| Project/Area Number |
15K08109
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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 |
Medical pharmacy
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| Research Institution | Tokai University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
小見山 智義 東海大学, 医学部, 准教授 (60439685)
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| Research Collaborator |
Yu Shyr Vanderbilt大学, 癌センター, 教授
Hande Kenneth R. Vanderbilt大学, 癌センター, 教授
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | がん / 薬剤反応性 / 抗腫瘍薬耐性 / ゲノム変化 / 国際情報交換 米国 / 国際情報交換 米国 |
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| Outline of Final Research Achievements |
Idarubicin (IDR), which inhibits DNA polymerase, is a key drug to treat leukemia. We investigated the mechanism of resistance using the human leukemia cell line MOLT-3 and its idarubicin-resistant MOLT-3/IDR by mitochondrial DNA and exome nuclear DNA analyses.
In resistant sublines, LIG1 DNA ligase 1 and helicase plurality genes showed amino acid-related changes. Amino acid mutations were also confirmed in polymerase-associated genes. GO enrichment testing was performed and lipid-related genes were selected based on the results. Flow cytometric method was used to determine whether IDR permeability was significantly different in MOLT-3/IDR and MOLT-3. The data showed that an IDR concentration of 0.5 μg resulted in slow permeability in MOLT-3/IDR. The slow IDR permeability seen in MOLT-3/IDR might be due to the effects of the amino acid changes found in polymerase- and lipid-associated genes.
Our findings suggest that multiple mutations in these genes play a role in IDR resistance.
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