ABSTRACT
INTRODUCTION: The identification of bladder detrusor muscle invasion in urothelial cancer is essential for prognosis and management. We studied the clinical, histological, and immunohistochemical expression of p16, p53, and Ki-67 in urothelial detrusor muscle-invasive bladder cancer (MIBC) and urothelial non-detrusor muscle-invasive bladder cancer (NMIBC) in Egyptian patients. METHODS: Sixty-two bladder urothelial cancer cases obtained through TURBT were included and divided into two groups: (MIBC, stage T2) and NMIBC (T1). Tissue blocks were recut and re-examined microscopically; then, the immunostaining of p16, p53, and Ki-67 was performed to compare both groups and evaluate the 13% cut-off for Ki-67, 20% for p53, and p16 intensity in various conditions aided by telepathology technology. RESULTS AND CONCLUSION: Hematuria was the main clinical first presentation, with no significant difference between either group. The mean age was 61.6 years, with male predominance (52 males and 10 females). The absence of papillary histological pattern was associated with a higher stage, including detrusor muscle invasion (p = 0.000). The overall average percent of p53 immunostaining was 12.9%, revealing no significant difference between MIBC and NMIBC when a cut-off of 20% was implicated. The Ki-67 expression was correlated with higher grade and muscle invasion; however, no association was found with the other two markers' expression. The negative immunostaining of p16 was associated with low grade and NMIBC in the case of the preservation of the papillary pattern. We recommend further studies on the cut-off of widely used markers and more immunohistochemical and genetic studies on the p16(INK4A), taking into consideration the histological pattern of conventional carcinomas.
ABSTRACT
Diabetes mellitus is an oxidative stress-related disease characterized by hyperglycemia and a variety of complications, including nephropathy. Vitamin D has variable functions extending beyond the calcium metabolism to prevent oxidative tissue damage. We aimed to investigate whether vitamin D supplements could enhance Glibenclamide's effectiveness in treating diabetes and minimize the risk of associated pathology. Wistar rats were divided into normal control (n = 10) and diabetic (n = 30), where animals received two low doses of Streptozotocin 30 mg/kg/BW intraperitoneally to develop diabetes. The diabetic rats were then randomly divided into three equal groups: untreated, treated with Glibenclamide (0.6â mg/kg), and treated with Glibenclamide and Vitamin D3 (500 IU/kg). After eight weeks, the animals were sacrificed, and blood samples and kidney tissues were collected to evaluate biochemical, anti-oxidant, and pro-inflammatory cytokine levels and histological and immunohistochemical changes. Diabetic animals had significantly increased fasting blood glucose, lipid profile, blood urea, serum creatinine, and Malondialdehyde levels, whereas serum insulin, albumin, and the anti-oxidant enzymes superoxide dismutase and catalase were significantly decreased compared to normal control (p < 0.01). Furthermore, some renal histological changes were observed together with significantly increased immunoreactivity of anti-p53, anti-TNF-α, and anti-IL-6 antibodies when compared to the normal control. All abnormal parameters improved significantly with Glibenclamide therapy (p < 0.01), but combination therapy with vitamin D produced a much better result. In conclusion, vitamin D supplementation along with anti-diabetic medication can help prevent or reduce the severity of diabetic nephropathy due to its potent antioxidant, anti-inflammatory, and anti-apoptotic properties.
