| Project/Area Number |
16K19059
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Keio University |
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Principal Investigator |
ICHIKAWA Daiju 慶應義塾大学, 薬学部(芝共立), 助教 (60462793)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 多発性骨髄腫 / IMiDs / IMiDs抵抗性 / TC11 / CRBN非依存 / 血液がん / 癌 / シグナル伝達 |
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| Outline of Final Research Achievements |
In this study, we focused on the mechanism of IMiDs resistance in MM. We examined gene profiles in lenalidomide-sensitive and -resistant cell lines with or without lenalidomide using DNA microarray following GSEA and cluster analyses. In GSEA, P53 PATHWAY gene group is enriched in lenalidomide- treated sensitive MM cells as compared to resistant cell line. In cluster analyses, 50 spots were down-regulated and 132 spots were upregulated under lenalidomide-treated sensitive MM cells. In those genes, BNIP3, DCAF4L2, and STAP2 proteins are concordantly increased. We next attempted knockdown of BNIP3, DCAF4L2, and STAP2 in lenalidomide-sensitive cells using retroviral delivery of shRNA against human those genes. However those genes knockdown did not rescue lenalidomide-induced cell. We need to reveal that P53 PATHWAY gene group and another up- or down-regulated genes in cluster analyses regulated the sensitivity of MM cells to IMiDs in the future.
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