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Please use this identifier to cite or link to this item: http://hdl.handle.net/10271/3334

Title: Autophagy is required for cell survival under L-asparaginase–induced metabolic stress in acute lymphoblastic leukemia cells
Other Titles: 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
Authors: Takahashi, Hiroyoshi
髙橋, 寛吉
Keywords: autophagy
acute lymphoblastic leukemia
L-asparaginase; reactive oxygen species
p53
Issue Date: 27-Mar-2017
Publisher: Nature Publishing Group
Abstract: 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.
Description: 浜松医科大学学位論文 医博第761号(平成29年4月21日)
URI: http://hdl.handle.net/10271/3334
ISSN: 1476-5594
DOI: info:doi/10.1038/onc.2017.59
PubMed ID: info:pmid/28346428
Academic Degrees and number: 13802甲第761号
Degree-granting date: 2017-04-21
Degree name: 博士(医学)
Degree-granting institutions: 浜松医科大学
Appears in Collections:2010 博士(論文)

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