Dual antitumor mechanisms of Notch signaling inhibitor in a T-cell acute lymphoblastic leukemia xenograft model
スポンサーリンク
概要
- 論文の詳細を見る
Constitutive activation of Notch signaling is required for the proliferation of a subgroup of human T-cell acute lymphoblastic leukemias (T-ALL). Previous in vitro studies have demonstrated the therapeutic potential of Notch signaling inhibitors for treating T-ALL. To further examine this possibility, we applied a γ-secretase inhibitor (GSI) to T-ALL xenograft models. Treatment of established subcutaneous tumors with GSI resulted in partial or complete regression of tumors arising from four T-ALL cell lines that were also sensitive to GSI in vitro. To elucidate the mechanism of action, we transduced DND-41 cells with the active form of Notch1 (aN1), which conferred resistance to in vitro GSI treatment. Nevertheless, in vivo treatment with GSI induced a partial but significant regression of subcutaneous tumors that developed from aN1-transduced DND-41 cells, whereas it induced complete regression of tumors that developed from mock-transduced DND-41 cells. These findings indicate that the remarkable efficacy of GSI might be attributable to dual mechanisms, directly via apoptosis of DND-41 cells through the inhibition of cell-autonomous Notch signaling, and indirectly via disturbance of tumor angiogenesis through the inhibition of non-cell-autonomous Notch signaling.
- Wiley-Blackwellの論文
- 2009-12-10
著者
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KUROKAWA Mineo
Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo
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SHIBUTANI Makoto
Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology
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MITSUMORI Kunitoshi
Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology
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Ogawa S
Department Of Pathology Graduate School Of Medicine University Of Tokyo
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TOJO Arinobu
Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo
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Ogawa Seishi
東京大学医学部附属病院 無菌治療部
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Ohta Satoshi
The 21st Century Coe Program Graduate School Of Medicine The University Of Tokyo
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OGAWA Seishi
Department of Cell Therapy & Transplantation Medicine University of Tokyo Hospital
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CHIBA Shigeru
Department of Cell Therapy & Transplantation Medicine University of Tokyo Hospital
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Suzuki Takahiro
Department Of Chemical Engineering Science Yokohama National University
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Hanazono Yutaka
Division of Regenerative Medicine, Jichi Medical School
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Chiba Shigeru
Department Of Cell Therapy And Transplantation Medicine University Of Tokyo Hospital
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Seto Motoko
Department Of Gastroenterology Graduate School Of Medicine The University Of Tokyo
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Mitsumori Kunitoshi
Laboratory Of Veterinary Pathology Division Of Animal Science Institute Of Symbiotic Science And Tec
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Ogawa Seishi
Department Of Pathology Graduate School Of Medicine University Of Tokyo
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IWATSUBO Takeshi
Department of Neuropathology and Neuroscience, Tokyo University
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KUMANO Keiki
Department of Cell Therapy and Transplantation Medicine, University of Tokyo Hospital
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Tojo Arinobu
Department Of Cell Processing And Transfusion Institute Of Medical Science University Of Tokyo
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Chiba S
Kyowa Hakko Kogyo Co. Ltd. Yamaguchi Jpn
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Kurokawa Mineo
Department Of Hematology And Oncology Graduate School Of Medicine University Of Tokyo
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Kurokawa Mineo
Department Of Hematology And Oncology University Of Tokyo
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Seto Masao
Division Of Molecular Medicine Aichi Cancer Center
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Iwatsubo Takeshi
Department Of Neuropathology And Neuroscience Graduate School Of Pharmaceutical Sciences University
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Iwatsubo Takeshi
Graduate School Of Pharmaceutical Sciences The University Of Tokyo
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Shibutani Makoto
Laboratory Of Veterinary Pathology Tokyo University Of Agriculture And Technology
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Natsugari Hideaki
Graduate School Of Pharmaceutical Sciences The University Of Tokyo
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Kumano Keiki
Department Of Cell Therapy And Transplantation Medicine University Of Tokyo Hospital
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Chiba S
Tokyo Research Laboratories Kyowa Hakko Kogyo Co. Ltd.
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Tojo Arinobu
Department Of Hematology And Oncology Institute Of Medical Sciences University Of Tokyo
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MASUDA Shigeo
Department of Cell Therapy and Transplantation Medicine, University of Tokyo Hospital
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TOMITA Taisuke
Department of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, Universit
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NATSUGARI Hideaki
Department of Rational Medicinal Science, Graduate School of Pharmaceutical Sciences, University of
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Natsugari Hideaki
Department Of Rational Medicinal Science Graduate School Of Pharmaceutical Sciences University Of To
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Sasaki Makoto
Laboratory Of Veterinary Pathology Tokyo University Of Agriculture And Technology
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Hanazono Yutaka
Division Of Regenerative Medicine Center For Molecular Medicine Jichi Medical University
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Tomita Taisuke
Department Of Neuropathology And Neuroscience Graduate School Of Pharmaceutical Sciences University
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Suzuki Takahiro
Department Of Anesthesiology Surugadai Nihon University Hospital
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Kurokawa Mineo
Department Of Hematology And Oncology The University Of Tokyo Hospital
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Hanazono Yutaka
Division Of Genetic Therapeutics Center For Molecular Medicine Department Of Medicine Jichi Medical
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Kurokawa Mineo
Department Of Hematology And Oncology Graduate School Of Medicine The University Of Tokyo
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Kurokawa Mineo
Department of Hematology & Oncology, The University of Tokyo
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KUROKAWA Mineo
Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo
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SUZUKI Takahiro
Department of Cell Therapy and Transplantation Medicine, University of Tokyo Hospital
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