{"created":"2023-05-15T14:52:25.394841+00:00","id":71575,"links":{},"metadata":{"_buckets":{"deposit":"b94d4213-443b-48e4-ac28-02ee9e19e504"},"_deposit":{"created_by":1,"id":"71575","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"71575"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00071575","sets":["10:28"]},"author_link":["703928","703931","703934","703933","703929","703932","703927","703935","703926","703930"],"item_10005_date_7":{"attribute_name":"発表年月日","attribute_value_mlt":[{"subitem_date_issued_datetime":"2014-09-14","subitem_date_issued_type":"Issued"}]},"item_10005_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Purpose/Objective(s): In a previous study, we reported that some zinc (II) chelators suppress radiation-induced p53-dependent apoptosis through inhibition of p53-dependent apoptotic pathways. As a result of further screening, we found an 8-quinolinol derivative KH-3 as a radioprotector that has an ability to modulate p53 transcription resulting in the up-regulation of p21, and that can protect mice from a sublethal dose of 7.5 Gy total-body irradiation (TBI), but not of a higher dose of TBI (8.0 Gy). These data indicate that KH-3 is effective only in a narrow range of radiation dose that causes sublethal hematopoietic syndrome in mouse TBI. In this study, we further investigated the effects and mechanism of KH-3, including RNA interference-mediated silencing analysis of p21. In addition, p53 and p21 have been reported as resistant factors in radiation-induced gastrointestinal (GI) syndrome in mice. The fact raises the possibility that KH-3 protects mice from GI syndrome by up-regulating p21. We then tested the possibility using the technique of abdominal subtotal-body irradiation (SBI) to avoid the hematopoietic syndrome.\n\\n Materials /Methods: In cell analysis, highly radiosensitive cell line MOLT-4, derived from human T-cell leukemia, was used and 10 Gy-irradiated. The suppressive effect of KH-3 and the reference compound PFTm on radiation-induced MOLT-4 apoptosis was evaluated using Annexin V-FITC or MitoTracker Red staining, and WST-8 colorimetric assay. To examine the specificity of KH-3 for p21 in the p53-mediated apoptosis, we used MOLT-4 cells and its p21-knockdown transformant. In mouse SBI model, ICR female mice, aged 8-week old, were irradiated with a gamma-ray generator with shielding lead walls at least 3.0 cm thick. KH-3 (60 mg/kg) or vehicle was ip injected 30 minutes before 18 or 24 Gy SBI, and the mice were anesthetized 5-10 minutes before SBI. The abdomen of the anesthetized mice was exposed to gamma rays at a dose rate of 0.70 Gy/min.\n\\n Results: RNA interference-mediated silencing of p21 revealed that KH-3 was ineffective against the radiation-induced apoptosis of p21-knockdown transformant, indictating that suppression of radiation-induced apoptosis by KH-3 was specifically mediated through p53-p21 signaling pathways. For the 30-day survival study, survival rates of mice in KH-3-treated groups were 90% (18 Gy-SBI) and 40% (24-Gy SBI) respectively, whereas those of the control vehicle-injected groups were 40% (18 Gy-SBI) and 0% (24-Gy SBI) respectively. The dose-reduction factor (DRF) of KH-3 in the SBI was about 1.3.\n \n Conclusion: KH-3 is a novel kind of radioprotector that upregulates p53-p21 pathway and protects mice from GI death. KH-3 may serve as a therapeutic radioprotector for protecting normal tissues against adverse side effects of radiation/chemotherapy in abdominal cancer.","subitem_description_type":"Abstract"}]},"item_10005_description_6":{"attribute_name":"会議概要（会議名, 開催地, 会期, 主催者等）","attribute_value_mlt":[{"subitem_description":" ASTRO's 56th Annual Meeting（第56回米国放射線治療学会議）","subitem_description_type":"Other"}]},"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":"高橋, 一平"}],"nameIdentifiers":[{"nameIdentifier":"703926","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"森田, 明典"}],"nameIdentifiers":[{"nameIdentifier":"703927","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"青木, 伸"}],"nameIdentifiers":[{"nameIdentifier":"703928","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"王, 冰"}],"nameIdentifiers":[{"nameIdentifier":"703929","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"笹谷, めぐみ"}],"nameIdentifiers":[{"nameIdentifier":"703930","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"有安, 真也"}],"nameIdentifiers":[{"nameIdentifier":"703931","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"神谷, 研二"}],"nameIdentifiers":[{"nameIdentifier":"703932","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"細井, 義夫"}],"nameIdentifiers":[{"nameIdentifier":"703933","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"稲葉, 俊哉"}],"nameIdentifiers":[{"nameIdentifier":"703934","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"王 冰","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"703935","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":"conference object","resourceuri":"http://purl.org/coar/resource_type/c_c94f"}]},"item_title":"KH-3, a Transcriptional Modulator of p53, Protects Mice from Radiation-Induced Gastrointestinal Syndrome","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"KH-3, a Transcriptional Modulator of p53, Protects Mice from Radiation-Induced Gastrointestinal Syndrome"}]},"item_type_id":"10005","owner":"1","path":["28"],"pubdate":{"attribute_name":"公開日","attribute_value":"2015-01-13"},"publish_date":"2015-01-13","publish_status":"0","recid":"71575","relation_version_is_last":true,"title":["KH-3, a Transcriptional Modulator of p53, Protects Mice from Radiation-Induced Gastrointestinal Syndrome"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T19:49:44.166050+00:00"}