Anti-adult T-cell leukemia effects of a novel synthetic retinoid, Am80 (Tamibarotene)
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概要
- 論文の詳細を見る
Clinical trials for treatment of adult T-cell leukemia (ATL) caused by human T-cell leukemia virus type I (HTLV-I) using all-trans-retinoic acid (ATRA) have shown satisfactory therapeutic responses, although efficacies were limited. Recently, many synthetic retinoids have been developed and among them, a novel synthetic retinoid, Am80 (Tamibarotene) is an RARα- and RARβ-specific retinoid expected to overcome ATRA resistance. The present study examined the inhibitory effects of Am80 on HTLV-I-infected T-cell lines and ATL cells. Am80 had negligible growth inhibition of peripheral blood mononuclear cells but marked growth inhibition of both HTLV-I-infected T-cell lines and ATL cells. Am80 arrested cells in the G1 phase of the cell cycle and induced apoptosis in HTLV-I-infected T-cell lines. It inhibited also the phosphorylation of IκBα and NF-κB-DNA binding, in conjunction with reduction of expression of proteins involved in the G1/S cell cycle transition and apoptosis. Am80 also inhibited the expression of JunD, resulting in suppression of AP-1-DNA binding. Furthermore, severe combined immunodeficient mice with tumors induced by subcutaneous inoculation of HTLV-I-infected T cells, responded to Am80 treatment with partial regression of tumors and no side-effects. These findings demonstrate that Am80 is a potential inhibitor of NF-κB and AP-1, and is a potentially useful therapeutic agent against ATL. (Cancer Sci 2008; 99: 2286–2294)
- Blackwell Publishingの論文
- 2008-11-10
著者
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Masuda M
Department Of Endocrinology And Metabolism Department Of Internal Medicine University Of The Ryukyus
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Tanaka Yuetsu
新潟大学 医歯学総合研究科ウィルス学
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Tanaka Yuetsu
Division Of Immunology Faculty Of Medicine University Of The Ryukyus
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Masuda Masato
Division Of Endocrinology And Metabolism Faculty Of Medicine University Of The Ryukyus
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Ishikawa Chie
Division Of Molecular Virology And Oncology Graduate School Of Medicine University Of The Ryukyus
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TOMITA Mariko
Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus
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MORI Naoki
Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus
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NAKAZATO Tetsuro
Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus
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OKUDAIRA Taeko
Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus
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NAKAMA Shinji
Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus
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SAWADA Shigeki
Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus
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UCHIHARA Jun-nosuke
Department of Internal Medicine, Naha City Hospital
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TAIRA Naoya
Department of Internal Medicine, Heartlife Hospital
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OHSHIRO Kazuiku
Department of Internal Medicine, Okinawa Prefectural Nanbu Medical Center & Children's Medical Cente
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TAKASU Nobuyuki
Division of Endocrinology and Metabolism, Faculty of Medicine, University of the Ryukyus
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Taira Naoya
Department Of Internal Medicine Heartlife Hospital
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Tomita Mariko
Division Of Molecular Virology And Oncology Graduate School Of Medicine University Of The Ryukyus
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Nakama Shinji
Division Of Molecular Virology And Oncology Graduate School Of Medicine University Of The Ryukyus
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Okudaira Taeko
The Second Department Of Internal Medicine Faculty Of Medicine The University Of Ryukyus
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Okudaira Taeko
Division Of Molecular Virology And Oncology Graduate School Of Medicine University Of The Ryukyus
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Sawada Shigeki
Division Of Molecular Virology And Oncology Graduate School Of Medicine University Of The Ryukyus
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Tanaka Y
Division Of Immunology Faculty Of Medicine University Of The Ryukyus
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Ohshiro Kazuiku
Department Of Internal Medicine Okinawa Prefectural Nanbu Medical Center & Children's Medic
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Takasu Nobuyuki
Department Of Endocrinology And Metabolism Department Of Internal Medicine University Of The Ryukyus
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Takasu Nobuyuki
The College Of Engineering University Of Osaka Prefecture
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Nakazato Tetsuro
Division Of Molecular Virology And Oncology Graduate School Of Medicine University Of The Ryukyus
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Uchihara Jun-nosuke
Department Of Internal Medicine Naha City Hospital
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Mori Naoki
Division Of Molecular Virology And Oncology Graduate School Of Medicine University Of The Ryukyus
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Masuda Masato
Department Of Endocrinology And Metabolism Department Of Internal Medicine University Of The Ryukyus
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Mori Naoki
Division Of Applied Life Sciences Graduate School Of Agriculture Kyoto University
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Taira Naoya
Department of Endocrinology and Metabolism, Internal Medicine, University of the Ryukyus School of Medicine
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