| Project/Area Number |
21590404
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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 |
Human pathology
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| Research Institution | Saitama Medical University |
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Principal Investigator |
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| Project Period (FY) |
2009 – 2011
|
| Project Status |
Completed (Fiscal Year 2011)
|
| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 分子病理 / 医歯薬学 / 基礎医学 / 人体病理学 / 基歴医学 |
|---|
| Research Abstract |
Everolimus(a derivative of rapamycin)-treated cells and non-treated cells were found not to show any difference in mTOR expression. But, phosphorylated-mTOR(p-mTOR) expression significantly decreased in the treated cells, and mTOR-related factors such as phosphorylated-4E-BP1(p-4E-BP1), HIF-1α, and vascular endothelial growth factor(VEGF) in the downstream region of mTOR revealed a marked decrease in expression. The analysis of influences of the drug on the HIF-1αdegradation system showed an increase in von-Hippel Lindau(VHL) expression in the treated cells. Increase of cleaved caspase-3, one of key factors involved in apoptosis, was also shown in the treated cells. In the next step, using nude mice implanted with RMG-1 cells, a decrease in tumor size was demonstrated in 4 of the 7 mice which were orally administered with everolimus. As a result, it was suggested that everolimus administration would be helpful as an anti-tumor therapy for CCA not only via down-regulation of p-mTOR but also degradation of HIF-1αby VHL and induction of apoptosis by cleaved caspase-3.
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