2017 Fiscal Year Final Research Report
Fundamental research for developing new therapeutic approach of multiple myeloma targeting its progenitor cells by reactive oxygen species (ROS)
Project/Area Number |
15K09490
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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 | Saitama Medical University |
Principal Investigator |
|
Co-Investigator(Renkei-kenkyūsha) |
OKUDA AKIHIKO 埼玉医科大学, 医学部, 教授 (60201993)
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Project Period (FY) |
2015-04-01 – 2018-03-31
|
Keywords | 多発性骨髄腫 / 前駆細胞 / 活性酸素 / 細胞死 / 細胞周期 / NF-κB / DNA修復 / プロテアソーム |
Outline of Final Research Achievements |
Multiple myeloma is one of the refractory hematological malignant disorder. It has reported that NF-κB signaling is important for the regulation of proliferation of myeloma cells and their stem/progenitor cells. In the present study, it has shown that the sensitivity of reactive oxygen species (ROS) in myeloma cells and their progenitor cells is higher than that of other hematological malignancies. New NF-κB inhibitor TM-233 was inhibited proliferation and induced cell death of myeloma cells and their progenitor cells via production of ROS in dose- and time-dependent manner. In addition, cell cycle checkpoint kinase WEE-1 inhibitor MK-1775 was also induced cell death of these cells via DNA repair process. From these results, new NF-κB inhibitor TM-233 and WEE-1 inhibitor MK-1775 might be possible novel therapeutic agents for the treatment of multiple myeloma.
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Free Research Field |
医歯薬学
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