Bladder cancer (BC) is the second most common malignant tumor of the urinary tract in the world. In this study, we found that ubiquitin-specific protease (USP21) was upregulated in BC and the ectopic expression of USP21 was closely associated with tumor size and metastasis. Moreover, patients with higher levels of USP21 had poorer survival rate. Multiple function analysis such as CCK-8, colony formation, wound healing, and transwell analysis indicated that USP21 regulated cell proliferation and metastasis in bladder carcinoma cell lines. We also found that USP21 could facilitate epithelial–mesenchymal transition. As EZH2 has been reported to promote cell metastasis in BC, our work identified that USP21 deubiquitinated EZH2 and stabilized it. Our data demonstrated that USP21 might play a crucial role in regulating BC progression and could provide a potential therapeutic strategy for BC.
The aim of this study was to compare the morbidity, mortality, oncological results and quality of life between laparoscopic radical cystectomy (LRC) and open radical cystectomy (ORC) in the elderly patients over 75 years old. Between January 2012 and January 2015, 60 patients were recruited into this study, who were randomly assigned in a 1:1 ratio to either LRC or ORC group. Baseline patient characteristics, pathological factors, operative and postoperative characteristics, postoperative complications and survival data were retrospectively collected, analyzed and compared between the two groups. Patients in LRC group and ORC group had comparable baseline characteristics and pathological factors (all P > 0.05). LRC group required longer operative time (408.2 ± 76.9 vs. 311.7 ± 65.3 min, P = 0.000) and had less EBL (621.6 ± 100.7 vs. 1088.5 ± 109.4 ml, P = 0.000) compared with ORC group. The incidence of infection and ileus within 90 days after surgery in ORC group was significantly higher than LRC group(6.9% vs. 28.6%, P = 0.041; 3.4% vs. 25%, P = 0.025). At a median follow-up of 28 months (range 12–48 months), the survival analysis showed that there were no significant differences between the LRC and ORC groups in overall survival (log-rank χ2 = 0.122; P = 0.726), or progress-free survival (log-rank χ2 = 0.153; P = 0.696). In conclusion, this study confirmed that LRC could achieve similar tumor treatment efficacy compared to ORC, with fewer perioperative complications and less blood loss. We suggest that LRC should be considered as the primary intervention for patients aged over 75 years old with muscle invasive bladder cancer or non-muscle invasive bladder cancer with high risk factors.
Bladder disorders associated with interstitial cystitis are frequently characterized by increased contractility and pain. The goals of this study were to examine 1) the effects of blocking proteinase-activated receptor-2 (PAR2) on the exaggerated bladder activity and pain evoked by cystitis and 2) the underlying mechanisms responsible for the role of PAR2 in regulating cystic sensory activity. The protein expression of PAR2 was amplified in rats with cystitis by inducing it with systemic administration of cyclophosphamide (CYP) as compared with control rats. Blocking PAR2 by intrathecal infusion of PAR2 antagonist FSLLRY-NH2 attenuated bladder hyperactivity and pain. In addition, blocking PAR2 attenuated the transient receptor potential A1 (TRPA1) signal pathway, whereas inhibition of the TRPA1 decreased bladder hyperactivity and pain. The data revealed specific signaling pathways leading to CYP-induced bladder hyperactivity and pain, including the activation of PAR2 and TRPA1. Inhibition of these pathways alleviates cystic pain. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of overactive bladder and pain often observed in cystitis.
BackgroundBladder disorders associated with interstitial cystitis are frequently characterized by increased contractility and pain. The purposes of this study were to examine (1) the effects of blocking mammalian target of rapamycin (mTOR) on the exaggerated bladder activity and pain evoked by cystitis and (2) the underlying mechanisms responsible for the role of mTOR in regulating cystic sensory activity.ResultsThe expression of p-mTOR, mTOR-mediated phosphorylation of p70 ribosomal S6 protein kinase 1 (p-S6K1), 4 E–binding protein 4 (p-4 E-BP1), as well as phosphatidylinositide 3-kinase (p-PI3K) pathway were amplified in cyclophosphamide rats as compared with control rats. Blocking mTOR by intrathecal infusion of rapamycin attenuated bladder hyperactivity and pain. In addition, blocking PI3K signal pathway attenuated activities of mTOR, which was accompanied with decreasing bladder hyperactivity and pain. Inhibition of either mTOR or PI3K blunted the enhanced spinal substance P and calcitonin gene-related peptide in cyclophosphamide rats.ConclusionsThe data for the first time revealed specific signaling pathways leading to cyclophosphamide-induced bladder hyperactivity and pain, including the activation of mTOR and PI3K. Inhibition of these pathways alleviates cystic pain. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of overactive bladder and pain often observed in cystitis.
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