{"created":"2023-06-19T10:43:57.949128+00:00","id":4320,"links":{},"metadata":{"_buckets":{"deposit":"230f0823-c5e3-4388-af3b-07fd204fd571"},"_deposit":{"created_by":11,"id":"4320","owners":[11],"pid":{"revision_id":0,"type":"depid","value":"4320"},"status":"published"},"_oai":{"id":"oai:shiga-med.repo.nii.ac.jp:00004320","sets":["30:68:267"]},"author_link":["679","9117","2869","2862"],"item_4_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2022-08-23","bibliographicIssueDateType":"Issued"},"bibliographicPageEnd":"9","bibliographicPageStart":"1","bibliographic_titles":[{},{"bibliographic_title":"Toxicology mechanisms and methods","bibliographic_titleLang":"en"}]}]},"item_4_creator_3":{"attribute_name":"著者別名","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"田川, 晃司"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"丸尾, 良浩"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"三村, 由卯"}],"nameIdentifiers":[{}]}]},"item_4_description_14":{"attribute_name":"フォーマット","attribute_value_mlt":[{"subitem_description":"pdf","subitem_description_type":"Other"}]},"item_4_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"The adverse effects (diarrhea and neutropenia) of irinotecan (7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin) are associated with genetic variants of uridine diphosphate glucuronosyltransferase 1A subfamilies (UGT1As). UGT1As are enzymes that metabolize the active form of irinotecan, 7-ethyl-10 hydroxycamptothecin (SN-38), by glucuronidation in the liver. They are widely known as predictive factors of severe adverse effects, such as neutropenia and diarrhea. Some studies have suggested that variants of UGT1As affect SN-38 glucuronidation activities, thus exerting severe adverse effects. We aimed to identify UGT1A isoforms that show SN-38 glucuronidation activity and determine the relationship between UGT1A variants and SN-38 glucuronidation in vitro. We found that UGT1A1 and UGT1A6-UGT1A10 displayed SN-38 glucuronidation activity. Among these, UGT1A1 was the most active. Furthermore, the variants of these isoforms showed decreased SN-38 glucuronidation activity. In our study, we compared the different variants of UGT1As, such as UGT1A1.6, UGT1A1.7, UGT1A1.27, UGT1A1.35, UGT1A7.3, UGT1A8.4, UGT1A10M59I, and UGT1A10T202I, to determine the differences in the reduction of glucuronidation. Our study elucidates the relationship between UGT1A variants and the level of glucuronidation associated with each variant. Therefore, testing can be done before the initiation of irinotecan treatment to predict potential toxicities and adverse effects. ","subitem_description_type":"Abstract"}]},"item_4_description_42":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"subitem_description":"Journal Article","subitem_description_type":"Other"}]},"item_4_publisher_32":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Taylor and Francis Ltd."}]},"item_4_relation_10":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"35930428","subitem_relation_type_select":"PMID"}}]},"item_4_relation_11":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"10.1080/15376516.2022.2109229"}],"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1080/15376516.2022.2109229","subitem_relation_type_select":"DOI"}}]},"item_4_rights_12":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"©2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group."}]},"item_4_source_id_7":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"1537-6524","subitem_source_identifier_type":"ISSN"}]},"item_4_version_type_15":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"TAGAWA, Kouji"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"MARUO, Yoshihiro"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"MIMURA, Yu"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"IKUSHIRO, Shinichi"}],"nameIdentifiers":[{},{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2022-09-05"}],"displaytype":"detail","filename":"15376516.2022.2109229.pdf","filesize":[{"value":"1.8 MB"}],"format":"application/pdf","license_note":"This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License \n(http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium,\nprovided the original work is properly cited, and is not altered, \ntransformed, or built upon in any way.","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"15376516.2022.2109229","url":"https://shiga-med.repo.nii.ac.jp/record/4320/files/15376516.2022.2109229.pdf"},"version_id":"de9f6649-5b0d-4030-837b-986309658508"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"Irinotecan","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"drug toxicity","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"UDP-glucuronosyltransferase 1","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"glucuronidation activities","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"variant","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"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":"Effects of common genetic variants of human uridine diphosphate glucuronosyltransferase subfamilies on irinotecan glucuronidation.","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Effects of common genetic variants of human uridine diphosphate glucuronosyltransferase subfamilies on irinotecan glucuronidation."}]},"item_type_id":"4","owner":"11","path":["267"],"pubdate":{"attribute_name":"公開日","attribute_value":"2022-09-05"},"publish_date":"2022-09-05","publish_status":"0","recid":"4320","relation_version_is_last":true,"title":["Effects of common genetic variants of human uridine diphosphate glucuronosyltransferase subfamilies on irinotecan glucuronidation."],"weko_creator_id":"11","weko_shared_id":-1},"updated":"2023-06-19T11:11:35.111323+00:00"}