Purpose: Cancer stem-like cells (CSCs) contribute to bladder cancer chemotherapy resistance and progression, but the associated mechanisms have not been elucidated. This study determined whether blocking an autocrine signaling loop in CSCs improves the therapeutic effects of cis-platinum on bladder cancer. Experimental Design: The expression of the epithelial marker OV6 and other markers in human bladder cancer specimens was examined by IHC. The CSC properties of magnetic-activated cell sorting (MACS)-isolated OV6 þ and OV6 À bladder cancer cells were examined. Molecular mechanisms were assessed through RNA-Seq, cytokine antibody arrays, co-immunoprecipitation (co-IP), chromatin immunoprecipitation (ChIP) and other assays. An orthotopic bladder cancer mouse model was established to evaluate the in vivo effects of a YAP inhibitor (verteporfin) and a PDGFR inhibitor (CP-673451) on the cis-platinum resistance of OV6 þ CSCs in bladder cancer. Results: Upregulated OV6 expression positively associated with disease progression and poor prognosis for bladder cancer patients. Compared with OV6 À cells, OV6 þ bladder cancer cells exhibited strong CSC characteristics, including self-renewal, tumor initiation in NOD/SCID mice, and chemotherapy resistance. YAP, which maintains the stemness of OV6 þ CSCs, triggered PDGFB transcription by recruiting TEAD1. Autocrine PDGF-BB signaling through its receptor PDGFR stabilized YAP and facilitated YAP nuclear translocation. Furthermore, blocking the YAP/TEAD1/ PDGF-BB/PDGFR loop with verteporfin or CP-673451 inhibited the cis-platinum resistance of OV6 þ bladder cancer CSCs in an orthotopic bladder cancer model. Conclusions: OV6 could be a helpful indicator of disease progression and prognosis for patients with bladder cancer, and targeting the autocrine YAP/TEAD1/PDGF-BB/PDGFR loop might serve as a remedy for cis-platinum resistance in patients with advanced bladder cancer.

Objective To evaluate the safety profile and short-term functional outcome of sustainable functional urethral reconstruction (SFUR) in robotic-assisted radical prostatectomy (RARP). Methods One hundred and sixty-two consecutive prostate cancer patients who underwent RARP were retrospectively analyzed, in which 53 had undergone SFUR while the other 109 had undergone conventional RARP procedures. Immediate, 2-week, 1-month and 3-month continence recovery and other perioperative data were compared to evaluate short-term surgical and functional outcome. Results The median age was 68 and 67 years in the experimental group and control group, respectively ( p =0.206), with a median prostate-specific antigen (PSA) of 13.6 ng/mL (interquartile range [IQR], 8.46–27.32 ng/mL) in the experimental group and 13.84 ng/mL (IQR, 9.12–26.80 ng/mL) in control group ( p =0.846). Immediate, 2-week, 1-month and 3-month continence recovery rates between the groups were 34.0% vs. 3.7%, 50.9% vs. 14.7%, 62.3% vs. 27.5%, and 79.2% vs. 63.3% (all p <0.05). The morphological changes made by the new reconstruction technique were maintained on magnetic resonance imaging (MRI) 3 months postoperatively. Nerve-sparing procedures and adoption of the new reconstruction technique were significantly relevant to continence recovery on logistics regression model ( p <0.001). Conclusions SFUR is a safe and easy-to-handle modification that may contribute to early continence return for RARP. Long-term follow-up and prospective studies are required to further evaluate its value in postoperative quality-of-life improvement.

Background The tripartite motif (TRIM) family proteins exhibit oncogenic roles in various cancers. The roles of TRIM27, a member of the TRIM super family, in renal cell carcinoma (RCC) remained unexplored. In the current study, we aimed to investigate the clinical impact and roles of TRIM27 in the development of RCC. Methods The mRNA levels of TRIM27 and Kaplan–Meier survival of RCC were analyzed from The Cancer Genome Atlas database. Real-time PCR and Western blotting were used to measure the mRNA and protein levels of TRIM27 both in vivo and in vitro. siRNA and TRIM27 were exogenously overexpressed in RCC cell lines to manipulate TRIM27 expression. Results We discovered that TRIM27 was elevated in RCC patients, and the expression of TRIM27 was closely correlated with poor prognosis. The loss of function and gain of function results illustrated that TRIM27 promotes cell proliferation and inhibits apoptosis in RCC cell lines. Furthermore, TRIM27 expression was positively associated with NF-κB expression in patients with RCC. Blocking the activity of NF-κB attenuated the TRIM27-mediated enhancement of proliferation and inhibition of apoptosis. TRIM27 directly interacted with Iκbα, an inhibitor of NF-κB, to promote its ubiquitination, and the inhibitory effects of TRIM27 on Iκbα led to NF-κB activation. Conclusions Our results suggest that TRIM27 exhibits an oncogenic role in RCC by regulating NF-κB signaling. TRIM27 serves as a specific prognostic indicator for RCC, and strategies targeting the suppression of TRIM27 function may shed light on future therapeutic approaches.