The effect of propolis on CCL5 and IFN-gamma expression by peripheral blood mononuclear cells from leishmaniasis patients

Objectives Mucocutaneous leishmaniasis is associated with a strong Th1 immune response to Leishmania, which modulates chemokines and their receptors expression, affecting their migratory capacity. There are no antileishmanial vaccines available and chemotherapy still relies on the potentially toxic pentavalent antimonials. Propolis is a bee product with immunomodulatory and antiparasite activities, and researchers have been attracted to its potential for the development of new drugs. This work investigated the effects of propolis on CCL5 and IFN-? expression by peripheral blood mononuclear cells (PBMC) in order to evaluate a possible immunomodulatory action of propolis in patients with leishmaniasis compared to healthy control subjects.Methods PBMC were incubated in the absence or presence of propolis and the evaluation of a possible cytotoxicity of propolis was carried out using MTT assay. The expression level of CCL5 and IFN-gamma was determined by real-time PCR.Key findings Our data indicated that propolis modulates the immune response of leishmaniasis patients in vitro, affecting CCL5 and IFN-gamma expression by PBMC.Conclusions Data suggested that propolis drives an anti-inflammatory response depending on concentration. Although propolis is a potential source of new and selective drugs for the treatment of leishmaniasis, its usefulness in the therapeutics should be further investigated.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

FOXP3 Transcription Factor: A Candidate Marker for Susceptibility and Prognosis in Triple Negative Breast Cancer

Triple negative breast cancer (TNBC) is a relevant subgroup of neoplasia which presents negative phenotype of estrogen and progesterone receptors and has no overexpression of the human epidermal growth factor 2 (HER2). FOXP3 (forkhead transcription factor 3) is a marker of regulatory T cells (Tregs), whose expression may be increased in tumor cells. This study aimed to investigate a polymorphism (rs3761548) and the protein expression of FOXP3 for a possible involvement in TNBC susceptibility and prognosis. Genetic polymorphism was evaluated in 50 patients and in 115 controls by allele-specific PCR (polymerase chain reaction). Protein expression was evaluated in 38 patients by immunohistochemistry. It was observed a positive association for homozygous AA (OR = 3.78; 95% CI = 1.02–14.06) in relation to TNBC susceptibility. Most of the patients (83%) showed a strong staining for FOXP3 protein in the tumor cells. In relation to FOXP3-positive infiltrate, 47% and 58% of patients had a moderate or intense intratumoral and peritumoral mononuclear infiltrate cells, respectively. Tumor size was positively correlated to intratumoral FOXP3-positive infiltrate (P=0.026). In conclusion, since FOXP3 was positively associated with TNBC susceptibility and prognosis, it seems to be a promising candidate for further investigation in larger TNBC samples

Protein Expression and Codon 72 Polymorphism of TP53 Gene in Triple Negative Breast Cancer

A subgroup of tumor that has received attention is triple-negative breast cancer (TNBC), which presents phenotype of negative estrogen receptor, negative progesterone receptor and has no overexpression of HER2. TP53 acts as a tumor suppressor limiting the proliferation of damaged cells. A polymorphic site (rs1042522) of TP53 encodes either an arginine or a proline amino acid, but its biological significance remains unclear. This study aimed to investigate this variant and its expression in search for a possible involvement in TNBC susceptibility and clinical outcome. Genetic polymorphism was evaluated in 50 patients and 115 controls by PCR based methodology and immunohistochemistry was done with monoclonal antibody. Case-control study showed no positive or negative association (OR= 0.95; CI95%= 0.48-1.89). Comparison of genotypes and clinical outcome showed no significant results. Despite most of patients presented p53 positive staining by immunohistochemistry, there was no significant association in relation to prognostic parameters. Results demonstrated a lack of association between codon 72 polymorphism, susceptibility and prognosis of TNBC. Immunohistochemistry analysis should be done more carefully, since most of the patients had the somatic mutation of p53, which could be an indicator of prognostic value in TNBC