Zhengyan Tang

Vascular endothelial growth factor-C expression in bladder transitional cell cancer and its relationship to lymph node metastasis.

To elucidate the role of vascular endothelial growth factor‐C (VEGF‐C) in bladder transitional cell carcinoma (TCC), examining VEGF‐C expression in bladder TCC tissue and the association of VEGF‐C with clinicopathological features, as the expression of VEGF‐C in several carcinomas is significantly associated with angiogenesis, lymphangiogenesis and regional lymph node metastasis, but there are few reports of VEGF‐C expression in bladder TCC.

Development and Validation of an Animal Model of Prostate Inflammation-Induced Chronic Pelvic Pain: Evaluating from Inflammation of the Prostate to Pain Behavioral Modifications

Background Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS) is the most common type of prostatitis. Due to the lack of a suitable animal model partly, the pathogenesis for this condition is obscure. In the current study we developed and validated an animal model for nonbacterial prostatitis and prostate inflammation-induced chronic pelvic pain in rats with the use of intraprostatic injection of λ-carrageenan. Methods Male Sprague-Dawley rats weighing 250–350 g were used for the experiments. After intraprostatic injection of 3% λ-carrageenan, at different time points(after 24 h, 7d, 14d and 30d of injection), radiant heat and von Frey filaments were applied to the scrotum of rats to measure the heat and mechanical thresholds respectively. Then the prostate was removed for histology, and cyclooxygenase (COX) 2 protein expression was determined by Western-blot. Evans blue(50 mg/kg) was also injected intravenously to assess for plasma protein extravasation at different time points after injection of λ-carrageenan. Results Compared to control group, inflamed animals showed a significant reduction in mechanical threshold (mechanical allodynia) at 24 h and 7d(p = 0.022,0.046, respectively), and a significant reduction in heat threshold (thermal hyperalgesia) at 24 h, 7d and 14d(p = 0.014, 0.018, 0.002, respectively) in the scrotal skin. Significant increase of inflammatory cell accumulation,COX2 expression and Evans blue extravasation were observed at 24 h, 7d and 14d after injection. Conclusions Intraprostatic λ-carrageenan injection induced neurogenic prostatitis and prostate inflammation pain, which lasted at least 2 weeks. The current model is expected to be a valuable preclinical tool to study the neurobiological mechanisms of male chronic pelvic pain.

Downregulation of VEGFA inhibits proliferation, promotes apoptosis, and suppresses migration and invasion of renal clear cell carcinoma

Objective The aim of this study was to investigate the effects of vascular endothelial growth factor A (VEGFA) on cell proliferation, apoptosis, migration, and invasion in renal clear cell carcinoma (RCCC). Methods Between June 2012 and June 2015, RCCC tissues were obtained for the experimental group, and RCCC adjacent tumor-free kidney parenchyma tissues were obtained for the control group. VEGFA mRNA and protein expressions and phosphoinositide 3-kinase, serine/threonine-specific protein kinase (AKT), and phosphorylated-AKT protein expressions were detected. The chemically synthesized specific siRNA using RNA interference technology was used to inhibit VEGFA gene expression in human RCCC 786-O cells. The negative control (NC) group was transfected with NC sequence, and the blank group was transfected with no sequence. Flow cytometry, scratch test, and cell-penetrating experiment were used to detect cell proliferation, apoptosis, migration, and invasion of 786-O cells. Results Positive expression of VEGFA protein was 60.62% in RCCC tissue and 18.34% in adjacent tissue with statistically significant difference (P<0.001). VEGFA protein and mRNA expressions were higher in RCCC tissue than those in adjacent tissue (both P<0.01). VEGF expression in RCCC tissue was associated with Fuhrman grading and American Joint Committee on Cancer staging (both P<0.05). After RCCC 786-O cells transfecting the VEGFA siRNA, the VEGFA mRNA and protein expressions and phosphoinositide 3-kinase and phosphorylated-AKT protein expressions were significantly decreased, cell proliferation was remarkably inhibited, cell apoptotic ratio was obviously increased, and migration distance and invasive cell number were markedly decreased compared to those in the NC group and the blank group (all P<0.05). Conclusion Inhibition of VEGFA inhibited proliferation, promoted apoptosis, and suppressed migration and invasion of RCCC 786-O cells. VEGF has a potential role in diagnosis and therapy of RCCC.

Metadherin regulates epithelial–mesenchymal transition in carcinoma

Metadherin (MTDH) was first identified in primary human fetal astrocytes exposed to HIV-1 in 2002 and then recognized as an important oncogene mediating tumorigenesis, progression, invasiveness, and metastasis of carcinomas. Epithelial–mesenchymal transition (EMT) is a vital process in embryonic development, organ repair, and cancer progression. MTDH and EMT have also been proved to be related to the prognosis of patients with cancers. Recent studies reveal a relationship between MTDH overexpression and EMT in some malignancies. This review highlights the overexpression of MTDH and EMT in cancers and their correlations in clinical studies. Positive correlations have been established between MTDH and mesenchymal biomarkers, and negative correlations between MTDH and epithelial biomarkers have also been established. Furthermore, experiments reveal EMT regulated by MTDH, and some signal pathways have been established. Some anticancer drugs targeting MTDH and EMT are introduced in this review. Some perspectives concerning EMT regulation by MTDH are also presented in this review.

Down-regulation of EZH2 by RNA Interference Inhibits Proliferation and Invasion of ACHN Cells via the Wnt/β- catenin Pathway

Although enhancer of zeste homolog 2 (EZH2) has been reported as an independent prognostic factor in renal cell carcinoma (RCC), little is known about the exact mechanism of EZH2 in promoting the genesis of RCC. However, several studies have shown that dysregulation of the Wnt/β-catenin signaling pathway plays a crucial role. Therefore, we determined whether EZH2 could affect ACHN human RCC cell proliferation and invasion via the Wnt/β-catenin pathway. In the present study, we investigated the effects of short interfering RNA (siRNA)-mediated EZH2 gene silencing on Wnt/β-catenin signaling in ACHN cells. EZH2-siRNA markedly inhibited the proliferation and invasion capabilities of ACHN, while also reducing the expression of EZH2, Wnt3a and β-catenin. In contrast, cellular expression of GSK-3β (glycogen synthase kinase-3β), an inhibitor of the Wnt/β-catenin pathway, was conspicuously higher after transfection of EZH2 siRNA. These preliminary findings suggest EZH2 may promote proliferation and invasion of ACHN cells via action on the Wnt/β-catenin signaling pathway.

Icariin improves the sexual function of male mice through the PI3K/AKT/eNOS/NO signalling pathway

We aimed to investigate the effect and mechanism of icariin on male sexual function. Forty‐eight Crl:CD1(ICR) male mice were randomly divided into control, low‐, medium‐ and high‐dose icariin group (intragastric administration of 50, 100 and 200 mg/kg/d for 21 days). Mating experiment was then performed at a ratio of 1: 3 (male: female). The mating behaviours of male mice were recorded. The genital indexes and serum testosterone, nitric oxide (NO), hypothalamic dopamine (DA) and 5‐ hydroxy tryptophan (5‐HT) concentrations were measured. The expression of endothelial nitric oxide (eNOS), phosphatidylinositol tallow alcohol 3‐kinase (PI3K) and phosphorylated protein kinase (p‐AKT) in penile tissue was detected by Western blot. All icariin groups exhibited shorter capture latency and ejaculation latency, increased number of capture and ejaculation, higher capture and ejaculation rate, and higher testicular and prostate indexes compared with controls (p < .001). These groups had higher serum testosterone and NO concentrations (p < .001), hypothalamic DA and 5‐HT levels, and eNOS, PI3K and phosphorylated AKT expressions in penile tissue (p < .05). The effect of icariin was dose‐dependently increased. Our study suggests that icariin improves the sexual function of male mice, which might be associated with the hypothalamic–pituitary–gonadal axis and the PI3K/AKT/eNOS/NO signalling pathway.

Use of the UPOINT phenotype system in treating Chinese patients with chronic prostatitis/chronic pelvic pain syndrome: a prospective study.

The urinary, psychosocial, organ-specific, infection, neurological/systemic and tenderness (UPOINT) phenotype system has been validated to be an effective phenotype system in classifying patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in western populations. To validate the utility of the UPOINT system and evaluate the effect of multimodal therapy based on the UPOINT system in Chinese patients with CP/CPPS, we performed this study. Chinese patients with CP/CPPS were prospectively offered multimodal therapy using the UPOINT system and re-examined after 6 months. A minimum 6-point drop in National Institutes of Health-Chronic Prostatitis Symptoms Index (NIH-CPSI) was set to be the primary endpoint. Finally, 140 patients were enrolled in the study. The percentage of patients with each domain was 59.3%, 45.0%, 49.3%, 22.1%, 37.9%, and 56.4% for the UPOINT, respectively. The number of positive domains significantly correlated with symptom severity, which is measured by total NIH-CPSI scores (r = 0.796, P< 0.001). Symptom duration was associated with a greater number of positive domains (r = 0.589, P< 0.001). With 6 months follow-up at least, 75.0% (105/140) had at least a 6-point improvement in NIH-CPSI after taking the therapy. All NIH-CPSI scores were significantly improved from original ones: pain 10.14 ± 4.26 to 6.60 ± 3.39, urinary 6.29 ± 2.42 to 3.63 ± 1.52, quality of life 6.56 ± 2.44 to 4.06 ± 1.98, and total 22.99 ± 7.28 to 14.29 ± 5.70 (all P< 0.0001). Our study indicates that the UPOINT system is clinically feasible in classifying Chinese patients with CP/CPPS and directing therapy.

Letter to the editor: “Urothelial barrier dysfunction: cause or outcome of ketamine-induced voiding dysfunction”

to the editor: Ketamine-induced cystitis was first reported by Shahani et al. in 2007 ([6][1]). Clinical presentations of this entity is characterized by lower urinary tract symptoms (LUTS), such as frequency, urgency, gross hematuria, and bladder pain ([2][2], [6][1]). The underlying mechanisms are

Clinical outcomes of transperitoneal laparoscopic unroofing and fenestration under seminal vesiculoscopy for seminal vesicle cysts

Symptomatic seminal vesicle cysts (SVCs), especially those of a large size, can be removed by surgical treatments. Currently, open surgeries for SVC are rarely performed due to their extensive surgical trauma, and minimally invasive surgical therapies for treating seminal vesicle cysts are still in the early stages. In addition, relevant studies are mostly confined to case reports. In this study, we retrospectively reviewed 53 patients who had received transperitoneal laparoscopic unroofing or fenestration under seminal vesiculoscopy for SVC in our institution. Both surgeries decreased the cyst volume to a significant extent; however, according to the remnant lesion size after rechecking images, seminal vesiculoscopic fenestration tended to have a higher recurrence than laparoscopic unroofing. Regarding complications, two individuals in the laparoscopic unroofing group experienced ureteral injury and rectal injury, while patients in the fenestration group only had temporary hemospermia, which indicates that fenestration surgery tends to have less severe complications than laparoscopic unroofing. There was no solid evidence confirming semen improvement after these surgical therapies in our study. Future studies with a prospective design, larger sample size, and longer follow-up period are required to verify and further explore our findings.

Ketamine‐induced upper urinary tract lesions deserve more attention

Ketamine has been used as an anesthetic agent since 1960s, and as a recreational drug since 1990s. Bladder dysfunction is one of the complications in patients with ketamine abusing, and ketamine-induced cystitis was first reported in 2007. Urologists had paid enough attentions to lower urinary tract syndromes since 2007; however, Wei and Yang considered the ketamine-induced urological lesions labelling as ‘‘ketemineinduced uropathy,’’ because complex cystic pathological changes and upper urinary tract damages could be coexist. Wood concluded that upper urinary tract should be paid enough attention because thewhole urinary system could be at risk in ketamine-abused patients. Wood also hold the viewpoint that CT may be not necessary if the renal function is within normal range and no hydronephrosis detected by ultrasound. Urologists focus on lower urinary symptoms because of several uncomfortable to the abusers, potential upper urinary lesions may be neglected by doctors. Recently, some serious upper urinary cases had been reported, and a separate attention should be paid on upper urinary tract including ketamine-induced cystitis. We would like to update recent evidences on ketamine-induced upper urinary tract lesions, and emphasis more attention on upper urinary tract system. According to clinical prospective researches and retrospective cases summaries, the incidence of hydronephrosis (bilateral or unilateral) ranged from 6% to 64.3% in different centers. Upper urinary tract lesions may be caused by these reasons: (i) contracted, overactive bladder, and decreased compliant bladder; (ii) vesicoureteric reflux; (iii) ureteric wall thickness or obstruction; (iv) abnormal ureter peristalsis; and (v) acute papillary necrosis. The actual mechanisms of katemineinduced upper urinary tract lesions need advanced investigations. Abstinence of ketamine has been an effective method to relief LUTS caused by ketamine-induced cystitis. However, some pathological damages could not be completely reversed after cessation of ketamine, such as fibrosis of bladder wall. Some urinary symptoms even deteriorate after cessation of ketamine. An earlier detection of upper urinary tract to monitor kidney function, a less burden and payment the patient would bear. Huang et al. thought that renal function and imaging should be closely monitored because upper urinary tract lesions may progress rapidly. CT has been an useful tool in the aid of diagnosis upper urinary tract lesions and detection potential etiologies, such as ureteric wall thickness, obstruction, and other lesions. We propose that renal function, plain and enhancement CT should be recommended in monitoring ketamine-induced uropathy, especially upper urinary tract involved, renal function, and lesions should be dynamically evaluated during long term follow-up. Upper urinary tract in ketamine-induced uropathy should be paidmore attention for clinicians. Renal function and CT should be taken into considerations in clinical practice.