| Project/Area Number |
23591156
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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 |
Respiratory organ internal medicine
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| Research Institution | Nagoya City University |
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Principal Investigator |
OGURI Tetsuya 名古屋市立大学, 医学(系)研究科(研究院), 准教授 (60363925)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 肺癌 / ペメトレキシド / ABCトランスポーター / 遺伝子多型 / thymidylate synthase / 予測バイオマーカー / ABCC11 / pemetrexed / methotrexate / Lung cancer / Pemetrexed / Thymidylate synthase |
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| Research Abstract |
We found that the mechanisms of the synergistic interaction of pemetrexed (MTA) and cytotoxic nucleoside analogues are multifactorial, and that the chemotherapeutic activity of the combination of MTA and cytotoxic nucleoside analogues is synergistic with regard to the alteration of metanotbolic molecules.
In a search for biomarkers for study of the efficacy of MTA treatment, we examined the thymidylate synthase (TS) copy number in NSCLC cell lines and in clinical NSCLC samples treated with MTA with platinum drugs. Significant correlation was found between the TS copy number and the sensitivity for MTA in both lung cancer cell lines and clinical NSCLC samples. Our results suggest that TS copy number could be a predictive biomarker for MTA.
We also focus on ABCC11 polymorphism 538G>A, and established cell liens expressing human ABCC11, one carrying allele G and another carrying allele A. Moreover we now examine the relationship between ABCC11 polymorphism and resistance to MTA clinically.
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