Mechanisms of dUTPase downregulation by oxaliplatin and its applications to combination chemotherapy
| Project/Area Number |
24701028
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Clinical oncology
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| Research Institution | Nagoya University |
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Principal Investigator |
KIYONARI Shinichi 名古屋大学, 医学(系)研究科(研究院), 助教 (70570836)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | オキサリプラチン / 5-フルオロウラシル / 併用化学療法 / 大腸癌 |
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| Research Abstract |
Oxaliplatin is used in 5-fluorouracil-based combination chemotherapy. Interestingly, the dUTPase gene expression was reportedly suppressed by p53 stabilization after oxaliplatin treatment, however, the detailed molecular mechanisms were unclear. We found that the suppression was not observed when colon cancer cells were treated with cisplatin and carboplatin. Because oxaliplatin and its analog, dachplatin, can suppress dUTPase expression, the DNA damage response induced by 1,2-diaminocyclohexane (DACH) carrier ligand would be critical for the suppression effect. Our results suggested that oxaliplatin could enhance the cytotoxicity of 5-fluorouracil by regulating the expression of the genes that are implicated in thymidylate biosynthesis.
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Report
(3 results)
Research Products
(5 results)
