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dc.provenanceUniversidad Nacional de Rosario.RepHipUNR-
dc.creatorMalvicini, Mariana-
dc.creatorRizzo, Miguel-
dc.creatorAlaniz, Laura-
dc.creatorPiñero, Federico-
dc.creatorGarcía, Mariana-
dc.creatorAtorrasagasti, Catalina-
dc.creatorAquino, Jorge B.-
dc.creatorRozados, Viviana R.-
dc.creatorScharovsky, O. Graciela-
dc.creatorMatar, Pablo-
dc.creatorMazzolini, Guillermo-
dc.date2009-11-
dc.date2009-11-
dc.date.accessioned2019-07-15T18:40:50Z-
dc.date.available2019-07-15T18:40:50Z-
dc.date.issued2009-11-
dc.date.issued2009-11-
dc.identifierMalvicini, M., Rizzo, M., Alaniz, L., Pinero, F., Garcia, M., Atorrasagasti, C., Aquino, J. B., ... Mazzolini, G. (November 30, 2009). A Novel Synergistic Combination of Cyclophosphamide and Gene Transfer of Interleukin-12 Eradicates Colorectal Carcinoma in Mice. Clinical Cancer Research, 15, 23, 7256-7265-
dc.identifier1078-0432-
dc.identifierhttp://hdl.handle.net/2133/2009-
dc.identifierhttp://hdl.handle.net/2133/2009-
dc.identifier.urihttp://rodna.bn.gov.ar/jspui/handle/bnmm/567931-
dc.descriptionPURPOSE: Interleukin-12 (IL-12) is an immunostimulatory cytokine with potent antitumor effects in several animal models. However, serious toxicity has been associated with its systemic application in humans. Gene transfer has emerged as a tool to specifically express therapeutic genes into the tumor/peritumoral milieu, thus avoiding systemic toxicity. The aim of this study was to analyze whether subtherapeutic doses of an adenovirus encoding IL-12 (AdIL-12) might synergize with low immunopotentiating doses of cyclophosphamide in the treatment of colorectal carcinoma. EXPERIMENTAL DESIGN: The antitumor effect of combining a single low dose of cyclophosphamide with an intratumoral injection of AdIL-12 was evaluated in an in vivo murine colorectal carcinoma model. The immune responses achieved with different treatments were monitored, comparing the effect of combining both therapies with individual treatments. RESULTS: The combined therapy induced a complete tumor regression in >50% of mice in a synergistic fashion, and it significantly prolonged their survival. This strategy was superior to each single treatment in reducing both peripheral and splenic CD4+CD25+Foxp3+ regulatory T cells, increasing the number of activated dendritic cells, and inducing IFN-gamma-secreting CD4-positive T lymphocytes. Importantly, the combined treatment generated a powerful tumor-specific CTL response. Consistently, a significant reduction in IL-10 levels was found. Our data suggest that the combination of nontoxic doses of cyclophosphamide with AdIL-12 allows the generation of good antitumoral responses, thus avoiding undesired side effects of both agents. CONCLUSIONS: Our data strongly support the use of a combination of cyclophosphamide and AdIL-12 as a novel therapeutic strategy against colorectal carcinoma.-
dc.formatapplication/pdf-
dc.languageeng-
dc.publisherAmerican Association for Cancer Research-
dc.relationhttp://clincancerres.aacrjournals.org/content/15/23/7256.full-
dc.rightsinfo:eu-repo/semantics/openAccess-
dc.sourcereponame:RepHipUNR (UNR)-
dc.sourceinstname:Universidad Nacional de Rosario-
dc.sourceinstacron:UNR-
dc.source.urihttp://hdl.handle.net/2133/2009-
dc.subjectCombined immunotherapy-
dc.subjectCyclophosphamide gene therapy-
dc.subjectInterleukin-12-
dc.subjectColorectal carcinoma-
dc.titleA Novel Synergistic Combination of Cyclophosphamide and Gene Transfer of Interleukin-12 Eradicates Colorectal Carcinoma in Mice-
dc.typeinfo:eu-repo/semantics/article-
dc.typeinfo:eu-repo/semantics/publishedVersion-
dc.typeartículo-
dc.typeinfo:ar-repo/semantics/articulo-
Aparece en las colecciones: Universidad Nacional de Rosario. RepHipUNR

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