Microparticles and cardiotoxicity secondary to doxorubicin-based chemotherapy in breast cancer patients.

Doxorubicin (DOXO)-cardiotoxicity is a limiting factor for breast cancer chemotherapy. The relationship between microparticles (MPs) and cardiotoxicity remains unclear. MPs can be released under varying pathophysiological conditions. Thereby, this study aimed to assess MPs derived from cardiomyocytes (CardioMPs), platelets (PMPs) and those that expresses tissue factor (TFMPs) in 80 women with breast cancer undergoing DOXO-based chemotherapy, with or without cardiotoxicity in a one-year follow-up. We observed in the cardiotoxicity group higher count of total-MPs at T0 (prior chemotherapy) (p = 0.034), CardioMPs at T0 and T1 (just after chemotherapy) (p = 0.009 and p = 0.0034) and TFMPs at T0 (p = 0.011) compared to non-cardiotoxicity group. The results suggest that MPs could be associated to cardiotoxicity due to DOXO treatment in breast cancer patients.

Circulating inflammatory mediators as biomarkers of ocular toxoplasmosis in acute and in chronic infection.

Toxoplasmosis is highly endemic worldwide. In Brazil, depending on the geographical region and socioeconomic status, 40-70% of individuals become seropositive at some point in their lives. A significant proportion of Toxoplasma gondii-chronically infected individuals who are otherwise immunocompetent develop recurrent ocular lesions. The inflammatory/immune mechanisms involved in development of ocular lesion are still unknown and, despite previous investigation, there are no reliable immune biomarkers to predict/follow disease outcome. To better understand the impact of the immune response on parasite control and immunopathology of ocular toxoplasmosis, and to provide insights on putative biomarkers for disease monitoring, we assessed the production of a large panel of circulating immune mediators in a longitudinal study of patients with postnatally acquired toxoplasmosis stratified by the presence of ocular involvement, both at the early acute stage and 6 months later during chronic infection, correlating them with presence of ocular involvement. We found that T. gondii-infected patients, especially during the acute stage of the disease, display high levels of chemokines, cytokines, and growth factors involved in the activation, proliferation, and migration of inflammatory cells to injured tissues. In particular, major increases were found in the IFN-induced chemokines CXCL9 and CXCL10 in T. gondii-infected patients regardless of disease stage or clinical manifestations. Moreover, a specific subgroup of circulating cytokines and chemokines including GM-CSF, CCL25, CCL11, CXCL12, CXCL13, and CCL2 was identified as potential biomarkers that accurately distinguish different stages of infection and predict the occurrence of ocular toxoplasmosis. In addition to serving as predictors of disease development, these host inflammatory molecules may offer promise as candidate targets for therapeutic intervention.

Increased frequencies of circulating CCR5+ memory T cells are correlated to chronic chagasic cardiomyopathy progression.

The infection with the protozoan parasite Trypanosoma cruzi causes Chagas disease, a neglected tropical disease in Latin America and an imported emerging disease worldwide. Chronic Chagasic cardiomyopathy (CCC), a progressive inflammatory and fibrosing disease, is the most prominent clinical form of Chagas disease, culminating in heart failure and high rates of sudden death. CCC pathogenesis is influenced by both host and parasite factors and is proposed to be mostly immune-driven. Chemokines are crucial players in orchestrating immune cell recruitment to infected tissues and inflammation. Herein, we investigated inflammatory chemokine receptor expression on circulating T cells in patients stratified by CCC severity. Compared to asymptomatic individuals, we found increased percentages of effector CD4+ T cells and central memory CD4+ and CD8+ T cells expressing CCR5 in patients with structural cardiopathy, but normal global ventricular function and no symptoms of chronic heart failure. Even naïve T cells expressed CCR5 in these patients. In contrast, reduced frequencies of CD4+ and CD8+ effector T cells expressing CXCR3 were observed in patients presenting with severe heart disease. Patients with increased left ventricular diameter, heart enlargement, and insufficiency had higher frequencies of CCR5+ effector and effector memory CD8+ T cells. Moreover, the percentage of effector CCR5+ CD8+ T cells was increased in patients with a reduced ejection fraction. Our results show that high expression CCR5 and low expression of CXCR3 on circulating T cells are associated with worse prognosis, possibly reflecting immune-mediated cardiac remodeling of CCC.