Diandong Yang

Efficacy and Safety of Flibanserin in Women with Hypoactive Sexual Desire Disorder: A Systematic Review and Meta-Analysis

INTRODUCTION Flibanserin, is a postsynaptic agonist of serotonin receptor 1A and an antagonist of serotonin receptor 2A, has been shown to increase sexual desire and reduce distress in women with hypoactive sexual desire disorder (HSDD). AIM We carried out a systematic review and meta-analysis to assess the efficacy and safety of the drug in women with HSDD. METHODS A literature review was performed to identify all published randomized double-blind, placebo-controlled trials of flibanserin for the treatment of HSDD. The search included the following databases: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. The reference lists of the retrieved studies were also investigated. MAIN OUTCOME MEASURES Four publications involving a total of 3,414 patients were used in the analysis, including four randomized controlled trials that compared flibanserin with placebo. RESULTS For the comparison of flibanserin with placebo, primary efficacy endpoints: satisfying sexual events (the standardized mean difference [SMD] = 0.59, 95% confidence interval [CI] = 0.37-0.80, P < 0.00001); sexual desire score (the SMD = 1.91, 95% CI = 0.21 to 3.60, P = 0.03) and Female Sexual Function Index (FSFI) desire domain score (the SMD = 0.32, 95% CI = 0.19-0.46, P < 0.00001) and key secondary efficacy endpoints: FSFI total score, Female Sexual Distress Scale-Revised (FSDS-R) total score, FSDS-R Item 13 score, Patients Global Impression of Improvement score and Patient Benefit Evaluation indicated that flibanserin was more effective than the placebo. Safety assessments included the proportion of women who experienced an adverse event (odds ratio = 1.54, 95% CI =  .34 to 1.76, P < 0.00001), nervous system disorders and fatigue indicated that flibanserin was well tolerated. CONCLUSIONS This meta-analysis indicates that flibanserin to be an effective and safe treatment for HSDD in women.

Androgen receptor in human prostate cancer-associated fibroblasts promotes prostate cancer epithelial cell growth and invasion

The androgens and androgen receptor (AR) play key roles in the prostate cancer (PCa) development and progression via epithelium-stroma cross talk. Prostate cancer-associated fibroblasts (CAFs) are dominant components in PCa stroma and are essential in the malignant progression by supporting tumorigenesis and metastasis. However, the AR roles in CAFs are still obscure. We isolated and immortalized the CAFs from human PCa tissues and found the CAFs are AR positive. We then knocked down their AR with siRNA and co-cultured the resultant CAFs with PCa cell line PC3. The MTT, invasion, and colony formation assays were performed to study the PC3 biological behavior. The results showed that the PCa epithelial growth, invasion, and colony formation abilities decreased when knocking down the CAFs AR. By using the real-time quantitative polymerase chain reaction, we found the IGF1, FGF7, FGF10, SDF1, HGF, and TGFb2 expression levels decreased in the AR knocked down CAFs. These results suggested that the AR in CAFs promoted PCa epithelial growth and invasion via regulating a series of growth factors. Targeting the AR in CAFs might be a potential therapeutic option for PCa in future.

Laparoscopic radical cystectomy with extracorporeal ileal conduit urinary diversion for treatment of Chinese bladder cancer patients.

Purpose: To present our experience in laparoscopic radical cystectomy with extracorporeal urinary diversion for treatment of Chinese bladder cancer patients. Methods: Between January 2003 and November 2005, 41 men and 5 women with organ-confined muscle-invasive transitional cell carcinoma of the bladder underwent laparoscopic radical cystectomy with the Bricker-type urinary diversion. The age range was 36–71 years. Laparoscopic radical cystectomy and bilateral pelvic lymphadenectomy were performed using five fan-shaped ports by a transperitoneal approach. An ileal conduit diversion was created through the site of specimen retrieval which was the second port at the region of the right pararectus. Results: 46 radical cystectomies with Bricker-type ileal conduits were performed. No conversion to open surgery was necessary. Mean operating time was 220 min (range 120–249 min) for laparoscopic radical cystectomy and 75 min (range 65–120 min) for creating the ileal conduits. Mean estimated blood loss was 276 ml (range 155–567 ml). Two of the 46 patients needed blood transfusion (400 ml each). Mean days to ambulation and oral intake was 4.1 (range 3–5 days) and 3.5 (range 3–6 days), respectively. Mean hospital stay was 17.6 days (range 12–35 days). Mean follow-up was 6.1 months (range 3–19 months). Histopathological examination of the specimens revealed stage T2N0M0 in 18 cases, T3aN0M0 in 14, T3bN0M0 in 9 and T3bN1M0 in 5 (TNM staging). WHO grading: G1 in 2 cases, G2 in 26 cases and G3 in 18 cases. Pelvic metastases appeared in one case and 44 patients are alive and free of disease. Intravenous pyelogram at 3 weeks postoperatively shows no evidence of upper urinary obstruction in 45 patients. Conclusion: Despite technical difficulties, laparoscopic radical cystectomy with Bricker-type urinary diversion is feasible. With more experience in the surgical technique, laparoscopic radical cystectomy with extracorporeal urinary diversion can become an alternative treatment of choice in the selected patients with organ- confined bladder cancer in China.

MicroRNA-294 promotes cellular proliferation and motility through the PI3K/AKT and JAK/STAT pathways by upregulation of NRAS in bladder cancer

In our study we examined the role of microRNA-294 (miR-294) in bladder cancer and related mechanisms. Realtime polymerase chain reaction (RT-PCR) was performed to determine the expression level of miR-294. Western blot was used to determine the expression of NRAS, mainly factors in the PI3K/AKT and JAK/STAT pathways. Cell counting kit8 assay, clonogenic assay, wound-healing assay, transwell and flow cytometry were used to explore, respectively, cell proliferation, survival, migration, invasion, and apoptosis of bladder cancer cell line T24. The expressions of miR-294 in bladder cancer cells including J82, HT1376, T24, and SW780 were significantly increased compared to those in human bladder epithelium cells (both HCV29 and SV-HUC-1). The proliferation rate, surviving fraction, migration, and invasion of T24 cells in miR-294 mimetic transfected group were significantly increased, while they were significantly decreased by miR294 inhibitor transfection. Moreover, miR-294 suppression could increase the apoptotic rate of T24 cells. In addition, drug resistance of T24 cells to cisplatin was increased in miR-294 mimetic-treated group, while it was decreased by miR-294 inhibitor compared to empty control. Overexpression of miR-294 could upregulate NRAS expression in T24 cells and activate PI3K/AKT and JAK/STAT pathways. We found that miR-294 expression was positively related with proliferation and motility of T24 cells. Moreover, miR-294 suppression could promote the sensitivity of T24 cells to cisplatin. We also found miR-294 could upregulate NRAS and activate the PI3K/AKT and JAK/STAT pathways in T24 cells.

Waterjet Dissection for Partial Nephrectomy Without Hilar Clamping in a Porcine Model

Hilar clamping is typically used in partial nephrectomy to control hemorrhage, which may damage the renal tissue under warm ischemia conditions. The purpose of this study was to evaluate waterjet technology in partial nephrectomy without renal hilar vascular control in a porcine model. Bilateral partial nephrectomy using waterjet was performed in 8 pigs (16 kidneys: 8 for wedge resections, 8 for pole resections). The operations were performed successfully in all animals. The mean dissection time was 30.6 ± 2.9 minutes for pole resections and 36.5 ± 3.5 minutes for wedge resections. The mean blood loss was 51.6 ± 11.7 mL for pole resections and 38.7 ± 9.2 mL for wedge resections. The novel waterjet technique provided precise and effective hydrodissection of the kidney, avoiding damage to the vascular structures or collecting system.

The efficacy and safety of silodosin for the treatment of ureteral stones: a systematic review and meta-analysis

BackgroundTo evaluate the efficacy and safety of silodosin as a medical expulsive therapy for ureteral stones by means of a systematic review and meta-analysis.MethodsWe searched MEDLINE, EMBASE and the Cochrane Controlled Trials Register to identify randomized controlled trials (RCTs) of silodosin in the treatment of ureteral stones. The reference lists of retrieved studies were also investigated.ResultsSix RCTs, including 916 participants and comparing silodosin with controls, were used in the meta-analysis. Silodosin was superior to controls in terms of stone expulsion rate, the primary efficacy end point in all six RCTs (odds ratio [OR] for expulsion 2.16, 95 % confidence interval [CI] 1.62 to 2.86, p <0.00001). Silodosin was also more effective for secondary efficacy end points; the stone expulsion time (standardized mean difference [SMD] −3.66, 95 % CI −6.61 to −0.71; p =0.01) and analgesic requirements (SMD −0.89, 95 % CI −1.19 to −0.60; p < 0.00001) were significantly reduced compared with those of controls. Other than the incidence of abnormal ejaculation, which was higher in the silodosin groups (OR 2.84, 95 % CI 1.56 to 5.16, p =0.0006), few adverse effects were observed.ConclusionThis meta-analysis indicates silodosin is an effective and safe treatment option for ureteral stones with a low occurrence of side effects.

Knockdown of mediator subunit Med19 suppresses bladder cancer cell proliferation and migration by downregulating Wnt/β-catenin signalling pathway

Mediator complex subunit 19 (Med19), a RNA polymerase II‐embedded coactivator, is reported to be involved in bladder cancer (BCa) progression, but its functional contribution to this process is poorly understood. Here, we investigate the effects of Med19 on malignant behaviours of BCa, as well as to elucidate the possible mechanisms. Med19 expression in 15 BCa tissues was significantly higher than adjacent paired normal tissues using real‐time PCR and Western blot analysis. Immunohistochemical staining of 167 paraffin‐embedded BCa tissues was performed, and the results showed that high Med19 protein level was positively correlated with clinical stages and histopathological grade. Med19 was knocked down in BCa cells using short‐hairpin RNA. Functional assays showed that knocking‐down of Med19 can suppress cell proliferation and migration in T24, UM‐UC3 cells and 5637 in vitro, and inhibited BCa tumour growth in vivo. TOP/FOPflash reporter assay revealed that Med19 knockdown decreased the activity of Wnt/β‐catenin pathway, and the target genes of Wnt/β‐catenin pathway were down‐regulated, including Wnt2, β‐catenin, Cyclin‐D1 and MMP‐9. However, protein levels of Gsk3β and E‐cadherin were elevated. Our data suggest that Med19 expression correlates with aggressive characteristics of BCa and Med19 knockdown suppresses the proliferation and migration of BCa cells through down‐regulating the Wnt/β‐catenin pathway, thereby highlighting Med19 as a potential therapeutic target for BCa treatment.

Cathelicidin LL37 promotes epithelial and smooth-muscle-like differentiation of adipose-derived stem cells through the Wnt/β-catenin and NF-κB pathways

Ureter reconstruction is a difficult procedure in urology. Adipose-derived stem cells (ADSCs), along with multipotency and self-renewal capacity, are a preferred choice for tissue engineering-based ureteral reconstruction. We explored the synergic role of cathelicidin LL37 (LL37) in epithelial and smooth-muscle-like differentiation. ADSCs were separated from adipose tissues of mouse and characterized by flow cytometry. The ADSCs were then stably transfected with pGC-FU-GFP (pGC) or pGC containing full-length LL37 (pGC-LL37), respectively. Cell viability and apoptosis were respectively estimated in the stably transfected cells and non-transfected cells. Then, qRT-PCR and Western blot analysis were used for determinations of epithelial marker expressions after induction by all-trans retinoic acid as well as smooth-muscle-like marker expressions after induction by transforming growth factor-β1. Then, possibly involved signaling pathways and extracellular expression of LL37 were detected. Cell viability and apoptosis were not changed after LL37 overexpression. Expression levels of epithelial and smooth-muscle-like markers were significantly upregulated by LL37 overexpression. Moreover, expressions of key kinases involved in the Wnt/β-catenin pathway as well as epithelial marker were upregulated by the LL37 overexpression, while it was reversed by Wnt/β-catenin inhibitor. Likewise, expressions of key kinases involved in the nuclear factor κB (NF-κB) pathway as well as smooth-muscle-like markers were upregulated by LL37 overexpression, which was reversed by NF-κB inhibitor. LL37 was found in the culture medium. LL37, which could be released into the medium, had no impact on cell proliferation and apoptosis of ADSCs. However, LL37 promoted epithelial and smooth-muscle-like differentiation through activating the Wnt/β-catenin and NF-κB pathways, respectively.

Investigation of key genes associated with prostate cancer using RNA-seq data

We aimed to identify key genes associated with prostate cancer using RNA-sequencing (RNA-seq) data. RNA-seq data, including 1 cancer sample and 1 adjacent normal sample, were downloaded from the NCBI SRA database and the differentially expressed genes (DEGs) were identified with the software Cufflinks. Functional enrichment analysis was performed to uncover the biological functions of DEGs. Regulatory information was retrieved from the IPA database and a network was established. A total of 147 DEGs were obtained, including 96 downregulated and 51 upregulated DEGs. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis suggested that metabolism and signal transduction were the 2 major functions that were significantly influenced. Moreover, an interaction network was built. In conclusion, a number of DEGs was identified and their roles in the pathogenesis of cancer were supported by previous studies. More studies are necessary to further validate their usefulness in the diagnosis and treatment of prostate cancer.