TMPRSS2/ERG fusion was found to be the most common genetic event in prostate adenocarcinoma. There is a strong correlation between the fusion and ERG-positive immunostaining. Many studies showed racial variation in ERG expression in prostate cancer patients. There is no data however on the rate of ERG-positive cancer in Jordanian or Arab population. We evaluated the frequency and the significance of ERG fusion in Jordanian-Arab population using immunohistochemistry for ERG. The cohort included 193 prostate cancer specimens: 109 needle core biopsies, 45 radical prostatectomies, 37 transurethral resections of prostate, and 2 enucleation specimens. We found ERG reactivity in 64 (33.2%) of evaluated cases. The observed ERG frequency in the Jordanian-Arab population is lower than the one documented in North America, but it is higher than in Asian patient cohorts. The ERG positivity was significantly associated with lower baseline prostate-specific antigen but was unrelated to patient age, Gleason Score, or the novel Gleason Grade Groups. In the 45 prostatectomy cases, ERG did not correlate with the pathologic stage, margin, nodal status, and the biochemical recurrence, and it did not appear to represent an important prognosticator.
While aromatase inhibitors (AIs) have been known to cause minor elevations in liver enzymes, severe hepatotoxicity is rare. To the best of our knowledge, this is the first reported case of Letrozole-induced hepatitis with autoimmune features. A 70-year-old female with estrogen positive, invasive ductal carcinoma of the breast, presented with jaundice 3 months after starting letrozole. Hepatic transaminases were markedly elevated and her ANA and anti-smooth muscle antibody was positive. Liver biopsy featured drug-induced hepatitis. After stopping letrozole, liver tests trended back to normal within 3 weeks. She scored 9 for Roussel-Uclaf Causality Assessment Method (RUCAM). Over the last 10 years, there have been reported cases of drug-induced hepatitis secondary to AIs. We anticipate that there will be more widespread use of AIs based on recommendations from the TEXT, SOFT and extended AI trials. Therefore, physicians must be aware of this rare but life-threatening complication.
Maternal undernutrition (MUN) during pregnancy leads to low-birth weight (LBW) neonates that have a reduced kidney nephron endowment and higher morbidity as adults. Using a severe combined caloric and protein-restricted mouse model of MUN to generate LBW mice, we examined the progression of renal insufficiency in LBW adults. Through 6 mo of age, LBW males experienced greater albuminuria (ELISA analysis), a more rapid onset of glomerular hypertrophy, and a worse survival rate than LBW females. In contrast, both sexes experienced a comparable progressive decline in renal vascular density (immunofluorescence analysis), renal blood flow (Laser-Doppler flowmetry analysis), glomerular filtration rate (FITC-sinistrin clearance analysis), and a progressive increase in systemic blood pressure (measured via tail-cuff method). Isolated aortas from both LBW sexes demonstrated reduced vasodilation in response to ACh, indicative of reduced nitric oxide bioavailability and endothelial dysfunction. ELISA and immunofluorescence analysis revealed a significant increase of circulating reactive oxygen species and NADPH oxidase type 4 (NOX4) expression in both LBW sexes, although these increases were more pronounced in males. Although more effective in males, chronic tempol treatment did improve all observed pathologies in both sexes of LBW mice. Chronic NOX4 inhibition with GKT137831 was more effective than tempol in preventing pathologies in LBW males. In conclusion, despite some minor differences, LBW female and male adults have a reduced nephron endowment comparable with progressive renal and vascular dysfunction, which is associated with increased oxidative stress and subsequent endothelial dysfunction. Tempol treatment and/or NOX4 inhibition attenuates renal and vascular dysfunction in LBW adults.
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