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Oral administration of an HSP90 inhibitor, 17-DMAG, intervenes tumor-cell infiltration into multiple organs and improves survival period for ATL model mice
http://hdl.handle.net/10069/33890
http://hdl.handle.net/10069/33890e6ef8fc8-f359-4de1-9b5f-6e0f8f7be19f
名前 / ファイル | ライセンス | アクション |
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BCJ3_132.pdf (2.4 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2013-10-10 | |||||
タイトル | ||||||
タイトル | Oral administration of an HSP90 inhibitor, 17-DMAG, intervenes tumor-cell infiltration into multiple organs and improves survival period for ATL model mice | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | 17-DMAG | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Apoptosis | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | ATL | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Molecular chaperon | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | ransgenic model | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Tax | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Ikebe, Emi
× Ikebe, Emi× Kawaguchi, Akira× Tezuka, K× Taguchi, S× Hirose, S× Matsumoto, Takashi× Mitsui, Takahiro× Senba, K× Nishizono, Akira× Hori, Mitsuo× Hasegawa, Hiroo× Yamada, Y× Ueno, T× Tanaka, Yuetsu× Sawa, H× Hall, William W.× Minami, Yasufumi× Jeang, K. T.× Ogata, Masao× Morishita, K× Hasegawa, Hideki× Fujisawa, J× Iha, Hidekatsu |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | In the peripheral blood leukocytes (PBLs) from the carriers of the human T-lymphotropic virus type-1 (HTLV-1) or the patients with adult T-cell leukemia (ATL), nuclear factor kappaB (NF-κB)-mediated antiapoptotic signals are constitutively activated primarily by the HTLV-1-encoded oncoprotein Tax. Tax interacts with the I κB kinase regulatory subunit NEMO (NF-κB essential modulator) to activate NF-κB, and this interaction is maintained in part by a molecular chaperone, heat-shock protein 90 (HSP90), and its co-chaperone cell division cycle 37 (CDC37). The antibiotic geldanamycin (GA) inhibits HSP90's ATP binding for its proper interaction with client proteins. Administration of a novel water-soluble and less toxic GA derivative, 17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride (17-DMAG), to Tax-expressing ATL-transformed cell lines, C8166 and MT4, induced significant degradation of Tax. 17-DMAG also facilitated growth arrest and cellular apoptosis to C8166 and MT4 and other ATL cell lines, although this treatment has no apparent effects on normal PBLs. 17-DMAG also downregulated Tax-mediated intracellular signals including the activation of NF-κB, activator protein 1 or HTLV-1 long terminal repeat in Tax-transfected HEK293 cells. Oral administration of 17-DMAG to ATL model mice xenografted with lymphomatous transgenic Lck-Tax (Lck proximal promoter-driven Tax transgene) cells or HTLV-1-producing tumor cells dramatically attenuated aggressive infiltration into multiple organs, inhibited de novo viral production and improved survival period. These observations identified 17-DMAG as a promising candidate for the prevention of ATL progression. | |||||
書誌情報 |
Blood Cancer Journal 巻 3, 号 8, p. e132, 発行日 2013-08-16 |
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出版者 | ||||||
出版者 | Nature Publishing Group | |||||
EISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 20445385 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1038/bcj.2013.30 | |||||
権利 | ||||||
権利情報 | © 2013 Macmillan Publishers Limited All rights reserved. | |||||
権利 | ||||||
権利情報 | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/. | |||||
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 | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Blood Cancer Journal, 3(8), e132; 2013 |