Mechanism of rapamycin-resistant translation in mouse hepatocellular carcinoma cells
| Project/Area Number |
20590392
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
OGAWA Katsuhiro Asahikawa Medical College, 医学部, 名誉教授 (50045514)
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| Co-Investigator(Kenkyū-buntansha) |
柳沼 裕二 旭川医科大学, 医学部, 准教授 (90250571)
玉川 進 旭川医科大学, 医学部, 助教 (70188415)
山本 雅大 旭川医科大学, 医学部, 助教 (30431399)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2009: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2008: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
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| Keywords | IRES / 肝癌 / 蛋白合成 / 蛋白翻訳 / 肝発癌 / マウス / ラバマイシン / HIF-1 / ラパマイシン |
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| Research Abstract |
Although protein translation is activated by the PI3K-Akt-mTOR pathway in mouse hepatocarcinogenesis, rapamycin, a mTOR inhibitor, shows the limited antitumor effect on hepatocellular carcinomas and no effect on hepatic adenomas despite the fact that the cap-dependent protein translation is inhibited by rapamycin. Under the condition with rapamycin treatment, HIF-1α can continue to be expressed by the internal ribosomal entry site (IRES) mechanism. Furthermore, the mechanism of tumor necrosis induced by rapamycin was not due to the direct action against hepatocellular carcinoma cells but rather due to the angiotoxic effect of rapamycin against the vasculature of hepatocellular carcinomas.
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Report
(4 results)
Research Products
(34 results)
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[Presentation] Rapamycin induces necrosis in mouse hepatocellular carcinomas by antiangiogenic activity, but also activates cap-independent translation of HIF-1α in hepatocellular carcinoma cells.2009
Author(s)
Tanaka H,, Yamamoto M, Hashimoto N, Miyakoshi M, Tamakawa S, Yoshie M, Tokusashi Y, Yokoyama K, Yaginuma Y, Ogawa K.
Organizer
American Association for Cancer Research Annual Meeting
Place of Presentation
Denver, CO
Related Report
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[Presentation] Reciprocal activation of PI3K/Akt signaling and HIF-1α in progression of mouse hepatocarcinogenesis.2007
Author(s)
Tanaka H, Yamamoto M, Hashimoto N, Miyakoshi M, Tamakawa S, Yoshie M, Tokusashi Y, Yokoyama K, Yaginuma Y, Ogawa K.
Organizer
American Association for Cancer Research Annual Meeting
Place of Presentation
Los Angeles, CA
Related Report
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[Presentation] Expression of hypoxia-inducible factor 1α in the early step of hepatic carcinogenesis.2005
Author(s)
Tanaka H, Yamamoto M, Hashimoto N, Miyakoshi M, Tamakawa S, Yoshie M, Tokusashi Y, Yokoyama K, Yaginuma Y, Ogawa K.
Organizer
American Association for Cancer Research Annual Meeting
Place of Presentation
Anaheim, CA
Related Report
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