{"created":"2023-07-27T06:50:46.502394+00:00","id":43873,"links":{},"metadata":{"_buckets":{"deposit":"aeecb61b-908c-4869-b8bf-50674e21cd62"},"_deposit":{"created_by":18,"id":"43873","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"43873"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00043873","sets":["2812:2813:2818"]},"author_link":["72419","72433"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2016-06-23","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"4p.","bibliographicVolumeNumber":"2014-04-01 – 2016-03-31","bibliographic_titles":[{"bibliographic_title":"平成27(2015)年度 科学研究費補助金 若手研究(B) 研究成果報告書"},{"bibliographic_title":"2015 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":"変異型EGFR選択的TKIは、2016年に本邦でも承認された肺癌の治療薬である。しかし、この薬にも耐性が獲得されることが予測され、これまでの研究より上皮間葉移行(EMT)がその原因であることが示唆された。まず、EMT耐性克服方法としてAXL阻害効果を検証したが、効果は得られずAXLのEMT耐性への関与は認められなかった。一方、EMT関連転写因子のZEB1を抑制した結果、耐性株の間葉系から上皮系への逆行（MET)が起こり、感受性が回復した。さらに、ZEB1を標的にできる薬剤を探索した結果、薬剤AがZEB1を低下させMETを誘導すること見出し、EMT耐性の治療薬として有望であると考えられた。","subitem_description_type":"Abstract"},{"subitem_description":"Irreversible tyrosine kinase inhibitor (ITKI) for the treatment of patients with mutant EGFR NSCLC has been approved in Japan recently. However, a lot of patients could be acquired resistance after treatment. While epithelial mesenchymal transition (EMT) was reported to be associated with the resistance, no optimal therapy has been identified. In this study, we first hypothesized that AXL plays an important role in EMT resistance and examined the effect of AXL inhibition on the EMT resistant cells. However, knock-down of AXL did not change the EMT phenotypes. Interestingly, we found that knock-down of ZEB1 induced mesenchymal-epithelial transition (MET) and restored sensitivity to EGFR-TKI. Furthermore, our drug screening revealed that Drug A strongly suppressed ZEB1 expression and induced MET, as well as restored ITKI sensitivity. These results suggest that Drug A could be a novel therapeutic strategy for overcoming EMT-associated ITKI resistance in mutant EGFR 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:26860603, 研究期間(年度):2014-04-01 – 2016-03-31","subitem_description_type":"Other"},{"subitem_description":"出典：研究課題「EGFR変異肺癌のEMTに起因する変異型EGFR選択的TKI耐性克服治療の開発」課題番号26860603\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-26860603/26860603seika/）を加工して作成","subitem_description_type":"Other"}]},"item_9_description_5":{"attribute_name":"提供者所属","attribute_value_mlt":[{"subitem_description":"金沢大学がん進展制御研究所","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00050215","subitem_identifier_reg_type":"JaLC"}]},"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=10722548"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=10722548","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-26860603/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-26860603/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-26860603/26860603seika/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-26860603/26860603seika/","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":"2018-02-19"}],"displaytype":"detail","filename":"CA-PR-FUKUDA-K-kaken 2016-4p.pdf","filesize":[{"value":"235.1 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"CA-PR-FUKUDA-K-kaken 2016-4p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/43873/files/CA-PR-FUKUDA-K-kaken 2016-4p.pdf"},"version_id":"f02bc474-c6e8-4b63-82bd-2e4aa6abb9c4"}]},"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EMTに起因する変異型EGFR選択的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EMTに起因する変異型EGFR選択的TKI耐性克服治療の開発"},{"subitem_title":"Development of therapies for overcoming EMT-associated irreversible tyrosine kinase inhibitor resistance in EGFR lung cancer","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2818"],"pubdate":{"attribute_name":"公開日","attribute_value":"2018-02-19"},"publish_date":"2018-02-19","publish_status":"0","recid":"43873","relation_version_is_last":true,"title":["EGFR変異肺癌のEMTに起因する変異型EGFR選択的TKI耐性克服治療の開発"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T10:57:05.087157+00:00"}