藤田 和利 (フジタ カズトシ)

  • 医学科 教授/主任
Last Updated :2024/04/23

コミュニケーション情報 byコメンテータガイド

  • コメント

    泌尿器腫瘍(前立腺癌、尿路上皮癌)、男性不妊症

研究者情報

学位

  • 博士(医学)(2006年03月 大阪大学)

ホームページURL

科研費研究者番号

  • 50636181

ORCID ID

J-Global ID

現在の研究分野(キーワード)

    泌尿器腫瘍(前立腺癌、尿路上皮癌)、男性不妊症

研究分野

  • ライフサイエンス / 泌尿器科学

経歴

  • 2020年04月 - 現在  近畿大学医学部泌尿器科

研究活動情報

論文

  • Wataru Fukuokaya; Yuhei Koike; Yuji Yata; Kazumasa Komura; Taizo Uchimoto; Takuya Tsujino; Masanobu Saruta; Kiyoshi Takahara; Kazutoshi Fujita; Takafumi Minami; Takahiro Adachi; Yosuke Hirasawa; Takeshi Hashimoto; Yoshio Ohno; Hirotsugu Uemura; Ryoichi Shiroki; Haruhito Azuma; Takahiro Kimura
    International journal of urology : official journal of the Japanese Urological Association 2023年12月 
    OBJECTIVES: To explore the characteristics of patients and assess the effectiveness of enfortumab vedotin (EV) in those with treatment-resistant advanced urothelial cancer in a real-world setting. PATIENTS AND METHODS: A multicenter observational study was conducted on 103 evaluable patients with advanced urothelial cancer who received EV. Outcomes were assessed by radiographic response, progression-free survival (PFS), and overall survival (OS), with treatment-related adverse events (trAEs). Radiographic response was assessed using Response Evaluation Criteria in Solid Tumors version 1.1, while trAEs were studied in line with Common Terminology Criteria for Adverse Events version 5.0. RESULTS: The median follow-up was 8.9 months (range, 0.1-16.4). The observed objective response rate was 50.5%. The median PFS was 6.0 months (95% CI: 4.7-9.8), and the median OS was 14.5 months (95% CI: 12.4-not reached). Out of the 103 patients, 19 (18.4%) had an Eastern Cooperative Oncology Group performance status of 2 or more, 14 (14.7%) had an non-urothelial carcinoma histology, and 40 (38.3%) had at least one pre-existing comorbidity. There were 26 (25.2%) patients who reported 49 trAEs, with 9 (18.3%) being grade 3 or higher. The most common trAEs included rash, occurring in 18.4%. CONCLUSIONS: This study describes the characteristics and outcomes of patients with previously treated advanced urothelial cancer receiving EV. The findings demonstrate that EV showed robust anti-tumor activity and had manageable safety profiles outside the clinical trial setting.
  • Yasunori Akashi; Yutaka Yamamoto; Mamoru Hashimoto; Shogo Adomi; Kazutoshi Fujita; Keisuke Kiba; Takafumi Minami; Kazuhiro Yoshimura; Akihide Hirayama; Hirotsugu Uemura
    Cancers 15 24 2023年12月 
    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年11月 
    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年11月 
    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.
  • 近畿大学病院における筋層浸潤性尿路上皮癌に対する術後補助化学療法としてのニボルマブ初期経験
    南 高文; 吹上 健; 桑原 賢; 豊田 信吾; 菊池 尭; 西本 光寿; 安富 正悟; 齋藤 允孝; 森 康範; 藤田 和利; 野澤 昌弘; 吉村 一宏; 植村 天受
    西日本泌尿器科学会総会抄録集 75回 216 - 216 (一社)西日本泌尿器科学会 2023年11月
  • 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; 浜口 守; 杉本 公一; 能勢 和宏; 南 高文; 藤田 和利; 野澤 昌弘; 吉村 一宏; 植村 天受
    西日本泌尿器科学会総会抄録集 75回 247 - 247 (一社)西日本泌尿器科学会 2023年11月
  • 近畿大学病院における5-ALA初期使用経験
    南 高文; 菊池 尭; 西本 光寿; 安富 正悟; 齋藤 允孝; 森 康範; 藤田 和利; 野澤 昌弘; 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 37回 P - 6 (一社)日本泌尿器内視鏡・ロボティクス学会 2023年11月
  • Koji Miki; Kazutoshi Fujita; Ken Kuwahara; Shogo Adomi; Takafumi Minami; Masahiro Nozawa; Kazuhiro Yoshimura; Misa Kojima; Osamu Maenishi; Hirotsugu Uemura
    IJU case reports 6 6 424 - 427 2023年11月 
    INTRODUCTION: The histological types of urethral cancer are mainly squamous cell or transitional cell carcinoma. Neuroendocrine tumor is extremely a rare type of urethral cancer. CASE PRESENTATION: A 72-year-old man visited with an erythema at the external urethral meatus. After 3 months, a 1-cm reddish solid tumor was found on the external urethral meatus. He had a history of bladder cancer (pTa with carcinoma in situ), including the prostatic urethra, and underwent radical cystectomy with urethrectomy and ileal conduit construction 11 years ago. After 3 months, a 1-cm reddish solid tumor was found on the external urethral meatus. The pathological diagnosis was a neuroendocrine tumor. Partial penectomy was performed. CONCLUSION: Small cell neuroendocrine tumor could occur on urethral remnant after radical cystectomy with urethrectomy for urothelial cancer. Inspection of the penis and urethral meatus is important during regular follow-up of patients after radical cystectomy.
  • 転移性上部尿路上皮癌患者における癌悪液質の腫瘍学的転帰への影響
    松村 直紀; 藤田 和利; 安富 正吾; 藤本 西蔵; 國重 玲紋; 吉田 和裕; 玉井 健; 豊田 信吾; 西本 光寿; 山本 豊; 南 高文; 花井 禎; 能勢 和宏; 田原 秀男; 植村 天受
    日本癌治療学会学術集会抄録集 61回 O40 - 5 2023年10月
  • Pten欠損前立腺癌進展における骨髄由来抑制細胞のプロファイリング(Profiling myeloid-derived suppressor cells during mouse prostate cancer progression)
    野澤 昌弘; デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 安富 正悟; 西本 光寿; 南 高文; 森 康範; 藤田 和利; 吉村 一宏; 西尾 和人; 植村 天受
    日本癌学会総会記事 82回 803 - 803 2023年09月
  • 前立腺癌と大腸癌そして潰瘍性大腸炎の関連性の探索(Systemic inflammation as a link between prostate cancer, colorectal cancer, and ulcerative colitis)
    倉 由吏恵; デベラスコ・マルコ; 坂井 和子; 藤田 和利; 安富 正悟; 森 康範; 南 高文; 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 82回 1416 - 1416 2023年09月
  • Satoshi Nojima; Tokimu Kadoi; Ayana Suzuki; Chiharu Kato; Shoichi Ishida; Kansuke Kido; Kazutoshi Fujita; Yasushi Okuno; Mitsuyoshi Hirokawa; Kei Terayama; Eiichi Morii
    Modern Pathology 100296 - 100296 2023年07月 [査読有り]
  • 藤田 和利; 南 高文; 吉村 一宏; 植村 天受
    日本臨床 81 増刊6 臨床前立腺癌学 76 - 80 (株)日本臨床社 2023年06月
  • Takero Hirata; Osamu Suzuki; Keisuke Otani; Akimitsu Miyake; Keisuke Tamari; Yuji Seo; Fumiaki Isohashi; Naoki Kai; Koji Hatano; Kazutoshi Fujita; Motohide Uemura; Ryoichi Imamura; Setsuo Tamenaga; Yutaro Yoshino; Yasutoshi Fumimoto; Yasuo Yoshioka; Norio Nonomura; Kazuhiko Ogawa
    Acta oncologica (Stockholm, Sweden) 62 5 1 - 7 2023年05月 
    BACKGROUND: This dose-escalation study evaluated the toxicity and efficacy of different stereotactic body radiation therapy (SBRT) doses for selecting an optimal dose for prostatic adenocarcinoma (PCa). MATERIALS AND METHODS: This clinical trial was registered at UMIN (UMIN000014328). Patients with low- or intermediate-risk PCa were equally assigned to 3 SBRT dose levels: 35, 37.5, and 40 Gy per 5 fractions. The primary endpoint was the occurrence rate of late grade ≥2 genitourinary (GU) and gastrointestinal (GI) adverse events at 2 years, while the secondary endpoint was the 2-year biochemical relapse-free (bRF) rate. Adverse events were evaluated using the Common Terminology Criteria for Adverse Events version 4.0. RESULTS: Seventy-five patients (median age, 70 years) were enrolled from March 2014 to January 2018, of whom 10 (15%) and 65 (85%) had low- and intermediate-risk PCa, respectively. The median follow-up time was 48 months. Twelve (16%) patients received neoadjuvant androgen deprivation therapy. The 2-year occurrence rates of grade 2 late GU and GI toxicities were 34 and 7% in all cohorts, respectively (35 Gy: 21 and 4%; 37.5 Gy: 40 and 14%; 40 Gy: 42 and 5%). The occurrence risk of GU toxicities significantly increased with dose escalation (p = 0.0256). Grades 2 and 3 acute GU toxicities were observed in 19 (25%) and 1 (1%), respectively. Grade 2 acute GI toxicity was observed in 8 (11%) patients. No grade ≥3 GI or ≥4 GU acute toxicity or grade ≥3 late toxicity was observed. Clinical recurrence was detected in 2 patients. CONCLUSIONS: An SBRT dose of 35 Gy per 5 fractions is less likely to cause adverse events in patients with PCa than 375- and 40-Gy SBRT doses. Higher doses of SBRT should be applied with caution.
  • 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年04月 
    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.
  • 高齢者男性の血中テストとステロン値に関係する腸内細菌叢の検討(Gut Microbiome corelated with Blood Testosterone Levels in Elderly Men)
    藤田 和利; 松下 慎; 波多野 浩士; 秦 淳也; 吉山 あずさ; 兼平 貢; 西本 光寿; 福原 慎一郎; 南 高文; 中村 昇太; 吉村 一宏; 野々村 祝夫; 植村 天受
    日本泌尿器科学会総会 110回 AOP01 - 04 2023年04月
  • 転移性去勢抵抗性前立腺癌に対するRadium-223治療における予後予測因子の検討(Prognostic factors of patients with metastatic CRPC treated by radium-223)
    西本 光寿; 藤田 和利; 藤本 西蔵; 桑原 賢; 菊池 尭; 安富 正悟; 齋藤 允孝; 森 康範; 南 高文; 野澤 昌弘; 吉村 一宏; 細野 眞; 植村 天受
    日本泌尿器科学会総会 110回 OP60 - 04 2023年04月
  • 筋層非浸潤性膀胱癌に対する5-ALAの初期経験(Initial experience of 5-ALA for non-muscle invasive bladder cancer)
    安富 正悟; 桑原 賢; 菊池 尭; 西本 光寿; 坂野 恵里; 斎藤 允孝; 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 110回 PP13 - 01 2023年04月
  • Pten欠損前立腺癌マウスモデルにおいてクルクミンモノグルクロニドは腫瘍免疫微小環境を改善する(Curcumin monoglucuronide reprograms the tumor micro-immune environment in mouse Pten-null prostate cancer)
    倉 由吏恵; デベラスコ・マルコ; 坂井 和子; 橋本 士; 西本 光寿; 安富 正悟; 森 康範; 南 高文; 野澤 昌弘; 藤田 和利; 吉村 一宏; 西尾 和人; 植村 天受
    日本泌尿器科学会総会 110回 PP62 - 04 2023年04月
  • 当院におけるIO+IO併用療法とIO+TKI併用療法の比較検討(Comparison of IO+IO combination therapy and IO+TKI combination therapy)
    桑原 賢; 西本 光寿; 安冨 正悟; 坂野 恵里; 斎藤 允孝; 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 110回 PP68 - 02 2023年04月
  • Masaru Tani; Akira Nagahara; Shingo Takada; Kazutoshi Fujita; Shinichiro Fukuhara; Motohide Uemura; Hiroshi Kiuchi; Ryoichi Imamura; Norio Nonomura
    IJU case reports 6 2 93 - 96 2023年03月 
    INTRODUCTION: Complete resection is essential for the treatment of teratoma with malignant transformation, and if metastasis occurs, it will be difficult to cure. We report a case of primary mediastinal teratoma with differentiation into angiosarcoma that caused bone metastases but was cured by multidisciplinary treatment. CASE PRESENTATION: A 31-year-old man with a primary mediastinal germ cell tumor underwent primary chemotherapy followed by post-chemotherapy resection, with angiosarcoma due to malignant transformation found in the surgical specimen. Femoral diaphyseal metastasis was manifested, and he underwent femur curettage followed by radiation therapy of 60 Gy in parallel with 4 cycles of chemotherapy combining gemcitabine and docetaxel. Although thoracic vertebral bone metastasis emerged 5 months after treatment, intensity-modulated radiation therapy was successful, and metastatic lesions have remained shrunken for 39 months after treatment. CONCLUSION: Even if complete resection is difficult, teratoma with malignant transformation may be cured by multidisciplinary treatment based on histopathology.
  • Nico C Grossmann; Francesco Soria; Tristan Juvet; Aaron M Potretzke; Hooman Djaladat; Alireza Ghoreifi; Eiji Kikuchi; Andrea Mari; Zine-Eddine Khene; Kazutoshi Fujita; Jay D Raman; Alberto Breda; Matteo Fontana; John P Sfakianos; John L Pfail; Ekaterina Laukhtina; Pawel Rajwa; Maximillian Pallauf; Cédric Poyet; Giovanni E Cacciamani; Thomas van Doeveren; Joost L Boormans; Alessandro Antonelli; Marcus Jamil; Firas Abdollah; Guillaume Ploussard; Axel Heidenreich; Enno Storz; Siamak Daneshmand; Stephen A Boorjian; Morgan Rouprêt; Michael Rink; Shahrokh F Shariat; Benjamin Pradere
    Cancers 15 5 2023年02月 
    OBJECTIVES: To identify correlates of survival and perioperative outcomes of upper tract urothelial carcinoma (UTUC) patients undergoing open (ORNU), laparoscopic (LRNU), and robotic (RRNU) radical nephroureterectomy (RNU). METHODS: We conducted a retrospective, multicenter study that included non-metastatic UTUC patients who underwent RNU between 1990-2020. Multiple imputation by chained equations was used to impute missing data. Patients were divided into three groups based on their surgical treatment and were adjusted by 1:1:1 propensity score matching (PSM). Survival outcomes per group were estimated for recurrence-free survival (RFS), bladder recurrence-free survival (BRFS), cancer-specific survival (CSS), and overall survival (OS). Perioperative outcomes: Intraoperative blood loss, hospital length of stay (LOS), and overall (OPC) and major postoperative complications (MPCs; defined as Clavien-Dindo > 3) were assessed between groups. RESULTS: Of the 2434 patients included, 756 remained after PSM with 252 in each group. The three groups had similar baseline clinicopathological characteristics. The median follow-up was 32 months. Kaplan-Meier and log-rank tests demonstrated similar RFS, CSS, and OS between groups. BRFS was found to be superior with ORNU. Using multivariable regression analyses, LRNU and RRNU were independently associated with worse BRFS (HR 1.66, 95% CI 1.22-2.28, p = 0.001 and HR 1.73, 95%CI 1.22-2.47, p = 0.002, respectively). LRNU and RRNU were associated with a significantly shorter LOS (beta -1.1, 95% CI -2.2-0.02, p = 0.047 and beta -6.1, 95% CI -7.2-5.0, p < 0.001, respectively) and fewer MPCs (OR 0.5, 95% CI 0.31-0.79, p = 0.003 and OR 0.27, 95% CI 0.16-0.46, p < 0.001, respectively). CONCLUSIONS: In this large international cohort, we demonstrated similar RFS, CSS, and OS among ORNU, LRNU, and RRNU. However, LRNU and RRNU were associated with significantly worse BRFS, but a shorter LOS and fewer MPCs.
  • Makoto Matsushita; Kazutoshi Fujita; Koji Hatano; Marco A De Velasco; Akira Tsujimura; Hirotsugu Uemura; Norio Nonomura
    The world journal of men's health 2023年02月 
    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年02月 
    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年 
    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年01月 [査読有り]
     
    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.
  • Toshiki Oka; Koji Hatano; Yohei Okuda; Akinaru Yamamoto; Toshihiro Uemura; Gaku Yamamichi; Eisuke Tomiyama; Yu Ishizuya; Yoshiyuki Yamamoto; Taigo Kato; Atsunari Kawashima; Kazutoshi Fujita; Norio Nonomura
    International journal of clinical oncology 28 3 427 - 435 2022年12月 
    BACKGROUND: Enzalutamide is effective against castration-resistant prostate cancer (CRPC). However, it is unclear which patients would benefit more from enzalutamide treatment. Here, we analyzed patients who received enzalutamide as first-line therapy for CRPC and evaluated the factors that predict treatment response and prognosis. METHODS: We retrospectively analyzed 101 patients treated with enzalutamide for CRPC at our institution. As primary endpoints we regarded the prostate-specific antigen (PSA) response rate and PSA-progression-free survival (PSA-PFS) from the start of enzalutamide treatment. Laboratory and imaging data were analyzed to predict treatment efficacy. RESULTS: PSA reductions of ≥ 50% and ≥ 90% were observed in 78 (77%) and 47 (47%) patients, respectively, compared with the baseline. During the follow-up period, 67 (66%) patients showed PSA progression, with a median PSA-PFS of 11 months. Moreover, 31 patients (31%) died, with a median overall survival of 64 months. On multivariate analysis, lymph node metastases at the start of enzalutamide treatment [odds ratio (OR) 0.0575, 95% confidence interval (CI) 0.0105-0.316, p = 0.0010] and time to CRPC (OR 0.177, 95% CI 0.0428-0.731, p = 0.0167] were associated with ≥ 90% PSA response. Lymph node metastases (hazard ratio [HR] 3.00, 95% CI 1.48-6.09, p = 0.0023) and time to CRPC (HR 1.84, 95% CI 1.02-3.30, p = 0.0419) were also predictors of PSA-PFS on a multivariate model. CONCLUSIONS: Time to CRPC and lymph node metastasis were predictors of the PSA response rate and PSA-PFS.
  • Koichi Okada; Kentaro Takezawa; Go Tsujimura; Takahiro Imanaka; Sohei Kuribayashi; Norichika Ueda; Koji Hatano; Shinichiro Fukuhara; Hiroshi Kiuchi; Kazutoshi Fujita; Daisuke Motooka; Shota Nakamura; Yoshihisa Koyama; Shoichi Shimada; Norio Nonomura
    Frontiers in Cellular and Infection Microbiology 12 2022年12月 
    Introduction We aimed to clarify the presence and localization of the prostate microbiota and examine its association with benign prostate enlargement (BPE). Methods The microbiota of prostate tissues and catheterized urine from 15 patients were analyzed by 16S metagenomic analysis and compared to show that the prostate microbiota was not a contaminant of the urinary microbiota. Fluorescence in situ hybridization (FISH) and in situ hybridization (ISH) using the specific probe for eubacteria was performed on prostate tissue to show the localization of bacteria in the prostate. The BPE group was defined as prostate volume ≥30 mL, and the non-BPE group as prostate volume &lt;30 mL. The microbiota of the two groups were compared to clarify the association between prostate microbiota and BPE. Results Faith’s phylogenetic diversity index of prostate tissue was significantly higher than that of urine (42.3±3.8 vs 25.5±5.6, P=0.01). Principal coordinate analysis showed a significant difference between the microbiota of prostate tissue and catheterized urine (P&lt;0.01). FISH and ISH showed the presence of bacteria in the prostatic duct. Comparison of prostate microbiota between the BPE and non-BPE groups showed that the Chao1 index of the BPE group was significantly lower than that of the latter [142 (50–316) vs 169 (97–665), P=0.047] and the abundance of Burkholderia was significantly higher in the BPE group than in the latter. Conclusions We demonstrated that the prostate microbiota was located in the prostatic duct and reduced diversity of prostate microbiota was associated with BPE, suggesting that prostate microbiota plays a role in BPE.
  • Maximilian Pallauf; David D'Andrea; Frederik König; Ekaterina Laukthina; Takafumi Yanagisawa; Morgan Rouprêt; Siamak Daneshmand; Hooman Djaladat; Alireza Ghoreifi; Francesco Soria; Kazutoshi Fujita; Stephen A Boorjian; Aaron M Potretzke; Andrea Mari; Mathieu Roumiguié; Alessandro Antonelli; Alberto Bianchi; Zine-Eddine Khene; John P Sfakianos; Marcus Jamil; Joost L Boormans; Jay D Raman; Nico C Grossmann; Alberto Breda; Axel Heidenreich; Francesco Del Giudice; Nirmish Singla; Sharokh F Shariat; Benjamin Pradere
    The Journal of urology 101097JU0000000000003085  2022年12月 
    PURPOSE: Treatment options for the management of upper tract urothelial cancer (UTUC) are based on accurate staging. However, the performance of conventional cross-sectional imaging (CCI) for clinical lymph node staging (N-staging) remains poorly investigated. This study aims to evaluate the diagnostic accuracy of CCI for UTUC N-staging. MATERIALS AND METHODS: This study was a multicenter, retrospective, observational study. We included 865 non-metastatic (M0) UTUC patients treated with curative intended surgery and lymph node dissection (LND) who had been staged with CCI before surgery. We compared clinical (c) and pathologic (p) N-staging results to evaluate the concordance of node-positive (N+) and node-negative (N0) disease and calculate cN-staging's diagnostic accuracy. RESULTS: CCI categorized 750 patients cN0 and 115 cN+. LND categorized 641 patients pN0 and 224 pN+. The cN-stage was pathologically downstaged in 6.8% of patients, upstaged in 19%, and found concordant in 74%. The sensitivity and specificity of cN-staging were 25% (95% Confidence Interval [CI] 20; 31) and 91% (95% CI 88; 93). Positive and negative likelihood ratios were 2.7 (95% CI 2.0; 3.8) and 0.83 (95% CI 0.76; 0.89). The area under the receiver operating characteristics curve (0.58, 95% CI 0.55; 0.61) revealed low diagnostic accuracy. CONCLUSIONS: CCI had low sensitivity in detecting UTUC pN + disease. However, cN + increased the likelihood of pN + by almost three-fold. Thus, CCI is a rule-in but not a rule-out test. LND should remain the standard during extirpative UTUC surgery to obtain accurate N-staging. cN + could be a strong argument for early systemic treatment.
  • 藤田 和利; 吹上 健; 西本 光寿; 安富 正悟; 斎藤 允孝; 南 高文; 吉村 一宏; 植村 天受
    泌尿器外科 35 12 1309 - 1312 医学図書出版(株) 2022年12月
  • 藤田 和利; 安富 正吾; 南 高文; 野澤 昌弘; 吉村 一宏; 植村 天受
    泌尿器科 16 6 711 - 715 (有)科学評論社 2022年12月
  • Castleman病治療中に膀胱癌肺転移を生じ,Pembrolizumabを投与した1例
    藤本 西蔵; 南 高文; 中山 尭仁; 橋本 士; 西本 光寿; 安富 正悟; 坂野 恵里; 斎藤 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
    泌尿器科紀要 68 12 395 - 395 泌尿器科紀要刊行会 2022年12月
  • 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 68 12 401 - 401 泌尿器科紀要刊行会 2022年12月
  • Kazutoshi Fujita; Hiroyoshi Suzuki; Nobuyuki Hinata; Yuji Miura; Kohei Edamura; Ken-Ichi Tabata; Gaku Arai; Nobuaki Matsubara; Yota Yasumizu; Takeo Kosaka; Mototsugu Oya; Mikio Sugimoto
    Translational andrology and urology 11 12 1771 - 1785 2022年12月 
    A multidisciplinary approach is necessary to manage advanced prostate cancer. The Advanced Prostate Cancer Consensus Conference (APCCC) in 2019 provided a practical guide to help clinicians consider therapeutic options in controversial areas, but healthcare systems vary across the world. At the 109th annual meeting of the Japanese Urological Association in December 2021, Japanese urologists voted on the questions in the APCCC 2019 guidelines regarding prostate-specific membrane antigen-positron emission tomography (PSMA-PET), management of oligometastatic prostate cancer, management of nonmetastatic castration-resistant prostate cancer (CRPC), management of a primary tumor in metastatic settings, systemic treatment of newly diagnosed metastatic castration-sensitive prostate cancer (CSPC), management of metastatic CRPC (mCRPC), and tumor genomic testing. We summarize the "real-world" status of the management of advanced prostate cancer in Japan. Several differences were noted in the management of advanced prostate cancer between Japanese urologists and the APCCC 2019 guidelines. Many Japanese urologists chose conventional imaging modalities for detecting metastasis instead of PSMA-PET. More Japanese urologists prefer androgen-deprivation therapy (ADT) alone in the management of low-volume metastatic CSPC than the APCCC panelists do, In the management of M0 CRPC, darolutamide and enzalutamide were chosen more by Japanese urologists than by the voters at the APCCC 2019. Bicalutamide remains one of the options for the management of mCRPC in Japan. More Japanese urologists do not recommend microsatellite instability (MSI) and BRCA1/2 tests than the voters at the APCCC 2019. Clinical evidence in Japan should be collected to address these discrepancies.
  • Satoshi Katayama; Benjamin Pradere; Nico C Grossman; Aaron M Potretzke; Stephen A Boorjian; Alireza Ghoreifi; Sia Daneshmand; Hooman Djaladat; John P Sfakianos; Andrea Mari; Zine-Eddine Khene; David D'Andrea; Nozomi Hayakawa; Alberto Breda; Matteo Fontana; Kazutoshi Fujita; Alessandro Antonelli; Thomas van Doeveren; Christina Steinbach; Keiichiro Mori; Ekaterina Laukhtina; Morgan Rouprêt; Vitaly Margulis; Pierre I Karakiewicz; Motoo Araki; Eva Compérat; Yasutomo Nasu; Shahrokh F Shariat
    International journal of urology : official journal of the Japanese Urological Association 30 1 63 - 69 2022年11月 
    OBJECTIVES: Technical limitations of ureteroscopic (URS) biopsy has been considered responsible for substantial upgrading rate in upper tract urothelial carcinoma (UTUC). However, the impact of tumor specific factors for upgrading remain uninvestigated. METHODS: Patients who underwent URS biopsy were included between 2005 and 2020 at 13 institutions. We assessed the prognostic impact of upgrading (low-grade on URS biopsy) versus same grade (high-grade on URS biopsy) for high-grade UTUC tumors on radical nephroureterectomy (RNU) specimens. RESULTS: This study included 371 patients, of whom 112 (30%) and 259 (70%) were biopsy-based low- and high-grade tumors, respectively. Median follow-up was 27.3 months. Patients with high-grade biopsy were more likely to harbor unfavorable pathologic features, such as lymphovascular invasion (p < 0.001) and positive lymph nodes (LNs; p < 0.001). On multivariable analyses adjusting for the established risk factors, high-grade biopsy was significantly associated with worse overall (hazard ratio [HR] 1.74; 95% confidence interval [CI], 1.10-2.75; p = 0.018), cancer-specific (HR 1.94; 95% CI, 1.07-3.52; p = 0.03), and recurrence-free survival (HR 1.80; 95% CI, 1.13-2.87; p = 0.013). In subgroup analyses of patients with pT2-T4 and/or positive LN, its significant association retained. Furthermore, high-grade biopsy in clinically non-muscle invasive disease significantly predicted upstaging to final pathologically advanced disease (≥pT2) compared to low-grade biopsy. CONCLUSIONS: High tumor grade on URS biopsy is associated with features of biologically and clinically aggressive UTUC tumors. URS low-grade UTUC that becomes upgraded to high-grade might carry a better prognosis than high-grade UTUC on URS. Tumor specific factors are likely to be responsible for upgrading to high-grade on RNU.
  • 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年11月 [査読有り]
     
    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.
  • 近畿大学病院における5-ALA初期使用経験
    南 高文; 安富 正悟; 坂野 恵里; 齋藤 允孝; 森 康範; 藤田 和利; 能勢 和宏; 野澤 昌弘; 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 36回 P - 9 (一社)日本泌尿器内視鏡・ロボティクス学会 2022年11月
  • 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 36回 V - 1 (一社)日本泌尿器内視鏡・ロボティクス学会 2022年11月
  • 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年10月 
    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年10月 
    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.
  • 化学療法を施行した転移性腎盂・尿管癌と転移性膀胱癌の予後の臨床的検討
    安富 正悟; 藤田 和利; 北 博行; 桑原 賢; 明石 泰典; 松村 直紀; 杉本 公一; 南 高文; 野澤 昌弘; 吉村 一宏; 田原 秀男; 平山 暁秀; 西岡 伯; 江左 篤宣; 植村 天受
    日本癌治療学会学術集会抄録集 60回 O33 - 5 2022年10月
  • 去勢抵抗性前立腺癌に対するRadium-223治療ラインの検討
    西本 光寿; 藤田 和利; 藤本 西蔵; 桑原 賢; 菊池 堯; 安富 正悟; 坂野 恵里; 齋藤 允孝; 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 60回 P48 - 2 2022年10月
  • 新規ホルモン剤抵抗性M0CRPC患者におけるダロルタミドへの切替療法
    藤本 西蔵; 藤田 和利; 西本 光寿; 浜口 守; 桑原 賢; 橋本 士; 安富 正悟; 坂野 恵里; 南 高文; 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 60回 P50 - 6 2022年10月
  • 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 57 総会臨時 265 - 265 (一社)日本移植学会 2022年10月
  • 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年09月 [査読有り]
     
    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.
  • 腸内細菌叢由来LPSはヒスタミンH1受容体シグナル経路を介して前立腺癌増殖を促進する(Lipopolysaccharide from gut microhiota promotes prostate cancer growth through histamine III receptor signaling)
    藤田 和利; 松下 慎; 元岡 大祐; 長谷 拓明; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 南 高文; マルコ・デベラスコ; 吉村 一宏; ジョージ・ネットー; 辻川 和丈; 中村 昇太; 森井 英一; 植村 天受; 野々村 祝夫
    日本癌学会総会記事 81回 E - 3077 2022年09月
  • 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 81回 J - 1001 2022年09月
  • 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 81回 E - 1056 2022年09月
  • マウス前立腺癌モデルを用いた抗アンドロゲン受容体治療による分子および免疫学的反応の検討(Use of a mouse model of prostate cancer to assess molecular and immune responses to anti-androgen receptor therapy)
    坂野 恵里; デベラスコ・マルコ; 倉 由吏恵; 藤田 和利; 坂井 和子; 橋本 士; 西本 光寿; 吉村 一宏; 野澤 昌弘; 西尾 和人
    日本癌学会総会記事 81回 J - 2061 2022年09月
  • 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 81回 P - 2387 2022年09月
  • 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 81回 E - 3011 2022年09月
  • 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 81回 P - 3286 2022年09月
  • 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年08月 
    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.
  • Matsumura N; Fujita K; Nishimoto M; Minami T; Tahara H; Yoshimura K; Uemura H
    World journal of urology 41 8 2063 - 2068 2022年08月 

    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.
  • 【泌尿器科領域の遺伝性疾患とゲノム医療の最前線】去勢抵抗性前立腺がんに対する個別化医療
    藤田 和利; 南 高文; 野澤 昌弘; 吉村 一宏; 植村 天受
    泌尿器科 16 2 144 - 148 (有)科学評論社 2022年08月
  • 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 37 2 137 - 137 (一社)日本性機能学会 2022年08月
  • 進行性腎細胞癌に対するイピリムマブとニボルマブの併用療法により発症した間質性腎炎の1例
    石井 信; 竹澤 健太郎; 今村 亮一; 福原 慎一郎; 藤田 和利; 植村 元秀; 木内 寛; 野々村 祝夫
    泌尿器科紀要 68 8 282 - 282 泌尿器科紀要刊行会 2022年08月
  • 123I-MIBGの高集積を認め褐色細胞腫を疑った散発性副腎髄質過形成の1例
    脇田 哲平; 波多野 浩士; 堀谷 弘; 竹澤 健太郎; 福原 慎一郎; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 野々村 祝夫; 前田 法一; 西澤 均; 向井 康祐; 大月 道夫
    泌尿器科紀要 68 8 282 - 282 泌尿器科紀要刊行会 2022年08月
  • 複数の免疫関連副作用によるイピリムマブ、ニボルマブ併用療法中止後も安全にニボルマブを再投与しえた転移性腎細胞癌の1例
    前川 洋子; 加藤 大悟; 藤田 和利; 福原 慎一郎; 植村 元秀; 木内 寛; 今村 亮一; 野々村 祝夫
    泌尿器科紀要 68 8 281 - 281 泌尿器科紀要刊行会 2022年08月
  • 進行性腎細胞癌に対するイピリムマブとニボルマブの併用療法により発症した間質性腎炎の1例
    石井 信; 竹澤 健太郎; 今村 亮一; 福原 慎一郎; 藤田 和利; 植村 元秀; 木内 寛; 野々村 祝夫
    泌尿器科紀要 68 8 282 - 282 泌尿器科紀要刊行会 2022年08月
  • 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 37 2 137 - 137 (一社)日本性機能学会 2022年08月
  • 123I-MIBGの高集積を認め褐色細胞腫を疑った散発性副腎髄質過形成の1例
    脇田 哲平; 波多野 浩士; 堀谷 弘; 竹澤 健太郎; 福原 慎一郎; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 野々村 祝夫; 前田 法一; 西澤 均; 向井 康祐; 大月 道夫
    泌尿器科紀要 68 8 282 - 282 泌尿器科紀要刊行会 2022年08月
  • 腸内細菌による前立腺癌増殖制御メカニズムの解明
    松下 慎; 藤田 和利; 林 拓自; 香山 尚子; 元岡 大祐; 長谷 拓明; 神宮司 健太郎; 山本 顕生; 植村 俊彦; 山道 岳; 冨山 栄輔; 洪 陽子; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 植村 元秀; 今村 亮一; 辻川 和丈; 中村 昇太; 竹田 潔; 野々村 祝夫
    泌尿器外科 35 8 858 - 859 医学図書出版(株) 2022年08月
  • 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年08月 [査読有り]
     
    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年07月 
    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年07月 [査読有り]
     
    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.
  • 上戸 賢; 角田 洋一; 福原 慎一郎; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 宮川 康; 野々村 祝夫
    泌尿器科紀要 68 7 239 - 243 泌尿器科紀要刊行会 2022年07月 
    54歳女性。左腰背部痛を主訴に近医を受診し、CT検査にて左副腎腫瘍を指摘され、当科へ紹介となった。精査にて左副腎皮質癌の疑いで副腎腫瘍摘除術が行われ、転移性の低分化型腺癌の病理結果が得られたが、原発巣の同定に難渋し、手術から2年後の検査で浸潤性乳管癌副腎転移と診断された。治療として左乳房切除術後に薬物療法を行った結果、術後3年9ヵ月現在、再発なく生存中である。
  • 上戸 賢; 角田 洋一; 福原 慎一郎; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 宮川 康; 野々村 祝夫
    泌尿器科紀要 68 7 239 - 243 泌尿器科紀要刊行会 2022年07月 [査読有り]
  • Satoshi Kamido; Yoichi Kakuta; Shinichiro Fukuhara; Kazutoshi Fujita; Motohide Uemura; Hiroshi Kiuchi; Ryoichi Imamura; Yasushi Miyagawa; Norio Nonomura
    Hinyokika kiyo. Acta urologica Japonica 68 7 239 - 243 2022年07月 
    A 54-year-old female underwent open left adrenalectomy for a left adrenal tumor in 2013. The pathology showed metastatic poorly differentiated adenocarcinoma. Despite a close examination, the primary tumor could not be identified. During the follow-up, a computed tomographic scan showed a hyper vascular tumor in the left breast in2015. A left mastectomy was performed for diagnosis and treatment. The pathology showed invasive ductal carcinoma of the breast. Comparing the histopathology and immunohistochemistry of the breast tumor with the adrenal tumor, the adrenal tumor was finally confirmed as metastatic invasive ductal carcinoma. Adrenal gland metastasis from invasive ductal carcinoma is said to be extremely rare. To our knowledge, there have been no reports of cases in which metastatic invasive ductal carcinoma of the adrenal gland was found before the primary site. We report this case with some literature review.
  • 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 29 6 3911 - 3921 2022年05月 [査読有り]
     
    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.
  • 南 高文; 安富 正悟; 坂野 恵里; 齋藤 允孝; 森 康範; 藤田 和利; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 植村 天受
    日本老年泌尿器科学会誌 35 1 174 - 174 日本老年泌尿器科学会 2022年05月
  • 藤本 西蔵; 南 高文; 西本 光寿; 森 康範; 藤田 和利; 野澤 昌弘; 能勢 和宏; 吉村 一宏; 植村 天受
    日本老年泌尿器科学会誌 35 1 176 - 176 日本老年泌尿器科学会 2022年05月
  • Makoto Matsushita; Kazutoshi Fujita; Koji Hatano; Takuji Hayashi; Hisako Kayama; Daisuke Motooka; Hiroaki Hase; Akinaru Yamamoto; Toshihiko Uemura; Gaku Yamamichi; Eisuke Tomiyama; Yoko Koh; Taigo Kato; Atsunari Kawashima; Motohide Uemura; Satoshi Nojima; Ryoichi Imamura; Aysha Mubeen; George J Netto; Kazutake Tsujikawa; Shota Nakamura; Kiyoshi Takeda; Eiichi Morii; Norio Nonomura
    International journal of cancer 151 4 623 - 636 2022年04月 [査読有り]
     
    Western high-fat diets (HFD) are regarded as a major risk factor for prostate cancer (PCa). Using prostate-specific Pten-knockout mice as a PCa model, we previously reported that HFD promoted inflammatory PCa growth. The composition of the gut microbiota changes under the influence of diet exert various effects on the host through immunological mechanisms. Herein, we investigated the etiology of HFD-induced inflammatory cancer growth and the involvement of the gut microbiome. The expression of Hdc, the gene responsible for histamine biosynthesis, and histamine levels were upregulated in large prostate tumors of HFD-fed mice, and the number of mast cells increased around the tumor foci. Administration of fexofenadine, a histamine H1 receptor antagonist, suppressed tumor growth in HFD-fed mice by reducing the number of myeloid-derived suppressor cells and suppressing IL6/STAT3 signaling. HFD intake induced gut dysbiosis, resulting in the elevation of serum lipopolysaccharide (LPS) levels. Intraperitoneal injection of LPS increased Hdc expression in PCa. Inhibition of LPS/Toll-like receptor 4 signaling suppressed HFD-induced tumor growth. The number of mast cells increased around the cancer foci in total prostatectomy specimens of severely obese patients. In conclusion, HFD promotes PCa growth through histamine signaling via mast cells. Dietary high-fat induced gut dysbiosis might be involved in the inflammatory cancer growth. This article is protected by copyright. All rights reserved.
  • 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年04月 [査読有り][招待有り]
     
    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.
  • Frederik König; Nico C Grossmann; Francesco Soria; David D'Andrea; Tristan Juvet; Aaron Potretzke; Hooman Djaladat; Alireza Ghoreifi; Eiji Kikuchi; Nozomi Hayakawa; Andrea Mari; Zine-Eddine Khene; Kazutoshi Fujita; Jay D Raman; Alberto Breda; Matteo Fontana; John P Sfakianos; John L Pfail; Ekaterina Laukhtina; Pawel Rajwa; Maximilian Pallauf; Giovanni E Cacciamani; Thomas van Doeveren; Joost L Boormans; Alessandro Antonelli; Marcus Jamil; Firas Abdollah; Jeffrey Budzyn; Guillaume Ploussard; Axel Heidenreich; Siamak Daneshmand; Stephen A Boorjian; Morgan Rouprêt; Michael Rink; Shahrokh F Shariat; Benjamin Pradere
    Cancers 14 7 2022年03月 
    BACKGROUND: Measuring quality of care indicators is important for clinicians and decision making in health care to improve patient outcomes. OBJECTIVE: The primary objective was to identify quality of care indicators for patients with upper tract urothelial carcinoma (UTUC) and to validate these in an international cohort treated with radical nephroureterectomy (RNU). The secondary objective was to assess the factors associated with failure to validate the pentafecta. DESIGN: We performed a retrospective multicenter study of patients treated with RNU for EAU high-risk (HR) UTUC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Five quality indicators were consensually approved, including a negative surgical margin, a complete bladder-cuff resection, the absence of hematological complications, the absence of major complications, and the absence of a 12-month postoperative recurrence. After multiple imputations and propensity-score matching, log-rank tests and a Cox regression were used to assess the survival outcomes. Logistic regression analyses assessed predictors for pentafecta failure. RESULTS: Among the 1718 included patients, 844 (49%) achieved the pentafecta. The median follow-up was 31 months. Patients who achieved the pentafecta had superior 5-year overall- (OS) and cancer-specific survival (CSS) compared to those who did not (68.7 vs. 50.1% and 79.8 vs. 62.7%, respectively, all p < 0.001). On multivariable analyses, achieving the pentafecta was associated with improved recurrence-free survival (RFS), CSS, and OS. No preoperative clinical factors predicted a failure to validate the pentafecta. CONCLUSIONS: Establishing quality indicators for UTUC may help define prognosis and improve patient care. We propose a pentafecta quality criteria in RNU patients. Approximately half of the patients evaluated herein reached this endpoint, which in turn was independently associated with survival outcomes. Extended validation is needed.
  • Kazutoshi Fujita
    Cancer science 2022年03月 
    Perioperative systemic chemotherapy improves the prognosis of upper tract urothelial carcinoma (UTUC). The first objective of this study is to verify whether perioperative circulating tumor DNA (ctDNA) analysis using a pan-cancer gene panel and next-generation sequencing can identify patients with poor prognosis who require perioperative chemotherapy. Secondly, we will investigate whether ctDNA is useful for minimal residual disease (MRD) detection and treatment monitoring in UTUC. This study included fifty patients with untreated UTUC, including 43 cases of localized UTUC. We performed targeted ultradeep sequencing of plasma cfDNA and buffy coat DNA and whole-exome sequencing of cancer tissues, allowing exclusion of possible false positives. We attempted to stratify the prognosis according to the perioperative ctDNA levels in patients with localized UTUC. In patients with metastatic UTUC, ctDNA was evaluated before, during, and after systemic treatment. Twenty-three (46%) of 50 patients with untreated UTUC were ctDNA-positive, and 17 (40%) of 43 patients with localized UTUC were ctDNA-positive. Of the detected TP53 mutations, 19% were false-positive due to clonal hematopoiesis of indeterminate potential (CHIP). Among preoperative risk factors, only the preoperative ctDNA fraction>2% was a significant and independent risk factor associated with worse recurrence-free survival (RFS). Furthermore, the existence of ctDNA early point after the operation was significantly associated with worse RFS, suggesting the presence of MRD. ctDNA also showed potential as a real-time marker for systemic therapy in patients with metastatic UTUC. Detection of ctDNA may indicate potential metastasis and guide decisions of perioperative chemotherapy.
  • 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年02月 [査読有り]
     
    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.
  • Takeshi Ujike; Motohide Uemura; Taigo Kato; Koji Hatano; Atsunari Kawashima; Akira Nagahara; Kazutoshi Fujita; Ryoichi Imamura; Norio Nonomura
    International journal of clinical oncology 27 4 774 - 780 2022年02月 
    BACKGROUND: Computer-assisted diagnosis (CAD) systems for bone scans have been introduced as clinical quality assurance tools, but few studies have reported on its utility for renal cell carcinoma (RCC) patients. The aim of this study was to assess the diagnostic validity of the CAD system for bone scans and to construct a novel diagnostic system for bone metastases in RCC patients. METHODS: We evaluated bone scan images of 300 RCC patients. Artificial neural network (ANN) values, which represent the probability of abnormality, were calculated by BONENAVI, the CAD software for bone scans. By analyzing ANN values, we assessed the diagnostic validity of BONENAVI. Next, we selected 108 patients who underwent measurements of bone turnover markers and assessed the combined diagnostic validity of BONENAVI and bone turnover markers. RESULTS: Forty-three out of 300 RCC patients had bone metastases. The AUC of ANN values was 0.764 and the optimum sensitivity and specificity were 83.7 and 62.7%. By logistic analysis of 108 cases, we found that ICTP, a bone resorption marker, could be a diagnostic marker. The AUC of ICTP was 0.776 and the optimum sensitivity and specificity were 57.1 and 86.8%. Subsequently, we developed a novel diagnostic model based on ANN values and ICTP. Using this model, the AUC was 0.849 and the optimum sensitivity and specificity were 76.2 and 80.7%. CONCLUSION: By combining the high sensitivity provided by BONENAVI and the high specificity provided by ICTP, we constructed a novel, high-accuracy diagnostic model for bone metastases in RCC patients.
  • 冨山 栄輔; 藤田 和利; 松崎 恭介; 白水 崇; 鳴海 良平; 神宮司 健太郎; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 植村 元秀; 高尾 徹也; 足立 淳; 朝長 毅; 野々村 祝夫
    日本分子腫瘍マーカー研究会誌 37 16 - 17 日本分子腫瘍マーカー研究会 2022年
  • Makoto Matsushita; Kazutoshi Fujita; Koji Hatano; Marco A De Velasco; Hirotsugu Uemura; Norio Nonomura
    Frontiers in endocrinology 13 852382 - 852382 2022年 [査読有り]
     
    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.
  • Kazutoshi Fujita; Koji Hatano; Mamoru Hashimoto; Eisuke Tomiyama; Eiji Miyoshi; Norio Nonomura; Hirotsugu Uemura
    International journal of molecular sciences 22 24 2021年12月 [査読有り]
     
    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.
  • 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年12月 

    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.
  • 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 2021年11月 
    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.
  • 非悪性尿路上皮のTERT Promoter変異に基づくBCG個別化医療の可能性
    林 裕次郎; 藤田 和利; 小西 雅俊; 前川 洋子; 谷 優; 朝倉 寿久; 角田 洋一; 蔦原 宏一; 高尾 徹也; 野々村 祝夫
    日本癌治療学会学術集会抄録集 59回 O17 - 3 2021年10月
  • Xin Li; Kenji Nakayama; Takayuki Goto; Hiroko Kimura; Shusuke Akamatsu; Yujiro Hayashi; Kazutoshi Fujita; Takashi Kobayashi; Koji Shimizu; Norio Nonomura; Osamu Ogawa; Takahiro Inoue
    Cancer science 112 10 4292 - 4302 2021年10月 
    The altered levels of phospholipids (PLs) and lysophospholipids (LPLs) in prostate cancer (CaP) and benign tissues in our previous findings prompted us to explore PLs and LPLs as potential biomarkers for CaP. Urinary lipidomics has attracted increasing attention in clinical diagnostics and prognostics for CaP. In this study, thirty-one prostate tissues obtained from radical prostatectomy were assessed using high-resolution matrix-assisted laser desorption/ionization imaging mass spectrometry (HR-MALDI-IMS). Urine samples were collected after digital rectal examination (DRE), and urinary lipids were extracted using the acidified Bligh-Dyer method. The discovery set comprised 75 patients with CaP and 44 with benign prostatic hyperplasia (BPH) at Kyoto University Hospital; the validation set comprised 74 patients with CaP and 59 with BPH at Osaka University Hospital. Urinary lipidomic screening was performed using MALDI time-of-flight MS (MALDI-TOF/MS). The level of urinary lysophosphatidylcholine (LPC) and phosphatidylcholines (PCs) were compared between the CaP and BPH groups. The [PC (34:2) + PC (34:1)]/LPC (16:0) ratio was significantly higher (p<0.001) in CaP tissues than in benign epithelial tissues. The urinary PCs/LPC ratio was significantly higher (p<0.001) in the CaP group than in the BPH group in the discovery and validation sets.
  • 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年10月 
    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.
  • Eisuke Tomiyama; Kazutoshi Fujita; Mamoru Hashimoto; Hiroshi Miyamoto; George J Netto; Norio Nonomura
    International journal of urology : official journal of the Japanese Urological Association 29 1 89 - 90 2021年09月
  • 腸内細菌が産生する短鎖脂肪酸はIGF-1を介して肥満マウスの前立腺癌の増殖を促進する
    松下 慎; 藤田 和利; 長谷 拓明; 神宮司 健太郎; 山本 顕生; 植村 俊彦; 山道 岳; 冨山 栄輔; 洪 陽子; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 植村 元秀; 辻川 和丈; 野々村 祝夫
    日本癌学会総会記事 80回 [P14 - 7] 2021年09月
  • 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 80回 [E3 - 4] 2021年09月
  • 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 80回 [E12 - 1] 2021年09月
  • 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 80回 [E17 - 3] 2021年09月
  • 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 80回 [J14 - 3] 2021年09月
  • 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年08月 
    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年08月 
    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.
  • Yosuke Sekii; Tsuyoshi Ujike; Akira Nagahara; Kazutoshi Fujita; Motohide Uemura; Hiroshi Kiuchi; Ryoichi Imamura; Yasushi Miyagawa; Hirofumi Nakayama; Noriyuki Nanba; Mitsugu Oowari; Koichi Deguchi; Norio Nonomura
    Hinyokika kiyo. Acta urologica Japonica 67 8 363 - 366 2021年08月 
    A 12-year-old girl was found to have decending colon diverticulum perforation and retroperitoneal abscess on computed tomography (CT) carried out to determine the cause of fever and stomachache. CT-guided drainage tube placement was performed. She was suspected of having MEN2B from her specific facial appearance, Marfan-like body shape and lingual mucosa neuroma. Cervical ultrasonography and serum tumor marker revealed medullary thyroid carcinoma and metastasis to cervical lymph node. Genetic examination revealed a mutation of RET gene codon 918. Therefore, she was diagnosed as having MEN2B. Laboratory data showed elevated urinary catecholamines. Metaiodobenzylguanidine (MIBG) adrenal scintigraphy showed bilateral adrenal uptake and a definitive diagnosis of bilateral adrenal pheochromocytomas was made. Discharge from the drainage tube persisted and it was difficult to continue conservative treatment. Therefore, laparoscopic bilateral adrenalectomy and transverse colon colostomy were performed. Subsequently, total thyroidectomy and cervical lymph node dissection were performed. At five years of follow up, bilateral lung metastases were observed, but the serum calcitonin level was normal and the patient is under observation.
  • 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年08月 [査読有り]
     
    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.
  • Makoto Matsushita; Kazutoshi Fujita; Takuji Hayashi; Hisako Kayama; Daisuke Motooka; Hiroaki Hase; Kentaro Jingushi; Gaku Yamamichi; Satoru Yumiba; Eisuke Tomiyama; Yoko Koh; Yujiro Hayashi; Kosuke Nakano; Cong Wang; Yu Ishizuya; Taigo Kato; Koji Hatano; Atsunari Kawashima; Takeshi Ujike; Motohide Uemura; Ryoichi Imamura; Maria D C Rodriguez Pena; Jennifer B Gordetsky; George J Netto; Kazutake Tsujikawa; Shota Nakamura; Kiyoshi Takeda; Norio Nonomura
    Cancer research 81 15 4014 - 4026 2021年08月 
    Excessive intake of animal fat and resultant obesity are major risk factors for prostate cancer (PCa). Because the composition of the gut microbiota is known to change with dietary composition and body type, we used prostate-specific Pten knockout mice as a PCa model to investigate whether there is a gut microbiota-mediated connection between animal fat intake and PCa. Oral administration of an antibiotic mixture (Abx) in PCa-bearing mice fed a high-fat diet containing a large proportion of lard drastically altered the composition of the gut microbiota including Rikenellaceae and Clostridiales, inhibited PCa cell proliferation, and reduced prostate Igf1 expression and circulating IGF-1 levels. In PCa tissue, MAPK and PI3K activities, both downstream of the IGF-1 receptor, were suppressed by Abx administration. IGF-1 directly promoted the proliferation of PCa cell lines DU145 and 22Rv1 in vitro. Abx administration also reduced fecal levels of short-chain fatty acids (SCFA) produced by intestinal bacteria. Supplementation with SCFAs promoted tumor growth by increasing IGF-1 levels. In humans, IGF-1 was found to be highly expressed in PCa tissue from obese patients. In conclusion, IGF-1 production stimulated by SCFAs from gut microbes influences the growth of PCa via activating local prostate MAPK and PI3K signaling, indicating the existence of a gut microbiota-IGF-1-prostate axis. Disrupting this axis by modulating the gut microbiota may aid in PCa prevention and treatment.
  • 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 2021年07月
  • 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 2021年07月
  • Marco A. De Velasco; Kazuko Sakai; Yurie Kura; Naomi Ando; Noriko Sako; Kazutoshi Fujita; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuto Nishio; Hirotsugu Uemura
    Immunology 2021年07月
  • Marco A. De Velasco; Yurie Kura; Kazuko Sakai; Kazutoshi Fujita; Masahiro Nozawa; Kazuhiro Yoshimura; Kazuto Nishio; Hirotsugu Uemura
    Clinical Research (Excluding Clinical Trials) 2021年07月
  • 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年07月 
    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.
  • Yuki Horibe; Takeshi Ujike; Shinichiro Fukuhara; Kazutoshi Fujita; Hiroshi Kiuchi; Motohide Uemura; Ryoichi Imamura; Norio Nonomura
    Hinyokika kiyo. Acta urologica Japonica 67 7 327 - 330 2021年07月 
    A 67-year-old man with non-muscle invasive bladder cancer (NMIBC) underwent transurethral resection (TUR) in January 2008. The pathological diagnosis was urothelial carcinoma (UC), grade 2, pT1. A second TUR was performed 2 months later, and no evidence of malignancy was found. After surgery, he was followed up via cystoscopy and urine cytology for 9 years, with no recurrence of the bladder tumor. In November 2017, he visited our orthopedic department complaining of pain in his left leg. Magnetic resonance imaging revealed an enlarged para-aortic lymph node (a suspected metastasis). Computed tomography (CT) revealed several enlarged lymph nodes but no recurrence in the bladder. A CT-guided biopsy was performed, and histopathological examination revealed a metastasis of the urothelial carcinoma. After definitive diagnosis, he received four cycles of gemcitabine-cisplatin chemotherapy. NMIBC with no local progression rarely causes distant metastases, but the possibility is always there.
  • Yujiro Hayashi; Kazutoshi Fujita; Eri Banno; Marie-Lisa Eich; George J Netto; Norio Nonomura
    International journal of urology : official journal of the Japanese Urological Association 28 7 774 - 776 2021年07月
  • Koichi Okada; Kazutoshi Fujita; Shinichiro Fukuhara; Hiroshi Kiuchi; Motohide Uemura; Ryoichi Imamura; Norio Nonomura
    The world journal of men's health 39 3 533 - 540 2021年07月 [査読有り]
     
    PURPOSE: Germ cell tumors (GCTs) are the most common malignant neoplasms in adolescents and young adults, and most patients with these tumors can be completely cured. Therefore, maintaining quality of life (QOL) is important. Erectile dysfunction (ED) is one factor that reduces the QOL of GCT survivors. We aimed to clarify the relationship between ED and age, follow-up period, serum levels of hormones, and treatment methods for GCT survivors. MATERIALS AND METHODS: We evaluated ED using the Sexual Health Inventory for Men questionnaire (SHIM) and measured serum levels of hormones in survivors after GCT treatment. The relationships between the SHIM score responses and age, serum levels of hormones, follow-up period, and treatment methods were assessed using a logistic analysis. RESULTS: Fifty-two GCT survivors were enrolled and 46 survivors completed the SHIM. The median age, follow-up period, and SHIM score were 38 years, 35 months, and 18, respectively. Regarding the SHIM scores, 85% had scores <22 and 46% had scores <17. The percentage of SHIM scores <17 was 69% in patients with under 2 years of follow-up. It significantly improved to 33% in patients with over 2 years of follow-up. The multivariate analysis identified the follow-up period as an independent factor for SHIM scores <17. Age, serum levels of hormone, and treatment method were not significant factors for SHIM scores <17. CONCLUSIONS: Improvement of SHIM score can be expected after GCT treatment regardless of age, serum levels of hormone, and treatment method.
  • Kazutoshi Fujita; Koji Hatano; Eisuke Tomiyama; Yujiro Hayashi; Makoto Matsushita; Mutsumi Tsuchiya; Tomoyasu Yoshikawa; Mutsuhiro Date; Eiji Miyoshi; Norio Nonomura
    International journal of cancer 148 12 3111 - 3118 2021年06月 
    It is known that core-type fucosylation is higher in prostate cancer cells than in other cancer cell types and is associated with high-risk prostate cancer. Here, we developed an automated microcapillary electrophoresis-based immunoassay system for measuring serum core-type fucosylated prostate-specific antigen (PSA) and evaluated whether the serum fucosylated PSA index (FPI) can detect high-risk prostate cancer. Core-type fucosylated-free PSA was measured by our automated microcapillary electrophoresis-based immunoassay system with Pholiota squarrosa lectin. The FPI was calculated from total PSA and the percentage of fucosylated-free PSA. The optimum model to predict Gleason grade (GG) ≥2 was constructed by multivariate logistic regression analysis. Discrimination was assessed by determining the area under the receiver operator characteristic curve (AUC). The study included 252 men who underwent prostate needle biopsy due to elevated serum PSA levels (4-20 ng/mL), including 138 with GG ≥2. A higher FPI was significantly associated with GG (P < .0001). Multivariate logistic regression analysis showed that age, prostate volume and FPI were significant predictors of GG ≥2. The AUC of FPI and the model were 0.729 (95% confidence interval [CI]: 0.668-0.790) and 0.837 (95% CI: 0.788-0.886), respectively, compared to 0.629 (95% CI: 0.561-0.698) for PSA. Decision curve analysis showed the superior benefit of FPI and the model when compared to PSA. In a cohort with serum PSA levels <20 ng/mL, FPI could differentiate high-risk prostate cancer from biopsy-negative or low-risk prostate cancer. Therefore, FPI could be a useful adjunct in prostate biopsy counseling for men with abnormal PSA levels.
  • Kentaro Takezawa; Sohei Kuribayashi; Koichi Okada; Yosuke Sekii; Yusuke Inagaki; Shinichiro Fukuhara; Hiroshi Kiuchi; Toyofumi Abe; Kazutoshi Fujita; Motohide Uemura; Ryoichi Imamura; Norio Nonomura
    Scientific reports 11 1 10587 - 10587 2021年05月 
    AbstractTo determine the pathophysiology of nocturnal polyuria associated with renal dysfunction, patients who underwent laparoscopic nephrectomy were prospectively studied. The diurnal variation in urine volume, osmolality, and salt excretion were measured on preoperative day 2 and postoperative day 7. The factors associated with an increase in the nighttime urine volume rate with decreased renal function were evaluated using multiple linear regression analysis. Forty-nine patients were included. The estimated glomerular filtration rate decreased from 73.3 ± 2.0 to 47.2 ± 1.6 mL/min/1.73 m2 (P < 0.01) and the nighttime urine volume rate increased from 40.6% ± 2.0% to 45.3% ± 1.5% (P = 0.04) with nephrectomy. The nighttime urine osmolality decreased from 273 ± 15 to 212 ± 10 mOsm/kg and the nighttime salt excretion rate increased from 38.7% ± 2.1% to 48.8% ± 1.7% (both P < 0.01) with nephrectomy. Multiple linear regression analysis showed that the increase in the nighttime urine volume rate was strongly affected by the increase in the nighttime salt excretion rate. A decrease in renal function causes an increase in the nighttime urine volume rate, mainly because of an increase in nighttime salt excretion.Trial registration number: UMIN000036760 (University Hospital Medical Information Network Clinical Trials Registry).Date of registration: From 1 June 2019 to 31 October 2020.
  • Satoshi Nojima; Kei Terayama; Saeko Shimoura; Sachiko Hijiki; Norio Nonomura; Eiichi Morii; Yasushi Okuno; Kazutoshi Fujita
    Cancer cytopathology 2021年05月 

    Background

    Although deep learning algorithms for clinical cytology have recently been developed, their application to practical assistance systems has not been achieved. In addition, whether deep learning systems (DLSs) can perform diagnoses that cannot be performed by pathologists has not been fully evaluated.

    Methods

    The authors initially obtained low-power field cytology images from archived Papanicolaou-stained urinary cytology glass slides from 232 patients. To aid in the development of a diagnosis support system that could identify suspicious atypical cells, the images were divided into high-power field panel image sets for training and testing of the 16-layer Visual Geometry Group convolutional neural network. The DLS was trained using linked information pertaining to whether urothelial carcinoma (UC) in the corresponding histology specimen was invasive or noninvasive, or high-grade or low-grade, followed by an evaluation of whether the DLS could diagnose these characteristics.

    Results

    The DLS achieved excellent performance (eg, an area under the curve [AUC] of 0.9890; F1 score, 0.9002) when trained on high-power field images of malignant and benign cases. The DLS could diagnose whether the lesions were invasive UC (AUC, 0.8628; F1 score, 0.8239) or high-grade UC (AUC, 0.8661; F1 score, 0.8218). Gradient-weighted class activation mapping of these images indicated that the diagnoses were based on the color of tumor cell nuclei.

    Conclusions

    The DLS could accurately screen UC cells and determine the malignant potential of tumors more accurately than classical cytology. The use of a DLS during cytopathology screening could help urologists plan therapeutic strategies, which, in turn, may be beneficial for patients.
  • Eisuke Tomiyama; Kyosuke Matsuzaki; Kazutoshi Fujita; Takashi Shiromizu; Ryohei Narumi; Kentaro Jingushi; Yoko Koh; Makoto Matsushita; Kosuke Nakano; Yujiro Hayashi; Cong Wang; Yu Ishizuya; Taigo Kato; Koji Hatano; Atsunari Kawashima; Takeshi Ujike; Motohide Uemura; Tetsuya Takao; Jun Adachi; Takeshi Tomonaga; Norio Nonomura
    Cancer science 112 5 2033 - 2045 2021年05月 
    Proteomic analysis of urinary extracellular vesicles (EVs) is a powerful approach to discover potential bladder cancer (BCa) biomarkers, however urine contains numerous EVs derived from the kidney and normal urothelial epithelium, which can obfuscate information related to BCa cell-derived EVs. In this study, we combined proteomic analysis of urinary EVs and tissue-exudative EVs (Te-EVs), which were isolated from culture medium of freshly resected viable BCa tissues. Urinary EVs were isolated from urine samples of 11 individuals (7 BCa patients and 4 healthy individuals), and Te-EVs were isolated from 7 BCa tissues. We performed tandem mass tag (TMT)-labeling liquid chromatography (LC-MS/MS) analysis for both urinary EVs and Te-EVs and identified 1960 proteins in urinary EVs and 1538 proteins in Te-EVs. Most of the proteins identified in Te-EVs were also present in urinary EVs (82.4%), with 55 of these proteins showing upregulated levels in the urine of BCa patients (fold change > 2.0; P < .1). Among them, we selected 22 membrane proteins as BCa biomarker candidates for validation using selected reaction monitoring/multiple reaction monitoring (SRM/MRM) analysis on urine samples from 70 individuals (40 BCa patients and 30 healthy individuals). Six urinary EV proteins (heat-shock protein 90, syndecan-1, myristoylated alanine-rich C-kinase substrate (MARCKS), MARCKS-related protein, tight junction protein ZO-2, and complement decay-accelerating factor) were quantified using SRM/MRM analysis and validated as significantly upregulated in BCa patients (P < .05). In conclusion, the novel strategy that combined proteomic analysis of urinary EVs and Te-EVs enabled selective detection of urinary BCa biomarkers.
  • Kazutoshi Fujita
    Translational andrology and urology 10 4 1827 - 1828 2021年04月
  • Yujiro Hayashi; Kazutoshi Fujita
    Translational andrology and urology 10 4 1865 - 1877 2021年04月 
    Liquid biopsy technique targeting urinary cell-free DNA (cfDNA) is getting a lot of attention to overcome limitations of the present treatment strategy for urothelial carcinoma, including urothelial bladder carcinoma (UBC) and upper tract urothelial carcinoma (UTUC). Analysis of tumor-derived DNA in urine focusing either on genomic or epigenomic alterations, holds great potential as a noninvasive method for the detection of urothelial carcinoma with high accuracy. It is also predictive of prognosis and response to drugs, and reveals the underlying characteristics of different stages of urothelial carcinoma. Although cfDNA methylation analyses based on a combination of several methylation profiles have demonstrated high sensitivity for UBC diagnosis, there have been few reports involving epigenomic studies of urinary cfDNA. In mutational analyses, frequent gene mutations (TERT promoter, TP53, FGFR3, PIK3CA, RAS, etc.) have been detected in urine supernatant by using remarkable technological innovations such as next-generation sequencing and droplet digital PCR. These methods allow highly sensitive detection of rare mutation alleles while minimizing artifacts. In this review, we summarize the current insights into the clinical applications of urinary cfDNA from patients with urothelial carcinoma. Although it is necessary to conduct prospective multi-institutional clinical trials, noninvasive urine biopsy is expected to play an important role in the realization of precision medicine in patients with urothelial carcinoma in the near future.
  • Koji Hatano; Kazutoshi Fujita
    Translational andrology and urology 10 4 1890 - 1907 2021年04月 [査読有り]
     
    Over the past decade, there has been remarkable progress in prostate cancer biomarker discovery using urine- and blood-based assays. A liquid biopsy is a minimally invasive procedure to investigate the cancer-related molecules in circulating tumor cells (CTCs), cell-free DNA, and extracellular vesicles (EVs). Liquid biopsies have the advantage of detecting heterogeneity as well as acquired resistance in cancer. EVs are cell-derived vesicles enclosed by a lipid bilayer and contain various molecules, such as nucleic acids, proteins, and lipids. In patients with cancer, EVs derived from tumors can be isolated from urine, plasma, and serum. The advances in isolation techniques provide the opportunity to use EVs as biomarkers in the clinic. Emerging evidence suggests that EVs can be useful biomarkers for the diagnosis of prostate cancer, especially high-grade cancer. EVs can also be potent biomarkers for the prediction of disease progression in patients with castration-resistant prostate cancer (CRPC). EVs shed from cancer and stromal cells are involved in the development of tumor microenvironments, enhancing cancer progression, metastasis, and drug resistance. Here, we provide an overview of the use of EVs for the diagnosis of clinically significant prostate cancer as well as for predicting disease progression. We also discuss the biological function of EVs, which regulate cancer progression.
  • Kyosuke Matsuzaki; Kazutoshi Fujita; Eisuke Tomiyama; Koji Hatano; Yujiro Hayashi; Cong Wang; Yu Ishizuya; Yoshiyuki Yamamoto; Takuji Hayashi; Taigo Kato; Kentaro Jingushi; Atsunari Kawashima; Takeshi Ujike; Akira Nagahara; Motohide Uemura; Kazutake Tsujikawa; Norio Nonomura
    Translational andrology and urology 10 4 1918 - 1927 2021年04月 [査読有り]
     

    Background

    Extracellular vesicles (EVs) including exosomes are present in blood, urine, and saliva and contain proteins, microRNAs, and messenger RNAs. We investigated microRNAs in urinary EVs to discover new biomarkers of prostate cancer (PCa).

    Methods

    We isolated EVs from urine obtained following digital rectal examination (DRE) of 14 men with elevated levels of serum prostate-specific antigen (PSA) [negative biopsy (n=4) and PCa with Gleason scores of 6 (n=3), 7 (n=3), and 8-9 (n=4)]. MicroRNAs extracted from EVs were analyzed by microRNA microarray.

    Results

    MicroRNAs miR-30b-3p and miR-126-3p were identified as being overexpressed in urinary EVs of the PCa patients versus the biopsy-negative men, but no microRNAs were associated with the Gleason score. In the independent cohort as well, these two microRNAs were overexpressed in urinary EVs from the PCa patients versus the negative-biopsy men. Logistic regression analysis adjusted by age and PSA showed that these two microRNAs were significantly associated with the prediction of PCa in biopsy specimens. Sensitivity and specificity of miR-30b-3p and miR-126-3p for the prediction of PCa were 46.4% and 88.0% and 60.7% and 80.0%, respectively, which were better than those of serum PSA (53.5% and 64.0%, respectively).

    Conclusions

    MiR-30b-3p and miR-126-3p in urinary EVs could be potential biomarkers of PCa.
  • Taigo Kato; Kazuma Kiyotani; Eisuke Tomiyama; Yoko Koh; Makoto Matsushita; Yujiro Hayashi; Kosuke Nakano; Yu Ishizuya; Cong Wang; Koji Hatano; Atsunari Kawashima; Takeshi Ujike; Kazutoshi Fujita; Norio Nonomura; Motohide Uemura
    Oncoimmunology 10 1 1862948 - 1862948 2021年01月 
    Immune checkpoint inhibitors (ICIs) offer significant clinical benefits to a subset of cancer patients via the induction of a systemic T cell-mediated anti-cancer immune response. Thus, the dynamic characterization of T cell repertoires in the peripheral blood has the potential to demonstrate noninvasive predictive biomarkers for the clinical efficacy of ICIs. In this study, we collected tumor tissues and peripheral blood samples from 25 patients with advanced kidney cancer before anti-programmed cell death protein 1 (PD-1) treatment and 1, 3, and 6 months after treatment initiation. Furthermore, we applied a next-generation sequencing approach to characterize T cell receptor (TCR) alpha and beta repertoires. TCR repertoire analysis revealed that the responders to anti-PD-1 showed an expansion of certain T cell clones even in the blood, as evidenced by the significant decrease in the TCR diversity index and increase in the number of expanded TCR clonotypes 1 month after treatment. Interestingly, these expanded TCR clonotypes in the peripheral blood were significantly shared with tumor-infiltrating T cells in responders, indicating that they have many circulating T cells that may recognize cancer antigens. Expression analysis also revealed that 1 month after treatment, T cells from the peripheral blood of responders showed significantly elevated transcriptional levels of Granzyme B, Perforin, CD39, and PD-1, markers of cancer-associated antigen-specific T cells. Altogether, we propose that global TCR repertoire analysis may allow identifying early surrogate biomarkers in the peripheral blood for predicting clinical responses to anti-PD-1 monotherapy.
  • Eisuke Tomiyama; Kazutoshi Fujita; Mamoru Hashimoto; Shogo Adomi; Atsunari Kawashima; Takafumi Minami; Kazuhiro Yoshimura; Hirotsugu Uemura; Norio Nonomura
    Translational Andrology and Urology 11 12 1747 - 1761 2021年01月 
    BACKGROUND AND OBJECTIVE: Although upper tract urothelial carcinoma (UTUC) shares the histological appearance of urinary bladder cancer (UBC), molecular studies suggest that UTUC and UBC represent two distinct disease entities. However, treatment approaches for UTUC are virtually extrapolated from the evidence on UBC. As targeted drugs-immune-checkpoint inhibitors, fibroblast growth factor receptor inhibitors, and antibody-drug conjugates-target specific molecules, gaining more knowledge about the target-molecular profiles of each drug can help formulate optimal treatment strategies for UTUC. METHODS: This narrative review summarized the subgroup analyses of clinical trials of FDA-approved targeted drugs to explore the differential effects of each targeted drug when administered for UTUC compared to UBC. We focused on the differences in mutation frequency, RNA expression subtype, and therapeutic target protein expressions (specifically PD-L1, Nectin-4, and Trop-2) between UTUC and UBC and discussed their relationship with the efficacy of each targeted drug. KEY CONTENT AND FINDINGS: A clinical trial of nivolumab in an adjuvant setting (CheckMate 274) implied that immune-checkpoint inhibitors might be less efficacious in UTUC than in UBC. Genomic and transcriptomic studies suggest that UTUC has a high frequency of FGFR3 mutations and predominantly shows the luminal papillary subtype, which is immunologically cold with low T-cell infiltration. These findings are consistent with a possible lower response rate to immunotherapy in UTUC than that in UBC. Clinical trials of enfortumab vedotin in a third-line setting (EV201 and EV301) implied that enfortumab vedotin might be less efficacious in UTUC than in UBC. Previous immunohistochemical analyses suggest that UTUC might have a slightly lower rate of Nectin-4 positivity than UBC, indicating that enfortumab vedotin was less efficacious in UTUC than in UBC. CONCLUSIONS: Clinical differences in the effects of targeted drugs for UTUC and UBC may highlight the molecular differences between these diseases. The treatment strategy should be optimized based on further investigation of the molecular characteristics of UTUC.
  • 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年 
    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.
  • Tomohiro Kanaki; Atsunari Kawashima; Shinichiro Fukuhara; Kazutoshi Fujita; Motohide Uemura; Hiroshi Kiuchi; Ryoichi Imamura; Norio Nonomura
    Nihon Hinyokika Gakkai zasshi. The japanese journal of urology 112 1 29 - 33 2021年 
    We present a case of 75 year's old man for whom small bowel resection was performed for a small intestinal tumor diagnosed as a gastrointestinal stromal tumor (GIST) with KIT exon 11 mutation and intermediate Miettinen risk. Computed tomography (CT) 18 months after surgery showed a right adrenal mass measuring 20 mm in size. Imatinib therapy couldn't show the tumor shrinkage, and the adrenal mass increased up to 37 mm in size 3 months later. He was referred to our department for further examination and treatment. We diagnosed this adrenal tumor as imatinib resistant GIST or adrenal primary malignancy and performed retroperitoneal laparoscopic right adrenalectomy. The pathological diagnosis was diffuse large B-cell lymphoma (DLBCL) not GIST and PET-CT revealed systemic metastasis of DLBCL one month later after surgery. Six courses of R-CHOP therapy achieved a complete response.
  • 小腸GIST術後の治療抵抗性副腎腫瘍に対し副腎摘除術を施行し副腎原発悪性リンパ腫であった1例
    金城 友紘; 河嶋 厚成; 福原 慎一郎; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 野々村 祝夫
    日本泌尿器科学会雑誌 112 1 29 - 33 (一社)日本泌尿器科学会 2021年01月
  • Yujiro Hayashi; Kazutoshi Fujita; George J Netto; Norio Nonomura
    Frontiers in oncology 11 705440 - 705440 2021年 
    Urothelial carcinoma (UC) is a common urological malignancy with a high rate of disease recurrence. Telomerase activity, a hallmark of cancer characterized by overcoming the replicative senescence, is upregulated in over 90% of patients with UC. Somatic mutations in the promoter region of telomerase reverse transcriptase (TERT) are frequently detected in UC, and drive telomerase activity. Recent studies have demonstrated a strong association between TERT promoter mutation and tumorigenesis of UC. Also, TERT promoter mutation has great potential for diagnosis, as well as prognosis in UC treatment, and this is also applicable for the liquid biopsy techniques. In this review, we discuss the progress in these areas and highlight the challenges, clinical potential, and future direction for developing UC treatment methods.
  • 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年 
    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.
  • Tetsuya Yamamoto; Taigo Kato; Koji Hatano; Atsunari Kawashima; Takeshi Ujike; Shinichiro Fukuhara; Hiroshi Kiuchi; Ryoichi Imamura; Naokazu Ibuki; Kazuma Kiyotani; Masako Kurashige; Eichi Morii; Kazutoshi Fujita; Norio Nonomura; Motohide Uemura
    Frontiers in oncology 11 691996 - 691996 2021年 
    Tuberous sclerosis complex is a genetic disorder characterized by facial angiofibromas, intellectual disability, epilepsy, and tumor formation in multiple organs, including the kidney. Renal cell carcinoma occurs in 2%-4% of patients with tuberous sclerosis complex, often developing multiply and bilaterally. Renal cell carcinoma associated with this genetic disorder may include complex tumor heterogeneity caused by the spatially different mutational landscape. Herein, we report the case of a female patient with tuberous sclerosis complex who developed multiple renal tumors. A 44-year-old female patient with tuberous sclerosis complex developed three different histological types of tumor-angiomyolipoma, clear cell renal cell carcinoma, and papillary renal cell carcinoma-in the left kidney at first renal cell carcinoma recurrence. The papillary renal cell carcinoma was morphologically atypical, indicating that its occurrence was associated with the genetic disorder. Furthermore, whole-exome sequencing revealed distinct patterns of somatic mutation in the three tumor types, and the atypical papillary renal cell carcinoma possessed a different mutational landscape than that of typical papillary renal cell carcinomas. Our findings indicate that tumors associated with tuberous sclerosis complex may be diagnosed with careful pathological examination. Furthermore, somatic mutation profiles of these tumors revealed their unique features, providing important information for further understanding the mechanism of multiple tumor development in patients with tuberous sclerosis complex.
  • TOSHIHIRO UEMURA; TAIGO KATO; AKIRA NAGAHARA; ATSUNARI KAWASHIMA; KOJI HATANO; TAKESHI UJIKE; YUSUKE ONO; HIROKI HIGASHIHARA; KAZUTOSHI FUJITA; SHINICHIRO FUKUHARA; HIROSHI KIUCHI; RYOICHI IMAMURA; NORIYUKI TOMIYAMA; NORIO NONOMURA; MOTOHIDE UEMURA
    In Vivo 35 3 1573 - 1579 2021年
  • Eisuke Tomiyama; Kazutoshi Fujita; Norio Nonomura
    Methods in molecular biology (Clifton, N.J.) 2292 173 - 181 2021年01月 [査読有り]
     
    Recently, urinary extracellular vesicles (EVs) have garnered interest as a potential source of noninvasive biomarkers of diseases related to urinary organs (kidney, bladder, urethra, and prostate).Ultracentrifugation is considered the gold standard method for isolation of EVs. However, the precipitates after ultracentrifugation steps are usually contaminated with soluble proteins, such as the Tamm-Horsfall protein (uromodulin).Therefore, ultracentrifugation on a sucrose-deuterium oxide (D2O) cushion for purer EV isolation is performed to remove these proteins. In addition, as a nonultracentrifugation method for EV isolation, we have also adopted the phosphatidylserine (PS) affinity method, which is a novel method for EV purification using the T-cell immunoglobulin domain and the mucin domain-containing protein 4 (Tim4).Here, we describe an ultracentrifugation protocol based on a sucrose-D2O cushion and the PS affinity method protocol for the isolation of urinary EVs.
  • Kosuke Nakano; Yoshiyuki Yamamoto; Gaku Yamamichi; Satoru Yumiba; Eisuke Tomiyama; Makoto Matsushita; Yoko Koh; Yujiro Hayashi; Cong Wang; Yu Ishizuya; Taigo Kato; Koji Hatano; Atsunari Kawashima; Takeshi Ujike; Kazutoshi Fujita; Norio Nonomura; Motohide Uemura
    Cancer science 112 1 168 - 177 2021年01月 [査読有り]
     
    Reliable biomarkers for upper-tract urothelial carcinoma (UTUC) have yet to be found. Plasma cell-free DNA (cfDNA) has been clinically applied as a minimally invasive blood biomarker for various types of cancer. We investigated the utility of plasma cfDNA as a blood biomarker in UTUC patients. The fragment size of plasma cfDNA was shorter and the concentration of plasma cfDNA was higher in UTUC patients than in healthy controls. The fragment size of plasma cfDNA had a moderate accuracy of diagnosing UTUC (area under the curve [AUC] = 0.72), and multivariate analysis indicated that the fragment size of plasma cfDNA was significantly associated with the presence of UTUC (odds ratio = 0.807, 95% confidence interval [CI] 0.653-0.955, P = .024). Furthermore, we found that the size of plasma cfDNA shortens alongside disease progression (P < .001). The fragment size of plasma cfDNA in UTUC patients may be an auxiliary tool for the diagnosis of UTUC patients. We also found a high correlation between the fragmentation of plasma cfDNA and serum levels of three inflammatory cytokines (TNFα [r = -.837], interleukin-6 [IL-6] [r = -.964], interleukin-1 receptor antagonist [IL-1ra] [r = -.911]), which were reported to associate with poor prognosis. Also, we found that the proportion of short fragments of cfDNA was significantly increased in the supernatant of peripheral blood mononuclear cells (PBMCs) from healthy controls cultured in media containing TNFα. These results supposed that cancer-associated systemic inflammation, especially tumor necrosis factor-α (TNFα), may contribute to the fragmentation of plasma cfDNA in UTUC patients.
  • Norichika Ueda; Makoto Kondo; Kentaro Takezawa; Hiroshi Kiuchi; Yosuke Sekii; Yusuke Inagaki; Tetsuji Soda; Shinichiro Fukuhara; Kazutoshi Fujita; Motohide Uemura; Ryoichi Imamura; Yasushi Miyagawa; Norio Nonomura; Shoichi Shimada
    Scientific reports 10 1 21167 - 21167 2020年12月 
    When bacteria enter the bladder lumen, a first-stage active defensive mechanism flushes them out. Although urinary frequency induced by bacterial cystitis is a well-known defensive response against bacteria, the underlying mechanism remains unclear. In this study, using a mouse model of acute bacterial cystitis, we demonstrate that the bladder urothelium senses luminal extracellular bacterial lipopolysaccharide (LPS) through Toll-like receptor 4 and releases the transmitter ATP. Moreover, analysis of purinergic P2X2 and P2X3 receptor-deficient mice indicated that ATP signaling plays a pivotal role in the LPS-induced activation of L6-S1 spinal neurons through the bladder afferent pathway, resulting in rapid onset of the enhanced micturition reflex. Thus, we revealed a novel defensive mechanism against bacterial infection via an epithelial-neural interaction that induces urinary frequency prior to bacterial clearance by neutrophils of the innate immune system. Our results indicate an important defense role for the bladder urothelium as a chemical-neural transducer, converting bacterial LPS information into neural signaling via an ATP-mediated pathway, with bladder urothelial cells acting as sensory receptor cells.
  • 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年12月 [査読有り]
  • Yoko Koh; Atsunari Kawashima; Takeshi Ujike; Akira Nagahara; Kazutoshi Fujita; Hiroshi Kiuchi; Ryoichi Imamura; Yasushi Miyagawa; Norio Nonomura; Motohide Uemura
    Anti-cancer drugs 31 10 1099 - 1102 2020年11月 
    We report the failure to achieve castrate level of serum testosterone during luteinizing hormone-releasing hormone agonist therapy in a patient with prostate cancer. A 76-year-old man was admitted to our hospital for evaluation of an elevated serum prostate specific antigen (PSA) level (191.10 ng/ml) in August 2011. He was diagnosed with T3aN0M1b prostate adenocarcinoma. A combined androgen blockade using luteinizing hormone-releasing hormone agonist (the 1-month depot of leuprorelin acetate) and antiandrogen was administered. Due to liver dysfunction, antiandrogens, both bicalutamide and flutamide, were stopped. The 1-month depot was switched to the 3-month depot in May 2013, but the patient complained of induration and abscess at the infection site. Leuprorelin acetate was replaced by goserelin acetate. Because no adverse event appeared after injection of the 1-month depot of goserelin acetate, the 3-month depot was administered in October 2013. The PSA level increased gradually, and the testosterone level was greater than 50 ng/dl, that is, above castrate range. The 3-month depot of both leuprorelin acetate and goserelin acetate was not effective for this patient. For this reason, the 1-month depot of leuprorelin acetate was started resulting in a rapid decrease in PSA and testosterone levels. Thereafter, androgen depriving therapy could be continued. Androgen deprivation therapy is the standard treatment for patients with advanced prostate cancer and luteinizing hormone-releasing hormone aims to suppress serum testosterone to castrate range. We recommend assessing the serum testosterone levels during luteinizing hormone-releasing hormone agonist therapy for monitoring treatment efficacy and verifying progression when the PSA level increases.
  • 久次米 雄馬; 河嶋 厚成; 河田 信彦; 竹澤 健太郎; 加藤 大悟; 波多野 浩士; 氏家 剛; 阿部 豊文; 福原 慎一郎; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 野々村 祝夫
    日本泌尿器科学会雑誌 111 4 145 - 149 (一社)日本泌尿器科学会 2020年10月 
    74歳,女性.入院半年前から間欠的に右側腹部痛を自覚していたが放置.腹部単純CTで右上腹部腫瘤と下大静脈の拡張を認め,当科紹介となった.腹部造影CTでは,右上腹部に15×12cmの不均一な造影効果を示す腫瘍を認め,栄養血管は副腎動脈と考えられた.下大静脈腫瘍栓と肝腫瘤も認め,副腎癌cT4N0M1 stage IVと診断した.約1ヵ月で病勢進行に伴う全身状態の増悪を認めた.腫瘍栓によりうっ血肝を呈しており,二次性Budd-Chiari症候群と診断した.転移巣を含む腫瘍根治切除術を施行したところ,摘出標本は1,100gで分葉状構造を呈していた.腫瘍と副腎に連続性は認めず,病理結果は平滑筋肉腫であった.術後6ヵ月時点で再発なく生存中である.(著者抄録)
  • Yujiro Hayashi; Kazutoshi Fujita; Satoshi Nojima; Eisuke Tomiyama; Makoto Matsushita; Yoko Koh; Kosuke Nakano; Cong Wang; Yu Ishizuya; Taigo Kato; Koji Hatano; Atsunari Kawashima; Takeshi Ujike; Motohide Uemura; Ryoichi Imamura; Eiichi Morii; Norio Nonomura
    Molecular oncology 14 10 2375 - 2383 2020年10月 [査読有り]
     
    Telomerase reverse transcriptase (TERT) promoter mutations are frequently found in tumors or urine from patients with urothelial carcinoma (UC). TERT promoter mutations are also detected in urine from patients with no evidence of cancer but are associated with subsequent UC development. Mutations in the TERT promoter are thought to be present in nonmalignant urothelium (NMU) during early stages of tumor formation prior to pathological change, but this has not been proven directly. In this proof-of-concept study, we investigated the clinical utility of TERT promoter mutation analysis in NMU of patients with non-muscle-invasive bladder cancer (NMIBC). This single-institute study included 53 primary tumors and 428 systematic bladder biopsy specimens from 54 patients with NMIBC. All patients underwent systematic random biopsy and transurethral resection of the bladder tumor. Genomic DNA was analyzed for TERT C228T and C250T mutations using droplet digital PCR (ddPCR). The association between TERT promoter mutation of NMU and bladder recurrence was examined by the Kaplan-Meier method and Cox proportional hazards model. Of the 54 patients, 16 (29.6%) had a TERT C228T mutation and three (5.6%) had a TERT C250T mutation in NMU. Of 428 biopsy specimens, the TERT C228T mutation was detected in 9% (31/364) of normal urothelium, 27% (4/15) of urothelial dysplasia (UD), 50% (9/18) of UD suspicious for carcinoma in situ (CIS), and 58% (18/31) of CIS. During follow-up (median: 3.7 years), 22 (40.7%) patients experienced bladder recurrence and five (9.3%) experienced disease progression. Cox proportional hazard analysis showed that TERT C228T mutation in NMU was significantly associated with bladder recurrence after adjustment for cofounding factors (P = 0.0128). Thus, TERT C228T mutation was detected in NMU, which was a reliable independent prognostic factor of bladder tumor recurrence.
  • Yoko Maegawa; Taigo Kato; Shinichiro Fukuhara; Hiroshi Kiuchi; Ryoichi Imamura; Motohide Uemura; Norio Nonomura; Kazutoshi Fujita
    IJU case reports 3 5 176 - 179 2020年09月 [査読有り]
     
    Introduction: Combined anti-cytotoxic-T-lymphocyte antigen 4 and programmed cell death 1 blockade induced high rates of immune-related adverse events in patients with renal cell carcinoma. However, the safety of reinitiating anti-programmed cell death 1 monotherapy for patients who discontinued combination therapy due to immune-related adverse events is largely unknown. Case presentation: We report the case of 74-year-old man who received combination therapy with anti-cytotoxic-T-lymphocyte antigen 4 and programmed cell death 1 inhibitors for advanced renal cell carcinoma. After three cycles of combination therapy, he complained severe immune-related adverse events including grade 3 nausea and anorexia, and grade 3 diarrhea, leading to discontinuation of the therapy. He started readministration of anti-programmed cell death 1 monotherapy at 41 weeks after discontinuation due to the new lung metastatic lesion. Importantly, he experienced only grade 1 diarrhea, which can be controlled with prednisolone. Conclusion: The readministration of anti-programmed cell death 1 monotherapy with close monitoring can be an acceptable treatment even after discontinuation of combination therapy.
  • Taigo Kato; Eisuke Tomiyama; Yoko Koh; Makoto Matsushita; Yujiro Hayashi; Kosuke Nakano; Y U Ishizuya; Cong Wang; Koji Hatano; Atsunari Kawashima; Takeshi Ujike; Keisuke Kawasaki; Eiichi Morii; Kunihito Gotoh; Hidetoshi Eguchi; Kazuma Kiyotani; Kazutoshi Fujita; Norio Nonomura; Motohide Uemura
    Anticancer research 40 9 4875 - 4883 2020年09月 [査読有り]
     
    BACKGROUND/AIM: Some reports showed encouraging efficacy of immune checkpoint inhibitors among patients who experienced immune-related adverse events (irAEs). Thus, characterization of T-cell repertoire and immune signatures in peripheral blood mononuclear cells (PBMCs) and tumors before and after immune checkpoint inhibitors treatment should contribute to better understanding of irAE-provoked anticancer immune responses. MATERIALS AND METHODS: We applied expression analysis of immune-related genes and T-cell receptor sequencing in tumor and PBMCs from five patients with renal cell carcinoma before combined immunotherapy and at the onset of severe irAEs. RESULTS: We found that the cluster of differentiation 8 (CD8)/forkhead box P3(FOXP3), granzyme B(GZMB)/CD3, perforin 1(PRF1)/CD3 and programmed cell death 1(PD1)/CD8 expression ratios were significantly elevated in PBMCs at the onset of irAEs. In addition, we found expansion of certain T-cell clones in metastatic tissue after irAEs, which were already increased in peripheral blood at the onset of irAEs. CONCLUSION: irAE-provoked T-cells may also circulate and attack distant tumors, leading to durable response in patients with irAEs.
  • Takuji Hayashi; Kazutoshi Fujita; Yujiro Hayashi; Koji Hatano; Atsunari Kawashima; David J McConkey; Norio Nonomura
    International journal of molecular sciences 21 17 2020年08月 [査読有り]
     
    Bladder cancer is the most common cancer of the urinary tract. Although nonmuscle-invasive bladder cancers have a good prognosis, muscle-invasive bladder cancers promote metastases and have a poor prognosis. Comprehensive analyses using RNA sequence of clinical tumor samples in bladder cancer have been reported. These reports implicated the candidate genes and pathways that play important roles in carcinogenesis and/or progression of bladder cancer. Further investigations for the function of each mutation are warranted. There is suggestive evidence for several environmental factors as risk factors of bladder cancer. Environmental factors such as cigarette smoking, exposure to chemicals and gases, bladder inflammation due to microbial and parasitic infections, diet, and nutrition could induce several genetic mutations and alter the tumor microenvironment, such as immune cells and fibroblasts. The detailed mechanism of how these environmental factors induce carcinogenesis and/or progression of bladder cancer remains unclear. To identify the relationship between the mutations and the lifestyle could be useful for prevention and treatment of bladder cancer.
  • Koji Hatano; Kazutoshi Fujita; Norio Nonomura
    Journal of clinical medicine 9 8 2020年08月 [査読有り]
     
    Chronic inflammation is a major cause of human cancers. The environmental factors, such as microbiome, dietary components, and obesity, provoke chronic inflammation in the prostate, which promotes cancer development and progression. Crosstalk between immune cells and cancer cells enhances the secretion of intercellular signaling molecules, such as cytokines and chemokines, thereby orchestrating the generation of inflammatory microenvironment. Tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) play pivotal roles in inflammation-associated cancer by inhibiting effective anti-tumor immunity. Anti-inflammatory agents, such as aspirin, metformin, and statins, have potential application in chemoprevention of prostate cancer. Furthermore, pro-inflammatory immunity-targeted therapies may provide novel strategies to treat patients with cancer. Thus, anti-inflammatory agents are expected to suppress the "vicious cycle" created by immune and cancer cells and inhibit cancer progression. This review has explored the immune cells that facilitate prostate cancer development and progression, with particular focus on the application of anti-inflammatory agents for both chemoprevention and therapeutic approach in prostate cancer.
  • 吉村 一宏; 藤田 和利; 植村 天受
    Uro-Lo: 泌尿器Care & Cure 25 4 530 - 533 (株)メディカ出版 2020年08月
  • Shogo Adomi; Kazutoshi Fujita; Kazuhiro Yoshimura; Hirotsugu Uemura
    International journal of urology : official journal of the Japanese Urological Association 27 8 655 - 656 2020年08月 [査読有り]
  • 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 21 15 2020年07月 [査読有り]
     
    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.
  • Kentaro Nishida; Atsunari Kawashima; Takayuki Kanazawa; Yujiro Kidani; Tetsuya Yoshida; Michinari Hirata; Kei Yamamoto; Yoko Yamamoto; Masaaki Sawada; Ryo Kato; Taigo Kato; Koji Hatano; Takeshi Ujike; Kazutoshi Fujita; Motohide Uemura; Akiko Morimoto-Okazawa; Kota Iwahori; Makoto Yamasaki; Naganari Ohkura; Shimon Sakaguchi; Norio Nonomura; Yuichiro Doki; Hisashi Wada
    International immunology 32 5 347 - 357 2020年05月 [査読有り]
     
    OBJECTIVE: CD4+CD8+ T cells are expressed in some cancer patients including those with renal cell carcinoma (RCC). However, no reports have mentioned the clinical importance of this expression. We evaluated the expression of CD4+CD8+ T cells in patients with various cancer types to clarify clinical characteristics and prognostic importance significantly correlating with these T cells. METHODS: Expression of CD4+CD8+ T cells was evaluated using flowcytometry in tissue-infiltrating lymphocytes extracted from 260 cancer tissues including 104 RCC samples. RNA sequencing and characterization and regression (Citrus) was used to determine characteristics. The prognostic importance of CD4+CD8+ T cells was evaluated by Cox regression analysis. RESULTS: Among eight cancer types, expression of CD4+CD8+ T cells was significantly highest in RCC patients. According to the expression of CD4+CD8+ T cells in adjacent normal tissue-infiltrating lymphocytes, 24 patients (23.1%) were defined as being positive for CD4+CD8+ with an expression higher than 9.29% in RCC patients. Citrus showed CD8+PD-1+TIM-3+CD103- T cells to be a specific subpopulation of CD4+CD8+ T cells. RNA sequencing revealed that CD4+CD8+ T cells had significantly lower diversity than the other T cells and shared most T-cell receptor clones with CD8+ not CD4+ T cells. Expression of CD4+CD8+ T cells was identified as an independent predictor of overall survival (hazard ratio: 0.11, 95% confidence interval: 0.01-0.86, P = 0.035) in multivariate analysis. CONCLUSIONS: The expression of CD4+CD8+ T cells was significantly up-regulated in RCC patients and correlated significantly with prognostic importance in surgically treated RCC patients.
  • Kazutoshi Fujita; Taigo Kato; Koji Hatano; Atsunari Kawashima; Takeshi Ujike; Motohide Uemura; Ryoichi Imamura; Koji Okihara; Osamu Ukimura; Tsuneharu Miki; Toshihiro Nakajima; Yasufumi Kaneda; Norio Nonomura
    Cancer science 111 5 1692 - 1698 2020年05月 [査読有り]
     
    Inactivated hemagglutinating virus of Japan envelope (HVJ-E) have an anti-tumor effect and tumor immunity. We conducted an open-label, phase I, dose-escalation study in patients with castration-resistant prostate cancer (CRPC) to determine the safety and efficacy of intratumoral and subcutaneous injection of HVJ-E (GEN0101). Patients with CRPC, who were resistant to or unable to receive standard of care, were included. GEN0101 was injected directly into the prostate and subcutaneously in two 28-day treatment cycles. The primary end points were to evaluate safety and tolerability of GEN0101 and determine its recommended dose. The secondary end points were to analyze anti-tumor effect and tumor immunity. Three patients received 30,000 mNAU of GEN0101 while 6 received 60,000 mNAU. There was no dose-limiting toxicity, and the recommended dose of GEN0101 was defined to be 60,000 mNAU. Radiographically, one patient had stable disease and 2 had progressive disease in the low-dose group, whereas 5 patients had stable disease and one had progressive disease in the high-dose group. Three patients in the high-dose group showed reduction in lymph node metastasis. PSA increase rates in the high-dose group were suppressed more than those in the low-dose group. NK cell activity was enhanced in 2 patients of the low-dose group and in 5 patients in the high-dose group. In conclusions, intratumoral and subcutaneous injections of GEN0101 were well tolerated and feasible to use. The study is registered at UMIN Clinical Trials Registry, number UMIN000017092.
  • Atsunari Kawashima; Takayuki Kanazawa; Yujiro Kidani; Tetsuya Yoshida; Michinari Hirata; Kentaro Nishida; Satoshi Nojima; Yoshiyuki Yamamoto; Taigo Kato; Koji Hatano; Takeshi Ujike; Akira Nagahara; Kazutoshi Fujita; Akiko Morimoto-Okazawa; Kota Iwahori; Motohide Uemura; Ryoichi Imamura; Naganari Ohkura; Eiichi Morii; Shimon Sakaguchi; Hisashi Wada; Norio Nonomura
    Scientific reports 10 1 6220 - 6220 2020年04月 [査読有り]
     
    It is important to evaluate the clinical importance of both CD8 T cells and CD4 T cells expression simultaneously because they have crucial networks in tumour targeting immune responses. In 97 RCC patients, RNA sequencing and gene set enrichment analysis of both CD8 and CD4 T cells based on the expression levels of PD-1 and TIM-3 implied that the populations of PD-1+TIM-3+ CD8 T cells and PD-1lowTIM-3 + CD4 T cells were characterized as exhausted CD8 T cells and regulatory CD4 T cells, respectively. These populations of CD4 and CD8 T cells were significantly upregulated in the patients with RCC of higher WHO/ISUP grade (grades 3, 4) (P < 0.001). Moreover, the cytokine productivities of each population in both CD4 and CD8 T cells of the higher-grade patients were significantly lower than those of the lower-grade patients (P < 0.05). Multivariate analysis showed the prognosis of patients with metastatic RCC of higher WHO/ISUP grade treated by nivolumab to be significantly worse than that of patients with lower grade (P = 0.026). This study showed that tumour grade significantly correlated with dysfunction of both CD4+ and CD8+ TILs and the efficacy of nivolumab treatment.
  • Ryosuke Nakamura; Takero Hirata; Osamu Suzuki; Keisuke Otani; Naoki Kai; Koji Hatano; Kazutoshi Fujita; Motohide Uemura; Ryoichi Imamura; Kazunori Tanaka; Yasuo Yoshioka; Norio Nonomura; Kazuhiko Ogawa
    Anticancer research 40 4 2053 - 2057 2020年04月 [査読有り]
     
    BACKGROUND: The present study aimed to evaluate the toxicity and efficacy of stereotactic body radiotherapy (SBRT) for localized prostate cancer. PATIENTS AND METHODS: We investigated 25 patients treated with SBRT of 35 Gy per five fractions from May 2014 to March 2015. RESULTS: The median age of patients was 70 years, four (16%) patients were low risk and 21 (84%) were intermediate risk. Seven (28%) patients received neoadjuvant androgen-deprivation therapy. The median follow-up time was 53 months. Grade 2 acute and late genitourinary toxicities were observed in five (20%) and two (8%) patients and there were no Grade 2 gastrointestinal toxicities. There were no Grade 3 or higher acute or late toxicities at 2 years follow-up. The biochemical relapse-free survival rate at 2 years was 100%. CONCLUSION: SBRT of 35 Gy per five fractions is a promising treatment method in the short term for prostate cancer.
  • Cong Wang; Motohide Uemura; Eisuke Tomiyama; Makoto Matsushita; Yoko Koh; Kosuke Nakano; Yujiro Hayashi; Yu Ishizuya; Kentaro Jingushi; Taigo Kato; Koji Hatano; Atsunari Kawashima; Takeshi Ujike; Akira Nagahara; Kazutoshi Fujita; Ryoichi Imamura; Kazutake Tsujikawa; Norio Nonomura
    Cancer science 111 4 1146 - 1155 2020年04月 [査読有り]
     
    Although several studies have reported that microRNA (miR)-92b-3p is involved in various cellular processes related to carcinogenesis, its physiological role in clear cell renal cell carcinoma (ccRCC) remains unclear. To clarify the role of miR-92b-3p in ccRCC, we compared miR-92b-3p expression levels in ccRCC tissues and adjacent normal renal tissues. Significant upregulation of miR-92b-3p was observed in ccRCC tissues. Overexpression of miR-92b-3p using a miRNA mimic promoted proliferation, migration, and invasion activities of ACHN cells. Functional inhibition of miR-92b-3p by a hairpin miRNA inhibitor suppressed Caki-2 cell growth and invasion activities in vitro. Mechanistically, it was found that miR-92b-3p directly targeted the TSC1 gene, a known upstream regulator of mTOR. Overexpression of miR-92b-3p decreased the protein expression of TSC1 and enhanced the downstream phosphorylation of p70S6 kinase, suggesting that the mTOR signaling pathway was activated by miR-92b-3p in RCC cells. Importantly, a multivariate Cox proportion hazard model, based on TNM staging and high levels of miR-92b-3p, revealed that miR-92b-3p expression (high vs. low hazard ratio, 2.86; 95% confidence interval, 1.20-6.83; P = .018) was a significant prognostic factor for overall survival of ccRCC patients with surgical management. Taken together, miR-92b-3p was found to act as an oncomiR, promoting cell proliferation by downregulating TSC1 in ccRCC.
  • Yu Ishizuya; Motohide Uemura; Ryohei Narumi; Eisuke Tomiyama; Yoko Koh; Makoto Matsushita; Kosuke Nakano; Yujiro Hayashi; Cong Wang; Taigo Kato; Koji Hatano; Atsunari Kawashima; Takeshi Ujike; Kazutoshi Fujita; Ryoichi Imamura; Jun Adachi; Takeshi Tomonaga; Norio Nonomura
    Biochemical and biophysical research communications 523 3 588 - 594 2020年03月 [査読有り]
     
    Prostate cancer is the second leading cause of cancer death in men in the United States. Several novel therapeutic agents have been developed for castration-resistant prostate cancer (CRPC), but the prognosis for patients with CRPC remains poor. The identification of novel therapeutic targets for CRPC is an urgent issue. Exosomes are small vesicles secreted by a variety of cells, and exosomes derived from cancer cells have been reported to circulate in the patient's bodily fluids, promoting metastasis and invasion. We aimed to identify novel therapeutic targets for CRPC by proteomic analysis of serum exosomes. Exosomes were isolated by ultracentrifugation of sera from 36 men with metastatic prostate cancer: untreated (n = 8), well-controlled with primary androgen deprivation therapy (ADT) (n = 8), and CRPC (n = 20). We identified 823 proteins in the serum exosomes. Six proteins were increased in CRPC patients compared with untreated patients. In contrast, only ACTN4 was increased in the CRPC patients compared to the ADT patients. We focused on ACTN4 as a candidate for targeted therapeutics. ACTN4 was highly expressed in the prostate cancer cell line DU145 as well as exosomes from this line. RNA interference-mediated downregulation of ACTN4 significantly attenuated cell proliferation and invasion in DU145 cells. ACTN4 could be a potential therapeutic target for CRPC.
  • 谷優; 阿部豊文; 福原慎一郎; 藤田和利; 植村元秀; 木内寛; 今村亮一; 野々村祝夫
    泌尿器科紀要 66 3 77 - 80 2020年03月 [査読有り]
     
    A 66-year-old man was referred to our hospital because of positive fecal occult blood test. Gastric and rectal cancers were diagnosed by upper and lower endoscopic biopsy, respectively. Enhanced computed tomography (CT) indicated a pulmonary tumor and a left adrenal mass with a diameter of 15 mm presenting heterogenous enhancement. The pulmonary tumor was diagnosed as adenocarcinoma by bronchoscopic biopsy. F18 fluoro-2-deoxy D-glucose (FDG) PET/CT showed abnormal FDG accumulation (maximum standardized uptake value=26. 1) in the left adrenal mass consistent with a metastatic adrenal tumor. Although radical surgical therapy was performed for the synchronous triple cancers of gastric, colon, and lung cancer, the patient refused adrenalectomy for the left adrenal tumor. One year after surgery, CT revealed an increase in the adrenal tumor diameter to 18 mm without development of new metastases. Laparoscopic adrenalectomy was performed for the left adrenal tumor which was strongly suspected of being a metastatic tumor. Pathological diagnosis was adrenal cortical adenoma. There has been no recurrence for 5 years after surgery for simultaneous triple cancer.
  • Makoto Matsushita; Kazutoshi Fujita; Norio Nonomura
    International journal of molecular sciences 21 4 1447 - 1447 2020年02月 [査読有り]
     
    The incidence of prostate cancer (PCa) displays widespread regional differences, probably owing to differences in dietary habits. Nutrients, including fat, protein, carbohydrates, vitamins (vitamin A, D, and E), and polyphenols, potentially affect PCa pathogenesis and progression, as previously reported using animal models; however, clinical studies have reported controversial results for almost all nutrients. The effects of these nutrients may be manifested through various mechanisms including inflammation, antioxidant effects, and the action of sex hormones. Dietary patterns including the Western and Prudent patterns also influence the risk of PCa. Recent studies reported that the gut microbiota contribute to tumorigenesis in some organs. Diet composition and lifestyle have a direct and profound effect on the gut bacteria. Human studies reported an increase in the abundance of specific gut bacteria in PCa patients. Although there are few studies concerning their relationship, diet and nutrition could influence PCa, and this could be mediated by gut microbiota. An intervention of dietary patterns could contribute to the prevention of PCa. An intervention targeting dietary patterns may thus help prevent PCa.
  • 松村 聡一; 永原 啓; 福原 慎一郎; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 大月 道夫; 野々村 祝夫
    日本泌尿器科学会雑誌 111 1 30 - 33 (一社)日本泌尿器科学会 2020年01月 
    症例は32歳,男性.中学生時より二次性徴の遅れを自覚していたが医療機関は受診しなかった.32歳時,二次性徴が来ないことを主訴に前医を受診し,性腺機能低下症が疑われ当院紹介受診となった.初診時,陰茎は小陰茎であり,左精巣は触知せず,右陰嚢内に矮小精巣を触知した.内分泌学的検査では総テストステロンは0.34ng/ml,LHは1mIU/mLと低値を示しており,低ゴナドトロピン性性腺機能低下症と診断された.腹部MRI検査では,外鼠経輪に最大径8mmの萎縮した左精巣を認めた.左停留精巣を伴った,低ゴナドトロピン性性腺機能低下症と診断しhCG補充療法を開始したところ,治療開始6ヵ月で左精巣の増大と陰嚢内への下降を認め,射精が確認された.成人の性腺機能低下症に伴う停留精巣に対しては,補充療法により手術を回避できる可能性があると考えられた.(著者抄録)
  • Soichi Matsumura; Akira Nagahara; Shinichiro Fukuhara; Kazutoshi Fujita; Motohide Uemura; Hiroshi Kiuchi; Ryoichi Imamura; Michio Otsuki; Norio Nonomura
    Nihon Hinyokika Gakkai zasshi. The japanese journal of urology 111 1 30 - 33 2020年 
    A 32-year-old Japanese man was referred to our hospital with a chief complaint of the delayed puberty with having been aware of it since he was in his teens. Physical examination demonstrated the small penis, the impalpable left testis, and the atrophic right testis in the scrotum. Abdominal magnetic resonance imaging showed the left testis of 8 mm in the external inguinal ring. Endocrinological blood tests revealed that testosterone and luteinizing hormone were 0.34 ng/mL and 1 mIU/mL, respectively, leading to a diagnosis of the left cryptorchidism with hypogonadotropic hypogonadism. The hCG therapy was initiated, resulting in the increased volume and spontaneous descent into the scrotum of the left testis after 6 months of the treatment. The hCG therapy could be an alternative treatment for surgery for cryptorchidism with hypogonadism in adults.
  • Yujiro Hayashi; Kazutoshi Fujita; Kyosuke Matsuzaki; Marie-Lisa Eich; Eisuke Tomiyama; Makoto Matsushita; Yoko Koh; Kosuke Nakano; Cong Wang; Yu Ishizuya; Taigo Kato; Koji Hatano; Atsunari Kawashima; Takeshi Ujike; Motohide Uemura; Ryoichi Imamura; George J Netto; Norio Nonomura
    Frontiers in oncology 10 755 - 755 2020年 [査読有り]
     
    Recent studies showed the clinical utility of next-generation sequencing of urinary cell-free DNA (cfDNA) from patients with urothelial bladder cancer (UBC). In this study, we aimed to develop urinary cfDNA analysis by droplet digital PCR (ddPCR) as a high-throughput and rapid assay for UBC detection and prognosis. We analyzed urinary cfDNA of 202 samples from 2 cohorts. Test cohort was designed for investigating clinical utility of urinary cfDNA, and was composed of 74 samples from patients with UBC, and 52 samples of benign hematuria patients. Validation cohort was designed for validation and assessment of clinical utility comparing urinary cfDNA with UroVysion (Abbott, Illinois, USA), and was composed of 40 samples from patients with UBC, and 36 prospectively collected samples from patients under surveillance after surgery for urothelial carcinoma. We performed ddPCR analysis of hotspot gene mutations (TERT promoter and FGFR3). In the test cohort, the sensitivity of urinary cfDNA diagnosis was 68.9% (51/74) and the specificity was 100% in patients with UBC. The sensitivity increased to 85.9% when used in conjunction with urine cytology. In addition, patients with high TERT C228T allele frequency (≥14%) had significantly worse prognosis in bladder tumor recurrence than patients with low TERT C228T allele frequency or negative TERT C228T (p = 0.0322). In the validation cohort, the sensitivity of urinary cfDNA was 57.5% (23/40) and the specificity was 100% in UBC patients. The sensitivity of the combination of urine cytology with our hotspot analysis (77.5%) was higher than that of urine cytology with UroVysion (68.9%). In the post-surgical surveillance group, patients positive for the TERT C228T mutation had significantly worse prognosis for bladder tumor recurrence than mutation negative patients (p < 0.001). In conclusion, ddPCR analysis of urinary cfDNA is a simple and promising assay for the clinical setting, surpassing UroVysion for detection and prognosis determination in UBC.
  • Kazutoshi Fujita; Norio Nonomura
    Gan to kagaku ryoho. Cancer & chemotherapy 47 1 27 - 29 2020年01月 [査読有り]
  • Uchida, H.; Hirata, T.; Otani, K.; Suzuki, O.; Oda, M.; Akino, Y.; Sumida, I.; Hatano, K.; Fujita, K.; Uemura, M.; Imamura, R.; Eino, D.; Yoshioka, Y.; Nonomura, N.; Ogawa, K.
    Anticancer Research 40 3 1677 - 1682 2020年 [査読有り]
     
    BACKGROUND: The present study aimed to estimate geometric changes in applicators and prostate over 3 days in patients with high-dose-rate brachytherapy (HDR-BT) and to assess the need for daily replanning. PATIENTS AND METHODS: This study retrospectively investigated 18 patients who underwent HDR-BT as monotherapy from February 2016 to October 2018. RESULTS: Without replanning, the planning target volume coverage significantly worsened on day 2 (p<0.001) and day 3 (p=0.003). The minimum dose distributed to the highest irradiated rectal volume of 5 cc became significantly higher on day 2 (p=0.02), and the maximum dose distributed to the urethra became significantly higher on day 2 (p=0.01). CONCLUSION: Conformal, high-dose delivery of HDR-BT is impaired without replanning not only on the second day but also on the third day. Daily replanning is required for achieving accuracy of HDR-BT.
  • Yujiro Hayashi; Kazutoshi Fujita
    Translational andrology and urology 8 Suppl 5 S497-S501  2019年12月 [査読有り]
  • Kato Taigo; Uemura Motohide; Hatano Koji; Kawashima Atsunari; Ujike Takeshi; Fujita Kazutoshi; Kioytani Kazuma; Nonomura Norio
    JOURNAL FOR IMMUNOTHERAPY OF CANCER 7 2019年11月 [査読有り]
  • Takahiro Yoshida; Max Kates; Kazutoshi Fujita; Trinity J Bivalacqua; David J McConkey
    International journal of urology : official journal of the Japanese Urological Association 26 11 1044 - 1053 2019年11月 
    Bladder cancer is a heterogeneous disease. Interpatient heterogeneity in response to a drug limits treatment options and impairs improvement of patient survival. For example, approximately half of patients do not respond to cisplatin-based combination chemotherapy, although it is the standard of care for muscle-invasive and metastatic bladder cancer. The development of robust predictive biomarkers is expected to improve outcomes by enabling clinicians to use chemotherapy only in the patients who will benefit from it. Recent advances in the molecular characterization of bladder cancer showed that the basal subtype of bladder cancer and tumors with inactivating mutations in DNA damage repair genes were associated with greater benefit from cisplatin-based chemotherapy. The present review summarizes current efforts to develop predictive biomarkers for drug response in bladder cancer, focusing on those that predict the response to cisplatin-based chemotherapy for advanced bladder cancer. We also review the current situation with regard to the identification of predictive biomarkers for response to intravesical therapy, immune checkpoint inhibitors and molecularly-targeted drugs. We also discuss the future applications of new technologies, including liquid biopsies and patient-derived organoids that will also serve as resources for the identification of biomarkers in bladder cancer.
  • 谷口 歩; 角田 洋一; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 宮川 康; 野々村 祝夫; 上田 豊
    泌尿器科紀要 65 11 479 - 484 泌尿器科紀要刊行会 2019年11月 [査読有り]
     
    54歳女。主訴は3ヵ月持続する不正性器出血、腹痛、倦怠感で、25歳時に腎血管筋脂肪腫(AML)に対する両側腎部分切除術、43歳時に肺リンパ脈管筋腫症の既往があった。血算・生化学検査にて貧血、凝固能低下、線溶系異常を認め、腹部造影CTでは子宮体部背側の腫瘤と連続した血腫をダグラス窩に多量に認め、腫瘤が出血源と考えられた。造影CT撮影直後に心肺停止となり、心肺蘇生後、出血コントロール目的に単純子宮全摘を施行した。病理所見で腫瘤は類上皮様や紡錘形の細胞の充実性増殖を認め、子宮筋層内には裂隙状の脈管構造を認め、免疫組織化学染色にて子宮PEComaと診断された。結節性硬化症(TSC)診断基準における7項目の大症状、2項目の小症状を満たしたためdefinitive TSCの診断となり、それに伴う子宮PEComaの破裂と診断した。
  • Marie-Lisa Eich; Maria Del Carmen Rodriguez Pena; Simeon U Springer; Diana Taheri; Aline C Tregnago; Daniela C Salles; Stephania Martins Bezerra; Isabela W Cunha; Kazutoshi Fujita; Dilek Ertoy; Trinity J Bivalacqua; Cristian Tomasetti; Nickolas Papadopoulos; Ken W Kinzler; Bert Vogelstein; George J Netto
    Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 32 10 1544 - 1550 2019年10月 
    Noninvasive approaches for early detection of bladder cancer are actively being investigated. We recently developed a urine- based molecular assay for the detection and surveillance of bladder neoplasms (UroSEEK). UroSEEK is designed to detect alterations in 11 genes that include most common genetic alterations in bladder cancer. In this study, we analyzed 527 cases, including 373 noninvasive and 154 invasive urothelial carcinomas of bladder from transurethral resections or cystectomies performed at four institutions (1991-2016). Two different mutational analysis assays of a representative tumor area were performed: first, a singleplex PCR assay for evaluation of the TERT promoter region (TERTSeqS) and second, a multiplex PCR assay using primers designed to amplify regions of interest of 10 (FGFR3, PIK3CA, TP53, HRAS, KRAS, ERBB2, CDKN2A, MET, MLL, and VHL) genes (UroSeqS). Overall, 92% of all bladder tumors were positive for at least one genetic alteration in the UroSEEK panel. We found TERT promoter mutations in 77% of low-grade noninvasive papillary carcinomas, with a relatively lower incidence of 65% in high-grade noninvasive papillary carcinomas and carcinomas in situ; p = 0.017. Seventy-two percent of pT1 and 63% of muscle-invasive bladder tumors harbored TERT promoter mutations with g.1295228C>T alteration being the most common in all groups. FGFR3 and PIK3CA mutations were more frequent in low-grade noninvasive papillary carcinomas compared with high-grade noninvasive papillary carcinomas and carcinomas in situ (p < 0.0001), while the opposite was true for TP53 (p < 0.0001). Significantly higher rates of TP53 and CDKN2A mutation rates (p = 0.005 and 0.035, respectively) were encountered in muscle-invasive bladder tumors compared with those of pT1 stage. The overwhelming majority of all investigated tumors showed at least one mutation among UroSEEK assay genes, confirming the comprehensive coverage of the panel and supporting its potential utility as a noninvasive urine-based assay.
  • Hiromu Horitani; Kentaro Takezawa; Shinichiro Fukuhara; Kazutoshi Fujita; Hiroshi Kiuchi; Motohide Uemura; Ryoichi Imamura; Norio Nonomura
    Hinyokika kiyo. Acta urologica Japonica 65 9 389 - 392 2019年09月 [査読有り]
     
    A 53-year-old man visited a doctor due to left inguinal enlargement. He was diagnosed with left inguinal hernia with omentum as the content by a computed tomography (CT)scan. He underwent open inguinal hernia repair ; however, an inguinal tumor was diagnosed intraoperatively and was resected as much as possible. Although the tumor resection was macroscopically incomplete, he was followed up without any treatment because the tumor was histologically diagnosed as lipoma. Sixteen months after surgery, a 15 cm inguinal mass and a 7 cm left intrascrotal mass were detected by follow-up CT, and he was referred to our hospital. He underwent open surgery for wide excision of the tumor with a diagnosis of spermatic cord liposarcoma and left hydrocele of testis. The spermatic cord tumor was histologically diagnosed as well differentiated liposarcoma. He has been alive without recurrence for more than 10 months after surgery. It is sometimes difficult to distinguish a spermatic cord liposarcoma from inguinal hernia by imaging examinations.
  • Takuji Hayashi; Kazutoshi Fujita; Makoto Matsushita; Norio Nonomura
    Cancers 11 8 2019年08月 [査読有り]
     
    Prostate cancer is the most common type of cancer and the leading cause of cancer deaths among men in many countries. Preventing progression is a major concern for prostate cancer patients on active surveillance, patients with recurrence after radical therapies, and patients who acquired resistance to systemic therapies. Inflammation, which is induced by various factors such as infection, microbiome, obesity, and a high-fat diet, is the major etiology in the development of prostate cancer. Inflammatory cells play important roles in tumor progression. Various immune cells including tumor-associated neutrophils, tumor-infiltrating macrophages, myeloid-derived suppressor cells, and mast cells promote prostate cancer via various intercellular signaling. Further basic studies examining the relationship between the inflammatory process and prostate cancer progression are warranted. Interventions by medications and diets to control systemic and/or local inflammation might be effective therapies for prostate cancer progression. Epidemiological investigations and basic research using human immune cells or mouse models have revealed that non-steroidal anti-inflammatory drugs, metformin, statins, soy isoflavones, and other diets are potential interventions for preventing progression of prostate cancer by suppressing inflammation. It is essential to evaluate appropriate indications and doses of each drug and diet.
  • Yoko Koh; Takeshi Ujike; Kazutoshi Fujita; Motohide Uemura; Hiroshi Kiuchi; Ryoichi Imamura; Yasushi Miyagawa; Norio Nonomura
    Hinyokika kiyo. Acta urologica Japonica 65 8 337 - 340 2019年08月 [査読有り]
     
    A 62-year-old man had been treated for urethral stricture developed after his right kidney was harvested for donation to his sister 34 years ago. Transurethral biopsy was performed because of positive urinary cytology and squamous cell carcinoma was detected from the site of urethral stricture. The patient with the desire to preserve the penis was referred to our department. Magneticresonanc e imaging showed no evidence of invasion to subepithelial tissue. Re-biopsy from the site of urethral stricture revealed squamous cell carcinoma in situ. Under the diagnosis of urethral carcinoma cTisN0M0, urethrectomy of anterior urethra with perineal urethrostomy was performed. Histopathological diagnosis was squamous cell carcinoma of the urethra pTis and surgical margins were negative. The patient reported complete urinary continence, normal erections and ejaculation from his urethrostomy. He showed no evidence of recurrence at 28 months after surgery.
  • Yamamoto Y; Fujita K; Munari E; Uemura M; Miyamoto H; Netto GJ
    International journal of urology : official journal of the Japanese Urological Association 26 6 678 - 679 2019年06月 [査読有り]
  • Yujiro Hayashi; Kazutoshi Fujita; Kyosuke Matsuzaki; Makoto Matsushita; Norihiko Kawamura; Yoko Koh; Kosuke Nakano; Cong Wang; Yu Ishizuya; Yoshiyuki Yamamoto; Kentaro Jingushi; Taigo Kato; Atsunari Kawashima; Takeshi Ujike; Akira Nagahara; Motohide Uemura; Ryoichi Imamura; Tetsuya Takao; Shingo Takada; George J Netto; Norio Nonomura
    Cancer science 110 5 1771 - 1779 2019年05月 
    Most upper tract urothelial carcinomas (UTUC) are muscle invasive at the time of diagnosis. Current standard methods for the diagnosis of UTUC are invasive. Urine cytology is the only non-invasive test for detecting UTUC, but its sensitivity is low. A novel non-invasive assay for UTUC detection would improve patient outcome. This study aimed to investigate the mutation of cell-free DNA (cfDNA) in urine supernatant to develop a reliable diagnostic biomarker for UTUC patients. We studied urinary cfDNA from 153 individuals, including 56 patients with localized UTUC, and carried out droplet digital PCR assay for TERT promoter and FGFR3 hotspot mutations. We could detect mutations of TERT C228T in 22/56 (39.3%), TERT C250T in 4/56 (7.1%), and FGFR3 S249C in 9/56 (16.1%) patients. FGFR3 mutation was detected only in ≤pT1 tumors (positive predictive value: 100.0%). In combination with cytology results, the sensitivity was 78.6%, and the specificity was 96.0%. Although these data need to be validated in a larger-scale cohort, mutation analysis of TERT promoter and FGFR3 in urinary cfDNA has the potential to be a non-invasive diagnostic marker and reliable factor for tumor staging.
  • Kazutoshi Fujita
    Journal of clinical medicine 8 2 201 - 201 2019年02月 
    The prevalence of obesity is increasing in the world, and obesity-induced disease, insulin-resistance, cardiovascular disease, and malignancies are becoming a problem. Epidemiological studies have shown that obesity is associated with advanced prostate cancer and that obese men with prostate cancer have a poorer prognosis. Obesity induces systemic inflammation via several mechanisms. High-fat diet-induced prostate cancer progresses via adipose-secretory cytokines or chemokines. Inflammatory cells play important roles in tumor progression. A high-fat diet or obesity changes the local profile of immune cells, such as myeloid-derived suppressor cells and macrophages, in prostate cancer. Tumor-associated neutrophils, B cells, and complements may promote prostate cancer in the background of obesity. Interventions to control systemic and/or local inflammation and changes in lifestyle may also be viable therapies for prostate cancer.
  • Yoshiyuki Yamamoto; Motohide Uemura; Masashi Fujita; Kazuhiro Maejima; Yoko Koh; Makoto Matsushita; Kosuke Nakano; Yujiro Hayashi; Cong Wang; Yu Ishizuya; Toshiro Kinouchi; Takuji Hayashi; Kyosuke Matsuzaki; Kentaro Jingushi; Taigo Kato; Atsunari Kawashima; Takeshi Ujike; Akira Nagahara; Kazutoshi Fujita; Ryoichi Imamura; Hidewaki Nakagawa; Norio Nonomura
    Cancer Science 110 2 617 - 628 2019年02月 [査読有り]
     
    Reliable biomarkers for renal cell carcinoma (RCC) have yet to be determined. Circulating tumor DNA (ctDNA) is an emerging resource to detect and monitor molecular characteristics of various tumors. The present study aims to clarify the clinical utility of ctDNA for RCC. Fifty-three patients histologically diagnosed with clear cell RCC were enrolled. Targeted sequencing was carried out using plasma cell-free DNA (cfDNA) and tumor DNA. We applied droplet digital PCR (ddPCR) to validate detected mutations. cfDNA fragment size was also evaluated using a microfluidics-based platform and sequencing. Proportion of cfDNA fragments was defined as the ratio of small (50-166 bp) to large (167-250 bp) cfDNA fragments. Association of mutant allele frequency of ctDNA with clinical course was analyzed. Prognostic potential was evaluated using log-rank test. A total of 38 mutations across 16 (30%) patients were identified from cfDNA, including mutations in TP53 (n = 6) and VHL (n = 5), and median mutant allele frequency of ctDNA was 10%. We designed specific ddPCR probes for 11 mutations and detected the same mutations in both cfDNA and tumor DNA. Positive ctDNA was significantly associated with a higher proportion of cfDNA fragments (P = .033), indicating RCC patients with ctDNA had shorter fragment sizes of cfDNA. Interestingly, the changes of mutant allele frequency in ctDNA concurrently correlated with clinical course. Positive ctDNA and fragmentation of cfDNA were significantly associated with poor cancer-specific survival (P < .001, P = .011). In conclusion, our study shows the clinical utility of ctDNA status and cfDNA fragment size as biomarkers for prognosis and disease monitoring in RCC.
  • Hiroki Ide; Guiyang Jiang; Taichi Mizushima; Kazutoshi Fujita; Satoshi Inoue; Seiji Yamaguchi; Hiroaki Fushimi; Norio Nonomura; Hiroshi Miyamoto
    Oncology letters 17 1 482 - 487 2019年01月 [査読有り]
     
    The transcription factor forkhead box O1 (FOXO1) can be inactivated via its phosphorylation, resulting in suppression of apoptosis. Using immunohistochemistry, the expression of a phosphorylated form of FOXO1 was assessed in upper urinary tract urothelial carcinoma (UUTUC) specimens. Overall, phospho-FOXO1 (p-FOXO1) was immunoreactive in all 99 UUTUC specimens [12 (12.1%) weak (1+), 46 (46.5%) moderate (2+) and 41 (41.4%) strong (3+)], which was significantly (P=0.018) increased, compared with benign urothelium specimens [77/82 (93.9%): 18 (22.0%) 1+, 41 (50.0%) 2+ and 18 (22.0%) 3+]. Muscle invasion (P=0.031) and lymphovascular invasion (P=0.025) were observed more frequently in p-FOXO1(2+/3+) tumor samples compared with p-FOXO1(1+) tumor samples. No statistically significant associations between p-FOXO1 expression and tumor grade or presence of concurrent carcinoma in situ, hydronephrosis or lymph node metastasis were observed. Furthermore, the levels of p-FOXO1 and estrogen receptor-β expression were significantly (P<0.05) correlated in UUTUC samples [correlation coefficient (CC)=0.244], particularly in tumor samples from male patients (CC=0.330). Additionally, patients with p-FOXO1(3+) tumors had a significantly increased risk of cancer-specific mortality (P=0.043), compared with those with p-FOXO1(1+/2+) tumors. Multivariate analysis further demonstrated a notable, albeit not significant, association between p-FOXO1 expression and cancer-specific survival (hazard ratio=2.204; P=0.053). These findings indicate that FOXO1 is inactivated in UUTUC specimens and p-FOXO1 overexpression may serve as a predictor of poor patient outcomes.
  • Fujita, K.; Nonomura, N.
    World Journal of Men?s Health 37 3 2019年 [査読有り]
  • Kentaro Jingushi; Motohide Uemura; Kosuke Nakano; Yujiro Hayashi; Cong Wang; Yu Ishizuya; Yoshiyuki Yamamoto; Takuji Hayashi; Toshiro Kinouchi; Kyosuke Matsuzaki; Taigo Kato; Atsunari Kawashima; Takeshi Ujike; Akira Nagahara; Kazutoshi Fujita; Koji Ueda; Kazutake Tsujikawa; Norio Nonomura
    Oncology Reports 41 2 1293 - 1303 2018年11月 
    Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, responsible for approximately 90‑95% of cases. We previously reported a novel method that enables direct extraction of extracellular vesicles (EVs) from surgically resected viable tissues, yielding what we term tissue‑exudative extracellular vesicles (Te‑EVs). Quantitative LC/MS analysis identified 3,871 proteins in Te‑EVs, among which leukocyte‑associated immunoglobulin‑like receptor 1 (LAIR1) was highly enriched in tumor Te‑EVs. In the present study, we found that LAIR1 was significantly upregulated in clinical specimens of human RCC tumor tissues compared to that noted in adjacent non‑cancerous renal tissues as determined by quantitative PCR analysis. LAIR1 overexpression resulted in accelerated cell proliferation and tumor growth in RCC cells. Moreover, knockdown of LAIR1 using siRNA significantly inhibited cell proliferation in RCC cells. Mechanistically, LAIR1 upregulated the phosphorylation status of Akt, which in turn increased cell proliferation in RCC cells. In clinical RCC specimens, RCC patients with high LAIR1 mRNA expression showed poor progression‑free survival compared to those with low LAIR1 expression. These findings indicate that LAIR1 promotes tumorigenesis in RCC.
  • Palsgrove DN; Taheri D; Springer SU; Cowan M; Guner G; Mendoza Rodriguez MA; Del Carmen Rodriguez Pena M; Wang Y; Kinde I; Ricardo BFP; Cunha I; Netto GJ
    Human pathology 85 1 - 9 2018年11月
  • Kawashima A; Kanazawa T; Jingushi K; Kato T; Ujike T; Nagahara A; Fujita K; Morimoto-Okazawa A; Iwahori K; Uemura M; Imamura R; Wada H; Nonomura N
    Clinical genitourinary cancer 17 2 114 - 124 2018年11月 [査読有り]
     
    BACKGROUND: There are no previous reports directly evaluating immunologic conditions in tumor microenvironment including both bladder cancer (BCa) and upper urinary tract carcinoma (UTUC). In this study, we aimed to clarify the difference of immunity status and its clinical significance depending on the tumor site in urothelial carcinoma. PATIENTS AND METHODS: Tumor tissue-infiltrating lymphocytes were extracted from 70 urothelial cancer patients who underwent surgical resection (52 cases of BCa and 18 cases of UTUC). The immunologic classification was established by unsupervised clustering analysis according to the expression ratio of 9 extracellular surface markers measured by flow cytometry, and we examined the relationship between immunologic classification and clinical importance such as pathologic status and prognosis (progression-free survival and cancer-specific survival). RESULTS: The immunologic condition was classified into 2 groups. Group 1 (n = 41) comprised the CD4 T-cell-dominant group and group 2 (n = 29) the immunologically activated group. This immunologic classification was significantly correlated with tumor grade (P = .020) but not tumor location in multivariate analysis. In invasive BCa patients (n = 33), progression-free survival and cancer-specific survival of group 2 were significantly worse than those of group 1 (P = .021 and P = .022, respectively), while there was no significant difference between groups 1 and 2 in patients with invasive UTUC (n = 17). CONCLUSION: Although there was no difference in the local immunologic condition of urothelial carcinoma between BCa and UTUC, its significance as a prognostic predictor might vary depending on tumor site.
  • Hayashi T; Fujita K; Matsushita M; Hayashi Y; Uemura M; Nonomura N
    International journal of urology : official journal of the Japanese Urological Association 2018年11月 [査読有り]
  • Shigeaki Nakazawa; Motohide Uemura; Takeshi Ujike; Kazutoshi Fujita; Tetsuya Takao; Yasushi Miyagawa; Norio Nonomura
    International cancer conference journal 7 4 159 - 159 2018年10月 [査読有り]
     
    [This corrects the article DOI: 10.1007/s13691-014-0198-y.].
  • Norichika Ueda; Makoto Kondo; Kentaro Takezawa; Hiroshi Kiuchi; Yosuke Sekii; Yusuke Inagaki; Tetsuji Soda; Shinichiro Fukuhara; Kazutoshi Fujita; Motohide Uemura; Ryoichi Imamura; Yasushi Miyagawa; Norio Nonomura; Shoichi Shimada
    Biochemical and Biophysical Research Communications 506 3 498 - 503 Elsevier {BV} 2018年10月 [査読有り]
     
    ATP in the suburothelial layer is released from the bladder urothelium by mechanical stimuli. ATP directly activates purinergic receptors that are expressed on primary bladder afferent neurons and induces the micturition reflex. Although ATP is also released to the bladder lumen from the bladder urothelium, the role of ATP in the bladder lumen is unknown. Recently, clinical studies have reported that urinary ATP levels are much higher in patients with an overactive bladder than healthy controls. These results suggest that ATP in the bladder lumen is also involved in the micturition reflex. In this study, we performed intravesical ATP instillation in the mouse bladder. We evaluated urinary function with novel reliable methods using improved cystometry and ultrasonography, which we previously established. We found that intravesical ATP instillation induced urinary frequency because of activation of bladder afferent nerves without inflammatory changes in the bladder or an increase in post-void residual urine. These results suggest that not only ATP in the suburothelial layer, but also ATP in the bladder lumen, are involved in enhancement of the micturition reflex.
  • Marie-Lisa Eich; Aline C. Tregnago; Sheila F. Faraj; Doreen N. Palsgrove; Kazutoshi Fujita; Stephania M. Bezerra; Enrico Munari; Rajni Sharma; Alcides Chaux; George J. Netto
    Virchows Archiv 2018年10月 [査読有り]
  • Takuji Hayashi; Kazutoshi Fujita; Satoshi Nojima; Yujiro Hayashi; Kosuke Nakano; Yu Ishizuya; Cong Wang; Yoshiyuki Yamamoto; Toshiro Kinouchi; Kyosuke Matsuzaki; Kentaro Jingushi; Taigo Kato; Atsunari Kawashima; Akira Nagahara; Takeshi Ujike; Motohide Uemura; Maria Del Carmen Rodriguez Pena; Jennifer B Gordetsky; Eiichi Morii; Kazutake Tsujikawa; George J Netto; Norio Nonomura
    Clinical cancer research : an official journal of the American Association for Cancer Research 24 17 4309 - 4318 2018年09月 [査読有り]
     
    Purpose: High-fat diet (HFD) could induce prostate cancer progression. The aim of this study is to identify mechanisms of HFD-induced prostate cancer progression, focusing on inflammation.Experimental Design: We administered HFD and celecoxib to autochthonous immunocompetent Pb-Cre+;Pten(fl/fl) model mice for prostate cancer. Tumor growth was evaluated by tumor weight and Ki67 stain, and local immune cells were assessed by flow cytometry at 22 weeks of age. Cytokines which correlated with tumor growth were identified, and the changes of tumor growth and local immune cells after inhibition of the cytokine signals were evaluated in the mice. IHC analyses using prostatectomy specimens of obese patients were performed.Results: HFD accelerated tumor growth and increased the myeloid-derived suppressor cells (MDSCs) fraction and M2/M1 macrophage ratio in the model mice. Celecoxib-suppressed tumor growth, and decreased both local MDSCs and M2/M1 macrophage ratio in HFD-fed mice. HFD-induced tumor growth was associated with IL6 secreted by prostatic macrophages, as were phosphorylated STAT3 (pSTAT3)-positive tumor cells. Anti-IL6 receptor antibody administration suppressed tumor growth, and decreased local MDSCs and pSTAT3-positive cell fractions in HFD-fed mice. The tumor-infiltrating CD11b-positive cell count was significantly higher in prostatectomy specimens of obese than those of nonobese patients with prostate cancer.Conclusions: HFD increased MDSCs and accelerated prostate cancer tumor growth via IL6/pSTAT3 signaling in the mice. This mechanism could exist in obese patients with prostate cancer. IL6-mediated inflammation could be a therapeutic target for prostate cancer. Clin Cancer Res; 24(17); 4309-18. ©2018 AACR.
  • Kawashima A; Uemura M; Kato T; Ujike T; Nagahara A; Fujita K; Imamura R; Yamanaka Y; Tomiyama E; Tanigawa G; Miyagawa Y; Yoshioka T; Miyake O; Nonomura N
    International journal of clinical oncology 24 1 78 - 86 2018年08月 [査読有り]
     
    BACKGROUND: Sunitinib is widely prescribed as first-line therapy for metastatic renal cell carcinoma. To reduce the ratio of severe adverse events and improve the relative dose intensity, we prospectively tried our own alternative medication schedule, which we called the "weekday-on and weekend-off regimen". Here we report the results of this regimen compared to the conventional medication schedule. METHODS: In total, 58 patients were enrolled in this study. Twenty patients were treated under the alternative schedule (group I: weekday-on and weekend-off regimen) and 38 patients were treated using the conventional schedule (group II: 4 weeks on and 2 weeks off regimen). The relative dose intensity (6W-RDI) and prognoses were compared between the two groups. RESULTS: Median 6W-RDI of all the patients was 75.0%. Group I patients demonstrated significantly higher 6W-RDI compared to group II (77.2 vs. 70.4%) (p = 0.019). Multivariate analysis showed that the alternative sunitinib administration schedule was significantly associated with maintaining 6W-RDI above 75% for RCC patients treated with sunitinib (OR 3.592, 95% CI 1.042-12.383, p = 0.043). On the other hand, there were no significant differences between 2 groups regarding occurrence rate of severe adverse events and prognosis by multivariate analysis. CONCLUSIONS: We report the results of an alternative medication schedule, the "weekday-on and weekend-off regimen", as a means of increasing 6W-RDI for metastatic RCC patients.
  • Fujita, K.; Nonomura, N.
    International Journal of Urology 25 9 770 - 779 2018年08月 [査読有り]
  • Koji Izumi; Satoshi Inoue; Hiroki Ide; Kazutoshi Fujita; Taichi Mizushima; Guiyang Jiang; Seiji Yamaguchi; Hiroaki Fushimi; Norio Nonomura; Hiroshi Miyamoto
    International journal of urology : official journal of the Japanese Urological Association 25 5 429 - 435 2018年05月 [査読有り]
     
    OBJECTIVE: To determine the expression status of uridine 5'diphospho-glucuronosyltransferase 1A, a major phase II drug metabolism enzyme, in upper urinary tract urothelial carcinoma, as well as to assess its prognostic significance. METHODS: We immunohistochemically stained for uridine 5'diphospho-glucuronosyltransferase 1A in tissue microarray consisting of 99 upper urinary tract urothelial carcinoma samples and paired non-neoplastic urothelial tissues. We also assessed the effect of uridine 5'diphospho-glucuronosyltransferase 1A knockdown on urothelial cancer cell growth. RESULTS: Uridine 5'diphospho-glucuronosyltransferase 1A was positive in 92.9% (27.3% weak [1+], 37.4% moderate [2+], 28.3% strong [3+]) of tumors, which was significantly (P < 0.001) lower than in benign urothelial tissues (98.8%; 3.5% 1+, 18.8% 2+, 76.4% 3+). All 37 (100%) non-muscle-invasive versus 55 (88.7%) of 62 muscle-invasive tumors (P = 0.043) were immunoreactive for uridine 5'diphospho-glucuronosyltransferase 1A. The rates of moderate-to-strong uridine 5'diphospho-glucuronosyltransferase 1A expression and its positivity were also strongly associated with the absence of concomitant carcinoma in situ (P = 0.034) and lymphovascular invasion (P = 0.016), respectively. However, there were no statistically significant associations between uridine 5'diphospho-glucuronosyltransferase 1A expression and tumor grade or pN/M status. Uridine 5'diphospho-glucuronosyltransferase 1A loss in M0 tumors was strongly associated with lower progression-free survival (P < 0.001) and cancer-specific survival (P < 0.001) rates. Multivariate analysis further identified a strong correlation of uridine 5'diphospho-glucuronosyltransferase 1A positivity with reduced cancer-specific mortality (hazard ratio 0.28, P = 0.018). Meanwhile, uridine 5'diphospho-glucuronosyltransferase 1A knockdown in urothelial cancer cells resulted in significant increases in their viability and migration. CONCLUSIONS: These results suggest a preventive role of uridine 5'diphospho-glucuronosyltransferase 1A signals in the development and progression of upper urinary tract urothelial carcinoma. Loss of uridine 5'diphospho-glucuronosyltransferase 1A expression might serve as an independent predictor of poor prognosis in patients with upper urinary tract urothelial carcinoma.
  • Yoshiyuki Yamamoto; Motohide Uemura; Kosuke Nakano; Yujiro Hayashi; Cong Wang; Yu Ishizuya; Toshiro Kinouchi; Takuji Hayashi; Kyosuke Matsuzaki; Kentaro Jingushi; Taigo Kato; Atsunari Kawashima; Takeshi Ujike; Akira Nagahara; Kazutoshi Fujita; Ryoichi Imamura; Norio Nonomura
    Oncotarget 9 29 20467 - 20475 2018年04月 [査読有り]
     
    Background: Reliable biomarkers for renal cell carcinoma (RCC) have yet to be found. Circulating cell-free DNA (cfDNA) is an emerging resource for the diagnosis and prognosis of various cancers. This study aims to identify novel blood biomarkers for RCC. Materials And Methods: Plasma cfDNA was extracted from RCC patients (n = 92) and healthy controls (n = 41). Levels of cfDNA were determined using quantitative real-time PCR of ACTB as the target gene, and cfDNA fragment size was measured using a microfluidics-based platform. Diagnostic potential was assessed using receiver operating characteristic (ROC) and logistic regression analysis, and prognostic potential was evaluated using log-rank test. Results: Median levels of cfDNA from RCC patients were significantly higher than those from healthy controls (3803 vs 2242 copies/ml, p < 0.001). Median fragment sizes of cfDNA in RCC patients were shorter than those in healthy controls (170 vs 171 bp, p = 0.052). To evaluate level of cfDNA as a diagnostic tool for RCC, ROC curve analysis revealed a sensitivity of 63.0% and a specificity of 78.1%. Multivariate analysis indicated that age, gender and the level of cfDNA were significantly associated with the presence of RCC (p < 0.001, p = 0.013, p < 0.001, respectively). Additionally, shorter cfDNA fragment size was negatively associated with progression-free survival (p = 0.006). Conclusions: Our study demonstrates the diagnostic and prognostic potential of plasma cfDNA as a biomarker for RCC.
  • Simeon U. Springer; Chung-Hsin Chen; Maria Del Carmen Rodriguez Pena; Lu Li; Christopher Douville; Yuxuan Wang; Joshua David Cohen; Diana Taheri; Natalie Silliman; Joy Schaefer; Janine Ptak; Lisa Dobbyn; Maria Papoli; Isaac Kinde; Bahman Afsari; Aline C. Tregnago; Stephania M. Bezerra; Christopher Vandenbussche; Kazutoshi Fujita; Dilek Ertoy; Isabela W. Cunha; Lijia Yu; Trinity J. Bivalacqua; Arthur P. Grollman; Luis A. Diaz; Rachel Karchin; Ludmila Danilova; Chao-Yuan Huang; Chia-Tung Shun; Robert J. Turesky; Byeong Hwa Yun; Thomas A. Rosenquist; Yeong-Shiau Pu; Ralph H. Hruban; Cristian Tomasetti; Nickolas Papadopoulos; Ken W. Kinzler; Bert Vogelstein; Kathleen G. Dickman; George J. Netto
    eLife 7 2018年03月 [査読有り]
     
    Current non-invasive approaches for detection of urothelial cancers are suboptimal. We developed a test to detect urothelial neoplasms using DNA recovered from cells shed into urine. UroSEEK incorporates massive parallel sequencing assays for mutations in 11 genes and copy number changes on 39 chromosome arms. In 570 patients at risk for bladder cancer (BC), UroSEEK was positive in 83% of those who developed BC. Combined with cytology, UroSEEK detected 95% of patients who developed BC. Of 56 patients with upper tract urothelial cancer, 75% tested positive by UroSEEK, including 79% of those with non-invasive tumors. UroSEEK detected genetic abnormalities in 68% of urines obtained from BC patients under surveillance who demonstrated clinical evidence of recurrence. The advantages of UroSEEK over cytology were evident in low-grade BCs UroSEEK detected 67% of cases whereas cytology detected none. These results establish the foundation for a new non-invasive approach for detection of urothelial cancer.
  • Satoshi Inoue; Hiroki Ide; Kazutoshi Fujita; Taichi Mizushima; Guiyang Jiang; Takashi Kawahara; Seiji Yamaguchi; Hiroaki Fushimi; Norio Nonomura; Hiroshi Miyamoto
    International journal of molecular sciences 19 3 2018年03月 [査読有り]
     
    Using preclinical models, we have recently found that ELK1, a transcriptional factor that activates downstream targets, including c-fos proto-oncogene, induces bladder cancer outgrowth. Here, we immunohistochemically determined the expression status of phospho-ELK1, an activated form of ELK1, in upper urinary tract urothelial carcinoma (UUTUC). Overall, phospho-ELK1 was positive in 47 (47.5%; 37 weak (1+) and 10 moderate (2+)) of 99 UUTUCs, which was significantly (P = 0.002) higher than in benign urothelium (21 (25.3%) of 83; 17 1+ and 4 2+) and was also associated with androgen receptor expression (P = 0.001). Thirteen (35.1%) of 37 non-muscle-invasive versus 34 (54.8%) of 62 muscle-invasive UUTUCs (P = 0.065) were immunoreactive for phospho-ELK1. Lymphovascular invasion was significantly (P = 0.014) more often seen in phospho-ELK1(2+) tumors (80.0%) than in phospho-ELK1(0/1+) tumors (36.0%). There were no statistically significant associations between phospho-ELK1 expression and tumor grade, presence of concurrent carcinoma in situ or hydronephrosis, or pN status. Kaplan-Meier and log-rank tests revealed that patients with phospho-ELK1(2+) tumor had marginally and significantly higher risks of disease progression (P = 0.055) and cancer-specific mortality (P = 0.008), respectively, compared to those with phospho-ELK1(0/1+) tumor. The current results thus support our previous observations in bladder cancer and further suggest that phospho-ELK1 overexpression serves as a predictor of poor prognosis in patients with UUTUC.
  • Yujiro Hayashi; Atsunari Kawashima; Kazutoshi Fujita; Taigo Kato; Toyofumi Abe; Takeshi Ujike; Akira Nagahara; Shinichiro Fukuhara; Motohide Uemura; Hiroshi Kiuchi; Ryoichi Imamura; Tetsuya Saito; Koichi Toda; Yoshiki Sawa; Kentaro Kishimoto; Keigo Osuga; Norio Nonomura
    Urology Case Reports 17 70 - 72 2018年03月 [査読有り]
  • Gaku Yamamichi; Toyofumi Abe; Yu Ishizuya; Kazutoshi Fujita; Motohide Uemura; Hiroshi Kiuchi; Ryoichi Imamura; Yasushi Miyagawa; Yusuke Ono; Hiroki Higashihara; Keigo Osuga; Norio Nonomura
    Hinyokika kiyo. Acta urologica Japonica 64 2 49 - 53 2018年02月 [査読有り]
     
    Renal angiomyolipoma (AML) and aneurysm are common in tuberous sclerosis complex (TSC) and represent the main causes of morbidity in adults with TSC. Herein, we report a 22-year-old woman with TSC-associated AMLs and renal aneurysms. She was referred to our hospital for the treatment of multiple renal aneurysms larger than 5 mm in diameter. The previous hospital considered that transcatheter arterial embolization (TAE) of bilateral renal aneurysms would cause deterioration of renal function. To estimate the impact of TAE on renal function, we superimposed contrast enhanced computed tomography (CT) over single-photon emission CT (SPECT)-CT. This fusion image, referred to as functional kidney mapping image, revealed the location of renal arteries and aneurysms, and normal renal parenchyma simultaneously. Functional kidney mapping image was useful to distinguish the AML region from the normal renal parenchyma, and revealed that the planned embolization site was a non-functioning parenchyma. Therefore, TAE for her multiple renal aneurysms was successfully performed without deterioration of her renal function.
  • Kentaro Jingushi; Motohide Uemura; Naomi Ohnishi; Wataru Nakata; Kazutoshi Fujita; Takuya Naito; Risa Fujii; Naomi Saichi; Norio Nonomura; Kazutake Tsujikawa; Koji Ueda
    INTERNATIONAL JOURNAL OF CANCER 142 3 607 - 617 2018年02月 [査読有り]
     
    Cancer-associated extracellular vesicles (EVs) are intimately involved in establishment of tumor microenvironment and occurrence of metastasis. However, previous studies have mainly relied on experiments with cultured cell lines or mouse models, making it difficult to gain a full understanding of EV functions in human body. Hence, we extracted EVs directly from surgically resected viable clear cell renal cell carcinoma (ccRCC) tissues and adjacent normal renal tissues (n=20). Quantitative LC/MS analysis identified 3,871 tissue-exudative EV (Te-EV) proteins, among which azurocidin (AZU1) was highly enriched in tumor Te-EVs (p=2.85 x 10(-3), fold-change=31.59). Importantly, AZU1 content was also significantly higher in serum EVs from ccRCC patients compared to those from healthy donors. We further found that ccRCC-derived EVs had AZU1-dependent membrane permeabilizing activity for the vascular endothelial cell layer. Thus Te-EVs should be ideal resource for investigation of physiological EV functions.
  • Teruo Inamoto; Naokazu Ibuki; Kazumasa Komura; Hiroshi Juri; Kiyohito Yamamoto; Kazuhiro Yamamoto; Kazutoshi Fujita; Norio Nonomura; Yoshifumi Narumi; Haruhito Azuma
    International journal of urology : official journal of the Japanese Urological Association 25 2 134 - 140 2018年02月 [査読有り]
     
    Decision-making in urological cancer care requires a multidisciplinary approach for refinement, but its impact on urothelial carcinoma of the bladder has not been fully addressed for the past three decades, except for the latest immunological checkpoint inhibitor approved by the U.S. Food and Drug Administration for metastatic muscle-invasive bladder cancer that is resistant to platinum-based chemotherapy. For the time being, radical cystectomy is the gold standard of curative therapy for muscle-invasive bladder cancer. Trimodal therapy that combines chemotherapy for the purpose of radiation sensitization, external beam radiotherapy and transurethral resection of bladder tumor has emerged as a potential alternative treatment option that preserves the bladder. In lack of randomized studies for bladder preservation therapy compared with surgery, the principles of management of urothelial carcinoma of the bladder have evolved in recent times, with an emphasis on bladder preservation. A number of bladder preservation techniques are available to the surgeon; however, appropriately selected patients with muscle-invasive bladder cancer should be offered the opportunity to discuss various treatment options, including organ-sparing trimodal therapy. The aim of the present study was to compare the primary outcomes of the available treatment methods and identify the sources of variance among studies. A review of various bladder preservation techniques in vogue for the management of urothelial carcinoma of the bladder is discussed.
  • Gaku Yamamichi; Toyofumi Abe; Yu Ishizuya; Kazutoshi Fujita; Motohide Uemura; Hiroshi Kiuchi; Ryoichi Imamura; Yasushi Miyagawa; Yusuke Ono; Hiroki Higashihara; Keigo Osuga; Norio Nonomura
    Hinyokika kiyo. Acta urologica Japonica 64 2 49 - 53 2018年02月 [査読有り]
     
    Renal angiomyolipoma (AML) and aneurysm are common in tuberous sclerosis complex (TSC) and represent the main causes of morbidity in adults with TSC. Herein, we report a 22-year-old woman with TSC-associated AMLs and renal aneurysms. She was referred to our hospital for the treatment of multiple renal aneurysms larger than 5 mm in diameter. The previous hospital considered that transcatheter arterial embolization (TAE) of bilateral renal aneurysms would cause deterioration of renal function. To estimate the impact of TAE on renal function, we superimposed contrast enhanced computed tomography (CT) over single-photon emission CT (SPECT)-CT. This fusion image, referred to as functional kidney mapping image, revealed the location of renal arteries and aneurysms, and normal renal parenchyma simultaneously. Functional kidney mapping image was useful to distinguish the AML region from the normal renal parenchyma, and revealed that the planned embolization site was a non-functioning parenchyma. Therefore, TAE for her multiple renal aneurysms was successfully performed without deterioration of her renal function.
  • Yamanaka Y; Kawashima A; Hayashi Y; Ujike T; Abe T; Nagahara A; Fukuhara S; Fujita K; Uemura M; Kiuchi H; Imamura R; Kitamura T; Otsuki M; Nonomura N
    Nihon Hinyokika Gakkai zasshi. The japanese journal of urology 109 3 164 - 168 2018年 [査読有り]
     
    A 64-year-old man was diagnosed as having Cushing's disease due to multiple lumbar compression fracture in 2009. Although various treatments including three times transsphenoidal surgery and twice radiotherapy were performed, his serum cortisol level rose again and intractable cutaneous ulcer occurred. Just after discontinuation of medication to treat the progression due of severe hepatic dysfunction, deep vein thrombosis and pulmonary artery embolism occurred. To control the Cushing's disease, laparoscopic bilateral adrenalectomy was performed.
  • Fujita, K.; Kaneda, Y.; Nonomura, N.
    Hormone Therapy and Castration Resistance of Prostate Cancer 419  2018年 [査読有り]
  • Kyosuke Matsuzaki; Kazutoshi Fujita; Yujiro Hayashi; Makoto Matsushita; Satoshi Nojima; Kentaro Jingushi; Taigo Kato; Atsunari Kawashima; Takeshi Ujike; Akira Nagahara; Motohide Uemura; Ryoichi Imamura; Seiji Yamaguchi; Hiroaki Fushimi; Hiroshi Miyamoto; Eiichi Morii; Norio Nonomura
    PloS one 13 8 e0201256  2018年 [査読有り]
     
    Signal transducer and activator of transcription 3 (STAT3) plays a prominent role in the growth and invasion of several types of solid tumors. In this study, to assess the expression status and prognostic significance of the STAT3 pathway in upper urinary tract urothelial carcinoma (UTUC), we immunohistochemically stained for STAT3 and STAT3 pathway proteins, sphingosine-1-phosphate receptor 1 (S1PR1) and interleukin-6 (IL-6), in a tissue microarray containing 99 UTUC specimens. There were no significant associations between STAT3, S1PR1, or IL-6 expression pattern and tumor grade or pT stage. However, the patients with high STAT3 tumor had a significantly higher risk of both disease progression (p = 0.009) and cancer-specific mortality (p = 0.009), but not with tumors expressing S1PR1 or IL-6. High STAT3 expression in the nucleus was also associated with a significantly higher risk of both disease progression (p = 0.003) and cancer-specific mortality (p = 0.034). Multivariate analysis revealed that high STAT3 expression in the nucleus was significantly associated with cancer-specific survival after adjustment for pathological stage, lymph node involvement, lymphovascular invasion, and tumor grade (HR = 2.136, 95% CI = 1.009-4.767, p = 0.047). Our findings indicated that STAT3 could be a cancer-promoting factor and potentially a significant prognostic factor in UTUC.
  • Atsunari Kawashima; Takayuki Kanazawa; Kumiko Goto; Mitsunobu Matsumoto; Akiko Morimoto-Okazawa; Kota Iwahori; Takeshi Ujike; Akira Nagahara; Kazutoshi Fujita; Motohide Uemura; Norio Nonomura; Hisashi Wada
    Cancer Immunology, Immunotherapy 67 1 113 - 125 2018年01月 [査読有り]
     
    Objectives: To clarify comprehensive immunological signature patterns of tumour tissue-infiltrating lymphocytes in patients with renal cell carcinoma and show its clinical significance. Materials and methods: We investigated the surface marker expressions of tumour tissue-infiltrating lymphocytes quantitatively and classified them based on their functional populations. We extracted 109 sets of tumour tissue-infiltrating lymphocytes from 80 patients who underwent surgical resection of renal cell carcinoma, of which 44 tumour tissue-infiltrating lymphocytes were multiply extracted from 15 patients. Each tumour tissue-infiltrating lymphocyte was characterised on the basis of functional T-cell populations using ten surface marker expressions measured by flow cytometry. Results: All sets of the tumour tissue-infiltrating lymphocytes were classified into three groups, which correlated significantly with Fuhrman grade (OR 0.253, 95% CI 0.094–0.678, P = 0.006). Importantly, both overall metastasis-free survival (HR 0.449, 95% CI 0.243–0.832, P = 0.011) and recurrence-free survival (HR 0.475, 95% CI 0.238–0.948, P = 0.035) of the patients with the higher marker expressions were significantly inferior to those of the patients with the lower marker expressions by multivariate analysis. Six specific genes for this classification identified by microarray analysis verified our results using the TCGA KIRC data set. In addition, we discovered the presence of intra-tumoural diversity in the classification of 3 (20%) of the 15 patients. Conclusions: This study showed that the presence of classable diversity in the immunological signature of tumour tissue-infiltrating lymphocytes correlated with prognosis and tumour aggressiveness that was observed even within individual tumours in some patients with renal cell carcinoma.
  • Takeshi Ujike; Motohide Uemura; Atsunari Kawashima; Akira Nagahara; Kazutoshi Fujita; Yasushi Miyagawa; Norio Nonomura
    Endocrine-Related Cancer 25 1 59 - 67 2018年01月 [査読有り]
     
    Circulating levels of prostate-specific antigen (PSA) and testosterone are widely used for the detection of prostate cancer prior to prostate biopsy however, both remain controversial. Effective screening strategies based on quantitative factors could help avoid unnecessary biopsies. Here, we sought to clarify the predictive value of free testosterone (FT) vs total testosterone (TT) in identifying patients likely to have positive biopsies. This study aims to develop a novel model for predicting positive prostate biopsy based on serum androgen levels. This study included 253 Japanese patients who underwent prostate biopsy at our institution. TT and FT, %FT (=FT/TT), age, PSA, prostate volume (PV) and PSA density (PSAD = PSA/PV) were assessed for association with prostate biopsy findings. The following results were obtained. Of 253 patients, 145 (57.3%) had positive biopsies. Compared to the negative biopsy group, the positive biopsy group demonstrated higher age, PSA and PSAD but lower PV, FT and %FT by univariate analysis. Multivariate logistic regression analysis indicated PSA, PSAD and %FT were independent predictors of cancer detection. We developed a predictive model based on PSAD and %FT, for which the area under the curve was significantly greater than that of PSA (0.82 vs 0.66), a well-known predictor. Applying this analysis to the subset of patients with PSA < 10 ng/mL yielded similar results. We confirmed the utility of this model in another independent cohort of 88 patients. In conclusion, lower %FT predicted a positive prostate biopsy. We constructed a predictive model based on %FT and PSAD, which are easily obtained prior to biopsy.
  • Toshiro Kinouchi; Motohide Uemura; Cong Wang; Yu Ishizuya; Yoshiyuki Yamamoto; Takuji Hayashi; Kyosuke Matsuzaki; Wataru Nakata; Takahiro Yoshida; Kentaro Jingushi; Atsunari Kawashima; Takeshi Ujike; Akira Nagahara; Kazutoshi Fujita; Ryoichi Imamura; Yuko Ueda; Kaori Kitae; Kazutake Tsujikawa; Norio Nonomura
    Cancer Science 108 12 2495 - 2502 2017年12月 [査読有り]
     
    There are no blood biomarkers for the diagnosis of renal cell carcinoma (RCC) in routine clinical use. We focused on the gene expression profile of peripheral blood cells obtained from RCC patients to discover novel biomarkers for RCC diagnosis. Using microarray analysis and quantitative verification, CXCL7 was shown to be significantly upregulated in the peripheral blood cells of RCC patients. Importantly, aberrant CXCL7 expression was confirmed even in peripheral blood cells obtained from early stage (pT1a) RCC patients, and the expression level of CXCL7 in peripheral blood cells was a potential independent biomarker for the diagnosis of RCC by receiver operating characteristic curve analysis (sensitivity, 70.0% specificity, 64.0% area under the curve = 0.722 multiple logistic regression analysis: odds ratio, 1.07 95% confidence interval, 1.03–1.11 P = 0.0004). Moreover, CXCL7 expression in peripheral blood cells significantly decreased after resection of the primary tumor. CXCL7 is more highly expressed in PBMCs than in neutrophils from both healthy controls and RCC patients. Interestingly, CXCL7 expression in PBMCs from healthy volunteers was significantly elevated following coculture with RCC cells compared to those cocultured with normal cells as a control. These results suggest that aberrant CXCL7 expression in peripheral blood cells is induced by RCC cells and may serve as a novel biomarker in the diagnosis of RCC.
  • Maria Del Carmen Rodriguez Pena; Aline C. Tregnago; Marie-Lisa Eich; Simeon Springer; Yuxuan Wang; Diana Taheri; Dilek Ertoy; Kazutoshi Fujita; Stephania M. Bezerra; Isabela W. Cunha; Maria Rosaria Raspollini; Lijia Yu; Trinity J. Bivalacqua; Nickolas Papadopoulos; Kenneth W. Kinzler; Bert Vogelstein; George J. Netto
    VIRCHOWS ARCHIV 471 6 761 - 767 2017年12月 [査読有り]
     
    Our group and others have previously demonstrated the presence of TERT promoter mutations (TERT-mut) in 60-80% of urothelial carcinomas and some of their histologic variants. Five other genes have been frequently implicated in bladder cancer: FGRF3, TP53, PIK3CA, HRAS, and CDKN2A. In the current study, we sought to determine the prevalence of mutations in TERT and these five other genes in de novo papillary urothelial neoplasms of low malignant potential (PUNLMP) of the urinary bladder. A retrospective search of our archives for PUNLMP was performed and 30 de novo cases were identified and included in the study. We found mutations in TERT (TERT-mut) and FGFR3 (FGFR3-mut) to be the most common alterations in the cohort (63 and 60%, respectively). The majority of the TERT-mut-positive tumors (84%) had a g. 1295228C > T alteration with the remaining tumors demonstrating g. 1295250C > T. Approximately one fourth of tumors had TP53 mutations. These findings support the potential utility of a uniform genetic mutation panel to detect bladder cancers of various subtypes.
  • Toshiro Kinouchi; Motohide Uemura; Cong Wang; Yu Ishizuya; Yoshiyuki Yamamoto; Takuji Hayashi; Kyosuke Matsuzaki; Wataru Nakata; Takahiro Yoshida; Kentaro Jingushi; Atsunari Kawashima; Takeshi Ujike; Akira Nagahara; Kazutoshi Fujita; Ryoichi Imamura; Yuko Ueda; Kaori Kitae; Kazutake Tsujikawa; Norio Nonomura
    CANCER SCIENCE 108 12 2495 - 2502 2017年12月 [査読有り]
     
    There are no blood biomarkers for the diagnosis of renal cell carcinoma (RCC) in routine clinical use. We focused on the gene expression profile of peripheral blood cells obtained from RCC patients to discover novel biomarkers for RCC diagnosis. Using microarray analysis and quantitative verification, CXCL7 was shown to be significantly upregulated in the peripheral blood cells of RCC patients. Importantly, aberrant CXCL7 expression was confirmed even in peripheral blood cells obtained from early stage (pT1a) RCC patients, and the expression level of CXCL7 in peripheral blood cells was a potential independent biomarker for the diagnosis of RCC by receiver operating characteristic curve analysis (sensitivity, 70.0%; specificity, 64.0%; area under the curve=0.722; multiple logistic regression analysis: odds ratio, 1.07; 95% confidence interval, 1.03-1.11; P=0.0004). Moreover, CXCL7 expression in peripheral blood cells significantly decreased after resection of the primary tumor. CXCL7 is more highly expressed in PBMCs than in neutrophils from both healthy controls and RCC patients. Interestingly, CXCL7 expression in PBMCs from healthy volunteers was significantly elevated following coculture with RCC cells compared to those cocultured with normal cells as a control. These results suggest that aberrant CXCL7 expression in peripheral blood cells is induced by RCC cells and may serve as a novel biomarker in the diagnosis of RCC.
  • Kazutoshi Fujita; Kei Taneishi; Teruo Inamoto; Yu Ishizuya; Shingo Takada; Masao Tsujihata; Go Tanigawa; Noriko Minato; Shigeaki Nakazawa; Tsuyoshi Takada; Toshichika Iwanishi; Motohide Uemura; Yasushi Okuno; Haruhito Azuma; Nonomura Norio
    BMC UROLOGY 17 2017年12月 [査読有り]
     
    Background: The purposes of this study were to determine whether adjuvant chemotherapy (AC) improved the prognosis of patients with high-risk upper urinary tract urothelial carcinoma (UTUC) and to identify the patients who benefited from AC. Methods: Among a multi-center database of 1014 patients who underwent RNU for UTUC, 344 patients with >= pT3 or the presence of lymphovascular invasion (LVI) were included. Cancer-specific survival (CSS) estimates were calculated by the Kaplan-Meier method, and groups were compared by the log-rank test. Each patient's probability of receiving AC depending on the covariates in each group was estimated by logistic regression models. Propensity score matching was used to adjust the confounding factors for selecting patients for AC, and log-rank tests were applied to these propensity score-matched cohorts. Cox proportional hazards regression modeling was used to identify the variables with significant interaction with AC. Variables included age, pT category, LVI, tumor grade, ECOG performance status and low sodium or hemoglobin score, which we reported to be a prognostic factor of UTUC. Results: Of the 344 patients, 241 (70%) had received RNU only and 103 (30%) had received RNU+AC. The median follow-up period was 32 (range 1-184) months. Overall, AC did not improve CSS (P = 0.12). After propensity score matching, the 5-year CSS was 69.0% in patients with RNU+AC versus 58.9% in patients with RNU alone (P = 0.030). Subgroup analyses of survival were performed to identify the patients who benefitted from AC. Subgroups of patients with low preoperative serum sodium (<= 140 mEq/ml) or hemoglobin levels below the normal limit benefitted from AC (HR 0.34, 95% CI 0.15-0.61, P = 0.001). In the subgroup of patients with normal sodium and normal hemoglobin levels, 5-year CSS was 77.7% in patients with RNU+AC versus 80.2% in patients with RNU alone (P = 0.84). In contrast, in the subgroup of patients with low sodium or low hemoglobin levels, 5-year CSS was 71.0% in patients with RNU+AC versus 38.5% in patients with RNU alone (P < 0.001). Conclusions: High-risk UTUC patients, especially subgroups of patients with lower sodium and hemoglobin levels, could benefit from AC after RNU.
  • 谷口 歩; 氏家 剛; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 宮川 康; 野々村 祝夫; 森井 英一
    泌尿器科紀要 63 11 465 - 469 泌尿器科紀要刊行会 2017年11月 
    61歳男。主訴は腹痛で、造影CTとMRI検査にて径7cm大の内部不均一な左副腎腫瘤を認めた。血算・生化学検査において腫瘍マーカーNSEは高値を認め、PET-CTでは左副腎腫瘤に一致してFDG集積像を認め、左副腎皮質癌(cT2N0M0)の診断で、第7病日に開腹左副腎摘除術を施行した。病理組織学的に腫瘍内部に副腎成分は認めず、免疫染色ではαSMA、caldesmon、desmin、CD34が染色され、副腎平滑筋肉腫(pT2bN0M0)と診断した。術後NSEは正常化し、16ヵ月経過して転移再発は認めていない。
  • Ayumu Taniguchi; Takeshi Ujike; Kazutoshi Fujita; Motohide Uemura; Hiroshi Kiuchi; Ryoichi Imamura; Yasushi Miyagawa; Norio Nonomura; Eiichi Morii
    Hinyokika kiyo. Acta urologica Japonica 63 11 465 - 469 2017年11月 [査読有り]
     
    A 61-year-oldman presentedwith a chief complaint of abdominal pain. Enhancedcomputed tomography andmagnetic resonance imaging showeda left adrenal mass with a diameter of 7 cm with heterogeneous enchancement. He was referredto our hospital for further treatment. No endocrinological abnormality was detected. The tumor showed abnormal uptake on fludeoxyglucose positron emission tomography scan. Preoperative diagnosis was left adrenocortical carcinoma (cT2N0M0). Tumor excision was performedandpathological findings on the resectedspecimen revealedleiomyosarcoma of the left adrenal grand. The patient has been followed up for 16 months with no additional treatment. No evidence of local recurrence or metastasis was seen.
  • Mai Kimakura; Akira Nagahara; Shinichiro Fukuhara; Kazutoshi Fujita; Motohide Uemura; Hiroshi Kiuchi; Ryoichi Imamura; Yasushi Miyagawa; Hiroki Higashihara; Keigo Osuga; Norio Nonomura
    Acta Urologica Japonica 63 11 493 - 497 2017年11月 [査読有り]
     
    Microscopic subinguinal varicocelectomy has a recurrence of less than 1%, and varicocele recurrence is supposed to be an uncommon post-surgery adverse event. At present, no guidelines exist for the management of recurrent varicoceles after surgery. In this report, we present two cases of post-surgery recurrent varicocele of the testis. Case-l: A 23-year-old male patient who had undergone microscopic subinguinal varicocelectomy for a grade 3 varicocele was referred to our hospital because of recurrent varicocele. Retrograde venography revealed the persistence of dilated spermatic veins. The former surgeon preserved the dilated vas deferens vein, and this was considered a possible cause of persistence of dilated spermatic veins. The vein considered as vas deferens vein was actually an internal spermatic vein. Case-2: A 28-year-old male patient complained of recurrence of varicocele two months after the original operation for a grade 3 varicocele. Internal spermatic vessels were slighdy visualized on retrograde venography. The possible cause of persistence in this case was insufficient ligation of the internal spermatic vessels. We performed embolization in both cases of recurrent varicocele. Both cases were successfully treated, and there has been no recurrence. Our findings suggest that percutaneous transcatheter embolization of the testicular vein may be effective in the management of postsurgical recurrent varicocele of the testis.
  • Takuji Hayashi; Kazutoshi Fujita; Satoshi Nojima; Yujiro Hayashi; Kosuke Nakano; Yu Ishizuya; Cong Wang; Yoshiyuki Yamamoto; Toshiro Kinouchi; Kyosuke Matsuzaki; Norihiko Kawamura; Kentaro Jingushi; Atsunari Kawashima; Akira Nagahara; Takeshi Ujike; Motohide Uemura; Ryoichi Imamura; Eiichi Morii; Norio Nonomura
    PROSTATE 77 14 1383 - 1388 2017年10月 [査読有り]
     
    BackgroundTumor-infiltrating macrophages, which are thought to be derived from blood monocytes, interact with tumor cells to promote cancer progression. The aim of this study was to assess the association of peripheral blood monocyte count with pathological findings and local tumor-infiltrating macrophages in prostatectomy specimens. MethodsPreoperative peripheral blood monocyte counts were retrospectively assessed for their associations with pathological findings (pathological T stage, Gleason Score, extraprostatic extension, seminal vesicle invasion, and surgical margin) and biochemical recurrence of 248 patients who underwent radical prostatectomy. Local tumor-infiltrating macrophages were also evaluated immunohistochemically for their association with peripheral monocyte counts. ResultsThe peripheral monocyte counts of the patients with extraprostatic extension, seminal vesicle invasion, or primary Gleason 4 were significantly higher than those of the patients without each of these pathological findings (P<0.001, P=0.034, and P=0.004, respectively). Peripheral monocyte count was a significant predictor of adverse pathology and postoperative biochemical recurrence in localized prostate cancer by multivariate analysis (P=0.001 and P=0.041, respectively). Both the density and the count of tumor-infiltrating macrophages correlated significantly with the peripheral blood monocyte count (Spearman rank correlation coefficients were 0.463 and 0.649, respectively, P<0.001). ConclusionsPeripheral blood monocyte count reflecting local tumor-infiltrating macrophages was a predictive factor for tumor progression and prognosis in patients with localized prostate cancer. Elucidating the mechanism of the interaction of peripheral monocytes with tumor-infiltrating macrophages is necessary.
  • Mari Wataya-Kaneda; Motohide Uemura; Kazutoshi Fujita; Haruhiko Hirata; Keigo Osuga; Kuriko Kagitani-Shimono; Norio Nonomura
    INTERNATIONAL JOURNAL OF UROLOGY 24 9 681 - 691 2017年09月 [査読有り]
     
    Tuberous sclerosis complex is an autosomal dominant inherited disorder characterized by generalized involvement and variable manifestations with a birth incidence of 1:6000. In a quarter of a century, significant progress in tuberous sclerosis complex has been made. Two responsible genes, TSC1 and TSC2, which encode hamartin and tuberin, respectively, were discovered in the 1990s, and their functions were elucidated in the 2000s. Hamartin-Tuberin complex is involved in the phosphoinositide 3-kinase-protein kinaseB-mammalian target of rapamycin signal transduction pathway, and suppresses mammalian target of rapamycin complex1 activity, which is a center for various functions. Constitutive activation of mammalian target of rapamycin complex1 causes variable manifestations in tuberous sclerosis complex. Recently, genetic tests were launched to diagnose tuberous sclerosis complex, and mammalian target of rapamycin complex1 inhibitors are being used to treat tuberous sclerosis complex patients. As a result of these advances, new diagnostic criteria have been established and an indispensable new treatment method; that is, a cross-sectional medical examination system, a system to involve many experts for tuberous sclerosis complex diagnosis and treatments, was also created. Simultaneously, the frequency of genetic tests and advances in diagnostic technology have resulted in new views on symptoms. The numbers of tuberous sclerosis complex patients without neural symptoms are increasing, and for these patients, renal manifestations and pulmonary lymphangioleiomyomatosis have become important manifestations. New concepts of tuberous sclerosis complex-associated neuropsychiatric disorders or perivascular epithelioid cell tumors are being created. The present review contains a summary of recent advances, significant manifestations and therapy in tuberous sclerosis complex.
  • K. Fujita; Y. Nakai; A. Kawashima; T. Ujike; A. Nagahara; T. Nakajima; T. Inoue; C. M. Lee; M. Uemura; Y. Miyagawa; Y. Kaneda; N. Nonomura
    Cancer Gene Therapy 24 7 277 - 281 2017年07月 [査読有り]
     
    Inactivated Sendai virus particles (hemagglutinating virus of Japan envelope (HVJ-E)) have a novel antitumor effect: HVJ-E fused to prostate cancer cells via cell surface receptor causes apoptosis of prostate cancer cells in vitro and in vivo. HVJ-E also induces antitumor immunity by activating natural killer (NK) cells and cytotoxic T cells and suppressing regulatory T cells in vivo. We conducted an open-label, single-arm, phase I/II clinical trial in patients with castration-resistant prostate cancer (CRPC) to determine the safety and efficacy of intratumoral and subcutaneous injection of HVJ-E. Patients with CRPC who were docetaxel-resistant or could not receive docetaxel treatment were eligible. HVJ-E was injected directly into the prostate on day 1 and subcutaneously on days 5, 8 and 12 in two 28-day treatment cycles using a 3+3 dose-escalation design. The primary end points were to evaluate safety and tolerability of HVJ-E. The secondary end points were to analyze tumor immunity and antitumor effect. The study is registered at UMIN Clinical Trials Registry, number UMIN000006142. Seven patients were enrolled, and six patients received HVJ-E. Grade 2 or 3 adverse events (Common Terminology Criteria for Adverse Events Ver. 4.0) were urinary retention and lymphopenia from which the patients recovered spontaneously. No Grade 4 adverse events were observed. Radiographically, three patients had stable disease in the low-dose group, and one patient had stable disease and two had progressive disease in the high-dose group. The prostatespecific antigen (PSA) declined from 14 to 1.9 ng ml- 1 in one patient in the low-dose group after two cycles of HVJ-E treatment, and the PSA response rate was 16.6%. NK cell activity was elevated from day 12 to day 28 after HVJ-E administration, whereas serum interleukin-6, interferon (IFN)-a, IFN-ß and IFN-? levels were not affected by HVJ-E treatment. Intratumoral and subcutaneous injections of HVJ-E are feasible and PSA response was observed in a subgroup of CRPC patients.
  • Kentaro Jingushi; Yuri Kashiwagi; Yuko Ueda; Kaori Kitae; Hiroaki Hase; Wataru Nakata; Kazutoshi Fujita; Motohide Uemura; Norio Nonomura; Kazutake Tsujikawa
    INTERNATIONAL JOURNAL OF ONCOLOGY 51 1 289 - 297 2017年07月 [査読有り]
     
    Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney, and clear cell RCC (ccRCC) represents its most common histological subtype. Although several studies have reported high expression of miR-122 in ccRCC, its physiological role remains unclear. To clarify the role of miR-122 in ccRCC, we compared miR-122 expression levels in non-cancerous tissue and ccRCC. Significant upregulation of miR-122 was observed in ccRCC specimens. Moreover, ccRCC patients with high miR-122 expression showed poor progression-free survival compared to those with low miR-122 expression. Overexpression of miR-122 using an miRNA mimic promoted proliferation, migration, and invasion activities of ccRCC cells. miR-122 directly targets occludin, a known component of tight junctions. Occludin knockdown promoted the cell migration activity but not proliferation or invasion activities of ccRCC cells. In human clinical specimens, miR-122 expression inversely correlated with occludin protein expression. These findings show that miR-122 is an oncomiR in ccRCC.
  • Takashi Kawahara; Satoshi Inoue; Kazutoshi Fujita; Taichi Mizushima; Hiroki Ide; Seiji Yamaguchi; Hiroaki Fushimi; Norio Nonomura; Hiroshi Miyamoto
    TRANSLATIONAL ONCOLOGY 10 3 318 - 323 2017年06月 [査読有り]
     
    We recently found that NFATc1, a member of the NFAT family and a key regulator of the immune response, could induce bladder carcinogenesis and cancer progression. In this study, we immunohistochemically stained for NFATc1 in upper urinary tract urothelial carcinoma (UUTUC) specimens and paired nonneoplastic urothelial tissues. NFATc1 was positive in 51 52%; 40 (40%) weak (1+), 9 (9%) moderate (2+), and 2 (2%) strong (3+)] of 99 UUTUCs, which was significantly higher than in benign urothelium 30 (36%) of 83; 28 (34%) weak and 2 (2%) moderate] (0 vs 1+/2+/3+, P = .038; 0/1+ vs 2+/3+, P = .023). There were no significant associations between NFATc1 expression pattern and tumor grade or pT stage. However, the positive rates of NFATc1 expression tended to be higher in renal pelvic tumors (60%) than in ureteral tumors (42%; P = .080) as well as in pN+ tumors (75%) than in pN0 tumors (49%; P = .089). Kaplan-Meier and log-rank tests revealed that moderate (2+) to strong (3+) NFATc1 expression correlated with lower progression-free survival (P = .032) and cancer-specific survival (P = .005) rates in the 99 cases. Patients with high (2+/3+) NFATc1 muscle-invasive tumor (n = 9) also had a significantly higher risk of cancer-specific mortality (P = .021) compared to those with low (0/1+) NFATc1 muscle-invasive tumor (n = 53). Thus, compared with nonneoplastic urothelium, a significant increase in the expression of NFATc1 in UUTUC was seen, implying the involvement of NFATc1 signals in the development of UUTUC. The current results further suggest that NFATc1 overexpression serves as a predictor of poor prognosis in patients with UUTUC.
  • Satoshi Inoue; Taichi Mizushima; Kazutoshi Fujita; Abdelrazak Meliti; Hiroki Ide; Seiji Yamaguchi; Hiroaki Fushimi; George J. Netto; Norio Nonomura; Hiroshi Miyamoto
    HUMAN PATHOLOGY 64 83 - 90 2017年06月 [査読有り]
     
    Immunohistochemistry of a transcription factor, GATA3, has been widely used as a promising urothelial marker in diagnostic surgical pathology practice. However, the expression status of GATA3 in upper urinary tract urothelial carcinomas (UUTUCs) and its prognostic significance have not been fully investigated. We immunohistochemically stained for GATA3 in 99 UUTUC samples and paired nonneoplastic urothelial tissues. GATA3 was positive in 51 (5 I.5%; 32 [32.3%] weak, I I [11.1%] moderate, 8 [8. 1%] strong) of 99 UUTUCs, which was significantly lower than in benign urothelium (79 [96.3%] of 82; 33 [40.2%] weak, 35 [42.7%] moderate, 11 [13.4%] strong; P < .001). However, there were no statistically significant associations between GATA3 expression and tumor grade, pT stage, lymph node involvement, or distant metastasis. Meanwhile, the rate of GATA3 positivity was significantly higher (P = .004) in ureteral tumors (66.0%) than in renal pelvic tumors (35.6%). Kaplan-Meier and log-rank tests revealed that GATA3 negativity was significantly associated with lower recurrence-free survival (P = .037 for all cases, P = .026 for muscle-invasive tumors) and cancer-specific survival (P = .007 for all cases, P = .012 for muscle invasive tumors, P = .035 for cases with adjuvant chemotherapy) rates. Multivariate analysis further identified strong correlations of GATA3 expression with tumor progression (all cases: hazard ratio [HR],0.479 [95% confidence interval {CI}, 0.229-1.003; P = .051]; muscle-invasive tumors: HR, 0.387 [95% CI, 0.166-0.903; P = .028) or cancer-specific mortality (all cases: HR, 0.354 [95% CI, 0.135-0.925; P = .034]; muscle-invasive tumors: HR, 0.402 [95% CI, 0.149-1.086; P = .072]). Thus, compared with nonneoplastic urothelium, a significant decrease in the expression of GATA3 in UUTUC was seen. Moreover, loss of GATA3 expression was found to be an independent predictor of poor patient outcomes. Of note was that only roughly half of high-grade and/or muscle-invasive UUTUCs were immunoreactive for GATA3. (C) 2017 Elsevier Inc. All rights reserved.
  • Phase I/II clinical trial to assess safety and efficacy of intratumoral and subcutaneous injection of HVJ-E to castration resistant prostate cancer patients.
    Fujita, K; Nakai, Y; Kawashima, A; Ujike, T; Nagahara, A; Uemura, M; Miyagawa Y; Lee, C-M; Inoue, T; Kaneda, Y; Nonomura, I
    Cancer Gene Ther. 2017年05月 [査読有り]
  • Takuji Hayashi; Kazutoshi Fujita; Go Tanigawa; Atsunari Kawashima; Akira Nagahara; Takeshi Ujike; Motohide Uemura; Tetsuya Takao; Seiji Yamaguchi; Norio Nonomura
    ONCOTARGET 8 21 35255 - 35261 2017年05月 [査読有り]
     
    Systemic inflammation and immune responses are reported to be associated with progressive prostate cancer. In this study, we explored which among the fractions of white blood cell (WBC) and C-reactive protein (CRP) level were associated with high Gleason score prostate cancer. Prostate needle biopsy was performed in 966 men with suspicion of prostate cancer. We assessed age, serum prostate-specific antigen (PSA), prostate volume, WBC count, fractions of WBCs (neutrophils, lymphocytes, monocytes, basophils, and eosinophils), and CRP level before biopsy for associations with biopsy findings. Among all men, 553 (57.2%) were positive for prostate cancer including 421 with high Gleason score cancer (Gleason score = 7). Age, PSA, PSA density (PSAD), serum monocyte fraction of WBC, monocyte-to-lymphocyte ratio (MLR), and CRP were significantly associated with high Gleason score cancer (p<0.01). Multivariate analysis showed that age, PSA, PSAD, and serum monocyte fraction were significantly associated with high Gleason score prostate cancer(p< 0.01).In 571 patients with PSA of < 10 ng/ml, age, PSA, PSAD, serum WBC count, neutrophil fraction, monocyte fraction, and MLR were significantly associated with high Gleason score prostate cancer (p<0.05). Multivariate analysis showed that age, PSAD, and serum monocyte fraction were significantly associated with high Gleason score prostate cancer (p< 0.01). The monocyte fraction of WBCs was increased in patients with high Gleason score prostate cancer, suggesting an interaction of monocytes with the progression of prostate cancer.
  • Taichi Mizushima; Kazutoshi Fujita; Satoshi Inoue; Hiroki Ide; Takashi Kawahara; Mehrsa Jalalizadeh; Seiji Yamaguchi; Hiroaki Fushimi; Eiji Kashiwagi; George Netto; Norio Nonomura; Hiroshi Miyamoto
    JOURNAL OF UROLOGY 197 4 E948 - E948 2017年04月 [査読有り]
  • Kyosuke Matsuzaki; Kazutoshi Fujita; Kentaro Jingushi; Atsunari Kawashima; Takeshi Ujike; Akira Nagahara; Yuko Ueda; Go Tanigawa; Iwao Yoshioka; Koji Ueda; Rikinari Hanayama; Motohide Uemura; Yasushi Miyagawa; Kazutake Tsujikawa; Norio Nonomura
    ONCOTARGET 8 15 24668 - 24678 2017年04月 [査読有り]
     
    Background: Extracellular vesicles are lipid bilayer vesicles containing protein, messengerRNA and microRNA. Cancer cell-derived extracellular vesicles may be diagnostic and therapeutic targets. We extracted extracellular vesicles from urine of urothelial carcinoma patients and the control group to identify cancer-specific microRNAs in urinary extracellular vesicles as new biomarkers. Materials and methods: microRNA from urinary extracellular vesicles extracted from 6 urothelial carcinoma patients and 3 healthy volunteers was analyzed. We verified candidate microRNAs in an independent cohort of 60 urinary extracellular vesicles samples. To normalize the microRNA expression level in extracellular vesicles, we examined the following in extracellular vesicles: protein concentration, CD9 intensity, amounts of whole miRNAs, RNA U6B small nuclear expression and the creatinine concentration of original urine correlating with the counts of extracted extracellular vesicles measured by the NanoSight (TM) system. Results: From the microarray results 5 microRNAs overexpressed in urinary extracellular vesicles of urothelial carcinoma patients were identified. Creatinine concentration of original urine correlated most with particle counts of extracellular vesicles, indicating that creatinine could be a new tool for normalizing microRNA expression. MiR-21-5p was the most potent biomarker in urinary extracellular vesicles (sensitivity, 75.0%; specificity, 95.8%) and was also overexpressed in urinary extracellular vesicles from urothelial carcinoma patients with negative urine cytology. For the subgroup with negative urine cytology, the sensitivity was 75.0% and specificity was 95.8%. Conclusion: MiR-21-5p in urinary extracellular vesicles could be a new biomarker of urothelial carcinoma, especially for urothelial carcinoma patients with negative urine cytology.
  • Soda T; Miyagawa Y; Ueda N; Takezawa K; Okuda H; Fukuhara S; Fujita K; Kiuchi H; Uemura M; Okamoto Y; Tsujimura A; Tanaka H; Nonomura N
    Human reproduction (Oxford, England) 32 3 514 - 522 2017年03月 [査読有り]
     
    STUDY QUESTION: Is actin capping protein (CP) β3 involved in human spermatogenesis and male infertility? SUMMARY ANSWER: Human CPβ3 (hCPβ3) is expressed in testis, changes its localization dynamically during spermatogenesis, and has some association with male infertility. WHAT IS KNOWN ALREADY: The testis-specific α subunit of CP (CPα3) was previously identified in human, and mutations in the cpα3 gene in mouse were shown to induce malformation of the sperm head and male infertility. However, CPβ3, which is considered to be a heterodimeric counterpart of CPα3, has been neither characterized in human nor reported in association with male infertility. STUDY DESIGN, SIZE, DURATION: To confirm the existence of CPβ3 in human testis, fresh semen samples from proven fertile men were analyzed. To investigate protein expression during spermatogenesis, cryopreserved testis obtained from men with obstructive azoospermia were examined by immunofluorescent analysis. To assess the association of CP with male infertility, we compared protein expression of human CPα3 (hCPα3) and hCPβ3 using immunofluorescent analysis of cryopreserved sperm between men with normozoospermia (volunteers: Normo group, n = 20) and infertile men with oligozoospermia and/or asthenozoospermia (O + A group, n = 21). PARTICIPANTS/MATERIALS, SETTING, METHODS: The tissue-specific expression of hCPβ3 was investigated by RT-PCR and Western blot analysis. To investigate whether hCPα3 and hCPβ3 form a heterodimer, a tandem expression vector containing hcpα3 tagged with monomeric red fluorescent protein 1 and hcpβ3 tagged with enhanced green fluorescent protein in a single plasmid was constructed and analyzed by co-immunoprecipitation (Co-IP) assay. The protein expression profiles of hCPα3 and hCPβ3 during spermatogenesis were examined by immunohistochemical analysis using human spermatogenic cells. The protein expressions of hCPα3 and hCPβ3 in sperm were compared between the Normo and O + A groups by immunohistochemical analysis. MAIN RESULTS AND THE ROLE OF CHANCE: RT-PCR showed that mRNA of hcpβ3 was expressed exclusively in testis. Western blot analysis detected hCPβ3 with anti-bovine CPβ3 antibody. Co-IP assay with recombinant protein showed that hCPα3 and hCPβ3 form a protein complex. At each step during spermatogenesis, the cellular localization of hCPβ3 changed dynamically. In spermatogonia, hCPβ3 showed a slight signal in cytoplasm. hCPβ3 expression was conspicuous mainly from spermatocytes, and hCPβ3 localization dynamically migrated from cytoplasm to the acrosomal cap and acrosome. In mature spermatozoa, hCPβ3 accumulated in the postacrosomal region and less so at the midpiece of the tail. Double-staining analysis revealed that hCPα3 localization was identical to hCPβ3 at every step in the spermatogenic cells. Most spermatozoa from the Normo group were stained homogenously by both hCPα3 and hCPβ3. In contrast, significantly more spermatozoa in the O + A versus Normo group showed heterogeneous or lack of staining for either hCPα3 or hCPβ3 (abnormal staining) (P < 0.001). The percentage of abnormal staining was higher in the O + A group (52.4 ± 3.0%) than in the Normo group (31.2 ± 2.5%). Even by confining the observations to morphologically normal spermatozoa selected in accordance with David's criteria, the percentage of abnormal staining was still higher in the O + A group (39.9 ± 2.9%) versus the Normo group (22.5 ± 2.1%) (P < 0.001). hCPβ3 in conjunction with hCPα3 seemed to play an important role in spermatogenesis and may be associated with male infertility. LARGE SCALE DATA: Not applicable. LIMITATIONS REASONS FOR CAUTION: Owing to the difficulty of collecting fresh samples of human testis, we used cryopreserved samples from testicular sperm extraction. To examine the interaction of spermatogenic cells or localization in seminiferous tubules, fresh testis sample of healthy males are ideal. WIDER IMPLICATIONS OF THE FINDINGS: The altered expression of hCPα3 and hCPβ3 may not only be a cause of male infertility but also a prognostic factor for the results of ART. They may be useful biomarkers to determine the fertilization ability of human sperm in ART.
  • Kazutoshi Fujita; Hideaki Kume; Kyosuke Matsuzaki; Atsunari Kawashima; Takeshi Ujike; Akira Nagahara; Motohide Uemura; Yasushi Miyagawa; Takeshi Tomonaga; Norio Nonomura
    SCIENTIFIC REPORTS 7 2017年02月 [査読有り]
     
    Extracellular vesicles (EVs) are microvesicles secreted from various cell types. We aimed to discover a new biomarker for high Gleason score (GS) prostate cancer (PCa) in urinary EVs via quantitative proteomics. EVs were isolated from urine after massage from 18 men (negative biopsy [n = 6], GS 6 PCa [n = 6], or GS 8-9 PCa [n = 6]). EV proteins were labeled with iTRAQ and analyzed by LC-MS/MS. We identified 4710 proteins and quantified 3528 proteins in the urinary EVs. Eleven proteins increased in patients with PCa compared to those with negative biopsy (ratio > 1.5, p-value < 0.05). Eleven proteins were chosen for further analysis and verified in 29 independent urine samples (negative [n = 11], PCa [n = 18]) using selected reaction monitoring/multiple reaction monitoring. Among these candidate markers, fatty acid binding protein 5 (FABP5) was higher in the cancer group than in the negative group (p-value = 0.009) and was significantly associated with GS (p-value for trend = 0.011). Granulin, AMBP, CHMP4A, and CHMP4C were also higher in men with high GS prostate cancer (p-value < 0.05). FABP5 in urinary EVs could be a potential biomarker of high GS PCa.
  • Hayashi Y; Nagahara A; Kawashima A; Kakuta Y; Ujike T; Abe T; Fukuhara S; Fujita K; Uemura M; Kiuchi H; Imamura R; Miyagawa Y; Ichimaru N; Maeda T; Nonomura N
    Nihon Hinyokika Gakkai zasshi. The japanese journal of urology 108 3 166 - 169 2017年01月 [査読有り]
     
    A 57-year-old female patient on hemodialysis with chronic renal failure due to chronic glomerular nephritis received deceased donor kidney transplantation. Induction immunosuppressive therapy was combination of tacrolimus, mycophenolate mofetil, everolimus, prednisolone, and basiliximab. She was diagnosed with secondary thrombotic microangiopathy (TMA) by clinical findings such as hemolytic anemia, thrombocytopenia and acute kidney injury not by pathological findings on the 4th post-operative date. Plasma exchange was performed with suspension of tacrolimus. General conditions recovered, and the graft function was preserved.
  • Mehrsa Jalalizadeh; Satoshi Inoue; Kazutoshi Fujita; Hiroki Ide; Taichi Mizushima; Seiji Yamaguchi; Hiroaki Fushimi; Norio Nonomura; Hiroshi Miyamoto
    Integrative Cancer Science and Therapeutics 4 3 2017年 [査読有り]
  • Handa A; Fujita K; Kono T; Komori K; Hirobe S; Fukuzawa R
    Journal of medical imaging and radiation oncology 2016年12月
  • Hiroko Yamaguchi; Masatoshi Hori; Osamu Suzuki; Yuji Seo; Fumiaki Isohashi; Yasuo Yoshioka; Iori Sumida; Motohide Uemura; Kazutoshi Fujita; Akira Nagahara; Takeshi Ujike; Atsunari Kawashima; Norio Nonomura; Noriyuki Tomiyama; Kazuhiko Ogawa
    ANTICANCER RESEARCH 36 12 6551 - 6556 2016年12月 [査読有り]
     
    Aim: We aimed to investigate the correlation between biochemical recurrence (BCR) and the pretreatment apparent diffusion coefficient (ADC) ratio of tumor to normal prostate tissue in patients with prostate cancer who underwent intensity-modulated radiotherapy (IMRT). Patients and Methods: Retrospective analyses were performed for 101 patients diagnosed with localized prostate cancer who underwent IMRT at a dose of 70-78 Gy to the prostate gland and medial part of the seminal vesicles. Before treatment, all patients underwent magnetic resonance imaging including diffusion-weighted imaging of the prostate. BCR was defined as a rising prostate-specific antigen level (the Phoenix criterion). Results: The median follow-up for all patients was 29 months, and BCR occurred in 10 patients (9.9%). ADC ratios and Gleason scores were significant independent prognostic factors of BCR by multivariate analysis. Conclusion: The pretreatment ADC ratio was an independent prognostic factor for BCR in patients with prostate cancer who underwent IMRT.
  • Takeshi Ujike; Motohide Uemura; Atsunari Kawashima; Akira Nagahara; Kazutoshi Fujita; Yasushi Miyagawa; Norio Nonomura
    ANTI-CANCER DRUGS 27 10 1038 - 1043 2016年11月 [査読有り]
     
    To evaluate the clinical and histopathological effects of presurgical treatment with sunitinib on inferior vena cava (IVC) tumor thrombus. Between 2010 and 2014, we treated seven patients with renal cell carcinoma and IVC tumor thrombus presurgically with sunitinib. We retrospectively evaluated primitive tumor size, the level of tumor thrombus according to Novick's classification, its distance above the renal vein, thrombus diameter at its widest segment, and histopathological change after sunitinib treatment. Three patients were diagnosed histologically. Percutaneous biopsy of the renal mass before sunitinib treatment was performed in two patients. One patient was diagnosed after sunitinib treatment following nephrectomy. The primitive tumors shrank upon sunitinib therapy in four cases; however, although the caval thrombus was downstaged (from level II to I) in one patient, the level of caval thrombus did not change in five patients and increased in one patient (from level III to IV). We evaluated the histopathological effects in two patients. In one patient, the IVC tumor thrombus was mostly replaced with necrotic tissue, but its thrombus level was not downstaged. In the other patient, the IVC tumor thrombus was downstaged, but tumor thrombus was not replaced with necrotic tissue and viable tumor cells remained. Presurgical treatment with sunitinib for renal cell carcinoma with IVC tumor thrombus appears to have limited effect on IVC tumor thrombus, in contrast to its effects on primitive tumor shrinkage. In the absence of evidence of presurgical benefits from prospective studies, this treatment may not be systematically advisable.
  • Jumpci Oshima; Kazutoshi Fujita; Kcntaro Kishimoto; Kcigo Osuga; Osamu Suzuki; Tctsuji Soda; Yasutomo Nakai; Hiroshi Kluchi; Tetsuya Takao; Yasushi Miyagawa; Akira Tsujimura; Norio Nonomura
    Acta Urologica Japonica 62 11 605 - 607 2016年11月 [査読有り]
     
    We report a ease of nonischemic priapism following brachytherapy. A 63-ycar-old man presented 22 days after brachytherapy for prostate cancer. He suffered painless sustained incomplete erection for a few days. The patient was diagnosed with nonischemic priapism by cavernosal blood gas analysis. Right internal pudendal arteriography showed blood pooling in the cavcrnosum caused by arteriovenous fistula. Selective arterial embolization with gelatin sponge particles was performed and dctumcsccnce achieved. To our knowledge, this is the first case of high flow priapism caused by brachytherapy for prostate cancer. In addition, we reviewed the mechanism of high flow priapism.
  • Takeshi Ujike; Motohide Uemura; Atsunari Kawashima; Akira Nagahara; Kazutoshi Fujita; Yasushi Miyagawa; Norio Nonomura
    ANTI-CANCER DRUGS 27 10 1038 - 1043 2016年11月 [査読有り]
     
    To evaluate the clinical and histopathological effects of presurgical treatment with sunitinib on inferior vena cava (IVC) tumor thrombus. Between 2010 and 2014, we treated seven patients with renal cell carcinoma and IVC tumor thrombus presurgically with sunitinib. We retrospectively evaluated primitive tumor size, the level of tumor thrombus according to Novick's classification, its distance above the renal vein, thrombus diameter at its widest segment, and histopathological change after sunitinib treatment. Three patients were diagnosed histologically. Percutaneous biopsy of the renal mass before sunitinib treatment was performed in two patients. One patient was diagnosed after sunitinib treatment following nephrectomy. The primitive tumors shrank upon sunitinib therapy in four cases; however, although the caval thrombus was downstaged (from level II to I) in one patient, the level of caval thrombus did not change in five patients and increased in one patient (from level III to IV). We evaluated the histopathological effects in two patients. In one patient, the IVC tumor thrombus was mostly replaced with necrotic tissue, but its thrombus level was not downstaged. In the other patient, the IVC tumor thrombus was downstaged, but tumor thrombus was not replaced with necrotic tissue and viable tumor cells remained. Presurgical treatment with sunitinib for renal cell carcinoma with IVC tumor thrombus appears to have limited effect on IVC tumor thrombus, in contrast to its effects on primitive tumor shrinkage. In the absence of evidence of presurgical benefits from prospective studies, this treatment may not be systematically advisable.
  • Jumpci Oshima; Kazutoshi Fujita; Kcntaro Kishimoto; Kcigo Osuga; Osamu Suzuki; Tctsuji Soda; Yasutomo Nakai; Hiroshi Kluchi; Tetsuya Takao; Yasushi Miyagawa; Akira Tsujimura; Norio Nonomura
    Acta Urologica Japonica 62 11 605 - 607 2016年11月 [査読有り]
     
    We report a ease of nonischemic priapism following brachytherapy. A 63-ycar-old man presented 22 days after brachytherapy for prostate cancer. He suffered painless sustained incomplete erection for a few days. The patient was diagnosed with nonischemic priapism by cavernosal blood gas analysis. Right internal pudendal arteriography showed blood pooling in the cavcrnosum caused by arteriovenous fistula. Selective arterial embolization with gelatin sponge particles was performed and dctumcsccnce achieved. To our knowledge, this is the first case of high flow priapism caused by brachytherapy for prostate cancer. In addition, we reviewed the mechanism of high flow priapism.
  • Doreen Nguyen; Diana Taheri; Simeon Springer; Morgan Cowan; Gunes Guner; Maria Angelica Mendoza Rodriguez; Yuxuan Wang; Isaac Kinde; Christopher J. VandenBussche; Matthew T. Olson; Bernardo F. P. Ricardo; Isabela Cunha; Kazutoshi Fujita; Dilek Ertoy; Kenneth W. Kinzler; Trinity J. Bivalacqua; Nickolas Papadopoulos; Bert Vogelstein; George J. Netto
    VIRCHOWS ARCHIV 469 4 427 - 434 2016年10月 [査読有り]
     
    Somatic activating mutations in the promoter of the telomerase reverse transcriptase (TERT) gene are the most common genetic alterations in urothelial carcinoma (UC) of the bladder and upper urinary tract. Little is known, however, about TERT-mutation status in the relatively uncommon but clinically aggressive micropapillary (MPC) variant. We evaluated the presence of TERT promoter mutations in MPC of the bladder and upper urinary tract. A retrospective search of our archives for MPC and UC with micropapillary features (2005-2014) was performed. All slides were reviewed to confirm the histologic diagnosis. Thirty-three specimens from 31 patients had FFPE blocks available for DNA analysis and were included in the study. Intratumoral areas of non-micropapillary histology were also evaluated when present. Samples were analyzed with Safe-SeqS, a sequencing error reduction technology, and sequenced using the Illumina MiSeq platform. TERT promoter mutations were detected in all specimens with pure MPC (18 of 18) and UC with focal micropapillary features (15 of 15). Similar to conventional UC, the predominant mutations identified occurred at positions -124 (C228T) (85 %) and -146 (C250T) (12 %) bp upstream of the TERT ATG start site. In heterogeneous tumors with focal variant histology, intratumoral concordant mutations were found in variant (MPC and non-MPC) and corresponding conventional UC. We found TERT promoter mutations, commonly found in conventional UC, to be frequently present in MPC. Our finding of concordant intratumoral mutational alterations in cases with focal variant histology lends support to the common oncogenesis origin of UC and its variant histology.
  • Kazutoshi Fujita; Norio Nonomura
    International Journal of Urology 23 10 838 - 839 2016年10月 [査読有り]
  • Kazutoshi Fujita
    INTERNATIONAL JOURNAL OF UROLOGY 23 9 724 - 725 2016年09月 [査読有り]
  • Kazutoshi Fujita; Takuji Hayashi; Kyosuke Matsuzaki; Wataru Nakata; Mika Masuda; Atsunari Kawashima; Takeshi Ujike; Akira Nagahara; Mutsumi Tsuchiya; Yuka Kobayashi; Satoshi Nojima; Motohide Uemura; Eiichi Morii; Eiji Miyoshi; Norio Nonomura
    ONCOTARGET 7 35 56643 - 56649 2016年08月 [査読有り]
     
    Fucosylation is an important oligosaccharide modification associated with cancer and inflammation. We investigated whether urinary fucosylated PSA (Fuc-PSA) levels could be used for the detection of high Gleason score prostate cancer. Urine samples were collected from men with abnormal digital rectal examination findings or elevated serum PSA levels, before prostate biopsy. Lectin-antibody ELISA was used to quantify the Lewis-type or core-type fucosylated PSA (PSA-AAL) and core-type fucosylated PSA (PSA-PhoSL) in the urine samples. Both types of urinary Fuc-PSA were significantly decreased in the men with prostate cancer compared with the men whose biopsies were negative for cancer (P = 0.026 and P < 0.001, respectively). Both were also significantly associated with the Gleason scores of the biopsy specimens (P = 0.001 and P < 0.001, respectively). Multivariate analysis showed that PSA density, urinary PSA-AAL, and urinary PSA-PhoSL were independent predictors of high Gleason score prostate cancer. The area under the receiver-operator characteristic curve (AUC) value for the prediction of cancers of Gleason score = 7 was 0.69 for urinary PSA-AAL and 0.72 for urinary PSA-PhoSL. In contrast, the AUC value was 0.59 for serum PSA, 0.63 for PSA density, and 0.58 for urinary PSA. In conclusion, a decreased urinary Fuc-PSA level is a potential marker for the detection of high Gleason score prostate cancer.
  • Morgan L. Cowan; Simeon Springer; Doreen Nguyen; Diana Taheri; Gunes Guner; Maria Angelica Mendoza Rodriguez; Yuxuan Wang; Isaac Kinde; Maria Del Carmen Rodriguez Pena; Christopher J. VandenBussche; Mathew T. Olson; Isabela Cunha; Kazutoshi Fujita; Dilek Ertoy; Kenneth Kinzler; Trinity Bivalacqua; Nickolas Papadopoulos; Bert Vogelstein; George J. Netto
    HUMAN PATHOLOGY 53 8 - 13 2016年07月 [査読有り]
     
    TERT promoter mutations (TERT-mut) have been detected in 60% to 80% of urothelial carcinomas. A molecular urine-based screening assay for the detection of TERT-mut is currently being pursued by our group and others. A small but significant number of bladder carcinomas are adenocarcinoma. The current study assesses the incidence of TERT-mut in primary adenocarcinomas of urinary bladder. A retrospective search of our institutional pathology records identified 23 cystectomy specimens with a diagnosis of adenocarcinoma (2000-2014). All slides were reviewed by a senior urologic pathologist to confirm tumor type and select a representative formalin-fixed, paraffin-embedded block for mutational analysis. Adequate material for DNA testing was available in 14 cases (7 enteric type and 7 not otherwise specified). TERT-mut sequencing analysis was performed using previously described SafeSeq technique. Overall, 28.5% of primary adenocarcinoma harbored TERT-mut. Interestingly, 57% of nonenteric adenocarcinomas were mutation positive, whereas none of the enteric-type tumors harbored mutations. Similar to urothelial carcinoma, we found a relatively higher rate of TERT-mut among nonenteric-type adenocarcinomas further supporting the potential utility of TERT-mut urine-based screening assay for bladder cancer. (C) 2016 Published by Elsevier Inc.
  • Kyosuke Matsuzaki; Kazutoshi Fujita; Takeshi Ujike; Motohide Uemura; Norio Nonomura; Yasushi Miyagawa
    INTERNATIONAL JOURNAL OF UROLOGY 23 7 623 - 624 2016年07月 [査読有り]
  • Shiro Takahashi; Taiki Sugiyama; Mayuka Shimomura; Yoshihiro Kamada; Kazutoshi Fujita; Norio Nonomura; Eiji Miyoshi; Miyako Nakano
    GLYCOCONJUGATE JOURNAL 33 3 471 - 482 2016年06月 [査読有り]
     
    Fucosylation is an important type of glycosylation involved in cancer, and fucosylated proteins could be employed as cancer biomarkers. Previously, we reported that fucosylated N-glycans on haptoglobin in the sera of patients with pancreatic cancer were increased by lectin-ELISA and mass spectrometry analyses. However, an increase in fucosylated haptoglobin has been reported in various types of cancer. To ascertain if characteristic fucosylation is observed in each cancer type, we undertook site-specific analyses of N-glycans on haptoglobin in the sera of patients with five types of operable gastroenterological cancer (esophageal, gastric, colon, gallbladder, pancreatic), a non-gastroenterological cancer (prostate cancer) and normal controls using ODS column LC-ESI MS. Haptoglobin has four potential glycosylation sites (Asn184, Asn207, Asn211, Asn241). In all cancer samples, monofucosylated N-glycans were significantly increased at all glycosylation sites. Moreover, difucosylated N-glycans were detected at Asn 184, Asn207 and Asn241 only in cancer samples. Remarkable differences in N-glycan structure among cancer types were not observed. We next analyzed N-glycan alditols released from haptoglobin using graphitized carbon column LC-ESI MS to identify the linkage of fucosylation. Lewis-type and core-type fucosylated N-glycans were increased in gastroenterological cancer samples, but only core-type fucosylated N-glycan was relatively increased in prostate cancer samples. In metastatic prostate cancer, Lewis-type fucosylated N-glycan was also increased. These data suggest that the original tissue/cell producing fucosylated haptoglobin is different in each cancer type and linkage of fucosylation might be a clue of primary lesion, thereby enabling a differential diagnosis between gastroenterological cancers and non-gastroenterological cancers.
  • Morgan Cowan; Simeon Springer; Doreen Nguyen; Diana Taheri; Gunes Guner; Maria Angelica Mendoza Rodriguez; Yuxuan Wang; Isaac Kinde; Christopher J. VandenBussche; Matthew T. Olson; Isabela Cunha; Kazutoshi Fujita; Dilek Ertoy; Trinity J. Bivalacqua; Kenneth Kinzler; Bert Vogelstein; George J. Netto; Nickolas Papadopoulos
    MODERN PATHOLOGY 29 5 511 - 515 2016年05月 [査読有り]
     
    TERT promoter mutations (TERT-mut) are detectable in the majority of urothelial carcinomas. The detection of TERT-mut in urine is under investigation as a potential urine-based molecular-screening assay for bladder cancer. A small but significant number of bladder carcinomas are pure squamous cell carcinoma. We sought to assess the incidence of TERT-mut in squamous cell carcinoma of the urinary bladder. A retrospective search of the institutional pathology archives yielded 15 cystectomy specimens performed for squamous cell carcinoma (2000-2014). Histologic slides were reviewed by a senior urologic pathologist to confirm the diagnosis and select a representative formalin-fixed paraffin-embedded tissue block for mutational analysis. All cases yielded adequate material for DNA analysis. Sequencing for TERT-mut was performed using previously described SafeSeq technique. We detected TERT-mut in 12/15 (80%) of bladder squamous cell carcinomas. TERT promoter mutations, commonly found in conventional urothelial carcinoma, are also highly prevalent in urinary bladder squamous cell carcinoma suggesting a common tumorigenesis and potential utility as a molecular urine-based-screening assay.
  • 淡明細胞型腎細胞癌においてlysyl oxidase like 2(LOXL2)の発現は予後に関係し、浸潤・遊走能を亢進させる
    木内 利郎; 植村 元秀; 長谷 拓明; 神宮司 健太郎; 藤田 和利; 辻川 和丈; 野々村 祝夫
    日本泌尿器科学会総会 104回 PP3 - 165 (一社)日本泌尿器科学会総会事務局 2016年04月 [査読有り]
  • miR-122は淡明細胞型腎細胞癌の再発予測因子であり、occludinを抑制することで浸潤、遊走能を亢進する
    中田 渡; 植村 元秀; 柏木 悠里; 神宮司 健太郎; 藤田 和利; 辻川 和丈; 野々村 祝夫
    日本泌尿器科学会総会 104回 PP3 - 167 (一社)日本泌尿器科学会総会事務局 2016年04月 [査読有り]
  • Mai Kimakura; Toyofumi Abe; Akira Nagahara; Kazutoshi Fujita; Hiroshi Kiuchi; Motohide Uemura; Norio Nonomura
    ANTI-CANCER DRUGS 27 4 364 - 368 2016年04月 [査読有り]
     
    A 25-year-old man was admitted to our hospital complaining of right scrotal pain and upper abdominal pain. A computed tomographic scan indicated a right scrotal mass, a huge liver mass, and multiple lung masses, although there was no enlarged retroperitoneal lymph node swelling. Laboratory tests showed severe liver and kidney dysfunction and high levels of serum alpha-fetoprotein (11 997 ng/ml). Although needle biopsies of the testicular and liver masses were performed, the tissues were insufficient for a pathological diagnosis. As liver and kidney function worsened, we started chemotherapy with bleomycin, etoposide, and cisplatin (BEP chemotherapy), which was modified because of the liver and renal dysfunction. We also used continuous hemodiafiltration and rasburicase to prevent tumor lysis syndrome. After induction of chemotherapy, the liver and kidney dysfunction improved immediately and the high orchiectomy was performed on day 8 after chemotherapy. The pathological diagnosis was a yolk sac tumor. He underwent four courses of the BEP regimen and five courses of the TIN regimen (paclitaxel, ifosphamide, and nedaplatin), followed by the resection of liver metastases. There was no evidence of viable cells in the resected liver and no recurrence was evident at 1 year postoperatively.
  • Akira Nagahara; Motohide Uemura; Atsunari Kawashima; Takeshi Ujike; Kazutoshi Fujita; Yasushi Miyagawa; Norio Nonomura
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 21 2 367 - 372 2016年04月 [査読有り]
     
    We investigated the association between the R.E.N.A.L. nephrometry score (RNS) and the postoperative recurrence of localized renal cell carcinoma (RCC). We retrospectively analyzed a database comprising 91 patients with non-small localized RCC (pT1b-T2b) treated by radical nephrectomy at our hospital from January 2002 to March 2010. RNS was scored based on imaging findings at diagnosis. The Cox proportional hazards model was used to predict recurrence-free survival (RFS) and to calculate hazard ratio (HR). The median age at operation was 63 years (range, 30-85 years). Postoperative recurrence occurred in 19 patients (21 %). Median RNS sum was 9 (range, 5-11). High RNS sum (10-12) was significantly associated with RFS (P = 0.0012). Multivariate analysis revealed that high RNS sum [HR, 9.05; 95 % confidence interval (CI), 2.11-63.9; P = 0.0019] were significantly associated with RFS. Regarding each component of RNS, only the L component, which referred to tumor location relative to the polar line, was associated with RFS (HR, 15.0; 95 % CI, 2.68-396; P = 0.0006). RNS was associated with RFS in cases of non-small localized RCC (pT1b-2b), thus supporting its utility as a prognostic factor.
  • Mai Kimakura; Toyofumi Abe; Akira Nagahara; Kazutoshi Fujita; Hiroshi Kiuchi; Motohide Uemura; Norio Nonomura
    ANTI-CANCER DRUGS 27 4 364 - 368 2016年04月 [査読有り]
     
    A 25-year-old man was admitted to our hospital complaining of right scrotal pain and upper abdominal pain. A computed tomographic scan indicated a right scrotal mass, a huge liver mass, and multiple lung masses, although there was no enlarged retroperitoneal lymph node swelling. Laboratory tests showed severe liver and kidney dysfunction and high levels of serum alpha-fetoprotein (11 997 ng/ml). Although needle biopsies of the testicular and liver masses were performed, the tissues were insufficient for a pathological diagnosis. As liver and kidney function worsened, we started chemotherapy with bleomycin, etoposide, and cisplatin (BEP chemotherapy), which was modified because of the liver and renal dysfunction. We also used continuous hemodiafiltration and rasburicase to prevent tumor lysis syndrome. After induction of chemotherapy, the liver and kidney dysfunction improved immediately and the high orchiectomy was performed on day 8 after chemotherapy. The pathological diagnosis was a yolk sac tumor. He underwent four courses of the BEP regimen and five courses of the TIN regimen (paclitaxel, ifosphamide, and nedaplatin), followed by the resection of liver metastases. There was no evidence of viable cells in the resected liver and no recurrence was evident at 1 year postoperatively.
  • Yasuo Yoshioka; Osamu Suzuki; Fumiaki Isohashi; Yuji Seo; Hirofumi Okubo; Hiroko Yamaguchi; Michio Oda; Yuki Otani; Iori Sumida; Motohide Uemura; Kazutoshi Fujita; Akira Nagahara; Takeshi Ujike; Atsunari Kawashima; Ken Yoshida; Hideya Yamazaki; Norio Nonomura; Kazuhiko Ogawa
    INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 94 4 675 - 682 2016年03月 [査読有り]
     
    Purpose: To present mature results of high-dose-rate brachytherapy (HDR-BT) as monotherapy for intermediate-and high-risk prostate cancer. Methods and Materials: From 1995 through 2012, 190 patients, 79 with intermediate-risk and 111 with high-risk prostate cancer, were treated with HDR-BT alone using 48 Gy/8 fractions, 54 Gy/9 fractions, or 45.5 Gy/7 fractions over 4 to 5 days. Neoadjuvant with or without adjuvant androgen deprivation therapy was administered to 139 patients, 35 intermediate-and 104 high-risk. Results: Median follow-up time was 92 months (range, 10-227 months), with a minimum of 2 years for surviving patients. Respective rates of cause-specific survival, overall survival, metastasis-free survival, and biochemical no evidence of disease for the intermediate-risk patients were 100%, 100%, 96%, and 93% at 5 years, and 100%, 96%, 91%, and 91% at 8 years. Corresponding rates for the high-risk patients were 97%, 93%, 84%, and 81% at 5 years, and 93%, 81%, 74%, and 77% at 8 years. The cumulative incidence of late grade 2 to 3 genitourinary toxicity was 5% at 5 years and 10% at 8 years, and that of late grade 3 was 0 at 5 years and 1% at 8 years. The cumulative incidence of late grade 2-3 gastrointestinal toxicity was 4% at 5 years and 6% at 8 years, and that of late grade 3 was 0 at 5 years and 2% at 8 years. No grade 4 or 5 toxicity was detected. Conclusions: Our single-institution study with a median 8-year follow-up showed that HDR-BT as monotherapy was safe and effective for patients with intermediate-and high-risk prostate cancer. (c) 2016 Elsevier Inc. All rights reserved.
  • Hiroshi Egawa; Kentaro Jingushi; Takayuki Hirono; Yuko Ueda; Kaori Kitae; Wataru Nakata; Kazutoshi Fujita; Motohide Uemura; Norio Nonomura; Kazutake Tsujikawa
    SCIENTIFIC REPORTS 6 2016年02月 [査読有り]
     
    Bladder cancer causes an estimated 150,000 deaths per year worldwide. Although 15% of the recurrent bladder cancer becomes an invasive type, currently used targeted therapy for malignant bladder cancer is still not efficient. We focused on the miR-130 family (miR-130b, miR-301a, and miR-301b) that was significantly upregulated in bladder cancer specimens than that of the normal urothelial specimens. We analyzed the functional significance of miR-130 family using a 5637 bladder cancer cell line and revealed that miR-130 family of inhibitors suppressed cell migration and invasion by downregulating focal adhesion kinase (FAK) and Akt phosphorylation. Mechanistic analyses indicate that the miR-130 family directly targets phosphatase and tensin homolog deleted from chromosome 10 (PTEN), resulting in the upregulation of FAK and Akt phosphorylation. In clinical bladder cancer specimens, downregulation of PTEN was found to be closely correlated with miR-130 family expression levels. Overall, the miR-130 family has a crucial role in malignant progression of bladder cancer and thus the miR-130 family could be a promising therapeutic target for invasive bladder cancer.
  • Nishimoto S; Tonooka M; Fujita K; Sotsuka Y; Fujiwara T; Kawai K; Kakibuchi M
    Journal of surgical case reports 2016年
  • Eiji Kashiwagi; Kazutoshi Fujita; Seiji Yamaguchi; Hiroaki Fushimi; Hiroki Ide; Satoshi Inoue; Taichi Mizushima; Leonardo O. Reis; Rajni Sharma; George J. Netto; Norio Nonomura; Hiroshi Miyamoto
    CANCER BIOLOGY & THERAPY 17 11 1188 - 1196 2016年 [査読有り]
     
    To assess the expression status of steroid hormone receptors in upper urinary tract urothelial carcinoma (UUTUC), we immunohistochemically stained for androgen receptor (AR), estrogen receptor-alpha (ER alpha), ER beta, glucocorticoid receptor (GR), and progesterone receptor (PR) in 99 UUTUC specimens and paired nonneoplastic urothelial tissues. AR/ER alpha/ER beta/GR/PR was positive in 20%/18%/62%/63%/16% of tumors, which was significantly lower (except PR) than in benign urothelial tissues [57% (P < 0.001)/40% (P = 0.001)/85% (P = 0.001)/84% (P = 0.002)/13% (P = 0.489)]. There were no significant associations between each receptor expression pattern and histopathological characteristic of the tumors including tumor grade/stage. Kaplan-Meier and log-rank tests revealed no significant prognostic value of each receptor expression in these 99 patients. However, patients with UUTUC positive for either ER alpha or PR had a significantly higher risk of disease-specific mortality (P = 0.025), compared with those with UUTUC negative for both. PR positivity alone in pT3 or pT4 tumors was also strongly associated with the risk of disease-specific mortality (P = 0.040). Multivariate analysis further identified the expression of ER alpha and/or PR as a strong predictor for disease-specific mortality in the entire cohort of the patients (hazard ratio, 2.434; P = 0.037). Thus, in accordance with previous observations in bladder specimens, significant decreases in the expression of AR/ER alpha/ER beta/GR in UUTUC, compared with that in non-neoplastic urothelium, were observed. Meanwhile, the negativity of both ERa and PR in UUTUC as well as the negativity of PR alone in deeply invasive tumor was suggested to serve as a prognosticator.
  • 今村 亮一; 藤田 和利; 植村 元秀; 木内 寛; 宮川 康; 野々村 祝夫
    Japanese Journal of Endourology 28 3 223 - 223 (一社)日本泌尿器内視鏡学会 2015年11月
  • Kazutoshi Fujita; Teruo Inamoto; Yoshiyuki Yamamoto; Go Tanigawa; Masashi Nakayama; Naoki Mori; Masao Tsujihata; Haruhito Azuma; Norio Nonomura; Motohide Uemura
    INTERNATIONAL JOURNAL OF UROLOGY 22 11 1006 - 1012 2015年11月 [査読有り]
     
    ObjectiveTo analyze the role of adjuvant chemotherapy in lymph node-positive patients with upper tract urothelial carcinoma undergoing radical nephroureterectomy, and identified the prognostic adjuvant chemotherapy parameters. MethodsThe clinicopathological records of 74 lymph node-positive upper tract urothelial carcinoma patients who underwent radical nephroureterectomy at multiple institutions were retrospectively reviewed. A total of 45 patients (60.8%) received adjuvant chemotherapy, and 29 (39.2%) underwent radical nephroureterectomy only. Kaplan-Meier analyses and Cox proportional hazard modeling were used to study the association between adjuvant chemotherapy status and both recurrence-free survival and cancer-specific survival. ResultsEstimated 5-year recurrence-free survival was 33.6% in patients undergoing radical nephroureterectomy plus adjuvant chemotherapy compared with 13.5% in patients undergoing radical nephroureterectomy only (hazard ratio 0.52; P=0.014, log-rank test). Estimated 5-year cancer-specific survival was 42.5% in patients undergoing radical nephroureterectomy plus adjuvant chemotherapy, compared with 12.0% in patients undergoing radical nephroureterectomy only (hazard ratio 0.36; P=0.0003, log-rank test). Multivariate analysis showed that adjuvant chemotherapy was a significant prognostic factor for cancer-specific survival (P=0.001), but not for recurrence-free survival (P=0.076). When patients undergoing radical nephroureterectomy plus adjuvant chemotherapy were dichotomized, based on preoperative C-reactive protein levels above or below the normal value, higher C-reactive protein levels were significantly associated with poor survival (P=0.012). ConclusionAdjuvant chemotherapy seems to improve cancer-specific survival in lymph node-positive patients with upper tract urothelial carcinoma. Preoperative C-reactive protein levels could carry a prognostic value in this setting, and lymph node-positive patients with low preoperative CRP values should be considered for adjuvant chemotherapy. Further studies are necessary to validate these observations.
  • Wataru Nakata; Motohide Uemura; Mototaka Sato; Kazutoshi Fujita; Kentaro Jingushi; Yuko Ueda; Kaori Kitae; Kazutake Tsujikawa; Norio Nonomura
    ONCOTARGET 6 25 21645 - 21654 2015年08月 [査読有り]
     
    MicroRNAs (miRNAs) are noncoding RNAs that regulate gene expression and function in tumor development and progression. We previously identified up-regulated miRNAs in clear cell renal cell carcinoma (ccRCC) compared to matched-pair normal kidney by microarray. Here, we identify miRNAs that are up-regulated in ccRCC and are also correlated with survival and/or recurrence. Twenty-four samples from ccRCC patients who underwent nephrectomies between 2011 and 2012 were divided into two groups: one of eleven patients who experienced recurrence (Group 1), and one of thirteen patients with no evidence of disease (Group 2) 2 years after surgery. Analyzing 22 miRNAs that were up-regulated in ccRCC in our previous study, we identify five miRNAs that were statistically up-regulated in Group 1 versus Group 2 by quantitative real-time PCR. We then evaluated these miRNAs in an independent cohort of 159 frozen ccRCC samples. High levels of miR-27a-3p (p < 0.01) correlated with a worse progression-free survival rate. Multivariate analysis revealed that miR-27a-3p was an independent predictive factor for recurrence. For functional analysis, miR-27a-3p controlled cell proliferation, migration and invasion in RCC cell lines. MiR-27a-3p could act as oncogenic miRNA and may be a candidate for targeted molecular therapy in ccRCC.
  • Wataru Nakata; Yasutomo Nakai; Takahiro Yoshida; Mototaka Sato; Koji Hatano; Akira Nagahara; Kazutoshi Fujita; Motohide Uemura; Norio Nonomura
    PROSTATE 75 8 806 - 814 2015年06月 [査読有り]
     
    BACKGROUNDRecent studies have reported that bone marrow-derived cells (BMDCs), which are recruited to sites of tissue injury and inflammation, can differentiate into epithelial cells, such as liver, lung, gastrointestinal tract, and skin cells. We investigated the role of BMDCs in contributing to regeneration of injured prostate epithelium. METHODSUsing chimera rats that received allogenic bone marrow grafts from green fluorescent protein (GFP) transgenic rats after lethal whole-body irradiation, we investigated the existence of epithelial marker-positive BMDCs in injured prostate tissue caused by transurethral injection of lipopolysaccharide. RESULTSProstate tissues were harvested 2 weeks after transurethral lipopolysaccharide injection. Immunofluorescence staining showed that some cells in the stroma co-expressed GFP and pan-cytokeratin, which suggested the existence of epithelial marker-positive BMDCs. To confirm the existence of such cells, we collected bone marrow-derived non-hematopoietic cells (GFP+/CD45- cells) from the prostate by fluorescence-activated cell sorter analysis and analyzed the characteristics of the GFP+/CD45- cells. The number of cells in this population significantly increased from 0.042% to 0.492% compared with normal prostate tissue. We found by immunofluorescent analysis and RT-PCR that GFP+/CD45- cells expressed cytokeratin, which suggested that these cells have some features of epithelial cells. In the prostate obtained from the chimera rats 34 weeks after lipopolysaccharide injection, GFP- and cytokeratin-positive cells were observed in the prostate gland, which suggested that some of the cells in the prostate gland regenerated after prostate inflammation derived from bone marrow. CONCLUSIONSBMDCs might be able to differentiate into prostate epithelial cells after prostatic injury. Prostate 75:806-814, 2015. (c) 2015 Wiley Periodicals, Inc.
  • Kazutoshi Fujita; Takeshi Ujike; Akira Nagahara; Motohide Uemura; Go Tanigawa; Kohki Shimazu; Hiroaki Fushimi; Seiji Yamaguchi; Norio Nonomura
    INTERNATIONAL JOURNAL OF UROLOGY 22 5 463 - 467 2015年05月 [査読有り]
     
    ObjectivesTo evaluate the expression and prognostic significance of endoglin in patients with upper urinary tract urothelial carcinoma. MethodszArchival formalin-fixed and paraffin-embedded tissues from 99 cases of primary upper urinary tract urothelial carcinomas treated with nephroureterectomy were retrieved. Tissue microarrays were constructed with triplicate tumor samples and paired non-neoplastic urothelium. Tissue microarrays were analyzed using immunohistochemistry for endoglin, and the associations between clinicopathological parameters and outcome were studied. ResultsEndoglin expression was significantly higher in the endothelium of upper urinary tract urothelial carcinomas than in paired benign urothelium (P<0.001). Endoglin expression was not associated with pathological Tstage or tumor grade, and it was not associated with increased hazard ratios for cancer-specific mortality, tumor recurrence in the lymph node or distant metastasis. However, expression of endoglin was significantly associated with intravesical recurrence, when adjusting for other relevant clinicopathological variables (P=0.015). ConclusionsEndoglin is overexpressed in the endothelium of upper urinary tract urothelial carcinomas when compared with normal urothelium, and this overexpression seems to be associated with a higher risk of intravesical recurrence. Therefore, endoglin could be a biomarker for the prediction of intravesical recurrence, as well as a potential therapeutic target.
  • Jumpei Oshima; Kazutoshi Fujita; Yasutomo Nakai; Takeshi Kainuma; Hiroyuki Nishi; Norio Nonomura
    Acta Urologica Japonica 61 5 207 - 210 2015年05月 [査読有り]
     
    A 64-year-old man presented with right renal cell carcinoma with tumoral thrombosis in the inferior vena cava. Transthoracic echocardiography and contrast-enhanced computed tomography 2 days before the scheduled surgery revealed a tumoral thrombus floating in the right atrium. The tumoral thrombus measured 2 by 3 centimeters and the patient was asymptomatic. An emergency surgey was performed to remove the tumoral thrombus from the right atrium and a temporary inferior vena cava filter was placed. Right nephrectomy and thrombectomy were carried out 3 weeks later. Pathological diagnosis made from both surgical specimens was clear cell renal cell carcinoma, and the tumoral thrombus was considered to have separated from the tumor thrombus in inferior vena cava. No obvious recurrence has been observed for 6 months after the surgery.
  • Wataru Nakata; Motohide Uemura; Toshiro Kinouchi; Takuji Hayashi; Kyosuke Matsuzaki; Norihiko Kawamura; Atsunari Kawashima; Takeshi Ujike; Akira Nagahara; Kazutoshi Fujita; Kentaro Jingushi; Kazutake Tsujikawa; Norio Nonomura
    JOURNAL OF UROLOGY 193 4 E552 - E552 2015年04月 [査読有り]
  • Eiji Kashiwagi; Kazutoshi Fujita; Seiji Yamaguchi; Hiroaki Fushimi; Leonardo Reis; George Netto; Norio Nonomura; Hiroshi Miyamoto
    JOURNAL OF UROLOGY 193 4 E69 - E69 2015年04月 [査読有り]
  • Jingushi K; Ueda Y; Kitae K; Hase H; Egawa H; Ohshio I; Kawakami R; Kashiwagi Y; Tsukada Y; Kobayashi T; Nakata W; Fujita K; Uemura M; Nonomura N; Tsujikawa K
    Molecular cancer research : MCR 13 3 565 - 574 2015年03月 [査読有り]
     
    Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney, and clear cell RCC (ccRCC) represents its most common histological subtype. To identify a therapeutic target for ccRCC, miRNA expression signatures from ccRCC clinical specimens were analyzed. miRNA microarray and real-time PCR analyses revealed that miR-629 expression was significantly upregulated in human ccRCC compared with adjacent noncancerous renal tissue. Functional inhibition of miR-629 by a hairpin miRNA inhibitor suppressed ccRCC cell motility and invasion. Mechanistically, miR-629 directly targeted tripartite motif-containing 33 (TRIM33), which inhibits the TGF beta/Smad signaling pathway. In clinical ccRCC specimens, downregulation of TRIM33 was observed with the association of both pathologic stages and grades. The miR-629 inhibitor significantly suppressed TGF beta-induced Smad activation by upregulating TRIM33 expression and subsequently inhibited the association of Smad2/3 and Smad4. Moreover, a miR-629 mimic enhanced the effect of TGF beta on the expression of epithelial-mesenchymal transition-related factors as well as on the motility and invasion in ccRCC cells. These findings identify miR-629 as a potent regulator of the TGF beta/Smad signaling pathway via TRIM33 in ccRCC.
  • Jingushi K; Ueda Y; Kitae K; Hase H; Egawa H; Ohshio I; Kawakami R; Kashiwagi Y; Tsukada Y; Kobayashi T; Nakata W; Fujita K; Uemura M; Nonomura N; Tsujikawa K
    Molecular cancer research : MCR 13 3 565 - 574 2015年03月 [査読有り]
     
    Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney, and clear cell RCC (ccRCC) represents its most common histological subtype. To identify a therapeutic target for ccRCC, miRNA expression signatures from ccRCC clinical specimens were analyzed. miRNA microarray and real-time PCR analyses revealed that miR-629 expression was significantly upregulated in human ccRCC compared with adjacent noncancerous renal tissue. Functional inhibition of miR-629 by a hairpin miRNA inhibitor suppressed ccRCC cell motility and invasion. Mechanistically, miR-629 directly targeted tripartite motif-containing 33 (TRIM33), which inhibits the TGF beta/Smad signaling pathway. In clinical ccRCC specimens, downregulation of TRIM33 was observed with the association of both pathologic stages and grades. The miR-629 inhibitor significantly suppressed TGF beta-induced Smad activation by upregulating TRIM33 expression and subsequently inhibited the association of Smad2/3 and Smad4. Moreover, a miR-629 mimic enhanced the effect of TGF beta on the expression of epithelial-mesenchymal transition-related factors as well as on the motility and invasion in ccRCC cells. These findings identify miR-629 as a potent regulator of the TGF beta/Smad signaling pathway via TRIM33 in ccRCC.
  • Kazutoshi Fujita; Motohide Uemura; Yoshiyuki Yamamoto; Go Tanigawa; Wataru Nakata; Mototaka Sato; Akira Nagahara; Hiroshi Kiuchi; Yasutomo Nakai; Kiyomi Matsumiya; Seiji Yamaguchi; Norio Nonomura
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 20 1 156 - 163 2015年02月 [査読有り]
     
    Background This study aimed to identify preoperative parameters for predicting cancer-specific survival (CSS) in patients with upper urinary tract urothelial carcinoma (UTUC) who have undergone radical nephroureterectomy (RNU). Methods The preoperative clinical and laboratory records of 357 UTUC patients who underwent RNU at three different institutions were retrospectively reviewed (256, training set; 101, test set). Univariate and multivariate analyses were performed on the training set data to identify preoperative prognostic factors, using which a risk stratification model was developed. The model was validated using test set data. Results In univariate analysis, clinical T stage classification and preoperative concentrations of hemoglobin, C-reactive protein, sodium, and albumin showed significant association with CSS. Multivariate analysis showed that low preoperative sodium and hemoglobin concentrations were significantly associated with a poor prognosis. A risk stratification model was developed using the preoperative sodium (<141 mEq/L) and hemoglobin concentrations (below normal). Three subgroups were formed depending on the presence of no (favorable group), one (intermediate), or two (poor) prognostic factors, and the 5-year CSS estimates were found to be 96.5, 75.5, and 47.0 %, respectively (P < 0.01). The risk model was significantly associated with the adverse pathological findings of stage pT3 or more and lymphovascular invasion (P = 0.005). Conclusion We identified low preoperative sodium and hemoglobin concentrations as prognostic factors for patients with UTUC treated with RNU. Our risk stratification model may help physicians design a therapeutic strategy.
  • Hiroaki Hase; Kentaro Jingushi; Yuko Ueda; Kaori Kitae; Hiroshi Egawa; Ikumi Ohshio; Ryoji Kawakami; Yuri Kashiwagi; Yohei Tsukada; Takumi Kobayashi; Wataru Nakata; Kazutoshi Fujita; Motohide Uemura; Norio Nonomura; Kazutake Tsujikawa
    MOLECULAR CANCER RESEARCH 12 12 1807 - 1817 2014年12月 [査読有り]
     
    Clear cell renal cell carcinoma (ccRCC) is the most common histologically defined subtype of renal cell carcinoma (RCC). To define the molecular mechanism in the progression of ccRCC, we focused on LOX-like protein 2 (LOXL2), which is critical for the first step in collagen and elastin cross-linking. Using exon array analysis and quantitative validation, LOXL2 was shown to be significantly upregulated in clinical specimens of human ccRCC tumor tissues, compared with adjacent noncancerous renal tissues, and this elevated expression correlated with the pathologic stages of ccRCC. RNAi-mediated knockdown of LOXL2 resulted in marked suppression of stress-fiber and focal adhesion formation in ccRCC cells. Moreover, LOXL2 siRNA knockdown significantly inhibited cell growth, migration, and invasion. Mechanistically, LOXL2 regulated the degradation of both integrins alpha 5 (ITGAV5) and beta 1 (ITGB1) via protease-and proteasome-dependent systems. In clinical ccRCC specimens, the expression levels of LOXL2 and integrin alpha 5 correlated with the pathologic tumor grades. In conclusion, LOXL2 is a potent regulator of integrin alpha 5 and integrin beta 1 protein levels and functions in a tumor-promoting capacity in ccRCC. (C)2014 AACR.
  • Hiroaki Hase; Kentaro Jingushi; Yuko Ueda; Kaori Kitae; Hiroshi Egawa; Ikumi Ohshio; Ryoji Kawakami; Yuri Kashiwagi; Yohei Tsukada; Takumi Kobayashi; Wataru Nakata; Kazutoshi Fujita; Motohide Uemura; Norio Nonomura; Kazutake Tsujikawa
    MOLECULAR CANCER RESEARCH 12 12 1807 - 1817 2014年12月 [査読有り]
     
    Clear cell renal cell carcinoma (ccRCC) is the most common histologically defined subtype of renal cell carcinoma (RCC). To define the molecular mechanism in the progression of ccRCC, we focused on LOX-like protein 2 (LOXL2), which is critical for the first step in collagen and elastin cross-linking. Using exon array analysis and quantitative validation, LOXL2 was shown to be significantly upregulated in clinical specimens of human ccRCC tumor tissues, compared with adjacent noncancerous renal tissues, and this elevated expression correlated with the pathologic stages of ccRCC. RNAi-mediated knockdown of LOXL2 resulted in marked suppression of stress-fiber and focal adhesion formation in ccRCC cells. Moreover, LOXL2 siRNA knockdown significantly inhibited cell growth, migration, and invasion. Mechanistically, LOXL2 regulated the degradation of both integrins alpha 5 (ITGAV5) and beta 1 (ITGB1) via protease-and proteasome-dependent systems. In clinical ccRCC specimens, the expression levels of LOXL2 and integrin alpha 5 correlated with the pathologic tumor grades. In conclusion, LOXL2 is a potent regulator of integrin alpha 5 and integrin beta 1 protein levels and functions in a tumor-promoting capacity in ccRCC. (C)2014 AACR.
  • 岸本 望; 今村 亮一; 岩西 利親; 中川 勝弘; 谷川 剛; 藤田 和利; 細見 昌弘; 山口 誓司
    泌尿器外科 27 10 1685 - 1688 医学図書出版(株) 2014年10月 
    61歳、男性。腹部CTにて左腎腫瘍および左副腎腫瘍を指摘され当科紹介受診となった。左腎細胞癌および左副腎myelolipomaが疑われるも左腎細胞癌の副腎転移も否定できず、開腹根治的左腎摘除術を施行した。病理結果は左腎細胞癌(clear cell type、G1>G2、INFα、pT1b)および左副腎myelolipomaであった。(著者抄録)
  • 岸本 望; 岩西 利親; 松崎 恭介; 中川 勝弘; 谷川 剛; 藤田 和利; 今村 亮一; 細見 昌弘; 山口 誓司
    泌尿器外科 27 9 1567 - 1570 医学図書出版(株) 2014年09月 
    上部尿路結石症に対して体外衝撃波砕石術(ESWL)、経尿道的尿管結石砕石術(TUL)が導入されて以来そのほとんどが開腹術によらず治療可能となっている。しかしながら、これらの治療に抵抗性の症例は依然として存在する。近年、腹腔鏡手術の普及に伴い腹腔鏡下尿路結石術の報告例も散見される。今回われわれは3例(症例1:70歳男性、右尿管結石/症例2:40歳男性、左尿管結石/症例3:72歳男性、右尿管結石)の後腹膜鏡下尿管切石術を経験した。3症例全てにおいて術後残石なく、水腎症も改善を認めている。(著者抄録)
  • 前立腺全摘除術の手技によるQOLの比較 導入期の症例における検討
    中井 康友; 高山 仁志; 永原 啓; 藤田 和利; 植村 元秀; 宮川 康; 野々村 祝夫
    泌尿器外科 27 8 1279 - 1282 医学図書出版(株) 2014年08月 
    導入期(初期10例)の鏡視下前立腺全摘術(LRP)とロボット支援下前立腺全摘術(RARP)のQOLの経時的な変化をEPIC調査票を用いて検討し、当院で行われてきた開腹恥骨後式前立腺全摘術(RRP)565例の結果と比較した。LRPの排尿(総合)、排尿機能、尿失禁スコアはRRPと比較して有意に低かったが、RARPでは差はみられなかった。性機能についてのQOLについては術式による差はみられなかった。(著者抄録)
  • Kazutoshi Fujita; Mayuka Shimomura; Motohide Uemura; Wataru Nakata; Mototaka Sato; Akira Nagahara; Yasutomo Nakai; Shinji Takamatsu; Eiji Miyoshi; Norio Nonomura
    PROSTATE 74 10 1052 - 1058 2014年07月 [査読有り]
     
    BACKGROUND. Fucosylation is an oligosaccharide modification associated with cancer and inflammation, which is catalyzed by fucosyltransferases. Fucosylated haptoglobin (Fuc-Hpt) has been identified as a novel biomarker for pancreatic cancer. In this study, we evaluated serum Fuc-Hpt as a biomarker for prostate cancer, and investigated the expression of fucosyltransferases and haptoglobin in prostate cancer cell lines. METHODS. We measured the preoperative serum Fuc-Hpt levels in 98 patients who underwent radical prostatectomy (RP) using an established lectin-antibody ELISA. Fucosyltransferase and haptoglobin mRNA and protein expressions in prostate cancer cell lines were determined using quantitative PCR and Western blotting. RESULTS. Serum Fuc-Hpt levels were significantly associated with Gleason score (GS), but not prostate-specific antigen (PSA) levels. The area under the receiver-operator characteristics curve (AUC) for the prediction of GS >= 7 in prostatectomy specimens by Fuc-Hpt was 0.753, in contrast to the PSA AUC of 0.561 and the PSAD AUC of 0.558. The Fuc-Hpt AUC for the prediction of GS upgrade from GS 6 at biopsy to GS >= 7 after RP was 0.689, in contrast to the PSA AUC of 0.588 and PSAD AUC of 0.557. Multivariable analysis revealed that Fuc-Hpt levels were significantly associated with biochemical recurrence after prostatectomy. A high expression of alpha-(1-6) fucosyltransferase (FUT8) and haptoglobin was observed in prostate cancer cell line, suggesting that certain kinds of prostate cancer cells produce Fuc-Hpt. CONCLUSION. Elevated serum Fuc-Hpt level could be a novel cancer biomarker for predicting the prognosis of patients with prostate cancer, particularly those with high GSs. (C) 2014 Wiley Periodicals, Inc.
  • 術前血清Na値およびHb値による上部尿路上皮癌の術前予後予測モデルの検討
    藤田 和利; 山本 致之; 中田 渡; 佐藤 元孝; 谷川 剛; 永原 啓; 植村 元秀; 中井 康友; 松宮 清美; 山口 誓司; 野々村 祝夫
    日本癌治療学会誌 49 3 1199 - 1199 (一社)日本癌治療学会 2014年06月
  • 岩西 利親; 谷川 剛; 岸本 望; 林 拓自; 中川 勝弘; 藤田 和利; 今村 亮一; 細見 昌弘; 山口 誓司; 伏見 博彰; 島津 宏樹
    泌尿器科紀要 60 6 299 - 301 泌尿器科紀要刊行会 2014年06月 
    67歳男。左陰嚢内腫瘤を主訴とした。左陰嚢内に長径5cmの無痛性腫瘤を触知したが、胸腹部理学所見や血液検査、検尿に異常はなく、腫瘍マーカーは正常であった。超音波検査では精巣頭側に内部不均一で辺縁不整な充実性腫瘤(長径5cm)を認め、骨盤MRIではT1強調画像で低信号、T2強調画像で高信号を呈する腫瘤を確認した。左陰嚢内腫瘍の診断で高位精巣摘除術を行い、周囲組織への明らかな浸潤は認めなかった。病理組織学的所見では異型に富み核分裂像を伴う紡錘形腫瘍細胞が束を形成して錯綜配列しており、免疫染色にてSMA(+)、desmin(+)、CD34(-/+)、S-100(-)、Mib-1 index 40%であった。以上より精索原発平滑筋肉腫と診断した。患者の希望により術後放射線療法は行っていないが、術後24ヵ月経過現在も再発・転移を認めていない。
  • 高尾 徹也; 藤田 和利; 植村 元秀; 木内 寛; 奥見 雅由; 中井 康友; 矢澤 浩治; 高山 仁志; 宮川 康; 辻村 晃; 野々村 祝夫
    Japanese Journal of Endourology 27 1 142 - 146 (一社)日本泌尿器内視鏡学会 2014年04月 
    【目的】腎悪性腫瘍、腎盂尿管悪性腫瘍の手術療法として現在は腹腔鏡下手術が広く行われている。今回、80歳以上の高齢者における腎悪性腫瘍、腎盂尿管悪性腫瘍に対する開腹手術と腹腔鏡下手術についてretrospectiveに術前後の評価を行った。【対象と方法】対象は、1975年から2012年までに当科で腎悪性腫瘍、腎盂尿管悪性腫瘍で腎摘除術または腎尿管全摘除術を施行した80歳以上の高齢者58例。術式、手術時間、出血量、合併症などについて解析した。【結果】腹腔鏡下手術は24例、開腹手術は34例に施行された。腹腔鏡下群と開腹群で患者背景に差はなかった。平均手術時間は、298分(腹腔鏡下)と189分(開腹)、平均出血量は、179ml(腹腔鏡下)と463ml(開腹)で有意差を認めた。周術期に重篤な合併症は認めなかった。【考察】80歳以上の高齢者に対する腹腔鏡下腎・腎盂尿管悪性腫瘍手術は開腹手術に比べて、安全に施行可能であると考えられた。(著者抄録)
  • Kazutoshi Fujita; Masahiro Hosomi; Masahiro Nakagawa; Go Tanigawa; Ryoichi Imamura; Motohide Uemura; Yasutomo Nakai; Hitoshi Takayama; Seiji Yamaguchi; Norio Nonomura
    INTERNATIONAL JOURNAL OF UROLOGY 21 3 308 - 312 2014年03月 [査読有り]
     
    ObjectivesTo determine whether low-grade systemic inflammation is associated with prostatic enlargement/benign prostatic hyperplasia. MethodsProstate volume was measured by transrectal ultrasonography in 576 Japanese men. The association between prostate volume and routine clinical inflammatory markers (C-reactive protein level, white blood cell count, or the differential white cell count [neutrophils, lymphocytes, basophils, eosinophils, and monocytes]) were analyzed. Contributors to prostate volume were identified in univariate and multivariable linear regression models. ResultsProstate volume was found to have a positive association with serum prostate-specific antigen level (P<0.001), white blood cell count (P=0.027) and absolute neutrophil count (P=0.010). In univariate linear regression models, a large prostate volume was associated with older age, higher prostate-specific antigen, and higher white blood cell and neutrophil counts. A multivariable model adjusted for age, prostate-specific antigen, and C-reactive protein showed that the white blood cell count and the neutrophil count were independently associated with prostate volume. An increased white blood cell count was also associated with higher total International Prostatic Symptom Scores (P<0.001). ConclusionsWhite blood cell count seems to be associated with the degree of prostate enlargement and lower urinary tract symptoms. Chronic low-grade systemic inflammation might be involved in the etiology of benign prostatic hyperplasia.
  • Mototaka Sato; Yasutomo Nakai; Wataru Nakata; Takahiro Yoshida; Koji Hatano; Atsunari Kawashima; Kazutoshi Fujita; Motohide Uemura; Hitoshi Takayama; Norio Nonomura
    INTERNATIONAL JOURNAL OF UROLOGY 21 2 130 - 134 2014年02月 [査読有り]
     
    Objectives: To analyze the presence of immature vessels as a predictive factor of prognosis in patients with renal cell carcinoma. Methods: Tissue samples were obtained from 50 renal cell carcinoma patients who underwent radical nephrectomy, and the blood vessels were stained using antibodies to cluster of differentiation 34 and a-smooth muscle actin. Immature vessels were defined as those positive for cluster of differentiation 34, and mature vessels as those positive for both cluster of differentiation 34 and a-smooth muscle actin. The extent of vascularization was quantified by calculating the microvessel area and microvessel density. Results: The microvessel area of immature vessels was positively associated with tumor grade (P < 0.0001), T stage (P < 0.0001) and American Joint Committee on Cancer stage (P < 0.0001), and was significantly higher in tumors with metastasis than in those without metastasis (P < 0.0001). The microvessel density did not associate with tumor grade or T stage. The disease-free survival and overall survival were significantly shorter in patients with high microvessel area. Conclusions: The microvessel area of immature vessels seems to be associated with renal cell carcinoma aggressiveness, suggesting this might be considered as a novel prognostic factor in patients with these tumors.
  • Toshichika Iwanishi; Go Tanigawa; Nozomu Kishimoto; Takuji Hayashi; Masahiro Nakagawa; Kazutoshi Fujita; Ryoichi Imamura; Masahiro Hosomi; Seiji Yamaguchi; Hiroki Shimadu; Hiroaki Fushimi
    Acta Urologica Japonica 60 6 299 - 301 2014年 [査読有り]
     
    Leiomyosarcomas of the spermatic cord are rare tumors which cause significant morbidity and mortality. We report a case of leiomyosarcoma in a 67-year-old man who presented with a left scrotal mass. Left orchiectomy with high ligation of the spermatic cord was performed with clinical diagnosis of scrotal tumor. The pathological examination revealed leiomyosarcoma arising from the spermatic cord. He was free of disease two years postoperatively.
  • Enrico Munari; Kazutoshi Fujita; Sheila Faraj; Alcides Chaux; Nilda Gonzalez-Roibon; Jessica Hicks; Alan Meeker; Norio Nonomura; George J. Netto
    Human Pathology 44 12 2668 - 2676 2013年12月 [査読有り]
     
    Upper tract urothelial carcinoma (UTUC) accounts for 5% to 10% of all urothelial carcinomas. Despite many shared features, key clinical and molecular genetic differences between upper tract and bladder urothelial carcinomas are becoming apparent. We have previously demonstrated alterations of mammalian target of rapamycin (mTOR) pathway in bladder carcinoma with a potential impact on biological behavior. In the current study, we evaluated the expression status and prognostic significance of mTOR pathway members in UTUC. Archival formalin-fixed and paraffin-embedded tissues from 99 primary UTUCs were retrieved from one of the authors' institution. Tissue microarrays were constructed with triplicate tumor samples and paired nonneoplastic urothelium. Tissue microarrays were analyzed using immunohistochemistry for mTOR pathway members: PTEN, phos-AKT, phos-mTOR, phos-S6, phos-4EBP1, and related markers p27 and c-MYC correlation with clinicopathologic parameters and outcome was performed. We found significantly lower expression of PTEN, phos-AKT, phos-mTOR, phos-S6, phos-4EBP1, p27, and c-MYC in UTUC compared with paired benign urothelium (P < .0005). We found a strong positive correlation between PTEN and phos-AKT. Moderate correlation was observed between phos-mTOR and phos-S6, PTEN and p27, phos-AKT and p27, phos-S6 and p27, phos-mTOR and c-MYC, phos-S6 and c-MYC, and p27 and c-MYC. None of the evaluated biomarkers were associated with increased hazard ratios for tumor recurrence or for cancer-specific mortality, when adjusting for relevant clinicopathologic variables. Dysregulation of the mTOR pathway was observed in UTUC compared with normal urothelium, implicating a potential pathogenic role in tumor development. In our cohort, expression of the evaluated biomarkers had no prognostic value. © 2013 Elsevier Inc. All rights reserved.
  • Inagaki Y; Fujita K; Nakai Y; Takayama H; Tsujimura A; Nonomura N
    Hinyokika kiyo. Acta urologica Japonica 59 11 723 - 727 泌尿器科紀要刊行会 2013年11月 [査読有り]
     
    A 32-year-old man was referred to our hospital for treatment of left renal cystic tumor, which was detected by computed tomographic (CT) scan 3 years ago. CT scan showed a multilocular cyst (5 cm in diameter) with a solid tumor in the left kidney which was enhanced with contrast. There was no evidence of extrarenal invasion or distant metastasis. We performed retroperitoneal laparoscopic radical nephrectomy. Pathological examinations revealed a cellular arrangement specific to carcinoid tumor and positive for CD56 (NCAM) and neuron-specific enolase. The cell proliferation rate was estimated to be under 2% with Ki67 staining. The pathological diagnosis was renal neuroendocrine tumor (carcinoid). At the 9-month follow up, he had no evidence of local recurrence or metastasis.
  • 後腹膜鏡下尿管切石術を施行した1例
    岸本 望; 岩西 利親; 中川 勝弘; 谷川 剛; 藤田 和利; 今村 亮一; 細見 昌弘; 山口 誓司
    泌尿器科紀要 59 9 634 - 635 泌尿器科紀要刊行会 2013年09月
  • 中井 康友; 吉岡 靖生; 川村 憲彦; 中田 渡; 吉田 栄弘; 佐藤 元孝; 永原 啓; 藤田 和利; 植村 元秀; 辻村 晃; 野々村 祝夫
    Japanese Journal of Endourology 26 2 279 - 283 (一社)日本泌尿器内視鏡学会 2013年09月 
    【目的】限局性前立腺癌に対して施行したHDR(high-dose rate)組織内照射単独療法(45.5 Gy/7 fraction)の治療成績について検討すること。【対象】2005年1月から2011年12月までに大阪大学医学部附属病院で限局性前立腺癌に対して45.5 Gy/7分割でHDR組織内照射を受けた73例。【結果】5例にPSA再発を認め、3年および5年非PSA再発生存率はそれぞれ95%、91%であった。2例に臨床再発を認め、3年および5年非臨床再発生存率はそれぞれ98%、96%であった。グレード2の急性期および晩期有害事象をそれぞれ7例(9.6%)、9例(12.3%)に認めた。【結論】限局性前立腺癌に対する45.5 Gy/7 fractionのHDR組織内照射は安全かつ有効に施行可能であることが示唆された。(著者抄録)
  • Koji Hatano; Souhei Yamaguchi; Keisuke Nimura; Kouki Murakami; Akira Nagahara; Kazutoshi Fujita; Motohide Uemura; Yasutomo Nakai; Mutsumi Tsuchiya; Masashi Nakayama; Norio Nonomura; Yasufumi Kaneda
    MOLECULAR CANCER RESEARCH 11 9 1088 - 1100 2013年09月 [査読有り]
     
    Despite an increasing prevalence of patients with docetaxel-refractory prostate cancer, little is known about the tumor biology of the docetaxel-resistant residual tumor cells compared with primary tumor cells. In this study, tumorigenic potential was increased in the docetaxel-resistant residual prostate cancer cell lines (DRD, 1G7 and PC3DR) compared with parental cells (DU145 or PC3). Enhanced tumorigenic potential was conferred by oncogenic c-Myc, which was stabilized by constitutively activated ERK1/2 in DRD, 1G7, and PC3DR cells. Constitutively activated ERK1/2 was maintained by CXCR4, which was upregulated in DRD, 1G7, and PC3DR cells. In docetaxel-treated DU145 cells, transiently activated ERK1/2 induced CXCR4 expression by stabilizing c-Myc. Furthermore, constitutive activation of CXCR4, ERK1/2, and c-Myc signaling was evident in clinical tissue samples from human patients with docetaxel-resistant prostate cancer. In DTX-resistant residual prostate cancer cells, the enhanced tumorigenic potential was reduced by ERK1/2 inhibition, or by AMD3100, a CXCR4 antagonist. Thus, docetaxel treatment constitutively activated the CXCR4, ERK1/2, and c-Myc signaling loop in docetaxel-resistant residual prostate cancer cells. (C) 2013 AACR.
  • Mototaka Sato; Yasutomo Nakai; Wataru Nakata; Takahiro Yoshida; Koji Hatano; Atsunari Kawashima; Kazutoshi Fujita; Motohide Uemura; Hitoshi Takayama; Norio Nonomura
    PLOS ONE 8 9 2013年09月 [査読有り]
     
    Purpose: Extracellular matrix metalloproteinase inducer (EMMPRIN) has been reported to play crucial roles, including in angiogenesis, in several carcinomas. However, the correlation between EMMPRIN levels and angiogenesis expression profile has not been reported, and the role of EMMPRIN in renal cell carcinoma (RCC) is unclear. In the present study, we evaluated the association of EMMPRIN with angiogenesis, its value in prognosis, and its roles in RCC. Experimental Design: EMMPRIN expression was examined in 50 RCC patients treated with radical nephrectomy. Angiogenesis, proliferation, and invasion activity were evaluated using EMMPRIN knockdown RCC cell lines. The size of EMMPRIN-overexpressing xenografts was measured and the degree of angiogenesis was quantified. EMMPRIN expression was evaluated in RCC patients who received sunitinib therapy and in sunitinib-resistant cells. Further, the relation between EMMPRIN expression and sensitivity to sunitinib was examined. Results: EMMPRIN score was significantly associated with clinicopathological parameters in RCC patients, as well as being significantly correlated with microvessel area (MVA) in immature vessels and with prognosis. Downregulation of EMMPRIN by siRNA led to decreased VEGF and bFGF expression, cell proliferation, and invasive potential. EMMPRIN over-expressing xenografts showed accelerated growth and MVA of immature vessels. EMMPRIN expression was significantly increased in patients who received sunitinib therapy as well as in sunitinib-resistant 786-O cells (786-suni). EMMPRIN-overexpressing RCC cells were resistant to sunitinib. Conclusion: Our findings indicate that high expression of EMMPRIN in RCC plays important roles in tumor progression and sunitinib resistance. Therefore, EMMPRIN could be a novel target for the treatment of RCC.
  • Koji Hatano; Souhei Yamaguchi; Keisuke Nimura; Kouki Murakami; Akira Nagahara; Kazutoshi Fujita; Motohide Uemura; Yasutomo Nakai; Mutsumi Tsuchiya; Masashi Nakayama; Norio Nonomura; Yasufumi Kaneda
    MOLECULAR CANCER RESEARCH 11 9 1088 - 1100 2013年09月 [査読有り]
     
    Despite an increasing prevalence of patients with docetaxel-refractory prostate cancer, little is known about the tumor biology of the docetaxel-resistant residual tumor cells compared with primary tumor cells. In this study, tumorigenic potential was increased in the docetaxel-resistant residual prostate cancer cell lines (DRD, 1G7 and PC3DR) compared with parental cells (DU145 or PC3). Enhanced tumorigenic potential was conferred by oncogenic c-Myc, which was stabilized by constitutively activated ERK1/2 in DRD, 1G7, and PC3DR cells. Constitutively activated ERK1/2 was maintained by CXCR4, which was upregulated in DRD, 1G7, and PC3DR cells. In docetaxel-treated DU145 cells, transiently activated ERK1/2 induced CXCR4 expression by stabilizing c-Myc. Furthermore, constitutive activation of CXCR4, ERK1/2, and c-Myc signaling was evident in clinical tissue samples from human patients with docetaxel-resistant prostate cancer. In DTX-resistant residual prostate cancer cells, the enhanced tumorigenic potential was reduced by ERK1/2 inhibition, or by AMD3100, a CXCR4 antagonist. Thus, docetaxel treatment constitutively activated the CXCR4, ERK1/2, and c-Myc signaling loop in docetaxel-resistant residual prostate cancer cells. (C) 2013 AACR.
  • Kazutoshi Fujita; Go Tanigawa; Ryoichi Imamura; Masahiro Nakagawa; Takuji Hayashi; Nozomu Kishimoto; Masahiro Hosomi; Seiji Yamaguchi
    INTERNATIONAL JOURNAL OF UROLOGY 20 6 594 - 601 2013年06月 [査読有り]
     
    Objectives To assess the impact of preoperative serum sodium concentration on the prognosis of patients with upper urinary tract urothelial carcinoma treated by nephroureterectomy. Methods The clinical records of 139 patients treated for upper urinary tract urothelial carcinoma by nephroureterectomy were retrospectively reviewed. Recurrence-free and cancer-specific survival curves were calculated using the Kaplan-Meier method, with the difference between curves evaluated using the log-rank test. A multivariate analysis was carried out by Cox's proportional hazard model to identify prognostic factors. Results The median (range) follow-up time was 27 (1-139)months. The median (range) preoperative serum sodium was 141 (134-147) mEq/L. Five-year cancer-specific survival estimates for patients above and below the median preoperative serum sodium were 81.7% (95% confidence interval: 68.7-89.7) and 50.6% (95% confidence interval: 30.3-67.8), respectively. In the multivariate analysis, preoperative sodium concentration, pathological T stage, and lymphovascular invasion were independent and significant prognostic factors for cancer-specific survival. A prognostic model of risk classification for cancer-specific survival involving these parameters was developed, and 5-year cancer-specific survival estimates were 29.9% (95% confidence interval: 14.5-47.0) for the poor risk group (hazard ratio 19.95 [95% confidence interval: 8.5-46.6]; P<0.001), 81.6% (95% confidence interval: 55.2-93.3) for the intermediate risk group (hazard ratio 5.70 [95% confidence interval: 1.27-25.5]; P=0.022) and 97.9% (95% confidence interval 85.9-99.7) for the favorable risk group. Conclusion These findings suggest for the first time that a low preoperative sodium level predicts a poor survival in upper urinary tract urothelial carcinoma patients treated by nephroureterectomy.
  • 左腎細胞癌と左副腎Myelolipoma同時発生の1例
    岸本 望; 藤田 和利; 岩西 利親; 林 拓自; 中川 勝弘; 谷川 剛; 今村 亮一; 細見 昌弘; 山口 誓司; 島津 宏樹; 伏見 博彰
    泌尿器科紀要 59 5 325 - 325 泌尿器科紀要刊行会 2013年05月
  • 精索Leiomyosarcomaの1例
    岩西 利親; 谷川 剛; 岸本 望; 林 拓自; 中川 勝弘; 藤田 和利; 今村 亮一; 細見 昌弘; 山口 誓司; 島津 宏樹; 伏見 博彰
    泌尿器科紀要 59 5 328 - 328 泌尿器科紀要刊行会 2013年05月
  • Kazutoshi Fujita; Sheila Faraj; Enrico Munari; Alcides Chaux; Nilda Gonzalez-Roibon; Jessica Hicks; Alan Meeker; Norio Nonomura; George Netto
    JOURNAL OF UROLOGY 189 4 E371 - E371 2013年04月 [査読有り]
  • 腎細胞癌特異的に高発現を示すマイクロRNA miR-629の同定とその機能解析
    中田 渡; 神宮司 健太郎; 植村 元秀; 藤田 和利; 長谷 拓明; 辻川 和丈; 野々村 祝夫
    日本泌尿器科学会雑誌 104 2 217 - 217 (一社)日本泌尿器科学会 2013年03月 [査読有り]
  • 山本 致之; 今村 亮一; 中澤 成晃; 林 拓自; 谷川 剛; 藤田 和利; 細見 昌弘; 島津 宏樹; 伏見 博彰; 山口 誓司
    泌尿器外科 26 2 231 - 234 医学図書出版(株) 2013年02月 
    69歳男性、主訴は体重減少。CTで膀胱腫瘍を認めた。血尿は認めなかった。高血圧の合併を認めた。膀胱鏡にて前壁に粘膜下腫瘍を認め、MRIにて腫瘍は膀胱粘膜下組織に限局していた。TUR-BTを施行した。病理組織所見より膀胱paragangliomaと診断した。術後、123I-MIBGシンチグラフィーでは、異常集積を認めず、血中、尿中カテコラミン値はともに異常所見を認めなかった。術後17ヵ月目の現在、再発を認めていない。(著者抄録)
  • 岩西 利親; 今村 亮一; 岸本 望; 林 拓自; 中川 勝弘; 谷川 剛; 藤田 和利; 細見 昌弘; 山口 誓司; 伏見 博彰
    大阪府立急性期・総合医療センター医学雑誌 35 1 85 - 87 (地独)大阪府立病院機構大阪急性期・総合医療センター 2013年02月 
    長期無尿期を経て心停止下腎移植に至り、移植後に良好な経過を得た症例を経験した。ドナーは40歳代、女性。クモ膜下出血のため、救急搬送された。集中治療行うも改善せず。無尿期60時間を経て腎提供となった。レシピエントは50歳代、男性。腎硬化症による慢性腎不全に対して献腎移植を行った。術後血液透析が必要となるも術後7日目より徐々に尿量は増加を認め、術後19日目に血液透析離脱となった。移植後15ヵ月が経過した現在、Cr1.2mg/dl前後で安定している。(著者抄録)
  • 中澤 成晃; 今村 亮一; 山本 致之; 林 拓自; 谷川 剛; 藤田 和利; 細見 昌弘; 山口 誓司
    泌尿器科紀要 59 2 103 - 106 泌尿器科紀要刊行会 2013年02月 
    15歳男性。両側低形成腎による慢性腎不全に対し父親をドナーとするABO血液型不一致生体腎移植術を施行したが、移植後35日目に右胸痛、呼吸困難、右鼠径部痛が出現した。当初、発熱、白血球の増加、軽度炎症反応高値を認めたため感染症を疑い、補液と抗生剤治療を開始したが、翌日の採血で著明な高尿酸血症、腎機能障害を呈したため、ミゾリビンによる副作用を考え、代謝拮抗薬をミコフェノール酸モフェチルに変更し、アロプリノール、クエン酸ナトリウムの内服を開始した。その結果、治療開始後血清尿酸値は速やかに低下し、腎機能や右胸痛などの症状も改善した。
  • 中澤 成晃; 今村 亮一; 林 拓自; 山本 致之; 谷川 剛; 藤田 和利; 細見 昌弘; 伏見 博彰; 山口 誓司
    泌尿器科紀要 59 2 117 - 120 泌尿器科紀要刊行会 2013年02月 
    69歳男性。患者は糖尿病性腎不全に対して弟をドナーにABO適合生体腎移植術が行われ、4年3ヵ月目に無症候性肉眼的血尿を自覚した。近医の膀胱鏡検査にて多発性膀胱腫瘍を指摘され、著者らの施設へ紹介後、MRIを行なったところ、右側壁を中心とした多発性膀胱腫瘍が認められた。治療として経尿道的膀胱腫瘍切除術(TURBT)と術後にpirarubicinが膀胱内へ注入された結果、病理組織学的に尿路上皮癌で、その後も近医にてpirarubicinの膀胱内注入を計8回行われた。しかし、尿細胞診で陰性化はみられず、初回TURBT後から4ヵ月目には右腎盂癌が認められた。以後、右腎尿管全摘が施行されるも、患者は化学療法を希望せず、最終的には更に左腎盂癌および膀胱上皮内癌も発症し、左腎尿管膀胱全摘、移植腎尿管温存、回腸導管造設術が行われるも、肝転移を認め、初診から1年3ヵ月目に癌死した。
  • Shigeaki Nakazawa; Ryoichi Imamura; Yoshiyuki Yamamoto; Takuji Hayashi; Go Tanigawa; Kazutoshi Fujita; Masahiro Hosomi; Seiji Yamaguchi
    Acta Urologica Japonica 59 2 103 - 106 2013年02月 [査読有り]
     
    We report a case of hyperuricemia and acute kidney injury associated with mizoribine (MZR). A 15-year-old male with congenital renal hypoplasia underwent kidney transplantation. We used tacrolimus extended release (0.15 mg/kg/day), mizoribine (MZR) (12 mg/kg/day), prednisolone and basiliximab as immunosuppressants. On the 35th post operative day, he complained of acute right chest pain, right inguinal pain and dyspnea. Serum uric acid and creatinine were elevated. Accordingly, we changed MZR to mycophenolate mofetil, and added allopurinol and potassium citrate. Gradually, the symptoms disappeared and renal function was improved. In this case, prolonged MZR metabolism, hyperuricemia and progressive renal dysfunction may have formed a vicious cycle. In conclusion, monitoring of serum uric acid level is necessary, especially when using a high dose MZR.
  • Shigeaki Nakazawa; Ryoichi Imamura; Takuji Hayashi; Yoshiyuki Yamamoto; Go Tanigawa; Kazutoshi Fujita; Masahiro Hosomi; Hiroaki Fushimi; Seiji Yamaguchi
    Acta Urologica Japonica 59 2 117 - 120 2013年02月 [査読有り]
     
    We report a case of urothelial carcinoma (UG) in a 69-year-old man that occurred after renal transplantation. He had started receiving hemodialysis therapy in 2004 due to diabetic nephropathy and underwent living related renal transplantation from his brother in 2005. He was referred to our hospital in May 2009 with asymptomatic microscopic hematuria. Cystoscopy findings revealed multiple bladder tumors, and transurethral resection of bladder tumor (TUR-BT) followed by intravesical instillation of pirarubicin was performed. Histopathological findings revealed UC (G1 > G2, pTa). Cytology findings after the operation did not become negative urine specimen from the native right ureter was positive, and abdominal computed tomography (CT) demonstrated a right pelvic tumor. In January 2010, a laparoscopic right nephroureterectomy was performed and pathological examination findings revealed UC in the right pelvis (G3> G2, INFβ, pT3). In March 2010, recurrence of the bladder tumor was demonstrated as carcinoma in situ (CIS) of the bladder and left native ureter. In June 2010, a radical cystectomy with left nephroureterectomy and ileal conduit diversion were performed. One week after that operation, laboratory results revealed abnormal hepatic function and CT showed multiple liver metastases. The patient died in August 2010, 2 months after surgery.
  • Rhabdoid featuresを伴った腎盂・尿管Sarcomatoid variantの1例
    岸本 望; 谷川 剛; 林 拓自; 中川 勝弘; 藤田 和利; 今村 亮一; 細見 昌弘; 山口 誓司; 島津 宏樹; 伏見 博彰
    泌尿器科紀要 59 1 69 - 70 泌尿器科紀要刊行会 2013年01月
  • 中澤 成晃; 奥見 雅由; 米田 傑; 竹澤 健太郎; 谷川 剛; 藤田 和利; 細見 昌弘; 伏見 博彰; 山口 誓司
    泌尿器科紀要 58 12 683 - 686 泌尿器科紀要刊行会 2012年12月 
    症例は55歳女性で、7年前に胃癌に対し胃全摘術を施行した。5年前にVirchowリンパ節転移を認め、TS-1内服開始後約2年でリンパ節転移は画像上消失した。今回、CT検査で右後腹膜腫瘍を認め、増大傾向であったため紹介となった。腫瘍マーカーは正常範囲内であった。腹部CTでは、右腎門部に辺縁整の類円形腫瘍を認め、下大動脈は背側から腹側に圧排されていた。FDG-PET CT検査では、同部位に一致して異常集積が認められたものの、I-MIBG scintigraphyでは異常集積を認めなかった。後腹膜鏡下腫瘍摘出術を施行した。腫瘍は表面平滑、弾性軟、滑面は黄白色、腫瘍径は1.5×1.5×2.5cmであった。腫瘍は病理組織学的にはリンパ節組織で、異型上皮組織の転移像を認た。異型上皮細胞は充実性で胃癌病理組織の形態と類似していたことから、胃癌のリンパ節転移と診断した。TS-1内服を再開し、術後3年で再発はなく経過良好である。
  • K. Fujita; R. Imamura; G. Tanigawa; M. Nakagawa; T. Hayashi; N. Kishimoto; M. Hosomi; S. Yamaguchi
    Prostate Cancer and Prostatic Diseases 15 4 386 - 390 2012年12月 [査読有り]
     
    BACKGROUND: Asymptomatic prostatic inflammation may cause increased PSA in some men, leading to unnecessary prostate biopsy. We investigated whether the differential white cell count could predict the result of prostate biopsy.METHODS: Prostate needle biopsy was carried out in 323 Japanese men with elevated PSA levels or abnormal digital rectal findings. White blood cell count (WBC), differential white cell count (neutrophils, lymphocytes, basophils, eosinophils, and monocytes), and serum C-reactive protein level were assessed for associations with biopsy findings.RESULTS: In all, 203 (62.1%) were positive for prostate cancer. WBC, neutrophil count, age, PSA, prostate volume, and PSA density (PSAD) were associated with the results of biopsy (P0.05). Multivariate analysis showed that neutrophil count, age, PSA, prostate volume and PSAD were independent predictors. When the cut-off neutrophil count was set at 2900 μl 1, 78 of 104 men (75.0%) with a count below this value had a positive biopsy, while 125 of 219 (57.0%) men with a count above this value were positive. The area under the receiver-operator characteristics curve (AUC) for the predicted probability of a positive biopsy for prostate cancer according to the optimum logistic model was 0.83 (95% confidence interval (CI) 0.78-0.87), while the AUC for PSA was 0.70 (95% CI 0.64-0.76) and that for PSAD was 0.79 (95% CI 0.74-0.84).CONCLUSIONS: An elevated neutrophil count may be a good indicator of a benign prostate biopsy. Men with a low neutrophil count and an increase of serum PSA should strongly be considered for biopsy. © 2012 Macmillan Publishers Limited All rights reserved.
  • Shigeaki Nakazawa; Masayoshi Okumi; Suguru Yoneda; Kentaro Takezawa; G. O. Tanigawa; Kazutoshi Fujita; Masahiro Hosomi; Hiroaki Fushimi; Seiji Yamaguchi
    Acta Urologica Japonica 58 12 683 - 686 2012年12月 [査読有り]
     
    A 55-year-old woman who presented with a retroperitoneal tumor was referred to our department. At the age of 51, she underwent a total gastrectomy for gastric cancer. Postoperatively, TS-1 administration was given for Virchow lymph node metastasis, which disappeared within 2 years and TS-1 was stopped. However, computed tomography revealed a retroperitoneal tumor adjacent to the inferior vena cava, which gradually increased and began to compress the inferior vena cava. Under a diagnosis of retroperitoneal tumor, laparoscopic resection was performed. Pathological findings led to a diagnosis of lymph node metastasis from an adenocarcinoma of the stomach.
  • 前立腺全摘術後の救済放射線療法
    中井 康友; 波多野 浩士; 藤田 和利; 植村 元秀; 高山 仁志; 原 恒男; 吉岡 靖雄; 小川 和彦; 野々村 祝夫
    泌尿器外科 25 8 1675 - 1677 医学図書出版(株) 2012年08月 
    前立腺全摘術後にPSA再発した症例は、転移が出現し癌死に至るまで極めて長い経過をとることが多いため、救済療法が必要な症例を見極め、また治療開始時期を適切に判断する必要がある。PSA倍加時間やGleason score、PSA再発までの期間、PSA velocityなどがその判断の一助になる。術後再発のリスクの高い症例に即時に行う補助放射線療法と、PSA再発した症例に対して行う救済放射線療法の優劣については明確なエビデンスはないのが現状である。(著者抄録)
  • Takuji Hayashi; Kazutoshi Fujita; Nozomu Kishimoto; Masahiro Nakagawa; Go Tanigawa; Ryoichi Imamura; Masahiro Hosomi; Seiji Yamaguchi
    Acta Urologica Japonica 58 5 227 - 229 2012年05月 [査読有り]
     
    A 42-year-old woman presented with left renal tumor. Computed tomography showed a left renal tumor (6 cm in diameter) and a tumor thrombus at the left renal vein, which had equal density to fat tissue. She was diagnosed with malignant tumor, and underwent radical left nephrectomy and resection of thrombus. Pathological diagnosis was angiomyolipoma with no findings of malignancy. No signs of recurrence or metastasis have been observed for 8 months after the operation.
  • 林 拓自; 藤田 和利; 岸本 望; 中川 勝弘; 谷川 剛; 今村 亮一; 細見 昌弘; 山口 誓司
    泌尿器科紀要 58 5 227 - 229 泌尿器科紀要刊行会 2012年05月 
    症例は42歳女性で、超音波検査で左腎腫瘍を指摘され紹介受診した。血液検査、尿沈渣で異常所見を認めず、尿細胞診は陰性であった。超音波検査で、左腎中央に高エコーを示す腫瘍を認め、造影CTで左腎中央に最大径6cmの腫瘍を認め、腫瘍内部は脂肪濃度を示していた。腫瘍は左腎静脈まで進展していたが、リンパ節や他臓器に転移を疑う所見を認めなかった。腫瘍塞栓を伴う腎悪性腫瘍と診断し、CTで脂肪濃度を示していたことから、脂肪肉腫などを疑った。シェブロン切開による経腹的アプローチで、根治的左腎摘除術、腫瘍塞栓摘除術を施行した。腫瘍塞栓は腎静脈内まであり、中枢側で腎静脈を結紮切離し、腫瘍と塞栓を一塊に摘除した。腫瘍塞栓は静脈壁とは癒着を認めず、可動性があった。手術時間は、同時に胆石症に対し施行した胆嚢摘除術を含め3時間48分(手術開始から腎摘除まで1時間57分)であった。出血量は180ml(胆嚢摘除術を含む)であった。術後経過は良好で術後8ヵ月現在、明らかな再発を認めていない。病理組織所見は血管筋脂肪腫(AML)に特徴的な所見で、脂肪塞栓を伴う左腎AMLと診断した。
  • Shigeaki Nakazawa; Suguru Yoneda; Kentaro Takezawa; Go Tanigawa; Kazutoshi Fujita; Masayoshi Okumi; Masahiro Hosomi; Shinichiro Fukuhara; Hiroaki Fushimi; Seiji Yamaguchi
    Acta Urologica Japonica 58 4 215 - 218 2012年04月 [査読有り]
     
    Neurofibromatosis type 1 (NF1) is an autosomal dominant disease with multiple neurofibroma and cafeau-lait spots. We report a case of plexiform neurofibroma of the bladder associated with NF1. A 34-yearold female was referred to our hospital for thickness of the bladder wall. Multiple cafe-au-lait spots and neurofibroma was found on her skin, and she was diagnosed with neurofibromatosis type 1. Ultrasound examination demonstrated bladder wall thickening, and cystoscopy revealed an irregular and erythematous mucosa. Transurethral biopsy of the bladder wall was performed. Histopathological diagnosis was plexiform neurofibroma of the bladder.
  • Yoshiyuki Yamamoto; Kazutoshi Fujita; Shigeaki Nakazawa; Takuji Hayashi; Go Tanigawa; Ryoichi Imamura; Masahiro Hosomi; Daiki Wada; Satoshi Fujimi; Seiji Yamaguchi
    BMC UROLOGY 12 2012年03月 [査読有り]
     
    Background: Acute pyelonephritis (APN) is a common complication of ureteral obstruction caused by urolithiasis, and it can be lethal if it progresses to septic shock. We investigated the clinical characteristics of patients undergoing emergency drainage and assessed risk factors for septic shock. Methods: A retrospective study was performed of 98 patients (101 events) requiring emergency drainage at our urology department for obstructive APN associated with upper urinary tract calculi from January 2003 to January 2011. Clinical characteristics were summarized, and risk factors for septic shock were assessed by logistic regression analysis. Results: Objective evidence of sepsis was found in 64 (63.4%) events, and 21 events (20.8%) were categorized as septic shock. Ninety-six patients recovered, but 2 patients died of septic shock. Multivariate analysis revealed that age and the presence of paralysis were independent risk factors for septic shock. Conclusions: APN associated with upper urinary tract calculi is a severe disease that should be treated with caution, particularly when risk factors are present.
  • 自然破裂を契機に発見された腎周囲脂肪肉腫の1例
    中澤 成晃; 林 拓自; 山本 致之; 谷川 剛; 藤田 和利; 今村 亮一; 細見 昌弘; 山口 誓司
    泌尿器科紀要 58 2 121 - 122 泌尿器科紀要刊行会 2012年02月
  • Takuji Hayashi; Go Tanigawa; Kazutoshi Fujita; Ryoichi Imamura; Shigeaki Nakazawa; Yoshiyuki Yamamoto; Masahiro Hosomi; Kohki Shimazu; Hiroaki Fushimi; Seiji Yamaguchi
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY 16 6 759 - 762 2011年12月 [査読有り]
     
    We report two cases of the plasmacytoid variant of urothelial carcinoma of urinary bladder in which systemic chemotherapy was effective. In the first case, a 76-year-old man presented with dysphasia. Magnetic resonance imaging (MRI) and computed tomography revealed a brain tumor and a bladder tumor. Resection of the brain tumor and transurethral resection of the bladder tumor were performed. The pathological diagnosis was plasmacytoid variant of urothelial carcinoma of urinary bladder with brain metastasis (pT1N0M1). Three cycles of adjuvant MVAC (methotrexate, vinblastine, adriamycin, and cisplatin) chemotherapy were performed. He has no evidence of recurrence 96 months after resection of brain metastasis. In the second case, a 76-year-old man presented with hematuria. MRI revealed a bladder tumor with abdominal wall invasion, and a transurethral biopsy was performed. The pathological diagnosis was plasmacytoid variant of urothelial carcinoma of urinary bladder (cT4bN0M0). After three cycles of neoadjuvant GC (gemcitabine and cisplatin) chemotherapy, MRI demonstrated a complete response. Radical cystectomy was performed, and the pathological diagnosis was pT0pN0. Although there was no evidence of recurrence 9 months after radical cystectomy, he died from other causes. Our two cases suggest that systemic chemotherapy might be effective for the plasmacytoid variant of urothelial carcinoma.
  • Kazutoshi Fujita; Yoshiyuki Yamamoto; Seiji Yamaguchi
    INTERNATIONAL JOURNAL OF UROLOGY 18 8 607 - 608 2011年08月 [査読有り]
  • Kazutoshi Fujita; Charles M. Ewing; William B. Isaacs; Christian P. Pavlovich
    INTERNATIONAL JOURNAL OF CANCER 129 2 424 - 432 2011年07月 [査読有り]
     
    Cytokines may play a role in the initiation and progression of prostate cancer. A cytokine antibody array was previously applied to prostatic fluid obtained from patients with prostate cancer, and interleukin 18 binding protein (IL-18BP), a potent inhibitor of interleukin 18, was noted to be significantly upregulated in cases with large volume disease. We sought to further characterize the association of IL-18BP with prostate cancer and determine whether IL-18BP levels in patient serum and urine samples had clinical relevance. IL-18BP was expressed and secreted by the prostate cancer cell lines DU145 and PC3 but not by LNCaP and CWR22, upon interferon-gamma (IFN-gamma) stimulation. IFN-gamma-induced secretion of IL-18BP was enhanced by added TNF-alpha, IFN-alpha and IFN-beta. The IL-18BP secreted from DU145 and PC3 functionally inhibited IL-18. Immunohistochemical analyses showed positive IL-18BP staining in prostate cancer cells as well as in macrophages in radical prostatectomy specimens. Significant differences in urinary IL-18BP levels (normalized by total protein) collected post-DRE were found between cases with and without cancer on biopsy (p = 0.02) and serum IL-18BP levels correlated with Gleason score (p = 0.03). Our finding of elevated IL-18BP secretion from prostate cancer cells suggests an attempt by cancer to escape immune surveillance. IL-18BP merits further study as a marker of aggressive prostate cancer and as a therapeutic target.
  • 竹澤 健太郎; 中澤 成晃; 米田 傑; 谷川 剛; 藤田 和利; 奥見 雅由; 細見 昌弘; 山口 誓司
    泌尿器外科 24 5 899 - 902 医学図書出版(株) 2011年05月 
    上部尿路CISに対するBCG療法の有効性を検討した。21例(35腎)の上部尿路CIS症例に対しBCG療法を施行した。DJカテーテルを留置しBCG80mg/生食40mlを膀胱内に注入した。週1回、計8回を1コースとした。観察期間中央値は33ヵ月であった。BCG療法により16例がCRを得た。再発は4例に認め、再発までの期間の中央値は15ヵ月であった。上部尿路CISに対するBCG療法の有効性が示唆されたが、長期追跡調査と症例蓄積が必要である。(著者抄録)
  • Kazutoshi Fujita; Masahiro Hosomi; Go Tanigawa; Masayoshi Okumi; Hiroaki Fushimi; Seiji Yamaguchi
    JOURNAL OF UROLOGY 185 5 1722 - 1727 2011年05月 [査読有り]
     
    Purpose: Asymptomatic prostatic inflammation may cause increased prostate specific antigen in some men, leading to unnecessary repeat prostate biopsy. We determined whether histological findings of inflammation in initial biopsy specimens and/or clinical indicators of inflammation could predict the outcome of subsequent biopsy in men with a negative initial biopsy. Materials and Methods: A total of 105 Japanese men with increased prostate specific antigen underwent repeat prostate biopsy after initial biopsy revealed no evidence of carcinoma. Of the cases 45 (42.8%) were positive for prostate cancer at repeat biopsy. We evaluated initial biopsy specimens for evidence of inflammation by mononuclear and polymorphonuclear leukocytes, serum and urinary white blood count, and C-reactive protein. Results: Polymorphonuclear leukocyte infiltrates, urinary white blood count, patient age, prostate specific antigen at repeat biopsy, prostate volume, prostate specific antigen velocity and prostate specific antigen density were associated with the repeat biopsy outcome (p < 0.05). Multivariate analysis revealed that age, prostate specific antigen density and urinary white blood count were independent predictors of outcome. On subgroup analysis of 63 men with serum prostate specific antigen less than 10 ng/ml before initial biopsy polymorphonuclear and mononuclear leukocyte inflammation, age, prostate specific antigen at repeat biopsy, prostate volume, prostate specific antigen velocity and prostate specific antigen density were associated with the outcome of repeat biopsy (p < 0.05). Multivariate analysis showed that polymorphonuclear leukocyte infiltrate, prostate specific antigen density and age were independent predictors. Conclusions: Age, prostate specific antigen density, polymorphonuclear leukocyte inflammation in initial biopsy specimens and urinary pyuria are indicators of benign repeat biopsy. They help avoid unnecessary repeat biopsy in men with increased prostate specific antigen.
  • Kentaro Takezawa; Shigeaki Nakazawa; Suguru Yoneda; Go Tanigawa; Kazutoshi Fujita; Masayoshi Okumi; Masahiro Hosomi; Seiji Yamaguchi
    Acta Urologica Japonica 57 4 213 - 216 2011年04月 [査読有り]
     
    A 31-year-old man visited our hospital complaining of swelling in the left scrotum. Five days previously, he had felt sudden pain in the left lower abdomen and noticed swelling in the left scrotum. He had been suffering from intermittent gross hematuria and left flank pain for 1 year. An elastic hard mass was palpable in the left scrotum. Scrotal hematoma and marked dilation of left renal vein and left gonadal vein were revealed by computed tomography. A diagnosis of varicocele rupture secondary to nutcracker phenomenon was made. One month later, he underwent retroperitoneal laparoscopic donor nephrectomy and subsequent renal autotransplantation into the left iliac fossa. The post-operative course was uneventful. Gross hematuria was resolved 3 days after the operation, and swelling in the left scrotum was resolved within 6 months of the operation. Surgical intervention to treat nutcracker phenomenon is considered controversial. We believe that our procedure is a reliable option for surgical treatment for nutcracker phenomenon.
  • 竹澤 健太郎; 中澤 成晃; 米田 傑; 谷川 剛; 藤田 和利; 奥見 雅由; 細見 昌弘; 山口 誓司
    泌尿器科紀要 57 4 213 - 216 泌尿器科紀要刊行会 2011年04月 
    31歳男。約1年前に左側腹部痛と血尿よりナットクラッカー現象と診断され保存的治療を受けていたが、症状は増悪傾向であった。今回、突然の左下腹部痛と左陰嚢腫脹で紹介受診となった。左陰嚢は硬く鶏卵大に腫大し左臍径部に圧痛を認めた。血液検査では軽度貧血、精巣腫瘍マーカーは陰性で、検尿は肉眼的血尿であった。膀胱鏡検査では左尿管口より血尿の流出を認め、超音波検査では左精巣は正常であったが周囲に液体成分の貯留を認めた。CTで左臍径部に腫大した左精索を認め、左腎静脈は上腸間膜動脈(SMA)、大動脈(Aorta)に圧迫され、末梢側が著明に拡張し、発達した側副血管を認めた。ナットクラッカー現象に伴う左精索静脈瘤の自然破裂と診断し、1年以上症状が増悪傾向にあったことから自家腎移植術を施行した。後腹鏡下に左腎を摘出して左腸骨窩に移植し、腎動脈・静脈をそれぞれ外腸骨動脈・静脈に端側吻合し、尿管は膀胱に新吻合した。術後3日より肉眼的血尿は消失し9日目に退院した。左陰嚢腫脹は徐々に改善し6ヵ月目には消失した。
  • 副腎神経節神経腫の1例
    中澤 成晃; 米田 傑; 竹澤 健太郎; 谷川 剛; 藤田 和利; 奥見 雅由; 細見 昌弘; 山口 誓司; 島津 彰宏; 伏見 博彰
    泌尿器科紀要 57 2 107 - 108 泌尿器科紀要刊行会 2011年02月
  • Nutcracker現象に対し自家腎移植術を施行した1例
    竹澤 健太郎; 中澤 成晃; 米田 傑; 谷川 剛; 藤田 和利; 奥見 雅由; 細見 昌弘; 山口 誓司
    泌尿器科紀要 57 2 111 - 111 泌尿器科紀要刊行会 2011年02月
  • 鏡視下に摘除した胃癌後腹膜リンパ節転移の1例
    中澤 成晃; 米田 傑; 竹澤 健太郎; 谷川 剛; 藤田 和利; 奥見 雅由; 細見 昌弘; 山口 誓司; 島津 彰宏; 伏見 博彰
    泌尿器科紀要 57 2 112 - 112 泌尿器科紀要刊行会 2011年02月
  • Keigo Madono; Suguru Yoneda; Go Tanigawa; Kazutoshi Fujita; Koji Yazawa; Masahiro Hosomi; Satoshi Tanaka; Atsuo Inoue; Kiichiro Ito; Sciji Yamaguchi
    Acta Urologica Japonica 57 1 29 - 31 2011年01月 [査読有り]
     
    Late side effects of ileal conduit are uncommon. Here we report a case of ileal conduit hemorrhage in a 78-year-old woman 8 years after radical cystectomy and ileal conduit diversion. The patient presented with gross hematuria and abdominal dynamic computed tomography showed extravasation of contrasts in ileal conduit and the patient was diagnosed with ileal conduit hemorrhage. Clipping hemostasis was performed under gastrointestinal endoscope and revealed that Dieulafoy's ulcer was the cause of ileal conduit hemorrhage. This is the first case of Dieulafoy's ulcer occurred in ileal conduit. Hemorrhage from ileal conduit is an important late side effect.
  • Suguru Yoneda; Shigeaki Nakazawa; Kentaro Takezawa; Taigo Kato; Go Tanigawa; Kazutoshi Fujita; Masayoshi Okumi; Masahiro Hosomi; Hiroaki Fushimi; Sciji Yamaguchi
    Acta Urologica Japonica 56 7 397 - 401 2010年07月 [査読有り]
     
    A 35-year-old male patient with Down's syndrome received radical inguinal orchitectomy for left testicular tumor in 2006. Histological examination revealed a typical seminoma. 18 months after the operation, we found a metastasis in the right retropcritoneum lymph node. He received adjuvant chemotherapy (bleomycin, etoposide, and cisplatin : BEP). After 3 cycles of chemothrapy, the tumor disappeared. There is no obvious reccurence sign and general condition is good after chemotherapy. As we treated a relapse of seminoma in Down's syndrome successfully, we report this case and review 41 cases in Japanese literatures.
  • 多発性内分泌腫瘍2型に発生した両側巨大褐色細胞腫に対して、二期的後腹膜鏡下副腎摘除術を施行した1例
    米田 傑; 中澤 成晃; 竹澤 健太郎; 谷川 剛; 藤田 和利; 奥見 雅由; 細見 昌弘; 山口 誓司; 島津 宏樹; 伏見 博彰; 矢澤 浩治
    泌尿器科紀要 56 7 412 - 413 泌尿器科紀要刊行会 2010年07月
  • 上部尿路上皮内癌に対するBCG注入療法の検討
    竹澤 健太郎; 中澤 成晃; 米田 傑; 谷川 剛; 藤田 和利; 奥見 雅由; 細見 昌弘; 山口 誓司
    泌尿器科紀要 56 7 416 - 416 泌尿器科紀要刊行会 2010年07月
  • 米田 傑; 中澤 成晃; 竹澤 健太郎; 加藤 大悟; 谷川 剛; 藤田 和利; 奥見 雅由; 細見 昌弘; 伏見 博彰; 山口 誓司
    泌尿器科紀要 56 7 397 - 401 泌尿器科紀要刊行会 2010年07月 
    35歳男。右精巣の腫大に家族が気付き精査加療目的に受診した。ダウン症候群に合併した精巣腫瘍の診断で右高位精巣摘除術を施行した。病理所見はセミノーマ(右精巣)stage I(pT2N0M0)で再発や転移は認めず経過観察とした。約1年4ヵ月後のCTで左総腸骨動脈周囲を中心とする後腹膜リンパ節腫脹を認め、術後化学療法目的に入院した。CT上再発は後腹膜リンパ節のみで、BEP計3コースを予定して開始した。再発巣は1、2コース目でpartial response、3コース目でcomplete responseであった。2コース目投与終了後より呼吸器症状が出現しCTで胸膜下にわずかな陰影を認め、3コース目はブレオマイシンを抜きEP療法とした。また3コースともgrade 4の好中球減少症および38度の発熱を認め、G-CSF製剤の投与や抗生剤の投与など適宜行って改善した。3コース終了後、間質性肺炎の所見を認めたためプレドニン投与を開始した。徐々に改善を認めプレドニンを漸減し退院した。術後3年以上、化学療法終了後1年以上を経て再発は認めなかった。
  • 悪性腫瘍との鑑別が困難であった尿膜管肉芽腫性病変の1例
    中澤 成晃; 米田 傑; 竹澤 健太郎; 谷川 剛; 藤田 和利; 奥見 雅由; 細見 昌弘; 山口 誓司; 真殿 佳吾; 矢澤 浩治; 島津 彰宏; 伏見 彰博
    泌尿器科紀要 56 4 249 - 249 泌尿器科紀要刊行会 2010年04月
  • Kazutoshi Fujita; Charles M. Ewing; Robert H. Getzenberg; J. Kellogg Parsons; William B. Isaacs; Christian P. Pavlovich
    PROSTATE 70 5 473 - 481 2010年04月 [査読有り]
     
    BACKGROUND. Chronic inflammation is commonly observed in benign prostate hyperplasia (BPH), and prostate tissue often contains increased inflammatory infiltrates, including T cells and macrophages. Cytokines are not only key mediators of inflammation but may also play important roles in the initiation and progression of BPH. METHODS. In order to determine what cytokines might be involved in prostatic enlargement, expressed prostatic secretions (EPS) from ex vivo prostates were analyzed by human cytokine antibody microarray and HASA. Prostate epithelial cells (PrEC) and prostate stromal cells (PrSC) were used for ELISA, proliferation, and Western blot assays. RESULTS. Monocyte chemotactic protein-1 (MCP-1/CCL2) was one of the most elevated proteins in secretions from large prostate glands. PrSC were found to secrete MCP-1; Western blotting showed that both PrSC and PrEC express the MCP-1 receptor CCR2 which by RT-PCR was the CCR2b isoform. Proliferation assays showed that MCP-1 stimulates the proliferation of PrEC, but not PrSC, and that a specific MCP-1 antagonist (RS102895) suppressed this effect. Conditioned medium from PrSC stimulated the proliferation of PrEC as well, an effect completely inhibited by both RS102895 and a neutralizing anti-MCP-1 monoclonal antibody. The inflammatory cytokines interleukin (IL)-1 beta, interferon-gamma, and IL-2 enhanced the secretion of MCP-1 from PrEC and PrSC. In addition, MCP-1 levels in EPS correlated with mRNA levels of the macrophage marker CD68 in the same secretions. CONCLUSIONS. The cytokine MCP-1, of apparent prostatic stromal cell origin, may play an important role in prostatic enlargement and BPH, and is a candidate biomarker for these pathologic processes. Prostate 70: 473-431, 2010. (C) 2009 Wiley-Liss, Inc.
  • Kazutoshi Fujita; Akira Tsujimura
    Reproductive Medicine and Biology 9 4 179 - 184 2010年 [査読有り]
     
    Childhood cancer is a curable disease due to the development of chemo- and radiation therapies, but long-term survivors suffer late side-effects including infertility. Cytotoxic agents and radiation impair spermatogenesis and cause oligospermia or azoospermia as well as genetic damage in sperm. To date, the only established option to preserve fertility is cryopreservation of sperm before treatment and artificial reproduction techniques, if men with cancer can ejaculate, but only a quarter of men have banked sperm. Lack of information is the most common reason for failing to bank sperm. However, prepubertal patients who have only spermatogonia and spermatocytes in their testes do not benefit from cryopreservation of their sperm and assisted reproductive techniques. Thus, the only available option is to harvest testicular tissues before treatment for cryopreservation, from which immature germ cells can somehow be maturated. Autotransplantation of germ cells into the testis holds promise for fertility restoration, but contamination by malignant cells may induce relapse. Fluorescence-activated cell sorting (FACS) with two surface markers could exclude contaminated leukemic cells from murine germ cells, and transplantation of sorted germ cells successfully restored fertility without transmission of leukemia. Human germ cells could be also isolated from human leukemia and lymphoma cell lines by FACS using surface markers. Before autotransplantation can be applied clinically, some issues, including the risk of contamination by malignant cells and in vitro propagation of spermatogonial stem cells, should be resolved. © 2010 Japan Society for Reproductive Medicine.
  • Kazutoshi Fujita; Patricia Landis; Brian K. McNeil; Christian P. Pavlovich
    JOURNAL OF UROLOGY 182 6 2664 - 2669 2009年12月 [査読有り]
     
    Purpose: We determined whether serial prostate needle biopsies predispose men to erectile dysfunction and/or lower urinary tract symptoms over time. Materials and Methods: Men with prostate cancer on an active surveillance protocol were administered the 5-item Sexual Health Inventory for Men and International Prostate Symptom Score questionnaires on protocol entry, and at a cross-sectional point in 2008. All men had at least 1, 10 to 12-core prostate biopsy at protocol entry and yearly surveillance biopsies thereafter were recommended. Results: Of 333 men 231 returned the followup questionnaires. Correlations were found between biopsy number and erectile dysfunction, with increasing biopsy number associated with a decrease in Sexual Health Inventory for Men score (p = 0.04) and a history of 3 or more biopsies associated with a greater decrease in Sexual Health Inventory for Men score than after 2 or fewer biopsies (p = 0.02). Multivariable analysis for biopsy number, age, prostate volume and prostate specific antigen showed that only biopsy number was associated with decreasing Sexual Health Inventory for Men score (p = 0.02). When men were stratified by baseline Sexual Health Inventory for Men, those without preexisting erectile dysfunction (Sexual Health Inventory for Men score 22 to 25) trended toward steeper decreases in Sexual Health Inventory for Men score after 3 or more biopsies (p = 0.06) than did men with baseline mild to moderate erectile dysfunction (Sexual Health Inventory for Men score 8 to 21). No correlation was found between biopsy number and International Prostate Symptom Score. Conclusions: Serial prostate biopsies appear to have an adverse effect on erectile function in men with prostate cancer on active surveillance but do not affect lower urinary tract symptoms.
  • 山口 誓司; 中澤 成晃; 米田 傑; 竹澤 健太郎; 谷川 剛; 藤田 和利; 奥見 雅由; 矢澤 浩治; 細見 昌弘
    Japanese Journal of Endourology and ESWL 22 3 135 - 135 (一社)日本泌尿器内視鏡・ロボティクス学会 2009年11月
  • Taigo Kato; Suguru Yoneda; Keigo Madono; Go Tanigawa; Kazutoshi Fujita; Koji Yazawa; Masahiro Hosomi; Seiji Yamaguchi; Kiichiro Itoh
    Acta Urologica Japonica 55 10 607 - 610 2009年10月 [査読有り]
     
    A 52-year-old male presented with left intermittent abdominal pain, and was subsequendy diagnosed with a tumor in the hilum of the left kidney based on computed tomography (CT) and magnetic resonance imaging (MRI) findings. Under suspicion of left renal cancer, we performed a retroperitoneoscopic left nephrectomy. Histopathological features of the resected specimen were compatible with leiomyosarcoma originating from the left renal vein. Immunohistologically, the tumor cells were spindle-shaped, arranged in bundles, and stained positive for α-smooth muscle actin and desmin. The patient was free from recurrence 2 years after surgery. The prognosis of leiomyosarcoma arising from the renal vein has been considered poor. Herein, we provide details of our case and also review 16 cases of leiomyosarcoma of the renal vein in Japan. We conclude that radical tumor resection is necessary for long-term survial.
  • 腎盂尿管癌術後の膀胱内再発の検討
    谷川 剛; 中澤 成晃; 米田 傑; 竹澤 健太郎; 藤田 和利; 奥見 雅由; 細見 昌弘; 山口 誓司
    日本癌治療学会誌 44 2 761 - 761 (一社)日本癌治療学会 2009年09月
  • 全摘前立腺組織の癌病変部位マッピングによる前立腺針生検法の評価
    細見 昌弘; 中澤 成晃; 米田 傑; 竹澤 健太郎; 谷川 剛; 藤田 和利; 奥見 雅由; 山口 誓司
    日本癌治療学会誌 44 2 891 - 891 (一社)日本癌治療学会 2009年09月
  • 前立腺再生検適応における尿中白血球数の意義
    藤田 和利; 細見 昌弘; 中澤 成晃; 米田 傑; 竹澤 健太郎; 谷川 剛; 奥見 雅由; 山口 誓司
    日本癌治療学会誌 44 2 891 - 891 (一社)日本癌治療学会 2009年09月
  • Suguru Yoneda; Keigo Madono; Go Tanigawa; Kazutoshi Fujita; Koji Yazawa; Masahiro Hosomi; Seiji Yamaguchi; Seiichi Kawamoto
    Acta Urologica Japonica 55 9 559 - 562 2009年09月 [査読有り]
     
    We report a case of giant left renal arteriovenous fistula (AVF). A 36-year-old man was diagnosed with chronic glomerulonephritis (CGN) by biopsy on the left kidney 11 years ago. He had been receiving hemodialysis for end-stage kidney disease from CGN since 10 years ago. A left renal cystic lesion was found and he was referred to our department for examination and treatment. He was diagnosed as having left AVF using imaging techniques (computed tomography, magnetic resonance imaging and Color Doppler ultra sonography). He underwent embolization of left renal artery using microcoils. After the surgery, there were no major complications, and there were no signs reccurence. AVF in a long-term dialysis patient is rare. We report this case and summarize the cases reported in Japan.
  • Kazutoshi Fujita; Christian P Pavlovich; George J Netto; Yuko Konishi; William B Isaacs; Syed Ali; Angelo De Marzo; Alan K Meeker
    Human pathology 40 7 924 - 33 2009年07月 [査読有り]
     
    Prostate cancer biomarkers are enriched in urine after prostatic manipulation, suggesting that whole cells might also be detectable for diagnosis. We tested multiplex staining of urinary sediments as a minimally invasive method to detect prostate cancer. Urine samples were collected from 35 men who had prostatic massage (attentive digital rectal examination) in a urology clinic and from 15 control men without urologic disease and without massage, for a total of 50 specimens (27 cancer-positive cases and 23 cancer-negative cases). LNCaP prostate cancer cells spiked into urine were used for initial marker optimization. Urine sediments were cytospun onto glass slides and stained. Multiplex urine cytology was compared with conventional urine cytology for cancer detection; anti-alpha-methylacyl-CoA racemase antibody was used as a marker of prostate cancer cells, anti-Nkx3.1 as a marker of prostate epithelial cells, anti-nucleolin as a marker of nucleoli, and 4'-6-diamidino-2-phenylindole to highlight nuclei. Prostate cancer cells were successfully visualized by combined staining for alpha-methylacyl-CoA racemase, Nkx3.1, and nucleolin. Of the 25 informative cases with biopsy-proven prostate cancer, 9 were diagnosed as suspicious or positive by multiplex immunofluorescence urine cytology, but only 4 were similarly judged by conventional cytology. All cases without cancer were read as negative by both methods. The multiplex cytology sensitivity for cancer detection in informative cases was 36% (9/25), and specificity was 100% (8/8). In conclusion, we have successfully achieved multiple staining for alpha-methylacyl-CoA racemase, Nkx3.1, nucleolin, and 4'-6-diamidino-2-phenylindole to detect prostate cancer cells in urine. Further refinements in marker selection and technique may increase sensitivity and applicability for prostate cancer diagnosis.
  • Kazutoshi Fujita; Masashi Nakayama; Yasutomo Nakai; Hitoshi Takayama; Kazuo Nishimura; Takeshi Ujike; Kensaku Nishimura; Katsuyuki Aozasa; Akihiko Okuyama; Norio Nonomura
    CANCER SCIENCE 100 6 1047 - 1050 2009年06月 [査読有り]
     
    Recent studies suggest that vascular endothelial growth factor receptor (VEGFR) 1-positive hematopoietic progenitor cells precede the arrival of tumor cells and form clusters that may portend sites of future metastatic disease. The aim of the present study was to clarify whether VEGFR1 expression in pelvic lymph nodes predicts the risk of prostate cancer progression after radical prostatectomy. VEGFR1 expression in pelvic lymph nodes was examined by immunohistochemistry in 95 patients who underwent radical prostatectomy for prostate cancer. A cluster of VEGFR1-positive cells was considered positive. Expression of VEGFR1 in pelvic lymph nodes and biochemical recurrence after radical prostatectomy were examined by univariate survival analysis and multivariate Cox proportional hazards regression analysis. Thirty-seven of 79 lymph node-negative patients (46.8%) were found to have VEGFR1-positive cells in their pelvic lymph nodes, whereas 16 of 16 lymph node metastasis-positive patients (100%) had VEGFR1 clusters. There was a significant correlation between pathological stage and VEGFR1 staining (P = 0.002). Univariate analysis showed that pathological stage >= pT3 and VEGFR1 expression in pelvic lymph nodes were each significantly associated with biochemical recurrence after radical prostatectomy. Multivariate analysis showed VEGFR1 expression to be an independent predictor of biochemical recurrence after radical prostatectomy (risk ratio = 5.715, P = 0.010), as was preoperative prostate-specific antigen (PSA) level >= 10 ng/mL. Although larger validation studies are required, our results suggest that VEGFR1 expression in pelvic lymph nodes predicts the risk of biochemical PSA recurrence after radical prostatectomy. (Cancer Sci 2009; 100: 1047-1050).
  • Toshiaki Hirai; Akira Tsujimura; Tomohiro Ueda; Kazutoshi Fujita; Yasuhiro Matsuoka; Tetsuya Takao; Yasushi Miyagawa; Nobuo Koike; Akihiko Okuyama
    JOURNAL OF UROLOGY 181 3 1487 - 1492 2009年03月 [査読有り]
     
    Purpose: We evaluated the morphological effect and alterations in gene expression caused by 1,25-dihydroxyvitamin D treatment in the mouse testis undergoing experimental cryptorchidism and subsequent orchiopexy. Materials and Methods: The mean modified Johnsen score and testicular weight were estimated after 4 weeks of treatment with a 1,25-dihydroxyvitamin D prodrug. We examined sites of vitamin D receptor and mRNA expression, and 1,25-dihydroxyvitamin D analogue accumulation in the mouse testis. Also, we compared alterations in gene expression in the cryptorchid mouse testis with or without 1,25-dihydroxyvitamin D administration by testis specific cDNA microarray. We confirmed protein synthesis of a candidate among up-regulated genes in primary cultures of Sertoli's cells by Western blotting. Results: Mean +/- SEM Johnsen score and testicular weight were increased by 1,25-dihydroxyvitamin D treatment but not significantly (6.12 +/- 0.33 vs 5.27 +/- 0.4 and 49.3 +/- 3.8 mg vs 42.6 +/- 5.5, p = 0.13 and 0.065, respectively). Vitamin D receptor and its mRNA were positive in Sertoli's cells. The 1,25-dihydroxyvitamin D analogue accumulated mainly in Sertoli's cells. Of 2,483 testis specific genes 19 showed up-regulation by 1,25-dihydroxyvitamin D treatment. Of these genes the regulator of cellular cholesterol homeostasis Abca1 was expressed mainly in Sertoli's cells and influenced male fertility. In primary cultures of Sertoli's cells the synthesis of Abca1 protein was increased by 1,25-dihydroxyvitamin D treatment but not by follicle-stimulating hormone or testosterone treatment. Conclusions: We noted that 1,25-dihydroxyvitamin D contributes to spermatogenesis by up-regulating certain specific genes in Sertoli's cells. Testis specific cDNA microarray analysis and vitamin D supplementation may have implications for managing male infertility.
  • Kazutoshi Fujita; Charles M. Ewing; David Y. S. Chan; Leslie A. Mangold; Alan W. Partin; William B. Isaacs; Christian P. Pavlovich
    INTERNATIONAL JOURNAL OF CANCER 124 3 664 - 669 2009年02月 [査読有り]
     
    We have previously shown that endoglin (CD105) is upregulated in prostatic fluid of men with large volume prostate cancer. We chose to assess endoglin levels in urine and serum from men with prostate cancer or at increased risk for the disease: Urine samples were collected after digital rectal examination (DRE) from 99 men whose cancer status was confirmed by biopsy, and serum samples were collected from 20 men without prostate cancer at low risk for the disease and from 69 men diagnosed with prostate cancer that subsequently underwent radical prostatectomy (30 pT2, 39 pT3). Endoglin levels were assessed by ELISA. Urinary endoglin was elevated in men with biopsy-positive prostate cancer compared to biopsy-negative men (p = 0.0014). Urinary endoglin levels in men with prostate cancer correlated with radical prostatectomy tumor volume. The area under the receiver operating characteristic (ROC) curve was 0.72 for urinary endoglin and 0.50 for serum prostate-specific antigen (PSA; sensitivity for cancer detection 73%, specificity 63%). There were no differences in serum endoglin between normal and cancer cases, but there were increases in serum endoglin in non-organ confined (NOC, pT3+) versus organ-confined (OC, pT2) cases (p = 0.0004). The area under the ROC curve was 0.75 for serum endoglin and 0.63 for PSA for predicting NOC status, with a sensitivity of 67% and a specificity of 80%. In conclusion, elevations in post-DRE urinary endoglin suggest there may be value in further studying endoglin as a urinary biomarker of prostate cancer. Endoglin levels in both urine and serum may aid in prostate cancer detection and prognostication. (C) 2008 Wiley-Liss. Inc.
  • Tetsuya Takao; Akira Tsujimura; Hiroshi Kiuchi; Kazuhiko Komori; Kazutoshi Fujita; Yasushi Miyagawa; Shingo Takada; Norio Nonomura; Akihiko Okuyama
    INTERNATIONAL JOURNAL OF UROLOGY 15 9 789 - 793 2008年09月 [査読有り]
     
    Objectives: To investigate changes in the management of cases over time, we undertook a retrospective analysis of urological surgeries carried out in patients aged 80 years and older in a single institution over the last 30 years. Methods: Between 1975 and 2004, 402 patients aged 80 years and older underwent 412 surgeries in our department. We reviewed the clinical records and analyzed changes in clinical data over time. We evaluated the observed comorbidities and postoperative complications in selected patients for whom complete clinical records were available. We then identified risk factors for postoperative complications by means of multiple logistic regression analysis. Results: The number of surgeries carried out in patients aged 80 years and older increased every 5 years. Over time, the number of endourological and laparoscopic surgeries increased. Of 255 patients, 225 (88.3%) had at least one comorbidity, and 51 patients had postoperative complications. The number of observed comorbidities, such as cardiovascular disorder, central nervous system disorder, and diabetes mellitus, increased over the most recent 10-year period. However, there were no differences in postoperative complications over time. Male sex and open surgery were found to be independent risk factors for postoperative complications. Conclusions: Although elderly patients had various comorbidities, the postoperative morbidity rate was acceptable in our selected cases. This study may provide useful detailed information for patients 80 years and older who will undergo urological surgery.
  • Kazutoshi Fujita; Akira Tsujimura; Toshiaki Hirai; Hiroshi Ohta; Yasuhiro Matsuoka; Yasushi Miyagawa; Tetsuya Takao; Shingo Takada; Norio Nonomura; Akihiko Okuyama
    INTERNATIONAL JOURNAL OF UROLOGY 15 8 733 - 738 2008年08月 [査読有り]
     
    Objectives: To preserve the fertility of prepubertal boys with childhood cancer, it has been proposed that testicular tissues could be harvested before treatment and then immature germ cells matured by xenografting under the skin of immunodeficient mice. However, malignant cells present in the testicular tissue may disturb spermatogenesis in the xenografts. Here we examined the effect of human leukemia cells on ectopic xenografts in immunodeficient mice. Methods: First, in order to evaluate the tumor forming ability of Human leukemia cells (Jurkat cells), different amounts of these cells were injected into nude mice and analyzed 8 weeks later. Testicular tissues from 5-week-old donor SCID mice injected with Jurkat cells were xenografted under the skin of recipient nude mice. After 8 weeks, xenografts were histologically evaluated and expression of testicular markers in xenografts was assessed. Results: More than 1 x 10(6) Jurkat cells were necessary to develop a tumor under the skin of nude mice. Eight weeks after xenografting, 5 of 20 xenografts (25%) developed tumors. Spermatogenesis was not detected in any xenografts. Testicular cells were not detected in the tumor by the reverse transcription-polymerase chain reaction technique. Conclusions: Human leukemia cells infiltrating testicular tissue may disturb spermatogenesis in xenografts. Xenografting cannot be considered a reliable method for the detection of human leukemic cells in testicular tissues before auto-transplantation. Other measures should be developed to preserve the fertility of prepubertal boys with leukemia.
  • Kazutoshi Fujita; Charles M. Ewing; Lori J. Sokoll; Debra J. Elliott; Mark Cunningham; Angelo M. De Marzo; William B. Isaacs; Christian P. Pavlovich
    PROSTATE 68 8 872 - 882 2008年06月 [査読有り]
     
    BACKGROUND. Cytokines are key mediators of inflammation that may relate to Prostate cancer initiation and progression, and that may be useful markers of prostatic neoplasia and related inflammation. In order to better understand the relationship between cytokines and prostate cancer, we profiled cytokines in prostatic fluids obtained from cancerous prostate glands and correlated them to both cancer status and inflammatory grade. METHODS. Prostatic fluid was collected from fresh radical prostatectomy specimens and analyzed by cytokine antibody microarray. For comparison, cases were selected from patients with either minimal or extensive cancer volume on final pathology. Among the cytokines with the greatest difference between the tumor volume groups, eight had their levels quantitated by ELISA. In addition, the grade of prostatic inflammation by neutrophils, macrophages and lymphocytes was scored for each case and examined for correlations with cytokine levels. RESULTS. Among 174 cytokines analyzed, HGF was the most increased (6.57-fold), and along with IL18Bpa was significantly elevated in patients with extensive disease compared to those with minimal disease. IL17, GITR, and ICAM-1 were elevated in specimens with significant neutrophilic inflammation into gland lumina, and IL1813pa, 11,17, GITR, and ICAM-1 were elevated in specimens with significant lymphocytic inflammation in prostatic stroma. CONCLUSIONS. Prostatic fluid cytokines were identified that may be useful for early cancer detection and prognostication efforts and for assessment of prostatic inflammation, particularly if they can be found not only in prostatic fluids obtained ex vivo, but in expressed prostatic secretions or urine samples from men with prostates still in situ.
  • Akira Tsujimura; Kazutoshi Fujita; Kazuhiko Komori; Tetsuya Takao; Yasushi Miyagawa; Shingo Takada; Kiyomi Matsumiya; Norio Nonomur; Akihiko Okuyama
    JOURNAL OF UROLOGY 178 2 686 - 691 2007年08月 [査読有り]
     
    Purpose: Identifying prostatic stem cells is important to elucidate the mechanisms by which the prostate develops and control prostate cancer. We recently reported that the proximal region of the mouse prostate contains a population of stem cells. However, to our knowledge the specific marker of stem cells in the proximal region remains unknown. Materials and Methods: We performed cDNA microarray analysis of cells obtained from the proximal region and from the remaining regions in dorsal prostates to identify several candidate stem cell markers. After we focused on 1 candidate among them we confirmed the expression of this candidate gene by reverse transcriptase-polymerase chain reaction analysis and immunohistochemistry. We also investigated the relation between positive cells for this marker and those for telomerase reverse transcriptase. Finally, we investigated the functional potential of prominin positive cells in 3-dimensional culture. Results: Seven of 4,800 genes analyzed showed proximal/remaining ratios greater than 20. Of these genes we focused on prominin because it is a cell surface marker widely used to identify and isolate stem cells from various organs. We found a prominin positive cell population enriched in the basal cell layer in the proximal region, and the coincidence of prominin and telomerase reverse transcriptase immunostaining. We also found that prominin positive cells gave rise to numerous and large-branched ducts, whereas prominin negative cells formed far fewer such structures in 3-dimensional culture. Conclusions: A small population of prominin positive cells in the mouse prostate basal layer of the proximal region represents a stem cell population.
  • Yasushi Miyagawa; Akira Tsujimura; Kazutoshi Fujita; Yasuhiro Matsuoka; Tohru Takahashi; Tetsuya Takao; Shingo Takada; Kiyomi Matsumiya; Yasuhiro Osaki; Masashi Takasawa; Naohiko Oku; Jun Hatazawa; Shigeo Kaneko; Akihiko Okuyama
    NEUROIMAGE 36 3 830 - 842 2007年07月 [査読有り]
     
    The human male psychosexual cycle consists of four phases: excitation, plateau, orgasm, and resolution. Identification of the specific neural substrates of each phase may provide information regarding the brain's pathophysiology of sexual dysfunction. We previously analyzed regional cerebral blood flow (rCBF) with H-2(15) O-positron emission tomography (PET) during the excitation phase (initiation of penile erection) induced by audiovisual sexual stimuli (AVSS) and identified activation of the cerebellar vermis, the bilateral extrastriate cortex, and right orbitofrontal cortex, suggesting a role of cognition/emotion in the excitement phase. In the present study, we analyzed rCBF of the same six healthy volunteers during the plateau phase (maintenance of penile erection) induced by AVSS and compared the results with those of the excitation phase. Penile rigidity was monitored in real time With RigiScan Plus (R) during PET scanning. Images were analyzed by statistical parametric mapping (SPM) software, and rCBF in the amygdala, hypothalamus, anterior cingulate, and insula was measured. During the plateau phase, primary subcortical activation was noted in the right ventral putamen, indicating motivational factors in the sexual response via the limbic reward circuit. A significant increase in rCBF in the left hypothalamus was also observed during the plateau phase. The right anterior cingulate and left insula were specifically activated during the excitation phase but not during the plateau phase. These results indicate a significant role of the ventral putamen and the hypothalamus in the plateau phase and confirm that paralimbic and limbic components of the human brain differentially coordinate the sexual response in a psychosexual phase-dependent manner. (c) 2007 Elsevier Inc. All rights reserved.
  • Kazutoshi Fujita; Akira Tsujimura; Yasushi Miyagawa; Hiroshi Kiuchi; Yasuhiro Matsuoka; Tetsuya Takao; Shingo Takada; Norio Nonomura; Akihiko Okuyama
    CANCER RESEARCH 66 23 11166 - 11171 2006年12月 [査読有り]
     
    More than 70% of patients survive childhood cancer, but chemotherapy and radiation therapy may cause irreversible impairment of spermatogenesis. To treat infertility secondary to anticancer treatment for childhood cancer, we have developed a procedure to isolate germ cells from leukemic mice by fluorescence-activated cell sorting with two surface markers, and transplantation of isolated germ cells successfully restored fertility without inducing leukemia. In the present study, we analyzed human germ cells and human malignant cells, including five leukemia cell lines and three lymphoma cell lines, by fluorescence-activated cell sorting with antibodies against MHC class I and CD45. Testicular specimens were obtained from a patient who underwent surgery for testicular rupture. In the high forward scatter and low side scatter region, no malignant cells were found in the MHC class I-negative and CD45-negative fraction (the germ cell fraction), with the exception of K562 cells. A total of 39.2% of the germ cells were found in the germ cell fraction. A total of 1.45% of K562 cells were found in the germ cell fraction. Treatment with IFN gamma induced the expression of MHC class I on K562 cells but not on germ cells and made it possible to isolate germ cells from K562 cells. In conclusion, we isolated human germ cells from malignant cells with two surface markers after treatment with IFN gamma. Immunophenotyping for each patient will be necessary before isolation and induction of surface marker will be clinically applicable.
  • Akira Tsujimura; Yasushi Miyagawa; Kazutoshi Fujita; Yasuhiro Matsuoka; Tohru Takahashi; Tetsuya Takao; Kiyomi Matsumiya; Yasuhiro Osaki; Masashi Takasawa; Naohiko Oku; Jun Hatazawa; Shigeo Kaneko; Akihiko Okuyama
    JOURNAL OF UROLOGY 176 2 679 - 683 2006年08月 [査読有り]
     
    Purpose: Penile erection is dependent on commands from the central nervous system. Although basic studies of animals and neuroimaging studies of humans have been conducted to identify key brain regions associated with sexual arousal, to our knowledge no reliable studies of the first excitation phase of sexual arousal leading to penile erection have been reported. Materials and Methods: We used (H2O)-O-15-positron emission tomography to analyze regional cerebral blood flow just before penile erection in heterosexual volunteers. The subjects viewed 3 different types of audiovisual materials-sexually explicit clips, nonsexual neutral clips and dynamic mosaic image control clips-presented in random order, and penile rigidity was monitored in real time with a RigiScan (R) Plus device. Positron emission tomography scanning was initiated simultaneously when each clip was started, and images obtained when the subjects showed appropriate penile response were analyzed and compared. Results: The advanced audiovisual cortices and cerebellar vermis in the right hemisphere were activated for sexually explicit-dynamic mosaic image control clip contrast, and only the right middle frontal gyrus was activated for sexually explicit- nonsexual neutral clip contrast. Several primary visual and audio regions were activated for dynamic mosaic image control-sexually explicit clip contrast and nonsexual neutral-sexually explicit clip contrast. Conclusions: We speculate that advanced audiovisual activity with imagination, not primary visual and audio activity, occurs when men experience sexual arousal inducing penile erection. Furthermore, the cerebellar vermis may be a key region for induction of penile erection in humans.
  • Fujita K; Miyagawa Y; Okuyama A
    Nihon rinsho. Japanese journal of clinical medicine 2006年04月 [査読有り]
  • A Tsujimura; K Fujita; K Komori; P Tanjapatkul; Y Miyagawa; S Takada; K Matsumiya; M Sada; Y Katsuyama; M Ota; A Okuyama
    ASIAN JOURNAL OF ANDROLOGY 8 2 213 - 218 2006年03月 [査読有り]
     
    Aim: To investigate the associations of autosomal and X-chromosome homologs of the RNA-binding-motif (RNA-binding-motif on the Y chromosome, RBMY) gene with non-obstructive azoospermia (NOA), as genetic factors for NOA may map to chromosomes other than the Y chromosome. Methods: Genomic DNA was extracted using a salting-out procedure after treatment of peripheral blood leukocytes with proteinase K from Japanese patients with NOA (n = 67) and normal fertile volunteers (n= 105). The DNA were analyzed for RBMX by expressed sequence tag (EST) deletion and for the like sequence on chromosome 9 (RBMXL9) by microsatellite polymorphism. Results: We examined six ESTs in and around RBMX and found a deletion of SHGC31764 in one patient with NOA and a deletion of DXS7491 in one other patient with NOA. No deletions were detected in control subjects. The association study with nine microsatellite markers near RBMXL9 revealed that D9S319 was less prevalent in patients than in control subjects, whereas D9S1853 was detected more frequently in patients than that in control subjects. Conclusion: We provide evidence that deletions in or around RBMX may be involved in NOA. In addition, analyses of markers in the vicinity of RBMXL9 on chromosome 9 suggest the possibility that variants of this gene may be associated with NOA. Although further studies are necessary, this is the first report of the association between RBMX and RBMXL9 with NOA.
  • Kazuhiko Komori; Akira Tsujimura; Sumio Ishijima; Phanu Tanjapatkul; Kazutoshi Fujita; Yasuhiro Matsuoka; Tetsuya Takao; Yasushi Miyagawa; Shingo Takada; Akihiko Okuyama
    Reproductive Medicine and Biology 5 3 195 - 200 2006年 [査読有り]
     
    Background and aim: Conventional manual sperm analysis still shows variations in structure, process and outcome although World Health Organization (WHO) guidelines present an appropriate method for sperm analysis. In the present study a new system for sperm analysis, Sperm Motility Analysis System (SMAS), was compared with manual semen analysis based on WHO guidelines. Materials and methods: Samples from 30 infertility patients and 21 healthy volunteers were subjected to manual microscopic analysis and SMAS analysis, simultaneously. We compared these two methods with respect to sperm concentration and percent motility. Results: Sperm concentrations obtained by SMAS (Csmas) and manual microscopic analyses on WHO guidelines (Cwho) were strongly correlated (Cwho = 1.325 × Csmas r = 0.95, P < 0.001). If we excluded subjects with Csmas values > 30 × 106 sperm/mL, the results were more similar (Cwho = 1.022 × Csmas r = 0.81, P < 0.001). Percent motility obtained by SMAS (Msmas) and manual analysis on WHO guidelines (Mwho) were strongly correlated (Mwho = 1.214 × Msmas r = 0.89, P < 0.001). Conclusions: The data indicate that the results of SMAS and those of manual microscopic sperm analyses based on WHO guidelines are strongly correlated. SMAS is therefore a promising system for sperm analysis. (Reprod Med Biol 2006 5: 195-200): © 2006 The Authors Journal compilation 2006 Japan Society for Reproductive Medicine.
  • K Fujita; A Tsujimura; T Takao; Y Miyagawa; K Matsumiya; M Koga; M Takeyama; H Fujioka; K Aozasa; A Okuyama
    HUMAN REPRODUCTION 20 8 2289 - 2294 2005年08月 [査読有り]
     
    BACKGROUND: Microdissection testicular sperm extraction (TESE) has provided new hope for successful sperm retrieval to patients with Sertoli cell-only syndrome (SCO). We determined expression of the inhibin alpha subunit, glial cell line-derived neurotrophic factor (GDNF) and stem cell factor (SCF) in Sertoli cells obtained from patients with SCO immunohistochemically and compared expression rates with rates of microdissection TESE sperm retrieval. METHODS: Testicular biopsy specimens were obtained from 52 men with non-obstructive azoospermia who underwent microdissection TESE and were diagnosed with SCO by histological analysis. RESULTS: All specimens showed intense staining for the inhibin alpha subunit. Moderate or intense staining for GDNF was observed in 65.8% of specimens. All but one showed moderate or intense staining for SCF. Among specimens negative for GDNF, the sperm retrieval rate was significantly higher (100%) for specimens with intense staining for SCF than for specimens with no or moderate staining (30.7%) (P < 0.05) for SCF. CONCLUSION: GDNF expression differs among patients with SCO. The sperm retrieval rate was high in cases of no staining for GDNF and intense staining for SCF.
  • K Fujita; H Ohta; A Tsujimura; T Takao; Y Miyagawa; S Takada; K Matsumiya; T Wakayama; A Okuyama
    JOURNAL OF CLINICAL INVESTIGATION 115 7 1855 - 1861 2005年07月 [査読有り]
     
    More than 70% of patients survive childhood leukemia, but chemotherapy and radiation therapy cause irreversible impairment of spermatogenesis. Although autotransplantation of germ cells holds promise for restoring fertility, contamination by leukemic cells may induce relapse. In this study, we isolated germ cells from leukemic mice by FACS sorting. The cell population in the high forward-scatter and low side-scatter regions of dissociated testicular cells from leukemic mice were analyzed by staining for MHC class I heavy chain (H-2K(b/) H-2D(b)) and for CD45. Cells that did not stain positively for H-2K(b)/H-2D(b) and CD45 were sorted as the germ cell-enriched fraction. The sorted germ cell-enriched fractions were transplanted into the testes of recipient mice exposed to alkylating agents. Transplanted germ cells colonized, and recipient mice survived. Normal progeny were produced by intracytoplasmic injection of sperm obtained from recipient testes. When unsorted germ cells from leukemic mice were transplanted into recipient testes, all recipient mice developed leukemia. The successful birth of offspring from recipient mice without transmission of leukemia to the recipients indicates the potential of autotransplantation of germ cells sorted by FACS to treat infertility secondary to anticancer treatment for childhood leukemia.
  • A Tsujimura; K Matsumiya; Y Miyagawa; T Takao; K Fujita; S Takada; M Koga; A Iwasa; M Takeyama; A Okuyama
    INTERNATIONAL JOURNAL OF IMPOTENCE RESEARCH 17 3 259 - 263 2005年05月 [査読有り]
     
    The International Society for the Study of the Aging Male (ISSAM) recommends that a diagnosis be based on a patient's total testosterone ( TT), calculated free testosterone (cFT), or calculated bioavailable testosterone (cBT) for partial androgen deficiency of the aging male (PADAM). The purpose of this study was to confirm whether hypogonadism of patients with PADAM is related to symptoms and clarify which criteria of testosterone recommended by ISSAM is suitable for Japanese patients. A total of 90 patients with PADAM symptoms were included in this study. Endocrinologic profiles were reviewed as appropriate, and PADAM symptoms were judged by means of several questionnaires. Laboratory values and symptoms were compared between patients with and without hypogonadism. Even when any criterion of testosterone was used for diagnosis of hypogonadism, AMS ( total and subscales), IIEF-5, or SDS scores of PADAM symptoms did not differ significantly between patients classified as having and not having hypogonadism. No other endocrinologic variables than testosterone differed significantly between them, either. PADAM symptoms are not related to testosterone level and it is still obscure whether ISSAM's criterion can be adopted for Japanese patients with PADAM. Other pathology needs to be addressed for evaluation and diagnosis of PADAM in Japan.
  • Akira Tsujimura; Yasushi Miyagawa; Tetsuya Takao; Kazutoshi Fujita; Kazuhiko Komori; Yasuhiro Matsuoka; Shingo Takada; Minoru Koga; Masami Takeyama; Hideki Fujioka; Kiyomi Matsumiya; Akihiko Okuyama
    Reproductive Medicine and Biology 4 1 53 - 57 2005年 [査読有り]
     
    Background: The spermatozoa retrieval rate achieved by microdissection testicular sperm extraction (TESE) for patients with non-obstructive azoospermia is still approximately 50%, despite technical advances. Predicting a successful outcome is important to avoid unnecessary surgery. A study was conducted to determine a method for calculating the predicted probability of successful microdissection TESE. Methods: Testicular spermatozoa were retrieved in 41 of 100 patients by microdissection TESE. Ten clinical factors were examined in the search for an optimal logistic model for predicting a good outcome. Once the best delimiting value was established, sensitivity and specificity were calculated. Results: Patient age, serum follicle stimulating hormone (FSH) concentration and Johnsen's score (JS) were shown to be influential factors by multivariate logistic analysis. The mathematical model for predicting the probability of a successful outcome was as follows: P = (1 + exp[0.144 × patient age - 0.059 × serum FSH concentration - 1.310 × JS]) -1. When a predictive probability of 49.7% was selected as the best cut-off value, sensitivity and specificity were 78.0% and 76.3%, respectively. Conclusion: This present model is very useful for predicting successful microdissection TESE. In addition, we suggest that a younger patient age would increase the probability of success with this procedure.
  • A Tsujimura; K Matsumiya; Y Miyagawa; T Takao; K Fujita; M Koga; M Takeyama; H Fujioka; A Okuyama
    JOURNAL OF UROLOGY 172 5 1944 - 1947 2004年11月 [査読有り]
     
    Purpose: Microsurgical techniques in testicular sperm extraction can improve sperm retrieval in patients with nonobstructive azoospermia (NOA). However, spermatozoa retrieval rates have still been reported to be around 50% for patients with NOA. Thus, a reliable prediction method for successful outcome is needed to avoid unnecessary surgery. In this retrospective study we determined the diagnostic and predictive values of noninvasive parameters used in the treatment of patients with NOA. Materials and Methods: We analyzed 9 preoperative factors including patient age, testicular volume and endocrinological data of 100 patients with NOA using multivariate logistic modeling. Testicular spermatozoa were retrieved successfully in 41 of the 100 patients (41%). Results: We found that the concentrations of follicle-stimulating hormone (FSH), total testosterone (TT) and inhibin B were considered the most influential preoperative factors. We developed a formula to calculate the probability of successful outcome, P = [1 + exp(5.201 - 0.048 x FSH - 0.449 x TT - 0.021 x inhibin B)](-1). Association of predicted probabilities and observed responses was 0.77. A predicted probability of more than 15.7% was found to be the best cutoff. Sensitivity was 71.0% and specificity was 71.4% as determined by receiver operating characteristic analysis. Conclusions: We concluded that our formula should be useful for doctors considering microdissection testicular sperm extraction for patients with NOA because our equation uses noninvasive parameters without a preoperative testicular biopsy, which is a relatively invasive examination.
  • K Fujita; H Sugao; T Gotoh; S Yokomizo; Y Itoh
    INTERNATIONAL JOURNAL OF UROLOGY 11 3 178 - 181 2004年03月 [査読有り]
     
    We report a case of primary signet ring cell carcinoma of the prostate in a 75-year-old man. Serum prostate specific antigen (PSA) level at presentation was 9.3 ng/mL. The tumor was confined within the right prostate lobe and the patient was treated with neoadjuvant hormonal therapy and radical prostatectomy. He was alive with no evidence of disease 12 months after surgery. None of the tumor was stained with periodic acid-Schiff and Alcian blue. Immunohistochemically, the tumor was positive for PSA and prostatic acid phosphatase and negative for carcinoembryonic antigen. We reviewed 41 previously reported cases of signet ring cell carcinoma of the prostate, examining both histopathological and clinical information.
  • K Fujita; H Sugao; K Tsujikawa
    INTERNATIONAL JOURNAL OF UROLOGY 11 1 53 - 55 2004年01月 [査読有り]
     
    We report a case of infectious perinephric urinoma in a 73-year-old woman who had a neurogenic bladder with vesico-ureteral reflux. The patient was admitted to our emergency room with right lumbago and high fever. Ultrasounds and computed tomography demonstrated a right large perinephric cystic mass, bilateral hydronephrosis and much residual urine. Percutaneous drainage of the cystic mass was performed with an indwelling urethral catheter. The content of the mass was urine infected with Escherichia coli. Antibiotic therapy was performed successfully and we then examined the cause of the urinoma. A urodynamic study demonstrated a low-compliance small bladder and detrusor-sphincter dyssynergia. A voiding cystourethrogram revealed right grade III vesicoureteral reflux. The patient was unable to be cleared with intermittent catheterization and had an indwelling urethral catheter inserted. In 1 year, the voiding cystourethrogram showed no vesicoureteral reflux and the patient was well with no evidence of recurrent urinoma without the urethral catheter. There have been only two reported cases of urinoma caused by neurogenic bladder with vesico-ureteral reflux in children and this is the first case reported in an adult.
  • K Fujita; K Nishimura; Y Yasunaga; O Miyake; S Hirota; A Okuyama
    INTERNATIONAL JOURNAL OF UROLOGY 10 9 492 - 494 2003年09月 [査読有り]
     
    A 36-year-old man presented with macroscopic hematuria associated with right flank pain. Examination of the patient revealed a cystic mass in the right kidney Because the mass had increased in size, enucleation of the mass was performed. Histopathological findings revealed nephroblastoma, therefore, radical nephrectomy was performed. We believe the pathogenesis of the cystic formation to be a process in which a tumor that had developed in the pericalyceal region spontaneously ruptured, exuding urine into the perinephric space, forming a cystic mass. The patient is alive with no evidence of disease 24 months after the operation.
  • K Fujita; H Sugao; K Tsujikawa; Y Itoh
    INTERNATIONAL JOURNAL OF UROLOGY 10 5 274 - 275 2003年05月 [査読有り]
     
    Desmoid tumor is a fibroblastic proliferation arising in musculoaponeurotic tissues. We report a case of abdominal desmoid tumor discovered 2 years after radical nephrectomy for right renal cell carcinoma. Surgical extirpation was performed and the patient remained well 2 years later with no evidence of disease. The possibility of desmoid tumors developing in the incised abdominal wall should be considered while following patients after surgery.
  • K Fujita; K Nishimura; N Nonomura; S Hirota; A Okuyama
    INTERNATIONAL JOURNAL OF UROLOGY 8 11 643 - 644 2001年11月 [査読有り]
     
    A 73-year-old man with primary small cell carcinoma of the bladder underwent radical cystectomy. The pathological findings revealed the tumor confined to the submucosal layer (pT1) without metastasis. No adjuvant chemotherapy was carried out. He is alive with no evidence of the disease 24 months after the operation.

MISC

  • ヒトおよびマウスの前立腺癌腸内細菌叢の包括的解析について(Integrative gut microbiome analysis of human and mouse prostate cancer)
    若森 千怜; デベラスコ・マルコ; 倉 由吏恵; 藤田 和利; 坂井 和子; 松下 慎; 森 康範; 野澤 昌弘; 西本 光寿; 吉村 一宏; 野々村 祝夫; 西尾 和人; 植村 天受 日本癌学会総会記事 82回 71 -71 2023年09月
  • 前立腺癌マウスにおける腫瘍浸潤ミエロイド細胞について(Targeting tumor immunosuppressive myeloid cells in mouse Pten-null prostate cancer)
    植村 天受; 倉 由吏恵; 藤田 和利; 坂井 和子; シュラー・アルウイン; サッハセンマイヤー・クリス; 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 82回 408 -408 2023年09月
  • 前臨床癌マウスモデルにおけるPD-L1に対する抗薬物抗体の制御について(Preclinical model to counter antidrug antibodies to programmed cell death-1 blockade)
    デベラスコ・マルコ; 倉 由吏恵; 藤田 和利; 西本 光寿; 坂井 和子; 吉村 一宏; 野澤 昌弘; ハモンド・スコット; ドベディ・シモン; デービス・バリー; 西尾 和人; 植村 天受 日本癌学会総会記事 82回 1019 -1019 2023年09月
  • 前立腺癌Ptenノックアウトマウスを用いたCD73とA2aR阻害の効果について(Efficacy of combined CD73 and A2aR blockade in mouse Pten-deficient prostate cancer)
    デベラスコ・マルコ; 倉 由吏恵; 坂井 和子; 藤田 和利; 橋本 士; 坂野 恵里; 西本 光寿; 野澤 昌弘; 吉村 一宏; 西尾 和人; 植村 天受 日本泌尿器科学会総会 110回 OP76 -02 2023年04月
  • アンドロゲン受容体シグナル阻害を標的とした分子および免疫応答を評価可能とする前臨床前立腺癌マウスモデルの活用について(Use of a preclinical prostate cancer model to assess molecular and immune responses to androgen receptor signaling axis blockade)
    植村 天受; 倉 由吏恵; 藤田 和利; 坂井 和子; 橋本 士; 西本 光寿; 吉村 一宏; 野澤 昌弘; 西尾 和人; デベラスコ・マルコ 日本泌尿器科学会総会 110回 OP76 -03 2023年04月
  • 加藤大悟; 森下康一; 冨山栄輔; 植村俊彦; 山本顕生; 奥田洋平; 藤田和利; 石津谷祐; 山本致之; 波多野浩士; 河嶋厚成; 三善英知; 野々村祝夫 日本泌尿器科学会総会(Web) 110th 2023年
  • 波多野浩士; 岡利樹; 二村圭祐; 石津谷祐; 奥田洋平; 植村俊彦; 山道岳; 冨山栄輔; 山本致之; 加藤大悟; 河嶋厚成; 藤田和利; 藤田和利; 野々村祝夫 日本泌尿器科学会総会(Web) 110th 2023年
  • 17歳時に発見された神経節芽腫の1例
    大平 僚祐; 竹澤 健太郎; 福原 慎一郎; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 野々村 祝夫 泌尿器科紀要 68 (1) 23 -23 2022年01月
  • 根治切除しえた下大静脈腫瘍栓・肝転移を伴う進行性後腹膜平滑筋肉腫の1例
    久次米 雄馬; 河嶋 厚成; 河田 信彦; 阿部 豊文; 福原 慎一郎; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 野々村 祝夫 泌尿器科紀要 68 (1) 24 -24 2022年01月
  • 完全重複尿管の異所開口による尿失禁に対して経カテーテル動脈塞栓術(TAE)を施行した1例
    隠岐 雄太; 中澤 成晃; 阿部 豊文; 福原 慎一郎; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 野々村 祝夫 泌尿器科紀要 68 (1) 27 -27 2022年01月
  • 【泌尿器がんにおけるリキッドバイオプシーの現状と展望】尿路上皮がんにおける尿中DNAを用いたリキッドバイオプシー
    林 裕次郎; 藤田 和利 泌尿器科 15 (1) 40 -46 2022年01月
  • 尿路上皮癌における尿中cell-free DNAの臨床的有用性
    林 裕次郎; 藤田 和利; 冨山 栄輔; 松下 慎; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 高尾 徹也; 高田 晋吾; 植村 元秀; 今村 亮一; 野々村 祝夫 日本分子腫瘍マーカー研究会誌 37 7 -7 2022年
  • 尿中および組織分泌細胞外小胞のプロテオミクス解析による新規膀胱癌バイオマーカーの探索
    冨山 栄輔; 藤田 和利; 松崎 恭介; 白水 崇; 鳴海 良平; 神宮司 健太郎; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 植村 元秀; 高尾 徹也; 足立 淳; 朝長 毅; 野々村 祝夫 日本分子腫瘍マーカー研究会誌 37 16 -17 2022年
  • 17歳時に発見された神経節芽腫の1例
    大平 僚祐; 竹澤 健太郎; 福原 慎一郎; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 野々村 祝夫 泌尿器科紀要 68 (1) 23 -23 2022年01月
  • 根治切除しえた下大静脈腫瘍栓・肝転移を伴う進行性後腹膜平滑筋肉腫の1例
    久次米 雄馬; 河嶋 厚成; 河田 信彦; 阿部 豊文; 福原 慎一郎; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 野々村 祝夫 泌尿器科紀要 68 (1) 24 -24 2022年01月
  • 完全重複尿管の異所開口による尿失禁に対して経カテーテル動脈塞栓術(TAE)を施行した1例
    隠岐 雄太; 中澤 成晃; 阿部 豊文; 福原 慎一郎; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 野々村 祝夫 泌尿器科紀要 68 (1) 27 -27 2022年01月
  • 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 109回 SY31 -7 2021年12月
  • 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 109回 AVP01 -05 2021年12月
  • 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 109回 AOP06 -09 2021年12月
  • 腸内細菌が産生する短鎖脂肪酸はIGF-1シグナル経路を介して前立腺癌の増殖に関与する
    松下 慎; 藤田 和利; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 植村 元秀; 今村 亮一; 辻川 和丈; 中村 昇太; 竹田 潔; 野々村 祝夫 日本泌尿器科学会総会 109回 AOP10 -02 2021年12月
  • 腸内細菌叢のFirmicutes/Bacteroidetes比と前立腺肥大との関連(The Firmicutes/Bacteroidetes ratio of the gut microbiota is associated with prostate enlargement)
    竹澤 健太郎; 栗林 宗平; 岡田 紘一; 関井 洋輔; 松下 慎; 福原 慎一郎; 木内 寛; 藤田 和利; 川村 憲彦; 高田 晋吾; 中村 昇太; 小島 祥敬; 野々村 祝夫 日本泌尿器科学会総会 109回 ISA01 -08 2021年12月
  • 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 109回 ISA03 -01 2021年12月
  • 尿中および組織滲出液中の細胞外小胞のプロテオミクス解析による膀胱癌バイオマーカー開発の新規戦略(A novel strategy for the development of bladder cancer biomarkers by proteomic analysis of urinary and tissue-exudate extracellular vesicles)
    冨山 栄輔; 藤田 和利; 松崎 恭介; 神宮司 健太郎; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 植村 元秀; 今村 亮一; 高尾 徹也; 朝長 毅; 野々村 祝夫 日本泌尿器科学会総会 109回 ISA03 -05 2021年12月
  • 前立腺癌の新規非侵襲的診断指標としての尿中ホスファチジルコリン/リゾホスファチジルコリン比(The Urinary Phosphatidyl-choline/Lysophosphatidylcholine Ratio as a Novel and Non-invasive Diagnostic Index for Prostate Cancer)
    後藤 崇之; 李 新; 中山 憲司; 井上 貴博; 木村 博子; 林 裕次郎; 澤田 篤郎; 赤松 秀輔; 藤田 和利; 小林 恭; 野々村 祝夫; 小川 修 日本泌尿器科学会総会 109回 ISA04 -10 2021年12月
  • 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 109回 ISP02 -03 2021年12月
  • 胚細胞腫瘍サバイバーにおける勃起障害および射精障害の改善(Improvement of erectile dysfunction and ejaculatory dysfunction in germ cell tumor survivors)
    福原 慎一郎; 藤田 和利; 岡田 紘一; 栗林 宗平; 関井 洋輔; 稲垣 裕介; 竹澤 健太郎; 植村 元秀; 木内 寛; 今村 亮一; 野々村 祝夫 日本泌尿器科学会総会 109回 ISP04 -04 2021年12月
  • 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 109回 OP01 -03 2021年12月
  • 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 109回 OP10 -03 2021年12月
  • 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 109回 OP12 -06 2021年12月
  • 上部尿路上皮癌におけるNectin-4およびPD-L1発現の臨床的検討
    冨山 栄輔; 藤田 和利; 坂野 恵里; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 植村 元秀; 今村 亮一; 高尾 徹也; 山口 誓司; Netto George J.; 野々村 祝夫 日本泌尿器科学会総会 109回 OP19 -04 2021年12月
  • 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 109回 OP20 -04 2021年12月
  • 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 109回 OP71 -01 2021年12月
  • 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 109回 OP71 -02 2021年12月
  • 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 109回 OP71 -03 2021年12月
  • 尿中cell-free DNAの膀胱癌新規バイオマーカーとしての臨床的有用性の検討
    林 裕次郎; 藤田 和利; 弓場 覚; 山道 岳; 冨山 栄輔; 洪 陽子; 松下 慎; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 植村 元秀; 野々村 祝夫 日本泌尿器科学会総会 109回 PP05 -03 2021年12月
  • 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 109回 PP08 -09 2021年12月
  • 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 109回 PP12 -01 2021年12月
  • 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 109回 PP25 -01 2021年12月
  • 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 109回 PP25 -06 2021年12月
  • TERT promoter変異と膀胱癌発癌の関連 数理アルゴリズムによる膀胱癌の進化ゲノミクス解析
    林 裕次郎; 藤田 和利; 弓場 覚; 山道 岳; 冨山 栄輔; 洪 陽子; 中野 剛佑; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 植村 元秀; 野々村 祝夫 日本泌尿器科学会総会 109回 PP26 -03 2021年12月
  • 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 109回 PP28 -05 2021年12月
  • 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 46 (3-4) 19A -19A 2021年12月
  • 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 109回 SY31 -7 2021年12月
  • 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 109回 AVP01 -05 2021年12月
  • 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 109回 AOP06 -09 2021年12月
  • 腸内細菌が産生する短鎖脂肪酸はIGF-1シグナル経路を介して前立腺癌の増殖に関与する
    松下 慎; 藤田 和利; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 植村 元秀; 今村 亮一; 辻川 和丈; 中村 昇太; 竹田 潔; 野々村 祝夫 日本泌尿器科学会総会 109回 AOP10 -02 2021年12月
  • A deep-learning-based system to diagnose tumor malignancy beyond classical morphological cytopathology techniques(和訳中)
    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 109回 ISA03 -01 2021年12月
  • A novel strategy for the development of bladder cancer biomarkers by proteomic analysis of urinary and tissue-exudate extracellular vesicles(和訳中)
    冨山 栄輔; 藤田 和利; 松崎 恭介; 神宮司 健太郎; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 植村 元秀; 今村 亮一; 高尾 徹也; 朝長 毅; 野々村 祝夫 日本泌尿器科学会総会 109回 ISA03 -05 2021年12月
  • The Urinary Phosphatidyl-choline/Lysophosphatidylcholine Ratio as a Novel and Non-invasive Diagnostic Index for Prostate Cancer(和訳中)
    後藤 崇之; 李 新; 中山 憲司; 井上 貴博; 木村 博子; 林 裕次郎; 澤田 篤郎; 赤松 秀輔; 藤田 和利; 小林 恭; 野々村 祝夫; 小川 修 日本泌尿器科学会総会 109回 ISA04 -10 2021年12月
  • 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 109回 ISP02 -03 2021年12月
  • Improvement of erectile dysfunction and ejaculatory dysfunction in germ cell tumor survivors(和訳中)
    福原 慎一郎; 藤田 和利; 岡田 紘一; 栗林 宗平; 関井 洋輔; 稲垣 裕介; 竹澤 健太郎; 植村 元秀; 木内 寛; 今村 亮一; 野々村 祝夫 日本泌尿器科学会総会 109回 ISP04 -04 2021年12月
  • 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 109回 OP01 -03 2021年12月
  • 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 109回 OP10 -03 2021年12月
  • 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 109回 OP12 -06 2021年12月
  • 上部尿路上皮癌におけるNectin-4およびPD-L1発現の臨床的検討
    冨山 栄輔; 藤田 和利; 坂野 恵里; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 植村 元秀; 今村 亮一; 高尾 徹也; 山口 誓司; Netto George J.; 野々村 祝夫 日本泌尿器科学会総会 109回 OP19 -04 2021年12月
  • 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 109回 OP20 -04 2021年12月
  • 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 109回 OP71 -01 2021年12月
  • 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 109回 OP71 -02 2021年12月
  • 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 109回 OP71 -03 2021年12月
  • 尿中cell-free DNAの膀胱癌新規バイオマーカーとしての臨床的有用性の検討
    林 裕次郎; 藤田 和利; 弓場 覚; 山道 岳; 冨山 栄輔; 洪 陽子; 松下 慎; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 植村 元秀; 野々村 祝夫 日本泌尿器科学会総会 109回 PP05 -03 2021年12月
  • 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 109回 PP08 -09 2021年12月
  • 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 109回 PP12 -01 2021年12月
  • 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 109回 PP12 -07 2021年12月
  • 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 109回 PP25 -01 2021年12月
  • 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 109回 PP25 -06 2021年12月
  • TERT promoter変異と膀胱癌発癌の関連 数理アルゴリズムによる膀胱癌の進化ゲノミクス解析
    林 裕次郎; 藤田 和利; 弓場 覚; 山道 岳; 冨山 栄輔; 洪 陽子; 中野 剛佑; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 植村 元秀; 野々村 祝夫 日本泌尿器科学会総会 109回 PP26 -03 2021年12月
  • 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 109回 PP28 -05 2021年12月
  • 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 46 (3-4) 19A -19A 2021年12月
  • 尿中ホスファチジルコリン/リゾホスファチジルコリン比は前立腺癌の新規診断マーカーとなり得る(京都大学大阪大学共同研究)
    後藤 崇之; 李 新; 中山 憲司; 井上 貴博; 木村 博子; 林 裕次郎; 澤田 篤郎; 赤松 秀輔; 藤田 和利; 小林 恭; 野々村 祝夫; 小川 修 西日本泌尿器科学会総会抄録集 73回 198 -198 2021年11月
  • 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 35回 P -3 2021年11月
  • 尿中ホスファチジルコリン/リゾホスファチジルコリン比は前立腺癌の新規診断マーカーとなり得る(京都大学大阪大学共同研究)
    後藤 崇之; 李 新; 中山 憲司; 井上 貴博; 木村 博子; 林 裕次郎; 澤田 篤郎; 赤松 秀輔; 藤田 和利; 小林 恭; 野々村 祝夫; 小川 修 西日本泌尿器科学会総会抄録集 73回 198 -198 2021年11月
  • オリゴ転移前立腺癌における転移巣に対する局所療法の治療成績
    波多野 浩士; 平田 岳郎; 渡部 直史; 山本 顕生; 植村 俊彦; 山道 岳; 冨山 栄輔; 洪 陽子; 松下 慎; 加藤 大悟; 河嶋 厚成; 氏家 剛; 藤田 和利; 植村 元秀; 野々村 祝夫 日本癌治療学会学術集会抄録集 59回 O64 -2 2021年10月
  • 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 59回 P27 -2 2021年10月
  • 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 59回 P29 -2 2021年10月
  • 【日本発の臨床研究からみた前立腺癌診療】前立腺癌に対する遺伝子治療の現状と展望 HVJ-E(GEN0101)
    藤田 和利; 野々村 祝夫 Prostate Journal 8 (2) 168 -171 2021年10月
  • 非悪性尿路上皮のTERT Promoter変異に基づくBCG個別化医療の可能性
    林 裕次郎; 藤田 和利; 小西 雅俊; 前川 洋子; 谷 優; 朝倉 寿久; 角田 洋一; 蔦原 宏一; 高尾 徹也; 野々村 祝夫 日本癌治療学会学術集会抄録集 59回 O17 -3 2021年10月
  • 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 59回 O62 -7 2021年10月
  • 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 59回 O63 -1 2021年10月
  • オリゴ転移前立腺癌における転移巣に対する局所療法の治療成績
    波多野 浩士; 平田 岳郎; 渡部 直史; 山本 顕生; 植村 俊彦; 山道 岳; 冨山 栄輔; 洪 陽子; 松下 慎; 加藤 大悟; 河嶋 厚成; 氏家 剛; 藤田 和利; 植村 元秀; 野々村 祝夫 日本癌治療学会学術集会抄録集 59回 O64 -2 2021年10月
  • 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 59回 P27 -2 2021年10月
  • 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 59回 P29 -2 2021年10月
  • 尿路上皮癌における尿中cell-free DNAの臨床的有用性
    林 裕次郎; 藤田 和利; 冨山 栄輔; 松下 慎; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 高尾 徹也; 高田 晋吾; 植村 元秀; 今村 亮一; 野々村 祝夫 日本分子腫瘍マーカー研究会プログラム・講演抄録 41回 40 -40 2021年09月
  • 尿中および組織分泌細胞外小胞のプロテオミクス解析による新規膀胱癌バイオマーカーの探索
    冨山 栄輔; 藤田 和利; 松崎 恭介; 白水 崇; 鳴海 良平; 神宮司 健太郎; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 植村 元秀; 高尾 徹也; 足立 淳; 朝長 毅; 野々村 祝夫 日本分子腫瘍マーカー研究会プログラム・講演抄録 41回 50 -51 2021年09月
  • 腸内細菌叢のFirmicutes/Bacteroidetes比は前立腺腫大と関連する
    竹澤 健太郎; 栗林 宗平; 岡田 紘一; 関井 洋輔; 松下 慎; 福原 慎一郎; 木内 寛; 藤田 和利; 川村 憲彦; 高田 晋吾; 中村 昇太; 小島 祥敬; 野々村 祝夫 日本排尿機能学会誌 32 (1) 186 -186 2021年09月
  • 藤田和利; 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 日本癌学会学術総会抄録集(Web) 80回 [S12 -6] 2021年09月
  • 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 日本癌学会学術総会抄録集(Web) 80回 [E3 -4] 2021年09月
  • 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 日本癌学会学術総会抄録集(Web) 80回 [E12 -1] 2021年09月
  • 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 80回 [E14 -4] 2021年09月
  • 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 日本癌学会学術総会抄録集(Web) 80回 [E17 -3] 2021年09月
  • 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 日本癌学会学術総会抄録集(Web) 80回 [J14 -3] 2021年09月
  • 腸内細菌が産生する短鎖脂肪酸はIGF-1を介して肥満マウスの前立腺癌の増殖を促進する
    松下 慎; 藤田 和利; 長谷 拓明; 神宮司 健太郎; 山本 顕生; 植村 俊彦; 山道 岳; 冨山 栄輔; 洪 陽子; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 植村 元秀; 辻川 和丈; 野々村 祝夫 日本癌学会総会記事 80回 [P14 -7] 2021年09月
  • 関井 洋輔; 氏家 剛; 永原 啓; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 宮川 康; 中山 尋文; 難波 範行; 大割 貢; 出口 幸一; 野々村 祝夫 泌尿器科紀要 67 (8) 363 -366 2021年08月
  • 堀部 祐輝; 氏家 剛; 福原 慎一郎; 藤田 和利; 木内 寛; 植村 元秀; 今村 亮一; 野々村 祝夫 泌尿器科紀要 67 (7) 327 -330 2021年07月
  • 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 67 (6) 249 -249 2021年06月
  • CRPCの予後改善を目指した基礎と臨床 前立腺癌CRPCの予後改善を目指した臨床
    藤田 和利 泌尿器科紀要 67 (6) 284 -284 2021年06月
  • 石井 信; 竹澤 健太郎; 今村 亮一; 福原 慎一郎; 藤田 和利; 植村 元秀; 木内 寛; 野々村 祝夫 日本泌尿器科学会雑誌 112 (2) 109 -112 2021年04月
  • Taigo Kato; Eisuke Tomiyama; Yoko Koh; Makoto Matsushita; Yujiro Hayashi; Kosuke Nakano; Yu Ishizuya; Cong Wang; Koji Hatano; Atsunari Kawashima; Takeshi Ujike; Kazutoshi Fujita; Kazuma Kiyotani; Motohide Uemura; Norio Nonomura CANCER SCIENCE 112 398 -398 2021年02月
  • 松村直紀; 浜口守; 永井康晴; 南高文; 藤田和利; 野澤昌弘; 能勢和宏; 田原秀男; 上島成也; 吉村一宏; 植村天受 日本泌尿器科学会中部総会プログラム・抄録集 71st 2021年
  • 藤田和利; 南高文; 野澤昌弘; 吉村一宏; 植村天受 日本泌尿器科学会中部総会プログラム・抄録集 71st 2021年
  • 藤田和利; 南高文; 野澤昌弘; 吉村一宏; 植村天受 日本泌尿器科学会中部総会プログラム・抄録集 71st 2021年
  • 松村直紀; 浜口守; 大森直美; 沖貴士; 田原秀男; 木野茂生; 西本光寿; 安富正吾; 坂野恵里; 南高文; 野澤昌弘; 藤田和利; 吉村一宏; 植村天受 日本泌尿器科学会東部総会プログラム・抄録集 86th 2021年
  • 藤田和利; 中山尭仁; 橋本士; 菊池堯; 齋藤允孝; 清水信貴; 南高文; 野澤昌弘; 吉村一宏; 植村天受 日本泌尿器内視鏡学会(Web) 35th P -7 2021年
  • 井之口舜亮; 藤田和利; 中山尭仁; 西本光寿; 坂野恵里; 南高文; 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(Web) 35th O -3 2021年
  • 松下慎; 藤田和利; 藤田和利; 林拓自; 香山尚子; 元岡大祐; 長谷拓明; 神宮司健太郎; 山道岳; 弓場覚; 冨山栄輔; 洪陽子; 林裕次郎; 加藤大悟; 波多野浩士; 河嶋厚成; 植村元秀; 今村亮一; 辻川和丈; 中村昇太; 竹田潔; 野々村祝夫 日本アンドロロジー学会総会記事 40th 2021年
  • 金城 友紘; 河嶋 厚成; 福原 慎一郎; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 野々村 祝夫 日本泌尿器科学会雑誌 112 (1) 29 -33 2021年01月
  • 環境因子による腸内細菌叢変化と宿主免疫相互作用による前立腺癌の発症・進展メカニズムの解明と予防・治療への応用
    藤田 和利 日本泌尿器科学会総会 108回 460 -460 2020年12月
  • 尿中cell-free DNAが切り拓く尿路上皮癌診療の未来
    林 裕次郎; 藤田 和利; 野々村 祝夫 日本泌尿器科学会総会 108回 461 -461 2020年12月
  • 腎細胞癌の腫瘍悪性度は腫瘍浸潤リンパ球の機能低下と相関し、ニボルマブ単剤の予後不良因子となりうる
    河嶋 厚成; 洪 陽子; 松下 慎; 中野 剛佑; 林 裕次郎; 加藤 大悟; 波多野 浩士; 氏家 剛; 藤田 和利; 植村 元秀; 今村 亮一; 和田 尚; 野々村 祝夫 日本泌尿器科学会総会 108回 788 -788 2020年12月
  • T細胞受容体レパトア解析を用いた免疫チェックポイント阻害剤早期奏効予測バイオマーカーの探索
    加藤 大悟; 冨山 栄輔; 洪 陽子; 松下 慎; 中野 剛佑; 林 裕次郎; 波多野 浩士; 河嶋 厚成; 氏家 剛; 藤田 和利; 清谷 一馬; 植村 元秀; 野々村 祝夫 日本泌尿器科学会総会 108回 800 -800 2020年12月
  • シリコンナノ粒子製剤は精索静脈瘤により悪化したラットの精液所見を改善させる
    稲垣 裕介; 岡田 紘一; 関井 洋輔; 竹澤 健太郎; 福原 慎一郎; 木内 寛; 藤田 和利; 植村 元秀; 今村 亮一; 小林 悠輝; 小林 光; 野々村 祝夫 日本泌尿器科学会総会 108回 841 -841 2020年12月
  • マイクロキャピラリー電気泳動免疫蛍光測定装置による血清core型フコシル化PSA測定法の開発
    藤田 和利; 吉川 友康; 山下 謙一郎; 冨山 栄輔; 松下 慎; 林 裕次郎; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 植村 元秀; 三善 英知; 野々村 祝夫 日本泌尿器科学会総会 108回 844 -844 2020年12月
  • CRISPRスクリーニングによる前立腺癌におけるPARPの合成致死遺伝子の網羅的探索
    石津谷 祐; 植村 元秀; 松下 慎; 中野 剛佑; 林 裕次郎; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 藤田 和利; 二村 圭佑; 金田 安史; 野々村 祝夫 日本泌尿器科学会総会 108回 861 -861 2020年12月
  • 筋層非浸潤性膀胱癌に対する新規リスク分類の提言 前向き臨床研究SIPRESスタディ
    植村 元秀; 永原 啓; 氏家 剛; 田中 亮; 中田 渡; 上戸 賢; 高田 剛; 山中 庸平; 宮川 康; 藤田 和利; 三宅 顕光; 池田 純一郎; 野々村 祝夫; 大阪SIPRESスタディ研究グループ 日本泌尿器科学会総会 108回 895 -895 2020年12月
  • 臨床的意義のある前立腺癌の診断における再生検時の前立腺multiparametric MRIの有用性
    波多野 浩士; 河嶋 厚成; 加藤 大悟; 氏家 剛; 藤田 和利; 植村 元秀; 野々村 祝夫 日本泌尿器科学会総会 108回 1212 -1212 2020年12月
  • 前立腺特異的Ptenノックアウトマウスの前立腺癌組織の網羅的遺伝子発現解析による高脂肪食がもたらす癌増大に関与する遺伝子の探索
    松下 慎; 藤田 和利; 林 拓自; 冨山 栄輔; 洪 陽子; 王 聡; 石津谷 祐; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 植村 元秀; 野々村 祝夫 日本泌尿器科学会総会 108回 1541 -1541 2020年12月
  • 上部尿路上皮癌患者における血中遊離DNAの血液バイオマーカーとしての有用性
    中野 剛佑; 植村 元秀; 冨山 栄輔; 洪 陽子; 松下 慎; 林 裕次郎; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 藤田 和利; 今村 亮一; 野々村 祝夫 日本泌尿器科学会総会 108回 1713 -1713 2020年12月
  • 腎癌における異なるクローンを用いたPD-L1免疫染色と予後との関連性の検討
    洪 陽子; 植村 元秀; 冨山 栄輔; 林 裕次郎; 石津谷 祐; 王 聡; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 藤田 和利; 今村 亮一; 野々村 祝夫 日本泌尿器科学会総会 108回 1797 -1797 2020年12月
  • 腎細胞癌の腫瘍悪性度は腫瘍浸潤リンパ球の機能低下と相関し、ニボルマブ単剤の予後不良因子となりうる
    河嶋 厚成; 洪 陽子; 松下 慎; 中野 剛佑; 林 裕次郎; 加藤 大悟; 波多野 浩士; 氏家 剛; 藤田 和利; 植村 元秀; 今村 亮一; 和田 尚; 野々村 祝夫 日本泌尿器科学会総会 108回 788 -788 2020年12月
  • T細胞受容体レパトア解析を用いた免疫チェックポイント阻害剤早期奏効予測バイオマーカーの探索
    加藤 大悟; 冨山 栄輔; 洪 陽子; 松下 慎; 中野 剛佑; 林 裕次郎; 波多野 浩士; 河嶋 厚成; 氏家 剛; 藤田 和利; 清谷 一馬; 植村 元秀; 野々村 祝夫 日本泌尿器科学会総会 108回 800 -800 2020年12月
  • マイクロキャピラリー電気泳動免疫蛍光測定装置による血清core型フコシル化PSA測定法の開発
    藤田 和利; 吉川 友康; 山下 謙一郎; 冨山 栄輔; 松下 慎; 林 裕次郎; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 植村 元秀; 三善 英知; 野々村 祝夫 日本泌尿器科学会総会 108回 844 -844 2020年12月
  • CRISPRスクリーニングによる前立腺癌におけるPARPの合成致死遺伝子の網羅的探索
    石津谷 祐; 植村 元秀; 松下 慎; 中野 剛佑; 林 裕次郎; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 藤田 和利; 二村 圭佑; 金田 安史; 野々村 祝夫 日本泌尿器科学会総会 108回 861 -861 2020年12月
  • 臨床的意義のある前立腺癌の診断における再生検時の前立腺multiparametric MRIの有用性
    波多野 浩士; 河嶋 厚成; 加藤 大悟; 氏家 剛; 藤田 和利; 植村 元秀; 野々村 祝夫 日本泌尿器科学会総会 108回 1212 -1212 2020年12月
  • 前立腺特異的Ptenノックアウトマウスの前立腺癌組織の網羅的遺伝子発現解析による高脂肪食がもたらす癌増大に関与する遺伝子の探索
    松下 慎; 藤田 和利; 林 拓自; 冨山 栄輔; 洪 陽子; 王 聡; 石津谷 祐; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 植村 元秀; 野々村 祝夫 日本泌尿器科学会総会 108回 1541 -1541 2020年12月
  • 上部尿路上皮癌患者における血中遊離DNAの血液バイオマーカーとしての有用性
    中野 剛佑; 植村 元秀; 冨山 栄輔; 洪 陽子; 松下 慎; 林 裕次郎; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 藤田 和利; 今村 亮一; 野々村 祝夫 日本泌尿器科学会総会 108回 1713 -1713 2020年12月
  • 腎癌における異なるクローンを用いたPD-L1免疫染色と予後との関連性の検討
    洪 陽子; 植村 元秀; 冨山 栄輔; 林 裕次郎; 石津谷 祐; 王 聡; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 藤田 和利; 今村 亮一; 野々村 祝夫 日本泌尿器科学会総会 108回 1797 -1797 2020年12月
  • 大平 僚祐; 竹澤 健太郎; 福原 慎一郎; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 野々村 祝夫 泌尿器外科 33 (10) 1363 -1366 2020年10月
  • 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 58回 P -393 2020年10月
  • 泌尿器がんにおける免疫チェックポイント阻害剤早期奏効予測のための血液バイオマーカーの開発
    加藤 大悟; 冨山 栄輔; 洪 陽子; 松下 慎; 林 裕次郎; 中野 剛佑; 石津谷 祐; 王 聡; 波多野 浩士; 河嶋 厚成; 氏家 剛; 藤田 和利; 清谷 一馬; 植村 元秀; 野々村 祝夫 日本癌学会総会記事 79回 OE12 -6 2020年10月
  • 腎臓由来循環エキソソームの自動分離技術の開発と大規模検証研究への応用
    大西 なおみ; 塩澤 久美子; 神宮司 健太郎; 植村 元秀; 中田 渡; 藤田 和利; 内藤 拓也; 野々村 祝夫; 辻川 和丈; 植田 幸嗣 日本癌学会総会記事 79回 OJ15 -1 2020年10月
  • 前立腺癌の新しい診断指標としての尿中ホスファチジルコリン/リゾホスファチジルコリン比(The Urinary Phosphatidylcholine/Lysophosphatidylcholine Ratio as a Novel Diagnostic Index for Prostate Cancer)
    李 新; 中山 憲司; 後藤 崇之; 木村 博子; Akamatsu Shusuke; 林 裕次郎; 藤田 和利; 小林 恭; 野々村 祝夫; 小川 修; 井上 貴博 日本癌学会総会記事 79回 PE14 -1 2020年10月
  • 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 79回 PE14 -3 2020年10月
  • 前立腺癌モデルマウスにおいてヒスタミンはH1レセプタを介して高脂肪食による癌の増殖に関与する
    松下 慎; 藤田 和利; 弓場 覚; 冨山 栄輔; 洪 陽子; 林 裕次郎; 中野 剛佑; 神宮司 健太郎; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 植村 元秀; 辻川 和丈; 森井 英一; 野々村 祝夫 日本癌学会総会記事 79回 PJ14 -6 2020年10月
  • 膀胱癌における尿中cell-free DNAの臨床的有用性の検討
    林 裕次郎; 藤田 和利; 山道 岳; 弓場 覚; 冨山 栄輔; 松下 慎; 洪 陽子; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 植村 元秀; 野々村 祝夫 日本癌学会総会記事 79回 PJ15 -3 2020年10月
  • 上部尿路上皮癌患者において、TNFαはcell-free DNAの断片化や濃度上昇を促進する
    中野 剛佑; 植村 元秀; 山道 岳; 弓場 覚; 冨山 栄輔; 洪 陽子; 松下 慎; 林 裕次郎; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 藤田 和利; 野々村 祝夫 日本癌学会総会記事 79回 PJ15 -5 2020年10月
  • 腎臓由来循環エキソソームの自動分離技術の開発と大規模検証研究への応用
    大西 なおみ; 塩澤 久美子; 神宮司 健太郎; 植村 元秀; 中田 渡; 藤田 和利; 内藤 拓也; 野々村 祝夫; 辻川 和丈; 植田 幸嗣 日本癌学会総会記事 79回 OJ15 -1 2020年10月
  • 藤田和利; 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(Web) 58回 WS12 -2 2020年10月
  • 泌尿器がんにおける免疫チェックポイント阻害剤早期奏効予測のための血液バイオマーカーの開発
    加藤 大悟; 冨山 栄輔; 洪 陽子; 松下 慎; 林 裕次郎; 中野 剛佑; 石津谷 祐; 王 聡; 波多野 浩士; 河嶋 厚成; 氏家 剛; 藤田 和利; 清谷 一馬; 植村 元秀; 野々村 祝夫 日本癌学会総会記事 79回 OE12 -6 2020年10月
  • 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 79回 PE14 -3 2020年10月
  • 前立腺癌モデルマウスにおいてヒスタミンはH1レセプタを介して高脂肪食による癌の増殖に関与する
    松下 慎; 藤田 和利; 弓場 覚; 冨山 栄輔; 洪 陽子; 林 裕次郎; 中野 剛佑; 神宮司 健太郎; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 植村 元秀; 辻川 和丈; 森井 英一; 野々村 祝夫 日本癌学会総会記事 79回 PJ14 -6 2020年10月
  • 膀胱癌における尿中cell-free DNAの臨床的有用性の検討
    林 裕次郎; 藤田 和利; 山道 岳; 弓場 覚; 冨山 栄輔; 松下 慎; 洪 陽子; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 植村 元秀; 野々村 祝夫 日本癌学会総会記事 79回 PJ15 -3 2020年10月
  • 上部尿路上皮癌患者において、TNFαはcell-free DNAの断片化や濃度上昇を促進する
    中野 剛佑; 植村 元秀; 山道 岳; 弓場 覚; 冨山 栄輔; 洪 陽子; 松下 慎; 林 裕次郎; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 藤田 和利; 野々村 祝夫 日本癌学会総会記事 79回 PJ15 -5 2020年10月
  • 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 31 (1) 266 -266 2020年10月
  • 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 31 (1) 266 -266 2020年10月
  • 尿中PCs/LPC比は前立腺癌に関する新規診断指標になるのか(Does the PCs/LPC ratio in the urine become a novel diagnostic index for prostate cancer?)
    中山 憲司; 李 新; 後藤 崇之; 木村 博子; 赤松 秀輔; 林 裕次郎; 藤田 和利; 小林 恭; 清水 公治; 野々村 祝夫; 小川 修; 井上 貴博 JSBMS Letters 45 (Suppl.) 54 -54 2020年08月
  • 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 33 (1) 33 -33 2020年08月
  • 大阪大学における人工尿道括約筋埋め込み術の経験
    木内 寛; 岡田 紘一; 関井 洋輔; 稲垣 裕介; 竹澤 健太郎; 福原 慎一郎; 藤田 和利; 植村 元秀; 今村 亮一; 野々村 祝夫 泌尿器科紀要 66 (6) 195 -195 2020年06月
  • 尿中Cell-free DNAを用いたLiquid biopsyによる上部尿路上皮癌の新規バイオマーカーの検討
    林 裕次郎; 藤田 和利; 松崎 恭介; 川村 憲彦; 山本 致之; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 植村 元秀; 今村 亮一; 高尾 徹也; 高田 晋吾; 野々村 祝夫 泌尿器科紀要 66 (6) 178 -178 2020年06月
  • 尿中Cell-free DNAを用いたLiquid biopsyによる上部尿路上皮癌の新規バイオマーカーの検討
    林 裕次郎; 藤田 和利; 松崎 恭介; 川村 憲彦; 山本 致之; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 植村 元秀; 今村 亮一; 高尾 徹也; 高田 晋吾; 野々村 祝夫 泌尿器科紀要 66 (6) 178 -178 2020年06月
  • 大阪大学における人工尿道括約筋埋め込み術の経験
    木内 寛; 岡田 紘一; 関井 洋輔; 稲垣 裕介; 竹澤 健太郎; 福原 慎一郎; 藤田 和利; 植村 元秀; 今村 亮一; 野々村 祝夫 泌尿器科紀要 66 (6) 195 -195 2020年06月
  • Taigo Kato; Eisuke Tomiyama; Yoko Koh; Makoto Matsushita; Kosuke Nakano; Yujiro Hayashi; Cong Wang; Yu Ishizuya; Koji Hatano; Takeshi Ujike; Kazutoshi Fujita; Kazuma Kiyotani; Motohide Uemura; Norio Nonomura JOURNAL OF UROLOGY 203 E234 -E234 2020年04月
  • 【前立腺癌治療の合併症・副作用マネージメント】CRPC治療 タキサン系治療薬のQOL障害・注意すべき副作用と対応
    藤田 和利; 野々村 祝夫 Prostate Journal 7 (1) 67 -70 2020年04月
  • コルヒチンおよびステロイド投与が有効であった陰茎海綿体膿瘍の1例
    河田 信彦; 阿部 豊文; 福原 慎一郎; 藤田 和利; 木内 寛; 植村 元秀; 今村 亮一; 野々村 祝夫; 外村 香子 泌尿器科紀要 66 (3) 101 -101 2020年03月
  • 臀部結合体に対して分離術を施行した1例
    吉村 明洋; 氏家 剛; 永原 啓; 福原 慎一郎; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 野々村 祝夫; 田附 裕子; 奥山 宏臣; 香川 尚己; 貴島 晴彦; 久保 盾貴; 松井 太; 松本 富美 泌尿器科紀要 66 (3) 99 -99 2020年03月
  • 停留精巣を伴った低ゴナドトロピン性性腺機能低下症に対し補充療法を施行し精巣の自然降下を認めた成人男性の1例
    松村 聡一; 永原 啓; 福原 慎一郎; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 野々村 祝夫; 大月 道夫 泌尿器科紀要 66 (2) 61 -61 2020年02月
  • 堀谷 弘; 竹澤 健太郎; 福原 慎一郎; 藤田 和利; 木内 寛; 植村 元秀; 今村 亮一; 野々村 祝夫 泌尿器科紀要 66 (2) 65 -65 2020年02月
  • 定型化した生体ドナー腎採取術を学ぶ 大阪大学における後腹膜鏡下ドナー腎採取術
    阿部 豊文; 谷口 歩; 川村 正隆; 中澤 成晃; 加藤 大悟; 藤田 和利; 今村 亮一; 野々村 祝夫 日本臨床腎移植学会プログラム・抄録集 53回 124 -124 2020年02月
  • 加藤大悟; 加藤大悟; 波多野浩士; 河嶋厚成; 氏家剛; 藤田和利; 清谷一馬; 植村元秀; 野々村祝夫 日本免疫治療学会学術集会プログラム・抄録集 17th 2020年
  • 藤田 和利; 野々村 祝夫 癌と化学療法 47 (1) 27 -29 2020年01月
  • 藤田和利; 藤田和利; 野島聡; 寺山慧; 下浦早英子; 日食祥子; 吉村一宏; 植村天受; 奥野恭史; 野々村祝夫; 森井英一 日本癌治療学会学術集会(Web) 58th O76 -3 2020年
  • 波多野浩士; 竹澤健太郎; 加藤大悟; 河嶋厚成; 氏家剛; 藤田和利; 藤田和利; 植村元秀; 木内寛; 今村亮一; 野々村祝夫 日本泌尿器内視鏡学会(Web) 34th AV -1 2020年
  • 松下慎; 藤田和利; 林拓自; 冨山栄輔; 洪陽子; 中野剛佑; 林裕次郎; 加藤大悟; 加藤大悟; 波多野浩士; 河嶋厚成; 氏家剛; 福原慎一郎; 木内寛; 植村元秀; 辻川和丈; 野々村祝夫 日本アンドロロジー学会総会記事 39th 2020年
  • 林裕次郎; 藤田和利; 冨山栄輔; 松下慎; 洪陽子; 中野剛佑; 加藤大悟; 加藤大悟; 波多野浩士; 河嶋厚成; 氏家剛; 植村元秀; 植村元秀; 今村亮一; 野々村祝夫 日本泌尿器科学会総会(Web) 108th 883 -883 2020年
  • 氏家剛; 植村元秀; 植村元秀; 渡部直史; 仲定弘; 加藤大悟; 加藤大悟; 波多野浩士; 河嶋厚成; 福原慎一郎; 木内寛; 藤田和利; 加藤弘樹; 今村亮一; 野々村祝夫 日本泌尿器科学会総会(Web) 108th 1213 -1213 2020年
  • 冨山栄輔; 藤田和利; 松崎恭介; 中野剛佑; 林裕次郎; 加藤大悟; 加藤大悟; 波多野浩士; 河嶋厚成; 氏家剛; 植村元秀; 植村元秀; 今村亮一; 朝長毅; 野々村祝夫 日本泌尿器科学会総会(Web) 108th 1823 -1823 2020年
  • 停留精巣を伴った低ゴナドトロピン性性腺機能低下症に対し補充療法を施行し精巣の自然下降を認めた成人男性の1例
    松村 聡一; 永原 啓; 福原 慎一郎; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 大月 道夫; 野々村 祝夫 日本泌尿器科学会雑誌 111 (1) 30 -33 2020年01月
  • 【腎泌尿器疾患のゲノム医療の進歩】尿路上皮がんにおけるゲノム医療
    林 裕次郎; 藤田 和利 腎臓内科・泌尿器科 10 (6) 522 -527 2019年12月
  • 赤外線発光尿管ステントIRIS U-kitの有用性と挿入時のコツ
    河嶋 厚成; 波多野 浩士; 氏家 剛; 阿部 豊文; 福原 慎一郎; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 野々村 祝夫 日本泌尿器内視鏡学会総会 33回 AV -4 2019年11月
  • 谷口 歩; 角田 洋一; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 宮川 康; 野々村 祝夫; 上田 豊 泌尿器科紀要 65 (11) 479 -484 2019年11月
  • 山本 哲也; 加藤 大悟; 福原 慎一郎; 藤田 和利; 木内 寛; 植村 元秀; 今村 亮一; 野々村 祝夫 泌尿器科紀要 65 (11) 486 -486 2019年11月
  • 筋層非浸潤性膀胱癌の術後10年目に傍大動脈リンパ節転移を認めた1例
    堀部 祐輝; 氏家 剛; 福原 慎一郎; 藤田 和利; 木内 寛; 植村 元秀; 今村 亮一; 野々村 祝夫 泌尿器科紀要 65 (11) 488 -488 2019年11月
  • 尿路上皮癌におけるLiquid Biopsy 尿中遺伝子変異解析による非侵襲的診断
    藤田 和利; 林 裕次郎; 植村 元秀; Netto George; 野々村 祝夫 日本癌治療学会学術集会抄録集 57回 RT20 -3 2019年10月
  • 植村元秀; 永原啓; 田中亮; 田中亮; 中田渡; 中田渡; 上戸賢; 上戸賢; 高田剛; 高田剛; 山中庸平; 山中庸平; 宮川康; 宮川康; 谷川剛; 谷川剛; 新井浩樹; 新井浩樹; 関井洋輔; 関井洋輔; 氏家剛; 藤田和利; 池田純一郎; 野々村祝夫 日本癌治療学会学術集会(Web) 57回 O13 -2 2019年10月
  • 膀胱癌のターゲット遺伝子シークエンスと予後の検討 多施設共同研究
    藤田 和利; 林 裕次郎; Eich Marie-Lisa; Del Carmen Rodriguez Pena Maria; 波多野 浩士; 加藤 大悟; 河嶋 厚成; 氏家 剛; 植村 元秀; Bivalacqua Trinity; Papadopoulos Nickolas; Kinzler Kenneth; Vogelstein Bert; Netto George; 野々村 祝夫 日本癌治療学会学術集会抄録集 57回 O13 -6 2019年10月
  • 去勢抵抗性前立腺癌に対するGEN0101の安全性及び抗腫瘍効果 第I相医師主導臨床試験
    藤田 和利; 波多野 浩士; 加藤 大悟; 河嶋 厚成; 氏家 剛; 植村 元秀; 沖原 宏治; 浮村 理; 三木 恒治; 金田 安史; 野々村 祝夫 日本癌治療学会学術集会抄録集 57回 O33 -2 2019年10月
  • 次世代シーケンスを用いた免疫チェックポイント阻害剤によるirAEs免疫応答機構の解明
    加藤 大悟; 洪 陽子; 松下 慎; 中野 剛佑; 林 裕次郎; 石津谷 祐; 王 聡; 波多野 浩士; 河嶋 厚成; 氏家 剛; 藤田 和利; 清谷 一馬; 後藤 邦仁; 植村 元秀; 野々村 祝夫 日本癌治療学会学術集会抄録集 57回 P42 -2 2019年10月
  • 氏家剛; 冨山栄輔; 洪陽子; 松下慎; 中野剛佑; 林裕次郎; 王聡; 石津谷佑; 加藤大悟; 波多野浩士; 河嶋厚成; 藤田和利; 植村元秀; 野々村祝夫 日本癌治療学会学術集会(Web) 57回 P162 -5 2019年10月
  • 腎癌の腫瘍悪性度は腫瘍内T細胞の機能低下と相関し、Nivolumab治療の予後因子となる
    河嶋 厚成; 金沢 崇之; 木谷 友次郎; 西田 謙太郎; 石津谷 祐; 王 聡; 加藤 大悟; 波多野 浩士; 氏家 剛; 藤田 和利; 植村 元秀; 今村 亮一; 大倉 永也; 和田 尚; 野々村 祝夫 日本癌治療学会学術集会抄録集 57回 PS -7 2019年10月
  • 稲垣裕介; 岡田紘一; 関井洋輔; 竹澤健太郎; 福原慎一郎; 藤田和利; 木内寛 日本生殖医学会雑誌 64 (4) 380 -380 2019年10月
  • 前立腺特異的Ptenノックアウトマウスにおいてメトホルミンは高脂肪食による前立腺癌の増殖を抑制する(Metformin inhibits cancer growth induced by high-fat diet in a mouse Pten-deficient prostate cancer model)
    松下 慎; 藤田 和利; 林 拓自; 林 裕次郎; 中野 剛佑; 石津谷 祐; 王 聡; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 植村 元秀; 野々村 祝夫 日本癌学会総会記事 78回 P -2148 2019年09月
  • 前立腺癌におけるフコシル化とバイオマーカーへの応用
    藤田 和利 日本分子腫瘍マーカー研究会プログラム・講演抄録 39回 31 -31 2019年09月
  • miR-92b-3pの高発現はTSC1-mTOR経路を介して、腎細胞癌の増殖を促進する(miR-92b-3p promotes the proliferation of renal cell carcinoma through mTOR signaling pathway by targeting TSC1)
    王 聡; 神宮司 健太郎; 冨山 栄輔; 洪 陽子; 松下 慎; 石津谷 祐; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 藤田 和利; 植村 元秀; 野々村 祝夫 日本癌学会総会記事 78回 P -1157 2019年09月
  • 血清エクソソームのプロテオミクスによる去勢抵抗性前立腺癌の新規治療標的の探索(Identification of a novel therapeutic target for castration-resistant prostate cancer by proteomics of serum exosomes)
    石津谷 祐; 松下 慎; 洪 陽子; 中野 剛佑; 林 裕次郎; 王 聡; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 藤田 和利; 植村 元秀; 野々村 祝夫 日本癌学会総会記事 78回 P -2147 2019年09月
  • 前立腺特異的Ptenノックアウトマウスにおいてメトホルミンは高脂肪食による前立腺癌の増殖を抑制する(Metformin inhibits cancer growth induced by high-fat diet in a mouse Pten-deficient prostate cancer model)
    松下 慎; 藤田 和利; 林 拓自; 林 裕次郎; 中野 剛佑; 石津谷 祐; 王 聡; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 植村 元秀; 野々村 祝夫 日本癌学会総会記事 78回 P -2148 2019年09月
  • 上部尿路上皮癌における血中遊離DNA(cfDNA)の血液バイオマーカーへの臨床応用(Clinical application of circulating cell free DNA in upper tract urothelial carcinoma patients plasma)
    中野 剛佑; 植村 元秀; 洪 陽子; 林 裕次郎; 王 聡; 石津谷 祐; 山本 致之; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 藤田 和利; 野々村 祝夫 日本癌学会総会記事 78回 P -3323 2019年09月
  • 異所性尿管開口に対して腎動脈分枝塞栓による部分的腎塞栓術を施行した1例
    関井 洋輔; 稲垣 裕介; 岡田 紘一; 竹澤 健太郎; 福原 慎一郎; 藤田 和利; 木内 寛; 植村 元秀; 今村 亮一; 野々村 祝夫 日本排尿機能学会誌 30 (1) 256 -256 2019年09月
  • 堀谷 弘; 竹澤 健太郎; 福原 慎一郎; 藤田 和利; 木内 寛; 植村 元秀; 今村 亮一; 野々村 祝夫 泌尿器科紀要 65 (9) 389 -392 2019年09月
  • miR-92b-3pの高発現はTSC1-mTOR経路を介して、腎細胞癌の増殖を促進する(miR-92b-3p promotes the proliferation of renal cell carcinoma through mTOR signaling pathway by targeting TSC1)
    王 聡; 神宮司 健太郎; 冨山 栄輔; 洪 陽子; 松下 慎; 石津谷 祐; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 藤田 和利; 植村 元秀; 野々村 祝夫 日本癌学会総会記事 78回 P -1157 2019年09月
  • 血清エクソソームのプロテオミクスによる去勢抵抗性前立腺癌の新規治療標的の探索(Identification of a novel therapeutic target for castration-resistant prostate cancer by proteomics of serum exosomes)
    石津谷 祐; 松下 慎; 洪 陽子; 中野 剛佑; 林 裕次郎; 王 聡; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 藤田 和利; 植村 元秀; 野々村 祝夫 日本癌学会総会記事 78回 P -2147 2019年09月
  • TERTプロモーターとFGFR3変異に注目した尿のリキッドバイオプシーによる上部尿路上皮癌の新規バイオマーカー探索(Urinary liquid biopsy analysis of TERT promoter and FGFR3 mutations in upper tract urothelial carcinoma)
    林 裕次郎; 藤田 和利; 松崎 恭介; 冨山 栄輔; 洪 陽子; 松下 慎; 山本 致之; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 植村 元秀; 野々村 祝夫 日本癌学会総会記事 78回 P -2349 2019年09月
  • 上部尿路上皮癌における血中遊離DNA(cfDNA)の血液バイオマーカーへの臨床応用(Clinical application of circulating cell free DNA in upper tract urothelial carcinoma patients plasma)
    中野 剛佑; 植村 元秀; 洪 陽子; 林 裕次郎; 王 聡; 石津谷 祐; 山本 致之; 加藤 大悟; 波多野 浩士; 河嶋 厚成; 氏家 剛; 藤田 和利; 野々村 祝夫 日本癌学会総会記事 78回 P -3323 2019年09月
  • 関井 洋輔; 稲垣 裕介; 岡田 紘一; 竹澤 健太郎; 福原 慎一郎; 藤田 和利; 木内 寛; 植村 元秀; 今村 亮一; 野々村 祝夫 日本排尿機能学会誌 30 (1) 256 -256 2019年09月
  • 洪 陽子; 氏家 剛; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 宮川 康; 野々村 祝夫 泌尿器科紀要 65 (8) 337 -340 2019年08月
  • 次世代シーケンスを用いた免疫チェックポイント阻害剤によるirAE免疫応答機構の解明
    加藤 大悟; 植村 元秀; 洪 陽子; 松下 慎; 中野 剛佑; 林 裕次郎; 石津谷 祐; 王 聡; 山本 致之; 河嶋 厚成; 氏家 剛; 永原 啓; 藤田 和利; 清谷 一馬; 後藤 邦仁; 今村 亮一; 野々村 祝夫 腎癌研究会会報 (49) 37 -37 2019年07月
  • 次世代シーケンスを用いた免疫チェックポイント阻害剤によるirAE免疫応答機構の解明
    加藤 大悟; 植村 元秀; 洪 陽子; 松下 慎; 中野 剛佑; 林 裕次郎; 石津谷 祐; 王 聡; 山本 致之; 河嶋 厚成; 氏家 剛; 永原 啓; 藤田 和利; 清谷 一馬; 後藤 邦仁; 今村 亮一; 野々村 祝夫 日本がん免疫学会総会プログラム・抄録集 23回 128 -128 2019年07月
  • 稲垣 裕介; 関井 洋輔; 上田 倫央; 竹澤 健太郎; 福原 慎一郎; 藤田 和利; 木内 寛; 植村 元秀; 今村 亮一; 野々村 祝夫 日本生殖医学会雑誌 64 (3) 103 -104 2019年07月
  • 腎細胞癌の腫瘍悪性度は癌組織内T細胞の機能低下と有意な相関を示す
    河嶋 厚成; 中野 剛祐; 林 裕次郎; 石津谷 祐; 王 聡; 山本 致之; 加藤 大悟; 氏家 剛; 永原 啓; 藤田 和利; 植村 元秀; 和田 尚; 野々村 祝夫 泌尿器科紀要 65 (6) 223 -224 2019年06月
  • 尿中cell-free DNAのTERT promoterとFGFR3のhotspot mutationに着目した上部尿路上皮癌のバイオマーカーとしての有用性の検討
    林 裕次郎; 藤田 和利; 山本 致之; 川村 憲彦; 加藤 大悟; 河嶋 厚成; 氏家 剛; 永原 啓; 高尾 徹也; 高田 晋吾; 植村 元秀; 今村 亮一; 野々村 祝夫 日本泌尿器科学会総会 107回 AOP -009 2019年04月
  • 腎細胞癌局所内制御性T細胞に特異的な表面発現分子CCR8の同定と治療標的としての可能性
    河嶋 厚成; 松本 光史; 吉田 哲也; 木谷 友次郎; 加藤 大悟; 氏家 剛; 永原 啓; 藤田 和利; 植村 元秀; 柳楽 盛男; 大倉 永也; 和田 尚; 野々村 祝夫 日本泌尿器科学会総会 107回 AOP -086 2019年04月
  • 腎癌における循環腫瘍DNAの遺伝子変異プロファイルと断片長は、モニタリング・予後マーカーとして有用である
    山本 致之; 植村 元秀; 洪 陽子; 中野 剛佑; 林 裕次郎; 加藤 大悟; 河嶋 厚成; 氏家 剛; 永原 啓; 藤田 和利; 今村 亮一; 中川 英刀; 野々村 祝夫 日本泌尿器科学会総会 107回 AOP -096 2019年04月
  • 去勢抵抗性前立腺癌患者の血清エクソソームの網羅的タンパク解析による新規治療標的の探索と同定
    石津谷 祐; 鳴海 良平; 洪 陽子; 王 聡; 神宮司 健太郎; 加藤 大悟; 河嶋 厚成; 氏家 剛; 永原 啓; 藤田 和利; 植村 元秀; 足立 淳; 野々村 祝夫 日本泌尿器科学会総会 107回 AOP -112 2019年04月
  • 去勢抵抗性再燃前立腺癌患者を対象としたGEN0101前立腺腫瘍内投与、皮下投与による安全性/忍容性及び予備的な有効性検討のためのオープンラベル用量漸増試験(第1相)
    藤田 和利; 中井 康友; 加藤 大悟; 河嶋 厚成; 氏家 剛; 永原 啓; 植村 元秀; 今村 亮一; 沖原 宏治; 浮村 理; 三木 恒治; 金田 安史; 野々村 祝夫 日本泌尿器科学会総会 107回 AOP -132 2019年04月
  • 当院における進行性腎癌に対するアキシチニブの使用経験
    加藤 大悟; 氏家 剛; 洪 陽子; 松下 慎; 中野 剛佑; 石津谷 祐; 王 聡; 河嶋 厚成; 永原 啓; 藤田 和利; 今村 亮一; 植村 元秀; 野々村 祝夫 日本泌尿器科学会総会 107回 OP -148 2019年04月
  • 前立腺癌発症モデルマウスにおける、高脂肪食による腫瘍増殖に対するメトホルミンの抑制効果の検討
    松下 慎; 藤田 和利; 林 拓自; 洪 陽子; 中野 剛佑; 林 裕次郎; 石津谷 裕; 加藤 大悟; 河嶋 厚成; 氏家 剛; 永原 啓; 植村 元秀; 野々村 祝夫 日本泌尿器科学会総会 107回 PP1 -002 2019年04月
  • 原発性アルドステロン症に対する治療介入後早期にeGFR低下を認める
    氏家 剛; 植村 元秀; 加藤 大悟; 河嶋 厚成; 永原 啓; 藤田 和利; 今村 亮一; 高尾 徹也; 宮川 康; 佐伯 絢; 向井 康佑; 大月 康夫; 野々村 祝夫 日本泌尿器科学会総会 107回 PP1 -110 2019年04月
  • 洪 陽子; 永原 啓; 植村 元秀; 松下 慎; 中野 剛佑; 石津谷 祐; 王 聡; 加藤 大悟; 河嶋 厚成; 氏家 剛; 藤田 和利; 今村 亮一; 野々村 祝夫 日本泌尿器科学会総会 107回 PP1 -133 2019年04月
  • 腎癌細胞放出エクソソームによる腫瘍増殖に対する影響についての検討
    王 聡; 神宮司 健太郎; 松下 慎; 林 裕次郎; 石津谷 祐; 加藤 大悟; 河嶋 厚成; 氏家 剛; 永原 啓; 藤田 和利; 植村 元秀; 辻川 和丈; 野々村 祝夫 日本泌尿器科学会総会 107回 PP1 -153 2019年04月
  • 上部尿路上皮癌における血中遊離DNAの血液バイオマーカーへの臨床応用
    中野 剛佑; 植村 元秀; 洪 陽子; 松下 慎; 林 裕次郎; 王 聡; 山本 致之; 加藤 大悟; 河嶋 厚成; 氏家 剛; 永原 啓; 藤田 和利; 野々村 祝夫 日本泌尿器科学会総会 107回 PP1 -249 2019年04月
  • 谷 優; 阿部 豊文; 福原 慎一郎; 藤田 和利; 木内 寛; 植村 元秀; 今村 亮一; 野々村 祝夫 泌尿器科紀要 65 (4) 134 -134 2019年04月
  • 金城 友紘; 河嶋 厚成; 福原 慎一郎; 藤田 和利; 木内 寛; 植村 元秀; 今村 亮一; 野々村 祝夫 泌尿器科紀要 65 (4) 134 -134 2019年04月
  • 植村 元秀; 山本 致之; 石津谷 祐; 片山 琴絵; 山口 類; 宮野 悟; 金田 眞理; 松田 浩一; 稲垣 裕介; 福原 慎一郎; 藤田 和利; 今村 亮一; 野々村 祝夫 日本泌尿器科学会総会 107回 AOP -022 2019年04月
  • 有骨転移前立腺癌患者に対するデガレリクス単独投与の効果及びその再燃に対する抗アンドロゲン剤追加投与の治療効果の検討 大阪大学関連多施設共同研究
    永原 啓; 植村 元秀; 谷口 歩; 新井 浩樹; 冨山 栄輔; 蔦原 宏一; 河嶋 厚成; 氏家 剛; 藤田 和利; 福原 慎一郎; 木内 寛; 今村 亮一; 野々村 祝夫 日本泌尿器科学会総会 107回 OP -260 2019年04月
  • 前立腺全摘後尿失禁に対する人工尿道括約筋埋め込み術の経験
    木内 寛; 関井 洋輔; 稲垣 裕介; 上田 倫央; 竹澤 健太郎; 福原 慎一郎; 藤田 和利; 植村 元秀; 今村 亮一; 野々村 祝夫 日本泌尿器科学会総会 107回 OP -322 2019年04月
  • ラットを用いた精索静脈瘤モデルの作成
    稲垣 裕介; 関井 洋輔; 上田 倫央; 竹澤 健太郎; 福原 慎一郎; 藤田 和利; 木内 寛; 植村 元秀; 今村 亮一; 野々村 祝夫 日本泌尿器科学会総会 107回 OP -424 2019年04月
  • 原発性アルドステロン症患者と健常人の下部尿路症状に関する比較検討
    関井 洋輔; 稲垣 裕介; 上田 倫央; 竹澤 健太郎; 氏家 剛; 福原 慎一郎; 藤田 和利; 木内 寛; 植村 元秀; 今村 亮一; 野々村 祝夫 日本泌尿器科学会総会 107回 PP3 -113 2019年04月
  • 谷 優; 永原 啓; 福原 慎一郎; 藤田 和利; 木内 寛; 植村 元秀; 今村 亮一; 野々村 祝夫 泌尿器科紀要 65 (3) 96 -96 2019年03月
  • Toshiro Kinouchi; Motohide Uemura; Cong Wang; Yu Ishizuya; Yoshiyuki Yamamoto; Kentaro Jingushi; Taigo Kato; Atsunari Kawashima; Takeshi Ujike; Akira Nagahara; Kazutoshi Fujita; Takahiro Ochiya; Norio Nonomura CANCER SCIENCE 109 980 -980 2018年12月
  • Kyosuke Matsuzaki; Kazutoshi Fujita; Takashi Shiromizu; Ryohei Narumi; Yujiro Hayashi; Kentaro Jingushi; Taigo Kato; Atsunari Kawashima; Takeshi Ujike; Akira Nagahara; Motohide Uemura; Takeshi Tomonaga; Norio Nonomura INTERNATIONAL JOURNAL OF UROLOGY 25 328 -328 2018年10月
  • 腎癌における次世代シークエンスによる循環腫瘍DNAの解析(Analysis of circulating-tumor DNA with next-generation sequencing in renal cell carcinoma patients)
    山本 致之; 植村 元秀; 洪 陽子; 松下 慎; 中野 剛佑; 林 裕次郎; 加藤 大悟; 河嶋 厚成; 氏家 剛; 永原 啓; 藤田 和利; 中川 英刀; 野々村 祝夫 日本癌学会総会記事 77回 1426 -1426 2018年09月
  • 血清中のエクソソーム内包miRNA発現解析による腎癌新規診断モデルの構築(miRNA expression profiling in serum exosomes for new diagnostic models of renal cell carcinoma)
    木内 利郎; 植村 元秀; 王 聡; 石津谷 祐; 山本 致之; 神宮司 健太郎; 加藤 大悟; 河嶋 厚成; 氏家 剛; 永原 啓; 藤田 和利; 落谷 孝広; 野々村 祝夫 日本癌学会総会記事 77回 1673 -1673 2018年09月
  • 泌尿器がんにおける近年の進歩 遺伝子変異解析による尿路上皮癌に対する尿中バイオマーカーの開発(Recent progress of urologic oncology Development of urinary tests for urothelial carcinoma through the analysis of gene mutations)
    藤田 和利; 林 裕次郎; 植村 元秀; ネット・ジョージ; 野々村 祝夫 日本癌学会総会記事 77回 1839 -1839 2018年09月
  • 膀胱癌と上部尿路上皮癌における癌局所内免疫状態の比較(Comparison of Immunological Condition in Tumor Microenvironment between Bladder Cancer and Upper Urinary Tract Carcinoma)
    河嶋 厚成; 金沢 崇之; 石津谷 祐; 王 聡; 山本 致之; 神宮司 健太郎; 加藤 大悟; 氏家 剛; 永原 啓; 藤田 和利; 植村 元秀; 和田 尚; 野々村 祝夫 日本癌学会総会記事 77回 2044 -2044 2018年09月
  • 稲垣裕介; 関井洋輔; 上田倫央; 竹澤健太郎; 福原慎一郎; 藤田和利; 木内寛; 惣田哲次; 宮川康; 土家真紀; 岡本吉夫; 野々村祝夫 日本生殖医学会雑誌 63 (3) 418 -418 2018年08月
  • 精子を知る,見る,作る 精子研究の臨床応用
    宮川 康; 福原 慎一郎; 藤田 和利; 木内 寛; 田中 宏光; 辻村 晃 日本生殖医学会雑誌 63 (3) 240 -240 2018年08月
  • 補助生殖医療における男性不妊の予測因子としての精巣特異的アクチンキャッピングプロテインの有用性の検討
    稲垣 裕介; 関井 洋輔; 上田 倫央; 竹澤 健太郎; 福原 慎一郎; 藤田 和利; 木内 寛; 惣田 哲次; 宮川 康; 土家 真紀; 岡本 吉夫; 野々村 祝夫 日本生殖医学会雑誌 63 (3) 418 -418 2018年08月
  • 両側副腎摘除を必要とした難治性クッシング病の1例
    山中 庸平; 河嶋 厚成; 林 裕次郎; 氏家 剛; 阿部 豊文; 永原 啓; 福原 慎一郎; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 北村 哲宏; 大月 道夫; 野々村 祝夫 日本泌尿器科学会雑誌 109 (3) 164 -168 2018年07月
  • 山中 庸平; 河嶋 厚成; 林 裕次郎; 氏家 剛; 阿部 豊文; 永原 啓; 福原 慎一郎; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 北村 哲宏; 大月 道夫; 野々村 祝夫 日本泌尿器科学会雑誌 109 (3) 164 -168 2018年07月
  • 前立腺肉腫術後局所再発とリンパ節転移に対して化学療法後、重粒子線治療を併用し完全寛解を得た1例
    金城 友紘; 阿部 豊文; 福原 慎一郎; 藤田 和利; 木内 寛; 植村 元秀; 今村 亮一; 野々村 祝夫 泌尿器科紀要 64 (7) 315 -315 2018年07月
  • 生体腎移植術を施行した、新規MUC1遺伝子変異を有する家族性尿細管間質性腎炎の1例
    谷口 歩; 阿部 豊文; 永原 啓; 藤田 和利; 木内 寛; 植村 元秀; 今村 亮一; 宮川 康; 野々村 祝夫 泌尿器科紀要 64 (6) 288 -288 2018年06月
  • 尿道部分切除術を行い陰茎を温存しえた尿道癌の1例
    洪 陽子; 氏家 剛; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 宮川 康; 野々村 祝夫 泌尿器科紀要 64 (6) 291 -291 2018年06月
  • T1 high grade膀胱癌に対するBCG治療後に出現した孤発性骨盤内リンパ節転移に対し膀胱温存をしえた2例
    山道 岳; 河嶋 厚成; 藤田 和利; 木内 寛; 植村 元秀; 今村 亮一; 宮川 康; 野々村 祝夫 泌尿器科紀要 64 (6) 291 -291 2018年06月 [査読有り]
  • T1 high grade膀胱癌に対するBCG治療後に出現した孤発性骨盤内リンパ節転移に対し膀胱温存をしえた2例
    山道 岳; 河嶋 厚成; 藤田 和利; 木内 寛; 植村 元秀; 今村 亮一; 宮川 康; 野々村 祝夫 泌尿器科紀要 64 (6) 291 -291 2018年06月
  • 稲垣裕介; 福原慎一郎; 上田倫央; 藤田和利; 木内寛; 植村元秀; 今村亮一; 惣田哲次; 惣田哲次; 宮川康; 宮川康; 中西佳子; 一谷有希子; 土屋真紀; 岡本吉夫; 野々村祝夫 日本アンドロロジー学会総会記事 37th 147 2018年05月
  • 福原慎一郎; 稲垣裕介; 上田倫央; 藤田和利; 植村元秀; 木内寛; 今村亮一; 野々村祝夫 日本泌尿器科学会総会(Web) 106th ROMBUNNO.OP‐273 (WEB ONLY) -273 2018年04月
  • 稲垣裕介; 上田倫央; 木内寛; 福原慎一郎; 藤田和利; 植村元秀; 今村亮一; 野々村祝夫 日本泌尿器科学会総会(Web) 106th ROMBUNNO.OP‐010 (WEB ONLY) -010 2018年04月
  • Yoshiyuki Yamamoto; Motohide Uemura; Kosuke Nakano; Yujiro Hayashi; Cong Wang; Yu Ishizuya; Kyosuke Matsuzaki; Takuji Hayashi; Toshiro Kinouchi; Kentaro Jingushi; Taigo Kato; Atsunari Kawashima; Takeshi Ujike; Akira Nagahara; Kazutoshi Fujita; Ryoichi Imamura; Norio Nonomura JOURNAL OF UROLOGY 199 (4) E1198 -E1199 2018年04月
  • 前立腺癌骨転移診断におけるBONENAVI単独での診断能および予後予測能の検討
    氏家 剛; 植村 元秀; 中野 剛祐; 林 裕次郎; 石津谷 祐; 王 聡; 山本 致之; 加藤 大悟; 河嶋 厚成; 永原 啓; 藤田 和利; 今村 亮一; 野々村 祝夫 日本泌尿器科学会総会 106回 PP2 -078 2018年04月
  • 腎尿管全摘除術を施行した腎盂・尿管癌における膀胱内再発の臨床的検討
    中野 剛佑; 永原 啓; 林 裕次郎; 石津谷 祐; 王 聡; 山本 致之; 加藤 大悟; 氏家 剛; 河嶋 厚成; 藤田 和利; 植村 元秀; 今村 亮一; 野々村 祝夫 日本泌尿器科学会総会 106回 PP2 -160 2018年04月
  • 腎癌特異的細胞外小胞(エクソソーム)の新規解析手法の開発および癌特異的エクソソーム中AZU1の血液バイオマーカーへの臨床応用
    植村 元秀; 神宮司 健太郎; 加藤 大悟; 河嶋 厚成; 氏家 剛; 永原 啓; 藤田 和利; 木内 寛; 今村 亮一; 植田 幸嗣; 辻川 和丈; 野々村 祝夫 日本泌尿器科学会総会 106回 PP2 -002 2018年04月 [査読有り]
  • 人工知能を用いた血清エクソソーム中マイクロRNA発現解析による新規腎癌診断モデルの構築
    木内 利郎; 植村 元秀; 山本 致之; 神宮司 健太郎; 加藤 大悟; 河嶋 厚成; 氏家 剛; 永原 啓; 藤田 和利; 大田 信行; 辻川 和丈; 落谷 孝広; 野々村 祝夫 日本泌尿器科学会総会 106回 PP2 -003 2018年04月 [査読有り]
  • miR-122の高発現はoccludinを介して淡明細胞型腎細胞癌の増殖、進展を促進する
    王 聡; 神宮司 健太郎; 柏木 悠里; 石津谷 祐; 山本 致之; 加藤 大悟; 河嶋 厚成; 氏家 剛; 永原 啓; 藤田 和利; 植村 元秀; 辻川 和丈; 野々村 紀夫 日本泌尿器科学会総会 106回 PP2 -015 2018年04月 [査読有り]
  • 術前末梢血中単球数は前立腺全摘除術標本におけるadverse pathologyの予測マーカーとなる
    林 裕次郎; 林 拓自; 藤田 和利; 野島 聡; 松崎 恭介; 神宮司 健太郎; 加藤 大悟; 河嶋 厚成; 氏家 剛; 永原 啓; 植村 元秀; 森井 英一; 野々村 祝夫 日本泌尿器科学会総会 106回 PP3 -193 2018年04月 [査読有り]
  • 尿中extracellular vesiclesのプロテオミクスによるHigh risk前立腺癌新規バイオマーカーの開発
    石津谷 祐; 藤田 和利; 久米 秀明; 松崎 恭介; 神宮司 健太郎; 加藤 大悟; 河嶋 厚成; 氏家 剛; 永原 啓; 植村 元秀; 今村 亮一; 朝長 毅; 野々村 祝夫 日本泌尿器科学会総会 106回 PP3 -347 2018年04月 [査読有り]
  • 腎癌特異的細胞外小胞(エクソソーム)の新規解析手法の開発および癌特異的エクソソーム中AZU1の血液バイオマーカーへの臨床応用
    植村 元秀; 神宮司 健太郎; 加藤 大悟; 河嶋 厚成; 氏家 剛; 永原 啓; 藤田 和利; 木内 寛; 今村 亮一; 植田 幸嗣; 辻川 和丈; 野々村 祝夫 日本泌尿器科学会総会 106回 PP2 -002 2018年04月
  • 木内 利郎; 植村 元秀; 山本 致之; 神宮司 健太郎; 加藤 大悟; 河嶋 厚成; 氏家 剛; 永原 啓; 藤田 和利; 大田 信行; 辻川 和丈; 落谷 孝広; 野々村 祝夫 日本泌尿器科学会総会 106回 PP2 -003 2018年04月
  • 王 聡; 神宮司 健太郎; 柏木 悠里; 石津谷 祐; 山本 致之; 加藤 大悟; 河嶋 厚成; 氏家 剛; 永原 啓; 藤田 和利; 植村 元秀; 辻川 和丈; 野々村 紀夫 日本泌尿器科学会総会 106回 PP2 -015 2018年04月
  • 氏家 剛; 植村 元秀; 中野 剛祐; 林 裕次郎; 石津谷 祐; 王 聡; 山本 致之; 加藤 大悟; 河嶋 厚成; 永原 啓; 藤田 和利; 今村 亮一; 野々村 祝夫 日本泌尿器科学会総会 106回 PP2 -078 2018年04月
  • 中野 剛佑; 永原 啓; 林 裕次郎; 石津谷 祐; 王 聡; 山本 致之; 加藤 大悟; 氏家 剛; 河嶋 厚成; 藤田 和利; 植村 元秀; 今村 亮一; 野々村 祝夫 日本泌尿器科学会総会 106回 PP2 -160 2018年04月
  • 術前末梢血中単球数は前立腺全摘除術標本におけるadverse pathologyの予測マーカーとなる
    林 裕次郎; 林 拓自; 藤田 和利; 野島 聡; 松崎 恭介; 神宮司 健太郎; 加藤 大悟; 河嶋 厚成; 氏家 剛; 永原 啓; 植村 元秀; 森井 英一; 野々村 祝夫 日本泌尿器科学会総会 106回 PP3 -193 2018年04月
  • 尿中extracellular vesiclesのプロテオミクスによるHigh risk前立腺癌新規バイオマーカーの開発
    石津谷 祐; 藤田 和利; 久米 秀明; 松崎 恭介; 神宮司 健太郎; 加藤 大悟; 河嶋 厚成; 氏家 剛; 永原 啓; 植村 元秀; 今村 亮一; 朝長 毅; 野々村 祝夫 日本泌尿器科学会総会 106回 PP3 -347 2018年04月
  • 尿道上皮内癌に対し尿道部分切除術を行い、性機能を温存しえた1例
    稲垣 裕介; 上田 倫央; 氏家 剛; 福原 慎一郎; 藤田 和利; 木内 寛; 植村 元秀; 今村 亮一; 宮川 康; 野々村 祝夫 日本生殖医学会雑誌 63 (1-2) 118 -118 2018年04月
  • RALP後の尿失禁改善に関する画像的評価についての検討
    稲垣 裕介; 上田 倫央; 木内 寛; 福原 慎一郎; 藤田 和利; 植村 元秀; 今村 亮一; 野々村 祝夫 日本泌尿器科学会総会 106回 OP -010 2018年04月
  • 前立腺癌治療後のHypogonadismとHypogonadism関連症状についての検討
    福原 慎一郎; 稲垣 裕介; 上田 倫央; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 野々村 祝夫 日本泌尿器科学会総会 106回 OP -273 2018年04月
  • 山道 岳; 阿部 豊文; 石津谷 祐; 藤田 和利; 木内 寛; 今村 亮一; 宮川 康; 野々村 祝夫; 小野 祐介; 東原 大樹; 大須賀 慶悟 泌尿器科紀要 64 (3) 136 -136 2018年03月
  • 子宮からの腹腔内出血を契機として診断に至った結節性硬化症の1例
    谷口 歩; 角田 洋一; 藤田 和利; 木内 寛; 植村 元秀; 今村 亮一; 宮川 康; 野々村 祝夫 泌尿器科紀要 64 (3) 135 -135 2018年03月
  • 山道 岳; 阿部 豊文; 石津谷 祐; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 宮川 康; 小野 祐介; 東原 大樹; 大須賀 慶悟; 野々村 祝夫 泌尿器科紀要 64 (2) 49 -53 2018年02月
  • Toshiro Kinouchi; Motohide Uemura; Kosuke Nakano; Yu Ishizuya; Cong Wang; Norihiko Kawamura; Kentaro Jingushi; Atsunari Kawashima; Takeshi Ujike; Akira Nagahara; Kazutoshi Fujita; Kazutake Tsujikawa; Norio Nonomura CANCER SCIENCE 109 334 -334 2018年01月
  • Kyosuke Matsuzaki; Kazutoshi Fujita; Yujiro Hayashi; Toshiro Kinouchi; Takuji Hayashi; Norihiko Kawamura; Kentaro Jingushi; Atsunari Kawashima; Takeshi Ujike; Akira Nagahara; Motohide Uemura; Kazutake Tsujikawa; Norio Nonomura CANCER SCIENCE 109 725 -725 2018年01月
  • Motohide Uemura; Kentaro Jingushi; Kazutoshi Fujita; Norio Nonomura; Kazutake Tsujikawa; Koji Ueda CANCER SCIENCE 109 18 -18 2018年01月
  • Yoshiyuki Yamamoto; Motohide Uemura; Cong Wang; Kyosuke Matsuzaki; Takuji Hayashi; Toshiro Kinouchi; Norihiko Kawamura; Kentaro Jingushi; Atsunari Kawashima; Takeshi Ujike; Akira Nagahara; Kazutoshi Fujita; Norio Nonomura CANCER SCIENCE 109 335 -335 2018年01月
  • 永原啓; 植村元秀; 加藤大悟; 河嶋厚成; 氏家剛; 藤田和利; 木内寛; 今村亮一; 東原大樹; 小野祐介; 中澤哲郎; 大須賀慶悟; 野々村祝夫 日本泌尿器科学会総会(Web) 106th ROMBUNNO.SY13‐4 (WEB ONLY) -4 2018年
  • 植村元秀; 永原啓; 加藤大悟; 河嶋厚成; 氏家剛; 福原慎一郎; 藤田和利; 木内寛; 今村亮一; 野々村祝夫 日本泌尿器科学会総会(Web) 106th ROMBUNNO.DB4‐2 (WEB ONLY) 2018年
  • 河嶋厚成; 加藤大悟; 加藤大悟; 氏家剛; 永原啓; 福原慎一郎; 藤田和利; 植村元秀; 植村元秀; 木内寛; 今村亮一; 野々村祝夫; 野々村祝夫 Japanese Journal of Endourology 31 (3 (Web)) 628 (WEB ONLY) -4 2018年
  • 癌におけるRNA修飾ヌクレオシドの解析とバイオマーカーとしての利用可能性
    大塩 郁幹; 上田 裕子; 長谷 拓明; 北惠 郁緒里; 西本 愛; 犬伏 智子; 里 章平; 藤井 晋太郎; 神宮司 健太郎; 藤田 和利; 植村 元秀; 野々村 祝夫; 辻川 和丈 生命科学系学会合同年次大会 2017年度 [1P -0641] 2017年12月 [査読有り]
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    中辻 由乃; 江川 博; 廣野 貴之; 廣瀬 遼; 川瀬 瑛崇; 北惠 郁緒里; 神宮司 健太郎; 上田 裕子; 長谷 拓明; 藤田 和利; 植村 元秀; 野々村 祝夫; 辻川 和丈 生命科学系学会合同年次大会 2017年度 [4P1T26 -0937)] 2017年12月 [査読有り]
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    永原 啓; 加藤 大悟; 河嶋 厚成; 氏家 剛; 阿部 豊文; 福原 慎一郎; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 野々村 祝夫 日本内視鏡外科学会雑誌 22 (7) EV3 -6 2017年12月
  • 木枕 舞; 永原 啓; 福原 慎一郎; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 宮川 康; 東原 大樹; 大須賀 慶悟; 野々村 祝夫 泌尿器科紀要 63 (11) 493 -497 2017年11月
  • 河嶋 厚成; 植村 元秀; 石津谷 祐; 王 聡; 山本 致之; 木内 利郎; 林 拓自; 松崎 恭介; 氏家 剛; 永原 啓; 藤田 和利; 吉岡 俊昭; 宮川 康; 三宅 修; 野々村 祝夫 日本癌治療学会学術集会抄録集 55回 WS14 -6 2017年10月
  • 氏家 剛; 植村 元秀; 林 裕次郎; 中野 剛佑; 石津谷 祐; 王 聡; 山本 致之; 木内 利郎; 林 拓自; 松崎 恭介; 加藤 大悟; 河嶋 厚成; 永原 啓; 藤田 和利; 野々村 祝夫 日本癌治療学会学術集会抄録集 55回 O5 -5 2017年10月
  • 血中フコシル化free PSAと前立腺生検グリソンスコアとの検討
    藤田 和利; 林 裕次郎; 林 拓自; 松崎 恭介; 桝田 実花; 河嶋 厚成; 永原 啓; 氏家 剛; 小林 夕佳; 植村 元秀; 三善 英知; 野々村 祝夫 日本癌治療学会学術集会抄録集 55回 P68 -1 2017年10月
  • 林 拓自; 藤田 和利; 谷川 剛; 山本 致之; 木内 利郎; 松崎 恭介; 川村 憲彦; 河嶋 厚成; 氏家 剛; 永原 啓; 植村 元秀; 高尾 徹也; 山口 誓司; 野々村 祝夫 日本癌治療学会学術集会抄録集 55回 P68 -4 2017年10月
  • 前立腺癌に対する定位照射 35Gy/5分割2年の治療成績
    鈴木 修; 吉岡 靖生; 黒須 圭太; 大谷 啓祐; 玉利 慶介; 水野 裕一; 太田 誠一; 井ノ上 信一; 隅田 伊織; 藤田 和利; 植村 元秀; 野々村 祝夫; 小川 和彦 日本癌治療学会学術集会抄録集 55回 O7 -3 2017年10月 [査読有り]
  • 低ゴナドトロピン性性腺機能低下症の治療方法別の成績についての検討
    福原 慎一郎; 稲垣 裕介; 上田 倫央; 藤田 和利; 木内 寛; 野々村 祝夫 日本生殖医学会雑誌 62 (4) 485 -485 2017年10月
  • 小径腎癌に対するCTガイド下凍結療法初期36例の臨床病理学的アウトカム
    永原 啓; 植村 元秀; 加藤 大悟; 河嶋 厚成; 氏家 剛; 藤田 和利; 福原 慎一郎; 木内 寛; 今村 亮一; 宮川 康; 東原 大樹; 小野 祐介; 中澤 哲郎; 大須賀 慶悟; 野々村 祝夫 日本癌治療学会学術集会抄録集 55回 P26 -8 2017年10月
  • 糖鎖修飾はazurocidinの細胞外小胞への搭載に重要である
    神宮司 健太郎; 植村 元秀; 植田 幸嗣; 藤田 和利; 河嶋 厚成; 氏家 剛; 辻川 和丈; 野々村 祝夫 日本癌学会総会記事 76回 J -1099 2017年09月
  • 末梢血液細胞の遺伝子発現解析による腎癌新規バイオマーカーの探索
    木内 利郎; 植村 元秀; 中野 剛佑; 石津谷 祐; 王 聡; 川村 憲彦; 神宮司 健太郎; 河嶋 厚成; 氏家 剛; 永原 啓; 藤田 和利; 辻川 和丈; 野々村 祝夫 日本癌学会総会記事 76回 P -1331 2017年09月
  • 淡明細胞型腎細胞癌における血中遊離DNAの解析
    山本 致之; 植村 元秀; 王 聡; 松崎 恭介; 林 拓自; 木内 利郎; 川村 憲彦; 神宮司 健太郎; 河嶋 厚成; 氏家 剛; 永原 啓; 藤田 和利; 野々村 祝夫 日本癌学会総会記事 76回 P -1332 2017年09月
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    松崎 恭介; 藤田 和利; 林 裕次郎; 木内 利郎; 林 拓自; 川村 憲彦; 神宮司 健太郎; 河嶋 厚成; 氏家 剛; 永原 啓; 植村 元秀; 辻川 和丈; 野々村 祝夫 日本癌学会総会記事 76回 P -2312 2017年09月
  • 癌組織内浸潤Tリンパ球の発現様式は腫瘍の悪性度と有意に相関する
    河嶋 厚成; 金沢 崇之; 後藤 久充子; 岩堀 幸太; 岡澤 晶子; 本; 神宮寺 健太郎; 氏家 剛; 永原 啓; 藤田 和利; 植村 元秀; 和田 尚; 野々村 祝夫 日本癌学会総会記事 76回 P -3173 2017年09月
  • 前立腺癌モデルマウスにおいて高脂肪食による腫瘍進展は免疫反応と関連する
    林 拓自; 藤田 和利; 野島 聡; 木内 利郎; 松崎 恭介; 神宮司 健太郎; 河嶋 厚成; 氏家 剛; 永原 啓; 植村 元秀; 辻川 和丈; 森井 英一; 野々村 祝夫 日本癌学会総会記事 76回 P -3218 2017年09月
  • 副腎平滑筋肉腫の1例
    谷口 歩; 氏家 剛; 藤田 和利; 木内 寛; 植村 元秀; 今村 亮一; 宮川 康; 野々村 祝夫 泌尿器科紀要 63 (8) 341 -341 2017年08月
  • LH-RHアナログ3ヵ月製剤による去勢域維持が困難であった前立腺癌の1例
    洪 陽子; 河嶋 厚成; 氏家 剛; 永原 啓; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 宮川 康; 野々村 祝夫 泌尿器科紀要 63 (8) 341 -341 2017年08月
  • 藤田 和利; 福原 慎一郎; 植村 元秀; 野々村 祝夫 日本性機能学会雑誌 32 (2) 157 -157 2017年08月
  • 福原 慎一郎; 藤田 和利; 木内 寛; 植村 元秀; 今村 亮一; 野々村 祝夫 日本性機能学会雑誌 32 (2) 161 -161 2017年08月
  • 腎尿管全摘除術を施行した腎盂・尿管癌における膀胱内再発の臨床的検討
    洪 陽子; 永原 啓; 河嶋 厚成; 氏家 剛; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 宮川 康; 野々村 祝夫 泌尿器科紀要 63 (7) 283 -283 2017年07月
  • 腎細胞癌組織内に浸潤する免疫担当細胞発現に腫瘍間・腫瘍内多様性は存在するのか?
    河嶋 厚成; 金沢 崇之; 氏家 剛; 永原 啓; 藤田 和利; 植村 元秀; 和田 尚; 野々村 祝夫 腎癌研究会会報 (47) 76 -76 2017年07月
  • ロボット支援腹腔鏡下前立腺全摘除術(RALP)後の尿失禁における画像的検討
    山道 岳; 木内 寛; 上田 倫央; 惣田 哲次; 氏家 剛; 阿部 豊文; 永原 啓; 福原 慎一郎; 藤田 和利; 植村 元秀; 今村 亮一; 宮川 康; 野々村 祝夫 泌尿器科紀要 63 (7) 280 -280 2017年07月
  • 林 裕次郎; 永原 啓; 河嶋 厚成; 角田 洋一; 氏家 剛; 阿部 豊文; 福原 慎一郎; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 宮川 康; 市丸 直嗣; 前田 哲生; 野々村 祝夫 日本泌尿器科学会雑誌 108 (3) 166 -169 2017年07月
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    山中 庸平; 永原 啓; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 宮川 康; 野々村 祝夫; 宮村 能子; 橋井 圭子; 出口 幸一; 上原 秀一郎; 奥山 宏臣 泌尿器科紀要 63 (5) 217 -217 2017年05月
  • 術後2年目に原発巣が判明した転移性副腎腫瘍の1例
    上戸 賢; 角田 洋一; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 宮川 康; 野々村 祝夫 泌尿器科紀要 63 (5) 218 -218 2017年05月
  • Atsunari Kawashima; Takayuki Kanazawa; Kumiko Goto; Mitsunobu Matsumoto; Yu Ishizuya; Cong Wang; Yoshiyuki Yamamoto; Takuji Hayashi; Toshiro Kinouchi; Kyosuke Matsuzaki; Norihiko Kawamura; Takeshi Ujike; Akira Nagahara; Kazutoshi Fujita; Motohide Uemura; Hisashi Wada; Norio Nonomura JOURNAL OF UROLOGY 197 (4) E963 -E963 2017年04月
  • Kazutoshi Fujita; Hideaki Kume; Kyosuke Matsuzaki; Atsunari Kawashima; Takeshi Ujike; Akira Nagahara; Motohide Uemura; Yasushi Miyagawa; Takeshi Tomonaga; Norio Nonomura JOURNAL OF UROLOGY 197 (4) E1320 -E1320 2017年04月
  • Satoshi Inoue; Kazutoshi Fujita; Hiroki Ide; Seiji Yamaguchi; Hiroaki Fushimi; George Netto; Norio Nonomura; Hiroshi Miyamoto JOURNAL OF UROLOGY 197 (4) E945 -E946 2017年04月
  • Takuji Hayashi; Kazutoshi Fujita; Yu Ishizuya; Cong Wang; Yoshiyuki Yamamoto; Toshiro Kinouchi; Kyosuke Matsuzaki; Norihiko Kawamura; Atsunari Kawashima; Akira Nagahara; Takeshi Ujike; Motohide Uemura; Satoshi Nojima; Eiichi Morii; Norio Nonomura JOURNAL OF UROLOGY 197 (4) E1322 -E1322 2017年04月
  • Hiroki Ide; Satoshi Inoue; Kazutoshi Fujita; Yi Li; Takashi Kawahara; Eiji Kashiwagi; Taichi Mizushima; Seiji Yamaguchi; Hiroaki Fushimi; Mototsugu Oya; Norio Nonomura; Hiroshi Miyamoto JOURNAL OF UROLOGY 197 (4) E1177 -E1177 2017年04月
  • ゲノム編集技術による、前立腺癌の進展に関わる遺伝子の機能解析について
    川村 憲彦; 河嶋 厚成; 氏家 剛; 永原 啓; 藤田 和利; 植村 元秀; 野々村 祝夫 日本泌尿器科学会総会 105回 UP11 -3 2017年04月
  • 松崎 恭介; 藤田 和利; 山本 致之; 木内 利郎; 林 拓自; 川村 憲彦; 河嶋 厚成; 氏家 剛; 永原 啓; 植村 元秀; 神宮司 健太郎; 辻川 和丈; 野々村 祝夫 日本泌尿器科学会総会 105回 OP64 -2 2017年04月
  • 前立腺癌患者に対するLHRHアンタゴニストを用いたCAB療法におけるPSA早期変化率の検討
    永原 啓; 植村 元秀; 高田 晋吾; 稲垣 裕介; 新井 浩樹; 中澤 成晃; 河嶋 厚成; 氏家 剛; 藤田 和利; 木内 寛; 今村 亮一; 宮川 康; 野々村 祝夫 日本泌尿器科学会総会 105回 OP67 -1 2017年04月
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    王 聡; 河嶋 厚成; 木内 利郎; 林 拓自; 松崎 恭介; 川村 憲彦; 氏家 剛; 永原 啓; 藤田 和利; 植村 元秀; 吉岡 俊昭; 三宅 修; 野々村 祝夫 日本泌尿器科学会総会 105回 PP07 -05 2017年04月
  • 山本 致之; 植村 元秀; 王 聡; 石津谷 祐; 木内 利郎; 林 拓自; 松崎 恭介; 川村 憲彦; 河嶋 厚成; 氏家 剛; 永原 啓; 藤田 和利; 野々村 祝夫 日本泌尿器科学会総会 105回 PP31 -06 2017年04月
  • 石津谷 祐; 松崎 恭介; 藤田 和利; 王 聡; 山本 致之; 木内 利郎; 林 拓自; 川村 憲彦; 河嶋 厚成; 氏家 剛; 永原 啓; 植村 元秀; 野々村 祝夫 日本泌尿器科学会総会 105回 PP40 -06 2017年04月
  • LOH症候群を合併した前立腺癌患者に対するアンドロゲン補充療法についての検討
    福原 慎一郎; 上田 倫央; 惣田 哲次; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 宮川 康; 野々村 祝夫 日本生殖医学会雑誌 62 (1-2) 113 -113 2017年04月
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    植村 元秀; 福原 慎一郎; 永原 啓; 河嶋 厚成; 氏家 剛; 惣田 哲次; 角田 洋一; 阿部 豊文; 藤田 和利; 今村 亮一; 木内 寛; 宮川 康; 野々村 祝夫 日本泌尿器科学会総会 105回 OP01 -4 2017年04月
  • 鈴木修; 吉岡靖生; 黒須圭太; 大谷啓祐; 玉利慶介; 水野裕一; 太田誠一; 井ノ上信一; 大久保裕史; 山口廣子; 隅田伊織; 藤田和利; 植村元秀; 植村元秀; 野々村祝夫; 小川和彦 日本放射線腫瘍学会高精度放射線外部照射部会学術大会プログラム・抄録集 30th 36 2017年03月 [査読有り]
  • Maria Del Carmen Rodriguez Pena; Aline C. Tregnago; Marie-Lisa Eich; Simeon Springer; Yuxuan Wang; Diana Taheri; Dilek Ertoy; Kazutoshi Fujita; Stephania M. Bezerra; Isabela W. Cunha; Trinity J. Bivalacqua; Nickolas Papadopoulos; Ken Kinzler; Bert Vogelstein; George J. Netto MODERN PATHOLOGY 30 252A -252A 2017年02月
  • Maria Del Carmen; Rodriguez Pena; Aline C. Tregnago; Marie-Lisa Eich; Simeon Springer; Yuxuan Wang; Diana Taheri; Dilek Ertoy; Kazutoshi Fujita; Stephania M. Bezerra; Isabela W. Cunha; Trinity J. Bivalacqua; Nickolas Papadopoulos; Ken Kinzler; Bert Vogelstein; George J. Netto LABORATORY INVESTIGATION 97 252A -252A 2017年02月
  • Aline C. Tregnago; Maria Del Carmen Rodriguez Pena; James A. Miller; Isabela W. Cunha; Stephanie M. Bezerra; Hirofumi Nonogaki; Rajni Sharma; Kazutoshi Fujita; George J. Netto MODERN PATHOLOGY 30 263A -263A 2017年02月
  • Aline C. Tregnago; Maria Del Carmen; Rodriguez Pena; James A. Miller; Isabela W. Cunha; Stephania M. Bezerra; Hirofumi Nonogaki; Rajni Sharma; Kazutoshi Fujita; George J. Netto LABORATORY INVESTIGATION 97 265A -265A 2017年02月
  • Y. Ishizuya; T. Ujike; A. Kawashima; A. Nagahara; K. Fujita; R. Imamura; H. Kiuchi; Y. Miyagawa; M. Uemura; N. Nonomura ANNALS OF ONCOLOGY 27 2016年12月
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    那須 信吾; 田中 彩子; 佐藤 真吾; 森田 沙斗武; 葉山 学; 白山 敬之; 森下 直子; 鈴木 秀和; 岡本 紀雄; 平島 智徳; 清水 一範; 森下 裕; 松岡 洋人; 河原 邦光; 山道 岳; 藤田 和利 肺癌 56 (7) 1076 -1076 2016年12月
  • 両肺浸潤影で発見された腎細胞癌、肺転移の1例
    那須 信吾; 田中 彩子; 佐藤 真吾; 森田 沙斗武; 葉山 学; 白山 敬之; 森下 直子; 鈴木 秀和; 岡本 紀雄; 平島 智徳; 清水 一範; 森下 裕; 松岡 洋人; 河原 邦光; 山道 岳; 藤田 和利 肺癌 56 (7) 1076 -1076 2016年12月
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    木枕 舞; 阿部 豊文; 中野 剛佑; 関井 洋輔; 河嶋 厚成; 角田 洋一; 氏家 剛; 永原 啓; 福原 慎一郎; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 宮川 康; 野々村 祝夫 泌尿器科紀要 62 (12) 671 -671 2016年12月
  • 経皮的陰茎動脈塞栓術にて止血を得た尿道出血の一例
    林 裕次郎; 河嶋 厚成; 角田 洋一; 阿部 豊文; 氏家 剛; 永原 啓; 福原 慎一郎; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 野々村 祝夫; 斎藤 哲也; 戸田 宏一; 岸本 健太郎; 大須賀 慶悟 泌尿器科紀要 62 (12) 671 -671 2016年12月
  • 前立腺癌小線源療法後に持続勃起症を来たした1例
    大島 純平; 藤田 和利; 岸本 健太郎; 大須賀 慶悟; 鈴木 修; 惣田 哲次; 中井 康友; 木内 寛; 高尾 徹也; 宮川 康; 辻村 晃; 野々村 祝夫 泌尿器科紀要 62 (11) 605 -607 2016年11月
  • 腎癌組織由来細胞外小胞は血管内皮細胞の透過性を上昇させる
    神宮司 健太郎; 植田 幸嗣; 植村 元秀; 木内 利郎; 松崎 恭介; 藤田 和利; 野々村 祝夫; 辻川 和丈 日本癌学会総会記事 75回 E -1027 2016年10月 [査読有り]
  • 宮川 康; 藤田 和利; 植村 元秀; 今村 亮一; 木内 寛; 野々村 祝夫 泌尿器外科 29 (10) 1527 -1532 2016年10月
  • 基礎研究と臨床を繋ぐ前立腺癌に対する新規バイオマーカー探索 前立腺がんにおける新規バイオマーカー探索研究
    植村 元秀; 河嶋 厚成; 氏家 剛; 永原 啓; 藤田 和利; 野々村 祝夫 日本癌学会総会記事 75回 SST3 -4 2016年10月
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    金沢 崇之; 河嶋 厚成; 後藤 久充子; 岩堀 幸太; 森本 晶子; 氏家 剛; 永原 啓; 藤田 和利; 植村 元秀; 野々村 祝夫; 和田 尚 日本癌学会総会記事 75回 E -1063 2016年10月
  • 末梢血細胞の遺伝子プロファイリングによる腎がんの新規バイオマーカーの探索
    木内 利郎; 植村 元秀; 山本 致之; 林 拓自; 松崎 恭介; 川村 憲彦; 河嶋 厚成; 氏家 剛; 永原 啓; 藤田 和利; 神宮司 健太郎; 辻川 和丈; 野々村 祝夫 日本癌学会総会記事 75回 P -2214 2016年10月
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    松崎 恭介; 藤田 和利; 山本 致之; 木内 利郎; 林 拓自; 河嶋 厚成; 氏家 剛; 永原 啓; 植村 元秀; 神宮司 健太郎; 辻川 和丈; 野々村 祝夫 日本癌学会総会記事 75回 P -2225 2016年10月
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    林 拓自; 藤田 和利; 石津谷 祐; 王 聡; 山本 致之; 木内 利郎; 松崎 恭介; 川村 憲彦; 河嶋 厚成; 氏家 剛; 永原 啓; 植村 元秀; 野々村 祝夫 日本癌学会総会記事 75回 P -2247 2016年10月
  • 河嶋 厚成; 金沢 崇之; 後藤 久充子; 松本 光史; 山本 致之; 木内 利郎; 林 拓自; 松崎 恭介; 川村 憲彦; 氏家 剛; 永原 啓; 藤田 和利; 植村 元秀; 和田 尚; 野々村 祝夫 日本癌治療学会学術集会抄録集 54回 MS6 -2 2016年10月
  • 氏家 剛; 石津谷 祐; 王 聡; 山本 致之; 木内 利郎; 林 拓自; 松崎 恭介; 川村 憲彦; 河嶋 厚成; 永原 啓; 藤田 和利; 植村 元秀; 野々村 祝夫 日本癌治療学会学術集会抄録集 54回 P54 -5 2016年10月
  • 尿路 尿路上皮がんの集学的治療 高リスク上部尿路上皮癌に対する術後補助化学療法の効果及び効果予測因子の検討
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  • 永原啓; 吉田栄宏; 河嶋厚成; 氏家剛; 藤田和利; 植村元秀; 木内寛; 今村亮一; 宮川康; 東原大樹; 小野祐介; 大須賀慶悟; 野々村祝夫 日本癌治療学会学術集会(Web) 54th ROMBUNNO.P48‐6 (WEB ONLY) -6 2016年10月
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  • Norihiko Kawamura; Keisuke Nimura; Atsunari Kawashima; Takeshi Ujike; Akira Nagahara; Kazutoshi Fujita; Motohide Uemura; Yasufumi Kaneda; Norio Nonomura CANCER RESEARCH 76 2016年07月
  • Atsunari Kawashima; Takayuki Kanazawa; Kayoko Maekawa Kato; Kumiko Goto; Mitsunobu Matsumoto; Akiko Morimoto; Kota Iwahori; Takeshi Ujike; Akira Nagahara; Kazutoshi Fujita; Motohide Uemura; Norio Nonomura; Hisashi Wada CANCER RESEARCH 76 2016年07月
  • 腎細胞癌組織内に浸潤する免疫担当細胞発現に腫瘍間・腫瘍内多様性は存在するのか?
    河嶋 厚成; 金沢 崇之; 氏家 剛; 永原 啓; 藤田 和利; 植村 元秀; 和田 尚; 野々村 祝夫 腎癌研究会会報 (46) 30 -30 2016年07月
  • 福原慎一郎; 上田倫央; 惣田哲次; 竹澤健太郎; 藤田和利; 木内寛; 宮川康; 野々村祝夫 日本アンドロロジー学会総会記事 35th 121‐122 2016年06月
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  • Norihiko Kawamura; Keisuke Nimura; Hiromichi Nagano; Takahiro Yoshida; Atsunari Kawashima; Takeshi Ujike; Akira Nagahara; Kazutoshi Fujita; Motohide Uemura; Yasufumi Kaneda; Norio Nonomura JOURNAL OF UROLOGY 195 (4) E872 -E872 2016年04月
  • Atsunari Kawashima; Takayuki Kanazawa; Kayoko Maekawa; Mitsunobu Matsumoto; Kumiko Goto; Akiko Morimoto; Kota Iwahori; Takeshi Ujike; Akira Nagahara; Kazutoshi Fujita; Motohide Uemura; Norio Nonomura; Hisashi Wada JOURNAL OF UROLOGY 195 (4) E308 -E308 2016年04月
  • Koji Izumi; Satoshi Inoue; Hiroki Ide; Kazutoshi Fujita; Seiji Yamaguchi; Hiroaki Fushimi; George Netto; Norio Nonomura; Hiroshi Miyamoto JOURNAL OF UROLOGY 195 (4) E362 -E362 2016年04月
  • 宮川 康; 藤田 和利; 今村 亮一; 植村 元秀; 木内 寛; 野々村 祝夫 Japanese Journal of Endourology 29 (1) 2 -5 2016年04月
  • T1 High Grade膀胱癌に対するBCG注入療法後に出現した骨盤内リンパ節転移診断に腹腔鏡下骨盤内リンパ節郭清術が有効であった2例
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    山中 庸平; 冨山 栄輔; 吉田 栄宏; 河嶋 厚成; 氏家 剛; 永原 啓; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 宮川 康; 野々村 祝夫; 吉岡 俊昭; 三宅 修 泌尿器科紀要 62 (4) 213 -214 2016年04月
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    氏家 剛; 河嶋 厚成; 永原 啓; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 高尾 徹也; 宮川 康; 野々村 祝夫 日本内分泌・甲状腺外科学会雑誌 33 (Suppl.1) S131 -S131 2016年04月
  • 山本 致之; 河嶋 厚成; 氏家 剛; 永原 啓; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 高尾 徹也; 宮川 康; 野々村 祝夫 日本泌尿器科学会総会 104回 PP1 -008 2016年04月
  • 永原 啓; 山本 致之; 木内 利郎; 林 拓自; 松崎 恭介; 川村 憲彦; 中田 渡; 吉田 栄宏; 河嶋 厚成; 氏家 剛; 藤田 和利; 植村 元秀; 野々村 祝夫 日本泌尿器科学会総会 104回 PP1 -039 2016年04月
  • 林 拓自; 藤田 和利; 山本 致之; 木内 利郎; 松崎 恭介; 川村 憲彦; 中田 渡; 吉田 栄宏; 河嶋 厚成; 氏家 剛; 永原 啓; 植村 元秀; 野々村 祝夫 日本泌尿器科学会総会 104回 PP1 -091 2016年04月
  • 筋層非浸潤性膀胱癌治療の現状と課題 筋層非浸潤性膀胱癌に対するセカンドTURの適応は? Ta high gradeに対しては進展予防の観点からは不要である
    植村 元秀; 河嶋 厚成; 氏家 剛; 永原 啓; 藤田 和利; 木内 寛; 今村 亮一; 宮川 康; 野々村 祝夫 日本泌尿器科学会総会 104回 FS01 -4 2016年04月
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    川村 憲彦; 二村 圭介; 長野 広通; 吉田 栄宏; 河嶋 厚成; 氏家 剛; 永原 啓; 藤田 和利; 植村 元秀; 金田 安史; 野々村 祝夫 日本泌尿器科学会総会 104回 PP2 -096 2016年04月
  • 氏家 剛; 山本 致之; 木内 利郎; 林 拓自; 松崎 恭介; 川村 憲彦; 中田 渡; 吉田 栄宏; 河嶋 厚成; 永原 啓; 藤田 和利; 植村 元秀; 野々村 祝夫 日本泌尿器科学会総会 104回 PP2 -108 2016年04月
  • 去勢抵抗性再燃前立腺癌患者を対象としたHVJ-E腫瘍内投与および皮下投与の安全性及び有効性の評価のための臨床試験(第I/II相臨床試験)
    藤田 和利; 川村 憲彦; 波多野 浩士; 吉田 栄宏; 河嶋 厚成; 氏家 剛; 永原 啓; 中井 康友; 植村 元秀; 金田 安史; 野々村 祝夫 日本泌尿器科学会総会 104回 PP2 -286 2016年04月
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    河嶋 厚成; 植村 元秀; 吉田 栄宏; 氏家 剛; 永原 啓; 藤田 和利; 金沢 崇之; 松本 光史; 森本 晶子; 岩堀 幸太; 和田 尚; 野々村 祝夫 日本泌尿器科学会総会 104回 FS19 -5 2016年04月
  • 小径腎癌に対するCTガイド下凍結療法の初期経験
    永原 啓; 植村 元秀; 吉田 栄宏; 河嶋 厚成; 氏家 剛; 藤田 和利; 木内 寛; 今村 亮一; 宮川 康; 野々村 祝夫; 東原 大樹; 前田 登; 中村 純寿; 大須賀 慶悟 泌尿器科紀要 62 (4) 221 -221 2016年04月
  • 当院における小径腎腫瘍に対するCT透視下経皮的凍結治療の初期治療成績
    東原 大樹; 大須賀 慶悟; 中村 純寿; 小野 祐介; 大平 亮介; 木村 廉; 前田 登; 河嶋 厚成; 氏家 剛; 永原 啓; 藤田 和利; 植村 元秀; 野々村 祝夫; 富山 憲幸 IVR: Interventional Radiology 31 (Suppl.) 184 -184 2016年04月
  • 筋層非浸潤性膀胱癌に対するピラルビシン即時単回膀胱内注入療法の再発予防効果の検討
    冨山 栄輔; 吉田 栄宏; 河嶋 厚成; 角田 洋一; 氏家 剛; 永原 啓; 阿部 豊文; 福原 慎一郎; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 宮川 康; 野々村 祝夫 泌尿器科紀要 62 (4) 214 -214 2016年04月
  • 腹腔鏡下性腺摘出術を行った性分化疾患8例の検討
    福原 慎一郎; 上田 倫央; 惣田 哲次; 竹澤 健太郎; 永原 啓; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 宮川 康; 野々村 祝夫 泌尿器科紀要 62 (4) 219 -219 2016年04月
  • 大阪大学医学部附属病院における精巣腫瘍ならびに性腺外胚細胞腫瘍患者の妊孕能温存の現状
    上戸 賢; 福原 慎一郎; 吉田 栄宏; 河嶋 厚成; 角田 洋一; 氏家 剛; 阿部 豊文; 永原 啓; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 宮川 康; 野々村 祝夫 泌尿器科紀要 62 (4) 219 -219 2016年04月
  • 福原 慎一郎; 河嶋 厚成; 角田 洋一; 阿部 豊文; 氏家 剛; 永原 啓; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 宮川 康; 野々村 祝夫 Japanese Journal of Endourology 29 (1) 101 -105 2016年04月
  • ロボット支援腹腔鏡下前立腺全摘術の施設導入時の手術合併症に関する検討
    宮川 康; 河島 厚成; 角田 洋一; 氏家 剛; 阿部 豊文; 永原 啓; 福原 慎一郎; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 野々村 祝夫 日本泌尿器科学会総会 104回 PP3 -093 2016年04月
  • 大阪大学泌尿器科におけるロボット支援腹腔鏡下前立腺全摘除術の治療成績および日本語版EPICを用いた術後尿禁制に関する検討
    今村 亮一; 角田 洋一; 河嶋 厚成; 永原 啓; 阿部 豊文; 氏家 剛; 福原 慎一郎; 藤田 和利; 植村 元秀; 木内 寛; 宮川 康; 野々村 祝夫 日本泌尿器科学会総会 104回 PP3 -232 2016年04月
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    西本 愛; 大塩 郁幹; 河口 恵; 小垣 孝弘; 小林 巧明; 北惠 郁緒里; 神宮司 健太郎; 上田 裕子; 深田 宗一朗; 中田 渡; 藤田 和利; 植村 元秀; 野々村 祝夫; 辻川 和丈 日本薬学会年会要旨集 136年会 (4) 74 -74 2016年03月 [査読有り]
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    島ノ江 知樹; 塚田 陽平; 大塩 郁幹; 北惠 郁緒里; 神宮司 健太郎; 上田 裕子; 深田 宗一朗; 足立 淳; 朝長 毅; 中田 渡; 藤田 和利; 植村 元秀; 野々村 祝夫; 辻川 和丈 日本薬学会年会要旨集 136年会 (4) 74 -74 2016年03月 [査読有り]
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    中辻 由乃; 江川 博; 廣野 貴之; 広瀬 遼; 北惠 郁緒里; 神宮司 健太郎; 上田 裕子; 深田 宗一朗; 中田 渡; 藤田 和利; 植村 元秀; 野々村 祝夫; 辻川 和丈 日本薬学会年会要旨集 136年会 (4) 74 -74 2016年03月 [査読有り]
  • Hiroshi Egawa; Kentaro Jingushi; Yuko Ueda; Kaori Kitae; Wataru Nakata; Kazutoshi Fujita; Motohide Uemura; Norio Nonomura; Kazutake Tsujikawa CANCER RESEARCH 76 2016年03月
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  • 大阪大学における筋層非浸潤性膀胱癌に対するBCG注入療法の検討
    河嶋 厚成; 関井 洋輔; 氏家 剛; 永原 啓; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 宮川 康; 野々村 祝夫 泌尿器科紀要 62 (3) 151 -151 2016年03月
  • 大阪大学における膀胱癌に対するセカンドTURの臨床的検討
    林 裕次郎; 氏家 剛; 永原 啓; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 宮川 康; 野々村 祝夫; 河嶋 厚成 泌尿器科紀要 62 (3) 160 -160 2016年03月
  • 氏家 剛; 植村 元秀; 角田 洋一; 河嶋 厚成; 永原 啓; 藤田 和利; 木内 寛; 今村 亮一; 高尾 徹也; 宮川 康; 野々村 祝夫 日本内分泌・甲状腺外科学会雑誌 33 (1) 41 -45 2016年03月
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    角田 洋一; 山中 和明; 加藤 大悟; 阿部 豊文; 福原 慎一郎; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 宮川 康; 野々村 祝夫; 奥見 雅由; 市丸 直嗣 泌尿器科紀要 62 (3) 149 -149 2016年03月
  • 山道岳; 木内寛; 上田倫央; 惣田哲次; 氏家剛; 阿部豊文; 永原啓; 福原慎一郎; 藤田和利; 植村元秀; 今村亮一; 宮川康; 野々村祝夫 日本泌尿器科学会中部総会プログラム・抄録集 66th 167 2016年
  • A. Kawashima; M. Uemura; A. Nagahara; Y. Yamamoto; S. Takada; Y. Inagaki; T. Kinouchi; O. Miyake; S. Nakazawa; K. Nishimura; H. Arai; M. Honda; K. Okada; M. Tsujihata; K. Tsutahara; S. Yamaguchi; T. Ujike; K. Fujita; N. Nonomura ANNALS OF ONCOLOGY 26 75 -75 2015年12月
  • 原発性アルドステロン症に対する鏡視下手術時間に影響を及ぼす因子の同定
    河嶋 厚成; 木内 利郎; 吉田 栄宏; 氏家 剛; 永原 啓; 角田 洋一; 阿部 豊文; 福原 慎一郎; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 宮川 康; 野々村 祝夫 日本内視鏡外科学会雑誌 20 (7) OS305 -4 2015年12月
  • 大腸憩室穿孔を合併し治療戦略の決定に苦慮した小児MEN2Bの1例
    関井 洋輔; 氏家 剛; 永原 啓; 藤田 和利; 角田 洋一; 河嶋 厚成; 阿部 豊文; 福原 慎一郎; 木内 寛; 植村 元秀; 今村 亮一; 宮川 康; 野々村 祝夫; 中山 尋文; 難波 範行; 大割 貢; 出口 幸一 泌尿器科紀要 61 (12) 527 -527 2015年12月
  • 顕微鏡下低位結紮術後再発に対して経皮的塞栓術を施行した精索静脈瘤の2例
    木枕 舞; 永原 啓; 福原 慎一郎; 惣田 哲次; 竹澤 健太郎; 藤田 和利; 木内 寛; 宮川 康; 野々村 祝夫 泌尿器科紀要 61 (12) 528 -528 2015年12月
  • 河嶋 厚成; 木内 利郎; 氏家 剛; 永原 啓; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 宮川 康; 野々村 祝夫 Japanese Journal of Endourology 28 (3) 173 -173 2015年11月
  • 永原 啓; 植村 元秀; 吉田 栄宏; 河嶋 厚成; 氏家 剛; 藤田 和利; 木内 寛; 今村 亮一; 宮川 康; 野々村 祝夫 Japanese Journal of Endourology 28 (3) 189 -189 2015年11月
  • 河嶋 厚成; 木内 利郎; 氏家 剛; 永原 啓; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 宮川 康; 野々村 祝夫 Japanese Journal of Endourology 28 (3) 198 -198 2015年11月
  • 宮川 康; 角田 洋一; 氏家 剛; 阿部 豊文; 福原 慎一郎; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 野々村 祝夫 Japanese Journal of Endourology 28 (3) 222 -222 2015年11月
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  • miR-130 familyはFAKとAktの活性化を介して膀胱癌細胞の遊走能と浸潤能を促進する
    江川 博; 神宮司 健太郎; 塚田 陽平; 木内 利郎; 松崎 恭介; 中田 渡; 藤田 和利; 植村 元秀; 野々村 祝夫; 辻川 和丈 日本癌学会総会記事 74回 P -3246 2015年10月 [査読有り]
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  • M. Uemura; A. Nagahara; Y. Yamamoto; S. Takada; Y. Inagaki; T. Kinouchi; O. Miyake; S. Nakazawa; K. Nishimura; H. Arai; M. Honda; K. Okada; M. Tsujihata; K. Tsutahara; S. Yamaguchi; A. Kawashima; T. Ujike; K. Fujita; N. Nonomura EUROPEAN JOURNAL OF CANCER 51 S493 -S493 2015年09月
  • 前立腺がん治療の治療個別化ストラテジー 前立腺がんの新規バイオマーカー開発とその臨床応用
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  • 下大静脈腫瘍塞栓を伴う腎癌に対するスニチニブの術前治療効果の検討
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  • 尿路上皮癌に対するゲムシタビン・ネダプラチン併用療法(GN療法)の臨床的検討
    永原 啓; 吉田 栄宏; 河嶋 厚成; 氏家 剛; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 宮川 康; 野々村 祝夫 日本癌治療学会誌 50 (3) 1939 -1939 2015年09月
  • 泌尿器 上部尿路上皮がんの疫学と臨床 上部尿路上皮癌リンパ節転移症例に対する術後補助化学療法の効果の検討
    藤田 和利; 稲元 輝生; 森 直樹; 山口 誓司; 高田 晋吾; 辻畑 正雄; 中山 雅志; 鯉田 容平; 高田 剛; 原 恒男; 氏家 剛; 永原 啓; 植村 元秀; 東 治人; 野々村 祝夫 日本癌治療学会誌 50 (3) 1192 -1192 2015年09月
  • 腎細胞癌における組織内浸潤T細胞のプロファイリング解析
    河嶋 厚成; 金沢 崇之; 松本 光史; 森本 晶子; 岩堀 幸太; 林 拓自; 木内 利郎; 松崎 恭介; 川村 憲彦; 中田 渡; 吉田 栄宏; 氏家 剛; 永原 啓; 藤田 和利; 植村 元秀; 和田 尚; 野々村 祝夫 腎癌研究会会報 (45) 31 -31 2015年07月
  • 心房内腫瘍塞栓子を認めた右腎癌の1例
    大島 純平; 藤田 和利; 角田 洋一; 永原 啓; 木内 寛; 植村 元秀; 奥見 雅由; 中井 康友; 高尾 徹也; 宮川 康; 辻村 晃; 西 宏之; 甲斐沼 盂; 野々村 祝夫 泌尿器科紀要 61 (7) 305 -305 2015年07月
  • 内分泌外科領域における分子標的治療薬 現状と課題 泌尿器科における分子標的薬導入時の経験と問題点(腎癌を中心に)
    野々村 祝夫; 河嶋 厚成; 氏家 剛; 永原 啓; 藤田 和利; 植村 元秀; 高尾 徹也; 宮川 康 日本内分泌・甲状腺外科学会雑誌 32 (Suppl.1) S90 -S90 2015年04月
  • 松崎 恭介; 藤田 和利; 山本 致之; 谷川 剛; 中田 渡; 河嶋 厚成; 氏家 剛; 永原 啓; 植村 元秀; 高田 晋吾; 山口 誓司; 野々村 祝夫 日本泌尿器科学会総会 103回 464 -464 2015年04月
  • microRNA-27a-3pは淡明細胞型腎細胞癌の予後規定因子である
    中田 渡; 植村 元秀; 木内 利郎; 林 拓自; 松崎 恭介; 川村 憲彦; 河嶋 厚成; 氏家 剛; 永原 啓; 藤田 和利; 神宮司 健太郎; 辻川 和丈; 野々村 祝夫 日本泌尿器科学会総会 103回 468 -468 2015年04月
  • 前立腺癌患者における血中フコシル化ハプトグロビンの解析および新規バイオマーカーとしての有用性の検討
    藤田 和利; 中田 渡; 河嶋 厚成; 氏家 剛; 永原 啓; 植村 元秀; 下村 真由香; 高松 真二; 中の 三弥子; 三善 英知; 野々村 祝夫 日本泌尿器科学会総会 103回 494 -494 2015年04月
  • 単一施設における下大静脈腫瘍塞栓を伴う腎癌に対するスニチニブの治療効果の検討
    氏家 剛; 植村 元秀; 木内 利郎; 林 拓自; 松崎 恭介; 川村 憲彦; 中田 渡; 吉田 栄宏; 河嶋 厚成; 永原 啓; 藤田 和利; 野々村 祝夫 日本泌尿器科学会総会 103回 510 -510 2015年04月
  • 原発性アルドステロン症における副腎静脈サンプリング(AVS)を用いた局在診断・手術成績の検討
    木内 利郎; 河嶋 厚成; 氏家 剛; 永原 啓; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 高尾 徹也; 宮川 康; 野々村 祝夫; 北村 哲宏; 大月 道夫 日本泌尿器科学会総会 103回 600 -600 2015年04月
  • 上部尿路上皮癌でのendoglin発現は腎尿管全摘除術後の膀胱内再発と関連する
    林 拓自; 藤田 和利; 氏家 剛; 河嶋 厚成; 永原 啓; 植村 元秀; 谷川 剛; 島津 彰宏; 伏見 博彰; 山口 誓司; 野々村 祝夫 日本泌尿器科学会総会 103回 648 -648 2015年04月
  • 尿路上皮癌に対するGN療法についての臨床的検討
    永原 啓; 木内 利郎; 林 拓自; 松崎 恭介; 川村 憲彦; 中田 渡; 吉田 栄宏; 河嶋 厚成; 氏家 剛; 藤田 和利; 植村 元秀; 野々村 祝夫 日本泌尿器科学会総会 103回 692 -692 2015年04月
  • ミトコンドリアDNAに対する次世代シークエンスを用いた前立腺全摘標本および前立腺生検標本におけるクローン解析
    河嶋 厚成; ジョン・オケロ; 氏家 剛; 永原 啓; 藤田 和利; デビッド・バーマン; 野々村 祝夫 日本泌尿器科学会総会 103回 708 -708 2015年04月
  • ドセタキセル抵抗性の前立腺癌細胞では、CXCR4・p-ERK1/2・c-Mycのsignaling loopが形成され、腫瘍造成能が亢進している
    川村 憲彦; 波多野 浩士; 中田 渡; 吉田 栄宏; 河嶋 厚成; 氏家 剛; 永原 啓; 藤田 和利; 植村 元秀; 金田 安史; 野々村 祝夫 日本泌尿器科学会総会 103回 709 -709 2015年04月
  • 植村元秀; 松崎恭介; 木内利郎; 林拓自; 川村憲彦; 中田渡; 河嶋厚成; 河嶋厚成; 氏家剛; 永原啓; 藤田和利; 中村純壽; 大須賀慶悟; 野々村祝夫 日本泌尿器科学会総会プログラム抄録集(CD-ROM) 103rd ROMBUNNO.OP‐466 -617 2015年04月
  • 大島純平; 藤田和利; 惣田哲次; 中井康友; 木内寛; 高尾徹也; 宮川康; 辻村晃; 野々村祝夫; 岸本健太郎; 大須賀慶悟; 鈴木修 泌尿器科紀要 61 (3) 127 -127 2015年03月
  • 泌尿器科癌PDXモデルマウスを用いた癌悪性化メカニズムの解析
    廣瀬 遼; 神宮司 健太郎; 江川 博; 川上 竜司; 塚田 陽平; 柏木 悠里; 小林 巧明; 北惠 郁緒里; 上田 裕子; 深田 宗一朗; 中田 渡; 藤田 和利; 植村 元秀; 野々村 祝夫; 辻川 和丈 日本薬学会年会要旨集 135年会 (4) 207 -207 2015年03月 [査読有り]
  • Sarah Karram; Sheila Faraj; Kazutoshi Fujita; Enrico Munari; Ie-Ming Shih; Alcides Chaux; George Netto MODERN PATHOLOGY 28 233A -233A 2015年02月
  • Sarah Karram; Sheila Faroj; Kazutoshi Fujita; Enrico Munari; Le-Ming Shih; Alcides Chaux; George Netto LABORATORY INVESTIGATION 95 233A -233A 2015年02月
  • 藤田和利; 下村真由香; 高松真二; 山本致之; 木内利郎; 林拓自; 松崎恭介; 中田渡; 河嶋厚成; 氏家剛; 永原啓; 植村元秀; 三善英知; 野々村祝夫 日本アンドロロジー学会総会記事 34th 2015年
  • 永原啓; 植村元秀; 吉田栄宏; 河嶋厚成; 氏家剛; 藤田和利; 木内寛; 今村亮一; 宮川康; 東原大樹; 前田登; 中村純寿; 大須賀慶悟; 野々村祝夫 日本泌尿器科学会中部総会プログラム・抄録集 65th 182 2015年
  • 福原慎一郎; 上田倫央; 惣田哲次; 竹澤健太郎; 永原啓; 藤田和利; 植村元秀; 木内寛; 今村亮一; 宮川康; 野々村祝夫 日本泌尿器科学会中部総会プログラム・抄録集 65th 174 2015年
  • 冨山栄輔; 吉田栄宏; 河嶋厚成; 角田洋一; 氏家剛; 永原啓; 阿部豊文; 福原慎一郎; 藤田和利; 植村元秀; 木内寛; 今村亮一; 宮川康; 野々村祝夫 日本泌尿器科学会中部総会プログラム・抄録集 65th 163 2015年
  • 上戸賢; 福原慎一郎; 吉田栄宏; 河嶋厚成; 角田洋一; 氏家剛; 阿部豊文; 永原啓; 藤田和利; 植村元秀; 木内寛; 今村亮一; 宮川康; 野々村祝夫 日本泌尿器科学会中部総会プログラム・抄録集 65th 174 2015年
  • 惣田哲次; 大島順平; 藤田和利; 中井康友; 木内寛; 高尾徹也; 宮川康; 辻村晃; 野々村祝夫; 岸本健太郎; 大須賀慶悟; 鈴木修 日本性機能学会中部総会プログラム・抄録集 24th (3) 32 -262 2014年12月
  • 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 氏家 剛; 永原 啓; 宮川 康; 野々村 祝夫 Japanese Journal of Endourology 27 (3) 321 -321 2014年11月
  • 植村 元秀; 木内 利郎; 角田 洋一; 氏家 剛; 永原 啓; 藤田 和利; 木内 寛; 今村 亮一; 宮川 康; 野々村 祝夫 Japanese Journal of Endourology 27 (3) 201 -201 2014年11月
  • 氏家 剛; 角田 洋一; 永原 啓; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 宮川 康; 野々村 祝夫 Japanese Journal of Endourology 27 (3) 316 -316 2014年11月
  • 木内 寛; 角田 洋一; 阿部 豊文; 永原 啓; 福原 慎一郎; 藤田 和利; 植村 元秀; 今村 良一; 宮川 康; 野々村 祝夫 Japanese Journal of Endourology 27 (3) 262 -262 2014年11月
  • 福原 慎一郎; 角田 洋一; 阿部 豊文; 永原 啓; 藤田 和利; 植村 元秀; 木内 寛; 今村 亮一; 宮川 康; 野々村 祝夫 Japanese Journal of Endourology 27 (3) 287 -287 2014年11月
  • Kentaro Jingushi; Wataru Nakata; Yuko Ueda; Kaori Kitae; Kazutoshi Fujita; Motohide Uemura; Norio Nonomura; Kazutake Tsujikawa CANCER RESEARCH 74 (19) 2014年10月
  • Kazutoshi Fujita; Motohide Uemura; Wataru Nakata; Mototaka Sato; Akira Nagahara; Yasutomo Nakai; Mayuka Shimomura; Miyako Nakano; Eiji Miyoshi; Norio Nonomura CANCER RESEARCH 74 (19) 2014年10月
  • 皆川 光; 難波 範行; 中山 尋文; 藤原 誠; 大幡 泰久; 高桑 聖; 北岡 太一; 窪田 拓生; 出口 幸一; 大割 貢; 関井 洋輔; 永原 啓; 藤田 和利; 大薗 恵一 日本内分泌学会雑誌 90 (3) 981 -981 2014年10月
  • アクチン調節蛋白質CAPZB3のヒト精子における発現およびその局在
    惣田 哲次; 宮川 康; 竹澤 健太郎; 奥田 英伸; 福原 慎一郎; 藤田 和利; 木内 寛; 野々村 祝夫; 田中 宏光 日本生殖医学会雑誌 59 (4) 442 -442 2014年10月
  • 淡明細胞型腎細胞癌においてmiR-629はTRIM33を介してTGF-β/Smadシグナルを促進する(MiR-629, a potent regulator of TGF-β/Smad signaling via TRIM33 in clear cell renal cell carcinoma)
    神宮司 健太郎; 江川 博; 中田 渡; 藤田 和利; 植村 元秀; 野々村 祝夫; 辻川 和丈 日本癌学会総会記事 73回 J -3015 2014年09月 [査読有り]
  • miR-130 family分子を標的とする膀胱癌治療創薬(Innovative drug discovery for bladder cancer by miR-130 family molecules-targeted locked nucleic acid)
    江川 博; 神宮司 健太郎; 中田 渡; 藤田 和利; 植村 元秀; 野々村 祝夫; 辻川 和丈 日本癌学会総会記事 73回 P -1083 2014年09月 [査読有り]
  • 腎癌におけるformalin-fixed paraffin-embedded sampleから抽出したRNAの質的評価(Comparison of microRNA from matched Formalin-Fixed Paraffin-Embedded and Frozen clear cell renal cell carcinoma samples)
    中田 渡; 植村 元秀; 木内 利郎; 林 拓自; 松崎 恭介; 川村 憲彦; 吉田 栄宏; 氏家 剛; 永原 啓; 藤田 和利; 神宮司 健太郎; 辻川 和丈; 野々村 祝夫 日本癌学会総会記事 73回 P -3225 2014年09月 [査読有り]
  • ドセタキセル療法後の前立腺癌細胞では、CXCR4・ERK1/2・c-Mycが恒常的に活性化し、腫瘍形成能が増加している(Chemoresistant prostate cancer cells increase the tumorigenicity via constitutive signaling of CXCR4, ERK1/2 and c-Myc)
    川村 憲彦; 波多野 浩士; 木内 利郎; 林 拓自; 松崎 恭介; 中田 渡; 吉田 栄宏; 氏家 剛; 永原 啓; 藤田 和利; 植村 元秀; 金田 安史; 野々村 祝夫 日本癌学会総会記事 73回 P -1286 2014年09月
  • 中・高リスク前立腺癌に対する高線量率 組織内照射単独療法の治療成績
    吉岡 靖生; 鈴木 修; 中井 康友; 植村 元秀; 藤田 和利; 野々村 祝夫; 小川 和彦 泌尿器外科 27 (8) 1243 -1245 2014年08月
  • 上部尿路上皮癌におけるmTOR pathwayの免疫組織学的検討
    藤田 和利; エンリコ・ムナリ; 永原 啓; 植村 元秀; 中井 康友; 中川 勝広; 谷川 剛; 今村 亮一; 島津 宏樹; ジョージ・ネットー; 伏見 博彰; 山口 誓司; 野々村 祝夫 日本泌尿器科学会総会 102回 539 -539 2014年04月
  • 腎癌におけるformalin-fixed paraffinembedded sampleから抽出したRNAの質的評価
    中田 渡; 植村 元秀; 川村 憲彦; 吉田 栄宏; 佐藤 元孝; 永原 啓; 藤田 和利; 中井 康友; 神宮司 健太郎; 辻川 和丈; 野々村 祝夫 日本泌尿器科学会総会 102回 596 -596 2014年04月 [査読有り]
  • Kazutoshi Fujita; Motohide Uemura; Akira Nagahara; Yasutomo Nakai; Go Tanigawa; Masahiro Nakagawa; Ryoichi Imamura; Wataru Nakata; Mototaka Sato; Koki Shimazu; Hiroaki Fushimi; Seiji Yamaguchi; Norio Nonomura JOURNAL OF UROLOGY 191 (4) E915 -E916 2014年04月
  • Wataru Nakata; Yasutomo Nakai; Norihiko Kawamura; Takahiro Yoshida; Mototaka Sato; Akira Nagahara; Kazutoshi Fujita; Motohide Uemura; Norio Nonomura JOURNAL OF UROLOGY 191 (4) E157 -E157 2014年04月
  • Kazutoshi Fujita; Motohide Uemura; Akira Nagahara; Yasutomo Nakai; Yoshiyuki Yamamoto; Go Tanigawa; Wataru Nakata; Mototaka Sato; Kiyomi Matsumiya; Seiji Yamaguchi; Norio Nonomura JOURNAL OF UROLOGY 191 (4) E891 -E891 2014年04月
  • 副腎手術の低侵襲アプローチ(単孔式、小切開、標準的腹腔鏡など) 大阪大学における腹腔鏡下副腎摘除術の臨床的検討 とくに腹腔アプローチによる単孔式副腎摘除の有用性と限界について
    宮川 康; 植村 元秀; 角田 洋一; 永原 啓; 藤田 和利; 奥見 雅由; 木内 寛; 中井 康友; 高尾 徹也; 辻村 晃; 野々村 祝夫 日本内分泌・甲状腺外科学会雑誌 31 (Suppl.1) S75 -S75 2014年04月
  • 淡明細胞型腎細胞癌において高発現するmiR-122の機能解析
    柏木 悠里; 長谷 拓明; 神宮司 健太郎; 上田 裕子; 北惠 郁緒里; 中田 渡; 藤田 和利; 植村 元秀; 野々村 祝夫; 辻川 和丈 日本薬学会年会要旨集 134年会 (4) 89 -89 2014年03月 [査読有り]
  • 角田洋一; 山中和明; 加藤大悟; 阿部豊文; 福原慎一郎; 藤田和利; 植村元秀; 奥見雅由; 木内寛; 今村亮一; 市丸直嗣; 宮川康; 野々村祝夫 日本泌尿器科学会中部総会プログラム・抄録集 64th 123 2014年
  • 腹腔鏡下前立腺全摘術とロボット支援下前立腺全摘術の導入期におけるQOLの検討
    中井 康友; 奥見 雅由; 永原 啓; 角田 洋一; 藤田 和利; 木内 寛; 植村 元秀; 宮川 康; 辻村 晃; 野々村 祝夫 Japanese Journal of Endourology 26 (3) 265 -265 2013年11月
  • 血中好中球数は前立腺生検の予測因子となる
    藤田 和利; 川村 憲彦; 中田 渡; 吉田 栄宏; 佐藤 元孝; 永原 啓; 植村 元秀; 中井 康友; 中川 勝広; 谷川 剛; 今村 亮一; 細見 昌弘; 山口 誓司; 野々村 祝夫 日本癌治療学会誌 48 (3) 1219 -1219 2013年09月
  • 多施設共同前向き試験による腎細胞癌治療におけるインターフェロンα製剤最適投与方法の検討
    中田 渡; 河嶋 厚成; 高山 仁志; 波多野 浩士; 佐藤 元孝; 藤田 和利; 植村 元秀; 中井 康友; 野々村 祝夫; 芝 政宏; 向井 雅俊; 中山 雅志; 西村 和郎; 井上 均 泌尿器科紀要 59 (9) 624 -624 2013年09月
  • Koji Hatano; Yasutomo Nakai; Taeko Matsushima-Miyagi; Motonari Nomura; Wataru Nakata; Takahiro Yoshida; Mototaka Sato; Atsunari Kawashima; Akira Nagahara; Kazutoshi Fujita; Motohide Uemura; Hitoshi Takayama; Yasufumi Kaneda; Norio Nonomura CANCER RESEARCH 73 (8) 2013年04月
  • Mototaka Sato; Yasutomo Nakai; Wataru Nakata; Takahiro Yoshida; Koji Hatano; Kazutoshi Fujita; Motohide Uemura; Hitoshi Takayama; Norio Nonomura JOURNAL OF UROLOGY 189 (4) E120 -E120 2013年04月
  • 膀胱上皮内癌(CIS)のマクロファージ(MΦ)の浸潤とCD34陽性細胞はBCG膀胱内注入療法の予後を反映する
    高山 仁志; 中田 渡; 吉田 栄宏; 波多野 浩士; 佐藤 元孝; 藤田 和利; 植村 元秀; 中井 康友; 野々村 祝夫 日本泌尿器科学会雑誌 104 (2) 390 -390 2013年03月
  • EMMPRINは腎細胞癌細胞の血管新生、増殖、浸潤を促進し、その予後規定因子となる
    佐藤 元孝; 中井 康友; 中田 渡; 吉田 栄宏; 波多野 浩士; 藤田 和利; 植村 元秀; 高山 仁志; 野々村 祝夫 日本泌尿器科学会雑誌 104 (2) 434 -434 2013年03月
  • 前立腺炎による組織傷害/再生過程における骨髄由来細胞(Bone marrow-derived cells)の検討
    中井 康友; 中田 渡; 佐藤 元孝; 波多野 浩士; 藤田 和利; 植村 元秀; 高山 仁志; 野々村 祝夫 日本泌尿器科学会雑誌 104 (2) 447 -447 2013年03月
  • 山本致之; 山本致之; 今村亮一; 中澤成晃; 中澤成晃; 林拓自; 林拓自; 谷川剛; 藤田和利; 藤田和利; 細見昌弘; 島津宏樹; 伏見博彰; 山口誓司 泌尿器外科 26 (2) 2013年
  • 尿管狭窄、吻合部狭窄に対する経尿路的拡張
    木内 寛; 河嶋 厚成; 藤田 和利; 植村 元秀; 中井 康友; 高尾 徹也; 高山 仁; 宮川 康; 辻村 晃; 野々村 祝夫 Japanese Journal of Endourology 25 (3) 222 -222 2012年11月
  • 術前血清Na値は上部尿路上皮癌の予後の予測因子である
    藤田 和利; 谷川 剛; 中川 勝広; 今村 亮一; 細見 昌弘; 植村 元秀; 中井 康友; 高山 仁志; 辻村 晃; 山口 誓司; 野々村 祝夫 日本癌治療学会誌 47 (3) 1059 -1059 2012年10月
  • 根治切除不能または転移性腎細胞癌に対するスニチニブ治療成績
    高山 仁志; 河嶋 厚成; 西村 和郎; 三好 進; 山口 誓司; 岡 聖次; 吉岡 俊昭; 目黒 則男; 松宮 清美; 藤田 和利; 植村 元秀; 中井 康友; 辻村 晃; 野々村 祝夫 日本癌治療学会誌 47 (3) 1367 -1367 2012年10月
  • 前立腺癌術後の生化学的再発症例の臨床的検討
    中井 康友; 中田 渡; 吉田 栄宏; 波多野 浩士; 佐藤 元孝; 河嶋 厚成; 藤田 和利; 植村 元秀; 高山 仁志; 野々村 祝夫 日本癌治療学会誌 47 (3) 2637 -2637 2012年10月
  • 藤田 和利; 今村 亮一; 岸本 望; 林 拓自; 中川 勝弘; 谷川 剛; 細見 昌弘; 山口 誓司 大阪透析研究会会誌 30 (2) 228 -228 2012年09月
  • 腎静脈内腫瘍塞栓を伴った腎血管筋脂肪腫の1例
    林 拓自; 藤田 和利; 岸本 望; 中川 勝弘; 谷川 剛; 今村 亮一; 細見 昌弘; 山口 誓司 泌尿器科紀要 58 (9) 529 -529 2012年09月
  • Motohide Uemura; Kazutoshi Fujita; Hiroshi Kiuchi; Masayoshi Okumi; Yasutomo Nakai; Koji Yazawa; Tetsuya Takao; Hitoshi Takayama; Yasushi Miyagawa; Kazuo Nishimura; Akira Tsujimura; Norio Nonomura JOURNAL OF ENDOUROLOGY 26 A277 -A277 2012年09月
  • A. Kawashima; H. Takayama; M. Sato; K. Hatano; K. Fujita; M. Uemura; Y. Nakai; K. Nishimura; A. Tsujimura; N. Nonomura UROLOGY 80 (3) S111 -S111 2012年09月
  • M. Sato; Y. Nakai; W. Nakata; T. Yoshida; K. Hatano; A. Kawashima; K. Fujita; H. Uemura; H. Takayama; N. Nonomura UROLOGY 80 (3) S247 -S247 2012年09月
  • Yasushi Miyagawa; Iwao Yoshioka; Fujita Kazutoshi; Hiroshi Kiuchi; Motohide Uemura; Masayoshi Okumi; Yasutomo Nakai; Koji Yazawa; Tetsuya Takao; Hitoshi Takayama; Akira Tsujimura; Norio Nonomura JOURNAL OF ENDOUROLOGY 26 A291 -A291 2012年09月
  • 中澤 成晃; 米田 傑; 竹澤 健太郎; 谷川 剛; 藤田 和利; 奥見 雅由; 細見 昌弘; 福原 慎一郎; 伏見 博彰; 山口 誓司 泌尿器科紀要 58 (4) 215 -218 2012年04月
  • 今村 亮一; 岸本 望; 林 拓自; 中川 勝弘; 谷川 剛; 藤田 和利; 細見 昌弘; 山口 誓司 大阪透析研究会会誌 30 (1) 82 -82 2012年03月
  • 体腔鏡下腎部分切除術の検討
    谷川 剛; 岸本 望; 林 拓自; 中川 勝弘; 藤田 和利; 今村 亮一; 細見 昌弘; 山口 誓司 日本泌尿器科学会雑誌 103 (2) 264 -264 2012年03月
  • 大阪府立急性期・総合医療センターにおけるpreemtive腎移植症例の検討
    今村 亮一; 岸本 望; 林 拓自; 中川 勝弘; 谷川 剛; 藤田 和利; 細見 昌弘; 山口 誓司 日本泌尿器科学会雑誌 103 (2) 349 -349 2012年03月
  • 神経温存腹腔鏡下前立腺全摘除術33例の導入期におけるLearning curveの検討
    藤田 和利; 岸本 望; 林 拓自; 中川 勝弘; 谷川 剛; 今村 亮一; 細見 昌弘; 七里 泰正; 山口 誓司 日本泌尿器科学会雑誌 103 (2) 380 -380 2012年03月
  • 膀胱Paragangliomaの1例
    山本 致之; 谷川 剛; 中澤 成晃; 林 拓自; 藤田 和利; 今村 亮一; 細見 昌弘; 山口 誓司; 島津 宏樹; 伏見 博彰 泌尿器科紀要 57 (11) 663 -663 2011年11月
  • 大阪府立急性期・総合医療センター泌尿器科における腎移植ドナー腎採取術の検討
    今村 亮一; 岸本 望; 林 拓自; 中川 勝弘; 谷川 剛; 藤田 和利; 細見 昌弘; 山口 誓司 Japanese Journal of Endourology 24 (3) 108 -108 2011年10月
  • 当院における腹腔鏡下腎部分切除術の検討
    谷川 剛; 岸本 望; 林 拓自; 中川 勝弘; 藤田 和利; 今村 亮一; 細見 昌弘; 山口 誓司 Japanese Journal of Endourology 24 (3) 116 -116 2011年10月
  • 後腹膜鏡下腫瘍摘出術を施行した原発性後腹膜粘液性嚢胞腺腫の1例
    中川 勝弘; 藤田 和利; 奥見 雅由; 岸本 望; 林 拓自; 谷川 剛; 今村 亮一; 細見 昌弘; 山口 誓司 Japanese Journal of Endourology 24 (3) 124 -124 2011年10月
  • 神経温存腹腔鏡下前立腺全摘除術28例の導入期におけるLearning curveの検討
    藤田 和利; 岸本 望; 林 拓自; 中川 勝広; 谷川 剛; 今村 亮一; 細見 昌弘; 七里 泰正; 山口 誓司 Japanese Journal of Endourology 24 (3) 133 -133 2011年10月
  • 前立腺再生検結果と白血球分画との関連についての検討
    藤田 和利; 岸本 望; 林 拓自; 中川 勝弘; 谷川 剛; 今村 亮一; 細見 昌弘; 山口 誓司 日本癌治療学会誌 46 (2) 950 -950 2011年09月
  • 初回BCG療法抵抗、再発例に対し、再度BCG療法を施行した症例の検討
    谷川 剛; 岸本 望; 林 拓自; 中川 勝弘; 藤田 和利; 今村 亮一; 細見 昌弘; 山口 誓司 日本癌治療学会誌 46 (2) 979 -979 2011年09月
  • 当科での単孔式腹腔鏡下左副腎摘除術の経験
    林 拓自; 中澤 成晃; 山本 致之; 谷川 剛; 藤田 和利; 奥見 雅由; 今村 亮一; 細見 昌弘; 山口 誓司 泌尿器科紀要 57 (5) 276 -276 2011年05月
  • 術前化学療法が奏功した膀胱癌Plasmacytoid variantの1例
    林 拓自; 谷川 剛; 竹澤 健太郎; 中澤 成晃; 山本 致之; 藤田 和利; 今村 亮一; 細見 昌弘; 山口 誓司; 島津 彰宏; 伏見 博彰 泌尿器科紀要 57 (4) 219 -219 2011年04月
  • Kazutoshi Fujita; Masahiro Hosomi; Shigeaki Nakazawa; Yoshiyuki Yamamoto; Takuji Hayashi; Go Tanigawa; Ryoichi Imamura; Hiroaki Fushimi; Seiji Yamaguchi JOURNAL OF UROLOGY 185 (4) E851 -E851 2011年04月
  • 今村 亮一; 谷川 剛; 藤田 和利; 細見 昌弘; 山口 誓司; 猪阪 善隆; Sandoval Ruben M.; Molitoris Bruce A.; 野々村 祝夫; 高原 史郎 日本泌尿器科学会雑誌 102 (2) 335 -335 2011年03月
  • 山本 致之; 藤田 和利; 中澤 成晃; 林 拓自; 谷川 剛; 今村 亮一; 細見 昌弘; 和田 大樹; 藤見 聡; 山口 誓司 日本泌尿器科学会雑誌 102 (2) 370 -370 2011年03月
  • 今村 亮一; 中澤 成晃; 山本 致之; 林 拓自; 谷川 剛; 藤田 和利; 細見 昌弘; 山口 誓司 日本泌尿器科学会雑誌 102 (2) 404 -404 2011年03月
  • 藤田 和利; 細見 昌弘; 中澤 成晃; 山本 致之; 林 拓自; 谷川 剛; 今村 亮一; 伏見 博彰; 山口 誓司 日本泌尿器科学会雑誌 102 (2) 548 -548 2011年03月
  • Von Recklinghausen病に合併した膀胱神経線維腫の1例
    中澤 成晃; 米田 傑; 竹澤 健太郎; 谷川 剛; 藤田 和利; 奥見 雅由; 細見 昌弘; 山口 誓司; 福原 慎一郎; 島津 彰宏; 伏見 博彰 泌尿器科紀要 57 (2) 116 -116 2011年02月
  • 米田 傑; 奥見 雅由; 矢澤 浩治; 中澤 成晃; 竹澤 健太郎; 谷川 剛; 藤田 和利; 山口 誓司 移植 45 (6) 665 -669 2010年12月
  • 山口 誓司; 谷川 剛; 藤田 和利; 今村 亮一; 中澤 成晃; 山本 致之; 林 拓自; 矢澤 浩治; 奥見 雅由; 細見 昌弘 Japanese Journal of Endourology and ESWL 23 (3) 166 -166 2010年10月
  • 緊急尿路ドレナージ術を要した結石性腎盂腎炎の検討
    山本 致之; 藤田 和利; 中澤 成晃; 林 拓自; 谷川 剛; 今村 亮一; 細見 昌弘; 山口 誓司 西日本泌尿器科 72 (増刊) 157 -157 2010年10月
  • YONEDA Suguru; NAKAZAWA Shigeaki; TAKEZAWA Kentaro; TANIGAWA Go; FUJITA Kazutoshi; OKUMI Masayoshi; YAZAWA Koji; HOSOMI Masahiro; YAMAGUCHI Seiji Japanese journal of endourology and ESWL 23 (2) 273 -276 2010年09月
  • 前立腺再生検適応における炎症所見の組織学的検討 初回PSA値Gray zoner症例について
    藤田 和利; 中澤 成晃; 林 拓自; 山本 致之; 谷川 剛; 今村 亮一; 細見 昌弘; 伏見 博彰; 山口 誓司 日本癌治療学会誌 45 (2) 836 -836 2010年09月
  • 前立腺再生検適応決定因子としてのPSA velocity及びその関連因子の有用性
    細見 昌弘; 今村 亮一; 藤田 和利; 谷川 剛; 山本 致之; 林 拓自; 中澤 成晃; 山口 誓司 日本癌治療学会誌 45 (2) 837 -837 2010年09月
  • 当院における高齢者腎盂尿管癌の臨床的検討
    谷川 剛; 中澤 成晃; 林 拓自; 山本 致之; 藤田 和利; 今村 亮一; 細見 昌弘; 山口 誓司 日本癌治療学会誌 45 (2) 1051 -1051 2010年09月
  • 藤田 和利; 高尾 徹也; 宮川 康; 辻村 晃; 谷川 剛; 今村 亮一; 細見 昌弘; 山口 誓司; Pavlovich Christian 日本性機能学会雑誌 25 (2) 192 -192 2010年08月
  • 竹澤 健太郎; 中澤 成晃; 米田 傑; 谷川 剛; 藤田 和利; 奥見 雅由; 細見 昌弘; 山口 誓司 日本泌尿器科学会雑誌 101 (2) 509 -509 2010年
  • 細見 昌弘; 中澤 成晃; 米田 傑; 竹澤 健太郎; 谷川 剛; 藤田 和利; 奥見 雅由; 山口 誓司 日本泌尿器科学会雑誌 101 (2) 475 -475 2010年
  • 藤田 和利; 中澤 成晃; 米田 傑; 竹澤 健太郎; 谷川 剛; 奥見 雅由; 細見 昌弘; 伏見 博彰; 山口 誓司 日本泌尿器科学会雑誌 101 (2) 262 -262 2010年
  • J. Kellogg Parsons; Kazutoshi Fujita; Charles M. Ewing; William B. Isaacs; Christian P. Pavlovich JOURNAL OF UROLOGY 181 (4) 595 -595 2009年04月
  • Masashi Nakayama; Kazutoshi Fujita; Atsunari Kawashima; Masatoshi Mukai; Akira Nagahara; Yasutomo Nakai; Hitoshi Takayama; Kazuo Nishimura; Katsuyuki Aozasa; Akihiko Okuyama; Norio Nonomura JOURNAL OF UROLOGY 181 (4) 99 -99 2009年04月
  • Kazutoshi Fujita; Charles M. Ewing; Robert H. Getzenberg; J. Kellogg Parsons; William B. Isaacs; Christian P. Pavlovich JOURNAL OF UROLOGY 181 (4) 505 -506 2009年04月
  • Kazutoshi Fujita; Charles M. Ewing; William B. Isaacs; Christian P. Pavlovich JOURNAL OF UROLOGY 181 (4) 478 -479 2009年04月
  • 中山 雅志; 藤田 和利; 河嶋 厚成; 向井 雅俊; 永原 啓; 芝 政宏; 中井 康友; 氏家 剛; 西村 健作; 高山 仁志; 西村 和郎; 野々村 祝夫; 奥山 明彦 日本泌尿器科学会雑誌 100 (2) 215 -215 2009年02月
  • 矢澤 浩治; 米田 傑; 真殿 佳吾; 谷川 剛; 藤田 和利; 細見 昌弘; 山口 誓司 日本泌尿器科学会雑誌 100 (2) 259 -259 2009年
  • 米田 傑; 真殿 佳吾; 谷川 剛; 藤田 和利; 矢澤 浩治; 細見 昌弘; 山口 誓司 日本泌尿器科学会雑誌 100 (2) 364 -364 2009年
  • 細見 昌弘; 米田 傑; 真殿 佳吾; 谷川 剛; 藤田 和利; 矢澤 浩治; 山口 誓司 日本泌尿器科学会雑誌 100 (2) 331 -331 2009年
  • 谷川 剛; 米田 傑; 真殿 佳吾; 藤田 和利; 矢澤 浩治; 細見 昌弘; 山口 誓司 日本泌尿器科学会雑誌 100 (2) 359 -359 2009年
  • Kazutoshi Fujita; Charles M. Ewing; David Chan; Leslie Magnold; Alan W. Partin; Robert H. Getzenberg; William B. Isaacs; Christian P. Pavlovich JOURNAL OF UROLOGY 179 (4) 720 -720 2008年04月
  • K. Fujita; A. Tsujimura; A. Okuyama HUMAN REPRODUCTION 22 (10) 2796 -2797 2007年10月
  • Kazutoshi Fujita; Akira Tsujimura; Yasushi Miyagawa; Hiroshi Kiuchi; Yasuhiro Matsuoka; Tetsuya Takao; Shingo Takada; Norio Nonomura; Akihiko Okuyama JOURNAL OF UROLOGY 177 (4) 620 -620 2007年04月
  • 宮川 康; 辻村 晃; 平井 利明; 藤田 和利; 中山 治郎; 植田 知博; 木内 寛; 小森 和彦; 松岡 庸洋; 高尾 徹也; 高田 晋吾; 奥山 明彦 日本泌尿器科学会雑誌 98 (2) 532 -532 2007年
  • 平井 利明; 中山 治郎; 植田 知博; 木内 寛; 小森 和彦; 藤田 和利; 松岡 庸洋; 高尾 徹也; 宮川 康; 高田 晋吾; 辻村 晃; 奥山 明彦 日本泌尿器科学会雑誌 98 (2) 531 -531 2007年
  • 藤田 和利; 松岡 庸洋; 高尾 徹也; 宮川 康; 高田 晋吾; 辻村 晃; 奥山 明彦; 松宮 清美; 大田 浩; 若山 照彦 日本生殖医学会雑誌 = Journal of Japan Society for Reproductive Medicine 51 (4) 236 -236 2006年10月
  • 初期尿意に関与する中枢神経機構の解析
    高尾 徹也; 辻村 晃; 木内 寛; 中山 治郎; 平井 利明; 植田 知博; 小森 和彦; 藤田 和利; 松岡 庸洋; 宮川 康; 高田 晋吾; 大崎 康宏; 榎本 圭佑; 奥 直彦; 畑澤 順; 奥山 明彦 日本排尿機能学会誌 17 (1) 131 -131 2006年09月
  • 小森 和彦; 辻村 晃; 高尾 徹也; 中山 治郎; 平井 利明; 植田 知博; 木内 寛; 藤田 和利; 松岡 庸洋; 宮川 康; 高田 晋吾; 奥山 明彦 日本性機能学会雑誌 = The japanese journal of Impotence Research 21 (2) 153 -153 2006年08月
  • 辻村 晃; 平井 利明; 藤田 和利; 植田 知博; 木内 寛; 小森 和彦; 松岡 庸洋; 高尾 徹也; 宮川 康; 高田 晋吾; 松宮 清美; 奥山 明彦; 山中 幹基; 古賀 実; 竹山 政美; 岩佐 厚 日本性機能学会雑誌 = The japanese journal of Impotence Research 21 (1) 13 -19 2006年06月
  • 小森 和彦; 辻村 晃; 高尾 徹也; 中山 治郎; 平井 利明; 植田 知博; 木内 寛; 藤田 和利; 松岡 庸洋; 宮川 康; 高田 晋吾; 奥山 明彦 日本平滑筋学会雑誌 10 (1) "J -37" 2006年04月
  • K Fujita; A Tsujimura; H Ohta; T Hirai; T Ueda; H Kiuchi; K Komori; Y Matsuoka; T Takao; Y Miyagawa; S Takada; K Matsumiya; T Wakayama; A Okuyama JOURNAL OF UROLOGY 175 (4) 457 -458 2006年04月
  • A Tsujimura; Y Miyagawa; K Fujita; T Takao; M Takeyama; M Yamanaka; K Matsumiya; H Fujioka; M Koga; A Okuyama JOURNAL OF UROLOGY 175 (4) 454 -454 2006年04月
  • Y Miyagawa; H Tanaka; Y Matsuoka; T Ueda; H Kiuchi; P Tanjapatkul; K Fujita; T Takao; S Takada; A Tsujimura; Y Nishimune; A Okuyama JOURNAL OF UROLOGY 175 (4) 522 -523 2006年04月
  • S Takada; A Tsujimura; Y Miyagawa; T Takao; Y Matsuoka; K Komori; H Kiuchi; K Fujita; T Hirai; P Tanjaptkul; A Okuyama; M Takeyama; K Matsumiya; H Fujioka JOURNAL OF UROLOGY 175 (4) 454 -455 2006年04月
  • 辻村 晃; 藤田 和利; Tanjapatkul Phanu; 平井 利明; 木内 寛; 小森 和彦; 松岡 庸洋; 高尾 徹也; 宮川 康; 高田 晋吾; 松宮 清美; 奥山 明彦 日本泌尿器科学会雑誌 97 (2) 259 -259 2006年
  • 藤田 和利; Tanjapatkul Phanu; 小森 和彦; 松岡 庸洋; 高尾 徹也; 宮川 康; 高田 晋吾; 辻村 晃; 松宮 清美; 大田 浩; 若山 照彦; 奥山 明彦 日本泌尿器科学会雑誌 97 (2) 265 -265 2006年
  • 小森 和彦; 辻村 晃; 高尾 徹也; 平井 利明; 植田 知博; 木内 寛; タンジャパトクル パヌ; 藤田 和利; 松岡 庸洋; 宮川 康; 高田 晋吾; 奥山 明彦 日本泌尿器科学会雑誌 97 (2) 437 -437 2006年
  • 平井 利明; 辻村 晃; 植田 知博; 木内 寛; パヌ タンジャパトクル; 小森 和彦; 藤田 和利; 松岡 庸洋; 高尾 徹也; 宮川 康; 高田 晋吾; 田中 宏光; 奥山 明彦 日本泌尿器科学会雑誌 97 (2) 520 -520 2006年
  • 宮川 康; 平井 利明; 植田 知博; 木内 寛; 小森 和彦; 藤田 和利; 松岡 庸洋; 高尾 徹也; 高田 晋吾; 辻村 晃; 田中 宏光; 西宗 義武; 奥山 明彦 日本泌尿器科学会雑誌 97 (2) 521 -521 2006年
  • 高田 晋吾; パヌ タンジャパクン; 平井 利明; 藤田 和利; 植田 知博; 木内 寛; 小森 和彦; 松岡 庸洋; 高尾 徹也; 宮川 康; 辻村 晃; 奥山 明彦; 宮崎 和典 日本泌尿器科学会雑誌 97 (2) 524 -524 2006年
  • 木内 寛; 平井 利明; 植田 知博; 小森 和彦; 藤田 和利; 松岡 庸洋; 高尾 徹也; 宮川 康; 高田 晋吾; 辻村 晃; 奥山 明彦; 山本 圭介; 竹山 政美 日本泌尿器科学会雑誌 97 (2) 376 -376 2006年
  • 選択的動脈塞栓術で治療した外傷牲持続勃起症の1例
    高尾 徹也; 平井 利明; 植田 知博; 木内 寛; Tanjapatkul Phanu; 小森 和彦; 藤田 和利; 松岡 庸洋; 宮川 康; 高田 晋吾; 辻村 晃; 奥山 明彦; 大須賀 慶悟; 中村 仁信; 松宮 清美 日本性機能学会雑誌 20 (3) 254 -254 2005年12月
  • 高田晋吾; タンジャパトクン パヌ; 平井利明; 藤田和利; 植田知博; 木内寛; 小森和彦; 松岡庸洋; 高尾徹也; 宮川康; 辻村晃; 奥山明彦; 大須賀慶悟; 中村仁信; 松宮清美 日本内分泌学会雑誌 81 (2) 498 2005年09月
  • A. Tsujimura; K. Komori; S. Ishijima; P. Tanjapatku; K. Fujita; Y. Matsuoka; T. Takao; Y. Miyagawa; S. Takada; A. Okuyama INTERNATIONAL JOURNAL OF ANDROLOGY 28 88 -88 2005年06月
  • S. Takada; A. Tsujimura; Y. Miyagawa; T. Takao; Y. Matsuoka; K. Komori; K. Fujita; P. Tanjapatkul; A. Okuyama; M. Koga; M. Takeyama; K. Maitsumiya; H. Fujioka INTERNATIONAL JOURNAL OF ANDROLOGY 28 96 -96 2005年06月
  • A Tsujimura; K Fujita; K Komori; Y Matsuoka; T Takahashi; T Takao; Y Miyagawa; S Takada; K Matsumiya; Y Osaki; N Oku; J Hatazawa; A Okuyama JOURNAL OF UROLOGY 173 (4) 339 -339 2005年04月
  • 宮川 康; 辻村 晃; 藤田 和利; 松岡 庸洋; 高橋 徹; 高尾 徹也; 高田 晋吾; 松宮 清美; 大崎 康宏; 高沢 正志; 奥 直彦; 畑澤 順; 奥山 明彦 日本泌尿器科学会雑誌 96 (2) 188 -188 2005年03月
  • 小森 和彦; 辻村 晃; 藤田 和利; 松岡 庸洋; 高尾 徹也; 宮川 康; 高田 晋吾; 松宮 清美; 奥山 明彦; 石島 純夫 日本泌尿器科学会雑誌 96 (2) 263 -263 2005年
  • 高田 晋吾; 藤田 和利; 小森 和彦; 松岡 庸洋; 高尾 徹也; 宮川 康; 辻村 晃; 松宮 清美; 奥山 明彦; 古賀 実; 竹山 政美; 藤岡 秀樹 日本泌尿器科学会雑誌 96 (2) 264 -264 2005年
  • 辻村 晃; 藤田 和利; 小森 和彦; 松岡 庸洋; 高尾 徹也; 宮川 康; 高田 晋吾; 松宮 清美; 太田 正穂; 勝山 善彦; 古賀 実; 藤岡 秀樹; 奥山 明彦 日本泌尿器科学会雑誌 96 (2) 221 -221 2005年
  • 藤田 和利; 小森 和彦; 松岡 庸洋; 高尾 徹也; 宮川 康; 高田 晋吾; 辻村 晃; 松宮 清美; 奥山 明彦; 大田 浩; 若山 照彦 日本泌尿器科学会雑誌 96 (2) 221 -221 2005年
  • A. Tsujimura; Y. Miyagawa; K. Fujita; Y. Matsuoka; T. Takahashi; T. Takao; K. Matsumiya; A. Okuyama; J. Hatazawa JOURNAL OF SEXUAL MEDICINE 1 44 -44 2004年11月
  • 古賀 実; 松本 穣; 野間 雅倫; 平井 利明; 竹山 政美; 藤田 和利; 松岡 庸洋; 高尾 徹也; 小森 和彦; 宮川 康; 高田 晋吾; 辻村 晃; 松宮 清美; 奥山 明彦 日本性機能学会雑誌 = The japanese journal of Impotence Research 19 (2) 167 -167 2004年08月
  • 山中 幹基; 吉岡 巌; 西村 憲二; 市川 靖二; 永野 俊介; 藤田 和利; 小森 和彦; 高尾 徹也; 松岡 庸洋; 宮川 康; 辻村 晃; 松宮 清美; 奥山 明彦; DAHIYA Rajvir 日本性機能学会雑誌 = The japanese journal of Impotence Research 19 (2) 197 -197 2004年08月
  • 辻村 晃; 宮川 康; 藤田 和利; 小森 和彦; 松岡 庸洋; 高橋 徹; 高尾 徹也; 松宮 清美; 大崎 康宏; 高沢 正志; 奥 直彦; 畑澤 順; 奥山 明彦 日本性機能学会雑誌 19 (2) 193 -193 2004年08月
  • K Matsumiya; A Tsujimara; K Fujita; Y Matsuoka; T Takahashi; T Takao; Y Miyagawa; M Koga; M Takeyama; H Fujioka; A Okuyama JOURNAL OF UROLOGY 171 (4) 418 -418 2004年04月
  • Y Miyagawa; A Tsujimura; K Fujita; Y Matsuoka; T Takahashi; T Takao; K Matsumiya; Y Osaki; M Takazawa; N Oku; J Hatazawa; A Okuyama JOURNAL OF UROLOGY 171 (4) 377 -377 2004年04月
  • T Takao; A Tsujimura; K Fujita; Y Matsuoka; T Takahashi; Y Miyagawa; K Matsumiya; A Okuyama JOURNAL OF UROLOGY 171 (4) 352 -352 2004年04月
  • Y Miyagawa; H Tanaka; K Fujita; Y Matsuoka; T Takahashi; T Takao; A Tsujimura; K Matsumiya; Y Nishimune; A Okuyama JOURNAL OF UROLOGY 171 (4) 371 -371 2004年04月
  • 宮川 康; 辻村 晃; 藤田 和利; 松岡 庸洋; 高橋 徹; 高尾 徹也; 松宮 清美; 大崎 康宏; 高沢 正志; 奥 直彦; 畑澤 順; 奥山 明彦 日本泌尿器科学会雑誌 95 (2) 341 -341 2004年03月
  • 古賀 実; 松本 穣; 野間 雅倫; 平井 利明; 竹山 政美; 藤田 和利; 高橋 徹; 松岡 庸洋; 高尾 徹也; 宮川 康; 辻村 晃; 松宮 清美; 奥山 明彦 日本泌尿器科学会雑誌 95 (2) 473 -473 2004年
  • 藤田 和利; 松岡 庸洋; 高橋 徹; 高尾 徹也; 宮川 康; 辻村 晃; 松宮 清美; 奥山 明彦; 古賀 実; 竹山 政美; 藤岡 秀樹 日本泌尿器科学会雑誌 95 (2) 517 -517 2004年
  • 辻川 浩三; 山本 暢朋; 藤田 和利; 菅尾 英木 西日本泌尿器科 65 (2) 51 -54 2003年02月
  • 藤田 和利; 辻川 浩三; 室崎 伸和; 菅尾 英木; 伊藤 裕啓; 高尾 徹也; 中井 康友; 三木 恒治 泌尿器科紀要 47 (8) 599 -604 2001年08月

産業財産権

受賞

  • 2021年12月 大阪大学医学部附属病院 大阪大学医学部附属病院病院長表彰論文賞最優秀論文賞
     Intratumoral and s.c. injection of inactivated hemagglutinating virus of Japan envelope (GEN0101) in metastatic castration-resistant prostate cancer.
  • 2021年12月 第109回日本泌尿器科学会総会 第109回日本泌尿器科学会総会 International Session Award
     A deep-learning-based system to diagnose tumor malignancy beyond classical morphological cytopathology techniques
  • 2021年12月 第109回日本泌尿器科学会総会 第109回日本泌尿器科学会総会 総会賞
     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
  • 2021年12月 International Journal of Urology Top Cited Article Award 2020
  • 2020年12月 International Journal of Urology IJU Top Cited Article Award of the Year 2019
     URINARY BIOMARKERS OF PROSTATE CANCER
  • 2017年06月 日本アンドロロジー学会 平成29年度日本アンドロロジー学会学術奨励賞
  • 2014年04月 日本泌尿器科学会 2014年度日本泌尿器科学会坂口賞
  • 2008年09月 The American Urological Association The Resident Prize Essay Contest of the 66th Annual Mid-Atlantic Meeting of the American Urological Association.
  • 2007年07月 日本アンドロロジー学会 第26回日本アンドロロジー学会賞
  • 2007年04月 日本泌尿器科学会 第14回日本泌尿器科学会学会賞
  • 2006年04月 日本泌尿器科学会 第94回日本泌尿器科学会総会総会賞
  • 2006年02月 泌尿器科分子・細胞研究会 第15回泌尿器分子細胞研究会研究奨励賞
  • 2005年11月 日本生殖医療学会 第50回日本生殖医療学会最優秀演題賞

共同研究・競争的資金等の研究課題

  • 日本学術振興会:科学研究費助成事業 基盤研究(C)
    研究期間 : 2023年04月 -2026年03月 
    代表者 : 藤田 和利
  • 日本学術振興会:科学研究費助成事業 基盤研究(B)
    研究期間 : 2022年04月 -2026年03月 
    代表者 : 野々村 祝夫; 柴 知史; 山田 拓司; 谷内田 真一; 松下 慎; 藤田 和利; 波多野 浩士; 岡田 随象; 中村 昇太
  • 日本学術振興会:科学研究費助成事業 基盤研究(C)
    研究期間 : 2022年04月 -2025年03月 
    代表者 : 波多野 浩士; 藤田 和利
  • 日本学術振興会:科学研究費助成事業 基盤研究(C)
    研究期間 : 2021年04月 -2024年03月 
    代表者 : 田中 宏光; 藤田 和利; 福原 慎一郎
     
    HASPINは、細胞分裂で機能するセリン/スレオニンキナーゼである。私たちは、家族性大腸がんの疾患モデルマウスにおいて、HASPIN阻害剤が際立った副作用なくポリープの形成を抑えること明らかにした。ここでは、前立腺がん疾患モデルマウスを用い、HASPIN阻害剤の抗がん作用機序を分子レベルで理解することにより、Evidence-Based Medicineに則った副作用の少ない細胞の新しい分子ターゲットに作用するがん治療薬の確立を目指す。今までに複数のHASPIN阻害剤が同定され、それら阻害剤を用いて様々なヒト由来のがん細胞(大腸、乳、皮膚、膵臓、肺、卵巣、膀胱、胆、などのがん)に対する増殖抑制効果が報告された。最新の国外の研究グループにより、HASPIN阻害剤が前立腺がんに対しても抗がん効果が示された。最新の研究成果を踏まえ、本年度私たちは、複数のヒト前立腺がん細胞ラインを入手し、それらの細胞に対してHASPIN阻害剤のうちCHR-6494の前立腺がん細胞に対する効果の解析を進めている。また、天然有機化合物のクメストロールがHASPINの機能を阻害することが報告された。一方、私たちは天然のHASPIN阻害剤であるクメストロールを多く含むモヤシの栽培法を開発した。そこで、in vitroで各種前立腺がん細胞に対するクメストロールの効果を解析し、さらに、クメストロールを多く含むモヤシを前立腺がん疾患モデルマウスに経口投与し抗がん作用を観察する。低濃度でHASPIN阻害効果を示す合成低分子化合物のCHR-6494結果とクメストロールの結果をもとに、抗がん作用の分子メカニズムについての詳細な解析のための計画とその準備を進めている。
  • 日本学術振興会:科学研究費助成事業 基盤研究(C)
    研究期間 : 2021年04月 -2024年03月 
    代表者 : 松下 慎; 藤田 和利
     
    我々は腸内細菌叢が前立腺癌の進展に与える影響とそのメカニズムについて、予定通りに研究を進め、高脂肪食接種前立腺癌マウスに抗生剤を経口投与すると、前立腺癌の増殖が抑制され、複数の短鎖脂肪酸産生菌が減少した。さらに、短鎖脂肪酸を投与することで抗生剤の癌増殖抑制効果が打ち消されるという実験結果から、腸内細菌代謝産物である短鎖脂肪酸がIGF-1を増加させることで癌細胞のMAPKやPI3Kを介して増殖を促進することを明らかにした。本内容は2021年8月にCancer Research誌にGut Microbiota-Derived Short-Chain Fatty Acids Promote Prostate Cancer Growth via IGF1 Signalingとして掲載された。 また、前立腺生検を受ける前立腺癌疑いの日本人男性152名の腸内細菌叢を16SリボソーマルRNA遺伝子解析を用いて同定し、生検結果や癌の悪性度に基づく層別化を行い比較した。その結果、高悪性度前立腺癌患者の腸内細菌叢ではAlistipesやLachnospiraといった短鎖脂肪酸産生菌が有意に増加していることや、腸内細菌叢の構成から算出される独自のスコアリングシステムにより、高悪性度の前立腺癌患者をPSAよりも高精度に判別できることを明らかにした。このスコアについては独立したテストコホートにおいても高精度な判別能を有することが確認された。本内容は2021年8月にThe gut microbiota associated with high-Gleason prostate cancerとしてCancer Science誌に掲載された。 2021年度に得られた結果は前立腺癌の進展において腸内細菌叢との関連が存在することを示唆していると考える。

委員歴

  • 2023年01月 - 現在   一般社団法人大阪透析研究会   一般社団法人大阪透析研究会評議員
  • 2022年10月 - 現在   大阪府医師会   大阪府医師会医学会評議員
  • 2022年06月 - 現在   大阪泌尿器臨床医会   大阪泌尿器臨床医会学術委員長
  • 2021年06月 - 現在   日本泌尿器科学会   日本泌尿器科学会雑誌編集幹事
  • 2021年06月 - 現在   International Journal of Urology   編集幹事
  • 2021年01月 - 現在   日本癌学会   評議員
  • 2018年03月 - 現在   泌尿器科分子・細胞研究会   評議員
  • 2016年10月 - 現在   日本性機能学会   代議員
  • 2016年06月 - 現在   日本アンドロロジー学会   評議員
  • 2016年05月 - 現在   日本泌尿器科内視鏡学会   代議員
  • 2017年06月 - 2019年05月   日本泌尿器科学会雑誌   編集幹事
  • 2017年06月 - 2019年05月   International Journal of Urology   編集幹事
  • 2015年06月 - 2017年05月   日本泌尿器科学会雑誌   編集主幹
  • 2015年06月 - 2017年05月   International Journal of Urology   編集主幹

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