{"created":"2023-06-20T16:48:41.421335+00:00","id":20701,"links":{},"metadata":{"_buckets":{"deposit":"ffb22c00-2f05-491a-bdb5-9ed2f42ee563"},"_deposit":{"created_by":3,"id":"20701","owners":[3],"pid":{"revision_id":0,"type":"depid","value":"20701"},"status":"published"},"_oai":{"id":"oai:kindai.repo.nii.ac.jp:00020701","sets":["14:2667:4550"]},"author_link":["43072","43073"],"control_number":"20701","item_8_biblio_info_21":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2019","bibliographicIssueDateType":"Issued"},"bibliographicPageEnd":"4","bibliographicPageStart":"1","bibliographic_titles":[{"bibliographic_title":"科学研究費助成事業研究成果報告書 (2018)"}]}]},"item_8_description_25":{"attribute_name":"リンクURL","attribute_value_mlt":[{"subitem_description":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16K18461/","subitem_description_type":"Other"}]},"item_8_description_33":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"研究成果の概要（和文）：本課題ではEGFR-T790M陽性肺癌細胞株を用いて、ASP8273およびオシメルチニブとSrc阻害薬ダサチニブの併用効果についてin vitroおよびin vivoで検討した。ダサチニブはASP8273およびオシメルチニブとの併用において単剤と比較して相乗的な細胞増殖抑制効果を示しアポトースも有意に増加させた。またダサニチブとオシメルチニブの併用はin vivoにおいても単剤と比較して有意に腫瘍増殖を抑制した。ダサニチブはSrcの抑制を介してBcl-xLを低下させアポトーシスを誘導することで、T790M陽性肺癌細胞株において第三世代EGFR-TKIの抗腫瘍効果を増強させることが示唆された。研究成果の概要（英文）：We evaluated the efficacy of dasatinib combined with the T790M-selective EGFR-TKI ASP8273 or osimertinib in EGFR mutation-positive NSCLC with or T790M mutation. A cell viability assay revealed that dasatinib had synergistic effects with these TKIs in T790M-positive cells and simultaneously inhibited Src, Akt, and Erk, which remained activated upon single-agent treatment. Dasatinib also increased the rate of apoptosis in T790M-positive cells induced by T790M-selective EGFR-TKIs, as determined by the Annexin-V binding assay; this was associated with downregulation of the antiapoptotic Bcl-2 family member Bc1-xL, a finding that was confirmed in mice bearing T790M-positive xenografts. Our results suggest that Bcl-xLplays a key role in the apoptosis resistance of T790M-positive NSCLC, and that dasatinib combined with clinically relevant T790M-selective EGFR-TKIs is potentially effective in overcoming resistance to first-generation EGFR-TKIs in NSCLC patients with acquired T790M.","subitem_description_type":"Abstract"}]},"item_8_description_36":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"研究種目：若手研究(B);  研究期間：2016～2018;   課題番号：16K18461;   研究分野：腫瘍内科学;   科研費の分科・細目：","subitem_description_type":"Other"}]},"item_8_description_37":{"attribute_name":"資源タイプ(WEKO2)","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_text_10":{"attribute_name":"著者 役割","attribute_value_mlt":[{"subitem_text_value":"研究代表者"},{"subitem_text_value":"研究協力者"}]},"item_8_text_7":{"attribute_name":"著者(英)","attribute_value_mlt":[{"subitem_text_language":"en","subitem_text_value":"Yoshida, Takeshi"},{"subitem_text_language":"en","subitem_text_value":"Watanabe, Satomi"}]},"item_8_text_8":{"attribute_name":"著者 所属","attribute_value_mlt":[{"subitem_text_value":"近畿大学医学部; 講師"}]},"item_8_text_9":{"attribute_name":"著者所属(翻訳)","attribute_value_mlt":[{"subitem_text_value":"Kindai University"}]},"item_8_version_type_12":{"attribute_name":"版","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_be7fb7dd8ff6fe43","subitem_version_type":"NA"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"吉田, 健史"},{"creatorName":"ヨシダ, タケシ","creatorNameLang":"ja-Kana"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"渡邉, 論美"},{"creatorName":"ワタナベ, サトミ","creatorNameLang":"ja-Kana"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-03-12"}],"displaytype":"detail","filename":"16K18461seika.pdf","filesize":[{"value":"595.2 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"16K18461seika.pdf","url":"https://kindai.repo.nii.ac.jp/record/20701/files/16K18461seika.pdf"},"version_id":"9c203648-9efa-465f-8695-e95f2ff347ed"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"非小細胞肺癌","subitem_subject_scheme":"Other"},{"subitem_subject":"分子標的治療","subitem_subject_scheme":"Other"},{"subitem_subject":"薬剤耐性","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":"非小細胞肺癌におけるEGFR-TKI耐性克服戦略の最適化に関わる研究","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"非小細胞肺癌におけるEGFR-TKI耐性克服戦略の最適化に関わる研究","subitem_title_language":"ja"},{"subitem_title":"T790M-Selective EGFR-TKI Combined with Dasatinib as an Optimal Strategy for Overcoming EGFR-TKI Resistance in T790M-Positive Non-Small Cell Lung Cancer","subitem_title_language":"en"}]},"item_type_id":"8","owner":"3","path":["4550"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2020-03-12"},"publish_date":"2020-03-12","publish_status":"0","recid":"20701","relation_version_is_last":true,"title":["非小細胞肺癌におけるEGFR-TKI耐性克服戦略の最適化に関わる研究"],"weko_creator_id":"3","weko_shared_id":-1},"updated":"2023-09-21T02:27:29.842684+00:00"}