Efecto protector de los componentes de la yerba mate sobre células óseas

El consumo de yerba mate (Ilex paraguariensis) es muy frecuente en varios países de América Latina. Varios fitoquímicos activos como xantinas (cafeína) y polifenoles (ácido clorogénico, quercetina, rutina) han sido identificados en extractos acuosos de Ilex paraguariensis. Entre los componentes de la yerba mate con efecto sobre el tejido óseo se destaca que la cafeína en altas concentraciones tendría un impacto negativo sobre la densidad mineral ósea (DMO) sobre todo cuando se asocia con dietas con bajo contenido de calcio. Contrariamente, los polifenoles han demostrado efectos beneficiosos a nivel del tejido óseo por su acción antioxidante. Se halló asociación entre la pérdida ósea con la edad y el estrés oxidativo por la determinación de productos avanzados de oxidación de proteínas, malondialdehído y superóxido dismutasa en fémures de ratas jóvenes, adultas y de edad avanzada.Una publicación previa mostró mayor DMO de columna lumbar (+9.7%) y cuello femoral (+6.2%) en mujeres postmenopáusicas que tomaban al menos 1 litro de mate/día en comparación con controles que no bebían mate. Nuestro grupo llevó a cabo un trabajo en ratas donde se evaluó el efecto de la yerba mate sobre el tejido óseo a través de estudios de densitometría, morfometría, histomorfometría, conectividad trabecular y biomecánica ósea. Se observó un efecto positivo sobre la DMO y el volumen de hueso trabecular en el grupo de animales que fue alimentado con una dieta con bajo contenido de calcio. Esto podría indicar que el efecto negativo de la baja ingesta de calcio en el volumen óseo se revierte, al menos en parte, por la yerba mate

Potential effect of chloroquine and propranolol combination to treat colorectal and triple-negative breast cancers

Drug repositioning explores the reuse of non-cancer drugs to treat tumors. In this work, we evaluated the effect of the combination of chloroquine and propranolol on colorectal and triple-negative breast cancers. Using as in vitro models the colorectal cancer cell lines HCT116, HT29, and CT26, and as triple-negative breast cancer models the 4T1, M-406, and MDA-MB-231 cell lines, we evaluated the effect of the drugs combination on the viability, apoptosis, clonogenicity, and cellular migratory capacity. To explore the in vivo effects of the combination on tumor growth and metastasis development we employed graft models in BALB/c, nude, and CBi mice. In vitro studies showed that combined treatment decreased cell viability in a dose-dependent manner and increased apoptosis. Also, we demonstrated that these drugs act synergically and that it affects clonogenicity and migration. In vivo studies indicated that this drug combination was effective on colorectal models but only partially on breast cancer. These results contributed to the search for new and safe treatments for colorectal and triple-negative carcinomas.Fil: Anselmino, L. E.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Baglioni, María Virginia. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Reynoso, G.. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Rozados, Viviana Rosa. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Scharovsky, Olga Graciela. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Rico, Maria Jose. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Menacho Márquez, Mauricio Ariel. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentin

Nonclassical roles for IFN-γand IL-10 in a murine model of immunoedition

Aims: to characterize, by means of univariate and multivariate approaches, the Th1 and Th2 responses during the different phases of tumor immunoediting. Materials & Methods: we used a multivariate principal component analysis applied to analyze the joint behavior of serum concentrations of IFN-γ, IL-2, IL-10 and IL-4, during the different phases of tumor immunoediting, in CBi/L mice challenged with M-406 mammary adenocarcinoma. Results & Conclusions: Animals in equilibrium phase showed the widest variations in values of the four cytokines. In this experimental model the role of IFN-γ would be related to tumor growth and progression, while IL-10 would participate in the antitumor immune response. Lay abstract: Breast cancer is a complex, multifactor disease that affects about 10% of women in industrialized countries. The immune system has the ability to monitor the appearance of tumors, but the tumors have the ability to escape such rejection. For this reason, in order to design different therapeutic strategies, it is important to know the different mechanisms that take place when a tumor grows or when it is rejected. Here we sought to elucidate some of these mechanismsFil: del Giúdice, Antonela. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genética Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Pagura, Lucas. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genética Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Capitani, María Celeste. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genética Experimental; ArgentinaFil: Mainetti, Leandro Ernesto. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genética Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Scharovsky, Olga Graciela. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genética Experimental; Argentina. Universidad Nacional de Rosario. Consejo de Investigaciones de la Universidad de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Di Masso, Ricardo Jose. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genética Experimental; Argentina. Universidad Nacional de Rosario. Consejo de Investigaciones de la Universidad de Rosario; ArgentinaFil: Rico, Maria Jose. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genética Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Rozados, Viviana Rosa. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genética Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentin

Losartan improves the therapeutic effect of metronomic cyclophosphamide in triple negative mammary cancer models

Metronomic chemotherapy refers to the minimum biologically effective doses of a chemotherapy agent given as a continuous regimen without extended rest periods. Drug repurposing is defined as the use of an already known drug for a new medical indication, different from the original one. In oncology the combination of these two therapeutic approaches is called “Metronomics”. The aim of this work is to evaluate the therapeutic effect of cyclophosphamide in a metronomic schedule in combination with the repurposed drug losartan in two genetically different mice models of triple negative breast cancer. Our findings showed that adding losartan to metronomic cyclophosphamide significantly improved the therapeutic outcome. In both models the combined treatment increased the mice's survival without sings of toxicity. Moreover, we elucidated some of the mechanisms of action involved, which include a decrease of intratumor hypoxia, stimulation of the immune response and remodeling of the tumor microenvironment. The remarkable therapeutic effect, the lack of toxicity, the low cost of the drugs and its oral administration, strongly suggest its translation to the clinical setting in the near future.Fil: Mainetti, Leandro Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Rico, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Kaufman, Cintia Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Grillo, Monica Carolina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Guercetti, Julian. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Baglioni, María Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: del Giúdice, Antonela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Capitani, María Celeste. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Fusini, Matías. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Rozados, Viviana Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Scharovsky, Olga Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina. Metronomics Global Health Initiative; Franci

Paclitaxel delivery system based on poly(lactide-co-glycolide) microparticles and chitosan thermo-sensitive gel for mammary adenocarcinoma treatment

Objectives: To evaluate the combination of more than one release system in the same formulation as a useful strategy to achieve paclitaxel delivery in a more sustained and controlled manner. Methods: The present study deals with the preparation of poly(lactide-co-glycolide) microparticles loaded with paclitaxel and included in a chitosan thermo-sensitive gelling solution. The microparticles were characterized by their size, shape and drug loading. The formulation was characterized by scanning electron microscopy, in vitro release experiments and was evaluated in mice bearing mammary adenocarcinoma. Key findings: The formation of paclitaxel crystals in a pharmaceutical formulation reduces its efficacy. In this work, the use of microparticles avoided this phenomenon. Combining more than one delivery system allowed delivering paclitaxel in a more sustained and controlled manner leading to a long-term effect in the site of action. The formulation showed an inhibition in tumour volume of 63.0% in comparison with the control group. Conclusions: One intratumour injection of gelling solution containing the microparticles was at least as efficacious as four intraperitoneal injections of a commercial formulation. In addition, the delivery system was nontoxic, and the treated mice presented the highest percentage of tumour regression and median survival time.Fil: Pesoa, Juan Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Rico, Maria Jose. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rozados, Viviana Rosa. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Scharovsky, Olga Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; ArgentinaFil: Luna, Julio Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Mengatto, Luciano Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentin

Quality of life in patients with metastatic breast cancer treated with metronomic chemotherapy

Aim: The objective of the study was to detect changes in quality of life (QoL) in metastatic breast cancer patients treated with metronomic chemotherapy with daily low doses of cyclophosphamide and celecoxib. Material & methods: Patients included in a Phase II trial, treated with metronomic cyclophosphamide and celecoxib were included in the QoL study. Assessment of QoL was carried out every 2 months by the Functional Assessment of Cancer Therapy Breast (FACT-B) questionnaire, Brief Pain Inventory and Eastern Cooperative Oncologic Group scale. Data were analyzed at three time points: baseline (BL); middle of treatment (MT); and end of treatment (ET). Results: A total of 20 patients were included. All patients were heavily pretreated. Treatment showed a good and safe therapeutic profile. With FACT-B questionnaire, no significant differences were observed during the response period (BL-MT). However, a significant increase was observed in the Emotional well-being and Additional concerns axes, when the last time point was included in the analysis (BL-MT-ET). A significant decrease in the proportion of patients with pain was found when comparing BL with ET (p = 0.046). The assessment with Eastern Cooperative Oncologic Group scale showed that 26.7% (4/15) of the patients improved their functional status and 40% (6/15) showed no changes, while 33.3% (5/10) worsened it. Conclusion: Patients treated metronomically for several months did not worsen their QoL. A high proportion of patients showed improvement or no changes and there were less patients with pain at the end of the treatment.Fil: Perroud, Herman Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Alasino, Carlos M. Instituto de Oncología de Rosario; ArgentinaFil: Rico, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Queralt, Francisco. Instituto de Oncología de Rosario; ArgentinaFil: Pezzotto, Stella Maris. Consejo de Investigación de la Universidad Nacional de Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología; ArgentinaFil: Rozados, Viviana Rosa. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Scharovsky, Olga Graciela. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina. Consejo de Investigación de la Universidad Nacional de Rosario; Argentin

Metformin and propranolol combination prevents cancer progression and metastasis in different breast cancer models

Discovery of new drugs for cancer treatment is an expensive and time-consuming process and the percentage of drugs reaching the clinic remains quite low. Drug repositioning refers to the identification and development of new uses for existing drugs and represents an alternative drug development strategy. In this work, we evaluated the antitumor effect of metronomic treatment with a combination of two repositioned drugs, metformin and propranolol, in triple negative breast cancer models. By in vitro studies with five different breast cancer derived cells, we observed that combined treatment decreased proliferation (P < 0.001), mitochondrial activity (P < 0.001), migration (P < 0.001) and invasion (P < 0.001). In vivo studies in immunocompetent mice confirmed the potential of this combination in reducing tumor growth (P < 0.001) and preventing metastasis (P < 0.05). Taken together our results suggest that metformin plus propranolol combined treatment might be beneficial for triple negative breast cancer control, with no symptoms of toxicity.Fil: Rico, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Baglioni, María Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Bondarenko, Maryna. Aix-Marseille Université; FranciaFil: Laluce, Nahuel Cesatti. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Rozados, Viviana Rosa. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: André, Nicolas. Aix-Marseille Université; Francia. Service d'Hématologie and Oncologie Pédiatrique; Francia. Metronomics Global Health Initiative; FranciaFil: Carré, Manon. Aix-Marseille Université; FranciaFil: Scharovsky, Olga Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina. Metronomics Global Health Initiative; FranciaFil: Menacho Márquez, Mauricio Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentin

Putative Biomarkers of Response to Treatment in Breast Cancer Patients: A Pilot Assay

Identifying tumor biomarkers associated with clinical behavior in breast cancer patients may allow higher accuracy in the selection of treatment. Different types of cells were determined in the primary tumors of stage I, II, and III of breast cancer patients, who were assigned to one of the two groups: (1) disease-free or (2) relapsed/progressed, at 5 years after primary treatment. We studied 32 tumor samples. CD4+ lymphocytes and CD44+CD24−/low cells (cancer stem cells) showed a significant association with clinical outcome at 5 years of primary treatment, while CD8+, Foxp3+, CD34+, and myeloid-derived suppressor cells did not show any association. Coincident with the results of individual analysis, we identified CD4+ cells and CD44+CD24−/low cells as good predictors of long-term clinical outcome in a logistic regression.Fil: Rico, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Perroud, Herman Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Herrera, Cintia. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Alasino, Carlos M.. Instituto de Oncología de Rosario; ArgentinaFil: Roggero, Eduardo Angel. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Pezzotto, Stella Maris. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentina. Universidad Nacional de Rosario. Consejo de Investigación; ArgentinaFil: Nocito, Ana Lía. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; ArgentinaFil: Rozados, Viviana Rosa. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Scharovsky, Olga Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; Argentina. Universidad Nacional de Rosario. Consejo de Investigación; Argentin

Antitumor activity of new chemical compounds in triple negative mammary adenocarcinoma models

Aim: According to the need for the development of new anticancer agents, we have synthetized novel bioactive compounds and aimed to determine their antitumor action. Materials & methods: We describe in vitro studies evaluating the effect of 35 novel chemical compounds on two triple negative murine mammary adenocarcinoma tumors. Results & conclusion: Three compounds were selected because of their high antitumor activity and their low toxicity to normal cells. Their effect on tumor cells apoptosis, clonogenicity and migratory capacity, were determined. We found that the selected compounds showed inhibition of viability and clonogenic capacity, and promotion of apoptosis. They also decreased the migratory capacity of tumor cells. The results obtained suggest the likelihood of their future use as antitumor and/or antimetastatic agents.In spite of the important progress achieved in cancer therapeutics, the percentage of people dying because of cancer is still high. Hence, we need to develop new, effective and nontoxic anticancer agents. We synthetized novel compounds and tested their antitumor effect and toxicity, in order to choose those that are effective and do not affect normal cells and therefore, are suitable for human cancer therapies. We selected three out of 35 compounds that show high antitumor action and low toxicity. Also, we studied the mechanisms by which that effect was achieved. Our next goal is to develop experiments with animals in order to have preclinical data that, hopefully, will lead to the clinical use of one or more of the selected compounds.Fil: Giolito, Maria Virginia. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; Argentin