| Project/Area Number |
16K09853
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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 |
Hematology
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
加藤 淳二 札幌医科大学, 医学部, 教授 (20244345)
宇佐美 信 札幌医科大学, 医学部, 研究員 (10773377)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | HDAC阻害剤 / 多発性骨髄腫 / アポトーシス誘導 / アポトーシス / IAP阻害剤 / ●血液腫瘍 |
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| Outline of Final Research Achievements |
Histone deacetylase (HDAC) are the enzyme acting on the epigenetic regulation. The aberrant recruitment of HDAC occurs in cancer cells and it`s associated with the onset and progression of cancer. Therefore HDAC inhibitors (HDACi) emerged as new cancer target and have been extensively investigated. In multiple myeloma (MM), non-selective and Class I or Class IIb-selective HDACi have shown the biological efficacy in preclinical setting. In clinical trials, non-selective HDACi (panobinostat and vorinostat) and Class I-selective HDACi (romidepsin) show clinical efficacy. However biologic significance of class IIa HDACs (HDAC4, HDAC5, HDAC7 and HDAC9) in cancer cells including MM has not yet been elucidated. Single agent therapy of TMP269 showed mild cytotoxic effect against MM cell lines. Death receptor-5 expression was upregulated by the TMP269 treatment in dose dependent fashion, suggesting apoptotic pathway was enhanced by the HDAC class IIa inhibition.
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| Academic Significance and Societal Importance of the Research Achievements |
これまで十分研究されてこなかったクラスIIa選択的ヒストン脱アセチル化酵素阻害剤の抗腫瘍効果および作用機序を解析し、多発性骨髄腫における新たな治療戦略の可能性を示した。クラスIIa選択的ヒストン脱アセチル化酵素阻害剤より効率的なアポトーシス誘導の治療戦略開発を目指しており、薬剤耐性の克服などが期待される。
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