研究活動情報

• Impact of Enterococcus faecium 129 BIO 3B-R on Helicobacter pylori eradication therapy side effects in adult patients: a randomized, double-blind, placebo-controlled study.

  Eri Tokunaga, Jun Inoue, Naoki Asaji, Katsuaki Oyama, Akihiro Soga, Yusaku Shimamoto, Masato Kinoshita, Takeshi Tanaka, Hiroki Hayashi, Takuya Ikegawa, Yuki Ito, Sayaka Ikeda, Norihiro Okamoto, Haruka Miyazaki, Yuna Ku, Daisuke Watanabe, Makoto Ooi, Namiko Hoshi, Hiroo Makimoto, Ikuko Yano, Eiji Umegaki, Yuzo Kodama

  Managing the side effects of diarrhea, which is associated with intestinal microbial dysbiosis, is a crucial challenge in Helicobacter pylori eradication therapy. The aim of this study is to explore whether administration of a probiotic strain Enterococcus faecium 129 BIO 3B-R, a multi-antibiotic resistant lactic acid bacterium, influences the side effects of Helicobacter pylori eradication therapy in adults. Seventy-six adults undergoing this therapy were randomized to receive either Enterococcus faecium 129 BIO 3B-R or a placebo in a double-blind manner. No significant difference was observed in the incidence of diarrhea, the primary endpoint, or in any other secondary endpoints, including intestinal microbiota diversity, between two groups in the overall study population. However, in a post-hoc age-stratified analysis, participants aged 70 and older who used Enterococcus faecium 129 BIO 3B-R experienced tended to have more diarrhea during the eradication period but subsequently experienced significantly less diarrhea after eradication compared to the control group (23.1% vs. 60%). Treatment with Enterococcus faecium 129 BIO 3B-R also maintained higher α-diversity in their intestinal microbiota than those in the placebo group. Those data suggest that the administration of Enterococcus faecium 129 BIO 3B-R could potentially alleviate diarrhea and intestinal dysbiosis in over 70-year-old elderly patients undergoing Helicobacter pylori eradication.

  2025年09月, Scientific reports, 15(1) (1), 32085 - 32085, 英語, 国際誌

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• 非がん性疼痛を有する患者のオピオイド使用状況モニタリングにおける薬剤師介入の効果

  飯田 真之, 大村 友博, 志田 有里, 番匠 咲帆, 大本 暢子, 山下 和彦, 槇本 博雄, 山本 和宏, 矢野 育子

  (一社)日本緩和医療薬学会, 2023年09月, 日本緩和医療薬学雑誌, 16(3) (3), 65 - 71, 日本語


• 抗がん薬調製ロボット導入前後における薬剤師のがん薬物療法関連業務の比較

  伊藤 雄大, 丹田 雅明, 水田 直美, 丸上 奈穂, 山口 由加里, 植田 梨沙, 梅山 遥, 伊藤 恵, 山本 和宏, 槇本 博雄, 大村 友博, 矢野 育子

  (一社)日本病院薬剤師会, 2022年06月, 日本病院薬剤師会雑誌, 58(6) (6), 627 - 632, 日本語


• Safety and Efficacy of Bis-Glyceryl Ascorbate as Prophylaxis for Hand-Foot Skin Reaction: A Single-Arm, Open-Label Phase I/II Study (DGA Study).

  Kazuhiro Yamamoto, Satoshi Nishiyama, Makoto Kunisada, Masashi Iida, Takahiro Ito, Takeshi Ioroi, Hiroo Makimoto, Tomohiro Omura, Kenichi Harada, Masato Fujisawa, Chikako Nishigori, Ikuko Yano

  BACKGROUND: Hand-foot skin reaction (HFSR) induced by multiple tyrosine kinase inhibitors (TKIs) is a serious side effect that can cause treatment interruption or decreased dosing. This study was conducted to evaluate the safety and efficacy of bis-glyceryl ascorbate (Amitose bis(di)-glyceryl ascorbate [DGA])-containing cream (DGA cream) for the prevention of sunitinib-induced HFSR. METHODS: A single-arm, open-label phase I/II study was conducted, targeting patients with metastatic renal cell carcinoma (mRCC) who were receiving sunitinib therapy with a schedule of 2 weeks on/1 week off. The participants applied DGA cream to both palmar and plantar surfaces in combination with a moisturizing agent as standard-of-care prophylaxis during two sunitinib treatment cycles (6 weeks). The primary endpoint in phase I was safety defined as dermatological abnormalities and it was determined in the first five participants. The primary endpoint in phase II was efficacy defined as development of grade 1 or higher HFSR defined by Common Terminology Criteria for Adverse Events within 6 weeks and it was determined on a full analysis set (FAS) defined as the population including all participants who used DGA cream once in the study duration. Efficacy in the per protocol set (PPS) defined as the population excluding seven patients whose study treatment was interrupted was evaluated as a secondary endpoint. RESULTS: Twenty-four patients were enrolled as a FAS. No dermatological abnormalities occurred in the first 5 patients enrolled in the phase I study. Three patients developed HFSR (grade 1: n = 2, grade 2: n = 1) in the observation period. The HFSR incidence rate was 12.5% (3/24; 95% confidence interval [CI]: 2.7%-32.4%) in the FAS, which was significantly lower than the incidence rate predefined as a threshold of 33.3% by a previous report from our hospital (P = .030). The incidence rate in the 17 patients of the PPS was 17.6% (3/17; 95%CI: 3.8%-43.4%). CONCLUSION: DGA cream may be safe and effective in the prophylaxis of HFSR in mRCC patients who receive sunitinib therapy (Trial ID: jRCTs051180051).

  2022年05月, The oncologist, 27(5) (5), e384-e392, 英語, 国際誌

  研究論文（学術雑誌）


• 経口抗がん薬治療における情報共有ツールおよびチーム基盤型学習を用いた病診薬連携の有用性の評価

  植田 梨沙, 丹田 雅明, 伊藤 雄大, 榎本 彩花, 飯田 真之, 水田 直美, 山本 和宏, 槇本 博雄, 大村 友博, 矢野 育子

  (一社)日本医療薬学会, 2020年12月, 医療薬学, 46(12) (12), 681 - 691, 日本語


• 疑義照会における検査値連動型の処方チェックシステムの有用性

  冨田 猛, 山本 和宏, 山下 和彦, 大本 暢子, 槇本 博雄, 矢野 育子

  (一社)日本医療薬学会, 2019年12月, 医療薬学, 45(12) (12), 698 - 705, 日本語


• 薬剤師教育におけるチーム基盤型学習の有用性の検討

  伊藤 雄大, 高田 麻季, 飯田 真之, 宇田 篤史, 住吉 霞美, 秋山 恵里, 丸上 奈穂, 丹田 雅明, 野間 千尋, 山本 和宏, 五百蔵 武士, 木村 丈司, 西岡 達也, 久米 学, 槇本 博雄, 矢野 育子

  (一社)日本医療薬学会, 2018年05月, 医療薬学, 44(5) (5), 236 - 243, 日本語


• 院外処方せんにおける疑義照会簡素化プロトコールの運用とアンケートによる評価

  石川 愛子, 宇田 篤史, 矢野 育子, 冨田 猛, 阪上 倫行, 野崎 晃, 西岡 達也, 久米 学, 槇本 博雄, 濱口 常男, 岩川 精吾, 北河 修治, 平井 みどり

  (一社)日本医療薬学会, 2018年04月, 医療薬学, 44(4) (4), 157 - 164, 日本語


• インスリンカートリッジの破損により著明な血糖上昇を来した1型糖尿病の1例

  谷藤 亜希子, 岡田 裕子, 西岡 達也, 久米 学, 槇本 博雄, 矢野 育子, 小川 渉, 平井 みどり

  (一社)日本くすりと糖尿病学会, 2017年12月, くすりと糖尿病, 6(2) (2), 207 - 211, 日本語


• 医療機関で普遍的に必要とされる医薬品情報の調査

  谷藤 亜希子, 野崎 晃, 槇本 博雄, 平野 剛, 平井 みどり

  (一社)日本医薬品情報学会, 2017年08月, 医薬品情報学, 19(2) (2), 82 - 90, 日本語


• Compatibility and Stability of Nab-Paclitaxel in Combination with Other Drugs.

  Naomi Mizuta, Tsutomu Nakagawa, Kazuhiro Yamamoto, Tatsuya Nishioka, Manabu Kume, Hiroo Makimoto, Ikuko Yano, Hironobu Minami, Midori Hirai

  Albumin-bound paclitaxel (Abraxane®, nab-paclitaxel) is not recommended to be administered concurrently or sequentially with other drugs due to concern for instability. The need to administer drugs separately increases infusion time. We evaluated the compatibility and stability of solutions containing nab-paclitaxel and other drugs, including gemcitabine hydrochloride, carboplatin, dexamethasone sodium phosphate, granisetron hydrochloride, and palonosetron hydrochloride. We visually examined changes in appearance, pH, and concentration of the mixed solutions of nab-paclitaxel and other drugs for up to 24 h. Concentration was measured using high-performance liquid chromatography (HPLC). The appearance and pH of the mixed solutions did not change for up to 24 h. The change in concentration up to 24 h was within 2%. The chromatogram did not change until 8 h. The results showed that the physical compatibility and chemical stability of nab-paclitaxel were not influenced when it was combined with other drugs until 8 h. This study suggests that nab-paclitaxel could be administered in a mixture or sequentially with other drugs to reduce administration time.

  2017年07月, The Kobe journal of medical sciences, 63(1) (1), E9-E16, 英語, 国内誌

  研究論文（学術雑誌）


• 日米の医薬品データベースの相互作用情報を迅速に検索できるシステムの構築と質疑への活用

  冨田 猛, 野崎 晃, 宇田 篤史, 山本 和宏, 西岡 達也, 久米 学, 槇本 博雄, 矢野 育子, 平井 みどり

  (一社)日本医薬品情報学会, 2017年05月, 医薬品情報学, 19(1) (1), 1 - 7, 日本語


• DVDを用いた副作用研修会の取り組みと評価

  小出 慶子, 西岡 達也, 五百蔵 武士, 久米 学, 槇本 博雄, 矢野 育子, 平井 みどり

  日本ファーマシューティカルコミュニケーション学会, 2017年04月, 日本ファーマシューティカルコミュニケーション学会会誌, 15(1) (1), 6 - 12, 日本語


• 「薬剤師外来」における薬学的処方介入とその評価

  栗村 朋子, 山本 和宏, 池田 剛久, 橋本 正良, 西岡 達也, 久米 学, 槇本 博雄, 矢野 育子, 平井 みどり

  (一社)日本医療薬学会, 2017年03月, 医療薬学, 43(3) (3), 169 - 175, 日本語


• Effects of Ascorbyl-2-phosphate Magnesium on Human Keratinocyte Toxicity and Pathological Changes by Sorafenib.

  Kazuhiro Yamamoto, Hiroaki Shichiri, Takahiro Ishida, Kenta Kaku, Tatsuya Nishioka, Manabu Kume, Hiroo Makimoto, Tsutomu Nakagawa, Takeshi Hirano, Toshinori Bito, Chikako Nishigori, Ikuko Yano, Midori Hirai

  Hand-foot skin reaction is recognized as one of the most common adverse events related to multiple tyrosine kinase inhibitors, but an effective prevention method has not been identified. The chief aim of this study was to find a mechanism-based preventive method for the skin toxicity induced by sorafenib using vitamin C derivatives. The effects of ascorbyl-2-phosphate magnesium (P-VC-Mg) on the molecular and pathological changes induced by sorafenib were investigated in human keratinocyte HaCaT cells. The cell growth inhibition and apoptotic effects of sorafenib were attenuated by P-VC-Mg. Moreover, P-VC-Mg inhibited the decrease of signal transducer and activator of transcription 3 (STAT3) phosphorylation and the expression of apoptosis suppressors treated by sorafenib. HaCaT cells transfected with the STAT3 dominant-negative form (STAT3DN) and STAT3 small interfering RNA (siRNA) combined with P-VC-Mg did not exhibit the attenuation of cell growth inhibition. Interestingly, after exposure to sorafenib in a three dimensional (3D) skin model assay, the basal layer was significantly thickened and the granular and spinous layers became thinner. In contrast, after exposure to sorafenib with P-VC-Mg, the thickness of the basal, granular, and spinous layers was similar to that of the control image. These findings suggest that P-VC-Mg attenuates sorafenib-induced apoptosis and pathological changes in human keratinocyte cells and in the 3D skin model mediated by the maintenance of STAT3 activity.

  2017年, Biological & pharmaceutical bulletin, 40(9) (9), 1530 - 1536, 英語, 国内誌

  研究論文（学術雑誌）


• STAT3 polymorphism rs4796793 may be a predictive factor of tumor response to multiple tyrosine kinase inhibitors in metastatic renal cell carcinoma in Japanese population.

  Kazuhiro Yamamoto, Takeshi Ioroi, Kazuya Kanaya, Kazuaki Shinomiya, Shiho Komoto, Sachi Hirata, Kenichi Harada, Aimi Watanabe, Manabu Suno, Tatsuya Nishioka, Manabu Kume, Hiroo Makimoto, Tsutomu Nakagawa, Takeshi Hirano, Hideaki Miyake, Masato Fujisawa, Midori Hirai

  Signal transducer and activator of transcription (STAT) 3 is a key factor in multiple tyrosine kinase inhibitor (mTKI)-induced growth inhibition and apoptosis of renal cell carcinoma (RCC) cells. This study aimed to identify associations between single-nucleotide polymorphisms (SNPs) in the STAT3 gene and tumor response to mTKIs in patients with metastatic RCC (mRCC). Seventy-one patients with clear cell RCC treated with any mTKI were retrospectively genotyped to elucidate a potential association between STAT3 SNPs and overall best response to drugs. Of 50 patients included for analysis, a partial or complete response was observed in 17. A significant association was found between rs4796793 alleles and tumor response [G vs. C, odds ratio (OR) 3.25, 95 % confidence interval (CI) 1.30-8.07]. There were a higher percentage of responders with the C/C genotype at rs4796793 than with the G/C + G/G genotypes (OR 4.46, 95 % CI 1.31-15.28). Time-to-event analysis demonstrated a statistically significant difference between patients with the CC genotype and those with G/C + G/G genotypes in time-to-treatment response, but not in progression-free survival or time-to-treatment failure. The rs4796793 genotype is a novel predictive factor of the response to mTKIs in patients with mRCC. However, prospective translational trials with larger patient cohorts are required to confirm these results.

  2016年03月, Medical oncology (Northwood, London, England), 33(3) (3), 24 - 24, 英語, 国際誌

  研究論文（学術雑誌）


• STOPP Criteriaを用いた高齢者のポリファーマシーに対する薬剤師による介入

  小倉 史愛, 木村 丈司, 宇田 篤史, 戸田 飛鳥, 赤澤 由子, 山本 和宏, 五百蔵 武士, 西岡 達也, 久米 学, 槇本 博雄, 平井 みどり

  (一社)日本医療薬学会, 2016年02月, 医療薬学, 42(2) (2), 78 - 86, 日本語


• Association of Single Nucleotide Polymorphisms in STAT3 with Hand-Foot Skin Reactions in Patients with Metastatic Renal Cell Carcinoma Treated with Multiple Tyrosine Kinase Inhibitors: A Retrospective Analysis in Japanese Patients.

  Kazuhiro Yamamoto, Kazuaki Shinomiya, Takeshi Ioroi, Sachi Hirata, Kenichi Harada, Manabu Suno, Tatsuya Nishioka, Manabu Kume, Hiroo Makimoto, Tsutomu Nakagawa, Takeshi Hirano, Toshinori Bito, Chikako Nishigori, Hideaki Miyake, Masato Fujisawa, Midori Hirai

  BACKGROUND: Signal transducer and activator of transcription (STAT)3 is a reported mediator of molecular-targeted drug-induced keratinocyte toxicity. AIM: Our purpose was to assess the association of single nucleotide polymorphisms (SNPs) in STAT3 with hand-foot skin reactions (HFSR) in patients with metastatic renal cell carcinoma (mRCC) treated with multiple tyrosine kinase inhibitors (mTKIs). PATIENTS AND METHODS: Sixty-five Japanese patients with clear cell renal cell carcinoma who were treated with any mTKI at Kobe University Hospital were retrospectively genotyped to elucidate a potential association between STAT3 polymorphisms and HFSR development. RESULTS: The final analysis included 60 patients. HFSR was observed in 46 patients. The GG, GC, and CC genotypes at rs4796793 were found in 9, 27, and 24 patients, respectively. Three other STAT3 polymorphisms exhibited tight linkage disequilibrium with rs4796793. A significant association was found between the rs4796793 allele and HFSR [G vs. C; odds ratio [OR], 4.33; 95 % confidence interval [CI], 1.80-10.45; P = 0.001]. The GG genotype had the highest OR compared with GC + CC genotypes (OR, 10.75; 95 % CI, 2.38-48.07; P = 0.001). In a time-to-event Kaplan-Meier analysis, a statistically significant difference was observed between the GC + CC and the GG genotypes (P = 0.009). CONCLUSIONS: The rs4796793 genotype appears to be a novel factor for mTKI-induced HFSR in patients with mRCC. Prospective translational trials with larger numbers of patients are required to confirm our results. This research suggests a potential benefit of STAT3 polymorphism screening in patients treated with mTKIs.

  2016年02月, Targeted oncology, 11(1) (1), 93 - 9, 英語, 国際誌

  研究論文（学術雑誌）


• Association of single nucleotide polymorphisms (SNP) in STAT3 gene with hand-foot skin reaction in metastatic renal cell carcinoma patients treated with multi-kinase inhibitor.

  Kazuhiro Yamamoto, Takeshi Ioroi, Kazuaki Shinomiya, Sachi Hirata, Kenichi Harada, Manabu Suno, Tatsuya Nishioka, Manabu Kume, Hiroo Makimoto, Tsutomu Nakagawa, Takeshi Hirano, Toshinori Bito, Chikako Nishigori, Hideaki Miyake, Masato Fujisawa, Midori Hirai

  2015年05月, JOURNAL OF CLINICAL ONCOLOGY, 33(15) (15), 英語

  [査読有り]


• Apoptotic Effects of the Extracts of Cordyceps militaris via Erk Phosphorylation in a Renal Cell Carcinoma Cell Line.

  Kazuhiro Yamamoto, Hiroaki Shichiri, Atsushi Uda, Kazuhiko Yamashita, Tatsuya Nishioka, Manabu Kume, Hiroo Makimoto, Tsutomu Nakagawa, Takeshi Hirano, Midori Hirai

  Cordyceps militaris (CM) is gaining attention as a traditional medicinal food, but its molecular biological mechanisms for anti-cancer activity are not identified or clarified. We aimed to elucidate the synthesizing apoptotic effects of CM extracts and to determine the biological effects of CM extract against cordycepin alone in a renal cell carcinoma (RCC) cell line. CM extract showed higher effects of growth inhibition, apoptotic effect, and cell cycle arrest than cordycepin alone. Moreover, CM extract activated extracellular signal-regulated kinase (Erk) highly more than cordycepin alone. We suggest that cordycepin and CM extract induced apoptosis via the activation of Erk dominantly and AMP-activated protein kinase slightly; CM extract has more potent effects on apoptotic effects associated with Erk activation than cordycepin alone.

  2015年05月, Phytotherapy research : PTR, 29(5) (5), 707 - 13, 英語, 国際誌

  研究論文（学術雑誌）


• 循環器内科病棟における病院薬剤師のフィジカルアセスメントの実践と成果

  栗村 朋子, 大本 暢子, 久米 学, 槇本 博雄, 平野 剛, 平井 みどり

  (一社)日本病院薬剤師会, 2014年03月, 日本病院薬剤師会雑誌, 50(3) (3), 323 - 328, 日本語


• Association of toxicity of sorafenib and sunitinib for human keratinocytes with inhibition of signal transduction and activator of transcription 3 (STAT3).

  Kazuhiro Yamamoto, Atsushi Mizumoto, Kohji Nishimura, Atsushi Uda, Akira Mukai, Kazuhiko Yamashita, Manabu Kume, Hiroo Makimoto, Toshinori Bito, Chikako Nishigori, Tsutomu Nakagawa, Takeshi Hirano, Midori Hirai

  Hand-foot skin reaction is a most common multi-kinase inhibitor-related adverse event. This study aimed to examine whether the toxicity of sorafenib and sunitinib for human keratinocytes was associated with inhibiting signal transduction and activator of transcription 3 (STAT3). We studied whether STAT3 activity affects sorafenib- and sunitinib-induced cell growth inhibition in HaCaT cells by WST-8 assay. Stattic enhanced the cell-growth inhibitory and apoptotic effects of sorafenib and sunitinib. HaCaT cells transfected with constitutively-active STAT3 (STAT3C) were resistant to the sorafenib- and sunitinib-induced cell growth inhibition. STAT3 activity decreased after short-term treatment with sorafenib and sunitinib in a dose-dependent manner and recovered after long-term treatment with sorafenib and sunitinib at low doses. Moreover, the expression of survivin and bcl-2 decreased after treatment with sorafenib and sunitinib was concomitant with variations in STAT3 activity. Sorafenib-induced STAT3 inhibition was mediated by regulation via MAPK pathways in HaCaT cells, while sunitinib-induced STAT3 inhibition was not. Thus, STAT3 activation mediating apoptosis suppressors may be a key factor in sorafenib and sunitinib-induced keratinocyte cytotoxicity.

  2014年, PloS one, 9(7) (7), e102110, 英語, 国際誌

  研究論文（学術雑誌）


• Everolimus-induced human keratinocytes toxicity is mediated by STAT3 inhibition.

  Kazuhiro Yamamoto, Atsushi Uda, Akira Mukai, Kazuhiko Yamashita, Manabu Kume, Hiroo Makimoto, Toshinori Bito, Chikako Nishigori, Takeshi Hirano, Midori Hirai

  BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors are associated with dermatological adverse events. The chief aim of this study was to examine the relation between the signal transducer and activator of transcription 3 (STAT3) protein and the dermatological adverse events associated with the mTOR inhibitor everolimus. METHODS: We evaluated the effects of STAT3 activity and related signal transduction activities on everolimus-induced cell growth inhibition in the human keratinocyte HaCaT cell line via a WST-8 assay, and on signal transduction mechanisms involved in everolimus treatments via a western blot analysis. Apoptosis was evaluated using an imaging cytometric assay. RESULTS: The cell growth inhibitory effects of everolimus were enhanced by stattic or STA-21, which are selective inhibitors of STAT3, treatment in HaCaT cells, although such effects were not observed in Caki-1 and HepG2 cells. Phosphorylation at tyrosine 705 of STAT3 was decreased by treatment with everolimus in a dose-dependent manner in HaCaT cells; in contrast, phosphorylation at serine 727 was not decreased by everolimus, but slightly increased. Furthermore, we found that pretreatment of p38 MAPK inhibitor and transfection with constitutively active form of STAT3 in HaCaT cells resisted the cytostatic activity of everolimus. CONCLUSIONS: These findings suggest that STAT3 activity may be a biomarker of everolimus-induced dermatological toxicity.

  2013年10月, Journal of experimental & clinical cancer research : CR, 32(1) (1), 83 - 83, 英語, 国際誌

  研究論文（学術雑誌）


• 土-10-O13-03 乳児血管腫に対するプロプラノロール内服療法の有用性について(薬物療法(その他),一般演題(口頭)13,再興、再考、創ろう最高の医療の未来)

  山下 和彦, 赤澤 由子, 山口 由加里, 平瀬 敏志, 加藤 威, 山本 暢之, 久保川 育子, 森 健, 矢内 友子, 久米 学, 槇本 博雄, 平野 剛, 早川 晶, 平井 みどり

  一般社団法人 日本医療薬学会, 2013年08月, 日本医療薬学会年会講演要旨集, 23, 218, 日本語


• シスプラチン分割投与に対するアプレピタントの効果に関する検討

  刈谷 美里, 田中 健太, 松本 久美子, 久米 学, 槇本 博雄, 平野 剛, 三宅 秀明, 藤澤 正人, 平井 みどり

  (株)癌と化学療法社, 2012年02月, 癌と化学療法, 39(2) (2), 245 - 250, 日本語


• [Effects of aprepitant in daily administrations of low-dose cisplatin].

  Misato Kariya, Kenta Tanaka, Kumiko Matsumoto, Manabu Kume, Hiroo Makimoto, Takeshi Hirano, Hideaki Miyake, Masato Fujisawa, Midori Hirai

  OBJECTIVE: While aprepitant is actually recommended for the prevention of nausea and vomiting induced by a single cisplatin administration, it is still unclear whether it has a clinical benefit when administered along with daily administrations of low- dose cisplatin(20mg/m2 days 1-5). This study was conducted to evaluate the efficacy of aprepitant in patients receiving daily administration of low-dose cisplatin. METHODS: Our study focused on 25 patients who received cancer therapy including cisplatin, with or without aprepitant (days 1-5). We performed a retrospective study to identify any significant positive effect of aprepitant in the prevention of nausea and vomiting for 10 days(days 1-10). Because cisplatin has a long half-life, we assessed the delayed phase nausea and vomiting(days 6-10). RESULTS AND CONCLUSION: Multiple-day dosing of aprepitant was effective for prevention of nausea(Odds ratio: 0. 30, p= 0. 0012)and vomiting(Odds ratio: 0. 04, p=0. 0001)throughout the observation. Furthermore, we observed a significant positive effect of aprepitant in the prevention of delayed nausea(Odds ratio: 0. 19, p=0. 0083)and vomiting(Odds ratio: 0. 07, p=0. 0040). These findings suggest that multiple-day dosing of aprepitant is useful for the inhibition of acute delayed nausea and vomiting caused by chemotherapy including daily administration of low-dose cisplatin.

  2012年02月, Gan to kagaku ryoho. Cancer & chemotherapy, 39(2) (2), 245 - 50, 日本語, 国内誌

  研究論文（学術雑誌）


• P-0031 東日本大震災における災害医療活動報告 : 災害医療における薬剤師の役割(一般演題 ポスター発表,東日本大震災,Enjoy Pharmacists' Lifestyles)

  阪上 倫行, 山下 和彦, 大松 秀明, 和田 敦, 田中 健太, 熊岡 穣, 干し野 賢悟, 久米 学, 槇本 博雄, 平野 剛, 平井 みどり

  一般社団法人 日本医療薬学会, 2011年09月, 日本医療薬学会年会講演要旨集, 21, 187, 日本語


• パクリタキセル・カルボプラチン併用療法とワルファリンとの薬物相互作用に関する調査 抗凝固効果への影響

  垣尾 尚美, 和田 敦, 宗 亜矢子, 久米 学, 角本 幹夫, 槇本 博雄, 平野 剛, 奥川 斉, 平井 みどり

  (一社)日本医療薬学会, 2011年08月, 医療薬学, 37(8) (8), 443 - 448, 日本語


• 手術部における薬剤師業務 手術部での医薬品の適正使用を目指して

  槇本 博雄, 平井 みどり

  (株)薬事新報社, 2011年03月, 薬事新報, (2671) (2671), 9 - 14, 日本語


• ACMIA法で異常高値を示す症例の判別法の検討

  植田 貴史, 山森 元博, 小野 由加里, 田中 健太, 松本 久美子, 大松 秀明, 角本 幹夫, 槇本 博雄, 平野 剛, 平井 みどり

  (一社)日本TDM学会, 2010年10月, TDM研究, 27(4) (4), 168 - 172, 日本語


• 薬剤師の新しい業務 手術室における関与

  槇本 博雄, 山下 和彦, 和田 敦, 平井 みどり

  (一社)日本病院薬剤師会, 2010年02月, 日本病院薬剤師会雑誌, 46(2) (2), 198 - 201, 日本語


• 食道がん化学放射線療法における病期、奏効と予後との相関

  桑原 晶子, 山森 元博, 槇本 博雄, 西口 工司, 八木 敬子, 奥野 達哉, 茶屋原 菜穂子, 三木 生也, 田村 孝雄, 平井 みどり, 栄田 敏之

  (一社)日本医療薬学会, 2008年01月, 医療薬学, 34(1) (1), 13 - 19, 日本語


• IL-1beta genotype-related effect of prednisolone on IL-1beta production in human peripheral blood mononuclear cells under acute inflammation.

  Svetlana Markova, Tsutomu Nakamura, Hiroo Makimoto, Tomoki Ichijima, Motohiro Yamamori, Akiko Kuwahara, Koichi Iwaki, Kohshi Nishiguchi, Noboru Okamura, Katsuhiko Okumura, Toshiyuki Sakaeda

  Glucocorticoids such as prednisolone are used for their anti-inflammatory properties. But there is evidence to suggest that under certain conditions, glucocorticoids have pro-inflammatory effects, for example, enhancement of IL-1beta production. To date, it has been reported that IL-1beta production intensity was associated with single nucleotide polymorphisms at positions -1470, -511, and -31 in the promoter region and at position 3954 in exon 5 of the IL-1beta gene. In the present study, it was examined whether these IL-1beta genotypes were associated with the suppressive effect of prednisolone on IL-1beta production in human peripheral blood mononuclear cells (PBMC) stimulated by lipopolysaccharide (LPS). A midrange concentration (10(-6) M) of prednisolone suppressed the LPS-induced increase in IL-1beta mRNA expression and protein release, while higher concentrations (10(-5) M, 10(-4) M) exhibited less suppression or had a synergistic stimulative effect on IL-1beta production in certain subjects. Under treatment with 10(-4) M prednisolone, the levels of IL-1beta protein production stimulated by LPS in PBMC extracted from the subjects with the IL-1beta TT(-31), TC(-31), and CC(-31) genotypes were suppressed to 6.0+/-3.4%, 31.4+/-57.0%, and 87.7+/-84.8%, respectively, of the level in prednisolone-untreated control cells (TT(-31) vs. CC(-31), p<0.05). Glucocorticoid-based anti-inflammatory therapy might be less effective in patients with the IL-1beta TC(-31) and CC(-31) genotypes than those with the TT(-31) genotype.

  2007年08月, Biological & pharmaceutical bulletin, 30(8) (8), 1481 - 7, 英語, 国内誌

  研究論文（学術雑誌）


• Genotype-dependent down-regulation of gene expression and function of MDR1 in human peripheral blood mononuclear cells under acute inflammation.

  Svetlana Markova, Tsutomu Nakamura, Toshiyuki Sakaeda, Hiroo Makimoto, Hitoshi Uchiyama, Noboru Okamura, Katsuhiko Okumura

  Recent advances in pharmacogenomics have suggested the association of clinical outcome of glucocorticoid-based anti-inflammatory therapy with a single nucleotide polymorphism at position 3435 in exon 26 (C3435T) of the MDR1 gene. In the present study, the effects of the MDR1 C3435T genotype on the time-dependent profiles of gene expression and function of MDR1/P-glycoprotein were evaluated in peripheral blood mononuclear cells (PBMCs) under lipopolysaccharide (LPS)-induced experimental acute inflammation. LPS treatment resulted in the rapid elevation of IL-1beta and TNF-alpha mRNA levels relative to beta-actin mRNA at 1 h, with a subsequent slight decrease at 3 h after the treatment, while the down-regulation of the relative concentration of MDR1 mRNA was found at 3 h, not at 1 h, after LPS treatment. Here, the C3435T genotype-dependent down-regulations of MDR1 mRNA level were found for CC(3435) and CT(3435), but not for TT(3435), and were 64.1+/-10.1%, 71.4+/-5.9% and 100.0+/-22.5% (+/-S.D.), respectively, of their respective baseline levels, which were independent of C3435T (0.010+/-0.005, 0.011+/-0.013 and 0.009+/-0.006 (+/-S.D.), respectively). The C3435T genotype-dependent down-regulation was supported by the increase of the intracellular accumulation of calcein in PBMCs treated with LPS for 72 h, and the increase was more predominant for CC(3435) than TT(3435). These data suggested that glucocorticoid-based anti-inflammatory therapy might be more effective for C(3435)-allele carriers than non-carriers.

  2006年06月, Drug metabolism and pharmacokinetics, 21(3) (3), 194 - 200, 英語, 国際誌

  研究論文（学術雑誌）


• Circadian variability of pharmacokinetics of 5-fluorouracil and CLOCK T3111C genetic polymorphism in patients with esophageal carcinoma.

  Ikuya Miki, Takao Tamura, Tsutomu Nakamura, Hiroo Makimoto, Noriko Hamana, Hitoshi Uchiyama, Daisuke Shirasaka, Yoshinori Morita, Hiroyuki Yamada, Nobuo Aoyama, Toshiyuki Sakaeda, Katsuhiko Okumura, Masato Kasuga

  The variations of plasma concentrations of 5-fluorouracil (5-FU) were investigated in 30 esophageal cancer patients treated with repetitive protracted venous infusion (PVI) of 5-FU-based chemoradiotherapy, and in an attempt to find a new possible candidate that explains their variations, CLOCK T3111C genetic polymorphism was examined. The patients have received 2 courses of chemoradiotherapy consisting of 2 cycles of 5-day PVI of 5-FU (400 mg/m/d) with cisplatin and concurrent radiation. The plasma concentrations of 5-FU were determined at 5 PM on day 3 and 5 AM on day 4 after the beginning of each 5-FU infusion. The CLOCK T3111C genotype was determined by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) and by direct sequencing. Plasma concentrations were measured in 239 samples. In the first course, the plasma concentrations of 5-FU at 5 AM were significantly lower than those at 5 PM in the first cycle, whereas a similar tendency was observed in the second cycle, although not significantly (Wilcoxon signed-rank test). The plasma concentrations of 5-FU at 5 PM and 5 AM in the second cycle were both significantly higher than those in the first cycle, and their coefficient of variation in the former was also significantly smaller than that in the latter. These phenomena in the first course were also observed in the second one. These results revealed the elevation of plasma drug concentration and its reduced circadian variation during repetitive PVI of 5-FU. In 5-FU-based chemotherapy, its administration schedule should be made in consideration of these phenomena. The CLOCK T3111C genotype did not have a significant impact on the variation of the plasma concentrations of 5-FU in this study population. Further studies are needed to clarify the mechanism of these phenomena and to identify an easy-to-assess marker of circadian rhythms for use in individualizing delivery of 5-FU.

  2005年06月, Therapeutic drug monitoring, 27(3) (3), 369 - 74, 英語, 国際誌

  研究論文（学術雑誌）


• Beta2-adrenergic receptor genotype-related changes in cAMP levels in peripheral blood mononuclear cells after multiple-dose oral procaterol.

  H Makimoto, T Sakaeda, K Nishiguchi, T Kita, T Sakai, F Komada, K Okumura

  PURPOSE: To evaluate the beta2-adrenergic receptor (beta2AR) genotype frequency in the Japanese population and the relationship between beta2AR genotype at amino acid position 16 (beta2AR-16) and desensitization to beta2-agonist ex vivo. METHODS: The beta2AR genotypes at amino acid positions 16, 27, and 164 of 92 healthy Japanese subjects were determined by polymerase chain reaction-restriction fragment-length polymorphism. The relationship between the beta2AR-16 genotype and the desensitization to beta2-agonist was examined in 10 male subjects ex vivo. Procaterol tablet (HCl salt, 50 microg, Meptin) was given orally for 5 days, and peripheral blood was obtained before and after 5 days of consecutive medications followed by the assessment of the intracellular cAMP levels in peripheral blood mononuclear cells after incubation with or without procaterol hydrochloride (0-1000 ng/mL). RESULTS: Allele frequency was Arg16:Gly16 = 46%:54%, Gln27: Glu27 = 92%:8%, and Thr164:Ile164 = 100%:0%, respectively. The cAMP levels were increased by incubation with procaterol hydrochloride, and the increase was suppressed after 5 days of consecutive medications. The suppression was more significant in the homozygote for Gly16 than the homozygote for Arg16. CONCLUSIONS: The desensitization to beta2-agonist was associated more frequently with the mutation at beta2AR-16 (Gly16).

  2001年12月, Pharmaceutical research, 18(12) (12), 1651 - 4, 英語, 国際誌

  研究論文（学術雑誌）


• Effective cancer targeting using an anti-tumor tissue vascular endothelium-specific monoclonal antibody (TES-23).

  Y Wakai, J Matsui, K Koizumi, S Tsunoda, H Makimoto, I Ohizumi, K Taniguchi, S Kaiho, H Saito, N Utoguchi, Y Tsutsumi, S Nakagawa, Y Ohsugi, T Mayumi

  Immunoconjugate targeting of solid tumors has not been routinely successful because the endo-thelial cells of blood vessels act as a physical barrier against the transport of macromolecules, such as antibodies. In the present study, we attempted to achieve tumor vascular targeting with an anti-tumor tissue endothelium-specific monoclonal antibody (TES-23). TES-23, an IgG1 monoclonal antibody raised against rat KMT-17 fibrosarcoma-derived endothelial cells, was covalently conjugated with neocarzinostatin (NCS) in a previous study. The TES-23-NCS conjugate induced tumor hemorrhagic necrosis, and showed marked anti-tumor effects against rat KMT-17 fibrosarcoma. This result prompted us to investigate whether this approach would be applicable to various other types of solid tumors. One hour after injection of (125)I-labeled TES-23 into BALB / c mice bearing Meth-A fibrosarcoma and Colon 26 adenocarcinoma, the tumor accumulation of TES-23 was greater than that of the control IgG. In the present study, we report the anti-tumor effects of this monoclonal antibody in mice bearing Meth-A fibrosarcoma. Mice treated with the immunoconjugate showed improved survival with no side effects. This result indicates that common antigens may be found in different kinds of tumor endothelial cells, and that TES-23 might recognize these antigens.

  2000年12月, Japanese journal of cancer research : Gann, 91(12) (12), 1319 - 25, 英語, 国内誌

  研究論文（学術雑誌）


• Specific binding of TES-23 antibody to tumour vascular endothelium in mice, rats and human cancer tissue: a novel drug carrier for cancer targeting therapy.

  S Tsunoda, I Ohizumi, J Matsui, K Koizumi, Y Wakai, H Makimoto, Y Tsutsumi, N Utoguchi, K Taniguchi, H Saito, N Harada, Y Ohsugi, T Mayumi

  The tissue distribution of anti-tumour vascular endothelium monoclonal antibody (TES-23) produced by immunizing with plasma membrane vesicles from isolated rat tumour-derived endothelial cells (TECs) was assessed in various tumour-bearing animals. Radiolabelled TES-23 dramatically accumulated in KMT-17 fibrosarcoma, the source of isolated TECs after intravenous injection. In Meth-A fibrosarcoma, Colon-26 adenocarcinoma in BALB/c mice and HT-1080 human tumour tissue in nude mice, radioactivities of 125I-labelled TES-23 were also up to 50 times higher than those of control antibody with little distribution to normal tissues. The selective recognition of TES-23 to TECs was competitively blocked by preadministration of unlabelled TES-23 in vivo. Furthermore, immunostaining of human tissue sections showed specific binding of TES-23 on endothelium in oesophagus cancers. These results indicate that tumour vascular endothelial cells express common antigen in different tumour types of various animal species. In order to clarify the efficacy of TES-23 as a drug carrier, an immunoconjugate, composed of TES-23 and neocarzinostatin, was tested for its anti-tumour effect in rats bearing KMT-17 fibrosarcomas. The immunoconjugate (TES-23-NCS) caused marked regression of the tumour, accompanied by haemorrhagic necrosis. Thus, from a clinical view, TES-23 would be a novel drug carrier because of its high specificity to tumour vascular endothelium and its application to many types of cancer.

  1999年12月, British journal of cancer, 81(7) (7), 1155 - 61, 英語, 国際誌

  研究論文（学術雑誌）


• Suppression of solid tumor growth by a monoclonal antibody against tumor vasculature in rats: involvement of intravascular thrombosis and fibrinogenesis.

  I Ohizumi, K Taniguchi, H Saito, H Kawata, S Tsunoda, H Makimoto, Y Wakai, Y Tsutsumi, S Nakagawa, N Utoguchi, S Kaiho, Y Ohsugi, T Mayumi

  We have reported that immunization of rat tumor-derived endothelial cells (TEC) isolated from KMT-17 solid tumors results in the generation of several monoclonal antibodies (MAbs). TES-23, one of these MAbs, recognizes a naturally occurring 80-kDa antigen expressed on endothelial cells of tumor blood vessels. To determine whether such MAbs can suppress solid tumor growth in vivo by impairment of endothelial cells in tumors following direct binding, we tested the biodistribution of (125)I-labeled TES-23 in rats bearing KMT-17 solid tumors. We also examined the effect of treatment using unconjugated TES-23 on tumor growth and histo-pathological changes in tumor tissues. Biodistribution studies showed localization of TES-23 into tumor tissues 60 min after intravenous injection. TES-23 suppressed significantly the growth of KMT-17 solid tumors following administration for 5 days. Histo-pathological examination showed that TES-23 caused degeneration, apoptosis and/or necrosis and denudation of endothelial cells in viable tumor areas following local aggregation and adhesion of lymphocytes, with subsequent intravascular thrombus formation by platelets and fibrin. Our results indicate that TES-23, which recognizes TEC, can target endothelial cells of solid tumor vasculature directly, resulting in growth suppression in vivo by reduction of blood flow due to intravascular thrombosis. Our results also suggest that targeting tumor vasculature is a potentially attractive approach for the treatment of solid tumors.

  1999年09月, International journal of cancer, 82(6) (6), 853 - 9, 英語, 国際誌

  研究論文（学術雑誌）


• Tumor vascular targeting using a tumor-tissue endothelium-specific monoclonal antibody as an effective strategy for cancer chemotherapy.

  H Makimoto, K Koizumi, S Tsunoda, Y Wakai, J Matsui, Y Tsutsumi, S Nakagawa, I Ohizumi, K Taniguchi, H Saito, N Utoguchi, Y Ohsugi, T Mayumi

  In this study, we attempted to develop tumor vascular targeting with a tumor tissue endothelium-specific monoclonal antibody. TES-23, which strongly and selectively recognizes tumor tissue endothelial cells, was chemically conjugated with Neocarzinostatin (NCS), and the anti-tumor effect was examined. The immunoconjugate, TES-23-NCS, showed, through the use of tumor hemorrhagic necrosis, a marked anti-tumor effect on KMT-17 tumors in rats at a dosage of 17 micrograms/kg (NCS equivalent) without any side effects, probably due to specific tumor vascular injury. By contrast, TES-23 alone (107 micrograms/kg), NCS alone (17 micrograms/kg), and Mopc-NCS (Mopc, 107 micrograms/kg; NCS, 17 micrograms/kg), the immunoconjugate of control antibody, did not have any anti-tumor activities. By tissue distribution analysis, TES-23 and TES-23-NCS showed high accumulation in KMT-17 tumors 1 h after intravenous administration. Moreover TES-23 also accumulated in Sarcoma-180 tumors in mice 1 h after intravenous administration. These results suggest that TES-23 may be a candidate for a potential tumor vascular targeting agent that is applicable to a wide variety of tumor types.

  1999年07月, Biochemical and biophysical research communications, 260(2) (2), 346 - 50, 英語, 国際誌

  研究論文（学術雑誌）


• Different reactions of aortic and venular endothelial cell monolayers to histamine on macromolecular permeability: role of cAMP, cytosolic Ca2+ and F-actin.

  K Ikeda, N Utoguchi, H Makimoto, H Mizuguchi, S Nakagawa, T Mayumi

  Endothelial cells assume a central role in the one process that the permeation of microvessels is accelerated in case of inflammation. We studied the effect of histamine on endothelial permeability, [Ca2+]i, cAMP and F-actin, using same origin aortic and venular cultured endothelial monolayers. When HUVEC were treated with histamine (10(-7)-10(-5) M), permeability of FITC-dextran (molecular weight 70,000) and [Ca2+]i were increased, while cAMP content was unchanged, and F-actin content was reduced. When bovine vein-derived endothelial cells were treated with histamine, [Ca2+]i was increased via H1 receptors, but permeability and F-actin content were not altered. When human aorta-derived endothelial cells were, [Ca2+]i was increased via H1 receptors and cAMP content was increased via H2 receptors, while permeability and F-actin content were not changed. When bovine aorta-derived endothelial cells were, cAMP and F-actin content were increased, while permeability was reduced. These findings suggest that endothelial cells derived from different tissues clearly showed the different reactions to histamine, the increase in [Ca2+]i led to the increase in endothelial permeability, while the increase in cAMP levels led to the reduction in permeability, and finally, F-actin regulated endothelial macromolecular permeability.

  1999年02月, Inflammation, 23(1) (1), 87 - 97, 英語, 国際誌

  研究論文（学術雑誌）


• Identification of tumor vascular antigens by monoclonal antibodies prepared from rat-tumor-derived endothelial cells.

  I Ohizumi, S Tsunoda, K Taniguchi, H Saito, K Esaki, K Koizumi, H Makimoto, Y Wakai, J Matsui, Y Tsutsumi, S Nakagawa, N Utoguchi, Y Ohsugi, T Mayumi

  We have reported the isolation and specific in vitro properties of tumor-derived endothelial cells (TEC) from rat KMT-17 fibrosarcomas transplanted into rats. To develop antibody-based tumor vascular targeting therapy for solid tumors, we have generated monoclonal antibodies (MAbs) using passive immunization of outside-out membrane vesicles of rat epididymal-fat-pad-derived capillary endothelial cells (FCEC) followed by active immunization of those of rat TEC. The MAbs produced were screened against TEC and FCEC. Of all cultured hybridomas, 75 (3.3%) of the secreted MAbs preferentially recognized TEC. We selected a total of 7 MAbs which detected antigens highly abundant in TEC, although 5 of the 7 MAbs were weakly positive for FCEC in cell-ELISA and FACS analyses. The antigens recognized by these MAbs, with the exception of MAb TES-7, were present on endothelial cells of tumor blood vessels in KMT-17 fibrosarcoma tissues, as shown by immunohistochemical analysis. Antigens of 40- and 80-kDa were recognized by MAbs TES-1, 7, 17, 21 and 26 and by MAbs TES-23 and 27 respectively. Although the function of these antigens, which are preferentially expressed on rat tumor-derived endothelial cells, is still unknown, we believe that future studies of such antigens will help elucidate the role of endothelial cells in tumor vasculature. Our results indicate that MAbs may provide a novel tool for the development of antibody-based therapy targeting tumor vasculature.

  1998年08月, International journal of cancer, 77(4) (4), 561 - 6, 英語, 国際誌

  研究論文（学術雑誌）


• Antibody-based therapy targeting tumor vascular endothelial cells suppresses solid tumor growth in rats.

  I Ohizumi, S Tsunoda, K Taniguchi, H Saito, K Esaki, H Makimoto, Y Wakai, Y Tsutsumi, S Nakagawa, N Utoguchi, S Kaiho, Y Ohsugi, T Mayumi

  We have developed a new approach to antibody-based therapy of solid tumors by targeting tumor vascular endothelial cells (EC) which are essential for the growth of solid tumors. We investigated the effect of an antibody against tumor-derived endothelial cells (TEC) on the growth of solid tumors in rats. Intravenous administration of TES-23, a monoclonal antibody generated by TEC isolated from rat KMT-17 solid tumors, at 1 mg/rat/day for 5 days resulted in significant suppression of KMT-17 tumor growth. Histopathological analysis of tumors administered with TES-23 showed that adhesion of lymphocytes to EC followed by denudation of EC in the viable tumor area. In contrast, little obvious toxicity was observed in most of the rat organs examined. These findings suggest that the concept of an antibody-based therapy with targeting tumor vascular EC would be promising in treatment of solid tumors.

  1997年07月, Biochemical and biophysical research communications, 236(2) (2), 493 - 6, 英語, 国際誌

  研究論文（学術雑誌）


• Bruceine B, a potent inhibitor of leukocyte-endothelial cell adhesion.

  N Utoguchi, T Nakata, H H Cheng, K Ikeda, H Makimoto, Y Mu, S Nakagawa, M Kobayashi, I Kitagawa, T Mayumi

  Leukocyte adhesion to vascular endothelial cells is an essential step in the development of inflammatory diseases. We have searched for inhibitors of leukocyte-endothelial cell adhesion that could be used as anti-inflammatory drugs and found that bruceine B (0.2 microgram/ml; 0.44 microM) inhibited human neutrophil or T cell adhesion to tumor necrosis factor-alpha (TNF) stimulated human umbilical vein endothelial cells (HUVEC). The inhibition of neutrophil adhesion to TNF-stimulated HUVEC by bruceine B was not derived from cytotoxic effects, as determined by measurement of the level of lactate dehydrogenase (LDH) activity in conditioned medium. The effect of bruceine B on neutrophil adhesion to HUVEC was not seen when the neutrophils were preincubated with bruceine B. However, inhibitory effects were evident when the HUVEC were preincubated with bruceine B. Bruceine B also inhibited neutrophil adhesion to lipopolysaccharide-stimulated HUVEC and T cell adhesion to TNF-stimulated HUVEC. These findings suggest that bruceine B may have anti-inflammatory activity.

  1997年04月, Inflammation, 21(2) (2), 223 - 33, 英語, 国際誌

  研究論文（学術雑誌）


• Effect of tumour cell-conditioned medium on endothelial macromolecular permeability and its correlation with collagen.

  N Utoguchi, H Mizuguchi, A Dantakean, H Makimoto, Y Wakai, Y Tsutsumi, S Nakagawa, T Mayumi

  Conditioned medium prepared from mouse melanoma B16 cells (B16-CM) increases the macromolecular permeability of bovine aortic, venous and human umbilical vein endothelial monolayer. Collagen, which is synthesised by endothelial cells, has an important function in regulating the permeability of endothelial monolayer. Briefly, low collagen content leads to hyperpermeable structure of the endothelial monolayer. In the present studies, we examined the relationship between the increase of endothelial permeability and content of synthesised collagen of endothelial cells cultured with B16-CM. The B16-CM reduced endothelial collagen content but did not digest collagen directly. Matrix metalloproteinase inhibitor, 1,10-phenanthroline, inhibited the increase in permeability due to addition of B16-CM. These data suggest that B16-CM acts on endothelial cells, stimulating the digestion of endothelial collagen, and that the reduced content of collagen leads to the hyperpermeability of the endothelial monolayer.

  1996年01月, British journal of cancer, 73(1) (1), 24 - 8, 英語, 国際誌

  研究論文（学術雑誌）


• Isolation and properties of tumor-derived endothelial cells from rat KMT-17 fibrosarcoma.

  N Utoguchi, A Dantakean, H Makimoto, Y Wakai, Y Tsutsumi, S Nakagawa, T Mayumi

  Rat KMT-17 fibrosarcoma-derived endothelial cells were isolated by Percoll gradient centrifugation with an attaching-speed separation technique, and their properties in culture were examined. The primary cultured tumor-derived endothelial cells (TEC) showed angiotensin-converting enzyme activity, positivity for Factor VIII-related antigen staining, and typical capillary-like formation on Matrigel. The primary cultured TEC monolayer showed greater permeability than normal tissue-derived endothelial cell (aorta, vena cava and epididymal fat capillary) monolayers on FITC-dextran diffusion (molecular weight 70,000). Leukocyte adhesion to TEC was reduced compared to that to fat-derived capillary endothelial cells. These characteristics resembled those of tumor vascular endothelium, and were observed both in the primary and first-passage cell cultures, but not in the fourth-passage cell cultures. Our findings indicate that primary or subcultured TEC are applicable for studies of the physiological characteristics of tumor endothelial cells.

  1995年02月, Japanese journal of cancer research : Gann, 86(2) (2), 193 - 201, 英語, 国内誌

  研究論文（学術雑誌）

• 薬剤師法改正に伴う外来服薬指導の充実化について

  山下 和彦, 池田 佳那子, 北村 直子, 澤田 有記美, 奥野 護, 西岡 達也, 久米 学, 槙本 博雄, 平野 剛, 平井 みどり

  (公社)日本薬学会, 2015年03月, 日本薬学会年会要旨集, 135年会(4) (4), 85 - 85, 日本語


• 精神科神経科病棟におけるフィジカルアセスメントの活用

  大本 暢子, 栗村 朋子, 久米 学, 槙本 博雄, 平野 剛, 平井 みどり

  日本シミュレーション医療教育学会, 2013年07月, 日本シミュレーション医療教育学会雑誌, 1, 29 - 29, 日本語


• 食道癌の術前FP療法施行患者における手術前後のシスタチンCとプラチナの濃度変動

  久米 学, 安井 裕之, 吉川 豊, 東口 佳苗, 小林 曜子, 槇本 博雄, 平野 剛, 平井 みどり, 中村 任

  (公社)日本薬学会, 2013年03月, 日本薬学会年会要旨集, 133年会(4) (4), 181 - 181, 日本語


• ボリコナゾール投与により筋肉炎が生じた1症例

  山下 和彦, 中村 任, 大松 秀明, 槙本 博雄, 西口 工司, 渋谷 由紀, 清水 政克, 岩井 愛雄, 金澤 健司, 秋田 穂束, 奥村 勝彦, 栄田 敏之

  (一社)日本TDM学会, 2006年07月, TDM研究, 23(3) (3), s176 - s176, 日本語


• 食道癌化学療法における5-FU血漿中濃度推移と副作用との相関

  山下 和彦, 末松 佳奈, 槙本 博雄, 中村 任, 岡村 昇, 栄田 敏之, 三木 生也, 田村 孝雄, 青山 伸郎, 春日 雅人, 奥村 勝彦

  (一社)日本TDM学会, 2006年04月, TDM研究, 23(2) (2), 75 - 76, 日本語


• 神戸大学医学部附属病院におけるCRCの医師主導型治験への関わりと問題点

  久米 学, 槙本 博雄, 佐々木 加代子, 中村 千恵, 塩谷 聡, 栄田 敏之, 尾原 秀史, 奥村 勝彦, 杉村 和朗

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