{"created":"2023-07-27T06:54:02.680100+00:00","id":49162,"links":{},"metadata":{"_buckets":{"deposit":"5631dead-8e58-410b-91e1-1e15b03f09d5"},"_deposit":{"created_by":18,"id":"49162","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"49162"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00049162","sets":["2812:2813:2819"]},"author_link":["88076","440"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2015-05-26","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"4p.","bibliographicVolumeNumber":"2013-04-01 - 2015-03-31","bibliographic_titles":[{"bibliographic_title":"平成26(2014)年度 科学研究費補助金 若手研究(B) 研究成果報告書"},{"bibliographic_title":"2014 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":"BIM遺伝子多型に起因するEGFR-TKI耐性を克服する治療としてHDAC阻害薬の有効性について検証した。BIM多型を有するEGFR変異肺癌細胞株PC-3はゲフィチニブによるアポトーシス誘導に抵抗性を示した。PC-3にボリノスタットを添加すると活性型BIM蛋白の発現が上昇し、ゲフィチニブとの併用によってアポトーシスが誘導された。マウスモデルにおいて、ゲフィチニブ単剤ではPC-3皮下腫瘍は縮小しなかったが、ボリノスタット併用によってアポトーシスが誘導され著明な腫瘍縮小効果を示した。以上より、HDAC阻害薬併用治療がBIM遺伝子多型に起因するEGFR-TKI耐性克服に有効であることが示唆された。","subitem_description_type":"Abstract"},{"subitem_description":"We investigated whether vorinostat, a histone deacetylase (HDAC) inhibitor, could circumvent EGFR-TKI resistance in the EGFR mutant lung cancer cell lines, which harbor the BIM polymorphism. We found that PC-3 cells with BIM polymorphism were much less sensitive to gefitinib-induced apoptosis than the EGFR mutant cell lines, which do not harbor this polymorphism. Vorinostat dose-dependently increased the expression of BIM with a pro-apoptotic BH3 domain and, together with gefitinib, induced apoptosis in cells with BIM polymorphism in vitro. In xenograft models, gefitinib did not induce regression of PC-3 subcutaneous tumors, whereas the combination of vorinostat and gefitinib induced marked regression of tumors, accompanied by tumor-cell apoptosis. These results indicate that the combination of HDAC inhibitor and EGFR-TKI may circumvent the resistance due to the BIM polymorphism in EGFR mutant lung cancer.","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:25860640, 研究期間(年度):2013-04-01 - 2015-03-31","subitem_description_type":"Other"},{"subitem_description":"出典：研究課題「EGFR変異肺癌のBIM遺伝子多型に起因するEGFR-TKI耐性克服治療の開発」課題番号25860640\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-25860640/25860640seika/)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":"10.24517/00055475","subitem_identifier_reg_type":"JaLC"}]},"item_9_publisher_17":{"attribute_name":"公開者","attribute_value_mlt":[{"subitem_publisher":"金沢大学附属病院がんセンター"}]},"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=90565384"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=90565384","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-25860640/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-25860640/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-25860640/25860640seika/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-25860640/25860640seika/","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":"2019-09-20"}],"displaytype":"detail","filename":"CA-PR-TAKEUCHI-S-kaken 2015-4p.pdf","filesize":[{"value":"506.1 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"CA-PR-TAKEUCHI-S-kaken 2015-4p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/49162/files/CA-PR-TAKEUCHI-S-kaken 2015-4p.pdf"},"version_id":"76206f02-4602-43f3-9064-691e15c6be09"}]},"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":"EGFR変異肺癌のBIM遺伝子多型に起因するEGFR-TKI耐性克服治療の開発","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"EGFR変異肺癌のBIM遺伝子多型に起因するEGFR-TKI耐性克服治療の開発"},{"subitem_title":"Development of therapy for circumvention of EGFR-TKI resistance due to BIM polymorphism in EGFR mutant lung cancer","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2819"],"pubdate":{"attribute_name":"公開日","attribute_value":"2019-09-20"},"publish_date":"2019-09-20","publish_status":"0","recid":"49162","relation_version_is_last":true,"title":["EGFR変異肺癌のBIM遺伝子多型に起因するEGFR-TKI耐性克服治療の開発"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T09:42:01.280819+00:00"}