Drug Polymorphic triple nucleotide alterations in cell cycle transactivator E2F-4 and sensitivity to the anlicancer agents
| Project/Area Number |
12671227
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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 |
Digestive surgery
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| Research Institution | Okayama University Hospital |
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Principal Investigator |
MATSUBARA Nagahide Okayama University Hospital, assistant, 医学部附属病院, 助手 (70314672)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMIZU Kenji Okayama University Graduate School of Medicine and Dentistry, Professor, 大学院・医歯学総合研究科, 教授 (10037286)
TANAKA Noriaki Okayama University Graduate School of Medicine and Dentistry, Professor, 大学院・医歯学総合研究科, 教授 (10127566)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2000: ¥3,000,000 (Direct Cost: ¥3,000,000)
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| Keywords | E2F-4 / polymorphism / choemoterapy / drug sensitivitv / 小腸移植 / 門脈内注入 / 免疫抑制 / 大腸癌 / microsatellite instability / 化学療法 |
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| Research Abstract |
Deficiency of mismatch repair system has been shown to cause hereditary non-polyposis coloredal cancer as well as approximately 15% of the sporadic cobrectal cancer. In advancement of molecular oncology, several molecular mechanisms of the resistance against antineoplastic agents have bee elucidated. Besides its function of mismatch repair (MMR), the MMR system also recognizes certain DNA adducts or distortion caused by chemotherapeulic agents, which ultimately leads to cell cycle arrest or cell death. MMR deficient cells acquire resistance- to some alkylathig agents, such as platinum, and 5FU because the detected MMR system cannot recognize, the DNA damage caused by such agents. The MMR target genes such as TGFbRII, BAX, and E2F-4 also have the potential to modify the drug sensitivity because these genes are on the down stream pathway of MMR deficiency. Here we demonstrale that the E2F-4 aherations, which we jdentified for the first time, is apparently modified the sensitivity of chemotherapeulic agents such as, VP-16 and CBDCA by transfecting various wild type and mutant E2F-4s in NIH3T3 cells. The knowledge of the resistance to some chemotherapeutic agents caused by MMR deficiency or downstream genes should be considered in a clinical setting near future.
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Report
(3 results)
Research Products
(17 results)
