Angiotensin receptor blockade attenuates cholangiocarcinoma cell growth by inhibiting the oncogenic activity of Yes-associated protein.

• 資料種別: 博士論文
• タイトル: Angiotensin receptor blockade attenuates cholangiocarcinoma cell growth by inhibiting the oncogenic activity of Yes-associated protein.
• 著者・編者: Saikawa, Soichiro; Kaji, Kosuke; Nishimura, Norihisa; Seki, Kenichiro; Sato, Shinya; Nakanishi, Keisuke; Kitagawa, Koh; Kawaratani, Hideto; Kitade, Mitsuteru; Moriya, Kei; Namisaki, Tadashi; Mitoro, Akira; Yoshiji, Hitoshi
• 著者標目: Saikawa, Soichiro; Kaji, Kosuke; Nishimura, Norihisa; Seki, Kenichiro; Sato, Shinya; Nakanishi, Keisuke; Kitagawa, Koh; Kawaratani, Hideto; Kitade, Mitsuteru; Moriya, Kei; Namisaki, Tadashi; Mitoro, Akira; Yoshiji, Hitoshi
• 出版事項: Elsevier
• 出版年月日等: 2018-10-10
• 出版年（W3CDTF）: 2018-10-10
• 並列タイトル等: アンギオテンシン受容体を遮断することによりYes関連蛋白質の発癌活性が阻害されて胆管癌細胞増殖が抑制される
• タイトル（掲載誌）: Cancer letters
• 巻号年月日等（掲載誌）: 434
• 掲載巻: 434
• 掲載ページ: 120-129
• ISSN（掲載誌）: ISSN : 0304-3835
• 授与機関名: 奈良県立医科大学
• 授与年月日: 2020-03-16
• 報告番号: 甲第728号
• 学位: 博士（医学）
• 本文の言語コード: eng
• 件名標目: Angiotensin receptor blocker; Cholangiocarcinoma; Yes-associated protein; Angiogenesis; G protein-coupled receptor
• 対象利用者: 一般
• 一般注記: type:Thesis; Cholangiocarcinoma (CCA) is a destructive malignancy with limited responsiveness to conventional chemotherapy. Although angiotensin receptor blockers (ARBs) have gained attention for their potential anticancer activity, little is known about their effects on CCA. The transcriptional co-activator, Yes-associated protein (YAP) is a critical oncogene in several cancers, including CCA. Following recent evidence showing that YAP is regulated by angiotensin II (AT-II), we investigated the effects of an ARB, losartan, on two human CCA cell lines (KKU-M213 and HuCCT-1) with regards to YAP oncogenic regulation. Losartan suppressed AT-II-induced CCA cell proliferation in a dose-dependent manner, induced apoptosis, decreased YAP (Ser127), and downregulated the YAP target genes CTGF, CYR61, ANKRD1, and MFAP5. However, losartan did not affect epithelial-mesenchymal transition, differentiation, or stemness in the CCA cells. Xenograft tumor growth assay showed that oral administration of a low clinical dose of losartan considerably reduced subcutaneous tumor burden and attenuated intratumor vascularization in CCA cell-derived xenograft tumors in BALB/c nude mice. These results indicate that ARB therapy could serve as a potential novel strategy for CCA treatment.; 博士（医学）・甲第728号・令和2年3月16日; Copyright © 2018 Elsevier B.V. All rights reserved.; identifier:Cancer letters Vol.434 p.120-129 (2018 Oct); identifier:03043835; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3719; identifier:Cancer letters, 434: 120-129
• オンライン閲覧公開範囲: インターネット公開
• 関連情報（DOI）: 10.1016/j.canlet.2018.07.021
• 連携機関・データベース: 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
• 提供元機関・データベース: 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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http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3719/1/01%e7%94%b2728%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3719/2/02%e7%94%b2728%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3719/3/03%e7%94%b2728%e6%9c%ac%e6%96%87.pdf fulltext