Docetaxel-based therapy is one of the first-line options for castration-resistant prostate cancer (CRPC). However, a large proportion of CRPC patients show different extents of docetaxel resistance. The current study aims to investigate the role of testicular nuclear receptor 4 (TR4) in docetaxel resistance in CRPC. TR4 expression level in prostate biopsy samples from CRPC patients treated with docetaxel was measured by immunohistochemistry (IHC). Alternation of TR4 expression in prostate cancer (PCa) cell line PC3 was applied to find out the influence of TR4 on half-maximal inhibitory concentration (IC50), cell viability and cell apoptosis. Patients who failed to achieve prostate-specific antigen (PSA) response (<50% PSA reduction from baseline) after docetaxel-based chemotherapy had a comparatively higher TR4 expression than those who achieved PSA response (⩾50% PSA reduction from baseline). Knocking down TR4 in PC3 cells led to a lower IC50 dose, poorer cell viability and more cell apoptosis when treated with docetaxel, whereas overexpression of TR4 in PC3 led to a higher IC50 dose, better cell viability and less cell apoptosis. TR4 enhances the chemo-resistance of docetaxel in CRPC. It may serve as a biomarker to determine the prognosis of docetaxel-based therapy and as a potential therapy target to combine with docetaxel to better suppress CRPC.
Being overweight or obese promotes microalbuminuria and increases the risk of chronic kidney disease. This study aimed to develop a mathematical model to estimate the risk of microalbuminuria in overweight Chinese men. Urine albumin/creatinine ratio and metabolic variables were assessed in 1179 subjects, randomly divided into estimation and validation groups that were comparable with respect to all variables. Regression analysis identified body mass index, systolic blood pressure, fasting plasma glucose and blood uric acid as significant variables; these were used to develop a mathematical model for estimating the risk of microalbuminuria. The model generated a receiver-operating characteristic curve indicative of strong predictive accuracy for microalbuminuria (area under the curve, 0.81). A probability cut-off point of 0.50 resulted in global predictive values for microalbuminuria of 86.4% and 84.1% in the validation group (n = 354) and in all subjects, respectively. This model provides a beneficial tool for identifying overweight Chinese men at risk of microalbuminuria; additional studies are required to examine the predictive ability of the model further.
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