@article{oai:nagasaki-u.repo.nii.ac.jp:00006868,
 author = {Ikebe, Emi and Kawaguchi, Akira and Tezuka, K and Taguchi, S and Hirose, S and Matsumoto, Takashi and Mitsui, Takahiro and Senba, K and Nishizono, Akira and Hori, Mitsuo and Hasegawa, Hiroo and Yamada, Y and Ueno, T and Tanaka, Yuetsu and Sawa, H and Hall, William W. and Minami, Yasufumi and Jeang, K. T. and Ogata, Masao and Morishita, K and Hasegawa, Hideki and Fujisawa, J and Iha, Hidekatsu},
 issue = {8},
 journal = {Blood Cancer Journal},
 month = {Aug},
 note = {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., Blood Cancer Journal, 3(8), e132; 2013},
 title = {Oral administration of an HSP90 inhibitor, 17-DMAG, intervenes tumor-cell infiltration into multiple organs and improves survival period for ATL model mice},
 volume = {3},
 year = {2013}
}