| Project/Area Number |
26293300
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Shinshu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
清水 明 信州大学, 学術研究院医学系(医学部附属病院), 講師 (00447773)
本山 博章 信州大学, 学術研究院医学系(医学部附属病院), 助教 (20569587)
小林 聡 信州大学, 学術研究院医学系, 准教授 (90334903)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000)
Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2015: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2014: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
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| Keywords | 肝臓外科学 / 胆管癌 / 抗癌剤治療 / 分子標的治療 / 薬物療法 / オートファジー / 化学療法 |
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| Outline of Final Research Achievements |
Cholangiocarcinoma (CCC) is a strongly aggressive malignancy for which surgical resection is the only curative therapy. We had identified Cop35, (CCA-binding oligopeptide 35), by bacteriophage biopanning. Cop35 binds to specifically CCC cells and internalizes mediated by clathrin-mediated endocytosis, and interact with endoplasmic reticulum chaperone GRP78. Everolimus inhibits the proliferation of cancer cells via the mTORC1 pathway while at the same time increasing autophagy. In CCC, everolimus suppressed cell proliferation and co-administered Cop35 enhanced the suppression via the inhibition of autophagy associated with suppressed GRP78 activity. Being a different measure from chemicals like chloroquine, cell growth inhibition enhanced by combined therapy of Cop35 with evelorimus in lesser concentration than that with 5FU may lead to a promising new approache in CCC therapy.
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