Autophagy is required for cell survival under L-asparaginase－induced metabolic stress in acute lymphoblastic leukemia cells

• Material Type: 博士論文
• ISSN: 1476-5594
• Title: Autophagy is required for cell survival under L-asparaginase－induced metabolic stress in acute lymphoblastic leukemia cells
• Volume: 36
• Author/Editor: Takahashi, Hiroyoshi
• Author Heading: Takahashi, Hiroyoshi
• Publication, Distribution, etc.: Nature Publishing Group
• Publication Date: 2017-03-27
• Publication Date (W3CDTF): 2017-03-27
• Alternative Title: オートファジーは急性リンパ性白血病細胞においてL-アスパラギナーゼ誘導性代謝ストレス下での細胞生存に必要である
• Periodical title: Oncogene
• Degree grantor/type: 浜松医科大学
• Date Granted: 2017-04-21
• Date Granted (W3CDTF): 2017-04-21
• Dissertation Number: 甲第761号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第761号
• Text Language Code: eng
• Subject Heading: autophagy; acute lymphoblastic leukemia; L-asparaginase; reactive oxygen species; p53
• Target Audience: 一般
• Note (General): doctoral; 医学系研究科; L-asparaginase has been used for more than three decades in acute lymphoblastic leukemia (ALL) patients and remains an essential drug in the treatment of ALL. Poor response to L-asparaginase is associated with increased risk of therapeutic failure in ALL. However, both the metabolic perturbation and molecular context of L-asparaginase?treated ALL cells has not been fully elucidated. Here we identify that treatment with L-asparaginase results in metabolic shutdown via the reduction of both glycolysis and oxidative phosphorylation, accompanied by mitochondrial damage and activation of autophagy. The autophagy is involved in reducing reactive oxygen species (ROS) level by eliminating injured mitochondria. Inhibition of autophagy enhances L-asparaginase-induced cytotoxicity and overcomes the acquired resistance to L-asparaginase in ALL cells. The ROS-p53 positive feedback loop is an essential mechanism of this synergistic cytotoxicity. Thus, our findings provide the rationale for the future development of combined treatment of L-asparaginase and anti-autophagy drug in ALL patients.
• DOI: info:doi/10.1038/onc.2017.59; https://doi.org/info:doi/10.1038/onc.2017.59
• Persistent ID (NDL): info:ndljp/pid/11092141; https://dl.ndl.go.jp/pid/11092141
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2018-05-04T12:13:37+09:00
• Date Created (W3CDTF): 2018-08-27
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://hdl.handle.net/10271/3334; https://hama-med.repo.nii.ac.jp/records/3188
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp

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