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KAKEN_26461432seika.pdf
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Download
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:179.1 KB
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| Last updated |
:Jul 26, 2019 |
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Total downloads since Jul 26, 2019 : 427
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| Title |
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治療法の進歩からとり残された高リスク骨髄腫に対する新しいコンセプトによる創薬研究
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| Kana |
チリョウホウ ノ シンポ カラ トリノコサレタ コウリスク コツズイシュ ニ タイスル アタラシイ コンセプト ニ ヨル ソウヤク ケンキュウ
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Chiryoho no shinpo kara torinokosareta korisuku kotsuzuishu ni taisuru atarashii konseputo ni yoru soyaku kenkyu
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Drug discovery based on novel concept for overcoming high-risk myeloma which is still intractable despite of recent progress in the treatment
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服部, 豊
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ハットリ, ユタカ
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Hattori, Yutaka
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慶應義塾大学・薬学部・教授
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Research team head
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科研費研究者番号 : 20189575
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柳川, 弘志
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ヤナガワ, ヒロシ
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Yanagawa, Hiroshi
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慶應義塾大学・薬学部・訪問教授
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Research team member
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科研費研究者番号 : 40327672
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山田, 健人
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ヤマダ, タケト
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Yamada, Taketo
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埼玉医科大学・医学部・教授
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Research team member
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科研費研究者番号 : 60230463
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須貝, 威
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スガイ, タケシ
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Sugai, Takeshi
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慶應義塾大学・薬学部・教授
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Research team member
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科研費研究者番号 : 60171120
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木内, 文之
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キウチ, フミユキ
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Kiuchi, Fumiyuki
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| Affiliation |
慶應義塾大学・薬学部・教授
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Research team member
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科研費研究者番号 : 60161402
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2017
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科学研究費補助金研究成果報告書
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2016
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| Abstract |
新規薬剤の登場により骨髄腫の予後は改善したが, 高リスク症例の予後は未だに不良であり, 髄外病変形成は深刻な問題である。当研究では, 高リスク骨髄腫細胞に各種cadherinを含む上皮間葉系遺伝子が高発現し, SCIDマウスへの造腫瘍性を有することを見出した。さらに, 高リスク骨髄腫治療薬として, 従来の免疫調節薬(IMiDs) とは異なる薬理作用を有する新規プタルイミド誘導体TC11の開発にも成功した。
Despite of the use of newly developed drugs, multiple myeloma (MM) with high-risk cytogenetic changes revealed significantly poor prognosis. Most patients acquired drug resistance and developed extra-medullary diseases. We found that N-cadherin and other mesenchymal genes were highly expressed in t (4 ; 14)-positive high-risk MM patients, and E-cadherin and other epithelial genes were expressed in MM patients with normal karyotype. Those cadherin-positive MM cells demonstrated tumorigenicity to SCID mice.We also developed a new immunomudulatory drug (IMiDs), TC11, which showed anti-tumor activity via cereblon-independent pathway unlike previously developed IMiDs. In addition, we tried structural modification of TC11 and succeeded in significantly increasing water-solublity of TC11.
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研究種目 : 基盤研究(C)(一般)
研究期間 : 2014～2016
課題番号 : 26461432
研究分野 : 血液内科学
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