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FCM - Instituto de Genética Experimental

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https://rephip.unr.edu.ar/handle/2133/1908

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Examinando FCM - Instituto de Genética Experimental por Autor "Atorrasagasti, Catalina"

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  • Miniatura
    ÍtemAcceso Abierto
    A Novel Synergistic Combination of Cyclophosphamide and Gene Transfer of Interleukin-12 Eradicates Colorectal Carcinoma in Mice
    (American Association for Cancer Research, 2009-11) Malvicini, Mariana; Rizzo, Miguel; Alaniz, Laura; Piñero, Federico; García, Mariana; Atorrasagasti, Catalina; Aquino, Jorge B.; Rozados, Viviana R.; Scharovsky, O. Graciela; Matar, Pablo; Mazzolini, Guillermo
    PURPOSE: 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.
  • Miniatura
    ÍtemAcceso Abierto
    Immunotherapy for liver tumors: present status and future prospects
    (BioMed Central, 2009-03-06) Matar, Pablo; Alaniz, Laura; Rozados, Viviana R.; Aquino, Jorge B.; Malvicini, Mariana; Atorrasagasti, Catalina; Gidekel, Manuel; Silva, Marcelo; Scharovsky, O. Graciela; Mazzolini, Guillermo
    Increasing evidence suggests that immune responses are involved in the control of cancer and that the immune system can be manipulated in different ways to recognize and attack tumors. Progress in immune-based strategies has opened new therapeutic avenues using a number of techniques destined to eliminate malignant cells. In the present review, we overview current knowledge on the importance, successes and difficulties of immunotherapy in liver tumors, including preclinical data available in animal models and information from clinical trials carried out during the lasts years. This review shows that new options for the treatment of advanced liver tumors are urgently needed and that there is a ground for future advances in the field.