{"created":"2023-07-27T06:55:24.311913+00:00","id":51238,"links":{},"metadata":{"_buckets":{"deposit":"ce57e1ce-7537-467a-a52e-b573ac8b57dd"},"_deposit":{"created_by":18,"id":"51238","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"51238"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00051238","sets":["2812:2813:4014"]},"author_link":["88081","2729"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2021-08-19","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"6p.","bibliographicVolumeNumber":"2018-04-01 – 2021-03-31","bibliographic_titles":[{"bibliographic_title":"令和2(2020)年度 科学研究費補助金 若手研究 研究成果報告書"},{"bibliographic_title":"2020 Fiscal Year Final Research Report","bibliographic_titleLang":"en"}]}]},"item_9_creator_33":{"attribute_name":"著者別表示","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{}],"nameIdentifiers":[{},{}]}]},"item_9_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"未治療のALK融合遺伝子陽性肺癌患者に対するALK阻害薬 (alectinib) の効果とTP53変異との相関関係を明らかにするため、肺がんの臨床情報と遺伝子情報が統合されたデータベースを解析した。その結果、TP53変異陽性群では野生型群よりも有意に無増悪生存期間が短かった。そして、TP53変異を有するALK融合遺伝子陽性肺癌細胞株に対してプロテアソーム阻害薬をalectinibに併用したところ、アポトーシスを強く誘導した。メカニズムとしてプロテアソーム阻害薬がアポトーシス蛋白であるNoxaの分解を阻害し、細胞内で増加したNoxaが抗アポトーシス蛋白であるMcl-1に結合することを見出した。","subitem_description_type":"Abstract"},{"subitem_description":"We used integrated clinical and next-generation sequencing data. ALK-rearranged NSCLC cell lines expressing wild-type or mutant TP53 were used to evaluate cellular apoptosis induced by ALK-TKIs.In 90 ALK-rearranged NSCLC patients who were treated with a selective ALK-TKI, alectinib, TP53 co-mutated patients showed significantly worse progression-free survival (PFS) than TP53 wild-type patients [median PFS, 11.7 months vs.NR; p=0.0008; hazard ratio, 0.33]. ALK-rearranged NSCLC cell lines which lost p53 function were resistant to alectinib-induced apoptosis, but a proteasome inhibitior, ixazommib markedly induced apoptosis in the alectinib-treated cells by increasing the expression of a pro-apoptotic protein, Noxa which bound to an anti-apoptotic protein, Mcl-1. In subcutaneous tumor models, combination of ixazomib and alectinib prominently induced tumor regression and apoptosis even though the tumors were generated from ALK-rearranged NSCLC cells with non-functional p53.","subitem_description_type":"Abstract"}]},"item_9_description_22":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"研究課題/領域番号:18K15922, 研究期間(年度):2018-04-01 – 2021-03-31","subitem_description_type":"Other"},{"subitem_description":"出典：「ALK融合遺伝子陽性肺癌におけるアポトーシス抵抗性因子の解明と克服治療の開発」研究成果報告書　課題番号18K15922\n（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） \n（https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-18K15922/18K15922seika/）を加工して作成","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00057541","subitem_identifier_reg_type":"JaLC"}]},"item_9_publisher_17":{"attribute_name":"公開者","attribute_value_mlt":[{"subitem_publisher":"金沢大学がん進展制御研究所"}]},"item_9_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/search/?qm=90776444"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=90776444","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18K15922/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18K15922/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-18K15922/18K15922seika/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-18K15922/18K15922seika/","subitem_relation_type_select":"URI"}}]},"item_9_version_type_25":{"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_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2022-02-28"}],"displaytype":"detail","filename":"CA-PR-TANIMOTO-A-kaken 2021-6p.pdf","filesize":[{"value":"449.0 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"CA-PR-TANIMOTO-A-kaken 2021-6p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/51238/files/CA-PR-TANIMOTO-A-kaken 2021-6p.pdf"},"version_id":"cd541762-6428-4e7e-b7b5-6d71e4b433ab"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"research report","resourceuri":"http://purl.org/coar/resource_type/c_18ws"}]},"item_title":"ALK融合遺伝子陽性肺癌におけるアポトーシス抵抗性因子の解明と克服治療の開発","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"ALK融合遺伝子陽性肺癌におけるアポトーシス抵抗性因子の解明と克服治療の開発"},{"subitem_title":"Elucidation of the mechanism of resistance to apoptosis in ALK rearranged NSCLC","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["4014"],"pubdate":{"attribute_name":"公開日","attribute_value":"2022-02-28"},"publish_date":"2022-02-28","publish_status":"0","recid":"51238","relation_version_is_last":true,"title":["ALK融合遺伝子陽性肺癌におけるアポトーシス抵抗性因子の解明と克服治療の開発"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T13:43:52.578691+00:00"}