The present investigation was undertaken to assess the effects of aflatoxin (AF) on the exocrine pancreas in quails by means of light and electron microscopy. A total of 30 quails were divided into three groups, each composed of ten animals. Total AF was incorporated into the diet of these groups, at doses of 0, 2.5, and 5.0 mg of AF/kg feed, ppm, respectively. The quails were raised in cages with electrical heating and 24-h lighting for a period of 3 weeks. Ad libitum access was provided to feed and drinking water. Pancreas samples were taken for light and electron microscopic examination from animals that were killed by means of cervical dislocation at the end of the study. Light microscopic examination demonstrated mild mononuclear cell infiltration of exocrine tissue and vacuolisation of acinar cells in the group fed on AF at 2.5 ppm. On the other hand, electron microscopic examination demonstrated degranulation of the rough endoplasmic reticulum (rER) of acinar cells, decrease in the number of zymogen granules and free ribosomes and polisomes, and dilatation of capillaries in the group fed on AF at a dose of 2.5 ppm. Numerous degenerative acinar cells were determined in the group fed a diet containing 5.0 ppm AF, in addition to the findings common with the other group exposed to the toxin.
Purpose: Vascular endothelial growth factor (VEGF), angiopoietins (Ang-1and Ang-2), and their receptor Tie2 are critically involved in both normal and pathologic angiogenesis. The aim of this study was to explore the role of Ang-1, Ang-2,VEGF, andTie2 in the development and progression of bladder cancer as well as to examine their prognostic value in this tumor type. Experimental Design:Tumor samples of 113 bladder cancer patients, normal bladder epithelium of 5 noncancer patients, and two low-grade (UMUC3 and RT4) and two high-grade (J82 and T24) bladder cancer cell lines were analyzed by quantitative real-time PCR. The expression data were analyzed performing Wilcoxon rank-sum and Kaplan-Meier log-rank tests as well as univariate Cox analyses and Cox proportional hazards regression model. Results: In tissues of noninvasive bladder tumors, Ang-1 expression was significantly lower (P < 0.001), whereasVEGF expression was significantly higher (P = 0.031) than in normal bladder tissue. These findings were also confirmed at the protein level by immunohistochemistry. In contrast, Tie2 and Ang-2 abundance in tumor did not differ significantly from that in normal bladder tissue. Multivariate analysis identified Ang-2 as a strong and independent predictor of tumor recurrence [hazard ratio (HR), 10.18; 95% confidence interval (95% CI), 2.69-38.49; P < 0.001] andTie2 expression as an independent favorable prognostic factor for both metastasis (HR, 0.31; 95% CI, 0.11-0.89; P = 0.029) and disease-specific survival (HR, 0.25; 95% CI, 0.10-0.62; P = 0.003). Conclusions: These data show the strongest change in expression of VEGF and Ang-1 in superficial bladder cancer in comparison with normal bladder epithelium and the invasive tumor stages. The prognostic significance of Ang-2 and Tie2 underlines the essential role of angiopoietins-Tie2 system in progression of bladder cancer.
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