Mass spectrometry-based (phospho)proteomics identified a prominent hub associated with collagens, receptor tyrosine kinase discoidin domain-containing receptor 2 (DDR2), and lysyl oxidase-like 2 (LOXL2) from patient-matched cancer-associated fibroblasts (CAF) and non-malignant prostate fibroblasts (NPF). The functional role of LOXL2 in regulating ECM organization and migration of both CAF and co-cultured prostate cancer cells was validated with LOXL2 inhibitors. Our data provide the first demonstration that prostate CAF-dependent LOXL2 production controls prostate tumor cell motility, highlighting LOXL2 as an attractive therapeutic target.
There is lack of consensus regarding the prognostic significance of primary tumor location of upper tract urothelial carcinoma(UTUC). We performed a meta-analysis to evaluate the impact of primary tumor location on prognosis in patients with UTUC who had undergone radical nephroureterectomy(RNU). We included eligible studies that reported hazard ratios(HRs) estimates with 95% confidence intervals(CIs) for the association between tumor location and recurrence-free survival(RFS) and cancer-specific survival(CSS) of UTUC. The local advanced tumors(pT3/4) and nodal positive(pN+) tumors in patients stratified by tumor location were also estimated. The review contained 17 studies including a total of 12094 patients were identified. Although it was not significant in univariable analysis, meta-analysis demonstrated that ureteral tumors had a worse prognosis than renal pelvic tumors on RFS and CSS in multivariable analysis after adjusted for all covariates. Multifocal tumors also showed a significantly association with both disease progression and cancer-specific mortality in univariable and multivariable analyses. However, no statistically significant differences were found between renal pelvic and ureteral tumors in presentation of pT3/4 and pN+ tumors. Our meta-analysis indicated that ureteral and multifocal tumors are independent prognosticators of disease progression and cancer-specific survival in patients with UTUC treated with RNU.
LP as a minimally invasive treatment for UPJO can be performed through both the transperitoneal and retroperitoneal approaches, and either approach is associated with a high success rate and a low complication rate, although TLP provides a shorter operative time and lower conversion rate.
Infertility due to low testosterone levels has increased in recent years. This has impacted the social well-being of the patients. This study was undertaken to investigate the potential of gonadotropins in facilitating differentiation of human bone marrow mesenchymal stem cells (BMSCs) into Leydig cells in vitro. BMSCs were isolated, cultured, and their biological characteristics were observed. BMSCs were induced with gonadotropins in vitro and their ability to differentiate into Leydig cells was studied. The level of expression of 3-beta hydroxysteroid dehydrogenase (3β-HSD) and secretion of testosterone were determined using flow cytometry and enzyme-linked immunosorbent assay, respectively, and the results were compared between the experimental and control groups. The cultured BMSCs showed a typical morphology of the fibroblast-like colony. The growth curve of cells formed an S-shape. After inducing the cells for 8-13 days, the cells in the experimental group increased in size and showed typical characteristics of Leydig cells, and the growth occurred in spindle or stellate shapes. Cells from the experimental group highly expressed 3β-HSD, and there was a gradual increase in the number of Leydig cells. The control group did not express 3β-HSD. The level of testosterone in the experimental group was higher than the control group (p < 0.05). Additionally, the cells in the experimental group secreted higher levels of testosterone with increased culture time. The expression of Leydig cell-specific markers in the experimental group was significantly higher (p < 0.05). With these findings, BMSCs can be considered a new approach for the treatment of patients with low androgen levels.
Silodosin is an effective and well-tolerated treatment for both voiding and storage symptoms in patients with LUTS associated with BPH. Despite with increased retrograde ejaculation, its overall efficacy is not inferior to tamsulosin, while at the same time being possibly superior to tamsulosin.
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