{"created":"2023-06-20T16:34:08.747489+00:00","id":3242,"links":{},"metadata":{"_buckets":{"deposit":"5dea1c56-daca-4af2-95c1-f8d82270a36d"},"_deposit":{"created_by":3,"id":"3242","owners":[3],"pid":{"revision_id":0,"type":"depid","value":"3242"},"status":"published"},"_oai":{"id":"oai:kindai.repo.nii.ac.jp:00003242","sets":["14:2667:2685:2686","21:2669:2687:2688"]},"author_link":["3708","3707","3709"],"item_8_alternative_title_3":{"attribute_name":"その他（別言語等）のタイトル","attribute_value_mlt":[{"subitem_alternative_title":"Molecular-based approach for overcoming acquired resistance to EGFR tyrosine kinase inhibitors"}]},"item_8_biblio_info_21":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2011-01-01","bibliographicIssueDateType":"Issued"},"bibliographicPageEnd":"6","bibliographicPageStart":"1","bibliographic_titles":[{"bibliographic_title":"科学研究費補助金研究成果報告書 (2011. )"}]}]},"item_8_description_33":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"研究成果の概要（和文）：臨床上喫緊の課題であるEGFR 遺伝子変異陽性非小細胞肺癌患者における、EGFR)チロシンキナーゼ阻害剤（EGFR-TKIs）に対する獲得耐性の克服を目指し、第2 世代EGFR-TKIs であるBIBW2992 とTS を標的とする抗癌剤(S-1 あるいはペメトレキセド)との相乗効果及び、EGFR-TKI とサバイビン抑制剤のYM155 の併用が有用であることを示した前臨床データを得た。              研究成果の概要（英文）：Most non–small cell lung cancer (NSCLC) tumors with activating mutations of the EGFR are initially responsive to EGFR tyrosine kinase inhibitors (TKIs), but they subsequently develop resistance to these drugs. The effects of the second-generation, irreversible EGFR-TKI BIBW2992 and the TS-targeting agents S-1 (or 5-fluorouracil) or pemetrexed synergistically inhibited the proliferation of NSCLC cells with the T790Mmutation in vitro. BIBW2992 induced down-regulation of TS in the gefitinib-resistant NSCLC cells, implicating depletion of TS in the enhanced antitumor effect of the combination therapy. The combination of BIBW2992 and either the oral fluoropyrimidine S-1 or pemetrexed also inhibited the growth of NSCLC xenografts with the T790Mmutation to an extent greater than that apparent with either agent alone. The addition of TS-targeting drugs to BIBW2992 is a promising strategy to overcome EGFR-TKI resistance inNSCLC with the T790Mmutation of EGFR. Loss of PTEN (phosphatase and tensin homolog) was recently shown to contribute to resistance to EGFR-TKIs in EGFRmutation–positiveNSCLC through activation of the protein kinaseAKT. The combination therapywithYM155 and erlotinib inhibited the growth of tumors formed by EGFRmutation–positive, PTEN-eficientNSCLC cells in nudemice to a greater extent than did treatment with either drug alone. These results thus indicate that persistent activation of signaling by theAKT-survivin pathway induced by PTENloss underlies a mechanismof resistance to erlotinib-induced apoptosis in EGFRmutation–positiveNSCLC. They further suggest that the targeting of survivin has the potential to overcome EGFR-TKI resistance in EGFRmutation–positiveNSCLC.","subitem_description_type":"Abstract"}]},"item_8_description_36":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"研究種目：基盤研究(C);  研究期間：2009～2011;   課題番号：21591011;   研究分野：呼吸器内科学;   科研費の分科・細目：呼吸器内科学・非閉塞性肺疾患〔癌、肺線維症、呼吸器感染症、その他〕","subitem_description_type":"Other"}]},"item_8_description_37":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"subitem_description":"Research Paper","subitem_description_type":"Other"}]},"item_8_description_41":{"attribute_name":"フォーマット","attribute_value_mlt":[{"subitem_description":"application/pdf","subitem_description_type":"Other"}]},"item_8_publisher_14":{"attribute_name":"出版者 名前","attribute_value_mlt":[{"subitem_publisher":"近畿大学"}]},"item_8_relation_11":{"attribute_name":"著者 外部リンク","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"http://kaken.nii.ac.jp/d/r/10411597.ja.html"}]},{"subitem_relation_name":[{"subitem_relation_name_text":"http://kaken.nii.ac.jp/d/r/40298964.ja.html"}]},{"subitem_relation_name":[{"subitem_relation_name_text":"http://kaken.nii.ac.jp/d/r/10208134.ja.html"}]}]},"item_8_text_10":{"attribute_name":"著者 役割","attribute_value_mlt":[{"subitem_text_value":"研究代表者"},{"subitem_text_value":"研究分担者"},{"subitem_text_value":"研究分担者"}]},"item_8_text_7":{"attribute_name":"著者(英)","attribute_value_mlt":[{"subitem_text_language":"en","subitem_text_value":"OKAMOTO, ISAMU"},{"subitem_text_language":"en","subitem_text_value":"NAKAGAWA, KAZUHIKO"},{"subitem_text_language":"en","subitem_text_value":"NISHIO, KAZUTO"}]},"item_8_text_8":{"attribute_name":"著者 所属","attribute_value_mlt":[{"subitem_text_value":"近畿大学医学部; 准教授"},{"subitem_text_value":"近畿大学医学部; 教授"},{"subitem_text_value":"近畿大学医学部; 教授"}]},"item_8_text_9":{"attribute_name":"著者所属(翻訳)","attribute_value_mlt":[{"subitem_text_value":"Kinki University"},{"subitem_text_value":"Kinki University"},{"subitem_text_value":"Kinki University"}]},"item_8_version_type_12":{"attribute_name":"版","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"岡本,  勇"},{"creatorName":"オカモト, イサム","creatorNameLang":"ja-Kana"}],"nameIdentifiers":[{"nameIdentifier":"3707","nameIdentifierScheme":"WEKO"},{"nameIdentifier":"10208134","nameIdentifierScheme":"研究者番号","nameIdentifierURI":" "}]},{"creatorNames":[{"creatorName":"中川,  和彦"},{"creatorName":"ナカガワ, カズヒコ","creatorNameLang":"ja-Kana"}],"nameIdentifiers":[{"nameIdentifier":"3708","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"西尾,  和人"},{"creatorName":"ニシオ, カズト","creatorNameLang":"ja-Kana"}],"nameIdentifiers":[{"nameIdentifier":"3709","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2016-02-17"}],"displaytype":"detail","filename":"KAKEN_21591011seika.pdf","filesize":[{"value":"90.3 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"KAKEN_21591011seika.pdf","url":"https://kindai.repo.nii.ac.jp/record/3242/files/KAKEN_21591011seika.pdf"},"version_id":"d206194b-aee5-4625-8ec1-24234936b0e8"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"非閉塞性肺疾患","subitem_subject_scheme":"Other"},{"subitem_subject":"肺線維症","subitem_subject_scheme":"Other"},{"subitem_subject":"呼吸器感染症","subitem_subject_scheme":"Other"},{"subitem_subject":"癌","subitem_subject_scheme":"Other"}]},"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チロシンキナーゼ阻害剤獲得耐性の分子メカニズムに基づいた耐性克服研究","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"EGFRチロシンキナーゼ阻害剤獲得耐性の分子メカニズムに基づいた耐性克服研究"}]},"item_type_id":"8","owner":"3","path":["2686","2688"],"pubdate":{"attribute_name":"公開日","attribute_value":"2012-11-13"},"publish_date":"2012-11-13","publish_status":"0","recid":"3242","relation_version_is_last":true,"title":["EGFRチロシンキナーゼ阻害剤獲得耐性の分子メカニズムに基づいた耐性克服研究"],"weko_creator_id":"3","weko_shared_id":-1},"updated":"2023-06-21T01:42:07.471955+00:00"}