According to data from the U.S. National Cancer Institute, cancer is one of the leading causes of death worldwide with approximately 14 million new cases and 8.2 million cancer-related deaths in 2018. More than 60% of the new annual cases in the world occur in Africa, Asia, Central America, and South America, with 70% of cancer deaths in these regions. Breast cancer is the most common cancer in women, with 266,120 new cases in American women and an estimated 40,920 deaths for 2018. Approximately one in six women diagnosed with breast cancer will die in the coming years. Recently, novel therapeutic strategies have been implemented in the fight against breast cancer, including molecules able to block signaling pathways, an inhibitor of poly [ADP-ribose] polymerase (PARP), growth receptor blocker antibodies, or those that reactivate the immune system by inhibiting the activities of inhibitory receptors like cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death protein 1 (PD-1). However, novel targets include reactivating the Th1 immune response, changing tumor microenvironment, and co-activation of other components of the immune response such as natural killer cells and CD8+ T cells among others. In this article, we review advances in the treatment of breast cancer focused essentially on immunomodulatory drugs in targeted cancer therapy. Based on this knowledge, we formulate a proposal for the implementation of combined therapy using an extracorporeal immune response reactivation model and cytokines plus modulating antibodies for co-activation of the Th1- and natural killer cell (NK)-dependent immune response, either in situ or through autologous cell therapy. The implementation of “combination immunotherapy” is new hope in breast cancer treatment. Therefore, we consider the coordinated activation of each cell of the immune response that would probably produce better outcomes. Although more research is required, the results recently achieved by combination therapy suggest that for most, if not all, cancer patients, this tailored therapy may become a realistic approach in the near future.
Macrophages play a crucial role in respiratory viral infections. However, the mechanisms by which these cells are recruited locally are not fully understood. The current authors studied the role of the chemokines monocyte chemotactic protein (MCP)-1, -2, -3 and -4 on monocyte/macrophage recruitment during respiratory viral infections. Levels of these chemokines were investigated in nasal aspirates from 6-12-yr-old children suffering from respiratory viral infections, caused by rhinoviruses, influenza viruses, parainfluenza viruses, adenoviruses and respiratory syncytial virus.MCP-3 and -4 were significantly higher in samples derived from virus-infected children compared with samples from the same children when they had been asymptomatic. Concentrations of both chemokines were found to significantly correlate with the number of recruited nasal macrophages. Chemotaxis assays showed that purified MCP-3 and -4 from nasal aspirates showed biological activity in vitro. There were no significant differences in MCP-1 and -2 levels between both groups.The present data indicates that monocyte chemotactic protein-3 and -4 may have an important role in macrophage recruitment in children with proven upper respiratory viral infections. These chemokines could be potential targets for therapeutic intervention in respiratory viral infections.
Bovine tuberculosis (bTB) has a direct impact in the productive and reproductive efficiency of dairy cattle. Nowadays, disease control programs based on tuberculin testing and removal of infected cattle are unaffordable for the developing countries, since there is no program of financial compensation, especially in high bTB-prevalence herds. Thus, control strategies based on vaccination are considered the best alternative. The aim of this study was to evaluate whether a low dose of BCG-Phipps vaccine induces reactivity to tuberculin skin test and its duration in neonatal calves and adult cows. For the analysis of the former, 69 TB-free Holstein-Friesian calves less than one-month old were used; of which, 54 calves were subcutaneously inoculated with 10 4 CFU of the BCG-Phipps vaccine, while the rest remained without vaccination. Under similar conditions of immunization, 133 single intradermal comparative cervical (SICCT) reactors and 133 non-reactors Holstein-Friesian cows of different age were also analyzed. In calves, the SICCT-reactivity was evaluated periodically in the first 14 months post-vaccination (mpv) while, in adult cows, the effect of vaccination on the test was evaluated at six months post-vaccination. A comparative ELISA was used by measuring the antibody levels in the groups. In calves, reactivity frequencies of 7.4 and 3.7% at 3 and 5 mpv, respectively were recorded. This reactivity disappeared at six months. None calves in the control group were reactor during the study. There were no variations in the degree of reactivity in the group adult reactor cows. However, in the non-reactor group, a conversion of 12.8% at six mpv was recorded. In addition, the conversion percentage was higher in older cows than in younger cows (p<0.05). The specific antibody levels did not increase in the vaccinated groups. Data indicate that the low dose of BCG-Phipps vaccine used had a reduced effect on the development of a delayed type hypersensitivity to tuberculin in neonatal calves, and heifers lesser than one-year-old.
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