| Project/Area Number |
11671017
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
MIYAZAWA Keisuke Tokyo Medical University, Medicine, Assistant Professor, 医学部, 講師 (50209897)
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| Co-Investigator(Kenkyū-buntansha) |
GOTOH Akihiko Tokyo Medical University, Medicinem assistant, 医学部, 助手 (00297293)
YAGUCHI Makoto Tokyo Medical University, Medicinem assistant, 医学部, 助手 (50246310)
矢口 誠 東京医科大学, 医学部, 助手 (90276949)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | vitamin K2 / myelodysplastic syndromes / leukemia / apoptosis / differentiation / vitamin D3 |
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| Research Abstract |
We have originally reported that vitamin K2 (VK2) induces apoptosis in primary cultured leukemia cells and leukemia cell lines. This apoptosis process was mediated through down-modulation of BCL-2 repression, up-modulation of BAX, depolarization of mitochondrial membrane potential, and activation of caspase-3. Enforced over expression of BCL-2 in H-60 cell (HL-60bcl-2) resulted in almost complete inhibition of apoptosis induction in response to VK2. However, monocytic differentiation via G0/G1 arrest was still observed in HL-60bcl-2 cells. This strongly suggests that VK2. Furthermore, we have reported that this monocytic differtntionan induction is synergistically enhanced by combined treatment with VK2 and vitamin D3 analog. Interestingly, apoptosis induction in response to VK2 was significantly suppressed along with enhanced moncytitc differentiation. In response to our in vitro observations, pilot studies of VK2 therapy in-patients with myelodysplastic syndromes (MDS) and post-MDS AML were performed in many institutions in Japan. These clinical trials demonstrate the therapeutic effects of VK2 for the patients with MDS. Further moleculer-based studies are still on going to explain the mechanisms of therapeutic effects of VK2 in MDS.
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