{"created":"2023-05-15T14:37:20.249562+00:00","id":48146,"links":{},"metadata":{"_buckets":{"deposit":"fd8b1b53-6d60-4e08-be08-a2511399879d"},"_deposit":{"created_by":1,"id":"48146","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"48146"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00048146","sets":["1"]},"author_link":["483493","483491","483488","483496","483489","483494","483495","483492","483490","483497"],"item_8_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2017-01","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"1","bibliographicPageEnd":"24","bibliographicPageStart":"16","bibliographicVolumeNumber":"16","bibliographic_titles":[{"bibliographic_title":"Molecular cancer therapeutics"}]}]},"item_8_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Hsp90 inhibitors have been investigated as cancer therapeutics in monotherapy and to augment radiotherapy; however, serious adverse effects of early-generation Hsp90 inhibitors limited their development. TAS-116 is a novel Hsp90 inhibitor with lower adverse effects than other Hsp90 inhibitors, and here, we investigated the radiosensitizing effects of TAS-116 in low linear energy transfer (LET) X-ray and high LET carbon ion-irradiated human cancer cells and mouse tumor xenografts. TAS-116 decreased cell survival of both X-ray and carbon ion-irradiated human cancer cell lines (HeLa and H1299 cells), and similar to other Hsp90 inhibitors, it did not affect radiosensitivity of noncancerous human fibroblasts. TAS-116 increased the number of radiation-induced γ-H2AX foci and delayed the repair of DNA double-strand breaks (DSB). TAS-116 reduced the expression of proteins that mediate repair of DSBs by homologous recombination (RAD51) and nonhomologous end joining (Ku, DNA-PKcs), and suppressed formation of RAD51 foci and phosphorylation/activation of DNA-PKcs. TAS-116 also decreased expression of the cdc25 cell-cycle progression marker, markedly increasing G2-M arrest. Combined treatment of mouse tumor xenografts with carbon ions and TAS-116 showed promising delay in tumor growth compared with either individual treatment. These results demonstrate that TAS-116 radiosensitizes human cancer cells to both X-rays and carbon ions by inhibiting the two major DSB repair pathways, and these effects were accompanied by marked cell-cycle arrest. The promising results of combination TAS-116 + carbon ion radiotherapy of tumor xenografts justify further exploration of TAS-116 as an adjunct to radiotherapy using low or high LET radiation. Mol Cancer Ther; 16(1); 16-24. ©2016 AACR.","subitem_description_type":"Abstract"}]},"item_8_relation_13":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"28062703","subitem_relation_type_select":"PMID"}}]},"item_8_relation_14":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1158/1535-7163.MCT-16-0573","subitem_relation_type_select":"DOI"}}]},"item_8_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"1535-7163","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":"Lee, Younghyun"}],"nameIdentifiers":[{"nameIdentifier":"483488","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Sunada, Shigeaki"}],"nameIdentifiers":[{"nameIdentifier":"483489","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Hirakawa, Hirokazu"}],"nameIdentifiers":[{"nameIdentifier":"483490","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Fujimori, Akira"}],"nameIdentifiers":[{"nameIdentifier":"483491","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"A, Nickoloff Jac"}],"nameIdentifiers":[{"nameIdentifier":"483492","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Okayasu, Ryuichi"}],"nameIdentifiers":[{"nameIdentifier":"483493","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"砂田 成章","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"483494","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"平川 博一","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"483495","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"藤森 亮","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"483496","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"岡安 隆一","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"483497","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":"TAS-116, a Novel Hsp90 Inhibitor, Selectively Enhances Radiosensitivity of Human Cancer Cells to X-rays and Carbon Ion Radiation.","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"TAS-116, a Novel Hsp90 Inhibitor, Selectively Enhances Radiosensitivity of Human Cancer Cells to X-rays and Carbon Ion Radiation."}]},"item_type_id":"8","owner":"1","path":["1"],"pubdate":{"attribute_name":"公開日","attribute_value":"2017-07-24"},"publish_date":"2017-07-24","publish_status":"0","recid":"48146","relation_version_is_last":true,"title":["TAS-116, a Novel Hsp90 Inhibitor, Selectively Enhances Radiosensitivity of Human Cancer Cells to X-rays and Carbon Ion Radiation."],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T23:31:25.274564+00:00"}