{"created":"2024-01-17T00:40:38.474394+00:00","id":2000435,"links":{},"metadata":{"_buckets":{"deposit":"905512a9-c6c9-4d3c-9e18-e1f089aeb9c8"},"_deposit":{"created_by":11,"id":"2000435","owner":"11","owners":[11],"pid":{"revision_id":0,"type":"depid","value":"2000435"},"status":"published"},"_oai":{"id":"oai:miyazaki-u.repo.nii.ac.jp:02000435","sets":["76","76:64"]},"author_link":["34885","34883","21835","31376","28595","31377","30742","28014","34318","34882"],"control_number":"2000435","item_10001_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2018-09-13","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"1","bibliographicPageStart":"13741","bibliographicVolumeNumber":"8","bibliographic_titles":[{"bibliographic_title":"Scientific Reports","bibliographic_titleLang":"en"}]}]},"item_10001_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"G protein-coupled receptor 56 (GPR56) is highly expressed in acute myeloid leukemia (AML) cells with high EVI1 expression (EVI1high AML). Because GPR56 is a transcriptional target of EVI1 and silencing of GPR56 expression induces apoptosis, we developed a novel drug to suppress GPR56 expression in EVI1high AML cells. For this purpose, we generated pyrrole-imidazole (PI) polyamides specific to GPR56 (PIP/56-1 or PIP/56-2) as nuclease-resistant novel compounds that interfere with the binding of EVI1 to the GPR56 promoter in a sequence-specific manner. Treatment of EVI1high AML cell lines (UCSD/AML1 and Kasumi-3) with PIP/56-1 or PIP/56-2 effectively suppressed GPR56 expression by inhibiting binding of EVI1 to its promoter, leading to suppression of cell growth with increased rates of apoptosis. Moreover, intravenous administration of PIP/56-1 into immunodeficient Balb/c-RJ mice subcutaneously transplanted with UCSD/AML1 cells significantly inhibited tumor growth and extended survival. Furthermore, organ infiltration by leukemia cells in immunodeficient Balb/c-RJ mice, which were intravenously transplanted using UCSD/AML1 cells, was successfully inhibited by PIP/56-1 treatment with no apparent effects on murine hematopoietic cells. In addition, PIP treatment did not inhibit colony formation of human CD34+ progenitor cells. Thus, PI polyamide targeting of GPR56 using our compound is promising, useful, and safe for the treatment of EVI1high AML.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_10001_description_6":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"citeation:\nSaha HR, Kaneda-Nakashima K, Shimosaki S, Suekane A, Sarkar B, Saito Y, Ogoh H, Nakahata S, Inoue K, Watanabe T, Nagase H, Morishita K. Suppression of GPR56 expression by pyrrole-imidazole polyamide represents a novel therapeutic drug for AML with high EVI1 expression. Sci Rep. 2018 Sep 13;8(1):13741. doi: 10.1038/s41598-018-32205-8. PMID: 30214063; PMCID: PMC6137133.","subitem_description_language":"en","subitem_description_type":"Other"}]},"item_10001_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Springer Nature","subitem_publisher_language":"en"}]},"item_10001_relation_14":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type":"isVersionOf","subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1038/s41598-018-32205-8","subitem_relation_type_select":"DOI"}}]},"item_10001_rights_15":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"© The Author(s) 2018","subitem_rights_language":"en"}]},"item_10001_version_type_20":{"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":[{"creatorAffiliations":[{"affiliationNameIdentifiers":[{"affiliationNameIdentifier":"","affiliationNameIdentifierScheme":"ISNI","affiliationNameIdentifierURI":"http://www.isni.org/isni/"}],"affiliationNames":[{"affiliationName":"","affiliationNameLang":"ja"}]}],"creatorNames":[{"creatorName":"Saha, Hasi Rani ","creatorNameLang":"en"},{"creatorName":"サハ, ハシ ラニ","creatorNameLang":"ja"},{"creatorName":"サハ, ハシ ラニ","creatorNameLang":"ja-Kana"}],"familyNames":[{"familyName":"Saha","familyNameLang":"en"},{"familyName":"サハ","familyNameLang":"ja"},{"familyName":"サハ","familyNameLang":"ja-Kana"}],"givenNames":[{"givenName":"Hasi Rani ","givenNameLang":"en"},{"givenName":"ハシ 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カズヒロ","creatorNameLang":"ja-Kana"}],"familyNames":[{"familyName":"Morishita","familyNameLang":"en"},{"familyName":"森下","familyNameLang":"ja"},{"familyName":"モリシタ","familyNameLang":"ja-Kana"}],"givenNames":[{"givenName":"Kazuhiro","givenNameLang":"en"},{"givenName":"和広","givenNameLang":"ja"},{"givenName":"カズヒロ","givenNameLang":"ja-Kana"}],"nameIdentifiers":[{"nameIdentifier":"21835","nameIdentifierScheme":"WEKO"},{"nameIdentifier":"80260321","nameIdentifierScheme":"e-Rad","nameIdentifierURI":"https://kaken.nii.ac.jp/ja/search/?qm=80260321"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2024-01-17"}],"filename":"article.pdf","filesize":[{"value":"3.9 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EVI1","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":"Suppression of GPR56 expression by pyrrole-imidazole polyamide represents a novel therapeutic drug for AML with high EVI1 expression","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Suppression of GPR56 expression by pyrrole-imidazole polyamide represents a novel therapeutic drug for AML with high EVI1 expression","subitem_title_language":"en"}]},"item_type_id":"10001","owner":"11","path":["76","64"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2024-01-16"},"publish_date":"2024-01-16","publish_status":"0","recid":"2000435","relation_version_is_last":true,"title":["Suppression of GPR56 expression by pyrrole-imidazole polyamide represents a novel therapeutic drug for AML with high EVI1 expression"],"weko_creator_id":"11","weko_shared_id":-1},"updated":"2025-01-16T04:41:31.251927+00:00"}