Benign prostatic hyperplasia (BPH) is a common chronic disease in older males. The pathogenesis of BPH remains elusive but may be associated with chronic inflammation. Chemokines and chemokine receptors have been implicated as critical mediators in the immune response and inflammatory processes. In the present study, the aim was to evaluate the association of three polymorphisms in chemokine genes, namely C-C motif chemokine ligand (CCL)2 rs1024611, CC chemokine receptor 2 (CCR2) rs1799864 and CCL5 rs2107538, with BPH risk. These polymorphisms were genotyped in 109 patients with BPH and 160 control subjects, using the polymerase chain reaction and multiple ligase detection reaction method. The CCL5 rs2107538 polymorphism was identified to be associated with a significantly lower risk of BPH [A/G vs. G/G: Odds ratio (OR)=0.37, 95% confidence interval (CI)=0.17-0.78; A/A + A/G vs. G/G: OR= 0.39, 95% CI= 0.19-0.79; A vs. G: OR= 0.58, 95% CI=0.35-0.96). However, this polymorphism was also associated with the development of larger prostate volumes in patients with BPH (A/G vs. G/G: OR=3.02, 95% CI=1.28-7.11; AA + AG vs. GG: OR=2.83, 95% CI=1.28-6.26; A vs. G: OR=1.94, 95% CI=1.08-3.49). The CCR2 rs1799864 polymorphism was associated with lower International Prostate Symptom Score values (A/A + A/G vs. G/G: OR=0.39, 95% CI=0.17-0.91; A vs. G: OR=0.43, 95% CI=0.20-0.90) and low Qmax (A/G vs. G/G: OR=0.38, 95% CI=0.16-0.92; AA + AG vs. GG: OR=0.39, 95% CI=0.17-0.91) in the patients. No association was observed between the CCL2 rs1024611 polymorphism and BPH. These results suggest that the CCR2 and CCL5 genes may contribute to the occurrence and progression of BPH.

Background New effective drugs for prostate cancer (PCa) treatment are urgently needed. Avasimibe was recently identified as a promising drug for anticancer therapies. The main purpose of this study was to explore the effects and the underlying mechanisms of avasimibe in prostate cancer. Methods In this study, MTT and clonogenic survival assays were performed to detect cell proliferation after avasimibe treatment. The effect of avasimibe on cell migration was measured by wound healing and transwell migration assays. Cell cycle distribution and apoptosis were detected by flow cytometry. Immunofluorescence staining and western blot analysis were used to detect the expression of cell cycle-related proteins and epithelial-mesenchymal transition (EMT)-related proteins. In vivo, the antitumour effects of avasimibe were evaluated using a xenograft model and pulmonary metastasis model. Results The study found that avasimibe suppresses tumour growth and triggers G1 phase arrest. Moreover, the expression of the cell cycle-related proteins CDK2/4/6, Cyclin D1 and Cyclin A1 + A2 was significantly increased and p21 expression was decreased after avasimibe treatment. The migration of PCa cells was attenuated after treatment with avasimibe, followed by the downregulation of the expression of the EMT-related proteins N-cadherin, β-catenin, vimentin, Snail and MMP9 and upregulation of E-cadherin expression. Moreover, E2F-1 was elevated after treatment with avasimibe. After knockdown of E2F-1 expression, the inhibition of cell proliferation and migration caused by avasimibe was significantly recovered. The results of the xenograft model showed that avasimibe suppressed tumour growth in vivo. Immunofluorescence staining revealed lower levels of Ki67 and higher levels of E2F-1 in tumour tissues of the avasimibe group than those of the control group. A pulmonary metastasis model also confirmed the inhibition of PCa metastasis by avasimibe. The number of lung metastatic foci in the avasimibe group was significantly decreased compared with that in the control group. Conclusions Our results suggest that avasimibe can suppress tumour proliferation and metastasis via the E2F-1 signalling pathway. These findings demonstrate the potential of avasimibe as a new effective drug for PCa treatment.

Background Penile cancer represents a rare pathology whose natural history of treatment is poorly understood. Objective To illustrate the dynamic survival profiles in surgically treated patients with squamous cell carcinoma of the penis (SCCP) using the conditional survival (CS) estimates. Materials and methods Patients with non‐metastatic SCCP were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Conditional 3‐yr overall survival (OS) rate and 3‐yr cancer‐specific survival (CSS) rate represented the primary outcomes of interest and were calculated using the Kaplan‐Meier method. The multivariable Cox regression model was employed to calculate proportional hazard ratios for the prediction of mortality. Results A total of 1887 SCCP patients who had undergone surgeries were identified. Given a 1‐, 2‐, 3‐, 4‐, and 5‐yr survivorship, the 3‐yr OS rates were, respectively, improved by + 9.8 (72.6%), +18.2 (78.1%), +23.4 (81.6%), +27.8 (84.5%), and + 26.6% (83.7%) from those calculated at baseline (time zero). As compared with the baseline calculations, patients who had survived 1, 2, 3, 4, or 5 yr after surgery could, respectively, harvest a + 7.8 (84.7%), +14.8 (90.2%), +19.5 (93.9%), +22.1 (96.0%), and + 22.4% (96.2%) improvement in 3‐yr CSS. Patients with the most aggressive disease at baseline ultimately benefited the most from event‐free survivorship. Multivariable Cox regression analyses showed that the impact of adverse pathological parameters (G2‐3, ≥ pT2, pN+) on OS and CSS mostly showed a decreasing trend over time and some could disappear after a minimum of 1‐yr survivorship. Discussion and conclusion The survival probability of SCCP patients increases with post‐operative survival. Patients with aggressive disease at baseline ultimately benefit the most from event‐free survivorship and may expect a better prognosis once they survive the critical few years after surgery. The recorded observations have crucial implications regarding patient counseling and follow‐up.