Clear cell urothelial carcinoma of the urinary bladder - a rare pathological entity. A case report and a systematic review of the literature

The most common histological type of urinary bladder cancer is urothelial carcinoma (UC). In contrast, the clear cell variant of urothelial carcinoma (CCUC) is quite a rare neoplasm. In this study, we report a case of an 81-year-old male, presenting with gross hematuria and acute urinary retention, which was subsequently diagnosed with CCUC at our pathology department. Furthermore, we provide a short systematic review of the literature (PubMed, Scopus, Science Citation Index) for this rare histopathological entity and a brief discussion about its morphological and immunohistochemical (IHC) characteristics

PERIPHERAL BLOOD CELL DNA METHYLATION AND HYDROXYMETHYLATION IN PROSTATE CANCER. A PILOT STUDY

Objective/Purpose: DNA methylation is an important epigenetic hallmark of cancer, including prostate cancer, with a general pattern of global hypomethylation accompanied by hypermethylation at certain gene promoters’ level in tissues. Limited evidence exists on the methylation pattern of blood cells in prostate cancer patients, which this pilot study is addressing. Material and Methods: DNA methylation and hydroxymethylation levels were assessed in peripheral nucleated blood cells from prostate cancer patients compared to controls using fluorimetric ELISA-type assays that directly measure the amount of 5mC and 5hmC, respectively. Results: There was significant difference in global DNA methylation levels between prostate cancer patients and controls, with almost two-fold hypomethylation observed in patients’ blood cell DNA (p<0.0001). There was no statistical significant difference regarding the hydroxymethylation levels. Conclusions: In this pilot study of limited sample sizewe found evidence of different levels of global DNA methylation in blood cells of prostate cancer patients compared to controls. These findings need further replication in future larger studies in order to assess the biomarker potential of blood cells DNA methylation and hydroxymetylation in prostate cancer

VEGF-A165b protects against proteinuria in a mouse model with progressive depletion of all endogenous VEGF-A splice isoforms from the kidney

Chronic kidney disease (CKD) is strongly associated with a decrease in the expression of VEGF-A. However, little is known about the contribution of VEGF-A splice isoforms to kidney physiology and pathology. Previous studies suggest that the splice isoform VEGF-A165b (resulting from alternative usage of a 3’ splice site in the terminal exon) is protective for kidney function. We show here, in a quad-transgenic model, that over-expression of VEGF-A165b alone is sufficient to rescue the increase in proteinuria as well as glomerular water permeability in the context of progressive depletion of all VEGF-A isoforms from the podocytes. Ultrastructural studies show that the glomerular basement membrane is thickened, podocyte slit width is increased and sub-podocyte space coverage is reduced when VEGF-A is depleted, all of which are rescued in VEGF-A165b over-expressors. VEGF-A165b restores the expression of PECAM-1 in glomerular endothelial cells and glomerular capillary circumference. Mechanistically, it increases VEGFR2 expression both in vivo and in vitro and down-regulates genes involved in migration and proliferation of endothelial cells, otherwise up-regulated by the canonical isoform VEGF-A165. Our study indicates that manipulation of VEGF-A splice isoforms could be a novel therapeutic avenue in chronic glomerular disease