and PD-L1 expression (separately and combined) was investigated using 770 surgical specimens and outcomes from patients enrolled in ARCHERY. A key objective was to determine overall survival (OS), defined as time from nephrectomy to death from any cause, by immune and PD-L1 subgroups. The median OS by immune phenotype was 28.8, 57.3, and 63.4 months in patients with inflamed, excluded, and desert tumours, respectively [hazard ratio (95% CI): inflamed 1.78 (1.27-2.49); excluded 1.08 (0.89-1.30); desert as reference]. PD-L1 positivity by SP142 showed a strong association with immune phenotype; 88.1%, 61.9%, and 8.7% of PD-L1-positive patients had inflamed, excluded, and desert phenotypes, respectively. PD-L1 positivity was also associated with worse OS in each phenotype, except for the inflamed phenotype (due to limited sample size in the PD-L1-negative immune inflamed subgroup; n=7). Additionally, the difference in OS by PD-L1 status was larger in the desert versus excluded phenotype [median OS in PD-L1 positive vs negative: 27.1 vs 67.2 months (desert), and 48.2 vs 78.1 months (excluded)]. Results show that PD-L1 expression was highly associated with immune phenotype, but both covariates should be evaluated when determining prognosis.
  • Saizo Fujmoto; Kazutoshi Fujita; Mitsuhisa Nishimoto; Mamoru Hamaguchi; Ken Kuwahara; Mamoru Hashimoto; Shogo Adomi; Takafumi Minami; Masahiro Nozawa; Kazuhiro Yoshimura; Hirotsugu Uemura
    Cancer medicine 2022/08 
    Enzalutamide, apalutamide, and darolutamide are currently recommended for patients with non-metastatic castration-resistant prostate cancer (nmCRPC), but cross-resistance of androgen receptor-axis-targeted therapies (ARAT) occurs. Because darolutamide has a distinct chemical structure to other non-steroidal antiandrogens, it may be effective for nmCRPC patients resistant to enzalutamide or apalutamide. We retrospectively evaluated the efficacy of switching to darolutamide in patients with nmCRPC. We included nine nmCRPC patients who experienced biochemical progression on enzalutamide or apalutamide and were switched over to darolutamide. Five patients (55.5%) had a PSA response >50% decline after starting darolutamide, with an average of 73% PSA decline. Median progression-free survival was 6 months. In conclusion, an ARAT switch from enzalutamide or apalutamide to darolutamide might be effective for nmCRPC. Although the validation in a large-scale cohort is necessary, the switch to darolutamide could be a promising therapeutic option after the progression of 1st line ARAT in nmCRPC patients.
  • Naoki Matsumura; Kazutoshi Fujita; Mitsuhisa Nishimoto; Takafumi Minami; Hideo Tahara; Kazuhiro Yoshimura; Hirotsugu Uemura
    World journal of urology 41 (8) 2063 - 2068 2022/08 
    PURPOSE: The therapeutic landscape for metastatic hormone-sensitive prostate cancer (mHSPC) has changed dramatically. Here, we provide the current status and future prospective of the management of mHSPC. METHODS: We reviewed recent literature of landmark studies on the managements of mHSPC. RESULTS: Upfront docetaxel or androgen receptor signaling inhibitor (ARSi) in addition to ADT has improved survival in mHSPC patients and has become the new standard of care. Triplet therapy with docetaxel, ARSi and ADT also improved survival. In the future, triplet therapy may become the standard of care. Oligometastatic mHSPC patients could benefit from local therapy. The inclusion of risk factors or the genetic biomarkers will provide the best treatment for individual mHSPC patients. CONCLUSION: Strong systemic therapy in the first-line treatment of mHSPC has been shown to improve survival and quality of life. Currently, several clinical trials are evaluating novel compounds such as PARP inhibitor, AKT inhibitor, and immune checkpoint inhibitor. The therapeutic landscape of mHSPC management will change dramatically.
  • 高齢男性における腸内細菌と血中総テストステロン値との関連
    西本 光寿; 藤田 和利; 松下 慎; 元岡 大祐; 波多野 浩士; 坂野 恵里; 秦 淳也; 福原 慎一郎; 中村 昇太; 南 高文; 吉村 一宏; 小原 航; 辻村 晃; 野々村 祝夫; 植村 天受
    日本性機能学会雑誌 (一社)日本性機能学会 37 (2) 137 - 137 1345-8361 2022/08
  • Mitsuhisa Nishimoto; Kazutoshi Fujita; Yutaka Yamamoto; Mamoru Hashimoto; Shogo Adomi; Eri Banno; Yoshitaka Saito; Nobutaka Shimizu; Yasunori Mori; Takafumi Minami; Masahiro Nozawa; Kazuhiro Nose; Akihide Hirayama; Kazuhiro Yoshimura; Hirotsugu Uemura
    Translational cancer research 11 (8) 2681 - 2687 2022/08 
    Background: Several therapeutic agents are available for metastatic castration-resistant prostate cancer (CRPC). However, prognosis is still not well developed. The Gleason score (GS) is a prognostic factor available for patients with metastatic CRPC. GSs ranging from 6 to 10 and GSs ≥8 are usually categorized as single prognostic factors. In this study, we evaluated the prognosis of high-GS metastatic CRPC in Japanese men. Methods: Overall, 105 patients with metastatic CRPC with a GS ≥8 were retrospectively analyzed. Multivariate analyses of patient age, GS, and Eastern Cooperative Oncology Group performance status (ECOG-PS) were performed using Cox proportional hazards analysis to predict overall survival (OS). Results: GS 8 had all Gleason patterns of 4+4. Thirty patients (28.6%) had GS of 8, and 75 (71.4%) had GS of 9 or 10. As a first-line treatment for metastatic CRPC, 42 patients (40%) received abiraterone, 35 (33.3%) received enzalutamide, and 26 (24.8%) received docetaxel. The 5-year OS in patients with GS of 8 was 65.0% [95% confidence interval (CI): 43.07-86.82%], while the 5-year OS in patients with GS of 9 or 10 was 37.0% (95% CI: 24.41-56.11%). There was a significant difference in OS between the GS 8 and GS 9-10 groups (log-rank test, P=0.038). Multivariate analysis showed that GS and ECOG-PS were significant prognostic factors for OS. Conclusions: Patients with metastatic CRPC with GS 9-10 had poor prognoses, suggesting the need for additional treatment options.
  • Taigo Kato; Kazutoshi Fujita; Takafumi Minami; Akira Nagahara; Yujiro Hyashi; Wataru Nakata; Kyosuke Matsuzaki; Kosuke Nakano; Koji Hatano; Atsunari Kawashima; Ryoichi Imamura; Shingo Takada; Kensaku Nishimura; Masao Tsujihata; Tetsuya Takao; Yasutomo Nakai; Masashi Nakayama; Kazuo Nishimura; Motohide Uemura; Hirotsugu Uemura; Norio Nonomura
    International journal of clinical oncology 27 (10) 1596 - 1604 2022/07 
    BACKGROUND: In metastatic renal-cell carcinoma (mRCC), recent clinical trials have shown efficacy of first-line combination therapy, as evidenced by better clinical outcome over target therapy. However, there are insufficient real-world evidences in mRCC patients in Japan. METHODS: We performed a multicenter retrospective study of 72 mRCC patients who received nivolumab plus ipilimumab as first-line treatment between September 2018 and July 2021. Patient's characteristics, clinical outcomes and safety were retrospectively reviewed. We analyzed overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) in patients treated with combination therapy. RESULTS: Of all patients, the median age was 70 years (range, 36-86) and the major type of histology was clear cell RCC (n = 55; 76.4%). Progressive disease (n = 25; 34.8%) and irAEs (n = 22; 30.6%) were the most common causes for discontinuing treatment. Median PFS and OS seemed similar between patients who discontinued treatment because of irAEs and for patients who did not (p = 0.360 and p = 0.069, respectively). Importantly, for patients with synchronous metastatic disease at diagnosis (n = 56), nephrectomy before initiating nivolumab plus ipilimumab had a significantly positive impact on better OS when compared to that in patients without nephrectomy (p = 0.028). CONCLUSION: This study confirms efficacy and safety of nivolumab plus ipilimumab for mRCC patients in real-world settings. Furthermore, nivolumab plus ipilimumab was associated with a better outcome in patients who had undergone nephrectomy at diagnosis for synchronous mRCC.
  • Eisuke Tomiyama; Kazutoshi Fujita; Kyosuke Matsuzaki; Ryohei Narumi; Akinaru Yamamoto; Toshihiro Uemura; Gaku Yamamichi; Yoko Koh; Makoto Matsushita; Yujiro Hayashi; Mamoru Hashimoto; Eri Banno; Taigo Kato; Koji Hatano; Atsunari Kawashima; Motohide Uemura; Ryo Ukekawa; Tetsuya Takao; Shingo Takada; Hirotsugu Uemura; Jun Adachi; Takeshi Tomonaga; Norio Nonomura
    British journal of cancer 127 (7) 1312 - 1323 2022/07 
    BACKGROUND: Urinary extracellular vesicles (uEVs) secreted from bladder cancer contain cancer-specific proteins that are potential diagnostic biomarkers. We identified and evaluated a uEV-based protein biomarker for bladder cancer diagnosis and analysed its functions. METHODS: Biomarker candidates, selected by shotgun proteomics, were validated using targeted proteomics of uEVs obtained from 49 patients with and 48 individuals without bladder cancer, including patients with non-malignant haematuria. We developed an enzyme-linked immunosorbent assay (ELISA) for quantifying the uEV protein biomarker without ultracentrifugation and evaluated urine samples from 36 patients with and 36 patients without bladder cancer. RESULTS: Thirteen membrane proteins were significantly upregulated in the uEVs from patients with bladder cancer in shotgun proteomics. Among them, eight proteins were validated by target proteomics, and Ephrin type-A receptor 2 (EphA2) was the only protein significantly upregulated in the uEVs of patients with bladder cancer, compared with that of patients with non-malignant haematuria. The EV-EphA2-CD9 ELISA demonstrated good diagnostic performance (sensitivity: 61.1%, specificity: 97.2%). We showed that EphA2 promotes proliferation, invasion and migration and EV-EphA2 promotes the invasion and migration of bladder cancer cells. CONCLUSIONS: We established EV-EphA2-CD9 ELISA for uEV-EphA2 detection for the non-invasive early clinical diagnosis of bladder cancer.
  • Eisuke Tomiyama; Kazutoshi Fujita; Kosuke Nakano; Ken Kuwahara; Takafumi Minami; Taigo Kato; Koji Hatano; Atsunari Kawashima; Motohide Uemura; Tetsuya Takao; Hiroaki Fushimi; Kotoe Katayama; Seiya Imoto; Kazuhiro Yoshimura; Ryoichi Imamura; Hirotsugu Uemura; Norio Nonomura
    Current Oncology MDPI AG 29 (6) 3911 - 3921 2022/05 
    Trophoblast cell surface antigen 2 (Trop-2, encoded by TACSTD2) is the target protein of sacituzumab govitecan, a novel antibody-drug conjugate for locally advanced or metastatic urothelial carcinoma. However, the expression status of Trop-2 in upper tract urothelial carcinoma (UTUC) remains unclear. We performed immunohistochemical analysis of 99 UTUC samples to evaluate the expression status of Trop-2 in patients with UTUC and analyze its association with clinical outcomes. Trop-2 was positive in 94 of the 99 UTUC samples, and high Trop-2 expression was associated with favorable progression-free survival (PFS) and cancer-specific survival (p = 0.0011, 0.0046). Multivariate analysis identified high Trop-2 expression as an independent predictor of favorable PFS (all cases, p = 0.045; high-risk group (pT3≤ or presence of lymphovascular invasion or lymph node metastasis), p = 0.014). Gene expression analysis using RNA sequencing data from 72 UTUC samples demonstrated the association between high TACSTD2 expression and favorable PFS (all cases, p = 0.069; high-risk group, p = 0.029). In conclusion, we demonstrated that Trop-2 is widely expressed in UTUC. Although high Trop-2 expression was a favorable prognostic factor in UTUC, its widespread expression suggests that sacituzumab govitecan may be effective for a wide range of UTUC.
  • 巣状分節状糸球体硬化症(FSGS)の生体腎移植後早期再発に対し選択的血漿交換およびLDL吸着療法を施行した一例
    坂野 恵里; 樋口 敦; 高橋 実代; 古林 法大; 菊池 尭; 齋藤 允孝; 森 康範; 坂口 美佳; 中谷 嘉寿; 能勢 和宏; 有馬 秀二; 植村 天受
    日本透析医学会雑誌 (一社)日本透析医学会 55 (Suppl.1) 637 - 637 1340-3451 2022/05
  • Kazutoshi Fujita; Makoto Matsushita; Eri Banno; Marco A De Velasco; Koji Hatano; Norio Nonomura; Hirotsugu Uemura
    International journal of urology : official journal of the Japanese Urological Association 29 (8) 793 - 798 2022/04 
    The gut microbiome is linked to several diseases such as Alzheimer's disease, rheumatoid arthritis, and colon cancer. The gut microbiome is also associated with the modulation of immune function, resulting in a different response to immune checkpoint therapy. The gut microbiome differs according to lifestyle, diet, sex, race, genetic background, and country. Lifestyle, especially diet, plays an important role in the development and progression of prostate cancer. Recent studies have revealed a connection between the gut microbiome and prostate cancer. A high-fat diet causes gut dysbiosis and gut bacterial metabolites, such as short-chain fatty acids and phospholipids that enter systemic circulation result in promoting prostate cancer growth. Additionally, the gut microbiota can serve as a source of testosterone, which affects prostate cancer progression. Men with castration-resistant prostate cancer have an increased abundance of gut bacteria with androgenic functions. Men with high-risk prostate cancer share a specific gut microbial profile and profiling gut microbiota could be a potentially effective tool to screen men with high-risk prostate cancer. Lifestyle modifications can improve the gut microbiome. Furthermore, altering the gut microbiome using prebiotic or probiotic interventions may prevent or delay prostate cancer development. Further study into the "Gut-Prostate Axis" would help in the discovery of new strategies for the prevention, screening, and treatment of prostate cancer.
  • 菊池 尭; 齋藤 允孝; 森 康範; 能勢 和宏; 吉村 一宏; 植村 天受; 玉井 健太郎; 林 泰司; 西岡 伯; 今西 正昭; 秋山 隆弘
    大阪透析研究会会誌 大阪透析研究会 39 (1) 23 - 29 0912-6937 2022/03
  • Koji Hatano; Tohru Yoneyama; Shingo Hatakeyama; Eisuke Tomiyama; Mutsumi Tsuchiya; Mitsuhisa Nishimoto; Kazuhiro Yoshimura; Eiji Miyoshi; Hirotsugu Uemura; Chikara Ohyama; Norio Nonomura; Kazutoshi Fujita
    British journal of cancer 126 (5) 764 - 770 2022/03 
    BACKGROUND: Altered prostate-specific antigen (PSA) glycosylation patterns can be useful biomarkers in detecting high-grade prostate cancer (HGPC). The microfluidic immunoassay system can analyse α2,3-linked sialylated PSA (α2,3-Sia-PSA) and α1,6-linked fucosylated PSA (α1,6-Fuc-PSA) using different lectins, Mackkia amurensis agglutinin and Pholiota squarrosa lectin, respectively. Here, we investigated the diagnostic value of simultaneous analysis of α2,3-Sia-PSA and α1,6-Fuc-PSA for the detection of HGPC. METHODS: Men with serum PSA levels of 4-20 ng/mL who underwent prostate biopsy were included. The model to predict HGPC (Gleason grade ≥2) was constructed by multivariate logistic regression analysis, in combination with α2,3-Sia-PSA and α1,6-Fuc-PSA (SF index). RESULTS: In the development cohort (n = 150), the SF index showed good discrimination for HGPC (area under the receiver-operating curve (AUC) 0.842; 95% confidence interval (CI) 0.782-0.903), compared to the single PSA test (AUC 0.632, 95% CI 0.543-0.721), α2,3-Sia-PSA (AUC 0.711, 95% CI 0.629-0.793) and α1,6-Fuc-PSA (AUC 0.738, 95% CI 0.657-0.819). Decision-curve analysis showed the superior benefit of the SF index. In the validation cohort (n = 57), the SF index showed good discrimination for HGPC (AUC 0.769, 95% CI 0.643-0.895). CONCLUSIONS: The SF index could differentiate HGPC, providing useful information for decision making for prostate biopsy in men with abnormal PSA levels.
  • Makoto Matsushita; Kazutoshi Fujita; Daisuke Motooka; Koji Hatano; Junya Hata; Mitsuhisa Nishimoto; Eri Banno; Kentaro Takezawa; Shinichiro Fukuhara; Hiroshi Kiuchi; Yue Pan; Toshifumi Takao; Akira Tsujimura; Shinichi Yachida; Shota Nakamura; Wataru Obara; Hirotsugu Uemura; Norio Nonomura
    The world journal of men's health 40 (3) 517 - 525 2022/02 
    PURPOSE: In males, testosterone levels have been implicated in various diseases. Recently, the influence of gut microbial-derived compounds on host metabolism has become evident, and it has been suggested that some gut bacteria may be involved in testosterone metabolism. In the present study, we examined the relationship between testosterone levels and gut microbiota in elderly Japanese men. MATERIALS AND METHODS: We collected samples from Japanese male subjects suspected of having prostate cancer and underwent prostate biopsies and excluded patients with positive biopsies to avoid the effect of prostate cancer on the gut microbiota. In total, 54 Japanese males with negative biopsy results were included in our study. The gut microbiota was analyzed by 16S rRNA gene sequencing of bacterial DNA extracted from rectal swabs. Gut microbiota compositions were compared between the two groups according to the level of serum testosterone (above or below 3.5 ng /mL). RESULTS: The median age of the cohort was 71 years, and the quartile range was 67 to 73 years. We observed no significant difference in alpha or beta diversity, but some bacteria belonging to the phylum Firmicutes (Clostridiales, Turicibacter, and Gemella) were increased in the high testosterone group. Serum testosterone levels positively correlated with the relative amount of Firmicutes (rS=0.3323, p=0.0141), and the amount of Firmicutes affected serum testosterone levels independent of host factors (age, body mass index, triglyceride, and total cholesterol; β=0.770, p=0.0396). CONCLUSIONS: Some intestinal bacteria belonging to the phylum Firmicutes were associated with testosterone levels in elderly males. Therefore, the gut microbiota could affect testosterone metabolism in elderly males.
  • 腎移植患者の腎性貧血に対するロキサデュスタット投与症例の検討
    林 泰司; 北 博行; 玉井 健太郎; 大關 孝之; 西岡 伯; 菊池 尭; 齋藤 允孝; 森 康範; 能勢 和宏; 吉村 一宏; 植村 天受; 今西 正昭; 秋山 隆弘
    日本臨床腎移植学会プログラム・抄録集 (一社)日本臨床腎移植学会 55回 238 - 238 2022/02
  • 当院における腎移植後の新型コロナウイルス感染症例の検討
    菊池 尭; 齋藤 允孝; 森 康範; 能勢 和宏; 吉村 一宏; 植村 天受; 玉井 健太郎; 林 泰司; 西岡 伯; 今西 正昭; 秋山 隆弘
    日本臨床腎移植学会プログラム・抄録集 (一社)日本臨床腎移植学会 55回 295 - 295 2022/02
  • 免疫チェックポイント阻害剤からパゾパニブへの薬剤変更後早期に血小板低下、肝機能障害を来たした1例
    高橋 智輝; 藤本 西蔵; 浜口 守; 橋本 士; 菊池 尭; 安富 正悟; 大關 孝之; 清水 信貴; 森 康範; 南 高文; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 植村 天受
    泌尿器科紀要 泌尿器科紀要刊行会 68 (1) 24 - 24 0018-1994 2022/01
  • 腎移植後に発症した同・異時性四重複癌の1例
    藤本 西蔵; 浜口 守; 高橋 智輝; 橋本 士; 菊池 尭; 安富 正悟; 大關 孝之; 清水 信貴; 森 康範; 南 高文; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 植村 天受; 林 泰司; 西岡 伯
    泌尿器科紀要 泌尿器科紀要刊行会 68 (1) 27 - 27 0018-1994 2022/01
  • Makoto Matsushita; Kazutoshi Fujita; Koji Hatano; Marco A De Velasco; Hirotsugu Uemura; Norio Nonomura
    Frontiers in endocrinology 13 852382 - 852382 2022 
    Prostate cancer (PCa) is the most common malignancy in men worldwide, thus developing effective prevention strategies remain a critical challenge. Insulin-like growth factor 1 (IGF-1) is produced mainly in the liver by growth hormone signaling and is necessary for normal physical growth. However, several studies have shown an association between increased levels of circulating IGF-1 and the risk of developing solid malignancies, including PCa. Because the IGF-1 receptor is overexpressed in PCa, IGF-1 can accelerate PCa growth by activating phosphoinositide 3-kinase and mitogen-activated protein kinase, or increasing sex hormone sensitivity. Short-chain fatty acids (SCFAs) are beneficial gut microbial metabolites, mainly because of their anti-inflammatory effects. However, we have demonstrated that gut microbiota-derived SCFAs increase the production of IGF-1 in the liver and prostate. This promotes the progression of PCa by the activation of IGF-1 receptor downstream signaling. In addition, the relative abundance of SCFA-producing bacteria, such as Alistipes, are increased in gut microbiomes of patients with high-grade PCa. IGF-1 production is therefore affected by the gut microbiome, dietary habits, and genetic background, and may play a central role in prostate carcinogenesis. The pro-tumor effects of bacteria and diet-derived metabolites might be potentially countered through dietary regimens and supplements. The specific diets or supplements that are effective are unclear. Further research into the "Gut-IGF-1-Prostate Axis" may help discover optimal diets and nutritional supplements that could be implemented for prevention of PCa.
  • Satoshi Tamada; Chihiro Kondoh; Nobuaki Matsubara; Ryuichi Mizuno; Go Kimura; Satoshi Anai; Yoshihiko Tomita; Masafumi Oyama; Naoya Masumori; Takahiro Kojima; Hiroaki Matsumoto; Mei Chen; Mengran Li; Kenji Matsuda; Yoshinobu Tanaka; Brian I Rini; Hirotsugu Uemura
    International journal of clinical oncology 27 (1) 154 - 164 2022/01 
    BACKGROUND: In the phase III open-label KEYNOTE-426 (NCT02853331) study, first-line pembrolizumab and axitinib improved overall survival (OS) and progression-free survival (PFS) versus sunitinib for metastatic renal cell carcinoma (mRCC). KEYNOTE-426 evaluated patients enrolled from 25 sites in Japan. METHODS: Patients enrolled in Japan were included in this post hoc subgroup analysis. Adults with clear cell mRCC were randomly assigned 1:1 to receive intravenous pembrolizumab 200 mg every 3 weeks plus oral axitinib 5 mg twice daily or oral sunitinib 50 mg once daily (4 weeks on/2 weeks off). Dual primary endpoints were OS and PFS as assessed by blinded independent central review. Objective response rate (ORR) and safety were secondary endpoints. RESULTS: The Japanese subgroup comprised 94 patients (pembrolizumab-axitinib, n = 44; sunitinib, n = 50; 11% of the intent-to-treat population). Median time from randomization to data cutoff (January 6, 2020) was 29.5 months (range 24.6-37.3). Consistent with the intent-to-treat population, the OS, PFS, and ORR suggested improvement with pembrolizumab-axitinib versus sunitinib in the Japanese subgroup. Grade ≥ 3 treatment-related adverse events (TRAEs) occurred in 70% of patients receiving pembrolizumab-axitinib versus 78% receiving sunitinib; 11 (25%) patients receiving pembrolizumab-axitinib and 13 (27%) patients receiving sunitinib discontinued the study medication due to AEs. TRAEs led to the discontinuation of pembrolizumab, axitinib, pembrolizumab-axitinib, or sunitinib in 32%, 34%, 14%, and 20%, respectively. No deaths from TRAEs occurred. CONCLUSIONS: Efficacy outcomes for the Japanese subgroup were consistent with those of the global population. Safety in Japanese patients was consistent with the results from the global population.
  • Kazutoshi Fujita; Koji Hatano; Mamoru Hashimoto; Eisuke Tomiyama; Eiji Miyoshi; Norio Nonomura; Hirotsugu Uemura
    International journal of molecular sciences 22 (24) 2021/12 
    Fucosylation is an oligosaccharide modification that plays an important role in immune response and malignancy, and specific fucosyltransferases (FUTs) catalyze the three types of fucosylations: core-type, Lewis type, and H type. FUTs regulate cancer proliferation, invasiveness, and resistance to chemotherapy by modifying the glycosylation of signaling receptors. Oligosaccharides on PD-1/PD-L1 proteins are specifically fucosylated, leading to functional modifications. Expression of FUTs is upregulated in renal cell carcinoma, bladder cancer, and prostate cancer. Aberrant fucosylation in prostate-specific antigen (PSA) could be used as a novel biomarker for prostate cancer. Furthermore, elucidation of the biological function of fucosylation could result in the development of novel therapeutic targets. Further studies are needed in the field of fucosylation glycobiology in urological malignancies.
  • 日本人未治療転移性腎細胞癌患者を対象としたニボルマブ・イピリムマブ併用療法の有効性と安全性に関する前向き観察研究(J-ENCORE)の中間解析結果
    内藤 整; 木村 剛; 西本 紘嗣郎; 野澤 昌弘; 溝上 敦; 永田 政義; 本郷 文弥; 濱本 周造; 穴井 智; 田嶋 洋平; 金子 裕和; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 LB02 - 02 2021/12
  • APCCC JAPAN:今こそ日本人泌尿器科医の常識を問う! 遺伝子診断に基づく個別化医療 遺伝子診断の今後と治療への応用
    藤田 和利; 南 高文; 野澤 昌弘; 吉村 一宏; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 SY31 - 7 2021/12
  • 馬蹄腎生体腎移植ドナーからgraftをHand-assisted Laparoscopic Nephrectomyにて摘出した1例
    齋藤 允孝; 西本 光寿; 菊池 尭; 安富 正悟; 坂野 恵里; 清水 信貴; 森 康範; 南 高文; 藤田 和利; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 AVP01 - 05 2021/12
  • 日本人における高悪性度前立腺癌に特徴的な腸内細菌叢の解析
    藤田 和利; 松下 慎; 波多野 浩士; 中村 昇太; 川村 憲彦; 高田 晋吾; 西本 光寿; 坂野 恵里; 南 高文; 野澤 昌弘; 吉村 一宏; 植村 天受; 野々村 祝夫
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 AOP06 - 09 2021/12
  • 古典的な形態学的細胞病理学的手法を超える深層学習を用いた腫瘍悪性度診断システム(A deep-learning-based system to diagnose tumor malignancy beyond classical morphological cytopathology techniques)
    藤田 和利; 野島 聡; 寺山 慧; 中山 尭仁; 藤本 西蔵; 橋本 士; 安富 正悟; 清水 信貴; 吉村 一宏; 植村 天受; 奥野 恭史; 野々村 祝夫; 森井 英一
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 ISA03 - 01 2021/12
  • 臨床的に重要な前立腺癌を検出するための血中α2,3-結合シアル酸およびコア型フコシル化PSAの同時解析(Simultaneous analysis of serum a 2,3-linked sialylation and core-type fucosylation of PSA for the detection of clinically significant prostate cancer)
    波多野 浩士; 米山 徹; 畠山 真吾; 藤田 和利; 三善 英知; 吉村 一宏; 植村 天受; 大山 力; 野々村 祝夫
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 ISP02 - 03 2021/12
  • 尿流動態検査を用いた男性患者の排尿後尿滴下に影響を与える因子の検討
    橋本 士; 西本 光寿; 清水 信貴; 南 高文; 藤田 和利; 野澤 昌弘; 吉村 一宏; 平山 暁秀; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 OP01 - 03 2021/12
  • 内分泌療法未治療転移性前立腺癌に対するアビラテロンとアンドロゲン遮断療法の比較
    松村 直紀; 藤田 和利; 西本 光寿; 山本 豊; 永井 康晴; 南 高文; 野澤 昌弘; 森本 康裕; 田原 秀男; 上島 成也; 平山 暁秀; 吉村 一宏; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 OP10 - 03 2021/12
  • 高Gleason Score転移性去勢抵抗性前立腺癌における予後の検討
    西本 光寿; 藤田 和利; 山本 豊; 橋本 士; 安富 正悟; 清水 信貴; 森 康範; 南 高文; 野澤 昌弘; 能勢 和宏; 平山 暁秀; 吉村 一宏; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 OP12 - 06 2021/12
  • 転移性腎盂・尿管癌と転移性膀胱癌の予後の比較
    安富 正悟; 藤田 和利; 橋本 士; 菊池 尭; 坂野 恵里; 斎藤 允孝; 清水 信貴; 森 康範; 南 高文; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 OP20 - 04 2021/12
  • アンドロゲン除去療法とJAK1/2およびPD-L1阻害による前立腺特異的Ptenノックアウトマウスモデルにおける抗腫瘍効果の改善について
    倉 由吏恵; 西本 光寿; 清水 信貴; 南 高文; 坂井 和子; 藤田 和利; 野澤 昌弘; 吉村 一宏; デベラスコ・マルコ; 西尾 和人; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 OP71 - 01 2021/12
  • A2aRの阻害はPten欠損前立腺癌マウスにおいてCTLA4抗体の抗腫瘍活性を高める
    デベラスコ・マルコ; 倉 由吏恵; 西本 光寿; 坂井 和子; 南 高文; 藤田 和利; 野澤 昌弘; 吉村 一宏; 西尾 和人; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 OP71 - 02 2021/12
  • 前立腺特異的Ptenノックアウトマウスにおけるアパルタミドの短期免疫反応について
    植村 天受; 倉 由吏恵; 西本 光寿; 南 高文; 坂井 和子; 藤田 和利; 野澤 昌弘; 吉村 一宏; 西尾 和人; デベラスコ・マルコ
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 OP71 - 03 2021/12
  • 限局性前立腺癌に対するBrachytherapy後膀胱癌発症例の検討
    南 高文; 橋本 士; 西本 光寿; 安富 正悟; 坂野 恵里; 齋藤 允孝; 清水 信貴; 森 康範; 藤田 和利; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 PP08 - 09 2021/12
  • マウスPTEN欠失前立腺癌に対するJAK1/2標的療法が腸内細菌叢に与える影響について
    橋本 士; De Velasco Marco; 坂野 恵里; 清水 信貴; 森 康範; 南 高文; 藤田 和利; 野澤 昌弘; 吉村 一宏; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 PP12 - 01 2021/12
  • 上部尿路上皮癌におけるVEGFR-2発現の免疫組織化学的検討
    藤本 西蔵; 藤田 和利; 冨山 栄輔; 氏家 剛; 中山 尭仁; 橋本 士; 西本 光寿; 坂野 恵里; 高尾 徹也; Netto George J.; 吉村 一宏; 野々村 祝子; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 PP25 - 01 2021/12
  • 転移性尿路上皮癌に対するペムブロリズマブの使用成績
    明石 泰典; 山本 豊; 安富 正悟; 橋本 士; 喜馬 啓介; 西本 光寿; 清水 信貴; 南 高文; 藤田 和利; 野澤 昌弘; 吉村 一宏; 平山 暁秀; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 PP25 - 06 2021/12
  • 前立腺再生検の結果予測因子としての前立腺周囲脂肪面積の有用性の検討
    中山 尭仁; 橋本 士; 坂野 恵里; 齋藤 允孝; 清水 信貴; 森 康範; 南 高文; 藤田 和利; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 PP28 - 05 2021/12
  • 倉 由吏恵; デベラスコ・マルコ; 坂井 和子; 橋本 士; 藤田 和利; 野澤 昌弘; 吉村 一宏; 植村 天受; 西尾 和人
    近畿大学医学雑誌 近畿大学医学会 46 (3-4) 19A - 19A 0385-8367 2021/12
  • 異種間遺伝子発現解析から免疫療法のための免疫表現型解析への応用
    坂野 恵里; 橋本 士; 安富 正悟; 西本 光寿; 倉 由吏恵; 藤田 和利; 野澤 昌弘; 吉村 一宏; De Velasco Marco; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 PP12 - 07 2021/12
  • 日本人未治療転移性腎細胞癌患者を対象としたニボルマブ・イピリムマブ併用療法の有効性と安全性に関する前向き観察研究(J-ENCORE)の中間解析結果
    内藤 整; 木村 剛; 西本 紘嗣郎; 野澤 昌弘; 溝上 敦; 永田 政義; 本郷 文弥; 濱本 周造; 穴井 智; 田嶋 洋平; 金子 裕和; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 LB02 - 02 2021/12
  • APCCC JAPAN:今こそ日本人泌尿器科医の常識を問う! 遺伝子診断に基づく個別化医療 遺伝子診断の今後と治療への応用
    藤田 和利; 南 高文; 野澤 昌弘; 吉村 一宏; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 SY31 - 7 2021/12
  • 馬蹄腎生体腎移植ドナーからgraftをHand-assisted Laparoscopic Nephrectomyにて摘出した1例
    齋藤 允孝; 西本 光寿; 菊池 尭; 安富 正悟; 坂野 恵里; 清水 信貴; 森 康範; 南 高文; 藤田 和利; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 AVP01 - 05 2021/12
  • 日本人における高悪性度前立腺癌に特徴的な腸内細菌叢の解析
    藤田 和利; 松下 慎; 波多野 浩士; 中村 昇太; 川村 憲彦; 高田 晋吾; 西本 光寿; 坂野 恵里; 南 高文; 野澤 昌弘; 吉村 一宏; 植村 天受; 野々村 祝夫
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 AOP06 - 09 2021/12
  • Simultaneous analysis of serum a 2,3-linked sialylation and core-type fucosylation of PSA for the detection of clinically significant prostate cancer(和訳中)
    波多野 浩士; 米山 徹; 畠山 真吾; 藤田 和利; 三善 英知; 吉村 一宏; 植村 天受; 大山 力; 野々村 祝夫
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 ISP02 - 03 2021/12
  • 尿流動態検査を用いた男性患者の排尿後尿滴下に影響を与える因子の検討
    橋本 士; 西本 光寿; 清水 信貴; 南 高文; 藤田 和利; 野澤 昌弘; 吉村 一宏; 平山 暁秀; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 OP01 - 03 2021/12
  • 内分泌療法未治療転移性前立腺癌に対するアビラテロンとアンドロゲン遮断療法の比較
    松村 直紀; 藤田 和利; 西本 光寿; 山本 豊; 永井 康晴; 南 高文; 野澤 昌弘; 森本 康裕; 田原 秀男; 上島 成也; 平山 暁秀; 吉村 一宏; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 OP10 - 03 2021/12
  • 高Gleason Score転移性去勢抵抗性前立腺癌における予後の検討
    西本 光寿; 藤田 和利; 山本 豊; 橋本 士; 安富 正悟; 清水 信貴; 森 康範; 南 高文; 野澤 昌弘; 能勢 和宏; 平山 暁秀; 吉村 一宏; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 OP12 - 06 2021/12
  • 転移性腎盂・尿管癌と転移性膀胱癌の予後の比較
    安富 正悟; 藤田 和利; 橋本 士; 菊池 尭; 坂野 恵里; 斎藤 允孝; 清水 信貴; 森 康範; 南 高文; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 OP20 - 04 2021/12
  • アンドロゲン除去療法とJAK1/2およびPD-L1阻害による前立腺特異的Ptenノックアウトマウスモデルにおける抗腫瘍効果の改善について
    倉 由吏恵; 西本 光寿; 清水 信貴; 南 高文; 坂井 和子; 藤田 和利; 野澤 昌弘; 吉村 一宏; デベラスコ・マルコ; 西尾 和人; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 OP71 - 01 2021/12
  • A2aRの阻害はPten欠損前立腺癌マウスにおいてCTLA4抗体の抗腫瘍活性を高める
    デベラスコ・マルコ; 倉 由吏恵; 西本 光寿; 坂井 和子; 南 高文; 藤田 和利; 野澤 昌弘; 吉村 一宏; 西尾 和人; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 OP71 - 02 2021/12
  • 前立腺特異的Ptenノックアウトマウスにおけるアパルタミドの短期免疫反応について
    植村 天受; 倉 由吏恵; 西本 光寿; 南 高文; 坂井 和子; 藤田 和利; 野澤 昌弘; 吉村 一宏; 西尾 和人; デベラスコ・マルコ
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 OP71 - 03 2021/12
  • 限局性前立腺癌に対するBrachytherapy後膀胱癌発症例の検討
    南 高文; 橋本 士; 西本 光寿; 安富 正悟; 坂野 恵里; 齋藤 允孝; 清水 信貴; 森 康範; 藤田 和利; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 PP08 - 09 2021/12
  • マウスPTEN欠失前立腺癌に対するJAK1/2標的療法が腸内細菌叢に与える影響について
    橋本 士; De Velasco Marco; 坂野 恵里; 清水 信貴; 森 康範; 南 高文; 藤田 和利; 野澤 昌弘; 吉村 一宏; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 PP12 - 01 2021/12
  • 異種間遺伝子発現解析から免疫療法のための免疫表現型解析への応用
    坂野 恵里; 橋本 士; 安富 正悟; 西本 光寿; 倉 由吏恵; 藤田 和利; 野澤 昌弘; 吉村 一宏; De Velasco Marco; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 PP12 - 07 2021/12
  • 上部尿路上皮癌におけるVEGFR-2発現の免疫組織化学的検討
    藤本 西蔵; 藤田 和利; 冨山 栄輔; 氏家 剛; 中山 尭仁; 橋本 士; 西本 光寿; 坂野 恵里; 高尾 徹也; Netto George J.; 吉村 一宏; 野々村 祝子; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 PP25 - 01 2021/12
  • 転移性尿路上皮癌に対するペムブロリズマブの使用成績
    明石 泰典; 山本 豊; 安富 正悟; 橋本 士; 喜馬 啓介; 西本 光寿; 清水 信貴; 南 高文; 藤田 和利; 野澤 昌弘; 吉村 一宏; 平山 暁秀; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 PP25 - 06 2021/12
  • 前立腺再生検の結果予測因子としての前立腺周囲脂肪面積の有用性の検討
    中山 尭仁; 橋本 士; 坂野 恵里; 齋藤 允孝; 清水 信貴; 森 康範; 南 高文; 藤田 和利; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 PP28 - 05 2021/12
  • Apalutamide induces acute immune responses in mouse Pten-deficient prostate cancer(和訳中)
    倉 由吏恵; デベラスコ マルコ; 坂井 和子; 橋本 士; 藤田 和利; 野澤 昌弘; 吉村 一宏; 植村 天受; 西尾 和人
    近畿大学医学雑誌 近畿大学医学会 46 (3-4) 19A - 19A 0385-8367 2021/12
  • 筋層浸潤性尿路上皮癌患者を対象としたニボルマブの術後補助療法 プラセボ対照国際共同第3相試験(CheckMate 274試験)の日本人サブグループ解析
    小林 皇; 木村 剛; 大家 基嗣; 植村 天受; 西山 博之; Bajorin Dean; Galsky Matthew D.; Nasroulah Federico; Collette Sandra; Broughton Edward; Unsal-Kacma Keziban; 紙透 幸則; 冨田 善彦
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 109回 LB01 - 04 2021/12
  • Kentaro Takezawa; Kazutoshi Fujita; Makoto Matsushita; Daisuke Motooka; Koji Hatano; Eri Banno; Nobutaka Shimizu; Tetsuya Takao; Shingo Takada; Koichi Okada; Shinichiro Fukuhara; Hiroshi Kiuchi; Hirotsugu Uemura; Shota Nakamura; Yoshiyuki Kojima; Norio Nonomura
    The Prostate 81 (16) 1287 - 1293 2021/12 
    BACKGROUND: The pathophysiology of the prostate enlargement underlying lower urinary tract symptoms is unknown. Meanwhile, the gut microbiota can contribute to various host conditions. We hypothesized that the gut microbiota plays a role in prostate enlargement. METHODS: We included 128 patients who underwent prostate biopsies at our hospitals between December 2018 and March 2020, excluding those who had used antibiotics within the past 6 months and those who were diagnosed with prostate cancer of cT3 or higher. Patients with prostate volumes ≥30 ml were defined as the prostate-enlargement (PE) group; those with prostate volumes <30 ml were defined as the non-PE group. Their gut microbiotas were analyzed via 16S rRNA metagenomic analyses of rectal swab samples and were compared between the groups. RESULTS: The PE group included 66 patients; the non-PE group included 62 patients. Age, body mass index, and prostate-specific antigen levels did not significantly differ between the groups. Linear discriminant analysis effect size analysis indicated a higher proportion of Firmicutes and Actinobacteria in the PE group and a higher proportion of Bacteroidetes in the non-PE group. The Firmicutes/Bacteroidetes (F/B) ratio was significantly higher in the PE group than in the non-PE group (2.21 ± 0.39 vs. 1.61 ± 0.40, p = 0.015). CONCLUSION: The F/B ratio of the gut microbiota was associated with prostate enlargement. Although the detailed mechanisms are unclear, the gut microbiota might affect prostate enlargement.
  • 近畿大学におけるロボット支援腹腔鏡下膀胱全摘除術(RALC)の初期経験
    南 高文; 井之口 舜亮; 藤本 西蔵; 安富 正悟; 森 康範; 藤田 和利; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 植村 天受
    日本泌尿器内視鏡学会総会 (一社)日本泌尿器内視鏡・ロボティクス学会 35回 P - 3 2021/11
  • 転移性腎細胞癌患者に対するニボルマブの有効性 日本人臨床カルテレビュー最終調査
    舛井 覚; 日向 信之; 米瀬 淳二; 中井 康友; 城武 卓; 武内 在雄; 稲元 輝生; 野澤 昌弘; 植田 浩介; 悦永 徹; 大澤 崇宏; 植村 元秀; 森島 直士; 伊藤 寛明; 植村 天受
    日本癌治療学会学術集会抄録集 (一社)日本癌治療学会 59回 ☆O54 - 2 2021/10
  • 近畿大学病院における転移性腎癌に対するipilimumab+nivolumab併用療法の初期使用経験
    南 高文; 藤田 和利; 橋本 士; 西本 光寿; 菊池 尭; 安富 正悟; 坂野 恵里; 齋藤 允孝; 清水 信貴; 森 康範; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 植村 天受
    日本癌治療学会学術集会抄録集 (一社)日本癌治療学会 59回 P27 - 2 2021/10
  • 非転移性去勢抵抗性前立腺癌の予後予測因子についての検討
    西本 光寿; 藤田 和利; 山本 豊; 橋本 士; 安富 正悟; 坂野 恵里; 齋藤 允孝; 清水 信貴; 森 康範; 南 高文; 野澤 昌弘; 能勢 和宏; 平山 暁秀; 吉村 一宏; 植村 天受
    日本癌治療学会学術集会抄録集 (一社)日本癌治療学会 59回 P29 - 2 2021/10
  • 高グリソン転移性去勢抵抗性前立腺癌における予後の検討
    藤田 和利; 西本 光寿; 山本 豊; 橋本 士; 安冨 正悟; 坂野 恵里; 齋藤 允孝; 清水 信貴; 森 康範; 南 高文; 野澤 昌弘; 能勢 和弘; 平山 暁秀; 吉村 一宏; 植村 天受
    日本癌治療学会学術集会抄録集 (一社)日本癌治療学会 59回 O62 - 7 2021/10
  • 内分泌療法未治療転移性前立腺癌に対するアビラテロンとアンドロゲン遮断療法の比較
    松村 直紀; 藤田 和利; 西本 光寿; 山本 豊; 桑原 賢; 永井 康晴; 南 高文; 野澤 昌弘; 森本 康裕; 田原 秀男; 上島 成也; 江左 篤宣; 平山 暁秀; 吉村 一宏; 植村 天受
    日本癌治療学会学術集会抄録集 (一社)日本癌治療学会 59回 O63 - 1 2021/10
  • 近畿大学病院における転移性腎癌に対するipilimumab+nivolumab併用療法の初期使用経験
    南 高文; 藤田 和利; 橋本 士; 西本 光寿; 菊池 尭; 安富 正悟; 坂野 恵里; 齋藤 允孝; 清水 信貴; 森 康範; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 植村 天受
    日本癌治療学会学術集会抄録集 (一社)日本癌治療学会 59回 P27 - 2 2021/10
  • 非転移性去勢抵抗性前立腺癌の予後予測因子についての検討
    西本 光寿; 藤田 和利; 山本 豊; 橋本 士; 安富 正悟; 坂野 恵里; 齋藤 允孝; 清水 信貴; 森 康範; 南 高文; 野澤 昌弘; 能勢 和宏; 平山 暁秀; 吉村 一宏; 植村 天受
    日本癌治療学会学術集会抄録集 (一社)日本癌治療学会 59回 P29 - 2 2021/10
  • 転移性腎細胞癌患者に対するニボルマブの有効性 日本人臨床カルテレビュー最終調査
    舛井 覚; 日向 信之; 米瀬 淳二; 中井 康友; 城武 卓; 武内 在雄; 稲元 輝生; 野澤 昌弘; 植田 浩介; 悦永 徹; 大澤 崇宏; 植村 元秀; 森島 直士; 伊藤 寛明; 植村 天受
    日本癌治療学会学術集会抄録集 (一社)日本癌治療学会 59回 ☆O54 - 2 2021/10
  • 菊池 尭; 齋藤 允孝; 森 康範; 能勢 和宏; 植村 天受; 玉井 健太郎; 林 泰司; 西岡 伯; 今西 正昭; 秋山 隆弘
    大阪透析研究会会誌 大阪透析研究会 38 (2) 226 - 226 0912-6937 2021/09
  • 腎移植患者の腎性貧血に対するロキサデュスタット投与症例の検討
    林 泰司; 北 博行; 玉井 健太郎; 大關 孝之; 西岡 伯; 菊池 堯; 齋藤 允孝; 森 康範; 能勢 和宏; 吉村 一宏; 植村 天受; 今西 正昭; 秋山 隆弘
    移植 (一社)日本移植学会 56 (総会臨時) P1 - 45 0578-7947 2021/09
  • Pten欠損前立腺癌マウスにおける糞便中の微生物とアンドロゲン除去の関係について
    若森 千怜; デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 橋本 士; 坂野 恵里; 藤田 和利; 野澤 昌弘; 吉村 一宏; 西尾 和人; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 80回 [E3 - 4] 0546-0476 2021/09
  • A2aR阻害はPten欠損前立腺癌マウスモデルにおいてCTLA4阻害薬の抗腫瘍活性を増強する
    デベラスコ・マルコ; 倉 由吏恵; 坂野 恵里; 坂井 和子; 清水 信貴; 藤田 和利; 野澤 昌弘; 吉村 一宏; 西尾 和人; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 80回 [E12 - 1] 0546-0476 2021/09
  • クルクミンモノグルクロニドはPten欠損前立腺癌の腫瘍微小環境を調節し抗腫瘍活性を示す
    倉 由吏恵; デベラスコ・マルコ; 坂井 和子; 藤田 至彦; 橋本 士; 森 康範; 南 高文; 藤田 和利; 掛谷 秀昭; 植村 天受; 西尾 和人
    日本癌学会総会記事 (一社)日本癌学会 80回 [E17 - 3] 0546-0476 2021/09
  • アパルタミドが惹起する短期免疫反応の前臨床評価について
    植村 天受; 倉 由吏恵; 坂野 恵里; 橋本 士; 坂井 和子; 藤田 和利; 野澤 昌弘; 吉村 一宏; 西尾 和人; デベラスコ・マルコ
    日本癌学会総会記事 (一社)日本癌学会 80回 [J14 - 3] 0546-0476 2021/09
  • 前立腺癌マウスにおける抗PD-L1免疫療法およびJAK1/2阻害と糞便中の細菌について
    坂野 恵里; デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 橋本 士; 藤田 和利; 野澤 昌弘; 吉村 一宏; 西尾 和人; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 80回 [E14 - 4] 0546-0476 2021/09
  • 腸内細菌叢とがん 高grade前立腺癌に関与する腸内細菌叢の解析
    藤田 和利; 松下 慎; 元岡 大祐; 波多野 浩士; 西本 光寿; 坂野 恵里; 南 高文; 野澤 昌弘; 高尾 徹也; 高田 晋吾; 吉村 一宏; 谷内田 真一; 中村 昇太; 植村 天受; 野々村 祝夫
    日本癌学会総会記事 (一社)日本癌学会 80回 [S12 - 6] 0546-0476 2021/09
  • Pten欠損前立腺癌マウスにおける糞便中の微生物とアンドロゲン除去の関係について
    若森 千怜; デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 橋本 士; 坂野 恵里; 藤田 和利; 野澤 昌弘; 吉村 一宏; 西尾 和人; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 80回 [E3 - 4] 0546-0476 2021/09
  • A2aR阻害はPten欠損前立腺癌マウスモデルにおいてCTLA4阻害薬の抗腫瘍活性を増強する
    デベラスコ・マルコ; 倉 由吏恵; 坂野 恵里; 坂井 和子; 清水 信貴; 藤田 和利; 野澤 昌弘; 吉村 一宏; 西尾 和人; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 80回 [E12 - 1] 0546-0476 2021/09
  • 前立腺癌マウスにおける抗PD-L1免疫療法およびJAK1/2阻害と糞便中の細菌について
    坂野 恵里; デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 橋本 士; 藤田 和利; 野澤 昌弘; 吉村 一宏; 西尾 和人; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 80回 [E14 - 4] 0546-0476 2021/09
  • クルクミンモノグルクロニドはPten欠損前立腺癌の腫瘍微小環境を調節し抗腫瘍活性を示す
    倉 由吏恵; デベラスコ・マルコ; 坂井 和子; 藤田 至彦; 橋本 士; 森 康範; 南 高文; 藤田 和利; 掛谷 秀昭; 植村 天受; 西尾 和人
    日本癌学会総会記事 (一社)日本癌学会 80回 [E17 - 3] 0546-0476 2021/09
  • アパルタミドが惹起する短期免疫反応の前臨床評価について
    植村 天受; 倉 由吏恵; 坂野 恵里; 橋本 士; 坂井 和子; 藤田 和利; 野澤 昌弘; 吉村 一宏; 西尾 和人; デベラスコ・マルコ
    日本癌学会総会記事 (一社)日本癌学会 80回 [J14 - 3] 0546-0476 2021/09
  • Motohide Uemura; Noboru Nakaigawa; Naoto Sassa; Katsunori Tatsugami; Kenichi Harada; Toshinari Yamasaki; Nobuaki Matsubara; Takuya Yoshimoto; Yuki Nakagawa; Tamaki Fukuyama; Mototsugu Oya; Nobuo Shinohara; Hirotsugu Uemura; Toyonori Tsuzuki
    International journal of clinical oncology SPRINGER JAPAN KK 26 (11) 2085 - 2086 1341-9625 2021/08
  • Mamoru Hashimoto; Takahito Nakayama; Saizo Fujimoto; Shunsuke Inoguchi; Mitsuhisa Nishimoto; Takashi Kikuchi; Shogo Adomi; Eri Banno; Marco A De Velasco; Yoshitaka Saito; Nobutaka Shimizu; Yasunori Mori; Takafumi Minami; Kazutoshi Fujita; Masahiro Nozawa; Kazuhiro Nose; Kazuhiro Yoshimura; Hirotsugu Uemura
    Anti-cancer drugs 33 (1) e818-e821  2021/08 
    Recently, combination therapy including immune checkpoint inhibition (ICI) has proven to be effective as first-line therapy for patients with metastatic renal cell carcinoma. Although the first-line combination therapies with ICI have shown clinical benefit, a number of patients require second-line treatment. We report a 60-year-old man with metastatic renal cell carcinoma who was treated with pazopanib soon after nivolumab plus ipilimumab combination therapy. He experienced Grade 3 disseminated intravascular coagulation (DIC). We suspect that this was caused by an interaction between pazopanib and nivolumab even though ICI therapy was discontinued. He was treated with thrombomodulin and platelet transfusion and recovered from DIC. Treatment with pazopanib was subsequently restarted. No evidence of DIC was observed thereafter. This severe adverse reaction may have been induced by an interaction between activated proinflammatory immune cells and cytokines from an exacerbated inflammatory state and pazopanib. This report highlights the need to perform careful monitoring of patients who receive molecular targeted therapy after ICI-based immunotherapy.
  • Marco A De Velasco; Yurie Kura; Naomi Ando; Noriko Sako; Eri Banno; Kazutoshi Fujita; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuko Sakai; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    Cancers 13 (16) 2021/08 
    Significant improvements with apalutamide, a nonsteroidal antiandrogen used to treat patients suffering from advanced prostate cancer (PCa), have prompted evaluation for additional indications and therapeutic development with other agents; however, persistent androgen receptor (AR) signaling remains problematic. We used autochthonous mouse models of Pten-deficient PCa to examine the context-specific antitumor activity of apalutamide and profile its molecular responses. Overall, apalutamide showed potent antitumor activity in both early-stage and late-stage models of castration-naïve prostate cancer (CNPC). Molecular profiling by Western blot and immunohistochemistry associated persistent surviving cancer cells with upregulated AKT signaling. While apalutamide was ineffective in an early-stage model of castration-resistant prostate cancer (CRPC), it tended to prolong survival in late-stage CRPC. Molecular features associated with surviving cancer cells in CRPC included upregulated aberrant-AR, and phosphorylated S6 and proline-rich Akt substrate of 40 kDa (PRAS40). Strong synergy was observed with the pan-AKT inhibitor GSK690693 and apalutamide in vitro against the CNPC- and CRPC-derived cell lines and tended to improve the antitumor responses in CNPC but not CRPC in vivo. Upregulation of signal transducer and activator of transcription 3 (STAT3) and proviral insertion in murine-1 (PIM-1) were associated with combined apalutamide/GSK690693. Our findings show that apalutamide can attenuate Pten-deficient PCa in a context-specific manner and provides data that can be used to further study and, possibly, develop additional combinations with apalutamide.
  • Nobuaki Matsubara; Hirotsugu Uemura; Satoshi Nagamori; Hiroyoshi Suzuki; Hiroji Uemura; Go Kimura
    Clinical Genitourinary Cancer Elsevier BV 1558-7673 2021/08
  • Makoto Matsushita; Kazutoshi Fujita; Daisuke Motooka; Koji Hatano; Shota Fukae; Norihiko Kawamura; Eisuke Tomiyama; Yujiro Hayashi; Eri Banno; Tetsuya Takao; Shingo Takada; Shinichi Yachida; Hirotsugu Uemura; Shota Nakamura; Norio Nonomura
    Cancer science 112 (8) 3125 - 3135 2021/08 
    We have found that intestinal bacteria and their metabolites, short-chain fatty acids (SCFAs), promote cancer growth in prostate cancer (PCa) mouse models. To clarify the association between gut microbiota and PCa in humans, we analyzed the gut microbiota profiles of men with suspected PCa. One hundred and fifty-two Japanese men undergoing prostate biopsies (96 with cancer and 56 without cancer) were included in the study and randomly divided into two cohorts: a discovery cohort (114 samples) and a test cohort (38 samples). The gut microbiota was compared between two groups, a high-risk group (men with Grade group 2 or higher PCa) and a negative + low-risk group (men with negative biopsy or Grade group 1 PCa), using 16S rRNA gene sequencing. The relative abundances of Rikenellaceae, Alistipes, and Lachnospira, all SCFA-producing bacteria, were significantly increased in high-risk group. In receiver operating characteristic curve analysis, the index calculated from the abundance of 18 bacterial genera which were selected by least absolute shrinkage and selection operator regression detected high-risk PCa in the discovery cohort with higher accuracy than the prostate specific antigen test (area under the curve [AUC] = 0.85 vs 0.74). Validation of the index in the test cohort showed similar results (AUC = 0.81 vs 0.67). The specific bacterial taxa were associated with high-risk PCa. The gut microbiota profile could be a novel useful marker for the detection of high-risk PCa and could contribute to the carcinogenesis of PCa.
  • Neeraj Agarwal; Kelly McQuarrie; Anders Bjartell; Simon Chowdhury; Andrea J Pereira de Santana Gomes; Byung Ha Chung; Mustafa Özgüroğlu; Álvaro Juárez Soto; Axel S Merseburger; Hirotsugu Uemura; Dingwei Ye; Robert Given; Ethan Basch; Branko Miladinovic; Angela Lopez-Gitlitz; Kim N Chi
    The Journal of urology 101097JU000000000000184103  2021/07
  • Motohide Uemura; Noboru Nakaigawa; Naoto Sassa; Katsunori Tatsugami; Kenichi Harada; Toshinari Yamasaki; Nobuaki Matsubara; Takuya Yoshimoto; Yuki Nakagawa; Tamaki Fukuyama; Mototsugu Oya; Nobuo Shinohara; Hirotsugu Uemura; Toyonori Tsuzuki
    International journal of clinical oncology 26 (11) 2073 - 2084 2021/07 
    BACKGROUND: Programmed death-ligand 1 (PD-L1) positivity is associated with poor prognosis in renal cell carcinoma (RCC). Because the prognostic impact and effect of confounding factors are less known, we investigated the prognostic significance of PD-L1 expression in Japanese patients with recurrent/metastatic RCC who started systemic therapy in 2010-2015. METHODS: This multicenter, retrospective study recruited patients from 29 Japanese study sites who had prior systemic therapy for RCC (November 2018 to April 2019) and stored formalin-fixed paraffin-embedded primary lesion samples. The primary outcome was overall survival (OS) by PD-L1 expression. Secondary outcomes included OS in subgroups and duration of first- and second-line therapies by PD-L1 expression. OS distributions were estimated using Kaplan-Meier methodology. RESULTS: PD-L1 expression (on immune cells [IC] ≥ 1%) was observed in 315/770 (40.9%) patients. PD-L1 positivity was more prevalent in patients with poor risk per both Memorial Sloan Kettering Cancer Center [MSKCC] and International Metastatic RCC Database Consortium, and high-risk pathological features (higher clinical stage, nuclear grade and sarcomatoid features). Median OS for PD-L1-positive patients was 30.9 months (95% CI 25.5-35.7) versus 37.5 months (95% CI 34.0-42.6) for PD-L1-negative patients (HR 1.04 [90% CI 0.89-1.22, p = 0.65]; stratified by MSKCC risk and liver metastases). Propensity score weight (PSW)-adjusted OS was similar between PD-L1-positive and -negative patients (median 34.4 versus 31.5 months; estimated PSW-adjusted HR 0.986). CONCLUSIONS: This study suggests PD-L1 status was not an independent prognostic factor in recurrent/metastatic RCC during the study period because PD-L1 positivity was associated with poor prognostic factors, especially MSKCC risk status.
  • Nobutaka Shimizu; Daisuke Gotoh; Mitsuhisa Nishimoto; Mamoru Hashimoto; Tetsuichi Saito; Kazutoshi Fujita; Akihide Hirayama; Naoki Yoshimura; Hirotsugu Uemura
    International journal of urology : official journal of the Japanese Urological Association 28 (10) 1068 - 1072 2021/07 
    OBJECTIVES: To investigate the effect of vibegron, a new clinically approved β3-adrenoceptor agonist in lower urinary tract dysfunction in mice with spinal cord injury. METHODS: Investigators performed cystometry under awake conditions in 4-week spinal cord injury female mice. Two weeks after spinal cord injury, saline or vibegron (30 mg/kg) was orally administered for 2 weeks prior to the urodynamic study. Investigators removed L6-S1 dorsal root ganglia from the saline- or vibegron-treated spinal cord injury mice as well as from saline-treated normal (spinal intact) mice to evaluate the levels of transient receptor potential cation channel subfamily V member 1, transient receptor potential cation channel subfamily A member 1, activating transcription factor 3, and inducible nitric oxide synthase transcripts using real-time polymerase chain reaction. RESULTS: In vibegron-treated spinal cord injury mice, nonvoiding contractions during bladder filling, which were increased in spinal cord injury compared to spinal intact mice, were significantly decreased. Micturition pressure or voiding efficiency was not significantly increased in comparison to measurements in saline-treated spinal cord injury mice. The expression of transient receptor potential cation channel subfamily V member 1, transient receptor potential cation channel subfamily A member 1, activating transcription factor 3, and inducible nitric oxide synthase messenger RNA was increased in spinal cord injury mice compared to spinal intact mice, but significantly decreased after vibegron treatment. CONCLUSIONS: Vibegron improves spinal cord injury-induced detrusor overactivity in addition to significantly reducing C-fiber afferent receptors such as transient receptor potential cation channel subfamily V member 1, transient receptor potential cation channel subfamily A member 1, and inflammatory cytokines/markers, such as activating transcription factor 3 and inducible nitric oxide synthase, in spinal cord injury mice. Thus, vibegron might be effective in the treatment of storage lower urinary tract dysfunction induced by C-fiber afferent activation after spinal cord injury.
  • Toshiharu Sakurai; Marco A De Velasco; Kazuko Sakai; Tomoyuki Nagai; Hiroki Nishiyama; Kentaro Hashimoto; Hirotsugu Uemura; Hisato Kawakami; Kazuhiko Nakagawa; Hiroyuki Ogata; Kazuto Nishio; Masatoshi Kudo
    Molecular oncology 2021/07 
    Immune checkpoint inhibitors (ICIs) are widely used to treat various malignancies. Although the gut microbiome is known to influence the efficacy of ICIs on epithelial tumors, the functional interactions between gut taxa and colonic mucosa remain poorly understood. Here we performed transcriptomic profiling and 16S rRNA sequencing to investigate the relationships between mucosal gene expression and microbial composition with ICI responses and gastrointestinal immune-related adverse events (GI irAEs). In responders, genes related to DNA repair and cell cycle signatures were enriched in responders whereas signatures related to innate immune response, NFAT and IFN-γ signaling pathways were enriched in nonresponders. Gut microbial composition revealed an association between moderate GI irAE and favorable response to ICI therapy. Favorable therapeutic responses to ICI and GI irAE treatments were associated with taxa classified as Enterobacteriaceae and were related to ribonucleoprotein complex biogenesis, cytokine-mediated signaling pathway, tRNA metabolic process, and ribonucleoprotein complex assembly in the colon. These findings open new perspectives for improving the efficacy and safety of cancer immunotherapy.
  • Byung Ha Chung; Jian Huang; Zhang-Qun Ye; Da-Lin He; Hirotsugu Uemura; Gaku Arai; Choung Soo Kim; Yuan-Yuan Zhang; Yusoke Koroki; SuYeon Jeong; Suneel Mundle; Spyros Triantos; Sharon McCarthy; Kim N Chi; Ding-Wei Ye
    Asian journal of andrology 2021/07 
    Ethnicity might be associated with treatment outcomes in advanced prostate cancer. This study aimed to evaluate the efficacy and safety of androgen deprivation therapy (ADT) combined with apalutamide in East Asians with metastatic castration-sensitive prostate cancer (mCSPC). The original phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial was conducted at 260 sites in 23 countries. This subgroup analysis included patients enrolled in 62 participating centers in China, Japan, and Korea. Radiographic progression-free survival (PFS), time to prostate-specific antigen (PSA) progression, and PSA changes from baseline were compared between groups in the East Asian population. The intent-to-treat East Asian population included 111 and 110 participants in the apalutamide and placebo groups, respectively. The 24-month radiographic PFS rates were 76.1% and 52.3% in the apalutamide and placebo groups, respectively (apalutamide vs placebo: hazard ratio [HR] = 0.506; 95% confidence interval [CI], 0.302-0.849; P = 0.009). Median time to PSA progression was more favorable with apalutamide than placebo (HR = 0.210; 95% CI, 0.124-0.357; P < 0.001). Median maximum percentages of PSA decline from baseline were 99.0% and 73.9% in the apalutamide and placebo groups, respectively. The most common adverse event (AE) was rash in the apalutamide group, with a higher rate than that in the placebo group (37.3% vs 9.1%). The most common grade 3 or 4 AEs were rash (12 [10.9%]) and hypertension (12 [10.9%]) for apalutamide. The efficacy and safety of apalutamide in the East Asian subgroup of the TITAN trial are consistent with the global results.
  • Kim N Chi; Simon Chowdhury; Anders Bjartell; Byung Ha Chung; Andrea J Pereira de Santana Gomes; Robert Given; Alvaro Juárez; Axel S Merseburger; Mustafa Özgüroğlu; Hirotsugu Uemura; Dingwei Ye; Sabine Brookman-May; Suneel D Mundle; Sharon A McCarthy; Julie S Larsen; Weili Sun; Katherine B Bevans; Ke Zhang; Nibedita Bandyopadhyay; Neeraj Agarwal
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology 39 (20) 2294 - 2303 2021/07 
    PURPOSE: The first interim analysis of the phase III, randomized, placebo-controlled TITAN study showed that apalutamide significantly improved overall survival (OS) and radiographic progression-free survival in patients with metastatic castration-sensitive prostate cancer (mCSPC) receiving ongoing androgen deprivation therapy (ADT). Herein, we report final efficacy and safety results after unblinding and placebo-to-apalutamide crossover. METHODS: Patients with mCSPC (N = 1,052) were randomly assigned 1:1 to receive apalutamide (240 mg QD) or placebo plus ADT. After unblinding in January 2019, placebo-treated patients were allowed to receive apalutamide. Efficacy end points were updated using the Kaplan-Meier method and Cox proportional-hazards model without formal statistical retesting and adjustment for multiplicity. Change from baseline in Functional Assessment of Cancer Therapy-Prostate total score was assessed. RESULTS: With a median follow-up of 44.0 months, 405 OS events had occurred and 208 placebo-treated patients (39.5%) had crossed over to apalutamide. The median treatment duration was 39.3 (apalutamide), 20.2 (placebo), and 15.4 months (crossover). Compared with placebo, apalutamide plus ADT significantly reduced the risk of death by 35% (median OS not reached v 52.2 months; hazard ratio, 0.65; 95% CI, 0.53 to 0.79; P < .0001) and by 48% after adjustment for crossover (hazard ratio, 0.52; 95% CI, 0.42 to 0.64; P < .0001). Apalutamide plus ADT delayed second progression-free survival and castration resistance (P < .0001 for both). Health-related quality of life, per total Functional Assessment of Cancer Therapy-Prostate, in both groups was maintained through the study. Safety was consistent with previous reports. CONCLUSION: The final analysis of TITAN confirmed that, despite crossover, apalutamide plus ADT improved OS, delayed castration resistance, maintained health-related quality of life, and had a consistent safety profile in a broad population of patients with mCSPC.
  • Marco A. De Velasco; Kazuko Sakai; Yurie Kura; Eri Banno; Naomi Ando; Noriko Sako; Nobutaka Shimizu; Kazutoshi Fujita; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuto Nishio; Hirotsugu Uemura
    Immunology American Association for Cancer Research 2021/07
  • Marco A. De Velasco; Yurie Kura; Noriko Sako; Naomi Ando; Kazuko Sakai; Alwin Schuller; Kazutoshi Fujita; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuto Nishio; Hirotsugu Uemura
    Immunology American Association for Cancer Research 2021/07
  • Marco A. De Velasco; Yurie Kura; Naomi Ando; Kazuko Sakai; Nobutaka Shimizu; Eri Banno; Masahiro Nozawa; Kazuhiro Fujita; Kazuhiro Yoshimura; Kazuto Nishio; Hirotsugu Uemura
    Experimental and Molecular Therapeutics American Association for Cancer Research 2021/07
  • Marco A. De Velasco; Kazuko Sakai; Yurie Kura; Naomi Ando; Noriko Sako; Kazutoshi Fujita; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuto Nishio; Hirotsugu Uemura
    Immunology American Association for Cancer Research 2021/07
  • Marco A. De Velasco; Yurie Kura; Kazuko Sakai; Kazutoshi Fujita; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuto Nishio; Hirotsugu Uemura
    Clinical Research (Excluding Clinical Trials) American Association for Cancer Research 2021/07
  • Mamoru Hashimoto; Kazutoshi Fujita; Takahito Nakayama; Saizo Fujimoto; Mamoru Hamaguchi; Mitsuhisa Nishimoto; Takashi Kikuchi; Shogo Adomi; Eri Banno; Marco A De Velasco; Yoshitaka Saito; Nobutaka Shimizu; Yasunori Mori; Takafumi Minami; Masahiro Nozawa; Kazuhiro Nose; Kazuhiro Yoshimura; Hirotsugu Uemura
    Translational andrology and urology 10 (7) 2838 - 2847 2021/07 
    Background: Inflammatory cytokines and immature myeloid derived suppressor cells (MDSCs), which increase during cancer progression, could lead to a neutrophil increase and lymphocyte reduction. Thus, the neutrophil-lymphocyte ratio (NLR) was used to predict survival of patients suffering from urological cancers including upper urinary tract carcinoma. We further determined whether the NLR during the first cycle of first-line chemotherapy could predict cancer specific survival. Methods: We recruited patients with locally advanced or metastatic upper urinary tract urothelial carcinoma (UTUC) who received chemotherapy between January 2014 and July 2019. We investigated the impact of various clinical variables, including age, sex, performance status, and estimated creatinine clearance (CCr), and NLR before and after the first cycle of the first-line chemotherapy on prognosis. Results: A total of 41 patients were included in our study. Cancer specific survival of the patients with lower NLR was significantly better than that of the patients with higher NLR measured after the first cycle of the first-line chemotherapy (log-rank test P=0.005, median 29.2 vs. 11.9 months, respectively). Cox proportional regression analysis showed that higher NLR after the first cycle of the first-line chemotherapy was a significant predictor of cancer specific survival. Conclusions: The NLR after the first cycle of the first-line chemotherapy could be an indication for patients with locally advanced or metastatic UTUC to maintain their first-line chemotherapy treatment.
  • Mamoru Harada; Yuichi Iida; Hitoshi Kotani; Takafumi Minami; Yoshihiro Komohara; Masatoshi Eto; Kazuhiro Yoshikawa; Hirotsugu Uemura
    Cancer immunology, immunotherapy : CII 71 (2) 339 - 352 2021/06 
    Renal cell carcinoma (RCC) is known to respond to immune checkpoint blockade (ICB) therapy, whereas there has been limited analysis of T-cell responses to RCC. In this study, we utilized human carbonic anhydrase 9 (hCA9) as a model neoantigen of mouse RENCA RCC. hCA9-expressing RENCA RCC (RENCA/hCA9) cells were rejected in young mice but grew in aged mice. CD8+ T cells were the primary effector cells involved in rejection in young mice, whereas CD4+ T cells participated at the early stage. Screening of a panel of hCA9-derived peptides revealed that mouse CD8+ T cells responded to hCA9288-296 peptide. Mouse CD4+ T cells responded to lysates of RENCA/hCA9, but not RENCA cells, and showed reactivity to hCA9 276-290, which shares three amino acids with hCA9 288-296 peptide. Immunohistochemistry analysis revealed that few T cells infiltrated RENCA/hCA9 tissues in aged mice. ICB therapy of anti-PD-1/anti-CTLA-4 antibodies promoted T-cell infiltration into tumor tissues, whereas no definite antitumor effect was observed. However, additional combination with cyclophosphamide or axitinib, a vascular endothelial growth factor receptor inhibitor, induced complete regression in half of the RENCA/hCA9-bearing aged mice with increased expression of PD-L1 in tumor tissues. These results indicate that hCA9 can be a useful model neoantigen to investigate antitumor T-cell responses in mice with RCC, and that RENCA/hCA9 in aged mice can serve as a non-inflamed 'cold' tumor model facilitating the development of effective combined immunotherapies for RCC.
  • 腎移植後血清尿酸値と移植腎機能の関連性について
    齋藤 允孝; 菊池 尭; 森 康範; 能勢 和宏; 吉村 一宏; 植村 天受; 玉井 健太郎; 林 泰司; 西岡 伯; 今西 正昭; 秋山 隆弘
    泌尿器科紀要 泌尿器科紀要刊行会 67 (6) 276 - 276 0018-1994 2021/06
  • パゾパニブにより治療された進行性腎細胞癌患者における栄養指数と予後の関連
    浜口 守; 橋本 士; 藤田 和利; 西本 光寿; 坂野 恵理; 齋藤 允孝; 清水 信貴; 森 康範; 南 高文; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 植村 天受
    泌尿器科紀要 泌尿器科紀要刊行会 67 (6) 249 - 249 0018-1994 2021/06
  • 藤田 和利; 吉村 一宏; 植村 天受
    Uro-Lo: 泌尿器Care & Cure (株)メディカ出版 26 (3) 416 - 417 2189-8545 2021/06
  • Neeraj Agarwal; Kelly McQuarrie; Anders Bjartell; Simon Chowdhury; Andrea J Pereira de Santana Gomes; Byung Ha Chung; Mustafa Özgüroğlu; Álvaro Juárez Soto; Axel S Merseburger; Hirotsugu Uemura; Dingwei Ye; Robert Given; Ethan Basch; Branko Miladinovic; Angela Lopez-Gitlitz; Kim N Chi
    The Journal of urology 101097JU0000000000001841  2021/05 
    PURPOSE: We performed exploratory analysis of prostate cancer-related pain and fatigue on health-related quality of life in patients with metastatic castration-sensitive prostate cancer receiving apalutamide (240 mg/day) or placebo, with continuous androgen deprivation therapy (ADT), in the phase 3, randomized, double-blind, placebo controlled TITAN trial (NCT02489318). MATERIALS AND METHODS: Patient-reported outcomes for pain and fatigue were evaluated using the Brief Pain Inventory-Short Form and Brief Fatigue Inventory. Time to deterioration (TTD) was estimated by Kaplan-Meier method; hazard ratios and 95% confidence intervals were calculated using Cox proportional hazards model. General estimating equations for logistic regression estimated treatment-related differences in the likelihood of worsening pain or fatigue. RESULTS: Compliance for completing the Brief Pain Inventory-Short Form and Brief Fatigue Inventory was high (96% to 97%) in the first year. Median followup times were similar between treatments (19 to 22 months). Median pain TTD was longer with apalutamide than placebo for "pain at its least in the last 24 hours" (28.7 vs 21.8 months, respectively; p=0.0146), "pain interfered with mood" (not estimable vs 22.4 months; p=0.0017), "pain interfered with walking ability" (28.7 vs 20.2 months; p=0.0027), "pain interfered with relations" (not estimable vs 23.0 months; p=0.0139) and "pain interfered with sleep" (28.7 vs 20.9 months; p=0.0167). Likelihood for fatigue and worsening fatigue were similar between groups. CONCLUSIONS: Patients with metastatic castration-sensitive prostate cancer receiving apalutamide plus ADT vs placebo plus ADT reported consistently favorable TTD of pain. No difference for change in fatigue was observed with apalutamide vs placebo.
  • 腎移植後血清尿酸値と移植腎機能の関連について
    齋藤 允孝; 菊池 尭; 森 康範; 能勢 和宏; 吉村 一宏; 植村 天受; 林 泰司; 西岡 伯; 今西 正昭; 秋山 隆弘
    日本透析医学会雑誌 (一社)日本透析医学会 54 (Suppl.1) 465 - 465 1340-3451 2021/05
  • Hirotsugu Uemura; Naoya Masumori; Shunji Takahashi; Makoto Hosono; Seigo Kinuya; Toshiyuki Sunaya; Tomoyo Horio; Yutaka Okayama; Yoshiyuki Kakehi
    International journal of clinical oncology 26 (4) 753 - 763 2021/04 
    BACKGROUND: Based on results from Japanese post-marketing surveillance, exploratory analyses were performed to investigate real-world outcomes of radium-223 for metastatic CRPC (mCRPC) according to patient characteristics. METHODS: This non-interventional, prospective study enrolled mCRPC patients selected for radium-223 treatment in clinical practice. Six-month safety and effectiveness were evaluated in subgroups who had/had not received prior chemotherapy (prior-chemo/no prior-chemo groups), and a subgroup who had not received concomitant androgen-receptor axis-targeted agents (ARATs). RESULTS: In the overall population (n = 296), the prior-chemo group (n = 126) tended to have more bone metastases, more analgesic use, and higher prostate-specific antigen values than the no prior-chemo group (n = 170). Incidences of treatment-emergent adverse events (TEAEs), drug-related TEAEs, and ≥ grade 3 drug-related hematological TEAEs were 47% vs. 53%, 25% vs. 29%, and 4% vs. 7% in the no prior-chemo and prior-chemo groups, respectively. Incidences of TEAEs (61%), drug-related TEAEs (36%), and ≥ grade 3 drug-related hematological events (12%) were numerically higher in 33 patients who had received two lines of prior chemotherapy. Multivariate analysis showed that two lines of prior chemotherapy, and hemoglobin, platelet, and lactate dehydrogenase values were baseline factors significantly related to ≥ grade 2 platelet count decreased. Safety and effectiveness in patients without concomitant ARATs (n = 201) were similar to those in the overall population. CONCLUSION: In a real-life setting, radium-223 was well tolerated irrespective of prior chemotherapy, but relatively higher incidences of TEAEs and hematotoxicities were suggested in patients with two lines of prior chemotherapy, possibly reflecting more advanced disease. Radium-223 safety and effectiveness in patients without concomitant ARATs were favorable.
  • Hiroji Uemura; Hisashi Matsushima; Kazuki Kobayashi; Hiroya Mizusawa; Hiroaki Nishimatsu; Karim Fizazi; Matthew Smith; Neal Shore; Teuvo Tammela; Ken-Ichi Tabata; Nobuaki Matsubara; Masahiro Iinuma; Hirotsugu Uemura; Mototsugu Oya; Tetsuo Momma; Mutsushi Kawakita; Satoshi Fukasawa; Tadahiro Kobayashi; Iris Kuss; Marie-Aude Le Berre; Amir Snapir; Toni Sarapohja; Kazuhiro Suzuki
    International journal of clinical oncology 26 (3) 578 - 590 2021/03 
    BACKGROUND: Darolutamide, an oral androgen receptor inhibitor, has been approved for treating nonmetastatic castration-resistant prostate cancer (nmCRPC), based on significant improvements in metastasis-free survival (MFS) in the ARAMIS clinical trial. Efficacy and safety of darolutamide in Japanese patients are reported here. METHODS: In this randomized, double-blind, placebo-controlled phase III trial, 1509 patients with nmCRPC and prostate-specific antigen (PSA) doubling time ≤ 10 months were randomized 2:1 to darolutamide 600 mg twice daily or matched placebo while continuing androgen deprivation therapy. The primary endpoint was MFS. RESULTS: In Japan, 95 patients were enrolled and randomized to darolutamide (n = 62) or placebo (n = 33). At the primary analysis (cut-off date: September 3, 2018), after 20 primary end-point events had occurred, median MFS was not reached with darolutamide vs. 18.2 months with placebo (HR 0.28, 95% CI 0.11-0.70). Median OS was not reached due to limited numbers of events in both groups but favored darolutamide in the Japanese subgroup. Time to pain progression, time to PSA progression, and PSA response also favored darolutamide. Among Japanese patients randomized to darolutamide vs. placebo, incidences of treatment-emergent adverse events (TEAEs) were 85.5 vs. 63.6%, and incidences of treatment discontinuation due to TEAEs were 8.1 vs. 6.1%. CONCLUSIONS: Efficacy outcomes favored darolutamide in Japanese patients with nmCRPC, supporting the clinical benefit of darolutamide in this patient population. Darolutamide was well tolerated; however, due to the small sample size, it is impossible to conclude with certainty whether differences in the safety profile exist between Japanese and overall ARAMIS populations.
  • Hirotsugu Uemura; Gaku Arai; Hiroji Uemura; Hiroyoshi Suzuki; Kazuyoshi Iijima; Kazuo Nishimura; Koji Fujii; Tomoyoshi Hatayama; Junya Aoyama; Kris Deprince; Angela Lopez-Gitlitz; Sharon McCarthy; Julie S Larsen; Jinhui Li; Kim N Chi
    International journal of urology : official journal of the Japanese Urological Association 28 (3) 280 - 287 2021/03 
    OBJECTIVE: To evaluate the efficacy and safety of apalutamide + androgen deprivation therapy versus androgen deprivation therapy alone in Japanese patients with metastatic castration-sensitive prostate cancer from the phase 3, randomized, global TITAN study. METHODS: Men with metastatic castration-sensitive prostate cancer randomly (1:1) received 240 mg apalutamide + androgen deprivation therapy or matching placebo + androgen deprivation therapy. The primary efficacy endpoints were radiographic progression-free survival and overall survival. Secondary efficacy endpoints were time to cytotoxic chemotherapy, pain progression, chronic opioid use, and skeletal-related events. Safety was also assessed. RESULTS: Of the 1052 patients included in the TITAN study, 51 (4.85%) were Japanese (apalutamide group, n = 28; placebo group, n = 23). In all, 81.8% of patients in the apalutamide and 71.8% in the placebo group did not experience radiographic progression or death, and the hazard ratio for radiographic progression-free survival favored treatment with apalutamide (hazard ratio 0.712, 95% confidence interval 0.205-2.466; P = 0.59). At 24 months, 85.7% of patients in the apalutamide group and 81.5% in the placebo group were alive, and the hazard ratio for overall survival favored apalutamide (hazard ratio 0.840, 95% confidence interval 0.210-3.361; P = 0.805). In the interim analysis, the median radiographic progression-free survival and overall survival were not reached in the apalutamide group and time to cytotoxic chemotherapy was delayed following apalutamide treatment. The safety profile of apalutamide in the Japanese subpopulation was comparable with that of the global population, except for skin rash. CONCLUSIONS: The results of the present analyses suggest that apalutamide + androgen deprivation therapy in Japanese patients had favorable efficacy compared with androgen deprivation therapy alone, and these findings are comparable to those in the overall population. Apalutamide + androgen deprivation therapy can be considered as one of the therapeutic options for a broad spectrum of metastatic castration-sensitive prostate cancer regardless of prior treatment and disease extent in Japanese patients.
  • Yasuhide Miyoshi; Sohgo Tsutsumi; Masato Yasui; Takashi Kawahara; Ko-Ichi Uemura; Naruhiko Hayashi; Masahiro Nozawa; Kazuhiro Yoshimura; Hiroji Uemura; Hirotsugu Uemura
    World journal of urology 39 (9) 3323 - 3328 2021/03 
    PURPOSE: We evaluated the predictive factors for completion of all six cycles of radium-223 (Ra-223) treatment in patients with metastatic castration-resistant prostate cancer (mCRPC). We also developed a novel prediction model for Ra-223 treatment completion using these predictors. METHODS: We retrospectively reviewed data from 122 patients with mCRPC who were treated with Ra-223. The predictive factors for the completion of six cycles of Ra-223 treatment were evaluated. Statistically significant predictive factors were then used to develop a prediction model for treatment completion. Finally, using this prediction model, we classified the overall survival (OS) of the entire cohort into three groups. RESULTS: We identified three significant variables as the predictive factors for treatment completion: baseline alkaline phosphatase (ALP) level, baseline hemoglobin (Hb) level, and baseline pain. The three groups generated using the prediction model were: group 1 (patients with three predictive factors, i.e., ALP < median, Hb ≥ median, and no pain), group 2 (patients with one to two predictive factors), and group 3 (patients without any predictive factors). The treatment completion rates differed between the three groups significantly. Furthermore, the OS also differed among the groups significantly. CONCLUSION: Our study suggested that the baseline ALP level, baseline Hb level, and baseline pain were the predictive factors of completion of all six cycles of Ra-223 treatment in patients with mCRPC. Our prediction model consisting of these factors could predict not only the completion of Ra-223 treatment, but also the post-treatment survival. This model can thus be useful for selection of patients for Ra-223 treatment.
  • 國重 玲紋; 大関 孝之; 浜口 守; 豊田 信吾; 橋本 士; 菊池 尭; 西本 光寿; 清水 信貴; 森 康範; 南 高文; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 植村 天受
    泌尿器科紀要 泌尿器科紀要刊行会 67 (2) 63 - 66 0018-1994 2021/02 
    症例は67歳男性で、数年前に左腎細胞癌に対して開腹下根治的左腎摘除術を施行し、病理診断はclear cell renal cell carcinoma、pT4、Fuhrman grade 2であった。単発の肺転移に対して胸腔鏡下右肺部分切除術を施行し、その後も二度単発の肺転移再発を認めたためそれぞれ肺部分切除術を施行した。その後、中縦隔に12mm大のリンパ節腫大と30mm大の脾転移を認め、脾転移出現後3ヵ月目には脾転移は60mm大まで増大した。スニチニブ投与12日目に38℃台の発熱がみられた。播種性血管内凝固症候群を合併するガス産生性脾膿瘍の診断にて、スニチニブを休薬の上、meropenem 1.5g/日とthrombomodulin 19200Uを開始した。入院5日目には、腹部単純CT画像で門脈ガス像は消失し脾内ガス像の減少も認めた。thrombomodulinの投与を終了し経過観察したが、38℃前半の発熱が持続し入院8日目に再度門脈ガス像が出現した。入院11日目に放射線科医師によりエコーガイド下経皮的脾臓ドレナージを施行した。その結果、排液培養からは嫌気性グラム陽性球菌(Anaerococcus属)が検出された。ドレナージを施行後は解熱傾向となり、入院15日目には肝内門脈内のガス像の消失を認めた。入院35日目ドレーンチューブを留置したまま、腹腔鏡下脾臓摘出術(術中高度癒着のため開腹へ移行)を施行した。病理学的所見より、内部に壊死組織を含む淡明細胞癌の脾転移と診断した。術後2日目より飲水・食事再開し、術後経過は良好であり術後7日目に退院となった。
  • Remon Kunishige; Takayuki Ozeki; Mamoru Hamaguchi; Shingo Toyoda; Mamoru Hashimoto; Takashi Kikuchi; Mitsuhisa Nishimoto; Nobutaka Shimizu; Yasunori Mori; Takafumi Minami; Masahiro Nozawa; Kazuhiro Nose; Kazuhiro Yoshimura; Hirotsugu Uemura
    Hinyokika kiyo. Acta urologica Japonica 67 (2) 63 - 66 2021/02 
    A 67-year-old man underwent open radical left nephrectomy for left renal cell carcinoma [pT4N0M1 (right lower lobe of lung)] and thoracoscopic partial right lung resection for lung metastasis. The patient subsequently developed a solitary lung metastasis at 10 months and then at 26 months postoperatively. He underwent partial lung resection on each occasion. During the 28 months postoperatively, he was found to have a 12 mm middle mediastinal lymph node metastasis and a 30 mm splenic metastasis, which gradually increased in size. Three months after discovery, sunitinib was initiated at 37.5 mg 2 weeks on/1 week off. Twelve days later, the patient presented with complaints of fever. A gas-producing splenic abscess was diagnosed and he was admitted on the same day. His condition improved with antibiotics and splenic drainage. On day 35 of hospitalization, he underwent laparoscopic splenectomy. The patient's postoperative clinical course was uneventful and he was discharged 7 days after the surgery.
  • Eisuke Tomiyama; Kazutoshi Fujita; Mamoru Hashimoto; Shogo Adomi; Atsunari Kawashima; Takafumi Minami; Kazuhiro Yoshimura; Hirotsugu Uemura; Norio Nonomura
    Translational Andrology and Urology AME Publishing Company 11 (12) 1747 - 1761 2223-4683 2021/01
  • Naoki Matsumura; Kazutoshi Fujita; Mitsuhisa Nishimoto; Yutaka Yamamoto; Ken Kuwahara; Yasuharu Nagai; Takafumi Minami; Yuji Hatanaka; Masahiro Nozawa; Yasuhiro Morimoto; Hideo Tahara; Shigeya Uejima; Atsunobu Esa; Akihide Hirayama; Kazuhiro Yoshimura; Hirotsugu Uemura
    Frontiers in oncology 11 769068 - 769068 2021 
    This study aimed to compare the effects of abiraterone acetate plus prednisone (AAP) with androgen deprivation therapy (ADT) with those of combined androgen blockade (CAB) therapy in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC). This study retrospectively identified 163 patients with high-risk mHSPC at Kindai University and affiliated hospitals between January 2014 and December 2020. Kaplan-Meier analysis was used to summarize progression-free survival (PFS) and overall survival (OS). Multivariate Cox proportional hazard modeling was used to identify the prognostic factors in the overall cohort. Propensity score matching was used to adjust the clinical characteristics, and log-rank test was applied to these propensity score-matched cohorts. Seventy-four patients who received AAP with ADT and 89 patients who received CAB were included in this study. The median follow-up duration was 27 months (range, 2-89 months). The median PFS and OS were not reached by the AAP+ADT group and 15 and 79 months, respectively, in the CAB group. The Eastern Cooperative Oncology Group (ECOG) performance status (PS) score and AAP+ADT were significant prognostic factors for PFS, whereas ECOG PS score, visceral metastasis, and AAP+ADT were significant prognostic factors for OS. The 2-year PFS was 76.1% in the AAP+ADT group and 38.6% in the CAB group (P < 0.0001), and the 2-year OS was 90.2% in the AAP+ADT group and 84.8% in the CAB group (P = 0.015). In conclusion, AAP+ADT had better PFS and OS than CAB in patients with high-risk mHSPC.
  • Masanori Noguchi; Kiyohide Fujimoto; Gaku Arai; Hiroji Uemura; Katsuyoshi Hashine; Hiroaki Matsumoto; Satoshi Fukasawa; Yasuo Kohjimoto; Hideomi Nakatsu; Atsushi Takenaka; Masato Fujisawa; Hirotsugu Uemura; Seiji Naito; Shin Egawa; Hiroyuki Fujimoto; Shiro Hinotsu; Kyogo Itoh
    Oncology reports 45 (1) 159 - 168 2021/01 
    First‑line chemotherapy for men with metastatic castration‑resistant prostate cancer (mCRPC) has been employed to improve overall survival (OS) and progression‑free survival (PFS). However, several new agents for CRPC after first‑line chemotherapy prolonged survival by only a few months. To develop a new treatment modality, we conducted a phase III randomized trial of personalized peptide vaccination (PPV) for human leukocyte antigen (HLA)‑A24‑positive patients with castration‑resistant prostate cancer (CRPC) for whom docetaxel chemotherapy failed. This randomized, double‑blind, placebo‑controlled, phase III trial was carried out at 68 medical centers in Japan. Patients were randomly assigned at a 2:1 ratio to receive PPV or placebo. Four of 12 warehouse peptides selected based on pre‑existing peptide‑specific immunoglobulin G levels or the corresponding placebo were subcutaneously injected in 6 doses weekly and then bi‑weekly following the maximum of 30 doses until disease progression. The primary end‑point was overall survival (OS). Efficacy analyses were performed by the full analysis set. Between August 2013 and April 2016, 310 patients were randomly assigned, and 306 patients were analyzed. Baseline characteristics were balanced between groups. The estimated median OS was 16.1 months [95% confidence interval (CI), 13‑18.2] with PPV and 16.9 months (95% CI, 13.1‑20.4) with placebo [hazard ratio (HR), 1.04, 95% CI, 0.80‑1.37; P=0.77]. Grade ≥3 adverse events were observed in 41% of both groups. The analysis of treatment arm effects among subgroups revealed lower HRs for OS in favor of the PPV arm in patients with <64% neutrophils (HR, 0.55, 95% CI, 0.33‑0.93; P=0.03) or ≥26% lymphocytes (HR, 0.70, 95% CI, 0.52‑0.92; P=0.02) at baseline. PPV did not prolong OS in HLA‑A24‑positive patients with CRPC progressing after docetaxel chemotherapy. Subgroup analysis suggested that the patients with a lower proportion of neutrophils or a higher proportion of lymphocytes at baseline can receive survival benefits from PPV treatment.
  • Mamoru Hashimoto; Nobutaka Shimizu; Mitsuhisa Nishimoto; Takafumi Minami; Kazutoshi Fujita; Kazuhiro Yoshimura; Akihide Hirayama; Hirotsugu Uemura
    Research and reports in urology 13 557 - 563 2021 
    Purpose: This study aimed to elucidate the relationship of psoas muscle atrophy and visceral obesity with lower urinary tract symptoms in geriatric female patients. Patients and Methods: We retrospectively reviewed the medical records of female patients aged ≥65 years. The psoas muscle index was defined, using computed tomography, as the cross-sectional area of the psoas muscle at the third lumbar vertebral level divided by the body surface area. We also measured visceral fat area at the umbilical level using computed tomography. We used logistic regression analysis to examine the relationships between the International Prostate Symptom Score (total score, voiding subscore, and storage subscore) and variables, such as age, body mass index, psoas muscle index, and visceral fat area. The International Prostate Symptom Score was categorized as mild, moderate, or severe. Results: One hundred thirty-nine patients were included in our study. In the logistic regression analysis, we found statistically significant relationships between severe (versus mild-to-moderate) International Prostate Symptom Score storage subscore and variables, including low and high levels of psoas muscle index and visceral fat area, respectively. We could not find any significant relationships between the International Prostate Symptom Score total score and voiding subscore and the variables. Conclusion: Psoas muscle atrophy and visceral fat accumulation are potential risk factors for severe storage symptoms in female patients aged ≥65 years.
  • 骨転移を有する去勢抵抗性前立腺癌を対象とした多施設共同前向き観察研究
    上村 博司; 小山 政史; 武田 正之; 原林 透; 大山 力; 小原 航; 宮澤 克人; 篠原 信雄; 舛森 直哉; 深沢 賢; 三宅 秀明; 河内 明宏; 木下 秀文; 江藤 正俊; 藤本 清秀; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 108回 1350 - 1350 2020/12
  • 当院における進行性腎細胞癌に対するパゾパニブ使用成績と骨格筋面積との関連
    浜口 守; 藤本 西蔵; 高橋 智輝; 橋本 士; 菊池 堯; 安富 正悟; 清水 信貴; 森 康範; 南 高文; 野澤 昌弘; 能勢 和宏; 吉村 一弘; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 108回 1192 - 1192 2020/12
  • 未治療日本人転移性腎細胞癌患者を対象としたニボルマブ・イピリムマブ併用療法の有効性と安全性に関する前向き観察研究(J-ENCORE)
    木村 剛; 立神 勝則; 玉田 聡; 都築 豊徳; 野澤 昌弘; 水野 隆一; 田嶋 洋平; 金子 裕和; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 108回 1593 - 1593 2020/12
  • イミダフェナシン投与後の夜間多尿改善と尿濃縮効果の関係について
    橋本 士; 杉本 公一; 清水 信貴; 森 康範; 南 高文; 野澤 昌弘; 能勢 和宏; 田原 秀男; 吉村 一宏; 平山 暁秀; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 108回 491 - 491 2020/12
  • リアルタイムPCRは前立腺癌の腫瘍免疫プロファイルと免疫反応性の評価を可能とする
    植村 天受; 倉 由吏恵; 坂井 和子; 清水 信貴; 森 康則; 野澤 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; デベラスコ・マルコ
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 108回 1159 - 1159 2020/12
  • 前立腺癌特異的Ptenノックアウトマウスモデルを用いたマルチチロシンキナーゼ阻害薬であるTAS-115の免疫調節について
    倉 由吏恵; デベラスコ・マルコ; 坂井 和子; 清水 信貴; 森 康範; 吉村 一宏; 吉川 和宏; 西尾 和人; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 108回 1161 - 1161 2020/12
  • アンドロゲン受容体標的治療による前立腺癌の腫瘍微小環境の変化
    デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 清水 信貴; 森 康範; 野澤 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 108回 1162 - 1162 2020/12
  • 遺伝子改変前立腺癌マウスモデルにおける食餌性イソフラボンの化学予防効果
    森 康範; デベラスコ・マルコ; 倉 由吏恵; 清水 信貴; 野澤 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; 植村 天受
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 108回 1162 - 1162 2020/12
  • 当院における腎移植後貧血の検討
    菊池 尭; 森 康範; 能勢 和宏; 吉村 一宏; 植村 天受; 玉井 健太郎; 林 泰司; 西岡 伯; 齋藤 允孝; 今西 正昭; 秋山 隆弘
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 108回 1648 - 1648 2020/12
  • Hiroji Uemura; Yosuke Koroki; Yuki Iwaki; Keiichiro Imanaka; Takeshi Kambara; Angela Lopez-Gitlitz; Andressa Smith; Hirotsugu Uemura
    BMC urology 20 (1) 166 - 166 2020/10 [Refereed]
     
    An amendment to this paper has been published and can be accessed via the original article.
  • Mitsuhisa Nishimoto; Kazutoshi Fujita; Takafumi Minami; Kazuhiro Yoshimura; Hirotsugu Uemura
    International journal of urology : official journal of the Japanese Urological Association 27 (12) 1093 - 1094 2020/10 [Refereed]
  • 移植腎機能廃絶時の管理と療法選択について
    能勢 和宏; 菊池 尭; 齋藤 允孝; 森 康範; 吉村 一宏; 植村 天受; 玉井 健太郎; 林 泰司; 西岡 伯; 秋山 隆弘; 今西 正昭
    日本透析医学会雑誌 (一社)日本透析医学会 53 (Suppl.1) 712 - 712 1340-3451 2020/10
  • ペプチドワクチン療法で長期生存を認めた化学療法未治療去勢抵抗性前立腺癌症例の検討
    南 高文; 藤田 和利; 野澤 昌弘; 吉村 一宏; 木村 高弘; 頴川 晋; 藤元 博行; 山田 亮; 伊東 恭悟; 植村 天受
    日本癌治療学会学術集会抄録集 (一社)日本癌治療学会 58回 P - 393 2020/10
  • Pten欠損前立腺癌におけるJAK1/2標的治療が糞便中のマイクロバイオームに与える影響について
    デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 野澤 昌弘; 吉川 和宏; 西尾 和人; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 79回 OE3 - 5 0546-0476 2020/10
  • 前立腺癌特異的Ptenノックアウトマウスにおけるマイクロバイオームについての検討
    倉 由吏恵; 坂井 和子; 藤田 至彦; 野澤 昌弘; 吉川 和宏; 西尾 和人; デベラスコ・マルコ; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 79回 OJ3 - 8 0546-0476 2020/10
  • アンドロゲン除去療法は前立腺特異的Ptenノックアウトマウスにおいて免疫療法の抗腫瘍効果を増強する
    植村 天受; 倉 由吏恵; 坂井 和子; 野澤 昌弘; 吉川 和宏; 西尾 和人; デベラスコ・マルコ
    日本癌学会総会記事 (一社)日本癌学会 79回 OE12 - 5 0546-0476 2020/10
  • 異種間遺伝子発現解析による免疫プロファイリングへの応用について
    坂野 恵理; 倉 由吏恵; 坂井 和子; 藤田 至彦; 野澤 昌弘; 吉川 和宏; 西尾 和人; デベラスコ・マルコ; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 79回 OE15 - 6 0546-0476 2020/10
  • 自動化マイクロキャピラリー電気泳動法による高Gleason前立腺癌診断法のための血中Core型フコシル化PSA測定法の開発
    藤田 和利; 林 裕次郎; 吉川 友康; 山下 謙一郎; 冨山 栄輔; 松下 慎; 中野 剛佑; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 植村 元秀; 吉村 一宏; 植村 天受; 三善 英知; 野々村 祝夫
    日本癌学会総会記事 (一社)日本癌学会 79回 PE14 - 3 0546-0476 2020/10
  • Liquid biopsyが変えるがん治療 膀胱癌診断における尿中cell free DNAを用いたリキッドバイオプシー解析
    藤田 和利; 林 裕次郎; 松崎 恭介; 冨山 栄輔; 松下 慎; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 植村 元秀; 今村 亮一; Netto George; 吉村 一宏; 植村 天受; 野々村 祝夫
    日本癌治療学会学術集会抄録集 (一社)日本癌治療学会 58回 WS12 - 2 2020/10
  • 自動化マイクロキャピラリー電気泳動法による高Gleason前立腺癌診断法のための血中Core型フコシル化PSA測定法の開発
    藤田 和利; 林 裕次郎; 吉川 友康; 山下 謙一郎; 冨山 栄輔; 松下 慎; 中野 剛佑; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 植村 元秀; 吉村 一宏; 植村 天受; 三善 英知; 野々村 祝夫
    日本癌学会総会記事 (一社)日本癌学会 79回 PE14 - 3 0546-0476 2020/10
  • Pten欠損前立腺癌におけるJAK1/2標的治療が糞便中のマイクロバイオームに与える影響について
    デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 野澤 昌弘; 吉川 和宏; 西尾 和人; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 79回 OE3 - 5 0546-0476 2020/10
  • 前立腺癌特異的Ptenノックアウトマウスにおけるマイクロバイオームについての検討
    倉 由吏恵; 坂井 和子; 藤田 至彦; 野澤 昌弘; 吉川 和宏; 西尾 和人; デベラスコ・マルコ; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 79回 OJ3 - 8 0546-0476 2020/10
  • アンドロゲン除去療法は前立腺特異的Ptenノックアウトマウスにおいて免疫療法の抗腫瘍効果を増強する
    植村 天受; 倉 由吏恵; 坂井 和子; 野澤 昌弘; 吉川 和宏; 西尾 和人; デベラスコ・マルコ
    日本癌学会総会記事 (一社)日本癌学会 79回 OE12 - 5 0546-0476 2020/10
  • 異種間遺伝子発現解析による免疫プロファイリングへの応用について
    坂野 恵理; 倉 由吏恵; 坂井 和子; 藤田 至彦; 野澤 昌弘; 吉川 和宏; 西尾 和人; デベラスコ・マルコ; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 79回 OE15 - 6 0546-0476 2020/10
  • 75歳以上の高齢女性患者におけるサルコペニア、内臓脂肪が下部尿路症状に与える影響
    橋本 士; 西本 光寿; 清水 信貴; 森 康範; 南 高文; 藤田 和利; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 平山 暁秀; 植村 天受
    日本排尿機能学会誌 (一社)日本排尿機能学会 31 (1) 266 - 266 1347-6513 2020/10
  • 脊髄損傷マウスモデルの膀胱機能障害に対するビベグロンの効果
    清水 信貴; 西本 光寿; 後藤 大輔; 橋本 士; 平山 暁秀; 吉村 直樹; 植村 天受
    日本排尿機能学会誌 (一社)日本排尿機能学会 31 (1) 210 - 210 1347-6513 2020/10
  • 75歳以上の高齢女性患者におけるサルコペニア、内臓脂肪が下部尿路症状に与える影響
    橋本 士; 西本 光寿; 清水 信貴; 森 康範; 南 高文; 藤田 和利; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 平山 暁秀; 植村 天受
    日本排尿機能学会誌 (一社)日本排尿機能学会 31 (1) 266 - 266 1347-6513 2020/10
  • Yasuhide Miyoshi; Masato Yasui; Sohgo Ttsutsumi; Takashi Kawahara; Ko‐ichi Uemura; Naruhiko Hayashi; Masahiro Nozawa; Kazuhiro Yoshimura; Hiroji Uemura; Hirotsugu Uemura
    BJUI Compass Wiley 2688-4526 2020/09
  • Hiroji Uemura; Yosuke Koroki; Yuki Iwaki; Keiichiro Imanaka; Takeshi Kambara; Angela Lopez-Gitlitz; Andressa Smith; Hirotsugu Uemura
    BMC UROLOGY BMC 20 (1) 139 - 139 1471-2490 2020/09 [Refereed]
     
    Background A higher incidence of apalutamide-related skin rash has been observed in Japanese patients with prostate cancer (PC). Methods This integrated analysis of data of Japanese patients from 2 global Phase 3 studies, SPARTAN (; patients with non-metastatic castration-resistant PC [nmCRPC]) and TITAN (; patients with metastatic castration-sensitive PC [mCSPC]), and the Phase 1 study 56021927PCR1008 (; patients with metastatic CRPC [mCRPC]), assessed clinical risk factors of apalutamide-related skin rash as well as the potential correlation with plasma exposure to apalutamide. Kaplan-Meier method was used for time-to-event analyses. Clinical risk factors for skin rash were assessed using odds ratio. Results Data from 68 patients (SPARTAN:n = 34, TITAN:n = 28, 56021927PCR1008:n = 6) receiving apalutamide 240 mg orally once-daily were analyzed. Rash (13 [19.1%]) and maculo-papular rash (11 [16.2%]) were the most frequently reported skin rash. All Grade and Grade 3 skin rash occurred in 35 (51.5%) and 10 (14.7%) patients, respectively. Most (85.7%) skin rash occurred within 4 months of apalutamide initiation and resolved in a median time of 1 month following the use of antihistamines, topical or systemic corticosteroids, with/without apalutamide dose interruptions/reductions. Median time-to-remission of first incidence of rash and maximum grade incidence of rash were 1.0 month (IQR: 0.36-1.81) and 1.0 month (IQR: 0.30-2.43), respectively. No significant clinical risk factors for the incidence of skin rash were observed. Areas under the curve (0-24 h) (AUC(0-24, ss)) at steady-state of plasma apalutamide concentration were numerically slightly higher in patients with skin rash than those without. Conclusions No clinical risk factors for rash could be detected. There is a potential correlation between incidence of skin rash and plasma exposure to apalutamide. In general, apalutamide-related skin rash is easily managed, with appropriate treatment with or without dose adjustment.
  • Hiroaki Matsumoto; Koji Shiraishi; Haruhito Azuma; Keiji Inoue; Hirotsugu Uemura; Masatoshi Eto; Chikara Ohyama; Osamu Ogawa; Eiji Kikuchi; Hiroshi Kitamura; Nobuo Shinohara; Satoru Takahashi; Toyonori Tsuzuki; Masayuki Nakagawa; Yoshifumi Narumi; Hiroyuki Nishiyama; Tomonori Habuchi; Shiro Hinotsu; Yasuhisa Fujii; Kiyohide Fujimoto; Hiroyuki Fujimoto; Takashi Mizowaki; Hideyasu Matsuyama
    INTERNATIONAL JOURNAL OF UROLOGY WILEY 27 (9) 702 - 709 0919-8172 2020/09 [Refereed]
     
    Objectives Despite just a 4-year interval from the last version (2015) of the Clinical Practice Guidelines for Bladder Cancer, several dramatic paradigm shifts have occurred in the latest clinical practice regarding both the diagnosis and treatment of bladder cancer. Herein, we updated the 2019 version of the Clinical Practice Guidelines for Bladder Cancer under the instruction of the Japanese Urological Association. Methods We previously reported in a revision working position paper for Clinical Practice Guidelines for Bladder Cancer 2019 edition and described the methods of revision detail. Results The major points of change in the 2019 version are presented and explanations are given as follows: (i) introduction of the new reference assessment system; (ii) modification of the risk classification for non-muscle-invasive bladder cancer; (iii) addition of clinical questions for the new tumor-visible techniques in non-muscle-invasive bladder cancer; (iv) inclusion of minimally invasive surgeries for muscle-invasive bladder cancer and immune checkpoint inhibitors for locally advanced/metastatic muscle-invasive bladder cancer; (v) overview chapter of the histological variant of urothelial cancer and rare cancers of the bladder; and (vi) recommendation of follow up in non-muscle-invasive bladder cancer and muscle-invasive bladder cancer. Conclusions Guidelines should be updated based on the current evidence and updates carried out without delay. The hope is that this guidelines will be assessed by many urologists and will be the cornerstone for the next revision.
  • 杉本 公一; 秋山 隆弘; 豊田 信吾; 安富 正悟; 齋藤 允孝; 能勢 和宏; 西岡 伯; 江左 篤宣; 植村 天受
    日本老年泌尿器科学会誌 日本老年泌尿器科学会 33 (1) 158 - 158 2187-3682 2020/08
  • 吉村 一宏; 藤田 和利; 植村 天受
    Uro-Lo: 泌尿器Care & Cure (株)メディカ出版 25 (4) 530 - 533 2189-8545 2020/08
  • 野澤 昌弘; 中山 尭仁; 藤本 西蔵; 浜口 守; 高橋 智輝; 橋本 士; 西本 光寿; 安富 正悟; 坂野 恵里; 齋藤 允孝; 清水 信貴; 森 康範; 南 高文; 藤田 和利; 能勢 和宏; 吉村 一宏; 植村 天受
    日本老年泌尿器科学会誌 日本老年泌尿器科学会 33 (1) 33 - 33 2187-3682 2020/08
  • 橋本 士; 西本 光寿; 清水 信貴; 森 康範; 南 高文; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 平山 暁秀; 植村 天受
    日本老年泌尿器科学会誌 日本老年泌尿器科学会 33 (1) 101 - 101 2187-3682 2020/08
  • 松村 直紀; 杉本 公一; 西本 光寿; 永井 康晴; 上島 成也; 南 高文; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 植村 天受
    日本老年泌尿器科学会誌 日本老年泌尿器科学会 33 (1) 148 - 148 2187-3682 2020/08
  • Eisuke Tomiyama; Kazutoshi Fujita; Maria Del Carmen Rodriguez Pena; Diana Taheri; Eri Banno; Taigo Kato; Koji Hatano; Atsunari Kawashima; Takeshi Ujike; Motohide Uemura; Tetsuya Takao; Seiji Yamaguchi; Hiroaki Fushimi; Kazuhiro Yoshimura; Hirotsugu Uemura; George J. Netto; Norio Nonomura
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES MDPI 21 (15) 2020/08 [Refereed]
     
    Enfortumab vedotin is a novel antibody-drug conjugate targeting Nectin-4, which is highly expressed in urothelial carcinoma. However, the expression status of Nectin-4 in upper tract urothelial carcinoma (UTUC) remains unclear. The relationship between Nectin-4 and Programmed Death Ligand 1 (PD-L1) in UTUC is also ambiguous. We performed immunohistochemical analysis of 99 UTUC tissue microarray to assess the expression of Nectin-4 and PD-L1 in UTUC. Nectin-4-positivity was detected in 65 (65.7%) samples, and PD-L1 was detected in 24 (24.2%) samples. There was no correlation between the expression of Nectin-4 and PD-L1. Patients with strong Nectin-4-expressing tumors had a significantly higher risk of progression (p= 0.031) and cancer-specific mortality (p= 0.036). Strong Nectin-4 expression was also an independent predictor of disease progression in the high-risk group (pT3 <= or presence of lymphovascular invasion or lymph node metastasis) (Hazard ratio, 3.32 [95% confidence interval, 1.20-7.98;p= 0.027]). In conclusion, we demonstrated that Nectin-4 expression rate in UTUC was 65.7% and independent of PD-L1 expression. Strong Nectin-4 expression was associated with worse progression-free survival in high-risk UTUC. These findings suggested that enfortumab vedotin may be effective in a broad range of patients with UTUC, regardless of PD-L1 expression.
  • Shogo Adomi; Kazutoshi Fujita; Kazuhiro Yoshimura; Hirotsugu Uemura
    INTERNATIONAL JOURNAL OF UROLOGY WILEY 27 (8) 655 - 656 0919-8172 2020/08 [Refereed]
  • Nobuyuki Hinata; Junji Yonese; Satoru Masui; Yasutomo Nakai; Suguru Shirotake; Katsunori Tatsugami; Teruo Inamoto; Masahiro Nozawa; Kosuke Ueda; Toru Etsunaga; Takahiro Osawa; Motohide Uemura; Go Kimura; Kazuyuki Numakura; Kazutoshi Yamana; Hideaki Miyake; Satoshi Fukasawal; Kenya Ochi; Hirokazu Kaneko; Hirotsugu Uemura
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY SPRINGER JAPAN KK 25 (8) 1533 - 1542 1341-9625 2020/08 [Refereed]
     
    Background In a phase III clinical trial, CheckMate 025, treatment of metastatic renal cell carcinoma (mRCC) with nivolumab demonstrated superior efficacy over everolimus. However, as the clinical trial excluded patients with specific complications and poor performance status (PS), the effectiveness and safety of nivolumab in clinical practice, in which patients with various clinical complications are treated, is unclear. This study explored real-world nivolumab treatment in Japanese mRCC patients. Methods This is an interim analysis of a multicenter, non-interventional, medical record review study (minimum follow-up: 9 months). All eligible Japanese mRCC patients who first received nivolumab between February and October 2017 were included; data cut-off was April 2019. We analyzed nivolumab treatment patterns, efficacy (including overall survival, progression-free survival, objective response rate, and duration of response) and safety (including immune-related adverse events). Results Of 208 evaluable patients, 31.7% received nivolumab as fourth- or later line of treatment. At data cut-off, 26.9% of patients were continuing nivolumab treatment. The major reason for discontinuation was disease progression (n = 100, 65.8%). Median overall survival was not reached; the 12-month survival rate was 75.6%. Median progression-free survival was 7.1 months, the objective response rate was 22.6%, and median duration of response was 13.3 months. Patients who were excluded or limited in number in CheckMate 025, such as those with non-clear cell RCC or poor PS, also received benefits from nivolumab treatment. Immune-related adverse events occurred in 27.4% of patients (grade >= 3, 10.1%). Conclusion Nivolumab was effective and well-tolerated in real-world Japanese mRCC patients.
  • Marco A. De Velasco; Yan Lu; Yurie Kura; Toshiyuki China; Yasuyuki Inoue; Akinori Nakayama; Hiroshi Okada; Shigeo Horie; Hirotsugu Uemura; Hisamitsu Ide
    HUMAN CELL SPRINGER JAPAN KK 33 (3) 730 - 736 0914-7470 2020/07 [Refereed]
     
    The present study investigated the antitumor activity and chemopreventive effects of a nanoparticle formulation of curcumin in preclinical models of mouse Pten-deficient prostate cancer. The antitumor activity of the nanoparticle curcumin was evaluated in mouse castration-naive (7113-D3) and castration-resistant prostate cancer (2945-E10) derived cell lines in vitro. Cell viability was reduced in both cell lines in a dose and time-dependent manner. The effects of long-term dietary supplementation with the nanoparticle curcumin formulation were evaluated in a conditionalPten-deficient mouse model. Prostate tissues fromPten-deficient prostate cancers were obtained after sixteen weeks of dietary supplementation of 76 mg/kg/day or 380 mg/kg/day nanoparticle curcumin. Daily supplementation of nanoparticle curcumin did not affect mouse bodyweights or spleen size but did result in enlargement of the liver. Dietary supplementation did not influence tumor burden, however, mice fed high-dose curcumin had lower cancer cell proliferation rates at 12 and 16 weeks of age. Together, these results show that daily supplementation of a nanoparticle formulation of curcumin is tolerable and suggest that curcumin could have chemopreventive activity in early-stage prostate cancer.
  • 巣状糸球体硬化症に対して生体腎移植後、長期間を経て再発した1症例
    菊池 尭; 森 康範; 能勢 和宏; 吉村 一宏; 植村 天受; 齋藤 允孝; 玉井 健太郎; 林 泰司; 西岡 伯; 今西 正昭; 秋山 隆弘
    泌尿器科紀要 泌尿器科紀要刊行会 66 (6) 207 - 207 0018-1994 2020/06
  • 近畿大学における前立腺癌密封小線源療法の検討
    藤本 西蔵; 浜口 守; 高橋 智輝; 橋本 士; 菊池 尭; 安富 正悟; 大關 孝之; 清水 信貴; 森 康範; 南 高文; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 植村 天受
    泌尿器科紀要 泌尿器科紀要刊行会 66 (6) 179 - 179 0018-1994 2020/06
  • 転移性尿路上皮癌に対するペムブロリズマブの使用経験
    高橋 智輝; 野澤 昌弘; 藤本 西蔵; 浜口 守; 橋本 士; 菊池 尭; 安富 正吾; 大關 孝之; 清水 信貴; 森 康範; 南 高文; 能勢 和宏; 吉村 一宏; 植村 天受
    泌尿器科紀要 泌尿器科紀要刊行会 66 (6) 190 - 190 0018-1994 2020/06
  • 当院におけるホルモン療法未治療前立腺癌(HNPC)に対するアビラテロンとプレドニゾロン併用療法の使用経験
    安富 正悟; 藤本 西蔵; 浜口 守; 高橋 智輝; 橋本 士; 菊池 尭; 大關 孝之; 清水 信貴; 森 康範; 南 高文; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 植村 天受
    泌尿器科紀要 泌尿器科紀要刊行会 66 (6) 196 - 197 0018-1994 2020/06
  • カバジタキセルにより再燃した潜在性結核感染の1例
    橋本 士; 藤本 西蔵; 浜口 守; 高橋 智輝; 菊池 尭; 安富 正悟; 大關 孝之; 清水 信貴; 森 康範; 南 高文; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 植村 天受
    泌尿器科紀要 泌尿器科紀要刊行会 66 (6) 199 - 199 0018-1994 2020/06
  • トピロキソスタット投与による腎機能保護作用の検討
    杉本 公一; 西本 光寿; 松村 直紀; 上島 成也; 秋山 隆弘; 安富 正悟; 能勢 和宏; 植村 天受; 西岡 伯
    泌尿器科紀要 泌尿器科紀要刊行会 66 (6) 181 - 181 0018-1994 2020/06
  • 高齢者のHSPCにおけるCAB療法の治療成績
    松村 直紀; 杉本 公一; 西本 光寿; 上島 成也; 大関 孝之; 清水 信貴; 森 康範; 南 高文; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 植村 天受
    泌尿器科紀要 泌尿器科紀要刊行会 66 (6) 196 - 196 0018-1994 2020/06
  • 松村 直紀; 杉本 公一; 西本 光寿; 上島 成也; 大関 孝之; 清水 信貴; 森 康範; 南 高文; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 植村 天受
    泌尿器外科 医学図書出版(株) 33 (臨増) 889 - 889 0914-6180 2020/06
  • Motokiyo Yoshikawa; Kazumasa Torimoto; Akihide Hirayama; Keisuke Kiba; Yutaka Yamamoto; Yasunori Akashi; Nobutaka Shimizu; Nobumichi Tanaka; Hirotsugu Uemura; Kiyohide Fujimoto
    NEUROUROLOGY AND URODYNAMICS WILEY 39 (5) 1550 - 1556 0733-2467 2020/06 [Refereed]
     
    Aims There is accumulating evidence that excessive salt intake contributes to nocturnal polyuria. We aimed to investigate the relationship between salt intake, leg edema, and nocturnal urine volume (NUV) to assess the etiology of nocturnal polyuria.Methods A total of 56 men aged >= 60 years who were hospitalized for benign prostatic hyperplasia or with suspected prostatic cancer were enrolled. Urine frequency-volume charts of the patients were maintained, and they underwent bioelectrical impedance analysis twice daily (at 5:00 pm and 6:00 am) and examination of blood (brain natriuretic peptide levels) and urine (sodium and creatinine levels and osmotic pressure) samples once daily (at 6:00 am). Free-water clearance, solute clearance, and sodium clearance at night were measured, and daily salt intake was estimated.Results The data of 52 patients were analyzed. Daily salt intake positively correlated with leg edema at 5:00 pm, differences in leg extracellular fluid levels between 5:00 pm and 6:00 am, and NUV, but not with diurnal urine volume. Partial correlation coefficients showed that salt intake was a factor of the correlation between NUV and change in extracellular volume in the legs between 5:00 pm and 6:00 am. A multivariate logistic model showed that sleep duration and sodium clearance were independent predictive factors for nocturnal polyuria.Conclusions Sodium intake correlates with diurnal leg edema and NUV in elderly men. These results provide evidence supporting sodium restriction as an effective treatment for nocturnal polyuria.
  • Hiroaki Matsumoto; Koji Shiraishi; Haruhito Azuma; Keiji Inoue; Hirotsugu Uemura; Masatoshi Eto; Chikara Ohyama; Osamu Ogawa; Eiji Kikuchi; Hiroshi Kitamura; Nobuo Shinohara; Satoru Takahashi; Toyonori Tsuzuki; Masayuki Nakagawa; Yoshifumi Narumi; Hiroyuki Nishiyama; Tomonori Habuchi; Shiro Hinotsu; Yasuhisa Fujii; Kiyohide Fujimoto; Hiroyuki Fujimoto; Takashi Mizowaki; Hideyasu Matsuyama
    INTERNATIONAL JOURNAL OF UROLOGY WILEY 27 (5) 362 - 368 0919-8172 2020/05 [Refereed]
     
    The Clinical Practice Guidelines for Bladder Cancer edited by the Japanese Urological Association were first published in 2009 and a revised edition was released in 2015. Four years has passed since the 2015 edition, and the clinical practice environment surrounding bladder cancer has drastically changed during that time. The main changes include: (i) insurance coverage of a new diagnostic method for non-muscle-invasive bladder cancer; (ii) insurance coverage of an immune checkpoint inhibitor in advanced and metastatic bladder cancer; and (iii) advances in robot-assisted radical cystectomy as a minimally invasive treatment for muscle-invasive bladder cancer. A paradigm shift in bladder cancer diagnosis and treatment is occurring day by day. Therefore, in this 2019 edition, while dealing with the above changes, we carefully selected clinical questions with clear evidence and included other clinically important points in the general statement. We also added a new chapter on rare cancers of the urinary tract. As a new method for the evaluation of study evidence level, we introduce "The Grading of Recommendations Assessment, Development and Evaluation" system modified to Japanese by the Medical Information Network Distribution Service.
  • Masanori Noguchi; Gaku Arai; Shin Egawa; Chikara Ohyama; Seiji Naito; Kazumasa Matsumoto; Hirotsugu Uemura; Masayuki Nakagawa; Yasutomo Nasu; Masatoshi Eto; Shigetaka Suekane; Tetsuro Sasada; Shigeki Shichijo; Akira Yamada; Tatsuyuki Kakuma; Kyogo Itoh
    CANCER IMMUNOLOGY IMMUNOTHERAPY SPRINGER 69 (5) 847 - 857 0340-7004 2020/05 [Refereed]
     
    A novel cancer vaccine consisting of 20 mixed peptides (KRM-20) was designed to induce cytotoxic T lymphocytes (CTL) against twelve different tumor-associated antigens. The aim of this phase II trial was to examine whether KRM-20 in combination with docetaxel and dexamethasone enhances the antitumor effects in patients with castration-resistant prostate cancer (CRPC). In this double-blind, placebo-controlled, randomized phase II study, we enrolled chemotherapy-naive patients with CRPC from ten medical centers in Japan. Eligible patients were randomly assigned 1:1 centrally to receive either KRM-20 combined with docetaxel and dexamethasone (n = 25) or placebo with docetaxel and dexamethasone (n = 26). The primary endpoint was the difference in prostate-specific antigen (PSA) decline between each treatment. The rates of > 50% PSA decline in the two arms were similar (56.5% versus 53.8%; P = 0.851). Human leukocyte antigen (HLA)-matched peptide-specific immunoglobulin G (P = 0.018) and CTL (P = 0.007) responses in the KRM-20 arm significantly increased after treatment. The addition of KRM-20 did not increase toxicity. There were no between-group differences in progression-free or overall survival (OS). The addition of KRM-20 was safe, and similar PSA decline and HLA-matched peptide-specific CTL and IgG responses increased in combination with docetaxel and dexamethasone in CRPC patients. Subgroup analysis suggested that this treatment is favorable for CRPC patients with >= 26% lymphocytes or PSA levels of < 11.2 ng/ml, but further clinical trials comparing OS are required.
  • Simon Chowdhury; Anders Bjartell; Neeraj Agarwal; Byung Ha Chung; Robert W. Given; Andrea J. Pereira de Santana Gomes; Axel S. Merseburger; Mustafa Ozguroglu; Alvaro Juarez Soto; Hirotsugu Uemura; Dingwei Ye; Angela Lopez-Gitlitz; Anil Londhe; Suneel Mundle; Julie S. Larsen; Sharon McCarthy; Kim N. Chi
    JOURNAL OF UROLOGY LIPPINCOTT WILLIAMS & WILKINS 203 E250 - E250 0022-5347 2020/04 [Refereed]
  • Katsunori Tatsugami; Motohide Uemura; Noboru Nakaigawa; Naoto Sassa; Kenichi Harada; Toshinari Yamasaki; Tamaki Fukuyama; Takuya Yoshimoto; Yuki Nakagawa; Nobuaki Matsubara; Mototsugu Oya; Nobuo Shinohara; Hirotsugu Uemura; Toyonori Tsuzuki
    JOURNAL OF UROLOGY LIPPINCOTT WILLIAMS & WILKINS 203 E1115 - E1115 0022-5347 2020/04 [Refereed]
  • Nobuaki Matsubara; Go Kimura; Hiroji Uemura; Hirotsugu Uemura; Motonobu Nakamura; Satoshi Nagamori; Atsushi Mizokami; Hiroaki Kikukawa; Makoto Hosono; Seigo Kinuya; Heiko Krissel; Jonathan Siegel; Yoshiyuki Kakehi
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY SPRINGER JAPAN KK 25 (4) 720 - 731 1341-9625 2020/04 [Refereed]
     
    Background ERA 223 compared concurrent abiraterone acetate/prednisolone (AAP) plus radium-223 with AAP plus placebo in men with chemotherapy-naive asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer (mCRPC) and bone metastases. We report data from a subgroup of Japanese patients in ERA 223. Methods Patients were randomized to radium-223 (55 kBq/kg) or placebo once every 4 weeks (max. 6 cycles), and also received oral abiraterone acetate 1000 mg once daily plus prednisone/prednisolone 5 mg twice daily during and after radium-223/placebo treatment, until a symptomatic skeletal event (SSE). The primary endpoint was SSE-free survival (SSE-FS); overall survival (OS) was a secondary endpoint. Results Of 806 patients randomized in ERA 223, 114 patients (57 per arm) were enrolled in Japan. SSE-FS was not improved significantly in the radium-223 arm [25.5 months, 95% CI 20.6-not estimated (NE)] compared with the placebo arm (28.7 months, 95% CI 19.7-NE) (HR = 0.907, 95% CI 0.501-1.642). OS and other secondary endpoints were not improved significantly in the radium-223 arm. The incidence of fracture was 23% and 11% in the radium-223 and placebo arms, respectively. The incidence of death was 32% and 36%, respectively. Conclusions In the Japanese ERA 223 subgroup, concurrent treatment with AAP and radium-223 did not significantly improve SSE-FS and increased the incidence of fracture, similar to outcomes achieved in the overall population, while an increased incidence of death was not evident. The combination of radium-223 with AAP is not recommended in Japanese patients with asymptomatic or mildly symptomatic mCRPC and bone metastases.
  • Hirotsugu Uemura; Dingwei Ye; Ravindran Kanesvaran; Edmund Chiong; Bannakij Lojanapiwat; Yeong-Shiau Pu; Sudhir Kumar Rawal; Azad Hassan Abdul Razack; Hao Zeng; Byung Ha Chung; Noor Ashani Md Yusoff; Chikara Ohyama; Choung Soo Kim; Sunai Leewansangtong; Yuh-Shyan Tsai; Yanfang Liu; Weiping Liu; Maximiliano van Kooten Losio; Marxengel Asinas-Tan
    BJU INTERNATIONAL WILEY 125 (4) 541 - 552 1464-4096 2020/04 [Refereed]
     
    Objectives To document the management of advanced prostate cancer including diagnosis, prognosis, treatment, and care, in real-world practice in Asia using the United in Fight against prOstate cancer (UFO) registry. Patients and Methods We established a multi-national, longitudinal, observational registry of patients with prostate cancer presenting to participating tertiary care hospitals in eight Asian countries. A total of 3636 eligible patients with existing or newly diagnosed high-risk localised prostate cancer (HRL), non-metastatic biochemically recurrent prostate cancer (M0), or metastatic prostate cancer (M1), were consecutively enrolled and are being followed-up for 5 years. Patient history, demographic and disease characteristics, treatment and treatment decisions, were collected at first prostate cancer diagnosis and at enrolment. Patient-reported quality of life was prospectively assessed using the European Quality of Life-five Dimensions, five Levels (EQ-5D-5L) and Functional Assessment of Cancer Therapy for Prostate Cancer questionnaires. In the present study, we report the first interim analysis of 2063 patients enrolled from study start (15 September 2015) until 18 May 2017. Results Of the 2063 enrolled patients, 357 (17%), 378 (19%), and 1328 (64%) had HRL, M0 or M1 prostate cancer, respectively. The mean age at first diagnosis was similar in each group, 56% of all patients had extracapsular extension of their tumour, 28% had regional lymph node metastasis, and 53% had distant metastases. At enrolment, 62% of patients had at least one co-morbidity (mainly cardiovascular disease or diabetes), 91.8% of M1 patients had an Eastern Cooperative Oncology Group performance score of <2 and the mean EQ-5D-5L visual analogue score was 74.6-79.6 across cohorts. Treatment of M1 patients was primarily with combined androgen blockade (58%) or androgen-deprivation therapy (either orchidectomy or luteinising hormone-releasing hormone analogues) (32%). Decisions to start therapy were mainly driven by treatment guidelines and disease progression. Decision to discontinue therapy was most often due to disease progression (hormonal drug therapy) or completion of therapy (chemotherapy). Conclusion In the UFO registry of advanced prostate cancer in Asia, regional differences exist in prostate cancer treatment patterns that will be explored more deeply during the follow-up period; prospective follow-up is ongoing. The UFO registry will provide valuable descriptive data on current disease characteristics and treatment landscape amongst patients with prostate cancer in Asia.
  • カバジタキセルにより再燃した潜在性結核感染の1例
    橋本 士; 南 高文; 浜口 守; 高橋 智輝; 菊池 尭; 西本 光寿; 安富 正悟; 大關 孝之; 清水 信貴; 森 康範; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 植村 天受
    泌尿器科紀要 泌尿器科紀要刊行会 66 (3) 98 - 98 0018-1994 2020/03
  • カバジタキセルにより再燃した潜在性結核感染の1例
    橋本 士; 南 高文; 浜口 守; 高橋 智輝; 菊池 尭; 西本 光寿; 安富 正悟; 大關 孝之; 清水 信貴; 森 康範; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 植村 天受
    泌尿器科紀要 泌尿器科紀要刊行会 66 (3) 98 - 98 0018-1994 2020/03 [Refereed]
  • Motohide Uemura; Yoshihiko Tomita; Hideaki Miyake; Shingo Hatakeyama; Hiro-omi Kanayama; Kazuyuki Numakura; Toshio Takagi; Tomoyuki Kato; Masatoshi Eto; Wataru Obara; Hirotsugu Uemura; Toni K. Choueiri; Robert J. Motzer; Yosuke Fujii; Yoichi Kamei; Yoshiko Umeyama; Alessandra Di Pietro; Mototsugu Oya
    CANCER SCIENCE WILEY 111 (3) 907 - 923 1347-9032 2020/03 [Refereed]
     
    The phase 3 JAVELIN Renal 101 trial of avelumab + axitinib vs sunitinib in patients with treatment-naive advanced renal cell carcinoma (RCC) demonstrated significantly improved progression-free survival (PFS) and higher objective response rate (ORR) with the combination vs sunitinib. Japanese patients enrolled in the study (N = 67) were randomized to receive avelumab + axitinib (N = 33) or sunitinib (N = 34); 67% vs 59% had PD-L1+ tumors (>= 1% of immune cells) and 6%/64%/27% vs 6%/82%/12% had International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) favorable/intermediate/poor risk status. In patients who received avelumab + axitinib vs sunitinib, median PFS (95% confidence interval [CI]) was not estimable (8.1 months, not estimable) vs 11.2 months (1.6 months, not estimable) (hazard ratio [HR], 0.49; 95% CI, 0.152, 1.563) in patients with PD-L1+ tumors and 16.6 months (8.1 months, not estimable) vs 11.2 months (4.2 months, not estimable) (HR, 0.66; 95% CI, 0.296, 1.464) in patients irrespective of PD-L1 expression. Median overall survival (OS) has not been reached in either arm in patients with PD-L1+ tumors and irrespective of PD-L1 expression. ORR (95% CI) was 60.6% (42.1%, 77.1%) vs 17.6% (6.8%, 34.5%) in patients irrespective of PD-L1 expression. Common treatment-emergent adverse events (all grade; grade >= 3) in each arm were hand-foot syndrome (64%; 9% vs 71%; 9%), hypertension (55%; 30% vs 44%; 18%), hypothyroidism (55%; 0% vs 24%; 0%), dysgeusia (21%; 0% vs 56%; 0%) and platelet count decreased (3%; 0% vs 65%; 32%). Avelumab + axitinib was efficacious and tolerable in treatment-naive Japanese patients with advanced RCC, which is consistent with results in the overall population.
  • 腎移植後に発症した同時性四重複癌の一例
    菊池 尭; 森 康範; 能勢 和宏; 吉村 一宏; 植村 天受; 玉井 健太郎; 林 泰司; 西岡 伯; 齋藤 允孝; 今西 正昭; 秋山 隆弘
    日本臨床腎移植学会プログラム・抄録集 (一社)日本臨床腎移植学会 53回 280 - 280 2020/02
  • Neeraj Agarwal; Simon Chowdhury; Anders Bjartell; Byung Ha Chung; Andrea Juliana Pereira de Santana Gomes; Robert W. Given; Alvaro Juarez Soto; Axel Stuart Merseburger; Mustafa Ozguroglu; Hirotsugu Uemura; Dingwei Ye; Anil Londhe; Angela Lopez-Gitlitz; Sharon Anne McCarthy; Suneel Mundle; Kim N. Chi
    JOURNAL OF CLINICAL ONCOLOGY AMER SOC CLINICAL ONCOLOGY 38 (6) 0732-183X 2020/02 [Refereed]
  • Mustafa Ozguroglu; Simon Chowdhury; Anders Bjartell; Hirotsugu Uemura; Byung Ha Chung; Neeraj Agarwal; Axel Stuart Merseburger; Alvaro Juarez Soto; Angela Lopez-Gitlitz; Amitabha Bhaumik; Julie S. Larsen; Sharon Anne McCarthy; Kim N. Chi
    JOURNAL OF CLINICAL ONCOLOGY AMER SOC CLINICAL ONCOLOGY 38 (6) 0732-183X 2020/02 [Refereed]
  • Shunji Takahashi; Yoshiyuki Kakehi; Naoya Masumori; Makoto Hosono; Seigo Kinuya; Yutaka Okayama; Toshiyuki Sunaya; Masafumi Okumura; Hirotsugu Uemura
    JOURNAL OF CLINICAL ONCOLOGY AMER SOC CLINICAL ONCOLOGY 38 (6) 0732-183X 2020/02 [Refereed]
  • Keisuke Kiba; Yasunori Akashi; Motokiyo Yoshikawa; Yutaka Yamamoto; Akihide Hirayama; Kiyohide Fujimoto; Hirotsugu Uemura
    Research and reports in urology 12 569 - 575 2020 
    Purpose: The aim of this study was to compare the safety and efficacy of photoselective vaporization of the prostate (PVP) and transurethral enucleation with a bipolar system (TUEB). Patients and Methods: Patients who underwent PVP or TUEB surgery for lower urinary tract symptoms due to bladder outlet obstruction at our institution from September 2015 to May 2019 were retrospectively reviewed. A total of 83 patients (PVP: n=45, TUEB: n=38) who were available for follow-up at least 12 months after surgery were included. Preoperative characteristics, perioperative parameters, and postoperative outcomes-such as International Prostate Symptom Score (IPSS), quality of life (QoL), maximum urinary flow rate (Qmax), post-void residual urine volume (PVR), and complications-at 3, 6, and 12 months after surgery were compared between the two groups. Results: Although differences in age, IPSS, and QoL were not significant, a significantly greater prostate volume, lower Qmax, and greater PVR were noted in the TUEB group. In perioperative parameters, a significantly shorter operation time, less change in serum hemoglobin, fewer days of catheterization, and shorter length of stay were observed in the PVP group. As for postoperative outcomes, the IPSS storage subscore and PVR were significantly improved in the TUEB group. As complications, stress urinary incontinence was more frequently observed in the TUEB group, and urethral stricture was more common in the PVP group. Conclusion: The present data suggest that PVP and TUEB are efficient and safe surgical treatment options. Management of patients undergoing PVP in the perioperative period appears easy. Improvements of subjective and objective parameters were superior after TUEB than after PVP.
  • Nobutaka Shimizu; Naoki Wada; Takahiro Shimizu; Takahisa Suzuki; Masahiro Kurobe; Anthony J. Kanai; William C. de Groat; Mamoru Hashimoto; Akihide Hirayama; Hirotsugu Uemura; Naoki Yoshimura
    NEUROUROLOGY AND URODYNAMICS WILEY 39 (1) 108 - 115 0733-2467 2020/01 [Refereed]
     
    Aim To investigate the role of p38 MAP kinase in lower urinary tract dysfunction in mice with spinal cord injury (SCI). Methods Cystometry and external urethral sphincter-electromyography were performed under an awake condition in 4-week SCI female mice. Two weeks after SCI, a catheter connected to an osmotic pump filled with a p38 mitogen-activated protein kinase (MAPK) inhibitor or artificial cerebrospinal fluid (CSF) was implanted into the intrathecal space of L6-S1 spinal cord for continuous intrathecal instillation at infusion rate of 0.51 mu L/h for 2 weeks before the urodynamic study. L6 dorsal root ganglia were then removed from CSF and p38 MAPK inhibitor-treated SCI mice as well as from CSF-treated normal (spinal intact) mice to evaluate the levels of transient receptor potential cation channel subfamily V member 1 (TRPV1), tumor necrosis factor-alpha (TNF-alpha), and inducible nitric oxide synthase (iNOS) transcripts by real-time polymerase chain reaction. Results In p38 MAPK inhibitor-treated SCI mice, nonvoiding contractions during bladder filling, bladder capacity, and post-void residual volume were significantly reduced while micturition pressure and voiding efficiency were significantly increased in comparison to these measurements in CSF-treated SCI mice. The expression of TRPV1, TNF-alpha, and iNOS messenger RNA was increased in SCI mice compared with expression in spinal intact mice and significantly decreased after p38 MAPK inhibitor treatment. Conclusions The p38 MAPK signaling pathway in bladder sensory neurons or in the spinal cord plays an important role in storage and voiding problems such as detrusor overactivity and inefficient voiding after SCI.
  • Yoshihiko Tomita; Tsunenori Kondo; Go Kimura; Takamitsu Inoue; Yoshiaki Wakumoto; Masahiro Yao; Takayuki Sugiyama; Mototsugu Oya; Yasuhisa Fujii; Wataru Obara; Robert J. Motzer; Hirotsugu Uemura
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY OXFORD UNIV PRESS 50 (1) 12 - 19 0368-2811 2020/01 [Refereed]
     
    Background Nivolumab plus ipilimumab (NIVO+IPI) demonstrated superior efficacy over sunitinib (SUN) for previously untreated advanced renal cell carcinoma (aRCC) in CheckMate 214, with a manageable safety profile. We report efficacy and safety with extended follow-up amongst Japanese patients.Methods CheckMate 214 patients received NIVO (3 mg/kg) plus IPI (1 mg/kg) every 3 weeks for four doses, then NIVO (3 mg/kg) every 2 weeks; or SUN (50 mg) once daily for 4 weeks (6-week cycle). This subgroup analysis assessed overall survival (OS), objective response rate (ORR) and progression-free survival (PFS) per investigator in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) intermediate/poor-risk and intent-to-treat (ITT) patients and safety (ITT patients).Results Of 550 and 546 patients randomized to NIVO+IPI and SUN, 38 and 34, respectively, were Japanese. Of these, 31 (NIVO+IPI) and 29 (SUN) patients were IMDC intermediate/poor-risk. In IMDC intermediate/poor-risk patients with 30 months' minimum follow-up, there was a delayed trend in OS benefit with NIVO+IPI (hazard ratio [HR] 0.56; 95% confidence interval [CI]: 0.19-1.59; P = 0.2670), and 24-month OS probability favoured NIVO+IPI (84%) versus SUN (76%). The ORR was 39% with NIVO+IPI and 31% with SUN (P = 0.6968). PFS was similar in both treatment arms (HR 1.17; 95% CI: 0.62-2.20; P = 0.6220). Efficacy in ITT patients was similar to IMDC intermediate/poor-risk patients. Grade 3-4 treatment-related adverse event incidence was lower with NIVO+IPI versus SUN (58 versus 91%).Conclusions Japanese patients with untreated aRCC in the NIVO+IPI arm had a numerically higher ORR and improved safety profile versus patients in the SUN arm. A delayed OS benefit appears to be emerging with NIVO+IPI. Longer follow-up is needed.https://clinicaltrials.gov/ct2/show/NCT02231749?term=NCT02231749&rank=1 identifier: NCT02231749.
  • 日本人セックスワーカーの性機能 アンケートのスコアを使用した評価(Sexual function in Japanese female sex workers: an assessment using questionnaire scores)
    永井 康晴; 清水 信貴; 西本 光寿; 植村 天受; 豊田 信吾; 花井 禎; 上島 成也; 小澤 千咲; 小畠 秀吾
    日本性機能学会雑誌 (一社)日本性機能学会 34 (3) 215 - 223 1345-8361 2019/12 
    目的:この研究の目的はthe Sexual Function Questionnaire(SFQ-J)とFemale Sexual Function Index(FSFI-J)を使用して、女性セックスワーカーのプライベート及び勤務中の性機能を評価することである。対象と方法:日本の女性セックスワーカーの性機能は調査されていない。我々はSFQ-JとFSFI-Jを用いて女性のセックスワーカーの性機能を評価することを目的とした。質問票は55人の女性セックスワーカーに実施された。質問票には、年齢、身長、体重、既往歴、性感染症の病歴、手術歴、性産業従事期間、国際前立腺症状スコア(IPSS)、および過活動膀胱症状スコア(OABSS)が含まれた。SFQ-J、FSFI-Jについては「プライベート」、「勤務中」での回答を比較した。主要評価項目はSFQ-JとFSFI-Jのスコア比較とした。結果:55例全ての女性セックスワーカーから回答を得た。平均年齢は31.1歳±6.94歳であった。平均性産業従事期間は75.4±63ヵ月であった。勤務中のFSFI-Jスコアはプライベートのスコアと比較し、全てのドメインと合計スコアで有意に低下していた。性産業従事期間ではなく、パートナーがいないことが、単変量及び多変量解析におけるプライベートFSFI-Jスコアの低下と有意に関連していた(オッズ比23.833;P<0.001;95%信頼区間5.175-109.769)。パートナーがいないことは、日本の女性セックスワーカーにおける性機能障害と有意に関連していた。結論:セックスワークは日本においてセックスワーカーの性機能障害の原因ではないかもしれない。(著者抄録)
  • Mamoru Hashimoto; Takafumi Minami; Mamoru Hamaguchi; Saizo Fujimoto; Tomoki Takahashi; Takashi Kikuchi; Shogo Adomi; Eri Banno; Takayuki Ohzeki; Nobutaka Shimizu; Yasunori Mori; Masahiro Nozawa; Kazuhiro Nose; Kazuhiro Yoshimura; Hirotsugu Uemura
    MEDICINE LIPPINCOTT WILLIAMS & WILKINS 98 (51) e18436  0025-7974 2019/12 [Refereed]
     
    Rationale: Latent tuberculosis infection (LTBI) describes the dormant state of tuberculosis (TB), in which persistent immune-related interaction between TB and T-cells maintain its state. Cabazitaxel (CBZ) is reported to improve overall survival in patients with castration-resistant prostate cancer (CRPC) after progression observed in regimens including docetaxel. CBZ is known for severe myelosuppression; however there is no recommendation for the treatment of LTBI before CBZ treatment. To the authors' knowledge, this is the first report to describe reactivation of LTBI induced by CBZ.Patient concerns: A 75-year-old Japanese male with a medical history of TB since 16 years of age had been treated for prostate cancer (PC) (initial prostate-specific antigen 532 ng/ml; cT4N1M1b; Gleason score4+4) with androgen deprivation therapy, abiraterone, and docetaxel. Calcified nodules and radiological findings of LTBI were present in the upper right lobe since the diagnosis of PC. After progression was observed during these treatments, CBZ was administered combined with pegfilgrastim, long-acting granulocyte colony-stimulating factor (G-CSF). Seven days after the third course of CBZ, he was admitted to the authors' hospital to treat febrile neutropenia (FN). High fever persisted even after myelosuppression had recovered. Computed tomography (CT) revealed distribution of small nodules in the bilateral lungs, for which miliary TB was included in the differential diagnosis. T-Spot, interferon-gamma-release assay, and bronchoscopy yielded no significant findings; however, sputum and urine culture confirmed the diagnosis of TB.Diagnosis: CT, sputum and urine culture confirmed the diagnosis of miliary TB.Interventions: The patient was treated with anti-bacterial therapy (cefepime) on hospital admission, which was not effective. After the diagnosis of miliary TB was confirmed, anti-TB drugs, including isoniazid, rifampicin, pyrazinamide and ethambutol, were administered.Outcomes: Despite anti-TB therapy, high fever persisted and radiological findings worsened. Fifty days after the third course of CBZ, the patient died of respiratory dysfunction caused by progression of miliary TB.Lessons: Management of LTBI is needed in cases of radiographic findings of LTBI and medical history of TB before CBZ treatment, despite the rarity of LTBI reactivation in patients with PC.
  • 近畿大学におけるロボット支援腹腔鏡下前立腺全摘除術(RALP)の成績
    南 高文; 菊池 尭; 安富 正悟; 大關 孝之; 清水 信貴; 森 康範; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 植村 天受
    日本泌尿器内視鏡学会総会 (一社)日本泌尿器内視鏡・ロボティクス学会 33回 P - 6 2019/11
  • 当施設におけるロボット支援腹腔鏡下腎部分切除術(RAPN)の初期成績
    菊池 尭; 安富 正悟; 大関 孝之; 清水 信貴; 森 康範; 南 高文; 野澤 晶弘; 能勢 和宏; 吉村 一宏; 植村 天受
    日本泌尿器内視鏡学会総会 (一社)日本泌尿器内視鏡・ロボティクス学会 33回 P - 7 2019/11
  • Neeraj Agarwal; Kelly McQuarrie; Anders Bjartell; Simon Chowdhury; Andrea J. Pereira de Santana Gomes; Byung Ha Chung; Mustafa Ozguroglu; Alvaro Juarez Soto; Axel S. Merseburger; Hirotsugu Uemura; Dingwei Ye; Robert Given; David Cella; Ethan Basch; Branko Miladinovic; Lindsay Dearden; Kris Deprince; Vahid Naini; Angela Lopez-Gitlitz; Kim N. Chi
    LANCET ONCOLOGY ELSEVIER SCIENCE INC 20 (11) 1518 - 1530 1470-2045 2019/11 [Refereed]
     
    Background In the phase 3 TITAN study, the addition of apalutamide to androgen deprivation therapy (ADT) significantly improved the primary endpoints of overall survival and radiographic progression-free survival in patients with metastatic castration-sensitive prostate cancer. We aimed to assess health-related quality of life (HRQOL) in TITAN, including pain and fatigue.Methods In this randomised, placebo-controlled, double-blind, phase 3 study, patients with metastatic castration-sensitive prostate cancer (defined as not receiving ADT at the time of metastatic disease progression) aged 18 years and older, receiving continuous ADT (selected at the investigator's discretion), and with an Eastern Cooperative Oncology Group performance status score of 0 or 1 were randomly assigned (1:1), using an interactive web response system, to receive oral apalutamide (four 60 mg tablets, once daily) or matching placebo. Previous localised disease treatment or previous docetaxel for metastatic castration-sensitive prostate cancer were allowed. Randomisation was stratified by Gleason score at diagnosis, region, and previous docetaxel treatment. Randomisation was done using randomly permuted blocks (block size of four). Investigators, research staff, sponsor study team, and patients were masked to the identities of test and control treatments. Patient-reported outcomes were prespecified exploratory endpoints and were the Brief Pain Inventory-Short Form (BPI-SF), Brief Fatigue Inventory (BFI), Functional Assessment of Cancer Therapy-Prostate (FACT-P), and EuroQoL 5D questionnaire 5 level (EQ-5D-5L). BPI and BFI were completed for 7 consecutive days (days-6 to 1 inclusive of each cycle visit), then at months 4, 8, and 12 in follow-up. FACT-P and EQ-5D-5L were completed during cycles 1-7, then every other cycle until the end of treatment, and at months 4, 8, and 12 in follow-up. Analyses were based on the intention-to-treat population. Missing patient-reported outcome assessments were calculated as the expected number of assessments for a visit minus the actual number of assessments received for that visit. For time-to-event endpoints, when median values could not be calculated because less than 50% of patients had degradation, 25th percentiles were compared. This study is registered with ClinicalTrials.gov, number NCT02489318, and is ongoing.Findings Between Dec 9, 2015, and July 25, 2017, 1052 eligible patients were enrolled randomly assigned to apalutamide (n=525) or placebo (n=527). Data cutoff for this analysis of patient-reported outcomes was Nov 23, 2018. Median followup for time to pain-related endpoints ranged from 19.4 to 22.1 months. Patients were mostly asymptomatic at baseline: on the BPI-SF pain severity scale of 0-10, median pain scores (indicating worst pain in the past 24 h) were 1.14 (IQR 0-3.17) in the apalutamide group and 1.00 (0-2.86) in the placebo group, and median worst fatigue scores on the BFI were 1.29 (IQR 0-3.29) in the apalutamide group and 1.43 (0.14-3.14) in the placebo group. Patient experience of pain and fatigue (intensity and interference) did not differ between the groups for the duration of treatment. Median time to worst pain intensity progression was 19.09 months (95% CI 11.04-not reached) in the apalutamide group versus 11.99 months (8.28-18.46) in the placebo group (HR 0.89 [95% CI 0.75-1.06]; p=0.20). Median time to pain interference progression was not reached in either group (95% CI 28.58-not reached in the apalutamide group; not reached-not reached in the placebo group). 25th percentiles for time to pain interference progression were 9.17 months (5.55-11.96) in the apalutamide group and 6.24 months (4.63-7.43) in the placebo group (HR 0.90 [95% CI 0.73-1.10]; p=0.29). FACT-P total scores and EQ-5D-5L data showed preservation of HRQOL in both groups. The median time to deterioration as determined by FACT-P total score was 8.87 months (95% CI 4.70-11.10) in the apalutamide group and 9.23 months (7.39-12.91) in the placebo group (HR 1.02 [95% CI 0.85-1.22]; p=0.85).Interpretation Apalutamide with ADT is a well-tolerated and effective option for men with metastatic castration-sensitive prostate cancer. The combination significantly improves survival outcomes compared with ADT alone while maintaining HRQOL despite additive androgen blockade.
  • 1st line進行腎細胞癌患者におけるavelumab+axitinibの第3相試験 日本人subgroup解析
    植村 元秀; 冨田 善彦; 三宅 秀明; 畠山 真吾; 金山 博臣; 沼倉 一幸; 高木 敏男; 加藤 智幸; 江藤 正俊; 小原 航; 植村 天受; Motzer Robert J.; 藤井 陽介; 亀井 陽一; 大家 基嗣
    日本癌治療学会学術集会抄録集 (一社)日本癌治療学会 57回 O13 - 1 2019/10
  • 抗癌剤治療による筋肉量減少が腎盂または尿管癌の予後に与える影響
    橋本 士; 藤本 西蔵; 浜口 守; 高橋 智輝; 菊池 尭; 安富 正悟; 大關 孝之; 清水 信貴; 森 康範; 南 高文; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 植村 天受
    日本癌治療学会学術集会抄録集 (一社)日本癌治療学会 57回 P42 - 7 2019/10 [Refereed]
  • 転移性尿路上皮癌に対するペムブロリズマブの使用経験
    山本 豊; 西本 光寿; 野澤 昌弘; 明石 泰典; 喜馬 啓介; 橋本 士; 菊池 尭; 大関 孝之; 清水 信貴; 森 康範; 南 高文; 能勢 和宏; 吉村 一宏; 平山 暁秀; 植村 天受
    日本癌治療学会学術集会抄録集 (一社)日本癌治療学会 57回 P97 - 3 2019/10 [Refereed]
  • 高リスク前立腺癌に対する永久挿入密封小線源療法とロボット支援前立腺全摘術の比較
    南 高文; 藤本 西蔵; 浜口 守; 高橋 智輝; 橋本 士; 菊池 堯; 安富 正悟; 大關 孝之; 清水 信貴; 森 康範; 能勢 和宏; 野澤 昌弘; 吉村 一宏; 植村 天受
    日本癌治療学会学術集会抄録集 (一社)日本癌治療学会 57回 P108 - 6 2019/10 [Refereed]
  • 腫瘍免疫環境プロファイルと抗腫瘍免疫反応(Profiling the tumor immune milieu to assess and predict immune responses)
    デベラスコ・マルコ; 倉 由吏恵; 森 康範; 清水 信貴; 大關 孝之; 坂井 和子; 野澤 昌弘; 吉村 一宏; 吉川 和宏; 西尾 和人; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 78回 E - 2067 0546-0476 2019/09
  • アパルタミドによる前立腺腫瘍内の免疫環境の変化(Apalutamide reworks the tumor immune microenvironment of prostate tumors)
    清水 信貴; デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 吉川 和宏; 西尾 和人; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 78回 P - 2267 0546-0476 2019/09
  • TAS-115マルチキナーゼ阻害薬のマウス前立腺癌モデルにおける免疫調整について(Immunomodulation of the multi-tyrosine kinase inhibitor TAS-115 in a mouse Pten-deficient prostate cancer)
    倉 由吏恵; デベラスコ・マルコ; 坂井 和子; 吉川 和宏; 西尾 和人; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 78回 P - 2360 0546-0476 2019/09
  • イソフラボン摂取はマウス前立腺癌転移モデルにおいて癌の進行を抑制し生存期間を延長させる(Chemopreventive effects of dietary isoflavone in conditional Pten/Trp53-deficient mouse model of prostate cancer)
    森 康範; デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 吉川 和宏; 西尾 和人; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 78回 J - 3030 0546-0476 2019/09
  • リアルタイムPCRを用いた腫瘍免疫プロファイルと免疫反応性の評価について(A real-time PCR-based approach to quantitatively assess tumor immune profiles and immune responses)
    野澤 昌弘; デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 吉川 和宏; 西尾 和人; 植村 天受
    日本癌学会総会記事 (一社)日本癌学会 78回 J - 3035 0546-0476 2019/09
  • 結節性硬化症における抗てんかん薬使用とキャリーオーバー問題
    西郷 和真; 露口 尚弘; 伊庭 慶典; 吉村 一宏; 大磯 直毅; 池川 敦子; 平野 牧人; 木戸 滋子; 三井 良之; 植村 天受; 楠 進
    てんかん研究 (一社)日本てんかん学会 37 (2) 605 - 605 0912-0890 2019/09
  • Marco A. De Velasco; Yurie Kura; Kazuko Sakai; Yuji Hatanaka; Barry R. Davies; Hayley Campbell; Stephanie Klein; Youngsoo Kim; A. Robert MacLeod; Koichi Sugimoto; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    JCI INSIGHT AMER SOC CLINICAL INVESTIGATION INC 4 (17) 2019/09 [Refereed]
     
    Sustained therapeutic responses from traditional and next-generation antiandrogen therapies remain elusive in clinical practice due to inherent and/or acquired resistance resulting in persistent androgen receptor (AR) activity. Antisense oligonucleotides (ASO) have the ability to block target gene expression and associated protein products and provide an alternate treatment strategy for castration-resistant prostate cancer (CRPC). We demonstrate the efficacy and therapeutic potential of this approach with a Generation-2.5 ASO targeting the mouse AR in genetically engineered models of prostate cancer. Furthermore, reciprocal feedback between AR and P13K/AKT signaling was circumvented using a combination approach of AR-ASO therapy with the potent pan-AKT inhibitor, AZD5363. This treatment strategy effectively improved treatment responses and prolonged survival in a clinically relevant mouse model of advanced CRPC. Thus, our data provide preclinical evidence to support a combination strategy of next-generation ASOs targeting AR in combination with AKT inhibition as a potentially beneficial treatment approach for CRPC.
  • Yanfang Liu; Hirotsugu Uemura; Dingwei Ye; Ji Y. Lee; Edmund Chiong; Yeong-S Pu; Azad H. A. Razack; Choosak Pripatnanont; Sudhir Rawal; Grace K. M. Low; Hong Qiu; Weng H. Chow; Maximiliano Van Kooten Losio
    PROSTATE INTERNATIONAL ELSEVIER INC 7 (3) 108 - 113 2287-8882 2019/09 [Refereed]
     
    Background: The incidence of prostate cancer (PC) in Asian countries is increasing for reasons that are not clear. Data describing how PC is diagnosed and treated are fragmented across Asia, with marked intercountry and intracountry differences in outcome and knowledge gaps in clinical diagnostic and treatment practices. To address these knowledge gaps, we have established a PC disease registry with the aim of providing a comprehensive picture of PC diagnosis, prognosis, treatment and outcome, population characteristics, and comorbidities in real-world clinical practice in Asia.Methods: This is a multinational, multicenter, longitudinal, and observational registry of PC patients presenting to participating tertiary-care hospitals in eight Asian countries (www.clinicaltrials.govNCT02546908. Registry Identifier: NOPRODPCR4001). Approximately 3500-4000 eligible patients with existing or newly diagnosed high-risk localized PC (cohort 1), nonmetastatic biochemically recurrent PC (cohort 2), or metastatic PC (cohort 3) will be consecutively enrolled and followed-up for 5 years. An enrollment cap of 600 patients each will be applied to cohorts 1 and 2. Disease status is collected at enrollment, and outcome variables captured at 3-monthly intervals include diagnostic/staging, treatments including reason for change, laboratory results, comorbidities, and concomitant medications. Treatments and survival outcomes will be captured real time until study end. Patient-reported quality-of-life will be measured every 6 months, and medical resource utilization summarized at study end. Data analysis will include exploratory analyses of potential associations between multiple risk factors and socioeconomic variables with disease progression and evaluation of various treatments for PC including novel therapies on clinical outcome and health-related quality-of-life outcomes.Results: 3636 men with PC were enrolled until July 2018; 416 in cohort 1, 399 in cohort 2 and 2821 in cohort 3.Discussion: A total of 3636 patients were enrolled until July 2018. The prospective disease registry will provide comprehensive and wide-ranging real-world information on how PC is diagnosed and treated in Asia. Such information can be used to inform policy development for best practice and direct clinical study design evaluating new treatments. (C) 2019 Asian Pacific Prostate Society, Published by Elsevier Korea LLC.
  • Chikara Ohyama; Takahiro Kojima; Tsunenori Kondo; Yoshio Naya; Takamitsu Inoue; Yoshihiko Tomita; Masatoshi Eto; Shinichi Hisasue; Hirotsugu Uemura; Wataru Obara; Eiji Kikuchi; Padmanee Sharma; Matthew D. Galsky; Arlene Siefker-Radtke; Gary Grossfeld; Sandra Collette; Kyna Gooden; Go Kimura
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY SPRINGER JAPAN KK 24 (9) 1089 - 1098 1341-9625 2019/09 [Refereed]
     
    Background Nivolumab has demonstrated antitumor activity and manageable safety in the single-arm, phase II CheckMate 275 study in patients with unresectable locally advanced or metastatic platinum-resistant urothelial carcinoma. We report updated results of the global population and a subanalysis of Japanese patients from this study. Methods Patients received nivolumab 3 mg/kg intravenously every 2 weeks until progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) confirmed by blinded independent review committee (BIRC) per Response Evaluation Criteria in Solid Tumors v1.1. Secondary endpoints included progression-free survival (PFS) by BIRC and overall survival (OS). Safety was also reported. The minimum follow-up was 21 months. Results Overall, 270 patients were treated with nivolumab globally; 23 patients were Japanese. In the global and Japanese populations, respectively, ORR per BIRC was 20.4% and 21.7%; median PFS was 1.9 (95% confidence interval [CI] 1.9-2.3) and 3.8 months (95% CI 1.9-7.2); and median OS was 8.6 (95% CI 6.1-11.3) and 21.0 months (95% CI 7.2-not reached). The most common any grade treatment-related adverse events were fatigue (18.1%) and diarrhea (12.2%) in the global population; the most common in the Japanese population were diarrhea (26.1%) and pyrexia (13.0%). Grade 3 or 4 treatment-related adverse events occurred in 61 (22.6%) and seven (30.4%) of the global and Japanese patients, respectively. Conclusions Nivolumab continues to show antitumor activity and survival in the global population of CheckMate 275. Meaningful clinical benefit was also observed in Japanese patients. No new safety signals were identified.
  • Koichi Sugimoto; Takahiro Akiyama; Naoki Matsumura; Takafumi Minami; Shigeya Uejima; Hirotsugu Uemura
    INTERNATIONAL JOURNAL OF UROLOGY WILEY 26 (8) 848 - 849 0919-8172 2019/08 [Refereed]
  • Marco A. De Velasco; Yurie Kura; Naomi Ando; Noriko Sato; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuko Sakai; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 79 (13) 0008-5472 2019/07 [Refereed]
  • Marco A. De Velasco; Yurie Kura; Noriko Sato; Naomi Ando; Kazuko Sakai; Yasunori Mori; Barry R. Davies; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 79 (13) 0008-5472 2019/07 [Refereed]
  • Marco A. De Velasco; Yurie Kura; Noriko Sato; Naomi Ando; Kazuko Sakai; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 79 (13) 0008-5472 2019/07 [Refereed]
  • Yasunori Mon; Marco A. De Velasco; Yurie Kura; Eh Benno; Naomi Ando; Noriko Sato; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuko Sakai; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 79 (13) 0008-5472 2019/07 [Refereed]
  • Kim N. Chi; Neeraj Agarwal; Anders Bjartell; Byung Ha Chung; Andrea J. Pereira de Santana Gomes; Robert Given; Alvaro Juarez Soto; Axel S. Merseburger; Mustafa Ozguroglu; Hirotsugu Uemura; Dingwei Ye; Kris Deprince; Vahid Naini; Jinhui Li; Shinta Cheng; Margaret K. Yu; Ke Zhang; Julie S. Larsen; Sharon McCarthy; Simon Chowdhury
    NEW ENGLAND JOURNAL OF MEDICINE MASSACHUSETTS MEDICAL SOC 381 (1) 13 - 24 0028-4793 2019/07 [Refereed]
     
    Background Apalutamide is an inhibitor of the ligand-binding domain of the androgen receptor. Whether the addition of apalutamide to androgen-deprivation therapy (ADT) would prolong radiographic progression-free survival and overall survival as compared with placebo plus ADT among patients with metastatic, castration-sensitive prostate cancer has not been determined. Methods In this double-blind, phase 3 trial, we randomly assigned patients with metastatic, castration-sensitive prostate cancer to receive apalutamide (240 mg per day) or placebo, added to ADT. Previous treatment for localized disease and previous docetaxel therapy were allowed. The primary end points were radiographic progression-free survival and overall survival. Results A total of 525 patients were assigned to receive apalutamide plus ADT and 527 to receive placebo plus ADT. The median age was 68 years. A total of 16.4% of the patients had undergone prostatectomy or received radiotherapy for localized disease, and 10.7% had received previous docetaxel therapy; 62.7% had high-volume disease, and 37.3% had low-volume disease. At the first interim analysis, with a median of 22.7 months of follow-up, the percentage of patients with radiographic progression-free survival at 24 months was 68.2% in the apalutamide group and 47.5% in the placebo group (hazard ratio for radiographic progression or death, 0.48; 95% confidence interval [CI], 0.39 to 0.60; P<0.001). Overall survival at 24 months was also greater with apalutamide than with placebo (82.4% in the apalutamide group vs. 73.5% in the placebo group; hazard ratio for death, 0.67; 95% CI, 0.51 to 0.89; P=0.005). The frequency of grade 3 or 4 adverse events was 42.2% in the apalutamide group and 40.8% in the placebo group; rash was more common in the apalutamide group. Conclusions In this trial involving patients with metastatic, castration-sensitive prostate cancer, overall survival and radiographic progression-free survival were significantly longer with the addition of apalutamide to ADT than with placebo plus ADT, and the side-effect profile did not differ substantially between the two groups. (Funded by Janssen Research and Development; TITAN ClinicalTrials.gov number, .)A randomized trial tested whether the addition of apalutamide, an androgen receptor blocker, to androgen-deprivation therapy might improve radiographic (including MRI-detected) progression-free survival and overall survival. Apalutamide was significantly more effective than placebo for both end points.
  • Yoshihiko Tomita; Satoshi Fukasawa; Nobuo Shinohara; Hiroshi Kitamura; Mototsugu Oya; Masatoshi Eto; Kazunari Tanabe; Mitsuru Saito; Go Kimura; Junji Yonese; Masahiro Yao; Hirotsugu Uemura
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY OXFORD UNIV PRESS 49 (6) 506 - 514 0368-2811 2019/06 [Refereed]
     
    Efficacy and safety results of CheckMate 025 were consistent between the global and the Japanese populations, with a notably higher OS and ORR in Japanese patients treated with nivolumab.AbstractBackground Nivolumab treatment resulted in superior efficacy and safety versus everolimus treatment in the 2-year follow-up of the CheckMate 025 Phase III study, with consistent results in the global population and the Japanese population. Here, we report the 3-year follow-up in both groups.Methods Patients were randomized 1:1 to nivolumab 3 mg/kg intravenously every 2 weeks or everolimus 10 mg orally once daily until progression/intolerable toxicity. The primary endpoint was overall survival (OS). Key secondary endpoints included objective response rate, progression-free survival, safety and patient-reported quality of life.Results Of 410 and 411 patients randomized to nivolumab and everolimus, 37 and 26 were Japanese, respectively. The median OS for the global population was 25.8 months with nivolumab and 19.7 months with everolimus (hazard ratio 0.74; 95.5% confidence interval [CI]: 0.63-0.88; P = 0.0005); in the Japanese population, median OS was 45.9 months and not reached (hazard ratio 1.08; 95% CI: 0.50-2.34; P = 0.85), respectively. The investigator-assessed objective response rate was 26% versus 5% with nivolumab versus everolimus (odds ratio [OR] 6.19; 95% CI: 3.82-10.06) in the global population and 43% versus 8% in the Japanese population (OR 6.80; 95% CI: 1.60-28.91; P = 0.0035), respectively. The incidence of any-grade treatment-related adverse events was lower with nivolumab versus everolimus in both the global patient population (80% versus 89%) and the Japanese population (81% versus 100%).Conclusions At the 3-year follow-up, the efficacy and safety results of CheckMate 025 are generally consistent in the global and the Japanese populations.
  • 森 康範; 菊池 尭; 齋藤 允孝; 林 泰司; 能勢 和宏; 今西 正昭; 吉村 一宏; 西岡 伯; 秋山 隆弘; 植村 天受
    日本老年泌尿器科学会誌 日本老年泌尿器科学会 32 (1) 188 - 188 2187-3682 2019/05
  • 橋本 士; 杉本 公一; 清水 信貴; 南 高文; 野澤 昌弘; 能勢 和宏; 田原 秀男; 吉村 一宏; 平山 暁秀; 植村 天受
    日本老年泌尿器科学会誌 日本老年泌尿器科学会 32 (1) 158 - 158 2187-3682 2019/05
  • Kim N. Chi; Neeraj Agarwal; Anders Bjartell; Byung Ha Chung; Andrea Juliana Pereira de Santana Gomes; Robert W. Given; Alvaro Juarez Soto; Axel Stuart Merseburger; Mustafa Ozguroglu; Hirotsugu Uemura; Dingwei Ye; Kris Deprince; Vahid Naini; Jinhui Li; Shinta Cheng; Margaret K. Yu; Ke Zhang; Julie S. Larsen; Sharon Anne McCarthy; Simon Chowdhury
    JOURNAL OF CLINICAL ONCOLOGY AMER SOC CLINICAL ONCOLOGY 37 (15) 0732-183X 2019/05 [Refereed]
  • Masanori Noguchi; Kiyohide Fujimoto; Gaku Arai; Hiroji Uemura; Katsuyoshi Hashine; Hiroaki Matsumoto; Satoshi Fukasawa; Hideomi Nakatsu; Atsushi Takenaka; Masato Fujisawa; Hirotsugu Uemura; Seiji Naito; Shin Egawa; Hiroyuki Fujimoto; Shiro Hinotsu; Kyogo Itoh; Yasuo Kohjimoto
    JOURNAL OF CLINICAL ONCOLOGY AMER SOC CLINICAL ONCOLOGY 37 (15) 0732-183X 2019/05 [Refereed]
  • 清水 信貴; 永井 康晴; 浜口 守; 高橋 智輝; 橋本 士; 大關 孝之; 南 高文; 野澤 昌弘; 吉村 一宏; 植村 天受
    日本老年泌尿器科学会誌 日本老年泌尿器科学会 32 (1) 159 - 159 2187-3682 2019/05 [Refereed]
  • 浜口 守; 植村 天受; 吉村 一宏; 能勢 和宏; 野澤 昌弘; 南 高文; 森 康範; 清水 信貴; 大關 孝之
    日本老年泌尿器科学会誌 日本老年泌尿器科学会 32 (1) 197 - 197 2187-3682 2019/05 [Refereed]
  • Hirotsugu Uemura; Hiroji Uemura; Satsohi Nagamori; Yoshiaki Wakumoto; Go Kimura; Hiroaki Kikukawa; Akira Yokomizo; Atsushi Mizokami; Takeo Kosaka; Naoya Masumori; Yoshihide Kawasaki; Junji Yonese; Yasutomo Nasu; Satoshi Fukasawa; Takayuki Sugiyama; Seigo Kinuya; Makoto Hosono; Iku Yamaguchi; Takashi Akagawa; Nobuaki Matsubara
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY SPRINGER JAPAN KK 24 (5) 557 - 566 1341-9625 2019/05 [Refereed]
     
    Background Radium-223 is a first-in-class targeted alpha therapy to prolong overall survival (OS) in castration-resistant prostate cancer with bone metastases (mCRPC). The aim of the present analysis was to assess the long-term safety with radium-223 in Japanese patients with mCRPC.Methods Patients with symptomatic mCRPC, >= 2 bone metastases and no known visceral metastases received up to 6 injections of radium-223 (55 kBq/kg), one every 4 weeks. Adverse events (AEs) considered to be related to radium-223 were reported until 3 years after the first injection. Pre-specified conditions, such as acute myelogenous leukemia, myelodysplastic syndrome, aplastic anemia, primary bone cancer, or other primary malignancies, were reported regardless of causality.Results Of the 49 patients enrolled in the study, 44 (89.8%) entered the survival follow-up period and 33 (67.3%) died. Throughout the entire study, there were no reports of second primary malignancy or other pre-specified conditions. Eight patients (16.3%) experienced post-treatment drug-related AEs, which were all hematological (anemia and decreased lymphocyte, platelet, and white blood cell counts). No serious post-treatment drug-related AEs were reported. Updated median OS was 19.3 months (95% CI: 14.2, 28.5).Conclusions In Japanese patients with symptomatic mCRPC and bone metastases, radium-223 had a favorable long-term safety profile with no second primary malignancies reported. Taken together with median OS, which was comparable to that in the pivotal phase III ALSYMPCA study, these results support continued benefit from radium-223 in Japanese patients with mCRPC.
  • Yuji Hatanaka; Marco A. de Velasco; Takashi Oki; Nobutaka Shimizu; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    PROSTATE WILEY 79 (5) 554 - 563 0270-4137 2019/04 [Refereed]
     
    BackgroundHOX genes encode transcription factors that play key roles in modulating normal tissue morphogenesis, differentiation and homeostasis. Disruption of normal HOX gene expression occurs frequently in human cancers and is associated with both tumor promoting and suppressing activities. Among these is, HOXA10, a pleiotropic gene that is critical for normal prostate development. In this study we characterized HOXA10 expression in human and mouse PCa to gain insights into its clinical significance.MethodsA meta-analysis of HOXA10 mRNA expression was carried out across several publicly available data sets. Expression of HOXA10 protein expression was assessed by immunohistochemistry (IHC) using human radical prostatectomy (RP) cases. We correlated HOXA10 expression to clinicopathological features and investigated its relationship to biochemical recurrence (BCR) after RP by the Kaplan-Meier method. HOXA10 mRNA and IHC protein expression was also examined in a mouse model of Pten-null PCa.ResultsA meta-analysis of HOXA10 gene expression indicated dysregulated expression of HOXA10 in human PCa. IHC profiling of HOXA10 revealed inverse correlations between HOXA10 expression and Gleason pattern, Gleason score, and pathological stage (P<0.01). Patients with low expression profiles of HOXA10 were associated with a higher risk of BCR, (OR, 3.54; 95%CI, 1.21-16.14; P=0.049) whereas patients with high HOXA10 expression experienced longer times to BCR (P=0.045). However, HOXA10 was not an independent predictor of BCR (OR, 1.52; 95%CI, 0.42-5.54; P=0.52). Evaluation of expression patterns of HOXA10 in mouse prostate tumors mimicked that of humans.ConclusionsOur findings show that HOXA10 expression is inversely associated with tumor differentiation and high HOXA10 expression is associated with improved BCR-free survival. This study provides human and mouse evidence to suggest tumor suppressive roles for HOXA10 in the context of prostate cancer.
  • Hiroji Uemura; Nobuaki Matsubara; Hirotsugu Uemura; Satoshi Nagamori; Hiroyoshi Suzuki; Go Kimura
    JOURNAL OF CLINICAL ONCOLOGY AMER SOC CLINICAL ONCOLOGY 37 (7) 0732-183X 2019/03 [Refereed]
  • Kenichi Harada; Masahiro Nozawa; Motohide Uemura; Katsunori Tatsugami; Takahiro Osawa; Kazutoshi Yamana; Go Kimura; Masato Fujisawa; Norio Nonomura; Masatoshi Eto; Nobuo Shinohara; Yoshihiko Tomita; Yukihiro Kondo; Kenya Ochi; Yoshio Anazawa; Hirotsugu Uemura
    INTERNATIONAL JOURNAL OF UROLOGY WILEY 26 (2) 202 - 210 0919-8172 2019/02 [Refereed]
     
    Objectives To clarify treatment patterns and outcomes for patients with unresectable or metastatic renal cell carcinoma in the molecular target therapy era in Japan. Methods A multicenter, retrospective medical chart review study was carried out. Patients diagnosed with unresectable or metastatic renal cell carcinoma between January 2012 and August 2015 were enrolled. Data extracted from medical records included treatment duration, grade >= 3 adverse events, reason for discontinuation for each targeted therapy and survival data until August 2016. Results Of 277 eligible patients, 266, 170 and 77 received first-, second- and third-line systemic treatment, respectively. Tyrosine kinase inhibitors were the most common first-line therapy (72.2%), followed by mammalian target of rapamycin inhibitors (14.3%) and cytokines (13.5%). Among 170 patients who received second-line treatment, tyrosine kinase inhibitor-tyrosine kinase inhibitor was the most common sequence (58.8%), followed by tyrosine kinase inhibitor-mammalian target of rapamycin inhibitor (14.1%) and cytokine-tyrosine kinase inhibitor (14.1%). With a median follow-up period of 19.8 months, median overall survival was not reached at 48 months. Patients who discontinued first-line tyrosine kinase inhibitors in Conclusions The present analysis illustrates the contemporary treatment patterns and prognosis for patients with unresectable or metastatic renal cancer in a real-world setting in Japan. Tyrosine kinase inhibitor-tyrosine kinase inhibitor represents the most commonly used sequence. Shorter treatment duration of first-line tyrosine kinase inhibitors is associated with poorer prognosis, suggesting the need for better treatment options.
  • Therapeutic effects of p38 MAP kinase inhibitor in storage and voiding dysfunction in mice with spinal cord injury (SCI).
    Shimizu N; Suzuki T; Takaoka E; Shimizu T; Hirayama A; Uemura H; Kanai AJ; de Groat WC; Yoshimura N
    Eur. Urol. Suppl. 18 e5 - e6 2019 [Refereed]
  • Yoshihiko Tomita; Hirotsugu Uemura; Mototsugu Oya; Nobuo Shinohara; Tomonori Habuchi; Yosuke Fujii; Yoichi Kamei; Yoshiko Umeyama; Angel H. Bair; Brian I. Rini
    BMC CANCER BMC 19 (1) 17 - 17 1471-2407 2019/01 [Refereed]
     
    BackgroundA prospective, randomised phase II study demonstrated clinical benefit of axitinib dose titration in a subset of treatment-naive patients treated with axitinib for metastatic renal cell carcinoma. This analysis evaluated patient baseline characteristics that may impact overall survival (OS) with axitinib dose titration.MethodsFollowing a 4-week lead-in period during which all patients received axitinib 5mg twice-daily (bid); patients meeting the predefined randomisation criteria were randomly assigned to receive axitinib 5mg bid plus either axitinib or placebo titration. In exploratory analyses, patients were grouped into those who achieved OS 24 versus <24months, and compared their baseline characteristics with Fisher's exact test or Cochran-Armitage trend exact test, with a 5% significance level. Potential predictive baseline characteristics associated with effect of axitinib dose titration on OS were investigated using a Cox proportional hazard model.ResultsOverall, 112 patients were randomised. Three of 56 patients receiving axitinib titration were censored; of the remaining 53, 33 (62%) achieved OS 24months versus 20 (38%) with OS <24months. Patients with OS 24 vs. <24months, respectively, had significantly fewer metastatic sites (2 metastases: 52% vs. 10%; 3 metastases: 48% vs. 90%), fewer lymph node (45% vs. 75%) or liver (15% vs. 45%) metastases, higher haemoglobin level (i.e., lower limit of normal: 67% vs. 25%) at baseline, lower neutrophil ( upper limit of normal, 97% vs. 75%) and platelet ( upper limit of normal, 82% vs. 50%) levels at baseline and1year between histopathological diagnosis and treatment (64% vs. 15%). The primary reason for treatment discontinuation in both OS groups was disease progression. The frequency of toxicity-related discontinuation was comparable between the 2 groups, indicating that it was not a factor for a shorter OS. The multivariate analysis showed that 1year from histopathological diagnosis to treatment and baseline haemoglobin level equal or greater than lower limit of normal were significant covariates associated with favourable OS in patients receiving axitinib titration.ConclusionsThe current analyses identified potentially predictive factors that could help selecting patients who may benefit from axitinib dose titration.Trial registrationClinicalTrials.gov identifier, NCT00835978. Registered prospectively, February 4, 2009.
  • Hirotsugu Uemura; Marco A. De Velasco
    CANCER SCIENCE WILEY 109 682 - 682 1349-7006 2018/12 [Refereed]
  • Marco A. De Velasco; Yurie Kura; Yasunori Mori; Nobutaka Shimizu; Takayuki Ozeki; Kazuko Sakai; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER SCIENCE WILEY 109 386 - 386 1349-7006 2018/12 [Refereed]
  • Mamoru Hashimoto; Marco A. De Velasco; Yurie Kura; Kazuko Sakai; Nobutaka Shimizu; Yasunori Mori; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER SCIENCE WILEY 109 534 - 534 1349-7006 2018/12 [Refereed]
  • Yasunori Mori; Marco A. De Velasco; Yurie Kura; Takayuki Ozeki; Nobutaka Shimizu; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuko Sakai; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER SCIENCE WILEY 109 211 - 211 1349-7006 2018/12 [Refereed]
  • Yurie Kura; Marco A. De Velasco; Yasunori Mori; Nobutaka Shimizu; Takayuki Ozeki; Kazuko Sakai; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER SCIENCE WILEY 109 230 - 230 1349-7006 2018/12 [Refereed]
  • Masahiro Nozawa; Marco A. De Velasco; Yurie Kura; Nobutaka Shimizu; Yasunori Mori; Kazuhiro Yoshimura; Kazuko Sakai; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER SCIENCE WILEY 109 231 - 231 1349-7006 2018/12 [Refereed]
  • Nobutaka Shimizu; Marco A. De Velasco; Yurie Kura; Takayuki Ozeki; Yasunori Mori; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuko Sakai; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER SCIENCE WILEY 109 1117 - 1117 1349-7006 2018/12 [Refereed]
  • Akiko Takao; Kazuhiro Yoshikawa; Sivasundaram Karnan; Akinobu Ota; Hirotsugu Uemura; Marco A. De Velasco; Yurie Kura; Susumu Suzuki; Ryuzo Ueda; Tokiko Nishino; Yoshitaka Hosokawa
    ONCOLOGY REPORTS SPANDIDOS PUBL LTD 40 (5) 2455 - 2466 1021-335X 2018/11 [Refereed]
     
    Phosphatase and tensin homolog (PTEN) deficiency is associated with development, progression, and metastasis of various cancers. However, changes in gene expression associated with PTEN deficiency have not been fully characterized. To explore genes with altered expression in PTEN-deficient cells, the present study generated a PTEN-knockout cell line (Delta PTEN) from a mouse prostate cancer-derived cell line using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (CRISPR/Cas9) gene editing system. Following transfection of the CRISPR/Cas9 construct, DNA sequencing was performed to identify deletion of the Pten locus and PTEN inactivation was verified by western blotting. The Delta PTEN cell line exhibited enhanced RAC-alpha serine/threonine-protein kinase phosphorylation and cyclin D1 expression. In addition, an increase in cell proliferation and colony formation was observed in the Delta PTEN cell line. Gene expression profiling experiments were analyzed with microarray and microRNA (miRNA) arrays. In the microarray analysis, 111 genes exhibited >= 10-fold increased expression compared with the parent strain and mock cell line and 23 genes were downregulated. The only miRNA with increased expression of 10-fold or more was mmu-miR-210-3p. Genes with enhanced expression included genes involved in the development, progression, and metastasis of cancer such as Tet methylcytosine dioxygenase 1, twist family BHLH transcription factor 2, C-fos-induced growth factor and Wingless-Type MMTV Integration Site Family, Member 3, and genes involved in immunosuppression such as Arginase 1. The results of the present study suggest that PTEN deficiency mobilizes a variety of genes critical for cancer cell survival and host immune evasion.
  • Nobutaka Shimizu; Takahisa Suzuki; Ei-Ichiro Takaoka; Naoki Wada; Takahiro Shimizu; Akihide Hirayama; Hirotsugu Uemura; Naoki Yoshimura
    INTERNATIONAL JOURNAL OF UROLOGY WILEY 25 400 - 400 0919-8172 2018/10 [Refereed]
  • Mamoru Hashimoto; Nobutaka Shimizu; Koichi Sugimoto; Takafumi Minami; Masahiro Nozawa; Kazuhiro Yoshimura; Hideo Tahara; Hirotsugu Uemura; Akihide Hirayama
    INTERNATIONAL JOURNAL OF UROLOGY WILEY 25 203 - 203 0919-8172 2018/10 [Refereed]
  • Nobutaka Shimizu; Naoki Wada; Takahiro Shimizu; Takahisa Suzuki; Ei-ichiro Takaoka; Anthony J. Kanai; William C. de Groat; Akihide Hirayama; Mamoru Hashimoto; Hirotsugu Uemura; Naoki Yoshimura
    NEUROSCIENCE LETTERS ELSEVIER IRELAND LTD 683 (14) 100 - 103 0304-3940 2018/09 [Refereed]
     
    Nerve growth factor (NGF) is reportedly involved in the changes in C-fiber bladder afferent pathways that induce detrusor overactivity (DO) following spinal cord injury (SCI). This study examined the roles of NGF in TRP channel expression in bladder afferent neurons in mice with SCI using laser-capture microdissection (LCM) methods. Spinal intact (SI) and SCI mice were divided into 3 groups: (1) SI with vehicle treatment; (2) SCI with vehicle treatment; and (3) SCI with anti-NGF antibody. Two weeks after SCI, an osmotic pump was placed subcutaneously into the back of the mice and vehicle or anti-NGF antibody was administered at a rate of 10 mu g/kg per hour for two weeks. Four weeks after SCI, the L6 dorsal root ganglia (DRG) were removed. Expression of the TRPV1, TRPC1, TRPC3, and TRPC6 genes was analyzed using real-time polymerase chain reaction (PCR) following LCM of the bladder afferent neurons, which were labeled by Fast Blue injected into the bladder wall 1 week prior to tissue removal. The mRNA expression of TRPV1 was found to be higher in vehicle-treated SCI mice than in SI mice. The expression level of TRPC3 and TRPC6 in vehicle-treated SCI mice was lower than in SI mice. However, in SCI mice treated with anti-NGF antibody, the mRNA expression of TRPV1 was lower, and the mRNA levels of TRPC3 and TRPC6 were higher than in vehicle-SCI mice. These results suggest that the NGF-dependent changes in specific TRP channel genes, such as TRPV1, TRPC3, and TRPC6, could be involved in SCI-induced afferent hyperexcitability and DO.
  • Keisuke Kiba; Akihide Hirayama; Motokiyo Yoshikawa; Yutaka Yamamoto; Kazumasa Torimoto; Nobutaka Shimizu; Nobumichi Tanaka; Kiyohide Fujimoto; Hirotsugu Uemura
    LUTS-LOWER URINARY TRACT SYMPTOMS WILEY 10 (3) 253 - 258 1757-5664 2018/09 [Refereed]
     
    ObjectiveTo investigate whether or not the leg fluid displacement observed when moving from the standing to recumbent position at bedtime reduces the hours of undisturbed sleep (HUS).MethodsMen aged 50 years or older who were hospitalized for urological diseases were investigated. Body water evaluation was performed three times with a bioelectric impedance method: (i) 17:00, (ii) 30min after (short-term), and (iii) waking up (long-term). A frequency volume chart was used to evaluate the status of nocturnal urine production, and the factors affecting HUS were investigated.ResultsA total of 50 patients (mean age: 68years) were enrolled. Short-term changes in extracellular fluid (ECF in the legs showed a significant positive correlation with urine production per unit of time at the first nocturnal voiding (UFN/HUS) (r=0.45, P=0.01). In the comparison between patients who had <3 HUS vs. those who had 3 HUS, the <3 HUS group showed significantly greater short-term changes in leg fluid volume, night-time water intake (17:00-06:00), and UFN/HUS. Multivariate analysis to assess the risk factors for <3 HUS indicated UFN/HUS as a risk factor in the overall model, and short-term changes in leg ECF and night-time water intake as risk factors in the model that only considered factors before sleep.ConclusionsNocturnal leg fluid displacement may increase urine production leading up to first voiding after going to bed, and consequently, induce early awakening after falling asleep.
  • Eri Banno; Marco A. De Velasco; Yurie Kura; Naomi Ando; Noriko Sato; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuko Sakai; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 78 (13) 0008-5472 2018/07 [Refereed]
  • Marco A. De Velasco; Yurie Kura; Naomi Ando; Kazuko Sakai; Barry R. Davies; Youngsoo Kim; A. Robert MacLeod; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 78 (13) 0008-5472 2018/07 [Refereed]
  • Marco A. De Velasco; Yurie Kura; Naomi Ando; Noriko Sato; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuko Sakai; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 78 (13) 0008-5472 2018/07 [Refereed]
  • Marco A. De Velasco; Masahiro Nozawa; Yurie Kura; Naomi Ando; Noriko Sato; Kazuhiro Yoshimura; Kazuko Sakai; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 78 (13) 0008-5472 2018/07 [Refereed]
  • Marco A. De Velasco; Yurie Kura; Naomi Ando Ando; Noriko Sato; Barry R. Davies; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 78 (13) 0008-5472 2018/07 [Refereed]
  • Kazuhiro Nose; Yoshitaka Saito; Yasunori Mori; Kazuhiro Yoshimura; Hirotsugu Uemura; Takashi Kikuchi; Taiji Hayashi; Tsukasa Nishioka
    Transplantation Reports Elsevier Inc 3 (2) 13 - 15 2451-9596 2018/06 [Refereed]
  • Nobutaka Shimizu; Mark F. Doyal; William F. Goins; Katsumi Kadekawa; Naoki Wada; Anthony J. Kanai; William C. de Groat; Akihide Hirayama; Hirotsugu Uemura; Joseph C. Glorioso; Naoki Yoshimura
    NEUROSCIENCE PERGAMON-ELSEVIER SCIENCE LTD 381 161 - 161 0306-4522 2018/06 [Refereed]
  • Jun Guo; Jie Jin; Mototsugu Oya; Hirotsugu Uemura; Shunji Takahashi; Katsunori Tatsugami; Sun Young Rha; Jae-Lyun Lee; Jinsoo Chung; Ho Yeong Lim; Hsi Chin Wu; Yen Hwa Chang; Arun Azad; Ian D. Davis; Marlene J. Carrasco-Alfonso; Bhupinder Nanua; Jackie Han; Qasim Ahmad; Robert Motzer
    JOURNAL OF HEMATOLOGY & ONCOLOGY BIOMED CENTRAL LTD 11 (1) 69 - 69 1756-8722 2018/05 [Refereed]
     
    Background: The international, phase 3 COMPARZ study demonstrated that pazopanib and sunitinib have comparable efficacy as first-line therapy in patients with advanced renal cell carcinoma, but that safety and quality-of- life profiles favor pazopanib. Our report analyzed pazopanib and sunitinib safety in Asian and non-Asian subpopulations.Methods: Patients were randomized 1: 1 to receive pazopanib 800 mg once daily (continuous dosing) or sunitinib 50 mg once daily in 6-week cycles (4 weeks on, 2 weeks off).Results: Safety population was composed of 363 Asian patients and 703 non-Asian patients. Asian patients had similar duration of exposure to either drug compared with non-Asian patients, although Asian patients had a higher frequency of dose modifications. Overall, hematologic toxicities, cytopenias, increased AST/ALT, and palmarplantar erythrodysesthesia (PPE) were more prevalent in Asian patients, whereas gastrointestinal toxicities were more prevalent in non-Asian patients. Among Asian patients, hematologic adverse events and most nonhematologic AEs were more common in sunitinib-treated versus pazopanib-treated patients. Among Asian patients, the most common grade 3/4 AEs with pazopanib were hypertension (grade 3, 22%) and alanine aminotransferase increased (grade 3, 12%; grade 4, 1%); the most common grade 3/4 AEs with sunitinib were thrombocytopenia/platelet count decreased (grade 3, 36%; grade 4, 10%), neutropenia/neutrophil count decreased (grade 3, 24%; grade 4, 3%) hypertension (grade 3, 20%), and PPE (grade 3, 15%).Conclusions: A distinct pattern and severity of adverse events was observed in Asians when compared with nonAsians with both pazopanib and sunitinib. However, the two drugs were well tolerated in both subpopulations.
  • Nobutaka Shimizu; Takahisa Suzuki; Ei-ichiro Takaoka; Joombeom Kwon; Naoki Wada; Takahiro Shimizu; Akihide Hirayama; Hirotsugu Uemura; Anthony J. Kanai; William C. de Groat; Naoki Yoshimura
    JOURNAL OF UROLOGY ELSEVIER SCIENCE INC 199 (4) E1057 - E1058 0022-5347 2018/04 [Refereed]
  • Nobutaka Shimizu; Ei-ichiro Takaoka; Takahisa Suzuki; Joonbeom Kwon; Mamoru Hashimoto; Hirotsugu Uemura; Akihide Hirayama; Anthony J. Kanai; William C. de Groat; Naoki Yoshimura
    JOURNAL OF UROLOGY ELSEVIER SCIENCE INC 199 (4) E396 - E397 0022-5347 2018/04 [Refereed]
  • Mamoru Hashimoto; Nobutaka Shimizu; Tomoki Takahashi; Koichi Sugimoto; Takafumi Minami; Hirotsugu Uemura; Akihide Hirayama
    JOURNAL OF UROLOGY ELSEVIER SCIENCE INC 199 (4) E1085 - E1086 0022-5347 2018/04 [Refereed]
  • Toni K. Choueiri; James Larkin; Mototsugu Oya; Fiona Thistlethwaite; Marcella Martignoni; Paul Nathan; Thomas Powles; David McDermott; Paul B. Robbins; David D. Chism; Daniel Cho; Michael B. Atkins; Michael S. Gordon; Sumati Gupta; Hirotsugu Uemura; Yoshihiko Tomita; Anna Compagnoni; Camilla Fowst; Alessandra di Pietro; Brian I. Rini
    LANCET ONCOLOGY ELSEVIER SCIENCE INC 19 (4) 451 - 460 1470-2045 2018/04 [Refereed]
     
    Background The combination of an immune checkpoint inhibitor and a VEGF pathway inhibitor to treat patients with advanced renal-cell carcinoma might increase the clinical benefit of these drugs compared with their use alone. Here, we report preliminary results for the combination of avelumab, an IgG1 monoclonal antibody against the programmed cell death protein ligand PD-L1, and axitinib, a VEGF receptor inhibitor approved for second-line treatment of advanced renal-cell carcinoma, in treatment-naive patients with advanced renal-cell carcinoma.Methods The JAVELIN Renal 100 study is an ongoing open-label, multicentre, dose-finding, and dose-expansion, phase 1b study, done in 14 centres in the USA, UK, and Japan. Eligible patients were aged 18 years or older (>= 20 years in Japan) and had histologically or cytologically confirmed advanced renal-cell carcinoma with clear-cell component, life expectancy of at least 3 months, an Eastern Cooperative Oncology Group performance status of 1 or less, received no previous systemic treatment for advanced renal cell carcinoma, and had a resected primary tumour. Patients enrolled into the dose-finding phase received 5 mg axitinib orally twice daily for 7 days, followed by combination therapy with 10 mg/kg avelumab intravenously every 2 weeks and 5 mg axitinib orally twice daily. Based on the pharmacokinetic data from the dose-finding phase, ten additional patients were enrolled into the dose-expansion phase and assigned to this regimen. The other patients in the dose-expansion phase started taking combination therapy directly. The primary endpoint was dose-limiting toxicities in the first 4 weeks (two cycles) of treatment with avelumab plus axitinib. Safety and antitumour activity analyses were done in all patients who received at least one dose of avelumab or axitinib. This trial is registered with ClinicalTrials.gov, number NCT02493751.Findings Between Oct 30, 2015, and Sept 30, 2016, we enrolled six patients into the dose-finding phase and 49 into the dose-expansion phase of the study. One dose-limiting toxicity of grade 3 proteinuria due to axitinib was reported among the six patients treated during the dose-finding phase. At the cutoff date (April 13, 2017), six (100%, 95% CI 54-100) of six patients in the dose-finding phase and 26 (53%, 38-68) of 49 patients in the dose-expansion phase had confirmed objective responses (32 [58%, 44-71] of all 55 patients). 32 (58%) of 55 patients had grade 3 or worse treatment-related adverse events, the most frequent being hypertension in 16 (29%) patients and increased concentrations of alanine aminotransferase, amylase, and lipase, and palmar-plantar erythrodysaesthesia syndrome in four (7%) patients each. Six (11%) of 55 patients died before data cutoff, five (9%) due to disease progression and one (2%) due to treatment-related autoimmune myocarditis. At the end of the dose-finding phase, the maximum tolerated dose established for the combination was avelumab 10 mg/kg every 2 weeks and axitinib 5 mg twice daily.Interpretation The safety profile of the combination avelumab plus axitinib in treatment-naive patients with advanced renal-cell carcinoma seemed to be manageable and consistent with that of each drug alone, and the preliminary data on antitumour activity are encouraging. A phase 3 trial is assessing avelumab and axitinib compared with sunitinib monotherapy.
  • 菊池 尭; 西岡 伯; 森 康範; 能勢 和宏; 吉村 一宏; 植村 天受; 齋藤 允孝; 林 泰司; 今西 正昭; 秋山 隆弘
    大阪透析研究会会誌 大阪透析研究会 36 (1) 84 - 85 0912-6937 2018/03
  • Masanori Noguchi; Gaku Arai; Shin Egawa; Chikara Ohyama; Seiji Naito; Kazumasa Matsumoto; Hirotsugu Uemura; Masayuki Nakagawa; Yasutomo Nasu; Masatoshi Eto; Shigetaka Suekane; Tetsuro Sasada; Shigeki Shichijo; Akira Yamada; Tatsuyuki Kakuma; Kyogo Itoh
    JOURNAL OF CLINICAL ONCOLOGY AMER SOC CLINICAL ONCOLOGY 36 (6) 0732-183X 2018/02 [Refereed]
  • Satoshi Fukasawa; Hiroyoshi Suzuki; Fuminori Sato; Katsuyoshi Hashine; Hisashi Hasumi; Hiroaki Matsumoto; Tomohiro Tsuchiya; Hirotsugu Uemura; Mototsugu Oya; Hiroomi Kanayama; Kazushiro Kawaguchi; Hidehisa Noguchi; Kentaro Enjo; Namphuong Tran; Mary Beth Todd; Karim Fizazi; Nobuaki Matsubara
    JOURNAL OF CLINICAL ONCOLOGY AMER SOC CLINICAL ONCOLOGY 36 (6) 0732-183X 2018/02 [Refereed]
  • Tsutsumi S; Kawahara T; Teranishi JI; Yao M; Uemura H
    Molecular and clinical oncology 8 (2) 320 - 322 2049-9450 2018/02 [Refereed]
  • Nobuaki Matsubara; Satsohi Nagamori; Yoshiaki Wakumoto; Hirotsugu Uemura; Go Kimura; Akira Yokomizo; Hiroaki Kikukawa; Atsushi Mizokami; Takeo Kosaka; Naoya Masumori; Yoshihide Kawasaki; Junji Yonese; Yasutomo Nasu; Satoshi Fukasawa; Takayuki Sugiyama; Seigo Kinuya; Makoto Hosono; Iku Yamaguchi; Hirokazu Tsutsui; Hiroji Uemura
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY SPRINGER JAPAN KK 23 (1) 173 - 180 1341-9625 2018/02 [Refereed]
     
    Radium-223 dichloride (radium-223) is the first targeted alpha therapy approved for the treatment of castration-resistant prostate cancer (CRPC) with bone metastases. This study investigated the efficacy and safety of radium-223 in Japanese patients with symptomatic CRPC and bone metastases.In this open-label, multicenter, phase II study, patients with progressive, symptomatic CRPC and bone metastases were treated with radium-223 (55 kBq/kg, intravenously) in a 4-week cycle for six cycles. The primary endpoint was the percent change in total alkaline phosphatase (ALP) from baseline at 12 weeks. Secondary endpoints included the percent ALP change from baseline to end of treatment (EOT), ALP response rates, percent change in prostate-specific antigen (PSA) from baseline to 12 weeks and EOT, PSA response rates, overall survival (OS), and time to symptomatic skeletal events (SSEs). Adverse events were monitored throughout the study period.Of the 49 Japanese patients (median age 74 years), 28 completed all infusions. Mean percent change in total ALP and PSA from baseline to 12 weeks was -19.3 and +97.4%, respectively. One-year OS and SSE-free rate at the end of active follow-up were 78 and 89%, respectively. The ALP response rate was 31%, while the PSA response rate was 6%. Grade 3/4 treatment-emergent adverse events observed in >= 10% of patients included decreased lymphocyte count (14%), anemia (14%), anorexia (10%), and bone pain (10%).Radium-223 is effective and well tolerated in Japanese patients with CRPC and bone metastases. Results were comparable with the Alpharadin in Symptomatic Prostate Cancer Patients (ALSYMPCA) trial.ClinicalTrials.gov NCT01929655.
  • Marco A. De Velasco; Yurie Kura; Kazuko Sakai; Kouichi Sugimoto; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER SCIENCE WILEY 109 281 - 281 1349-7006 2018/01 [Refereed]
  • Yasunori Mori; Marco A. De Velasco; Yuji Hatanaka; Yurie Kura; Kouichi Sugimoto; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER SCIENCE WILEY 109 1075 - 1075 1349-7006 2018/01 [Refereed]
  • Yurie Kura; Marco A. De Velasco; Kouichi Sugimoto; Kazuko Sakai; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER SCIENCE WILEY 109 568 - 568 1349-7006 2018/01 [Refereed]
  • Nobutaka Shimizu; Marco A. De Velasco; Yurie Kura; Kazuko Sakai; Kouichi Sugimoto; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER SCIENCE WILEY 109 292 - 292 1349-7006 2018/01 [Refereed]
  • Kouichi Sugimoto; Marco A. De Velasco; Yurie Kura; Kazuko Sakai; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER SCIENCE WILEY 109 357 - 357 1349-7006 2018/01 [Refereed]
  • Hirotsugu Uemura; Yurie Kura; Kouichi Sugimoto; Yasunori Mori; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Marco A. De Velasco
    CANCER SCIENCE WILEY 109 897 - 897 1349-7006 2018/01 [Refereed]
  • Takafumi Minami; Koichi Sugimoto; Nobutaka Shimizu; Marco De Velasco; Masahiro Nozawa; Kazuhiro Yoshimura; Nanae Harashima; Mamoru Harada; Hirotsugu Uemura
    CANCER SCIENCE WILEY 109 331 - 331 1349-7006 2018/01 [Refereed]
  • Inhibition of phosphodiesterase type 9 (PDE9) improves storage and voiding dysfunction in mice with spinal cord injury
    Shimizu N; Hashimoto M; Suzuki T; Takaoka E; Kwon J; Shimizu T; Wada N; Hirayama A; Uemura H; Kanai AJ; de Groat WC; Yoshimura N
    Neurourol. Urodyn. 37 S96 - S97 2018 [Refereed]
  • Yutaka Yamamoto; Yasunori Akashi; Takahumi Minami; Masahiro Nozawa; Keisuke Kiba; Motokiyo Yoshikawa; Akihide Hirayama; Hirotsugu Uemura
    Case reports in urology 2018 1414395 - 1414395 2018 [Refereed]
     
    Introduction: The treatment strategy for castration-resistant prostate cancer (CRPC) has changed with the approval of several new agents. In 2011, abiraterone acetate was approved for the treatment of metastatic CRPC; however abiraterone is known to cause mineralocorticoid excess syndrome characterized by hypokalemia, fluid retention, and hypertension. We experienced two cases of grade 4 hypokalemia associated with abiraterone treatment. Case Presentation: Case 1: a 71-year-old male with metastatic CRPC presented with convulsive seizures two weeks after receiving abiraterone plus prednisone. The serum potassium level was 2.1mEq/l. We determined that convulsive seizure was caused by hypokalemia associated with abiraterone. Case 2: a 68-year-old male with metastatic CRPC presented with severe lethargy one month after receiving abiraterone plus prednisone. The serum potassium level was 1.7mEq/l and we concluded that severe lethargy was caused by hypokalemia associated with abiraterone. They were treated with potassium supplementation and increased prednisone following withdrawal of abiraterone. Discussion: The two patients had been on glucocorticoid therapy before abiraterone therapy. Prolonged administration of exogenous glucocorticoid can lead adrenocortical insufficiency and consequently reduce endogenous glucocorticoid production. This situation may increase the risk of abiraterone-induced mineralocorticoid excess. To reduce the risk of abiraterone-induced hypokalemia, evaluation of adrenocortical insufficiency is required.
  • Marco A. De Velasco; Hirotsugu Uemura
    CURRENT OPINION IN UROLOGY LIPPINCOTT WILLIAMS & WILKINS 28 (1) 15 - 24 0963-0643 2018/01 [Refereed]
     
    Purpose of reviewIn this review, we present the progress and current landscape for prostate cancer immunotherapy and overview recent scientific findings that shed novel insights into immunoresistance and discuss potential therapeutic strategies.Recent findingsProstate cancer immunogenicity is hampered by a highly immunosuppressive microenvironment and low mutation burden. Complex interactions between resident immunosuppressive cells such regulatory T cells, macrophages, myeloid-derived suppressor cells, and cancer cells cooperate to suppress antitumor immune responses and promote disease progression. A biphasic approach that boosts tumor immunogenicity and blockade of immunosuppressive pathways will most likely be required in order to produce meaningful therapeutic responses.SummarySignificant advances have shed new light on prostate cancer immunology. These findings should enhance the development of immunotherapeutic strategies, especially when used in combination with other cancer treatments.
  • Mamoru Hashimoto; Naoki Matsumura; Takayuki Ohzeki; Sachiko Hongo; Koichi Sugimoto; Nobutaka Shimizu; Yasunori Mori; Takafumi Minami; Masahiro Nozawa; Kazuhiro Nose; Hideo Tahara; Kazuhiro Yoshimura; Hirotsugu Uemura
    UROLOGIA INTERNATIONALIS KARGER 101 (1) 74 - 79 0042-1138 2018 [Refereed]
     
    Introduction: We investigated whether the change in the neutrophil lymphocyte ratio (NLR) from the first to the last repeat prostate biopsy (Delta NLR) could be the diagnostic tool or not for prostate cancer (PCa) detection. Materials and Methods: We retrospectively evaluated medical records of men who had undergone repeat prostate biopsy. The investigated parameters were white blood cell, neutrophil, lymphocyte counts, NLR at the last prostate biopsy,Delta NLR, prostate-specific antigen (PSA), PSA density (PSAD), and PSA velocity. Exclusion criteria were the presence of cancers other than prostate origin, medication, and diseases which induce the change of NLR. Results: A total of 301 men who had undergone repeat prostate biopsy were selected for this study. After applying exclusion criteria, 223 patients were included. Of these patients, 94 were diagnosed with PCa (Group I) and 129 with no malignancy (Group II). Only a single patient had metastasis. On evaluating the area under the receiver operating characteristic curve of all study parameters,Delta NLR was the most accurate marker, followed by PSAD and then NLR measured at the last biopsy. Conclusions:Delta NLR was the most accurate marker to improve the total predictive value in repeat prostate biopsy for diagnosing PCa. (C) 2018 S. Karger AG, Basel
  • Nobutaka Shimizu; Mark F. Doyal; William F. Goins; Katsumi Kadekawa; Naoki Wada; Anthony J. Kanai; William C. De Groat; Akihide Hirayama; Hirotsugu Uemura; Joseph C. Glorioso; Naoki Yoshimura
    NEUROSCIENCE PERGAMON-ELSEVIER SCIENCE LTD 364 190 - 201 0306-4522 2017/11 [Refereed]
     
    Functional and morphological changes in C-fiber bladder afferent pathways are reportedly involved in neurogenic detrusor overactivity (NDO) after spinal cord injury (SCI). This study examined the morphological changes in different populations of bladder afferent neurons after SCI using replication-defective herpes simplex virus (HSV) vectors encoding the mCherry reporter driven by neuronal cell-type-specific promoters. Spinal intact (SI) and SCI mice were injected into the bladder wall with HSV mCherry vectors driven by the cytomegalovirus (CMV) promoter, CGRP promoter, TRPV1 promoter or neurofilament 200 (NF200) promoter. Two weeks after vector inoculation into the bladder wall, L1 and L6 dorsal root ganglia (DRG) were removed bilaterally for immunofluorescent staining using anti-mCherry antibody. The number of CMV promoter vector-labeled neurons was not altered after SCI. The number of CGRP and TRPV1 promoter vector-labeled neurons was significantly increased whereas the number of NF200 vector-labeled neurons was decreased in L6 DRG after SCI. The median size of CGRP promoter-labeled C-fiber neurons was increased from 247.0 in SI mice to 271.3 mu m(2) in SCI mice whereas the median cell size of TRPV1 promoter vector-labeled neurons was decreased from 245.2 in SI mice to 216.5 mu m(2) in SCI mice. CGRP and TRPV1 mRNA levels of laser-captured bladder afferent neurons labeled with Fast Blue were significantly increased in SCI mice compared to SI mice. Thus, using a novel HSV vector-mediated neuronal labeling technique, we found that SCI induces expansion of the CGRP-and TRPV1-expressing C-fiber cell population, which could contribute to C-fiber afferent hyperexcitability and NDO after SCI. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.
  • Hiroji Uemura; Hirotsugu Uemura; Nobuaki Matsubara; Seigo Kinuya; Makoto Hosono; Yoko Yajima; Toshihiko Doi
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY SPRINGER JAPAN KK 22 (5) 954 - 963 1341-9625 2017/10 [Refereed]
     
    Radiation therapy with radium-223 dichloride improves overall survival, reduces symptomatic skeletal events in Caucasian patients with castration-resistant prostate cancer (CRPC) and bone metastases, and is well tolerated. We report here the results of the first efficacy and safety study of radium-223 dichloride in a Japanese population.In this open-label, uncontrolled, non-randomized, phase I trial, radium-223 dichloride was given to Japanese patients with CRPC and ae2 bone metastases in 4-week cycles. The patients were divided into three cohorts, with cohort 1 and the expansion cohort receiving injections of radium-223 dichloride [55 kBq/kg body weight (BW)] every 4 weeks (Q4W) for up to six injections, and cohort 2 receiving an initial single radium-223 dichloride injection of 110 kBq/kg BW followed by up to five injections of 55 kBq/kg BW Q4W. Safety was determined via adverse event (AE) reporting, and biochemical bone markers were assessed for treatment efficacy.In total 19 patients received at least one dose of radium-223 dichloride and 18 patients experienced at least one treatment-emergent AE (TEAE) of which the most common were anemia, thrombocytopenia, and lymphocytopenia. Serious AEs were reported in three patients but none were drug-related. In the patients of cohort 1 + expansion cohort (55 kBq/kg BW Q4W treatment; n = 16), prostate-specific antigen levels remained stable or slightly increased while the bone alkaline phosphatase (ALP) level significantly decreased. The response rates of bone ALP (ae30 and ae50% reductions) were 81.8 and 36.4% at week 12, and 81.3 and 50.0% at the end of treatment.Radium-223 dichloride was well tolerated in these Japanese patients and, at a dose of 55 kBq/kg BW, efficacy on biomarkers was as expected. The outcomes in Japanese patients were consistent with those reported in other non-Japanese populations.ClinicalTrials.gov record NCT01565746.
  • Mamoru Hashimoto; Nobutaka Shimizu; Koichi Sugimoto; Sachiko Hongoh; Takafumi Minami; Masahiro Nozawa; Kazuhiro Yoshimura; Akihide Hirayama; Hideo Tahara; Hirotsugu Uemura
    LUTS-LOWER URINARY TRACT SYMPTOMS WILEY 9 (3) 157 - 160 1757-5664 2017/09 [Refereed]
     
    ObjectivesTo assess the efficacy of dutasteride add-on therapy for patients with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) with small prostates who have been treated with -blocker therapy for >3 months.MethodsA total of 110 men with clinical BPH were enrolled. There were 17 and 93 subjects with a prostate volume (PV) <30 and 30 mL, respectively. All subjects had been treated with -blocker therapy for >3 months. Subjective and objective clinical variables were assessed using the total International Prostate Symptom Score (IPSS-T), IPSS quality of life (IPSS-QoL), IPSS voiding subscore (IPSS-V), IPSS storage subscore (IPSS-S), overactive bladder symptom score (OABSS), PV, prostate specific antigen (PSA) level, post-void residual (PVR), and maximum flow rate (Qmax). These variables were assessed at baseline and every 3 months for 1 year.ResultsIn the small prostate group, IPSS-T and IPSS-V showed improvements from baseline at 6 and 9 months, storage subscore at 6 months, and OABSS at 3 months, but no sustained improvements were observed. During the study period, only the IPSS QoL scores did not show any improvement. Conversly, dutasteride was significantly effective at improving IPSS-T, IPSS-V, IPSS-S, and IPSS-QoL scores throughout the study period in the large prostate BPH group. PSA levels and PV significantly decreased in both groups throughout the study.ConclusionsBenign prostatic hyperplasia in LUTS patients with small prostates did not show a sustainable benefit from the addition of dutasteride to -blocker therapy.
  • Takahiro Kimura; Shin Egawa; Hirotsugu Uemura
    NATURE REVIEWS UROLOGY NATURE PUBLISHING GROUP 14 (8) 501 - 510 1759-4812 2017/08 [Refereed]
     
    Immunotherapy is an important therapeutic modality for urological cancers and several immunological agents for their treatment, such as sipuleucel-T and immune checkpoint inhibitors, have been approved by the FDA. Personalized peptide vaccines (PPVs) are an immunotherapy that uses multiple cancer peptides that are selected to complement pre-existing host immunity. Vaccination with an appropriate, individualized selection of peptides, chosen from a list of candidates, induces stronger and more rapid antitumour immunity in comparison with inoculation of conventional peptide vaccines. Phase I and phase II trials have shown that PPVs are safe and effective in urological cancers. Randomized trials in patients with castration-resistant prostate cancer showed that PPVs can significantly improve progression-free survival and overall survival. However, further studies are needed to evaluate the utility of PPVs in other urological cancers, to identify those patients who will derive the greatest benefit from this approach and to optimize the protocols for combination therapies involving PPVs.
  • N. Shimizu; T. Suzuki; E. Takaoka; J. Kwon; N. Wada; T. Shimizu; A. Hirayama; H. Uemura; A. Kanai; W. de Groat; N. Yoshimura
    NEUROUROLOGY AND URODYNAMICS WILEY 36 S538 - S540 0733-2467 2017/07 [Refereed]
  • Rich Woessner; Vasu Sah; Patricia McCoon; Shaun Grosskurth; Nanhua Deng; Rachel DuPont; Deborah Lawson; Lourdes Pablo; Corinne Reimer; Marco A. De Velasco; Hirotsugu Uemura; Juliana Candido; Paul Lyne
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 77 0008-5472 2017/07 [Refereed]
  • Yoshihiko Tomita; Satoshi Fukasawa; Nobuo Shinohara; Hiroshi Kitamura; Mototsugu Oya; Masatoshi Eto; Kazunari Tanabe; Go Kimura; Junji Yonese; Masahiro Yao; Robert J. Motzer; Hirotsugu Uemura; M. Brent McHenry; Elmer Berghorn; Seiichiro Ozono
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY OXFORD UNIV PRESS 47 (7) 639 - 646 0368-2811 2017/07 [Refereed]
     
    Nivolumab improved overall survival (OS) and objective response rate (ORR) versus everolimus in previously treated patients with advanced renal cell carcinoma in the phase III CheckMate 025 study (minimum follow-up: 14 months). We report efficacy and safety in the global and Japanese populations (minimum follow-up: 26 months).Patients were randomized 1:1 to receive nivolumab 3 mg/kg intravenously every 2 weeks or everolimus 10-mg tablet orally once daily. Primary endpoint: OS, key secondary endpoints: ORR, progression-free survival and safety.Of 410 (nivolumab) and 411 (everolimus) patients, 37 (9%) and 26 (6%), respectively, were Japanese. Median OS for the global population was 26.0 months (nivolumab) and 19.7 months (everolimus; hazard ratio 0.73 [95% confidence interval [CI]: 0.61-0.88]; P = 0.0006), with medians not reached for Japanese patients. ORR for the global population was 26% (nivolumab) versus 5% (everolimus; odds ratio 6.13; 95% CI: 3.77-9.95); ORR for Japanese patients: 43% versus 8% (odds ratio 9.14; 95% CI: 1.76-88.33). In Japanese patients, any-grade treatment-related adverse events (AEs) occurred in 78% (Grade 3-4, 19%; most common, anemia [5%]) treated with nivolumab and 100% (Grade 3-4, 58%; most common, hypertriglyceridemia [12%]) treated with everolimus; the most common with nivolumab was diarrhea (19%) and with everolimus was stomatitis (77%). Quality of life was stable in the nivolumab arm.With > 2 years of follow-up, Japanese patients had a higher response rate with nivolumab versus everolimus that was more pronounced yet consistent with the global population, with median OS not reached, and a favorable safety profile.
  • Yoshihiko Tomita; Satoshi Fukasawa; Nobuo Shinohara; Hiroshi Kitamura; Mototsugu Oya; Masatoshi Eto; Kazunari Tanabe; Go Kimura; Junji Yonese; Masahiro Yao; Robert J Motzer; Hirotsugu Uemura; M Brent McHenry; Elmer Berghorn; Seiichiro Ozono
    Japanese journal of clinical oncology 47 (7) 639 - 646 0368-2811 2017/07 [Refereed]
     
    Background: Nivolumab improved overall survival (OS) and objective response rate (ORR) versus everolimus in previously treated patients with advanced renal cell carcinoma in the phase III CheckMate 025 study (minimum follow-up: 14 months). We report efficacy and safety in the global and Japanese populations (minimum follow-up: 26 months). Methods: Patients were randomized 1:1 to receive nivolumab 3 mg/kg intravenously every 2 weeks or everolimus 10-mg tablet orally once daily. Primary endpoint: OS, key secondary endpoints: ORR, progression-free survival and safety. Results: Of 410 (nivolumab) and 411 (everolimus) patients, 37 (9%) and 26 (6%), respectively, were Japanese. Median OS for the global population was 26.0 months (nivolumab) and 19.7 months (everolimus; hazard ratio 0.73 [95% confidence interval [CI]: 0.61-0.88]; P = 0.0006), with medians not reached for Japanese patients. ORR for the global population was 26% (nivolumab) versus 5% (everolimus; odds ratio 6.13; 95% CI: 3.77-9.95); ORR for Japanese patients: 43% versus 8% (odds ratio 9.14; 95% CI: 1.76-88.33). In Japanese patients, any-grade treatment-related adverse events (AEs) occurred in 78% (Grade 3-4, 19%; most common, anemia [5%]) treated with nivolumab and 100% (Grade 3-4, 58%; most common, hypertriglyceridemia [12%]) treated with everolimus; the most common with nivolumab was diarrhea (19%) and with everolimus was stomatitis (77%). Quality of life was stable in the nivolumab arm. Conclusions: With >2 years of follow-up, Japanese patients had a higher response rate with nivolumab versus everolimus that was more pronounced yet consistent with the global population, with median OS not reached, and a favorable safety profile.
  • Mototsugu Oya; Yoshihiko Tomita; Satoshi Fukasawa; Nobuo Shinohara; Tomonori Habuchi; Brian I. Rini; Yosuke Fujii; Yoichi Kamei; Yoshiko Umeyama; Angel H. Bair; Hirotsugu Uemura
    CANCER SCIENCE WILEY 108 (6) 1231 - 1239 1349-7006 2017/06 [Refereed]
     
    Subgroup analyses of a randomized global phase II study of axitinib showed objective response rate of 66% and median progression-free survival of 27.6months in treatment-naive Japanese patients with metastatic renal cell carcinoma (RCC). This analysis evaluated overall survival (OS) and safety in 44 Japanese patients and compared the results with 169 non-Japanese patients. In addition, baseline characteristics for predictive factors that may influence OS in first-line metastatic RCC were explored in all patients using a Cox proportional hazard model. With median follow-up of 33months, fewer than half (16 of 44) of the Japanese patients had died and median OS was not reached (95% confidence interval [CI], 38.8months-not estimable), whereas 107 of 169 (63%) non-Japanese patients had died and median OS was 33.9months (95% CI, 28.9-42.7). Estimated 1-year, 2-year and 3-year survival probability (95% CI) was 86.4% (76.2-96.5), 75.0% (62.2-87.8) and 68.2% (54.4-81.9), respectively, in Japanese patients, and was higher than that in non-Japanese patients (75.1% [68.4-81.8], 62.1% [54.5-69.7] and 47.2% [39.3-55.1], respectively). The updated safety analysis did not reveal any new adverse events of concern among Japanese or non-Japanese patients. The multivariate analysis identified that lower baseline Eastern Cooperative Oncology Group performance status, lower baseline tumor burden, and longer time from histopathological diagnosis to treatment were significant positive predictors of OS. The current analysis confirmed the clinical activity of axitinib in treatment-naive Japanese patients with metastatic RCC, with an acceptable toxicity profile.
  • Mototsugu Oya; Yoshihiko Tomita; Satoshi Fukasawa; Nobuo Shinohara; Tomonori Habuchi; Brian I Rini; Yosuke Fujii; Yoichi Kamei; Yoshiko Umeyama; Angel H Bair; Hirotsugu Uemura
    Cancer science 108 (6) 1231 - 1239 1347-9032 2017/06 [Refereed]
     
    Subgroup analyses of a randomized global phase II study of axitinib showed objective response rate of 66% and median progression-free survival of 27.6 months in treatment-naïve Japanese patients with metastatic renal cell carcinoma (RCC). This analysis evaluated overall survival (OS) and safety in 44 Japanese patients and compared the results with 169 non-Japanese patients. In addition, baseline characteristics for predictive factors that may influence OS in first-line metastatic RCC were explored in all patients using a Cox proportional hazard model. With median follow-up of 33 months, fewer than half (16 of 44) of the Japanese patients had died and median OS was not reached (95% confidence interval [CI], 38.8 months-not estimable), whereas 107 of 169 (63%) non-Japanese patients had died and median OS was 33.9 months (95% CI, 28.9-42.7). Estimated 1-year, 2-year and 3-year survival probability (95% CI) was 86.4% (76.2-96.5), 75.0% (62.2-87.8) and 68.2% (54.4-81.9), respectively, in Japanese patients, and was higher than that in non-Japanese patients (75.1% [68.4-81.8], 62.1% [54.5-69.7] and 47.2% [39.3-55.1], respectively). The updated safety analysis did not reveal any new adverse events of concern among Japanese or non-Japanese patients. The multivariate analysis identified that lower baseline Eastern Cooperative Oncology Group performance status, lower baseline tumor burden, and longer time from histopathological diagnosis to treatment were significant positive predictors of OS. The current analysis confirmed the clinical activity of axitinib in treatment-naïve Japanese patients with metastatic RCC, with an acceptable toxicity profile.
  • Nobutaka Shimizu; William F. Goins; Shun Takai; Naoki Wada; Takahiro Shimizu; Takahisa Suzuki; Ei-ichiro Takaoka; Akihide Hirayama; Hirotsugu Uemura; Joseph C. Glorioso; Naoki Yoshimura
    JOURNAL OF UROLOGY ELSEVIER SCIENCE INC 197 (4) E544 - E544 0022-5347 2017/04 [Refereed]
  • Takafumi Minami; Naold Matsumura; Koichi Sugimoto; Nobutaka Shimizu; Marco De Velasco; Masahiro Nozawa; Kazuhiro Yoshimura; Nanae Harashima; Mamoru Harada; Hirotsugu Uemura
    INTERNATIONAL IMMUNOPHARMACOLOGY ELSEVIER SCIENCE BV 44 197 - 202 1567-5769 2017/03 [Refereed]
     
    Hypoxic tumor microenvironment makes cancer cells to be therapy-resistant and hypoxia-inducing factors (HIFs) play a central role in hypoxic adaptation. Especially, renal cell carcinoma (RCC) is often associated with von Hippel-Lindau (VHL) gene mutations, leading to up-regulation of HIFs. However, from a different point of view, this suggests the possibility that HIFs could be promising targets in anti-cancer therapy. In this study, we searched for HIF-l alpha-derived peptides that are able to induce RCC-reactive cytotoxic T lymphocytes (CTLs) from HLA-A24(+) RCC patients. Among five peptides derived from HIF-1 alpha, which were prepared based on the binding motif to the HLA-A24 allele, a HIF-1 alpha(278-287) peptide induced peptide-specific CTLs from peripheral blood mononuclear cells of HLA-A24(+) RCC patients most effectively. In immunoblot assays, the expression of HIF-l alpha was lowly detected in whole and nuclear lysates of RCC cell lines even under normoxia (20% O-2), and their expression in whole lysates was increased under hypoxia (1% O-2). Additionally, HIP-1 alpha(278-287) peptide stimulated T cells showed a higher cytotoxicity against HLA-A24(+) HIF-l alpha-expressing RCC cells than against HLA-A24-HIF-l alpha-expressing RCC cells. The cytotoxicity was inhibited by the addition of HIF-1 alpha(278-287) peptide-pulsed cold target cells. Altogether, these results indicate that the HIF-1 alpha(278-287) peptide could be a candidate for peptide-based anti-cancer vaccines for HLA-A24(+) RCC patients. (C) 2017 Published by Elsevier B.V.
  • Yoshihiko Tomita; Hirotsugu Uemura; Mototsugu Oya; Nobuo Shinohara; Tomonori Habuchi; Yosuke Fujii
    JOURNAL OF CLINICAL ONCOLOGY AMER SOC CLINICAL ONCOLOGY 35 (6) 0732-183X 2017/02 [Refereed]
  • Koichi Sugimoto; Takahiro Akiyama; Nobutaka Shimizu; Naoki Matsumura; Mamoru Hashimoto; Takafumi Minami; Kazuhiro Nose; Masahiro Nozawa; Kazuhiro Yoshimura; Hirotsugu Uemura
    RESEARCH AND REPORTS IN UROLOGY DOVE MEDICAL PRESS LTD 9 141 - 143 2253-2447 2017 [Refereed]
     
    Acute urinary retention is the most common urological emergency. To resolve this emergency, urethral catheterization is performed. If the procedure fails and permanent transurethral catheterization is required, the patient's quality of life is significantly affected. Therefore, catheter-free treatment is the ideal goal of therapy for patients with acute urinary retention. Especially, for women, placement of a catheter poses a cosmetic problem. Therefore, the aim of this study was to treat female patients who had already received urapidil/distigmine bromide with acotiamide. Acotiamide was administered at a dose of 100 mg three times daily for 2 weeks, and the outcome of trial without catheter was evaluated. Only female patients were enrolled for this study. Treatment proved successful and all patients become catheter free.
  • Brian I. Rini; Yoshihiko Tomita; Bohuslav Melichar; Takeshi Ueda; Viktor Gruenwald; Mayer N. Fishman; Hirotsugu Uemura; Mototsugu Oya; Angel H. Bair; Glen I. Andrews; Brad Rosbrook; Eric Jonaschl
    CLINICAL GENITOURINARY CANCER CIG MEDIA GROUP, LP 14 (6) 499 - 503 1558-7673 2016/12 [Refereed]
     
    In a randomized phase II trial in treatment-naive patients with metastatic renal cell carcinoma, axitinib dose titration was associated with significantly higher objective response rate compared with placebo dose titration. In this updated analysis, median overall survival was numerically longer with axitinib versus placebo titration (42.7 vs. 30.4 months). No new safety concerns were observed after long-term axitinib treatment.Background: In a randomized phase II trial in metastatic renal cell carcinoma (mRCC), objective response rate was significantly higher with axitinib versus placebo titration (54% vs. 34%; 1-sided P = .019). Patients and Methods: Treatment-naive patients with mRCC (n = 213) received axitinib 5 mg twice per day (b.i.d.) for 4 weeks. Patients meeting dose titration criteria were randomized to receive axitinib 5 mg b.i.d. with axitinib or placebo titration (n = 56 each); 91 patients ineligible for randomization continued axitinib 5 mg b.i.d.; 10 discontinued before randomization. Results: Median overall survival (95% confidence interval [Cl]) was 42.7 months (24.7-not estimable) with axitinib titration versus 30.4 months (23.7-45.0) with placebo titration (stratified hazard ratio, 0.785; 95% CI, 0.485-1.272; 1-sided P = .162), and 41.6 months (95% CI, 33.0-not estimable) in nonrandomized patients. Safety data were consistent with previous reports. Conclusion: Median overall survival was numerically longer in patients with first-line mRCC who feceived axitinib versus placebo titration. No new safety signal was observed after long-term axitinib treatment in first-line mRCC. (C) 2016 Elsevier Inc. All rights reserved.
  • Yoshihiko Tomita; Satoshi Fukasawa; Mototsugu Oya; Hirotsugu Uemura; Nobuo Shinohara; Tomonori Habuchi; Brian I. Rini; Ying Chen; Angel H. Bair; Seiichiro Ozono; Seiji Naito; Hideyuki Akaza
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY OXFORD UNIV PRESS 46 (11) 1031 - 1041 0368-2811 2016/11 [Refereed]
     
    Axitinib demonstrated clinical activity and safety in treatment-na < ve Japanese patients with metastatic renal cell carcinoma. Multivariate analyses identified potential predictive factors for axitinib efficacy in first-line metastatic renal cell carcinoma.To conduct Japanese subgroup analyses of a randomized, global Phase II study of axitinib with and without dose titration in first-line metastatic renal cell carcinoma and to explore predictive factors for axitinib efficacy in first-line metastatic renal cell carcinoma.The data included 44 Japanese and 169 non-Japanese treatment-na < ve patients with metastatic renal cell carcinoma. Patients received twice-daily axitinib 5 mg during a 4-week lead-in period. Patients who met the pre-defined randomization criteria were stratified by Eastern Cooperative Oncology Group performance status and randomly assigned (1:1) to axitinib or placebo titration. The primary endpoint was objective response rate; secondary endpoints included progression-free survival and safety. Predictive factors were analyzed using data from all patients.The objective response rate (95% confidence interval) was 66% (50-80%) vs. 44% (36-52%) in Japanese and non-Japanese patients, respectively. At the primary analysis, median progression-free survival could not be estimated for Japanese patients, and was 27.6 months (95% confidence interval: 16.6-33.2) in an updated analysis. Hypertension, diarrhea, hand-foot syndrome, dysphonia, hypothyroidism and proteinuria were common adverse events in Japanese patients. Due to a small number of randomized patients, effects of axitinib dose titration could not sufficiently be confirmed among Japanese patients. The multivariate analysis identified time from histopathological diagnosis to treatment and sum of the longest diameter for target lesion at baseline as independent predictive factors for progression-free survival.Axitinib is effective and well tolerated as first-line metastatic renal cell carcinoma therapy in Japanese patients. Predictive factors for axitinib efficacy endpoints identified in this setting warrant further investigation.
  • Hideyuki Akaza; Hirotsugu Uemura; Taiji Tsukamoto; Seiichiro Ozono; Osamu Ogawa; Hideki Sakai; Mototsugu Oya; Mikio Namiki; Satoshi Fukasawa; Akito Yamaguchi; Hiroji Uemura; Yasuo Ohashi; Hideki Maeda; Atsushi Saito; Kentaro Takeda; Seiji Naito
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY SPRINGER JAPAN KK 21 (4) 773 - 782 1341-9625 2016/08 [Refereed]
     
    Trial registration: ClinicalTrials.gov NCT01284920.
  • N. Shimizu; W. Goins; S. Takai; T. Shimizu; N. Wada; A. Hirayama; H. Uemura; P. Tyagi; J. Glorioso; N. Yoshimura
    NEUROUROLOGY AND URODYNAMICS WILEY-BLACKWELL 35 S115 - S116 0733-2467 2016/08 [Refereed]
  • Masahiro Nozawa; Koichi Sugimoto; Takayuki Ohzeki; Takafumi Minami; Nobutaka Shimizu; Shogo Adomi; Yoshitaka Saito; Kazuhiro Nose; Kazuhiro Yoshimura; Hirotsugu Uemura
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY SPRINGER JAPAN KK 21 (4) 748 - 755 1341-9625 2016/08 [Refereed]
     
    No report has evaluated axitinib-induced proteinuria as a biomarker for predicting treatment efficacy and survival of patients with metastatic renal cell carcinoma (mRCC).The subjects were patients with mRCC treated with axitinib at Kinki University Hospital from February 2008 to November 2014. Clinical records were retrospectively reviewed including baseline patient characteristics, time-dependent changes of urinary protein status, computed tomography scans of metastatic lesions, treatment duration with axitinib, and survival time.A total of 45 patients were evaluable. Median tumor shrinkage rates were 32.3 and 35.0 % in patients with urinary protein increases a parts per thousand yen+2 and <+2, respectively (p = 0.496). Objective response rates were also similar between the two groups. Median progression-free survival (PFS) times with axitinib were 13.5 months [95 % confidence interval (CI) 0.0-27.5] and 11.0 months (95 % CI 0.0-26.7) in patients with urinary protein increases a parts per thousand yen+2 and <+2, respectively (p = 0.975). The maximum tumor shrinkage rate with axitinib was significantly associated with PFS with axitinib as a result of multivariate analysis (p = 0.002). Median overall survival (OS) times were 39.8 months (95 % CI 12.7-67.0) and 25.4 months (95 % CI 11.2-39.6) in patients with axitinib-induced urinary protein increases a parts per thousand yen+2 and <+2, respectively (p = 0.250). The number of metastatic sites (p = 0.006), the MSKCC risk (p = 0.009), and the maximum tumor shrinkage rate with axitinib (p = 0.019) were significantly associated with OS as a result of multivariate analysis.The degree of urinary protein increase during axitinib treatment was not associated with objective response, PFS, and OS in mRCC patients treated with axitinib.
  • Taiji Hayashi; Yoshitaka Saitou; Yasunori Mori; Kazuhiro Nose; Masaaki Imanishi; Tsukasa Nishioka; Hirotsugu Uemura; Takahiro Akiyama
    TRANSPLANTATION LIPPINCOTT WILLIAMS & WILKINS 100 (7) S755 - S755 0041-1337 2016/07 [Refereed]
  • Marco A. De Velasco; Yurie Kura; Naomi Ando; Emiko Fukushima; Yuji Hatanaka; Takashi Oki; Kazuhiro Yoshimura; Masahiro Nozawa; Barry R. Davies; Dennis Huszdar; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 76 0008-5472 2016/07 [Refereed]
  • Marco A. De Velasco; Koichi Sugimoto; Yurie Kura; Yuji Hatanaka; Yutaka Yamamoto; Takashi Oki; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 76 0008-5472 2016/07 [Refereed]
  • Marco A. De Velasco; Yurie Kura; Yuji Hatanaka; Takashi Oki; Yutaka Yamamoto; Koichi Sugimoto; Yasunori Mori; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 76 0008-5472 2016/07 [Refereed]
  • Kawano Yoshiaki; Takahashi Wataru; Eto Masatoshi; Kamba Tomomi; Miyake Hideaki; Fujisawa Masato; Kamai Takao; Uemura Hirotsugu; Tsukamoto Taiji; Azuma Haruhito; Matsubara Akio; Nishimura Kazuo; Nakamura Tsuyoshi; Ogawa Osamu; Naito Seiji
    Cancer science Wiley-Blackwell 107 (7) 1013 - 1017 1347-9032 2016/07 
    The RCC-SELECT study showed the correlation between single nucleotide polymorphisms (SNP) in STAT3 gene and survival in metastatic renal cell carcinoma (mRCC) patients with first-line interferon-alpha (IFN-alpha). In that study, even patients with STAT3 SNP linked to shorter overall survival (OS) exhibited remarkably improved prognosis. All 180 patients evaluated in the above study were further analyzed for correlation between OS and demographics/clinicopathological parameters. OS was estimated using the Kaplan-Meier method. Associations between OS and potential prognostic factors were assessed using the log-rank test and the Cox proportional hazards model. The median OS was 42.8 months. Univariate analysis showed that worse Eastern Cooperative Oncology Group-performance status (ECOG-PS), high T stage, regional lymph node metastasis, distant metastasis, higher grade, infiltrative growth pattern, the presence of microscopic vascular invasion (MVI), hypercalcemia, anemia, thrombocytopenia and elevated C-reactive protein were significantly associated with OS. Multivariate analysis revealed that ECOG-PS (hazard ratio [HR] = 3.665, P = 0.0004), hypercalcemia (HR = 6.428, P = 0.0005) and the presence of MVI (HR = 2.668, P = 0.0109) were jointly significant poor prognostic factors. This is the first study analysing prognostic factors of mRCC patients with first-line IFN-alpha using large cohort of the prospective study. The present study suggests that first-line IFN-alpha is still a useful therapy for mRCC even in the era of molecular targeted therapy.
  • Kazuhiro Yoshimura; Takafumi Minami; Masahiro Nozawa; Takahiro Kimura; Shin Egawa; Hiroyuki Fujimoto; Akira Yamada; Kyogo Itoh; Hirotsugu Uemura
    EUROPEAN UROLOGY ELSEVIER 70 (1) 35 - 41 0302-2838 2016/07 [Refereed]
     
    Background: It is well known that the prognosis of castration-resistant prostate cancer (CRPC) is poor, and several immunotherapeutic strategies have been applied to the clinical trials. Research on immunotherapy has been of special interest for the treatment of CRPC for years.Objective: To evaluate the safety of personalized peptide vaccine (PPV) immunotherapy and its clinical outcomes.Design, setting, and participants: A phase 2 randomized controlled trial of PPV immunotherapy with low-dose dexamethasone versus dexamethasone alone for chemotherapy-naive CRPC began in 2008. Eligible patients (prostate-specific antigen [PSA] < 10 ng/ml) were human leukocyte antigen (HLA) A02, A24, or A03 superfamily positive and had asymptomatic or minimally symptomatic CRPC. Patients were allocated (1: 1) to PPV plus dexamethasone (1 mg/d) or to dexamethasone (1 mg/d) alone. A maximum of four HLA-matched peptides (each 3 mg) was selected based on the preexisting immunoglobulin G responses against the 24 warehouse peptides and administered every 2 wk.Outcome measurements and statistical analysis: PSA, progression-free survival (PFS), time to initiation of chemotherapy, and overall survival (OS) were analyzed using the Kaplan-Meier method, a log-rank test, and proportional hazard analysis.Results and limitations: Overall, 37 patients received peptide vaccinations and 35 received dexamethasone alone. The primary end point was PSA PFS, which was significantly longer in the vaccination group than in the dexamethasone group (22.0 vs 7.0 mo; p = 0.0076). Median OS was also significantly longer in the vaccination group (73.9 vs 34.9 mo; p = 0.00084). The relatively small number of patients enrolled is the major limitation of the study.Conclusions: PPV immunotherapy was well tolerated and associated with longer PSA PFS and OS in men with chemotherapy-naive CRPC. A larger phase 3 study is needed to confirm our findings.Patient summary: We compared clinical outcomes of the treatment with personalized peptide vaccine plus dexamethasone versus dexamethasone alone. Our data provide promising evidence of clinical benefit for peptide vaccines. Trial registration: UMIN-CTR: 000000959. (C) 2016 European Association of Urology. Published by Elsevier B.V.
  • Kazuhiro Yoshimura; Hirotsugu Uemura
    Nihon rinsho. Japanese journal of clinical medicine 74 Suppl 3 238 - 43 0047-1852 2016/05 [Refereed]
  • Masahiro Nozawa; Hirotsugu Uemura
    Nihon rinsho. Japanese journal of clinical medicine 74 Suppl 3 644 - 8 0047-1852 2016/05 [Refereed]
  • Takuya Koie; Chikara Ohyama; Hiroyuki Fujimoto; Hiroyuki Nishiyama; Jun Miyazaki; Shiro Hinotsu; Eiji Kikuchi; Mizuaki Sakura; Junichi Inokuchi; Tomohiko Hara; Chikara Ohyama; Hiroyuki Nishiyama; Masato Fujisawa; Hirotsugu Uemura; Hiroyuki Fujimoto; Kazuhiro Suzuki; Masatoshi Eto; Isao Hara; Akio Matsubara; Norio Nonomura; Hiroyuki Nakanishi; Takuya Koie; Hiroomi Kanayama; Tsuneharu Miki; Tomoharu Fukumori; Seiji Naito
    Japanese journal of clinical oncology 46 (5) 468 - 74 2016/05 [Refereed]
     
    OBJECTIVE: We aimed to survey treatment modalities for the patients with Stage II/III urothelial cancer in Japan. METHODS: We used the multi-institutional national database of the Japanese Urological Association from 348 Japanese institutions, in which a total of 3707 patients with muscle-invasive bladder cancer and 1538 with upper urinary tract urothelial carcinoma were registered in 2008 and 2011, respectively. Primary treatment was classified as surgery alone, surgery with chemotherapy, surgery with radiation, radiation alone, chemotherapy alone, combination of radiation and chemotherapy and observation. Overall and cancer-specific survivals were examined using the Kaplan-Meier method, and survival in the subgroups was analyzed using the log-rank test. RESULTS: In Stage II/III bladder cancer patients, 49.7% of those were treated with radical operation and 22.3% received observation only. A total 97.2% of Stage II/III upper urinary tract urothelial carcinoma patients treated with radical surgery. A total 30.4% of Stage II/III bladder cancer patients received chemotherapy. Majority of the patients received cisplatin-based regimen, however, regimens of chemotherapy was rich in variety up to 13 regimens. Chemotherapy regimens for the patients with upper urinary tract urothelial carcinoma were also various up to eight regimens. Overall and cancer-specific survivals were statistically significantly stratified according to the clinical stage. The upper urinary tract urothelial carcinoma patients diagnosed with clinical stage T3 had significantly poor prognosis compared with those diagnosed with clinical stage T2. CONCLUSIONS: This study demonstrated the variety of treatments used for Japanese patients with Stage II/III urothelial cancer. Treatment standardization for these entities may be necessary.
  • Keisuke Kiba; Akihide Hirayama; Motokiyo Yoshikawa; Yutaka Yamamoto; Kazumasa Torimoto; Kiyohide Fujimoto; Hirotsugu Uemura
    Hinyokika kiyo. Acta urologica Japonica 62 (5) 243 - 8 0018-1994 2016/05 [Refereed]
     
    A total of 29 men 60 years and older (mean age 74 years) who complained at least once about nocturnal voiding and were diagnosed with nocturnal polyuria in the frequency volume chart (FVC) were enrolled in this study. Body water was measured by bioelectric impedance analysis just after lying down at 4 pm and after raising legs 30 minutes later. Nocturnal urine production was measured by FVC, and urine production per unit of time at first nocturnal voiding (urine volume at first nocturnal voiding/hours of undisturbed sleep (HUS) : UFN/HUS), urine production per unit of time during sleep (total nocturnal urine volume/hours of sleep : TNV/HS), etc was evaluated. Extra cellular water (ECW) of 0.19 l (4.0%) in legs was reduced caused by body position changing. There was a significant positive correlation between the amount of ECW in legs and UFN/HUS, TNV/HS (r=0. 57, p=0.001 ; r=0. 38, p=0.042, respectively). Moreover, UFN/HUS had a significant correlation with soft lean mass in legs, ECW in legs and daytime water intake. This study suggested that a change in leg fluids caused by a change in position results in increased urine production and decreased HUS.
  • J. Teranishi; Y. Hattori; T. Mochizuki; T. Kawahara; K. Makiyama; H. Uemura
    Transplantation Proceedings Elsevier USA 48 (3) 946 - 948 1873-2623 2016/04 [Refereed]
     
    Background Granulomatous interstitial nephritis (GIN) is a rare renal disease, and its etiology remains unknown. We report recurrent GIN in renal allograft successfully treated with everolimus (EVR). Case Report A 22-year-old man with GIN received a kidney from his mother. On follow-up 8 months later, his serum creatinine level was increased, from 1.3 mg/dL to 1.7 mg/dL, and he had microhematuria and proteinuria. A protocol graft biopsy at 1 year after transplantation showed epithelioid granuloma with multinucleated giant cells. He received steroid pulse therapy for recurrent GIN twice, but he developed allograft dysfunction, hematuria, and proteinuria. EVR was started in combination with maintenance immunosuppressants at 28 months after transplantation. Thereafter, the serum creatinine level decreased, from 2.1 mg/dL to 1.6 mg/dL, and microhematuria and proteinuria were stable despite reduction of steroid dose. Conclusions Maintenance immunosuppressive therapy combined with EVR may be effective for the recurrence of idiopathic GIN in renal allograft.
  • Preclinical studyに有用な遺伝子改変動物モデルの開発
    Kura Yurie; Yoshimura Kazuhiro; Nozawa Masahiro; Minami Takafumi; Sugimoto Kouichi; Yoshikawa Kazuhiro; Nishio Kazuhiro; De Velasco Marco; Uemura Hirotsugu
    日本泌尿器科学会総会 (一社)日本泌尿器科学会総会事務局 104回 AOP - 55 2016/04 [Refereed]
  • Kazuhiro Yoshimura; Hirotsugu Uemura
    INTERNATIONAL JOURNAL OF UROLOGY WILEY-BLACKWELL 23 (3) 194 - 202 0919-8172 2016/03 [Refereed]
     
    The standard treatment for advanced renal cell carcinoma has changed dramatically in the past decade, from cytokine therapy to targeted therapy. Since sorafenib was approved in April 2008, four tyrosine kinase inhibitors and two mammalian target of rapamycin inhibitors have become available in Japan. Most Japanese renal cell carcinoma patients are treated by urologists who are involved in not only kidney surgeries, but also targeted therapy using tyrosine kinase inhibitors, as well as mammalian target of rapamycin inhibitors. Optimal treatment methods are selected from theoretically-based global recommendations, such as the National Comprehensive Cancer Network and European Society for Medical Oncology guidelines; however, real-world clinical practice might be different from that in non-Asian countries. This might be because of different practical conditions; for example, different adverse events and efficacy profiles, different healthcare system, and so on. In the present review, we examine current pharmacotherapy for renal cell carcinoma from evidence-based global data, and compare the reality of Japanese clinical practice to explore the importance of individualized patient therapy.
  • Marco A. De Velasco; Yurie Kura; Kazuhiro Yoshikawa; Kazuto Nishio; Barry R. Davies; Hirotsugu Uemura
    ONCOTARGET IMPACT JOURNALS LLC 7 (13) 15959 - 15976 2016/03 [Refereed]
     
    The PI3K/AKT pathway is frequently altered in advanced human prostate cancer mainly through the loss of functional PTEN, and presents as potential target for personalized therapy. Our aim was to determine the therapeutic potential of the pan-AKT inhibitor, AZD5363, in PTEN-deficient prostate cancer. Here we used a genetically engineered mouse (GEM) model of PTEN-deficient prostate cancer to evaluate the in vivo pharmacodynamic and antitumor activity of AZD5363 in castration-naive and castration-resistant prostate cancer. An additional GEM model, based on the concomitant inactivation of PTEN and Trp53 (P53), was established as an aggressive model of advanced prostate cancer and was used to further evaluate clinically relevant endpoints after treatment with AZD5363. In vivo pharmacodynamic studies demonstrated that AZD5363 effectively inhibited downstream targets of AKT. AZD5363 monotherapy significantly reduced growth of tumors in castration-naive and castration-resistant models of PTEN-deficient prostate cancer. More importantly, AZD5363 significantly delayed tumor growth and improved overall survival and progression-free survival in PTEN/P53 double knockout mice. Our findings demonstrate that AZD5363 is effective against GEM models of PTEN-deficient prostate cancer and provide lines of evidence to support further investigation into the development of treatment strategies targeting AKT for the treatment of PTEN-deficient prostate cancer.
  • Siew-Kee Low; Koya Fukunaga; Atsushi Takahashi; Koichi Matsuda; Fumiya Hongo; Hiroyuki Nakanishi; Hiroshi Kitamura; Takamitsu Inoue; Yoichiro Kato; Yoshihiko Tomita; Satoshi Fukasawa; Tomoaki Tanaka; Kazuo Nishimura; Hirotsugu Uemura; Isao Hara; Masato Fujisawa; Hideyasu Matsuyama; Katsuyoshi Hashine; Katsunori Tatsugami; Hideki Enokida; Michiaki Kubo; Tsuneharu Miki; Taisei Mushiroda
    PLOS ONE PUBLIC LIBRARY SCIENCE 11 (2) e0148177  1932-6203 2016/02 [Refereed]
     
    Sunitinib is a tyrosine kinase inhibitor and used as the first-line treatment for advanced renal cell carcinoma (RCC). Nevertheless, inter-individual variability of drug's toxicity was often observed among patients who received sunitinib treatment. This study is to investigate the association of a functional germline variant on ABCG2 that affects the pharmacokinetics of sunitinib with sunitinib-induced toxicity of RCC patients in the Japanese population. A total of 219 RCC patients were recruited to this pharmacogenetic study. ABCG2 421C> A (Q141K) was genotyped by using PCR-Invader assay. The associations of both clinical and genetic variables were evaluated with logistic regression analysis and subsequently receiver operating characteristic (ROC) curve was plotted. About 43% (92/216) of RCC patients that received sunitinib treatment developed severe grade 3 or grade 4 thrombocytopenia according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 3.0, the most common sunitinib-induced adverse reaction in this study. In the univariate analysis, both age (P = 7.77x10(-3), odds ratio (OR) = 1.04, 95% CI = 1.01-1.07) and ABCG2 421C> A (P = 1.87x10(-2), OR = 1.71, 95% CI = 1.09-2.68) showed association with sunitinib-induced severe thrombocytopenia. Multivariate analysis indicated that the variant ABCG2 421C> A is suggestively associated with severe thrombocytopenia (P = 8.41x10(-3), OR = 1.86, 95% CI = 1.17-2.94) after adjustment of age as a confounding factor. The area under curve (AUC) of the risk prediction model that utilized age and ABCG2 421C>A was 0.648 with sensitivity of 0.859 and specificity of 0.415. Severe thrombocytopenia is the most common adverse reaction of sunitinib treatment in Japanese RCC patients. ABCG2 421C>A could explain part of the inter-individual variability of sunitinib-induced severe thrombocytopenia.
  • Masahiro Nozawa; Koichi Sugimoto; Yasuharu Nagai; Takahide Sugiyama; Yuji Hatanaka; Takashi Oki; Hideo Tahara; Hisao Matsuda; Yutaka Yamamoto; Hirotsugu Uemura
    JOURNAL OF CLINICAL ONCOLOGY AMER SOC CLINICAL ONCOLOGY 34 (2) 0732-183X 2016/01 [Refereed]
  • Kazuhiro Nagao; Hideyasu Matsuyama; Masahiro Nozawa; Isao Hara; Tsukasa Nishioka; Takahiro Komura; Atsunobu Esa; Shigeya Uejima; Masaaki Imanishi; Yasunari Uekado; Takatoshi Ogawa; Hiroshi Kajikawa; Hirotsugu Uemura
    ASIAN JOURNAL OF UROLOGY ELSEVIER SINGAPORE PTE LTD 3 (1) 33 - 38 2214-3882 2016/01 [Refereed]
     
    Objective: To clarify the oncological benefit of zoledronic acid for hormone-naive metastatic prostate cancer, patient outcome of androgen deprivation therapy with zoledronic acid (ADT + Z) and androgen deprivation therapy alone (ADT) was compared.Methods: Fifty-two patients with pathologically confirmed metastatic prostate cancer were prospectively enrolled and treated with combined androgen blockade (goserelin and bicalutamide) with zoledronic acid (4 mg every 4 weeks for 24 months). A propensity score-match with logistic regression analysis was applied to select 50 pair-matched cohorts (both from ADT + Z and from historical control cohorts who had undergone ADT alone), and patient outcomes were compared.Results: Patients with ADT + Z had significantly longer time to progression (TTP) than those with ADT (median TTP; 24.2 vs. 14.0 months, p = 0.0092), while no significant difference of overall survival between two groups (p = 0.1502). Multivariate analysis for biochemical recurrence revealed treatment with ADT was the sole independent prognostic factor (HR: 1.724, 95% CI: 1.06-2.86, p = 0.0297).Conclusion: Combination of zoledronic acid with ADT may prolong time to castration resistant prostate cancer. (C) 2016 Editorial Office of Asian Journal of Urology. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
  • Hidenori Tsuji; Wei Wang; Joshi Sunil; Nobutaka Shimizu; Kazuhiro Yoshimura; Hirotsugu Uemura; Ammon B. Peck; Saeed R. Khan
    WORLD JOURNAL OF UROLOGY SPRINGER 34 (1) 89 - 95 0724-4983 2016/01 [Refereed]
     
    Introduction and objectives Reactive oxygen species (ROS) are produced during the interaction between oxalate/calcium oxalate monohydrate (COM) crystals and renal epithelial cells and are responsible for the various cellular responses through the activation of NADPH oxidase (Nox). Ox and COM also activate the renin-angiotensin-aldosterone system (RAAS). Aldosterone stimulates ROS production through activation of Nox with the involvement of mineralocorticoid receptor (MR), Rac1 and mitogen-activated protein kinases (MAPK). We investigated RAAS pathways in vivo in an animal model of hyperoxaluria and in vitro by exposing renal epithelial cells to COM crystals.Methods Hyperoxaluria was induced in male SD rats by administering ethylene glycol. One group of rats was additionally given spironolactone. Total RNA was extracted and subjected to genomic microarrays to obtain global transcriptome data. Normal rat kidney cell line (NRK-52E) was incubated with aldosterone(10(-7) M) and COM(67 mu g/cm(2)) with or without spironolactone(10(-5) M), a selective inhibitor of SRC family of kinases; protein phosphatase 2(pp2) (10(-5) M) and Nox inhibitor; diphenylene iodonium (DPI) (10(-5) M).Results Relative expression of genes encoding for AGT, angiotensin receptors 1b and 2, Renin 1, Cyp11b, HSD11B2, Nr3c2, NOx4 and Rac1 was upregulated in the kidneys of rats with hyperoxaluria. Treatment with spironolactone reversed the effect of hyperoxaluria. Both aldosterone and COM crystals activated Nox and Rac1 expression in NRK52E, while spironolactone inhibited Nox and Rac1 expression. Increased Rac1 expression was significantly attenuated by treatment with PP2 and spironolactone.Conclusions Results indicate that hyperoxaluria-induced production of ROS, injury and inflammation are in part associated with the activation of Nox through renin-angiotensin-aldosterone pathway.
  • Masanori Noguchi; Kazumasa Matsumoto; Hirotsugu Uemura; Gaku Arai; Masatoshi Eto; Seiji Naito; Chikara Ohyama; Yasutomo Nasu; Masatoshi Tanaka; Fukuko Moriya; Shigetaka Suekane; Satoko Matsueda; Nobukazu Komatsu; Tetsuro Sasada; Akira Yamada; Tatsuyuki Kakuma; Kyogo Itoh
    CLINICAL CANCER RESEARCH AMER ASSOC CANCER RESEARCH 22 (1) 54 - 60 1078-0432 2016/01 [Refereed]
     
    Purpose: The prognosis of platinum-based chemotherapy-resistant metastatic urothelial cancer of the bladder remains poor. Personalized selection of the right peptides for each patient could be a novel approach for a cancer vaccine to boost anticancer immunity.Experimental Design: In this randomized, open-label, phase II study, patients ages >= 18 years with progressive bladder cancer after first-line platinum-based chemotherapy were randomly assigned (1: 1) to receive personalized peptide vaccination (PPV) plus best supportive care (BSC) or BSC. PPV treatment used a maximum of four peptides chosen from 31 candidate peptides according to human leukocyte antigen types and peptide-reactive IgG titers, for 12 s.c. injections (8 injections, weekly; 4 injections, bi-weekly). The primary endpoint was progression-free survival (PFS). Secondary end-points were overall survival (OS), immune response, and toxicity.Results: Eighty patients were randomly assigned to receive either PPV plus BSC (n = 39) or BSC (n = 41). No significant improvement in PFS was noted [HR, 0.7; 95% confidence interval (CI), 0.4-1.2, P = 0.17]. For the secondary endpoints, PPV plus BSC significantly prolonged OS compared with BSC (HR, 0.58; 95% CI, 0.34-0.99, P = 0.049), with median OS of 7.9 months (95% CI, 3.5-12.0) in the PPV plus BSC and 4.1 months (95% CI, 2.8-6.9) in the BSC. PPV treatment was well tolerated, without serious adverse drug reactions.Conclusions: PPV could not prolong PFS, but OS appeared to be improved with low toxicity and immune responses. Further large-scale, randomized trials are needed to confirm these results. (C) 2015 AACR.
  • Yutaka Yamamoto; Keisuke Kiba; Motokiyo Yoshikawa; Akihide Hirayama; Seiji Kunikata; Hirotsugu Uemura
    RESEARCH AND REPORTS IN UROLOGY DOVE MEDICAL PRESS LTD 8 225 - 231 2253-2447 2016 [Refereed]
     
    Objective: The aim of this study was to evaluate the biochemical recurrence (BCR) in patients with high-risk prostate cancer (PCa) treated with radical prostatectomy (RP) or radiotherapy (RT) plus androgen deprivation therapy (ADT).Methods: Subjects were patients with National Comprehensive Cancer Network-defined high-risk PCa treated with either RP or RT plus ADT. We calculated BCR-free survival in patients with those treatments and evaluated risk factor against BCR.Results: A total of 114 patients, 71 RP and 43 RT plus ADT, were evaluated. A total of 59 and 20.9% of patients experienced BCR in the RP and RT treatment groups, respectively. The 5-year BCR-free survival probabilities improved significantly for patients who received RT compared to those who received RP (81.3 vs 37.3%, P< 0.001). According to the number of risk factors, 59.2% of patients in the RP and 51.2% of patients in the RT treatment groups were classified with one risk factor (P< 0.014). The 5-year BCR-free survival probabilities for patients treated with RP were 46.6 and 21.7% for one and multiple risk factors, respectively (P= 0.008). On univariate analysis, only the number of risk factors had a significant impact on the risk of BCR. Meanwhile, there were no significant differences in the 5-year BCR-free survival probabilities between one and multiple risk factors in patients treated with RT.Conclusion: Among patients treated with RP, a marked heterogeneity existed in the oncological outcomes. Based on these findings, the number of risk factors should be emphasized to decide the optimal treatments for patients with high-risk PCa.
  • Yasuharu Nagai; Nobutaka Shimizu; Takafumi Minami; Shingo Toyoda; Mamoru Hashimoto; Mitsuhisa Nishimoto; Takashi Kikuti; Yoshitaka Saitou; Yutaka Yamamoto; Taiji Hayashi; Hidenori Tsuji; Masahiro Nozawa; Kazuhiro Yoshimura; Hirotsugu Uemura
    Hinyokika kiyo. Acta urologica Japonica 61 (10) 383 - 7 0018-1994 2015/10 [Refereed]
     
    OBJECTIVES: We compared sexual function by the expanded prostate cancer index composite (sexual domains of EPIC), health-related quality of life (SF-8), and International Prostate Symptom Score (I-PSS) inpatients using tadalafil after prostate brachytherapy (PB). Forty-five patients who underwent PB between April 2011 and January 2014 were included in this study. Patients were divided into the tadalafil (20 mg,once/week or once/two weeks) treated and non-treated (NT) groups. Sexual function was assessed prior to PB treatment and followed up to 24 weeks after PB. SF-8, sexual domains of EPIC, IPSS and subjective symptoms were assessed pre-PB and at 4, 8, 16, and 24 weeks post-PB. Patients in the tadalafil group achieved higher sexual function scores compared to NT group at all time points. For SF8, the patients in the tadalafil group significantly improved in mental health by the eighth week, and significantly worsened in the NT group (8 w ; p = 0.04). The voiding domains of EPIC score were found to worsen significantly after 4 weeks from PB in both groups, but the score tended to improve over 24 weeks. There was no significant difference between two groups. The I-PSS total score was found to worsen significantly in both groups post-PB, but the tadalafil group had a tendency to worsen less. PB treatment of localized prostate cancer is preferred for the preservation of sexual function. Management of sexual dysfunction with tadalafil after PB does not worsen sexual functions. We concluded that tadalafil might be applicable to mental health care in the treatment of patients with a high interest in sexual function before PB.
  • Masahiro Nozawa; Isao Hara; Hideyasu Matsuyama; Masayuki Iki; Kazuhiro Nagao; Tsukasa Nishioka; Takahiro Komura; Atsunobu Esa; Shigeya Uejima; Masaaki Imanishi; Yasunari Uekado; Takatoshi Ogawa; Hiroshi Kajikawa; Hirotsugu Uemura
    WORLD JOURNAL OF UROLOGY SPRINGER 33 (9) 1263 - 1268 0724-4983 2015/09 [Refereed]
     
    This study evaluated the baseline patient characteristics associated with the time to biochemical progression and overall survival in patients who participated in a phase II trial on zoledronic acid combined with the initial androgen-deprivation therapy for treatment-na < ve bone-metastatic prostate cancer.Patients received zoledronic acid 4 mg intravenously every 4 weeks for up to 24 months, concomitantly started with bicalutamide 80 mg orally every day and goserelin acetate 10.8 mg subcutaneously every 12 weeks.A total of 53 Japanese patients were enrolled between July 2008 and April 2010, and 52 patients were evaluable. Median follow-up period was 41.6 months. Updated median time to biochemical progression was 25.9 months (95 % confidence interval 14.5-49.9). Higher serum bone-specific alkaline phosphatase was an independent risk factor for time to biochemical progression based on multivariate analysis (hazard ratio 6.51; 95 % confidence interval 2.71-15.62; P < 0.001). Median time to biochemical progression for patients with serum bone-specific alkaline phosphatase level higher than 26 mu g/L was 12.7 months. Multivariate analysis indicated that higher serum C-terminal telopeptide of type I collagen independently increased the risk of death (hazard ratio 9.62; 95 % confidence interval 2.11-43.89; P = 0.003). Median overall survival for patients with serum C-terminal telopeptide of type I collagen level higher than 8.0 ng/ml was 31.1 months.Baseline bone markers can be useful as predictors for disease progression and survival time in patients with bone metastasis from treatment-na < ve prostate cancer treated with upfront zoledronic acid concomitantly started with androgen-deprivation therapy.
  • Takafumi Minami; Tomoko Minami; Nobutaka Shimizu; Yutaka Yamamoto; Marco De Velasco; Masahiro Nozawa; Kazuhiro Yoshimura; Nanae Harashima; Mamoru Harada; Hirotsugu Uemura
    JOURNAL OF IMMUNOTHERAPY LIPPINCOTT WILLIAMS & WILKINS 38 (7) 285 - 291 1524-9557 2015/09 [Refereed]
     
    Molecular therapy targeting tumor angiogenesis has been the standard treatment for metastatic renal cell carcinoma (mRCC). However, despite their significant antitumor effects, most of patients with mRCC have not been cured. Under such circumstances, anticancer immunotherapy has been considered a promising treatment modality for mRCC, and cancer-reactive cytotoxic T lymphocytes (CTLs) are the most powerful effectors among several immune cells. However, anticancer CTLs can be inhibited by several immune inhibitory mechanisms, including the interaction between programmed death 1 (PD-1) and its ligand PD-L1, on T cells and cancer cells, respectively. Alternatively, this also means that PD-L1 could be a promising target for anticancer immunotherapy. Therefore, we searched for PD-L1-derived peptides that are applicable for anticancer vaccine for HLA-A24(+) RCC patients. Among 5 peptides derived from PD-L1, which were prepared based on the binding motif to the HLA-A24 allele, both PD-L1(11-19) and PD-L1(41-50) peptides induced peptide-specific CTLs from peripheral blood mononuclear cells of HLA-A24(+) RCC patients. Such PD-L1 peptide-stimulated CD8(+) T cells showed cytotoxicity against HLA-A24(+) and PD-L1-expressing RCC cells. Although IFN- treatment increased PD-L1 expression on PD-L1(low) RCC cells, their sensitivity to cytotoxicity of PD-L1 peptide-stimulated CD8(+) T cells varied between patients. Altogether, these results indicate that both PD-L1(11-19) and PD-L1(41-50) peptides could be candidates for peptide-based anticancer vaccines for HLA-A24(+) mRCC patients.
  • Yurie Kura; Marco A. De Velasco; Naomi Ando; Emiko Fukushima; Barry R. Davies; Dennis Huzdar; Yutaka Yamamoto; Yuji Hatanaka; Takashi Oki; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 75 0008-5472 2015/08 [Refereed]
  • Marco A. De Velasco; Takashi Oki; Yurie Kura; Naomi Ando; Emiko Fukushima; Barry R. Davies; Dennis Huszar; Yutaka Yamamoto; Yuji Hatanaka; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 75 0008-5472 2015/08 [Refereed]
  • Marco A. De Velasco; Yuji Hatanaka; Yurie Kura; Emiko Fukushima; Naomi Ando; Barry R. Davies; Yutaka Yamamoto; Takashi Oki; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 75 0008-5472 2015/08 [Refereed]
  • Marco A. De Velasco; Yutaka Yamamoto; Yurie Kura; Emiko Fukushima; Naomi Ando; Barry Davies; Yuji Hatanaka; Takashi Oki; Nobutaka Shimizu; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuhiro Yoshimura; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 75 0008-5472 2015/08 [Refereed]
  • Marco A. De Velasco; Yurie Kura; Naomi Ando; Emiko Fukushima; Barry R. Davies; Hayley Campbell; Yuji Hatanaka; Yutaka Yamamoto; Nobutaka Shimizu; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 75 0008-5472 2015/08 [Refereed]
  • Masahiro Nozawa; Takayuki Ohzeki; Satoshi Tamada; Fumiya Hongo; Satoshi Anai; Kiyohide Fujimoto; Tsuneharu Miki; Tatsuya Nakatani; Satoshi Fukasawa; Hirotsugu Uemura
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY SPRINGER JAPAN KK 20 (4) 790 - 795 1341-9625 2015/08 [Refereed]
     
    Background There have been few reports of the differences in safety between the mammalian target of rapamycin inhibitors, everolimus and temsirolimus. The purpose of this study is to compare the adverse event profiles of both agents and to estimate the risk factors for non-infectious pneumonitis in patients with advanced renal cell carcinoma on the basis of our real-world clinical experience.Methods Data from 218 consecutive patients that received either everolimus or temsirolimus for advanced renal cell carcinoma at five Japanese centers were retrospectively analyzed. Chi-squared test and univariate and multivariate logistic regression analyses were performed to investigate the differences in adverse event profiles and the risk factors associated with non-infectious pneumonitis, respectively.Results A total of 196 patients were evaluable. In the everolimus group compared with temsirolimus, stomatitis (56 vs 30 %, p < 0.001) and non-infectious pneumonitis (38 vs 22 %, p = 0.018) were more frequently observed, and asthenia (11 vs 23 %, p = 0.027), rash (20 vs 36 %, p = 0.018), and fatigue (33 vs 48 %, p = 0.032) occurred less frequently in all grades. On multivariate analysis, male gender (odds ratio 3.65; 95 % confidence interval 1.44-9.26, p = 0.007) and everolimus treatment (odds ratio 2.00; 95 % confidence interval 1.01-3.96, p = 0.046) were significantly associated with development of non-infectious pneumonitis.Conclusion Our findings suggest that adverse event profiles may differ between everolimus and temsirolimus and that non-infectious pneumonitis may occur more frequently in patients treated with everolimus than temsirolimus. Further investigations are needed to confirm these results.
  • Shingo Toyoda; Takafumi Minami; Mamoru Hashimoto; Mitsutaka Saito; Nobutaka Shimizu; Yutaka Yamamoto; Taiji Hayashi; Hidenori Tsuji; Masahiro Nozawa; Kazuhiro Yoshimura; Tokumi Ishii; Hirotsugu Uemura
    Hinyokika kiyo. Acta urologica Japonica 61 (6) 223 - 6 0018-1994 2015/06 [Refereed]
     
    The aim of our study was to identify risk factors that may influence outcomes for patients presenting with Fournier gangrene. Twelve patients hospitalized and treated between August 2007 and August 2013 were included in this study. Distinct features were noted after one or two weeks of hospitalization. We did not observe a significant correlation between death risk and the extent of necrosis in this patient set. However, the extent of necrosis tended to correlate with the duration of hospitalization in the survivors. We also compared the results of blood biochemical analyses between the surviving and non-surviving groups. A significant difference was noted in the levels of glucose (Glu) after two weeks. In the non-surviving group, Glu levels were increased. These findings suggest a relationship between glycemic control after the initiation of therapy and death. We also examined the results of blood biochemical analyses according to the duration of hospitalization. The lactate dehydrogenase (LDH) levels at admission and LDH levels after two weeks were significantly higher in the patients with a duration of hospitalization longer than the median duration of 61.5 days. These findings suggest a relationship between the duration of hospitalization and the extent of necrosis at diagnosis.
  • Yutaka Yamamoto; Marco A De Velasco; Yurie Kura; Masahiro Nozawa; Yuji Hatanaka; Takashi Oki; Takayuki Ozeki; Nobutaka Shimizu; Takafumi Minami; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    Journal of translational medicine 13 150 - 150 2015/05 [Refereed]
     
    BACKGROUND: Despite recent advances in the treatment for advanced prostate cancer, outcomes remain poor. This lack of efficacy has prompted the development of alternative treatment strategies. In the present study we investigate the effects of the multikinase inhibitor sorafenib in a genetically engineered mouse model of prostate cancer and explore the rational combination with the mTOR inhibitor everolimus. METHODS: Conditional prostate specific PTEN-deficient knockout mice were utilized to determine the pharmacodynamic and chemopreventive effects of sorafenib. This mouse model was also used to examine the therapeutic efficacy of sorafenib alone or in combination with everolimus. Preclinical efficacy was assessed by comparing the reduction of tumor burden, proliferation, angiogenesis and the induction of apoptosis. Molecular responses were assessed by immunohistochemical, TUNEL and western blot assays. RESULTS: Pharmacodynamic analysis revealed that a single dose of sorafenib decreased activation of the PI3K/AKT/mTOR signaling axis at doses of 30-60 mg/kg, but activated JAK/STAT3 signaling. Levels of cleaved casapase-3 increased in a dose dependent manner. Chemoprevention studies showed that chronic sorafenib administration was capable of inhibiting tumor progression through the reduction of cancer cell proliferation, angiogenesis and the induction of apoptosis. In intervention models of established castration-naïve and castration-resistant prostate cancer, treatment with sorafenib provided modest but statistically insignificant reduction in tumor burden. However, sorafenib significantly inhibited cancer cell proliferation and MVD but had minimal effects on the induction of apoptosis. Interestingly, the administration of sorafenib increased the expression levels of the androgen receptor, p-GSK3β and p-ERK1/2 in castration-resistant prostate cancers. In both intervention models, combination therapy demonstrated a clear tendency of enhanced antitumor effects over monotherapy. Notably, the treatment combination of sorafenib and everolimus overcame therapeutic escape from single agent therapy in castration-resistant prostate cancers. CONCLUSIONS: In summary, we provide insights into the molecular responses of sorafenib therapy in a clinically relevant model of prostate cancer and present preclinical evidence for the development of targeted treatment strategies based on the use of multikinase inhibitors in combination with mTOR inhibitors for the treatment of advanced prostate cancer.
  • Masahiro Nozawa; Takahide Sugiyama; Koichi Sugimoto; Tasuharu Nagai; Yuji Hatanaka; Takashi Oki; Hideo Tahara; Hisao Matsuda; Hirotsugu Uemura
    JOURNAL OF CLINICAL ONCOLOGY AMER SOC CLINICAL ONCOLOGY 33 (15) 0732-183X 2015/05 [Refereed]
  • Yutaka Yamamoto; Marco A. De Velasco; Yurie Kura; Masahiro Nozawa; Yuji Hatanaka; Takashi Oki; Takayuki Ozeki; Nobutaka Shimizu; Takafumi Minami; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    JOURNAL OF TRANSLATIONAL MEDICINE BMC 13 2015/05 [Refereed]
     
    Background: Despite recent advances in the treatment for advanced prostate cancer, outcomes remain poor. This lack of efficacy has prompted the development of alternative treatment strategies. In the present study we investigate the effects of the multikinase inhibitor sorafenib in a genetically engineered mouse model of prostate cancer and explore the rational combination with the mTOR inhibitor everolimus.Methods: Conditional prostate specific PTEN-deficient knockout mice were utilized to determine the pharmacodynamic and chemopreventive effects of sorafenib. This mouse model was also used to examine the therapeutic efficacy of sorafenib alone or in combination with everolimus. Preclinical efficacy was assessed by comparing the reduction of tumor burden, proliferation, angiogenesis and the induction of apoptosis. Molecular responses were assessed by immunohistochemical, TUNEL and western blot assays.Results: Pharmacodynamic analysis revealed that a single dose of sorafenib decreased activation of the PI3K/AKT/mTOR signaling axis at doses of 30-60 mg/kg, but activated JAK/STAT3 signaling. Levels of cleaved casapase-3 increased in a dose dependent manner. Chemoprevention studies showed that chronic sorafenib administration was capable of inhibiting tumor progression through the reduction of cancer cell proliferation, angiogenesis and the induction of apoptosis. In intervention models of established castration-naive and castration-resistant prostate cancer, treatment with sorafenib provided modest but statistically insignificant reduction in tumor burden. However, sorafenib significantly inhibited cancer cell proliferation and MVD but had minimal effects on the induction of apoptosis. Interestingly, the administration of sorafenib increased the expression levels of the androgen receptor, p-GSK3 beta and p-ERK1/2 in castration-resistant prostate cancers. In both intervention models, combination therapy demonstrated a clear tendency of enhanced antitumor effects over monotherapy. Notably, the treatment combination of sorafenib and everolimus overcame therapeutic escape from single agent therapy in castration-resistant prostate cancers.Conclusions: In summary, we provide insights into the molecular responses of sorafenib therapy in a clinically relevant model of prostate cancer and present preclinical evidence for the development of targeted treatment strategies based on the use of multikinase inhibitors in combination with mTOR inhibitors for the treatment of advanced prostate cancer.
  • Osamu Yokoyama; Akira Tsujimura; Hironobu Akino; Naoki Segawa; Satoshi Tamada; Naoki Oguchi; Yasuhide Kitagawa; Hidenori Tsuji; Akihiko Watanabe; Teruo Inamoto; Nobutaka Shimizu; Yasuyoshi Fujiuchi; Yoji Katsuoka; Haruhito Azuma; Tadashi Matsuda; Mikio Namiki; Hirotsugu Uemura; Akihiko Okuyama; Norio Nonomura; Hideki Fuse; Tatsuya Nakatani
    WORLD JOURNAL OF UROLOGY SPRINGER 33 (5) 659 - 667 0724-4983 2015/05 [Refereed]
     
    To evaluate the efficacy and safety of imidafenacin (IM), a novel short half-life anticholinergic, as add-on therapy for male LUTS with nocturia and nocturnal polyuria.This multicenter, prospective, randomized, open-labelled study was conducted and involved men who had frequency, urgency, and nocturia despite receiving a stable dose of alpha 1-blocker for a parts per thousand yen1 month. Subjects were randomised to control (alpha 1-blocker alone), IM twice/day (alpha 1-blocker +0.1 mg imidafenacin twice daily), or IM nightly (alpha 1-blocker plus 0.1 mg imidafenacin nightly) group; the treatment period was 8 weeks. Primary endpoints included improvements in night-time frequency and Nocturia Quality of Life Questionnaire (N-QOL) scores. Secondary endpoints included changes from the baseline in frequency volume chart variables, and post-void residual volume.Compared with the controls, IM twice/day and IM nightly patients had a significantly lower night-time frequency (changes from baseline: 0.1 +/- A 0.8 in control, -0.6 +/- A 0.9 in IM twice/day, and -0.4 +/- A 1.0 in IM nightly, p = 0.5227, 0.0006 and 0.0143, respectively). The hours of undisturbed sleep and N-QOL score were significantly improved in IM twice/day group, though not IM nightly group. Nocturnal urine volume was significantly reduced in IM nightly group, although total urine volume remained unchanged.A short half-life anticholinergic is suggested to be safe and effective as an add-on therapy for residual nocturia in patients with male LUTS receiving alpha 1-blocker treatment. Anticholinergic administration nightly could reduce the nocturnal urine volume.
  • Takafumi Minami; Tomoko Minami; Nobutaka Shimizu; Yutaka Yamamoto; Marco A. De Velasco; Masahiro Nozawa; Kazuhiro Yoshimura; Nanae Harashima; Mamoru Harada; Hirotsugu Uemura
    INTERNATIONAL IMMUNOPHARMACOLOGY ELSEVIER SCIENCE BV 26 (1) 133 - 138 1567-5769 2015/05 [Refereed]
     
    Analyses on reactivity of anti-cancer cytotoxic T lymphocytes (CTLs) and clinical application of peptide-based anti-cancer vaccine have been mainly focused on patients with HLA-A2 or -A24 alleles. In this study, we identified an enhancer of zeste homolog (EZH) 2-derived peptide applicable for anti-cancer vaccine for prostate cancer patients with HLA-A3 supertype alleles. Five EZH2-derived peptides that were prepared based on the binding motif to the HLA-A3 supertype alleles (HLA-A11, -A31, and -A33) were functionally screened for their potential to induce peptide-specific CTLs from peripheral blood mononuclear cells (PBMCs) of HLA-A3 supertype allele prostate cancer patients. As a result, EZH2(733-741) peptide was found to efficiently induce peptide-specific CTLs. The EZH2(733-741) peptide-stimulated and purified CD8(+) T cells from PBMCs of HLA-A3 supertype allele + prostate cancer patients showed higher cytotoxicity against HLA-A3 supertype allele-expressing LNCaP prostate cancer cells than against parental LNCaP cells. This cytotoxicity against HLA-A3 supertype allele-expressing LNCaP cells was partially but significantly inhibited by the addition of EZH2(733-741) peptide-pulsed competitive cells. These results indicate that the EZH2(733-741) peptide could be a promising candidate for peptide-based immunotherapy for HLAA3 supertype allele(+) prostate cancer patients. (C) 2015 Elsevier B.V. All rights reserved.
  • Koichi Sugimoto; Takahiro Akiyama; Nobutaka Shimizu; Naoki Matsumura; Taiji Hayashi; Tsukasa Nishioka; Hirotsugu Uemura
    RESEARCH AND REPORTS IN UROLOGY DOVE MEDICAL PRESS LTD 7 81 - 83 2253-2447 2015 [Refereed]
     
    Aim: To investigate the clinical efficacy of acotiamide hydrochloride hydrate in patients with detrusor underactivity.Methods: We measured the post-void residual urinary volume in 19 patients with underactive bladders. All these patients had been under treatment with distigmine bromide and were prescribed acotiamide hydrochloride hydrate at a dose of 100 mg three times daily for 2 weeks.Results: Compared with the post-void residual urinary volume value at baseline (161.4 +/- 90.0 mL) a statistically significant reduction was observed at the end of treatment (116.3 +/- 63.1 mL) (P= 0.006). The drug was generally well tolerated by the majority of patients.Conclusion: Maybe, acotiamide hydrochloride hydrate showed clinical efficacy in patients with underactive bladders and may, therefore, be used alternatively in patients who do not respond sufficiently to distigmine bromide.
  • Hiroyuki Koike; Masahiro Nozawa; Marco A De Velasco; Yurie Kura; Naomi Ando; Emiko Fukushima; Yutaka Yamamoto; Yuji Hatanaka; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    Asian Pacific journal of cancer prevention : APJCP 16 (5) 1827 - 31 1513-7368 2015 [Refereed]
     
    BACKGROUND: We generated a mouse model of prostate cancer based on the adult-prostate-specific inactivation of phosphatase and tensin homolog (PTEN) using the Cre-loxP system. The potential of our mice as a useful animal model was examined by evaluating the chemopreventive efficacy of the anti-androgen, chlormadinone acetate (CMA). MATERIALS AND METHODS: Six-week-old mice were treated subcutaneously with 50 μg/g of CMA three times a week for 9 or 14 weeks and sacrificed at weeks 15 and 20. Macroscopic change of the entire genitourinary tract (GUT) and histologically evident prostate gland tumor development were evaluated. Proliferation and apoptosis status in the prostate were examined by immunohistochemistry. RESULTS: CMA triggered significant shrinkage of not only the GUT but also prostate glands at 15 weeks compared to the control (p=0.017 and p=0.010, respectively), and the trend became more marked after a further five-weeks of treatment. The onset of prostate adenocarcinoma was not prevented but the proliferation of cancer cells was inhibited by CMA, which suggested the androgen axis is critical for cancer growth in these mice. CONCLUSIONS: Conditional PTEN-deficient mice are useful as a preclinical model for chemoprevention studies and serve as a valuable tool for the future screening of potential chemopreventive agents.
  • Masahiro Nozawa; Hirotsugu Uemura
    TRANSLATIONAL CANCER RESEARCH AME PUBL CO 3 (6) 555 - 557 2218-676X 2014/12 [Refereed]
     
    Axitinib is a highly potent and selective VEGF receptor inhibitor. Previous trials suggested a significant advantage of axitinib versus sorafenib in progression-free survival (PFS) of patients with metastatic renal cell carcinoma (RCC) treated with prior cytokine therapy. Recently an important negative study was reported, which evaluated the PFS with axitinib and with sorafenib in treatment-naive metastatic RCC. This study was underpowered but conveyed an important message on the limit of current VEGF signal targeted drugs as a first-line therapy. In the future, more emphasis should be put on arrangement of dosing and scheduling of drugs already approved as well as development of new agents targeting novel molecules in this disease.
  • Nobutaka Shimizu; Takafumi Minami; Koichi Sugimoto; Yoshitaka Saito; Yutaka Yamamoto; Taiji Hayashi; Hidenori Tsuji; Masahiro Nozawa; Kazuhiro Yoshimura; Tokumi Ishii; Hirotsugu Uemura; Kiyoshi Nakamatsu
    WORLD JOURNAL OF UROLOGY SPRINGER 32 (6) 1423 - 1432 0724-4983 2014/12 [Refereed]
     
    The purpose of the study is to investigate the efficacy of an alpha-1 adrenergic receptor antagonist (silodosin) for the treatment of lower urinary tract symptoms (LUTS) associated with interstitial I-125 implantation for prostate cancer.This randomized single-center study involved 105 patients (53 with and 52 without silodosin). Silodosin was postoperatively administered, daily, for 6 months (8 mg/day). Urinary symptoms and pressure flow were evaluated preoperatively and postoperatively at 1, 3, 6, and 12 months.At 12 months, interstitial I-125 implantation had induced a significant decrease in prostate volume (28.3 +/- A 11.1-20.5 +/- A 8.1 g in the silodosin group and 26.1 +/- A 9.7-17.7 +/- A 4.9 g in the controls) and the prostate-specific antigen level (7.1 +/- A 3.6-1.4 +/- A 1.7 ng/mL in the silodosin group and 8.1 +/- A 4.3-1.3 +/- A 1.2 ng/mL in the controls). Significant improvements in the international prostate symptom voiding subscores at 6 months and quality of life at 3 months were observed in those receiving silodosin. The pressure flow studies demonstrated that silodosin had significantly enlarged the bladder capacity when the first non-voiding contraction was seen at 3 and 12 months (3M: 127.1 +/- A 74.8 vs. 118.2 +/- A 83.9 mL, p = 0.001; 12M: 123.7 +/- A 79.3 vs. 100.3 +/- A 73.4 mL, p = 0.01); however, there were no improvements in the bladder outlet obstruction index (BOOI) or urinary flow.Silodosin temporarily improved LUTS, but did not improve the BOOI after I-125 implantation in the prostate.
  • Masatoshi Eto; Hirotsugu Uemura; Yoshihiko Tomita; Hiroomi Kanayama; Nobuo Shinohara; Yoichi Kamei; Yosuke Fujii; Yoshiko Umeyama; Seiichiro Ozono; Seiji Naito; Hideyuki Akaza
    CANCER SCIENCE WILEY 105 (12) 1576 - 1583 1347-9032 2014/12 [Refereed]
     
    In an open-label, multicenter phase II study of Japanese patients with cytokine-refractory metastatic renal cell carcinoma, axitinib showed substantial antitumor activity with an acceptable safety profile. Here, we report overall survival and updated efficacy and safety results. Sixty-four Japanese patients with metastatic renal cell carcinoma following prior therapy with cytokines were treated with axitinib at a starting dose of 5mg b.i.d. Following median treatment duration of 14.2months, median overall survival was 37.3months (95% CI, 28.6-49.9). The objective response rate, the primary endpoint of the study, was 51.6% (95% CI, 38.7-64.2); the median duration of response, 11.1months (95% CI, 8.2-13.7); and the median progression-free survival was 11.0months (95% CI, 9.2-12.0), assessed by the independent review committee. Common treatment-related all-grade adverse events were hypertension (88%), hand-foot syndrome (75%), diarrhea (66%), proteinuria (63%), fatigue (55%) and dysphonia (53%). In an exploratory analysis, median overall survival was found to be significantly longer in patients who had greater decreases in plasma levels of soluble vascular endothelial growth factor receptor-2 during the first cycle of treatment. In conclusion, the present study showed axitinib to be effective, and toxicities with long-term treatment were generally controllable with axitinib dose modification and/or standard medications in these Japanese patients. Some frequently reported adverse events warrant close monitoring and management. Changes in the plasma levels of soluble vascular endothelial growth factor receptor-2 may be used as a prognostic factor for overall survival in metastatic renal cell carcinoma following axitinib treatment. This study is registered at (identifier NCT00569946).
  • Nobuaki Matsubara; Hirotsugu Uemura; Takefumi Satoh; Hiroyoshi Suzuki; Tsutomu Nishiyama; Hiroji Uemura; Katsuyoshi Hashine; Keiichiro Imanaka; Seiichiro Ozono; Hideyuki Akaza
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY OXFORD UNIV PRESS 44 (12) 1216 - 1226 0368-2811 2014/12 [Refereed]
     
    Abiraterone acetate has been approved in > 70 countries for chemotherapy-na < ve metastatic castration-resistant prostate cancer patients. Efficacy and safety of abiraterone acetate (1000 mg/once daily) with prednisolone (5 mg/twice daily) in chemotherapy-na < ve Japanese patients with metastatic castration-resistant prostate cancer was evaluated.Men, a parts per thousand yen20 years, with prostate-specific antigen levels of a parts per thousand yen5 ng/ml and evidence of progression were enrolled in this Phase 2, multicenter, open-label study. Primary efficacy endpoint was proportion of patients achieving a prostate-specific antigen decline of a parts per thousand yen50% from baseline (prostate-specific antigen response) after 12 week of treatment. Secondary efficacy endpoints and safety were assessed.A confirmed prostate-specific antigen response was observed in 29/48 (60.4%) patients by week 12; lower limit of two-sided 90% confidence interval was > 35% (threshold response rate), demonstrating efficacy of abiraterone acetate. Secondary efficacy endpoints: prostate-specific antigen response rate during treatment period: 62.5%; objective radiographic response, partial response: 4/18 (22.2%) patients; complete response: none; stable disease: 11/18 (61.1%) patients; median percent change in prostate-specific antigen level from baseline at Week 12: -66.62%. Median prostate-specific antigen response duration and progression-free survival were not reached, and median radiographic progression-free survival was 253 days. Of 31/48 (64.6%) patients experienced adverse events of special interest; most common was hepatic function abnormality (37.5%, Grade 3: 10.4%). One Grade 3 hypertension was the only mineralocorticoid adverse event > Grade 1/2.Efficacy of abiraterone acetate plus prednisolone was demonstrated by decline in prostate-specific antigen levels with evidence of antitumor activity by radiography in Japanese patients with chemotherapy-na < ve metastatic castration-resistant prostate cancer. Abiraterone acetate plus prednisolone had an acceptable safety profile.NCT01756638.
  • Yutaka Yamamoto; Masahiro Nozawa; Nobutaka Shimizu; Takafumi Minami; Kazuhiro Yoshimura; Hirotsugu Uemura
    INTERNATIONAL JOURNAL OF UROLOGY WILEY-BLACKWELL 21 (11) 1183 - 1184 0919-8172 2014/11 [Refereed]
  • Marco A. De Velasco; Yuji Hatanaka; Takashi Oki; Yurie Kura; Yutaka Yamamoto; Kazuhiro Yoshimura; Nobutaka Shimizu; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 74 (19) 0008-5472 2014/10 [Refereed]
  • Marco A. De Velasco; Yurie Kura; Naomi Ando; Emiko Fukushima; Yuji Hatanaka; Yutaka Yamamoto; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 74 (19) 0008-5472 2014/10 [Refereed]
  • Marco A. De Velasco; Yurie Kura; Naomi Ando; Emiko Fukushima; Yuji Hatanaka; Yutaka Yamamoto; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 74 (19) 0008-5472 2014/10 [Refereed]
  • Hirotsugu Uemura; Yurie Kura; Naomi Ando; Emiko Fukushima; Yuji Hatanaka; Yutaka Yamamoto; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Marco A. De Velasco
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 74 (19) 0008-5472 2014/10 [Refereed]
  • Yurie Kura; Marco A. De Velasco; Naomi Ando; Emiko Fukushima; Yutaka Yamamoto; Yuji Hatanaka; Nobutaka Shimizu; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 74 (19) 0008-5472 2014/10 [Refereed]
  • Kazuhiro Yoshikawa; Marco A. De Velasco; Yurie Kura; Naomi Ando; Emiko Fukushima; Yuji Hatanaka; Yutaka Yamamoto; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 74 (19) 0008-5472 2014/10 [Refereed]
  • Hideyasu Matsuyama; Tomoyuki Shimabukuro; Isao Hara; Yasuo Kohjimoto; Kazuhiro Suzuki; Hidekazu Koike; Hirotsugu Uemura; Taiji Hayashi; Munehisa Ueno; Kiichiro Kodaira; Yoshihiko Tomita; Toshihiko Sakurai; Nobuaki Shimizu
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY SPRINGER JAPAN KK 19 (5) 946 - 954 1341-9625 2014/10 [Refereed]
     
    We aimed to find the prognostic factors predicting overall survival (OS) in patients with castration-resistant prostate cancer (CRPC) who had docetaxel (DTX) chemotherapy, and to construct a model predicting the optimum number of cycles of DTX.A total of 279 CRPC patients who received DTX (a parts per thousand yen50 mg/m(2)) every 3-4 weeks were studied retrospectively. Prognostic factors predicting treatment cycles as well as OS were analyzed, and a risk table for predicting treatment cycles was constructed.The longer treatment group (> 10 cycles) had a significantly longer OS than the standard treatment group (p < 0.0001). Multivariate analysis demonstrated that a decrease of a parts per thousand yen50 % in prostate-specific antigen (PSA), serum markers at the start of DTX therapy [PSA, alkaline phosphatase (ALP), and C-reactive protein (CRP)], and the number of DTX courses were independent predictors of OS. The risk table employing the combination of three factors [ALP (cut-off 189 IU/L), hemoglobin (11.3 g/dL), and age (65 years) at the start of DTX therapy], and scoring based on the hazard ratio of each risk factor (ALP 4, hemoglobin 2, age 3) could effectively predict the probability of the length of DTX therapy, with lower score (0-6) predicting > 10 cycles, and higher score (7-9) predicting a parts per thousand currency sign5 cycles (p < 0.0001). No significant difference was found regarding grade 3/4 adverse events between the two groups.A model using three factors prior to chemotherapy may be beneficial for deciding the duration of DTX therapy in patients with CRPC.
  • Takayuki Ohzeki; Satoshi Fukasawa; Atsushi Komaru; Takeshi Namekawa; Yosuke Sato; Kimiaki Takagi; Masayuki Kobayashi; Hirotsugu Uemura; Tomohiko Ichikawa; Takeshi Ueda
    INTERNATIONAL JOURNAL OF UROLOGY WILEY-BLACKWELL 21 (10) 1065 - 1068 0919-8172 2014/10 [Refereed]
     
    We report the adverse events and efficacy of traditional (4weeks on 2weeks off) and alternative sunitinib treatment schedules for Japanese patients with metastatic renal cell carcinoma. We retrospectively investigated 54 patients who received sunitinib for metastatic renal cell carcinoma between May 2006 and June 2012: 32 received a traditional treatment schedule and 22 received an alternative schedule. According to the Memorial Sloan-Kettering Cancer Center risk classification, five patients had favorable prognoses, 42 had intermediate prognoses and seven had poor prognoses. The mean observation periods were 16.3 and 20months for the traditional and alternative schedule groups, respectively. Adverse events were significantly less common in the alternative schedule group, including most high-grade events. In the traditional and alternative schedule groups, median times to failure were 4.1 and 11.6months (P=0.040), median progression-free survival times were 4.1 and 11.3months (P=0.031), and median overall survival times were 12.0 and 32.1months (P=0.018), respectively. Each of these measures was better in the group of patients who received an alternative treatment schedule, suggesting that individualized changes to the sunitinib administration schedule can be effective.
  • Marco A. De Velasco; Motoyoshi Tanaka; Yutaka Yamamoto; Yuji Hatanaka; Hiroyuki Koike; Kazuto Nishio; Kazuhiro Yoshikawa; Hirotsugu Uemura
    CARCINOGENESIS OXFORD UNIV PRESS 35 (9) 2142 - 2153 0143-3334 2014/09 [Refereed]
     
    Castration-resistant prostate cancer is an incurable heterogeneous disease that is characterized by a complex multistep process involving different cellular and biochemical changes brought on by genetic and epigenetic alterations. These changes lead to the activation or overexpression of key survival pathways that also serve as potential therapeutic targets. Despite promising preclinical results, molecular targeted therapies aimed at such signaling pathways have so far been dismal. In the present study, we used a PTEN-deficient mouse model of prostate cancer to show that plasticity in castration-resistant tumors promotes therapeutic escape. Unlike castration-naive tumors which depend on androgen receptor and PI3K/AKT signal activation for growth and survival, castration-resistant tumors undergo phenotypic plasticity leading to increased intratumoral heterogeneity. These tumors attain highly heterogeneous phenotypes that are characterized by cancer cells relying on alternate signal transduction pathways for growth and survival, such as mitogen-activated protein kinase and janus kinase/signal transducer and activator of transcription, and losing their dependence on PI3K signaling. These features thus enabled castration-resistant tumors to become insensitive to the therapeutic effects of PI3K/AKT targeted therapy. Overall, our findings provide evidence that androgen deprivation drives phenotypic plasticity in prostate cancer cells and implicate it as a crucial contributor to therapeutic resistance in castration-resistant prostate cancer. Therefore, incorporating intratumoral heterogeneity in a dynamic tumor model as a part of preclinical efficacy determination could improve prediction for response and provide better rationale for the development of more effective therapies.
  • Maiko Kato; Naoki Oiso; Mitsuhisa Nishimoto; Yasunori Mori; Yoshinari Katoh; Hirotsugu Uemura; Akira Kawada
    EUROPEAN JOURNAL OF DERMATOLOGY JOHN LIBBEY EUROTEXT LTD 24 (5) 622 - 623 1167-1122 2014/09 [Refereed]
  • Nanae Harashima; Takafumi Minami; Hirotsugu Uemura; Mamoru Harada
    MOLECULAR CANCER BIOMED CENTRAL LTD 13 217 - 217 1476-4598 2014/09 [Refereed]
     
    Background:Synthetic double-stranded RNA poly(I:C) is a useful immune adjuvant and exhibits direct antitumor effects against several types of cancers. In this study, we elucidated the mechanisms underlying the effects induced in poly(I:C)-transfected human renal cell carcinoma (RCC) cells.Results: In contrast to the lack of an effect of adding poly(I:C), poly(I:C) transfection drastically decreased RCC cell viability. Poly(I:C) transfection induced reactive oxygen species (ROS)-dependent apoptosis in RCC cells and decreased the mitochondrial membrane potential (Delta psi m). Treatment with N-acetyl-L-cysteine (NAC), a ROS scavenger, suppressed apoptosis and restored the Delta psi m. Although the levels of phosphorylated gamma H2A.X, an indicator of DNA damage, increased in poly(I:C)-transfected RCC cells, NAC treatment decreased their levels, suggesting ROS-mediated DNA damage. Furthermore, poly(I:C) transfection increased the levels of phosphorylated p53, NOXA, and tBid. Immunoblots and assays with a panel of caspase inhibitors revealed that poly(I:C) transfection-induced apoptosis was dependent on caspase-8 and -9, as well as caspase-2. Alternatively, poly(I:C) transfection increased mRNA expression of interferon (IFN)-beta, and treatment with IFN-beta suppressed growth of RCC cells without apoptosis. In addition, cyclinD1 and c-Myc expression decreased in poly(I:C)-transfected RCC cells. Moreover, RNA interference experiments revealed that poly(I:C) transfection exerted apoptotic effects on RCC cells through innate adjuvant receptors and the 2-5A system, the latter of which induces apoptosis in virus-infected cells.Conclusions:These results suggest that poly(I:C) transfection induced two types of effects against RCC cells such as apoptosis, as a result of ROS-mediated DNA damage, and IFN-beta-mediated growth arrest, both of which were exerted via innate adjuvant receptors and the 2-5A system.
  • Masahiro Nozawa; Takeshi Inagaki; Kazuhiro Nagao; Tsukasa Nishioka; Takahiro Komura; Atsunobu Esa; Michio Kitagawa; Masaaki Imanishi; Yasunari Uekado; Takatoshi Ogawa; Hiroshi Kajikawa; Shigeya Uejima; Hideyasu Matsuyama; Isao Hara; Hirotsugu Uemura
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY SPRINGER JAPAN KK 19 (4) 693 - 701 1341-9625 2014/08 [Refereed]
     
    The efficacy of zoledronic acid in patients with treatment-na < ve prostate cancer is unclear. We conducted a phase II study to investigate the benefits of combined zoledronic acid and androgen deprivation therapy in treatment-na < ve prostate cancer with bone metastasis. The primary endpoint was skeletal-related event-free survival at 24 months.Subjects were treatment-na < ve patients with histologically confirmed adenocarcinoma of the prostate and radiological evidence of bone metastasis. Treatment consisted of bicalutamide 80 mg daily, goserelin acetate 10.8 mg every 12 weeks, and zoledronic acid 4 mg every 4 weeks. Zoledronic acid was continued for 24 months.Of the patients enrolled between July 2008 and April 2010, 52 were included in the analyses. The median age of the patients was 72 years. The median baseline prostate-specific antigen level was 249.4 ng/mL. The median follow-up period was 33.3 months. The 24-month skeletal-related event-free survival rate was 84.4 % (95 % confidence interval 71.2-91.9). The median time to prostate-specific antigen progression was 25.9 months (95 % confidence interval 14.7-36.3). The median overall survival time was not reached. Improvement in pain or maintenance of no pain during the first 12 weeks was observed in 70 % of patients and the extent of bone disease was decreased in 10 % of patients at 12 months. Grade 3 osteonecrosis of the jaw was observed in three patients (5.8 %).Zoledronic acid concomitant with androgen deprivation therapy as initial treatment in patients with treatment-na < ve prostate cancer with bone metastasis resulted in an encouraging skeletal-related event-free survival rate at 24 months.
  • Dingwei Ye; Masatoshi Eto; Jin Soo Chung; Go Kimura; Wen-Cheng Chang; Yen-Hwa Chang; See-Tong Pang; Jae Lyun Lee; Yuanjie Niu; Howard Gurney; Hirotsugu Uemura
    CLINICAL GENITOURINARY CANCER CIG MEDIA GROUP, LP 12 (4) 225 - 233 1558-7673 2014/08 [Refereed]
     
    Rates of renal cell carcinoma (RCC) morbidity and mortality vary widely by geography, with increasing incidence in most countries. Interestingly, RCC incidence is significantly lower in Asian countries relative to other regions, which is attributed to environmental and genetic influences. Additionally, it has been demonstrated that different ethnic groups differ in their RCC characteristics which might lead to varied responses to therapy. In this review, physicians drawn from countries across the Asia-Pacific region-China, Japan, Taiwan, Republic of Korea, and Australia-take all available data into consideration to develop the first opinion statement on treatment of advanced RCC in the region. We have sought to determine what factors influence treatment patterns and availability of therapeutic agents in our respective countries, discussed whether these factors are fully justified or should be modified, and considered what additional efforts should be undertaken to optimize treatment outcomes in RCC. Additionally, we have addressed the limitations on treatment of RCC in the region, capturing the restrictive situations of targeted therapy use in the Asia-Pacific region, mainly because of drug availability and treatment reimbursement. Often this illustrates the gap between Western and regional or even among local guidelines, the opinions of leading physicians regarding the treatment, and the realistic access to agents for most patients. Proposals made in this document are based on clinical experience and data from clinical trials of RCC therapies in which Asian patients have been included. (C) 2014 Elsevier Inc. All rights reserved.
  • Mamoru Hashimoto; Nobutaka Shimizu; Shingo Toyoda; Yoshitaka Saito; Yutaka Yamamoto; Takafumi Minami; Taiji Hayashi; Hidenori Tsuji; Masahiro Nozawa; Kazuhiro Yoshimura; Tokumi Ishii; Hirotsugu Uemura
    Hinyokika kiyo. Acta urologica Japonica 泌尿器科紀要刊行会 60 (6) 269 - 273 0018-1994 2014/06 
    We report a case of a patient with a fistula between the right ureter and external iliac artery. The patient was a 75-year-old woman who had undergone abdominal radical hysterectomy for uterine cancer, and whole pelvis radiotherapy for right external iliac lymph node metastasis. Her post-operative course was complicated by hydronephrosis of the right kidney, which was treated by the insertion of a double-J stent. While removing the frequently obstructed double-J stent after percutaneous nephrostomy, arterial hemorrhage occurred from the external urethral meatus. Computed tomographic scan demonstrated right ureteral external iliac artery fistula formation located adjacent to the pseudoaneurysm. The patient was treated successfully with endovascular stent grafting and has showed no episode of hematuria since then.
  • Hidenori Tsuji; Nobutaka Shimizu; Masahiro Nozawa; Tohru Umekawa; Kazuhiro Yoshimura; Marco A. De Velasco; Hirotsugu Uemura; Saeed R. Khan
    UROLITHIASIS SPRINGER 42 (3) 195 - 202 2194-7228 2014/06 [Refereed]
     
    Osteopontin (OPN) expression is increased in kidneys of rats with ethylene glycol (EG) induced hyperoxaluria and calcium oxalate (CaOx) nephrolithiasis. The aim of this study is to clarify the effect of OPN knockdown by in vivo transfection of OPN siRNA on deposition of CaOx crystals in the kidneys. Hyperoxaluria was induced in 6-week-old male Sprague-Dawley rats by administering 1.5 % EG in drinking water for 2 weeks. Four groups of six rats each were studied: Group A, untreated animals (tap water); Group B, administering 1.5 % EG; Group C, 1.5 % EG with in vivo transfection of OPN siRNA; Group D, 1.5 % EG with in vivo transfection of negative control siRNA. OPN siRNA transfections were performed on day 1 and 8 by renal sub-capsular injection. Rats were killed at day 15 and kidneys were removed. Extent of crystal deposition was determined by measuring renal calcium concentrations and counting renal crystal deposits. OPN siRNA transfection resulted in significant reduction in expression of OPN mRNA as well as protein in group C compared to group B. Reduction in OPN expression was associated with significant decrease in crystal deposition in group C compared to group B. Specific suppression of OPN mRNA expression in kidneys of hyperoxaluric rats leads to a decrease in OPN production and simultaneously inhibits renal crystal deposition.
  • Takafumi Minami; Tomoko Minami; Nobutaka Shimizu; Yutaka Yamamoto; Marco De Velasco; Masahiro Nozawa; Kazuhiro Yoshimura; Nanae Harashima; Mamoru Harada; Hirotsugu Uemura
    INTERNATIONAL IMMUNOPHARMACOLOGY ELSEVIER SCIENCE BV 20 (1) 59 - 65 1567-5769 2014/05 [Refereed]
     
    Molecular targeting therapy with anti-angiogenic agents, including sunitinib and sorafenib, has been proven to be the first- and second-line standard treatments for metastatic renal cell carcinoma (mRCC) worldwide. Despite their significant antitumor effects, most of the patients with mRCC have not been cured. Under such circumstances, anti-cancer immunotherapy has been considered as a promising treatment modality for mRCC, and cytotoxic T lymphocytes (CTLs) are the most powerful effectors among several immune cells and molecules. Therefore, we previously conducted anti-cancer vaccine therapy with peptides derived from carbonic anhydrase-9 and vascular endothelial growth factor receptor-1 as phase-I/II trials for mRCC patients and reported their clinical benefits. Alternatively, up-regulated expression of erythropoietin (Epo) and its receptor (EpoR) in RCC has been reported, and their co-expression is involved in tumorigenesis. In order to increase options for peptide-based vaccination therapy, we searched for novel EpoR-peptides for HLA-A24(+) RCC patients. Among 5 peptides derived from EpoR, which were prepared based on the binding motif to the HLA-A24 allele, EpoR(52-60) peptide had the potential to induce peptide-specific CTLs from peripheral blood mononuclear cells of HLA-A24(+) RCC patients. Cytotoxicity toward HLA-A24 and EpoR-expressing RCC cells was ascribed to peptide-specific CD8(+) T cells. These results indicate that the EpoR(52-60) peptide could be a promising candidate for a peptide-based anti-cancer vaccine for HLA-A24(+) mRCC patients. (C) 2014 Elsevier B.V. All rights reserved.
  • Yasuyuki Kobayashi; Taiji Hayashi; Tokumi Ishii; Hirotsugu Uemura
    EXPERIMENTAL AND CLINICAL TRANSPLANTATION BASKENT UNIV 12 (2) 162 - 164 1304-0855 2014/04 [Refereed]
     
    To our knowledge, this is the first report of an ABO-incompatible living-donor renal transplant without a splenectomy performed in a patient with renal coloboma syndrome, a rare disorder caused by PAX2 gene mutations, and that presents with renal and optic nerve hypodysplasia and disorders of the central nervous system. Many patients with renal coloboma syndrome develop end-stage renal disease requiring renal replacement therapy. Few reports of a well-defined course of renal transplant for coloboma syndrome have been published. We treated a 22-year-old man who had end-stage renal disease from renal coloboma syndrome. We performed an ABO-incompatible living-donor renal transplant with a kidney donated by his father. Two years after the transplant, the patient has good preserved renal function, and his compliance with the immunosuppressive regimen was good.
  • T. Ishii; M. Yasuda; Y. Saito; Y. Mori; T. Hayashi; H. Uemura; K. Nose; T. Nishioka
    TRANSPLANTATION PROCEEDINGS ELSEVIER SCIENCE INC 46 (2) 492 - 495 0041-1345 2014/03 [Refereed]
     
    Background. Azilsartan, an angiotensin receptor blocker (ARB), was administered to renal transplant recipients to investigate the safety and antihypertensive effect in addition to its ARB-characteristic organ-protective effect. Methods. The subjects were 20 patients (18 males, 2 females; baseline serum creatinine 2.39 +/- 1.33 mg/dL) responding poorly to candesartan, who suffered albuminuria (>0.3 g/g creatinine) and hypertension (>140/90 mm Hg) following renal transplantation. Three months after candesartan was switched to azilsartan 20 mg/d, blood pressure, creatinine-corrected urinary albumin excretion, urinary L-type acid binding protein, urinary 8-hydroxydeoxyguano-sine, serum creatinine, and estimated glomerular filtration rate were evaluated. Thirteen patients received cyclosporine (65.0%) and 7 received tacrolimus (35.0%). Another hypertensive (calcium antagonist) agent was combined in 7 (35.0%). Results. Systolic blood pressure significantly decreased from 139.5 mm Hg (baseline) from 128.7 mm Hg (at 3 months), whereas no significant changes were observed for diastolic blood pressure. The percentage of patients achieving the target level of antihypertensive effect (blood pressure < 130/80 mm Hg) significantly improved from 30.0% (baseline) to 70.0% (at 3 months). No significant changes were observed in renal graft function, oxidative stress marker level, or biochemical examination findings. Conclusion. Sufficient antihypertensive effect was demonstrated soon after switching to azilsartan. However, no significant change was found in renal damage markers. Long-term study must be conducted to confirm the protective effect azilsartan on the transplanted kidney, as found with candesartan. The safety of azilsartan was demonstrated. If the transplanted kidney protection is demonstrated, this drug is expected to contribute to the improved long-term prognosis of renal transplant recipients.
  • Shunji Takahashi; Hirofumi Mukai; Hirotsugu Uemura; Hiroji Uemura; Takeo Kosaka; Hiroyuki Nishiyama; Kazuhiro Suzuki; Yoshiyuki Kakehi; Koji Okihara; Shunichi Namiki; Osamu Ogawa; Masashi Kato; Yasutomo Nakai; Keiji Ohno
    JOURNAL OF CLINICAL ONCOLOGY AMER SOC CLINICAL ONCOLOGY 32 (4) 0732-183X 2014/02 [Refereed]
  • Hirotsugu Uemura; Takahiro Kimura; Takafumi Minami; Kazuhiro Yoshimura; Masahiro Nozawa; Shin Egawa; Hiroyuki Fujimoto; Akira Yamada; Kyogo Itoh
    JOURNAL OF CLINICAL ONCOLOGY AMER SOC CLINICAL ONCOLOGY 32 (4) 0732-183X 2014/02 [Refereed]
  • Teruo Inamoto; Haruhito Azuma; Norio Nonomura; Tatsuya Nakatani; Tadashi Matsuda; Masahiro Nozawa; Takeshi Ueda; Hidefumi Kinoshita; Kazuo Nishimura; Hiro-omi Kanayama; Tsuneharu Miki; Yoshihiko Tomita; Toshiaki Yoshioka; Masao Tsujihata; Hirotsugu Uemura
    ASIAN PACIFIC JOURNAL OF CANCER PREVENTION ASIAN PACIFIC ORGANIZATION CANCER PREVENTION 15 (4) 1811 - 1815 1513-7368 2014 [Refereed]
     
    Background: In clinical trials with no upper age limit, the proportion of older patients is usually small, probably reflecting the more conservative approach adopted by clinicians when treating the elderly. An exploratory analysis of elderly patients in the RECORD-1 Trial showed that patients >= 65 y.o. had superior median PFS than overall RECORD-1 population (5.4 months and 4.9 months, respectively). We investigated the efficacy, relative benefit and safety of Everolimus (EVE) as sequential therapy after failure of VEGFr-TKI therapy for older patients with metastatic renal cell cancer (mRCC), in daily practice. Materials and Methods: 172 consecutive IRB approved patients with mRCC (median age 65, M: F 135/37, 78% clear cell) who received salvage EVE at 39 tertiary institutions between October 2009 and August 2011 were included in this analysis. Some 31% had progressed on sunitinib, 22% on sorafenib, 1% on axitinib, 41% on sequential therapy, and 5% had received other therapy. Patients with brain metastases were not included and 95% of the patients had a ECOG (Eastern Cooperative Oncology Group) performance status (PS) of 0 or 1. Previous radiotherapy was an exclusion criterion, but prior chemotherapy was permitted. Adequate organ function and hematologic parameters were mandatory. EVE administration was approved by the institutional review board at each participating institution and signed informed consent was obtained from all patients. Results: Median time of the whole cohort to last follow-up was 3.5 months (range 0.4-15.2 months). Forty four percent were continuing to take EVE at last follow-up. There were 86 (50%) patients >= 65 y.o. and 86 (50%) <65 y.o. The percentage of patients who showed PR/SD was higher in the older group than in the younger one (5.9%/61.2% vs 1.2%/46.5%, respectively). Median survival of older patients was also significantly longer (3.5 +/- 0.31 vs 3.1 +/- 0.34, hazard ratio=0.45, CI; 0.255-0.802). Analysis using Cox regression model adjusted for gender, PS, number of metastases, site of metastases, histology, smoking history and age detected an association between age and PFS (p=0.011). The frequency of adverse events in elderly patients treated with EVE was no greater than that in younger patients, although such toxicity may have had a greater impact on their quality of life. Conclusions: Older patients should not generally be excluded from accepted therapies (mTOR inhibitors after failure of VEGFr-TKI therapy) for mRCC.
  • Masahiro Nozawa; Hirotsugu Uemura
    Translational andrology and urology 2 (4) 324 - 7 2013/12 [Refereed]
     
    The number of molecular targeted agents for advanced renal cell carcinoma (RCC) has gradually increased, but evidence on the optimal order of selection for such agents has not yet caught up with this trend. In addition, timing of switching molecular targeted drugs may also become an important issue for controlling the disease as types of these drugs grow in number. Based on the fact that the efficacy of a rechallenge of the drug previously used suggests the recovery of the sensitivity, a cyclic therapy in which drugs are changed before exacerbation to repeatedly administer several drugs in a rotated manner, may also be an effective sequential therapy.
  • Mitsuhisa Nishimoto; Nobutaka Shimizu; Takashi Kikuchi; Yasuyuki Kobayashi; Yutaka Yamamoto; Takafumi Minami; Taiji Hayashi; Hidenori Tsuji; Masahiro Nozawa; Kazuhiro Yoshimura; Tokumi Ishii; Hirotsugu Uemura
    Hinyokika kiyo. Acta urologica Japonica 59 (11) 753 - 7 0018-1994 2013/11 [Refereed]
     
    Testicular tumors of ovarian epithelial types are rare, and their etiology is unknown. Moreover, a clear treatment policy has not become settled. Under the diagnosis of a testicular tumor, this patient underwent a high orchiectomy, and the pathology revealed testicular tumor of ovarian epithelial type. CA125 was elevated for three years post-operatively and a recurrence was discovered in the left inguinal region by positron emission tomography-computed tomography. Therefore, tumor extirpation was performed. The pathology result confirmed the recurrence of testicular tumor of ovarian epithelial type. After the surgery, the patient was given combined therapy with paclitaxel and carboplatin, which is a regimen of ovarian cancer, on a triweekly basis. After five courses of this therapy, the patient remains in remission.
  • Nobutaka Shimizu; Marco A. De Velasco; Tohru Umekawa; Hirotsugu Uemura; Kazuhiro Yoshikawa
    INTERNATIONAL JOURNAL OF UROLOGY WILEY 20 (11) 1136 - 1143 0919-8172 2013/11 [Refereed]
     
    ObjectiveTo evaluate the effect of the Rho kinase inhibitor, hydroxyfasudil, on bladder function in a rat model of HCl-induced chemical cystitis, and to elucidate the possible mechanisms associated with its therapeutic effect.MethodsFemale Sprague-Dawley rats with HCl-induced cystitis were given hydroxyfasudil (10mg/kg, i.p.) for 7 days. Treatment efficacy was determined by comparing bladder function and histopathology to sham and untreated control rats. Bladder function was determined by cystometric analysis. Rho kinase activity was determined by quantitative reverse transcription polymerase chain reaction and signal inhibition of downstream Ras homolog memberA/Rho kinase signaling molecules by western blot and immunohistochemistry.ResultsTreatment with hydroxyfasudil significantly improved bladder intercontraction intervals. Rats treated with hydroxyfasudil also showed a significant reduction of histopathological features associated with cystitis. Western blot and immunohistochemistry findings showed that hydroxyfasudil inhibited downstream molecules of Rho kinase that ameliorated changes associated with HCl-induced chemical cystitis, such as inflammatory cell recruitment and smooth muscle cell proliferation.ConclusionThe findings from the present study suggest a promising therapeutic role for hydroxyfasudil in bladder inflammation associated with cystitis.
  • Masahiro Nozawa; Norio Nonomura; Takeshi Ueda; Kazuo Nishimura; Hiro-Omi Kanayama; Tsuneharu Miki; Tatsuya Nakatani; Yoshihiko Tomita; Haruhito Azuma; Toshiaki Yoshioka; Masao Tsujihata; Hirotsugu Uemura
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY OXFORD UNIV PRESS 43 (11) 1132 - 1138 0368-2811 2013/11 [Refereed]
     
    Objective: The aim of the study was to assess the safety and efficacy of everolimus therapy for advanced renal cell carcinoma in Japanese patients receiving real-world care.Methods: Patients who had been treated with everolimus for advanced renal cell carcinoma at 39 Japanese medical centers between January 2010 and November 2011 were retrospectively investigated to assess adverse events and the time to treatment failure.Results: A total of 180 patients were identified. Their median age was 65 years (range 23-93). The median time to treatment failure was 2.9 months (95% confidence interval 2.4-3.4). The median time to treatment failure was significantly longer in patients with dose modification (4.2 months; 95% confidence interval 3.4-5.0) than in patients without dose modification (1.7 months; 95% confidence interval 1.0-2.3; P < 0.01) after experiencing adverse events. Stomatitis (44%) was the most frequent adverse event, followed by thrombocytopenia (31%), anemia (22%), interstitial pneumonia (22%) and hyperglycemia (17%). Interstitial pneumonia was the most frequent cause of discontinuation in patients who discontinued everolimus due to intolerability regardless of the dose modification status. None of the patients with dose modification of everolimus discontinued everolimus due to thrombocytopenia or leukopenia.Conclusions: The adverse event profile of everolimus may differ between Japanese and Caucasian patients. Dose modification of everolimus might be associated with longer treatment duration in patients with advanced renal cell carcinoma. Further studies are required to clarify this association. Interstitial pneumonia may be difficult to overcome by dose modification.
  • Yasuharu Nagai; Takafumi Minami; Yoshitaka Itami; Yasuyuki Kobayashi; Nobutaka Shimizu; Yutaka Yamamoto; Taiji Hayashi; Masahiro Nozawa; Kazuhiro Yoshimura; Tokumi Ishii; Hirotsugu Uemura
    Hinyokika kiyo. Acta urologica Japonica 59 (10) 693 - 7 0018-1994 2013/10 [Refereed]
     
    We experienced a case of testicular cancer that was successfully treated by salvage chemotherapy comprised of methotrexate, actinomycin D and etoposide (MEA). A 25-year-old man was admitted to our hospital with a diagnosis of stage III B2 (JUA classification) testicular cancer. The patient had multiple lung metastases, and underwent a left orchiectomy. A histopathological examination revealed a choriocarcinoma, embryonal carcinoma, mature teratoma, and a yolk sac tumor. Tumor marker levels were elevated ; human chorionic gonadotropin β was 46 mIU/ml and alpha fetoprotein was 437 ng/ml. Although he was treated post-operatively with two courses of bleomycin, etoposide and cisplatin therapy, four courses of high-dose carboplatin, etoposide and iphosphamide (VIP) therapy, and two courses of CPT-11+ cisplatin therapy, tumor maker levels remained elevated and lung metastases were stable. Accordingly, he received three courses of MEA therapy. MEA therapy is regimen used to treat gestational trophoblastic neoplasia. After MEA therapy, levels of the tumor markers normalized. He then underwent a partial resection of lung and enucleation of lung metastasis by the video assisted thoracoscopic surgery method. Histopathological examination of the lung metastasis revealed only necrotic tissue. Tumor recurrence has not been observed in the 14 months since the MEA therapy.
  • YOSHIMURA Kazuhiro; UEMURA Hirotsugu
    International journal of urology WILEY 20 (8) 744 - 755 0919-8172 2013/08 
    Renal cell carcinoma is the most common malignant tumor originating from the kidney. Compared with other solid tumors, it does not respond to traditional management modalities, such as chemotherapy and radiotherapy. However, it is well known that renal cell carcinoma represents one of the most immune-responsive cancers and several immunotherapeutic strategies have been investigated in the management of renal cell carcinoma with variable degrees of success. The development of immunotherapy with a-interferon or high-dose interleukin-2 is the best established treatment, and is associated with durable disease control. Although the lack of defined antigens in renal cell carcinoma has hindered more specific vaccine development, research regarding vaccination therapy has been of special interest for the treatment of renal cell carcinoma for more than 30 years. At present, there are three types of cell-based vaccines in renal cell carcinoma treatment: autologous tumor-cell vaccines, genetically modified tumor vaccines and dendritic cell-based vaccines. A further type is peptide-based vaccination with tumor-associated antigens as possible targets, such as carbonic anhydrase IX, survivin and telomerase that are overexpressed in renal cell carcinoma. In the present article, we review data from completed clinical trials of vaccine therapy, and discuss future trials to assess the current knowledge and future role of vaccine therapy for renal cell carcinoma in the era of recently developed targeted therapy.
  • Robert J. Motzer; Thomas E. Hutson; David Cella; James Reeves; Robert Hawkins; Jun Guo; Paul Nathan; Michael Staehler; Paul de Souza; Jaime R. Merchan; Ekaterini Boleti; Kate Fife; Jie Jin; Robert Jones; Hirotsugu Uemura; Ugo De Giorgi; Ulrika Harmenberg; Jinwan Wang; Cora N. Sternberg; Keith Deen; Lauren McCann; Michelle D. Hackshaw; Rocco Crescenzo; Lini N. Pandite; Toni K. Choueiri
    NEW ENGLAND JOURNAL OF MEDICINE MASSACHUSETTS MEDICAL SOC 369 (8) 722 - 731 0028-4793 2013/08 [Refereed]
     
    BACKGROUNDPazopanib and sunitinib provided a progression-free survival benefit, as compared with placebo or interferon, in previous phase 3 studies involving patients with metastatic renal-cell carcinoma. This phase 3, randomized trial compared the efficacy and safety of pazopanib and sunitinib as first-line therapy.METHODSWe randomly assigned 1110 patients with clear-cell, metastatic renal-cell carcinoma, in a 1:1 ratio, to receive a continuous dose of pazopanib (800 mg once daily; 557 patients) or sunitinib in 6-week cycles (50 mg once daily for 4 weeks, followed by 2 weeks without treatment; 553 patients). The primary end point was progression-free survival as assessed by independent review, and the study was powered to show the noninferiority of pazopanib versus sunitinib. Secondary end points included overall survival, safety, and quality of life.RESULTSPazopanib was noninferior to sunitinib with respect to progression-free survival (hazard ratio for progression of disease or death from any cause, 1.05; 95% confidence interval [CI], 0.90 to 1.22), meeting the predefined noninferiority margin (upper bound of the 95% confidence interval, <1.25). Overall survival was similar (hazard ratio for death with pazopanib, 0.91; 95% CI, 0.76 to 1.08). Patients treated with sunitinib, as compared with those treated with pazopanib, had a higher incidence of fatigue (63% vs. 55%), the hand-foot syndrome (50% vs. 29%), and thrombocytopenia (78% vs. 41%); patients treated with pazopanib had a higher incidence of increased levels of alanine aminotransferase (60%, vs. 43% with sunitinib). The mean change from baseline in 11 of 14 health-related quality-of-life domains, particularly those related to fatigue or soreness in the mouth, throat, hands, or feet, during the first 6 months of treatment favored pazopanib (P<0.05 for all 11 comparisons).CONCLUSIONSPazopanib and sunitinib have similar efficacy, but the safety and quality-of-life profiles favor pazopanib.
  • Yasuharu Nagai; Nobutaka Shimizu; Takafumi Minami; Yutaka Yamamoto; Taiji Hayashi; Hidenori Tsuji; Masahiro Nozawa; Kazuhiro Yoshimura; Tokumi Ishii; Hirotsugu Uemura
    JOURNAL OF SEXUAL MEDICINE WILEY-BLACKWELL 10 244 - 244 1743-6095 2013/06 [Refereed]
  • Nobutaka Shimizu; Takafumi Minami; Yasuharu Nagai; Yutaka Yamamoto; Taiji Hayashi; Hidenori Tsuji; Masahiro Nozawa; Kazuhiro Yoshimura; Tokumi Ishii; Hirotsugu Uemura
    JOURNAL OF SEXUAL MEDICINE WILEY-BLACKWELL 10 243 - 243 1743-6095 2013/06 [Refereed]
  • Takeshi Ueda; Hirotsugu Uemura; Yoshihiko Tomita; Taiji Tsukamoto; Hiroomi Kanayama; Nobuo Shinohara; Jamal Tarazi; Connie Chen; Sinil Kim; Seiichiro Ozono; Seiji Naito; Hideyuki Akaza
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY OXFORD UNIV PRESS 43 (6) 616 - 628 0368-2811 2013/06 [Refereed]
     
    Axitinib is a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors 1, 2 and 3. The efficacy and safety of axitinib in Japanese patients with metastatic renal cell carcinoma were evaluated.A subgroup analysis was conducted in Japanese patients enrolled in the randomized Phase III trial of axitinib versus sorafenib after failure of one prior systemic therapy for metastatic renal cell carcinoma.Twenty-five (of 361) and 29 (of 362) patients randomized to the axitinib and sorafenib arms, respectively, were Japanese and included in this analysis. Median progression-free survival in Japanese patients was 12.1 months (95 confidence interval 8.6 to not estimable) for axitinib and 4.9 months (95 confidence interval 2.86.6) for sorafenib (hazard ratio 0.390; 95 confidence interval 0.1301.173; stratified one-sided P 0.0401). The objective response rate was 52.0 for axitinib and 3.4 for sorafenib (P 0.0001). The common all-causality adverse events (all grades) in Japanese patients were dysphonia (68), hypertension (64), handfoot syndrome (64) and diarrhea (56) for axitinib, and handfoot syndrome (86), hypertension (62) and diarrhea (52) for sorafenib. The safety profiles of axitinib and sorafenib in Japanese patients were generally similar to those observed in the overall population, with the exceptions of higher incidences of hypertension, dysphonia, handfoot syndrome, hypothyroidism and stomatitis.Axitinib is efficacious and well tolerated in Japanese patients with previously treated metastatic renal cell carcinoma, consistent with the results in the overall population, providing a new targeted therapy for these Japanese patients.
  • Masahiro Nozawa; Isao Hara; Kazuhiro Nagao; Hideyasu Matsuyama; Hirotsugu Uemura
    JOURNAL OF CLINICAL ONCOLOGY AMER SOC CLINICAL ONCOLOGY 31 (15) 0732-183X 2013/05 [Refereed]
  • Nobutaka Shimizu; Koichi Sugimoto; Masahiro Nozawa; Yasuyuki Kobayashi; Yutaka Yamamoto; Takafumi Minami; Taiji Hayashi; Kazuhiro Yoshimura; Tokumi Ishii; Hirotsugu Uemura; Kazuhiro Nose; Tsukasa Nishioka
    LUTS-LOWER URINARY TRACT SYMPTOMS WILEY 5 (2) 69 - 74 1757-5664 2013/05 [Refereed]
     
    Objectives: To study the efficacy of ramelteon for patients with insomnia and nocturia. Methods: Forty-nine patients experiencing insomnia and two or more nocturnal voids were included. The degree of lower urinary tract symptoms and sleep disorders was evaluated using the International Prostate Symptom Score (IPSS), Pittsburg Sleep Quality Index (PSQI) score, and frequency/volume chart (FVC). The patients were treated with ramelteon (8 mg) for four weeks and then reexamined by questionnaire and FVC to evaluate the therapeutic efficacies. Results: The mean IPSS score was 16.1 +/- 6.9 at baseline and 12.4 +/- 7.1 at four weeks. The subject scores for the number of nocturnal voids also decreased significantly from 3.3 +/- 0.9 to 2.9 +/- 1.0. In addition, PSQI scores improved significantly from 7.4 +/- 2.9 to 5.4 +/- 2.8. According to the FVC, the number of nocturnal voids decreased significantly from 3.1 +/- 1.2 at baseline to 2.2 +/- 1.1 at four weeks, and nighttime bladder capacity improved significantly from 181.4 +/- 79.9 to 201.1 +/- 93.7 mL. Conclusion: Ramelteon alleviated nocturia and disturbed sleep in patients with insomnia and nocturia and led to increased nighttime bladder capacity.
  • Yasuyuki Kobayashi; Masahiro Nozawa; Takashi Kikuchi; Mitsuhisa Nishimoto; Nobutaka Shimizu; Yutaka Yamamoto; Takafumi Minami; Taiji Hayashi; Hidenori Tsuji; Kazuhiro Yoshimura; Tokumi Ishii; Hirotsugu Uemura
    Hinyokika kiyo. Acta urologica Japonica 59 (5) 315 - 8 0018-1994 2013/05 [Refereed]
     
    A 61-year-old man visited our department with the complaint ofa palpable hard mass in the penile shaft which showed a significant uptake on fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT). He had undergone a surgery for local invasive esophageal cancer and had received adjuvant chemotherapy. Open biopsy revealed metastases in the carvenous body and the glans of the penis from esophageal squamous cell carcinoma. He died from the cancer 5 months after the biopsy in spite of additional chemotherapy.
  • Atsushi Ochiai; Koji Okihara; Kazumi Kamoi; Takehiro Oikawa; Toru Shimazui; Shin-Ichiro Murayama; Kyoichi Tomita; Tohru Umekawa; Hirotsugu Uemura; Tsuneharu Miki
    BJU INTERNATIONAL WILEY-BLACKWELL 111 (6) 928 - 933 1464-4096 2013/05 [Refereed]
     
    What's known on the subject? and What does the study add? It is known that a prostate cancer gene 3 (PCA3) urine assay is superior to serum PSA level or PSA-related indices for predicting a positive biopsy result in European and US men. This is the first report on PCA3 in a large cohort of Japanese men. The diagnostic value of the PCA3 score in Japanese men was similar to those reported in European and US men. The study concludes that a combination of PSA density and PCA3 score may be useful for selecting patients who could avoid an unnecessary biopsy. Objective To examine the diagnostic performance of the prostate cancer gene 3 (PCA3) score for prostate cancer in Japanese men undergoing prostate biopsy. Patients and Methods This Japanese, multicentre study included 647 Asian men who underwent extended prostate biopsy with elevated prostate-specific antigen (PSA) and/or abnormal digital rectal examination (DRE). Urine samples were collected after DRE. The PCA3 score was determined using a PROGENSA PCA3 assay and correlated with biopsy outcome. Its diagnostic accuracy was compared with that of serum PSA level, prostate volume (PV), PSA density (PSAD), and free/total PSA ratio (f/t PSA). Results A total of 633 urine samples were successfully analysed (the informative rate was 98%). Median PSA was 7.6ng/mL. Biopsy revealed cancer in 264 men (41.7%). The PCA3 score for men with prostate cancer was significantly higher than that for men with negative biopsies (median PCA3 score: 49 vs. 18; P < 0.001). The rate of positive biopsy was 16.0% in men with a PCA3 score of <20 and 60.6% in those with a PCA3 score of 50. Using a PCA3 score threshold of 35, sensitivity and specificity were 66.5 and 71.6%, respectively. The area under the curve of the PCA3 score was significantly higher than that of the f/t PSA in men with PSA 410ng/mL (0.742 vs 0.647; P < 0.05). In men with PSAD < 0.15 and PCA3 < 20, only three (4.2%) out of 72 men had prostate cancer. Conclusions The PCA3 score was significantly superior to f/t PSA in predicting a positive biopsy result for prostate cancer in Japanese men with PSA 410ng/mL. The combination of PSAD and PCA3 score may be useful for selecting patients who could avoid an unnecessary biopsy.
  • Marco A. De Velasco; Yutaka Yamamoto; Yuji Hatanaka; Yurie Kura; Naomi Ando; Emiko Fukushima; Masahiro Nozawa; Nobutaka Shimizu; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 73 (8) 0008-5472 2013/04 [Refereed]
  • Marco A. De Velasco; Yurie Kura; Naomi Ando; Emiko Fukushima; Yuji Hatanaka; Yutaka Yamamoto; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 73 (8) 0008-5472 2013/04 [Refereed]
  • K. Yoshimura; T. Minami; M. Nozawa; H. Uemura
    BRITISH JOURNAL OF CANCER NATURE PUBLISHING GROUP 108 (6) 1260 - 1266 0007-0920 2013/04 [Refereed]
     
    Background: It is well known that renal cell carcinoma (RCC) represents one of the most immune-responsive cancers. Although the lack of defined antigens in RCC has hindered more specific vaccine development, research regarding vaccination therapy has been of special interest for the treatment of RCC for more than 30 years. Methods: To evaluate the safety of the vascular endothelial growth factor receptor 1 (VEGFR1) peptide vaccination and its clinical outcomes, data from 18 metastatic RCC (mRCC) patients treated with VEGFR1 vaccine were collected. Toxicity assessments were performed. Clinical outcomes included assessment using CT scanning, magnetic resonance imaging or X-ray examination in accordance with the WHO Response Evaluation Criteria in Solid Tumors. Results: No patient showed any toxicities of grade 3 or greater. Of the 18 patients, 2 patients showed a partial response during treatment. Stable disease for more than 5 months was observed in eight patients with a median duration of 16.5 months (4-32 months). At the time of the analysis in this study, six patients were alive with a median follow-up of 30 months (26-36 months). Conclusion: These results suggest that VEGFR1 peptide vaccine is safe and is recommended for further trials for patients with mRCC.
  • Masatoshi Eto; Tomomi Kamba; Hideaki Miyake; Masato Fujisawa; Takao Kamai; Hirotsugu Uemura; Taiji Tsukamoto; Haruhito Azuma; Akio Matsubara; Kazuo Nishimura; Tsuyoshi Nakamura; Osamu Ogawa; Seiji Naito
    EUROPEAN UROLOGY ELSEVIER 63 (4) 745 - 752 0302-2838 2013/04 [Refereed]
     
    Background: In our 2007 retrospective study, we reported that single nucleotide polymorphisms (SNPs) in the signal transducer and activator of transcription 3 (acute-phase response factor) (STAT3) gene were significantly associated with better response to interferon (IFN)-alpha in patients with metastatic renal cell carcinoma (mRCC).Objective: To prospectively confirm those results, the Japan Immunotherapy SNPs-Study Group for Kidney Cancer conducted this trial.Design, setting, and participants: In this multicenter, prospective study, 203 eligible patients were enrolled. We evaluated the correlation between the antitumor effects of IFN-alpha and 11 SNPs (STAT3-2, STAT3-0, SOCS3-1, IL4R-34, PTGS1-3, PTGS1-4, PTGS1-5, PTGS2-12, IRF2-67, ICSBP-38, and TAP2-5) in eight genes in 180 patients who received IFN-alpha for >12 wk.Interventions: Patients were treated with three doses per week of IFN-alpha 5 million IU.Outcome measurements and statistical analysis: We analyzed the association of response to IFN-alpha and overall survival (OS) with genetic polymorphisms using a chi-square test and a logistic regression model.Results and limitations: The response rate of IFN-alpha was 13.8% (28 of 203 patients; 9 complete responses [CRs], 19 partial responses [PRs]). The CR rate of 4.4% was higher than we expected. Response to IFN-alpha was not associated with any of the 11 SNPs examined. However, when we assessed patients with CR, PR, and stable disease >24 wk as a group representing those with clinical response, a significant association was observed between STAT3-2 (rs1905341) and the clinical response of IFN-alpha (p = 0.039). Namely, C/C genotype of STAT3-2 was significantly associated with the clinical response of IFN-alpha and OS. These results were generated in Japanese patients and should be studied in other ethnic groups.Conclusions: This is the first prospective study demonstrating that a STAT3 polymorphism can be a predictive marker for treatment with IFN-alpha for patients with mRCC. (c) 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.
  • Masahiro Nozawa; Takashi Kikuchi; Mitsutoshi Nishimoto; Yasuyuki Kobayashi; Hirotsugu Uemura
    JOURNAL OF CLINICAL ONCOLOGY AMER SOC CLINICAL ONCOLOGY 31 (6) 0732-183X 2013/02 [Refereed]
  • Toru Shimazui; Kazuhiro Yoshikawa; Jun Miyazaki; Takahiro Kojima; Hiromu Inai; Satoshi Ando; Hirotsugu Uemura; Kazuhiko Uchida; Hiroyuki Nishiyama
    INTERNATIONAL JOURNAL OF ONCOLOGY SPANDIDOS PUBL LTD 42 (2) 543 - 548 1019-6439 2013/02 [Refereed]
     
    p16(INK4a) (p16), a key molecule in bladder tumor development, inhibits the activities of cyclin-dependent kinases (CDKs) and maintains the retinoblastoma protein (pRb) in its active hypophosphorylated state. Following the finding that the p16 antitumor peptide dramatically inhibits the growth of aggressive leukemia/lymphoma through the restoration of p16 function using the Wr-T peptide transporter system, in this study, we developed a systemic therapy using mouse-p16 peptide (m-p16) in subcutaneous p16-null mouse bladder tumors. In vitro analysis showed that the growth of p16-null bladder tumor cells and the hyperphosphorylation of their pRbs were inhibited by p16 transduction in a concentration-dependent manner. In an animal model, p16-null MBT-2 cells were injected subcutaneously into KSN/SKC nude mice. The systemic delivery of the m-p16 peptide using Wr-T by cardiac injection significantly inhibited the growth of solid MBT-2 tumors compared with the control phosphate-buffered saline (PBS) injection. Histological examination by TUNEL staining revealed that apoptosis was increased and pRb phosphorylation was inhibited. Thus, the systemic peptide delivery of p16 restores the hypophosphorylation of pRb and may be a useful tool for the treatment of bladder tumors.
  • Impact of initial time to prostate-specific antigen nadir on survival in prostate cancer with bone metastasis initially treated with maximum androgen blockade therapy
    Yamamoto Y; Nozawa M; Itami Y; Kobayashi Y; Saito N; Shimizu N; Minami T; Hayashi T; Tuji H; Yoshimura K; Ishii T; Uemura H
    J Cancer Res Ther 2013 [Refereed]
  • Nobutaka Shimizu; Yasuharu Nagai; Yutaka Yamamoto; Takafumi Minami; Taiji Hayashi; Hidenori Tsuji; Masahiro Nozawa; Kazuhiro Yoshimura; Tokumi Ishii; Hirotsugu Uemura; Takashi Oki; Koichi Sugimoto; Kazuhiro Nose; Tsukasa Nishioka
    Nature and science of sleep 5 7 - 13 2013 [Refereed]
     
    OBJECTIVES: This study examined the association between sleep disorders and lower urinary tract symptoms in patients who had visited urology departments. METHODS: This was an independent cross-sectional, observational study. Outpatients who had visited the urology departments at the Kinki University School of Medicine or the Sakai Hospital, Kinki University School of Medicine, between August 2011 and January 2012 were assessed using the Athens Insomnia Scale and the International Prostate Symptom Score. RESULTS: In total, 1174 patients (mean age, 65.7 ± 13.7 years), with 895 men (67.1 ± 13.2 years old) and 279 women (61.4 ± 14.6 years old), were included in the study. Approximately half of these patients were suspected of having a sleep disorder. With regard to the International Prostate Symptom Score subscores, a significant increase in the risk for suspected sleep disorders was observed among patients with a post-micturition symptom (the feeling of incomplete emptying) subscore of ≥1 (a 2.3-fold increase), a storage symptom (daytime frequency + urgency + nocturia) subscore of ≥5 (a 2.7-fold increase), a voiding symptom (intermittency + slow stream + hesitancy) subscore of ≥2 (a 2.6-fold increase), and a nocturia subscore of ≥2 (a 1.9-fold increase). CONCLUSION: The results demonstrated that the risk factors for sleep disorders could also include voiding, post-micturition, and storage symptoms, in addition to nocturia.
  • Koichi Sugimoto; Nobutaka Shimizu; Takashi Oki; Kazuhiro Nose; Tsukasa Nishioka; Shogo Adomi; Takayuki Ohzeki; Atsunobu Esa; Hirotsugu Uemura
    Cancer management and research 5 85 - 9 2013 [Refereed]
     
    BACKGROUND: This study was undertaken to investigate the growth rate and clinical outcome of patients with a small renal mass (SRM) after delayed surgery. METHODS: We reviewed the clinical records of 34 patients with SRMs ≤ 4 cm at diagnosis, who underwent delayed surgical intervention during surveillance from January 2000 to December 2011. Radiographic evaluations using computed tomography (CT) scan and magnetic resonance imaging (MRI) were performed at least every 6 months, and the tumor size was determined at least twice. RESULTS: The mean follow-up time was 26.6 ± 18.6 months and mean tumor doubling time was 23.4 ± 16.0 months. Histopathological analysis revealed that 32 of the 34 patients were malignant in pT1aN0M0. Only one patient showed tumor recurrence, who subsequently died due to tumor progression. CONCLUSION: The growth rate of the small renal mass was slow in the majority of our patients. Delayed intervention does not have a detrimental effect on cancer-specific outcomes.
  • Koichi Sugimoto; Nobutaka Shimizu; Kazuhiro Nose; Hideo Tahara; Masaaki Imanishi; Tsukasa Nishioka; Atsunobu Esa; Hiroshi Kajikawa; Hirotsugu Uemura
    JOURNAL OF CANCER IVYSPRING INT PUBL 4 (6) 514 - 518 1837-9664 2013 [Refereed]
     
    Background: This study was undertaken to investigate the growth rate and clinical outcome of patients with a small renal mass (SRM) after delayed surgery versus immediate surgery.Methods: We reviewed the clinical records of 328 patients with SRM <= 4cm at diagnosis, who underwent delayed or immediate surgical intervention from January 2000 to December 2011. Radiographic evaluation using CT scan and MRI were performed at least every 6 months and the tumor size was determined at least twice in the delayed surgery group.Results: A total of 292 RCC patients with pT1aN0M0 were identified; among them, 32 patients had been managed with delayed surgery intervention. No statistically significant difference was observed in overall survival rate (OSR) and cancer recurrence-free rate (CRFR). But cancer-specific survival rate (CSSR) was significantly lower in the delayed surgery group (p= 0.0002).Conclusions: The overall survival rate of delayed surgery was not inferior compared with that after immediate surgery. Delayed surgery intervention for SRMs is a treatment option in the current study.
  • Koichi Sugimoto; Nobutaka Shimizu; Naoki Matsumura; Takashi Oki; Kazuhiro Nose; Tsukasa Nishioka; Hirotsugu Uemura
    Infection and drug resistance 6 83 - 6 2013 [Refereed]
     
    BACKGROUND: Because the use of procalcitonin has been advocated as a marker of bacterial infection, this study was carried out to determine the usefulness of serum PCT as an early marker to decide upon intervention for urinary tract infection. METHODS: The subjects were 68 patients with urinary tract infection (UTI) in whom we measured serum procalcitonin concentration at the start of treatment. RESULTS: There were 47 patients with nonobstructed UTI and 21 with obstructed UTI. All patients with obstructed UTI were subjected to intervention. There were significant differences in procalcitonin, white blood cells, and creatinine levels between patients with nonobstructed and obstructed UTI (P < 0.05). CONCLUSION: Although this retrospective study comprised a small number of patients, we found that procalcitonin was a useful marker to decide upon urinary intervention.
  • Nobutaka Shimizu; Masahiro Nozawa; Koichi Sugimoto; Yutaka Yamamoto; Takafumi Minami; Taiji Hayashi; Kazuhiro Yoshimura; Tokumi Ishii; Hirotsugu Uemura
    Research and reports in urology 5 113 - 9 2013 [Refereed]
     
    OBJECTIVES: This study was conducted to examine the therapeutic efficacy and anti-inflammatory effect of ramelteon in elderly patients with insomnia associated with lower urinary tract symptoms (LUTS), who visited our urology department. METHODS: The study included 115 patients (102 men, 13 women) who scored ≥4 on the Athens Insomnia Scale and who wished to receive treatment. The assessment scales for therapeutic efficacy included the International Prostate Symptom Score (IPSS) for LUTS and the Insomnia Severity Index (ISI) for sleep disorders. The high-sensitivity C-reactive protein (hs-CRP) test was used to an objective assessment. The patients were treated with ramelteon (8 mg/day) for an average of 10 weeks and were then reexamined using the questionnaires and hs-CRP test to evaluate therapeutic efficacy. RESULTS: IPSS total scores declined significantly from 11.39 ± 8.78 to 9.4 ± 7.72. ISI total scores improved significantly from 11.6 ± 5.2 to 9.2 ± 5.3 (P < 0.0001). The levels of hs-CRP decreased significantly from 0.082 (standard deviation [SD] upper limit, 0.222; SD lower limit, -0.059) to 0.06 (SD upper limit, 0.152; SD lower limit, -0.032). The ISI scores ≥ 10 (n = 51) showed a weak correlation with the hs-CRP levels. CONCLUSION: Ramelteon had a systemic anti-inflammatory effect and improved sleep disorders and LUTS, suggesting that it may be a useful treatment for patients with LUTS-associated insomnia.
  • Masahiro Nozawa; Hirotsugu Uemura
    Translational andrology and urology 1 (4) 202 - 3 2012/12 [Refereed]
  • Masahiro Nozawa; Hirotsugu Uemura
    Hinyokika kiyo. Acta urologica Japonica 58 (11) 655 - 7 0018-1994 2012/11 [Refereed]
     
    Targeted therapy has survival benefit for patients with advanced renal cell carcinoma. However, intolerability often causes discontinuation of treatment. Therefore management of adverse events and maintenance of treatment duration as long as possible are absolutely essential for patient care. Hypertension is a common adverse event of vascular endothelial growth factor receptor (VEGFR) inhibitors. General symptoms such as fatigue or asthenia and gastrointestinal disorders including diarrhea, nausea, and anorexia are also frequently produced by VEGFR inhibitors as well as other targeted agents under development. Development of a new drug which does not cause any severe adverse event may be an ultimate strategy against adverse events of current targeted agents. Here we review the adverse-event profiles of targeted therapies being developed, including axitinib, tivozanib, dovitinib, AS1411, vorinostat, AMG386, BMS-936558, carfilzomib, IMA901, and AGS-003, for renal cell carcinoma.
  • Hirotsugu Uemura
    Nihon rinsho. Japanese journal of clinical medicine 70 Suppl 8 480 - 5 0047-1852 2012/11 [Refereed]
  • 植村 天受; 松山 豪泰; 井手 久満
    外来癌化学療法 メディカルレビュー社 3 (3) 209 - 220 2185-0372 2012/10
  • Masahiro Nozawa; Yutaka Yamamoto; Takafumi Minami; Nobutaka Shimizu; Yuji Hatanaka; Hidenori Tsuji; Hirotsugu Uemura
    BJU INTERNATIONAL WILEY 110 (6B) E228 - E234 1464-4096 2012/09 [Refereed]
     
    What's known on the subject? and What does the study add?Targeted agents with a similar or different target molecule are often used sequentially in the treatment of metastatic RCC. Two tyrosine kinase inhibitors, sorafenib and sunitinib, have been reported to show little cross-resistance, when used sequentially. In addition, a recent report showed that sunitinib rechallenge could potentially benefit selected patients.This case series shows that patients once refractory to sorafenib could regain disease control on rechallenge with sorafenib during sequential treatment. Outcomes of the sorafenib rechallenge were not significantly affected by the response to the initial sorafenib treatment or by the duration of intervening treatments between first sorafenib and rechallenge.OBJECTIVETo investigate clinical outcomes of sorafenib rechallenge during sequential therapy for patients with metastatic renal cell carcinoma (RCC).PATIENTS AND METHODSPatients with metastatic RCC who received sorafenib rechallenge after failed treatment first with sorafenib and subsequently with other agents, were retrospectively reviewed for patient characteristics, best response, progression-free survival (PFS), and adverse events (AEs).RESULTSOf the 14 patients who received sorafenib rechallenge, 12 were evaluable for response. Eleven patients had previously undergone nephrectomy, and 10 had previously received systemic therapy, mostly interferon-a (nine patients) and interleukin-2 (six patients), with a median duration of 9 months.The best responses after the first sorafenib therapy were partial response (PR) in two patients, stable disease (SD) in seven, and progressive disease (PD) in two. The median PFS was 5.7 months. Initial sorafenib therapy was discontinued because of PD in eight patients and AEs in four patients.Rechallenge with sorafenib was undertaken after a 7.6 month median interval from the initial sorafenib challenge. Eight patients achieved SD on sorafenib rechallenge and median PFS was 5.4 (95% confidence interval, 3.8 -7.0) months.The outcome of the sorafenib rechallenge was not significantly affected by the response to the initial sorafenib treatment or by the duration of treatments received between first sorafenib and rechallenge.No severe AE was newly observed on the rechallenge.CONCLUSIONIn the systemic treatment of advanced RCC, it was suggested that patients once refractory to sorafenib could regain disease control on rechallenge with sorafenib during sequential treatment.
  • 食事誘導性レプチンは前立腺癌の進行に寄与する(Diet-induced leptin contributes to prostate cancer progression)
    De Velasco Marco A.; Hatanaka Yuji; Yamamoto Yutaka; Yoshimura Kazuhiro; Shimizu Nobutaka; Nozawa Masahiro; Yoshikawa Kazuhiro; Nishio Kazuto; Uemura Hirotsugu
    日本癌学会総会記事 日本癌学会 71回 430 - 430 0546-0476 2012/08 [Refereed]
  • Yoshitaka Itami; Yasuharu Nagai; Yasuyuki Kobayashi; Nobutaka Shimizu; Yutaka Yamamoto; Takafumi Minami; Taiji Hayashi; Masahiro Nozawa; Kazuhiro Yoshimura; Tokumi Ishii; Hirotsugu Uemura
    Hinyokika kiyo. Acta urologica Japonica 58 (7) 349 - 53 0018-1994 2012/07 [Refereed]
     
    A 70-year-old man with the complaint of macrohematuria and hematospermia was admitted to our hospital for further examination of a cystic formation of the right seminal vesicle, 3.6 cm in diameter, detected by magnetic resonance imaging(MRI). Cystoscopy revealed no remarkable change, but urine cytology was class III. The serum concentration of prostate specific antigen (PSA) was within the normal range of 1.83 ng/ml. Transperineal needle biopsy of the prostate and cystic tumor of the seminal vesicle revealed adenocarcinoma of the prostate and seminal vesicle, but immunostaining for PSA was negative, so we diagnosed the case as primary adenocarcinoma of the seminal vesicle. Bloody fluid of the cyst was obtained by transperineal aspiration, but no cancer cells were detected by cytological examination. Total prostatectomy was performed, and pathological findings was infiltration of prostate cancer into the seminal vesicle (pT3b) because immunostaining of the PSA was positive.
  • Homma Y; Kakizaki H; Smith JA Jr; Namiki S; Arai Y; Tomita Y; Uzzo R; Tsuchiya N; Takahashi M; Ichikawa T; Quek ML; Uemura H; Mizokami A; Kakizaki H; Steers WD; Gotoh M; Ogawa T; Chancellor MB; Yamamoto S; Takahashi S; Ichihara K
    International journal of urology : official journal of the Japanese Urological Association 19 (4) 374 - 385 0919-8172 2012/04 [Refereed]
  • Teruo Inamoto; Akira Tsujimura; Norio Nonomura; Hauhito Azuma; Hironobu Akino; Naoki Oguchi; Yasuhide Kitagawa; Naoki Segawa; Satoshi Tamada; Nobutaka Shimizu; Akihiko Watanabe; Mitsuyoshi Urashima; Akihiko Okuyama; Yoji Katsuoka; Hirotsugu Uemura; Tatsuya Nakatani; Mikio Namiki; Hideki Fuse; Tadashi Matsuda; Yokoyama Osamu
    JOURNAL OF UROLOGY ELSEVIER SCIENCE INC 187 (4) E506 - E506 0022-5347 2012/04 [Refereed]
  • T. Ishii; M. Yasuda; Y. Itami; T. Hayashi; H. Uemura; K. Nose; T. Nishioka
    TRANSPLANTATION PROCEEDINGS ELSEVIER SCIENCE INC 44 (3) 638 - 641 0041-1345 2012/04 [Refereed]
     
    Background. The renoprotective effects of angiotensin II type 1 receptor blockers (ARBs) have been demonstrated in a number of clinical studies, but there are few evaluations of long-term ARB treatment. We measured blood pressure, urine protein, and estimated glomerular filtration rate (eGFR) among patients under long-term (up to 9 years) treatment with candesartan cilexetil to evaluate its safety and effectiveness to protect renal graft function. Methods. This study of 41 patients (31 male and 10 female) who presented with proteinuria and hypertension (blood pressure >140/90 mm Hg) after receiving a renal graft. Their serum creatinine level at baseline was 1.51 +/- 0.53 mg/dL. Cyclosporine or tacrolimus were concomitantly prescribed for 18 (43.9%) and 22 (53.7%) subjects, respectively. The ARB treatment period was >= 12 months (up to 9 years, mean 4.8 years). Combination with other antihypertensive drugs (calcium antagonists) was necessary in 14/41 subjects (34.1%). Results. Significant declines in blood pressure were observed during the treatment period; blood pressure reduction target (blood pressure <130/80 mm Hg) was met in 56.1% for systolic and 68.3% for diastolic pressure. No significant increase in serum creatinine level or eGFR was observed. Urinary protein was reduced to negative or marginal in 63.4% of the subjects, demonstrating a significant decrease. Conclusions. Candesartan cilexetil was considered to be safe even for long-term treatment in renal transplant patients, and effective to protect renal graft function.
  • Mitsuyama Kodama; Marco A. De Velasco; Yutaka Yamamoto; Nobutaka Shimizu; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 72 0008-5472 2012/04 [Refereed]
  • Yutaka Yamamoto; Marco A. De Velasco; Yuji Hatanaka; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Mitsumasa Kodama; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 72 0008-5472 2012/04 [Refereed]
  • Yasuyuki Kobayashi; Marco A. De Velasco; Yuji Hatanaka; Yutaka Yamamoto; Motoyoshi Tanaka; Nozawa Masahiro; Nobutaka Shimizu; Kazuhiro Yoshimura; Mitsuyama Kodama; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 72 0008-5472 2012/04 [Refereed]
  • Kazuhiro Yoshimura; Marco A. De Velasco; Yuji Hatanaka; Yutaka Yamamoto; Mitsumasa Kodama; Motoyoshi Tanaka; Nobutaka Shimizu; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 72 0008-5472 2012/04 [Refereed]
  • Hideyasu Matsuyama; Masahiro Nozawa; Takeshi Inagaki; Kazuhiro Nagao; Isao Hara; Hirotsugu Uemura
    JOURNAL OF UROLOGY ELSEVIER SCIENCE INC 187 (4) E312 - E312 0022-5347 2012/04 [Refereed]
  • Yuji Hatanaka; Marco A. De Velasco; Yurie Kura; Yuji Yamamoto; Mitsumasa Kodama; Masahiro Nozawa; Nobutaka Shimizu; Kazuhiro Yoshimura; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 72 0008-5472 2012/04 [Refereed]
  • Yoshitaka Itami; Nobutaka Shimizu; Taiji Hayashi; Yasuharu Nagai; Yasuyuki Kobayashi; Yutaka Yamamoto; Takafumi Minami; Masahiro Nozawa; Kazuhiro Yoshimura; Tokumi Ishii; Hirotsugu Uemura
    Hinyokika kiyo. Acta urologica Japonica 58 (4) 203 - 7 0018-1994 2012/04 [Refereed]
     
    A 63-year-old man visited our hospital with body weight loss. Laboratory examination revealed a high serum level of carbohydrate antigen 19-9 (CA19-9) and LDH. There were no abnormal findings in the gastrointestinal tract. Enhanced abdominal computed tomography (CT) revealed a renal tumor, 5×3 cm in diameter, in the right lower pole and multiple lymph node swelling. The right renal tumor was not a typical renal cell carcinoma, so we considered the presence of bellini duct carcinoma and renal pelvis carcinoma, we performed right nephroureterectomy. Histopathological diagnosis was urothelial carcinoma with glandular differentiation of the renal pelvis. Post operation chemotherapy with GC (gemcitabine/cisplatin: 3-cycle), MVAC (methotrexate/vinblastine/doxorubicin/cisplatin: 1-cycle), TS-1 + CBDCA (tegafur-gimeracil-oteracil potassium/carboplatin: 3-cycle) was performed for lymph node metastasis, but he died of cachexia 18 months after operation.
  • T. Hayashi; K. Nose; M. Nozawa; T. Nishioka; K. Yoshimura; T. Ishii; H. Uemura
    TRANSPLANTATION PROCEEDINGS ELSEVIER SCIENCE INC 44 (1) 30 - 31 0041-1345 2012/01 
    Objective. Laparoscopic living donor nephrectomy (LLDN) has become the standard procedure for renal transplantation. This technique is considered less invasive for the donor, allowing lower postoperative analgesic requirements and a faster return to daily activities. In Japan, 1123 renal transplantation were performed in 2009. And, almost 83% were living related procedures. The aim of this study was a retrospective assessment of the safety and outcomes of LLDN on renal transplantations. Material and methods. We retrospectively analyzed the intraoperative data and surgical complications for 21 patients who underwent retroperitoneoscopic living donor nephrectomy between June 2009 and March 2011. Results. LLDN was successfully completed in all patients, without conversion to open surgery. Mean operative time was 243.5 +/- 46.0 minutes with an average blood loss of 46.0 +/- 46.1 mL. Warm ischemic time was 2.1 +/- 0.62 minutes. Hospital stay was 11.1 +/- 2.7 days. There were no major donor complications. One patient presented a wound infection responding to conservative treatment. Conclusions. LLDN is a safe effective procedure. The vascular stapler is useful to manage the renal vessels.
  • Yoshitaka Saitou; Yuji Hatanaka; Masaaki Imanishi; Takayuki Ohzeki; Kiyoshi Hashimoto; Koichi Sugimoto; Atsunobu Esa; Hiroshi Kajikawa; Muneo Yasuda; Yutaka Yamamoto; Hirotsugu Uemura
    Hinyokika kiyo. Acta urologica Japonica 58 (1) 7 - 11 0018-1994 2012/01 [Refereed]
     
    The prognostic factor was retrospectively analyzed in 52 castration-resistant prostate cancer treated with docetaxel (DTX) in our institutions from April, 2006 to August, 2009. The treatment outcomes were decided with prostate specific antigen (PSA) progression-free survival and overall survival. These were calculated by Kaplan-Meier methods and tested with Log-rank test. Median PSA progression-free survival was 8.8 months and median overall survival was 24.1 months. Prognostic factors on PSA progression were PSA value before DTX treatment and rate of PSA decrement after DTX treatment. Prognostic factors on overall survival were Gleason score (GS), PSA value before DTX treatment, rate of PSA decrement after DTX treatment and positive of bone metastasis in Log-rank test. Odds ratio of PSA ≧20 ng/ml before DTX treatment was 2.99 and PSA decreasing rate < 30% was 3.65. These were statistically significant (p < 0.001) risk factors in the overall survival.
  • Marco A De Velasco; Hirotsugu Uemura
    Advances in urology 2012 419348 - 419348 1687-6369 2012 [Refereed]
     
    Knowledge gained from the identification of genetic and epigenetic alterations that contribute to the progression of prostate cancer in humans is now being implemented in the development of functionally relevant translational models. GEM (genetically modified mouse) models are being developed to incorporate the same molecular defects associated with human prostate cancer. Haploinsufficiency is common in prostate cancer and homozygous loss of PTEN is strongly correlated with advanced disease. In this paper, we discuss the evolution of the PTEN knockout mouse and the cooperation between PTEN and other genetic alterations in tumor development and progression. Additionally, we will outline key points that make these models key players in the development of personalized medicine, as potential tools for target and biomarker development and validation as well as models for drug discovery.
  • Hirotsugu Uemura; Colleen Nelson; Jack A Schalken; Laurence Klotz
    Advances in urology 2012 298105 - 298105 1687-6369 2012 [Refereed]
  • Hiroko Okutsu; Seiji Matsumoto; Akiyoshi Ohtake; Masanori Suzuki; Shuichi Sato; Masao Sasamata; Hirotsugu Uemura
    JOURNAL OF UROLOGY LIPPINCOTT WILLIAMS & WILKINS 186 (6) 2470 - 2477 0022-5347 2011/12 [Refereed]
     
    Purpose: Decreased bladder blood flow was the subject of a recent study as a pathophysiological cause of bladder overactivity. We developed a rat model of bladder over distention/emptying induced bladder overactivity and investigated the effect of the alpha(1)-adrenoceptor antagonist tamsulosin on bladder blood flow and bladder function in this model.Materials and Methods: The bladder was distended with 2 ml saline using anesthesia for 2 hours (over distention) and then emptied. Bladder blood flow was measured using a perfusion imager. Micturition behavior and parameters were observed using a metabolic cage and a cystometry method, respectively, from 2 hours after bladder emptying. After model establishment was confirmed we examined the participation of afferent C-fibers and the effects of tamsulosin in rats pretreated with capsaicin (Sigma-Aldrich (R)) (125 mg/kg) and tamsulosin (1 mu g/kg per hour), respectively, using a metabolic cage.Results: Decreased bladder blood flow was observed upon over distention with partial recovery at emptying. Bladder over distention/emptying increased micturition frequency and decreased mean voided volume in the micturition recording study, and decreased the intercontraction interval and voided volume without affecting micturition pressure, threshold pressure or post-void residual volume in the cystometry study. Capsaicin pretreatment did not affect bladder overactivity. However, 1-week continuous treatment with tamsulosin increased bladder blood flow after bladder emptying, resulting in decreased micturition frequency and increased voided volume.Conclusions: Bladder over distention/emptying induced bladder blood flow decrease/partial recovery and caused bladder overactivity via a mechanism other than capsaicin sensitive C-fiber activation. Findings in tamsulosin treated rats confirmed the potency of tamsulosin to increase bladder blood flow and ameliorate bladder overactivity.
  • Brian I. Rini; Bernard Escudier; Piotr Tomczak; Andrey Kaprin; Cezary Szczylik; Thomas E. Hutson; M. Dror Michaelson; Vera A. Gorbunova; Martin E. Gore; Igor G. Rusakov; Sylvie Negrier; Yen-Chuan Ou; Daniel Castellano; Ho Yeong Lim; Hirotsugu Uemura; Jamal Tarazi; David Cella; Connie Chen; Brad Rosbrook; Sinil Kim; Robert J. Motzer
    LANCET ELSEVIER SCIENCE INC 378 (9807) 1931 - 1939 0140-6736 2011/12 [Refereed]
     
    Background The treatment of advanced renal cell carcinoma has been revolutionised by targeted therapy with drugs that block angiogenesis. So far, no phase 3 randomised trials comparing the effectiveness of one targeted agent against another have been reported. We did a randomised phase 3 study comparing axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor (VEGF) receptors, with sorafenib, an approved VEGF receptor inhibitor, as second-line therapy in patients with metastatic renal cell cancer.Methods We included patients coming from 175 sites (hospitals and outpatient clinics) in 22 countries aged 18 years or older with confirmed renal clear-cell carcinoma who progressed despite first-line therapy containing sunitinib, bevacizumab plus interferon-alfa, temsirolimus, or cytokines. Patients were stratified according to Eastern Cooperative Oncology Group performance status and type of previous treatment and then randomly assigned (1: 1) to either axitinib (5 mg twice daily) or sorafenib (400 mg twice daily). Axitinib dose increases to 7 mg and then to 10 mg, twice daily, were allowed for those patients without hypertension or adverse reactions above grade 2. Participants were not masked to study treatment. The primary endpoint was progression-free survival (PFS) and was assessed by a masked, independent radiology review and analysed by intention to treat. This trial was registered on ClinicalTrials.gov, number NCT00678392.Findings A total of 723 patients were enrolled and randomly assigned to receive axitinib (n=361) or sorafenib (n=362). The median PFS was 6.7 months with axitinib compared to 4.7 months with sorafenib (hazard ratio 0.665; 95% CI 0.544-0.812; one-sided p<0.0001). Treatment was discontinued because of toxic effects in 14 (4%) of 359 patients treated with axitinib and 29 (8%) of 355 patients treated with sorafenib. The most common adverse events were diarrhoea, hypertension, and fatigue in the axitinib arm, and diarrhoea, palmar-plantar erythrodysaesthesia, and alopecia in the sorafenib arm.Interpretation Axitinib resulted in significantly longer PFS compared with sorafenib. Axitinib is a treatment option for second-line therapy of advanced renal cell carcinoma.
  • Yoshihiko Tomita; Hirotsugu Uemura; Hiroyuki Fujimoto; Hiro-omi Kanayama; Nobuo Shinohara; Hayakazu Nakazawa; Keiji Imai; Yoshiko Umeyama; Seiichiro Ozono; Seiji Naito; Hideyuki Akaza
    EUROPEAN JOURNAL OF CANCER ELSEVIER SCI LTD 47 (17) 2592 - 2602 0959-8049 2011/11 [Refereed]
     
    Background: Axitinib (AG-013736) is an oral, selective and potent inhibitor of vascular endothelial growth factor receptors (VEGFR)-1, 2 and 3. This phase II study investigated axitinib efficacy, safety and biomarkers in Japanese patients with cytokine-refractory metastatic renal cell carcinoma (mRCC).Patients and methods: In an open-label, multicentre study, 64 patients received an axitinib starting dose of 5 mg twice daily.Results: Objective response rate (ORR) was 50.0% and median progression-free survival (PFS) was 11.0 months per independent review committee. Common treatment-related adverse events were hypertension (84%; 70% grade >= 3), hand foot syndrome (75%; 22% grade >= 3) and diarrhoea (64%; 5% grade >= 3). Eighteen patients (28%) developed proteinuria >= 2 g/24 h and required dose reduction or treatment interruption/discontinuation. Proteinuria was a major cause for treatment discontinuation. Baseline urine protein levels were associated with development of proteinuria >= 2 g/24 h (hazard ratio [HR] = 5.457, P = 0.0035 in patients with baseline proteinuria >= 1+ versus <1+). Baseline urine protein levels correlated more strongly with axitinib-related proteinuria than other baseline renal function test values or blood pressure. Patients with greater decreases in soluble VEGFR-2 concentrations had significantly higher ORR and longer PFS than those with smaller decreases (ORR: 64.5% versus 37.5%, P = 0.045; median PFS: 12.9 months versus 9.2 months, HR = 0.42, P = 0.01).Conclusions: Axitinib showed significant antitumour activity and was well tolerated in Japanese mRCC patients. Baseline proteinuria and soluble VEGFR-2 levels may be key indicators of axitinib-induced proteinuria and efficacy, respectively. (C) 2011 Elsevier Ltd. All rights reserved.
  • Taiji Hayashi; Masahiro Nozawa; Kazuhiro Nose; Kazuhiro Yoshimura; Tokumi Ishii; Hirotsugu Uemura
    JOURNAL OF ENDOUROLOGY MARY ANN LIEBERT INC 25 A214 - A214 0892-7790 2011/11 [Refereed]
  • Masahiro Nozawa; Yasuharu Nagai; Yoshitaka Itami; Yasuyuki Kobayashi; Taiji Hayashi; Kazuhiro Yoshimura; Hirotsugu Uemura
    JOURNAL OF ENDOUROLOGY MARY ANN LIEBERT INC 25 A217 - A217 0892-7790 2011/11 [Refereed]
  • Yasuyuki Kobayashi; Nobutaka Shimizu; Yutaka Yamamoto; Takafumi Minami; Taiji Hayashi; Masahiro Nozawa; Kazuhiro Yoshimura; Tokumi Ishii; Hirotsugu Uemura
    JOURNAL OF ENDOUROLOGY MARY ANN LIEBERT INC 25 A205 - A205 0892-7790 2011/11 [Refereed]
  • Egbert Oosterwijk; W. Kimryn Rathmell; Kerstin Junker; A. Rose Brannon; Frederic Pouliot; David S. Finley; Peter F. A. Mulders; Ziya Kirkali; Hirotsugu Uemura; Arie Belldegrun
    EUROPEAN UROLOGY ELSEVIER SCIENCE BV 60 (4) 622 - 633 0302-2838 2011/10 
    Context: Advances in basic research will enhance prognosis, diagnosis, and treatment of renal cancer patients. Objective: To discuss advances in our understanding of the molecular basis of renal cancer, targeted therapies, renal cancer and immunity, and genetic factors and renal cell carcinoma (RCC). Evidence acquisition: Data on recently published (2005-2011) basic science papers were reviewed. Evidence synthesis: Advances in basic research have shown that renal cancers can be subdivided based on specific genetic profiles. Now that this molecular basis has been established, it is becoming clear that additional events play a major role in the development of renal cancer. For example, aberrant chromatin remodelling appears to be a main driving force behind tumour progression in clear cell RCC. A large number of potential biomarkers have emerged using various high-throughput platforms, but adequate biomarkers for RCC are still lacking. To bring the potential biomarkers and biomarker profiles to the clinical arena is a major challenge for the field. The introduction of tyrosine kinase inhibitors (TKIs) for therapy has shifted the interest away from immunologic approaches. Nevertheless, a wealth of evidence supports immunotherapy for RCC. Interestingly, studies are now appearing that suggest a combination of TKI and immunotherapy may be beneficial. Thus far, little attention has been paid to patient-specific differences. With high-throughput methods becoming cheaper and with the advances in sequencing possibilities, this situation is expected to change rapidly. Conclusions: Great strides have been made in the understanding of molecular mechanisms of RCC. This has led this field to the enviable position of having a range of molecularly targeted therapies. Large sequencing efforts are now revealing more and more genes responsible for tumour development and progression, offering new targets for therapy. It is foreseen that through integration of high-throughput platforms, personalised cancer treatment for RCC patients will become possible. (C) 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.
  • Muneo Yasuda; Naoki Matsumura; Yasuto Okuda; Nobutaka Shimizu; Yutaka Yamamoto; Takahumi Minami; Taiji Hayashi; Hidenori Tsuji; Masahiro Nozawa; Tokumi Ishii; Kazuhiro Yoshimura; Hirotsugu Uemura
    Hinyokika kiyo. Acta urologica Japonica 57 (10) 585 - 8 0018-1994 2011/10 [Refereed]
     
    We report a case of prostate cancer in a 41-year-old male. The patient initially visited another institution with a chief complaint of left breech pain. He was referred to our hospital for further investigation. Serum level of PSA was 267ng/ml and multiple bone metastases were found on bone scintigram. Digital rectal examination revealed a stony-hard prostate. Computed tomography showed multiple lung and lymph node metastases. Transperineal needle biopsy of the prostate revealed moderately differentiated adenocarcinoma (Gleason score 4+5) frombilateral lobes (the 3th Edition). The patient was diagnosed with cT4N1M1c prostate cancer and maximal androgen blockade therapy was commenced.
  • Kenji Zennami; Kazuhiro Yoshikawa; Eisaku Kondo; Kogenta Nakamura; Yoshiaki Yamada; Marco A. De Velasco; Motoyoshi Tanaka; Hirotsugu Uemura; Toru Shimazui; Hideyuki Akaza; Shinsuke Saga; Ryuzo Ueda; Nobuaki Honda
    ONCOLOGY REPORTS SPANDIDOS PUBL LTD 26 (2) 327 - 333 1021-335X 2011/08 [Refereed]
     
    Molecular targeting agents have become formidable anticancer weapons showing much promise against refractory tumors and functional peptides and are among the more desirable of these nanobio-tools. Intracellular delivery of multiple functional peptides forms the basis for a potent, non-invasive mode of delivery, providing distinctive therapeutic advantages. We examine the growth suppression efficiency of human renal cell carcinoma (RCC) by single-peptide targeting. We simultaneously introduced p16(INK4a) tumor suppressor peptides by Wr-T-mediated peptide delivery. Wr-T-mediated transport of p16(INK4a) functional peptide into 10 RCC lines, lacking expression of the p16(INK4a) molecule, reversed the specific loss of p16 function, thereby drastically inhibiting tumor growth in all but 3 lines by >95% within the first 96 h. In vivo analysis using SK-RC-7 RCC xenografts in nude mice demonstrated tumor growth inhibition by the p16(INK4a) peptide alone, however, inoculation of Wr-T and the p16(INK4a) a functional peptide mixture, via the heart resulted in complete tumor regression. Thus, restoration of tumor suppressor function with Wr-T peptide delivery represents a powerful approach, with mechanistic implications for the development of efficacious molecular targeting therapeutics against intractable RCC.
  • Shiro Hinotsu; Hideyuki Akaza; Seiji Naito; Seiichiro Ozono; Yoshiteru Sumiyoshi; Sumio Noguchi; Akito Yamaguchi; Satoshi Nagamori; Akito Terai; Yasutomo Nasu; Haruki Kume; Yoshihiko Tomita; Yoshinori Tanaka; Shoji Samma; Hirotsugu Uemura; Hirofumi Koga; Tomoyasu Tsushima
    BJU international 108 (2) 187 - 95 2011/07 [Refereed]
     
    OBJECTIVE: • To confirm the recurrence-preventing efficacy and safety of 18-month bacillus Calmette-Guérin (BCG) maintenance therapy for non-muscle-invasive bladder cancer. PATIENTS AND METHODS: • The enrolled patients had been diagnosed with recurrent or multiple non-muscle-invasive bladder cancer (stage Ta or T1) after complete transurethral resection of bladder tumours (TURBT). • The patients were randomized into three treatment groups: a maintenance group (BCG, 81 mg, intravesically instilled once weekly for 6 weeks as induction therapy, followed by three once-weekly instillations at 3, 6, 12 and 18 months after initiation of the induction therapy), a non-maintenance group (BCG, 81 mg, intravesically instilled once weekly for 6 weeks) and an epirubicin group (epirubicin, 40 mg, intravesically instilled nine times). The primary endpoint was recurrence-free survival (RFS). RESULTS: • Efficacy analysis was performed for 115 of the full-analysis-set population of 116 eligible patients, including 41 maintenance group patients, 42 non-maintenance group patients and 32 epirubicin group patients. • At the 2-year median point of the overall actual follow-up period, the final cumulative RFS rates in the maintenance, non-maintenance and epirubicin groups were 84.6%, 65.4% and 27.7%, respectively. • The RFS following TURBT was significantly prolonged in the maintenance group compared with the non-maintenance group (generalized Wilcoxon test, P= 0.0190). CONCLUSION: • BCG maintenance therapy significantly prolonged the post-TURBT RFS compared with BCG induction therapy alone or epirubicin intravesical therapy.
  • Shiro Hinotsu; Hideyuki Akaza; Seiji Naito; Seiichiro Ozono; Yoshiteru Sumiyoshi; Sumio Noguchi; Akito Yamaguchi; Satoshi Nagamori; Akito Terai; Yasutomo Nasu; Haruki Kume; Yoshihiko Tomita; Yoshinori Tanaka; Shoji Samma; Hirotsugu Uemura; Hirofumi Koga; Tomoyasu Tsushima
    BJU INTERNATIONAL WILEY 108 (2) 187 - 195 1464-4096 2011/07 [Refereed]
     
    OBJECTIVETo confirm the recurrence-preventing efficacy and safety of 18-month bacillus Calmette-Guerin (BCG) maintenance therapy for non-muscle-invasive bladder cancer.PATIENTS AND METHODSThe enrolled patients had been diagnosed with recurrent or multiple non-muscle-invasive bladder cancer (stage Ta or T1) after complete transurethral resection of bladder tumours (TURBT).The patients were randomized into three treatment groups: a maintenance group (BCG, 81 mg, intravesically instilled once weekly for 6 weeks as induction therapy, followed by three once-weekly instillations at 3, 6, 12 and 18 months after initiation of the induction therapy), a non-maintenance group (BCG, 81 mg, intravesically instilled once weekly for 6 weeks) and an epirubicin group (epirubicin, 40 mg, intravesically instilled nine times). The primary endpoint was recurrence-free survival (RFS).RESULTSEfficacy analysis was performed for 115 of the full-analysis-set population of 116 eligible patients, including 41 maintenance group patients, 42 non-maintenance group patients and 32 epirubicin group patients.At the 2-year median point of the overall actual follow-up period, the final cumulative RFS rates in the maintenance, non-maintenance and epirubicin groups were 84.6%, 65.4% and 27.7%, respectively.The RFS following TURBT was significantly prolonged in the maintenance group compared with the non-maintenance group (generalized Wilcoxon test, P = 0.0190).CONCLUSIONBCG maintenance therapy significantly prolonged the post-TURBT RFS compared with BCG induction therapy alone or epirubicin intravesical therapy.
  • Kazuhiro Yoshimura; Hirotsugu Uemura
    Japanese journal of clinical medicine 日本臨床社 69 (0) 19 - 24 0047-1852 2011/06
  • Kazuhiro Yoshimura; Hirotsugu Uemura
    Nihon rinsho. Japanese journal of clinical medicine 69 Suppl 5 174 - 8 0047-1852 2011/06 [Refereed]
  • Masanori Noguchi; Hirotsugu Uemura; Seiji Naito; Hideyuki Akaza; Akira Yamada; Kyogo Itoh
    PROSTATE WILEY 71 (5) 470 - 479 0270-4137 2011/04 [Refereed]
     
    BACKGROUND. To evaluate the safety, tolerability, immune response, and antitumor activity of a combination of personalized peptide vaccination (PPV) and estramustine phosphate (EMP) in patients with castration-resistant prostate cancer (CRPC).METHODS. In a phase I dose-escalation study, four peptides showing the highest levels of peptide-specific immunoglobulin G(IgG) to 14 vaccine candidates (ITK-1) were subcutaneously injected every week in three different dose settings (1, 3, and 5 mg per peptide) for 6 weeks with a low dose of EMP, and the patients were followed by maximum 2 years extension study either weekly or bi-weekly six times PPV as one course with a low dose of EMP.RESULTS. Fifteen patients were enrolled in the phase I study. No serious treatment-related adverse events were observed. The most common adverse events were grade 2 skin reactions at the injection sites. The maximum acceptable dose of ITK-1 was 8.643 mg. There were no treatment-related systemic adverse events of grade 3 or more, and maximum tolerated dose could not be determined. Cytotoxic T lymphocyte responses measured by interferon-gamma release assay were boosted in 10 of 15 (67%) patients, and IgG responses were boosted in 7 of 15 (47%) patients. Twelve patients proceeded to the extension study, and the median survival time was 23.8 months during a median follow-up of 23.8 months.CONCLUSIONS. PPV treatment for HLA-A24 positive patients with CRPC could be recommended for further stages of clinical trials because of its safety and the higher frequency of boosting immune responses. Prostate 71: 470-479, 2011. (C) 2010 Wiley-Liss, Inc.
  • Masanori Noguchi; Hirotsugu Uemura; Seiji Naito; Hideyuki Akaza; Akira Yamada; Kyogo Itoh
    The Prostate 71 (5) 470 - 9 2011/04 [Refereed]
     
    BACKGROUND: To evaluate the safety, tolerability, immune response, and antitumor activity of a combination of personalized peptide vaccination (PPV) and estramustine phosphate (EMP) in patients with castration-resistant prostate cancer (CRPC). METHODS: In a phase I dose-escalation study, four peptides showing the highest levels of peptide-specific immunoglobulin G (IgG) to 14 vaccine candidates (ITK-1) were subcutaneously injected every week in three different dose settings (1, 3, and 5 mg per peptide) for 6 weeks with a low dose of EMP, and the patients were followed by maximum 2 years extension study either weekly or bi-weekly six times PPV as one course with a low dose of EMP. RESULTS: Fifteen patients were enrolled in the phase I study. No serious treatment-related adverse events were observed. The most common adverse events were grade 2 skin reactions at the injection sites. The maximum acceptable dose of ITK-1 was 8.643 mg. There were no treatment-related systemic adverse events of grade 3 or more, and maximum tolerated dose could not be determined. Cytotoxic T lymphocyte responses measured by interferon-γ release assay were boosted in 10 of 15 (67%) patients, and IgG responses were boosted in 7 of 15 (47%) patients. Twelve patients proceeded to the extension study, and the median survival time was 23.8 months during a median follow-up of 23.8 months. CONCLUSIONS: PPV treatment for HLA-A24 positive patients with CRPC could be recommended for further stages of clinical trials because of its safety and the higher frequency of boosting immune responses.
  • Hirotsugu Uemura; Yuji Hatanaka; Ayaka Izumi; Erina Okazaki; Makiko Doi; Motoyoshi Tanaka; Yutaka Yamamoto; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Marco A. De Velasco
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 71 0008-5472 2011/04 [Refereed]
  • Yuji Hatanaka; Marco A. De Velasco; Motoyoshi Tanaka; Makiko Doi; Erina Okazaki; Ayaka Izumi; Yutaka Yamamoto; Nobutaka Shimizu; Kazuhiro Yoshimura; Masahiro Nozawa; Kazuhiro Yoshikawa; Kazuto Nishio; Hirotsugu Uemura
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 71 0008-5472 2011/04 [Refereed]
  • Nobutaka Shimizu; Yoshitaka Saito; Takafumi Minami; Taiji Hayashi; Hidenori Tsuji; Masahiro Nozawa; Kazuhiro Yoshimura; Tokumi Ishii; Hirotsugu Uemura; Kiyoshi Nakamatsu
    JOURNAL OF UROLOGY ELSEVIER SCIENCE INC 185 (4) E865 - E865 0022-5347 2011/04 [Refereed]
  • Hirotsugu Uemura; Marco De Velasco; Kazuhiro Yoshimura; Masahiro Nozawa; Takafumi Minami
    JOURNAL OF UROLOGY ELSEVIER SCIENCE INC 185 (4) E710 - E710 0022-5347 2011/04 [Refereed]
  • Koichi Sugimoto; Hiroyuki Koike; Kiyoshi Hashimoto; Atsunobu Esa; Yoshitaka Saitou; Yuji Hatanaka; Masaaki Imanishi; Nobutaka Shimizu; Hideo Taharac; Marco De Velasco; Hirotsugu Uemura
    Current Urology 5 (1) 41 - 45 1661-7649 2011/04 [Refereed]
     
    Background: Bacillus Calmette-Guerin (BCG) instillation has been considered to be the most effective method of treatment for non-muscle invasive bladder cancer. The objective of the study was to evaluate the efficacy of between 6 and 8 intravesical BCG instillations after transurethral resection of bladder tumor (TUR-Bt) for Grade 3 nonmuscle invasive bladder cancer. Methods: Between January 2000 and December 2007, a total of 68 cases (58 males and 10 females) with nonmuscle invasive bladder cancer (pTa-1 G3, without carcinoma in situ) were used in the study. After TUR-Bt, patients were divided into a non-infusion group (group A) and BCG (Tokyo 172 strain BCG, 80 mg in 40 ml saline or Connaught BCG, 81 mg in 40 ml saline) infusion groups administered weekly for 6 (group B) and 8 weeks (group C). Recurrence rates were used as endpoints for this study. Also, a single variable and multivariable analysis in a T classification (Ta or T1), tumor multiplicity, tumor size (diameter) and presence or absence of concomitant carcinoma in situ was conducted. Results: In group A, one-year recurrence free survival was 59.1%, and three-year recurrence free survival was 45.2%. In group B, one-year recurrence free survival was 63.6%, and three-year recurrence free survival was 53%. In group C, one-year recurrence free survival was 81%, and three-year recurrence free survival was 72%. Conclusion: This study showed that there may be an increased advantage from adjuvant treatment therapy consisting of 8 weekly intravesical administrations of BCG following TUR-Bt for patients suffering from grade 3 non-muscle invasive bladder cancer. © 2011 S. Karger AG, Basel.
  • Taiji Tsukamoto; Nobuo Shinohara; Norihiko Tsuchiya; Yasuo Hamamoto; Masayuki Maruoka; Hiroyuki Fujimoto; Masashi Niwakawa; Hirotsugu Uemura; Michiyuki Usami; Akito Terai; Hiro-omi Kanayama; Yoshiteru Sumiyoshi; Masatoshi Eto; Hideyuki Akaza
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY OXFORD UNIV PRESS 41 (1) 17 - 24 0368-2811 2011/01 [Refereed]
     
    To assess the efficacy and safety of everolimus in Japanese patients with metastatic renal cell carcinoma.A subgroup analysis of the pivotal Phase III, randomized, double-blind, placebo-controlled trial of everolimus 10 mg/day in patients with disease progression after treatment with sorafenib, sunitinib or both assessed outcomes in Japanese participants. Results were compared with those for the overall study population.The final trial analysis included 24 Japanese patients (everolimus, n= 15; placebo, n = 9). Median progression-free survival in the Japanese subpopulation was 5.75 months (95% confidence interval, 4.90 months to not reached) with everolimus and 3.61 months (95% confidence interval, 1.91-9.03 months) with placebo (hazard ratio, 0.19; 95% confidence interval, 0.05-0.83). Median overall survival was not reached with everolimus and was 14.9 months (95% confidence interval, 11.0-16.8 months) with placebo (hazard ratio, 0.30; 95% confidence interval, 0.07-1.27). Overall, efficacy and safety were similar when comparing the Japanese and overall populations. In the Japanese subpopulation, the most common adverse events with everolimus were stomatitis, infections and rash. Four Japanese subjects (27%) developed Grade 1 (n = 2) or 2 (n = 2) pneumonitis (all reversible and allowing for continuation of therapy, after interruption, steroids and dose reduction for both Grade 2 cases), with a lower pneumonitis incidence of 14% in the overall population (albeit associated with a Grade 3 incidence of 4%).These findings suggest that the demonstrated benefits of everolimus in the overall trial population are similar in Japanese patients with metastatic renal cell carcinoma.
  • Hidenori Tsuji; Tohru Umekawa; Hirotsugu Uemura
    Acta urologica Japonica 泌尿器科紀要刊行会 57 (1) 49 - 54 0018-1994 2011/01 
    Osteopontin (OPN) is the major constituent of calcium-containingurinary stones and is involved in the inhibition of nucleation and aggregation of calcium oxalate (CaOx) crystals, promotion of the adherence of CaOx crystals to cultured renal epithelial cells, and regulation of inflammatory cells as chemokine. OPN has different effects (inhibitor and promoter) at each stage of stone formation in vitro and these multifunctional actions of OPN have not been fully elucidated. We developed a modified crystal method using collagen granules (CG) and immobilized OPN. OPN had strong inhibitory activity on the aggregation/growth of CaOx crystals, but the inhibitory activity decreased by use of OPN-immobilized CG. OPN is also a critical promoter of adherence for CaOx crystals to cultured renal epithelial cells in an in vitro experimental system. We examined the effect of OPN in vivo, by OPN siRNA transfection in rats. Hydrodynamic intravenous and renal subcapsular injections with lipofection were performed on days 1 and 8. The calcium concentration in the kidney was significantly lower and the frequency of CaOx crystal deposits in the tubules was lower in the OPN siRNA transfection group (drinking 1.5% ethylene glycol (EG)), than in the EG drinkingg roup (sham operation) at day 15. We examined the effect of candesartan, an angiotensin II (Ang II) type 1 receptor blockers (ARB) in hyperoxaluric rats. ARB reduced crystal formation and calcium concentrations in the whole kidney. Hyperoxaluria leads to CaOx crystallization and the development of tubulointerstitial lesions in the kidney. AngII mediates OPN synthesis, which is involved in both macrophage recruitment and CaOx crystallization. OPN synthesis and production increased with hyperoxaluria but to a lesser extent in ARB-treated hyperoxaluric rats. These results show that oxalate can activate the renal renin-angiotensin system and that oxalate-induced upregulation of OPN is in part mediated via the renal renin-angiotensin system.
  • Yoshihiko Tomita; Nobuo Shinohara; Takeshi Yuasa; Hiroyuki Fujimoto; Masashi Niwakawa; Soichi Mugiya; Tsuneharu Miki; Hirotsugu Uemura; Norio Nonomura; Masayuki Takahashi; Yoshihiro Hasegawa; Naoki Agata; Brett Houk; Seiji Naito; Hideyuki Akaza
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY OXFORD UNIV PRESS 40 (12) 1166 - 1172 0368-2811 2010/12 [Refereed]
     
    In a phase II, open-label, multicentre Japanese study, sunitinib demonstrated antitumour activity and acceptable tolerability in metastatic renal cell carcinoma patients. Final survival analyses and updated results are reported.Fifty-one Japanese patients with a clear-cell component of metastatic renal cell carcinoma (25 treatment-naive; 26 cytokine-refractory) received sunitinib 50 mg orally, once daily (Schedule 4/2). Overall and progression-free survivals were estimated by the Kaplan-Meier method. Objective response rate (per Response Evaluation Criteria in Solid Tumours) and safety were assessed with an updated follow-up.First-line and pretreated patients received a median 6.0 and 9.5 treatment cycles, respectively. Investigator-assessed, end-of-study objective response rate was 52.0, 53.8 and 52.9% in first-line, pretreated and overall intent-to-treat populations, respectively. The median progression-free survival was 12.2 and 10.6 months in first-line and pretreated patients, respectively. Fourteen patients per group died (56 and 54%), and the median overall survival was 33.1 and 32.5 months, respectively. The most common treatment-related Grade 3 or 4 adverse events and laboratory abnormalities were fatigue (24%), hand-foot syndrome (18%), decreased platelet count (55%), decreased neutrophil count (53%) and increased lipase (49%). No Grade 5 treatment-related adverse events occurred. Forty patients (78%) required dose reduction, and 13 (25%) discontinued, due to treatment-related adverse events.With the median overall survival benefit exceeding 2.5 years, and acceptable tolerability, in first-line and pretreated Japanese metastatic renal cell carcinoma patients with Eastern Cooperative Oncology Group performance status 0/1, sunitinib showed a favourable risk/benefit profile, similar to Western studies. However, there was a trend towards greater efficacy and more haematological adverse events in Japanese patients.
  • Masanori Noguchi; Takashi Mine; Nobukazu Komatsu; Shigetaka Suekane; Fukuko Moriya; Kei Matsuoka; Shigeru Yutani; Shigeki Shichijo; Akira Yamada; Uhi Toh; Kouichiro Kawano; Kouichi Azuma; Hirotsugu Uemura; Kiyotaka Okuno; Kazumasa Matsumoto; Hiroaki Yanagimoto; Ryuya Yamanaka; Masaaki Oka; Satoru Todo; Tetsuro Sasada; Kyogo Itoh
    CANCER BIOLOGY & THERAPY TAYLOR & FRANCIS INC 10 (12) 1266 - 1279 1538-4047 2010/12 [Refereed]
     
    To investigate immunological biomarkers to predict overall survival of advanced cancer patients under treatment with personalized peptide vaccination, correlations between overall survival and biomarkers, including cytotoxic T lymphocyte (CTL) and immunoglobulin G (IgG) responses to the vaccinated peptides, were investigated in 500 advanced cancer patients who received a personalized peptide vaccination from October 2000-October 2008. The best clinical response was assessed for in 436 patients, 43 patients (10%) had partial response, 144 patients (33%) had stable disease and 249 patients (57%) had progressive, with a median overall survival of 9.9 months. Both lymphocyte counts prior to the vaccination (p = 0.0095) and increased IgG response (p = 0.0116) to the vaccinated peptides, along with performance status (p < 0.0001), well correlated with overall survival. To confirm the superiority of IgG response to CTL response, the samples from advanced castration-resistant prostate cancer patients who survived more than 900 days (n = 20) and those who died within 300 days (n = 23) were analyzed further. As a result, both the numbers of peptides, to which increased IgG responses were observed, and the fold increases in IgG levels were significantly higher in long-term survivors (p = 0.000282 and p = 0.00045). In contrast, CTL responses were not statistically different between the two groups. Both lymphocyte numbers and IgG response were thus suggested to be biomarkers of cancer vaccine for advanced cancer patients.
  • HAYASHI Taiji; ANTONIO DE VELASCO Marco; SAITOU Yoshitaka; NOSE Kazuhiro; NISHIOKA Tsukasa; ISHII Tokumi; UEMURA Hirotsugu
    Int. J. Urol. WILEY-BLACKWELL PUBLISHING, INC 17 (12) 989 - 995 0919-8172 2010/12 
    Objectives:Renal ischemia-reperfusion injury (IRI), leading to acute kidney injury, is a frequent complication with renal transplantation and it is associated with graft function. Its pathogenesis involves ischemia, vascular congestion and reactive oxygen metabolites. Carvedilol is an antihypertensive drug with potent anti-oxidant properties. In this study we investigated the protective effects of carvedilol in a rat renal IRI model.Methods:Twenty-four rats were randomized into sham, untreated control and carvedilol (2 mg/kg 30 min before surgery and 12 hr after reperfusion) treatment groups and were subjected to 60 min of left renal ischemia followed by reperfusion at 24, 48, 96 and 168 hr.Results:Treatment with carvedilol significantly decreased plasma creatinine levels after IRI (up to 168 hr) compared to controls (P < 0.001), suggesting an improvement in renal function. Histopathological analysis revealed decreased IRI-induced damage in kidneys from carvedilol-treated rats. A significant increase in the expression levels of Cu/Zn superoxide dismutase and reduction of 8-hydroxydeoxyguanosine and apoptosis levels (P < 0.005) suggested a protective effect after treatment with carvedilol.Conclusions:Our findings suggest that carvedilol ameliorates IRI resulting in improved renal function.
  • Seiji Naito; Yoshihiko Tomita; Sun Young Rha; Hirotsugu Uemura; Mototsugu Oya; He Zhi Song; Li Han Zhong; Mohamed Ibrahim Bin A. Wahid
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY OXFORD UNIV PRESS 40 (1) i51 - i56 0368-2811 2010/09 [Refereed]
     
    Kidney cancer accounts for approximately 2% of all cancers worldwide, with renal cell carcinoma being the most common form and this report is focused on renal cell carcinoma. Globally, the incidence and mortality rates are increasing by 2-3% per decade. Kidney cancer is less common in Asia compared with the West. Cigarette smoking, obesity, acquired cystic kidney disease and inherited susceptibility are known risk factors for kidney cancer. The National Comprehensive Cancer Network Guidelines recommend surgical excision as first line of treatment for Stage I, II or III kidney cancer patients and Stage IV patients with resectable tumours. Immunotherapy has a 20-year history in treatment of metastatic kidney cancer. High-dose interleukin-2 (IL-2) is administered in some countries, whereas low-dose IL-2 and interferon-alpha (IFN-alpha) are popular in Japan. Molecular-targeted drugs, including sunitinib, bevacizumab and sorafenib, are being used for previously untreated and refractory patients. Asian and non-Asian populations have shown large differences in the incidences of adverse events with sorafenib and sunitinib. Consensus Statement: Kidney cancer is relatively uncommon in Asia compared with the West, but its incidence is increasing in more developed Asian nations. Guidelines from the National Comprehensive Cancer Network , etc., for treating metastatic renal cell carcinoma are based on Phase III clinical trials conducted primarily in Western patients. Targeted therapies are now becoming primary recommendations, but efficacy/toxicity data from Asian patients are lacking. Some drugs cause adverse effects in Asians because their recommended dosages are optimal for Caucasians but may be too high for Asians. Further research is necessary to develop optimal treatment strategies for Asians.
  • 植村 天受; 南 高文; 吉村 一宏; 児玉 光正; 平尾 佳彦; 藤本 清秀; 山田 亮; 伊東 恭悟; 角田 卓也; 中村 祐輔
    Biotherapy (株)癌と化学療法社 24 (5) 365 - 374 0914-2223 2010/09 
    われわれはこれまでにMHC class Iペプチドワクチン療法の安全性、特異的免疫誘導能、臨床効果を検討するため、転移性腎細胞癌(n=60)およびホルモン不応再燃前立腺癌(n=23)において臨床研究を施行した。腎細胞癌においては三つの第I相あるいは第II相ワクチン療法を施行した。始めに、HLA-A24拘束性CA9ペプチドワクチン(CA9p219、CA9p288、CA9p323)療法を転移性腎細胞癌患者23人に施行した。続いて18名にCA9ペプチドワクチン・IFN-α併用療法を行い、その後VEGFR1のペプチドワクチンR1-770(HLA-A02)およびR1-1084(HLA-A24)を用いた第I相研究を19人に施行した。結果は重篤な有害事象を認めず、75%の患者に特異的なCTL反応が認められた。また、腫瘍が縮小したPR症例を数人認め、6ヵ月以上のSD症例が50%以上あった。次に、ホルモン不応再燃前立腺癌については、テーラーメイド型ペプチドワクチン療法を23人のHLA-A02あるいはHLA-A24陽性患者に施行した。用意したペプチドはHLA-A24拘束性25種類、HLA-A02拘束性32種類で、ワクチン投与前に各患者から得た血液検体のCTL・IgG免疫反応の結果に基づいて、候補ペプチドを最大4種類選択し、投与した。結果は、ほとんどの患者でワクチン投与部にgrade 1/2の腫脹(しこり)を認めたものの容認性が確認できた。約75%の患者で特異的免疫反応が認められ、9人において血清PSA値の低下を認めた。そのなかの2症例において、明らかな転移巣の縮小を認めた。以上の結果から、転移性腎細胞癌および再燃前立腺癌において、ペプチドワクチン療法は安全かつ臨床的に有用であると思われた。このような状況から、われわれは再燃前立腺癌患者におけるテーラーメイドワクチン療法の有用性について、前向きランダム化臨床研究を進行している。(著者抄録)
  • Koichi Sugimoto; Seiji Matsumoto; Hiroyuki Ito; Hirotsugu Uemura
    LUTS-LOWER URINARY TRACT SYMPTOMS WILEY-BLACKWELL 2 (2) 71 - 75 1757-5664 2010/09 [Refereed]
     
    Objectives: Elastin, in association with collagen, allows the body's organs to stretch and relax. Collagen and elastin, the major components of connective tissue, are present throughout the bladder wall and are intimately related to bladder compliance. The present study was undertaken to evaluate elastin morphologically using immunostaining and electron microscopy in the rabbit model of partial bladder outlet obstruction (PBOO).Methods: Four groups of Japanese white rabbits underwent either PBOO by mild ligation of the urethra (2- and 4-week PBOO) or no obstruction (2- and 4-week sham). Histopathological examination was performed by Elastica van Gieson staining, scanning electron microscopy, transmission electron microscopy, and ultra-high voltage electron microscopy. The number of pixels representing elastin fibers in computerized images was analyzed using Adobe Photoshop Version 2.0.Results: Bladder weight significantly increased after PBOO. Increase in the thickness of the bladder wall was observed after obstruction on histopathological examination. On scanning electron microscopy, elastin was very thick and was found in large configurations. 3-D analysis using electron microscopic tomography revealed that elastic fibers in the bladder had a coil-like appearance in the muscle layer, with each fiber composed of several fibrils. Such structures may be closely related to the physiological function of the bladder.Conclusion: Elastin in the bladder assumes the form of a coil during micturition. We examined that the increase in elastin makes it difficult for elastin to stretch linearly resulting in reduced elasticity. This change may be one of the factors involved in the decrease in compliance mediated by PBOO.
  • Dorothy A. White; Philippe Camus; Masahiro Endo; Bernard Escudier; Emiliano Calvo; Hideyuki Akaza; Hirotsugu Uemura; Euloge Kpamegan; Andrea Kay; Matthew Robson; Alain Ravaud; Robert J. Motzer
    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE AMER THORACIC SOC 182 (3) 396 - 403 1073-449X 2010/08 [Refereed]
     
    Rationale: Noninfectious pneumonitis is a known class effect of mammalian target of rapamycin (mTOR) inhibitors.Objectives: To assess the incidence, radiographic patterns, management, and outcome of pneumonitis in patients with advanced renal cell carcinoma receiving everolimus.Methods: Clinical study data from 416 patients, randomized to receive everolimus versus placebo, were analyzed for adverse events of pneumonitis. Radiographic studies performed every 8 weeks were subject to a prospective, independent, blinded central review for the presence of findings indicative of pneumonitis.Measurements and Main Results: Of 274 patients receiving everolimus, clinical pneumonitis was suspected for 37 patients (13.5%) (none with placebo). Nine cases (3.3%) were grade 1 (asymptomatic), 18 (6.6%) were grade 2 (not interfering with daily living), and 10 (3.6%) were grade 3 (interfering with daily living or oxygen indicated). No grade 4 (life-threatening) pneumonitis was observed. Of the 10 patients with grade 3 pneumonitis, 5 had baseline radiological evidence of pneumonitis before everolimus therapy. Twenty of the 37 cases (54.0%) were reversible within the follow-up period; resolution followed dose reduction for 20 patients and treatment discontinuation in 10 patients. Corticosteroid therapy was initiated in 16 cases. Dedicated radiological review of available serial radiographic studies (245 patients receiving everolimus and 132 receiving placebo) found a higher percentage of new radiographic findings even in patients without a diagnosis of clinical pneumonitis who were receiving everolimus versus placebo (38.9 vs. 15.2%).Conclusions: Early recognition, prompt intervention, and a conservative approach are important in managing the risk associated with noninfectious pneumonitis in association with everolimus. Clinical trial registered with www.clinicaltrials.gov (NCT 00410124).
  • がんの予防・化学予防 前立腺癌に対する酢酸クロルマジノンの術前化学予防効果(Cancer prevention and chemoprevention Pre-clinical chemopreventive efficacy of chlormadinone acetate against prostate cancer)
    Koike Hiroyuki; De Velasco Marco A.; Shimada Keiji; Yoshikawa Kazuhiro; Arao Tokuzu; Nishio Kazuto; Konishi Noboru; Uemura Hirotsugu
    日本癌学会総会記事 日本癌学会 69回 234 - 234 0546-0476 2010/08 [Refereed]
  • ドラッグデリバリーシステム、その他 前臨床マウスモデル系における前立腺癌に対するeverolimusと酢酸クロルマジノンの抗腫瘍作用(Drug delivery system, others Anti-tumor effects of everolimus and chlormadinone acetate against prostate cancer in a pre-clinical mouse model)
    De Velasco Marco A.; Koike Hiroyuki; Shimada Keiji; Yoshikawa Kazuhiro; Konishi Noboru; Arao Tokuzu; Nishio Kazuto; Uemura Hirotsugu
    日本癌学会総会記事 日本癌学会 69回 424 - 424 0546-0476 2010/08 [Refereed]
  • Masanori Noguchi; Tatsuyuki Kakuma; Hirotsugu Uemura; Yasutomo Nasu; Hiromi Kumon; Yasuhiko Hirao; Fukuko Moriya; Shigetaka Suekane; Kei Matsuoka; Nobukazu Komatsu; Shigeki Shichijo; Akira Yamada; Kyogo Itoh
    CANCER IMMUNOLOGY IMMUNOTHERAPY SPRINGER 59 (7) 1001 - 1009 0340-7004 2010/07 [Refereed]
     
    Personalized peptide vaccination (PPV) combined with chemotherapy could be a novel approach for many cancer patients. In this randomized study, we evaluated the anti-tumor effect and safety of PPV plus low-dose estramustine phosphate (EMP) as compared to standard-dose EMP for HLA-A2- or -A24-positive patients with castration resistant prostate cancer. Patients were randomized into groups receiving either PPV plus low-dose EMP (280 mg/day) or standard-dose EMP (560 mg/day). After disease progression, patients were switched to the opposite regime. The primary end point was progression-free survival (PFS). We randomly assigned 28 patients to receive PPV plus low-dose EMP and 29 patients to receive standard-dose EMP. Nineteen events in the PPV group and 20 events in the EMP group occurred during the first treatment. Median PFS for the first treatment was 8.5 months in the PPV group and 2.8 months in the EMP group with a hazard ratio (HR) of 0.28 (95% CI, 0.14-0.61; log-rank P = 0.0012), while there was no difference for median PFS for the second treatment. The HR for overall survival was 0.3 (95% CI, 0.1-0.91) in favor of the PPV plus low-dose EMP group (log-rank, P = 0.0328). The PPV plus low-dose EMP was well tolerated without major adverse effects and with increased levels of IgG and cytotoxic-T cell responses to the vaccinated peptides. PPV plus low-dose EMP was associated with an improvement in PSA-based PFS as compared to the standard-dose EMP alone.
  • UEMURA Hirotsugu; FUJIMOTO Kiyohide; MINE Takashi; UEJIMA Shigeya; DE VELASCO Marco A.; HIRAO Yoshihiko; KOMATSU Nobukazu; YAMADA Akira; ITOH Kyogo
    Cancer Sci. WILEY 101 (3) 601 - 608 1347-9032 2010/03 
    We previously reported that personalized peptide vaccine (PPV) therapy in combination with leutenizing hormone-releasing hormone (LH-RH) analog and estramustine phosphate in certain cases is safe and capable of inducing both immune responses and clinical responses for metastatic castration-resistant prostate cancer (CRPC) patients. In the present study, PPV monotherapy was given to CRPC patients. Twenty-three patients with metastatic CRPC were treated with PPV without any additional treatment modalities, including LH-RH analogs. Samples were analyzed for peptide-specific cytotoxic T-lymphocyte (CTL) precursor analysis and peptide-reactive IgG. Toxicity and immunological and clinical responses were assessed on a three-monthly basis. Seventeen patients were available for immunological and clinical evaluation. The vaccines were well tolerated, with grade 3 erythema at injection sites in only one patient. Augmentation of CTL or IgG responses to at least one of the peptides was observed in six of 17 (35%) and 15 of 17 (88%) patients tested, respectively. Among 57 peptides used, 9 and 36 peptides induced CTL and IgG responses, respectively. Delayed-type hypersensitivity reaction was observed in eight of 17 patients. More than 30% prostate-specific antigen (PSA) decline was observed in four of 17 patients. Of these, one patient achieved a complete PSA response and another patient showed a partial PSA response with profound shrinking of lymph node metastases and prostate. The overall median survival time was 24 months (range, 5-37 months). These results suggest that PPV monotherapy appears to be safe and capable of inducing peptide-specific immune responses and clinical responses in CRPC patients. This trial was registered with University Hospital Medical Information Network (UMIN) number R000003339. (Cancer Sci 2010; 101: 601-608)
  • KISHIDA Takeshi; YAO Masahiro; UEMURA Hirotsugu; OHLMANN Carsten; TOMITA Yoshihiko; BUKOWSKI Ronald M; NAITO Sei; TOMITA Yoshihiko
    International journal of urology WILEY 17 (3) 198 - 205 0919-8172 2010/03
  • Hirotsugu Uemura; Nobuo Shinohara; Takeshi Yuasa; Yoshihiko Tomita; Hiroyuki Fujimoto; Masashi Niwakawa; Soichi Mugiya; Tsuneharu Miki; Norio Nonomura; Masayuki Takahashi; Yoshihiro Hasegawa; Naoki Agata; Brett Houk; Seiji Naito; Hideyuki Akaza
    Japanese journal of clinical oncology 40 (3) 194 - 202 2010/03 [Refereed]
     
    OBJECTIVE: This study aims to assess the efficacy and safety of sunitinib in Japanese patients with metastatic renal cell carcinoma (RCC). METHODS: Fifty-one Japanese patients with prior nephrectomy, 25 treatment-naive patients (first-line group) and 26 cytokine-refractory patients (pretreated group) were enrolled in this phase II trial. Patients received sunitinib 50 mg orally, once daily, in repeated 6-week cycles (4 weeks on treatment, 2 weeks off). The primary endpoint was RECIST-defined objective response rate (ORR) with tumour assessments every 6 weeks via computed tomography or magnetic resonance imaging. Toxicity was assessed regularly. In the primary efficacy analysis of the intent-to-treat (ITT) population, ORR and 95% confidence interval were calculated based on independent review. Secondary time-to-event endpoints, such as progression-free survival (PFS), were estimated using the Kaplan-Meier method. RESULTS: In the ITT population, ORR was 48.0% in the first-line group (after a median 4 cycles), 46.2% in the pretreated group (5 cycles) and 47.1% overall, with median times to tumour response of 7.1, 10.7 and 10.0 weeks, respectively. Median PFS was 46.0, 33.6 and 46.0 weeks, respectively. The most common treatment-related grade 3/4 adverse events and laboratory abnormalities were fatigue (20%), hand-foot syndrome (14%) and hypertension (12%), decreased platelet count (55%), decreased neutrophil count (51%), increased lipase (39%) and decreased lymphocyte count (33%). CONCLUSIONS: In Japanese patients with RCC, sunitinib is consistently effective and tolerable with similar risk/benefit as that in Western patients, though there was a trend toward greater antitumour efficacy and higher incidence of haematological adverse events in Japanese patients.
  • Seiji Matsumoto; Tadashi Hanai; Hirotsugu Uemura
    INTERNATIONAL UROLOGY AND NEPHROLOGY SPRINGER 42 (1) 53 - 56 0301-1623 2010/03 [Refereed]
     
    We have previously shown that a phosphodiesterase 5 (PDE5) inhibitor, vardenafil, possesses bladder protective effects in bladder outlet obstruction (BOO) rats by preserving contractile force. In this study, we examined the effects of vardenafil to obtain clues for further research elucidating the mechanism of action of vardenafil on rat normal bladder.In all, twenty 12-week-old female Sprague-Dawley rats were divided into two equal groups: group 1, water-treated rats; and group 2, vardenafil-treated rats. Vardenafil (8 mg/kg/day) was given by drinking water. Four weeks after, vardenafil was washed out by giving water for 24-48 h, and then bladder was excised and dissected into four longitudinal strips for isometric organ bath assay. Contractile profile of bladder strips to electrical field stimulation (EFS), carbachol, and potassium chloride (KCl) was investigated.Vardenafil had no effect on body and bladder weight. Contractile forces to EFS, carbachol, and KCl were all increased significantly in group 2 by chronic vardenafil treatment.These effects were consistent with those observed in BOO rats for carbachol response, suggesting that effects of vardenafil are not limited to diseased condition, but also apply in normal condition. Chronic treatment with vardenafil increased contractile force of rat normal bladder strips.
  • Takayuki Ohzeki; Taiji Hayashi; Tadashi Hanai; Hirotsugu Uemura
    Acta urologica Japonica 泌尿器科紀要刊行会 56 (3) 181 - 184 0018-1994 2010/03 
    A 67-year-old male was referred to our hospital with septicemia from necrotizing fasciitis of the genitalia of unknown origin. He had a history of diabetes and cerebral infarction. Extensive debridement of necrotizing tissue was performed over an area extending from the lower abdomen to the light inguinal,scrotal and perianal regions. At a suitable point,Flexi-Seal TM was applied to the wound as a preventive measure against infection. There was no contamination of perianal wounds,allowing them to be closed without infection. The Flexi-SealTM was successfully removed after around 3 weeks. This is the second case in which Flexi-SealTM was used in Japan to treat Fourier's gangrene.
  • Hirotsugu Uemura; Nobuo Shinohara; Takeshi Yuasa; Yoshihiko Tomita; Hiroyuki Fujimoto; Masashi Niwakawa; Soichi Mugiya; Tsuneharu Miki; Norio Nonomura; Masayuki Takahashi; Yoshihiro Hasegawa; Naoki Agata; Brett Houk; Seiji Naito; Hideyuki Akaza
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY OXFORD UNIV PRESS 40 (3) 194 - 202 0368-2811 2010/03 [Refereed]
     
    This study aims to assess the efficacy and safety of sunitinib in Japanese patients with metastatic renal cell carcinoma (RCC).Fifty-one Japanese patients with prior nephrectomy, 25 treatment-naive patients (first-line group) and 26 cytokine-refractory patients (pretreated group) were enrolled in this phase II trial. Patients received sunitinib 50 mg orally, once daily, in repeated 6-week cycles (4 weeks on treatment, 2 weeks off). The primary endpoint was RECIST-defined objective response rate (ORR) with tumour assessments every 6 weeks via computed tomography or magnetic resonance imaging. Toxicity was assessed regularly. In the primary efficacy analysis of the intent-to-treat (ITT) population, ORR and 95% confidence interval were calculated based on independent review. Secondary time-to-event endpoints, such as progression-free survival (PFS), were estimated using the Kaplan-Meier method.In the ITT population, ORR was 48.0% in the first-line group (after a median 4 cycles), 46.2% in the pretreated group (5 cycles) and 47.1% overall, with median times to tumour response of 7.1, 10.7 and 10.0 weeks, respectively. Median PFS was 46.0, 33.6 and 46.0 weeks, respectively. The most common treatment-related grade 3/4 adverse events and laboratory abnormalities were fatigue (20%), hand-foot syndrome (14%) and hypertension (12%), decreased platelet count (55%), decreased neutrophil count (51%), increased lipase (39%) and decreased lymphocyte count (33%).In Japanese patients with RCC, sunitinib is consistently effective and tolerable with similar risk/benefit as that in Western patients, though there was a trend toward greater antitumour efficacy and higher incidence of haematological adverse events in Japanese patients.
  • Hirotsugu Uemura; Kiyohide Fujimoto; Takashi Mine; Shigeya Uejima; Marco A de Velasco; Yoshihiko Hirao; Nobukazu Komatsu; Akira Yamada; Kyogo Itoh
    Cancer science 101 (3) 601 - 8 1347-9032 2010/03 [Refereed]
     
    We previously reported that personalized peptide vaccine (PPV) therapy in combination with leutenizing hormone-releasing hormone (LH-RH) analog and estramustine phosphate in certain cases is safe and capable of inducing both immune responses and clinical responses for metastatic castration-resistant prostate cancer (CRPC) patients. In the present study, PPV monotherapy was given to CRPC patients. Twenty-three patients with metastatic CRPC were treated with PPV without any additional treatment modalities, including LH-RH analogs. Samples were analyzed for peptide-specific cytotoxic T-lymphocyte (CTL) precursor analysis and peptide-reactive IgG. Toxicity and immunological and clinical responses were assessed on a three-monthly basis. Seventeen patients were available for immunological and clinical evaluation. The vaccines were well tolerated, with grade 3 erythema at injection sites in only one patient. Augmentation of CTL or IgG responses to at least one of the peptides was observed in six of 17 (35%) and 15 of 17 (88%) patients tested, respectively. Among 57 peptides used, 9 and 36 peptides induced CTL and IgG responses, respectively. Delayed-type hypersensitivity reaction was observed in eight of 17 patients. More than 30% prostate-specific antigen (PSA) decline was observed in four of 17 patients. Of these, one patient achieved a complete PSA response and another patient showed a partial PSA response with profound shrinking of lymph node metastases and prostate. The overall median survival time was 24 months (range, 5-37 months). These results suggest that PPV monotherapy appears to be safe and capable of inducing peptide-specific immune responses and clinical responses in CRPC patients. This trial was registered with University Hospital Medical Information Network (UMIN) number R000003339.
  • Seiji Matsumoto; Tadashi Hanai; Takahiro Matsui; Michiko Oka; Mitsushi Tanaka; Hirotsugu Uemura
    PHYTOTHERAPY RESEARCH JOHN WILEY & SONS LTD 24 (2) 301 - 303 0951-418X 2010/02 [Refereed]
     
    Eviprostat is a phytotherapeutic agent that has been used widely for more than 40 years in the treatment of benign prostatic hyperplasia (BPH) in Japan and Germany, and is known to have antioxidant activity,. The present study, investigated the effect of Eviprostat on the levels of the urinary oxidative stress marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) in a rabbit model of surgical partial bladder outlet obstruction (PBOO) and in patients with lower urinary, tract symptoms (LUTS) associated with BPH. In the rabbit model, 8-OHdG levels in urine collected after 3 weeks of PBOO were 3.8-fold higher than in the urine of sham-operated rabbits. When twice-daily Eviprostat was administered orally, throughout the 3-week PBOO period, the increase in urinary 8-OHdG levels was suppressed by 70%. In the clinical study, nine patients who received Eviprostat for 4 weeks showed 2.5-fold lower urinary, 8-OHdG levels than before treatment. During Eviprostat treatment, the total International Prostate Symptom Score (IPSS) decreased from 16.56 +/- 2.74 to 13.67 +/- 2.30 and the quality of life score from 4.22 +/- 0.40 to 3.22 +/- 0.46. The findings provide evidence that the antioxidant activity, of Eviprostat is responsible for its beneficial effects in the treatment of BPH. Copyright (C) 2009 John Wiley & Sons, Ltd.
  • Sei Naito; Naoki Yamamoto; Tatsuya Takayama; Masatoshi Muramoto; Nobuo Shinohara; Kenryu Nishiyama; Atsushi Takahashi; Ryo Maruyama; Takashi Saika; Senji Hoshi; Kazuhiro Nagao; Shingo Yamamoto; Issei Sugimura; Hirotsugu Uemura; Shigehiko Koga; Masayuki Takahashi; Fumio Ito; Seiichiro Ozono; Toshiro Terachi; Seiji Naito; Yoshihiko Tomita
    EUROPEAN UROLOGY ELSEVIER 57 (2) 317 - 325 0302-2838 2010/02 [Refereed]
     
    Background: Incidence rate of renal cell carcinoma (RCC) differs among countries. The rates of Asian countries are lower than those of countries in North America or Europe but are exceptionally high in Japanese males. Approximately 30% of patients with RCC have metastasis at initial diagnosis, and another 30% have metastasis after nephrectomy. Clinical studies of risk factors in patients with metastatic RCC (mRCC) are mainly based on data from non-Asian patients.Objectives: We aimed to investigate the prognosis of Japanese patients and their prognostic factors.Design, setting, and participants: The subjects of this study were 1463 patients who were clinically diagnosed with RCC with metastasis in 40 Japanese hospitals between January 1988 and November 2002.Measurements: The primary end point was overall survival calculated from first diagnosis of mRCC to death or last follow-up. We also investigated the relationship between survival and clinical features.Results and limitations: The median overall survival time was 21.4 mo. The estimated survival rates at 1, 3, 5, and 10 yr were 64.2%, 35.2%, 22.5%, and 9.1%, respectively; they contrasted with data from the United States of 54%, 19%, 10%, and 6%, respectively for the same periods. A high percentage of patients had undergone nephrectomy (80.5%) and metastasectomy (20.8%), both of which were shown to prolong survival.Conclusions: The median survival time in the present study was approximately twice as long as that of previous studies from North America or Europe. Early diagnosis of metastasis, nephrectomy, metastasectomy, and cytokine-based therapy seemed to improve the prognosis of RCC patients in the present study. (c) 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.
  • Hiroko Okutsu; Seiji Matsumoto; Tadashi Hanai; Yukiko Noguchi; Noriko Fujiyasu; Akiyoshi Ohtake; Masanori Suzuki; Shuichi Sato; Masao Sasamata; Hirotsugu Uemura; Takashi Kurita
    UROLOGY ELSEVIER SCIENCE INC 75 (1) 235 - 240 0090-4295 2010/01 [Refereed]
     
    OBJECTIVES To investigate the mechanism underlying the ameliorating effect of tamsulosin, an alpha(1)-adrenoceptor antagonist, on storage symptoms associated with benign prostatic hyperplasia, the effects of tamsulosin on bladder blood flow (BBF) and bladder function was evaluated in rats with bladder outlet obstruction ( BOO).METHODS BOO was produced by partial ligature of the proximal urethra, which was maintained for 2 weeks. Tamsulosin was subcutaneously administered via an osmotic pump for 2 weeks immediately after the BOO surgery. The BBF in the sham-operated rats, the control BOO rats, and the tamsulosin-treated BOO rats was measured using the fluoromicrosphere method. Each rat was kept in a metabolic cage for observation of micturition behavior. Expression of the alpha(1)-adrenoceptor subtype mRNA in the vesical artery was measured by reverse transcriptase-polymerase chain reaction.RESULTS BBF was significantly reduced in BOO rats compared with sham-operated rats, and tamsulosin significantly increased the BBF in BOO rats. Tamsulosin ameliorated the decrease in mean voided volume in BOO rats with bladder masses <500 mg. Expression of the alpha(1)-adrenoceptor subtype in the vesical artery was alpha(1a)- > alpha(1d)-adrenoceptors; almost no expression was observed of alpha(1b)-adrenoceptors in either sham-operated or BOO rats.CONCLUSIONS Tamsulosin increased BBF in BOO rats via an antagonistic effect, presumably on the alpha(1A)- and/or alpha(1D)-adrenoceptor in the vesical artery mainly, and improved the decrease in mean voided volume. Therefore, the results of this study suggest that tamsulosin improves bladder overactivity via improvement of BBF. UROLOGY 75: 235-240, 2010. (C) 2010 Elsevier Inc.
  • S. Matsumoto; T. Hanai; N. Shimizu; K. Sugimoto; H. Uemura
    AKTUELLE UROLOGIE GEORG THIEME VERLAG KG 41 S46 - S49 0001-7868 2010/01 [Refereed]
     
    Edaravone is a newly developed radical scavenging agent that has been widely used for protection against ischemia/reperfusion (I / R) injury in patients with cerebral infarction. The present study investigated the effects of edaravone on the I / R injury in rat urinary bladder. Adult male rats were divided in the four groups: groups 1-3 received 1 hour of ischemia followed by 1 hour of reperfusion with saline and with edaravone (1 and 3 mg/kg body weight), and group 4 were age-matched control rats. The in vivo ischemia was created by clamping the vesical arteries for 1 hour and reperfusion was accomplished by removing the clips and lasted for 1 hour. Edaravone or saline were administered after reperfusion for 30 min. Following reperfusion, the bladder was excised and separated. Bladder smooth muscle cell (SMC) phenotypic expression was investigated in the electron microscope. The number of contractile and non-contractile bladder SMC phenotype according to the morphological criteria was counted and the ratio of non-contractile to contractile phenotype was calculated. The responses to electrical field stimulation and carbachol were recorded. Edaravone administration resulted in the protection of the morphological changes and contractile responses to both EFS and carbachol that were affected by the agent. Our findings demonstrate that edaravone has a potentially protective effect on I / R-induced damage in the rat bladder.
  • Kawahara T; Sekiguchi Z; Makiyama K; Nakayama T; Nagashima Y; Kita K; Namura K; Itou H; Sano F; Hayashi N; Nakaigawa N; Ogawa T; Uemura H; Yao M; Kubota Y
    Case reports in oncology 2 (3) 189 - 193 2009/10 [Refereed]
  • 個別化治療マウスモデルにおける抗腫瘍薬の薬効測定におけるヒト腫瘍移植片の利用(Use of human tumor explants for the determination of anti-tumor drug efficacy in a personalized medicine mouse model)
    Yoshimura Kazuhiro; De Velasco Marco A.; Tanaka Motoyoshi; Nishio Kazuto; Uemura Hirotsugu
    日本癌学会総会記事 日本癌学会 68回 188 - 188 0546-0476 2009/08 [Refereed]
  • 遺伝子改変マウスにおける近赤外蛍光画像による腫瘍量の測定(Use of near infrared fluorescence imaging to determine tumor burden in genetically engineered mice)
    Uemura Hirotsugu; Yoshikawa Kazuhiro; Tanaka Motoyoshi; Nishio Kazuto; De Velasco Marco A.
    日本癌学会総会記事 日本癌学会 68回 457 - 457 0546-0476 2009/08 [Refereed]
  • Tohru Umekawa; Hidenori Tsuji; Hirotsugu Uemura; Saeed R. Khan
    BJU INTERNATIONAL WILEY 104 (1) 115 - 120 1464-4096 2009/07 [Refereed]
     
    OBJECTIVETo test the hypothesis that exposure of a renal epithelial cell line, NRK52E, to calcium oxalate monohydrate crystals (COM) would up-regulate NADPH oxidase subunit p47 phox, enhance superoxide production and increase monocyte chemoattractant protein-1 (MCP-1) and osteopontin mRNA levels.MATERIALS AND METHODSConfluent cultures of NRK52E cells were exposed to COM (66.7 mu g/cm(2)) with or with no pretreatment with diphenileneiodium chloride (DPI, 10 x 10(-6) M) an inhibitor for NADPH oxidase, under serum-free conditions. The conditioned medium was collected and total cellular RNA isolated from the cells, and subjected to enzyme-linked immunosorbent assay and real-time polymerase chain reaction (PCR). Production of reactive oxygen species (ROS) was estimated by dihydroethidium (DHE) staining using a fluorescence microscope. Immunohistochemistry and real-time PCR were used to analyse p47 phox in NRK52E cells.RESULTSIn COM treated NRK52E cells there was enhanced expression of p47 phox and production of superoxide. COM-induced production of MCP-1 and osteopontin was significantly reduced after treatment with DPI.CONCLUSIONSWhile the generation of a lot of ROS might play a major role in tissue injury or death, the regulated generation of low concentration of ROS, possibly by NADPH oxidase, may represent a second messenger system for generation of COM-induced MCP-1 and osteopontin production in the renal tubules.
  • Shigeki Horikawa; Seiji Matsumoto; Tadashi Hanai; Toshiya Yamamoto; Tomomi Kishimoto; Hirotsugu Uemura
    Acta urologica Japonica 泌尿器科紀要刊行会 55 (6) 311 - 314 0018-1994 2009/06 
    Using International Prostate Symptom Score (IPSS)/Quality of life (QOL) and Urinary Incontinence Questionnaires,we collected a total of 89 questionnaires from 48 pregnant women (average age of 31.4± 3.42) and data 4 times during each pregnancy (during the 14th,26th and 36th weeks of pregnancy) and 1 month after delivery. We examined whether there was a relationship between the number of incontinence incidences listed in the questionnaires and other parameters : the body mass index (BMI),previous deliveries, the weight of the baby delivered,the use of episiotomy,etc. The average IPSS score was 5.84±4.65,5.33± 2.73,7.35 ±4.51 for the 14,26 and 36th week,respectively and 1.82±1.76 one month after delivery. The major symptom reported was storage symptom and the scores increased as the pregnancy progressed and recovered by one month after delivery. The average score on the Urinary Incontinence Questionnaires was 3.32±2.69,5.05 ±3.02,6.15 ±2.89 for the 14,26 and 36th week,respectively and 1.59±2.03 one month after delivery. The major symptom reported was stress incontinence. The scores increased significantly as the pregnancy progressed and,one month after delivery,returned to the level at the 14th week of pregnancy. We found a positive correlation between the number of incidences of incontinence at the 36th week and the subject's BMI. Among the lower urinary tract symptoms,storage symptom and stress incontinence were found in the early stage of pregnancy. Storage symptom disappeared after delivery,but stress incontinence was reduced only to the level in the early stage of pregnancy.
  • Makito Miyake; Kiyohide Fujimoto; Chie Matsushita; Yoshitomo Chihara; Masahiro Tanaka; Akihide Hirayama; Yoshihiko Hirao; Hirotsugu Uemura
    Acta urologica Japonica 泌尿器科紀要刊行会 55 (6) 371 - 375 0018-1994 2009/06 
    A 24-year-old man was referred to our hospital with a painless mass on the left side of his neck. Ultrasonographydetected right testicular tumor and computerized tomographyscanning revealed a left supraclavicular lymph node mass and bulky retroperitoneal lymph node mass. He initially underwent right high orchiectomy, combination chemotherapy and retroperitoneal lymph node dissection for advanced testicular non-seminomatous germ cell tumor. Six years later, late relapse was detected in the lung. After complete remission of the lung metastasis with chemotherapy, the serum alpha-fetoprotein began to increase because of superior vena caval thrombus extending into the right atrium. Emergencysurgical excision was performed successfullyusing extracorporeal circulation to prevent pulmonaryembolism and the resected specimen pathologicallyrevealed adenocarcinoma interpreted as teratoma malignant transformation. Adjuvant chemotherapyconsisting of paclitaxel, ifosfamide and nedaplatin were administered for subsequent slight elevation of serum F-human chorionic gonadotropin β, resulting in successful normalization again. Later, he suddenlydied of cerebral infarction without anyevidence of recurrence 138 months after his initial presentation. We report herein an extremelyuncommon case of advanced testicular germ cell tumor with development of superior vena caval thrombus extending into the right atrium.
  • Seiji Matsumoto; Nobutaka Shimizu; Tadashi Hanai; Hirotsugu Uemura; Robert Levin
    BJU INTERNATIONAL WILEY-BLACKWELL PUBLISHING, INC 103 (10) 1436 - 1439 1464-4096 2009/05 [Refereed]
     
    To examine the correlation between partial bladder outlet obstruction (PBOO) and bladder carcinogenesis.Female Wistar rats (6 weeks old) were divided into three groups of 10 each: group 1 was exposed to n-butyl-n-butanol nitrosamine (BBN, a carcinogen) in drinking water for 8 weeks; group 2 had PBOO induced surgically after exposure to BBN for 8 weeks; group 3 had a sham operation and the rats drank normal water (control group). After 20 weeks, all of the rats were killed humanely and their bladders analysed.There were no significant differences in body weight among the groups. The bladder weight of group 2 was significantly greater than either group 1 or group 3. Histopathologically, bladder smooth muscle hypertrophy was the major cause of the increased bladder weight for group 2. In group 2 there were increases in bladder wall thickness and many nipple-shaped urothelial tumours. Basic fibroblast growth factor and hypoxia-inducible factor-1 alpha expression were significantly greater in group 2 than in groups 1 and 3.Exposure of the bladder to carcinogens during bladder hyperplasia and hypertrophy induced by PBOO results in a greater incidence of superficial bladder carcinoma.
  • Tadashi Hanai; Seiji Matsumoto; Sunao Shouji; Yukio Usui; Xian Yan Tang; Yoshinari Kato; Masanori Iguchi; Hirotsugu Uemura; Toshirou Terachi
    Hinyokika kiyo. Acta urologica Japonica 泌尿器科紀要刊行会 55 (4) 187 - 191 0018-1994 2009/04 
    The aims of this study were to define the relationships between prostate-specific antigen (PSA) and alpha 1-adrenergic receptor antagonist (alpha 1 blocker). A prospective clinical study of 48 male patients examined between May 2004 and December 2007 was performed. 4.0-9.9 ng/ml PSA level who had no notable clinical findings of urinary retention, urinary tract infections and prostate cancer (PC) received tamusulosin 0.2 mgonce daily for 3 months, and then received prostate biopsy. We divided the patients into two groups : PC and benign prostate hyperplasia (BPH)/lower urinary tract symptom (LUTS) group. In total, the PSA level showed no significant change after treatment. In the PC group, PSA significantly increased after treatment. However, PSA decreased in the BPH/LUTS group. The alpha 1 blocker significantly improved urination status (the subjective symptoms and urodynamics parameters) in the BPH/LUTS group. In two groups, prostate volume showed no significant difference. Among those patients in the BPH/LUTS group, their urination status was significantly improved with alpha 1 blocker and their PSA level dropped slightly. On the other hand, the PSA level was significantly increased in the PC group. This study shows that by usingan alpha 1 blocker, it may be possible to avoid conductingthe prostate biopsy at an early stage or indeed one may not be needed at all for patients with only slight increases in PSA.
  • Seiji Matsumoto; Tadashi Hanai; Hirotsugu Uemura; Robert M. Levin
    BJU INTERNATIONAL WILEY 103 (7) 987 - 990 1464-4096 2009/04 [Refereed]
     
    To investigate whether vardenafil, a phosphodiesterase 5 (PDE-5) inhibitor, would protect the bladder from decompensatory changes in a 4-week rat bladder outlet obstruction (BOO) model, as evidence has been accumulating that PDE-5 inhibitors improve lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH).In all, 50 12-week-old female Sprague-Dawley rats were divided into five equal groups; group 1, sham operated vehicle control rats; group 2, BOO vehicle rats; group 3-5, BOO rats given oral vardenafil at 5, 20, 80 mg/L, respectively. Vardenafil was given in drinking water from the day of surgery. At 4-weeks after the introduction of BOO, vardenafil was washed-out by giving water for 24-48 h, and then the bladder was excised and dissected into four longitudinal strips for isometric organ-bath assay. Contractile responses of bladder strips to electrical field stimulation (EFS), carbachol and KCl was determined for each group.BOO induced a significant increase in bladder weight in group 2 compared with group 1. Bladder weights of groups 3-5 were not significantly different from that of group 2. The contractile forces in response to EFS, carbachol and KCl in group 2 were 30.7-51.7% of those in group 1. Vardenafil treatment in groups 3-5 generally did not block the BOO-induced reduction of contractile force in the bladder strips. However, treatment with a high dose of vardenafil resulted in a significant increase in the contractile response to carbachol (78.4% group 5 vs 51.7% group 2).Chronic treatment with a high dose of vardenafil protected the rat bladder from BOO-induced contractile dysfunction to carbachol.
  • 植村 天受
    臨床泌尿器科 医学書院 63 (3) 233 - 239 0385-2393 2009/03 
    転移性腎癌に対する標準治療は,近年,サイトカイン療法から分子標的治療へと大きく転換しているが,長期予後を考えると分子標的薬が必ずしも特効薬ではない。腎癌はその生物学的特性を鑑みると,免疫療法が適した数少ない癌腫であり,癌ワクチン療法はいわゆる分子標的免疫療法で,最近,多くの難治性癌において盛んに臨床研究が行われている。本稿では,筆者が開発・経験した腎癌に対するワクチン療法について解説する。(著者抄録)
  • 【クリティカルケアにおける腎臓管理Q&A】慢性腎不全をどうするか? 慢性腎不全の維持療法患者に対する救急集中治療室での管理 慢性腎不全でステロイドまたは免疫療法を施行している患者の救急集中治療管理上の注意点
    植村 天受; 石井 徳味
    救急・集中治療 (株)総合医学社 21 (1-2) 175 - 179 1346-0935 2009/02 
    <point>慢性腎不全でステロイド、または免疫療法を施行している患者の対象疾患を理解する。免疫抑制薬・ステロイドの特性を理解し、使用方法を熟知する。カルシニューリン阻害薬(CNI)投与患者では、集中治療管理上、血中濃度測定による薬物濃度モニタリング(TDM)が必要である。ステロイドが長期投与されている患者では減量方法に注意する。(現疾患のリバウンド、副腎クリーゼ予防のため)。免疫抑制下ならびに慢性腎不全の場合、病状が急速に重症化することに留意する。(著者抄録)
  • 南 高文; 石井 徳味; 植村 天受; 大関 孝之; 吉川 元清; 中川 勝弘; 林 泰司; 辻 秀憲; 野澤 昌弘; 田中 基幹; 梅川 徹
    日本泌尿器科学会雑誌 一般社団法人 日本泌尿器科学会 100 (2) 460 - 460 0021-5287 2009
  • Tadashi Hanai; Seiji Matsumoto; Nobutaka Shimizu; Hirotsugu Uemura; Takahide Sugiyama
    Nihon Hinyokika Gakkai zasshi. The japanese journal of urology 99 (7) 723 - 8 0021-5287 2008/11 [Refereed]
     
    OBJECTIVES: At present, there are almost no report concerning post micturition dribble (PMD) in lower urinary tract symptoms (LUTS). PMD may have a negative effect on the quality of life (QOL) of afflicted patients. However, question concerning PMD are not included in the International Prostate Symptom Score (IPSS) questionnaire, and a number of questions about PMD remain to be addressed, such as the correlation between PMD and QOL. Therefore, we investigated PMD using an original question form (IPSS added PMD) we created. METHODS: Between June 2006 and March 2007, the self-administered modified IPSS (IPSS with new questions included concerning PMD) was 5 obtained from 621 outpatients (394 men and 227 women) visiting our hospital. RESULTS: The PMD scores were 1.2 +/- 1.7 in men, and 0.6 +/- 1.2 in women, and thus we see that the men had a significantly higher than the women. Men's PMD scores rise from age 50 and reach a peak in the 70's. On the other hand, there is no significant change for women from the 20s and thereafter. Those with higher PMD scores were male patients with benign prostatic hyperplasia (BPH) and females with stress urinary incontinence. In BPH group, the average PMD score was higher than patients with another urological disease. The PMD scores were appreciably high at 1.59 +/- 1.90 for the LUTS group, and had the lower value of 0.36 +/- 0.90 for the non-LUTS group. Therefore, the LUTS group was found to have a significantly higher PMD score. Men in the LUTS group (especially those with BPH) had a positive correlation between their QOL scores and PMD scores. CONCLUSION: The following points may be revealed from the present study. In patients with LUTS (especially BPH), PMD score is higher and may impair their QOL. Even women and youth may experience PMD. A more detailed evidence concerning PMD will be needed.
  • T. Hayashi; Y. Saitou; K. Nose; T. Nishioka; T. Ishii; H. Uemura
    TRANSPLANTATION PROCEEDINGS ELSEVIER SCIENCE INC 40 (7) 2139 - 2141 0041-1345 2008/09 
    In renal transplantation, ischemia/reperfusion (I/R) injury is related to production of reactive oxygen species. In addition to its anti hypertensive action due to nonselective beta-adrenergic blocking activity, carvedilol has potent antioxidant activity. This study was designed to investigate the effects of carvedilol on I/R injury in rats. On postoperative days 2 and 4, serum creatinine levels were higher among the control and the metoprolol treatment groups compared with the carvedilol treatment group (P < .005). However, there were no significant differences on postoperative day 7. In conclusion, increased antioxidant modulation by carvedilol attenuated renal I/R injury.
  • Marco A. De Velasco; Motoyoshi Tanaka; Satoshi Anai; Atsushi Tomioka; Kazuto Nishio; Hirotsugu Uemura
    ONCOLOGY REPORTS SPANDIDOS PUBL LTD 20 (3) 543 - 547 1021-335X 2008/09 [Refereed]
     
    Precise and objective measurements of tumor response have yet to be standardized in the mouse orthotopic bladder cancer model. In this study, we used image analysis and green fluorescent protein (GFP) to objectively measure tumor size in response to chemotherapy. KU-7 human bladder cancer cells transfected with GFP were intravesically inoculated into 8-week-old female nude mice. Fourteen days after tumor cell inoculation, the mice were assigned into a control (PBS) group or a doxorubicin (conc. 1.0 mg/ml) treatment group and received a single instillation of treatment. Fourteen days after treatment, the bladders were surgically exposed and fluorescent images were captured and later analyzed using image analysis. Bladders were processed for histological examination. Tumor incidence determined by GFP expression and histology was 100 and 80%, respectively, in the doxorubicin treatment group. A 9-fold (histology) vs. 12-fold (GFP expression) difference in tumor regression measured by tumor area (P < 0.05) and a 5-fold (histology) vs. 9-fold (GFP expression) difference in tumor regression measured by the percent of tumor area in the bladder (P < 0.001) were observed in the doxorubicin treatment group. Our findings suggest that using image analysis provides a precise, sensitive and objective means to measure tumor growth and treatment response in the mouse orthotopic bladder cancer model in lieu of histological methods. Consequently, the number of mice required in an experiment can be reduced since tissue samples are not needed for histology, thus making tissue samples readily available for additional assays in both a labor-effective and cost-effective manner.
  • 植村 天受; 野澤 昌弘
    Urology View (株)メジカルビュー社 6 (4) 73 - 77 1347-9636 2008/08
  • Atsushi Tomioka; Motoyoshi Tanaka; Marco A. De Velasco; Satoshi Anai; Satoshi Takada; Toshihiro Kushibiki; Yasuhiko Tabata; Charles J. Rosser; Hirotsugu Uemura; Yoshihiko Hirao
    MOLECULAR CANCER THERAPEUTICS AMER ASSOC CANCER RESEARCH 7 (7) 1864 - 1870 1535-7163 2008/07 [Refereed]
     
    The tumor suppressor gene MMAC/PTEN located on chromosome 10q23.3 has dual phosphatase activity in the phosphoinositide-3-kinase signaling pathway and inhibits Akt activation, a serine-threonine kinase, which is involved in proliferative and antiapoptotic pathways. Furthermore, MMAC/PTEN is frequently inactivated in a variety of tumors including prostate cancer. In this study we generated a new type of gene transfer drug, GelaTen: which is a microsphere of cationized gelatin hydrogels incorporating PTEN plasmid DNA. Using our previously reported radiation-resistant PC3-Bcl-2 human prostate cancer cells (PTEN deleted), we examined the efficacy of GelaTen to force the expression of PTEN in vivo to inhibit tumor growth after intratumoral injection alone or with irradiation. Combinational therapy with GelaTen and irradiation improved both the in vitro and in vivo efficacy of growth inhibition compared with GelaTen or irradiation alone. These data show that GelaTen gene therapy, enabling radiosensitization, can potentially treat prostate cancers that have MMAC/PTEN gene alterations associated with radioresistance.
  • Seiji Matsumoto; Hirotsugu Uemura
    Hinyokika kiyo. Acta urologica Japonica 54 (6) 453 - 6 0018-1994 2008/06 [Refereed]
     
    To investigate the mechanism of the ameliorating effect of alpha1-blocker on storage symptoms associated with benign prostatic hyperplasia (BPH), we evaluated the effect of tamsulosin on the bladder blood flow in rats with bladder outlet obstruction (BOO). BOO was produced by ligature in the part around a proximal urethra and kept for 2 weeks. Tamsulosin was subcutaneously administered with an osmotic pump for 2 weeks immediately after the BOO operation. Bladder blood flow in the sham-operated rats, the control BOO rats and the tamsulosin-treated BOO rats was measured by the fluoro-microsphere method. Bladder blood flow was significantly reduced in BOO rats compared with sham-operated rats, and tamsulosin significantly increased the bladder blood flow in BOO rats. The present results suggest that the increase in bladder blood flow by tamsulosin contributes to the improvement of storage symptoms associated with BPH.
  • Koichi Sugimoto; Seiji Matsumoto; Hirotsugu Uemura; Hiroyuki Ito
    Hinyokika kiyo. Acta urologica Japonica 54 (5) 321 - 4 0018-1994 2008/05 [Refereed]
     
    We examined prostate specimens from 5 patients (median age; 71.8 years, range 57-83), with benign prostatic hyperplasia (BPH) removed during surgery, and 4 autopsied cadavers (median age at death; 68.8 years, range 46-92) who had either obstructive or neurogenic voiding dysfunction. The prostate specimens were severed anatomically into samples of the base, middle, and apex of the prostate. They served as samples for a comparative study of the distribution of elastin fibers by means of a pathology study, using the Elastica Van Gieson (EV) staining method. The number of pixels representing elastin fibers in computerized images was analyzed using Adobe Photoshop Ver. 2.0. There was a larger proportion of elastin in the area of the urethra and at the base of prostate than in the remainder of the organ. The percentage of elastin at the base of the prostate was significantly greater among BPH patients than cadavers. Thus, it was demonstrated that elastin a stromal component was increased in BPH patients.
  • Hirotsugu Uemura; Marco A. De Velasco
    WORLD JOURNAL OF UROLOGY SPRINGER 26 (2) 147 - 154 0724-4983 2008/04 [Refereed]
     
    Introduction Although most vaccines target foreign infectious agents, therapeutic cancer vaccines target both well-established and metastatic tumor cells expressing tumor antigens. Active immunotherapy is intended to enhance or activate the immunosurveillance of an individual through a therapeutic vaccine. Renal cell carcinoma (RCC) is one of the most immunoresponsive cancers in humans, which in turn makes it an ideal candidate for immune based therapies.Method Several types of therapeutic vaccines have been tested and applied in the clinical setting and can be divided into cell-based vaccines including direct application of inactivated autologous tumor cells, gene modified tumor cell-based, dendritic cell-based (expressing RCC derived tumor antigens), and non-cell-based vaccines. This review will examine the current status of cell-based vaccine immunotherapy and focuses on non-cell-based vaccine strategies.Conclusion Recent advances in molecular targeting therapy have introduced a battery receptor tyrosine kinase (RTK) and mTOR inhibitors that provide promising treatment options, however, the tolerability of tumor vaccines and the success of clinical effectiveness in selected populations combined with recent advances in cellular therapies warrant the continued exploration of novel methods of tumor vaccine therapies in the clinical setting.
  • Matsumoto Seiji; Hanai Tadashi; Shimizu Nobutaka; Uemura Hirotsugu
    Acta urologica Japonica 泌尿器科紀要刊行会 54 (3) 179 - 184 0018-1994 2008/03 
    Twenty-eight adult male Sprague-Dawley rats were divided into four groups: Group 1 received 1 hour (h) of bilateral ischemia alone. Groups 2 and 3 received 1 h ischemia followed by 1 and 4 h of reperfusion (I-R), respectively. Group 4 consisted of age-matched control rats. Bladder strips were studied using electrical field stimulation (EFS) and KCl stimulation. Maximal contractile responses were recorded and analyzed. Temporal patterns of changes in phenotypic (non-contractile and contractile) expression of bladder smooth muscle cells were investigated using electron microscopy. The mean ratio of non-contractile to contractile phenotype (nc/c) of smooth muscle cells (SMCs) in the control group was 0.169. In the ischemia alone group, the ratio was 0.991. In the 1 h I-R group, the ratio 0.865 whereas in 4 h I-R group the ratio 1.601. The contractile responses to EFS and KCl showed decreased responses in all groups. These results clearly demonstrated that the ratio of nc/c increased significantly in the ischemia group and further increased significantly in both I-R groups. The contractile responses decreased in all ischemic groups although the magnitude of the contractile changes did not correspond in the change of phenotype ratio.
  • Tomioka Atsushi; Tanaka Motoyoshi; Anai Satoshi; Ikeda Tomohiro; Shimada Keiji; Velasco Marco; Saito Keigo; Hirao Yoshihiko; Uemura Hirotsugu
    日本泌尿器科学会雑誌 (一社)日本泌尿器科学会 99 (2) 149 - 149 0021-5287 2008/02 [Refereed]
  • 泌尿器科疾患 尿道腫瘍(尿道カルンクルを含む)
    植村 天受
    今日の診療指針 848  2008
  • 植村 天受
    泌尿器科紀要 泌尿器科紀要刊行会 54 (1) 49 - 52 0018-1994 2008/01
  • changes in smooth muscle cell phenotype and contractile function following ischemia-reperfusion injury in the rat urinary bladder
    松本成史; 清水 信貴; 植村 天受; 花井 禎
    Acta Urol.Jpn. 54 (179) 184  2008/01
  • Hirotsugu Uemura
    Acta urologica Japonica 泌尿器科紀要刊行会 54 (1) 49 - 52 0018-1994 2008/01 
    In this review, pathogenesis and genetic alterations of urologic malignancies and their therapeutic target molecule are summarized briefly. In bladder cancer, only a little has been revealed. Loss of heterozygosity of 9p/q is frequently observed in low grade, low stage tumors. In invasive or carcinoma in situ tumors, alteration of p53 and Rb tumor suppressor gene is frequently found. In prostate cancer, the process of carcinogenesis from normal epithelium to cancer hypothesized by Nelson et al. (N Engl J Med 24; 349 : 366-381) seems to be logic. Androgen independency of tumor cells is associated with androgen receptor gene mutation and amplification, however, the mechanism is not well clarified. It is a turning point, therapeutic strategy is changing from cytokine immunotherapy to molecular targeting therapy in metastatic renal cell carcinoma. The pathway from growth factors such as vascular endothelial growth factor and platelet derived growth factor, and their receptors to mTOR is a central controller of tumor angiogenesis and proliferation.
  • シロドシンの射精障害:ヘルシーボランティアでの検討
    松本 成史; 花井 禎; 齋藤 允孝; 中西 道政; 杉本 公一; 清水 信貴; 森 康範; 南 高文; 林 泰司; 植村 天受; 杉山 高秀
    泌尿器外科 20 (10) 773 - 778 2007/10
  • Nobutaka Shimizu; Seiji Matsumoto; Yasunori Mori; Nobuhiro Yoshioka; Hirotsugu Uemura; Naoki Nakano; Mamoru Taneda
    Acta urologica Japonica 泌尿器科紀要刊行会 53 (9) 609 - 612 0018-1994 2007/09 
    Electric stimulation therapy is one of the surgical treatments for Parkinson's disease whereby a chronic stimulating electrode is placed on the subthalmic nucleus (STN). Because medical treatments centered around L-dopa have limitations in severe Parkinson's disease, electric stimulation therapy is regarded as an appropriate treatment modality. Most Parkinson's disease patients experience lower urinary tract disorders such as urgency, daytime frequency or nocturia, due to detrusor overactivity. We conducted an International Prostate Symptom Score (IPSS) analysis and a pressure flow study (PFS) on 6 patients before and after a chronic stimulating electrode was placed on the STN and evaluated how the subjective symptoms and bladder functions changed. As a result, the IPSS total value, involuntary detrusor contraction threshold volume and maximum bladder capacity were all found to significantly improve (P<0.05). The average IPSS decreased from 11.2 to 7.0. The average involuntary detrusor contraction threshold volume increased from 90.7 ml to 172.7 ml. The average maximal bladder capacity increased from 104.0 ml to 177.2 ml. These findings suggest that the STN the positively contributes to an improvement in urinary function.
  • 松本 成史; 畑中 祐二; 杉本 公一; 清水 信貴; 森 康範; 林 泰司; 花井 禎; 植村 天受; 秋山 隆弘
    日本小児泌尿器科学会雑誌 日本小児泌尿器科学会 15 (2) 184 - 188 1341-0784 2007/07 
    膀胱尿道逆流症(VUR)に対して幼少時にPolitano-Leadbetter(PL)法のような膀胱内より膀胱後壁の壁外操作を行った女性は、術後の合併症として妊娠の経過と共に高度水腎症、更には腎後腎不全をきたす場合があるが、長期経過症例における合併症はあまり確認されていない。今回著者等が経験した小児期にPL法による逆流防止術の既往があり、妊娠中に高度両側水腎症から腎後性急性腎不全をきたしたため腎瘻造設を行い腎瘻管理にて出産した3症例の臨床経過を呈示し解説した。いずれも両側VURに対して症例1(妊娠時27歳)は7歳時に、症例2(19歳)は6歳時に、症例3(30歳)は4歳時にPL法を施行された初産婦であった。症例1・2では第2子の希望があったため産後尿管閉塞の解除手術を施行し、母子共に問題なく第2子を出産できた。以上より第2子の希望があれば閉塞解除術の施行により妊娠時の腎後腎不全などの合併症を未然に防ぐことが可能と考えられた。
  • TSUJI Hidenori; UMEKAWA Tohru; UEMURA Hirotsugu; IGUCHI Masanori; HATANAKA Yuji; KURITA Takashi
    INTERNATIONAL JOURNAL OF UROLOGY WILEY 14 (7) 630 - 634 0919-8172 2007/07 
    Objectives: In this study, we measured urinary osteopontin (OPN) concentrations in urolithiasis patients as well as in healthy volunteers, and investigated the relationship between urinary excretion of OPN and urinary supersaturation level.Methods: Supersaturation levels (AP indexes) were determined by using Tiselius's index. Crystals with a maximum diameter of 12 im or larger and less than 5 im were counted by scanning electron microscopy. A sum of cross-sectional areas of crystals was also calculated as the total crystal volume (VT).Results: Urinary OPN concentrations in the group with no urinary stone were significantly higher than that in the urolithiasis patients with a tendency toward stone enlargement. AP indexes were observed to be significantly higher in patients with stone enlargement, whereas urinary OPN concentrations bore no definite relation to the urinary supersaturation levels. VT and number of large crystals (12 im or larger) in patients with a tendency toward stone enlargement were higher than healthy volunteers, but no differences were found between the number of micro-crystal with the diameter of less than 5 im. On the basis of the plots of VT and OPN concentrations, regression analysis revealed that VT and log OPN had a significant correlation.Conclusion: Urinary OPN tended to be lower in cases with larger crystal volumes and is potentially associated with crystal growth for inhibitory effect.
  • Noriyuki Ito; Masatoshi Eto; Eijiro Nakamura; Atsushi Takahashi; Taiji Tsukamoto; Hiroshi Toma; Hayakazu Nakazawa; Yoshihiko Hirao; Hirotsugu Uemura; Susumu Kagawa; Hiroomi Kanayama; Yoshiaki Nose; Naoko Kinukawa; Tsuyoshi Nakamura; Nobuyoshi Jinnai; Toyokazu Seki; Masanobu Takamatsu; Yoshihiro Masui; Seiji Naito; Osamu Ogawa
    JOURNAL OF CLINICAL ONCOLOGY AMER SOC CLINICAL ONCOLOGY 25 (19) 2785 - 2791 0732-183X 2007/07 [Refereed]
     
    PurposeTo clarify the effect of genetic polymorphisms on the response to interferon alfa (IFN-alpha) for metastatic renal cell carcinoma (MRCC), and to find a reliable molecular marker to select those patients with MRCC who would benefit from IFN-alpha immunotherapy.Patients and MethodsWe carried out an association study in which 463 single nucleotide polymorphisms (SNPs) in 33 candidate genes were genotyped in 75 Japanese patients who had received IFN-alpha for MRCC.ResultsAfter adjusting for lung metastasis, stepwise logistic regression analysis revealed that the SNPs in signal transducer and activator 3 (STAT3) were most significantly associated with better response to IFN-alpha. Linkage disequilibrium mapping revealed that the SNP in the 5' region of STAT3, rs4796793, was the most significant predictor of IFN-alpha response (odds ratio [OR] = 2.73; 95% CI, 1.38 to 5.78). The highest OR was shown in the CC genotype at rs4796793 compared to the GG + GC genotypes (OR = 8.38, 95% CI, 1.63 to 42.96). Genotype-dependent expressions of STAT3 in B lymphocyte cell lines and the enhanced growth inhibitory effects of IFN-alpha by STAT3 suppression in an RCC cell line supported the results of the present association study.ConclusionThe present study suggested that the STAT3 polymorphism is a useful diagnostic marker to predict the response to IFN-alpha therapy in patients with MRCC. An efficient response marker for IFN-alpha needs to be utilized to establish individual optimal treatment strategies, even when newer drug therapies are used as first line treatments for MRCC.
  • Takafumi Minami; Satoko Matsueda; Hiroko Takedatsu; Masahiro Tanaka; Masanori Noguchi; Hirotsugu Uemura; Kyogo Itoh; Mamoru Harada
    CANCER IMMUNOLOGY IMMUNOTHERAPY SPRINGER 56 (5) 689 - 698 0340-7004 2007/05 [Refereed]
     
    SART3-derived peptides applicable to prostate cancer patients with HLA-A3 supertype alleles were identified in order to expand the possibility of an anti-cancer vaccine, because the peptide vaccine candidates receiving the most attention thus far have been the HLA-A2 and HLA-A24 alleles. Twenty-nine SART3-derived peptides that were prepared based on the binding motif to the HLA-A3 supertype alleles (HLA-A11, -A31, and -A33) were first screened for their recognizability by immunoglobulin G (IgG) of prostate cancer patients and subsequently for the potential to induce peptide-specific cytotoxic T lymphocytes (CTLs) from HLA-A3 supertype(+) prostate cancer patients. As a result, five SART3 peptides were frequently recognized by IgG, and two of them-SART3 (511-519) and SART3 (734-742)-efficiently induced peptide-specific and cancer-reactive CTLs. Their cytotoxicity toward prostate cancer cells was ascribed to peptide-specific and CD8(+) T cells. These results indicate that these two SART3 peptides could be promising candidates for peptide-based immunotherapy for HLA-A3 supertype(+) prostate cancer patients.
  • Hirotsugu Uemura; Motoyoshi Tanaka; Shigeya Uejima; Takafumi Minami; Kiyohide Fujimoto; Yoshihiko Hirao; Kyogo Itoh
    JOURNAL OF UROLOGY ELSEVIER SCIENCE INC 177 (4) 202 - 202 0022-5347 2007/04 [Refereed]
  • Satoshi Anai; Atsushi Tomioka; Yoshihiko Hirao; Ikumi Sugiyama; Yasuyuki Sadzuka; Motoyoshi Tanaka; Marco DeVelasco; Hirotsugu Uemura
    JOURNAL OF UROLOGY ELSEVIER SCIENCE INC 177 (4) 293 - 293 0022-5347 2007/04 [Refereed]
  • 植村 天受
    泌尿器外科 医学図書出版(株) 20 (1) 17 - 23 0914-6180 2007/01 
    腎細胞癌において高率に発現しているCA9抗原よりHLA-A24拘束性ペプチドワクチンを開発し、既存の治療に無効な転移性腎癌患者23例を対象にペプチドワクチン療法の第1相臨床研究を行った。全例でワクチン投与部位の発赤腫脹を認めたが重篤な有害事象なく安全と思われた。また、腫瘍の縮小・消失を示す有効症例を3例認め、新しい治療戦略としての可能性が示唆された。ペプチドワクチンの理論、実際の臨床研究から得られた結果について解説する。(著者抄録)
  • 林 泰司; 森 康範; 松本 成史; 植村 天受
    Acta urologica Japonica 泌尿器科紀要刊行会 52 (12) 915 - 917 0018-1994 2006/12 
    A female patient gave birth to a child while receiving hemodialysis, six years later, she gave birth to another child after cadavatic renal transplantation. Both children showed normal growth without any congenital defects. During the term of pregnancy after renal transplantation, there was no significant rejection episode, and graft function was stable. It seems rare for a patient to bear children during dialysis and after renal transplantation.
  • 兼子 美帆; 松本 成史; 田原 秀男; 石井 徳味; 植村 天受
    Acta urologica Japonica 泌尿器科紀要刊行会 52 (12) 929 - 931 0018-1994 2006/12 
    A 70-year-old man underwent right nephrectomy for clear cell renal carcinoma in 1985. After nephrectomy, he was routinely followed up as an outpatient. Solitary chest tumor was detected on pulmonary CT in 2005. A wedge resection of pulmonary tumor was performed under diagnosis of primary lung cancer. The histological feature was not of primary lung cancer, but the previous nephrectomised specimen, i.e., clear cell renal carcinoma.
  • Taiji Hayashi; Yasunori Mori; Seiji Matsumoto; Hirotsugu Uemura
    Hinyokika kiyo. Acta urologica Japonica 52 (12) 915 - 7 0018-1994 2006/12 [Refereed]
     
    A female patient gave birth to a child while receiving hemodialysis, six years later, she gave birth to another child after cadavatic renal transplantation. Both children showed normal growth without any congenital defects. During the term of pregnancy after renal transplantation, there was no significant rejection episode, and graft function was stable. It seems rare for a patient to bear children during dialysis and after renal transplantation.
  • Miho Kaneko; Seiji Matsumoto; Hideo Tahara; Tokumi Ishii; Hirotsugu Uemura
    Hinyokika kiyo. Acta urologica Japonica 52 (12) 929 - 31 0018-1994 2006/12 [Refereed]
     
    A 70-year-old man underwent right nephrectomy for clear cell renal carcinoma in 1985. After nephrectomy, he was routinely followed up as an outpatient. Solitary chest tumor was detected on pulmonary CT in 2005. A wedge resection of pulmonary tumor was performed under diagnosis of primary lung cancer. The histological feature was not of primary lung cancer, but the previous nephrectomised specimen, i.e., clear cell renal carcinoma.
  • SHIMIZU Nobutaka; MATSUMOTO Seiji; YOSHIOKA Nobuhiro; HANAI Tadashi; SUGIYAMA Takahide; UEMURA Hirotsugu
    The Japanese Journal of Urology The Japanese Urological Association 97 (7) 839 - 843 0021-5287 2006/11 
    (Purpose) Clinical study of acute urinary retention seen by this department.
    (Materials and Methods) Subjects were 206 cases seen during office hours and during after-hours emergency care by the department of Urology at the Kinki University Hospital for acute urinary retention for the 12-year-period from April 1993 to April 2005.
    (Results) By gender, the 206 cases of acute urinary retention included 175 men (85%) and 31 women (15%). The ratio of men to women was 5.6:1, with a markedly larger number of male cases. Ages of the 206 cases overall were distributed from 6 to 93 years old and the mean age was 66 years old. In male cases, the mean age was 69.6 years old while in female cases it was 46.3 years old. With regard to the cause, bladder outlet obstruction (BOO) accounted for 123 (70.3%) of the 175 male cases; benign prostatic hyperplasia (BPH) was noted in 92 cases and accounted for 52.6%of the total. Detrusor Weakness (DW) was noted in 35 cases (20%). DW was most prevalent in women, being noted in 20 cases (64.5%). With regard to treatment, in male cases surgery was performed for BOO in 69 (56%) of 123 cases; surgery was performed for BPH in 56 (60.8%) of 92 cases, drug therapy was used in 19 cases, and 3 cases were observed. In female cases, 10 cases were able to urinate on their own through treatment of the causative disorder. With regard to outcome, ultimately a total of 139 cases (67.5%), 125 men and 14 women, were able to urinate on their own.
    (Conclusions)
    1.85% of acute urinary retention cases were men. Of these, 70% were caused by some form of BOO. DW due to a cause other than obstruction accounted for about 70% of the remaining 30%.
    2. Overall, 70% of cases were able to urinate on their own after treatment while 30% required catheterization.
    3. After the cause of BOO was eliminated, cases were likely to be able to urinate on their own; CIC (clean intermittent catheterization) was frequently used in treatment of causes other than BOO.
    4.15 % of acute urinary retention cases were women.
  • 兼子 美帆; 松本 成史; 杉本 公一; 上島 成也; 植村 天受
    Acta urologica Japonica 泌尿器科紀要刊行会 52 (11) 871 - 873 0018-1994 2006/11 
    This is a case report of left renal pelvic tumor found 32 years after left calico-ileo-vesiconeostomy. The patient has undergone right nephrectomy for absence of renal function at 26 years-old and left urinary reconstruction was performed using the intestine for pyelo-ureteral junction obstruction at 28 years old because of bilateral congenital hydronephrosis. Later he was treated for recurrent left renal stone with percutaneous nephrolithotripsy, nephrolithotomy and extracorporeal shock wave lithotripsy. When he was 56 years old, macrohematuria appeared. He received left nephrectomy under the diagnosis of left renal pelvic tumor.
  • Nobutaka Shimizu; Seiji Matsumoto; Nobuhiro Yoshioka; Tadashi Hanai; Takahide Sugiyama; Hirotsugu Uemura
    Nihon Hinyokika Gakkai zasshi. The japanese journal of urology 97 (7) 839 - 43 0021-5287 2006/11 [Refereed]
     
    PURPOSE: Clinical study of acute urinary retention seen by this department. MATERIALS AND METHODS: Subjects were 206 cases seen during office hours and during after-hours emergency care by the department of Urology at the Kinki University Hospital for acute urinary retention for the 12-year-period from April 1993 to April 2005. RESULTS: By gender, the 206 cases of acute urinary retention included 175 men (85%) and 31 women (15%). The ratio of men to women was 5.6:1, with a markedly larger number of male cases. Ages of the 206 cases overall were distributed from 6 to 93 years old and the mean age was 66 years old. In male cases, the mean age was 69.6 years old while in female cases it was 46.3 years old. With regard to the cause, bladder outlet obstruction (BOO) accounted for 123 (70.3%) of the 175 male cases; benign prostatic hyperplasia (BPH) was noted in 92 cases and accounted for 52.6%of the total. Detrusor Weakness (DW) was noted in 35 cases (20%). DW was most prevalent in women, being noted in 20 cases (64.5%). With regard to treatment, in male cases surgery was performed for BOO in 69 (56%) of 123 cases; surgery was performed for BPH in 56 (60.8%) of 92 cases, drug therapy was used in 19 cases, and 3 cases were observed. In female cases, 10 cases were able to urinate on their own through treatment of the causative disorder. With regard to outcome, ultimately a total of 139 cases (67.5%), 125 men and 14 women, were able to urinate on their own. CONCLUSIONS: 1. 85% of acute urinary retention cases were men. Of these, 70% were caused by some form of BOO. DW due to a cause other than obstruction accounted for about 70% of the remaining 30%. 2. Overall, 70% of cases were able to urinate on their own after treatment while 30% required catheterization. 3. After the cause of BOO was eliminated, cases were likely to be able to urinate on their own; CIC (clean intermittent catheterization) was frequently used in treatment of causes other than BOO. 4.15% of acute urinary retention cases were women.
  • Miho Kaneko; Seiji Matsumoto; Koichi Sugimoto; Shigeya Uejima; Hirotsugu Uemura
    Hinyokika kiyo. Acta urologica Japonica 52 (11) 871 - 3 0018-1994 2006/11 [Refereed]
     
    This is a case report of left renal pelvic tumor found 32 years after left calico-ileo-vesiconeostomy. The patient has undergone right nephrectomy for absence of renal function at 26 years-old and left urinary reconstruction was performed using the intestine for pyelo-ureteral junction obstruction at 28 years old because of bilateral congenital hydronephrosis. Later he was treated for recurrent left renal stone with percutaneous nephrolithotripsy, nephrolithotomy and extracorporeal shock wave lithotripsy. When he was 56 years old, macrohematuria appeared. He received left nephrectomy under the diagnosis of left renal pelvic tumor.
  • S. Matsumoto; T. Hanai; T. Matsuura; H. Uemura; T. Nishioka; T. Akiyama
    TRANSPLANTATION PROCEEDINGS ELSEVIER SCIENCE INC 38 (7) 2009 - 2011 0041-1345 2006/09 
    Creatol (CTL, 5-hydroxycreatinine) is a creatinine (Cr) oxidative metabolite, which was originally isolated from the urine of patients with chronic renal failure, representing a candidate for a uremic toxin. The effectiveness of CTL as an indicator of oxidative stress after kidney transplantation has not been reported. Therefore, we examined the relation between the change in oxidative stress (using CTL) in renal transplant patients and their change in renal function (using Cr). The serum Cr and serum and urine CTL were examined in five renal transplant patients. Serum CTL closely correlated with serum Cr. Serum CTL also correlated with urine CTL, but in some cases there was a time lag. Both the ratio of CTL/(Cr) and serum CTL observed in patient 2 were slow to improve after transplantation. The process through which oxidative stress was reduced was shown by the index of renal damage correlated with kidney function oxidative stress (using serum CTL) after transplantation. Our data suggested that CTL/Cr may be a good indicator of graft prognosis.
  • S. Matsumoto; T. Hanai; T. Matsuura; H. Uemura; T. Nishioka; T. Akiyama
    TRANSPLANTATION PROCEEDINGS ELSEVIER SCIENCE INC 38 (7) 2014 - 2015 0041-1345 2006/09 
    8-Hydroxy-2'-deoxyguanosine (8-OHdG) is an oxidant of deoxyguanosine, a base in the construction of DNA. We examined the extent of DNA damage to the graft through oxidative stress after renal transplantation. Seven renal transplant patients were enrolled in this study. Before reperfusion of the grafts, the level of serum 8-OHdG was measured using enzyme-linked immunosorbent assay. No relationship was found between the level of serum 8-OHdG just before reperfusion and the postoperative course. In all cases, the level of serum 8-OHdG increased after reperfusion and decreased within 2 hours. In six cases, it remained almost the same as the preoperative level. A faster rate of decrease from the first peak of serum 8-OHdG was associated with a lower nadir serum creatinine and reduced occurrence of acute rejection. This study suggested that immediate calming of the oxidative stress following reperfusion may potentially have a positive influence on graft prognosis. In addition, biomarkers of oxidative stress may predict graft prognosis.
  • T. Hayashi; H. Tahara; Y. Hara; T. Ishii; H. Uernura
    TRANSPLANTATION PROCEEDINGS ELSEVIER SCIENCE INC 38 (7) 1985 - 1986 0041-1345 2006/09 
    A 25-year-old male, blood type A, was admitted to our hospital for renal transplantation from his father of AB blood type. Before transplant, we performed laparoscopic splenectomy. The serum anti-B antibody titer fell from 1:8 to 1:2. Therefore, plasmapheresis was not performed. The total ischemic time was 80 minutes. Five immunosuppressive agents, including tacrolimus, mycophenolate mofetil, prednisolone, basiliximab, and deoxyspergualine, were administered in the initial period. On the 47th day, value of cytomegalovirus antibody, which was routinely measured, became positive. Hence, we administered ganciclovir, with a fall in antibody. Sixty-five days after transplant, he was discharged with a serum creatinine of 1.0 mg/dL. We concluded that it was possible to perform ABO-incompatible renal transplantation with no need for plasmapheresis or rituximab.
  • Tohru Umekawa; Masanori Iguchi; Hirotsugu Uemura; Saeed R. Khan
    BJU INTERNATIONAL BLACKWELL PUBLISHING 98 (3) 656 - 660 1464-4096 2006/09 [Refereed]
     
    OBJECTIVE To examine the responses of renal fibroblasts to high oxalate (Ox) and calcium Ox (CaOx) crystals, as the latter are found in the renal interstitium of patients with primary or enteric hyperoxaluria, and in animals with experimental CaOx nephrolithiasis, and are associated with tubulointerstitial inflammation (TI). TI might begin with the production of chemoattractants by the renal epithelial cells exposed to high Ox and/or CaOx crystals; as Ox levels are also high in the renal interstitium and crystal deposition in nephrolithiasis might start in the interstitium, we hypothesized that renal fibroblasts might also be involved in the development of TI.MATERIALS AND METHODS We exposed renal fibroblast cells of line NRK 49F in vitro to Ox ions (500 mu mol/L) or CaOx monohydrate crystals (67 mu g/cm(2)). We assessed the production of osteopontin and monocyte chemoattractant protein-1 (MCP-1), and expression of their mRNA, in the cells. We also determined the cellular malondialdehyde content as a marker of reactive oxygen species (ROS)-induced lipid peroxidation, and Trypan blue staining and the release of lactate dehydrogenase as markers of injury.RESULTS Similar to renal epithelial cells, renal fibroblasts were stimulated by exposure to Ox and CaOx crystals. They showed signs of injury and ROS-induced lipid peroxidation. The mRNA expression and production of osteopontin and MCP-1 increased significantly.CONCLUSIONS These results indicate that fibroblasts respond to high Ox and CaOx crystals by up-regulating specific pathways producing proinflammatory conditions. Migration of monocytes/macrophages to sites of interstitial crystal deposits can lead to localized interstitial inflammation and fibrosis.
  • 女性尿閉患者の臨床的検討
    清水 信貴; 兼子 美帆; 吉岡 伸浩; 花井 禎; 松本 成史; 杉山 高秀; 植村 天受
    日本女性骨盤底医学会誌 日本女性骨盤底医学会 3 (1) 50 - 53 2187-5669 2006/05 
    【目的】女性の急性尿閉に対する臨床的検討を行った。【対象・方法】1993年4月から2005年4月まで12年間に、急性尿閉にて近畿大学医学部泌尿器科を診療時間内および救急診療時間帯に受診した206症例中女性31例を対象とした。【結果】急性尿閉症例206症例の性別は男性175例(85%)、女性31例(15%)であった。年齢分布は女性例では7歳から77歳にわたり平均46.3歳であった。女性例では40歳未満の症例が31例中14例で45.2%を占めた。排尿筋収縮力低下が20例(64.5%)で最も多く、次いで原因不明4例(12.9%)、心因性3例(9.6%)の順に多かった。他、術後(尿路、骨盤内手術を除く)、子宮筋腫があった。【考察】圧倒的に男性が多いが女性例も約15%は存在しており、日常診療においてはしばしば遭遇する。男性例とは異なり40歳代未満の症例が約半数を占めた。女性例の原因に精神科関連の薬剤によるものや心因性のものが多く含まれているためと考えられる。(著者抄録)
  • 中高年女性OAB患者に対するエストロゲン補充療法の臨床的検討
    松本 成史; 兼子 美帆; 清水 信貴; 吉岡 伸浩; 花井 禎; 杉山 高秀; 植村 天受
    日本女性骨盤底医学会誌 日本女性骨盤底医学会 3 (1) 54 - 58 2187-5669 2006/05 
    (目的)更年期障害はその病因の一つとしてエストロゲンの欠乏が重要視されており、多くの不定愁訴はエストロゲン補充により改善する。頻尿、尿失禁等を主訴とする中高年女性に対するエストラジオール補充療法の効果を臨床的に検討し、近年ICSで提唱されたOABへの有用性を評価した。(対象と方法)頻尿、尿失禁を訴えた更年期以降の中高年女性10名を対象とした。エストラジオール貼付療法単独で検討を行い、効果判定は8週間の投薬前後での自覚症状の変化を中心に行った。(結果)尿失禁症例は7例で、その結果は尿失禁重症度分類では、全例grade downを示し、特に切迫性尿失禁症例では有用性を認めた。頻尿症例では、尿意切迫感の訴えはなく、その結果は全例不変であった。(結論)今回の検討では、症例数も少なく短期治療の結果であるが、切迫性尿失禁症例の改善が良好であった。エストラジオール貼付療法は中高年女性のOABに対する一治療法としては十分有用と思われた。(著者抄録)
  • Motoyoshi Tanaka; Madoka Tonosaki; Masafumi Umekage; Tomio Konaka; Ikeda Hisafumi; Hirotsugu Uemura
    MOLECULAR THERAPY NATURE PUBLISHING GROUP 13 S79 - S79 1525-0016 2006/05 [Refereed]
  • Hirotsugu Uemura; Shigeya Uejima; Motoyoshi Tanaka; Kiyohide Fujimoto; Yoshihiko Hirao; Kyogo Itoh
    CANCER RESEARCH AMER ASSOC CANCER RESEARCH 66 (8) 0008-5472 2006/04 [Refereed]
  • Hirotsugu Uemura; Kiyohide Fujimoto; Motoyoshi Tanaka; Motoyoshi Yoshikawa; Yoshihiko Hirao; Shigeya Uejima; Kazuhiro Yoshikawa; Kyogo Itoh
    Clinical cancer research : an official journal of the American Association for Cancer Research The American Association for Cancer Research 12 (6) 1768 - 75 1078-0432 2006/03 [Refereed]
     
    PURPOSE: A phase I peptide vaccination trial was done in patients with progressive cytokine-refractory metastatic renal cell carcinoma (RCC) to assess both the toxicity and capability to induce immune responses of three peptides (CA9p219-227, p288-296, and p323-331) derived from CA9, a tumor-associated antigen ubiquitously expressed in RCC. EXPERIMENTAL DESIGN: Twenty-three patients positive for human leukocyte antigen (HLA)-A24 with histologically confirmed RCC were enrolled. Eligibility included progressive disease after standard cytokine therapy with interleukin-2 and/or IFN-alpha. Patients were vaccinated s.c. with the three peptides emulsified in incomplete Freund's adjuvant at 2-week intervals. Pre- and post-vaccination blood samples were obtained for toxicity assessment and immunologic studies. Patients were monitored for clinical responses on a 3-monthly basis. RESULTS: Vaccinations were well tolerated without any major adverse event. Most of the patients developed peptide-specific CTLs and/or immunoglobulin G reactive to the peptides after the 6th or 9th vaccination, followed by a gradual increase in both CTL frequency and levels of peptide-reactive serum IgG. Three patients with multiple lung metastases showed partial responses with disappearance and shrinking of metastatic lesions. Additionally, stable disease for >6 months was observed in six patients (median duration, 12.2 months). Moreover, the median survival time of all patients who were progressive at trial enrollment after failing immunotherapy was 21.0 months (5-35 months). CONCLUSIONS: These results suggest that vaccination of these peptides is safe and recommended for further trials for HLA-A24-positive metastatic RCC patients.
  • H Uemura; K Fujimoto; M Tanaka; M Yoshikawa; Y Hirao; S Uejima; K Yoshikawa; K Itoh
    CLINICAL CANCER RESEARCH AMER ASSOC CANCER RESEARCH 12 (6) 1768 - 1775 1078-0432 2006/03 
    Purpose: A phase I peptide vaccination trial was done in patients with progressive cytokine-refractory metastatic renal cell carcinoma (RCC) to assess both the toxicity and capability to induce immune responses of three peptides (CA9p219-227, p288-296, and p323-331) derived from CA9, a tumor-associated antigen ubiquitously expressed in RCC. Experimental Design: Twenty-three patients positive for human leukocyte antigen (HLA) -A24 with histologically confirmed RCC were enrolled. Eligibility included progressive disease after standard cytokine therapy with interleukin-2 and/or IFN-alpha. Patients were vaccinated s.c. with the three peptides emulsified in incomplete Freund's adjuvant at 2-week intervals. Pre- and post-vaccination blood samples were obtained for toxicity assessment and immunologic studies. Patients were monitored for clinical responses on a 3-monthly basis. Results: Vaccinations were well tolerated without any major adverse event. Most of the patients developed peptide-specific CTLs and/or immunoglobulin G reactive to the peptides after the 6th or 9th vaccination, followed by a gradual increase in both CTL frequency and levels of peptide-reactive serum IgG. Three patients with multiple lung metastases showed partial responses with disappearance and shrinking of metastatic lesions. Additionally, stable disease for >6 months was observed in six patients (median duration, 12.2 months). Moreover, the median survival time of all patients who were progressive at trial enrollment after failing immunotherapy was 21.0 months (5-35 months). Conclusions: These results suggest that vaccination of these peptides is safe and recommended for further trials for HLA-A24-positive metastatic RCC patients.
  • 植村 天受
    Urology View (株)メジカルビュー社 4 (1) 83 - 89 1347-9636 2006/02
  • Seiji Matsumoto; Nobutaka Shimizu; Naohiko Moriguchi; Makoto Yagi; Hirotsugu Uemura
    INTERNATIONAL UROLOGY AND NEPHROLOGY SPRINGER 38 (3-4) 549 - 551 0301-1623 2006 [Refereed]
     
    Leiomyosarcoma of the urinary bladder in childhood is uncommon. We reported bladder leiomyosarcoma in a 10-year-old boy. He had underwent the extirpation of the tumor and performed adjuvant chemotherapy in combination with radiotherapy according to the Intergroup Rhabdomyosarcoma Study-4 regimens. He had no evidence of recurrence of disease after 3 years.
  • Koichi Sugimoto; Seiji Matsumoto; Kazuhiro Nose; Takashi Kurita; Hirotsugu Uemura; Young-Chol Park; June Hanai
    INTERNATIONAL UROLOGY AND NEPHROLOGY SPRINGER 38 (2) 291 - 292 0301-1623 2006 [Refereed]
     
    A 40-year-old man was referred to our hospital with gynecomastia and painless swelling of the right scrotum. Ultrasonography revealed a 15 x 10 mm mass with low echogenicity of the right testis. We performed right high orchiectomy. Histologically, Reinke's crystals and capsular invasion by tumor cells were found. Final diagnosis, the tumor was a malignant Leydig cell tumor of the testis.
  • MATSUMOTO Seiji; HANAI Tadashi; YOSHIOKA Nobuhiro; SHIMIZU Nobutaka; SUGIYAMA Takahide; UEMURA Hirotsugu
    Neurosci. Res. 54 (1) 66 - 70 0168-0102 2006/01 
    The medial prefrontal cortex is thought to participate in the control of micturition and urinary continence, based on evidence from clinical reports, but its exact role is not fully understood. This study investigated whether ibotenic acid lesions of the medial prefrontal cortex would influence volume-evoked micturition in urethane-anesthetized rats. The incidence and amplitude of bladder contractions were recorded during continuous saline infusion (0.1 ml/min) immediately before and 1 week after ibotenic acid (0.5 microg) or vehicle (0.5 microl) was injected into the medial prefrontal cortex. Vehicle injection did not change the incidence or amplitude of bladder contractions compared to pre-injection values. Ibotenic acid lesions prolonged the time interval between bladder contractions significantly although it did not affect the amplitude of bladder contractions. Histological analysis revealed that ibotenic acid lesions were restricted primarily to the anterior cingulate and prelimbic cortices. Larger ibotenic acid lesions extending ventrally into the infralimbic cortex produced a variable response but did not change the overall incidence or amplitude of bladder contractions significantly. These data indicate that the medial prefrontal cortex influences the timing of bladder contractions but does not affect contraction amplitudes.
  • SUGIYAMA Takahide; SHIMIZU Nobutaka; HASHIMOTO Kiyoshi; YOSHIOKA Nobuhiro; HANAI Tadashi; MATSUMOTO Seiji; UEMURA Hirotsugu
    The Japanese Journal of Urology The Japanese Urological Association 96 (7) 670 - 677 0021-5287 2005/11 
    (Purpose) The clinical benefit of propiverine hydrochloride against overactive bladder was evaluated, and the relationships between urinary voiding functions and the pharmacokinetics were investigated by means of clinical pharmacology with PK/PD approach.
    (Patients and Methods) Total 7 patients suffering urgency with urinary frequency and incontinence received propiverine hydrochloride in doses of 10mg qd or 20mg qd for 4 weeks, and then the doses were switched in cross-over manner to continue the treatment for further 4 weeks. The urody-namic measurements as well as pharmacokinetic samplings were done before the medication, 4 weeks and 8 weeks after the starting medication, to examine the dose-response and concentration-response relationships.
    (Results) The volume at first desire to void increased according to dose increased, and the volume at first involuntary contraction tended to increase according to both dose and drug concentration in plasma. However, no apparent dose-response relationships were observed for maximum urinary flow rate and the detrusor pressure at the maximum urinary flow rate. The PK/PD analysis using Emax model suggested that, approximately 75ng/mL of the propiverine concentration in plasma allowed the increase in the volume at first involuntary contraction for 50%. The urinary residual volume increased in dose-dependent manner only in the patients with severe grade of lower urinary tract obstruction, but scarcely increased in the patients with moderate grade or below.
    (Conclusion) Propiverine hydrochloride improved the urinary voiding functions with a tendency to depend on both dose and concentration in plasma. After the administration of propiverine hydrochloride, the concentration in plasma will immediately reach the level at which the drug can increase in the volume at first involuntary contraction for 50%, and then the concentration level will sustain the effect ranging from 10% to 50% increase in bladder volume. Furthermore, the lower urinary tract obstruction will be a predictor of increase in urinary residual volume.
  • Takahide Sugiyama; Nobutaka Shimizu; Kiyoshi Hashimoto; Nobuhiro Yoshioka; Tadashi Hanai; Seiji Matsumoto; Hirotsugu Uemura
    Nihon Hinyokika Gakkai zasshi. The japanese journal of urology 96 (7) 670 - 7 0021-5287 2005/11 [Refereed]
     
    PURPOSE: The clinical benefit of propiverine hydrochloride against overactive bladder was evaluated, and the relationships between urinary voiding functions and the pharmacokinetics were investigated by means of clinical pharmacology with PK/PD approach. PATIENTS AND METHODS: Total 7 patients suffering urgency with urinary frequency and incontinence received propiverine hydrochloride in doses of 10 mg qd or 20 mg qd for 4 weeks, and then the doses were switched in cross-over manner to continue the treatment for further 4 weeks. The urodynamic measurements as well as pharmacokinetic samplings were done before the medication, 4 weeks and 8 weeks after the starting medication, to examine the dose-response and concentration-response relationships. RESULTS: The volume at first desire to void increased according to dose increased, and the volume at first involuntary contraction tended to increase according to both dose and drug concentration in plasma. However, no apparent dose-response relationships were observed for maximum urinary flow rate and the detrusor pressure at the maximum urinary flow rate. The PK/PD analysis using Emax model suggested that, approximately 75 ng/mL of the propiverine concentration in plasma allowed the increase in the volume at first involuntary contraction for 50%. The urinary residual volume increased in dose-dependent manner only in the patients with severe grade of lower urinary tract obstruction, but scarcely increased in the patients with moderate grade or below. CONCLUSION: Propiverine hydrochloride improved the urinary voiding functions with a tendency to depend on both dose and concentration in plasma. After the administration of propiverine hydrochloride, the concentration in plasma will immediately reach the level at which the drug can increase in the volume at first involuntary contraction for 50%, and then the concentration level will sustain the effect ranging from 10% to 50% increase in bladder volume. Furthermore, the lower urinary tract obstruction will be a predictor of increase in urinary residual volume.
  • Seiji Matsumoto; Tadashi Hanai; Nobuhiro Yoshioka; Nobutaka Shimizu; Takahide Sugiyama; Hirotsugu Uemura; Robert M Levin
    Urology Soci?t? Internationale d'Urologie (SIU) 66 (4) 892 - 6 2005/10 [Refereed]
     
    OBJECTIVES: To investigate the effects of edaravone on ischemia/reperfusion (I/R) injury in the rat bladder. Increasing evidence has shown that I/R are major etiologic factors in the progression of bladder dysfunction induced by partial outlet obstruction, and that part of the damage is due to the generation of free radicals. Edaravone is a newly developed radical scavenging agent that has been used for protection against I/R injury in patients with cerebral infarction. METHODS: Thirty-five adult male rats were divided into five groups. Groups 1 to 4 underwent 1 hour of ischemia followed by 1 hour of reperfusion. Groups 1 to 3 were treated with edaravone at 1, 3, or 10 mg/kg body weight and group 4 with saline. Group 5 consisted of age-matched control rats. In vivo ischemia was created by clamping the vesical arteries for 1 hour. Reperfusion was accomplished by removing the clips and also lasted for 1 hour. Edaravone or saline was administered into the femoral artery after reperfusion for 30 minutes. After reperfusion, the bladder was excised and separated. The responses to electrical field stimulation, carbachol, and KCl were recorded. Other materials were analyzed for malondialdehyde as a measure of lipid peroxidation. RESULTS: Edaravone administration resulted in protection of the contractile responses to both field stimulation and carbachol, although the responses to KCl were not affected. I/R resulted in an increase in malondialdehyde, which was reduced to control levels by edaravone. CONCLUSIONS: These results suggest that edaravone has a potential protective effect against I/R-induced damage in the rat bladder.
  • 植村 天受
    Urology View (株)メジカルビュー社 3 (3) 102 - 107 1347-9636 2005/06
  • Tohru Umekawa; Karen Byer; Hirotsugu Uemura; Saeed R Khan
    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 20 (5) 870 - 8 0931-0509 2005/05 [Refereed]
     
    BACKGROUND: Our earlier studies have demonstrated upregulation of monocyte chemoattractant protein-1 (MCP-1) in NRK52E rat renal epithelial cells by exposure to oxalate (Ox) ions and crystals of calcium oxalate monohydrate (COM) or the brushite (Br) form of calcium phosphate. The upregulation was mediated by reactive oxygen species (ROS). This study was performed to investigate whether NADPH oxidase is involved in ROS production. METHODS: Confluent cultures of NRK52E cells were exposed to Ox ions or COM and Br crystals. They were exposed for 1, 3, 6, 12, 24 and 48 h for isolation of MCP-1 mRNA and 24 h for enzyme-linked immunosorbent assay (ELISA) to determine the secretion of protein into the culture medium. We also investigated the effect of free radical scavenger, catalase, and the NADPH oxidase inhibitor diphenyleneiodium (DPI) chloride, on the Ox- and crystal-induced expression of MCP-1 mRNA and protein. The transcription of MCP-1 mRNA in the cells was determined using real-time polymerase chain reaction. Hydrogen peroxide and 8-isoprostane were measured to investigate the involvement of ROS. RESULTS: Exposure of NRK52E cells to Ox ions as well as the crystals resulted in increased expression of MCP-1 mRNA and production of the chemoattractant. Treatment with catalase reduced the Ox- and crystal-induced expression of both MCP-1 mRNA and protein. DPI reduced the crystal-induced gene expression and protein production but not Ox-induced gene expression and protein production. CONCLUSIONS: Exposure to Ox ions, and COM and Br crystals stimulates a ROS-mediated increase in MCP-1 mRNA expression and protein production. Reduction in ROS production, lipid peroxidation, low-density lipoprotein release, and inducible MCP-1 gene and protein in the presence of DPI indicates an involvement of NADPH oxidase in the production of ROS.
  • TSUJI HIDENORI; UMEKAWA TOHRU; KURITA TAKASHI; UEMURA HIROTSUGU; IGUCHI MASANORI; KIN KOKAI; KUSHIDA KAZUHIRO
    International journal of urology 12 (4) 335 - 339 0919-8172 2005/04 
    BACKGROUND: The association between hypercalciuria and bone mineral density (BMD) has been already recognized. The aim of the present study is to relate BMD to age and sex and to evaluate the calcium metabolism and hypercalciuria-defined dietary or non-dietary category in patients with urolithiasis. METHODS: The BMI of the L2-L4 lumbar vertebrae was measured in 310 renal stone patients (191 men and 119 women). Percent age matched score (%AMS), which is the percent ratio of measured BMD to the mean BMD of age-matched control subjects, was utilized for the appraisal of BMD. Low BMD groups were defined by lower than 90% of %AMS. RESULTS: Low BMD was observed in 27.7% of urinary stone patients, which was not a significant difference to that of control subjects (23.5%) who were measured in the health examination. In male patients with urolithiasis, the frequency of patients in whom BMD had been apt to decrease since youth was high, but there was not a proven significant difference among the three age groups (20-39 years old, 40-59 years old and 60 years old or older). In contrast, for female stone patients, the frequency of low BMD markedly increased in patients aged 40 years or older, when menopause occurs. Furthermore, in female stone patients with hypercalciuria, the frequency of reduced BMD reached more than 40%. When the cause was non-dietary hypercalciuria (classified mainly on the daily amount of urinary calcium excretion after ingestion of calculus test diet), the frequency of reduced BMD reached 65% (P < 0.01). CONCLUSIONS: In case female stone patients with non-dietary hypercalciuria become menopausal, not only the risk of recurrent lithiasis increases, but the possibility of developing osteopenia in the future also increases. Appropriate treatments for prophylactic effects on urolithiasis or osteopenia should be considered, as judged from BMD, diet, sex, urinary calcium excretion and other factors synthetically.
  • 松本 成史; 花井 禎; 杉本 公一; 森本 康裕; 上島 成也; 植村 天受
    日本小児泌尿器科学会雑誌 日本小児泌尿器科学会 13 (2) 145 - 150 1341-0784 2005/04
  • 癌ワクチン療法
    植村 天受
    奈医報 18 (1) 15 - 20 2005
  • 治療法 腎細胞癌のワクチン療法
    植村 天受
    Annual Review腎臓 (株)中外医学社 2005 221 - 225 2005/01
  • 杉山 高秀; 清水 信貴; 吉岡 伸浩; 花井 禎; 松本 成史; 植村 天受
    日本排尿機能学会誌 (一社)日本排尿機能学会 15 (2) 191 - 197 1347-6513 2004/12 
    目的:前立腺肥大症患者に過活動膀胱(OAB)症状を高頻度に認める.OAB症状に対しては,抗コリン剤による薬物療法が一般に行われている.しかし,前立腺肥大で閉塞の強い患者にこのような治療を行うと,急性尿閉等の危険があるために投与を慎んでいる.今回,前立腺肥大症に伴う蓄尿症状を有する患者にα1ブロッカーと抗コリン剤を併用することによる臨床的有用性について検討した.方法:前立腺肥大症と診断された患者105例で,α1ブロッカーとして塩酸タムスロシンあるいはナフトピジルが1ヵ月以上投与されているにもかかわらず,蓄尿症状を有する患者35名を対象とした.抗コリン剤として塩酸プロピベリンを4週間以上投与した.評価は塩酸プロピベリン投与前後で自覚症状としてI-PSS,QOLスコアー,昼間・夜間の排尿回数,尿失禁回数の変化を検討した.他覚的には尿流測定検査を行い最大尿流率,残尿量の変化を検討した.結果:塩酸プロピベリン併用投与により自覚症状であるI-PSS,QOLはそれぞれ投与前15.3±5.88,4.5±0.74から投与後13.0±5.85,3.6±1.09と改善していた.最大尿流率は投与前10.4±4.64ml/sに対し投与後9.6±5.0mlと減少した.残尿量は併用投与前29.5±35.06mlに対し投与後42.6±57.24mlと増加を認めた.しかしながら,塩酸プロピベリン併用投与前の排尿機能で最大尿流率が10ml/sを超える症例あるいは残尿量が50ml未満の症例ではI-PSS,QOLは改善し,最大尿流率,残尿量は変動しなかった.考察:前立腺肥大症によるOAB症状に対してα1ブロッカーと塩酸プロピベリンの併用投与は有効な療法である.しかし,排尿機能の有意な悪化がみられた.塩酸プロピベリンの排尿機能に対する影響は併用投与開始時の排尿機能に関連し併用に際しては,自覚症状のみに因われることなく,他覚所見を十分に留意すべきである.なお,α1ブロッカーと塩酸プロピベリン併用療法が有用な因子として最大尿流率が10ml/sを超える症例,残尿量が50ml未満の症例ではよりよい効果が期待される(著者抄録)
  • 松本 成史; 花井 禎; 栗田 孝; 植村 天受; Millington William R.
    日本排尿機能学会誌 (一社)日本排尿機能学会 15 (2) 186 - 190 1347-6513 2004/12 
    目的:大脳が尿禁制に関わっていることは広く知られている.近年の画像診断の発達により,健常人における大脳上位中枢と膀胱機能の関連について検討がなされ,橋,中脳中心灰白質(PAG)や前部帯状回(aCGC)等の部位が蓄尿や尿意に関わっていることが報告されている.われわれは,aCGC領域が排尿にどのような影響を与えるかをその部位の破壊前後の排尿反射の変化で検討した.方法:Sprague Dawley系雌性ラットを,ウレタン麻酔下に経尿道的カテーテルを留置し膀胱内圧を測定した.その後,脳定位固定装置に固定し,aCGC領域にイボテン酸を注入した群(aCGC破壊群)と,生理食塩水を注入した群(sham群)を作製した.1週間経過後,再度前述と同様の手技で麻酔下に膀胱内圧を測定し,手術前後での各排尿パラメーターで検討した.結果:病理組織学的に破壊部位を確認し,aCGC破壊群(n=7)とsham群(n=4)に分類した.排尿間隔はaCGC破壊群で有意に延長した.しかし,sham群では有意な変化を認めなかった.一方,排尿時膀胱内圧は両群ともに破壊前後で有意差を認めなかった.結論:aCGC領域は排尿の閾値に強く関連している可能性が示唆された.アルツハイマー病や脳血管障害等でこれらの領域が障害を受けた症例の排尿モデルとして活用出来る可能性があり,今後aCGC破壊モデルは大脳上位中枢からの神経経路の解明やより効果的な治療法の確立に一役を担えると考えられた(著者抄録)
  • Mitsuhiro Tambo; Kiyohide Fujimoto; Takeshi Inoue; Motoyoshi Tanaka; Akihide Hirayama; Hirotsugu Uemura; Katsunori Yoshida; Yoshihiko Hirao; Kunio Ichijima
    Nihon Hinyokika Gakkai zasshi. The japanese journal of urology 95 (7) 809 - 12 0021-5287 2004/11 [Refereed]
     
    A 61-year-old man presented with an asymptomatic intrapelvic retrovesical tumor, measuring 8.5 cm in maximum diameter, which was revealed by preoperative diagnostic imaging for transverse colon cancer. When he was referred to our department one year after hemi-colectomy, this tumor showed no change in size, but there was some suspicion of concomitant malignancy because of large tumor size and contrast enhancement in a region adherent to the right seminal vesicle. En-bloc resection of the tumor along with the right seminal vesicle was performed retroperitoneally. The tumor was diagnosed histopathologically as retroperitoneal ganglioneuroma. Herein, we report this rare case of intrapelvic retroperitoneal ganglioneuroma, and present a brief review of the relevant literature including the present case.
  • SUGIYAMA Takahide; YOSHIOKA Nobuhiro; MATSUMOTO Seiji; HANAI Tadashi; PARK Young-Chol; UEMURA Hirotsugu
    Jpn J Endourol ESWL 17 (2) 225 - 228 0914-9635 2004/10
  • Toru Shimazui; Kazuhiro Yoshikawa; Hirotsugu Uemura; Yoshihiko Hirao; Shinsuke Saga; Hideyuki Akaza
    Cancer 101 (5) 963 - 8 0008-543X 2004/09 [Refereed]
     
    BACKGROUND: To evaluate the significance of the presence of circulating renal cell carcinoma (RCC) cells in the development of metastases, the authors extended a previous study to quantify cadherin-6 mRNA levels in association with the pattern of metastasis. METHODS: Cadherin-6 mRNA levels were measured in peripheral blood samples from 66 patients with RCC, including 55 patients who had newly diagnosed RCC (43 without metastases and 12 with metastases) and 11 patients who had recurrent RCC. For quantitative polymerase chain reaction analysis, a cutoff value was determined in blood samples from 25 healthy volunteers and was verified in samples from 5 healthy controls and from 10 patients who had other malignancies. The correlation between the site of metastases and the cadherin-6 mRNA level was analyzed, and a follow-up study (median, 39 months) to track subsequent metastases was performed after patients underwent nephrectomy. RESULTS: Cadherin-6 was found in 69.9% of patients with metastases and in 34.9% of patients without apparent metastases (P = 0.0099). In the group of patients with recurrent RCC, patients who had only pulmonary metastases had a significantly lower positivity rate (25.0%) compared with patients who had distant metastases (85.7%; P = 0.044). Among 43 patients with newly diagnosed RCC, 5 of 15 patients who were positive for cadherin-6 had metastases after nephrectomy, whereas only 2 of the 28 patients with negative cadherin-6 status had recurrent disease (P = 0.0398). In addition, the recurrence-free survival of patients who were positive for cadherin-6 was poorer compared with the survival of patients who were negative for cadherin-6 (P = 0.062). CONCLUSIONS: The quantification of cadherin-6 mRNA in peripheral blood may be a significant predictive marker for current and future metastases. However, subsequent metastases did not always correlate with levels of cadherin-6 mRNA. This may have been due either to the small numbers of circulating tumor cells or to the low levels cadherin-6 mRNA in circulating tumor cells.
  • 杉山 高秀; 清水 信貴; 松本 成史; 秋山 隆弘; 国方 聖司; 植村 天受
    泌尿器外科 医学図書出版(株) 17 (7) 769 - 775 0914-6180 2004/07 
    塩酸プロピベリンの有用性を検証するため,過活動膀胱による頻尿・尿失禁19例を対象に自覚症状およびQOLの改善効果をIPSS,ICIQ-SF,KHQで評価し,排尿日誌を用いて排尿回数や排尿量についても検討した.IPSSでは,尿意切迫感,夜間頻尿を含むStorage SymptomおよびQOLについて有意な改善が認められた.ICIQ-SFでは,生活への影響について有意な改善が,尿失禁頻度および尿失禁の量に関して改善傾向が認められた.KHQでは,自覚的重症度について有意な改善が,全般的健康感および生活への影響に関しては改善傾向が認められた.排尿日誌では,1日排尿回数の減少および1回排尿量の増加傾向が認められた.総合的に検討して,塩酸プロピベリンは切迫感を有する頻尿・尿失禁の自覚症状に対する改善傾向が期待でき,QOL向上に寄与していると考えられた
  • OAB
    杉山 高秀; 清水信貴; 松本成史; 植村 天受; 秋山隆弘; 国方聖司
    泌尿器外科 7 (*) 769 - 775 2004/07 
    過活動膀胱による頻尿・尿失禁に対する塩酸プロピベリンのQOL改善効果の検討した。
  • Mitsuhiro Tambo; Kiyohide Fujimoto; Fumiaki Hoshiyama; Michimasa Nakanishi; Takeshi Inoue; Akihide Hirayama; Hirotsugu Uemura; Yoshihiko Hirao
    Hinyokika kiyo. Acta urologica Japonica 泌尿器科紀要刊行会 50 (7) 497 - 499 0018-1994 2004/07 
    We herein report a rare case of leiomyoma in the retroperitoneal space posterior to the urinary bladder. A 61-year-old man came to our department complaining of lower abdominal discomfort. Abdominal and pelvic computed tomographic scan revealed a retrovesical solid tumor on the cranial side to the left seminal vesicle. Diagnostic imaging suggested that the retrovesical tumor was a benign tumor such as leiomyoma or fibroma, and he underwent simple resection of this retrovesical tumor via reroperitoneal approach. Histopathological diagnosis was well compatible with image diagnosis of leiomyoma. He has been followed up for 6 months without recurrence.
  • 植村 天受
    泌尿器外科 医学図書出版(株) 17 (6) 661 - 666 0914-6180 2004/06 
    腎細胞癌は手術療法以外有用な治療法が無く,早期発見・早期治療が重要であることは言うまでもない.しかし,診断の助けとなるよい腫瘍マーカがなく,USやCTなど画像診断に頼っているのが現状である.こうした中,最近では特異的な各種分子をターゲットとしてPCR法を用いた循環血液中腎癌細胞ITC(isolated tumor cell)の検出に関する報告が散見される.そこで,我が国で行われた代表的な分子を標的としたITC検出を結果を検討するとともに,そのバイオマーカとしての有用性について述べた
  • Takanobu Kaido; Hirotsugu Uemura; Yoshihiko Hirao; Ryunosuke Uranishi; Noriyuki Nishi; Toshisuke Sakaki
    Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 10 (6) 703 - 5 2003/11 [Refereed]
     
    We present a case of brain metastases of the urachal carcinoma, which is extremely rare and malignant. Contrast-enhanced MRI was employed to detect them. A large mass was removed surgically and 4 other small metastases were treated by gamma knife radiosurgery. Six weeks after radiosurgery, the 4 lesions had disappeared on MRI. We emphasise the importance of early diagnosis using MRI and treatment by radiosurgery for this rare condition.
  • Toru Shimazui; Kazuhiro Yoshikawa; Hirotsugu Uemura; Risa Kawamoto; Koji Kawai; Katsunori Uchida; Yoshihiko Hirao; Shinsuke Saga; Hideyuki Akaza
    International journal of oncology 23 (4) 1049 - 54 1019-6439 2003/10 [Refereed]
     
    To detect circulating RCC cells, we established a nested RT-PCR system for cadherin-6 mRNA, which is specifically expressed in RCC. A total of 121 samples of peripheral blood (34 healthy volunteers and 87 patients with RCC) were analyzed in this study. Total RNA of the monocyte fraction of the blood was extracted, then nested RT-PCR using specific primers was performed to detect mRNA of N-cadherin or cadherin-6. Nested RT-PCR revealed that expression of cadherin-6 mRNA was not present in the blood of most healthy volunteers (absent in 32/34), but positive expression was observed in the blood at concentrations of 10 cells/ml or greater of the SKRC-33 RCC cell line, which is a strong expresser of cadherin-6. In peripheral blood from patients with metastatic disease, cadherin-6 mRNA was detected in 70.4% (19/27). Messenger RNA of cadherin-6 was detectable in 45.0% (27/60) of patients with localized tumors. The PCR-based detection system for peripheral blood samples from patients with metastatic disease could reveal the presence of circulating RCC cells in the blood. Detection of cadherin-6 mRNA in non-metastatic presurgical RCC patients suggests that careful follow-up study is necessary in these patients.
  • K Shimizu; H Uemura; M Yoshikawa; K Yoshida; Y Hirao; K Iwashima; S Saga; K Yoshikawa
    ONCOLOGY REPORTS PROFESSOR D A SPANDIDOS 10 (5) 1307 - 1311 1021-335X 2003/09 [Refereed]
     
    We investigated the induction of the specific immunity for renal cell carcinomas (RCC) using MN/CA IX, a tumor-associated antigen frequently expressed in RCC. We have generated 9-mer peptide derived from MN/CA IX and examined the antigenicity as a vaccine to induce specific immunity for RCC. To use mouse syngeneic system, we transfected human MN/CA9 cDNA into RenCa and BALB-3T3 cells originally from BALB/c mouse, and established MN/CA IX expressing mouse cell lines, i.e., MN-RenCa and MN-3T3. The immunization of BALB/c mouse with MN-RenCa cells resulted in the induction of cytotoxic T lymphocytes (CTL) against MN/CA IX expressing cells and the CTL clone was established from bulked CTL. This CTL clone specifically lyzed MN-3T3 cells, but not parental cells. To identify the targeted epitope binding to H=2K(d) antigen, three 9-mer peptides (A, B, C-peptide) of human MN/CA IX compatible with the H-2K(d) as well as HLA-A24 binding motif was synthesized. The cloned CTL targeted the B-peptide pulsed BALB-3T3 cells as well as MN-3T3 cells. Furthermore, spleen cells from BALB/c mouse immunized with B-peptide reacted against MN-RenCa cells. These results suggest that the peptides derived from MN/CA IX containing HLA-A24 binding motif may be useful as a potent tumor vaccine for the treatment of human RCC, and in mouse models.
  • H Uemura; Y Nakagawa; A Iwai; E Okajima; E Okajima; K Yoshikawa; Y Hirao
    AKTUELLE UROLOGIE GEORG THIEME VERLAG KG 34 (4) 270 - 272 0001-7868 2003/07 
    Our previous study demonstrated the clear detection of MN/CA9 mRNA in peripheral blood samples from RCC patients. However, approximately 30% of control blood samples from healthy volunteers showed MN/CA9 expression. We have developed a new primer set and optimized the PCR conditions, now resulting in a specificity of 100%. In tissue samples, all clear cell type carcinomas but none of the spindle cell type and pleomorphic cell type tumors expressed the MN/CA9 message. Analysis of MN/CA9 messages in peripheral blood samples from RCC patients gave positive results for 0/2, 1/9, 0/4 and 4/12 of stage I, II, III and IV cases, respectively. RT-PCR analysis using preoperative renal venous blood samples resulted in clear detection of MN/CA9 positive cells in 2/4, 3/13, 2/6 and 1/1 of stage I, II, III and IV cases, respectively. Our results suggest that assessment of MN/CA9 expression by RT-PCR is a promising method for detecting cancer cells in the circulation of patients with RCC.
  • E. Okajima; H. Uemura; S. Ohnishi; M. Tanaka; M. Ohta; M. Tani; K. Fujimoto; S. Ozono; E. Okajima; Yoshihiko Hirao
    Aktuelle Urologie 34 (4) 256 - 258 0001-7868 2003/07 [Refereed]
     
    A new modality is necessary to prevent recurrence of superficial bladder cancer after complete transurethral resection (TUR) because of the high recurrence rate even with current prophylaxis protocols. Prostaglandins (PGs) are known to be produced more in transitional cell carcinoma, and etiologically bladder cancer risk is negatively associated with the intake of non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit cyclooxygenase (COX), the rate-limiting enzyme of the PG production. We have shown the chemopreventive effect of piroxicam, an NSAID, on the N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced rat bladder cancer model. To avoid gastrointestinal side effects of regular NSAIDs, we also showed the chemopreventive effect of nimesulide, a selective inhibitor of the second isoform of COX, COX-2, which does not affect COX-1 house-keeping activity in gastrointestinal mucosa on the same model. We also observed induction of COX-2 protein in the rat bladder tumor. In this study, we screened COX-2 protein expression in primary superficial bladder cancer tissues, to elucidate if COX-2 selective inhibitors can be a candidate chemopreventive agent for bladder cancer recurrence. Five and 6 samples of superficial bladder cancer cases with and without recurrence after complete TUR were examined by immunohistochemical analysis. We found more COX-2 protein positive samples in the cases with recurrence than in cases without recurrence. Even though the number of cases examined is small, this result supports our hypothesis that COX-2 contributes to superficial bladder cancer recurrence, thus, selective COX-2 inhibitors can be a candidate chemopreventive agent for the recurrence.
  • Hiroshi Morikawa; Masaki Cho; Satoshi Takada; Kiyohide Fujimoto; Hirotsugu Uemura; Seiichiro Ozono; Yoshihiko Hirao; Osamu Natsume
    Hinyokika kiyo. Acta urologica Japonica 泌尿器科紀要刊行会 49 (6) 357 - 360 0018-1994 2003/06 
    A 77-year-old man was referred to our hospital with a complaint of dysuria and right ischiodynia. He had had a hemi-thyroidectomy for thyroid cancer and right cervical lymphadenectomy three years and one year, respectively, before this visit. Prostate cancer was strongly suspected by transrectal examination with prostate specific antigen (PSA) elevated to 77.8 ng/ml. Pathological diagnosis of prostate biopsy specimen was transitional cell carcinoma with grade 3 malignancy and negative staining for PSA. Endoscopic examination showed a normal appearance of bladder and prostatic urethral epithelium. Urine cytology showed no malignant cells. However, immunostaining for PSA revealed that the cervical lymph node specimen resected before was moderately differentiated adenocarcinoma of prostate. He had multiple metastases to mediastinal and retroperitoneal lymph nodes and right ischium. Endocrine therapy (goserelin acetate depot, bicalutamide) and systemic chemotherapy (methotrexate, epirubicin, cisplatin) were performed combined with irradiation to right ischium metastasis. Two months later, he showed a complete response in PSA and partial response in lymph node metastases, but died of cancer 13 months later.
  • Hirotsugu Uemura; Masaki Cho; Yoshihiko Hirao; Noboru Konishi
    Hinyokika kiyo. Acta urologica Japonica 泌尿器科紀要刊行会 48 (11) 719 - 723 0018-1994 2002/11 
    We investigated whether the histopathological effect (cell viability) of neoadjuvant hormonal treatment before radical prostatectomy for clinically localized prostate cancer is involved in the biochemical outcome, i.e., androgen independency. Non-randomized prospective trial was carried out between September 1996 and April 2001 involving the patients with clinical stage T1-3 prostate cancer, including 62 who underwent radical prostatectomy after receiving neoadjuvant hormonal treatment for an average of 6.3 months and 76 who underwent radical prostectomy only. All resected specimens were histopathologically diagnosed by whole section analysis. The patients receiving neoadjuvant hormonal treatment were categorized into 4 groups according to the histological change in the resected prostate. There were 8 patients in G0 (all viable cells), 11 patients in G1 (more than 50% viable cells), 26 patients G2 (more than 50% non-viable cells) and 17 patients in G3 (no cancer cells). No difference in the patient background (prostate specific antigen, stage, Gleason score, positive core Nr, duration of neoadjuvant therapy) was observed in any group, except for the duration of (p < 0.05). Multivariate hazards analyses revealed that only the duration of neoadjuvant hormonal treatment was independently associated with excellent responders with grade 3 histological effect. Neoadjuvant hormonal therapy prior to radical operation resulted in various histopathological changes in the prostate, but it is not clear whether the histological effects of hormonal treatment might be involved in the outcome. A longer follow-up randomized prospective trial is necessary.
  • Hirotsugu Uemura; Yoshihiko Hirao
    Gan to kagaku ryoho. Cancer & chemotherapy 29 (10) 1712 - 8 0385-0684 2002/10 [Refereed]
     
    Renal cell carcinoma has a very poor prognosis since various therapeutic modalities other than radical operation are not effective. Early detection and treatment are of considerable importance to cure the patients; however, early diagnosis of renal cell carcinoma is not easy because no specific tumor marker, like PSA for prostate cancer, is available. MN/CA9 is considered to be one of the carbonic anhydrase isoenzymes, and is expressed in approximately 90% of renal cell carcinomas. Expression of MN/CA9 in normal tissues is very limited. Using optimal RT-PCR with specific primers, MN/CA9 positive cells were clearly detected in the blood. The sensitivity and specificity were found to be approximately 40% and 90% respectively. The detection of circulating renal cell carcinoma cells using RT-PCR for MN/CA9 mRNA is useful for diagnosis of the presence of renal cell carcinomas. This RT-PCR assay may also be able to provide information with which to predict the prognosis of the patients.
  • Karin Grabmaier; Mirjam de Weijert; Hirotsugu Uemura; Jack Schalken; Egbert Oosterwijk
    Urology 60 (2) 357 - 62 2002/08 [Refereed]
     
    OBJECTIVES: In renal cell carcinoma (RCC) cell lines, expression of the RCC-associated antigen G250 correlates with hypomethylation of the investigated CpG dinucleotides in the G250 promoter region, despite the absence of a CpG island. To gain insight into the molecular mechanism leading to G250 expression in vivo, we ascertained whether this correlation between G250 gene expression and the methylation status of the G250 gene also existed in primary RCC and normal kidney tissue. METHODS: G250 mRNA and protein expression was determined by reverse transcriptase-polymerase chain reaction, fluorescence activated cell sorting analysis, and immunohistochemistry in 15 RCC cell lines and 13 paired primary RCC/normal kidney tissue specimens. The methylation status of the G250 gene was determined by bisulfite genomic sequencing. RESULTS: RCC cell lines revealed a clear correlation between G250 expression and hypomethylation. In contrast, no hypomethylation was observed in primary RCC compared with normal kidney tissue. The CpG dinucleotides investigated were generally completely methylated in RCC, as well as in normal kidney tissue. Furthermore, a primary culture of RCC tissue revealed increasing hypomethylation of the G250 gene in successive passages, suggesting that the G250 hypomethylation observed in vitro is tissue culture induced. CONCLUSIONS: The methylation status of the G250 gene correlated with G250 expression in vitro but not in vivo.
  • Yoshihiko Hirao; Kiyohide Fujimoto; Masahito Yoshii; Nobumichi Tanaka; Yoshiki Hayashi; Hitoshi Momose; Shoji Samma; Eijiro Okajima; Hirotsugu Uemura; Katsunori Yoshida; Seiichiro Ozono
    Japanese journal of clinical oncology 32 (3) 95 - 102 0368-2811 2002/03 [Refereed]
     
    OBJECTIVE: To determine the methodological usefulness of non-ischemic complete enucleation for small renal cell carcinomas (RCC) using a microwave tissue coagulator (MTC). METHODS: Fifty-nine patients (61 kidneys) underwent non-ischemic complete tumor enucleation by MTC. Of the 59 patients, 46 had an elective indication and 15 kidneys of 13 patients had an imperative indication. RCC was exposed with minimal peri-renal detachment. The demarcation line, 7-10 mm from the tumor, was coagulated at 8-10 mm intervals with a microwave antenna needle for 30-40 s at 50-60 W. The renal tumor was excised along the coagulated zone with normal surrounding tissue. The enucleation bed was covered with fibrin glue or fat tissue without approximation. RESULTS: The operations were successfully completed in all intended cases. The mean operation time was 160 +/- 43 (median: 160) min and the mean blood loss was 313 +/- 370 (median: 158) ml. No major bleeding or urine leakage from the enucleation bed was observed in 62.2 and 88.5% of cases, respectively. The minor bleeding and urine leakage were controlled easily with absorbable sutures. None of the cases presented with postoperative bleeding or urine leakage from the enucleation bed. Severe impairment of the renal function was not observed in any case evaluated by means of serum creatinine, creatinine clearance and radioisotope examination. The 5-year overall survival rate was 87% without recurrence up to 23.1 +/- 19.5 months of the mean follow-up. CONCLUSION: Non-ischemic complete tumor enucleation using MTC constitutes a simple, reliable and less invasive alternative to ordinary nephron-sparing surgeries for small RCC.
  • Katsunori Yoshida; Takanori Kitauchi; Shouki Kimura; Tatsuo Yoneda; Hirotsugu Uemura; Seiichirou Ozono; Yoshihiko Hirao
    Artificial organs 26 (1) 54 - 7 0160-564X 2002/01 [Refereed]
     
    The exposure of blood to hemodialysis membranes results in numerous phenomena and/or complications in hemodialyzed patients, which have an influence on the quality of life (QOL) of those patients. A vitamin E-modified regenerated cellulose membrane (E-membrane) was developed to act as a scavenger for reactive oxygen species causing complications in hemodialysis patients. Neopterin (NEOP) is a metabolite derived from guanosine triphosphate with the production and release of NEOP being induced in monocytes and macrophages by cytokines such as interferon-gamma (IFN-gamma). Serum neopterin levels are shown to be a reactive marker of bioincompatibility of dialysis membranes in hemodialysis patients. The following report evaluates the usefulness of serum NEOP as a marker for the biocompatibility of the E-membrane hemodialyzer in a clinical study. In the clinical study, where extracorporeal ultrafiltration strategies with E-membranes were employed, the serum levels of NEOP were lower than those in patients using cellulose triacetate membranes (C-membranes). In the long-term evaluation of the biocompatibility of E- and C-membranes, the increase of serum neopterin levels in the C-membrane was higher than those in the E-membrane. In conclusion, the evaluation of serum neopterin levels during hemodialysis shows that the E-membrane has a good biocompatibility in hemodialyzed patients.
  • KAWADA Yoichi; NAKAMURA Mitsutoshi; ISHIDA Eiwa; SHIMADA Keiji; OOSTERWIJK Egbert; UEMURA Hirotsugu; HIRAO Yoshihiko; CHUL Kim Sung; KONISHI Noboru
    Jpn J Cancer Res BUSINESS CENTER ACADEMIC SOCIETIES JAPAN 92 (12) 1293 - 1299 0910-5050 2001/12 
    The INK4a/ARF locus on chromosome 9p21, which encodes two distinct genes, p14(ARF) and p16(INK4a), is frequently altered in human neoplasms. To investigate the potential roles of p14ARF and p16(INK4a) genes in human renal cell carcinomas (RCCs), we analyzed 6 human RCC cell lines and 91 primary RCCs for homozygous deletion, promoter hypermethylation and expression of the p14(ARF) and p16(INK4a) gene products using differential PCR, methylation-specific PCR, and immunohistochemistry, respectively. Five cell lines showed homozygous co-deletion of both genes and one demonstrated promoter hypermethylation of the p16(INK4a) gene only. Eight of 91 RCCs showed aberrations of p14(ARF) or p16(INK4a) status and six of these featured gross extension into the renal vein. The results suggest that p14(ARF) and p16(INK4a) aberrations may play roles in the relatively late stage of renal tumorigenesis associated with tumor progression.
  • M Cho; H Uemura; SC Kim; Y Kawada; K Yoshida; Y Hirao; N Konishi; S Saga; K Yoshikawa
    BRITISH JOURNAL OF CANCER CHURCHILL LIVINGSTONE 85 (4) 563 - 567 0007-0920 2001/08 [Refereed]
     
    MN/CA9 is a cancer-related gene, frequently activated in human renal cell carcinomas (RCCs). To reveal the activation mechanism, we investigated the relationship between methylation status of the MN/CA9 promoter region and gene expression using 13 human RCCs, and examined the effect of in vitro CpG methylation on the MN/CA9 promoter activity using a human RCC cell line (SK-RC-44), expressing MN/CA9. MN/CA9 expression was evaluated by RT-PCR and observed in 10 of 13 RCCs (77%). A total of 9 out of 10 MN/CA9-positive RCCs (90%) contained clear cell components. Methylation status of 6 CpGs in the MN/CA9 promoter region was decided by using the bisulfite genomic sequencing protocol. Out of 13 RCCs 9 (69%) showed partial hypomethylation of the CpG at -74 bp, while the other 4 RCCs and 3 normal kidney tissue samples showed complete methylation. Hypomethylation of the CpG at -74 bp was strongly correlated with MN/CA9 expression. Luciferase assay revealed that the MN/CA9 promoter activity was strongly suppressed by methylation of the CpG at -74 bp. These findings suggest that hypomethylation of the CpG at -74 bp in the MN/CA9 promoter region might play an important role in this gene activation of human RCC. (C) 2001 Cancer Research Campaign http://www.bjcancer.com.
  • 植村 天受
    臨床泌尿器科 (株)医学書院 55 (5) 329 - 335 0385-2393 2001/04 
    腎細胞癌は泌尿器癌の中でも有効な治療法のない予後不良の疾患である.そのため,早期発見,早期診断の助けとなるマーカーの開発が急務である.MN/CA IX抗原は細胞膜に存在する癌関連抗原で,腎細胞癌では約90%と高率に発現しており,抗体を使った臨床試験では診断のターゲットとして既に有用性が証明されている.MN抗原を標的分子とした診断法は特異的で,腎細胞癌の新しいバイオマーカーとして有用と思われる
  • H Uemura; Y Nakagawa; Y Hirao; E Okajima; K Yoshikawa; E Oosterwijk
    AKTUELLE UROLOGIE GEORG THIEME VERLAG 31 52 - 54 0001-7868 2000/09 [Refereed]
     
    In the present study, we investigated MN/G250 expression with immunohistochemistry and RT-PCR in urologic cancers. in addition, we applied PCR technology to detect circulating MN/G250-positive cells in patient blood samples. Frozen specimens of 92 RCC, 54 bladder carcinoma (BT) 42 prostate carcinoma (PCa), and 19 germ cell tumor (GCT) were studied by immunohistochemistry with MAbG250 as well as RT-PCR analysis with primers derived from cDNA sequence of MN/G250 antigen, in RCC, 81 of 92 (88%) specimens showed strong and homogeneous MN/G250 expression, in accordance with our previous studies. PCR analysis resulted in clear detection of WIN mRNA signals in 86 RCC (93%), more than protein lever. All 81 positive staining RCC showed MN/CA9 gene expression. No correlation between MNG250 expression and tumor stage was observed, however, tumor grade significantly correlated with MN expression, i.e., high grade tumors showed the decrease of MN expression (5/16, only 31 %). in BT, 21 of 54 (39 %) primary tumors showed MN expression. Comparing to RCC, immunostaining pattern of BT demonstrated heterogeneous and weak. MN expression in BT appeared to correlate with tumor grade, i.e., low grade and papillary tumor had positive immunoreactivity with MAbG250 but not in high grade, invasive cases. In contrast, no MN expression was observed in PCa, GCT specimens and other normal tissues. For molecular detection of circulating cancer cells, one third of blood samples from RCC patients demonstrated MN/G250 mRNA. Our findings suggest that MN/G250 antigen may be potential target molecule in RCC.
  • Y Hirao; M Yoshi; S Tsujimoto; H Uemura; K Yoshida; S Ozono; E Okajima
    AKTUELLE UROLOGIE GEORG THIEME VERLAG 31 2 - 3 0001-7868 2000/09 [Refereed]
  • M Cho; K Grabmaier; Y Kitahori; Y Hiasa; Y Nakagawa; H Uemura; Y Hirao; T Ohnishi; K Yoshikawa; E Ooesterwijk
    MOLECULAR CARCINOGENESIS WILEY-LISS 27 (3) 184 - 189 0899-1987 2000/03 [Refereed]
     
    The MN/CA9 (G250) gene expressed in the normal alimentary tract in a tissue-specific manner is often activated in renal cell carcinomas. To cast light on the activation mechanism, we examined the methylation status of this gene in seven human renal cell carcinoma cell lines (SKRC-01, -06, -10, -12, -14, -44, and -59) and three normal kidney tissue samples by using the bisulfite genomic sequencing protocol. CpG methylation was measured at seven locations in the MN/CA9 5' region. MN/CA9 transcripts were detected by reverse transcription-polymerase chain reaction in five of the renal cell carcinoma cell lines (SKRC-01, -06, -10, -44, and -59). These MN/CA9 positive cell lines showed hypomethylation, whereas the remaining two cell lines (SKRC-12, and -14), and three normal kidney tissue samples without transcripts demonstrated hypermethylation. Treatment with the demethylating agent 5-aza-2'-deoxycytidine resulted in activation of the MN/CA9 gene in the negative cell lines (SKRC-12 and -14). These data suggest that hypomethylation in the 5' region may have a major role in expression of the MN/CA9 gene in renal cell carcinoma cells. Mol. Carcinog. 27:184-189, 2000. (C) 2000 Wiley-Liss, Inc.
  • YOSHIDA Katsunori; YANEDA Tatsuo; KANEKO Yoshiteru; MARUYAMA Yoshio; IJYUIN Masumi; KAGEBAYASHI Yoriaki; NAKAGAWA Yoshiki; UEMURA Hirotsugu; OZONO Seiichirou; OKAJIMA Eigoro; HIRAO Yoshihiko
    JAPANESE JOURNAL OF TRANSPLANTATION JAPANESE SOC TRANSPLANTATION 34 (6) 372 - 378 0578-7947 1999/12 
    Fifty-eight patients with end stage renal failure underwent living graft (27 cases) and cadaveric graft: (31 cases) renal transplantations between Nov. 1974 and Jun. 1999. As immunosuppressive therapy, two drugs (azathioprine [AZA] and steroids [STR]) were used until 1984. Since then, three drugs (AZA, STR and cyclosporine-A[CYA]) have been used for living renal transplantation, and anti-lymphocyte globulin (ALG) was also used for cadaveric renal transplantation. Additionally, tacrolimus (TAC) has been used in some cases since 1997. Survival rates of all recipients at 1 year, 3 years, 5 years, and 10 years are 94.8%, 92.6%, 90.3% and 85.6%, respectively, and graft survival of the same periods are 85.5%, 77.6%, 57.4%, and 50.2%, respectively. The possession rate of cadaveric renal transplantations of all recipients is 54%. It is particular to Nara Medical University, in comparison of other institutions of Japan.
  • H Uemura; Y Nakagawa; K Yoshida; S Saga; K Yoshikawa; Y Hirao; E Oosterwijk
    BRITISH JOURNAL OF CANCER CHURCHILL LIVINGSTONE 81 (4) 741 - 746 0007-0920 1999/10 
    The monoclonal antibody G250 (mAbG250) raised against a human renal cell carcinoma (RCC) has been shown to react with a large number of RCCs. Recently G250 antigen was isolated and found to be homologous to the MN/CA9 gene originally identified in HeLa cells. To determine whether G250 antigen (MN/CA IX/G250) could be a potential therapeutic target and a tumour marker, a total of 147 cases of RCC were investigated immunohistochemically as well as by reverse transcriptase polymerase chain reaction (RT-PCR) analysis. In addition, total RNAs extracted from patients' peripheral blood samples were analysed for MN/CA9/G250 mRNA signals. Immunohistochemistry demonstrated strong expression in 128/147 (87.1%) of RCCs, in contrast to the lack of expression observed in normal tissues. RT-PGR analyses of frozen specimens resulted in the clear detection of MN/CA9/G250 mRNA signals in 137/147 (93.2%), and despite subtle differences the results were almost identical to those for immunohistochemistry. Although high-grade and -stage tumours exhibited significantly lower expression than low-grade and -stage tumours, a large proportion of tumours expressed MN/G250 protein as well as mRNA. RT-PCR analysis of patients' blood samples revealed the presence of circulating MN/CA9/G250 expressing cells. These findings suggest that this antigen may be a potential therapeutic target as well as diagnostic marker for RCCs. (C) 1999 Cancer Research Campaign.
  • Noboru Konishi; Mitsutoshi Nakamura; Shingo Nakaoka; Yoshio Hiasa; Masaki Cho; Hirotsugu Uemura; Yoshihiko Hirao; Takashi Muramatsu; Kenji Kadomatsu
    Oncology 57 (3) 253 - 257 0030-2414 1999/10 [Refereed]
     
    Midkine (MK) is a growth/differentiation factor frequently expressed at high levels in some types of human malignancies. To investigate whether MK is a useful marker in prostate carcinogenesis, immunohistochemical analysis was performed on samples of both latent and clinical prostate cancers of various stages, as well as on specimens of normal gland and prostatic intraepithelial neoplasia (PIN). Of the 80 clinical cancers examined, 69 specimens (86.3%) were immunoreactive for MK, with metastatic lesions generally showing higher expression than the corresponding primaries normal prostate tissues were negative or showed only weak staining. Midkine was also detected in 12 of 15 latent cancers (80%) and in 12 of 16 cases of PIN (75%). In sections of whole prostate, MK showed variable expression through tumorous sections, probably in reflection of heterogeneous cell populations. The results demonstrate the possible value of MK as a marker for early and latent disease, as well as for more advanced clinical stages of prostate cancer.
  • H Uemura; Y Nakagawa; K Yoshida; S Saga; K Yoshikawa; Y Hirao; E Oosterwijk
    BRITISH JOURNAL OF CANCER CHURCHILL LIVINGSTONE 81 (4) 741 - 746 0007-0920 1999/10 [Refereed]
     
    The monoclonal antibody G250 (mAbG250) raised against a human renal cell carcinoma (RCC) has been shown to react with a large number of RCCs. Recently G250 antigen was isolated and found to be homologous to the MN/CA9 gene originally identified in HeLa cells. To determine whether G250 antigen (MN/CA IX/G250) could be a potential therapeutic target and a tumour marker, a total of 147 cases of RCC were investigated immunohistochemically as well as by reverse transcriptase polymerase chain reaction (RT-PCR) analysis. In addition, total RNAs extracted from patients' peripheral blood samples were analysed for MN/CA9/G250 mRNA signals. Immunohistochemistry demonstrated strong expression in 128/147 (87.1%) of RCCs, in contrast to the lack of expression observed in normal tissues. RT-PGR analyses of frozen specimens resulted in the clear detection of MN/CA9/G250 mRNA signals in 137/147 (93.2%), and despite subtle differences the results were almost identical to those for immunohistochemistry. Although high-grade and -stage tumours exhibited significantly lower expression than low-grade and -stage tumours, a large proportion of tumours expressed MN/G250 protein as well as mRNA. RT-PCR analysis of patients' blood samples revealed the presence of circulating MN/CA9/G250 expressing cells. These findings suggest that this antigen may be a potential therapeutic target as well as diagnostic marker for RCCs. (C) 1999 Cancer Research Campaign.
  • KONISHI Noboru; NAKAOKA Shingo; MATSUMOTO Kyoichi; NAKAMURA Mitsutoshi; KUWASHIMA Shin-ichi; HIASA Yoshio; CHO Masaki; UEMURA Hirotsugu; HIRAO Yoshihiko
    Pathology International Published by Blackwell Science for the Japanese Society of Pathology 49 (3) 203 - 207 1320-5463 1999/03 
    The expression of pepsinogen II (PG II), an aspartyl proteinase usually involved in the digestion of proteins in the stomach, was immunohistochemically investigated in conjunction with androgen (AR) and estrogen receptor (ER) status in prostate adenocarcinomas. Of a total of 38 samples obtained from radical prostatectomies, 23 tumors (60.5%) were positive for PG II and there was a significant positive correlation to the expression of AR but not to ER. Cells positive for PG II were localized mainly to the peripheral zones of tumorous glands which, in normal prostate, are negative, and in areas also expressing AR. In addition, a significant correlation between AR and ER was detected in the prostate carcinomas examined, which suggests a hormone-dependent status. On the basis of these results, PG II expression might be closely related to hormonal alterations associated with the development of prostate tumors.
  • M Cho; N Konishi; K Yamamoto; T Inui; Y Kitahori; Y Nakagawa; H Uemura; Y Hirao; Y Hiasa
    EUROPEAN JOURNAL OF CANCER PERGAMON-ELSEVIER SCIENCE LTD 34 (13) 2112 - 2118 0959-8049 1998/12 [Refereed]
     
    In order to reveal and characterise genetic events occurring in renal tumorigenesis, samples of sporadic renal cell carcinomas (RCCs) were examined using restriction landmark genomic scanning (RLGS), an electrophoretic separation technique which detects gene amplification and deletion. We were able to find two fragments frequently amplified and 10 others commonly showing reduced signal intensity within the 16 tumour samples analysed. These altered spots were located on chromosomes 2, 3, 9-12, 16, 17 and 18 according to chromosomal assigned RLGS;. A subset of reduced fragments appeared to be correlated to tumour type and were located within a new chromosomal region, suggesting genetic specificity within the process of renal carcinogenesis. (C) 1998 Elsevier Science Ltd. All rights reserved.
  • Y Nakagawa; H Uemura; Y Hirao; K Yoshida; S Saga; K Yoshikawa
    GENOMICS ACADEMIC PRESS INC 53 (1) 118 - 119 0888-7543 1998/10 [Refereed]
  • M Cho; N Konishi; Y Kitahori; Y Hiasa; YI Nakagawa; H Uemura; Y Hirao; E Oosterwijk
    CELLULAR AND MOLECULAR BIOLOGY CELLULAR & MOLECULAR BIOLOGY 44 (6) 913 - 918 0145-5680 1998/09 [Refereed]
     
    Gene amplification, which has often been observed in various human cancers, appears to be associated with the development and progression of malignant phenotypes. However, in renal cell carcinoma (RCC), conventional analytic methods requiring specific primers and probes have revealed infrequent amplification of known oncogenes. We attempted to determine if gene amplification was truly uncommon in RCC. The genomic DNAs extracted from 5 human RCC cell lines were examined by restriction landmark genomic scanning (RLGS), a two-dimensional gel analysis which allows evaluation of approximately 2,000 radiolabelled DNA fragments. By this method, we detected 24 distinct spots commonly amplified in at least 2 RCC cell lines compared to normal kidneys. Comparing the present results with chromosomal assigned-RLGS, approximately one half of these DNA fragments proved to be located on chromosome 2, 5 or 7. Our data suggest that amplification of unknown genes is likely to occur in RCC cell lines.
  • Eigoro Okajima; Seiichiro Ozono; Katsunori Yoshida; Shoji Samma; Hitoshi Momose; Akio Iwai; Hirotsugu Uemura; Shoichi Tabata; Kenichi Tsumatani; Yoshihiko Hirao; Kunihiko Tsunemi
    Urological Research 25 (5) 315 - 323 0300-5623 1997/10 [Refereed]
     
    Bladder tumors were induced by N-butyl-N(4-hydroxybutyl)nitrosamine (BBN) in five Beagles and four mongrel dogs. The tumors were observed for long periods and the tumor progression was traced using histopathological mapping. The results indicated (1) that low-dose BBN over a long period induced multiple low-grade (G1-2) and low-stage (pTa-1) papillary tumors, resembling superficial bladder cancer in humans (2) that high-dose BBN over a short period induced high-grade (G2-3) and high-stage (pT3b) nonpapillary tumors and carcinoma in situ (CIS) resembling invasive cancer and CIS in humans (3) that beagle dogs required longer periods and higher total doses of BBN as compared with mongrel dogs (4) that the tumors induced by low- dose BBN in beagles were observed without BBN as long as the animals lived, and neither increasing numbers of tumors nor malignant features such as deep infiltration and metastasis was observed and (5) that low-dose BBN seems to induce mild dysplasia, which is followed by Brunn's nest-like proliferation in the lamina propria and nodular change, eventually leading to the development of papillary noninvasive transitional cell carcinoma (TCC) and that high-dose BBN seems to induce severe dysplasia which leads to CIS and nonpapillary invasive TCC. These results may contribute to clarifying the natural history of human bladder cancer.
  • K Tsumatani; Y Nakagawa; Y Kitahori; N Konishi; H Uemura; S Ozono; Y Hirao; E Okajima; K Hirao; Y Hiasa
    TOXICOLOGIC PATHOLOGY SOC TOXICOLOGIC PATHOLOGISTS 25 (4) 363 - 371 0192-6233 1997/07 [Refereed]
     
    We previously reported that treatment of Fischer-344 rats with 2-amino-4,5-diphenylthiazole (DPT) results in renal cystic changes. The present study was undertaken to examine the effects of long-term DPT treatment after initiation of kidney carcinogenesis with N-ethyl-N-hydroxyethylnitrosoamine (EHEN) in Wistar rats. One hundred forty-four 6-wk-old male Wistar rats were divided into 6 equal receiving groups: 1000 ppm EHEN or normal tap water for 2 wk followed by 1.06% DPT or basal diet for the subsequent 14 or 30 wk. Controls were maintained without treatment throughout. Subgroups of 6 animals from each group were sacrificed after 8, 16, 24, and 32 wk for histopathological assessment of lesion development in the kidneys and liver. Animals treated with DPT first developed cystic changes of the kidneys (primarily at the corticomedullary border) after 8 wk of treatment, and these changes progressed with time thereafter. In the groups in which DPT treatment was discontinued after 14 wk, cysts then gradually decreased in size. All tumors detected in the kidneys were histopathologically diagnosed as renal cell adenomas. The tumor multiplicity after 32 wk of treatment was significantly higher in Group I, receiving EHEN + DPT for 30 wk (6.33 +/- 4.36), and Group III, receiving EHEN + DPT for 14 wk (3.83 +/- 1.57), than in Group V, EHEN alone (1.00 +/- 0.58) (p < 0.05). Renal cell tumors within cysts were only seen in Groups I and III. The general bromodeoxyuridine labeling indices for the kidneys at week 32 were significantly higher in Group I (55.94 +/- 21.08 cells/mm(2)) and Group III (53.75 +/- 12.38 cells/mm(2)) than in Group V (22.38 +/- 6.98 cells/mm(2)) (p < 0.05). In conclusion, DPT caused cystic changes in rat kidneys, which, however, gradually decreased in size after the treatment was discontinued, suggesting a reversible nature. DPT clearly also promotes renal tumor development after EHEN initiation, and this effect persists, to a certain extent, even after the insult is removed.
  • TSUMATANI Kenichi; OZONO Seiichiro; UEMURA Hirotsugu; YAMAGUCHI Hisako; HIRAO Yoshihiko; MOTOMIYA Yoshihiro; OKAJIMA Eigoro; KITAHORI Yoshiteru; HIASA Yoshio; OKABE Hiroaki; UJI Yoshinori
    Journal of Toxicologic Pathology JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY 9 (2) 151 - 159 0914-9198 1996/06 
    Changes in the kidneys were studied histopathologically and biochemically in F344 rats treated for long periods with 2-amino-4, 5-diphenylthiazole (DPT), with and without prior application of the renal carcinogen N-ethyl-N-hydroxyethylnitrosamine (EHEN). Experiment I: A total of 45 male 6-week-old F344 rats were divided into two groups; one receiving DPT at 1.06% in the diet (n=30) and the other being untreated (n=15). The observation period was 52 weeks. DPT caused cystic changes in the corticomedullary border, which were seen from the 4th week, progressed with time. Urine osmolarity began to decrease from the 6th week, however no biochemical signs of renal failure were noted before the 32nd week. High-performance liquid chromatography (HPLC) revealed 6 fractions, representing metabolites of DPT, in urine from DPT-treated rats. Experiment II: A total of 132 male 6-week-old F344 rats were divided into four groups: Group 1 (2-weeks 1, 000 ppm EHEN treatment followed by 1.06% DPT treatment), Group 2 (1.06% DPT treatment), Group 3 (2-weeks 1, 000 ppm EHEN treatment), and Group 4 (untreated controls). They were observed for 60 weeks. Cystic changes in the kidneys, as seen in Experiment I, were noted in Groups 1 and 2. Preneoplastic changes were seen only in Group 1, at incidences of 20% and 75% at weeks 48 and 60, respectively. Adenomas were seen in Groups 1 and 3, at incidences of 20% and 0%, and 25% and 20% at weeks 48 and 60, respectively. A carcinoma was diagnosed in 1 (20%) of the 5 rats from Group 1 in the 48th week. These results suggest that the DPT-treated rat can serve as a valid experimental model of congenital cystic kidney disease and chronic renal failure, and that DPT may promote EHEN-induced renal carcinogenesis.
  • Y Hirao; H Uemura; K Fujimoto; K Yoshida; S Ozono; E Okajima
    AKTUELLE UROLOGIE GEORG THIEME VERLAG 27 17 - 19 0001-7868 1996/04 [Refereed]
     
    Non-ischemic enucleation of small renal cell carcinoma using microwave tissue coagulator was performed on 13 kidneys of 12 patients (average 64.2 years old) at Nara Medical University Hospital and its affiliated hospitals between September 1993 and June 1995. The indication for nephron-sparing surgery were elective in 8 cases and imperative in 5 kidneys of 4 cases. The renal cell carcinoma size was on average 36.8 mm (20-50 mm). The demarcation line, 7-10 mm apart from the tumor margin, was defined under ultrasonography, and was coagulated at every 8-10 mm interval along the demarcation line with the microwave monopolar antenna needle. The renal tumor was excised along the middle of coagulated zone with scissors and blunt dissection. The operation time was on average 174.2 minutes, and perioperative bleeding was average 249.5 ml, excluding case 2 who underwent partial hepatectomy for metastatic rectal cancer simultaneously. No major complication was encountered. Local recurrence and severe impairment of the remaining kidney were not observed in all cases at the median 9.6 months of follow-up. In situ non-ischemic tumor enucleation using microwave tissue coagulator constitutes a simple, reliable, and less invasive alternative to ordinary nephron-sparing surgery, and is indicated for small asymptomatic renal cell carcinoma.
  • Hirotsugu Uemura; Eigoro Okajima; Frans M.J. Debruyne; Egbert Oosterwijk
    Urologic Oncology: Seminars and Original Investigations 1 (2) 73 - 79 1078-1439 1995 [Refereed]
     
    We have shown that six different internal image antiidiotype antibodies (Ab2) raised against the combining site of the murine monoclonal antibody G250 (MAbG250 Abl), which specifically reacts with a human renal cell carcinoma (RCC)-associated antigen, induce antigen specific humoral and cellular responses in mice. These six Ab2 can be divided into four mutually exclusive groups: (1) NUH31 and NUH51, (2) NUH44 and NUH82, (3) NUH71, and (4) NUH91. Immunization with NUH82 or NUH91 resulted in Ab3 sera that gave complete protection against tumor challenge. In this study, we tested the antitumor efficacy of NUH82- and NUH91-induced mouse sera (Ab3 sera Ab3-82 and Ab3-91) in mice with established subcutaneous human RCC xenografts. Mice were treated 3 times per week by intraperitoneal injection of Ab3 sera (0.2 ml) or MAbG250 (250 μg) for 6 weeks. Treatment of NU12 human RCC xenografts of approximately 20 mm3 expressed as tumor size index (TSI) with NUH-Ab3 sera or MAbG250 resulted in significant tumor growth inhibition compared with tumors treated with Ab3 sera from mice immunized with control immunoglobulin (Ab3-MOPC). In all Ab3-NUH treated mice, tumors stabilized or disappeared completely. In contrast, Ab3-MOPC treatment did not result in any antitumor effects. Tumor remnants in Ab3-NUH treated animals contained viable tumor cells surrounded by infiltrating mouse cells, whereas no infiltration was observed in control tumors. These findings demonstrate that Ab3 sera obtained from NUH82- or NUH91-immunized mice are very effective in eradicating established RCC [i.e., Ab2 vaccination may be able to eradicate (minimal) residual disease in RCC patients]. © 1995.
  • H UEMURA; E OKAJIMA; FMJ DEBRUYNE; E OOSTERWIJK
    INTERNATIONAL JOURNAL OF CANCER WILEY-LISS 59 (6) 802 - 807 0020-7136 1994/12 [Refereed]
     
    We have previously isolated and characterized 6 anti-idiotype antibodies (Ab2s) directed against monoclonal antibody G250 (MAbG250) which reacts with a tumor-associated antigen (TAA) expressed in a large proportion of human renal-cell carcinomas (RCC). These 6 Ab2s (NUH31, 51, 71, 82, 91: IgG(1), NUH44: IgG(2a)) showed MAbG250 binding site specificity and induction of anti-TAA antibody resembling MAbG250 (so-called Ab1') in rabbits, indicating that they are internal image antibodies. To investigate whether these Ab2s could induce G250-TAA-specific cell-mediated immunity, delayed-type hypersensitivity (DTH) tests were carried out with G250 antigen-positive and/or -negative cells in the ears of BALB/c mice. Mice primed with Ab2 showed antigen-specific DM responses, whereas no significant DTH response was observed with G250-negative cells. This antigen-specific DTH could be transferred to naive mice by lymphocytes harvested from Ab2-sensitized mice. In addition to the classical DTH responses observed 24 and 48 hr after tumor challenge, an early-phase antigen-specific hypersensitivity response was seen 2 hr after challenge. This early component of the specific hypersensitivity reaction but not the classical DTH could be transferred to naive mice by serum from Ab2-sensitized mice, indicating that the early reaction was due to serum factors. These findings demonstrate that all AbZs induced tumor-specific cellular immune responses directed against human RCC, and suggest that they may be useful as RCC-TAA surrogates, i.e., as tumor vaccines for RCC patients. (C) 1994 Wiley-Liss, Inc.
  • H UEMURA; AJMC BENIERS; E OKAJIMA; FMJ DEBRUYNE; E OOSTERWIJK
    INTERNATIONAL JOURNAL OF CANCER WILEY-LISS 58 (4) 555 - 561 0020-7136 1994/08 [Refereed]
     
    We have previously isolated and characterized 6 different internal image mouse monoclonal anti-idiotype antibodies (Ab2) directed against the paratope of mouse monoclonal antibody G250 (MAbG250, Ab1), which specifically reacts with human renal cell carcinoma (RCC). These Ab2s (NUH31, 44, 51, 71, 82 and 91) demonstrated specificity for the combining site of Ab1, and appeared to recognize 2 partly overlapping idiotopes on Ab1. In this study. we further characterize the fine specificity of the Ab2, investigate whether the immunogenicity of Ab2 could be enhanced by conjugation to a carrier and investigate the anti-tumor efficacy of Ab3 sera in mice challenged with RCC. Immunization of animals with Ab2 conjugated to keyhole limpet hemocyanin as carrier protein resulted in a 2-fold increase in antigen-specific anti-anti-idiotype antibodies (Ab3) as compared with immunization using Ab2 alone. Specific reactivity was observed with antigen-positive cell lysates, and all Ab3 sera contained immunoglobulin resembling Ab1 (Ab1'), as shown by competitive Ab1-antigen binding assays. Fine-specificity studies of Ab3 sera revealed that the Ab2s can be divided into 4 mutually exclusive groups, showing that the 6 Ab2s recognize 4 slightly different idiotopes in the Ab1 binding pocket. Treatment of RCC-challenged mice with Ab3 sera resulted in significant tumor growth inhibition and lower tumor take rates as compared with control groups. Ab3 sera obtained from NUH-91-immunized animals showed superior characteristics as compared to the other Ab3 sera: no tumors remained after 5 weeks of Ab3-NUH91 treatment. Our findings indicate that the Ab2 elicit powerful anti-tumor effects in immune-competent animals. (C) 1994 Wiley-Liss, Inc.
  • H UEMURA; E OKAJIMA; FMJ DEBRUYNE; E OOSTERWIJK
    INTERNATIONAL JOURNAL OF CANCER WILEY-LISS 56 (4) 609 - 614 0020-7136 1994/02 [Refereed]
     
    The potential usefulness of internal-image anti-idiotype antibodies (Ab2s) in modulating hosts' immune responses to tumor-associated antigen (TAA) have stimulated considerable interest in the development and characterization of Ab2s. Six different mouse monoclonal Ab2s (NUH31, 44, 51, 71, 82 and 91) were generated against murine monoclonal antibody G250 (MAbG250) which recognizes a human renal-cell carcinoma-associated antigen. All 6 Ab2s showed specificity for the MAbG250 paratope in Western-blot analysis. In inhibition assays, all Ab2s were able to compete with the nominal antigen, albeit with differing efficiency. Based on cross-blocking studies for idiotope mapping, the Ab2s could be divided into 2 groups (group I; NUH31, 51, 71, group 2; NUH44, 82, 91). However, cross-reactivity between these 2 groups was observed, indicating that they recognized partly overlapping epitopes on the paratope of MAbG250. Sera from rabbits immunized with Ab2s showed reactivity with G250 antigen-positive cell lysates, but not with antigen-negative cell lysates. Additional studies revealed that all Ab2s were able to induce anti-anti-idiotype antibodies resembling MAbG250 (Ab 1'). These findings suggest that the Ab2s functionally mimic the original G250 antigen and may be of use in the immunotherapy of human renal-cell carcinoma. (C) 1994 Wiley-Liss, Inc.
  • Eijiro Okajima; Seiichiro Ozono; Junichi Nagayoshi; Hirotsugu Uemura; Yoshihiko Hirao; Yoshiyuki Nakajima; Hiroshige Nakano; Masumi Yoshida; Masahito Sugimura; Eigoro Okajima
    Japanese Journal of Clinical Oncology 24 (3) 166 - 170 1465-3621 1994 [Refereed]
     
    We report a unique case of a patient with synchronous renal cell carcinoma, hepatocellular carcinoma and squamous cell carcinoma of the oral floor. All three tumors were resected during a single operation. The patient was a 75-year-old man with masses in the liver and right kidney discovered by ultrasound examination during a routine checkup. Further examination also revealed a squamous cell carcinoma of the oral floor. The patient underwent a simultaneous radical nephrectomy, enucleation of the liver tumor and resection of the tumor of the oral floor. The diagnoses were histopathologically confirmed. The number of patients with multiple cancers has recently been increasing. The possibility of a second or third malignant lesion should be considered, not only in patients with a known malignancy but also in those without malignancy. The importance of screening procedures in the early detection of malignancy before the appearance of clinical symptoms should be emphasized. © 1994 Oxford University Press.
  • Clinical aspects of renal cell carcinoma.
    UEMURA Hirotsugu; Oosterwijk E; Debruyne FMJ
    Revista Romana de Urol. 1 81 - 88 1994 [Refereed]
  • J VANDIJK; H UEMURA; AJMC BENIERS; WP PEELEN; ST ZEGVELD; GJ FLEUREN; SO WARNAAR; E OOSTERWIJK
    INTERNATIONAL JOURNAL OF CANCER WILEY-LISS 56 (2) 262 - 268 0020-7136 1994/01 [Refereed]
     
    Because renal-cell carcinoma (RCC) is considered relatively resistant to radio- and chemotherapy, RCC patients may benefit from new treatment modalities, e.g. immunotherapy. In vitro and in vivo studies suggest that combinations of cytokines such as interferon gamma or interferon alpha (IFN-gamma, IFN-alpha) and tumor necrosis factor alpha (TNF-alpha) may act synergistically. In this study we tested whether a monoclonal antibody (MAb) G250, reactive with a RCC-associated antigen, showed anti-tumor effects in vivo in nude mice with established s.c. human RCC xenografts, and also whether this MAb could enhance the anti-tumor effect of combinations of IFNs and TNF-alpha. Treatment with combinations of IFN-alpha/TNF-alpha or IFN-gamma/TNF-alpha, or with MAb G250 alone, resulted in a significant inhibition of tumor growth. Treatment with MAb G250, in combination with IFN-gamma/TNF-alpha, did not result in an improve anti-tumor effect as compared to that of either treatment alone. In contrast, MAb G250 combined with IFN-alpha/TNF-alpha resulted in a significantly enhanced anti-tumor response. In one experiment, 3 out of 10 mice showed complete tumor regression, with no recurrence after 90 days. Large numbers of infiltrating macrophages were found surrounding viable and necrotic tumor tissue after treatment with G250 combined with IFN-alpha/TNF-alpha. These results suggest that combination therapy, consisting of IFN-alpha, TNF-alpha and MAbs, may have therapeutic value in the treatment of RCC. (C) 1994 Wiley-Liss, Inc.
  • H. Uemura; K. Fujimoto; C. Kawasaki; H. Fujii; Y. Kinoshita; M. Hosaka; T. Miura; I. Kondo; M. Harada; S. Fukushima; K. Miyai; E. Ishizuka; H. Fukuoka; K. Sasaki
    Japanese Journal of Urology 83 (1) 48 - 52 0021-5287 1992 [Refereed]
  • S SAMMA; K YOSHIDA; S OZONO; S OHARA; Y HAYASHI; S TABATA; H UEMURA; A IWAI; A HIRAYAMA; Y HIRAO; E OKAJIMA
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY FOUNDATION PROMOTION CANCER RESEARCH 21 (5) 340 - 345 0368-2811 1991/10 [Refereed]
     
    The significance of two types of vascular invasion (macroscopic tumor thrombus into the renal vein or vena cava inferior and microvascular invasion) as prognostic factors in renal cell carcinoma is analyzed in 121 patients treated at the Department of Urology, Nara Medical University. The data indicate there to be close correlations between tumor thrombus, microvascular invasion and distant metastasis. In patients with tumor thrombus, however, the prognosis is not as poor when surgical removal of the tumor thrombus is successfully performed as when it is not. In contrast, the prognosis of patients with positive microvascular invasion is significantly worse than that of those with a negative finding. Microvascular invasion appears to be a significant prognostic factor in renal cell carcinoma in addition to well-known factors such as tumor stage, tumor grade, tumor thrombus and distant metastasis. To detect microvascular invasion, the histological examination should be extended to give as much detail as possible.
  • Tabata Shoichi; Kitahori Yoshiteru; Hiasa Yoshio; Ozono Seiichiro; Yamaguchi Hisako; Kitagawa Hisayo; Uemura Hirotsugu; Matsuki Hisashi; Samma Shoji; Hirao Yoshihiko; Okajima Eigoro
    Journal of Toxicologic Pathology JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY 4 (1) 67 - 73 0914-9198 1991 
    The present study was conducted to examine nephrotoxicity of β-cyclodextrin (β-C) in dogs. Five female Beagle dogs were divided into 3 groups: Group 1 (2 dogs treated with 0.9g/kg of β-C), Group 2 (2 dogs treated with 0.45g/kg of β-C), and Group 3 (1 dog treated with saline). Durations of β-C injection were 7 and 10 consecutive days in Groups 1 and 2. Histopathological and histo-chemical examinations of the kidney were performed. Following 0.9g/kg or long-term 0.45g/kg treatment with β-C, the animals showed marked fatigue and elevated BUN and Cr. Histopathologically, β-C treatment resulted in vacuolation, necrosis, and regeneration in the proximal tubules. Activities of succinic dehydrogenase, β-glucuronidase, and glucose-6-phosphatase decreased histochemically after β-C treatment. Because signs of nephrotoxicity represented were noted in dogs after β-C treatment, as has been reported in rats, it seems likely that dogs also can serve as a model of nephrosis. If this model is to be applied to the study of renal carcinogenesis, the present study suggests the optimum dosing regimen for β-C to be 7-day 0.45g/kg treatment.
  • Yamaguchi Hisako; Kitahori Yoshiteru; Hiasa Yoshio; Ozono Seiichiro; Kitagawa Hisayo; Uemura Hirotsugu; Tabata Shoichi; Matsuki Hisashi; Samma Shoji; Hirao Yoshihiko; Okajima Eigoro
    Journal of Toxicologic Pathology JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY 3 (2) 239 - 243 0914-9198 1990 
    Renal carcinomas were induced by N-ethyl-N-hydroxyethylnitrosamine (EHEN) followed by trisodium nitrilotriacetate monohydrate (NTA) in Wistar rats. In these rats, various parameters which are clinically used as tumor markers were examined. Renal tumors developed in 6 (37.5%) of 16 rats treated with EHEN alone and in 14 (82.4%) of 17 rats treated with EHEN and subsequently with NTA. When various parameters were compared between these two groups and the control group, RBC, Hb Al-P, LDH, BUN, Cr, and Ca in the former two groups differed significantly from those values of the untreated controls. In the EHEN-treated rats (Group 1 and 2), erythropoietin (EP) was higher in the tumor-bearing group than in the tumor-free group (p<0.025), although no other significant difference was observed. As compared to the untreated controls, tumor-bearing rats showed significant elevation in RBC (p<0.005). Cr (p<0.005), and EP (p<0.05) and significant reduction in Hb (p<0.005). Al-P (p<0.005), and LDH (p<0.05). Therefore, the significant difference in RBC, Hb, Al-P, LDH, and Cr seems to be attributable to the effect of EHEN and NTA. These results suggest that EP is specifically elevated in rats with renal tumor.
  • SAMMA Shoji; UEMURA Hirotsugu; TABATA Shoichi; IWAI Akio; NAKATSUJI Fumiyoshi; MATSUKI Hisashi; BABAYA Katsuhiro; HIRAO Yoshihiko; OKAJIMA Eigoro
    GANN Japanese Journal of Cancer Research The Japanese Cancer Association 75 (5) 385 - 387 0016-450X 1984 
    A highly atypical intraepithelial proliferation, which was interpreted as carcinoma in situ, developed in the urinary bladder of 2 beagle dogs after repeated intravesical instillations of N-methyl-N'-nitrosourea followed by oral administration of N-butyl-N-(4-hydroxybutyl)nitrosamine. The latent period was 37 weeks. The technique may provide a useful model to study the natural history of bladder cancer, particularly carcinoma in situ.

Books etc

Conference Activities & Talks

  • 腎細胞がんの診断と治療  [Not invited]
    植村天受
    大阪泌尿器科臨床医会 40周年記念式典企業セミナ- 〜泌尿器がん治療の未来〜  2017/11  大阪
  • CRPC治療の現状と最適化にむけた取り組み  [Not invited]
    植村天受
    千葉CRPC講演会2017  2017/10  千葉
  • 明らかになってきたロゼレムの可能性  [Not invited]
    植村天受
    現代型不眠エキスパートフォーラム〜ロゼレムの可能性を探る〜  2017/07  福岡
  • 腎細胞癌治療における免疫チェックポイント阻害薬1-0 drug の位置づけ  [Not invited]
    植村天受
    Tokyo RCC Immuno-Oncology Seminar  2017/03  東京
  • 前立腺癌治療UPDATE  [Not invited]
    植村天受
    Expert Seminar  2017/03  新潟
  • 去勢抵抗性前立腺癌の治療を再考する  [Not invited]
    植村天受
    前立腺癌学術講演  2017/02  姫路
  • CRPC における抗がん剤の位置づけ  [Not invited]
    植村天受
    CRPC 治療戦略講演会  2017/02  札幌
  • PTENノックアウト前立腺癌マウスモデルにおけるJAK 1/2 阻害による腫瘍増殖及び転移抑制効果の検討  [Not invited]
    植村天受; 倉 由吏恵; 森 康範; 畑中祐二; 沖 貴士; 杉本公一; 吉村一宏; 野澤昌弘; 吉川和宏; 西尾和人; 近大ゲノム; デベラスコ・マルコ(近大; 近大ゲノム
    第75回 日本癌学会学術総会  2016/10  横浜
  • CRPC治療の現状tp最適化にむけた取り組み・ジェブタナの使用経験から見えてきた新たな治療選択  [Not invited]
    植村天受
    第54回 日本癌治療学会学術集会  2016/10  横浜
  • 実臨床における腎がん薬物療法  [Not invited]
    植村天受
    第35回 うつくしま泌尿器科研究会  2016/09  福島
  • Controversy in treatment of advanced prostate cancer  [Not invited]
    植村天受
    第14回 日本臨床腫瘍学会学術集会  2016/07  神戸
  • ヴォトリエントの使用経験から学んだこと  [Not invited]
    植村天受
    CORE@Webcast 2016  2016/04  大阪狭山
  • Effects of increased dieyary fat consumption on prostate cancer progression in genetically engineered mice  [Not invited]
    植村天受
    AACR  2016/04  New Orlesns
  • マウス前立腺癌モデルを用いたAKT阻害薬 AZD 5356の抗腫瘍効果  [Not invited]
    植村天受; 倉 由吏恵; 清水信貴; 吉村一宏; 野澤昌弘; 吉川和宏; 西尾和人; 近大ゲノム; デベラスコマルコ(近大; 近大ゲノム
    第74回 日本癌学会学術総会  2015/10  名古屋
  • mRCCにおける新しい治療戦略  [Not invited]
    植村天受
    わかしゃち泌尿器科セミナ-  2015/10  名古屋
  • 転移性腎癌に対する集学的治療 −ソラフェニブの立ち位置は-  [Not invited]
    植村天受
    第7回 信州腎癌研究会  2015/10  松本
  • 前立腺癌に対する基礎研究から臨床研究  [Not invited]
    植村天受
    第5回 千葉21世紀泌尿器科セミナ-  2015/09  千葉
  • 前立腺癌の基礎研究から臨床応用まで  [Not invited]
    植村天受
    第106回 徳島県泌尿器科疾患研究会  2015/08  徳島
  • mRCCにおける新しい治療戦略  [Not invited]
    植村天受
    RCC Forum 栃木  2015/07  宇都宮
  • CRPCにおける抗がん剤の位置付け  [Not invited]
    植村天受
    ナナクマ Urologic Cancer Seminar  2015/07  福岡
  • CRPCにおける抗がん剤の位置づけ  [Not invited]
    植村天受
    高値前立腺がんフォ−ラム  2015/06  高知
  • m RCCにおける新しい治療戦略  [Not invited]
    植村天受
    RCC Clinical Camp in 茨城  2015/06  つくば
  • CRPCにおける抗がん剤の位置づけ  [Not invited]
    植村天受
    前立腺がん治療を考える会  2015/05  呉
  • 進行性腎細胞癌に対する集学的治療と今後の展望  [Not invited]
    植村天受
    山口RCCチ−ム医療懇話会  2015/04  山口
  • 進行性腎細胞癌に対する集学的治療と今後の展望  [Not invited]
    植村天受
    第258回 岡山泌尿器科カンファレンス  2015/02  岡山
  • 今後のCRPCに対する治療戦略  [Not invited]
    植村天受
    ジェブタナ?発売記念学術講演会  2014/11  仙台
  • 高齢者における不眠症の課題  [Not invited]
    植村天受
    睡眠医療UP-TO-DATE  2014/10  北九州市
  • 進行性腎細胞癌に対する集学的治療と今後の展望  [Not invited]
    植村天受
    第17回奈良県医師会泌尿器科部会分科会 奈良腎腫瘍研究会  2014/10  奈良
  • 去勢抵抗性前立腺癌の新たな治療戦略  [Not invited]
    植村天受
    Fujita Zytiga Launch Symposium  2014/10  名古屋
  • 去勢抵抗性前立腺癌に対する新規治療薬(アビラテロン・エンザリタミド・カバジタキセル)の使用経験について  [Not invited]
    植村天受; 吉村一宏; 野沢昌弘; 能勢和宏; 南高文; 山本豊; 清水信貴; 齋藤允孝; 大關孝之; 安富正悟; 橋本士; 明石泰典
    第79回 日本泌尿器科学会東部総会  2014/10  横浜
  • 去勢抵抗性前立腺癌の新たな治療戦略〜CYP17阻害剤アビラテロンとは〜  [Not invited]
    植村天受
    CRPC講演会in Nagoya  2014/10  名古屋
  • 今後のCRPCに対する治療戦略  [Not invited]
    植村天受
    山形前立腺癌 学会講演会  2014/09  山形
  • 去勢抵抗性前立腺癌に挑む〜ジェブタナ〜  [Not invited]
    植村天受
    ジェブタナ発売記念 WEBカンファレンス  2014/09
  • Optimal Sequencing of Current Medical Therapies  [Not invited]
    植村天受
    The 31st Japn-Korea Urological Congress 第31回日韓泌尿器科会議 ランチョンセミナ-  2014/09  東京
  • Management of Advanced Renal Cell Carcinoma  [Not invited]
    植村天受
    The 31st Japn-Korea Urological Congress 第31回日韓泌尿器科会議  2014/09  東京
  • 前立腺癌自然発生マウスモデル PTEN KO マウスより、 PTEN/p53ダブルKOマウスを確立し、その有用性について報告する  [Not invited]
    植村天受; 倉由吏恵; 畑中祐二; 山本豊; 清水信貴; 吉村一宏; 野澤昌弘; 吉川和宏; 西尾和人; 近大ゲノム; デベラスコマルコ(近大; 近大ゲノム
    第73回 日本癌学会学術総会  2014/09  横浜
  • 去勢抵抗線前立腺癌の新たな治療戦略〜CYP17阻害薬アビラテロンとは〜  [Not invited]
    植村天受
    ザイティガ錠発売記念講演会  2014/09  高松
  • 転移性腎細胞癌における集学的治療アプローチ  [Not invited]
    植村天受
    第52回 日本癌治療学会学術集会  2014/08  横浜
  • 去勢抵抗性前立腺癌の治療 UP TO DATE  [Not invited]
    植村天受
    第75回 TEUS Tokyo Expert Urology Seminar  2014/08  東京
  • 腎細胞癌に対するヴォトリエントの使用経験  [Not invited]
    植村天受
    神戸腎細胞がん治療講演会  2014/07  神戸
  • 進行性腎細胞癌の集学的治療と今後の展開  [Not invited]
    植村天受
    壬生腎がんセミナ-  2014/05  宇都宮
  • Functional evaluation of synchronous inactivation of PTEN and P53 in a murine model of prostate cancer  [Not invited]
    植村天受; 倉由吏恵; 安藤直美; 福島恵美子; 畑中祐二; 山本豊; 清水信貴; 吉村一宏; 野沢昌弘; 吉川和宏; 西尾和人; 近大ゲノム; デベラスコマルコ(近大; 近大ゲノム
    AACR  2014/04  San Diego,CA
  • 腎癌に対する分子標的薬を用いたPresurgical therapy  [Not invited]
    植村天受
    第102回日本泌尿器科学会総会  2014/04  神戸
  • アビラテロン酢酸エステル(AA)の第?相試験:化学療法末治療の転移性去勢抵抗性前立腺癌(mCRPC)患者に対する有効性と安全性  [Not invited]
    植村天受; 松原伸晃; 独立行政法人国立がん研究センター東病院; 佐藤威文; 時田大輔; ヤンセンファーマ; 研究開発本部; 赤座英之; 東京大学先端科学技術研究センター
    第102回日本泌尿器科学会総会  2014/04  神戸
  • 前立腺癌マウスモデルにおけるがん抑制遺伝子PTENおよびp53の相互作用の検討  [Not invited]
    植村天受; 倉由吏恵; 安藤直美; 福島恵美子; 畑中祐二; 山本豊; 清水信貴; 野沢昌弘; 吉村一宏; 吉川和宏; 愛知医科大学病院細胞治療センタ; 西尾和人; 近大ゲノム; マルコデベラスコ(近大; 近大ゲノム
    第102回日本泌尿器科学会総会  2014/04  神戸
  • 腎癌治療の変革-腎癌における分子標的治療の成績と問題点  [Not invited]
    植村天受
    第12回 日本泌尿器科学会プレスセミナ−  2014/03  東京
  • 腎がん薬物治療レビュ-  [Not invited]
    植村天受
    CORE-J 2014  2014/03  東京
  • Peptide vaccines with low-dose dexamethasone versus dexamethasone alone for chemotherapy-naive castration resistant prostate cancer a randomized phase II study  [Not invited]
    植村天受; Kimura T; 南高文; 吉村一宏; 野澤昌弘; Egawa S; Fujimoto H; Yamada A; Itou K
    ASCO-GU  2014/01  San Francisco
  • 今後のCRPCに対する治療戦略  [Not invited]
    植村天受
    前立腺癌化学療法学術講演会  2014/01  熊本
  • 腎細胞がんにおける ヴォトリエントの使用経験  [Not invited]
    植村天受
    GSK Urology Conference in 盛岡 〜First Announcement〜  2014/01  盛岡
  • 最新知見に基づく腎がんの最適な薬物治療 −今できる個別化医療とは何か-  [Not invited]
    植村天受
    Pfizer Oncology Web Symposium RCC2014  2014/01  全国Web
  • 前立腺癌治療の歴史  [Not invited]
    植村天受
    Prostate Cancer Seminar in Sapporo〜去勢抵抗性前立腺癌治療のパラダイムシフト〜  2014/01  札幌
  • 泌尿器科医による進行性腎細胞癌に対する集学的治療  [Not invited]
    植村天受
    腎細胞癌 学術講演会  2014/01  東京
  • 去勢抵抗性前立腺癌に対する治療の最前線  [Not invited]
    植村天受
    宮崎泌尿器セミナ-のご案内  2014/01  宮崎
  • 進行性腎細胞癌に対する集学的治療  [Not invited]
    植村天受
    RCC大阪メディカルスタッフseminar  2013/11  大阪
  • 泌尿器科医からみた転移性腎癌治療の新たなる展開  [Not invited]
    植村天受
    平成25年度 大阪泌尿器科臨床医会 第64回 学術集会(大阪府医師会協賛)  2013/11  大阪
  • 泌尿器がんに対するペプチドワクチン療法  [Not invited]
    植村天受
    第10回 がんワクチン療法研究会(AsCaVaTh)学術集会  2013/11  東京
  • 維持透析患者に対するカルニチン製剤補充療法の検討  [Not invited]
    米田 雅美; 原 弘道; 早川 敬; 嶋津 秀紀; 今西 正昭; 畑中 祐二; 安田 宗生; 佐藤 弘章; 石井 徳味; 谷山 佳弘; 植村 天受; 有馬 秀二
    第58回日本透析医学会学術集会・総会  2013/10  福岡  第58回日本透析医学会学術集会・総会
  • 前立腺癌におけるBone Management  [Not invited]
    植村天受
    第6回 千葉泌尿器オンコロジ-研究会  2013/10  千葉
  • 睡眠障害と夜間頻尿  [Not invited]
    植村天受
    第20回 日本排尿機能学会  2013/09  静岡
  • 腎細胞癌薬物療法における現状と展望  [Not invited]
    植村天受
    秋田腎癌分子標的治療カンファレンス〜インライタ発売12周年記念〜  2013/08  秋田県
  • Paradigm shift for treatment of mRCC by urologist  [Not invited]
    植村天受
    第11回日本臨床腫瘍学会学術集会  2013/08  仙台
  • 腹膜透析中に左腰背部痛を契機として診断された左腎癌の一例  [Not invited]
    中野 志仁; 大西 佐代子; 井上 裕紀; 高見 勝弘; 松岡 稔明; 中谷 嘉寿; 谷山 佳弘; 有馬 秀二; 石井 徳味; 小林 泰之; 植村 天受
    第58回日本透析医学会学術集会・総会  2013/06  福岡  第58回日本透析医学会学術集会・総会
  • Preclinical responses of the MEK inhibitor AZD6244 in a genetically modified mouse model of prostate cancer.  [Not invited]
    植村天受; 倉由吏恵; 安藤直美; 福島恵美子; 畑中祐二; 山本豊; 清水信貴; 野澤昌弘; 吉村一宏; 吉川和宏; 愛知医科大細胞治療センター; 西尾和人; 近大ゲノム; デベラスコマルコ(近大; 近大ゲノム
    American Association for Cancer Research ANNUAL MEETING2013  2013/04  ワシントン
  • Combination therapy of peptide vaccines and dexamethasone for chemotherapy naive castration resistant prostate cancer - a randomized phase-2 study  [Not invited]
    植村天受; 木村高弘; 吉村一宏; 南高文; 野澤昌弘; 近大; T.Nakagawa; 藤本博行; 研究センター; 頴川晋; 慈恵医大; 山田亮; 伊藤恭悟
    28th Annual EAU Congress  2013/03  ミラノ
  • 腎細胞癌薬物療法の新たなる展開 〜インライタ登場によりアルゴリズムはどう変わるか〜  [Not invited]
    植村天受
    大阪メデイカルスタッフ懇話会2013  2013/03  大阪
  • 腎細胞癌薬物療法の新たなる展開 〜インライタ登場によりアルゴリズムはどう変わるか〜  [Not invited]
    植村天受
    RCC治療戦略 in 北九州  2013/02  北九州
  • Synchronous inacilvation of PTEN and p53 accelerates 前立腺癌のPTEN・P53ダブルノックアウトによる相乗効果  [Not invited]
    植村天受; 倉由史恵; 安藤直美; 福島恵美子; 畑中祐二; 山本豊; 清水信貴; 吉村一宏; 野澤昌弘; 吉川和宏; 西尾和人; デベラスコマルコ(近大; 近大ゲノム
    第72回日本癌学会学術総会  2013/01  横浜
  • 腎細胞癌薬物療法の新たなる展開 〜インライタ登場によりアルゴリズムはどう変わるか〜  [Not invited]
    植村天受
    千葉泌尿器疾患セミナ-  2013/01  千葉
  • 腎細胞癌薬物療法の新たなる展開〜インライタ登場によりアルゴリズムはどう変わるか〜  [Not invited]
    植村天受
    徳島腎細胞癌フォーラム2012〜インライタ錠 新発売記念〜  2012/11  徳島
  • 腎細胞癌薬物療法の新たな展開 〜インライタ登場によりアルゴリズムはどう変わるか?〜  [Not invited]
    植村天受
    インライタ発売記念講演 in Matsumoto  2012/11  松本
  • 腎癌治療最新トピックス〜分子標的薬新時代におけるネクサバールの使い方〜  [Not invited]
    植村天受
    第64回日本泌尿器科学会西日本総会  2012/11  徳島
  • 長期継続のための副作用対策の実際  [Not invited]
    植村天受
    Pfizer Oncology Web Symposium RCC  2012/10  東京
  • 腎癌薬物治療における新しい時代の幕開け  [Not invited]
    植村天受; 三宅秀明; 大大学院医学研
    第50回 日本癌治療学会学術集会  2012/10  横浜
  • 去勢抵抗性再燃前立腺癌に対するペプチドワクチン療法-第2相前向きランダム化試験-  [Not invited]
    植村天受
    第50回 日本癌治療学会学術集会  2012/10  横浜
  • Breakout session I facilitators  [Not invited]
    植村天受
    Asia Pacific Prostate Cancer Regional Conference  2012/10  香港
  • 泌尿器科癌治療の UP TO DATE  [Not invited]
    植村天受
    第8回 南大阪がん地域連携会  2012/10  堺
  • 腎細胞癌薬物療法の新たなる展開〜インライタ登場によりアルゴリズムはどう変わるか〜  [Not invited]
    植村天受
    インライタ錠 新発売記念 Pfizer RCC Symposium in 愛媛  2012/10  愛媛
  • The Clinical Role of Peptide Vaccines for CRPC-Prospective Randomized Study of Peptide Vaccination vs Steroid Hormone Alone  [Not invited]
    植村天受
    6th Annual WUOF Conference  2012/09  福岡
  • 転移性腎がんに対するMHCクラス1療法の役割  [Not invited]
    植村天受; 吉村一宏; 南高文; デベラスコマルコ
    第71回 日本癌学会学術総会  2012/09  札幌
  • 転移性腎癌に対する治療戦略 −本邦における Sorafenibの位置づけー  [Not invited]
    植村天受
    四国泌尿器腫瘍講演会  2012/08  東京
  • 腎癌分子標的薬治療の現状と展望  [Not invited]
    植村天受
    第13回泌尿器科CPC  2012/07  仙台
  • Phase III AXIS trial of axitinib vs sorafenib in patients with metastatic renal cell carcinoma:Asian subgroup analysis  [Not invited]
    植村天受; Yen-Chuan Ou; 台湾ベテラン総合病院; Ho Yeong Li; 医療センター; 冨田善彦; 植田 健(千葉県がんセンター; Hari Menon; Jinsoo Chang; Jun Guo; Jamal Tarazi; Sinil Kim; 内藤誠二; 赤座英之; 東京大学先端科学技術研究センター
    The 10th Annual Meeting of Japanese Society of Medical Oncology 第10回日本臨床腫瘍学会学術集会  2012/07  大阪
  • 「腎細胞癌薬物療法の新たな展開」 〜インライタ登場によりアルゴリズムはどう変わるか?〜  [Not invited]
    植村天受
    Tokyo Metrolitan Torisel Study Kick off Meeting  2012/07  東京
  • 腎癌の分子標的薬−自験例からみた適正使用−  [Not invited]
    植村天受
    第28回腎移植・血管外科研究会  2012/07  神奈川
  • 日本人転移性腎癌患者におけるaxitinibの有効性・安全性の検討-axitinib国際共同第?相試験(AXIS TRIAL)サブグループ解析-  [Not invited]
    植村天受; 植田 健(千葉県がんセンタ; 冨田善彦; 塚本泰司; 幌医科大; 金山博臣; 徳島大大学院ヘルスバイオサイエンス研
    第100回日本泌尿器科学会総会  2012/04  横浜
  • 不完全型房室中隔欠損を伴った腎盂尿管移行部狭窄症の1例  [Not invited]
    三宅 俊治; 岡田 満; 篠原 徹; 竹村 司; 林 泰司; 植村 天受
    第44回近畿小児腎臓病研究会  2012/03  大阪市  第44回近畿小児腎臓病研究会
     
    症例は4歳7か月の女児.主訴:腹痛・嘔吐.既往歴:計8回同様の腹痛・嘔吐.腹痛・嘔吐で受診した急病センターで心雑音・発育不良を指摘され.近医で不完全型房室中隔欠損と診断.心臓精査目的で当科受診前日の夕食後から腹痛・嘔吐を認めた.腹部は平坦で,腸雑音の亢進はなく.左下腹部に便塊を触知.腹部立位XPでは,イレウス像(−).尿検査でアセトン体(+++),潜血(-).浣腸・点滴で,症状は軽快し,便秘症・アセトン血性嘔吐症と診断.心エコーで不完全型房室中隔欠損,僧帽弁閉鎖不全,左上大静脈左房還流と診断.腹痛発作後8日目の腹部超音波検査で左腎盂拡張・腎盂壁の著明な肥厚を認めた.順行性尿路造影で,腎盂尿管移行部狭窄と診断,腹腔鏡下腎盂尿管新吻合術を施行.術後4日の多量の排便後,浣腸は不要となり,以後腹痛・嘔吐を認めず,5歳7か月で心内修復術を施行したが,術後に腹部症状を認めず.結語:繰り返す腹痛・嘔吐症では,間欠的水腎
  • 前立腺疾患治療―最近の話題―  [Not invited]
    植村 天受
    臨床泌尿器科懇話会〜今後の泌尿器科診療を考える〜  2012/03  福岡市  臨床泌尿器科懇話会〜今後の泌尿器科診療を考える〜
  • “Triggers”for SRM Treatment (Markers for SRM Progression)  [Not invited]
    植村天受
    32nd SIU Conference  2012/01  福岡
  • 本邦におけるmTOR阻害剤エベロリムス使用腎癌患者に関する後方観察研究―第3報―  [Not invited]
    植村 天受; 大阪泌尿器腫瘍研究会; 大阪泌尿器腫瘍研究会; 大阪泌尿器腫瘍研究会; 大阪泌尿器腫瘍研究会; 大阪泌尿器腫瘍研究会; 大阪泌尿器腫瘍研究会; 大阪泌尿器腫瘍研究会; 大阪泌尿器腫瘍研究会; 大阪泌尿器腫瘍研究会; 千葉県がんセンター
    第61回日本泌尿器科学会中部総会  2011/11  京都市  第61回日本泌尿器科学会中部総会
  • New therapies for kidney cancer  [Not invited]
    植村 天受
    C2 Retreat 2011  2011/11  Canada  C2 Retreat 2011
  • 「進行腎癌に対する薬物療法の現状」  [Not invited]
    植村天受
    NEXT ERA IN RCC  2011/11  札幌
  • 大学病院における標準癌治療と先進医療  [Not invited]
    植村 天受
    泌尿器科フォーラムSAKAI  2011/10  堺市  泌尿器科フォーラムSAKAI
  • 前立腺がんの手術療法と薬物療法について  [Not invited]
    植村 天受
    Blue Clover Campaign 2011  2011/10  大阪市  Blue Clover Campaign 2011
  • Use of prostate-specific PTEN conditional knockout mice in prostate cancer prevention and intervention research  [Not invited]
    植村 天受; 田中 基幹; 小池 浩之; 山本 豊; 畑中 祐二; 王 一; 清水 信貴; 野澤 昌弘; 吉村 一宏; 西尾 和人; デベラスコ マルコ アントニオ
    第70回日本癌学会総会  2011/10  名古屋市  第70回日本癌学会総会
  • Lumican expression prostate cancer  [Not invited]
    植村 天受; デベラスコ マルコ アントニオ; 畑中 祐二; 山本 豊; 田中 基幹; 清水 信貴; 児玉 光正; 荒尾 徳三; 西尾 和人; 医学部泌尿器科学教室
    第70回日本癌学会学術総会  2011/10  名古屋市  第70回日本癌学会学術総会
  • F-FDG PET/CT にてsuperscanを呈した腎癌骨転移の1例  [Not invited]
    兵頭 朋子; 石井 一成; 植村 天受; 村上 卓道; 阪本 祐一; 中村
    第44回日本核医学会近畿地方会  2011/07  兵庫  第44回日本核医学会近畿地方会
  • 「分子標的薬による腎癌治療の進歩」  [Not invited]
    植村天受
    弘前RCC学術講演会  2011/07  弘前
  • 「分子標的薬による腎細胞癌治療の進歩」  [Not invited]
    植村天受
    第1回 千葉オンコロジ−・ベイフォ−ラム  2011/06  浦安
  • Systemic transduction of p16 INK4A anti-tumor peptide inhibits growth of mbt-2 bladder tumor cell line graft in mice  [Not invited]
    植村 天受; Tsukuba, Aichi; Hitachi, Tsukuba; Nasushiobara, Nagoya
    AUA Annual Meeting  2011/05  Washington, USA  AUA Annual Meeting
  • A phase I trial of vegfr1 peptide vaccines for patients with metastatic renal cell carcinoma  [Not invited]
    植村 天受; デベラスコ マルコ アントニオ; 吉村 一宏; 野澤 昌弘; 南 高文
    AUA Auual Meeting  2011/05  Washington, USA  AUA Auual Meeting
  • 進行性腎癌に対する分子標的薬を用いた今後の治療  [Not invited]
    植村 天受
    第99回日本泌尿器科学会総会  2011/04  名古屋市  第99回日本泌尿器科学会総会
  • サイトカイン治療抵抗性腎細胞癌患者に対するアキシチニブの第II相試験―有効性、安全性及びバイオマーカーの検討―  [Not invited]
    植村 天受; 国立がん研究センタ; 中央病院; 東京女子医科大学東医療センター; 静岡県立静岡がんセンター; 東京大学先端科学技術研究センターシステム生物医学
    第99回日本泌尿器科学会総会  2011/04  名古屋市  第99回日本泌尿器科学会総会
  • Sorafenib inhibits tumor development and growth in a transgenic mouse model of prostate cancer  [Not invited]
    植村 天受; 畑中 祐二; 泉 あやか; 岡崎 絵莉奈; 土井 万貴子; 田中 基幹; 山本 豊; 清水 信貴; 吉村 一宏; 野澤 昌弘; 西尾 和人; デベラスコ マルコ アントニオ
    102nd Auual Meeting AACR  2011/04  Orland, USA  102nd Auual Meeting AACR
  • 「(仮)トーリセルの副作用マネジメントから見たmRCC治療の考え方」  [Not invited]
    植村天受
    腎細胞癌薬物療法学術講演会  2011/04  札幌
  • アフィニト−ルの日本人における使用経験−1年で学んだこと(仮題)  [Not invited]
    植村天受
    CORE-J 2011 Meeting Agenda  2011/04  東京
  • 腎癌に対する分子標的治療 〜使用経験と工夫〜  [Not invited]
    植村天受
    Cutting edge of Urology 2011  2011/03  東京
  • Experience sharing for sequential use of targeted agents and AE management in mRCC  [Not invited]
    植村 天受
    Asia-Pacific Uro-Oncology Summit 2011  2011/01  Taiwan  Asia-Pacific Uro-Oncology Summit 2011
  • Anti-cancer effect of zoledronic acid in prostate cancer  [Not invited]
    植村 天受
    Asia-Pacific Uro-Oncology Summit 2011  2011/01  Taiwan  Asia-Pacific Uro-Oncology Summit 2011
  • 「大学病院における標準癌治療と先進医療」  [Not invited]
    植村天受
    泌尿器科フォ−ラムSAKAI  2011/01  堺
  • 「前立腺がんの手術療法と薬物療法について」  [Not invited]
    植村天受
    Blue Clouer Campaign 2011 前立腺がんを考える〜大阪府の前立腺がん治療について〜  2011/01  大阪
  • 「腎細胞癌に対する分子標的薬治療の変遷ー現状と今後の課題-」  [Not invited]
    植村天受
    鳥取 腎細胞癌学術セミナ-  2011/01  米子
  • 腎癌治療における分子標的薬の今後の展望  [Not invited]
    植村 天受
    第60回日本泌尿器科学会中部総会  2010/12  名古屋市  第60回日本泌尿器科学会中部総会
  • 転移性腎がんに対する薬物治療の新展開  [Not invited]
    植村 天受
    第48回日本癌治療学会学術集会  2010/10  京都市  第48回日本癌治療学会学術集会
  • 再燃前立腺癌に対する治療戦略  [Not invited]
    植村 天受
    第2回山口ウロ・オンコロジーフォーラム  2010/10  山口市  第2回山口ウロ・オンコロジーフォーラム
  • Breast and renal cell carcinomas; Improving outcomes by targeting shared signaling pathways.  [Not invited]
    植村 天受; 浜松オンコロジーセンター; San Camillo Forlanini
    第48回日本癌治療学会学術集会  2010/10  京都市  第48回日本癌治療学会学術集会
  • 転移性腎癌に対する薬物治療の新展開  [Not invited]
    植村天受
    第48回日本癌治療学会学術集会  2010/10  京都
  • アフィニトールによる転移性腎細胞癌の新治療戦略  [Not invited]
    植村天受
    アフィニトール発売記念講演会 in Kanagawa  2010/10  海老名
  • 進行性腎細胞癌治療の新しい戦略  [Not invited]
    植村 天受
    第3回千葉Urology Forum  2010/09  千葉市  第3回千葉Urology Forum
  • Systemic transduction of p16INK4A anti-tumor peptide inhibits growth of MBT-2 bladder tumor cell line graft in mice  [Not invited]
    植村 天受; 筑波大学医学部泌尿器科学; 愛知医科大学臨床試験センター; 日立総合病院泌尿器科; 筑波大学医学部泌尿器科学
    第69回日本癌学会学術総会  2010/09  大阪市  第69回日本癌学会学術総会
  • 転移性腎癌に対する薬物療法の現状と今後の展望  [Not invited]
    植村天受
    第23回泌尿器癌懇話会 学術講演会  2010/09  札幌
  • 腎細胞がんにおける治療最前線  [Not invited]
    植村 天受
    アフィニトール発売記念講演会  2010/08  熊本市  アフィニトール発売記念講演会
  • 知って得する前立腺がん  [Not invited]
    植村 天受
    市民がん撲滅講座  2010/07  大阪狭山市  市民がん撲滅講座
  • (仮) 転移性腎細胞癌の薬物治療の今後の展望 〜エベロリムスの使用経験を踏まえて〜  [Not invited]
    植村天受
    徳島 腎細胞癌治療セミナ― アフィニトール 発売記念講演会  2010/07  徳島
  • 転移性腎癌の薬物治療  [Not invited]
    植村天受
    腎癌治療セミナーin OITA  2010/07  大分
  • 転移性腎細胞癌に対する薬物治療と今後の展望〜エベロリムスの使用経験を踏まえて〜  [Not invited]
    植村天受
    多摩アフィニトール発売記念講演会  2010/07  立川
  • 転移性腎細胞癌に対する薬物治療と今後の展望〜エベロリムスの使用経験を踏まえて〜  [Not invited]
    植村天受
    アフィニトール学術講演会  2010/06  金沢
  • 日本人腎細胞癌患者におけるスニチニブ単剤投与の全生存期間-第?相臨床試験(第2報)  [Not invited]
    植村 天受; 徳島大学大学院泌尿器科学; 国立がんセンター中央病院泌尿器科; 北海道大学大学院泌尿器科学; 山形大学医学部泌尿器科学; 静岡がんセンター泌尿器科; 秋田大学医学部泌尿器科学; 九州がんセンター泌尿器科; 浜松医科大学泌尿器科学; 大阪大学大学院泌尿器科学; 京都府立医科大学泌尿器科学; 九州大学大学院泌尿器科学; 筑波大学大学院泌尿器科学
    第98回日本泌尿器科学会総会  2010/04  盛岡市  第98回日本泌尿器科学会総会
  • 転移を有する腎細胞癌患者に対するエベロリムス(RAD001)のランダム化、二重盲検、ブラセボ対照、多施設共同第?相試験(RECORD-1試験)日本人サブグループでの検討  [Not invited]
    植村 天受; 静岡がんセンター泌尿器科; 北海道大学大学院泌尿器科学; 札幌医科大学泌尿器科学; 秋田大学医学部泌尿器科学; 栃木県立がんセンター泌尿器科; 千葉県立がんセンタ; 泌尿器科; 国立がんセンター中央病院泌尿器科; 大阪府立成人病センタ; 泌尿器科; 倉敷中央病院泌尿器科; 徳島大学大学院泌尿器科学; 四国がんセンター泌尿器科; 九州大学大学院泌尿器科学; ノバルティスファーマ; ノバルティスファーマ; 筑波大学大学院泌尿器科学
    第98回日本泌尿器科学会総会  2010/04  盛岡市  第98回日本泌尿器科学会総会
  • 酢酸クロルマジノンによる前立腺肥大症患者の血中PSA値に与える影響  [Not invited]
    植村 天受; 辻 秀憲; 朴 英哲; 群馬大学大学院泌尿器科学; 群馬大学大学院泌尿器科学; 奈良県立医科大学泌尿器科学; 奈良県立医科大学泌尿器科学; 東京大学大学院泌尿器科学; 昭和大学医学部泌尿器科学; 昭和大学医学部泌尿器科学; 昭和大学医学部泌尿器科学
    第98回日本泌尿器科学会総会  2010/04  盛岡市  第98回日本泌尿器科学会総会
  • 機能性ペプチド導入による腎細胞癌に対する新しい分子標的治療  [Not invited]
    植村 天受; デベラスコ マルコ; アントニオ; 愛知医科大学泌尿器科学臨床試験センター; 愛知医科大学泌尿器科学臨床試験センター; 愛知医科大学泌尿器科学臨床試験センター; 愛知医科大学泌尿器科学臨床試験センター; 愛知医科大学泌尿器科学臨床試験センター; 筑波大学大学院人間総合科学研究科泌尿器科学; 筑波大学大学院人間総合科学研究科泌尿器科学; 岡山大学大学院医歯薬学総合研究科病理学; 名古屋市立大学腫瘍免疫内科
    第98回日本泌尿器科学会総会  2010/04  盛岡市  第98回日本泌尿器科学会総会
  • The inhibitory effect of renal stone formation by osteopontin siRNA transfection  [Not invited]
    辻 秀憲; 清水 信貴; 梅川 徹; 植村 天受
    第98回日本泌尿器科学会総会  2010/04  盛岡市  第98回日本泌尿器科学会総会
     
    【目的】オステオポンチン(OPN)は尿路結石形成に対して重要な働きをもつが、その作用はin vitroでは多機能性を有する。今回、結石形成ラット腎にin vivo OPNsiRNA transfectionを行い、結石形成への影響をみた。【方法】target sequenceは、5’AAGGCGCATTACAGCAAACAC3’(5’167―185 3’)。A:コントロール群, B:1.5%エチレングリコール(EG)投与群, C:ラットの尾静脈よりリポフェクションにてOPNsiRNAをtransfectionさせた群, D:腎被膜下にAteloGeneTMを用いてOPNsiRNAを注入した群 を作成。C,D群は1週毎の投与で、3週目に摘出腎のOPN mRNA/OPNタンパク質レベルをリアルタイムPCRにより測定した。尿細管内の結晶沈着と腎組織のカルシウム含有量を原子吸光分析で計測した。【結果・考察】OPNの発現はmRNAで&&蛋白で&&&。尿細管内の結晶沈着はC,D群で有意な減少を認めた。カルシウム含有量はB群:0.143±0.036,C群:0.077±0.003,D群:0.065±0.021でOPNsiRNA transfection群では有意に減少した。OPNはin vivoで全体としては結石形成に促進的に作用
  • Use of nesr infrared fluorescence imaging to determine tumor burden in genetically engineered mice  [Not invited]
    植村 天受; デベラスコ マルコ アントニオ; 西尾 和人; 愛知医科大学臨床試験センター; 中外製薬; 近畿大学農学部; 近畿大学農学部; 近畿大学農学部
    101th Annunal Meeting of the American for Cancer Research  2010/04  Washington DC  101th Annunal Meeting of the American for Cancer Research
  • The effects of whole body hyperthermia on tumor growth by a novel far infrared emitter  [Not invited]
    植村 天受; デベラスコ マルコ; アントニオ; 近畿大学農学部; 近畿大学農学部; 近畿大学農学部; 愛知医科大学臨床試験センター
    101st Annual Meeting of American for Cancer Research  2010/04  Washington DC  101st Annual Meeting of American for Cancer Research
  • 泌尿器科臨床医と基礎研究  [Not invited]
    植村天受
    第98回 日本泌尿器科学会総会  2010/04  盛岡  第98回日本泌尿器科学会総会
  • 「mTOR 阻害剤による転移性腎細胞癌の新治療戦略」  [Not invited]
    植村天受
    第98回 日本泌尿器科学会総会  2010/04  盛岡
  • Asian experience with the use of novel agents for the treatement of mRCC  [Not invited]
    植村 天受
    8th Asia Pacific Oncology Summit  2010/03  Tokyo, Japan  8th Asia Pacific Oncology Summit
  • A phase II study of VEGFR1 peptide vaccines for metastatic renal cell carcinoma  [Not invited]
    植村 天受; デベラスコ マルコ アントニオ; 野澤 昌弘; 南 高文; 吉村 一宏
    2010 ASCO-GU  2010/03  San Francisco, USA  2010 ASCO-GU
  • 「転移性腎癌に対する薬物療法」 -分子標的治療の現状と展望−  [Not invited]
    植村天受
    旭川RCC セミナ−2010  2010/03  旭川
  • 転移性腎細胞がんに対する薬物治療  [Not invited]
    植村天受
    第8回日本臨床腫瘍学会学術集会  2010/03  東京
  • A phase ?/?study of VEGFR1 peptide vaccines for metastatic renal cell carcinoma  [Not invited]
    植村天受; デベラスコ・マルコ; 野澤昌弘; 南 高文; 吉村一宏
    2010 Genitourinary Cancer Symposium  2010/03  San Francisco,USA
  • 転移性腎癌に対する治療戦略の実際  [Not invited]
    植村天受
    奈良県スーテント学術講演会  2010/02  奈良
  • 進行性腎細胞癌における治療の実際  [Not invited]
    植村天受
    福岡腎癌フォーラム2010  2010/02  福岡
  • 進行性腎細胞癌に対する分子標的薬の役割  [Not invited]
    植村天受
    スーテント発売1周年記念講演会  2010/02  筑波
  • 腎細胞癌の薬物療法  [Not invited]
    植村天受
    Clinical Oncology Meeting RCC2010  2010/02  東京
  • 転移性腎癌に対する薬物治療と今後の展望  [Not invited]
    植村天受
    第12回秋田県尿路腫瘍研究会 第72回秋田県泌尿器科集談会  2010/02  秋田
  • 腎細胞癌に対するTKI-mTOR阻害薬治療:現状と課題  [Not invited]
    植村天受
    ト−リセル発売記念講演会 in Tokyo  2010/01  東京
  • 前立腺肥大症治療における5α還元酵素阻害剤の有用性  [Not invited]
    植村 天受
    南大阪アボルブ発売1周年記念講演会  2010  堺市  南大阪アボルブ発売1周年記念講演会
  • 泌尿器癌治療における医師主導多施設共同研究について  [Not invited]
    植村天受
    第22回日本バイオセラピィ学会学術集会総会  2009/11  大阪
  • 分子標的薬治療を最適化するDuration戦略  [Not invited]
    植村天受
    Pfizer Oncology Symposium RCC -For Achieving Optimal Benefit-  2009/11  東京
  • 膀胱原発腺癌に対しTS-1+CDDP療法を行った2症例  [Not invited]
    林 泰司; 野澤 昌弘; 大関 孝之; 石井 徳味; 植村 天受
    第59回日本泌尿器科学会中部総会  2009/10  石川県金沢市  第59回日本泌尿器科学会中部総会
  • 抗CMV抗体陽性ドナーから陰性レシピエントへの腎移植症例の検討  [Not invited]
    林 泰司; 石井 徳味; 沖 貴士; 吉村 一宏; 植村 天受
    第21回腎移植免疫研究会  2009/10  大阪市  第21回腎移植免疫研究会
  • Use of near infrared fluorescence imaging to determine tumor burden in genetically engineered mice  [Not invited]
    植村天受; 吉川和宏; 田中基幹; 西尾和人; マルコデべラスコ(近大ゲノム
    第68回日本癌学会学術総会  2009/10  横浜
  • 転移性腎細胞癌の薬物療法の行方は? ケーススタディとQ&A− あなたならどう治療する  [Not invited]
    植村天受
    第59回日本泌尿器科学会中部総会  2009/10  金沢
  • 転移性腎癌に対する治療の行方は?ーケーススタディとQ&Aー  [Not invited]
    植村天受
    第2回広島RCCコロキウム  2009/10  広島
  • Prostate cancer  [Not invited]
    植村天受
    Apssam Osaka Japan 2009  2009/10  大阪
  • A phase I/II study of personalized peptide vaccination therapy for castration resistant prostate cancer  [Not invited]
    植村 天受; 南 高文; デベラスコ マルコ アントニオ; 上島 成也; 奈良県立医科大学泌尿器科; 奈良県立医科大学泌尿器科; 久留米大学免疫学
    URS 25th Annual Meeting  2009/08  Australia  URS 25th Annual Meeting
  • A phase ?/?study of personalized peptide vaccination therapy for castration Resistant prostate cancer.  [Not invited]
    植村天受; 南 高文; デベラスコ・マルコ; 藤本清秀; 平尾佳彦; 奈良医大; 上島成也; 伊東恭吾
    URS 25th Annual Meeting  2009/08  Thala ,Australia
  • 「スーテント処方の工夫について」 −ケース study と Q&A -  [Not invited]
    植村天受
    スーテント発売1周年講演会  2009/07  大阪
  • 腎がんの予防・診断・治療と今後  [Not invited]
    植村 天受
    もっと知ってほしい「泌尿器のがん」のことin神戸  2009/06  神戸  もっと知ってほしい「泌尿器のがん」のことin神戸
  • 進行性前立腺癌の治療  [Not invited]
    植村 天受
    日本臨床泌尿器科医会広島講演会  2009/06  広島  日本臨床泌尿器科医会広島講演会
  • 転移性腎癌に対する治療の現状  [Not invited]
    植村天受
    目黒区泌尿器科医会  2009/06  東京  目黒区泌尿器科医会
  • 分子標的薬の効果と副作用ー投与の工夫についてー  [Not invited]
    植村天受
    スーテント発売1周年記念講演会  2009/05  川越
  • 難治性サイトメガロウイルスに苦慮した生体腎移植の2症例  [Not invited]
    林 泰司; 石井 徳味; 能勢 和宏; 森 康範; 植村 天受
    第97回日本泌尿器科学会総会  2009/04  岡山市  第97回日本泌尿器科学会総会
  • Insights into treatment efficacy in Japanese patients with metastatic renal cell carcinoma  [Not invited]
    植村 天受
    24th Annual EAU Congress  2009/03  Stockholm, Sweden  24th Annual EAU Congress
  • 転移性腎癌に対する分子標的治療 -使用経験と副作用対策-  [Not invited]
    植村天受
    スーテント発売記念講演会  2009/03  鹿児島
  • A phase II study of carbonic anhydrase 9 peptide vaccines with interferon-alfa in advanced renal cell carcinoma  [Not invited]
    植村 天受; 上島 成也; 田中 基幹; 南 高文
    2009 Genitourinary Cancers Symposium  2009/02  Florida, USA  2009 Genitourinary Cancers Symposium
  • 転移性腎癌に対する分子標的治療薬の使用経験  [Not invited]
    植村天受
    第7回Tokyo Expert Urology Seminar  2009/02  東京
  • 過活動膀胱患者へのイミダフェナシンの使用意義  [Not invited]
    植村天受
    南大阪排尿障害セミナー  2009/02  堺
  • 転移性腎細胞癌に対する新規分子標的薬による治療経験  [Not invited]
    植村天受
    SUTENT発売記念 三重県/腎癌フォーラム  2008/12  津
  • 慢性透析患者に発生した進行腎がんに対するソラフェニブの使用経験  [Not invited]
    植村 天受; 大関 孝之; 野澤 昌弘; 吉川 元清; 中川 勝弘; 南 高文; 林 泰司; 辻 秀憲; 田中 基幹; 梅川 徹; 石井 徳味
    第58回日本泌尿器科学会中部総会  2008/11  大津  第58回日本泌尿器科学会中部総会
  • 難治性前立腺癌に対する治療戦略ーBench to bed side back to benchーについて  [Not invited]
    植村 天受
    第50回日本泌尿器科学会群馬地方会  2008/11  前橋  第50回日本泌尿器科学会群馬地方会
  • mRCC治療における分子標的治療薬の挑戦  [Not invited]
    植村 天受
    第58回日本泌尿器科学会中部総会サテライトシンポジウム  2008/11  大津  第58回日本泌尿器科学会中部総会サテライトシンポジウム
  • 泌尿器癌骨転移における治療戦略  [Not invited]
    植村天受
    山口県 泌尿器癌骨転移セミナー  2008/11  宇部
  • 難治性腎細胞癌に対するペプチドワクチン療法  [Not invited]
    植村天受; 南高文; 田中基幹; 上島成也; 平尾佳彦; 角田卓也; 中村祐輔
    第21回日本バイオセラピィ学術集会総会  2008/11  東京  第21回日本バイオセラピィ学会学術集会
  • 転移性腎細胞癌に対する新規分子標的薬による治療経験  [Not invited]
    植村天受
    第46回日本癌治療学会総会  2008/10  名古屋  第46回日本癌治療学会総会
  • あきらめないで男性の排尿困難 −前立腺肥大症-  [Not invited]
    植村天受
    第2回 河内長野市、大阪狭山市民のための公開講座 「わかりやすい排尿のお話」  2008/10  河内長野  第2回河内長野市・大阪狭山市民のための公開講座「わかりやすい排尿のお話」
  • 転移性腎癌に対する分子標的治療 - 標準治療アルゴリズムと使用経験 -  [Not invited]
    植村天受
    腎細胞癌薬物療法学術講演会  2008/10  松本  腎細胞癌薬物療法学術講演会
  • A phase II study of the efficacy and safety of sunitinib in Japanese patients with metastatic renal cell carcinoma (mRCC)  [Not invited]
    植村 天受; 北海道大学医学部泌尿器科; 九州大学医学部泌尿器科; 筑波大学医学部泌尿器科
    Urological Research Society  2008/09  Amsterdam, The Netheriands  Urological Research Society
  • A phase ll study of the efficacy and safety of sunitinib in Japanese patients with metastatic renal cell carcinoma(mRCC)  [Not invited]
    植村天受; 篠原 N; 内藤誠二; 赤座英之
    Urological Research Society  2008/09  Amsterdam,The Netherlands
  • Using targeted treatments: case discussions  [Not invited]
    植村 天受
    5th Asia Pacific Urology Summit  2008/08  Penang, Malaysia  5th Asia Pacific Urology Summit
  • アンドロゲン非依存性前立腺がんに対する新しい治療戦略  [Not invited]
    植村 天受
    Expert Meeting in Urology  2008/07  堺  Expert Meeting in Urology
  • ASCO 2008ー腎癌治療を中心にー  [Not invited]
    植村 天受
    ファイザーウロロジーTVシンポジム  2008/06  東京  ファイザーウロロジーTVシンポジム
  • 転移性腎癌に対する治療の現状 ―新しい治療に対する期待と注意点―  [Not invited]
    植村天受
    第74回神奈川県泌尿器科医会  2008/06  伊勢原  第74回神奈川県泌尿器科医会
  • 転移性腎癌に対する治療の現状〜新しい治潦に対する期待と注意点〜  [Not invited]
    植村天受
    ネクサバール錠発売記念学術講演会  2008/06  前橋
  • 転移性腎癌に対する治療の変遷  [Not invited]
    植村天受
    第1回 名古屋腎癌治療セミナー  2008/06  名古屋
  • 本邦におけるPhase「臨床試験の有効性と安全性(RCC症例)」  [Not invited]
    植村 天受
    Pfizer Oncology Symposium  2008/05  東京  Pfizer Oncology Symposium
  • 進行性腎細胞癌に対する分子標的薬の展望  [Not invited]
    植村 天受
    RCC臨床治療研究会  2008/05  京都  RCC臨床治療研究会
  • Phase I/II study of individualized peptide vaccines for HLA-A2/A24 positive patients with hormonerefractory prostate cancer  [Not invited]
    植村 天受; 南 高文; 田中 基幹; 上島 成也; 奈良県立医科大学泌尿器科; 奈良県立医科大学泌尿器科; 久留米大学免疫学
    ASCO 2008 Annual Meeting  2008/05  Chicago, USA  ASCO 2008 Annual Meeting
  • A phase ll study of the efficacy and safety of sunitinib in treatment-naive and pretreated japanese patients (pts)with metastatic renal cell carcinoma (mRCC)  [Not invited]
    植村天受; 篠原信雄; 内藤誠二; 赤座英之
    44th Annual Meeting of the American Society of ccccclinical oncology  2008/05  アメリカ
  • 脳外傷モデルを用いた排尿の変化  [Not invited]
    清水 信貴; 伊藤 龍生; 伊藤 浩行; 植村 天受; 松本成史; 花井禎
    第96回日本泌尿器科学会総会  2008/04  パシフィコ横浜  第96回日本泌尿器科学会総会
  • 進行性腎細胞癌に対する分子標的薬の展望  [Not invited]
    植村天受
    腎癌分子標的治療勉強会  2008/04  神戸
  • 転移性腎癌に対する治療の現状ー新しい治療に対する期待と注意点ー  [Not invited]
    植村 天受
    第38回愛媛県泌尿器科医会  2008/03  松山  第38回愛媛県泌尿器科医会
  • ホルモン不応性再燃前立腺癌に対するぺプチドワクチンの有用性  [Not invited]
    植村天受
    第8回ASPC研究会  2008/03  名古屋
  • 転移性腎癌に対する治療の現状−新しい治潦に対する期待と注意点-  [Not invited]
    植村天受
    第38回愛媛県泌尿器科医会  2008/03  松山
  • 前立腺癌密封小線源治療後の排尿状態についての検討  [Not invited]
    清水 信貴; 林 泰司; 南 高文; 辻 秀憲; 野澤 昌弘; 田中 基幹; 石井 徳味; 植村 天受; 田原秀男
    第9回 南近畿排尿障害懇話会  2008/02  スイスホテル南海大阪  第9回 南近畿排尿障害懇話会
  • 国内における分子標的治療薬の臨床展開(ネクサバール国内第?相試験結果より)  [Not invited]
    植村 天受
    ネクサバール錠 承認記念シンポジウム  2008/02  東京  ネクサバール錠 承認記念シンポジウム
  • 「国内における分子標的治潦薬の臨床展開」 (ネクサバール国内弟?相試験結果より)  [Not invited]
    植村天受
    ネクサバール錠 承認記念シンポジウム  2008/02  東京
  • 腎癌治療の新たなる時代を迎えて  [Not invited]
    植村 天受
    Nexavar Kickoff Meeting  2007/12  大阪  Nexavar Kickoff Meeting
  • 腎癌治療の新展開ー分子標的治療薬の使用経験について  [Not invited]
    植村 天受
    第43回茨城腎癌研究会講演会  2007/11  第43回茨城腎癌研究会講演会
  • 腎癌の外科手術:腹腔鏡手術  [Not invited]
    植村 天受
    第57回日本泌尿器科学会中部総会  2007/11  奈良  第57回日本泌尿器科学会中部総会
  • 近畿大学医学部人工透析部開設後30年間の臨床的検討  [Not invited]
    植村 天受; 石井 徳味; 林 泰司; 佐藤 弘章; 鮫島 謙一
    第57回日本泌尿器科学会中部総会  2007/11  奈良  第57回日本泌尿器科学会中部総会
  • 腎癌治潦の新展開ー分子標的治療薬の使用経験について  [Not invited]
    植村天受
    第43回茨城腎研究会講演会  2007/11  つくば
  • 尿道部分閉塞(BOO)ラットの膀胱血流量に対する塩酸タムスロシンの作用  [Not invited]
    松本 成史; 花井 禎; 植村 天受; 奥津 紘子; 野口; 由紀子; 大竹; 昭良; 鈴木; 雅徳; 笹又 理央; 栗田 孝
    第14回日本排尿機能学会  2007/10  福島  第14回日本排尿機能学会
  • 難治性腎細胞癌に対する分子標的薬の使用経験  [Not invited]
    植村 天受; 田中 基幹; 野澤 昌弘; 上島 成也
    第45回日本癌治療学会総会  2007/10  京都  第45回日本癌治療学会総会
  • 進行腎癌に対するCA9ペプチドワクチン療法  [Not invited]
    植村 天受
    第44回 日本癌治療学会総会  2007/10  第44回 日本癌治療学会総会
  • 新しい非侵襲ウロダイナミクス装置(膀胱内圧テレメトリー法)の開発とその有用性  [Not invited]
    松本 成史; 植村 天受; 竹内 康人
    第14回日本排尿機能学会  2007/10  福島  第14回日本排尿機能学会
  • Hypertension Promotes BBN-induced Bladder Carcinogenesis in Spontaneously Hypertensive Rat  [Not invited]
    松本 成史; 田中 基幹; 上島 成也; 植村 天受
    第66回日本癌学会総会  2007/10  横浜  第66回日本癌学会総会
  • ラット閉塞膀胱を用いたPDE5 inhibitor(vardenafil)の膀胱保護効果についての検討  [Not invited]
    松本 成史; 花井 禎; 清水 信貴; 杉本 公一; 植村 天受
    第14回日本排尿機能学会  2007/10  福島  第14回日本排尿機能学会
  • サイトカイン療法抵抗性腎癌に対する新しい治療戦略  [Not invited]
    植村 天受; 石井 徳味; 上島 成也; 清水 信貴; 秋山 隆弘; 市立貝塚病院
    第37回日本腎臓学会西部学術大会  2007/10  福井  第37回日本腎臓学会西部学術大会
  • Phase I/II study if CA9 peptide vaccination with interferon-alpha in cytokine refractory renal cancer patients  [Not invited]
    植村 天受; 田中 基幹; 野澤 昌弘; 松本 成史; 上島 成也
    66th Annual Meeting of the Japanese Cancer Association  2007/10  66th Annual Meeting of the Japanese Cancer Association
  • CA9 peptide vaccination in combination with interferon-alpha in HLA-A24 positive patients with cytokine refractory renal cell carcinoma  [Not invited]
    植村 天受; 上島 成也; 清水 信貴; 田中 基幹; 奈良県立医科大学泌尿器科; 奈良県立医科大学泌尿器科
    23rd Annual Meeting Urological Research Society  2007/10  California, USA  23rd Annual Meeting Urological Research Society
  • 前立腺癌の早期発見の重要性と最新治療  [Not invited]
    植村 天受
    ブルークローバー・キャンペーン2007  2007/09  大阪  ブルークローバー・キャンペーン2007
  • 高血圧と膀胱発癌の関係 −SHRを用いた膀胱発癌による検討−  [Not invited]
    松本 成史; 清水 信貴; 花井 禎; 植村 天受
    第43回高血圧関連疾患モデル学会学術総会  2007/09  大阪  第43回高血圧関連疾患モデル学会学術総会
  • SHR、SHRSPを用いた高血圧と過活動膀胱の関連性に関する検討  [Not invited]
    松本 成史; 清水 信貴; 花井 禎; 植村 天受
    第43回高血圧関連疾患モデル学会学術総会  2007/09  大阪  第43回高血圧関連疾患モデル学会学術総会
  • 右低形成腎由来尿管が膀胱憩室に開口し、逆流症を呈していた1症例  [Not invited]
    松本 成史; 大関 孝之; 花井 禎; 植村 天受
    第2回大阪小児泌尿器疾患検討会  2007/08  大阪  第2回大阪小児泌尿器疾患検討会
  • The Role of Elastin Fibers in the Bladder and Bladder Functions - Related with Bladder Outlet Obstruction -  [Not invited]
    松本 成史; 杉本 公一; 花井 禎; 植村 天受; 伊藤 浩行
    37th Annual Meeting of the International Continence Society (ICS)  2007/08  Rotterdam, Netherland  37th Annual Meeting of the International Continence Society (ICS)
  • PDE5 inhibitor (vardenafil) protects rat bladder from partial outlet obstruction-induced contractile dysfunction  [Not invited]
    松本 成史; 花井 禎; 清水 信貴; 杉本 公一; 渡邊 絵美; 植村 天受
    37th Annual Meeting of the International Continence Society (ICS)  2007/08  Rotterdam, Netherland  37th Annual Meeting of the International Continence Society (ICS)
  • Effects of deep brain stimulation on urodynamic findings in patients with Parkinson's disease  [Not invited]
    松本 成史; 清水 信貴; 花井 禎; 植村 天受; 中野 直樹
    37th Annual Meeting of the International Continence Society (ICS)  2007/08  Rotterdam, Netherland  37th Annual Meeting of the International Continence Society (ICS)
  • A Correlative study on the effect of Eviprostat between the clinical parameters and oxidative stress (urinary 8-OHdG) in the treatment of the lower urinary tract symptoms associated with BPH (BPH/LUTS) and on urinary 8-OHdG content in rabbit BOO model  [Not invited]
    松本 成史; 花井 禎; 堀川 重樹; 植村 天受; Matsui T Oka; M; Tanaka M
    37th Annual Meeting of the International Continence Society (ICS)  2007/08  Rotterdam, Netherland  37th Annual Meeting of the International Continence Society (ICS)
  • 畜尿症状における排尿治療薬の使い方  [Not invited]
    植村 天受
    南大阪OAB学術講演会  2007/07  大阪市  南大阪OAB学術講演会
  • 先天性副腎皮質過形成症に対する治療が原因と考えられた両側Leydig cell tumorの1例  [Not invited]
    松本 成史; 齋藤 允孝; 森 康範; 林 泰司; 植村 天受
    第16回日本小児泌尿器科学会総会  2007/07  神戸  第16回日本小児泌尿器科学会総会
  • 腎細胞癌におけるCA9を標的分子とした診断と治療  [Not invited]
    植村 天受
    第34回 尿路悪性腫瘍研究会  2007/07  東京都  第34回 尿路悪性腫瘍研究会
  • 蓄尿症状における排尿治療薬の使い方  [Not invited]
    植村天受
    南大阪OAB学術講演会  2007/07  堺市
  • 近畿大学医学部附属病院における血液浄化30年の臨床統計  [Not invited]
    植村 天受; 石井 徳味; 森 康範; 林 泰司; 嶋津 秀紀; 松岡 稔明; 杉山 昌史; 木下 浩二; 船内 正憲; 坂口 美佳; 長谷川 廣文
    第52回 (社)日本透析医学会学術集会・総会  2007/06  大阪市  第52回 (社)日本透析医学会学術集会・総会
  • 蓄尿障害における抗コリン剤・αブロッカーの使用経験  [Not invited]
    植村天受; 仲谷達也; 大阪市立大学院泌尿器病態
    OSAKA OAB学術講演会  2007/06  大阪
  • CA9ペプチドワクチン Bench to Bedside  [Not invited]
    植村天受
    第3回北海道癌免疫制御研究会  2007/06  札幌市
  • 腎細胞癌に対する新しい治療戦略  [Not invited]
    植村天受
    第6回熊本尿路悪性腫瘍研究会  2007/06  熊本
  • Distribution of elastin fiber in prostate  [Not invited]
    杉本 公一; 松本 成史; 花井 禎; 伊藤 浩行; 植村 天受
    102th Annual Meeting of American Urological Association (AUA)  2007/05  Anaheim, CA, USA  102th Annual Meeting of American Urological Association (AUA)
  • Bladder protective effects of PDE5 inhibitor -Efficacy of vardenafil on rat bladder with outlet obstruction-  [Not invited]
    松本 成史; 渡邊 絵美; 中田 裕佳; 杉本 公一; 清水 信貴; 花井 禎; 植村 天受
    102th Annual Meeting of American Urological Association (AUA)  2007/05  Anaheim, CA, USA  102th Annual Meeting of American Urological Association (AUA)
  • A phase I traial of vaccination of personalized peptides for HLA-A2/A24 positive patients with hormone-refractory prostate cancer  [Not invited]
    植村 天受; 田中 基幹; 上島成也; 南 高文; 藤本 清秀; 平尾; 伊東 恭悟
    AUA 2007  2007/05  USA  AUA 2007
  • A PHASE l TRlAL OF VACClNATlON OF PERSONALlZED PEPTlDES FOR HLA-A2/A24POSlTlVE PATlENTS WlTH HORMONE REFRACTORY PROSTATE CANCER  [Not invited]
    植村天受; 田中基幹; 上島成也; 南高文(近大; 藤本清秀; 平尾佳彦; 伊東恭悟; 留米
    Aua2007 Annual Meeting  2007/05  Anahelm,USA
  • VardenafilはBPH/LUTSを改善する−ラット閉塞膀胱に対するVardenafilの有効性について−  [Not invited]
    松本 成史; 花井 禎; 吉岡 伸浩; 堀川 重樹; 清水 信貴; 植村 天受
    第95回日本泌尿器科学会総会  2007/04  神戸  第95回日本泌尿器科学会総会
  • 再燃前立腺癌に対するペプチドワクチン療法  [Not invited]
    植村天受
    第16回秋田県前立腺癌研究会  2007/04  秋田市  第16回 秋田県前立腺癌研究会
  • Edaravone protects against ischemia / reperfusion-induced morphological and functional changes in rat urinary bladder  [Not invited]
    松本 成史; 花井 禎; 吉岡 伸浩; 清水 信貴; 植村 天受
    8th Triennial Meeting of the German-Japanese Confederation of Urology  2007/03  Tokyo, Japan  8th Triennial Meeting of the German-Japanese Confederation of Urology
  • CA9 peptide vaccination as a new therapeutic strategy for advanced renal cancer  [Not invited]
    植村 天受; 上島成也; 南 高文; 藤本 清秀; 平尾
    The 8th Triennial Meeting of the German-Japanese Confederation of Urology  2007/03  Japan  The 8th Triennial Meeting of the German-Japanese Confederation of Urology
  • Presentation time (12min.)+Discussion time(3min)=Total 15 min. Underlined doctor is the presenter.  [Not invited]
    植村天受; 上島成也; 南高文; 藤本清秀; 平尾佳彦
    The 8th Triennial Meeting of the German-Japanese Confederation of Urology  2007/03  東京
  • α遮断薬の射精障害の検討 ―特にシロドシンでの影響―  [Not invited]
    松本 成史; 杉本 公一; 清水 信貴; 植村 天受; 杉山 高秀
    第46回NGB研究会  2007/02  大阪  第46回NGB研究会
  • 腎細胞癌の治療と最近の知見について  [Not invited]
    植村天受
    茨城泌尿器疾患QOL研究会2007  2007/02  つくば市
  • 腎細胞癌に対する新しい治療戦略  [Not invited]
    植村天受
    学術講演会  2007/01  福岡市  学術講演会
  • 転移性腎癌に対する新しい治療戦略  [Not invited]
    植村天受
    KMU泌尿器科セミナー  2007/01  高松市  第6回 KMU泌尿器科セミナー
  • シロドシンの射精障害:ヘルシーボランティアでの検討  [Not invited]
    松本 成史; 齋藤 允孝; 中西 道政; 杉本 公一; 清水 信貴; 森 康範; 南 高文; 林 泰司; 植村 天受; 杉山 高秀
    第197回日本泌尿器科学会関西地方会  2006/12  枚方  第197回日本泌尿器科学会関西地方会
  • ホルモン不応再燃前立腺癌に対するペプチドワクチン療法ー第I/II相臨床試験ー  [Not invited]
    植村 天受; 上島成也; 田中 基幹; 南 高文; 藤本 清秀; 平尾; 伊東 恭悟
    第19回 日本バイオセラピィ学会学術集会総会  2006/11  第19回 日本バイオセラピィ学会学術集会総会
  • LUTS症例に対するエビプロスタットの抗酸化作用の検討  [Not invited]
    松本 成史; 堀川 重樹; 清水 信貴; 吉岡 伸浩; 花井 禎; 植村 天受; 杉山 高秀
    第45回NGB研究会  2006/11  大阪  第45回NGB研究会
  • Effect of alpha-blocker before TURP in terms of its dosing period  [Not invited]
    吉岡 伸浩; 松本 成史; 清水 信貴; 花井 禎; 植村 天受
    36th Annual Meeting of the International Continence Society (ICS)  2006/11  Christchurch, New Zealand  36th Annual Meeting of the International Continence Society (ICS)
  • Edaravone protects against ischemia / reperfusion-induced morphological and functional changes in rat urinary bladder  [Not invited]
    松本 成史; 花井 禎; 吉岡 伸浩; 清水 信貴; 植村 天受
    36th Annual Meeting of the International Continence Society (ICS)  2006/11  Christchurch, New Zealand  36th Annual Meeting of the International Continence Society (ICS)
  • Distribution of elastin fiber in prostate  [Not invited]
    松本 成史; 杉本 公一; 清水 信貴; 花井 禎; 植村 天受
    36th Annual Meeting of the International Continence Society (ICS)  2006/11  Christchurch, New Zealand  36th Annual Meeting of the International Continence Society (ICS)
  • 近未来的前立腺癌対策 ホルモン抵抗性再燃前立腺癌に対する癌ワクチン療法の現状と将来  [Not invited]
    植村天受
    第56回日本泌尿器科学会中部総会  2006/10  名古屋市
  • 泌尿器科腫瘍と癌抑制因子  [Not invited]
    植村 天受
    第56回 日本泌尿器科学会中部総会  2006/10  名古屋市  第56回 日本泌尿器科学会中部総会
  • 妊娠中の高度両側水腎症で緊急処置を要した小児期逆流防止手術の合併症:4症例の経験  [Not invited]
    畑中 祐二; 松本 成史; 清水 信貴; 森 康範; 林 泰司; 植村 天受; 秋山 ?弘; 栗田 孝
    第56回日本泌尿器科学会中部総会  2006/10  名古屋  第56回日本泌尿器科学会中部総会
  • 高血圧と過活動膀胱 −SHR, SHRSPを用いた実験的検討―  [Not invited]
    吉岡 伸浩; 松本 成史; 植村 天受
    第56回日本泌尿器科学会中部総会  2006/10  名古屋  第56回日本泌尿器科学会中部総会
  • ホルモン抵抗性再燃前立腺癌に対する癌ワクチン療法の現状と将来  [Not invited]
    植村 天受
    第56回 日本泌尿器科学会中部総会  2006/10  名古屋市  第56回 日本泌尿器科学会中部総会
  • パーキンソン病の脳深部電気刺激治療の排尿反射への影響  [Not invited]
    清水 信貴; 松本 成史; 森 康範; 吉岡 伸浩; 植村 天受; 渡邉 啓; 中野 直樹; 種子田 護
    第56回日本泌尿器科学会中部総会  2006/10  名古屋  第56回日本泌尿器科学会中部総会
  • Clinically malignant behavior を呈した骨盤内multilocular cystic epithelial-stromal tumorの1例  [Not invited]
    清水 信貴; 森 康範; 南 高文; 林 泰司; 辻 秀憲; 松本 成史; 能勢 和宏; 野澤 昌弘; 田中 基幹; 石井 徳味; 植村 天受; 土手 健作; 伊藤 浩行; 杉山 高秀
    第44回日本癌治療学会総会学術集会  2006/10  東京・京王プラザホテル  第44回日本癌治療学会総会学術集会
     
    症例は33歳男性で、2003年10月頃より軽度排尿困難を認め12月に尿閉となり近医受診、超音波および膀胱鏡検査にて膀胱腫瘍を疑われ精査加療目的で当科紹介となった。既往はファロー四徴症手術(2歳時)のみで、染色体異常は認めなかった。膀胱尿道鏡検査で腫瘍は尿道精阜付近より膀胱内に突出する形状の腫瘍で、骨盤CTおよびMRIでは左側前立腺および精嚢腺から膀胱側に占拠するモザイク状パタンを示す充実性腫瘍と左側後腹膜腔を占拠する充実性腫瘍であった。尿路側と後腹膜腔側の腫瘍の交通性は不明であった。まず経尿道的腫瘍切除術を施行、病理診断はmultilocular cystic epithelial-stromal tumorで悪性所見は認められなかった。経過観察していたが半年後に再度腫瘍の膀胱尿道内再発による尿閉状態となり、後腹膜腫瘍摘除術および経尿道的腫瘍切除術を施行した。病理診断は同様で悪性所見は認めなかった。その後も度々腫瘍の再発による尿閉を繰り返し、経尿道的腫瘍切除術を計3回
  • BPH/LUTSに対するエビプロスタットの抗酸化作用の検討  [Not invited]
    堀川 重樹; 松本 成史; 花井 禎; 吉岡 伸浩; 清水 信貴; 植村 天受
    第56回日本泌尿器科学会中部総会  2006/10  名古屋  第56回日本泌尿器科学会中部総会
  • 難治性サイトメガロウイルス感染症を発症したABO不適合生体腎移植の一例  [Not invited]
    林 泰司; 能勢 和宏; 田原 秀男; 石井 徳味; 植村 天受
    第42回日本移植学会総会  2006/09  千葉市  第42回日本移植学会総会
  • 前立腺におけるエラスチンの分布  [Not invited]
    杉本 公一; 松本 成史; 花井 禎; 吉岡 伸浩; 清水 信貴; 植村 天受; 伊藤 浩行; 永井 信夫; 中林 洋; 木野
    第13回日本排尿機能学会  2006/09  東京  第13回日本排尿機能学会
  • 高血圧と過活動膀胱 −SHR, SHRSPを用いた実験的検討―  [Not invited]
    吉岡 伸浩; 松本 成史; 植村 天受
    第13回日本排尿機能学会  2006/09  東京  第13回日本排尿機能学会
  • 経尿道的前立腺切除術(TUR-P)前後における尿中8-OHdGの推移  [Not invited]
    堀川 重樹; 松本 成史; 花井 禎; 吉岡 伸浩; 清水 信貴; 植村 天受
    第13回日本排尿機能学会  2006/09  東京  第13回日本排尿機能学会
  • Bladder outlet obstruction (BOO) promotes BBN-induced bladder carcinogenesis in rat  [Not invited]
    松本 成史; 田中 基幹; 上島 成也; 植村 天受
    第65回日本癌学会総会  2006/09  横浜  第65回日本癌学会総会
  • 下部尿路閉塞と膀胱発癌の関係 −ラットを用いた実験的検討−  [Not invited]
    松本 成史; 清水 信貴; 花井 禎; 田中 基幹; 植村 天受
    第13回日本排尿機能学会  2006/09  東京  第13回日本排尿機能学会
  • Effect of Edaravone on ischemia/reperfusion injury in rat urinary bladder -Changes in smooth muscle cell phenotype and contractile function-  [Not invited]
    松本 成史; 花井 禎; 吉岡 伸浩; 堀川 重樹; 清水 信貴; 植村 天受
    The 23rd Japan Korea Urological Congress  2006/09  Nara, Japan  The 23rd Japan Korea Urological Congress
  • A phase I trial of vaccination of tailor-made peptides for HLA-A2/A24 positive patients with hormone-refractory prostate cancer  [Not invited]
    植村 天受
    Urological Research Society  2006/09  Austira  Urological Research Society
  • 「夜間頻尿」がQOLにどの程度関与しているか ―IPSSにnocturia QOLを加えた調査による検討−  [Not invited]
    清水 信貴; 松本 成史; 植村 天受; 堀川 重樹; 吉岡 伸浩; 花井 禎; 江左 篤宣
    第13回日本排尿機能学会  2006/09  東京  第13回日本排尿機能学会
  • A phase I trial of vaccination of tailor-made peptides for HLA-A2/A24 positivepatients with hormone-refractory prostate cancer  [Not invited]
    植村天受
    22th Annual Meeting Urological Research Society  2006/09  Salzburg, Austria
  • Bladder Outlet Obstruction Promotes BBN - induced Bladder Carcinogenesis in Rat  [Not invited]
    松本 成史; 清水 信貴; 土手 健作; 花井 禎; 田中 基幹; 伊藤 浩行; 植村 天受
    8th Asian Congress of Urology  2006/08  Nusa Dua, Bali, Indonesia  8th Asian Congress of Urology
  • 転移性腎細胞癌に対する新しい治療戦略  [Not invited]
    植村天受
    第5回大分県腎癌研究会  2006/07  大分市
  • 妊娠中の高度両側水腎症で緊急処置を要した小児期逆流防止手術の合併症:4症例の経験  [Not invited]
    松本 成史; 杉本 公一; 清水 信貴; 森 康範; 林 泰司; 畑中 祐二; 森本 康裕; 花井 禎; 上島 成也; 植村 天受; 秋山 ?弘
    第15回日本小児泌尿器科学会総会  2006/07  新潟  第15回日本小児泌尿器科学会総会
  • 前立腺癌密封小線源治療の初期経験  [Not invited]
    林 泰司; 森 康範; 田原 秀男; 田中 基幹; 植村 天受; 中松 清志; 西村 恭昌
    第60回近畿大学医学会学術講演会  2006/07  大阪狭山市  第60回近畿大学医学会学術講演会
  • 極めて稀な後腸形成不全・外陰部形成不全の1症例  [Not invited]
    松本 成史; 林 泰司; 吉田 洋; 八木 誠; 植村 天受
    第15回日本小児泌尿器科学会総会  2006/07  新潟  第15回日本小児泌尿器科学会総会
  • 清水 信貴; 松本 成史; 田中 基幹; 石井 徳味; 植村 天受
    第195回日本泌尿器科学会関西地方会  2006/06  大阪市立大学  第195回日本泌尿器科学会関西地方会
     
    68歳女性。1999年(62歳)に左腎癌の診断で根治的左腎摘除施行。RCC,alveolar type,clear cell subtype,G2,INFβ,pT2 N0 M0であった。糖尿病で内科通院中に甲状腺の腫大を指摘され、頸部超音波、単純CTで甲状腺左葉に4.9×2.7×5.5cmの腫瘤性病変を認めた。201TLシンチでは、左葉外側に異常集積を認めた。穿刺吸引細胞診ではclass?、甲状腺悪性腫瘍疑いで2006年2月16日に甲状腺左葉摘出術を行った。甲状腺内に多発する腫瘍を認め、淡明な胞体と異型な小型濃染核を有する異型細胞を認めた。TTF(-)、サイログロブリン(-)で甲状腺以外由来であり腎癌の甲状腺転移と診断した。他転移部位はなく追加治療なしで経過観察をしている。
  • Novel gene transduction technology by Credia TF  [Not invited]
    田中 基幹; 植村 天受; 外崎 円; 梅影; 政文; 小中; 富雄; 池田 寿文
    The 9th Annual Meeting of the American Society of Gene Therapy  2006/05  Washington, DC, USA  The 9th Annual Meeting of the American Society of Gene Therapy
  • 進行性腎細胞癌に対する治療戦略  [Not invited]
    植村 天受
    第94回日本泌尿器科学会総会  2006/04  福岡市  第94回日本泌尿器科学会総会
  • 下部尿路閉塞により膀胱の発癌は促進される  [Not invited]
    松本 成史; 花井 禎; 清水 信貴; 上島 成也; 植村 天受
    第94回日本泌尿器科学会総会  2006/04  福岡  第94回日本泌尿器科学会総会
  • Phase-1 syudy of carbonic anhydrase 9 peptide vaccines in patients with metastatic renal cell carcinoma  [Not invited]
    植村 天受; 田中 基幹; 上島 成也; 平尾 佳彦; 伊東 恭悟
    Annual EAU Congress  2006/04  France  Annual EAU Congress
  • Novel gene transduction technology by Credia TF  [Not invited]
    田中 基幹; 植村 天受; 外崎 円; 梅影; 政文; 小中; 富雄; 辻; 良平; 池田 寿文
    The 97th Annual Meeting, American Association for Cancer Research  2006/03  Washington, DC, USA  The 97th Annual Meeting, American Association for Cancer Research
  • 腎癌について  [Not invited]
    植村 天受
    筑後泌尿器科医会  2006/02  久留米市  筑後泌尿器科医会
  • 極めて稀な後腸形成不全・外陰部形成不全の1症例  [Not invited]
    林 泰司; 松本 成史; 兼子 美帆; 植村 天受; 吉田 洋; 八木 誠
    第194回日本泌尿器科学会関西地方会  2006/02  和歌山  第194回日本泌尿器科学会関西地方会
  • 腎細胞癌に対する新しい治療戦略  [Not invited]
    植村天受
    ウロロジカルキャンサーフォーラム2006  2006/01  仙台市
  • 腹腔鏡下脾摘術後で血漿交換をせずに行ったABO不適合生体腎移植の1例  [Not invited]
    林 泰司; 兼子 美帆; 石井 徳味; 植村 天受; 耳原総合病院泌尿器科; 原 靖
    第39回日本臨床腎移植学会  2006/01  栃木県  第39回日本臨床腎移植学会
  • HLA-A24陽性難治性腎細胞癌に対するCA9ペプチドワクチン療法ー第1/2相臨床試験ー  [Not invited]
    植村 天受; 上島成也; 藤本清秀; 田中基幹; 平尾佳彦; 吉川和宏
    第18回日本バイオセラピー学会学術集会総会  2005/12  宇部市  第18回日本バイオセラピー学会学術集会総会
  • 前立腺癌に対する治療経験〜過去・現在・未来〜  [Not invited]
    植村 天受
    第3回群馬前立腺癌フォーラム  2005/11  前橋市  第3回群馬前立腺癌フォーラム
  • Phase-I/II trial of CA9 peptide vaccines in HLA-A24 positive patients with cytokine refractory renal cell carcinoma  [Not invited]
    植村 天受
    Urological Research Society  2005/11  Boston, Massachusetts  Urological Research Society
  • Creatol, an Oxidative Product of Creatinine in Kidney Tansplant Patients, as a Useful Determinant of Renal Function; A Preliminary Study  [Not invited]
    松本 成史; 花井 禎; 松浦 健; 植村 天受; 西岡 伯; 秋山 ?弘
    9th Congress of the Asian Society of Transplantation  2005/11  Karachi, Pakistan  9th Congress of the Asian Society of Transplantation
  • Can monitoring of serum 8-OHdG level for two hours after renal transplantation predict prognosis of the graft?  [Not invited]
    松本 成史; 花井 禎; 松浦 健; 植村 天受; 西岡 伯; 秋山 ?弘
    9th Congress of the Asian Society of Transplantation  2005/11  Karachi, Pakistan  9th Congress of the Asian Society of Transplantation
  • Bladder outlet obstruction accelerates carcinogenesis of the bladder  [Not invited]
    松本 成史; 植村 天受; Robert M. Levin
    21th Urological Research Society  2005/11  Boston, USA  21th Urological Research Society
  • 難治性腎癌に対するCA9ペプチドワクチン療法ー第1相・早期2相臨床試験ー第  [Not invited]
    植村 天受
    第43回日本癌治療学会総会  2005/10  名古屋市  第43回日本癌治療学会総会
  • 特発性正常圧水頭症症例における排尿筋過活動の意義  [Not invited]
    松本 成史; 清水 信貴; 吉岡 伸浩; 花井 禎; 杉山 高秀; 植村 天受; 北口正孝
    第55回日本泌尿器科学会中部総会  2005/10  神戸  第55回日本泌尿器科学会中部総会
  • 清水 信貴; 松本 成史; 花井 禎; 吉岡 伸浩; 杉山 高秀; 植村 天受; 北口 正孝
    第12回排尿機能学会  2005/10  松本市  第12回排尿機能学会
     
    【目的】特発性正常圧水頭症(Idiopathic Normal Pressure Hydrocephalus: iNPH)は、明らかな原因が特定できないにもかかわらず、脳室の拡大を認め、歩行障害・痴呆症状・尿失禁の三徴候を有する症候群である。歩行障害が重要な症状で、歩行障害が認められれば外科的治療(髄液シャント手術)の効果が期待できるとされている。脳脊髄液の循環障害が改善されると、歩行をはじめ痴呆や尿失禁も改善することが知られている。しかし、iNPHにおける膀胱機能についての報告はなく、特に尿失禁についての詳細は不明である。今回、われわれはiNPH症例における治療(検査)前後における膀胱機能の変化について検討したので報告する。 【対象・方法】平成16年2月から平成17年5月までに馬場記念病院脳神経内科でiNPHと診断され、治療(検査)を受けた患者で、治療(検査)前後(CSF Tap test、VP shunt)に検査出来た18例 (M/F=14/4、平均年齢: 76歳) をIPSS、尿失禁質問表、痴呆、歩行障害などの諸検査(日
  • 女性尿閉患者の臨床的検討  [Not invited]
    堀川 重樹; 松本 成史; 清水 信貴; 吉岡 伸浩; 兼子 美帆; 花井 禎; 杉山 高秀; 植村 天受
    第12回日本排尿機能学会  2005/10  第12回日本排尿機能学会
  • 近畿大学医学部泌尿器科において浸潤性膀胱癌に対する膀胱全摘除術  [Not invited]
    堀川 重樹; 兼子 美帆; 清水 信貴; 森 康範; 林 泰司; 辻 秀憲; 松本 成史; 田原 秀男; 原 靖; 石井 徳味; 杉山 高秀; 松浦 健; 植村 天受
    第55回日本泌尿器科学会中部総会  2005/10  第55回日本泌尿器科学会中部総会
  • ラット膀胱虚血・再還流モデルにおけるフリーラジカル消去剤Edaravoneの効果と膀胱平滑筋細胞の形態学的phenotypeの変化  [Not invited]
    松本 成史; 花井 禎; 吉岡 伸浩; 清水 信貴; 杉山 高秀; 植村 天受; 堀内 喜高; 奥本 勝美
    第12回日本排尿機能学会  2005/10  松本  第12回日本排尿機能学会
  • シクロスポリン投与腎移植患者における高脂血症の検討  [Not invited]
    石井 徳味; 植村 天受; 田原 秀男; 林 泰司; 原靖, 森康範
    2005/10  第55回日本泌尿器科学会中部総会(神戸市)
  • 難治性腎細胞癌に対するCA9ペプチドワクチン療法ー第1相・早期2相臨床試験ー  [Not invited]
    植村 天受; 上島成也; 藤本清秀; 田中基幹; 平尾佳彦
    第64回日本癌学会学術総会  2005/09  札幌市  第64回日本癌学会学術総会
  • 前立腺癌におけるPTEN癌抑制遺伝子の役割  [Not invited]
    田中 基幹; 植村 天受; 冨岡 厚志; 高田; 聡; 穴井; 智; 平尾 佳彦
    第16回前立腺癌ワークショップ  2005/09  東京  第16回前立腺癌ワークショップ
  • Inductive Coupling Wireless Sensor-Transmitter for Continuous Monitoring of Intra-Bladder Pressure for Unconstrained Urodynamic Study  [Not invited]
    松本 成史; 植村 天受; Nakazono K; Takeuchi Y
    5th International Workshop on Biosignal Interpretation (BSI 2005)  2005/09  Tokyo, JAPAN  5th International Workshop on Biosignal Interpretation (BSI 2005)
  • 下部尿路におけるエラスチンの役割 −病理学的検討−  [Not invited]
    松本 成史; 清水 信貴; 杉山 高秀; 植村 天受; 杉本 公一
    第41回NGB研究会(第10回高野山セミナー)  2005/08  高野山  第41回NGB研究会(第10回高野山セミナー)
  • 8OHdG before and after TUR  [Not invited]
    花井 禎; 松本 成史; 杉山 高秀; 植村 天受
    35th International Continence Society  2005/08  Montreal, Canada  35th International Continence Society
  • 小児膀胱平滑筋肉腫(spindle cell sarcoma)の1例  [Not invited]
    松本 成史; 清水 信貴; 植村 天受; 兼子 美帆; 杉本 公一; 上島 成也; 森口 直彦; 八木 誠; 花井 禎; 森本 康裕
    第14回日本小児泌尿器科学会総会  2005/07  福岡  第14回日本小児泌尿器科学会総会
  • Phase-I study of CA9 peptide vaccines in patients with stage IV renal cell carcinoma  [Not invited]
    植村 天受; 上島成也; 中西 まこ; 藤本清秀; 平尾佳彦
    AUA 2005  2005/05  San Antonio  AUA 2005
  • Enhanced efficacy of radiation sensitivity by controlled gene delivery of PTEN expression vector conjugated with cationized gelatin in prostate cancer cells  [Not invited]
    田中 基幹; 植村 天受; 高田 聡; 冨岡; 厚志; 松村; 善昭; 平尾 佳彦
    The 100th Annual Meeting, American Urological Association, Inc.  2005/05  San Antonio, USA  The 100th Annual Meeting, American Urological Association, Inc.
  • 松本 成史; 清水 信貴; 杉山 高秀; 植村 天受; 吉岡 伸浩; 花井 禎; Robert M. Levin
    100th American Urological Association  2005/05  San Antonio, Texas, USA  100th American Urological Association
  • 腎癌治療における常識は、本当に常識といえるのか? ーガイドライン作成を目指してー  [Not invited]
    植村天受
    第29回腎癌研究会  2005/04  東京都
  • 蓚酸イオンはNADPH Oxidaseを活性を亢進しNRK52E細胞におけるオステオポンチンとMCP-1の産生亢進に至る  [Not invited]
    梅川 徹; 辻 秀憲; 畑中 祐二; 植村 天受
    第93回日本泌尿器科学会総会  2005/04  東京  第93回日本泌尿器科学会総会
  • 当科および関連病院で施行したpre-emptive腎移植症例の検討  [Not invited]
    能勢 和宏; 林 泰司; 田原 秀男; 原 靖; 松浦 健; 植村 天受; 南 高文; 森本 康裕; 永野 哲郎; 西岡 伯; 秋山 ?弘; 今西 正昭
    第93回日本泌尿器科学会総会  2005/04  東京  第93回日本泌尿器科学会総会
  • 電気メスの切除と凝固時間は経尿道的手術の分析ツールになるか?  [Not invited]
    堀川 重樹; 植村 天受; 能勢 和宏; 永井 信夫; 際本 宏; 小池 浩之
    第93回日本泌尿器科学会総会  2005/04  第93回日本泌尿器科学会総会
  • 腎移植後の蛋白尿に対するカンデサルタン(ARB)無効症例の検討  [Not invited]
    原 靖; 森本 康裕; 能勢 和宏; 田原 秀男; 松浦 健; 植村 天受; 秋山 ?弘
    第93回日本泌尿器科学会総会  2005/04  東京都  第93回日本泌尿器科学会総会
  • ラット膀胱虚血・再還流モデルにおける膀胱平滑筋細胞の形態学的phenotypeと膀胱機能の検討  [Not invited]
    松本 成史; 花井 禎; 吉岡 伸浩; 清水 信貴; 杉山 高秀; 植村 天受; 堀内喜高; 奥本勝美
    第93回日本泌尿器科学会総会  2005/04  東京  第93回日本泌尿器科学会総会
  • ニカラベン投与によるエチレングリコール投与ラット腎における結晶形成抑制効果の検討‐Angiotensin ? type ? receptor blocker(ARB)との比較‐  [Not invited]
    畑中 祐二; 辻 秀憲; 梅川 徹; 植村 天受; 井口 正典
    第93回日本泌尿器科学会総会  2005/04  東京  第93回日本泌尿器科学会総会
  • PSA10ng/ml以下の前立腺生検症例における生検数の検討  [Not invited]
    杉本 公一; 清水 信貴; 兼子 美帆; 吉岡 伸浩; 松浦 健; 松本 成史; 辻 秀憲; 植村 天受
    第93回日本泌尿器科学会総会  2005/04  ホテル日航東京/ホテルグランパシフィックメリディアン  第93回日本泌尿器科学会総会
  • Enhanced efficacy of radiation sensitivity by controlled gene delivery of PTEN expression vector conjugated with cationized gelatin in prostate cancer cells  [Not invited]
    田中 基幹; 植村 天受; 穴井 智; 高田; 聡; 松村; 善昭; 冨岡; 厚志; 平尾 佳彦
    The 96th Annual Meeting, American Association for Cancer Research  2005/04  Anaheim, USA  The 96th Annual Meeting, American Association for Cancer Research
  • 泌尿器科癌に対するペプチドワクチン療法  [Not invited]
    植村天受
    第8回北海道泌尿器科癌研究会  2005/03  札幌市
  • ホルモン抵抗性前立腺癌の治療 ーペプチドワクチン療法の現況ー  [Not invited]
    植村 天受
    北九州市泌尿器科医会・平成16年度第6回研修会  2005/03  北九州市  北九州市泌尿器科医会・平成16年度第6回研修会
  • Prostate cancer detected from multiple pulmonary metastases: A case report.  [Not invited]
    杉本 公一; 松本 成史; 田原 秀男; 松浦 健; 植村 天受
    第190回日本泌尿器科学会関西地方会  2005/02  奈良  第190回日本泌尿器科学会関西地方会
     
    55才、男性。健診にて胸部異常陰影を指摘され精査施行。CTガイド下針生検にてPSA染色陽性腺癌を認め当科紹介。前立腺生検にて確定診断となった。MAB+PE療法にて転移性肺腫瘍は縮小した。
  • 腎癌に対するペプチド癌ワクチン療法 ー開発から臨床応用ー  [Not invited]
    植村 天受
    第263回日本泌尿器科学会岡山地方会  2005/02  岡山市  第263回日本泌尿器科学会岡山地方会
  • 腎癌におけるトランスレーショナル・リサーチ ーCA9ペプチドワクチン開発からの応用ー  [Not invited]
    植村 天受
    第2回イムネース学術講演会  2005/02  山梨県  第2回イムネース学術講演会
  • 浸潤性膀胱癌に対して放射線療法、末梢血幹細胞移植併用M-VAC療法を施行した1症例  [Not invited]
    清水 信貴; 松本 成史; 田原 秀男; 原 靖; 松浦 健; 植村 天受
    第190回日本泌尿器科学会関西地方会  2005/02  奈良県文化会館  第190回日本泌尿器科学会関西地方会
     
    4歳、男性。嘔吐、肉眼的血尿を主訴に近医受診。浸潤性膀胱癌による腎後性腎不全で当科紹介受診。T4aN2M1の診断のもと放射線療法、末梢血幹細胞移植併用M-VAC療法を施行し、良好な結果を得た。
  • 清水 信貴; 松本 成史; 吉岡 伸浩; 杉山 高秀; 植村 天受
    4th International congress of the Egyptian society of Uro-gynaecology and Pelvic Floor Studies(ESUG)  2005/02  Sharm El-Shikh, Egypt  4th International congress of the Egyptian society of Uro-gynaecology and Pelvic Floor Studies(ESUG)
     
    Efforts to resolve female stress urinary incontinence spread in the latter half of the 1980s, fueled by the introduction of the Stamey procedure. Afterwards, various techniques to treat stress urinary incontinence were developed and attempted. However, the decline in long-term results with needle bladder neck suspension and anterior colporrhaphy has been criticized in recent years, and the first choice for treatment is shifting to urethral sling surgery with a TVT procedure. Thus, we studied the changes in surgery for female stress urinary incontinence at this hospital. Subjects were diagnosed with stress urinary incontinence by the Urology Department of the Kinki University School of Medicine from 1984-2004 and underwent surgery. Until the early half of the 1990s, Stamey, Raz, and Gittes suspensions and later Vesica and collagen injection were attempted, although TVT was used in all cases starting in the latter half of the 1990s.
  • HLA-A24陽性難治性腎細胞癌に対するCA9ペプチドワクチン療法ー第1/2相臨床試験ー  [Not invited]
    植村天受; 藤本清秀; 田中基幹; 平尾佳彦; 上島成也
    第18回日本バイオセラピィ学会学術集会総会  2005/01  宇部市
  • Phase-I/II trial of CA9 peptide vaccines in HLA-A24 positive patientswith cytokine refractory renal cell carcinoma  [Not invited]
    植村天受
    21th annual meeting Urological Research Society  2005/01  Boston, USA
  • 当科および当科関連施設における夫婦間移植の8例  [Not invited]
    南高文; 森 康範; 森本康裕; 能勢 和宏; 田原 秀男; 原 靖; 石井 徳味; 松浦 健; 植村 天受; 永野 哲郎; 西岡 伯; 秋山 隆弘; 江左 篤宣
    第38回日本臨床腎移植学会  2005/01  岐阜  第38回日本臨床腎移植学会
  • 当科および当科関連施設における夫婦間移植8例の検討  [Not invited]
    南 高文; 森 康範; 能勢 和宏; 田原 秀男; 原 靖; 石井 徳味; 松浦 健; 植村 天受; 森本 康裕; 永野 哲郎; 西岡 伯; 秋山 ?弘; 江左 篤宣
    第38回日本臨床腎移植学会  2005/01  大津市  第38回日本臨床腎移植学会
  • Drug-induced interstitial pneumonia after post-living renal transplantation  [Not invited]
    杉本 公一; 松本 成史; 能勢 和宏; 田原 秀男; 原 靖; 松浦 健; 植村 天受
    第38回日本臨床腎移植学会  2005/01  大津  第38回日本臨床腎移植学会
     
    28歳、男性.2002年より慢性腎不全にて腹膜透析導入。2004年5月19日母親(55歳)をドナ−とした生体腎移植術を施行いあた。HLA:A、B;1ミスマッチ、DR;0ミスマッチ、また血液型はドナ−A型、レシピエントAB型の血液型不一致であった。初期免疫抑制はタクロリムス、ミゾリビン、プレドニゾロンおよびバシリキシマブの4剤であった。術後経過は良好であったが、3日目より急に呼吸困難が出現し、間質性肺炎象を認めた。薬剤性間質性肺炎の診断下に免疫抑制剤を変更(Tac→CyA、Mz中止)し、ステロイドパルス療法施行後、肺炎像は軽快し、呼吸困難も改善した。今回われわれは薬剤性間質性肺炎の1例を経験したので若干の文献的考察を加えて報告した。
  • 腎移植術における血清8OHdGの検討  [Not invited]
    花井 禎; 松本 成史; 秋山 ?弘; 原 靖; 植村 天受; 西岡 伯
    第38回日本臨床腎移植学会  2005/01  大津  第38回日本臨床腎移植学会
  • 腎移植術におけるクレアトール値の検討  [Not invited]
    松本 成史; 花井 禎; 田原 秀男; 原 靖; 植村 天受; 西岡 伯; 秋山 ?弘
    第38回日本臨床腎移植学会  2005/01  大津  第38回日本臨床腎移植学会
  • 心停止無脳児ドナーから成人への死体腎移植  [Not invited]
    林 泰司; 森本 康裕; 能勢 和宏; 原 靖; 松浦 健; 植村 天受; 西岡 伯; 秋山 ?弘; 池上雅久
    第38回日本臨床腎移植学会  2005/01  大津市  第38回日本臨床腎移植学会
  • 癌ワクチン療法 ー開発から応用までー  [Not invited]
    植村 天受
    第32回Shizuoka Uro-Oncology Forum  2005/01  浜松市  第32回Shizuoka Uro-Oncology Forum
  • TUR前後における尿中8-OHdGの推移  [Not invited]
    花井 禎; 松本 成史; 植村 天受
    第14回排尿管理研究会  2005/01  京都  第14回排尿管理研究会
  • 難治性腎癌および前立腺癌に対する癌ワクチン療法  [Not invited]
    植村 天受
    学術講演会  2004/12  宇部市  学術講演会
  • PSA 3.1〜10 ng/ ml の前立腺生検における生検数の検討  [Not invited]
    杉本 公一; 兼子 美帆; 清水 信貴; 吉岡 伸浩; 辻 秀憲; 松本 成史; 田原 秀男; 原 靖; 植村 天受
    前立腺シンポジウム  2004/12  東京  前立腺シンポジウム
  • 蓚酸イオンはNADPH Oxidaseを活性化しオステオポンチンとMCP-1の発現を亢進する  [Not invited]
    梅川 徹; 辻 秀憲; 畑中 祐二; 植村 天受
    第54回日本泌尿器科学会中部総会  2004/11  泉佐野市  第54回日本泌尿器科学会中部総会
  • 難治性腎細胞癌に対するペプチドワクチン療法  [Not invited]
    植村 天受
    第54回日本泌尿器科学会中部総会  2004/11  泉佐野市  第54回日本泌尿器科学会中部総会
  • 前立腺に発生したsolitary fibrous tumor(SFT)の1症例  [Not invited]
    能勢 和宏; 植村 天受; 堀川重樹; 中林 洋
    第54回日本泌尿器科学会中部総会  2004/11  大阪  第54回日本泌尿器科学会中部総会
  • 前立腺に発生したsolitaly fibrous tumor(SFT)の1例  [Not invited]
    能勢 和宏; 堀川 重樹; 植村 天受; 永井 信夫; 中林 洋
    2004/11
  • 進行性腎細胞癌に対するCA9癌枠林療法  [Not invited]
    植村 天受
    第二回泌尿器腫瘍免疫研究会  2004/11  東京  第二回泌尿器腫瘍免疫研究会
  • 浸潤性膀胱癌に対する放射線療法、末梢血幹細胞移植併用化学療法を施行した1症例  [Not invited]
    清水 信貴; 松本 成史; 田原 秀男; 原 靖; 松浦 健; 植村 天受; 西村 恭昌
    第1回 南大阪細胞移植療法研究会  2004/11  近畿大学医学部円形小講堂  第1回 南大阪細胞移植療法研究会
  • ラット膀胱虚血・再灌流障害におけるフリーラジカル消去剤Edaravoneの効果  [Not invited]
    松本 成史; 花井 禎; 吉岡 伸浩; 清水 信貴; 杉山 高秀; 植村 天受
    第54回日本泌尿器科学会中部総会  2004/11  泉佐野 2004年11月5日  第54回日本泌尿器科学会中部総会
  • ニカラベン投与によるエチレングリコール投与ラット腎における結晶形成抑制効果の検討  [Not invited]
    畑中 祐二; 辻 秀憲; 梅川 徹; 植村 天受; 井口 正典
    第54回 日本泌尿器科学科会中部総会  2004/11  大阪  第54回 日本泌尿器科学科会中部総会
  • SSRI投与における排尿の変化  [Not invited]
    清水 信貴; 花井 禎; 松本 成史; 吉岡 伸浩; 杉山 高秀; 植村 天受
    第54回日本泌尿器科学会中部総会  2004/11  全日空ゲートタワーホテル大阪  第54回日本泌尿器科学会中部総会
     
    セロトニンは中枢神経系に作用し過活動膀胱を抑制することが報告されており、頻尿や尿失禁に対する治療薬として期待されている。抗うつ薬として開発された選択的セロトニン再取り込み阻害薬Selective Serotonin Reuptake Inhibitor (SSRI)は直接5-HT神経系に作用するため、頻尿が改善されることが予想される。そこでSSRIを処方した症例を対象とし、SSRI投与直後と投与2-4週後のFVCおよび自覚症状スコアの変化について検討した。合併症によっては排尿障害を助長させるため抗コリン作用のないSSRIを使用することが推奨されているが、排尿障害を改善させる可能性が示唆された。
  • 松本 成史; 清水 信貴; 吉岡 伸浩; 花井 禎; 杉山 高秀; 植村 天受
    第11回日本排尿機能学会  2004/10  大手前サンケイプラザ  第11回日本排尿機能学会
  • 難治性腎癌ならびに前立腺癌に対するペプチドワクチン療法治療成績  [Not invited]
    植村 天受; 上島成也; 田中基幹; 藤本清秀; 平尾佳彦; 吉川和宏; 伊東恭悟
    第42回日本癌治療学会総会  2004/10  京都市  第42回日本癌治療学会総会
  • 清水 信貴; 吉岡 伸浩; 花井 禎; 松本 成史; 杉山 高秀; 植村 天受
    第11回日本排尿機能学会  2004/10  大手前サンケイプラザ  第11回日本排尿機能学会
     
    急性尿閉の危険因子やその後の臨床経過の実状を把握し、bladder outlet obstruction(BOO) groupとdetrusor weakness(DW) groupに別けて違いがあるかを調べる目的で以下の検討を行った。【対象と方法】1993年から2003年までの10年間に近畿大学泌尿器科を急性尿閉で受診し、導尿が必要であった170例を対象とした。治療後、排尿が可能となった時点でのPressure-Flow StudyにおいてBOO group(n=100)とDW group(n=36)に別けた。全体およびBOO groupとDW groupに別けて、年齢、性別、原因、発症時期、排尿に関する治療歴における急性尿閉の発症率を検討した。さらに、その後の臨床経過について検討した。【結果】急性尿閉の85%は男性であった。60歳以上は男性のなかでは86%、女性のなかでは36%であった。発症時期は8月が最も多かった。男性において、BOO groupが70%、DW groupが20%であった。排尿に関する治療歴を有する症例は、BOO groupが50%、DW groupが30%であった。臨床経過は、BOO groupでは排尿可能となった症例が83%(operatio
  • 吉岡 伸浩; 清水 信貴; 松本 成史; 花井 禎; 杉山 高秀; 植村 天受
    第11回日本排尿機能学会  2004/10  大手前サンケイプラザ  第11回日本排尿機能学会
  • 花井 禎; 清水 信貴; 松本 成史; 吉岡 伸浩; 杉山 高秀; 植村 天受
    第11回日本排尿機能学会  2004/10  大手前サンケイプラザ  第11回日本排尿機能学会
  • Induction of anti-tumor responses in patients with metastatic renal cell caricinoma by vaccination with peptides-a phase I study  [Not invited]
    植村 天受; Fujimoto K; Tanaka M; Yoshikawa M; Nakanishi M; Hirao Y
    27th Congress of the Societe Internatiolale d'Urologie  2004/10  USA  27th Congress of the Societe Internatiolale d'Urologie
  • Controlled gene delivery of PTEN expression vector conjugated with cationized gelatin in prostate cancer cells  [Not invited]
    田中 基幹; 植村 天受; 穴井 智; 高田; 聡; 松村; 善昭; 冨岡; 厚志; 平尾 佳彦
    The 27th Congress of International Society of Urology  2004/10  Honolulu, USA  The 27th Congress of International Society of Urology
  • 尿閉を契機に発見された骨盤内腫瘍の1例  [Not invited]
    清水 信貴; 松本 成史; 杉山 高秀; 松浦 健; 植村 天受
    第188回 日本泌尿器科学会関西地方会  2004/09  兵庫医科大学  第188回 日本泌尿器科学会関西地方会
     
    33歳、男性。尿閉を主訴に紹介受診。諸検査にて前立腺部尿道より膀胱内に突出する有茎性腫瘍を認め、また左骨盤腔に巨大な腫瘤を認めた。骨盤内腫瘍として摘出術施行。病理所見を中心に文献的考察を加え報告する。
  • 難治性腎細胞癌に対するCA9抗原ペプチドを用いた特異的免疫療法  [Not invited]
    植村 天受; 上島成也; 松本 成史; 藤本清秀; 平尾佳彦
    第63回日本癌学会学術総会  2004/09  福岡市  第63回日本癌学会学術総会
  • 徐放性PTEN遺伝子薬を用いた、前立腺癌における放射線感受性増強効果  [Not invited]
    田中 基幹; 植村 天受; 高田 聡; 冨岡; 厚志; 平尾佳彦; 田畑 泰彦
    第63回日本癌学会総会  2004/09  福岡  第63回日本癌学会総会
  • 最近の腎癌治療の話題  [Not invited]
    植村 天受
    第2回宮崎県腎癌講演会  2004/09  宮崎市  第2回宮崎県腎癌講演会
  • カルシニューリン インヒビター導入以降における腎移植後の死亡症例の検討  [Not invited]
    原 靖; 森本 康裕; 能勢 和宏; 田原 秀男; 松浦 健; 植村 天受; 西岡 伯; 秋山 ?弘
    第40回日本移植学会総会  2004/09  岡山市  第40回日本移植学会総会
  • SHRにおける腎阻血再灌流障害モデルおよびtacrolimus腎毒性に対する抗酸化剤の有用性  [Not invited]
    林 泰司; 能勢 和宏; 田原 秀男; 原 靖; 松浦 健; 植村 天受; 西岡 伯; 秋山 ?弘
    第40回日本腎移植学会総会  2004/09  岡山市  第40回日本腎移植学会総会
  • Patients-oriented vaciene tehrapy for hormone refractory prostate cancer  [Not invited]
    植村 天受; Fujimoto K; Tanaka M; Tanaka N; Okajima E; Hirao Y
    20th urological Research Society Meeting  2004/09  Korea  20th urological Research Society Meeting
  • 蓚酸イオンはNADPH Oxidaseを活性化しオステオポンチンとMCP-1の発現を亢進する  [Not invited]
    梅川 徹; 辻 秀憲; 畑中 祐二; 植村 天受; 井口正典
    第14回日本尿路結石学会  2004/08  金沢市  第14回日本尿路結石学会
  • ニカラベン投与によるエチレングリコール投与ラット腎における結晶形成抑制効果の検討---Angiotensin?type?receptor blockerとの比較---  [Not invited]
    辻 秀憲; 畑中 祐二; 梅川 徹; 植村 天受; 井口正典
    第14回日本尿路結石症学会  2004/08  金沢市  第14回日本尿路結石症学会
  • Tailor-made peptide vaccines for hormone refractory prostate cancer patients  [Not invited]
    植村天受; Fuimoto K; Tanaka M; Tanak N; Okajima E; Hirao H
    The 7th Triennial Meeting of the German-Japanese Confederation of Urology  2004/06  Salzburg-Munich
  • 難治性腎細胞癌と再燃前立腺癌の癌ワクチン療法  [Not invited]
    植村 天受
    第60回日本泌尿器科学会茨城地方会  2004/06  つくば市  第60回日本泌尿器科学会茨城地方会
  • Tailor-made peptide vaccines for hormone refractory prostate cancer patients  [Not invited]
    植村 天受; Fujimoto K; Tanaka M; Tanaka N; Okajima E; Hirao H
    7th Triennial Meeting of the German-Japanese Confederation of Urology  2004/06  Germany  7th Triennial Meeting of the German-Japanese Confederation of Urology
  • 腎癌に対する免疫療法(癌ワクチン療法)について  [Not invited]
    植村天受
    第13回大阪化学療法研究会(OCUU化学療法研究会)  2004/05  大阪市
  • VHL-dependent and independent regulation of MN/CA9 in renal cell carcinoma cell lines  [Not invited]
    植村天受; Kawada Y; Hirao Y
    第6回VHL病国際シンポジウム  2004/05  高知市
  • 当院における20年間の女性腹圧性尿失禁の手術変遷  [Not invited]
    清水 信貴; 松本 成史; 吉岡 伸浩; 杉山 高秀; 植村 天受
    第11回 排尿管理研究会  2004/05  ぱ・る・るプラザ京都  第11回 排尿管理研究会
     
    女性腹圧性尿失禁への取り組みが広がったのは1980年代後半であり、その起爆剤となったのが、Stamey法の導入であった。その後、腹圧性尿失禁に対する様々な術式が開発され試みられてきた。しかし、近年では針式膀胱頚部挙上術や前膣壁形成術での長期成績の下降が批判され、TVT法を含む尿道スリング手術に第一選択の地位は移ったといえる。 そこで当院における女性腹圧性尿失禁の手術変遷を調査した。対象は1984年〜2004年まで近畿大学医学部泌尿器科で腹圧性尿失禁と診断され、手術を施行した患者である。1990年代前半までは、Stamey 、Raz 、Gittes等のsuspention、その後Vesica やコラーゲン注入術が試みられ、1990年代後半からは全例TVTである。手術変遷をもとに女性腹圧性尿失禁に対する治療について考察する。
  • VHL-dependent and independent regulation of MN/CA9 in renal fell carcinoma cell lines  [Not invited]
    植村 天受; Kawada Y; Hirao Y
    第6回VHL国際シンポジウム  2004/05  第6回VHL国際シンポジウム
  • 当院で施行した腎移植におけるMinimum immunosuppressionの臨床的検討  [Not invited]
    森本 康裕; 原 靖; 田原 秀男; 松浦 健; 植村 天受; 西岡 伯; 秋山 ?弘
    第93回日本泌尿器科学会総会  2004/04  東京都  第93回日本泌尿器科学会総会
  • Sensitization of radiotherapy by PTEN gene microcapsule in prostate cancer  [Not invited]
    田中 基幹; 植村 天受; 穴井 智; 高田; 聡; 松村; 善昭; 平尾 佳彦; Charles J Rosser; H Barton Grossman
    The 95th Annual Meeting, American Association for Cancer Research  2004/03  Orlando, USA  The 95th Annual Meeting, American Association for Cancer Research
  • 腎細胞癌における診断治療の最前線  [Not invited]
    植村天受
    第一回福島県RCC講演会  2004/01  郡山市
  • 前立腺癌における術前Neoadjuvant内分泌療法の臨床的意義  [Not invited]
    植村 天受; 趙 順規; 藤本清秀; 田中基幹; 田中宣道; 田中洋造; 渡辺秀次; 丸山良夫; 林 美樹; 小西 登; 大園誠一郎; 平尾佳彦
    第41回日本癌治療学会総会  2003  第41回日本癌治療学会総会
  • 腎細胞癌に対するMN/CA9抗原ペプチドを用いた癌ワクチン療法−第1相臨床試験−  [Not invited]
    植村 天受; 田中基幹; 清水一宏; 田中宣道; 平尾佳彦; 吉川和宏
    第62回日本癌学会総会  2003  第62回日本癌学会総会
  • 腎細胞癌に対するMN/CA9抗原ペプチドワクチン療法−第1相臨床試験−  [Not invited]
    植村 天受; 趙 順規; 田中基幹; 吉川元祥; 清水一宏; 中西まこ; 吉田克法; 平尾佳彦; 吉川和宏
    第41回日本癌治療学会総会  2003  第41回日本癌治療学会総会
  • 腎細胞癌に対するMN/CA9 抗原ペプチド療法  [Not invited]
    植村 天受; 田中基幹; 中西まこ; 大園誠一郎; 平尾佳彦
    泌尿器がん治療フォーラム2003  2003  泌尿器がん治療フォーラム2003
  • 進行性腎癌に対するMN/CA9ペプチドワクチン療法:第1相臨床試験  [Not invited]
    植村 天受; 吉川和宏; 平尾佳彦
    第33回日本腎臓学会西部学術大会  2003  第33回日本腎臓学会西部学術大会
  • 術中患側腎静脈血液中癌細胞の検出と臨床的意義  [Not invited]
    植村 天受; 吉川和宏; 佐賀信介; 鳥居 徹; 赤座英之; 平尾佳彦
    第91回日本泌尿器科学会総会  2003  第91回日本泌尿器科学会総会
  • The development of anti-tumour vaccines derived from MN/CA9 in renal cell carcinoma  [Not invited]
    植村 天受; K Shimizu; M Yoshikawa; M Tanaka; Y Hirao; K Yoshikawa
    18th Annual Meeting of European Association of Urology  2003  Madrid  18th Annual Meeting of European Association of Urology
  • Early phase ? trial with MN/CA9 antigen peptide vaccines restricted to HLA-A24 in renal cell carcinomas  [Not invited]
    植村 天受; M Tanaka; M Cho; M Yoshikawa; Y Hirao
    94th Annual Meeting of American Association for Cancer Research  2003  Washington  94th Annual Meeting of American Association for Cancer Research
  • 小児の低形成腎に合併したxanthogranulomaの1例  [Not invited]
    森本 康裕; 植村 天受; 松浦 健; 上島 成也; 山本 豊; 栗田 孝; 八木 誠; 磯川 貞之
    第52回日本泌尿器科学会中部総会  2002/11  名古屋市  第52回日本泌尿器科学会中部総会
  • 腎細胞癌に対するMN/CA9ペプチドワクチンによる特異的免疫療法  [Not invited]
    植村 天受; 平尾佳彦; 吉川和宏
    第90回日本泌尿器科学会総会  2002  第90回日本泌尿器科学会総会
  • 腎細胞癌における標的分子MN/CA9−基礎から臨床へ  [Not invited]
    植村 天受
    第52回日本泌尿器科学会中部総会  2002  第52回日本泌尿器科学会中部総会
  • 腎細胞癌におけるMN/CA9抗原ペプチドを用いた特異的免疫療法  [Not invited]
    植村 天受; 趙 順規; 藤本清秀; 田中基幹; 大園誠一郎; 平尾佳彦; 吉川和宏
    第40回日本癌治療学会総会  2002  第40回日本癌治療学会総会
  • 腎細胞癌におけるHLA-A24拘束性MN/CA9ペプチドを用いた特異的CTLの誘導  [Not invited]
    植村 天受; 趙 順規; 清水一宏; 吉川元祥; 平尾佳彦; 佐賀信介; 吉川和宏
    第61回日本癌学会総会  2002  第61回日本癌学会総会
  • 治療に難渋した膀胱瘻の2例  [Not invited]
    森本 康裕; 植村 天受; 清水 信貴; 能勢 和宏; 尼崎 直也; 杉山 高秀; 栗田 孝; 南 幸
    第177回日本泌尿器科学会関西地方会  2001/12  草津市  第177回日本泌尿器科学会関西地方会
  • 無治療経過観察:肯定VS否定  [Not invited]
    植村 天受; 中本貴久
    第17回前立腺シンポジウム  2001  第17回前立腺シンポジウム
  • 前立腺全割標本を用いたネオアジュバント内分泌療法の臨床病理組織学的検討  [Not invited]
    植村 天受
    第51回日本泌尿器科学会中部総会  2001  第51回日本泌尿器科学会中部総会
  • 腎細胞癌におけるMN抗原ペプチドを用いた癌ワクチン療法の検討  [Not invited]
    植村 天受; 吉川元祥; 清水一宏; 趙 順規; 岡島英二郎; 青木勝也; 平尾佳彦; 吉川和宏
    第89回日本泌尿器科学会総会  2001  第89回日本泌尿器科学会総会
  • NUORGグループ研究:腎細胞癌における循環血液中細胞検出について  [Not invited]
    植村 天受
    第4回奈良県医師会泌尿器科部会 奈良腎腫瘍研究会  2001  第4回奈良県医師会泌尿器科部会 奈良腎腫瘍研究会
  • MN/CA9による腎癌の診断と治療  [Not invited]
    植村 天受
    第44回日本腎臓学会学術総会  2001  第44回日本腎臓学会学術総会
  • Detection of circulating RCC cells in the renal vein during radical nephrectomy  [Not invited]
    植村 天受; M Cho; Y Hirao; K Yoshikawa
    18th Urological Research Society Annual Meeting  2001  Izumir, Turkey  18th Urological Research Society Annual Meeting
  • Cancer vaccines targeting MN/CA? antigen for renal cell carcinoma  [Not invited]
    植村 天受; K Shimizu; M Cho; Eijiro Okajima; Y Hirao; S Saga; K Yoshikawa
    92th Annual Meeting of American Association for Cancer Research  2001  New Orleans  92th Annual Meeting of American Association for Cancer Research
  • 腎細胞癌におけるMN抗原ペプチドを用いた癌ワクチン療法  [Not invited]
    植村 天受; 清水一宏; 趙 順規; 吉川元祥; 平尾佳彦; 吉川和宏
    第13回日本バイオセラピィ学会総会  2000  第13回日本バイオセラピィ学会総会
  • 腎細胞癌におけるMN/CA9抗原ペプチドによる特異的免疫療法  [Not invited]
    植村 天受; 吉川元祥; 清水一宏; 趙 順規; 金 聖哲; 吉田克法; 岡島英五郎; 平尾佳彦; 佐賀信介; 吉川和宏
    第59回日本癌学会総会  2000  第59回日本癌学会総会
  • Vaccination of antigen peptide derived from MN/CA? induces specific immunity  [Not invited]
    植村 天受; K Shimizu; M Cho; Y Hirao; K Yoshikawa
    International Symposium Cancer Research Institute Tumor Vaccines 2000  2000  New York  International Symposium Cancer Research Institute Tumor Vaccines 2000
  • Peptide vaccination of MN/CA? antigen induces specific tumor immunity  [Not invited]
    植村 天受; K Shimizu; M Cho; M Yoshikawa; Y Hirao; K Yoshikawa; E Oosterwijk
    91th Annual Meeting of American Association for Cancer Research  2000  San Francisco  91th Annual Meeting of American Association for Cancer Research
  • MN/CA?抗原ペプチドを用いた腎細胞癌特異的免疫療法  [Not invited]
    植村 天受; 吉川元祥; 趙 順規; 仲川嘉紀; 田中洋造; 大園誠一郎; 平尾佳彦; 清水一宏; 吉田和宏; 佐賀信介
    第9回泌尿器科細胞解析研究会  2000  第9回泌尿器科細胞解析研究会
  • MN/CA? as a potential therapeutic target for active specific immunotherapy of renal cell carcinoma  [Not invited]
    植村 天受; M Cho; H Shimizu; Y Nakagawa; K Yoshida; Y Hirao; K Yoshikawa; E Oosterwijk
    15th Congress of the European Association of Urology  2000  Brussels  15th Congress of the European Association of Urology
  • Active specific immunotherapy for RCC ?Vaccination of MN/CA? Ag peptide induces specific tumor immunity-  [Not invited]
    植村 天受; K Shimizu; M Cho; M Yoshikawa; Y Hirao; K Yoshikawa
    17th Urological Research Society Annual Meeting  2000  Washington  17th Urological Research Society Annual Meeting
  • 造血幹細胞移植の現状と将来  [Not invited]
    植村 天受
    第87回日本泌尿器科学会中部総会  1999  第87回日本泌尿器科学会中部総会
  • 腎細胞癌標的MN/CA9の臨床的意義  [Not invited]
    植村 天受
    第49回日本泌尿器科学会中部総会  1999  第49回日本泌尿器科学会中部総会
  • 腎細胞癌患者における末梢血中癌細胞の検出  [Not invited]
    植村 天受; 仲川嘉紀; 米田龍生; 影林頼明; 山本雅司; 吉田克法; 大園誠一郎; 平尾佳彦
    第42回日本腎臓学会学術総会  1999  第42回日本腎臓学会学術総会
  • 腎細胞癌患者における血中癌細胞の検出  [Not invited]
    植村 天受; 仲川嘉紀; 清水一宏; 趙 順規; 平尾佳彦; 吉川和宏
    第8回泌尿器科細胞解析研究会  1999  第8回泌尿器科細胞解析研究会
  • 腎細胞癌における患者血液中癌細胞の検出について  [Not invited]
    植村 天受; 仲川嘉紀; 金 聖哲; 清水一宏; 趙 順規; 岩井哲郎; 平尾佳彦; 吉川元祥; 杉村芳樹; 井坂茂夫
    第87回日本泌尿器科学会総会  1999  第87回日本泌尿器科学会総会
  • 高感度RT-PCR法を用いた循環血液中腎細胞癌細胞の検出  [Not invited]
    植村 天受
    第26回尿路悪性腫瘍研究会  1999  第26回尿路悪性腫瘍研究会
  • MN/CA IX 抗原ペプチドを用いた腎細胞癌特異的免疫療法の試み  [Not invited]
    植村 天受; 趙 順規; 仲川嘉紀; 吉川元祥; 山本雅司; 山口 旭; 岡島英五郎; 平尾佳彦; 吉川和宏
    第37回日本癌治療学会総会  1999  第37回日本癌治療学会総会
  • G250 antigen as a potential target for immunotherapy of renal cell carcinomas  [Not invited]
    植村 天受; Y Nakagawa; Y Hirao; K Yoshikawa; F Debruyne; E Oosterwijk
    14th Congress of the European Association of Urology  1999  Stockholm  14th Congress of the European Association of Urology
  • マルチチロシンキナーゼ阻害薬であるTAS-115は前立腺特異的 PTS-115は前立腺特異的 Pten ノックアウトマウスの腫瘍微小環境を変動させる  [Not invited]
    野澤 昌弘
    第23回 日本がん分子標的治療学会学術集会  大阪
  • 去勢抵抗性前立腺癌における分子標的薬と次世代アンチセンスオリゴの併用効果について  [Not invited]
    近畿大学ゲノム
    第23回 日本がん分子標的治療学会学術集会  大阪
  • 前立腺癌における遺伝子改変マウスモデル:新たな発見と発展のツールとして  [Not invited]
    倉 由吏恵
    第107回 日本泌尿器科学会総会  名古屋
  • 個別化ペプチドワクチンによるがんの最適治療を目指す3つの臨床的アプロ−チ  [Not invited]
    伊東 恭悟
    第56回日本癌治療学会学術集会  横浜
  • 去勢抵抗性前立腺がんに対する20種混合ペプチドワクチンの有効性の検討  [Not invited]
    野口 正典; 久留米大; がんワクチンセンタ
    第56回日本癌治療学会学術集会  横浜
  • 腎細胞癌に対するNivolumab+IpiIimumabとSunitinib比較試験(CheckMate214):日本人解析  [Not invited]
    冨田 善彦
    第56回日本癌治療学会学術集会  横浜
  • 悪性軟部腫瘍の治療〜泌尿器科の立場から〜  [Not invited]
    野澤 昌弘
    第56回日本癌治療学会学術集会  横浜
  • 骨転移を有するCRP患者を対象とした塩化ラジウム・223の使用成績調査:中間解析結果  [Not invited]
    舛森 直哉
    第56回日本癌治療学会学術集会  横浜
  • 当院および関連病院における二次腎移植症例の検討  [Not invited]
    森 康範
    第54回日本移植学会総会  東京
  • 下部尿路症状を有する患者に対するUDSを用いたアコチアミド塩酸塩水和物追加投与の検討  [Not invited]
    杉本 公一
    第68回日本泌尿器科学会中部総会  名古屋
  • 下部尿路症状を有する患者に対するUDSを用いたアコチアミド塩酸塩水  [Not invited]
    秋山 隆弘
    第25回 日本排尿機能学会  名古屋
  • Inhibition of phosphodiesterase Type 9(PDE9) Improves storage and voiding Dysfunction in mice with spinal cord injury  [Not invited]
    清水 信貴(ピッバ-グ大
    ICS2018  Philadelphia
  • Genetically engineered mouse modeks of prostate cancer:tools for taget discovery and development 前立腺癌の遺伝子改変マウス  [Not invited]
    デベラスコ・マルコ(近大; 近大ゲノム
    第5回 前立腺生物シンポジウム 伊勢志摩2018  三重
  • Nocturnal antidiuresis after administration of imidafenacin is induced by conentration of urine osmolality  [Not invited]
    橋本 士
    AUA2018  San Francisco
  • 騎乗型フィットンネス器具使用時における体幹筋活動の検討  [Not invited]
    本郷 祥子
    第31回 日本老年泌尿器科学会  福井
  • 腎細胞癌に対する免疫チェックポイント阻害薬  [Not invited]
    野澤 昌弘
    第31回 日本老年泌尿器科学会  福井
  • DSA陽性症例における低用量IVIG療法併用脱感作療法が奏功した生体腎移植3症例の検討  [Not invited]
    能勢 和宏
    第106 回 日本泌尿器科学会総会  京都
  • 転移性腎細胞がん患者を対象とした薬物治療の後方視的観察研究  [Not invited]
    野澤 昌弘
    第106 回 日本泌尿器科学会総会  京都
  • T1b腎細胞癌に対する腹腔鏡下腎摘除術  [Not invited]
    野澤 昌弘
    第106 回 日本泌尿器科学会総会  京都
  • Inhibition of STAT3 by antisense oligonucleotide treatment decreases the immune suppressive tumor microenvironment in syngeneic and GEM tumor modeis  [Not invited]
    Woessner R
    AACR  Washinton
  • Clinical significance of lidocaine pressure flow studies for LUTS in older male subjects without neurological disorler  [Not invited]
    貴馬 K
    ICS  Florence
  • 長期の死線期を経た心停止ドナ-からの献腎移植を施行し、1年で廃絶に至った症例  [Not invited]
    齋藤 允孝
    第2回 近畿献腎移植症例検討会  大阪
  • 当科における先行的腎移植症例の検討  [Not invited]
    森康範
    第51回 日本臨床腎移植学会  神戸
  • 足背壊死性筋膜炎と陰?創部治癒遅延に対しPICOを用いて治癒した2症例  [Not invited]
    菊池 尭
    日本スト−マ・排泄リハビリテ-ション学会誌 第35回 学会総会  札幌
  • Effects of Hangesyainto for Everolimus Induced Stomatitis.  [Not invited]
    林 泰司
    15th Congress of the Asian Society of Transplantation  CEBU
  • 去勢抵抗性前立腺癌に対するカバジタキセル療法の検討  [Not invited]
    松村 直紀
    第55回 日本癌治療学会学術集会  横浜
  • 妊婦における残尿測定の実際 〜Bladder Scan(BVI6100)と医師による超音波法の比較〜  [Not invited]
    本郷 祥子
    第24回 日本排尿機能学会  東京
  • ROLE OF P38 MAP KINASE SIGNALLING PATHWAYS IN STORAGE AND VOIDING DYSFUNCTION IN MICE WITH SPINAL CORD INJURY  [Not invited]
    清水信貴
    ICS 2017  FLORENCE
  • 騎乗型フィットネスマシンは骨盤底筋収縮を強化するか?  [Not invited]
    本郷 祥子
    第19回 日本女性骨盤底医学会  福井
  • 当科および関連病院における先行的腎移植(preemptive kidney transplantation:PEKT)症例の検討  [Not invited]
    森 康範
    日本泌尿器科学会総会  鹿児島
  • 分子標的薬の有害事象とその管理  [Not invited]
    野澤 昌弘
    日本泌尿器科学会総会  鹿児島
  • 免疫チェックポイント阻害薬の膀胱がんにおけるエビデンス  [Not invited]
    野澤 昌弘
    日本泌尿器科学会総会  鹿児島
  • リドカイン注入 Pressure Flow study(LPFS)による高齢男性の排尿機能の変化について  [Not invited]
    喜馬 啓介
    第105回 日本泌尿器科学会総会  鹿児島
  • A randomized control trial comparing silodosin and urapidil in female patients with lower urinary tract symptom-interim report  [Not invited]
    杉本 公一
    ICS  東京
  • Efficacy of Valganciclovir for prevention of Cytomegalovirus in High-Risk Renal Transplantation.  [Not invited]
    林 泰司
    26th International Congress of The Transplantation Society  Hongkong
  • 腎細胞癌治療の新たな幕開け  [Not invited]
    RCC expert consensus meeting in Osaka  大阪
  • LSC手術における尿管の走行  [Not invited]
    本郷祥子; 近大; 大阪南医療センタ
    第11回 日本骨盤臓器脱手術学会学術集会  東京
  • テ−マ 男性の健康と腎泌尿器疾患  [Not invited]
    市民公開講座  大阪
  • エベロリムス内服により遅発性器質化肺炎をきたした腎移植症例  [Not invited]
    菊池 尭
    第66回 日本泌尿器科学会中部総会  四日市
  • PTENノックアウトマウス前立腺癌におけて選択的スプライシングは頻繁に認められる  [Not invited]
    デベラスコ・マルコ(近大; 近大ゲノム
    第75回 日本癌学会学術総会  横浜
  • PTENノックアウトマウス前立腺癌におけるノンコ−ディング RNAの検討  [Not invited]
    倉 由吏恵
    第75回 日本癌学会学術総会  横浜
  • 腎移植後悪性腫瘍のマネ−ジメント 〜特に消化器腫瘍について〜  [Not invited]
    能勢和宏
    第61回 日本透析医学会学術集会・総会  大阪
  • Phase II study of degarelix/bicalutamide combination for prostate cancer.  [Not invited]
    野澤昌弘
    ASCO
  • 巣状糸球体硬化症再発に対し集学的治療が奏功した1症例  [Not invited]
    菊池 尭
    第49回 日本臨床腎移植学会  米子
  • 脂質異常症合併腎移植患者に対するw−3脂肪酸エチルの短期成績  [Not invited]
    齋藤允孝
    第49回 日本臨床腎移植学会  米子
  • 泌尿器科がん:診断・治療の最前線  [Not invited]
    第14回 市民公開講座 泌尿器科がん:診断・治療の最前線  大阪
  • Degarelix/bicalutamide combination versus degarelix alone as initial androgen-deprivation therapy  [Not invited]
    野澤昌弘
    ASCO-GU  San Francisco
  • 当院におけるPVPの初期成績の検討  [Not invited]
    吉川 元清
    第29回 日本泌尿器内視鏡学会総会  東京
  • 夜間睡眠中の体水分変化が夜間尿量へ及ぼす影響の検討・電気インピ−ダンス法による解析  [Not invited]
    喜馬 啓介
    第65回 日本泌尿器科学会中部総会  岐阜
  • Female sex workers(FSWs)の性機能の検討  [Not invited]
    永井康晴; 近大; 大阪南医療セン
    日本性機能学会 第26回 学術総会/第25回 西部総会  福岡
  • Preclinical effects of dual AKT/MAPK inhibition in PTEN-deficient prostate cancer  [Not invited]
    デベラスコ・マルコ
    AACR  フィラデルフィア
  • 臥位による下肢水分移行が夜間尿量へ及びぼす影響の検討  [Not invited]
    喜馬 啓介
    第22回 日本排尿機能学会  旭川
  • Efficacy and safety of everol imus and mizoribine based early phase deep cni minimization immunosuppressant therapy for de novo kidney transplant recipients  [Not invited]
    林泰司
    CAST
  • 前立腺癌に対するデガレリスク/ビカルタミド併用療法  [Not invited]
    野澤昌弘
    第13回 日本臨床腫瘍学会学術集会  札幌
  • Female sex workers(FSWs)の性機能、下部尿路症状の検討  [Not invited]
    永井 康晴; 医療センタ
    第103回 日本泌尿器科学会総会  金沢
  • 繰り返す尿閉患者のカテ−テル抜去  [Not invited]
    杉本公一
    第103回 日本泌尿器科学会総会  金沢
  • Bone management in patients with prostate cancer:FRAX combined with bone mineral density can prevent unnecessary treatment  [Not invited]
    Kawahara T
    The30th Annual Congress of the European Association of Urology(EAU15)  マドリッド
  • 腎移植後悪性腫瘍症例の検討  [Not invited]
    齋藤允孝
    第48回 日本臨床腎移植学会  名古屋
  • テ-マ 前立腺疾患の最新治療薬・手術の期待と展望  [Not invited]
    市民公開講座  大阪
  • カバジタセルの使用経験  [Not invited]
    野沢昌弘
    第64回 日本泌尿器科学会中部総会  浜松
  • 腎移植後妊娠・出産例の検討  [Not invited]
    森 康範
    第64回 日本泌尿器科学会中部総会  浜松
  • 泌尿器がんに対する集学的治療Up to Date  [Not invited]
    第52回 日本癌治療学会学術集会  横浜
  • 腎移植後BKウイルス感染症の検討  [Not invited]
    林 泰司
    第30回 腎移植・血管外科研究会  沖縄
  • 副作用の対処方法について  [Not invited]
    ヴォトリエント錠200mg 承認記念講演会  東京
  • Sequential therapyにおける薬剤切り替えのタイミング  [Not invited]
    野沢昌弘
    第102回日本泌尿器科学会総会  神戸
  • 腎移植後BKウィルス感染症の検討  [Not invited]
    林泰司
    第102回日本泌尿器科学会総会  神戸
  • 小径腎腫瘍における腫瘍増殖因子の検討  [Not invited]
    杉本公一; 畿大学医学部堺病院; 泌尿器科
    第102回日本泌尿器科学会総会  神戸
  • 進行性腎癌に対するエベロリムスの治療成績と有害事象の検討  [Not invited]
    大關孝之; 千葉県がんセンター; 泌尿器科前立腺センター
    第102回日本泌尿器科学会総会  神戸
  • 骨代謝マーカーによる骨転移の評価  [Not invited]
    野沢昌弘
    第102回日本泌尿器科学会総会  神戸
  • 多施設前向き研究によるT1b腎癌の術後再発に関する検討  [Not invited]
    立神勝則
    第102回日本泌尿器科学会総会  神戸
  • 日本人の去勢抵抗性前立腺癌患者に対するカバジタキセルの忍容性、安全性および有効性(国内第1相臨床試験)  [Not invited]
    上村博司
    第102回日本泌尿器科学会総会  神戸
  • TKI 抵抗性高齢進行性腎癌に対するエベロリムスの有効性と安全性  [Not invited]
    稲本輝生
    第102回 日本泌尿器科学会総会  神戸
  • スニチニブの4投2休レジメン(Traditionnal Schedule)とAIternative Scheduleへのスケジュ−ル変更による有効性の検討  [Not invited]
    大關孝之
    第78回 日本泌尿器科学会東部総会  新潟
  • The Difference in adverse event profiles between the mTOR inhibitors,everolim and temsirolimus,in advanced renal cell carcinoma  [Not invited]
    野澤昌弘
    ESMO2013  Amsterdam
  • Zoledronic acid for hormone-naive prostate cancer with bone metastasis  [Not invited]
    野澤昌弘
    ASCO2013  Chicago
  • Difference in adverse event profiles between mTOR inhibitors temsirolimus and everolimus for advanced renal cell carcinoma  [Not invited]
    野澤昌弘
    ASCO-GU2013  Orland
  • Significance of basic research by Urologists. -present and future-  [Not invited]
    第23回 泌尿器科分子・細胞研究会  山形
  • Case Disucussion 患者背景を考慮した個別化治療の検討  [Not invited]
    Nexavar RCC Web Conference
  • 薬剤治療 最新のRCC薬物治療トピックス  [Not invited]
    Nexavar RCC Web Conference
  • 出産を契機に診断され、包括的がん医療モデルに則って加療した転移性腎細胞癌の1例  [Not invited]
    上島成也
    第63回日本泌尿器科学会中部総会  愛知
  • 生体腎移植後、エンドトキシンショックに対し吸着療法にて救命し得た一例  [Not invited]
    齋藤 允孝
    第63回日本泌尿器科学会中部総会  愛知
  • Recent advances of canser vaccines with CTL epitope peptides CTLエピトープワクチン療法  [Not invited]
    伊東恭悟
    第72回日本癌学会学術総会  横浜
  • 生体腎移植後、エンドトキシンショックに対し吸着療法にて救命し得た1例  [Not invited]
    齋藤允孝
    第81回 大阪透析研究会  大阪
  • Renal transplantation in patients with lower urinary tract dysfunction who have undergone bladder augmentation and urinary diversion in their childhood  [Not invited]
    安田宗生
    CAST2013 The 13th Congress of the Asian society of transplantation  京都
  • 生体腎移植におけるエベロリムスとミゾリビンを用いた新規免疫抑制法の安全性と有効性に関する検討  [Not invited]
    林泰司
    CAST2013 The 13th Congress of the Asian society of transplantation  京都
  • Examination of the effect of changing azilsartan from candesartan in renal transplant recipients.  [Not invited]
    石井徳味
    CAST2013 The 13th Congress of the Asian society of transplantation  京都
  • シンポジウム 人材育成〜技術の継承と倫理観の育成、プレイヤ-&リ−ダ−の育成  [Not invited]
    第4 回泌尿器科フロンティアセミナ-  大阪
  • Omparison of PFS and safety for Asian compared to North American and european population in the phase lll trial of pazopanib versus sunitinib in patients with treatment-naive RCC(COMPARZ)  [Not invited]
    Jun Gu
    ASCO  Chicago
  • Investiga of automatic nervous system activity of overactive bladder syndrome patients using an ”autonomic reflex orthostatic test”  [Not invited]
    清水信貴
    10th German-Japanese Urological Meeting  神戸、京都&大阪,日本
  • 小児期に膀胱拡大術などの尿路手術を施行した患者に対する生体腎移植の経験  [Not invited]
    安田 宗生
    第24回腎移植免疫研究会  大阪
  • 前立腺癌のバイオマ−カ−を発見するためのマウスモデルの作製  [Not invited]
    畑中祐二
    第101回日本泌尿器科学会総会  札幌
  • 多発性尿路奇形に対して回腸利用膀胱拡大術後、生体腎移植術を施行した2例  [Not invited]
    安田宗生
    第101回 日本泌尿器科学会総会  札幌
  • ラット腎阻血再灌流障害モデルにおけるPioglitazone投与の腎保護効果についてのけんとう  [Not invited]
    森康範
    第101回 日本泌尿器科学会総会  札幌
  • 小径腎腫瘍に対する待機手術療法VS即時手術療法の治療成績  [Not invited]
    杉本公一
    第101回日本泌尿器科学会総会  札幌
  • 生体腎移植における新規5剤免疫抑制療法の安全性と有効性に関する検討  [Not invited]
    林泰司
    第101回日本泌尿器科学会総会  札幌
  • 進行性腎癌に対するテムシロリムスの治療成績と有害事象の検討  [Not invited]
    齋藤允孝; 千葉県がんセンター前立センタ
    第101回日本泌尿器科学会総会  札幌
  • IMidafenacin Reduces Night time urine production as well as increases Bladder Capacity in BPH patients with nocturia and oab.Results from prospective randomized controlled trial,good-night study.  [Not invited]
    清水信貴
    ICS 2012  中国
  • α-blocker+eviprostatを長期内服 しているLUTS症例におけるeviprostat 休薬後の排尿状態の検討  [Not invited]
    杉本公一
    第14回 南近畿排尿障害懇話会  大阪
  • 重複膣の女児に対してTURを用いて中隔切開を行った1例  [Not invited]
    菊池尭
    第13回 大阪小児泌尿器疾患検討会  大阪
  • 5剤新規免疫抑制療法の有効性についての検討  [Not invited]
    西岡伯
    第46回 日本臨床腎移植学会  千葉
  • 5剤新規免疫抑制療法の安全性についての検討  [Not invited]
    林泰司
    第46回 日本臨床腎移植学会  千葉
  • Phase ? Study of Zoledronic Acid Concomitant with Androgen Deprivation Therapy for Patients with Treatment-Na?ve Bone-Metastatic Prostate Cancer:An Interim Analysis  [Not invited]
    原 勲; 和
    32nd SIU Conference  福岡
  • ケーススタデイー 心の危機管理:職場でみられる症例  [Not invited]
    第3回 泌尿器科フロンティアセミナー  東京
  • Role of Stat3 transcriptional activation in a preclinical mouse model of prostate cancer and potential as a therapeutic traget  [Not invited]
    デベラスコ・マルコ(近大ゲノム
    AACR ANNUAL MEETING 2012  Chicago
  • 中葉肥大(IPP;intravesical prostatic protrusion)に対するα遮断薬の効果の違いについて  [Not invited]
    清水信貴
    第13回南近畿排尿障害懇話会  大阪
  • LOH症候群に男性ホルモン補充療法を施行した1例  [Not invited]
    上島成也
    第11回日本Men’s Heaslth医学会  鎌倉
  • 生体腎移植後に発生した後腹膜神経鞘腫の1例  [Not invited]
    安田宗生
    第23回腎移植免疫研究会  大阪
  • Randomized controlled trial of nocturia in patients with benign prostatic hyperplasia with OAB using an alpha-blocker combined with a novel anticholinergic,lmidafenacin;GooD- NIGHT Study  [Not invited]
    鞍作克之; 大阪市立大学大学院医学研究科泌尿器病態
    The27th Annual congress of the EAU  paris
  • 前立腺癌におけるHOXA-10の発現意義  [Not invited]
    畑中祐二
    第100回日本泌尿器科学会総会  横浜
  • 前立腺癌増殖進展におけるSTAT3活性化の役割について−マウス前立腺癌モデルによる検討-  [Not invited]
    De Velasco Marco; 近大ゲノム
    第100回日本泌尿器科学会総会  横浜
  • 本邦におけるmTOR阻害剤エベロリムス使用腎癌患者に関する後方観察研究-第4報-  [Not invited]
    野澤昌弘
    第100回日本泌尿器科学会総会  横浜
  • CMV抗体donor+/recipient-(D+/R-)のhigh risk腎移植症例に術後prophylactic valganciclovir療法を施行した3症例  [Not invited]
    能勢和宏
    第100回日本泌尿器科学会総会  横浜
  • 近畿大学泌尿器科で施行したpre-emptive腎移植症例の検討  [Not invited]
    安田宗生
    第100回日本泌尿器科学会総会  横浜
  • 尿中PCA3測定の有用性に関する国内多施設共同研究  [Not invited]
    冨田京一
    第100回日本泌尿器科学会総会  横浜
  • グレーゾーンPSA症例の初回生検時における尿中PCA3測定の有用性  [Not invited]
    落合 厚
    第100回日本泌尿器科学会総会  横浜
  • 泌尿器科とは?  [Not invited]
    日本泌尿器科学会 創立百周年記念 市民公開講座  大阪
  • Baseline Bone Metabolism Markers as predictors for grogression-free survival of patients with treatment-Naive Bone-Metastatic prostate cancer treated with Zoledronic Acid plus combined Androgen BIockade.  [Not invited]
    野澤昌弘
    The27th Annual congress of the EAU  Paris
  • 医療的ケアの観点から見た介助導尿  [Not invited]
    松田久雄
    第61回 日本泌尿器科学会中部総会  京都
  • 「前立腺がんとのつきあい方〜患者、医師の立場から〜  [Not invited]
    Blue Clouer Campaign 2011 前立腺がんを考える  大阪
  • Impact of the primary tumor in situ on the response of metastatic lesions to targeted therapy in patients with metastatic renal cell carcinoma  [Not invited]
    野澤昌弘
    31st Congress of the SIU  Berlin
  • HOXA10 is aberrantly expressed in prostate cancer  [Not invited]
    畑中祐二
    第70回 日本癌学会学術総会  名古屋
  • Pre-clinical efficacy of sorafenib on a pten knockout mouse prostate cancer model  [Not invited]
    山本 豊
    第70回 日本癌学会学術総会  名古屋
  • Lumican expression in prostate cancer  [Not invited]
    王 一
    第70回 日本癌学会学術総会  名古屋
  • The long term renoprotective effect of candesartan in renal transplant patients  [Not invited]
    石井徳味
    12th congress of the asian society of transplantation  Seoul
  • The prostate-specific PTEN conditional knockout mouse  [Not invited]
    デベラスコマルコ
    30th anniversary conference  canada
  • 介助導尿を必要とする二分脊椎患者の介護負担度調査よりの考察  [Not invited]
    松田久雄
    日本二分脊椎患者の介護負担度調査よりの考察  大阪
  • 外国人介護人による泌尿器科関連の研修実体  [Not invited]
    松田久雄
    第23回 日本老人泌尿器学会  東京
  • The Role of cytoreductive nephrectomy in the era of molecular targeting drugs  [Not invited]
    AUA Annual Meeting  washingcon
  • systemic transduction of p16 ink44 anti-tumor peptide inhibits growth of mbt-2 bladder tumor cell line graft in mice  [Not invited]
    島居徹
    AUA Annual Meeting  Wasington
  • 高脂肪食摂取増加は前立腺癌発生トランスジェニックマウスモデルにおいて腫瘍増悪因子の一つになる  [Not invited]
    畑中祐二
    第99回日本泌尿器科学会総会  名古屋
  • 泌尿器科領域での介助導尿などの医療的ケアの実情  [Not invited]
    松田久雄
    第99回日本泌尿器科学会総会  名古屋
  • PTENコンディショナルノックアウト前立腺癌マウスを用いたエベロリムス・酢酸クロルマジノン の治療効果  [Not invited]
    デベラスコマルコ(近大; 近大ゲノム
    第99回日本泌尿器科学会総会  名古屋
  • PTEN遺伝子改変マウスを用いた酢酸クロルマジノンによる前立腺癌発癌抑制効果  [Not invited]
    小池浩之; TT西日本大
    第99回日本泌尿器科学会総会  名古屋
  • サイトカイン治療抵抗性腎細胞癌患者に対するアキシチニブの国内第?相試験 ー有効性安全性及びバイオマーカーの検討ー  [Not invited]
    篠原信雄
    第99回日本泌尿器科学会総会  名古屋
  • Everolimus reduces androgen dependent and independent prostate cancer in the prostate specific PTEN conditional gene targeting mouse model  [Not invited]
    デベラスコマルコ
    101st Annual meeting of the american association  washington
  • 前立腺神経内分泌癌に対してドセタキセル+シスプラチン療法が奏功した症例  [Not invited]
    林泰司
    第99回日本泌尿器科学会総会  名古屋
  • マウス膀胱癌、腎癌に対しての温熱療法の抗腫瘍効果  [Not invited]
    山本豊
    第99回日本泌尿器科学会総会  名古屋
  • 塩酸誘発膀胱炎ラットモデルにおける Rho-kinaseの発現とRho-kinase阻害剤の効果  [Not invited]
    清水信貴
    第99回 日本泌尿器科学会総会  名古屋
  • Targeting prostate cancer chemoprevention via the androgen receptor in a preclinical mouse model.  [Not invited]
    小池浩之
    101st annual meeting of the american association  washington
  • 腎盂尿管移行部狭窄症に対するアキュサイスを用いた切開手術の長期予後  [Not invited]
    梅川徹
    第99回 日本泌尿器科学会総会  名古屋市
  • 進行性陰茎癌に対して広範切除および皮弁を用いた形成術を施行した1例  [Not invited]
    松村直紀
    第213回日本泌尿器科学会関西地方会  大阪
  • ダブルル−メンカテ-テル使用時における再循環発生の要因について  [Not invited]
    石井徳味
    第60回 日本泌尿器科学会中部総会  名古屋
  • 前/後期高齢者の過活動膀胱に対するイミダフェナシンの有効性に関する検討  [Not invited]
    清水信貴
    第60回 日本泌尿器科学会中部総会  名古屋
  • スニチニブにてPSA低下を認めたドセタキセル抵抗性前立腺癌の1例  [Not invited]
    松村直紀
    第60回 日本泌尿器科学会中部総会  名古屋
  • ホルモン抵抗性前立腺癌に対しドセタキセルを使用した71例の臨床的検討  [Not invited]
    齋藤允孝
    第60回 日本泌尿器科学会中部総会  名古屋
  • 腎移植後の悪性腫瘍症例の検討  [Not invited]
    齋藤允孝
    第46回 日本移植学会総会  京都
  • Breast and renal cell carcinomas;Improving outcomes by targeting shared signaling pathways an educational seminar in conjunction with the 48th annual meeting of the japanese society of clinical oncology  [Not invited]
    第48回日本癌治療学会学術集会  京都
  • The prostate-specific PTEN conditional knockout mouse as a model for human prostate cancer  [Not invited]
    デべラスコ・マルコ(近大ゲノム
    69th Annual Meeting of the Japanease Cancer Association 第69回日本癌学会学術総会がん征圧へ向けての知の統合  大阪
  • Anti-tumor effects of everolimus and chlormadinone acetate against prostate cancer in a pre-clinical mouse model  [Not invited]
    デベラスコ・マルコ(近大ゲノム
    69th Annual Meeting of the Japanease Cancer Association 第69回日本癌学会学術総会がん征圧へ向けての知の統合  大阪
  • Systemic transduction of p16INK4 anti-tumor peptide inhibits growth of MBT-2 bladder tumor cell line graft in mice  [Not invited]
    島居 徹
    69th Annual Meeting of the Japanease Cancer Association 第69回日本癌学会学術総会がん征圧へ向けての知の統合  大阪
  • Pre-clinical chemopreventive efficacy of chlormadinone acetate against prostate cancer  [Not invited]
    小池浩之
    69th Annual Meeting of the Japanease Cancer Association 第69回日本癌学会学術総会がん征圧へ向けての知の統合  大阪
  • Phase ?study of sunitinib in Japanese patients (pts)with metastatic renal cell carcinoma (mRCC):Overall survival (OS)and updated results  [Not invited]
    麦谷荘一
    2010 Genitourinary Cancer Symposium  San Francisco,USA
  • Activity of sunitinib as third-line treatment of metastatic renal cell carcinoma(mRCC)  [Not invited]
    野澤昌弘
    2010 Genitourinary Cancer Symposium  San Francisco,USA
  • 脳転移を契機に発見された転移性腎細胞