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 Materia "Antineoplastic Agents, Alkylating/therapeutic use"

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    ÍtemAcceso Abierto
    Inmunomodulación y antiangiogénesis en la terapéutica oncológica. De la investigación básica a la clínica
    (Fundación Revista Medicina (Buenos Aires), 2012-02) Scharovsky, O. Graciela; Matar, Pablo; Rozados, Viviana R.; Rico, María José; Zacarías Fluck, Mariano; Mainetti, Leandro Ernesto; Fernández Zenobi, María Virginia
    La investigación básica y pre-clínica en oncología celular y molecular son pilares fundamentales en los que se apoyan la mayoría de los adelantos en la terapéutica del cáncer. Los hallazgos obtenidos y su aplicación en la práctica clínica constituyen la causa del avance sostenido en el tratamiento de la enfermedad neoplásica. El objetivo de este trabajo es resumir y discutir los resultados pre-clínicos en inmunomodulación y anti-angiogénesis para el tratamiento de diversos tipos de tumores, obtenidos en nuestro Instituto durante los últimos 15 años, y la posterior traslación y aplicación del conocimiento experimental en un Ensayo Clínico Fase I/II. Se describen los resultados que contribuyeron a descifrar los mecanismos de acción de la inmunomodulación antimetastásica con ciclofosfamida, la quimioterapia metronómica con diferentes drogas únicas o combinaciones, y finalmente el diseño y resultados preliminares de un ensayo clínico de quimioterapia metronómica para pacientes con cáncer de mama avanzado.
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    ÍtemAcceso Abierto
    The Immune Response and the Therapeutic Effect of Metronomic Chemotherapy With Cyclophosphamide
    (Cognizant Communication Corporation, 2010-11-01) Rozados, Viviana R.; Mainetti, Leandro Ernesto; Rico, María José; Zacarías Fluck, Mariano; Matar, Pablo; Scharovsky, O. Graciela
    Metronomic chemotherapy (MCT) is a novel therapeutic strategy for cancer treatment endowed with an antiangiogenic effect. It refers to regular administration of low doses of cytotoxic drugs, with minimal or no drug-free breaks. Previously, we demonstrated the immunomodulating activity of a single low-dose of cyclophosphamide (Cy) and the antitumor effect of MCT with Cy on established rat lymphomas and sarcomas. Here, we examined whether the immune response is responsible for the antitumor effect of MCT with Cy on L-TACB lymphoma. Inbred e rats and nude mice were subcutaneously challenged with L-TACB. After 7 days, they were distributed into two experimental groups: 1) treated animals, which were injected IP with Cy (10 mg/kg body weight) three times per week, and 2) control animals, which received IP saline injections. Exponential growth and decay and tumor doubling time were calculated. Also, serum IL-10 levels were measured. One hundred percent of treated rats showed tumor regression versus 0% of control rats. The increase of tumor-induced IL-10 levels was reverted by the treatment with Cy. On the other hand, there were no tumor regressions, in treated or control nude mice. However, the tumor doubling times of treated nude mice were significantly higher than those of control mice, implying that other antitumor mechanism(s), independent of the adaptive immune response, might be taking place. Our present results indicate that modulation of the immune response would be involved in the antitumor effect of MCT with Cy, because the absence of the specific immune response impairs, at least in part, its therapeutic effect in a lymphoma tumor model.