{"data":{"id":"10.6084/m9.figshare.1344830","type":"dois","attributes":{"doi":"10.6084/m9.figshare.1344830","prefix":"10.6084","suffix":"m9.figshare.1344830","identifiers":[],"alternateIdentifiers":[],"creators":[{"name":"Srivastava, Pragya","nameType":"Personal","givenName":"Pragya","familyName":"Srivastava","affiliation":[],"nameIdentifiers":[]},{"name":"Paluch, Benjamin E","nameType":"Personal","givenName":"Benjamin E","familyName":"Paluch","affiliation":[],"nameIdentifiers":[]},{"name":"Matsuzaki, Junko","nameType":"Personal","givenName":"Junko","familyName":"Matsuzaki","affiliation":[],"nameIdentifiers":[]},{"name":"Smitha R James","affiliation":[],"nameIdentifiers":[]},{"name":"Collamat-Lai, Golda","nameType":"Personal","givenName":"Golda","familyName":"Collamat-Lai","affiliation":[],"nameIdentifiers":[]},{"name":"Taverna, Pietro","nameType":"Personal","givenName":"Pietro","familyName":"Taverna","affiliation":[],"nameIdentifiers":[]},{"name":"Karpf, Adam R","nameType":"Personal","givenName":"Adam R","familyName":"Karpf","affiliation":[],"nameIdentifiers":[]},{"name":"Griffiths, Elizabeth A","nameType":"Personal","givenName":"Elizabeth A","familyName":"Griffiths","affiliation":[],"nameIdentifiers":[]}],"titles":[{"title":"Immunomodulatory action of the DNA methyltransferase inhibitor SGI-110 in epithelial ovarian cancer cells and xenografts"}],"publisher":"Taylor \u0026 Francis","container":{},"publicationYear":2015,"subjects":[{"subject":"Cancer"},{"subject":"Developmental Biology"},{"subject":"Immunology"},{"subject":"FOS: Clinical medicine","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Clinical medicine","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Chemistry"},{"subject":"Molecular Biology"},{"subject":"Genetics"},{"subject":"FOS: Biological sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Biological sciences","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Cell Biology"},{"subject":"Microbiology"},{"subject":"Engineering"},{"subject":"Biochemistry"}],"contributors":[],"dates":[{"date":"2015-03-20","dateType":"Created"},{"date":"2015-12-03","dateType":"Updated"},{"date":"2015","dateType":"Issued"}],"language":null,"types":{"ris":"DATA","bibtex":"misc","citeproc":"dataset","schemaOrg":"Dataset","resourceType":"Dataset","resourceTypeGeneral":"Dataset"},"relatedIdentifiers":[{"relationType":"IsSupplementTo","relatedIdentifier":"10.1080/15592294.2015.1017198","relatedIdentifierType":"DOI"}],"relatedItems":[],"sizes":["945224 Bytes"],"formats":[],"version":null,"rightsList":[{"rights":"Creative Commons Attribution 4.0 International","rightsUri":"https://creativecommons.org/licenses/by/4.0/legalcode","schemeUri":"https://spdx.org/licenses/","rightsIdentifier":"cc-by-4.0","rightsIdentifierScheme":"SPDX"}],"descriptions":[{"description":"We aimed to determine the effect of SGI-110 on methylation and expression of the cancer testis antigens (CTAs) NY-ESO-1 and MAGE-A in epithelial ovarian cancer (EOC) cells \u003ci\u003ein vitro\u003c/i\u003e and \u003ci\u003ein vivo\u003c/i\u003e and to establish the impact of SGI-110 on expression of major histocompatibility (MHC) class I and Intracellular Adhesion Molecule 1 (ICAM-1) on EOC cells, and on recognition of EOC cells by NY-ESO-1-specific CD8+ T-cells. We also tested the impact of combined SGI-110 and NY-ESO-1-specific CD8+ T-cells on tumor growth and/or murine survival in a xenograft setting. EOC cells were treated with SGI-110 \u003ci\u003ein vitro\u003c/i\u003e at various concentrations and as tumor xenografts with 3 distinct dose schedules. Effects on global methylation (using \u003ci\u003eLINE-1\u003c/i\u003e), \u003ci\u003eNY-ESO-1\u003c/i\u003e and \u003ci\u003eMAGE-A\u003c/i\u003e methylation, mRNA, and protein expression were determined and compared to controls. SGI-110 treated EOC cells were evaluated for expression of immune-modulatory genes using flow cytometry, and were co-cultured with NY-ESO-1 specific T-cell clones to determine immune recognition. \u003ci\u003eIn vivo\u003c/i\u003e administration of SGI-110 and CD8+ T-cells was performed to determine anti-tumor effects on EOC xenografts. SGI-110 treatment induced hypomethylation and CTA gene expression in a dose dependent manner both \u003ci\u003ein vitro\u003c/i\u003e and \u003ci\u003ein vivo\u003c/i\u003e, at levels generally superior to azacitidine or decitabine. SGI-110 enhanced the expression of MHC I and ICAM-1, and enhanced recognition of EOC cells by NY-ESO-1-specific CD8+ T-cells. Sequential SGI-110 and antigen-specific CD8+ cell treatment restricted EOC tumor growth and enhanced survival in a xenograft setting. SGI-110 is an effective hypomethylating agent and immune modulator and, thus, an attractive candidate for combination with CTA-directed vaccines in EOC.","descriptionType":"Abstract"}],"geoLocations":[],"fundingReferences":[],"xml":"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