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

• Material Type: 博士論文
• Title: Angiotensin receptor blockade attenuates cholangiocarcinoma cell growth by inhibiting the oncogenic activity of Yes-associated protein.
• Author/Editor: 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
• Author Heading: 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
• Publication, Distribution, etc.: Elsevier
• Publication Date: 2018-10-10
• Publication Date (W3CDTF): 2018-10-10
• Alternative Title: 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
• Periodical title: Cancer letters
• No. or year of volume/issue: 434
• Volume: 434
• Pages: 120-129
• ISSN (Periodical Title): ISSN : 0304-3835
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2020-03-16
• Dissertation Number: 甲第728号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: Angiotensin receptor blocker; Cholangiocarcinoma; Yes-associated protein; Angiogenesis; G protein-coupled receptor
• Target Audience: 一般
• Note (General): 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
• Source: fulltext; 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; 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; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3719/3/03%e7%94%b2728%e6%9c%ac%e6%96%87.pdf
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1016/j.canlet.2018.07.021
• Periodical Title (NCID): AA00598513; https://ci.nii.ac.jp/ncid/AA00598513
• 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