Pro-chemotherapeutic effects of antibody against extracellular domain of claudin-4 in bladder cancer.

• Material Type: 博士論文
• Title: Pro-chemotherapeutic effects of antibody against extracellular domain of claudin-4 in bladder cancer.
• Author/Editor: Kuwada, Masaomi; Chihara, Yoshitomo; Luo, Yi; Li, Xiangru; Nishiguchi, Yukiko; Fujiwara, Rina; Sasaki, Takamistu; Fujii, Kiyomu; Ohmori, Hitoshi; Fujimoto, Kiyohide; Kondoh, Masuo; Kuniyasu, Hiroki
• Author Heading: Kuwada, Masaomi; Chihara, Yoshitomo; Luo, Yi; Li, Xiangru; Nishiguchi, Yukiko; Fujiwara, Rina; Sasaki, Takamistu; Fujii, Kiyomu; Ohmori, Hitoshi; Fujimoto, Kiyohide; Kondoh, Masuo; Kuniyasu, Hiroki
• Publication, Distribution, etc.: Elsevier
• Publication Date: 2015-12-01
• Publication Date (W3CDTF): 2015-12-01
• Alternative Title: 膀胱癌における抗クローディン4細胞外ドメイン中和抗体の化学療法増感効果
• Periodical title: Cancer letters
• No. or year of volume/issue: 369 1
• Volume: 369
• Issue: 1
• Pages: 212-221
• ISSN (Periodical Title): ISSN : 0304-3835
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2016-03-15
• Dissertation Number: 甲第649号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: Claudin; Tight junction; Antibody therapy; Microenvironment
• Target Audience: 一般
• Note (General): type:Thesis; Bladder cancer displays an aggressive phenotype in the muscle-invasive phase, and is associated with a high mortality rate. Therefore, novel molecular therapeutic targets are needed to improve patient survival. A monoclonal antibody against the extracellular domain of the claudin-4 (CLDN4) tight junction protein was established by immunizing rats with a plasmid vector encoding human CLDN4. A hybridoma clone, producing a rat monoclonal antibody recognizing CLDN4 (clone 4D3), was obtained. Immunohistochemistry by using the 4D3 antibody showed that CLDN4 expression was associated with local invasion, nodal metastasis, distant metastasis, and advanced stage in 86 cases of bladder cancer. The 4D3 antibody inhibited growth, invasion, and survival, associated with abrogation of the intratumoral microenvironment; lowered concentrations of epidermal growth factor and vascular endothelial growth factor were found in three-dimensional cultures of T24 and RT4 cells. In combination with cisplatin therapy, 4D3 enhanced cisplatin cytotoxicity by increasing cellular permeability, leading to increased intracellular cisplatin concentrations. In mouse models of subcutaneous tumors and lung metastasis, 4D3 enhanced tumor growth inhibition, alone and with concurrent cisplatin treatment. The anti-tumor activity of the newly established 4D3 antibody suggests that it may be a powerful tool in CLDN4-targeting therapy, and in combination with chemotherapy.; 博士（医学）・甲第649号・平成28年3月15日; Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.; identifier:Cancer letters Vol.369 No.1 p.212-221(2015.12); identifier:03043835; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3186; identifier:Cancer letters, 369(1): 212-221
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1016/j.canlet.2015.08.019
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU

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