Mechanisms of resistance against histone deacetylase inhibitors in refractory lymphoid malignancies
Project/Area Number |
24591406
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Hematology
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Research Institution | Nagoya City University |
Principal Investigator |
IIDA SHINSUKE 名古屋市立大学, 医学(系)研究科(研究院), 教授 (50295614)
|
Co-Investigator(Kenkyū-buntansha) |
RI Masaki 名古屋市立大学, 大学院医学研究科, 助教 (00567539)
|
Project Period (FY) |
2012-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
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Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Keywords | 医療 / がん / 薬剤耐性 / リンパ腫 / 骨髄腫 / HDAC阻害剤 / 癌 / 薬剤反応性 |
Outline of Final Research Achievements |
Histone deacetylase inhibitor (HDACI) has been demonstrated to be effective for the patients with cutaneous T-cell lymphoma (CTCL) and multiple myeloma (MM). To elucidate the mechanisms of acquired resistance against HDACI in these tumors, we established various vorinostat-resistant cell lines. Comparison between these resistant and their parental cell lines has shown the following differences. Pan-HDAC activity was generally low in HDACI-resistant cells, but reduced HDAC3 activity was commonly shared in HDACI-resistant cell lines. Reduced expression of HDAC3 by shRNA decreases the sensitivity to HDACI, whereas that of other HDACs do not. Neither genetic mutation nor promoter methylation exists in HDAC3 gene in HDACI-resistant cells. Thus, reduced expression of HDAC3 is responsible for the acquired resistance against HDACI in part, although the underlying mechanism remains to be clarified.
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Report
(4 results)
Research Products
(2 results)
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[Presentation] Reduced expression of HDAC3 contributes to the resistance against HDAC inhibitor, vorinostat (SAHA) in mature lymphoid malignancies.
Author(s)
Ding J, Ri, M, Narita T, Masaki A, Mori F, Ito A, Kusumoto S, Ishida T, Komatsu H, Shiotsu Y, Niimi A, Iida S
Organizer
54th. Annual Meeting of American Society of Hematology
Place of Presentation
Georgia World Congress Center (Atlanta, USA)
Related Report
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