Benign prostatic hyperplasia (BPH) is the most common benign disease of the prostate gland and is caused by benign hyperplasia of the smooth muscle cells and stromal cells in this important gland. BPH is also the most common disease underlying lower urinary tract symptoms (LUTS). The incidence of BPH increases with age and affects more than half of all men 50 years or older. BPH mainly exerts effects on urinary function and can seriously reduce a patient's quality of life. At present, treatment for BPH aims primarily to improve the quality of life and reduce the risk of BPH-related complications. Pharmacological therapy is recommended for moderate-to-severe cases of LUTS that are suggestive of BPH. A range of drugs is currently available to treat this condition, including a1adrenoceptor antagonists, 5a-reductase inhibitors (5-ARIs), phosphodiesterase type 5 inhibitors (PDE5Is), muscarinic receptor antagonists (MRAs), b3-adrenoceptor agonists, and plant extracts. Of these, the most commonly used drugs in the clinic are a1adrenoceptor antagonists, 5-ARIs, and combination therapy. However, these drugs exert their effects via various mechanisms and are associated with adverse reactions. The purpose of this review is to provide current comprehensive perspectives on the mechanisms of action, efficacy, and adverse reactions associated with the drugs most commonly used for the treatment of BPH.
Background Better prognostic outcome is closely correlated with early detection of bladder cancer. Current non-invasive urianalysis relies on simultaneously testing multiple methylation markers to achieve relatively high accuracy. Therefore, we have developed an easy-to-use, convenient, and accurate single-target urine-based DNA methylation test for the malignancy. Methods By analyzing TCGA data, 344 candidate markers with 424 primer pairs and probe sets synthesized were systematically screened in cancer cell lines, paired tissue specimens, and urine sediments from bladder cancer patients and normal controls. The identified marker was further validated in large case-control cohorts. Wilcoxon rank sum tests and c2 tests were performed to compare methylation levels between case-control groups and correlate methylation levels with demographic and clinical characteristics. In addition, MSP, qMSP, RT-PCR, western blot analysis, and immunohistochemistry were performed to measure levels of DNA methylation, mRNA transcription, and protein expression in cancer cell lines and tissues. Results A top-performing DMRTA2 marker identified was tested in both discovery and validation sets, showing similar sensitivity and specificity for bladder cancer detection. Overall sensitivity in the aggregate set was 82.9%(179/216). The specificity, from a control group consisting of patients with lithangiuria, prostatoplasia, and prostatitis, is 92.5%(468/506). Notably, the methylation assay had the highest sensitivities for tumors at stages of T1(90.4%) and T2(95.0%) compared with Ta (63.0%), T3(81.8%), and T4(81.8%). Furthermore, the test showed admirable detection rate of 80.0%(24/30) for recurring cancers. While methylation was observed in 39/54(72.2%) urine samples from patients with carcinomas of renal pelvis and ureter, it was detected at extremely low rate of 6.0%(8/133) in kidney and prostate cancers. Compared with SV-HUC-1, the normal bladder epithelial cell line, DMRTA2 was hypermethylated in 8/9 bladder cancer cell lines, consistent with the results of MSP and qMSP, but not correlated with mRNA and protein expression levels in these cell lines. Similarly, DMRTA2 immunostaining was moderate in some tissues but weak in others. Further studies are needed to address functional implications of DMRTA2 hypermethylation. Conclusions Our data demonstrated that a single-target DNA methylation signature, mDMRTA2, could be highly effective to detect both primary and recurring bladder cancer via urine samples.
BackgroundBiochemical recurrence (BCR) is common in prostate cancer (PCa), but its prediction is based predominantly on clinicopathological characteristics with low accuracy. We intend to identify a potential prognostic biomarker related to the BCR and construct a nomogram for improving the risk stratification of PCa patients.MethodsThe transcriptome and clinical data of PCa patients were obtained from TCGA and GEO databases. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were used to screen out differentially expressed genes (DEGs) related to the BCR of PCa. Cox regression analysis was further applied to screen out DEGs related to BCR-free survival (BFS). Time-dependent receiver operating curve (ROC) analysis and Kaplan–Meier (K-M) survival analysis were conducted to assess the prognostic value. Then, a prognostic nomogram was established and evaluated. The clinicopathological correlation analysis, GSEA analysis, and immune analysis were used to explore the biological and clinical significance of the biomarker. Finally, the qRT-PCR, western blotting, and immunohistochemistry (IHC) were conducted to validate the expression of the biomarker.ResultsBIRC5 was identified to be the potential prognostic biomarker. The clinical correlation analysis and K-M survival analysis found that the BIRC5 mRNA expression was positively associated with disease progression and negatively associated with the BFS rate. Time-dependent ROC curves verified its accurate prediction performance. The GSEA and immune analysis suggested that the BIRC5 was related to immunity. A nomogram with an accurate prediction for BFS of PCa patients was constructed. qRT-PCR, western blotting, and IHC results validated the expression level of BIRC5 in PCa cells and tissues.ConclusionOur study identified BIRC5 as a potential prognostic biomarker related to BCR of PCa and constructed an efficacy nomogram for predicting BFS to assist clinical decision-making.
Purpose To explore the application of the neobladder-urethral drag-and-bond anastomosis technique in laparoscopic radical cystectomy (LRC) with ileal orthotopic neobladder (IONB) reconstruction. Patients and Methods This is a retrospective cohort study on a procedure performed by a single surgeon. From January 2014 to December 2018, we identified 43 male bladder cancer patients who received LRC with IONB reconstruction. These patients were divided into two groups, with 22 patients undergoing neobladder-urethral drag-and-bond anastomosis (NUDA) and 21 patients undergoing neobladder-urethral anastomosis under laparoscopy (NUAL). Anastomosis time, catheter removal time, postvoid residual (PVR), maximum urinary flow rate (Q-max), urine leakage and anastomotic stenosis were used to evaluate the simplicity and surgical effect of the two groups. Results Both groups demonstrated similar tumor characteristics. A significant difference in neobladder-urethral anastomosis time was found between the NUDA group and the NUAL group (14.6 ± 0.4 vs 70 ± 2.5 min, P<0.0001), and there was no significant difference in other characteristics. Conclusion The neobladder-urethral drag-and-bond anastomosis technique in LRC and IONB reconstruction, with its shorter learning curve, was easier and more convenient than neobladder-urethral anastomosis under laparoscopy.
Given its high recurrence and rapid progress, bladder cancer (BLCA) treatment has become a major problem for clinicians. BLCA is difficult to control even with surgical resection and extensive use of chemotherapeutic drugs. The non-toxicity and ease of accessibility of natural compounds have attracted much attention in recent years. Flavonoids serve an essential role given their antioxidant, antibacterial, anticancer and cardiovascular properties. They are mainly divided into several subclasses; flavones, flavanones, flavonols, flavanols, anthocyanins isoflavones and chalcones. Over the years, the role of flavonoids in BLCA has been extensively studied. The present review provided a comprehensive overview of the classification of flavonoids and substantiate the role of epithelial-mesenchymal transition, cancer stem cells, angiogenesis, epigenetic regulation and programmed cell death in BLCA. The present review emphasized that flavonoids for BLCA treatment are worthy of further study and anti-BLCA drugs have huge prospects for clinical use. Contents 1. Introduction 2. Mechanism 3. Flavonoids on BLCA 4. Discussion and outlook 5. Conclusion
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