{"created":"2023-06-20T15:48:40.046047+00:00","id":3188,"links":{},"metadata":{"_buckets":{"deposit":"bc8c9d70-8ab1-49bb-8517-1a81b4d76337"},"_deposit":{"created_by":4,"id":"3188","owners":[4],"pid":{"revision_id":0,"type":"depid","value":"3188"},"status":"published"},"_oai":{"id":"oai:hama-med.repo.nii.ac.jp:00003188","sets":["2:15:17"]},"author_link":["9475"],"control_number":"3188","item_5_alternative_title_1":{"attribute_name":"その他のタイトル","attribute_value_mlt":[{"subitem_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","subitem_alternative_title_language":"ja"}]},"item_5_biblio_info_5":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2017-03-27","bibliographicIssueDateType":"Issued"},"bibliographicPageEnd":"4276","bibliographicPageStart":"4267","bibliographicVolumeNumber":"36","bibliographic_titles":[{"bibliographic_title":"Oncogene","bibliographic_titleLang":"en"}]}]},"item_5_date_granted_17":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2017-04-21"}]},"item_5_degree_grantor_15":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"浜松医科大学"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"13802","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_5_degree_name_12":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（医学）","subitem_degreename_language":"ja"}]},"item_5_description_13":{"attribute_name":"学位の区分","attribute_value_mlt":[{"subitem_description":"doctoral","subitem_description_language":"en","subitem_description_type":"Other"}]},"item_5_description_14":{"attribute_name":"学位の分野","attribute_value_mlt":[{"subitem_description":"医学系研究科","subitem_description_language":"ja","subitem_description_type":"Other"}]},"item_5_description_9":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"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.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_5_dissertation_number_18":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第761号"}]},"item_5_publisher_6":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Nature Publishing Group","subitem_publisher_language":"en"}]},"item_5_relation_26":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"28346428","subitem_relation_type_select":"PMID"}}]},"item_5_relation_28":{"attribute_name":"出版社DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1038/onc.2017.59","subitem_relation_type_select":"DOI"}}]},"item_5_source_id_19":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0950-9232","subitem_source_identifier_type":"PISSN"}]},"item_5_source_id_20":{"attribute_name":"EISSN","attribute_value_mlt":[{"subitem_source_identifier":"1476-5594","subitem_source_identifier_type":"EISSN"}]},"item_5_version_type_32":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Takahashi, Hiroyoshi","creatorNameLang":"en"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2018-08-27"}],"displaytype":"detail","filename":"DT_761ronbun.pdf","filesize":[{"value":"3.4 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"論文本文","objectType":"fulltext","url":"https://hama-med.repo.nii.ac.jp/record/3188/files/DT_761ronbun.pdf"},"version_id":"6a9f2223-2bc7-4b55-8be1-1387b96124ea"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"autophagy","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"acute lymphoblastic leukemia","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"L-asparaginase; reactive oxygen species","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"p53","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"Autophagy is required for cell survival under L-asparaginase－induced metabolic stress in acute lymphoblastic leukemia cells","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Autophagy is required for cell survival under L-asparaginase－induced metabolic stress in acute lymphoblastic leukemia cells","subitem_title_language":"en"}]},"item_type_id":"5","owner":"4","path":["17"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2018-03-31"},"publish_date":"2018-03-31","publish_status":"0","recid":"3188","relation_version_is_last":true,"title":["Autophagy is required for cell survival under L-asparaginase－induced metabolic stress in acute lymphoblastic leukemia cells"],"weko_creator_id":"4","weko_shared_id":-1},"updated":"2023-10-19T01:28:10.249209+00:00"}