| Project/Area Number |
26890022
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Tumor therapeutics
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| Research Institution | Tokai University |
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Principal Investigator |
ABD Aziz 東海大学, 医学部, 奨励研究員 (50738789)
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| Project Period (FY) |
2014-08-29 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 幹細胞 / がん幹細胞 / 白血病 / 線維素溶解系 / 分子標的薬 / 完全寛解 |
|---|
| Outline of Final Research Achievements |
Extracellular Plaminogen Activator Inhibitor type-1 (PAI-1) regulates production of chemokines such as SDF-1a, G-CSF and TGF-b in bone marrow niche. On the other hand, intracellular PAI-1 in hematopoietic stem cell (HSC) down-regulates both Furin activity and MT1-MMP expression and regulates HSC motility. Intracellular PAI-1 plays an important role in HSC motility through TGF-b signal pathway. In addition, inhibition of PAI-1 in leukemic cell, enhances motility of leukemic stem cell (LSC) by increase MT1-MMP expression, and finally induces sensitivity of anti-leukemia therapy. Our findings revealed that intracellular PAI-1 maintains resistivity of LSC in the niche. Inhibition of PAI-1 with anti-leukemic agent is new therapy strategy that targeting LSC.
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