{"created":"2023-07-27T06:55:24.402837+00:00","id":51240,"links":{},"metadata":{"_buckets":{"deposit":"4cf3c0ce-905c-47e8-bb46-8adb6730fa3a"},"_deposit":{"created_by":18,"id":"51240","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"51240"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00051240","sets":["2812:2813:4014"]},"author_link":["88083","88084"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2021-05-31","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"5p.","bibliographicVolumeNumber":"2019-04-01 - 2021-03-31","bibliographic_titles":[{"bibliographic_title":"令和2(2020)年度 科学研究費補助金 若手研究 研究成果報告書"},{"bibliographic_title":"2020 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":"髄膜癌腫症（LMC）における第2世代ALK-TKIであるアレクチニブの耐性機構解明および新たな治療戦略の発見を目的とし、マウスLMCモデルにおいてアレクチニブ耐性を誘導し、耐性株であるAR細胞を樹立した。AR細胞は、リガンドであるAREGの発現上昇によりEGFRが活性化して耐性を獲得しており、AR細胞を用いたマウスLMCモデルでは、アレクチニブとEGFR-TKIを併用することで腫瘍の進展抑制が見られた。さらに、アレクチニブ耐性LMCを有するALK肺癌患者の髄液では、EGFR-TKI耐性LMCを有するEGFR変異非小細胞肺癌患者やLMCを伴わない患者と比較して高いレベルでAREGが検出された。","subitem_description_type":"Abstract"},{"subitem_description":"This study aimed to clarify the mechanism of resistance to alectinib, a second-generation ALK-TKI, in Leptomeningeal carcinomatosis (LMC) and seek a novel therapeutic strategy. First, we induced alectinib resistance in an LMC mouse model using the ALK-rearranged NSCLC cell line A925L by continuous oral alectinib treatment, established AR cells from this model. AR cells acquired resistance through EGFR activation due to overexpression of its ligand, amphiregulin (AREG). In the LMC model with AR cells, combined treatment with alectinib and an EGFR-TKI successfully controlled LMC progression. Moreover, notably high AREG levels were detected in the cerebrospinal fluid from ALK-rearranged NSCLC patients with alectinib-resistant LMC compared with those in EGFR-mutated NSCLC patients with EGFR-TKI-resistant LMC or patients without LMC.\nThese findings indicate the potential of novel therapies dual-targeting ALK and EGFR against ALK-TKI-resistant LMC in ALK-rearranged NSCLC patients.","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:19K16738, 研究期間(年度):2019-04-01 - 2021-03-31","subitem_description_type":"Other"},{"subitem_description":"出典：「ALK肺癌の髄膜癌腫症におけるALK-TKI耐性克服治療の開発」研究成果報告書　課題番号19K16738\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-19K16738/19K16738seika/）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":"10.24517/00057543","subitem_identifier_reg_type":"JaLC"}]},"item_9_publisher_17":{"attribute_name":"公開者","attribute_value_mlt":[{"subitem_publisher":"金沢大学がん進展制御研究所"}]},"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=80824870"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=80824870","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19K16738/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19K16738/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-19K16738/19K16738seika/https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-19K16738/19K16738seika/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-19K16738/19K16738seika/","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":"2022-02-10"}],"displaytype":"detail","filename":"CA-PR-ARAI-S-kaken 2021-5p.pdf","filesize":[{"value":"294.4 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"CA-PR-ARAI-S-kaken 2021-5p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/51240/files/CA-PR-ARAI-S-kaken 2021-5p.pdf"},"version_id":"0bee5c4f-8df1-4df6-9f8e-a4a3b73d9f3c"}]},"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":"ALK肺癌の髄膜癌腫症におけるALK-TKI耐性克服治療の開発","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"ALK肺癌の髄膜癌腫症におけるALK-TKI耐性克服治療の開発"},{"subitem_title":"Identification of resistance mechanism to ALK-TKIs in leptomeningeal carcinomatosis (LMC) model with EML4-ALK NSCLC cells","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["4014"],"pubdate":{"attribute_name":"公開日","attribute_value":"2022-02-10"},"publish_date":"2022-02-10","publish_status":"0","recid":"51240","relation_version_is_last":true,"title":["ALK肺癌の髄膜癌腫症におけるALK-TKI耐性克服治療の開発"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T13:51:44.266771+00:00"}