{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1050580328307515648.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"HDL","@value":"http://hdl.handle.net/10458/0002000435"}},{"identifier":{"@type":"URI","@value":"https://miyazaki-u.repo.nii.ac.jp/records/2000435"}},{"identifier":{"@type":"DOI","@value":"10.1038/s41598-018-32205-8"}},{"identifier":{"@type":"URI","@value":"https://www.nature.com/articles/s41598-018-32205-8.pdf"}},{"identifier":{"@type":"URI","@value":"https://www.nature.com/articles/s41598-018-32205-8"}},{"identifier":{"@type":"PMID","@value":"30214063"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@language":"en","@value":"Suppression of GPR56 expression by pyrrole-imidazole polyamide represents a novel therapeutic drug for AML with high EVI1 expression"}],"dc:language":"en","description":[{"type":"Abstract","notation":[{"@language":"en","@value":"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."}]},{"type":"Other","notation":[{"@language":"en","@value":"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."}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1070580405834736640","@type":"Researcher","foaf:name":[{"@language":"en","@value":"Saha, Hasi Rani"},{"@language":"ja","@value":"サハ, ハシ ラニ"},{"@language":"ja-Kana","@value":"サハ, ハシ ラニ"}]},{"@id":"https://cir.nii.ac.jp/crid/1420282801204134272","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"00533209"},{"@type":"NRID","@value":"1000000533209"},{"@type":"NRID","@value":"9000414250678"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/read0131912"}],"foaf:name":[{"@language":"en","@value":"Kaneda-Nakashima, Kazuko"}]},{"@id":"https://cir.nii.ac.jp/crid/1070580328307515657","@type":"Researcher","foaf:name":[{"@language":"ja","@value":"下崎, 俊介"},{"@language":"ja-Kana","@value":"シモサキ, シュンスケ"},{"@language":"en","@value":"Shimosaki, Shunsuke"}]},{"@id":"https://cir.nii.ac.jp/crid/1070580405834736646","@type":"Researcher","foaf:name":[{"@language":"en","@value":"Suekane, 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Kazuhiro"},{"@language":"ja","@value":"森下, 和広"},{"@language":"ja-Kana","@value":"モリシタ, カズヒロ"}]}],"publication":{"publicationIdentifier":[{"@type":"EISSN","@value":"20452322"}],"prism:publicationName":[{"@language":"en","@value":"Scientific Reports"}],"dc:publisher":[{"@value":"Springer Nature"}],"prism:publicationDate":"2018-09-13","prism:volume":"8","prism:number":"1","prism:startingPage":"13741"},"reviewed":"false","dcterms:accessRights":"http://purl.org/coar/access_right/c_abf2","dc:rights":["© The Author(s) 2018"],"url":[{"@id":"https://miyazaki-u.repo.nii.ac.jp/records/2000435"},{"@id":"https://www.nature.com/articles/s41598-018-32205-8.pdf"},{"@id":"https://www.nature.com/articles/s41598-018-32205-8"}],"foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=GPR56%20Expression","dc:title":"GPR56 Expression"},{"@id":"https://cir.nii.ac.jp/all?q=Ecotropic%20Viral%20Integration%20Site%20(EVI1)","dc:title":"Ecotropic Viral Integration Site (EVI1)"},{"@id":"https://cir.nii.ac.jp/all?q=Pyrrole-imidazole%20Polyamides%20(PIP)","dc:title":"Pyrrole-imidazole Polyamides (PIP)"},{"@id":"https://cir.nii.ac.jp/all?q=G%20Protein-coupled%20Receptors%20(GPR56)","dc:title":"G Protein-coupled Receptors (GPR56)"},{"@id":"https://cir.nii.ac.jp/all?q=High%20EVI1","dc:title":"High EVI1"}],"dcterms:subject":[{"subjectScheme":"Other","notation":[{"@language":"en","@value":"GPR56 Expression"}]},{"subjectScheme":"Other","notation":[{"@language":"en","@value":"Ecotropic Viral Integration Site (EVI1)"}]},{"subjectScheme":"Other","notation":[{"@language":"en","@value":"Pyrrole-imidazole Polyamides (PIP)"}]},{"subjectScheme":"Other","notation":[{"@language":"en","@value":"G Protein-coupled Receptors (GPR56)"}]},{"subjectScheme":"Other","notation":[{"@language":"en","@value":"High 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