髙橋 克之 (タカハシ カツユキ)

  • 薬学部 医療薬学科 講師
Last Updated :2024/02/02

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

    がん専門薬剤師・がん指導薬剤師としての臨床経験を活かし、抗がん剤やその副作用管理に関する 薬学的問題を解決し、より良いがん治療の提供に繋がる研究に取り組んでいます。

研究者情報

学位

  • 博士(医学)(2016年03月 大阪市立大学)

ホームページURL

科研費研究者番号

  • 10597751

J-Global ID

研究キーワード

  • 臨床薬学   抗癌剤耐性   分子シャペロン   熱ショックタンパク質   シャペロン   プロテオミクス   

現在の研究分野(キーワード)

    がん専門薬剤師・がん指導薬剤師としての臨床経験を活かし、抗がん剤やその副作用管理に関する
    薬学的問題を解決し、より良いがん治療の提供に繋がる研究に取り組んでいます。

研究分野

  • ライフサイエンス / 医療薬学
  • ライフサイエンス / 腫瘍診断、治療学

経歴

  • 2023年12月 - 現在  大阪公立大学医学部 医療の質・安全管理学講座客員研究員
  • 2022年04月 - 現在  大阪公立大学医学部非常勤講師
  • 2022年04月 - 現在  近畿大学薬学部 医療薬学科講師

所属学協会

  • 日本臨床腫瘍学会   日本医療薬学会   日本薬学会   日本臨床腫瘍薬学会   

研究活動情報

論文

  • Masaya Takahashi; Katsuyuki Takahashi; Hiroyasu Kaneda; Tomoya Kawaguchi; Toru Otori; Yasutaka Nakamura
    Oncology 2023年12月 [査読有り]
     
    Introduction Febrile neutropenia (FN) is an oncologic emergency requiring immediate empiric antibiotic therapy. Although carboplatin plus etoposide combination chemotherapy is associated with a relatively high frequency of FN, the risk factors are unclear. Hence, this retrospective study aimed to identify predictive markers of carboplatin/etoposide-induced FN. Methods We conducted a retrospective cohort analysis of patients with previously untreated small-cell lung cancer who received combination chemotherapy with carboplatin (area under the concentration curve: 5 mg/mL·min, day 1) and etoposide (80 or 100 mg/m2, days 1-3) between July 2007 and June 2022. FN was assessed during the 21 days after initiation of carboplatin and etoposide therapy according to the Japanese Society of Medical Oncology's definition. Fisher's exact test for categorical variables and Mann-Whitney U-test for continuous variables were used to compare the two groups. Statistical significance was set at p values <0.05. Explanatory variables with p values <0.05 in the univariate analysis were included in the multivariate logistic regression analysis. Results Among the 176 eligible patients, the incidence of FN during the first cycle of chemotherapy was 25.0% (44/176). Multivariate analysis revealed that co-administration of proton pump inhibitors (PPIs) or potassium-competitive acid blockers (PCABs) and body mass index (BMI) were significantly associated with FN (p=0.0035 and 0.0011, respectively). Patients with both co-administration of PPIs or PCABs and a BMI ≤22.509 kg/m2 presented with significantly higher frequencies of FN compared with the other patients (13/24 [54.2%] vs. 31/152 [20.4%] patients; odds ratio: 4.56, 95% confidence interval: 1.70-12.48; p=0.00147). Conclusion Patients who received carboplatin plus etoposide for SCLC with co-administration of PPIs or PCABs and a BMI ≤22.509 kg/m2 more frequently present with FN than those without the two factors.
  • Satoshi Dote; Eiji Shiwaku; Emiko Kohno; Ryohei Fujii; Keiji Mashimo; Naomi Morimoto; Masaki Yoshino; Naoki Odaira; Hiroaki Ikesue; Masaki Hirabatake; Katsuyuki Takahashi; Masaya Takahashi; Mari Takagi; Satoshi Nishiuma; Kaori Ito; Akane Shimato; Shoji Itakura; Yoshitaka Takahashi; Yutaka Negoro; Mina Shigemori; Hiroyuki Watanabe; Dai Hayasaka; Masahiko Nakao; Misaki Tasaka; Emi Goto; Noriaki Kataoka; Ayako Yokomizo; Ayako Kobayashi; Yoko Nakata; Mafumi Miyake; Yaeko Hayashi; Yoshie Yamamoto; Taiki Hirata; Kanako Azuma; Katsuya Makihara; Rino Fukui; Akira Tokutome; Keiji Yagisawa; Shinji Honda; Yuji Meguro; Shota Suzuki; Daisuke Yamaguchi; Hitomi Miyata; Yuka Kobayashi
    International journal of clinical oncology 28 8 1054 - 1062 2023年08月 [査読有り]
     
    BACKGROUND: The association between prior bevacizumab (BEV) therapy and ramucirumab (RAM)-induced proteinuria is not known. We aimed to investigate this association in patients with metastatic colorectal cancer (mCRC). METHODS: mCRC patients who received folinic acid, fluorouracil, and irinotecan (FOLFIRI) plus RAM were divided into with and without prior BEV treatment groups. The cumulative incidence of grade 2-3 proteinuria and rate of RAM discontinuation within 6 months (6M) after RAM initiation were compared between the two groups. RESULTS: We evaluated 245 patients. In the Fine-Gray subdistribution hazard model including prior BEV, age, sex, comorbidities, eGFR, proteinuria ≥ 2 + at baseline, and later line of RAM, prior BEV treatment contributed to proteinuria onset (P < 0.01). A shorter interval between final BEV and initial RAM increased the proteinuria risk; the adjusted odds ratios (95% confidence intervals) for the intervals of < 28 days, 28-55 days, and > 55 days (referring to prior BEV absence) were 2.60 (1.23-5.51), 1.51 (1.01-2.27), and 1.04 (0.76-1.44), respectively. The rate of RAM discontinuation for ≤ 6M due to anti-VEGF toxicities was significantly higher in the prior BEV treatment group compared with that in the no prior BEV treatment group (18% vs. 6%, P = 0.02). Second-line RAM discontinuation for ≤ 6M without progression resulted in shorter overall survival of 132 patients with prior BEV treatment (P < 0.01). CONCLUSION: Sequential FOLFIRI plus RAM after BEV failure, especially within 55 days, may exacerbate proteinuria. Its escalated anti-VEGF toxicity may negatively impact the overall survival.
  • R Harabayashi; M Takahashi; K Takahashi; T Sugimoto; J Uchida; Y Nakamura; K Nagayama
    Die Pharmazie 78 5 47 - 50 2023年05月 [査読有り]
     
    Cyclosporine (CyA) and atorvastatin (AT) are often administered concomitantly to treat dyslipidemia in renal transplant recipients. However, CyA greatly increases the plasma concentration of AT; therefore, concomitant use might increase the frequency of statin-induced adverse effects. The aim of this study was to investigate whether concomitant use of CyA and AT increases intolerance of the latter agent in Japanese renal transplantation recipients. We performed a retrospective cohort analysis of renal transplant recipients aged 18 years and older who had concomitantly received AT and CyA, or tacrolimus (Tac) therapy. We defined statin intolerance as a decrease in dose or discontinuation of AT due to adverse effects. We evaluated the incidence of statin intolerance in concomitant therapy with CyA for 100 days after the initial administration of AT in comparison with Tac. A total of 144 renal transplant recipients who received AT and CyA, or Tac between January 2013 and December 2019 were included. There was no statistical difference in the incidence of statin intolerance in both the CyA (1.8%; 1/57 patients) and Tac (3.4%; 3/87 patients) groups. Concomitant use of CyA and AT might not increase the incidence of statin intolerance in Japanese renal transplant recipients.
  • Masahito Shibano; Katsuyuki Takahashi; Masaya Takahashi; Sawako Uchida-Kobayashi; Norifumi Kawada; Yasutaka Nakamura; Toru Otori; Katsuya Nagayama
    Anticancer research 42 12 6019 - 6026 2022年12月 [査読有り]
     
    BACKGROUND/AIM: Lenvatinib (LEN) has been approved as an oral tyrosine kinase inhibitor for advanced hepatocellular carcinoma (HCC). However, in some patients, LEN does not provide adequate therapeutic benefits. In this study, we examined the factors that affect the therapeutic response to LEN. PATIENTS AND METHODS: This retrospective cohort study involved patients with HCC who received LEN therapy at Osaka Metropolitan University Hospital. We used the delivered dose intensity to body surface area ratio for 60 days (2M-DBR) as an index of the therapeutic response. RESULTS: This study included 83 patients divided into two groups, the high 2M-DBR group (47 patients, 56.7%) and low 2M-DBR group (36 patients, 43.4%). Univariate analysis showed that Child-Pugh class, C-reactive protein, and prognostic nutrition index (PNI) were significant factors for high 2M-DBR. Furthermore, multivariate logistic regression analysis revealed that a PNI>39.15 was significantly associated with high 2M-DBR. CONCLUSION: A PNI cut-off value of less than 39.15 may indicate a poor response to LEN therapy. PNI, an easy, simple, and inexpensive tool, may be useful in identifying patients in need of early intervention.
  • カペシタビンと胃酸分泌抑制薬の薬物間相互作用の解明に向けた多施設共同臨床研究及び基礎研究
    河添 仁; 北爪 賀子; 魚住 龍史; 吉澤 朝枝; 飯原 大稔; 藤井 宏典; 高橋 正也; 新井 隆広; 村地 康; 佐藤 由美子; 三上 貴弘; 橋口 宏司; 山崎 朋子; 高橋 克之; 藤田 行代志; 細川 祐岐; 諸角 一成; 土屋 雅美; 横山 敦; 橋本 浩伸; 山口 正和; 古川 哲也; 関口 真由; 平井 光成; 秋山 雅博; 金 倫基; 中村 智徳
    医療の広場 62 10 11 - 14 (公財)政策医療振興財団 2022年10月
  • Hitomi Nakatsukasa; Masaya Takahashi; Katsuyuki Takahashi; Tsutomu Takashima; Yuka Asano; Tamami Morisaki; Shinichiro Kashiwagi; Satoru Noda; Yasutaka Nakamura
    Biological & pharmaceutical bulletin 45 10 1476 - 1481 2022年10月 [査読有り]
     
    The cyclin-dependent kinase (CDK) 4/6 inhibitors, palbociclib and abemaciclib, have been approved in Japan. However, the selection criteria for these drugs have not been established. Hence, we aimed to identify the risk factors for CDK4/6 inhibitor-induced intolerable adverse events requiring dose reduction or therapy cessation and to establish useful markers for choosing the appropriate CDK4/6 inhibitor, based on the incidence of the intolerable adverse events. This retrospective cohort analysis included patients with advanced breast cancer who received 125 mg/d palbociclib or 300 mg/d abemaciclib. We defined significant adverse events (SAEs) as side effects requiring dose reduction or therapy cessation. Thirty-six percent of the patients who received palbociclib (9/25) and 27.3% of those who received abemaciclib (9/33) experienced SAEs. In palbociclib and abemaciclib groups, baseline white blood cell (WBC) counts and serum albumin (ALB) levels, respectively, were significantly lower in patients who experienced SAEs than in those who did not (palbociclib: p = 0.007; abemaciclib: p = 0.004). According to the receiver operating characteristic curve analysis, the optimal cutoff values for baseline WBC count and ALB level were 5700/µL and 4.0 g/dL, respectively. Among patients with ALB levels >4.0 g/dL, the incidence of abemaciclib-induced SAEs was significantly lower than that of the palbociclib-induced SAEs (1/17 (5.9%) vs. 6/14 (42.9%), odds ratio: 11.0, 95% confidence interval: 1.07-583, p = 0.0281). Thus, a baseline WBC count ≤5700/µL and ALB level ≤4.0 g/dL may be risk factors for palbociclib and abemaciclib-induced SAEs, respectively. Also, high ALB levels can serve as a useful marker for choosing abemaciclib.
  • Tomoko Yamazaki; Ryuji Uozumi; Hitoshi Kawazoe; Yoshiko Kitazume; Hirotoshi Iihara; Hironori Fujii; Masaya Takahashi; Takahiro Arai; Yasushi Murachi; Yumiko Sato; Takahiro Mikami; Koji Hashiguchi; Tomoe Yoshizawa; Katsuyuki Takahashi; Yukiyoshi Fujita; Yuki Hosokawa; Issei Morozumi; Masami Tsuchiya; Atsushi Yokoyama; Hironobu Hashimoto; Tetsuya Furukawa
    Journal of Cancer 13 10 3073 - 3083 2022年08月 [査読有り]
     
    Background: The association between the effectiveness of capecitabine and the concomitant administration of gastric acid suppressants remains controversial. We aimed to clarify whether the effectiveness of capecitabine is affected by the co-administration of histamine H2 receptor antagonists (H2RAs) in early-stage colorectal cancer (CRC) patients using real-world data. Methods: This multicenter, retrospective, observational study included consecutive patients with stage II-III CRC who received either capecitabine monotherapy or the CapeOX regimen (capecitabine and oxaliplatin) as adjuvant therapy between January 2009 and December 2014 in Japan. Relapse-free survival (RFS) and overall survival were estimated using the Kaplan-Meier method. Additionally, multivariable Cox proportional hazards model, propensity score adjustment, and inverse probability of treatment weighting analyses were performed. Results: In total, 552 patients were included in this study, of which 30 were co-administered H2RAs. RFS at five years was 76.7% (95% confidence interval [CI]: 57.2-88.1%) and 79.8% (95% CI: 76.0-83.0%) in the H2RA and non-H2RA groups, respectively. Multivariable Cox proportional hazards model and propensity score-adjusted analyses showed that the co-administration of H2RAs was associated with a poor RFS among those receiving capecitabine monotherapy (hazard ratio [HR], 2.01; 95% CI: 0.86-4.70 and HR, 1.81; 95% CI: 0.77-4.22, respectively). In contrast, these results were inconsistent with the group receiving the CapeOX regimen. Conclusions: The study findings suggest that the co-administration of H2RAs may not reduce the effectiveness of capecitabine therapy in patients with early-stage CRC. To confirm this relationship, a prospective study with a pharmacokinetic approach is needed.
  • 食道がんに対するドセタキセル+シスプラチン+フルオロウラシル療法における 急性腎障害発症の予測因子の検討
    古原 優也; 髙橋 克之; 豕瀬 諒; 髙橋 正也; 永山 勝也
    医療薬学 48 6 259 - 266 2022年06月 [査読有り]
  • Mayuko Osada-Oka; Hikaru Kuwamura; Risa Imamiya; Keiko Kobayashi; Yukiko Minamiyama; Katsuyuki Takahashi; Masako Tanaka; Masayuki Shiota
    European journal of pharmacology 920 174845 - 174845 2022年04月 [査読有り]
     
    Hypoxia-inducible factor-1α (HIF-1α) and p53 are involved in anticancer drug resistance under hypoxic conditions. Here, we found that the cytotoxicity of anticancer drugs (doxorubicin, gemcitabine, and cisplatin) was lower at 1% O2 than at 5% O2. We examined the effects of these drugs on HIF-1α and p53 expression under different hypoxic oxygen concentrations. At 5% O2, the drugs decreased HIF-1α expression and increased p53 levels. At 1% O2, the drugs increased HIF-1α expression but did not alter p53 levels. When the HIF-1α protein was stabilized by DMOG under normoxic conditions, doxorubicin did not increase the level of p53 expression. These results show that the maintenance of HIF-1α expression blocked doxorubicin-dependent increases in p53 expression. We hypothesized the mechanism of HIF-1α protein translation might be different between at 5% and at 1% O2, because many reports indicate that the same mechanism of HIF-1α protein stabilization occurs under hypoxic conditions, such as 5% and 1% O2. The level of phosphorylated-4E-BP1, which causes translation of HIF-1α, was higher at 1% O2 than at 5% O2. Our results suggest that the sensitivity of tumor cells to anticancer drugs is dependent oxygen concentrations under hypoxic conditions, and involves 4E-BP1-dependent stabilization of the HIF-1α protein.
  • Ryo Inose; Katsuyuki Takahashi; Masaya Takahashi; Takashi Sugimoto; Satoru Nanno; Masayuki Hino; Katsuya Nagayama
    Transplant infectious disease : an official journal of the Transplantation Society e13804  2022年02月 [査読有り]
     
    BACKGROUND: Foscarnet is an important drug for the treatment of cytomegalovirus infection in patients undergoing hematopoietic stem cell transplantation (HSCT). Foscarnet is often discontinued because of the development of acute kidney injury (AKI). Thus, the identification of factors leading to the development of AKI is beneficial. This study aimed to investigate the incidence of AKI and the factors influencing AKI development in HSCT patients treated with foscarnet. METHODS: This was a retrospective observational study. Patients who underwent HSCT and received foscarnet at the Department of Hematology, Osaka City University Hospital, were identified from medical records. The patients were classified into AKI and non-AKI groups, and the risk factors associated with AKI were evaluated. For continuous variables, receiver-operating characteristic (ROC) curve analysis was used to calculate the optimal cutoff value. RESULTS: Thirty-five patients (47 cases) were assigned to the AKI (51.1%, 24/47) and non-AKI groups (48.9%, 23/47). The AKI group had a significantly longer foscarnet administration period than the non-AKI group (p = 0.049). The appropriate cutoff value for the foscarnet administration period using the ROC curve was 27 days. The incidence of AKI was significantly higher in cases who received foscarnet for more than 27 days (11/14, 78.6%) compared to those who received less than 27 days (13/33, 39.4%) (odds ratio: 5.64, 95% confidence interval 1.32-24.2, p = 0.024). CONCLUSION: The incidence of AKI was 51.1% in HSCT patients treated with foscarnet, and foscarnet administration for more than 27 days may be associated with the incidence of AKI.
  • Masaya Takahashi; Katsuyuki Takahashi; Kazuya Muguruma; Masaichi Ohira; Katsuya Nagayama
    International journal of clinical oncology 27 2 348 - 353 2022年02月 [査読有り]
     
    BACKGROUND: It is known that the area under the plasma concentration curve of nedaplatin (AUCNDP) is associated with the relative reduction ratio of platelets and that the AUCNDP is based on nedaplatin dose normalized by creatinine clearance (CrCL) (AUCdose/CrCL). Based on these relationships, in this retrospective study, we aimed to determine the unestablished doseNDP safe for patients with impaired renal function who received an initial combination chemotherapy with nedaplatin and 5-fluorouracil. METHODS: We performed a retrospective cohort analysis of consecutive patients with esophageal cancer who received an initial combination chemotherapy with ≤ 90 mg m-2 day-1 of nedaplatin on day 1 and 800 mg m-2 day-1 of 5-fluorouracil on days 1-5. AUCdose/CrCL was estimated using the formula, 3.2134 × doseNDP/CrCL + 4.4185. Data obtained during the first 28 days following nedaplatin administration were analyzed to compare AUCdose/CrCL between the patients with and without grade ≥ 3 thrombocytopenia. Receiver-operating characteristic (ROC) curve analysis was performed to determine the optimal AUCdose/CrCL cutoff value. RESULTS: Of the 136 patients included in this study, 8 (5.9%) presented with grade ≥ 3 thrombocytopenia. There were statistically significant differences in the AUCdose/CrCL between the patients with and those without grade ≥ 3 thrombocytopenia (11.79 vs. 10.09 µg h-1 mL-1; P = 0.00828). We found that the appropriate cutoff value for the AUCdose/CrCL using the ROC curve was 10.945 µg h-1 mL-1. CONCLUSIONS: Our results indicate that safe doseNDP should be estimated to satisfy the following formula: DoseNDP (mg) < CrCL × 2.031.
  • Yoshiko Kitazume; Hitoshi Kawazoe; Ryuji Uozumi; Tomoe Yoshizawa; Hirotoshi Iihara; Hironori Fujii; Masaya Takahashi; Takahiro Arai; Yasushi Murachi; Yumiko Sato; Takahiro Mikami; Koji Hashiguchi; Tomoko Yamazaki; Katsuyuki Takahashi; Yukiyoshi Fujita; Yuki Hosokawa; Issei Morozumi; Masami Tsuchiya; Atsushi Yokoyama; Hironobu Hashimoto; Masakazu Yamaguchi
    Scientific Reports 12 1 2022年01月 [査読有り]
     
    Abstract The association between capecitabine efficacy and proton pump inhibitors (PPIs) is controversial. Here, we determined whether co-administration of PPIs affects the real-world effectiveness of capecitabine. This retrospective observational study included consecutive patients with stage II–III colorectal cancer (CRC) who received adjuvant capecitabine monotherapy or CapeOX (capecitabine and oxaliplatin) between January 2009 and December 2014 at nine participating institutions. The primary endpoint was the difference in relapse-free survival (RFS) between patients who received PPIs and those who did not and was estimated using the Kaplan–Meier method. Overall survival (OS) was the secondary endpoint. Multivariable analysis of RFS and OS was performed using a Cox proportional hazards model, propensity score adjustment, and inverse probability of treatment weighting (IPTW) analyses. Data from 606 patients were evaluated, 54 of whom had received a PPI. PPI-treated patients tended to have poorer RFS and OS than patients treated without PPIs. The hazard ratio for RFS with capecitabine monotherapy was 2.48 (95% confidence interval: 1.22–5.07). These results were consistent with sensitivity analyses performed using propensity score adjustment and IPTW methods. Co-administration of PPIs may reduce the effectiveness of capecitabine and negatively impact patients with stage II–III CRC.
  • Masaya Takahashi; Katsuyuki Takahashi; Hiroyasu Kaneda; Tomoya Kawaguchi; Katsuya Nagayama
    Anticancer research 41 11 5729 - 5737 2021年11月 [査読有り]
     
    BACKGROUND/AIM: This study aimed to identify the predictive markers for carboplatin-induced severe thrombocytopenia. PATIENTS AND METHODS: We conducted a retrospective cohort analysis of inpatients who received carboplatin and pemetrexed. RESULTS: Among the 106 eligible patients, the incidence rate of grade ≥3 thrombocytopenia was 29.2% (31/106). Multivariate analysis revealed that grade ≥3 thrombocytopenia was associated with platelet count ≤26.6×104/mm3 [odds ratio (OR)=24.70, 95% confidence interval (CI)=5.75-106.00; p<0.001], neutrophil/lymphocyte ratio (NLR) >2.856 (OR=15.10, 95%CI=2.89-78.60; p=0.0013) and prognostic nutritional index ≤42.511 (OR=6.25, 95%CI=1.53-25.60; p=0.011). In particular, patients with both platelet counts ≤26.6×104/mm3 and NLR >2.856 presented with significantly higher frequencies of thrombocytopenia compared to those without these two factors [23/34 patients (67.6%) vs. 8/72 patients (11.1%), OR=16.1, 95%CI=5.40-53.6; p<0.001]. CONCLUSION: Platelet counts ≤26.6×104/mm3 and NLR >2.856 are predictive markers for carboplatin-induced thrombocytopenia.
  • Wataru Goto; Shinichiro Kashiwagi; Yuka Asano; Koji Takada; Tamami Morisaki; Katsuyuki Takahashi; Hisakazu Fujita; Masatsune Shibutani; Ryosuke Amano; Tsutomu Takashima; Shuhei Tomita; Kosei Hirakawa; Masaichi Ohira
    BMC cancer 20 1 1215 - 1215 2020年12月 [査読有り]
     
    BACKGROUND: Iron is required for the proliferation of cancer cells, and its depletion suppresses tumor growth. Eribulin mesylate (eribulin), a non-taxane microtubule inhibitor, disrupts the tumor microenvironment via vascular remodeling and obstruction of the epithelial-mesenchymal transition (EMT). Herein, we investigated the effects of the iron chelator on tumor-related properties of breast cancer cells and the effects of iron chelator plus eribulin on tumor growth in vivo. METHODS: Two triple-negative breast cancer (TNBC) cell lines, MDA-MB-231 and BT-549, and one hormone-receptor positive breast cancer cell line, MCF-7, were used in our study. Cell proliferation, cell migration, cell cycle position, and gene expression were analyzed via MTT assays, wound-healing assays, flow cytometry, and quantitative real-time-polymerase chain reaction, respectively. For the in vivo experiments, mice with breast cancer xenografts were treated with the inhibitors, alone or together, and tumor volume was determined. RESULTS: Iron chelator inhibited breast cancer cell proliferation and decreased the proportion of S-phase cells. Conversely, it induced hypoxia, angiogenesis, EMT, and immune checkpoints, as determined by quantifying the expression of marker mRNAs in MDA-MB-231 and MCF-7 cells. Eribulin suppressed the expression of the hypoxia and EMT related marker mRNAs in the presence of iron chelator. Iron chelator plus eribulin inhibited tumor growth in vivo to a greater extent than did either inhibitor alone. CONCLUSIONS: Although iron chelator induces oncogenic events (hypoxia, angiogenesis, EMT, and immune checkpoints), it may be an effective treatment for breast cancer when administered in combination with eribulin.
  • Koji Takada; Shinichiro Kashiwagi; Yuka Asano; Wataru Goto; Tamami Morisaki; Katsuyuki Takahashi; Masatsune Shibutani; Ryosuke Amano; Tsutomu Takashima; Shuhei Tomita; Kosei Hirakawa; Masaichi Ohira
    Oncology letters 20 5 180 - 180 2020年11月 [査読有り]
     
    Currently, when determining treatment regimens, there is an emphasis on the quality of life (QOL), in addition to treatment efficacy. Especially in hormone receptor-positive breast cancer with distant metastases, unless death is imminent, a common first-line treatment is endocrine therapy, which has fewer side effects. In the present study, the differences in QOL were evaluated based on the age and prognostic indicators of 46 patients with hormone receptor-positive breast cancer with distant metastases (stage IV), who received first-line endocrine therapy at the Osaka City University Hospital (Osaka, Japan) between November 2007 and November 2016. QOL score before and after endocrine therapy was retrospectively analyzed, using the Quality of Life Questionnaire for Cancer Patients Treated with Anti-Cancer Drugs-Breast (QOL-ACD-B). There was no significant association between age and any of the clinicopathological features investigated. However, the QOL score of the elderly patient group was significantly higher compared with that of the younger group in the 'Satisfaction with treatment and coping with disease' subcategory (P=0.008). The QOL score of the younger age group in the same subcategory was significantly improved by the treatment (P=0.013). The patients that had an increased overall QOL score 3 months after treatment initiation had a significant extension of progression-free survival (PFS) rate compared to the patients with decreased or no change in QOL (P=0.032). In conclusion, psychological stress was more prominent in younger patients with stage IV breast cancer treated with hormonal therapy compared with elderly patients. Importantly, improving QOL within the 3 months after treatment initiation could lead to longer PFS rate.
  • Yuka Asano; Shinichiro Kashiwagi; Wataru Goto; Koji Takada; Katsuyuki Takahashi; Masatsune Shibutani; Ryosuke Amano; Tsutomu Takashima; Shuhei Tomita; Kosei Hirakawa; Masaichi Ohira
    Molecular and clinical oncology 13 2 195 - 202 2020年08月 [査読有り]
     
    The tumor immune environment not only modulates the effects of immunotherapy, but also the effects of other anticancer drugs and treatment outcomes. These immune responses may be evaluated by measuring tumor-infiltrating lymphocytes (TILs), which has been frequently verified clinically. In the present study, the prediction of the therapeutic effect of endocrine therapy by TILs on stage IV breast cancer was clinically analyzed. Data from 40 patients who underwent endocrine therapy as the initial drug therapy for stage IV breast cancer were used. The correlation between TILs, evaluated according to standard methods, and prognosis, including the efficacy of endocrine therapy, was investigated retrospectively. Patients with ≥50% lymphocytic infiltration were considered to have lymphocyte-predominant breast cancer (LPBC). An analysis of outcomes revealed no difference in progression-free survival (PFS; P=0.171), time to treatment failure (TTF; P=0.054), or overall survival (OS; P=0.641) between the high TIL (>10%) and low TIL (≤10%) groups. Patients with LPBC (≥50%) exhibited a significant prolongation of PFS (P=0.005, log-rank), TTF (P=0.001) and OS (P=0.027) compared with non-LPBC patients. On receiver operating characteristics (ROC) curve analysis, better results were obtained with LPBCs [area under the curve (AUC)=0.700] than with TILs (AUC=0.606). The present findings suggest that a high level of lymphocytic infiltration in the tumor stroma may serve as a predictor of the therapeutic efficacy of endocrine therapy in patients with stage IV estrogen receptor-positive breast cancer.
  • Masaya Takahashi; Katsuyuki Takahashi; Saya Matsumoto; Tsutomu Takashima; Yuka Asano; Tamami Morisaki; Shinichiro Kashiwagi; Satoru Noda; Naoyoshi Onoda; Masaichi Ohira; Katsuya Nagayama
    Anticancer research 40 7 4047 - 4051 2020年07月 [査読有り]
     
    BACKGROUND/AIM: Infusion reactions (IRs) often occur with trastuzumab. Although premedication by non-steroidal anti-inflammatory drugs can be effective to a certain extent, IRs are still common and infrequently severe. Therefore, a predictive marker that can select patients requiring further prophylaxis is useful for appropriate prevention, but remains unclear. PATIENTS AND METHODS: We conducted a retrospective analysis for 136 consecutive female inpatients aged 18 years and older who received 8 mg/kg of the initial trastuzumab administration for breast cancer with a 25-mg dose of rectal diclofenac before trastuzumab infusion between May 2007 and April 2019, in order to assess IRs. RESULTS: Overall, 57 patients were eligible for inclusion in the study. IRs were observed in 17.5% (10/57) of the patients. Univariate analysis showed that patients with a low eosinophil percentage (≤2%) were associated with IRs (p=0.016). CONCLUSION: A low eosinophil percentage can be a useful new predictive marker for trastuzumab-induced IRs in patients with breast cancer.
  • Koji Takada; Shinichiro Kashiwagi; Yuka Asano; Wataru Goto; Tamami Morisaki; Katsuyuki Takahashi; Hisakazu Fujita; Tsutomu Takashima; Shuhei Tomita; Kosei Hirakawa; Masaichi Ohira
    BMC cancer 20 1 513 - 513 2020年06月 [査読有り]
     
    BACKGROUND: Invasion is often found during postoperative pathological examination of cases diagnosed as ductal carcinoma in situ (DCIS) by histological examinations such as core needle biopsy (CNB) or vacuum-assisted biopsy (VAB). A meta-analysis reported that 25.9% of invasive ductal carcinoma (IDC) cases are preoperatively diagnosed by CNB as DCIS. Risk factors for invasion have been studied by postoperative examination, but no factors have been found that could be obtained preoperatively from blood tests. In this study, we investigated factors predictive of invasion based on preoperative blood tests in patients diagnosed with DCIS by preoperative biopsy. METHODS: In this study, 118 patients who were diagnosed with DCIS by preoperative biopsy were included. Biopsies were performed with 16-gauge CNB or VAB. Peripheral blood was obtained at the time of diagnosis. This study evaluated absolute platelet count, absolute lymphocyte count, lactate dehydrogenase, carcinoembryonic antigen, and cancer antigen 15-3 (CA15-3). The platelet-lymphocyte ratio (PLR) was calculated by dividing the absolute platelet count by the absolute lymphocyte count, and patients were grouped into high PLR (≥160.0) and low PLR (< 160.0) groups. RESULTS: Invasion was found more frequently after surgery in pathologically high-grade cases than in pathologically not-high-grade cases (p = 0.015). The median PLR was 138.9 and 48 patients (40.7%) were classified into the high PLR group. The high PLR group was significantly more likely to have invasion detected by the postoperative pathology than the low PLR group (p = 0.018). In multivariate analysis of factors predictive of invasion in postoperative pathology, a high PLR (p = 0.006, odds ratio [OR] = 3.526) and biopsy method (VAB vs. CNB, p = 0.001, OR = 0.201) was an independent risk factor. CONCLUSIONS: The PLR may be a predictor of invasion in the postoperative pathology for patients diagnosed with DCIS by preoperative biopsy.
  • Masaya Takahashi; Katsuyuki Takahashi; Ryo Inose; Takashi Sugimoto; Hideo Koh; Masayuki Hino; Katsuya Nagayama
    Transplant infectious disease : an official journal of the Transplantation Society 22 1 e13239  2020年02月 [査読有り]
     
    BACKGROUND: Concomitant use of foscarnet and intravenous pentamidine can very frequently cause severe hypocalcemia. However, it is unknown whether aerosolized pentamidine has a similar adverse interaction with foscarnet. The present study was aimed at examining the safety profile of concomitantly used foscarnet and aerosolized pentamidine in patients receiving allogeneic hematopoietic stem cell transplantation. METHODS: Data from allogeneic hematopoietic stem cell recipients who had been administered foscarnet therapy for over 7 days were analyzed. We compared electrolyte abnormalities and serum creatinine level between patients who received aerosolized pentamidine concomitantly and those who did not. RESULTS: A total of 84 consecutive patients and 135 episodes of foscarnet therapy between May 2011 and April 2016 were evaluable. Of these 135 episodes, 25 episodes of therapy included concurrent therapy with 300 mg dose of aerosolized pentamidine once a month (pentamidine group) and 110 episodes did not (non-pentamidine group). The incident rates of grade 3/4 hypocalcemia did not significantly differ between the pentamidine and non-pentamidine groups (P = .207; 0/25 [0%] vs 10/110 [9.1%], respectively). In addition, we observed no significant difference in the incident rates of grade 3/4 serum creatinine increase between the two groups (P = 1.00; 0/25 [0%] vs 4/110 [3.6%], respectively). CONCLUSION: Our results suggest that the drug interactions between foscarnet and aerosolized pentamidine may not be clinically significant.
  • Koji Takada; Shinichiro Kashiwagi; Yuka Asano; Wataru Goto; Katsuyuki Takahashi; Masatsune Shibutani; Ryosuke Amano; Tsutomu Takashima; Shuhei Tomita; Kosei Hirakawa; Masaichi Ohira
    Anticancer research 39 10 5581 - 5588 2019年10月 [査読有り]
     
    BACKGROUND/AIM: The utility of peripheral blood neutrophil-to-lymphocyte ratios (NLRs) and platelet-to-lymphocyte ratios (PLRs) as prognostic predictors of surgery and chemotherapy in breast cancer has been reported. In this study, NLRs and PLRs were calculated before treatment and during cancer progression in primary hormone receptor-positive breast cancer (HRBC) patients who chose endocrine therapy (ET) as the primary treatment, and prognostic prediction and factor analysis were performed. PATIENTS AND METHODS: A total of 55 patients diagnosed with stage IIIB, IIIC, or IV HRBC who received ET as the primary treatment were included. RESULTS: Increased NLRs were found to significantly contribute to a shorter overall survival from cancer progression (OS-CP) (p=0.040, log-rank). Increased PLRs were similarly associated with a shorter OS-CP (p=0.036, log-rank). In multivariate analysis, an increased NLR was an independent prognostic factor (p=0.035, hazard ratio(HR)=5.221). CONCLUSION: Changes in NLRs and PLRs become prognostic indicators when the therapeutic effect of ET is limited.
  • Wataru Goto; Shinichiro Kashiwagi; Yuka Asano; Koji Takada; Katsuyuki Takahashi; Hisakazu Fujita; Tsutomu Takashima; Masatsune Shibutani; Ryosuke Amano; Shuhei Tomita; Kosei Hirakawa; Masaichi Ohira
    Anticancer research 39 8 4031 - 4041 2019年08月 [査読有り]
     
    BACKGROUND/AIM: Eribulin is currently used to treat advanced and metastatic breast cancer in the clinical setting; however, its efficacy is inhibited by resistance acquisition in many cases. Thus, the present study established two eribulin-resistant breast-cancer cell lines, and used these to investigate the mechanisms that underly eribulin-resistance acquisition. MATERIALS AND METHODS: Eribulin-resistant breast-cancer cell lines were generated by culturing MDA-MB-231 and MCF-7 cells with increasing concentrations of eribulin. RESULTS: The eribulin-resistant cells acquired resistance to eribulin, as well as several other anticancer drugs. After eribulin treatment, the eribulin-resistant cell lines showed no morphological change, no increased expression of epithelial-cadherin, nor any significant alteration in cell-cycle distribution. In contrast, the expression levels of programmed death-ligand 1 were increased in the MCF-7/eribulin-resistant compared to MCF-7 cells. CONCLUSION: The herein developed eribulin-resistant cell lines acquired cross-resistance to various anticancer agents, and displayed resistance to eribulin-induced effects on microtubule function and epithelial-mesenchymal transition (EMT).
  • Koji Takada; Shinichiro Kashiwagi; Yuka Asano; Wataru Goto; Katsuyuki Takahashi; Hisakazu Fujita; Tsutomu Takashima; Shuhei Tomita; Kosei Hirakawa; Masaichi Ohira
    BMC cancer 19 1 615 - 615 2019年06月 [査読有り]
     
    BACKGROUND: A higher density of tumor-infiltrating lymphocytes (TILs) can lead to greater therapeutic effects and improved prognoses in cancer treatment. Similar results have been observed in breast cancer, particularly in triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2-enriched breast cancer. Calcium channel blockers (CCBs) are antihypertensive drugs (AHTs) that have also been reported to suppress the functions of T cells and macrophages. In this study, we evaluated TILs before pre-operative chemotherapy (POC) in breast cancer and retrospectively analyzed the correlation between CCBs and TILs or prognosis. METHODS: Of the patients treated with POC, 338 who had evaluable TILs were enrolled in this study. The correlations among TILs were evaluated according to standard methods, and CCB use and prognosis were investigated retrospectively. RESULTS: Before POC, 65 patients (19.2%) took AHTs (CCBs: 41/338, 12.1%). The TIL density was significantly lower among patients administered CCBs for the group of all patients and for patients with TNBC (p = 0.040, p = 0.009, respectively). Additionally, patients with TNBC who were administered CCBs showed significantly lower response rates for POC (p = 0.040). In all patients receiving POC, no significant differences in disease-free survival (DFS) or overall survival (OS) were observed in patients administered CCBs (p = 0.712, p = 0.478, log-rank tests, respectively). Furthermore, no significant differences were found, even in patients with TNBC (DFS: p = 0.441, OS: p = 0.727, log-rank tests, respectively). CONCLUSIONS: In patients with TNBC undergoing treatment for hypertension with CCBs, TILs in the needle biopsy specimens before treatment were significantly lower, and the response rate of POC was not sufficient. Thus, the immunosuppressive effects of CCBs may also affect the immune microenvironment.
  • Koji Takada; Shinichiro Kashiwagi; Yuka Asano; Wataru Goto; Katsuyuki Takahashi; Masatsune Shibutani; Ryosuke Amano; Tsutomu Takashima; Shuhei Tomita; Kosei Hirakawa; Masaichi Ohira
    Anticancer research 39 6 2941 - 2950 2019年06月 [査読有り]
     
    BACKGROUND: Several studies have established a positive relationship between quality of life (QOL) and prognosis in patients with various cancer types. This study investigated QOL of elderly patients with primary hormone receptor-positive breast cancer who chose endocrine therapy as their first-line treatment. PATIENTS AND METHODS: QOL-ACD-B scores were evaluated before and after endocrine therapy for 75 patients. The results of the interviews were used to determine the Charlson Comorbidity Index. RESULTS: In a univariate analysis, baseline objective response rate (p=0.009), and increase in QOL (p=0.037) significantly correlated with longer progression-free survival time. There was a correlation between 3-month QOL score and longer overall survival in the multivariate analysis (p=0.035). CONCLUSION: In elderly patients with breast cancer who underwent first-line endocrine therapy, improved QOL at 3 months after treatment initiation correlated with prolonged progression-free survival. High QOL scores were associated with prolonged overall survival.
  • Shinichiro Kashiwagi; Yuka Asano; Katsuyuki Takahashi; Masatsune Shibutani; Ryosuke Amano; Shuhei Tomita; Kosei Hirakawa; Masaichi Ohira
    Anticancer research 39 5 2259 - 2264 2019年05月 [査読有り]
     
    Disseminated intravascular coagulation (DIC) that occurs during cancer therapy prevents continuation of therapy, contributing to a worse prognosis. While recombinant human-soluble thrombomodulin (rhTM), a new DIC drug, has occasionally shown its efficacy in DIC associated with infection and blood cancer, its efficacy in patients with solid tumors has been unproven. This review presents the results on the efficacy and safety of rhTM as a DIC drug in patients with solid tumors that have been confirmed by the clinical data of three previous reports. The number of cases in each study was 101, 123 and 40. The respective DIC resolution rate was 34.0%, 35.2% and 32.5%, and the 28-day survival rate was 55.4%, 52.0% and 40.0%. Although comparison with other anti-DIC therapies is required, rhTM therapy is considered one of the treatment options of DIC in patients with solid tumors.
  • Ryo Inose; Kouichi Hosomi; Katsuyuki Takahashi; Satoshi Yokoyama; Mitsutaka Takada
    International journal of clinical pharmacology and therapeutics 57 2 63 - 72 2019年02月 [査読有り]
     
    OBJECTIVE: This study investigated whether using biological disease-modifying antirheumatic drugs (bDMARDs) further increases the risk of malignant lymphoma in patients with rheumatoid arthritis undergoing methotrexate therapy using spontaneous adverse reaction databases in different countries. MATERIALS AND METHODS: Patient data were acquired from the US Food and Drug Administration's Adverse Event Reporting System (FAERS), the Japanese Adverse Drug Event Report (JADER), and the Canada Vigilance Adverse Reaction Online Database (CVARD) from the first quarter of 2004 to the end of 2015. Data subset analysis was performed to investigate whether the use of bDMARDs further increased the risk of malignant lymphoma in patients receiving methotrexate therapy. RESULTS: The FAERS subset data indicated a significant association between Hodgkin lymphoma and methotrexate with infliximab (reporting odds ratio (ROR): 8.28. 95% CI: 5.70 - 12.02; information component (IC): 2.04, 95% CI: 1.59 - 2.49). In addition, signal scores suggested that methotrexate with infliximab (ROR: 3.26. 95% CI: 2.68 - 3.98; IC: 1.31, 95% CI: 1.04 - 1.58) was significantly associated with non-Hodgkin lymphoma (NHL). The CVARD subset data also indicated a significant association between NHL and methotrexate with infliximab (ROR: 22.82. 95% CI: 5.02 - 103.78; IC: 1.77, 95% CI: 0.13 - 3.41). However, the JADER subset data revealed no significant associations. CONCLUSION: The present study shows that using infliximab further increases the risk of malignant lymphoma in patients receiving methotrexate therapy.
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  • Inose R; Takahashi K; Nanno S; Hino M; Nagayama K
    Journal of chemotherapy (Florence, Italy) 31 1 30 - 34 2019年02月 [査読有り]
     
    Delayed elimination of plasma methotrexate (MTX), which leads to elevated toxicity, is often observed in patients receiving high-dose methotrexate (HD-MTX) therapy, despite of the preventive measures. In this study, we investigated the factors that delay elimination of plasma MTX in patients on HD-MTX therapy. Fifteen patients who received HD-MTX therapy (21 cycles) were classified into two groups: delayed elimination of plasma MTX (38.1%, 8/21) and normal elimination of plasma MTX (61.9%, 13/21). Patient characteristics, plasma MTX concentrations, laboratory values, and adverse reactions were compared between the two groups using Fisher's exact test. Univariate analysis showed that co-administration of calcium channel blockers was significantly associated with delayed elimination of plasma MTX (p = 0.042). This is the first report demonstrating that co-administration of calcium channel blockers may be a predictive factor of delayed elimination of plasma MTX in patients receiving HD-MTX therapy.
  • Takada K; Kashiwagi S; Asano Y; Goto W; Takahashi K; Fujita H; Takashima T; Tomita S; Hirakawa K; Ohira M
    Journal of translational medicine 17 1 13 - 13 2019年01月 [査読有り]
     
    BACKGROUND: The immune tumor microenvironment (iTME) is thought to affect the response to chemotherapy, and tumor-infiltrating lymphocytes (TILs) are often used as an indicator to evaluate the iTME. Smoking is involved in carcinogenesis, the relationship between smoking and the iTME of lung cancer has been reported. We hypothesized that smoking would affect the iTME of breast cancer and aimed to examine this relationship based on the amount of pre-diagnosis smoking and the subsequent effects on treatment response and prognosis. METHODS: This retrospective study evaluated data from 149 patients who underwent preoperative chemotherapy for triple-negative or HER2-enriched breast cancer. TILs were assessed in biopsy specimens at diagnosis. The data of all patients were used to calculate each patient's smoking amount based on pack-years. RESULTS: Relative to the low smoking group, the high smoking group had a significant greater TILs density (p = 0.043) and a significantly better pathological complete response (pCR) rate (p = 0.042). However, there was no significant difference according to smoking amount in disease-free survival (p = 0.114) or overall survival (p = 0.347). CONCLUSIONS: Smoking may influence the iTME, with an activated iTME being associated with pCR rate. Therefore, controlled activation of the microenvironment in this setting may help improve patients' prognosis.
  • Takahashi M; Takahashi K; Ogawa K; Takashima T; Asano Y; Kashiwagi S; Noda S; Onoda N; Ohira M; Nagayama K
    Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 27 8 2829 - 2836 2018年12月 [査読有り]
     
    PURPOSE: The purpose of this study was to compare the efficacy of the pre-prescription of garenoxacin mesylate hydrate (GRNX) with that of moxifloxacin hydrochloride (MFLX) in the management of breast cancer patients with low-risk febrile neutropenia. METHODS: Data from female patients who had been instructed to take previously prescribed oral GRNX or MFLX for 3 days during adjuvant and neoadjuvant chemotherapy if their body temperature exceeded 38 °C were analyzed. This study compared the effectiveness between these fluoroquinolones using a propensity score matching analysis. RESULTS: The 330 patients received 1192 administrations of chemotherapy between May 2007 and April 2014 and 136 (41.2%) patients had a total of 212 (17.8%) febrile episodes. The frequencies of febrile episodes were 19.5% (113/579) and 16.2% (99/613) in the GRNX and MFLX groups, respectively. After propensity score matching, 384 episodes were matched in each group. Febrile events occurred in 80 and 56 cases in the GRNX and MFLX groups, respectively. Treatment success was identified in 80.0% (64/80) of cases in the GRNX group and 64.3% (36/56) of cases in the MFLX group (P = 0.0494). Additionally, the therapeutic use of granulocyte-colony stimulating factor was 6.3% (5/80) of cases in the GRNX group and 17.9% (10/56) of cases in the MFLX group (P = 0.0498). There were few differences in the frequency of adverse effects between the two groups. CONCLUSIONS: These results indicate that the pre-prescription of GRNX may be a more effective option for the management of low-risk febrile neutropenia during adjuvant and neoadjuvant chemotherapy for breast cancer.
  • Goto W; Kashiwagi S; Takada K; Asano Y; Takahashi K; Fujita H; Takashima T; Tomita S; Hirakawa K; Ohira M
    Journal of translational medicine 16 1 307 - 307 2018年11月 [査読有り]
     
    BACKGROUND: The prognosis of breast cancer and the treatment response to neoadjuvant chemotherapy (NAC) differ depending on the intrinsic molecular subtypes. We evaluated the prognostic significance of immunohistological subtypes in patients with recurrent breast cancer after treatment with NAC and surgery. METHODS: A total of 237 patients with breast cancer treated with NAC and subsequent curative surgery between 2007 and 2015 were analyzed. The correlation between intrinsic molecular subtypes and clinicopathological features, prognosis, and pathological complete response (pCR) rate of NAC were investigated retrospectively. RESULTS: There were 55 (23.2%) patients with recurrence after surgery. No significant difference in post-recurrence survival (PRS) was noted among the subtypes (p = 0.397). In patients with estrogen receptor-positive human epidermal growth factor receptor (HER) 2-negative (luminal) malignancy, PRS was significantly better in the pCR group than in the non-pCR group (p = 0.031). Conversely, pCR was not a significant predictor of improved PRS in patients with triple-negative breast cancer (TNBC; p = 0.329). Multivariate analysis revealed that the efficacy of NAC [hazard ratio (HR) 300.204, p < 0.001] and the initial metastasis site (HR 15.037, p = 0.005) were independent predictors for PRS in patients with luminal breast cancer, while Ki-67 (HR 51.171, p = 0.020) and the initial metastasis site (HR 13.318, p = 0.048) were independent predictors for PRS in patients with TNBC. CONCLUSIONS: The prognostic factors for each intrinsic subtype should be evaluated separately in patients with recurrent breast cancer following NAC and surgery.
  • Goto W; Kashiwagi S; Asano Y; Takada K; Takahashi K; Hatano T; Takashima T; Tomita S; Motomura H; Hirakawa K; Ohira M
    BMC cancer 18 1 1137 - 1137 2018年11月 [査読有り]
     
    BACKGROUND: The lymphocyte-to-monocyte ratio (LMR) has been used as a parameter reflecting systemic inflammation in several tumors, and is reportedly associated with prognosis in cancer patients. In this study, we evaluated the predictive value of LMR for progression and chemosensitivity in breast cancer patients treated with preoperative chemotherapy. METHODS: LMR was evaluated in 239 patients with breast cancer treated with neoadjuvant chemotherapy (NAC) with 5-fluorouracil, epirubicin, and cyclophosphamide, followed by weekly paclitaxel with or without trastuzumab, and subsequent curative surgery. The correlations between LMR and clinicopathological features, prognosis, and pathological complete response (pCR) rate of NAC were evaluated retrospectively. We also evaluated the predictive value of neutrophil-to-lymphocyte ratio (NLR), and compared the predictive values of LMR and NLR. RESULTS: We set 6.00 as the cut-off level for LMR based on the receiver operating characteristic (ROC) curve. A total of 119 patients (49.8%) were classified in the high-LMR group and 120 (50.2%) were classified in the low-LMR group. The low-LMR group had significantly worse disease-free survival rate (DFS) in all patients (p = 0.005) and in triple-negative breast cancer patients (p = 0.006). However, there was no significant correlation between LMR and pCR. Multivariate analysis showed that low LMR was an independent risk factor for DFS (p = 0.008, hazard ratio = 2.245). However, there was no significant difference in DFS (p = 0.143, log-rank) between patients in the low- and high-NLR groups. CONCLUSIONS: LMR may be a useful prognostic marker in patients with breast cancer.
  • Takada K; Kashiwagi S; Goto W; Asano Y; Takahashi K; Fujita H; Takashima T; Tomita S; Hirakawa K; Ohira M
    Journal of translational medicine 16 1 318 - 318 2018年11月 [査読有り]
     
    BACKGROUND: The diagnosis of metastasis by sentinel lymph node biopsy (SLNB) in early breast cancer surgery provides an accurate view of the state of metastases to the axillary lymph nodes, and it has now become the standard procedure. In the present study, whether omission of axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC) is possible by evaluation of tumor-infiltrating lymphocytes (TILs) before NAC in cases without metastasis on diagnostic imaging, but with metastasis on SLNB, was retrospectively investigated. METHODS: A total of 91 patients with resectable, early-stage breast cancer, diagnosed as cT1-2, N0, M0, underwent SLNB and were treated with NAC. A semi-quantitative evaluation of lymphocytes infiltrating the peritumoral stroma as TILs in biopsy specimens of primary tumors prior to treatment was conducted. RESULTS: In cases with a low number of TILs, estrogen receptor expression was significantly higher (p = 0.044), and human epidermal growth factor receptor 2 (HER2) expression was significantly lower than in other cases (p = 0.019). The number of TILs was significantly lower in cases in which the intrinsic subtype was hormone receptor-positive breast cancer (HRBC) (p = 0.044). Metastasis to axillary lymph nodes was significantly more common in HER2-negative cases and cases with a low number of TILs (p = 0.019, p = 0.005, respectively). CONCLUSIONS: Even if macrometastases are found on SLNB in cN0 patients, it appears that ALND could be avoided after NAC in cases with a good immune tumor microenvironment of the primary tumor.
  • Takada K; Kashiwagi S; Goto W; Asano Y; Takahashi K; Hatano T; Takashima T; Tomita S; Motomura H; Ohsawa M; Hirakawa K; Ohira M
    British journal of cancer 119 5 572 - 579 2018年08月 [査読有り]
     
    BACKGROUND: Immune responses in a tumour microenvironment can be evaluated by analysing tumour-infiltrating lymphocyte (TIL) density; this has been verified in the clinical setting. Although there are many reports on TIL density in primary tumours, little is known about its density in recurrent tumours. METHODS: Of 300 patients treated with neoadjuvant chemotherapy during the study period, 29 were considered for evaluation of TIL density in primary and recurrent tumours. We performed a retrospective analysis of the association between TIL density and prognosis. RESULTS: TIL density was significantly lower in recurrent tumours than in primary tumours (P = 0.007). There was no correlation between post-recurrence survival and TIL density in core-needle biopsy specimens obtained from primary tumours (P = 0.837). However, patients with high TIL density in recurrent tumours had significantly better post-recurrence survival than did the corresponding group with low TIL density (P = 0.041). Multivariate analysis revealed that high TIL density contributed significantly towards improving post-recurrence survival in all patients (P = 0.035; hazard ratio, 0.167). CONCLUSIONS: In recurrent breast cancer, a decrease in TILs density was observed as compared to the primary tumour, and this affects the poor prognosis after relapse.
  • Koji Takada; Shinichiro Kashiwagi; Wataru Goto; Yuka Asano; Katsuyuki Takahashi; Tamami Morisaki; Tsutomu Takashima; Shuhei Tomita; Kosei Hirakawa; Masaichi Ohira
    Journal of Cancer Research and Clinical Oncology 144 8 1 - 13 2018年05月 [査読有り]
     
    Purpose: Quality-of-life (QOL) has been reported to affect the prognosis of many types of cancer, and several studies used various QOL assessment tools to determine the relationship between QOL and cancer prognosis. In this study, QOL-Questionnaire for Cancer Patients Treated with Anti-Cancer Drugs-the Breast (QOL-ACD-B) was modified to be suitable for preoperative chemotherapy (POC) and was named the QOL-ACD-BP. Methods: A total of 300 patients were treated with POC after being diagnosed with breast cancer between February 2007 and December 2016 at our institute. We evaluated novel evaluation scale for QOL (QOL-ACD-BP) before and after POC in a retrospective manner. Results: In the multivariate analysis with overall survival, the high QOL before [p = 0.048, hazard ratio (HR) 0.441] or after POC (p = 0.030, HR 0.273) was an independent factor. Conclusion: Our study shows that QOL after POC may also affect prognosis and supported the importance of maintaining QOL in cancer treatment. In patients with breast cancer treated with POC, QOL-ACD-BP, which is a new QOL evaluation index, was found to be a useful tool for predicting the patients’ prognosis.
  • Nozomi Iimori; Shinichiro Kashiwagi; Yuka Asano; Wataru Goto; Koji Takada; Katsuyuki Takahashi; Takaharu Hatano; Tsutomu Takashima; Shuhei Tomita; Hisashi Motomura; Kosei Hirakawa; Masaichi Ohira
    In Vivo 32 3 669 - 675 2018年05月 [査読有り]
     
    Background: Studies have found that patients with cancer exhibit abnormal leukocyte fractions, such as elevated neutrophil count and diminished lymphocyte count, and that the neutrophil-to-lymphocyte ratio (NLR) provides a surrogate marker for prognosis and response to treatment of patients after radical surgery for several different types of cancer. However, few reports have addressed the association between the NLR and response to endocrine therapy. In this study, we carried out a clinical investigation to confirm whether or not the NLR predicted the response to endocrine therapy of stage IV breast cancer. Patients and Methods: The study subjects were 34 patients who underwent endocrine therapy as initial drug therapy for stage IV breast cancer. The correlation between NLR and prognosis, including the efficacy of endocrine therapy, was evaluated retrospectively. Results: Among the 34 patients, the NLR was high in 10 (29.4%) and low in 24 (70.6%). In analysis of outcomes, the group with low NLR had a significant prolongation of progression-free survival (p=0.003), time to treatment failure (p=0.031), and overall survival (p=0.013) compared to the group with high NLR. Univariate analysis of progression-free survival found that responding to treatment [hazard ratio (HR)=4.310, p=0.004] and low NLR (HR=3.940, p=0.016) were factors associated with a favorable prognosis. Multivariate analysis also showed that responding to treatment (HR=4.329, p=0.006) and low NLR (HR=3.930, p=0.008) were independent factors associated with a favorable prognosis. Conclusion: Our results suggested that the NLR may represent a predictive marker for response to endocrine therapy in stage IV breast cancer.
  • Yuka Asano; Shinichiro Kashiwagi; Wataru Goto; Koji Takada; Katsuyuki Takahashi; Tamami Morisaki; Hisakazu Fujita; Tsutomu Takashima; Shuhei Tomita; Masahiko Ohsawa; Kosei Hirakawa; Masaichi Ohira
    Journal of Translational Medicine 16 1 87 - 87 2018年04月 [査読有り]
     
    Background: "Avoiding immune destruction" has recently been established as one of the hallmarks of cancer. The programmed cell death (PD)-1/programmed cell death-ligand (PD-L) 1 pathway is an important immunosuppression mechanism that allows cancer cells to escape host immunity. The present study investigated how the expressions of these immune checkpoint proteins affected responses to neo-adjuvant chemotherapy (NAC) in breast cancer. Methods: A total of 177 patients with resectable early-stage breast cancer were treated with NAC. Estrogen receptor, progesteron receptor, human epidermal growth factor receptor 2, Ki67, PD-L1, PDL-2 and PD-1 status were assessed by immunohistochemistry. Results: There were 37 (20.9%) patients with high PD-1 expression, 42 (23.7%) patients had high PD-L1 expression, and 52 (29.4%) patients had high PD-L2 expression. The patients with high PD-1 and PD-L1 expressions had a significantly higher rate of triple-negative breast cancer (TNBC) (p = 0.041) (p < 0.001). In TNBC, patients with high PD-1 and PD-L1 expressions had significantly higher rates of non-pCR (p = 0.003) (p < 0.001). Univariate analysis showed that PD-1 and PD-L1 expressions also significantly shortened disease free survival in TNBC (p = 0.048, HR = 3.318) (p = 0.007, HR = 8.375). However, multivariate analysis found that only PD-L1 expression was an independent prognostic factor (p = 0.041, HR = 9.479). Conclusions: PD-1 and PD-L1 expressions may be useful as biomarkers to predict treatment responses to NAC in breast cancer. Above all, PD-L1 expression may also be useful as biomarkers for more effective chemotherapy in TNBC.
  • Koji Takada; Shinichiro Kashiwagi; Wataru Goto; Yuka Asano; Katsuyuki Takahashi; Tsutomu Takashima; Shuhei Tomita; Masahiko Ohsawa; Kosei Hirakawa; Masaichi Ohira
    Journal of Translational Medicine 16 1 86 - 86 2018年04月 [査読有り]
     
    Background: The trastuzumab, pertuzumab, and docetaxel (TPD) regimen is strongly recommended as a treatment option for first-line therapy for advanced human epidermal growth factor receptor (HER) 2-positive breast cancer. Monitoring the host microenvironments in cancer plays a significant role in predicting prognoses and curative effects. It is important to clarify the role of immune related gene expression in tumor-infiltrating lymphocytes in the tumor microenvironment. In this study, we evaluated the impact of chemotherapy with a TPD regimen, on immune micro environments in HER2-positive breast cancer using immune related proteins as indicators. Methods: The subjects consisted of 30 patients who received the TPD regimen. The expression levels of estrogen receptor, progesterone receptor, Ki67, CD8, forkhead box protein (FOXP) 3, programmed death (PD) 1, programmed death ligand (PD-L) 1, CD163, phosphatase and tensin homolog and lymphocyte activation gene 3 were evaluated in biopsy specimens, by immunostaining. Results: CD8+, CD8/FOXP3 ratio (CFR)high and PD-L1- group had significantly longer PFS than the CD8-, CFRlow and PDL1+ group (p = 0.045, log-rank) (p = 0.007, log-rank) (p = 0.040, log-rank), respectively. The CFRhigh group had significantly better OS than the CFRlow group (p = 0.034, log-rank). In the univariate analysis, CD8+, CFRhigh groups extended PFS significantly (p = 0.027, hazard ratio [HR] = 0.162) (p = 0.008, HR = 0.195), respectively. The receiver operating characteristic (ROC) analyses showed that the results for CFR [area under the curve (AUC): 0.708] were better than those for other factors (AUC: CD8 = 0.681, FOXP3 = 0.639, PD1 = 0.528, PD-L1 = 0.681). Conclusions: This study shows with the TPD regimen, a high CFR leads to a high ORR and long PFS in HER2-positive breast cancer. CFR, therefore, may be one of the important prognostic factors for this disease.
  • Yuka Asano; Shinichiro Kashiwagi; Wataru Goto; Koji Takada; Katsuyuki Takahashi; Takaharu Hatano; Tsutomu Takashima; Shuhei Tomita; Hisashi Motomura; Masahiko Ohsawa; Kosei Hirakawa; Masaichi Ohira
    Anticancer Research 38 4 2311 - 2321 2018年04月 [査読有り]
     
    Background/Aim: Recent interest has focused on the significance of tumor-infiltrating lymphocytes (TILs) on the efficacies and outcomes of the treatment in breast cancer (BC). Based on the recent international recommendation to standardize the evaluation method, the clinical validity and utility of TILs in patients who underwent neoadjuvant chemotherapy (NAC) were investigated in the present study. Patients and Methods: TILs were evaluated in 177 patients with BC treated with NAC and subsequent curative surgery. The correlation between TILs evaluated according to the standard method and prognosis, including the efficacy of NAC, was investigated retrospectively. Results: In the high-TIL group (n=96) compared to the low-TIL group (n=81), triple-negative breast cancer (TNBC) (p< 0.001) and human epidermal growth factor receptor 2-enriched breast cancer (HER2BC) (p=0.040) were significantly more frequent, and the pathological complete response (pCR) rate was significantly higher (p=0.003). Among patients with TNBC and those with HER2BC, the pCR rate was significantly higher in the high-TIL group than in the low-TIL group (p=0.013 and p=0.014, respectively). Multivariable analysis also showed that high-TIL status was an independent factor predicting favorable prognosis (hazard ratio(HR)=0.24, p=0.023 and HR=0.13, p=0.036). Biopsy specimens from local recurrence after successful NAC frequently showed TILs decreased. Conclusion: TILs may be a biomarker for predicting treatment response to NAC in patients with TNBC and HER2BC. A decrease in TILs may also be associated with tumor recurrence.
  • Shinichiro Kashiwagi; Gen Tsujio; Yuka Asano; Wataru Goto; Koji Takada; Katsuyuki Takahashi; Tamami Morisaki; Hisakazu Fujita; Tsutomu Takashima; Shuhei Tomita; Masahiko Ohsawa; Kosei Hirakawa; Masaichi Ohira
    Journal of Translational Medicine 16 1 54 - 54 2018年03月 [査読有り]
     
    Background: Recently, the concepts of progression due to pre-existing lesions (PPL) and progression due to new metastasis (PNM) have been proposed to differentiate the progression types of treatment-resistant cancers. Previously, the differences between these two progression types did not affect the determination of treatment strategies since both PPL and PNM are classified as progressive disease based on the response evaluation criteria in solid tumors (RECIST) diagnostic criteria. On the other hand, tumor infiltrating lymphocytes (TILs) are effective when used as indicators for monitoring the immune tumor microenvironment (iTME) in the cancer host, and TILs play an important role as biomarkers in predicting prognosis and therapeutic effects. This study focused on the progression types of cancer in patients undergoing eribulin chemotherapy. In addition, the iTME in individuals with PPL and PNM was evaluated using TILs as a marker. Methods: Of the 52 patients with locally advanced or metastatic breast cancer who underwent chemotherapy with eribulin, 40 remained in the study, and 12 patients were dropout cases. The antitumor effect was evaluated based on the RECIST criteria using version 1.1. TILs were defined as the infiltrating lymphocytes within tumor stroma and were expressed in proportion to the field investigated. In PPL cases, the high-TIL group was considered as type I and the low-TIL group was classified as type II. In PNM cases, the high-TIL group was considered as type III and the low-TIL group was classified as type IV. Results: In 19 cases, individuals with type I progression had significantly longer progression free survival and overall survival (OS) compared to those with type III progression (p = 0.040, p < 0.001, log-rank). Individuals with type I progression had significantly prolonged survival post progression compared to those with type II progression (p = 0.048, log-rank). A multivariate analysis that validate the effect of OS showed that these were independent factors of good prognosis (p = 0.003 hazard ratio [HR] = 0.065) (p = 0.006 HR = 0.105). Conclusions: The effects of eribulin chemotherapy suggested that patients with progressive-type breast cancer that proliferates in a good iTME may have a good prognosis.
  • Inose R; Takahashi K; Yoshimura N; Kawaguchi T; Takada M; Nagayama K
    Oncomedicine 3 9 - 14 2018年01月 [査読有り]
  • Shinichiro Kashiwagi; Yuka Asano; Wataru Goto; Koji Takada; Katsuyuki Takahashi; Takaharu Hatano; Sayaka Tanaka; Tsutomu Takashima; Shuhei Tomita; Hisashi Motomura; Masahiko Ohsawa; Kosei Hirakawa; Masaichi Ohira
    Anticancer Research 38 1 401 - 410 2018年01月 [査読有り]
     
    Background/Aim: Eribulin mesylate (eribulin) is currently used for the treatment of locally advanced or metastatic breast cancer (MBC). It is a cytotoxic agent with unique mechanisms that suppress the epithelial-mesenchymal transition (EMT) of cancer cells and promote tumor vascular remodeling. In this study, we investigated the expression of markers for EMT and hypoxia in sets of clinical specimens collected before and after eribulin treatment to verify its unique mechanisms. Patients and Methods: The expression of markers for EMT and cellular hypoxia [E-cadherin, N-cadherin, vimentin, and carbonic anhydrase 9 (CA9)] was examined immunohistochemically in MBC tissues collected from 20 patients before and after chemotherapy with either eribulin (n=10) or paclitaxel (n=10). Results: An increase of E-cadherin and decrease of CA9 expression were observed in MBC tissues from patients with objective clinical responses to eribulin treatment. Patients with E-cadherin-positive conversion and CA9-negative conversion had significantly higher response rates (p=0.004 and p=0.024, respectively) and prolonged time to treatment failure (p=0.018 and p=0.038, respectively) than patients without changes in marker expression. Conclusion: Expression of EMT and hypoxia markers in clinical samples from patients with MBC was suppressed by eribulin treatment. The results provide additional clinical data on improved survival of patients treated with eribulin and the mechanism of response.
  • Goto W; Kashiwagi S; Asano Y; Takada K; Takahashi K; Hatano T; Takashima T; Tomita S; Motomura H; Ohsawa M; Hirakawa K; Ohira M
    ESMO open 3 6 e000305  2018年 [査読有り]
     
    Background: Tumour-infiltrating lymphocytes (TILs) can be used to monitor the immune tumour microenvironment (iTME) and predict treatment response and outcome in breast cancer. We evaluated the prognostic significance of the levels of CD8+ TILs and forkhead box protein (FOXP3)-positive TILs before and after neoadjuvant chemotherapy (NAC). Patients and methods: We examined 136 patients with breast cancer treated with NAC. The number of CD8+ TILs and FOXP3+ TILs in biopsy specimens and residual tumours was evaluated by immunohistochemistry. Results: Patients with a high rate of change in the CD8/FOXP3 ratio (CFR) had significantly better recurrence-free survival (RFS) (p<0.001, log-rank). In multivariate analysis, the rates of change in the CD8+ TIL levels and the CFR were independent predictors for RFS (HR=2.304, p=0.036 and HR=4.663, p<0.001). In patients with triple-negative and hormone receptor-positive breast cancer, the rate of change in the CFR was an independent predictor for RFS (HR=13.021, p=0.002 and HR=4.377, p=0.003). Conclusion: Improvement in the iTME following NAC is correlated with good outcome. The rate of change in the CFR may be a useful biomarker to predict prognosis of patients treated with NAC.
  • Goto, W.; Kashiwagi, S.; Asano, Y.; Takada, K.; Takahashi, K.; Hatano, T.; Takashima, T.; Tomita, S.; Motomura, H.; Ohsawa, M.; Hirakawa, K.; Ohira, M.
    Biomarker Research 6 1 2018年
  • Goto Wataru; Kashiwagi Shinichiro; Asano Yuka; Takada Koji; Takahashi Katsuyuki; Noda Satoru; Takashima Tsutomu; Onoda Naoyoshi; Tomita Shuhei; Hirakawa Kosei; Ohira Masaichi
    CANCER SCIENCE 109 123  2018年01月 [査読有り]
  • Yuka Asano; Shinichiro Kashiwagi; Wataru Goto; Koji Takada; Katsuyuki Takahashi; Takaharu Hatano; Satoru Noda; Tsutomu Takashima; Naoyoshi Onoda; Shuhei Tomita; Hisashi Motomura; Masahiko Ohsawa; Kosei Hirakawa; Masaichi Ohira
    BMC Cancer 17 1 888 - 888 2017年12月 [査読有り]
     
    Background: The tumor immune environment not only modulates the effects of immunotherapy, but also the effects of other anticancer drugs and treatment outcomes. These immune responses can be evaluated with tumor-infiltrating lymphocytes (TILs), which has frequently been verified clinically. On the other hand, residual cancer burden (RCB) evaluation has been shown to be a useful predictor of survival after neoadjuvant chemotherapy (NAC). In this study, RCB and TILs evaluations were combined to produce an indicator that we have termed "RCB-TILs", and its clinical application to NAC for breast cancer was verified by subtype-stratified analysis. Methods: A total of 177 patients with breast cancer were treated with NAC. The correlation between RCB and TILs evaluated according to the standard method, and prognosis, including the efficacy of NAC, was investigated retrospectively. The RCB and TILs evaluations were combined to create the "RCB-TILs". Patients who were RCB-positive and had high TILs were considered RCB-TILs-positive, and all other combinations were RCB-TILs-negative. Results: On multivariable analysis, being RCB-TILs-positive was an independent factor for recurrence after NAC in all patients (p < 0.001, hazard ratio = 0.048), triple-negative breast cancer (TNBC) patients (p = 0.018, hazard ratio = 0.041), HER2-positive breast cancer (HER2BC) patients (p = 0.036, hazard ratio = 0.134), and hormone receptor-positive breast cancer (HRBC) patients (p = 0.002, hazard ratio = 0.081). Conclusions: The results of the present study suggest that RCB-TILs is a significant predictor for breast cancer recurrence after NAC and may be a more sensitive indicator than TILs alone.
  • 乳がん周術期化学療法中の発熱性好中球減少症に対するモキシフロキサシン塩酸塩事前処方の有用性評価
    高橋 正也; 高橋 克之; 小川 和樹; 高島 勉; 光川 康子; 柏木 伸一郎; 野田 諭; 小野田 尚佳; 大平 雅一; 永山 勝也
    医療薬学 43 10 577 - 584 (一社)日本医療薬学会 2017年10月 [査読有り]
  • Shinichiro Kashiwagi; Yuka Asano; Wataru Goto; Koji Takada; Katsuyuki Takahashi; Takaharu Hatano; Tsutomu Takashima; Shuhei Tomita; Hisashi Motomura; Masahiko Ohsawa; Kosei Hirakawa; Masaichi Ohira
    ANTICANCER RESEARCH 37 10 5623 - 5630 2017年10月 [査読有り]
     
    Background/Aim: Recently, reports of the clinical implications of tumor-infiltrating lymphocytes (TILs) in breast cancer treatment have increased. We evaluated that chemotherapy with a TPD regimen (trastuzumab, pertuzumab, docetaxel) against HER2-positive breast cancer, using TILs as indicators. Patients and Methods: The subjects were 24 patients who had received TPD-chemotherapy. A semi-quantitative evaluation of lymphocytes invading the stroma in needle biopsy specimens prior to treatment as TILs was conducted, after which, sensitivity to chemotherapy and patient prognosis were evaluated. Results: Overall response rate was significantly higher in the high-TILs group than in the low-TILs group. Significant extension of the progression-free survival (PFS) and overall survival was found in the high-TILs group compared to the low-TILs group. In addition, high TILs numbers significantly contributed to the extension of PFS. Conclusion: Monitoring antitumor immune response using TILs might be a useful indicator for predicting the curative effects of TPD chemotherapy for HER2-positive breast cancer.
  • Asano Yuka; Kashiwagi Shinichiro; Goto Wataru; Takahashi Katsuyuki; Takashima Tsutomu; Noda Satoru; Onoda Naoyoshi; Tomita Shuhei; Hirakawa Kosei; Ohira Masaichi
    CANCER RESEARCH 77 2017年07月 [査読有り]
  • Goto Wataru; Kashiwagi Shinichiro; Takada Koji; Takahashi Katsuyuki; Takashima Tsutomu; Noda Satoru; Onoda Naoyoshi; Tomita Shuhei; Hirakawa Kosei; Ohira Masaichi
    CANCER RESEARCH 77 2017年07月 [査読有り]
  • 河端 志保; 中村 安孝; 松下 直樹; 高橋 克之; 高橋 典子; 西川 武司; 井口 広義; 永山 勝也
    日本緩和医療薬学雑誌 = Japanese journal of pharmaceutical palliative care and sciences 10 1 13 - 18 日本緩和医療薬学会 2017年03月 [査読有り]
  • 豕瀬諒; 高橋克之; 永井大地; 永井大地; 徳和目篤史; 光川康子; 六車一哉; 平川弘聖; 大平雅一; 永山勝也
    医療薬学 43 3 154‐160  2017年03月 [査読有り]
  • Shinichiro Kashiwagi; Yuka Asano; Wataru Goto; Koji Takada; Katsuyuki Takahashi; Satoru Noda; Tsutomu Takashima; Naoyoshi Onoda; Shuhei Tomita; Masahiko Ohsawa; Kosei Hirakawa; Masaichi Ohira
    PLOS ONE 12 2 e0170634  2017年02月 [査読有り]
     
    Background Eribulin mesylate (eribulin) is currently indicated for treatment of locally advanced or metastatic breast cancer (MBC). It is a cytotoxic agent with unique mechanisms that suppress epithelial-mesenchymal transition (EMT) of cancer cells. On the other hand, Tumor-infiltrating lymphocytes (TILs), which are considered indicators of immune response monitoring, have been reported as prognostic factors and predictors of therapeutic efficacy. We thought that eribulin, which has an EMT-inhibiting mechanism, may produce an antitumor effect by improving the immune microenvironment, and in this study investigated the effects of breast cancer eribulin chemotherapy on the immune microenvironment with TILs as a marker. Methods TILs was evaluated in 52 patients with MBC who underwent chemotherapy with eribulin. The correlation between TILs evaluated according to the standard method, and prognosis, including the efficacy of eribulin chemotherapy, was investigated retrospectively. Results Of the 52 MBC patients, 29 (55.8%) were in the high TILs group and 23 (44.2%) were in the low TILs group. The high TILs group included significantly more triple-negative breast cancer (TNBC) (p = 0.008) than the low TILs group. In an analysis of outcomes, TNBC patients in the high TILs group had significantly longer disease-free survival than TNBC patients in the low TILs group (p = 0.033, log-rank), but no significant differences were seen in all breast cancer patients (p = 0.489, log-rank) or in non-TNBC patients (p = 0.878, log-rank). In a multivariate analysis of recurrence in TNBC patients, being in the high TILs group was again an independent factor for a good outcome (p = 0.031, HR = 0.063). Conclusion The results of this study suggest that TILs may be useful as a predictive marker of the therapeutic effect of eribulin chemotherapy in TNBC.
  • Goto W; Kashiwagi S; Asano Y; Takada K; Takahashi K; Hatano T; Takashima T; Tomita S; Motomura H; Ohsawa M; Hirakawa K; Ohira M
    Biomarker research 5 19 - 19 2017年 [査読有り]
     
    BACKGROUND: Circulating tumor cells (CTCs) are linked to metastatic relapse and are regarded as a prognostic marker for human cancer. High expression of plakoglobin, a cell adhesion protein, within the primary tumor is positively associated with CTC clusters in breast cancer. In this study, we investigated the correlation between plakoglobin expression and survival of breast cancer. METHODS: We evaluated 121 breast cancer patients treated with neoadjuvant chemotherapy. Expression of plakoglobin was identified by immunohistochemical staining in the cell membrane. We also examined the relation between the expression of plakoglobin and E-cadherin, an epithelial-mesenchymal transition (EMT) marker. RESULTS: Patients with high plakoglobin expression had significantly worse distant-metastasis-free survival (DMFS) (P = 0.016, log rank). Plakoglobin expression had no correlation with pathological complete response rate (P = 0.627). On univariate analysis with respect to distant metastasis, high plakoglobin expression showed worse prognosis than low plakoglobin expression [P = 0.036, hazard ratio (HR) = 3.719]. Multivariate analysis found the same result (P = 0.013, HR = 5.052). In addition, there was a significant relationship between the expression of plakoglobin and E-cadherin (P = 0.023). CONCLUSIONS: Plakoglobin expression is an independent prognostic factor in patients with breast cancer, particularly for DMFS, and this is related to EMT.
  • Katsuyuki Takahashi; Masako Tanaka; Masakazu Yashiro; Masaki Matsumoto; Asuka Ohtsuka; Keiichi I. Nakayama; Yasukatsu Izumi; Katsuya Nagayama; Katsuyuki Miura; Hiroshi Iwao; Masayuki Shiota
    CANCER LETTERS 378 1 8 - 15 2016年08月 [査読有り]
     
    Heat shock protein 72 (Hsp72) is a molecular chaperone that assists in the folding of nascent polypeptides and in the refolding of denatured proteins. In many cancers, Hsp72 is constitutively expressed at elevated levels, which can result in enhanced stress tolerance. Similarly, following treatment with anticancer drugs, Hsp72 binds to denatured proteins that may be essential for survival. We therefore hypothesized that Hsp72 client proteins may play a crucial role in drug resistance. Here, we aimed to identify proteins that are critical for oxaliplatin (OXA) resistance by analyzing human gastric cancer cell lines, as well as OXA-resistant cells via a mass spectrometry-based proteomic approach combined with affinity purification using anti-Hsp72 antibodies. Stromal cell-derived factor 2 (SDF-2) was identified as an Hsp72 client protein unique to OCUM-2M/OXA cells. SDF-2 was overexpressed in OXA-resistant cells and SDF-2 silencing promoted the apoptotic effects of OXA. Furthermore, Hsp72 prevented SDF-2 degradation in a chaperone activity-dependent manner. Together, our data demonstrate that Hsp72 protected SDF-2 to avoid OXA-induced cell death. We propose that inhibition of SDF-2 may comprise a novel therapeutic strategy to counteract OXA-resistant cancers. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
  • 豕瀬 諒; 髙橋 克之; 西川 武司; 永山 勝也
    医療薬学 42 6 460 - 467 一般社団法人日本医療薬学会 2016年06月 [査読有り]
     
    Pegylated liposomal doxorubicin (PLD) is a liposomal formulation of doxorubicin hydrochloride. It was approved for the treatment of ovarian cancer aggravated after chemotherapy. The occurrence of hand-foot syndrome (HFS) associated with the administration of PLD is considered one of the major adverse side effects. The development of Grade2 ≦ HFS (Serious HFS) during the course of PLD therapy calls for dose reduction or discontinuation of subsequent PLD administration. However, the factors that influence the development of HFS are unclear in Japan. Therefore, we focused on the factors influencing the development of HFS in patients receiving PLD therapy for ovarian cancer. The study population consisted of 36 patients. Twenty patients (55.6%) developed HFS while 10 patients (27.8%) developed serious HFS. The patients who did not develop stomatitis during PLD therapy, also never developed serious HFS. In contrast, 37.0% (10/27) of the patients who had developed stomatitis during PLD therapy were reported to have developed serious HFS (P = 0.0390). For the 10 patients with serious HFS, the median time for the occurrence of serious HFS and stomatitis after the initiation of PLD therapy was 3 cycles and 1 cycle, respectively. In conclusion, patients who developed stomatitis during the course of PLD therapy were more likely to develop serious HFS than those who did not. Additionally, stomatitis has been reported to develop prior to serious HFS. Therefore, the occurrence of stomatitis during PLD therapy can aid in the prediction of serious HFS development in future.
  • Masako Tanaka; Masayuki Shiota; Takafumi Nakao; Ryo Uemura; Satoshi Nishi; Yasuyuki Ohkawa; Masaki Matsumoto; Maki Yamaguchi; Mayuko Osada-Oka; Azusa Inagaki; Katsuyuki Takahashi; Keiichi I. Nakayama; Min Gi; Yasukatsu Izumi; Katsuyuki Miura; Hiroshi Iwao
    JOURNAL OF PROTEOMICS 136 214 - 221 2016年05月 [査読有り]
     
    Heat shock protein 72 (HSP72) is an intracellular molecular chaperone that is overexpressed in tumor cells, and has also been detected in extracellular regions such as the blood. HSP72 forms complexes with peptides and proteins that are released from tumors. Accordingly, certain HSP72-binding proteins/peptides present in the blood of cancer patients may be derived from tumor cells. In this study, to effectively identify low-abundance proteins/peptides in the blood as tumor markers, we established a method for isolating HSP72-binding proteins/peptides from serum. Nine HSP72-specific monoclonal antibodies were conjugated to N-hydroxysulfosuccinimide-activated Sepharose beads (NHq) and used to isolate HSP72 complexes from serum samples. Precipitated proteins were then identified by LC-MS/MS analysis. Notably, this approach enabled the isolation of low-abundance proteins from serum without albumin removal. Moreover, by subjecting the serum samples of ten patients with multiple myeloma (MM) to NHq analysis, we identified 299 proteins present in MM HSP72 complexes, including 65 intracellular proteins. Among the intracellular proteins detected, 21 were present in all serum samples tested, while 11 were detected in both the conditioned media from cultured multiple myeloma cells and serum from MM patients. These results suggest that the NHq method can be applied to discover candidate tumor markers. (C) 2016 Elsevier B.V. All rights reserved.
  • Ryo Inose; Katsuyuki Takahashi; Takeshi Nishikawa; Katsuya Nagayama
    YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN 135 12 1403 - 1407 2015年12月 [査読有り]
     
    Cetuximab was approved in Japan as the only clinically available molecular targeted drug for the treatment of head and neck cancer. Hypomagnesemia associated with cetuximab is considered one of the most serious adverse events. However, the factors influencing the development of hypomagnesemia are not clear, although the drug was previously approved for the treatment of patients with colorectal cancer. Thus, we studied the factors involved in the development of hypomagnesemia in patients receiving cetuximab therapy for head and neck cancer. Patients' background data and laboratory values before starting cetuximab therapy did not affect the development of hypomagnesemia. Among patients who had never been treated with cisplatin (NT group), 36.4% developed hypomagnesemia. In contrast, all patients who had previously been treated with cisplatin (T group) developed hypomagnesemia (p=0.034). Magnesium is reabsorbed by transient receptor potential subfamily melastatin 6 (TRPM6) in the distal convoluted tubule. The expression level of TRPM6 is controlled by the epidermal growth factor (EGF) pathway. Cetuximab is an EGF receptor inhibitor and reduces the expression of TRPM6. Additionally, recent studies have shown that the expression of TRPM6 is reduced by cisplatin. Therefore, we considered that the serum magnesium level was cumulatively reduced by cetuximab and cisplatin. In conclusion, the T group was more likely to develop hypomagnesemia than the NT group, and therefore the serum magnesium level in the T group requires careful monitoring so that magnesium supplementation can be provided to patients when the level decreases.
  • Katsuyuki Takahashi; Yasuki Suda; Hiroshi Kawaguchi; Yasutaka Nakamura; Shiho Kawabata; Noriko Kawakami; Takeshi Nishikawa; Katsuya Nagayama
    YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN 135 9 1077 - 1082 2015年09月 [査読有り]
     
    Long-term clinical training based on a model core curriculum was conducted to nurture highly competent pharmacists in the clinical field. Pharmacists' responsibilities are expanding, and a system has been developed to help pharmacists gain accreditation, identify specialties, and improve their training. However, this system requires research competency. Therefore clinical research should be considered a part of clinical training to encourage high competency among pharmacists. Because the model core curriculum does not include a section on clinical research. Osaka City University Hospital introduced a hands-on clinical research experience program and evaluated its usefulness. A significant improvement in the level of knowledge and awareness of clinical research was seen among students who underwent the clinical research experience program. In addition, the level of student satisfaction was higher. These findings suggest that a clinical research experience program may be useful to nurture a greater awareness of clinical research and knowledge acquisition among pharmacists.
  • 中村安孝; 杉本崇; 外間まみ; 児玉典子; 高橋克之; 川口博資; 須田泰記; 西川武司; 永山勝也
    日本病院薬剤師会雑誌 51 6 751 - 755 2015年06月 [査読有り]
  • 須田泰記; 中村安孝; 高橋克之; 川口博資; 西川武司; 永山勝也
    日本病院薬剤師会雑誌 50 12 1475 - 1479 2014年12月 [査読有り]
  • Masako Tanaka; Maki Yamaguchi; Masayuki Shiota; Yukiko Kawamoto; Katsuyuki Takahashi; Azusa Inagaki; Mayuko Osada-Oka; Akihito Harada; Hideki Wanibuchi; Yasukatsu Izumi; Katsuyuki Miura; Hiroshi Iwao; Yasuyuki Ohkawa
    Monoclonal Antibodies in Immunodiagnosis and Immunotherapy 33 4 261 - 269 2014年08月 [査読有り]
     
    Fibroblast growth factor-2 (FGF-2) plays a critical role in endothelial survival, proliferation, and angiogenesis and is localized on the cell membrane by binding to heparan sulfate proteoglycans. Here we established a neutralizing monoclonal antibody, 1B9B9, against FGF-2 using the rat medial iliac lymph node method. 1B9B9 blocked the binding of FGF-2 to its receptor, inhibiting FGF-2-induced proliferation and corresponding downstream signaling in endothelial cells. Treatment of human umbilical vein endothelial cells with 1B9B9 reduced the basal phosphorylation levels of Akt and MAPK. Furthermore, continued treatment with 1B9B9 induced cell death by apoptosis. Compared with FGF-2 knockdown, 1B9B9 significantly reduced cell survival. In addition, the combination of FGF-2 siRNA and 1B9B9 showed a synergistic effect. The data indicate that 1B9B9 established by the rat iliac lymph node method is a fully compatible neutralizing antibody. © 2014 Mary Ann Liebert, Inc.
  • Junko Inagaki; Katsuyuki Takahashi; Hiroko Ogawa; Keiichi Asano; Omer Faruk Hatipoglu; Mehmet Zeynel Cilek; Masanari Obika; Takashi Ohtsuki; Matthias Hofmann; Shozo Kusachi; Yoshifumi Ninomiya; Satoshi Hirohata
    Experimental cell research 323 2 263 - 75 2014年05月 [査読有り]
     
    Angiogenesis and lymphangiogenesis play roles in malignant tumor progression, dissemination, and metastasis. ADAMTS1, a member of the matrix metalloproteinase family, is known to inhibit angiogenesis. Recombinant ADAMTS1 was shown to strongly inhibit angiogenesis. We investigated whether ADAMTS1 inhibited lymphangiogenesis in the present study. We examined cell proliferation and cell migration in normal human dermal lymphatic microvascular endothelial cells (HMVEC-dLy) transduced with or without adenoviral human ADAMTS1 gene therapy. We then examined the VEGFC/VEGFR3 signal transduction pathway in ADAMTS1-transduced HMVEC-dLy. Cell proliferation and tube formation in Matrigel were significantly lower with transduced ADAMTS1 than with control (non-transduced HMVEC-dLy). The phosphorylation of VEGFR3 was also attenuated by ADAMTS1 gene therapy in HMVEC-dLy. Immunoprecipitation assays revealed that ADAMTS1 formed a complex with VEGFC. Our results demonstrated that ADAMTS1 inhibited lymphangiogenesis in vitro. The data highlight the new function of ADAMTS1 in the regulation of lymphangiogenesis and the therapeutic potential of ADAMTS1 in cancer therapy.
  • Masako Tanaka; Saya Mun; Akihito Harada; Yasuyuki Ohkawa; Azusa Inagaki; Soichi Sano; Katsuyuki Takahashi; Yasukatsu Izumi; Mayuko Osada-Oka; Hideki Wanibuchi; Masayo Yamagata; Tokihito Yukimura; Katsuyuki Miura; Masayuki Shiota; Hiroshi Iwao
    PLOS ONE 9 5 e96785  2014年05月 [査読有り]
     
    Heat shock cognate protein 70 (Hsc70) acts as a molecular chaperone for the maintenance of intracellular proteins, which allows cancer cells to survive under proteotoxic stress. We attempted to use Hsc70 to identify key molecules in cancer cell survival. Here, we performed mass-spectrometry-based proteomics analysis utilizing affinity purification with anti-Hsc70 antibodies; as a result, 83 differentially expressed proteins were identified under stress conditions. This result implies that there was a change in the proteins with which Hsc70 interacted in response to stress. Among the proteins identified under both serum-depleted and 5-fluorouracil-treated conditions, Rab1A was identified as an essential molecule for cancer cell survival. Hsc70 interacted with Rab1A in a chaperone-dependent manner. In addition, Hsc70 knockdown decreased the level of Rab1A and increased the level of its ubiquitination under stress conditions, suggesting that Hsc70 prevented the degradation of Rab1A denatured by stress exposure. We also found that Rab1A knockdown induced cell death by inhibition of autophagosome formation. Rab1A may therefore contribute to overcoming proteotoxic insults, which allows cancer cells to survive under stress conditions. Analysis of Hsc70 interactors provided insight into changes of intracellular status. We expect further study of the Hsc70 interactome to provide a more comprehensive understanding of cancer cell physiology.
  • 高橋克之; 尾上雅英; 福土将秀; 池見泰明; 小林政彦; 深津祥央; 矢野育子; 永山勝也; 松原和夫
    日本病院薬剤師会雑誌 49 12 1305 - 1309 2013年12月 [査読有り]
  • Katsuyuki Takahashi; Masako Tanaka; Azusa Inagaki; Hideki Wanibuchi; Yasukatsu Izumi; Katsuyuki Miura; Katsuya Nagayama; Masayuki Shiota; Hiroshi Iwao
    INTERNATIONAL JOURNAL OF ONCOLOGY 43 6 1985 - 1991 2013年12月 [査読有り]
     
    Triple-negative breast cancers (TNBCs) are defined as tumors that lack expression of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2. Clinically, TNBC patients are treated with cytotoxic drugs including 5-fluorouracil (5-FU). However, TNBCs develop resistance to such drugs after a series of treatments. To elucidate the mechanisms of drug resistance, establishment of drug-resistant cancer cell lines should be one of the most useful model systems. However, 5-FU-resistant TNBC cell lines have not been previously reported. In this study, we established a 5-FU-resistant cell line, MDA-MB-231/5-FU, from the human TNBC cell line MDA-MB-231, by repeated exposure to stepwise increases in the concentration of 5-FU. The IC50 value of 5-FU for MDA-MB-231/5-FU was 5.5-fold that for the parental cells. The MDA-MB-231/5-FU cell line acquired resistance to not only 5-FU, but also vinorelbine, paclitaxel and gemcitabine. Additionally, we performed iTRAQ-based quantitative proteomics in MDA-MB-231/5-FU cells and the parental cells in order to characterize MDA-MB-231/5-FU. The proteins upregulated in the newly established cells were mainly classified into the categories of DNA recombination', cell cycle', complex assembly', cytoskeleton organization', transport' and negative regulation of cell death'. These proteins may be related to mechanisms of drug resistance in TNBCs. Our established MDA-MB-231/5-FU cell line should be a useful tool for identifying new mechanisms of drug resistance and new drug targets in TNBCs.
  • 高橋克之; 中村安孝; 南野優子; 川口博資; 西川武司; 永山勝也; 岩尾洋
    医療薬学 39 3 166 - 173 Japanese Society of Pharmaceutical Health Care and Sciences 2013年03月 [査読有り]
     
    Drug testing is widely performed at the competitive level, both professional and amateur, and efforts to prevent doping are underway on a global scale.The sports-pharmacist system was launched by the Japan Anti-Doping Agency (JADA) in 2009 and recommends the anti-doping activities to be conducted by sports-pharmacists.In this study, we surveyed the awareness of doping among high school athletes enrolled in physical education and sports courses and their coaches, with the objective of identifying anti-doping activities that require intervention by sports-pharmacists and pharmacists.Responses were obtained from 1052 athletes (collection rate: 93.2%) and 83 coaches (collection rate: 100.0%). The questionnaire results revealed a low level of knowledge on doping-related issues such as "careless doping" and "therapeutic use exemptions." The results also suggest that the coaches showed a greater willingness to attend training sessions on doping than the high school athletes. Activities by pharmacists and sports-pharmacists will be important in the future in order to protect athletes and coaches from suffering the disadvantages of doping.
  • Masanari Obika; Hiroko Ogawa; Katsuyuki Takahashi; Jiayi Li; Omer Faruk Hatipoglu; Mehmet Zeynel Cilek; Toru Miyoshi; Junko Inagaki; Takashi Ohtsuki; Shozo Kusachi; Yoshifumi Ninomiya; Satoshi Hirohata
    Cancer science 103 10 1889 - 97 2012年10月 [査読有り]
     
    Angiogenesis plays an important role in tumor progression. Several reports have demonstrated that a disintegrin and metalloproteinase with thrombospondin motifs1 (ADAMTS1) inhibited angiogenesis via multiple mechanisms. The aim of this study was to investigate the effect of ADAMTS1 on endothelial cells in vitro and on tumor growth with regard to angiogenesis in vivo. We examined the effects of the transfection of ADAMTS1 using two constructs, full-length ADAMTS1 (full ADAMTS1) and catalytic domain-deleted ADAMTS1 (delta ADAMTS1). Transfection of both the full ADAMTS1 and delta ADAMTS1 gene constructs demonstrated the secretion of tagged-ADAMTS1 protein into the conditioned medium, so we examined the effects of ADAMTS1-containing conditioned medium on endothelial cells. Both types of conditioned media inhibited endothelial tube formation, and this effect was completely abolished after immunoprecipitation of the secreted protein from the medium. Both types of conditioned media also inhibited endothelial cell migration and proliferation. We then examined the impact of ADAMTS1 on endothelial cell apoptosis. Both conditioned media increased the number of Annexin V-positive endothelial cells and caspase-3 activity and this effect was attenuated when z-vad was added. These results indicated that ADAMTS1 induced endothelial cell apoptosis. We next examined the effects of ADAMTS1 gene transfer into tumor-bearing mice. Both full ADAMTS1 and delta ADAMTS1 significantly inhibited the subcutaneous tumor growth. Collectively, our results demonstrated that ADAMTS1 gene transfer inhibited angiogenesis in vitro and in vivo, likely as a result of the induction of endothelial cell apoptosis by ADAMTS1 that occurs independent of the protease activity.
  • Hitoshi Yamawaki; Satoshi Hirohata; Toru Miyoshi; Katsuyuki Takahashi; Hiroko Ogawa; Ryoko Shinohata; Kadir Demircan; Shozo Kusachi; Kazuhide Yamamoto; Yoshifumi Ninomiya
    GLYCOBIOLOGY 19 1 83 - 92 2009年01月 [査読有り]
     
    During inflammation, lower molecular weight fragments of hyaluronan accumulate, and this is known to be inflammatory and immune-stimulatory. In diseases such as inflammatory bowel disease, inflammatory cells bind to hyaluronan; however, the cellular response and molecular mechanism of hyaluronan-hyaluronan receptor interactions in mononuclear cells are not well understood. The expression of hyaluronan receptors in peripheral blood mononuclear cells (PBMC) was examined. PBMC were stimulated with lower and higher molecular weight hyaluronan (molecular weight 100-150 kDa and 2700 kDa) and the induction of proinflammatory cytokines (interleukin-6 (IL-6) and monocyte chemoattractant protein (MCP-1)) was compared by enzyme-linked immunoabsorbant assay (ELISA). Cells were coincubated with various signaling pathway inhibitors. In addition, neutralizing antibodies against CD44 and TLR4 were added and the effects on PBMC were investigated. Finally, mononuclear cells from CD44-null and toll-like receptor 4 (TLR4) mutant mice were both stimulated with lower molecular weight hyaluronan. Among the hyaluronan receptors, TLR4 and CD44 were markedly expressed on PBMC. Hyaluronan-stimulated PBMC enhanced the attachment to the extracellular matrix. Lower molecular weight hyaluronan induced IL-6 and MCP-1 production in PBMC, but high-molecular-weight hyaluronan did not induce IL-6 and MCP-1 production. An anti-CD44 antibody attenuated the induction of both IL-6 and MCP-1 in lower molecular weight hyaluronan-stimulated PBMC. In both TLR4 mutant and CD44-null mice, the induction of IL-6 by lower molecular weight hyaluronan stimulation was decreased. SB203580 completely abolished IL-6 production in both TLR4 mutant and CD44-null mononuclear cells, while PD98059 abolished IL-6 production in CD44-null mononuclear cells. Hyaluronan receptors, CD44 and TLR4, play distinct roles in cytokine induction in hyaluronan-stimulated mononuclear cells.

書籍

  • こんなときはどの検定? 臨床研究から学ぶ“逆引き”統計
    岩城 正宏 (担当:分担執筆範囲:2.4 比率の差のマクネマー検定、2.8 代表値の差の「マン・ホイットニーのU検定」 、2.9 代表値の差の「ウィルコクソンの符号付順位和検定」)じほう 2023年07月
  • 青山, 剛; 池末, 裕明; 内田, まやこ; 佐藤, 淳也; 高田, 慎也; 土屋, 雅美; 濱, 敏弘 (担当:分担執筆範囲:第3章 大腸がん FOLFIRI±AFL)医学書院 2023年02月 ISBN: 9784260050289 xvii, 908p
  • がん看護 Vol.27. No.2 明日から使える免疫関連有害事象マネジメント~免疫チェックポイント阻害薬の看護ケア~
    (担当:分担執筆範囲:第Ⅲ章 筋炎・横紋筋融解症)南江堂 2022年02月
  • 川上, 和宜; 松尾, 宏一; 吉村, 知哲 (担当:分担執筆範囲:CHAPTER2 3. 腹痛)南江堂 2021年09月 ISBN: 9784524228362 v, 274p
  • 望月, 敬浩; 中村, 安孝; 川上, 和宜; 大橋, 養賢; 原田, 知彦 (担当:分担執筆範囲:がん(症例124,症例125,症例134,症例157,症例192))南山堂 2020年08月 ISBN: 9784525706814 xii, 417p
  • 薬局 がん薬物療法と腎機能低下 腎機能を考慮したマネジメントの基礎と実践
    寺田 智祐 (担当:分担執筆範囲:抗EGFR(epidermal growth factor receptor)抗体)2020年06月
  • 松尾, 宏一; 緒方, 憲太郎; 林, 稔展 (担当:分担執筆範囲:3段目 14. 乳がん)医学書院 2020年04月 ISBN: 9784260041805 xii, 456p
  • 青山, 剛; 東, 加奈子; 池末, 裕明; 内田, まやこ; 佐藤, 淳也; 高田, 慎也; 濱, 敏弘 (担当:分担執筆範囲:第3章 大腸がん FOLFIRI±Cmab±Pmab)医学書院 2019年08月 ISBN: 9784260038379 xiv, 617p

講演・口頭発表等

  • シンポジウム36 社会のニーズに応える薬学教育・薬剤師育成を考える ー「医療薬学」から「臨床薬学」への進展 ー これからの薬剤師に必要な能力-薬物療法の個別最適化
    第33回日本医療薬学会年会 2023年11月 シンポジウム・ワークショップパネル(公募)
  • Prognostic Nutritional Indexは肝細胞がん患者に対するレンバチニブ療法の治療効果予測因子となりうる  [通常講演]
    高橋 克之; 柴野 雅仁; 高橋 正也; 中村 安孝; 大鳥 徹
    日本薬学会第143年会 2023年03月 ポスター発表
  • プロトンポンプ阻害薬またはボノプラザンの使用は小細胞肺がんに対するカルボプラチン+エトポシド療法による発熱性好中球減少症の発症を助長する  [通常講演]
    高橋 正也; 高橋 克之; 金田 裕靖; 川口 知哉; 大鳥 徹; 中村 安孝
    日本薬学会第143年会 2023年03月 ポスター発表
  • 医療費削減のために薬物相互作用を考慮したアキシチニブ投与量の検討  [通常講演]
    森山 隆史; 白井 浩一郎; 吉井 悠真; 佐藤 希美; 松尾 朱夏; 辻 あいみ; 松野 純男; 高橋 克之; 北小路; 大鳥 徹
    日本薬学会第143年会 2023年03月 ポスター発表
  • 非小細胞がん患者のQOL改善を目指した経口ペメトレキセドプロドラッグの開発  [通常講演]
    矢本 理絹; 山本 信児; 小畑 秀雄; 中田 匠; 前川 智弘; 中村 光; 太田 彪嗣; 来海 徹太郎; 三好 加純; 詫見 亜由子; 松野 純男; 北小路; 髙橋 克之; 大鳥 徹; 松山 賢治
    日本薬学会第143年会 2023年03月 ポスター発表
  • Regorafenib exposure relationship with clinical efficacy, toxicity, and pharmacogenomics in the treatment of advanced colorectal cancer in the observational exploratory prospective study  [通常講演]
    Satoshi Noda; Satoshi Dote; Tetsuji Terazaw; Emi Goto; Katsuyuki Takahashi; Daiki Hira; Makoto Sanomura; Masaji Tani; Akira Andoh; Masatomo Miura; Masahiro Goto; Shin-ya Morita; Tomohiro Terada
    第60回日本癌治療学会学術集会 2022年10月 ポスター発表
  • 大腸がん患者のラムシルマブ誘発性蛋白尿に及ぼすベバシズマブ前治療歴の影響
    土手 賢史; 塩飽 英二; 河野 えみ子; 眞下 惠次; 吉野 真樹; 池末 裕明; 高橋 克之; 高木 麻里; 伊藤 佳織; 板倉 祥嗣; 根來 寛; 渡邊 裕之; 山口 大介; 宮田 仁美; 小林 由佳
    第60回日本癌治療学会学術集会 2022年10月 口頭発表(一般)
  • シンポジウム 44 進むべき道は自ら切り開く!! 薬剤師のキャリアパスを考える~次世代の薬剤師に向けてメッセージ~ ミドルエイジは何を思い、臨床・研究を頑張るのか
    髙橋克之
    第32回日本医療薬学会年会 2022年09月 シンポジウム・ワークショップパネル(公募)
  • 大腸がん患者におけるカペシタビン療法の有効性に対するヒスタミンH2受容体拮抗薬の併用の影響:多施設共同後方視的観察研究
    細川祐岐; 北爪賀子; 河添仁; 魚住龍史; 吉澤朝枝; 飯原大稔; 藤井宏典; 高橋正也; 新井隆広; 佐藤由美子; 三上貴弘; 横山敦; 山﨑朋子; 高橋克之; 藤田行代志; 村地康; 諸角一成; 土屋雅美; 橋本浩伸; 山口 正和
    日本臨床腫瘍薬学会学術大会2022 2022年03月 口頭発表(一般)
  • 非慢性便秘症患者に対する酸化マグネシウムによるオピオイド誘発性便秘症予防効果に及ぼす胃酸分泌抑制剤の影響
    石神友介; 高橋克之; 高橋正也; 中村安孝
    日本臨床腫瘍薬学会学術大会2022 2022年03月 ポスター発表
  • Pretreatment Platelet Count and NLR are Predictive Markers for Carboplatin-Induced Thrombocytopenia.
    Masaya Takahashi; Katsuyuki Takahashi; Hiroyasu Kaneda; Tomoya Kawaguchi; Katsuya Nagayama
    第19回日本臨床腫瘍学会学術集会 2022年02月 ポスター発表
  • シンポジウム7 がん臨床研究の実践ポイントを学ぶ ~臨床的問題の解決を目指して がん領域における臨床研究のすすめ
    高橋 克之
    第43回日本病院薬剤師会近畿学術大会 2022年01月 シンポジウム・ワークショップパネル(公募)
  • 副作用の観点から見たパルボシクリブとアベマシクリブの使い分けに関する検討
    中務ひとみ; 高橋正也; 高橋克之; 高島勉; 浅野有香; 森崎珠実; 柏木伸一; 郎; 野田諭; 中村安孝
    第31回日本医療薬学会年会 2022年01月 ポスター発表
  • 当院における薬剤費削減を目的とした化学療法レジメンの端数切捨ての取り組み  [通常講演]
    佐野和沙; 古原優也; 高橋克之; 高橋正也; 岡田和也; 中務ひとみ; 原林六華; 松本咲耶; 柴野雅仁; 中村安孝
    第43回日本病院薬剤師会近畿学術大会 2022年01月 ポスター発表
  • プロトンポンプ阻害薬は早期大腸がん患者におけるカペシタビン療法の有効性を低下させる:多施設共同後方視的観察研究  [通常講演]
    髙橋克之; 北爪賀子; 河添仁; 魚住龍史; 吉澤朝枝; 飯原大稔; 藤井宏典; 新井隆広; 村地康; 佐藤由美子; 三上貴弘; 橋口宏司; 山﨑朋子; 高橋正也; 藤田行代志; 細川祐岐; 諸角一成; 土屋雅美; 横山敦; 橋本浩伸; 山口正和
    第31回 日本医療薬学会年会 2021年10月 口頭発表(一般)
  • Association between capecitabine efficacy and proton pump inhibitors in patients with stage II-III colorectal cancer: A retrospective multicenter study.
    Hironori Fujii; Yoshiko Kitazume; Ryuji Uozumi; Hirotoshi Iihara; Masaya Takahashi; Takahiro Arai; Tomoe Yoshizawa; Yasushi Murachi; Yumiko Sato; Takahiro Mikami; Koji Hashiguchi; Katsuyuki Takahashi; Yukiyoshi Fujita; Tomoko Yamazaki; Yuki Hosokawa; Issei Morozumi; Masami Tsuchiya; Atsushi Yokoyama; Hironobu Hashimoto; Masakazu Yamaguchi
    ESMO congress 2021 2021年09月 ポスター発表
  • 進行大腸がん患者におけるレゴラフェニブの血中濃度と治療効果の関連
    野田哲史; 土手賢史; 石塚保亘; 寺澤哲志; 後藤愛実; 高橋克之; 佐野村誠; 谷眞至; 安藤朗; 三浦昌朋; 後藤昌弘; 寺田智祐
    第29回クリニカルファーマシーシンポジウム 2021年07月 ポスター発表
  • 多職種連携による外来がん化学療法副作用マネジメントの取り組み  [招待講演]
    高橋 克之
    日本医療マネジメント学会雑誌 2021年06月 公開講演,セミナー,チュートリアル,講習,講義等 (NPO)日本医療マネジメント学会
  • 肺がんの治療と新型コロナウイルス感染症  [通常講演]
    高橋克之
    日本臨床腫瘍薬学会 学術大会2021 2021年03月 シンポジウム・ワークショップパネル(公募)
  • 肺がんの薬物療法における薬剤師の役割  [招待講演]
    高橋克之
    日本臨床腫瘍薬学会学術大会2021 2021年03月 公開講演,セミナー,チュートリアル,講習,講義等
  • 血清β2-ミクログロブリンは食道がん患者に対するシスプラチン誘発性急性腎障害発症のリスク因子である  [通常講演]
    古原優也; 高橋克之; 豕瀬諒; 髙橋正也; 永山勝也
    第30回 日本医療薬学会年会 2020年10月 口頭発表(一般)
  • 肝細胞癌に対するレンバチニブ療法の治療継続に関する影響因子の検討
    柴野雅仁; 高橋克之; 髙橋正也; 永山勝也
    第30回日本医療薬学会年会 2020年10月 ポスター発表
  • シクロスポリン内服腎移植患者におけるアトルバスタチンの安全性の検討  [通常講演]
    原林六華; 高橋正也; 髙橋克之; 杉本崇; 内田潤次; 永山勝也
    第30回日本医療薬学会年会 2020年10月 ポスター発表
  • 渡邊 裕之; 木村 錦子; 子守 晶子; 樋野 光夫; 高橋 克之; 飯原 大稔; 鎌田 宏和; 橋本 浩伸; 東 光久; 神野 正敏; 辻 力夫
    日本臨床腫瘍薬学会雑誌 2020年05月 (一社)日本臨床腫瘍薬学会
  • 古原 優也; 高橋 克之; 豕瀬 諒; 高橋 正也; 永山 勝也
    日本臨床腫瘍薬学会雑誌 2020年05月 (一社)日本臨床腫瘍薬学会
  • 高橋 克之
    日本臨床腫瘍薬学会雑誌 2020年05月 シンポジウム・ワークショップパネル(公募) (一社)日本臨床腫瘍薬学会
  • 長期経口抗がん剤治療におけるアドヒアランス向上・維持の方策  [招待講演]
    高橋克之
    第34回 日本がん看護学会学術集会 2020年02月 公開講演,セミナー,チュートリアル,講習,講義等
  • 乳癌術前化学療法症例の長期予後におけるサブタイプ別評価の意義  [通常講演]
    後藤 航; 柏木 伸一郎; 高田 晃次; 浅野 有香; 高橋 克之; 藤田 寿一; 高島 勉; 冨田 修平; 平川 弘聖; 大平 雅一
    大阪市医学会雑誌 2019年12月 大阪市医学会
  • 再発乳癌におけるRe-biopsyによる免疫微小環境変化の検証  [通常講演]
    高田 晃次; 柏木 伸一郎; 後藤 航; 浅野 有香; 高橋 克之; 羽多野 隆治; 高島 勉; 冨田 修平; 元村 尚嗣; 大澤 政彦; 平川 弘聖; 大平 雅一
    大阪市医学会雑誌 2019年12月 大阪市医学会
  • 乳癌術前化学療法症例の長期予後におけるサブタイプ別評価の意義
    後藤 航; 柏木 伸一郎; 高田 晃次; 浅野 有香; 高橋 克之; 藤田 寿一; 高島 勉; 冨田 修平; 平川 弘聖; 大平 雅一
    大阪市医学会雑誌 2019年12月 大阪市医学会
  • 再発乳癌におけるRe-biopsyによる免疫微小環境変化の検証
    高田 晃次; 柏木 伸一郎; 後藤 航; 浅野 有香; 高橋 克之; 羽多野 隆治; 高島 勉; 冨田 修平; 元村 尚嗣; 大澤 政彦; 平川 弘聖; 大平 雅一
    大阪市医学会雑誌 2019年12月 大阪市医学会
  • 肝細胞癌治療におけるチーム医療 レンバチニブ治療における薬剤師介入の効果の検討  [通常講演]
    打田 佐和子; 高橋 克之; 周防 舞仁; 高橋 正也; 小田桐 直志; 吉田 香奈子; 小谷 晃平; 元山 宏行; 萩原 淳司; 藤井 英樹; 榎本 大; 田守 昭博; 河田 則文
    肝臓 2019年11月 (一社)日本肝臓学会
  • Cetuximabによる低マグネシウム血症発現に及ぼす影響因子の基礎的・臨床的検討  [通常講演]
    高橋 克之
    薬学研究の進歩 2019年03月 (公財)薬学研究奨励財団
  • 服薬アドヒアランス向上のための薬剤師の取り組み  [招待講演]
    高橋克之
    第33回日本がん看護学会学術集会 2019年02月 公開講演,セミナー,チュートリアル,講習,講義等
  • 川口 博資; 中村 安孝; 矢野 翼; 高橋 克之; 須田 泰記; 南部 敦子; 高橋 典子; 西川 武司; 山田 康一; 掛屋 弘; 永山 勝也
    日本病院薬剤師会雑誌 2018年10月 (一社)日本病院薬剤師会
     
    バンコマイシン塩酸塩(vancomycin:以下、VCM)は、治療薬物モニタリング(therapeutic drug monitoring:以下、TDM)が治療効果と副作用防止につながる。今回、病棟専任薬剤師の介入によるVCMの急性腎障害発現への影響について検討を行った。VCMが投与された症例を病棟薬剤業務開始前(before inpatient pharmaceutical services:before IPS)群と、病棟薬剤業務開始後(after inpatient pharmaceutical services:以下、after IPS)群に分類した。after IPS群で、TDM実施率が有意に上昇し(p<0.001)、また、中毒域到達率が有意に低下し(p=0.029)、VCMによる急性腎障害発現率は有意に減少した(p=0.039)。これらの結果より、病棟専任薬剤師による介入は、VCMの急性腎障害を減少する可能性が示唆された。(著者抄録)
  • 乳癌術前化学療法における癌免疫微小環境の経時的変化から捉えた予後予測  [通常講演]
    後藤 航; 柏木 伸一郎; 浅野 有香; 高田 晃次; 高橋 克之; 野田 諭; 高島 勉; 小野田 尚佳; 富田 修平; 平川 弘聖; 大平 雅一
    日本外科学会定期学術集会抄録集 2018年04月
  • 膵臓がんに対するゲムシタビン+アルブミン懸濁型パクリタキセル療法の治療強度低下に関する影響因子の検討  [通常講演]
    高橋 克之; 豕瀬 諒; 高橋 正也; 永山 勝也
    日本薬学会年会要旨集 2018年03月
  • Heat shock protein 72によるStromal cell-derived factor 2の保護はオキサリプラチン耐性ヒト胃癌細胞においてオキサリプラチン誘導性の細胞死を抑制する  [通常講演]
    高橋 克之; 田中 昌子; 八代 正和; 松本 雅記; 大塚 明日香; 中山 敬一; 泉 康雄; 永山 勝也; 三浦 克之; 岩尾 洋; 塩田 正之
    大阪市医学会雑誌 2017年12月 大阪市医学会
  • 乳癌術前化学療法における癌免疫微小環境の経時的変化の検証  [通常講演]
    後藤 航; 柏木 伸一郎; 浅野 有香; 高田 晃次; 高橋 克之; 高島 勉; 野田 諭; 小野田 尚佳; 富田 修平; 平川 弘聖; 大平 雅一
    日本癌治療学会学術集会抄録集 2017年10月
  • Hsp72によるSDF-2の分解抑制はオキサリプラチン耐性の一因である  [通常講演]
    塩田 正之; 高橋 克之; 八代 正和; 田中 昌子
    日本癌学会総会記事 2017年09月
  • 乳癌術前化学療法による免疫微小環境の経時的変化の検証  [通常講演]
    後藤 航; 柏木 伸一郎; 浅野 有香; 高田 晃次; 高橋 克之; 野田 諭; 高島 勉; 小野田 尚佳; 富田 修平; 平川 弘聖; 大平 雅一
    日本癌学会総会記事 2017年09月
  • 乳癌エリブリン化学療法の耐性機構の検証と免疫微小環境の関与  [通常講演]
    後藤 航; 柏木 伸一郎; 浅野 有香; 高田 晃次; 高橋 克之; 高島 勉; 野田 諭; 小野田 尚佳; 富田 修平; 平川 弘聖; 大平 雅一
    日本乳癌学会総会プログラム抄録集 2017年07月
  • 後藤航; 柏木伸一郎; 浅野有香; 高田晃次; 高橋克之; 高島勉; 野田諭; 小野田尚佳; 富田修平; 平川弘聖; 大平雅一
    日本外科系連合学会誌 2017年05月
  • From Bench to Bedside 臨床と基礎の連携研究 乳癌術前化学療法による免疫微小環境の経時的変化  [通常講演]
    後藤 航; 柏木 伸一郎; 浅野 有香; 高田 晃次; 高橋 克之; 高島 勉; 野田 諭; 小野田 尚佳; 富田 修平; 平川 弘聖; 大平 雅一
    日本外科系連合学会誌 2017年05月
  • From Bench to Bedside 臨床と基礎の連携研究 乳癌術前化学療法による免疫微小環境の経時的変化  [通常講演]
    後藤 航; 柏木 伸一郎; 浅野 有香; 高田 晃次; 高橋 克之; 高島 勉; 野田 諭; 小野田 尚佳; 富田 修平; 平川 弘聖; 大平 雅一
    日本外科系連合学会誌 2017年05月
  • 高橋正也; 高橋克之; 小川和樹; 高島勉; 光川康子; 柏木伸一郎; 野田諭; 小野田尚佳; 大平雅一; 永山勝也
    日本薬学会年会要旨集(CD-ROM) 2017年03月
  • 高橋克之; 豕瀬諒; 永山勝也
    日本薬学会年会要旨集(CD-ROM) 2017年03月
  • 大塚明日香; 田中昌子; 高橋克之; 塩田正之; 松永慎司; 冨田修平; 三浦克之
    日本薬理学会近畿部会プログラム・要旨集 2016年
  • Stromal cell-derived factor 2はoxaliplatin耐性に寄与する  [通常講演]
    高橋 克之; 田中 昌子; 塩田 正之
    日本癌学会総会記事 2015年10月
  • 田中昌子; 高橋克之; 泉康雄; 塩田正之; 三浦克之
    日本薬理学会近畿部会プログラム・要旨集 2015年06月
  • 岩見明子; 中野妙子; 高橋克之; 徳和目篤史; 光川康子; 高島勉; 吉村成央; 川口知哉
    日本臨床腫瘍学会学術集会(CD-ROM) 2015年
  • 櫻井紀宏; 中村安孝; 山田康一; 信田佳克; 高橋克之; 川口博資; 須田泰記; 西川武司; 掛屋弘; 永山勝也
    日本薬学会年会要旨集(CD-ROM) 2015年
  • 中村安孝; 高橋克之; 西川武司; 永山勝也
    日本薬学会年会要旨集(CD-ROM) 2015年
  • 河崎尚史; 川口博資; 中村安孝; 須田泰紀; 高橋克之; 西川武司; 絵本正憲; 稲葉雅章; 永山勝也
    糖尿病 2014年11月
  • 膵癌細胞株PANC-1の環境ストレス耐性株樹立とゲムシタビン感受性への影響(Pancreatic cancer cells resistant to microenvironmental stress have acquired cross-resistance to gemcitabine)  [通常講演]
    市坪 大将; 田中 昌子; 高橋 克之; 鰐渕 英機; 塩田 正之
    日本癌学会総会記事 2014年09月
  • Hsp72-TGFBI複合体はエンドリソソーム系によって分泌される(Hsp72-TGFBI complex is secreted by endolysosomal system under hypoxia)  [通常講演]
    田中 昌子; 高橋 克之; 市坪 大将; 鰐渕 英機; 塩田 正之
    日本癌学会総会記事 2014年09月
  • 高橋 克之; 橋野 美穂; 豕瀬 諒; 川口 博資; 須田 泰記; 中村 安孝; 西川 武司; 高島 勉; 永山 勝也
    日本医療薬学会年会講演要旨集 2014年08月
  • 高橋克之; 橋野美穂; 豕瀬諒; 川口博資; 須田泰記; 中村安孝; 西川武司; 高島勉; 永山勝也
    日本医療薬学会年会講演要旨集 2014年08月
  • Heat shock protein 72 is a key molecule in oxaliplatin resistance in human gastric cancer cell  [通常講演]
    Katsuyuki Takahashi; Masako Tanaka; Masayuki Shiota; Yasukatsu Izumi; Katsuyuki Miura; Hiroshi Iwao
    JOURNAL OF PHARMACOLOGICAL SCIENCES 2014年 JAPANESE PHARMACOLOGICAL SOC
  • 稲垣純子; 高橋克之; 小川弘子; 浅野恵一; HATIPOGLU; Omer Faruk; CILEK Mehmet Zeynel; 小比賀真就; 大月孝志; HOFMANN Matthias; 草地省蔵; 二宮善文; 廣畑聡
    日本結合組織学会学術大会抄録集 2014年
  • 岩見明子; 中野妙子; 竹林房代; 高橋克之; 川上紀子; 光川康子; 中村和徳; 吉村成央; 高島勉; 藤長久美子
    日本癌治療学会学術集会(CD-ROM) 2014年
  • 市坪大将; 田中昌子; 高橋克之; 泉康雄; 塩田正之; 三浦克之; 岩尾洋
    日本薬理学会近畿部会プログラム・要旨集 2014年
  • 中野妙子; 吉村成央; 川端京子; 井上加津子; 堤淳子; 谷口珠美; 徳和目篤史; 高橋克之; 高島勉; 工藤新三
    日本臨床腫瘍学会学術集会(CD-ROM) 2014年
  • 抗癌剤耐性トリプルネガティブ乳がんのプロテオーム解析(Identification of drug resistance-related protein in Triplenegative breast cancer using a proteomic approach)  [通常講演]
    高橋 克之; 田中 昌子; 鰐渕 英機; 塩田 正之
    日本癌学会総会記事 2013年10月
  • 腫瘍マーカー探索のためのHSP72結合解析による血中微量タンパク質同定法の確立(Isolation of HSP72-binding protein in the serum)  [通常講演]
    塩田 正之; 田中 昌子; 高橋 克之; 鰐渕 英機
    日本癌学会総会記事 2013年10月
  • HSP72結合解析による多発性骨髄腫診断マーカーの探索(The search for diagnostic biomarkers of multiple myeloma by analysis of HSP72 interactome)  [通常講演]
    田中 昌子; 高橋 克之; 鰐渕 英機; 塩田 正之
    日本癌学会総会記事 2013年10月
  • 高橋 克之; 尾上 雅英; 福土 将秀; 池見 泰明; 小林 政彦; 深津 祥央; 矢野 育子; 永山 勝也; 松原 和夫
    日本医療薬学会年会講演要旨集 2013年08月
  • 川口 博資; 中村 安孝; 須田 泰記; 高橋 克之; 西川 武司; 絵本 正憲; 稲葉 雅章; 永山 勝也
    日本医療薬学会年会講演要旨集 2013年08月
  • 河端 志保; 中村 安孝; 川口 博資; 須田 泰記; 高橋 克之; 西川 武司; 永山 勝也
    日本医療薬学会年会講演要旨集 2013年08月
  • 河端志保; 中村安孝; 川口博資; 須田泰記; 高橋克之; 西川武司; 永山勝也
    日本医療薬学会年会講演要旨集 2013年08月
  • 高橋克之; 尾上雅英; 福土将秀; 池見泰明; 小林政彦; 深津祥央; 矢野育子; 永山勝也; 松原和夫
    日本医療薬学会年会講演要旨集 2013年08月
  • 川口博資; 中村安孝; 須田泰記; 高橋克之; 西川武司; 絵本正憲; 稲葉雅章; 永山勝也
    日本医療薬学会年会講演要旨集 2013年08月
  • 光川康子; 高橋克之; 川上紀子; 岩見明子; 中野妙子; 松本佳也; 李栄柱; 吉村成央; 高島勉; 工藤新三; 西川武司; 永山勝也
    医療薬学フォーラム講演要旨集 2013年07月
  • 樽井亜紀子; 平田真由美; 竹田律子; 岩見明子; 中野妙子; 佐々木由美子; 川端京子; 高橋克之; 光岡茂樹; 工藤新三
    日本臨床腫瘍学会学術集会(CD-ROM) 2013年
  • 高橋克之; 須田泰記; 川口博資; 中村安孝; 西川武司; 永山勝也
    日本薬学会年会要旨集(CD-ROM) 2013年
  • 稲垣純子; 高橋克之; 小川弘子; OMER F. Hatipoglu; MEHMET Zeynel Cilek; 小比賀真就; 廣畑聡; 二宮善文
    日本生化学会大会(Web) 2012年12月
  • 高橋 克之; 清水 久実代; 須田 泰記; 川口 博資; 中村 安孝; 川上 紀子; 光川 康子; 西川 武司; 永山 勝也
    日本医療薬学会年会講演要旨集 2012年10月
  • 高橋克之; 清水久実代; 須田泰記; 川口博資; 中村安孝; 川上紀子; 光川康子; 西川武司; 永山勝也
    日本医療薬学会年会講演要旨集 2012年10月
  • 分子シャペロンHsc70を標的とした癌のストレス応答分子同定法の確立  [通常講演]
    田中 昌子; 塩田 正之; 三嶋 梨花; 下條 真未; 岡田 麻代実; 高橋 克之; 山形 雅代; 岡 真優子; 泉 康雄; 雪村 時人; 三浦 克之; 岩尾 洋
    日本薬理学雑誌 2012年10月
  • 新規FGF-2機能阻害抗体による内皮細胞の生存抑制効果(A novel neutralizing antibodies against FGF-2 induced endothelial cell death)  [通常講演]
    塩田 正之; 田中 昌子; 高橋 克之; 鰐渕 英機
    日本癌学会総会記事 2012年08月
  • 抗癌剤耐性胃癌細胞を用いたHsp72クライアントタンパク質のプロテオーム解析(Proteomic analysis of heat shock protein 72 client proteins in drug-resistant gastric cancer cell)  [通常講演]
    高橋 克之; 田中 昌子; 鰐渕 英機; 塩田 正之
    日本癌学会総会記事 2012年08月
  • 癌のストレス応答を標的としたHsc70クライアントタンパク質のプロテオーム解析(Proteomic analysis of Hsc70 client proteins targeting stress response in cancer cells)  [通常講演]
    田中 昌子; 高橋 克之; 鰐渕 英機; 塩田 正之
    日本癌学会総会記事 2012年08月
  • 高橋克之; 木村錦子; 中村瑞穂; 須田泰記; 川口博資; 徳和目篤史; 池浦啓博; 川上紀子; 光川康子; 西川武司; 永山勝也
    日本薬学会年会要旨集 2012年03月
  • 高橋 克之; 中村 瑞穂; 小池 敦資; 徳和目 篤史; 池浦 啓博; 川上 紀子; 光川 康子; 西川 武司; 永山 勝也
    日本医療薬学会年会講演要旨集 2011年09月
  • 高橋克之; 中村瑞穂; 小池敦資; 徳和目篤史; 池浦啓博; 川上紀子; 光川康子; 西川武司; 永山勝也
    日本医療薬学会年会講演要旨集 2011年09月
  • 泉康雄; 山下直人; 高橋克之; 田中昌子; 南野優子; 文沙や; 山口麻貴; 塩田正之; 中尾隆文; 岩尾洋
    血管 2011年01月
  • 稲垣純子; 高橋克之; 小川弘子; HATIPOGLU; Omer F; MEHMET ZEYNEL Cilek; 小比賀真就; 米澤朋子; 大橋俊孝; 廣畑聡; 二宮善文
    生化学 2011年
  • 高橋克之; 南野優子; 西川武司; 永山勝也; 岩尾洋
    日本医療薬学会年会講演要旨集 2010年10月
  • 高橋 克之; 南野 優子; 西川 武司; 永山 勝也; 岩尾 洋
    日本医療薬学会年会講演要旨集 2010年10月
  • 廣畑聡; 小比賀真就; HATIPOGLU; Omer Faruk; 小川弘子; CILEK Mehmet Zeynel; 高橋克之; 稲垣純子; 三好亨; 大月孝志; 石井裕子; 草地省蔵; 米澤朋子; 大橋俊孝; 二宮善文
    日本結合組織学会学術大会抄録集 2010年08月
  • 稲垣純子; 高橋克之; 小川弘子; HATIPOGLU; Omer F; CILEK Mehmet Zeynel; 小比賀真就; 米澤朋子; 大橋俊孝; 廣畑聡; 二宮善文
    日本結合組織学会学術大会抄録集 2010年08月
  • 高橋克之; 廣畑聡; 小比賀真就; 三好亨; 小川弘子; 草地省蔵; 二宮善文
    日本薬学会年会要旨集 2009年03月
  • 高橋克之; 廣畑聡; 山脇均; 三好亨; 小川弘子; 二宮善文
    日本軟骨代謝学会プログラム・抄録集 2009年

MISC

  • カペシタビンと胃酸分泌抑制薬の薬物間相互作用の解明に向けた多施設共同臨床研究及び基礎研究
    河添 仁; 北爪 賀子; 魚住 龍史; 吉澤 朝枝; 飯原 大稔; 藤井 宏典; 高橋 正也; 新井 隆広; 村地 康; 佐藤 由美子; 三上 貴弘; 橋口 宏司; 山崎 朋子; 高橋 克之; 藤田 行代志; 細川 祐岐; 諸角 一成; 土屋 雅美; 横山 敦; 橋本 浩伸; 山口 正和; 古川 哲也; 関口 真由; 平井 光成; 秋山 雅博; 金 倫基; 中村 智徳 医療の広場 62 (10) 11 -14 2022年10月
  • 乳癌術前化学療法における癌免疫微小環境の経時的変化から捉えた予後予測
    後藤 航; 柏木 伸一郎; 浅野 有香; 高田 晃次; 高橋 克之; 野田 諭; 高島 勉; 小野田 尚佳; 富田 修平; 平川 弘聖; 大平 雅一 日本外科学会定期学術集会抄録集 118回 1040 -1040 2018年04月
  • Heat shock protein 72によるStromal cell-derived factor 2の保護はオキサリプラチン耐性ヒト胃癌細胞においてオキサリプラチン誘導性の細胞死を抑制する
    高橋 克之; 田中 昌子; 八代 正和; 松本 雅記; 大塚 明日香; 中山 敬一; 泉 康雄; 永山 勝也; 三浦 克之; 岩尾 洋; 塩田 正之 大阪市医学会雑誌 66 40 -41 2017年12月
  • 乳癌術前化学療法における癌免疫微小環境の経時的変化の検証
    後藤 航; 柏木 伸一郎; 浅野 有香; 高田 晃次; 高橋 克之; 高島 勉; 野田 諭; 小野田 尚佳; 富田 修平; 平川 弘聖; 大平 雅一 日本癌治療学会学術集会抄録集 55回 P10 -6 2017年10月
  • 乳癌術前化学療法による免疫微小環境の経時的変化の検証
    後藤 航; 柏木 伸一郎; 浅野 有香; 高田 晃次; 高橋 克之; 野田 諭; 高島 勉; 小野田 尚佳; 富田 修平; 平川 弘聖; 大平 雅一 日本癌学会総会記事 76回 E -1033 2017年09月
  • Hsp72によるSDF-2の分解抑制はオキサリプラチン耐性の一因である
    塩田 正之; 高橋 克之; 八代 正和; 田中 昌子 日本癌学会総会記事 76回 J -1017 2017年09月
  • 外来癌化学療法中の発熱に対するメシル酸ガレノキサシン水和物事前処方の有用性評価
    高橋 正也; 高橋 克之; 小川 和樹; 高島 勉; 光川 康子; 柏木 伸一郎; 野田 諭; 小野田 尚佳; 大平 雅一; 永山 勝也 日本薬学会年会要旨集 137年会 (4) 174 -174 2017年03月
  • ADAMTS1はVEGFCと結合してリンパ管新生を抑制する
    稲垣 純子; 高橋 克之; 小川 弘子; 浅野 恵一; Hatipoglu Omer Faruk; Cile Mehmet Zeynel; 小比賀 真就; 大月 孝志; Hofmann Matthias; 草地 省蔵; 二宮 善文; 廣畑 聡 日本結合組織学会学術大会・マトリックス研究会大会合同学術集会プログラム・抄録集 46回・61回 137 -137 2014年06月
  • リンパ管内皮細胞に対するADAMTS1の作用とシグナル伝達
    稲垣 純子; 高橋 克之; 小川 弘子; Hatipoglu Omer F; Zeynel Cilek Mehmet; 小比賀 真就; 廣畑 聡; 二宮 善文 日本生化学会大会プログラム・講演要旨集 85回 2P -832 2012年12月
  • 分子シャペロンHsc70を標的とした癌のストレス応答分子同定法の確立
    田中 昌子; 塩田 正之; 三嶋 梨花; 下條 真未; 岡田 麻代実; 高橋 克之; 山形 雅代; 岡 真優子; 泉 康雄; 雪村 時人; 三浦 克之; 岩尾 洋 日本薬理学雑誌 140 (4) 12P -12P 2012年10月
  • ADAMTS1のin vitroでのリンパ管新生阻害効果
    稲垣 純子; 高橋 克之; 小川 弘子; Hatipoglu Omer F; Cilek Mehmet Zeynel; 小比賀 真就; 米澤 朋子; 大橋 俊孝; 廣畑 聡; 二宮 善文 日本生化学会大会プログラム・講演要旨集 84回 2P -0343 2011年09月
  • 心肥大に対する抗線維化薬の効果
    泉 康雄; 山下 直人; 高橋 克之; 田中 昌子; 南野 優子; 文 沙耶; 山口 麻貴; 塩田 正之; 中尾 隆文; 岩尾 洋 血管 34 (1) 45 -45 2011年01月

受賞

  • 2017年03月 大阪市医学会 第62回大阪市医学会賞
     
    受賞者: 高橋克之
  • 2016年03月 大阪市医学会 第61回大阪市医学会賞
     
    受賞者: 高橋克之

共同研究・競争的資金等の研究課題

  • 文部科学省:科学研究費補助金(若手研究)
    研究期間 : 2019年04月 -2022年03月 
    代表者 : 高橋克之
  • 文部科学省:科学研究費補助金(若手研究B)
    研究期間 : 2017年04月 -2019年03月 
    代表者 : 高橋 克之
  • Cetuximab による低マグネシウム血症発現及ぼす影響因子の基礎的・臨床的検討
    公益財団法人 薬学研究奨励財団:薬学及び関連諸分野の研究に対する助成
    研究期間 : 2016年04月 -2017年03月 
    代表者 : 高橋 克之
  • 日本学術振興会:科学研究費助成事業
    研究期間 : 2012年04月 -2014年03月 
    代表者 : 高橋 克之
     
    熱ショック蛋白質72(Hsp72)は蛋白質の立体構造の維持や癌遺伝子の安定化、ストレス回避反応を担っている。また胃癌においてHsp72過剰発現が抗癌剤耐性に関与しているとの報告がある。我々はHsp72の結合蛋白質が抗癌剤耐性に重要な役割を果たしていると考えた。 ヒト胃癌細胞株2Mおよびoxaliplatin(OXA)耐性株2M/OXAを用いた。LC/MS/MSにより2M/OXA特異的なHsp72結合蛋白質を同定した。その中の1つ、stromal cell derived factor2を機能阻害することでOXAによる細胞死が増強された。 Hsp72結合蛋白質は薬剤耐性を克服する標的となりうる。

担当経験のある科目

  • 総合薬学研究3近畿大学 薬学部
  • 総合薬学研究2近畿大学 薬学部
  • 総合薬学研究1近畿大学 薬学部
  • 実務実習事前学習近畿大学 薬学部
  • 医薬連携学習近畿大学 薬学部
  • フィジカルアセスメント近畿大学 薬学部
  • 実践病態と治療近畿大学 薬学部
  • ファーマシューティカルケア近畿大学 薬学部
  • 生命倫理近畿大学 薬学部
  • 医療・薬事関係法規2近畿大学 薬学部
  • 医療・薬事関係法規1近畿大学 薬学部
  • 生体と薬物大阪市立大学 医学部
  • 模擬患者による多職種参加型個別化医療課題演習大阪市立大学大学院 医学研究科
  • 多職種参加型症例検討演習大阪市立大学大学院 医学研究科

社会貢献活動

  • 令和元年度 奈良県がん化学療法薬剤師研修会
    期間 : 2019年08月31日
    役割 : 助言・指導
    種別 : セミナー・ワークショップ
    主催者・発行元 : 奈良県立医科大学附属病院
  • 肺がんの基礎知識
    期間 : 2019年06月09日
    役割 : 講師
    種別 : 資格認定講習
    主催者・発行元 : 日本臨床腫瘍薬学会
    イベント・番組・新聞雑誌名 : スタートアップセミナー 2019 大阪
  • 肺がんの基礎知識
    期間 : 2019年05月26日
    役割 : 講師
    種別 : 資格認定講習
    主催者・発行元 : 臨床腫瘍薬学会
    イベント・番組・新聞雑誌名 : スタートアップセミナー 2019 東京
  • 大阪府におけるがん化学療法に関わる薬剤師の地域リーダー養成研修
    期間 : 2018年09月15日 - 2019年02月09日
    役割 : 助言・指導
    種別 : セミナー・ワークショップ
    主催者・発行元 : 大阪府立病院機構 大阪国際がんセンター
  • 平成30年度 奈良県がん化学療法薬剤師研修会
    期間 : 2018年09月01日
    役割 : 助言・指導
    種別 : セミナー・ワークショップ
    主催者・発行元 : 奈良県立医科大学附属病院
  • 肺がんの基礎知識
    期間 : 2018年06月24日
    役割 : 講師
    種別 : 資格認定講習
    主催者・発行元 : 日本臨床腫瘍薬学会
    イベント・番組・新聞雑誌名 : スタートアップセミナー 2018 大阪
  • がん専門薬剤師・がん薬物療法認定薬剤師海外派遣事業研修報告
    期間 : 2017年06月19日
    役割 : 講師
    種別 : 講演会
    主催者・発行元 : 小林がん学術振興会
  • 薬剤師の副作用マネジメント
    期間 : 2016年09月25日
    役割 : パネリスト
    種別 : 講演会
    主催者・発行元 : 肺がん医療向上委員会(日本肺癌学会)
    イベント・番組・新聞雑誌名 : 医療従事者向けセミナー2016 大阪

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