{"created":"2023-07-27T06:50:46.413152+00:00","id":43871,"links":{},"metadata":{"_buckets":{"deposit":"1ff279cf-d0e4-4a1c-b48a-2a994b6070e8"},"_deposit":{"created_by":18,"id":"43871","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"43871"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00043871","sets":["2812:2813:2818"]},"author_link":["72417","72431"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2016-05-20","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"5p.","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":"肺がん細胞株を用いた検討から、ERKの上流タンパクであるMEKの阻害は、ERKシグナルを一時的に遮断するが、24時間後にはERKを再活性化するとともにPI3Kシグナルの活性上昇も誘導した。そのメカニズムについて検討した結果、MEK阻害薬はフィードバック機構を介し、受容体型チロシンキナーゼの活性を誘導していた。活性化される受容体キナーゼは上皮系マーカー陽性細胞ではERBB3、間葉系マーカー陽性細胞ではFGFR1であった。それぞれの阻害薬とMEK阻害薬の併用は、ERKシグナルの完全な遮断と、MEK阻害薬により誘導されるPI3Kシグナルの上昇を抑制するとともに、細胞のアポトーシスを誘導した。","subitem_description_type":"Abstract"},{"subitem_description":"KRAS is frequently mutated in a variety of cancers including lung cancer. Whereas the mitogen-activated protein kinase (MAPK) is a well-known effector pathway of KRAS, blocking this pathway with clinically-available MAPK inhibitors is relatively ineffective. Treatment with MEK inhibitors in KRAS mutant lung cancers lead to feedback activation of the MAPK pathway. In epithelial-like KRAS mutant lung cancers, this feedback was attributed to ERBB3-mediated re-activation of MEK. In contrast, in mesenchymal-like KRAS mutant lung cancers, the feedback was contributed to the fibroblast growth factor receptor 1 (FGFR1) pathway. Combination of MEK inhibitor trametinib with an FGFR inhibitor induced cell death in vitro in mesenchymal-like KRAS mutant cancers. These observations indicate that feedback activation of FGFR1 signaling mitigates the effect of MEK inhibitor in mesenchymal-like KRAS mutant lung tumors, and could establish a therapeutic approach to treat these cancers.","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:26830105, 研究期間(年度):2014-04-01 – 2016-03-31","subitem_description_type":"Other"},{"subitem_description":"出典：研究課題「PI3 KおよびERKパスウエイを標的としたKRAS変異腫瘍に対する新規治療開発」課題番号26830105\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-26830105/26830105seika/）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":"10.24517/00050213","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=00645145"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=00645145","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-26830105/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-26830105/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-26830105/26830105seika/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-26830105/26830105seika/","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-EBI-H-kaken 2016-5p.pdf","filesize":[{"value":"693.2 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"CA-PR-EBI-H-kaken 2016-5p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/43871/files/CA-PR-EBI-H-kaken 2016-5p.pdf"},"version_id":"38907db4-156d-4642-92b8-111636f596ab"}]},"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":"PI3 KおよびERKパスウエイを標的としたKRAS変異腫瘍に対する新規治療開発","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"PI3 KおよびERKパスウエイを標的としたKRAS変異腫瘍に対する新規治療開発"},{"subitem_title":"Development of treatment strategy against KRAS mutant cancer by targeting PI3K and ERK","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":"43871","relation_version_is_last":true,"title":["PI3 KおよびERKパスウエイを標的としたKRAS変異腫瘍に対する新規治療開発"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T10:57:06.617643+00:00"}