Study design: Retrospective longitudinal study of short-and long-term urinary complications in chronic spinal cord injury (SCI) patients managed at the Midlands Centre for Spinal Injuries (MCSI). Setting: MCSI, Oswestry, UK. Method: A total of 185 SCI patients were admitted to the MCSI between 1984 and 1989. Only 119 patients who met the following criteria were included: traumatic SCI, Frankel grade A-D, admission within 6 weeks post injury, regular annual follow-up or alternate year at MCSI, follow-up longer than 8 years. Follow-up ranged between 8 and 21 years with a mean of 17.7 (s.d. ¼ 1.98). The method of bladder drainage varied from the time of injury. Drainage was by indwelling urethral catheterisation (IndUC) before admission to the MCSI. Within 24 h of admission, assisted clean intermittent catheterisation (ACIC) by the nursing staff was commenced. This was followed by clean intermittent self catheterisation (CISC) once the patient was mobilised in the wheel chair and trained in the procedure. When detrusor reflex activity develops, patients with good hand function were given a choice between CISC and reflex voiding (RV). Patients with poor hand function are given the choice between RV, suprapubic catheters or ACIC during hospitalisation and after discharge. Only a minority of these patients choose ACIC following discharge. RV was supplemented occasionally by sphincterotomy. There were 99 males and 20 females (5:1). The age at the time of injury was 16-63 years with a mean of 29 (s.d. ¼ 12). Instead of a single method, a pattern of bladder management was analysed in the context of three continuous phases: Phase1 preadmission to MCSI. Phase2 during first hospitalisation at MCSI. Phase3 post discharge. In each phase, the patients were divided into those with and without complications. The complications were analysed in relation to the management and other relevant factors. Results: The total complication rate at all stages was 62%. Complications of the upper urinary tract accounted for 22.6%. These results compared favourably with published material. Conclusion: The sequential system of supervised bladder management commencing with brief IndUC followed by IntC and/or RV remains effective in keeping the complication rate relatively low in SCI patients, who undergo regular surveillance and timely intervention. Sponsorship: The project was supported by SPIRIT, a charitable not for profit trust that supports teaching, training, clinical research and dissemination of knowledge about all aspects of spinal paralysis in the UK.

Aim JQ1, a BET bromodomain inhibitor, is a promising therapeutic approach for bladder cancer (BC). Our study aimed to determine whether autophagy is induced by JQ1 and its potential role toward proliferation in BC. Methods Cell proliferation was determined by methylthiazolyldiphenyl‐tetrazolium bromide (MTT) assay, cell counting assay, and colony formation assay. Autophagosomes and autolysosomes were observed by transmission electron microscopy and mRFP‐EGFP‐LC3 fluorescence assay. 3‐MA, BAFA1, NH 4 Cl, and siATG5 were used to inhibit autophagy. AMPK siRNA was used to knock down AMPK. T24 xenograft model in mice was chosen to perform in vivo studies. Autophagy markers LC‐3B and p62, p‐AMPK α , p‐ACC, p‐ULK1, p‐mTOR and p‐LKB1 were determined by western blot in vitro studies and by immunohistochemistry (IHC) in vivo specimens. Results We found that BC cell proliferation was suppressed by JQ1; moreover, JQ1 induced the accumulation of autophagosomes and autolysosomes, and autophagy flux, and the growth suppression capacity of JQ1 was attenuated by autophagy inhibitors. Furthermore, we found that JQ1 induced the phosphorylation of AMPK α , and AMPK α knockdown attenuated autophagy induction and anti‐proliferation effect induced by JQ1 in BC cells, indicating that autophagy induced by JQ1 is dependent on AMPK α . Through endogenous immunoprecipitation analysis, we found that JQ1 dramatically increased the interaction between LKB1 and AMPK α , which may lead to more AMPK activation. Proliferation inhibition, autophagy induction, and LKB1/AMPK activation capacities of JQ1 were further confirmed in vivo. Conclusions Taken together, our results demonstrate that autophagy is induced by JQ1 through activation of LKB1/AMPK pathway, and the autophagy induced by JQ1 positively contributes to the inhibition of BC cell proliferation. These findings provide a novel point of view to understand the mechanism of how targeting BET bromodomain suppress cancer cell growth and suggest that targeting BET bromodomain might be a potential approach to treat BC in the future.

KIFC1 (kinesin motor) plays a critical role in clustering of extra centrosomes in various cancer cells and thus to be considered as a promising therapeutic target. However, whether KIFC1 is involved in the procession of renal cell carcinoma (RCC) still remains unclear. In this study, we found that KIFC1 was upregulated in RCC tissues and responsible for RCC tumorigenesis (P < 0.001). The high expression of KIFC1 correlates with aggressive clinicopathologic parameters. Kaplan-Meier analysis suggested that KIFC1 was associated with poor survival prognosis in RCC. Silencing KIFC1 dramatically resulted in inhibition of the proliferation, delayed cell cycle at G2/M phase, suppression of cell invasion and migration in vitro. Moreover, antiproliferative effect of KIFC1 silencing was also observed in xenografted tumor in vivo. miR-338-3p could directly binding to the 3'-untranslated region (UTR) of KIFC1, and ectopic miR-338-3p expression mimicked the inhibitory functions of KIFC1 silencing on RCC cells through inactivation of P13K/AKT signaling pathway. Therefore, these results revealed that KIFC1 may be a novel biomarker and an effective therapeutic target for the treatment of RCC.

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BackgroundThe aquaporins (AQPs), water channel proteins, are known playing a major role in transcellular and transepithelial water movement; they also exhibit several properties related to tumor development. The aim of the present study is to elucidate whether the expression of AQP5 is a strong prognostic biomarker for prostate cancer, and the potential role in the progression of prostate cancer cells.MethodsAQP5 expression was measured in 60 prostate cancer tissues and cells (both PC-3 and LNCaP) by immunohistochemistry and immunofluorescence assay. AQP5 gene amplification was detected with FISH (fluorescence in situ hybridization). Proliferation and migration of cells and AQP5 siRNA cells were detected with MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and Boyden chambers. Circulating tumor cells (CTCs) were detected by imFISH staining (CEP8-CD45-DAPI) assay.ResultsThe results showed that in 60 tumor specimens, 19 (31.7%) patients showed high level of AQP5 expression, while 30 (50.0%) showed a moderate, intermediate level of staining, and 11 (18.3%) showed an absence of AQP5 staining, respectively. High-expression of AQP5 protein frequently accompanied gene amplification detection with FISH. The AQP5 over-expression was also associated with TNM stage (P = 0.042), and lymph node metastasis (P = 0.001). The relationships between age or tumor size with the expression of AQP5 were not significant (P > 0.05). A positive correlation between the number of CTCs and AQP5 expression (P < 0.05) was demonstrated. In addition, patients who were negative for AQP5 had superior cumulative survival rate than those who were positive for it. Over-expression of AQP5 protein was also found in prostate cancer cells and cell proliferation and migration were significantly attenuated by AQP5-siRNA.ConclusionsWe concluded that AQP5 in prostate cancer was an independent prognostic indicator. AQP5 over-expression was likely to play a role in cell growth and metastasis. These conclusions suggest that AQP5 may be an effective therapeutic target for prostate cancer.

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