Moderate-intensity aerobic exercise training improves CD8+ tumor-infiltrating lymphocytes effector function by reducing mitochondrial loss.

Aerobic exercise training (AET) has emerged as a strategy to reduce cancer mortality, however, the mechanisms explaining AET on tumor development remain unclear. Tumors escape immune detection by generating immunosuppressive microenvironments and impaired T cell function, which is associated with T cell mitochondrial loss. AET improves mitochondrial content and function, thus we tested whether AET would modulate mitochondrial metabolism in tumor-infiltrating lymphocytes (TIL). Balb/c mice were subjected to a treadmill AET protocol prior to CT26 colon carcinoma cells injection and until tumor harvest. Tissue hypoxia, TIL infiltration and effector function, and mitochondrial content, morphology and function were evaluated. AET reduced tumor growth, improved survival, and decreased tumor hypoxia. An increased CD8+ TIL infiltration, IFN-γ and ATP production promoted by AET was correlated with reduced mitochondrial loss in these cells. Collectively, AET decreases tumor growth partially by increasing CD8+ TIL effector function through an improvement in their mitochondrial content and function.

Correlation of MGMT promoter methylation status with gene and protein expression levels in glioblastoma

OBJECTIVES: 1) To correlate the methylation status of the O6-methylguanine-DNA-methyltransferase (MGMT) promoter to its gene and protein expression levels in glioblastoma and 2) to determine the most reliable method for using MGMT to predict the response to adjuvant therapy in patients with glioblastoma. BACKGROUND: The MGMT gene is epigenetically silenced by promoter hypermethylation in gliomas, and this modification has emerged as a relevant predictor of therapeutic response. METHODS: Fifty-one cases of glioblastoma were analyzed for MGMT promoter methylation by methylation-specific PCR and pyrosequencing, gene expression by real time polymerase chain reaction, and protein expression by immunohistochemistry. RESULTS: MGMT promoter methylation was found in 43.1 percent of glioblastoma by methylation-specific PCR and 38.8 percent by pyrosequencing. A low level of MGMT gene expression was correlated with positive MGMT promoter methylation (p = 0.001). However, no correlation was found between promoter methylation and MGMT protein expression (p = 0.297). The mean survival time of glioblastoma patients submitted to adjuvant therapy was significantly higher among patients with MGMT promoter methylation (log rank = 0.025 by methylation-specific PCR and 0.004 by pyrosequencing), and methylation was an independent predictive factor that was associated with improved prognosis by multivariate analysis. DISCUSSION AND CONCLUSION: MGMT promoter methylation status was a more reliable predictor of susceptibility to adjuvant therapy and prognosis of glioblastoma than were MGMT protein or gene expression levels. Methylation-specific polymerase chain reaction and pyrosequencing methods were both sensitive methods for determining MGMT promoter methylation status using DNA extracted from frozen tissue.

O seqüenciamento do genoma humano, uma nova forma de fazer ciência? / The sequencing of human genome: a new form of making science?

Nesta palestra a pesquisadora apresenta alguns conceitos elucidativos sobre a genômica, a metodologia empregada - em que há uma inversão: não há uma hipótese inicial, o objetivo a ser perseguido é a coleta de dados-, as principais etapas, as características de um projeto Genoma, suas aplicações, para, no final, expôr o confronto com as estruturas clássicas de fazer ciência, de estar em uma universidade. Verifica-se assim que a genômica, por ser uma área muito nova, como a Gerontologia, ao contrário do que se pensa, enfrenta algumas dificuldades comuns: reconhecimento e financiamento.

O seqüenciamento do genoma humano, uma nova forma de fazer ciência? / The sequencing of human genome: a new form of making science?

Nesta palestra a pesquisadora apresenta alguns conceitos elucidativos sobre a genômica, a metodologia empregada - em que há uma inversão: não há uma hipótese inicial, o objetivo a ser perseguido é a coleta de dados-, as principais etapas, as características de um projeto Genoma, suas aplicações, para, no final, expôr o confronto com as estruturas clássicas de fazer ciência, de estar em uma universidade. Verifica-se assim que a genômica, por ser uma área muito nova, como a Gerontologia, ao contrário do que se pensa, enfrenta algumas dificuldades comuns: reconhecimento e financiamento