![](https://www.kindai.ac.jp/data/images/professor/2753.jpg)
TAKAHASHI Katsuyuki
Department of Pharmacy | Lecturer |
Last Updated :2024/08/31
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10597751
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- 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
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- Analysis of Factors Influencing Hospital Recommendations Using the Outpatient Satisfaction SurveyKatsuyuki Takahashi; Sumio Matzno; Chiyuki Kurisu; Manabu Kitakouji; Toru Otori; Kenji YasukaThe Japanese Journal of Quality and Safety in Healthcare 19 (2) 145 - 155 2024/05 [Refereed]
- Hironori Fujii; Masami Tsuchiya; Daichi Watanabe; Ryo Otsuka; Daisuke Hirate; Katsuyuki Takahashi; Makiko Go; Toshihiro Kudo; Kazuhiro Shimomura; Yosuke Ando; Shinya Tani; Takao Takahashi; Katsuhisa Hayashi; Miki Chin; Naomi Matsunami; Masaya Takahashi; Akiko Hasegawa; Takashi Uchida; Hironobu Hashimoto; Akiko Kubo; Nobuhisa Matsuhashi; Akio Suzuki; Junichi Nishimura; Naoki Inui; Hirotoshi IiharaSupportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 32 (5) 291 2024/04 [Refereed]
BACKGROUND: Trifluridine/tipiracil (TAS-102) is an oral anticancer drug with adequate efficacy in unresectable colorectal cancer, but frequently also induces chemotherapy-induced nausea and vomiting (CINV). To investigate the occurrence of CINV and antiemetic therapy in patients with colorectal cancer treated with TAS-102 (JASCC-CINV 2001). METHODS: We conducted a multicenter, prospective, observational study in patients with colorectal cancer who received TAS-102 without dose reduction for the first time. Primary endpoint was the incidence of vomiting during the overall period. Secondary endpoints were the incidence of nausea, significant nausea, anorexia, other adverse events (constipation, diarrhea, insomnia, fatigue, dysgeusia) and patient satisfaction. Patient diaries were used for primary and secondary endpoints. All adverse events were subjectively assessed using PRO-CTCAE ver 1.0. and CTCAE ver 5.0. RESULTS: Data from 100 of the 119 enrolled patients were analyzed. The incidence of vomiting, nausea, and significant nausea was 13%, 67%, and 36%, respectively. The incidence of vomiting in patients with and without prophylactic antiemetic therapy were 20.8% and 10.5%, respectively. Prophylactic antiemetics were given to 24% of patients, of whom 70% received D2 antagonists. Multivariate Cox proportional hazards analysis showed that experience of CINV in previous treatment tended to be associated with vomiting (hazard ratio [HR]: 7.13, 95% confidence interval [CI]: 0.87-58.5, P = 0.07), whereas prophylactic antiemetic administration was not (HR: 1.61, 95 CI: 0.50-5.21, P = 0.43). With regard to patient satisfaction, the proportion of patients who were "very satisfied," "satisfied," "slightly satisfied" or "somewhat satisfied" was 81.8%. CONCLUSIONS: The low incidence of vomiting and high patient satisfaction suggest that TAS-102 does not require the use of uniform prophylactic antiemetic treatments. However, patients with the experience of CINV in previous treatment might require prophylactic antiemetic treatment. - Masaya Takahashi; Katsuyuki Takahashi; Hiroyasu Kaneda; Tomoya Kawaguchi; Toru Otori; Yasutaka NakamuraOncology 2023/12 [Refereed]
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 KobayashiInternational journal of clinical oncology 28 (8) 1054 - 1062 2023/08 [Refereed]
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 NagayamaDie Pharmazie 78 (5) 47 - 50 2023/05 [Refereed]
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 NagayamaAnticancer research 42 (12) 6019 - 6026 2022/12 [Refereed]
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 (公財)政策医療振興財団 62 (10) 11 - 14 2022/10
- Hitomi Nakatsukasa; Masaya Takahashi; Katsuyuki Takahashi; Tsutomu Takashima; Yuka Asano; Tamami Morisaki; Shinichiro Kashiwagi; Satoru Noda; Yasutaka NakamuraBiological & pharmaceutical bulletin 45 (10) 1476 - 1481 2022/10 [Refereed]
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 FurukawaJournal of Cancer Ivyspring International Publisher 13 (10) 3073 - 3083 1837-9664 2022/08 [Refereed]
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. - Analysis of Factors Influencing Acute Kidney Injury with Docetaxel, Cisplatin, and 5-fluorouracil in Patients with Esophageal CancerYuya Kohara; Katsuyuki Takahashi; Ryo Inose; Masaya Takahashi; Katsuya Nagayama医療薬学 48 (6) 259 - 266 2022/06 [Refereed]
- Mayuko Osada-Oka; Hikaru Kuwamura; Risa Imamiya; Keiko Kobayashi; Yukiko Minamiyama; Katsuyuki Takahashi; Masako Tanaka; Masayuki ShiotaEuropean journal of pharmacology 920 174845 - 174845 2022/04 [Refereed]
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 NagayamaTransplant infectious disease : an official journal of the Transplantation Society e13804 2022/02 [Refereed]
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 NagayamaInternational journal of clinical oncology 27 (2) 348 - 353 2022/02 [Refereed]
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 YamaguchiScientific Reports Springer Science and Business Media LLC 12 (1) 2022/01 [Refereed]
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 NagayamaAnticancer research 41 (11) 5729 - 5737 2021/11 [Refereed]
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 OhiraBMC cancer 20 (1) 1215 - 1215 2020/12 [Refereed]
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 OhiraOncology letters 20 (5) 180 - 180 2020/11 [Refereed]
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 OhiraMolecular and clinical oncology 13 (2) 195 - 202 2020/08 [Refereed]
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 NagayamaAnticancer research 40 (7) 4047 - 4051 2020/07 [Refereed]
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 OhiraBMC cancer 20 (1) 513 - 513 2020/06 [Refereed]
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 NagayamaTransplant infectious disease : an official journal of the Transplantation Society 22 (1) e13239 2020/02 [Refereed]
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 OhiraAnticancer research 39 (10) 5581 - 5588 2019/10 [Refereed]
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 OhiraAnticancer research 39 (8) 4031 - 4041 2019/08 [Refereed]
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 OhiraBMC cancer 19 (1) 615 - 615 2019/06 [Refereed]
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 OhiraAnticancer research 39 (6) 2941 - 2950 2019/06 [Refereed]
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 OhiraAnticancer research 39 (5) 2259 - 2264 2019/05 [Refereed]
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 TakadaInternational journal of clinical pharmacology and therapeutics 57 (2) 63 - 72 0946-1965 2019/02 [Refereed]
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. . - Inose R; Takahashi K; Nanno S; Hino M; Nagayama KJournal of chemotherapy (Florence, Italy) 31 (1) 30 - 34 1120-009X 2019/02 [Refereed]
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 MJournal of translational medicine 17 (1) 13 - 13 2019/01 [Refereed]
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 KSupportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 27 (8) 2829 - 2836 0941-4355 2018/12 [Refereed]
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 MJournal of translational medicine 16 (1) 307 - 307 2018/11 [Refereed]
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 MBMC cancer 18 (1) 1137 - 1137 2018/11 [Refereed]
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 MJournal of translational medicine 16 (1) 318 - 318 2018/11 [Refereed]
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 MBritish journal of cancer 119 (5) 572 - 579 0007-0920 2018/08 [Refereed]
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 OhiraJournal of Cancer Research and Clinical Oncology Springer Verlag 144 (8) 1 - 13 1432-1335 2018/05 [Refereed]
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 OhiraIn Vivo International Institute of Anticancer Research 32 (3) 669 - 675 1791-7549 2018/05 [Refereed]
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 OhiraJournal of Translational Medicine BioMed Central Ltd. 16 (1) 87 - 87 1479-5876 2018/04 [Refereed]
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 OhiraJournal of Translational Medicine BioMed Central Ltd. 16 (1) 86 - 86 1479-5876 2018/04 [Refereed]
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 OhiraAnticancer Research International Institute of Anticancer Research 38 (4) 2311 - 2321 1791-7530 2018/04 [Refereed]
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 OhiraJournal of Translational Medicine BioMed Central Ltd. 16 (1) 54 - 54 1479-5876 2018/03 [Refereed]
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 KOncomedicine 3 9 - 14 2018/01 [Refereed]
- 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 OhiraAnticancer Research International Institute of Anticancer Research 38 (1) 401 - 410 1791-7530 2018/01 [Refereed]
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 MESMO open 3 (6) e000305 2018 [Refereed]
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
- Goto Wataru; Kashiwagi Shinichiro; Asano Yuka; Takada Koji; Takahashi Katsuyuki; Noda Satoru; Takashima Tsutomu; Onoda Naoyoshi; Tomita Shuhei; Hirakawa Kosei; Ohira MasaichiCANCER SCIENCE 109 123 1349-7006 2018/01 [Refereed]
- 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 OhiraBMC Cancer BioMed Central Ltd. 17 (1) 888 - 888 1471-2407 2017/12 [Refereed]
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 (一社)日本医療薬学会 43 (10) 577 - 584 1346-342X 2017/10 [Refereed]
- Shinichiro Kashiwagi; Yuka Asano; Wataru Goto; Koji Takada; Katsuyuki Takahashi; Takaharu Hatano; Tsutomu Takashima; Shuhei Tomita; Hisashi Motomura; Masahiko Ohsawa; Kosei Hirakawa; Masaichi OhiraANTICANCER RESEARCH INT INST ANTICANCER RESEARCH 37 (10) 5623 - 5630 0250-7005 2017/10 [Refereed]
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 MasaichiCANCER RESEARCH 77 0008-5472 2017/07 [Refereed]
- Goto Wataru; Kashiwagi Shinichiro; Takada Koji; Takahashi Katsuyuki; Takashima Tsutomu; Noda Satoru; Onoda Naoyoshi; Tomita Shuhei; Hirakawa Kosei; Ohira MasaichiCANCER RESEARCH 77 0008-5472 2017/07 [Refereed]
- 高橋克之; 豕瀬諒; 高橋正也; 永山勝也医療薬学 43 (6) 336‐343 1346-342X 2017/06 [Refereed]
- Using Opioids to Control Pain Due to Mucosal Damage after Radiotherapy to Treat Head and Neck Cancer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 日本緩和医療薬学会 10 (1) 13 - 18 1882-9783 2017/03 [Refereed]
- 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 1346-342X 2017/03 [Refereed]
- Shinichiro Kashiwagi; Yuka Asano; Wataru Goto; Koji Takada; Katsuyuki Takahashi; Satoru Noda; Tsutomu Takashima; Naoyoshi Onoda; Shuhei Tomita; Masahiko Ohsawa; Kosei Hirakawa; Masaichi OhiraPLOS ONE PUBLIC LIBRARY SCIENCE 12 (2) e0170634 1932-6203 2017/02 [Refereed]
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 MBiomarker research 5 19 - 19 2017 [Refereed]
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 ShiotaCANCER LETTERS ELSEVIER IRELAND LTD 378 (1) 8 - 15 0304-3835 2016/08 [Refereed]
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. - Inose Ryo; Takahashi Katsuyuki; Nishikawa Takeshi; Nagayama KatsuyaIryo Yakugaku (Japanese Journal of Pharmaceutical Health Care and Sciences) Japanese Society of Pharmaceutical Health Care and Sciences 42 (6) 460 - 467 1346-342X 2016/06 [Refereed]
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 IwaoJOURNAL OF PROTEOMICS ELSEVIER SCIENCE BV 136 214 - 221 1874-3919 2016/05 [Refereed]
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 NagayamaYAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN PHARMACEUTICAL SOC JAPAN 135 (12) 1403 - 1407 0031-6903 2015/12 [Refereed]
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 NagayamaYAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN PHARMACEUTICAL SOC JAPAN 135 (9) 1077 - 1082 0031-6903 2015/09 [Refereed]
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. - NAKAMURA YASUTAKA; SUGIMOTO TAKASHI; SOTOMA MAMI; KODAMA NORIKO; TAKAHASHI KATSUYUKI; KAWAGUCHI HIROSHI; SUDA YASUKI; NISHIKAWA TAKESHI; NAGAYAMA KATSUYA日本病院薬剤師会雑誌 51 (6) 751 - 755 1341-8815 2015/06 [Refereed]
- SUDA YASUKI; NAKAMURA YASUTAKA; TAKAHASHI KATSUYUKI; KAWAGUCHI HIROSHI; NISHIKAWA TAKESHI; NAGAYAMA KATSUYA日本病院薬剤師会雑誌 50 (12) 1475 - 1479 1341-8815 2014/12 [Refereed]
- 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 OhkawaMonoclonal Antibodies in Immunodiagnosis and Immunotherapy Mary Ann Liebert Inc. 33 (4) 261 - 269 2167-9436 2014/08 [Refereed]
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 HirohataExperimental cell research 323 (2) 263 - 75 0014-4827 2014/05 [Refereed]
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 IwaoPLOS ONE PUBLIC LIBRARY SCIENCE 9 (5) e96785 1932-6203 2014/05 [Refereed]
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. - TAKAHASHI KATSUYUKI; ONOUE MASAHIDE; FUKUDO MASAHIDE; IKEMI YASUAKI; KOBAYASHI MASAHIKO; FUKATSU SACHIO; YANO IKUKO; NAGAYAMA KATSUYA; MATSUBARA KAZUO日本病院薬剤師会雑誌 49 (12) 1305 - 1309 1341-8815 2013/12 [Refereed]
- Katsuyuki Takahashi; Masako Tanaka; Azusa Inagaki; Hideki Wanibuchi; Yasukatsu Izumi; Katsuyuki Miura; Katsuya Nagayama; Masayuki Shiota; Hiroshi IwaoINTERNATIONAL JOURNAL OF ONCOLOGY SPANDIDOS PUBL LTD 43 (6) 1985 - 1991 1019-6439 2013/12 [Refereed]
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. - TAKAHASHI KATSUYUKI; NAKAMURA YASUTAKA; MINAMINO YUKO; KAWAGUCHI HIROSHI; NISHIKAWA TAKESHI; NAGAYAMA KATSUYA; IWAO HIROSHI医療薬学 Japanese Society of Pharmaceutical Health Care and Sciences 39 (3) 166 - 173 1346-342X 2013/03 [Refereed]
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 HirohataCancer science 103 (10) 1889 - 97 1347-9032 2012/10 [Refereed]
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 NinomiyaGLYCOBIOLOGY OXFORD UNIV PRESS INC 19 (1) 83 - 92 0959-6658 2009/01 [Refereed]
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.
MISC
Books and other publications
- 松尾, 宏一; 緒方, 憲太郎; 林, 稔展 (Contributor3段目 がん薬物療法 15. 乳がん)医学書院 2024/05 4260053566 568
- 川上, 和宜; 松尾, 宏一; 林, 稔展; 大橋, 養賢; 小笠原, 信敬; 吉村, 知哲; 田村, 和夫 (Contributor24 腎障害)医学書院 2024/02 9784260053679 xviii, 398p
- 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 (Contributor2.4 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 2023/07
- 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 (Contributor第3章 大腸がん FOLFIRI±AFL)医学書院 2023/02 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~(Contributor第Ⅲ章 筋炎・横紋筋融解症)南江堂 2022/02
- 川上, 和宜; 松尾, 宏一; 吉村, 知哲 (ContributorCHAPTER2 3. 腹痛)南江堂 2021/09 9784524228362 v, 274p
- 望月, 敬浩; 中村, 安孝; 川上, 和宜; 大橋, 養賢; 原田, 知彦 (Contributorがん(症例124,症例125,症例134,症例157,症例192))南山堂 2020/08 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 (Contributor抗EGFR(epidermal growth factor receptor)抗体)2020/06
- 松尾, 宏一; 緒方, 憲太郎; 林, 稔展 (Contributor3段目 14. 乳がん)医学書院 2020/04 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 (Contributor第3章 大腸がん FOLFIRI±Cmab±Pmab)医学書院 2019/08 9784260038379 xiv, 617p
Lectures, oral presentations, etc.
- 在宅施設患者における痒みとスキンケアに関する実態調査倉橋 翔太; 松野 純男; 石川 佳奈; 川畑 篤史; 高橋 克之; 大鳥 徹; 山本 卓資; 榊原 幹夫日本薬学会第144年会 2024/03
- シンポジウム19 臨床現場と大学の協働によるエビデンスの創出と次世代を担う後進育成 臨床マインドと研究マインドを兼ね備えた次世代を担う薬剤師の育成 [Not invited]高橋克之日本臨床腫瘍薬学会学術大会2024 2024/03
- 36高橋克之The 33rd Annual Meeting of the Japanese Society of Pharmaceutical Health Care and Sciences 2023/11
- Prognostic nutrition index as an indicator of therapeutic response to Lenvatinib therapy in hepatocellular carcinoma [Not invited]高橋 克之; 柴野 雅仁; 高橋 正也; 中村 安孝; 大鳥 徹The 143rd Annual Meeting of the Pharmaceutical Society of Japan 2023/03
- Proton pump inhibitor or vonoprazan use are associated with occurrence of febrile neutropenia in patients with small-cell lung cancer receiving carboplatin plus etoposide [Not invited]高橋 正也; 高橋 克之; 金田 裕靖; 川口 知哉; 大鳥 徹; 中村 安孝The 143rd Annual Meeting of the Pharmaceutical Society of Japan 2023/03
- Drug interaction : A study on the use of Axitinib drug therapy to reduce medical expenses [Not invited]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The 143rd Annual Meeting of the Pharmaceutical Society of Japan 2023/03
- The development of the prodrug oral Pemetrexed to improve the QOL of non-small cell lung cancer patients [Not invited]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The 143rd Annual Meeting of the Pharmaceutical Society of Japan 2023/03
- Regorafenib exposure relationship with clinical efficacy, toxicity, and pharmacogenomics in the treatment of advanced colorectal cancer in the observational exploratory prospective study [Not invited]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 TeradaThe 60th Annual Meeting of the Japan Society of Clinical Oncology 2022/10
- Impact of prior bevacizumab therapy on the incidence of ramucirumab-induced proteinuria in colorectal cancer: a multi-institutional (IMBERA) cohort studyDote Satoshi; Shiwaku Eiji; Kohno Emiko; Mashimo Keiji; Yoshino Masaki; Ikesue Hiroaki; Takahashi Katsuyuki; Takagi Mari; Ito Kaori; Itakura Shoji; Negoro Yutaka; Watanabe Hiroyuki; Yamaguchi Daisuke; Miyata Hitomi; Kobayashi Yuka60th Annual Meeting of the Japan Society of Clinical Oncology2022 2022/10
- 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 2022/09
- 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 2022/03
- 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 2022/03
- 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 2022/02
- 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 2022/01
- 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 2022/01
- 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 [Not invited]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 2022/01
- 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 [Not invited]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 2021/10
- 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 YamaguchiESMO congress 2021 2021/09
- 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 2021/07
- 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 [Invited]高橋 克之日本医療マネジメント学会雑誌 2021/06 (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 [Not invited]高橋克之日本臨床腫瘍薬学会 学術大会2021 2021/03
- 肺がんの薬物療法における薬剤師の役割 [Invited]高橋克之日本臨床腫瘍薬学会学術大会2021 2021/03
- 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 [Not invited]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 2020/10
- 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 2020/10
- 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 [Not invited]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 2020/10
- 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 2020/05 (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 2020/05 (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 [Invited]高橋克之第34回 日本がん看護学会学術集会 2020/02
- 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 [Not invited]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 2019/12 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 [Not invited]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 2019/12 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 2019/12 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 2019/12 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 [Not invited]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 2019/11 (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 [Not invited]高橋 克之薬学研究の進歩 2019/03 (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 [Invited]高橋克之第33回日本がん看護学会学術集会 2019/02
- 病棟薬剤業務によるVCMの急性腎障害防止効果の検討 [Not invited]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 2018/10 (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 [Not invited]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 2018/04
- 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 [Not invited]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 2018/03
- 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 [Not invited]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 2017/12 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 [Not invited]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 2017/10
- 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 [Not invited]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 2017/09
- 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 [Not invited]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 2017/09
- 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 [Not invited]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 2017/07
- 乳癌術前化学療法による免疫微小環境の経時的変化 [Not invited]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 2017/05
- 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 [Not invited]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 2017/05
- 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 [Not invited]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 2017/05
- 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 [Not invited]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) 2017/03
- 高橋克之; 豕瀬諒; 永山勝也日本薬学会年会要旨集(CD-ROM) 2017/03
- SDF‐2はHsp72による発現が保持されることでオキサリプラチン耐性に関与する [Not invited]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
- Stromal cell-derived factor 2はoxaliplatin耐性に寄与する [Not invited]高橋 克之; 田中 昌子; 塩田 正之日本癌学会総会記事 2015/10
- ゲムシタビン耐性ヒト膵癌細胞株における生存因子の同定 [Not invited]TANAKA MASAKO; TAKAHASHI KATSUYUKI; IZUMI YASUO; SHIOTA MASAYUKI; MIURA KATSUYUKI日本薬理学会近畿部会プログラム・要旨集 2015/06
- 曝露対策教育でのDVD視聴と演習活用の効果 [Not invited]IWAMI AKIKO; NAKANO TAEKO; TAKAHASHI KATSUYUKI; TOKUWAME ATSUSHI; MITSUKAWA YASUKO; TAKASHIMA TSUTOMU; YOSHIMURA NARUO; KAWAGUCHI TOMOYA日本臨床腫瘍学会学術集会(CD-ROM) 2015
- 小児の発熱性好中球減少症へのリネゾリドの使用に関する検討 [Not invited]SAKURAI NORIHIRO; NAKAMURA YASUTAKA; YAMADA KOICHI; SHINODA YOSHIKATSU; TAKAHASHI KATSUYUKI; KAWAGUCHI HIROSHI; SUDA TAIKI; NISHIKAWA TAKESHI; KAKEYA HIROSHI; NAGAYAMA KATSUYA日本薬学会年会要旨集(CD-ROM) 2015
- ヒト近位尿細管細胞の生存に対する抗MRSA薬の影響 [Not invited]NAKAMURA YASUTAKA; TAKAHASHI KATSUYUKI; NISHIKAWA TAKESHI; NAGAYAMA KATSUYA日本薬学会年会要旨集(CD-ROM) 2015
- 糖尿病におけるメトホルミン増量の治療効果と安全性 [Not invited]KAWASAKI NAOFUMI; KAWAGUCHI HIROSHI; NAKAMURA YASUTAKA; SUDA YASUNORI; TAKAHASHI KATSUYUKI; NISHIKAWA TAKESHI; EMOTO MASANORI; INABA MASAAKI; NAGAYAMA KATSUYA糖尿病 2014/11
- 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) [Not invited]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 2014/09
- 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) [Not invited]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 2014/09
- 27-P4AM-143 乳がんに対するエリブリン療法の有害反応解析と治療継続に関する影響因子の検討(がん薬物療法(その他),一般演題(ポスター),新時代を拓く医療薬学フロンティア) [Not invited]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 2014/08
- 乳がんに対するエリブリン療法の有害反応解析と治療継続に関する影響因子の検討 [Not invited]TAKAHASHI KATSUYUKI; HASHINO MIHO; INOSE RYO; KAWAGUCHI HIROSHI; SUDA YASUKI; NAKAMURA YASUTAKA; NISHIKAWA TAKESHI; TAKASHIMA TSUTOMU; NAGAYAMA KATSUYA日本医療薬学会年会講演要旨集 2014/08
- Heat shock protein 72 is a key molecule in oxaliplatin resistance in human gastric cancer cell [Not invited]Katsuyuki Takahashi; Masako Tanaka; Masayuki Shiota; Yasukatsu Izumi; Katsuyuki Miura; Hiroshi IwaoJOURNAL OF PHARMACOLOGICAL SCIENCES 2014 JAPANESE PHARMACOLOGICAL SOC
- ADAMTS1はVEGFCと結合してリンパ管新生を抑制する [Not invited]INAGAKI JUNKO; TAKAHASHI KATSUYUKI; OGAWA HIROKO; ASANO KEIICHI; HATIPOGLU; OMER FARUK; CILEK MEHMET ZEYNEL; OBIKA MASANARI; OTSUKI TAKASHI; HOFMANN MATTHIAS; KUSACHI SHOZO; NINOMIYA YOSHIFUMI; HIROHATA SATOSHI日本結合組織学会学術大会抄録集 2014
- 当院における抗がん剤の安全な取り扱いについてのデモンストレーションの教育効果 [Not invited]IWAMI AKIKO; NAKANO TAEKO; TAKEBAYASHI FUSAYO; TAKAHASHI KATSUYUKI; KAWAKAMI NORIKO; MITSUKAWA YASUKO; NAKAMURA KAZUNORI; YOSHIMURA NARIO; TAKASHIMA TSUTOMU; FUJINAGA KUMIKO日本癌治療学会学術集会(CD-ROM) 2014
- 膵癌細胞における低血清・低酸素耐性株の樹立とGemcitabine感受性の評価 [Not invited]ICHITSUBO TAISHO; TANAKA MASAKO; TAKAHASHI KATSUYUKI; IZUMI YASUO; SHIOTA MASAYUKI; MIURA KATSUYUKI; IWAO HIROSHI日本薬理学会近畿部会プログラム・要旨集 2014
- がん性疼痛の改善を目的としたフィードバック式質問紙調査 [Not invited]NAKANO TAEKO; YOSHIMURA NARUO; KAWABATA KYOKO; INOUE KATSUKO; TSUTSUMI JUNKO; TANIGUCHI MEGUMI; TOKUWAME ATSUSHI; TAKAHASHI KATSUYUKI; TAKASHIMA TSUTOMU; KUDO SHINZO日本臨床腫瘍学会学術集会(CD-ROM) 2014
- 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) [Not invited]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 2013/10
- 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) [Not invited]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 2013/10
- 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) [Not invited]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 2013/10
- 土-P3-476 胆道がんに対するゲムシタビン+シスプラチン療法の有害反応解析と治療継続に関する影響因子の検討(がん薬物療法(その他),ポスター発表,一般演題,再興、再考、創ろう最高の医療の未来) [Not invited]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 2013/08
- 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 2013/08
- 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 2013/08
- 脳腫瘍摘出術後の抗てんかん薬の発作予防効果に関する検討 [Not invited]KAWABATA SHIHO; NAKAMURA YASUTAKA; KAWAGUCHI HIROSHI; SUDA YASUKI; TAKAHASHI KATSUYUKI; NISHIKAWA TAKESHI; NAGAYAMA KATSUYA日本医療薬学会年会講演要旨集 2013/08
- 胆道がんに対するゲムシタビン+シスプラチン療法の有害反応解析と治療継続に関する影響因子の検討 [Not invited]TAKAHASHI KATSUYUKI; ONOUE MASAHIDE; FUKUDO MASAHIDE; IKEMI YASUAKI; KOBAYASHI MASAHIKO; FUKATSU YOSHIHIRO; YANO IKUKO; NAGAYAMA KATSUYA; MATSUBARA KAZUO日本医療薬学会年会講演要旨集 2013/08
- メトホルミン増量後の治療効果と副作用についての検討 [Not invited]KAWAGUCHI HIROSHI; NAKAMURA YASUTAKA; SUDA YASUKI; TAKAHASHI KATSUYUKI; NISHIKAWA TAKESHI; EMOTO MASANORI; INABA MASAAKI; NAGAYAMA KATSUYA日本医療薬学会年会講演要旨集 2013/08
- 嘔吐コントロール不良症例における制吐目的で追加された薬剤の使用状況と課題 [Not invited]MITSUKAWA YASUKO; TAKAHASHI KATSUYUKI; KAWAKAMI NORIKO; IWAMI AKIKO; NAKANO TAEKO; MATSUMOTO YOSHINARI; RI SHIGERU; YOSHIMURA NARIO; TAKASHIMA TSUTOMU; KUDO SHINZO; NISHIKAWA TAKESHI; NAGAYAMA KATSUYA医療薬学フォーラム講演要旨集 2013/07
- 肺癌化学療法に対する看護師の症状マネジメント能力の向上に向けた取り組み [Not invited]TARUI AKIKO; HIRATA MAYUMI; TAKEDA RITSUKO; IWAMI AKIKO; NAKANO TAEKO; SASAKI YUMIKO; KAWABATA KYOKO; TAKAHASHI KATSUYUKI; MITSUOKA SHIGEKI; KUDO SHINZO日本臨床腫瘍学会学術集会(CD-ROM) 2013
- 病院実務実習における臨床研究体験実習の導入と評価 [Not invited]TAKAHASHI KATSUYUKI; SUDA TAIKI; KAWAGUCHI HIROSHI; NAKAMURA YASUTAKA; NISHIKAWA TAKESHI; NAGAYAMA KATSUYA日本薬学会年会要旨集(CD-ROM) 2013
- リンパ管内皮細胞に対するADAMTS1の作用とシグナル伝達 [Not invited]INAGAKI JUNKO; TAKAHASHI KATSUYUKI; OGAWA HIROKO; OMER F. HATIPOGLU; MEHMET ZEYNEL CILEK; OBIKA MASANARI; HIROHATA SATOSHI; NINOMIYA YOSHIFUMI日本生化学会大会(Web) 2012/12
- P2-244 ワルファリンカリウムとフッ化ピリミジン系抗癌剤併用の現状と課題(薬物相互作用,ポスター,一般演題,岐路に立つ医療〜千年紀の目覚め〜よみがえれ!ニッポン!薬の改革は我らが手で!) [Not invited]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 2012/10
- ワルファリンカリウムとフッ化ピリミジン系抗癌剤併用の現状と課題 [Not invited]TAKAHASHI KATSUYUKI; SHIMIZU KUMIYO; SUDA YASUKI; KAWAGUCHI HIROSHI; NAKAMURA YASUTAKA; KAWAKAMI NORIKO; MITSUKAWA YASUKO; NISHIKAWA TAKESHI; NAGAYAMA KATSUYA日本医療薬学会年会講演要旨集 2012/10
- 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 [Not invited]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 2012/10
- 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) [Not invited]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 2012/08
- 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) [Not invited]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 2012/08
- 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) [Not invited]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 2012/08
- 当院における腎細胞癌患者,肝細胞癌患者に対するソラフェニブの有害事象及び服用期間の比較調査 [Not invited]TAKAHASHI KATSUYUKI; KIMURA KINKO; NAKAMURA MIZUHO; SUDA YASUKI; KAWAGUCHI HIROSHI; TOKUWAME ATSUSHI; IKEURA YOSHIHIRO; KAWAKAMI NORIKO; MITSUKAWA YASUKO; NISHIKAWA TAKESHI; NAGAYAMA KATSUYA日本薬学会年会要旨集 2012/03
- P-0107 当院における肝細胞癌患者に対するソラフェニブの投与量及び有害事象調査(一般演題 ポスター発表,がん薬物療法(副作用対策),Enjoy Pharmacists' Lifestyles) [Not invited]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 2011/09
- 当院における肝細胞癌患者に対するソラフェニブの投与量及び有害事象調査 [Not invited]TAKAHASHI KATSUYUKI; NAKAMURA MIZUHO; KOIKE ATSUSHI; TOKUWAME ATSUSHI; IKEURA YOSHIHIRO; KAWAKAMI NORIKO; MITSUKAWA YASUKO; NISHIKAWA TAKESHI; NAGAYAMA KATSUYA日本医療薬学会年会講演要旨集 2011/09
- 心肥大に対する抗線維化薬の効果 [Not invited]IZUMI YASUO; YAMASHITA NAOTO; TAKAHASHI KATSUYUKI; TANAKA MASAKO; MINAMINO YUKO; BUN SAYA; YAMAGUCHI MAKI; SHIOTA MASAYUKI; NAKAO TAKAFUMI; IWAO HIROSHI血管 2011/01
- ADAMTS1のin vitroでのリンパ管新生阻害効果 [Not invited]INAGAKI JUNKO; TAKAHASHI KATSUYUKI; OGAWA HIROKO; HATIPOGLU; OMER F; MEHMET ZEYNEL CILEK; OBIKA MASANARI; YONEZAWA TOMOKO; OHASHI TOSHITAKA; HIROHATA SATOSHI; NINOMIYA YOSHIFUMI生化学 2011
- 高校生競技者及び指導者のドーピングに対する意識調査 [Not invited]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 2010/10
- 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 2010/10
- ADAMTS1遺伝子治療はプロテアーゼ非依存的に血管新生阻害効果を発揮し,腫瘍増大を阻害する [Not invited]HIROHATA SATOSHI; OBIKA MASANARI; HATIPOGLU; OMER FARUK; OGAWA HIROKO; CILEK MEHMET ZEYNEL; TAKAHASHI KATSUYUKI; INAGAKI JUNKO; MIYOSHI TOORU; OTSUKI TAKASHI; ISHII HIROKO; KUSACHI SHOZO; YONEZAWA TOMOKO; OHASHI TOSHITAKA; NINOMIYA YOSHIFUMI日本結合組織学会学術大会抄録集 2010/08
- ADAMTS1のin vitroでのリンパ管新生阻害効果 [Not invited]INAGAKI JUNKO; TAKAHASHI KATSUYUKI; OGAWA HIROKO; HATIPOGLU; OMER F; CILEK MEHMET ZEYNEL; OBIKA MASANARI; YONEZAWA TOMOKO; OHASHI TOSHITAKA; HIROHATA SATOSHI; NINOMIYA YOSHIFUMI日本結合組織学会学術大会抄録集 2010/08
- ADAMTS1の血管新生阻害機能の解析:血管内皮細胞に対する影響 [Not invited]TAKAHASHI KATSUYUKI; HIROHATA SATOSHI; OBIKA MASANARI; MIYOSHI TOORU; OGAWA HIROKO; KUSACHI SHOZO; NINOMIYA YOSHIFUMI日本薬学会年会要旨集 2009/03
- 低分子ヒアルロン酸によるサイトカイン誘導とヒアルロン酸レセプター [Not invited]TAKAHASHI KATSUYUKI; HIROHATA SATOSHI; YAMAWAKI HITOSHI; MIYOSHI TOORU; OGAWA HIROKO; NINOMIYA YOSHIFUMI日本軟骨代謝学会プログラム・抄録集 2009
Courses
- Studies in Pharmacy and PharmaceuticalSciences 3Studies in Pharmacy and PharmaceuticalSciences 3 Kindai University, Faculty of Pharmacy
- Studies in Pharmacy and PharmaceuticalSciences 2Studies in Pharmacy and PharmaceuticalSciences 2 Kindai University, Faculty of Pharmacy
- Studies in Pharmacy and PharmaceuticalSciences 1Studies in Pharmacy and PharmaceuticalSciences 1 Kindai University, Faculty of Pharmacy
- Pharmacy Practice PretrainingPharmacy Practice Pretraining Kindai University, Faculty of Pharmacy
- Interprofessional EducationInterprofessional Education Kindai University, Faculty of Pharmacy
- Practice for Physical AssessmentPractice for Physical Assessment Kindai University, Faculty of Pharmacy
- Practical Pathophysiology and PharmacotherapyPractical Pathophysiology and Pharmacotherapy Kindai University, Faculty of Pharmacy
- Pharmaceutical CarePharmaceutical Care Kindai University, Faculty of Pharmacy
- BioethicsBioethics Kindai University, Faculty of Pharmacy
- Pharmaceutical Affairs Law 2Pharmaceutical Affairs Law 2 Kindai University, Faculty of Pharmacy
- Pharmaceutical Affairs Law 1Pharmaceutical Affairs Law 1 Kindai University, Faculty of Pharmacy
Affiliated academic society
Research Themes
- Ministry of Education, Culture, Sports, Science and Technology:Grants-in-Aid for Scientific Research(若手研究)Date (from‐to) : 2019/04 -2022/03Author : KATSUYUKI TAKAHASHI
- Ministry of Education, Culture, Sports, Science and Technology:Grants-in-Aid for Scientific Research(若手研究B)Date (from‐to) : 2017/04 -2019/03Author : KATSUYUKI TAKAHASHI
- 日本学術振興会:科学研究費助成事業Date (from‐to) : 2019 -2019Author : 豕瀬 諒; 髙田 充隆; 細見 光一; 髙橋 克之有害事象自発報告データベースを用いて、口内炎の発現リスクを低下させる可能性のある薬剤をスクリーニングした結果、8剤が候補薬として選抜された。次に、ヒト口腔ケラチノサイト細胞に対して、5-フルオロウラシル(5-FU)および候補薬を添加し、細胞生存率を検討した結果、3剤の候補薬で5-FU添加による細胞生存率の低下が軽減された。今後は、選抜された候補薬についてin vivo研究などを実施し、有効性をさらに検証していく予定である。
- 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Date (from‐to) : 2016/04 -2017/03Author : 高橋 克之
- Japan Society for the Promotion of Science:Grants-in-Aid for Scientific ResearchDate (from‐to) : 2012/04 -2014/03Author : TAKAHASHI KATSUYUKIHeat shock protein 72 (Hsp72) has functions such as promotion of protein folding, stabilizing oncogenic proteins, and avoiding stress. It has reported that Hsp72 overexpressed in gastric cancer was associated with resistance to chemotherapy. We think that Hsp72 client proteins would play an important role in drug resistance. All experiments used human gastric cancer cell line, 2M and oxaliplatin (OXA) resistant 2M (2M/OXA). We identified 22 specific Hsp72-client proteins in 2M/OXA by LC/MS/MS. One of the client proteins, stromal cell derived factor 2 siRNA enhanced OXA inducing cell death in 2M/OXA. Hsp72-client proteins in drug-resistant cells may target molecules to overcome drug resistance.
Social Contribution Activities
- 令和元年度 奈良県がん化学療法薬剤師研修会Date (from-to) : 2019/08/31Role : AdvisorCategory : SeminarSponser, Organizer, Publisher : 奈良県立医科大学附属病院肺がんの基礎知識Date (from-to) : 2019/06/09Role : LecturerCategory : Qualification seminarSponser, Organizer, Publisher : 日本臨床腫瘍薬学会Event, Program, Title : スタートアップセミナー 2019 大阪肺がんの基礎知識Date (from-to) : 2019/05/26Role : LecturerCategory : Qualification seminarSponser, Organizer, Publisher : 臨床腫瘍薬学会Event, Program, Title : 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Date (from-to) : 2018/09/15-2019/02/09Role : AdvisorCategory : SeminarSponser, Organizer, Publisher : 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Date (from-to) : 2018/09/01Role : AdvisorCategory : SeminarSponser, Organizer, Publisher : 奈良県立医科大学附属病院肺がんの基礎知識Date (from-to) : 2018/06/24Role : LecturerCategory : Qualification seminarSponser, Organizer, Publisher : 日本臨床腫瘍薬学会Event, Program, Title : 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Date (from-to) : 2017/06/19Role : LecturerCategory : LectureSponser, Organizer, Publisher : 小林がん学術振興会薬剤師の副作用マネジメントDate (from-to) : 2016/09/25Role : PanelistCategory : LectureSponser, Organizer, Publisher : 肺がん医療向上委員会(日本肺癌学会)Event, Program, Title : 医療従事者向けセミナー2016 大阪
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