{"created":"2023-05-15T15:01:08.657539+00:00","id":82949,"links":{},"metadata":{"_buckets":{"deposit":"b44b03f7-d940-4f9b-83ae-1548d1ab7a74"},"_deposit":{"created_by":1,"id":"82949","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"82949"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00082949","sets":["1"]},"author_link":["1025190","1025195","1025191","1025192","1025196","1025194","1025198","1025193","1025197"],"item_8_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2021-06","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"1","bibliographicPageEnd":"271","bibliographicPageStart":"260","bibliographicVolumeNumber":"111","bibliographic_titles":[{"bibliographic_title":"International journal of radiation oncology, biology, physics"}]}]},"item_8_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Purpose: Autophagy and cell-cycle checkpoints act in concert to confer cellular radioresistance. We investigated the functional\ninteraction between radiation-induced autophagy and G2 checkpoint activation in highly radioresistant human pancreatic\nductal adenocarcinoma (PDAC) cells.\nMethods and Materials: Four human PDAC cell lines (MIA PaCa-2, KP-4, Panc-1, and SUIT-2) were analyzed. These cells\nwere first irradiated using x-rays, and their cell cycle status, autophagy, and cell cycle checkpoint marker expression and ATP\nproduction levels were evaluated. Autophagic flux assays and siRNA knockdown were used to evaluate autophagy activity.\nDouble thymidine block experiments were performed to synchronize the cells. Two inhibitors (MK-1775 and SCH 900776)\nwere used to attenuate G2 checkpoint activation. Cell survival assays and animal experiments were performed to evaluate the\nradiosensitizing effects of the G2 checkpoint inhibitors.\nResults: Autophagy and G2/M accumulation were synchronously induced in human PDAC cells with an activated G2 checkpoint\nat 12 hours after x-ray irradiation of 6 Gy. Radiation-induced autophagy produced the ATP levels required for cell survival.\nDouble thymidine block experiments revealed that no autophagy occurred in cells that were solely in G2 phase. MK-\n1775 or SCH 900776 exposure attenuated not only G2 checkpoint activation but also postirradiation autophagy, indicating\nthe dependence of radiation-induced autophagy on an activated G2 checkpoint. The inhibitors demonstrated a higher radiosensitizing\neffect in the PDAC cells than the autophagy inhibitor chloroquine. MK-1775 in combination with x-rays significantly suppressed the tumor growth of MIA PaCa-2 xenografts compared with other treatment groups, including radiation\nor drug exposure alone, to enhance the radiosensitivity of PDAC cells in vivo.\nConclusions: Biological crosstalk exists between the G2 checkpoint activation and radiation-induced autophagy processes\nthat are believed to independently contribute to the radioresistance of human PDAC cells. These findings have important\nimplications for the development of future radiation therapy strategies for PDAC.","subitem_description_type":"Abstract"}]},"item_8_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Elsevier"}]},"item_8_relation_14":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1016/j.ijrobp.2021.04.001","subitem_relation_type_select":"DOI"}}]},"item_8_relation_17":{"attribute_name":"関連サイト","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://www.sciencedirect.com/science/article/pii/S0360301621003618?via%3Dihub","subitem_relation_type_select":"URI"}}]},"item_8_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0360-3016","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":"Motofumi, Suzuki"}],"nameIdentifiers":[{"nameIdentifier":"1025190","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Mayuka, Anko"}],"nameIdentifiers":[{"nameIdentifier":"1025191","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Maki, Ohara"}],"nameIdentifiers":[{"nameIdentifier":"1025192","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kenichiro, Matsumoto"}],"nameIdentifiers":[{"nameIdentifier":"1025193","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Sumitaka, Hasegawa"}],"nameIdentifiers":[{"nameIdentifier":"1025194","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Mayuka, Anko","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1025195","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Maki, Ohara","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1025196","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kenichiro, Matsumoto","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1025197","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Sumitaka, Hasegawa","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1025198","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":"Radiation-Induced Autophagy in Human Pancreatic Cancer Cells is Critically Dependent on G2 Checkpoint Activation: A Mechanism of Radioresistance in Pancreatic Cancer","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Radiation-Induced Autophagy in Human Pancreatic Cancer Cells is Critically Dependent on G2 Checkpoint Activation: A Mechanism of Radioresistance in Pancreatic Cancer"}]},"item_type_id":"8","owner":"1","path":["1"],"pubdate":{"attribute_name":"公開日","attribute_value":"2021-06-08"},"publish_date":"2021-06-08","publish_status":"0","recid":"82949","relation_version_is_last":true,"title":["Radiation-Induced Autophagy in Human Pancreatic Cancer Cells is Critically Dependent on G2 Checkpoint Activation: A Mechanism of Radioresistance in Pancreatic Cancer"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T18:03:36.227870+00:00"}