{"created":"2023-05-15T14:38:11.668615+00:00","id":49284,"links":{},"metadata":{"_buckets":{"deposit":"c0243c41-0e4e-46c7-9722-c7d2c8ec0e9c"},"_deposit":{"created_by":1,"id":"49284","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"49284"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00049284","sets":["1"]},"author_link":["497344","497335","497334","497332","497337","497338","497341","497333","497339","497342","497343","497340","497336","497346","497345"],"item_8_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2017-11","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"42","bibliographicPageEnd":"7562","bibliographicPageStart":"7551","bibliographicVolumeNumber":"23","bibliographic_titles":[{"bibliographic_title":"World Journal of Gastroenterology"}]}]},"item_8_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"AIM\nTo investigate the therapeutic effect of combined\nintegrin α6β4-targeted radioimmunotherapy (RIT) and\nPI3K/mTOR inhibitor BEZ235 in a pancreatic cancer\nmodel.\nMETHODS\nPhosphorylation of Akt, mTOR, the downstream\neffectors eukaryotic initiation factor 4E binding\nprotein 1 (4EBP1) and S6 ribosomal protein (S6) were\nevaluated in BxPC-3 human pancreatic cancer cells\ntreated with Yttrium-90 (90Y) labeled anti-integrin α6β4\nantibody (ITGA6B4) and BEZ235 by western blotting.\nThe cytotoxic effect of BEZ235 was investigated\nusing a colony formation assay. Therapeutic efficacy\nenhancement by oral BEZ235 administration was\nassessed using mice bearing BxPC-3 xenograft tumors.\nTumor volume measurements and immunohistochemical\nanalyses (cell proliferation marker Ki-67, DNA damage\nmarker p-H2AX and p-4EBP1 staining) of tumors were\nperformed for evaluation of combined treatment with\n90Y-ITGA6B4 plus BEZ235, or each arm alone.\nRESULTS\nWe found that phosphorylation of Akt (p-Akt), 4EBP1\n(p-4EBP1) and S6 (p-S6) was inhibited by BEZ235.\nColony formation in BxPC-3 cells was additively\nsuppressed by the combination of 90Y-ITGA6B4 and\nBEZ235. Pretreatment with BEZ235 before 90Y-ITGA6B4\nexposure resulted in significant reduction of cells plating\nefficiency (PE) (0.54 ± 0.11 vs 2.81 ± 0.14 with 185\nkBq/mL 90Y-ITGA6B4 exposure, P < 0.01; 0.39 ± 0.08\nvs 1.88 ± 0.09 with 370 kBq/mL 90Y-ITGA6B4 exposure,\nP < 0.01) when 5 × 103 cells per dish were plated. In\nvivo , the combined treatment with 90Y-ITGA6B4 plus\nBEZ235 enhanced the inhibition of tumor growth and\nstatistically significant differences of relative tumor\nvolume were observed for 27 d after the treatment\nstart date when compared with the 90Y-ITGA6B4 single\ninjection treatment (1.03 ± 0.38 vs 1.5 ± 0.15 at Day\n27, P < 0.05), and for 41 d when compared with the\nBEZ235 treatment alone (1.8 ± 0.7 vs 3.14 ± 1.19\nat Day 41, P < 0.05). Tumors from treatment groups\nshowed reduction in volumes, decreased Ki-67-positive\ncells, increased p-H2AX-positive cells and decreased\np-4EBP1 expression.\nCONCLUSION\nThe therapeutic efficacy of 90Y-ITGA6B4-RIT can be\nimproved by combining with dual PI3K and mTOR\ninhibitor, BEZ235, in a pancreatic cancer model\nsuggesting potential clinical application.\nKey words: Radioimmunotherapy; Pancreatic cancer;\nanti-integrin α6β4 antibody; Yttrium-90; NVP-BEZ235","subitem_description_type":"Abstract"}]},"item_8_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Baishideng Publishing Group Inc"}]},"item_8_relation_13":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"29204055","subitem_relation_type_select":"PMID"}}]},"item_8_relation_14":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"10.3748/wjg.v23.i42.7551","subitem_relation_type_select":"DOI"}}]},"item_8_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"1007-9327","subitem_source_identifier_type":"ISSN"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"metadata only access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_14cb"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Winn, Aung"}],"nameIdentifiers":[{"nameIdentifier":"497332","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Tsuji, Atsushi"}],"nameIdentifiers":[{"nameIdentifier":"497333","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Sudo, Hitomi"}],"nameIdentifiers":[{"nameIdentifier":"497334","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Sugyo, Aya"}],"nameIdentifiers":[{"nameIdentifier":"497335","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ukai, Yoshinori"}],"nameIdentifiers":[{"nameIdentifier":"497336","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kouda, Katsushi"}],"nameIdentifiers":[{"nameIdentifier":"497337","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kurosawa, Yoshikazu"}],"nameIdentifiers":[{"nameIdentifier":"497338","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Furukawa, Takako"}],"nameIdentifiers":[{"nameIdentifier":"497339","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Saga, Tsuneo"}],"nameIdentifiers":[{"nameIdentifier":"497340","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Higashi, Tatsuya"}],"nameIdentifiers":[{"nameIdentifier":"497341","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ｕ Ｗｉｎｎ Ａｕｎｇ","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"497342","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"辻 厚至","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"497343","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"須藤 仁美","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"497344","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"須尭 綾","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"497345","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"東 達也","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"497346","nameIdentifierScheme":"WEKO"}]}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"Combined treatment of pancreatic cancer xenograft with 90Y-ITGA6B4-mediated radioimmunotherapy and PI3K/ mTOR inhibitor","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Combined treatment of pancreatic cancer xenograft with 90Y-ITGA6B4-mediated radioimmunotherapy and PI3K/ mTOR inhibitor"}]},"item_type_id":"8","owner":"1","path":["1"],"pubdate":{"attribute_name":"公開日","attribute_value":"2018-11-27"},"publish_date":"2018-11-27","publish_status":"0","recid":"49284","relation_version_is_last":true,"title":["Combined treatment of pancreatic cancer xenograft with 90Y-ITGA6B4-mediated radioimmunotherapy and PI3K/ mTOR inhibitor"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T23:20:18.198336+00:00"}