Silvério Cabrita

Influence of 0.1 or 0.2% cholesterol-enriched diets on the induction of atherosclerosis and aorta reactivity in vitro

Current knowledge of atherogenesis is largely based on animal models of hypercholesterolemia, which rarely show changes similar to the lesions described in humans. We studied the influence of two low cholesterol-enriched diets on the development of anatomopathologic lesions and on the reactivity of the isolated aorta in rabbits. Compared with controls (rabbits fed a normal diet), a 0.1% cholesterol-enriched diet over a 6- or 9-month period produced increases of the 5-hydroxytryptamine (5-HT)-induced contractile responses, as well as a decreases in acetylcholine (ACh)-induced relaxing response (endothelium-dependent, through the production of NO). Noradrenaline (NA)-induced contractions and relaxations elicited by sodium nitroprusside (SNP; endothelium independent) were not significantly modified. Because at 6 months, significant anatomopathologic intimal early lesions were not found, functional endothelial changes can explain such findings. There was a defect in NO synthesis, release, or diffusion; 5 HT, but not NA, may be responsible for inducing NO production. In 0.2% cholesterol-fed rabbits at 4 and 12 weeks, increases of 5-HT- and NA-induced contractile responses were found. In both cases, there was a decrease of ACh-induced relaxing effect, whereas responses to SNP remained unchanged. Intimal early and advanced lesions were present at both the 4- and 12-week periods. These data suggest abnormalities of the NO system. The effects obtained with NA may be explained by a possible decrease of catechol-O-methyltransferase (COMT) or monoamine oxidase (MAO) activities or both or by decreased amine uptake. The extent to which NA may induce NO production is small, because changes in NA-induced contractions are verified only in the presence of significant alterations in the endothelium. The use of a 0.2% cholesterol diet for a short time may induce atherosclerotic lesions, whereas the 0.1% cholesterol diet for a 9-month period, besides being closer to the human diet, allows the detection of functional abnormalities before the evidence of structural lesions.

In vivo pulmonary metastatic profile of breast cancer cell lines expressing hormonal receptors versus triple negative

Breast cancer metastized to lungs is a challenge considering clinical management and molecular processes. The interaction between tumor cells and lung environment as well as the influence of hormonal receptor (HR) are a question of debate. The aim of this study is the characterization of pulmonary metastatic spread in vivo of breast cancer cell lines that express HR comparing with triple negative (TN) after injection in the tail vein. It was performed injection in the tail vein of female mice Balb/c nude with 1.5×106 cells of each breast cancer cell line (MCF7 and HCC1806) previously labeled with 99mTc-HMPAO. Imagiological studies with 99mTc-HMDP and 99mTc-MIBI were performed between 7th and 8th weeks and then sacrificed. The lungs were submitted to histological image analysis focusing on regions of interest (ROI), in order to obtain lesion areas. Tumor cells injected labeled with 99mTc-HMPAO showed a preference embolization to the lungs. The ROI analysis of imagiological studies with 99mTc-HMDP and 99mTc- MIBI did not reveal significant differences according to each cell type. Histology showed metastatic lung foci in all animals injected. On one hand, the number of lung foci was not significantly different considering MCF7 and HCC1806 injection. On the other hand, the mean area of lung metastasis in MCF7 cases were significantly higher than in HCC1806 (p = 0.023). The mice injected with HR positive breast cancer cells in the tail vein were associated with higher lung metastatic areas than TN cells. This emphasizes the influence of HR in the expression of growth factors and pulmonary neovascularization that is not still delineated.