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Ítem Acceso Abierto Lovastatin enhances in vitro radiation-induced apoptosis of rat B-cell lymphoma cells(BioMed Central; "Regina Elena" National Cancer Institute, Italy, 1905-06-27) Rozados, Viviana R.; Hinrichsen, Lucila Isabel; McDonnel, José; Scharovsky, O. GracielaOur previous demonstration of an antimetastatic effect of lovastatin, both in rat sarcoma and lymphoma tumor-models, as well as the fact that lovastatin and radiation are able to stop the cell cycle in different phases, suggested the feasibility of a combined treatment. We studied the effect of the in vitro combined treatment of a B-cell rat lymphoma (L-TACB) with lovastatin and irradiation. The results herein obtained provide new information about the role of statins as radiosensitizers. The antitumor effect of the combined treatment was higher than that elicited by either treatment alone. This effect could be a consequence, at least in part, of an enhanced apoptosis.Ítem Acceso Abierto Metronomic therapy with cyclophosphamide induces rat lymphoma and sarcoma regression, and is devoid of toxicity(Oxford University Press, 2004-10) Rozados, Viviana R.; Sánchez, Andrea M.; Gervasoni, Silvia I.; Berra, Héctor H.; Matar, Pablo; Scharovsky, O. GracielaBACKGROUND: Our aim was to investigate the clinical efficacy and toxicity of metronomic administration of low-dose cyclophosphamide (Cy) in lymphoma and sarcoma rat tumour models. METHODS: Adult inbred rats were challenged with lymphoma TACB and sarcoma E100 s.c. on day 0. Animals were divided into two groups: group I, control, injected with saline three times a week; and group II, treated with Cy 10 mg/kg three times a week, from day 10 until the tumour was non-palpable, or 5 mg/kg three times a week from day 7. Tumours were measured and animals were weighed twice weekly. Periodic blood samples were taken for determination of urea, creatinine, serum glutamic-oxaloacetic transaminase, lactate dehydrogenase and haematological parameters. RESULTS: The administration of low-dose Cy eradicated established rat lymphomas and sarcomas; there was neither metastatic growth nor recurrence at primary sites for 100% of the lymphomas and 83% of the sarcomas. In addition, the treatment did not cause weight loss, and was devoid of haematological, cardiac, hepatic and renal toxicity. CONCLUSIONS: Metronomic administration of Cy at low doses on a thrice weekly schedule to already grown rat lymphomas and sarcomas demonstrated itself to be a successful antitumour therapy that did not cause weight loss and was devoid of haematological, cardiac, hepatic and renal toxicity.Ítem Acceso Abierto Lovastatin enhances the antitumoral and apoptotic activity of doxorubicin in murine tumor models(Spandidos (Grecia), 2008-05) Rozados, Viviana R.; Hinrichsen, Lucila Isabel; Binda, María Mercedes; Gervasoni, Silvia I.; Matar, Pablo; Bonfil, Daniel R.; Scharovsky, O. GracielaDespite its effectiveness as an antineoplastic drug, doxorubicin (DOX) is usually associated with cardiotoxicity. Lovastatin (LOV), a hypolipidemic agent used in the clinic, has been demonstrated to have antitumoral and antimetastatic effects in murine models. Since the two agents arrest tumor cells in different phases of the cell cycle and induce apoptosis, the goal of this study was to examine the efficacy of a combination therapy with LOV and low doses of DOX, in an attempt to obtain an improved antitumoral effect devoid of toxicity, by using a rat B-cell lymphoma and a mouse mammary tumor. In the two models, the combined treatment showed a synergistic antitumoral effect, which is mainly ascribed to an increased apoptotic response elicited by a LOV/DOX combination than either agent alone. The therapeutic benefit demonstrated by the combination treatment is further emphasized by the lack of toxicity.Ítem Acceso Abierto Metronomic chemotherapy: changing the paradigm that more is better(Multimed Inc., 2009-03) Scharovsky, O. Graciela; Mainetti, Leandro Ernesto; Rozados, Viviana R.The introduction of the “maximum tolerated dose” in usual treatment protocols (and its concomitant overt toxicity) made necessary the imposition of rest periods between cycles of therapy—a practice that not only involves re-growth of tumour cells, but also growth of selected clones resistant to the therapy. To avoid the problems caused by traditional chemotherapeutic regimens, a new modality of drug administration called “metronomic chemotherapy” has been proposed. This name makes reference to the chronic, equally spaced administration of (generally) low doses of various chemotherapeutic drugs without extended rest periods. The novelty of this treatment modality lies not only in its antitumour efficacy with very low toxicity, but also in a cell target switch, now aiming at tumour endothelial cells. The knowledge acquired in the experimental field of metronomic chemotherapy, plus the increasing experience that is being obtained in the clinical setting, will help to lead a change in the design of therapeutic protocols against cancer.Ítem Acceso 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, GuillermoIncreasing 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.Ítem Acceso Abierto Short treatment with the tumour necrosis factor-α blocker infliximab diminishes chronic chagasic myocarditis in rats without evidence of Trypanosoma cruzi reactivation(British Society for Immunology, 2009-08) Pérez, Ana Rosa; Fontenella, Germán Héctor; Nocito, Ana Lía; Revelli, Silvia; Bottasso, OscarÍtem Acceso Abierto TNF-α Is Involved in the Abnormal Thymocyte Migration during Experimental Trypanosoma cruzi Infection and Favors the Export of Immature Cells(PLOS (Public Library of Science), 2012-03-26) Pérez, Ana Rosa; Berbert, Luiz Ricardo; Lepletier, Ailin; Revelli, Silvia; Bottasso, Oscar; Silva-Barbosa, Suse Dayse; Savino, WilsonPrevious studies revealed a significant production of inflammatory cytokines together with severe thymic atrophy and thymocyte migratory disturbances during experimental Chagas disease. Migratory activity of thymocytes and mature T cells seem to be finely tuned by cytokines, chemokines and extracellular matrix (ECM) components. Systemic TNF-α is enhanced during infection and appears to be crucial in the response against the parasite. However, it also seems to be involved in disease pathology, since it is implicated in the arrival of T cells to effector sites, including the myocardium. Herein, we analyzed the role of TNF-α in the migratory activity of thymocytes in Trypanosoma cruzi (T. cruzi) acutely-infected mice. We found increased expression and deposition of TNF-α in the thymus of infected animals compared to controls, accompanied by increased co-localization of fibronectin, a cell migration-related ECM molecule, whose contents in the thymus of infected mice is also augmented. In-vivo studies showed an enhanced export of thymocytes in T. cruzi-infected mice, as ascertained by intrathymic injection of FITC alone or in combination with TNF-α. The increase of immature CD4+CD8+ T cells in secondary lymphoid organs was even more clear-cut when TNF-α was co-injected with FITC. Ex-vivo transmigration assays also revealed higher number of migrating cells when TNF-α was added onto fibronectin lattices, with higher input of all thymocyte subsets, including immature CD4+CD8+. Infected animals also exhibit enhanced levels of expression of both mRNA TNF-α receptors in the CD4+CD8+ subpopulation. Our findings suggest that in T. cruzi acute infection, when TNF-α is complexed with fibronectin, it favours the altered migration of thymocytes, promoting the release of mature and immature T cells to different compartments of the immune system. Conceptually, this work reinforces the notion that thymocyte migration is a multivectorial biological event in health and disease, and that TNF-α is a further player in the process.Ítem Acceso Abierto Modulation of IL-10/IL-10R expression by mafosfamide, a derivative of 4-hydroxycyclophosphamide, in a rat B-cell lymphoma(Sociedad Latinoamericana de Microscopía Electrónica. Centro Regional de Investigaciones Científicas y Tecnológicas (Mendoza, Argentina), 2012-08) Rico, María José; Matar, Pablo; Scharovsky, O. GracielaWe have already shown that IL-10 plays an important role in immunosuppression and metastatic dissemination in the rat B-cell lymphoma L-TACB model. It was suggested that the up-regulation of IL-10 production and IL-10 receptor (IL-10R) expression would be part of the transition from primary tumor to metastatic phenotype and that IL-10, besides its immunosuppressive activity, may act as a growth factor for metastatic L-TACB cells. The treatment of L-TACB-bearing rats with a single low-dose cyclophosphamide decreased IL-10 production, reverted immunosuppression and induced the immunologic rejection of tumor metastasis without any effect on primary tumor growth. Our current aim was to investigate the effects of cyclophosphamide on the expression of IL-10 and IL-10R on primary and metastatic L-TACB cells. Considering that cyclophosphamide is a prodrug, we used mafosfamide, a compound that yields in vitro the same active metabolites as cyclophosphamide does in vivo. Mafosfamide induced down-regulation of IL-10 production and IL-10R expression on metastatic cells and, concomitantly, inhibited metastatic cell proliferation. We suggest that mafosfamide would inhibit the regulatory loop mediated by the IL-10/IL-10R system and, as a consequence, metastatic cell proliferation. These results may have a considerable impact on the design of new therapies for metastatic lymphomas.Ítem Acceso Abierto Safety and therapeutic effect of metronomic chemotherapy with cyclophosphamide and celecoxib in advanced breast cancer patients(Future Medicine Ltd, 2013-03-08) Perroud, Herman A; Rico, María José; Alasino, Carlos María; Queralt, Francisco ; Mainetti, Leandro Ernesto; Pezzotto, Stella Maris; Rozados, Viviana R.; Scharovsky, O. GracielaÍtem Acceso Abierto Therapeutic efficacy of metronomic chemotherapy with cyclophosphamide and doxorubicin on murine mammary adenocarcinomas(Oxford University Press, 2013-09-01) Mainetti, Leandro Ernesto; Rico, María José; Fernández Zenobi, María Virginia; Perroud, Herman A.; Roggero, Eduardo; Rozados, Viviana R.; Scharovsky, O. GracielaÍtem Acceso Abierto Comparative Effectiveness of Two Metronomic Chemotherapy Schedules. Our Experience in the Preclinical Field(Taylor & Francis, 2014-02-05) Rico, María José; Perroud, Herman A; Mainetti, Leandro Ernesto; Rozados, Viviana R.; Scharovsky, O. GracielaÍtem Acceso Abierto Características clínico-epidemiológicas de la estrongiloidiasis en pacientes portadores de co-morbilidades(Sociedad Chilena de Infectología, 2017-02) Regueira Fernandes, Amanda; Romero, Sebastián; Alcântara de Souza Melo, Paula Fernanda; Ramos Araújo, Paulo Sérgio; Bottasso, Oscar; Rocha, Abraham; Brandão, EduardoÍtem Acceso Abierto Clinical response in patients with ovarian cancer treated with metronomic chemotherapy(Cancer Intelligence, 2017-02-28) Perroud, Herman A; Scharovsky, O. Graciela; Rozados, Viviana R.; Alasino, Carlos MaríaÍtem Acceso Abierto Recomendaciones diagnósticas y terapéuticas ante la Respuesta Inmune Trombótica Asociada a COVID-19 (RITAC)(Cardiocentro "Ernesto Che Guevara", 2020-03) Gauna Belcuore, Mauricio Esteban; Bernava, Juan LuisÍtem Acceso Abierto Recomendaciones de diagnóstico y tratamiento de la respuesta inmune trombótica en pacientes con COVID-19(Universidad Autónoma de Centro América, 2020-05-19) San Juan González, Juanita; Gauna Belcuore, Mauricio Esteban; Bernava, Juan LuisThe SARS-CoV-2 virus responsible for COVID-19 has affected more than 180 countries around the world. Reports of the disease have revealed an increase in thromboembolic events in hospitalized patients. As well as the observation in some of these reports of clinical improvement in hospitalized patients with moderate and severe forms of the disease when treated with low molecular weight heparins.Ítem Acceso Abierto The SARS-CoV-2 Coronavirus and the COVID-19 Outbreak(Brazilian Society of Urology, 2020-07-27) Lauxmann, Martin Alexander; Santucci, Natalia Estefanía; Autrán-Gómez, Ana MaríaÍtem Acceso Abierto Recomendaciones del Comité de Ecocardiografía e Imágenes Cardíacas para la protección de pacientes y del personal de salud durante la pandemia del COVID-19(Federación Argentina de Cardiología, 2020-10) Garófalo, Pablo; Albisu, Juan Pablo; Solano Benítez, Sebastián; Ruarte López, Celina; Ros, Germán; Simondi, Horacio; Vega, Gustavo