Molecular targeting therapy against intracellular signaling network in gallbladder cancer
| Project/Area Number |
24591008
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
SASAKI Takashi 東京大学, 医学部附属病院, 助教 (10569106)
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| Co-Investigator(Kenkyū-buntansha) |
MOURI Dai 東京大学, 医学部附属病院, 助教 (20582513)
IJICHI Hideaki 東京大学, 医学部附属病院, 講師 (70463841)
IKENOUE Tsuneo 東京大学, 医科学研究所, 准教授 (80396712)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 胆嚢癌 / MAPKシグナル / PI3Kシグナル / MEK阻害剤 / mTOR阻害剤 / ＭＡＰＫシグナル / ｍTOR阻害剤 |
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| Outline of Final Research Achievements |
Gallbladder cancer is the most common type with the worst prognosis among the bile duct cancers. The mechanism of disease and novel effective therapeutics still remain to be fully investigated. Analysis of human gallbladder cancer tissues demonstrated that MAPK and PI3K signaling pathways were frequently coordinately dysregulated in one third of the patients examined. We report here that the combination therapy using CI-1040, an inhibitor of MEK and RAD001, an inhibitor of mTOR, synergistically inhibited human gallbladder cancer cell proliferation in vitro and tumor growth of the xenograft model in vivo. Compared to the single treatment with CI-1040 or RAD001, the combination therapy significantly induced cell cycle arrest and apoptosis with decreased cyclin D1 expression.
These findings suggest that the double blockade of MAPK and mTOR signaling pathways might inhibit the signal crosstalk and benefit patients with advanced gallbladder cancer with hyperactivated these signalings.
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Report
(4 results)
Research Products
(11 results)
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[Journal Article] A randomized phase II study of gemcitabine and S-1 combination therapy versus gemcitabine monotherapy for advanced biliary tract cancer.2013
Author(s)
Sasaki T, Isayama H, Nakai Y, Ito Y, Yasuda I, Toda N, Kogure H, Hanada K, Maguchi H, Sasahira N, Kamada H, Mukai T, Okabe Y, Hasebe O, Maetani I, Koike K.
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Journal Title
Cancer Chemother Pharmacol.
Volume: 71
Issue: 4
Pages: 973-979
DOI
Related Report
Peer Reviewed
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