High-fat diet fuels prostate cancer progression by rewiring the metabolome and amplifying the MYC program

Systemic metabolic alterations associated with increased consumption of saturated fat and obesity are linked with increased risk of prostate cancer progression and mortality, but the molecular underpinnings of this association are poorly understood. Here, we demonstrate in a murine prostate cancer model, that high-fat diet (HFD) enhances the MYC transcriptional program through metabolic alterations that favour histone H4K20 hypomethylation at the promoter regions of MYC regulated genes, leading to increased cellular proliferation and tumour burden. Saturated fat intake (SFI) is also associated with an enhanced MYC transcriptional signature in prostate cancer patients. The SFI-induced MYC signature independently predicts prostate cancer progression and death. Finally, switching from a high-fat to a low-fat diet, attenuates the MYC transcriptional program in mice. Our findings suggest that in primary prostate cancer, dietary SFI contributes to tumour progression by mimicking MYC over expression, setting the stage for therapeutic approaches involving changes to the diet

Dosagem sérica de troponina I em cães com desnível do segmento ST utilizando quimioluminescência

Com o intuito de verificar algum dano nas células do miocárdio, utilizaram-se 38 cães, 20 com traçado eletrocardiográfico normal, grupo 1, e 18 com desníveis do segmento ST, grupo 2, em registro na derivação II, velocidade de 50mm/s e sensibilidade N (1mV=1cm). No grupo 1, a dosagem sérica da troponina I (cTnI) destinou-se à obtenção dos valores referenciais (ng/mL) que seriam confrontados com os obtidos no grupo 2. A média e o desvio-padrão foram, respectivamente, 0,16ng/mL e 0,11ng/mL e 0,20ng/mL e 0,11ng/mL, nos grupos 1 e 2. A cTnI não apresentou evidências de associação com idade, massa corpórea, creatinafosfoquinase total e potássio nos dois grupos. Não houve diferenças significativas nos valores de cTnI entre os grupos. Conclui-se que é possível a utilização do kit de ensaio imunométrico quimioluminescente humano para a espécie canina e que a hipóxia-isquemia, revelada pelo desnível do segmento ST não acarreta dano miocárdico ou este é mínimo e indetectável

Vorapaxar in the secondary prevention of atherothrombotic events

Item does not contain fulltextBACKGROUND: Thrombin potently activates platelets through the protease-activated receptor PAR-1. Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1. METHODS: We randomly assigned 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease to receive vorapaxar (2.5 mg daily) or matching placebo and followed them for a median of 30 months. The primary efficacy end point was the composite of death from cardiovascular causes, myocardial infarction, or stroke. After 2 years, the data and safety monitoring board recommended discontinuation of the study treatment in patients with a history of stroke owing to the risk of intracranial hemorrhage. RESULTS: At 3 years, the primary end point had occurred in 1028 patients (9.3%) in the vorapaxar group and in 1176 patients (10.5%) in the placebo group (hazard ratio for the vorapaxar group, 0.87; 95% confidence interval [CI], 0.80 to 0.94; P<0.001). Cardiovascular death, myocardial infarction, stroke, or recurrent ischemia leading to revascularization occurred in 1259 patients (11.2%) in the vorapaxar group and 1417 patients (12.4%) in the placebo group (hazard ratio, 0.88; 95% CI, 0.82 to 0.95; P=0.001). Moderate or severe bleeding occurred in 4.2% of patients who received vorapaxar and 2.5% of those who received placebo (hazard ratio, 1.66; 95% CI, 1.43 to 1.93; P<0.001). There was an increase in the rate of intracranial hemorrhage in the vorapaxar group (1.0%, vs. 0.5% in the placebo group; P<0.001). CONCLUSIONS: Inhibition of PAR-1 with vorapaxar reduced the risk of cardiovascular death or ischemic events in patients with stable atherosclerosis who were receiving standard therapy. However, it increased the risk of moderate or severe bleeding, including intracranial hemorrhage. (Funded by Merck; TRA 2P-TIMI 50 ClinicalTrials.gov number, NCT00526474.)