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Heat shock protein 90 inhibitor NVP-AUY922 exerts potent activity against adult T-cell leukemia?lymphoma cells
http://hdl.handle.net/10069/35887
http://hdl.handle.net/10069/358871f2b4aa1-c5a8-445e-a792-1f7858148a86
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Supple.pdf (99.5 kB)
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ISYK761_Taniguchi.pdf (851.8 kB)
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||
---|---|---|---|---|---|---|
公開日 | 2015-10-14 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Heat shock protein 90 inhibitor NVP-AUY922 exerts potent activity against adult T-cell leukemia?lymphoma cells | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Adult T-cell leukemia-lymphoma | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | HSP90 inhibitors | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | NF-κB | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | NVP-AUY922 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | PIM kinases | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||
資源タイプ | doctoral thesis | |||||
アクセス権 | ||||||
アクセス権 | open access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
著者 |
谷口, 広明
× 谷口, 広明 |
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著者別名 | ||||||
姓名 | Taniguchi, Hiroaki | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Adult T-cell leukemia-lymphoma (ATL), an aggressive neoplasm etiologically associated with HTLV-1, is a chemoresistant malignancy. Heat shock protein 90 (HSP90) is involved in folding and functions as a chaperone for multiple client proteins, many of which are important in tumorigenesis. In this study, we examined NVP-AUY922 (AUY922), a second generation isoxazole-based non-geldanamycin HSP90 inhibitor, and confirmed its effects on survival of ATL-related cell lines. Analysis using FACS revealed that AUY922 induced cell-cycle arrest and apoptosis; it also inhibited the growth of primary ATL cells, but not of normal PBMCs. AUY922 caused strong upregulation of HSP70, a surrogate marker of HSP90 inhibition, and a dose-dependent decrease in HSP90 client proteins associated with cell survival, proliferation, and cell cycle in the G1 phase, including phospho-Akt, Akt, IKKα, IKKβ, IKKγ, Cdk4, Cdk6, and survivin. Interestingly, AUY922 induced downregulation of the proviral integration site for Moloney murine leukemia virus (PIM) in ATL cells. The PIM family (PIM-1, -2, -3) is made up of oncogenes that encode a serine/threonine protein kinase family. As PIM kinases have multiple functions involved in cell proliferation, survival, differentiation, apoptosis, and tumorigenesis, their downregulation could play an important role in AUY922-induced death of ATL cells. In fact, SGI-1776, a pan-PIM kinase inhibitor, successfully inhibited the growth of primary ATL cells as well as ATL-related cell lines. Our findings suggest that AUY922 is an effective therapeutic agent for ATL, and PIM kinases may be a novel therapeutic target. This report first describes the effectiveness of a novel HSP90 inhibitor NVP-AUY922 to adult T-cell leukemia-lymphoma (ATL) cells. | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 長崎大学学位論文 学位記番号:博(医歯薬)甲第761号 学位授与年月日:平成27年3月18日 | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Author: Hiroaki Taniguchi, Hiroo Hasegawa, Daisuke Sasaki, Koji Ando, Yasushi Sawayama, Daisuke Imanishi, Jun Taguchi, Yoshitaka Imaizumi, Tomoko Hata, Kunihiro Tsukasaki, Naoki Uno, Yoshitomo Morinaga, Katsunori Yanagihara, Yasushi Miyazaki | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Citation: Cancer Science, 105(12), pp.1601-1608; 2014 | |||||
書誌情報 |
Cancer Science 巻 105, 号 12, p. 1601-1608, 発行日 2015-03-18 |
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ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 13479032 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1111/cas.12540 | |||||
権利 | ||||||
権利情報 | c 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association. | |||||
権利 | ||||||
権利情報 | This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
その他のタイトル | ||||||
その他のタイトル | 成人T細胞白血病・リンパ腫細胞に対する熱ショック蛋白90阻害薬NVP-AUY922の有効性の検証 | |||||
出版者 | ||||||
出版者 | 日本癌学会 | |||||
関係URI | ||||||
識別子タイプ | HDL | |||||
関連識別子 | http://hdl.handle.net/10069/35637 | |||||
学位名 | ||||||
学位名 | 博士(医学) | |||||
学位授与機関 | ||||||
学位授与機関識別子Scheme | kakenhi | |||||
学位授与機関識別子 | 17301 | |||||
学位授与機関名 | Nagasaki University (長崎大学) | |||||
学位授与年月日 | ||||||
学位授与年月日 | 2015-03-18 | |||||
学位授与番号 | ||||||
学位授与番号 | 甲医歯薬第761号 | |||||
学位の種類 | ||||||
課程博士 | ||||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Nagasaki University (長崎大学), 博士(医学) (2015-03-18) |