ABSTRACT
BACKGROUND TcP21 is a ubiquitous secreted protein of Trypanosoma cruzi and its recombinant form (rP21) promotes parasite cell invasion and acts as a phagocytosis inducer by activating actin polymerisation in the host cell. OBJECTIVE Our goal was to evaluate if the additional supplementation of rP21 during a prime/boost/challenge scheme with T. cruzi TCC attenuated parasites could modify the well-known protective behavior conferred by these parasites. METHODS The humoral immune response was evaluated through the assessment of total anti-T. cruzi antibodies as well as IgG subtypes. IFN-γ, TNF-α and IL-10 were measured in supernatants of splenic cells stimulated with total parasite homogenate or rP21. FINDINGS Our results demonstrated that, when comparing TCC+rP21 vs. TCC vaccinated animals, the levels of IFN-γ were significantly higher in the former group, while the levels of IL-10 and TNF-α were significantly lower. Further, the measurement of parasite load after lethal challenge showed an exacerbated infection and parasite load in heart and skeletal muscle after pre-treatment with rP21, suggesting the important role of this protein during parasite natural invasion process. MAIN CONCLUSION Our results demonstrated that rP21 may have adjuvant capacity able to modify the cytokine immune profile elicited by attenuated parasites.
Subject(s)
Humans , Vaccines, Attenuated/therapeutic use , rho GTP-Binding Proteins/analysis , Trypanosoma cruzi , Chagas Disease/transmissionABSTRACT
Introdução: O carcinoma de vulva é um tumor de baixa ocorrência, sendo responsável por menos de 3% de todos os tumores malignos que acometem mulheres. Em mulheres jovens a ocorrência da doença está atrelada a fatores de risco como tabagismo e infecção por HPV, entretanto em mulheres acima dos 50 anos ocorre por mecanismos genéticos ainda pouco elucidados. Nos últimos anos poucos autores estudaram alterações genômicas em carcinomas vulvares, contudo nenhum deles determinou um fator prognóstico definitivo, nem tampouco correlacionou esses achados com a expressão gênica, mesmo representando pontos-chave na compreensão do processo de carcinogênese. A partir da análise de arranjos de hibridação genômica comparativa (CGH-array) realizada previamente em nosso laboratório, dois genes candidatos, ROCK1 e RhoD, localizados em regiões com alta frequência de ganhos em nossas amostras de neoplasias vulvares, foram selecionados para este estudo. Objetivo: Validar a expressão dos genes candidatos, ROCK1 e RhoD, que foram identificados em regiões com ganho de cópias nas amostras de carcinoma vulvar pelo método de CGHarray, a fim de determinar melhores e mais acurados valores prognósticos no carcinoma vulvar...
Introduction: The vulvar carcinoma is a low occurrence tumor, accounting for less than 3% of all malignant tumors that affect women. In young women the occurrence of the disease is linked to risk factors such as smoking and HPV infection, but the majority of cases of vulvar cancer occurs in women over 50 years by genetic mechanisms still poorly understood. Recently, few authors studied genomic changes in vulvar carcinomas, however none of them determined on prognostic factor, nor correlate these findings with gene expression, even representing key points in understanding the carcinogenesis process. From the analysis of comparative genomic hybridization arrays (array CGH) previously performed in our laboratory, two candidate genes, ROCK1 and Rhod, located in regions with high frequency gains in our samples of vulvar cancer were selected for this study. Objective: To validate the expression of the candidate genes, RhoD and ROCK1, which have been identified in regions with a gain of copies in vulvar carcinoma samples by CGH-array method, in order to determine the best and most accurate prognostic values in vulvar carcinoma. Methods: 16 cases of vulvar cancer were rescued from AC Camargo Cancer Centers Biobank...