{"created":"2023-05-15T12:03:50.925558+00:00","links":{},"metadata":{"_buckets":{"deposit":"03a40b1a-d241-4f9a-9a55-e2413d6ebf1b"},"_deposit":{"id":"5840.1","owners":[2],"pid":{"revision_id":0,"type":"depid","value":"5840.1"},"status":"published"},"_oai":{"id":"oai:miyazaki-u.repo.nii.ac.jp:00005840.1","sets":["76:63"]},"author_link":["31377"],"item_10006_date_granted_11":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2019-03-22"}]},"item_10006_degree_grantor_9":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_name":"宮崎大学"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"17601","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_10006_degree_name_8":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士(医学)"}]},"item_10006_description_7":{"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 effectivelysuppressed 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. 1 Thus, PI polyamide targeting of GPR56 using our compound is promising, useful, and safe for the treatment of EVI1high AML.","subitem_description_type":"Abstract"}]},"item_10006_dissertation_number_12":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第84号"}]},"item_10006_publisher_5":{"attribute_name":"公開者","attribute_value_mlt":[{"subitem_publisher":"Elsevier"}]},"item_10006_textarea_22":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_textarea_value":"以下に掲載: Scientific Reports .2018,Volume 8.Article number: 13741 (2018)"}]},"item_10006_version_type_18":{"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_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Hasi, Rani Saha","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"31377","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-06-21"}],"displaytype":"detail","filename":"youshi.pdf","filesize":[{"value":"1.1 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"url":"https://miyazaki-u.repo.nii.ac.jp/record/5840.1/files/youshi.pdf"},"version_id":"f81ac5ac-3879-4334-9197-12858ea2fd83"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-06-21"}],"displaytype":"detail","filename":"shinsakekka.pdf","filesize":[{"value":"452.2 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"url":"https://miyazaki-u.repo.nii.ac.jp/record/5840.1/files/shinsakekka.pdf"},"version_id":"0088b9af-97f3-4c3b-8182-b4f2ca40a6fb"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-06-21"}],"displaytype":"detail","filename":"honbun.pdf","filesize":[{"value":"1.4 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"url":"https://miyazaki-u.repo.nii.ac.jp/record/5840.1/files/honbun.pdf"},"version_id":"5842cd43-88c9-4008-90f5-088139d5ddfc"}]},"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":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"Suppression of GPR56 expression by pyrrole-imidazole polyamide represents a novel therapeutic drug for AML with high EVI1 expressio","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 expressio"},{"subitem_title":"GPR56の転写を阻害するピロール-イミダゾールポリアミドはEVIl高発現AMLの新規治療薬となる","subitem_title_language":"en"}]},"item_type_id":"10006","owner":"2","path":["63"],"pubdate":{"attribute_name":"公開日","attribute_value":"2020-06-21"},"publish_date":"2020-06-21","publish_status":"0","recid":"5840.1","relation_version_is_last":true,"title":["Suppression of GPR56 expression by pyrrole-imidazole polyamide represents a novel therapeutic drug for AML with high EVI1 expressio"],"weko_creator_id":"2","weko_shared_id":2},"updated":"2023-10-30T04:03:03.361137+00:00"}