{"created":"2023-05-15T14:37:20.032293+00:00","id":48141,"links":{},"metadata":{"_buckets":{"deposit":"f75aa13f-365b-4fa6-b350-246bbac44bf9"},"_deposit":{"created_by":1,"id":"48141","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"48141"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00048141","sets":["1"]},"author_link":["483414","483416","483417","483424","483413","483411","483412","483419","483415","483408","483420","483422","483425","483409","483423","483418","483410","483421"],"item_8_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2016-09","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"9","bibliographicPageEnd":"1255","bibliographicPageStart":"1250","bibliographicVolumeNumber":"107","bibliographic_titles":[{"bibliographic_title":"Cancer science"}]}]},"item_8_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"High-linear energy transfer (LET) heavy ions have been increasingly employed as a useful alternative to conventional photon radiotherapy. As recent studies suggested that high LET radiation mainly affects the nonhomologous end-joining (NHEJ) pathway of DNA double strand break (DSB) repair, we further investigated this concept by evaluating the combined effect of an NHEJ inhibitor (NU7441) at a non-toxic concentration and carbon ions. NU7441-treated non-small cell lung cancer (NSCLC) A549 and H1299 cells were irradiated with X-rays and carbon ions (290 MeV/n, 50 keV/μm). Cell survival was measured by clonogenic assay. DNA DSB repair, cell cycle distribution, DNA fragmentation and cellular senescence induction were studied using a flow cytometer. Senescence-associated protein p21 was detected by western blotting. In the present study, 0.3 μM of NU7441, nontoxic to both normal and tumor cells, caused a significant radio-sensitization in tumor cells exposed to X-rays and carbon ions. This concentration did not seem to cause inhibition of DNA DSB repair but induced a significant G2/M arrest, which was particularly emphasized in p53-null H1299 cells treated with NU7441 and carbon ions. In addition, the combined treatment induced more DNA fragmentation and a higher degree of senescence in H1299 cells than in A549 cells, indicating that DNA-PK inhibitor contributes to various modes of cell death in a p53-dependent manner. In summary, NSCLC cells irradiated with carbon ions were radio-sensitized by a low concentration of DNA-PK inhibitor NU7441 through a strong G2/M cell cycle arrest. Our findings may contribute to further effective radiotherapy using heavy ions.","subitem_description_type":"Abstract"}]},"item_8_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Wiley Publishing on behalf of the Japanese Cancer Association"}]},"item_8_relation_13":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"27341700","subitem_relation_type_select":"PMID"}}]},"item_8_relation_14":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1111/cas.12998","subitem_relation_type_select":"DOI"}}]},"item_8_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"1347-9032","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":"Sunada, Shigeaki"}],"nameIdentifiers":[{"nameIdentifier":"483408","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kanai, Hideki"}],"nameIdentifiers":[{"nameIdentifier":"483409","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Lee, Younghyun"}],"nameIdentifiers":[{"nameIdentifier":"483410","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Yasuda, Takeshi"}],"nameIdentifiers":[{"nameIdentifier":"483411","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Hirakawa, Hirokazu"}],"nameIdentifiers":[{"nameIdentifier":"483412","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Liu, Cuihua"}],"nameIdentifiers":[{"nameIdentifier":"483413","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Fujimori, Akira"}],"nameIdentifiers":[{"nameIdentifier":"483414","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Uesaka, Mitsuru"}],"nameIdentifiers":[{"nameIdentifier":"483415","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Okayasu, Ryuichi"}],"nameIdentifiers":[{"nameIdentifier":"483416","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"砂田 成章","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"483417","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"金井 英樹","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"483418","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ｌｅｅ Ｙｏｕｎｇｈｙｕｎ","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"483419","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"安田 武嗣","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"483420","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"平川 博一","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"483421","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"劉 翠華","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"483422","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"藤森 亮","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"483423","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"上坂 充","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"483424","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"岡安 隆一","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"483425","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":"Nontoxic concentration of DNA-PK inhibitor NU7441 radio-sensitizes lung tumor cells with little effect on double strand break repair.","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Nontoxic concentration of DNA-PK inhibitor NU7441 radio-sensitizes lung tumor cells with little effect on double strand break repair."}]},"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":"48141","relation_version_is_last":true,"title":["Nontoxic concentration of DNA-PK inhibitor NU7441 radio-sensitizes lung tumor cells with little effect on double strand break repair."],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T23:31:28.869090+00:00"}