Identification of novel therapeutic target molecules and the molecular mechanism for refractory multiple myeloma
| 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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Report
(3 results)
Research Products
(6 results)
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[Journal Article] Synthesis and biological evaluation of the natural product komaroviquinone and related compounds aiming at a potential therapeutic lead compound for high-risk multiple myeloma.2017
Author(s)
Suto Y, Sato M, Fujimori K, Kitabatake S, Okayama M, Ichikawa D, Matsushita M, Yamagiwa N, Iwasaki G, Kiuchi F, Hattori Y.
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Journal Title
Bioorganic & Medicinal Chemistry Letters
Volume: 27
Issue: 19
Pages: 4558-4563
DOI
Related Report
Peer Reviewed
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[Journal Article] A novel phenylphthalimide derivative, pegylated TC11, improves pharmacokinetic properties and induces apoptosis of high-risk myeloma cells via G2/M cell-cycle arrest.2017
Author(s)
Aida S, Hozumi M, Ichikawa D, Iida K, Yonemura Y, Tabata N, Yamada T, Matsushita M, Sugai T, Yanagawa H, Hattori Y
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Journal Title
Biochem. Biophysic. Res. Commun.
Volume: 493
Issue: 1
Pages: 514-520
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Cereblon-independent anti-myeloma pathway of TC11, a novel compound of immunomodulatory drugs2017
Author(s)
Misa Nakamura, Daiju Ichikawa, Shuji Aida, Nahoko Hashimoto, Wakana Murota, Ryo Uozaki, Mikio Okayama, Kota Fujimori,Yuko Yonemura, Noriko Tabata, Hiroshi Yanagawa, Maiko Matsushita, Yutaka Hattori
Organizer
第79回日本血液学会
Related Report
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[Presentation] PEG(E)-TC11, a novel polyethylene glycol-linked phthalimide derivative, inhibited high-risk MM cell growth in vivo and in vitro via cell cycle G2/M arrest in a CRBN-independent manner.2017
Author(s)
Shuji Aida, Daiju Ichikawa, Kazuki Iida, Masashi Hozumi, Misa Nakamura, Ryo Uozaki, Nahoko Hashimoto, Mikio Okayama, Yuko Yonemura, Noriko Tabata, Taketo Yamada, Maiko Matsushita, Takeshi Sugai, Hiroshi Yanagawa, Yutaka Hattori
Organizer
American association for cancer research annual meeting 2017
Related Report
Int'l Joint Research
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[Presentation] PEG(E)-TC11はCRBN非依存的に細胞周期の調節を介してハイリスク骨髄腫の増殖を抑制する2017
Author(s)
會田 宗司, 市川 大樹, 中村 美沙, 宇於崎 涼, 飯田 和樹, 穂積 暢史, 岡山 幹夫, 藤森 宏太, 米村 裕子, 田畠 典子, 山田 健人, 松下 麻衣子, 須貝 威, 柳川 弘志, 服部 豊
Organizer
第42回日本骨髄腫学会学術集会
Related Report
