Zhiquan Hu

LncRNAs expression signatures of renal clear cell carcinoma revealed by microarray

Background Long noncoding RNAs (lncRNAs) are an important class of pervasive genes involved in a variety of biological functions. They are aberrantly expressed in many types of cancers. In this study, we described lncRNAs profiles in 6 pairs of human renal clear cell carcinoma (RCCC) and the corresponding adjacent nontumorous tissues (NT) by microarray. Methodology/Principal Findings With abundant and varied probes accounting 33,045 LncRNAs in our microarray, the number of lncRNAs that expressed at a certain level could be detected is 17157. From the data we found there were thousands of lncRNAs that differentially expressed (≥2 fold-change) in RCCC tissues compared with NT and 916 lncRNAs differentially expressed in five or more of six RCCC samples. Compared with NT, many lncRNAs were significantly up-regulated or down-regulated in RCCC. Our data showed that down-regulated lncRNAs were more common than up-regulated ones. ENST00000456816, X91348, BC029135, NR_024418 were evaluated by qPCR in sixty-three pairs of RCCC and NT samples. The four lncRNAs were aberrantly expressed in RCCC compared with matched histologically normal renal tissues. Conclusions/Significance Our study is the first one to determine genome-wide lncRNAs expression patterns in RCCC by microarray. The results displayed that clusters of lncRNAs were aberrantly expressed in RCCC compared with NT samples, which revealed that lncRNAs differentially expressed in tumor tissues and normal tissues may exert a partial or key role in tumor development. Taken together, this study may provide potential targets for future treatment of RCCC and novel insights into cancer biology.

Microwave ablation versus partial nephrectomy for small renal tumors: Intermediate-term results†

Prospective randomized comparison of intermediate‐term outcomes of patients with small renal tumors who were treated with partial nephrectomy (PN) or microwave ablation.

Robotic vs. open radical cystectomy in bladder cancer: A systematic review and meta-analysis

AIMS To evaluate the safety and efficacy of robot-assisted radical cystectomy (RARC) compared with open radical cystectomy (ORC) in the treatment of bladder cancer. METHODS A systematic search of Medline, Embase databases and the Cochrane Library was performed to identify studies that compared RARC and ORC and were published up to December 2012. Outcomes of interest included demographic and clinical characteristics, perioperative, pathologic variables and complications. RESULTS Although there was a significant difference in the operating time in favor of ORC (WMD: 70.69 min; p < 0.001), patients having RARC might benefit from significantly fewer total complications (OR: 0.54; p < 0.001), less blood loss (WMD: -599.03 ml; p < 0.001), shorter length of hospital stay (WMD: -4.56 d; p < 0.001), lower blood transfusion rate (OR: 0.13; p = 0.002), less transfusion needs (WMD: -2.14 units; p < 0.001), shorter time to regular diet (WMD: -1.57 d; p = 0.002), more lymph node yield (WMD: 2.18 n; p = 0.001) and fewer positive lymph node (OR: 0.64; p = 0.03). There was no significant difference between the RARC and ORC regarding positive surgical margins. CONCLUSIONS In early experience, our data suggest that RARC appears to be a safe, feasible and minimally invasive alternative to its open counterpart when performed by experienced surgeons in selected patients.

Mesenchymal stem cells and their secretome partially restore nerve and urethral function in a dual muscle and nerve injury stress urinary incontinence model

Childbirth injures muscles and nerves responsible for urinary continence. Mesenchymal stem cells (MSCs) or their secretome given systemically could provide therapeutic benefit for this complex multisite injury. We investigated whether MSCs or their secretome, as collected from cell culture, facilitate recovery from simulated childbirth injury. Age-matched female Sprague-Dawley rats received pudendal nerve crush and vaginal distension (PNC+VD) and a single intravenous (iv) injection of 2 million MSCs or saline. Controls received sham injury and iv saline. Additional rats received PNC+VD and a single intraperitoneal (ip) injection of concentrated media conditioned by MSCs (CCM) or concentrated control media (CM). Controls received a sham injury and ip CM. Urethral and nerve function were assessed with leak point pressure (LPP) and pudendal nerve sensory branch potential (PNSBP) recordings 3 wk after injury. Urethral and pudendal nerve anatomy were assessed qualitatively by blinded investigators. Quantitative data were analyzed using one-way ANOVA and Holm-Sidak post hoc tests with P < 0.05 indicating significant differences. Both LPP and PNSBP were significantly decreased 3 wk after PNC+VD with saline or CM compared with sham-injured rats, but not with MSC or CCM. Elastic fiber density in the urethra increased and changed in orientation after PNC+VD, with a greater increase in elastic fibers with MSC or CCM. Pudendal nerve fascicles were less dense and irregularly shaped after PNC+VD and had reduced pathology with MSC or CCM. MSC and CCM provide similar protective effects after PNC+VD, suggesting that MSCs act via their secretions in this dual muscle and nerve injury.

Fluid intake and the risk of bladder cancer: results from the South and East China case-control study on bladder cancer

Although several studies have assessed the association between total fluid intake, specific drinks and bladder cancer, no firm conclusions can yet be drawn. Four hundred thirty two bladder cancer cases and 392 frequency matched hospital‐based controls recruited in the South and East of China between October 2005 and June 2008 were interviewed on their intake of 6 nonalcoholic and 3 alcoholic drinks. Age, sex, smoking and hospital‐adjusted odds ratios (OR) and 95 percent confidence intervals (95% CI) were calculated for all drinks and for total fluid intake using logistic regression. For 381 cases (81.9% men) and 371 controls (76.3% men), total fluid intake could be calculated. In men, an increase in total fluid intake was associated with a significantly decreased bladder cancer risk (OR 0.93, 95% CI: 0.88–0.99, per cup fluid consumed). Neither green nor black tea consumption was associated with bladder cancer. Daily consumption of milk significantly reduced the risk of bladder cancer by a half (OR 0.49, 95% CI: 0.32–0.76), which strengthens earlier suggestions that milk is probably associated with a decreased bladder cancer risk. Consumption of wine (OR 0.49, 95% CI: 0.34–0.70) and liquor/spirits (OR 0.65, 95% CI: 0.47–0.92) were associated with a significantly reduced risk. Consumption of water, fruit juice and beer appeared not associated with bladder cancer. There is no clear indication that the risks observed in this Chinese population are substantially different from those observed in Caucasian populations.

Epigenetic alterations of Krüppel-like factor 4 and its tumor suppressor function in renal cell carcinoma

Krüppel-like factor 4 (KLF4) is a transcription factor that can have divergent functions in different malignancies. The expression and role of KLF4 in renal cell cancer remain unclear. The purpose of this study is to determine epigenetic alterations and possible roles of KLF4 in renal cell carcinoma. The KLF4 expression in primary renal cell cancer tissues and case-matched normal renal tissues was determined by protein and messenger RNA analyses. The epigenetic alterations were detected by methylation-specific PCR and Sequenom MassARRAY. Kaplan-Meier curves and the log-rank test were used for the survival analysis. The effects of KLF4 on cell growth and epithelial-to-mesenchymal transition (EMT) were determined in renal cancer cell lines after viral-based and RNA activation-mediated overexpression of KLF4. In vivo antitumor activity of KLF4 was evaluated by using stably KLF4-transfected renal cancer cells. KLF4 expression was dramatically decreased in various pathological types of renal cancer and associated with poor survival after nephrectomy. Hypermethylation of KLF4 promoter mainly contributed to its expression suppression. In vitro assays indicated that KLF4 overexpression inhibited renal cancer cell growth and survival. KLF4 overexpression also suppressed renal cancer cell migration and invasion by altering the EMT-related factors. In vivo assay showed that ectopic expression of KLF4 also inhibited tumorigenicity and metastasis of renal cancer. Our results suggest that KLF4 is a putative tumor suppressor gene epigenetically silenced in renal cell cancers by promoter CpG methylation and that it has prognostic value for renal cell progression.

Laparoscopic versus Open Radical Cystectomy in Bladder Cancer: A Systematic Review and Meta-Analysis of Comparative Studies

Background and Objective More recently laparoscopic radical cystectomy (LRC) has increasingly been an attractive alternative to open radical cystectomy (ORC) and many centers have reported their early experiences in the treatment of bladder cancer. Evaluate the safety and efficacy of LRC compared with ORC in the treatment of bladder cancer. Methods A systematic search of Medline, Scopus, and the Cochrane Library was performed up to Mar 1, 2013. Outcomes of interest assessing the two techniques included demographic and clinical baseline characteristics, perioperative, pathologic and oncological variables, and post-op neobladder function and complications. Results Sixteen eligible trials evaluating LRC vs ORC were identified including seven prospective and nine retrospective studies. Although LRC was associated with longer operative time (p<0.001), patients might benefit from significantly fewer overall complications (p<0.001), less blood loss (p<0.001), shorter length of hospital stay (p<0.001), less need of blood transfusion (p<0.001), less narcotic analgesic requirement (p<0.001), shorter time to ambulation (p = 0.03), shorter time to regular diet (p<0.001), fewer positive surgical margins (p = 0.006), fewer positive lymph node (p = 0.05), lower distant metastasis rate (p = 0.05) and fewer death (p = 0.004). There was no significant difference in other demographic parameters except for a lower ASA score (p = 0.01) in LRC while post-op neobladder function were similar between the two groups. Conclusions Our data suggest that LRC appears to be a safe, feasible and minimally invasive alternative to ORC with reliable perioperative safety, pathologic & oncologic efficacy, comparable post-op neobladder function and fewer complications. Because of the inherent limitations of the included studies, further large sample prospective, multi-centric, long-term follow-up studies and randomized control trials should be undertaken to confirm our findings.

Epigenetic Inactivation of KLF4 is Associated with Urothelial Cancer Progression and Early Recurrence

PURPOSE KLF4 is a transcription factor with divergent functions in different malignancies. We analyzed KLF4 expression and DNA methylation, and their clinical relevance and biological function in urothelial cancer. MATERIALS AND METHODS Immunohistochemistry and Sequenom™ MassARRAY® were done to detect the expression and promoter methylation of KLF4 in urothelial cancer tissues. The association of the recurrence-free survival rate and decreased KLF4 or KLF4 methylation status was analyzed by the Kaplan-Meier method, Cox regression analysis and ROC assay. Lentivirus based KLF4 over expression and dsRNA mediated knockdown were used to detect KLF4 functions in urothelial cancer in vitro and in vivo. RESULTS KLF4 was down-regulated in urothelial cancer due to promoter hypermethylation. Each correlated with recurrence-free survival in patients with nonmuscle invasive bladder cancer after transurethral resection of bladder cancer, which potentiates them as valuable predictive biomarkers for early recurrence. Moreover, in and ex vivo experiments showed that KLF4 suppressed urothelial cancer cell growth, migration and invasion inhibited the epithelial-to-mesenchymal transition. CONCLUSIONS KLF4 may function as a tumor suppressor gene in urothelial cancer since down-regulation of KLF4 by promoter hypermethylation would promote cancer progression. In addition, decreased expression of KLF4 or its promoter hypermethylation may have predictive value for early recurrence in patients with nonmuscle invasive bladder cancer.

Early Outcomes of Thulium Laser Versus Transurethral Resection of the Prostate for Managing Benign Prostatic Hyperplasia: A Systematic Review and Meta-Analysis of Comparative Studies

PURPOSE To assess the efficacy and safety of thulium laser resection of the prostate (TmLRP) vs transurethral resection of the prostate (TURP) for treating patients with benign prostatic hyperplasia (BPH). METHODS A systematic search of the electronic databases, including Medline, Scopus, China National Knowledge Infrastructure, and the Cochrane Library was performed up to May 1, 2013. The pooled outcomes of interest assessing the two techniques included demographic and clinical baseline characteristics, perioperative variables, complications, and postoperative efficacy including maximum flow rate (Qmax), postvoid residual (PVR), quality of life (QoL) and International Prostate Symptom Score (IPSS). RESULTS Nine trials assessing TmLRP vs. TURP were considered suitable for meta-analysis including three randomized controlled trials (RCTs), two prospective, and four retrospective studies. Compared with TURP, although TmLRP needed a longer operative time (weighted mean difference [WMD]: 9.00 min; 95% confidence interval [CI], 2.53-15.47; P=0.006), patients having TmLRP might benefit from significantly less serum sodium decreased (-3.58 mmol/L; 95% CI, -4.04 to -3.12; P<0.001), less serum hemoglobin decreased (WMD: -0.94 mmol/L; 95% CI, -1.44 to -0.44; P<0.001), shorter time of catheterization (WMD: -2.07 days; 95% CI, -2.66 to -1.49; P<0.001), shorter length of hospital stay (WMD: -1.87 days; 95% CI, -2.41 to -1.33; P<0.001), and fewer total complications (odds ratio [OR]: 0.29; 95% CI, 0.20-0.41; P<0.001). During the 1, 3, 6, and 12 months of postoperative follow-up, the procedures did not demonstrate a significant difference in Qmax, IPSS, PVR, and QoL. CONCLUSIONS Our data suggest that as a promising minimally invasive technique, TmLRP appears to be a safe, feasible, and efficient alternative to TURP for treating patients with BPH with reliable perioperative safety, fewer complications, and comparable efficacy in relation to Qmax, PVR, QoL, and IPSS. Because of the inherent limitations of the included studies, further large sample prospective, multicentric, long-term follow-up studies and RCTs should be undertaken to confirm our findings.

Anti-tumor activity of curcumin against androgen-independent prostate cancer cells via inhibition of NF-κB and AP-1 pathway in vitro.

The anti-tumor activity of curcumin against androgen-independent prostate cancer cells in vitro and the possible mechanism were investigated. After curcumin treatment, the effect of curcumin on the proliferation of prostate cancer PC-3 cells was assessed by CFSE staining. Flow cytometery (FCM) was performed to analyze the cell cycle and the induction of apoptosis of tumor cells. A luciferase reporter gene assay was used to determine the effects of curcumin on the activities of intracellular NF-κB and AP-1 signaling pathways. The results showed curcumin could effectively inhibit the proliferation of PC-3 cells in vitro (P<0.05). Cells were arrested at G2/M phase. After curcumin treatment, the percentage of apoptotic cells was significantly higher than in control group (P<0.05). The results of the luciferase assay revealed that curcumin selectively inhibited the activities of the NF-κB and AP-1 signaling pathways in PC-3 cells significantly. It was suggested that curcumin could exert anti-tumor activity against androgen-independent prostate cancer cells in vitro by inhibiting cellular proliferation and inducing apoptosis, which was probably contributed to the inhibition of transcription factors NF-κB and AP-1.SummaryThe anti-tumor activity of curcumin against androgen-independent prostate cancer cells in vitro and the possible mechanism were investigated. After curcumin treatment, the effect of curcumin on the proliferation of prostate cancer PC-3 cells was assessed by CFSE staining. Flow cytometery (FCM) was performed to analyze the cell cycle and the induction of apoptosis of tumor cells. A luciferase reporter gene assay was used to determine the effects of curcumin on the activities of intracellular NF-κB and AP-1 signaling pathways. The results showed curcumin could effectively inhibit the proliferation of PC-3 cells in vitro (P<0.05). Cells were arrested at G2/M phase. After curcumin treatment, the percentage of apoptotic cells was significantly higher than in control group (P<0.05). The results of the luciferase assay revealed that curcumin selectively inhibited the activities of the NF-κB and AP-1 signaling pathways in PC-3 cells significantly. It was suggested that curcumin could exert anti-tumor activity against androgen-independent prostate cancer cells in vitro by inhibiting cellular proliferation and inducing apoptosis, which was probably contributed to the inhibition of transcription factors NF-κB and AP-1.