microRNA-27b inhibits cell proliferation and invasion in bladder cancer by targeting engrailed-2.

BACKGROUND: Bladder cancer is considered a malignant tumour characterised by great heterogeneity. Engrailed-2 may be a gene implicated in bladder cancer. Bioinformatics analysis found base pair complementation between microRNA-27b and engrailed-2. The present study aimed to investigate the reciprocal association between microRNA-27b and engrailed-2 in bladder cancer. METHODS: The microRNA-27b and the protein of engrailed-2 in the tissues and cells of the bladder were detected. The processes of apoptosis, proliferation, invasion, and migration of tumour cells were evaluated. The co-action between microRNA-27b and engrailed-2 was detected by a luciferase reporter system. Finally, the interaction between microRNA-27b and engrailed-2 was further verified in vivo. RESULTS: The study found that the expression level of microRNA-27b is lower in bladder cancer tissues and cells than that in neighbouring ordinary tissues, whereas the opposite outcome was observed regarding the expression level of engrailed-2. Furthermore, microRNA-27b expression level is not significantly linked to the age of patients with bladder cancer; however, it is significantly associated with the clinicopathological grade of bladder cancer. Notably, engrailed-2 is negatively regulated by microRNA-27b. Transfection with microRNA-27b was associated with a significant reduction in the activity of bladder cancer cells and promoted apoptosis, while engrailed-2 restoration effectively reversed the above effects of microRNA-27b on bladder cancer in vitro and in vivo. CONCLUSIONS: In conclusion, engrailed-2 is engaged in the development and process of bladder cancer through the negative mediation of microRNA-27b; additionally, microRNA-27b/engrailed-2 could form a signalling pathway with a significant effect on the process of bladder cancer.

Triptorelin relieves lower urinary tract symptoms in Chinese advanced prostate cancer patients: a multicenter, non-interventional, prospective study.

BACKGROUND: Although triptorelin is increasingly used in China for biochemical castration, its effects on primary prostate cancer symptoms remain unclear. This study aimed to assess the prevalence of lower urinary tract symptoms (LUTS) in Chinese prostate cancer patients and the effectiveness of triptorelin on LUTS. METHODS: In this 48-week multicenter, non-interventional, prospective study, we enrolled patients with locally advanced or metastatic prostate cancer. Patients received triptorelin (15 mg) intramuscularly at baseline and at weeks 12, 24, and 36 with symptom assessment using the International Prostate Symptoms Score (IPSS). The primary endpoints were the prevalence of LUTS at baseline per IPSS categories and the percentage of patients with moderate to severe LUTS (IPSS > 7) at baseline, having at least a 3-point reduction of IPSS score at week 48. RESULTS: A total of 398 patients were included; 211 (53.0%) and 160 (40.2%) among them had severe and moderate LUTS, respectively. Of the patients with IPSS scores available at baseline and at week 48 (n = 213), 81.2% achieved a reduction in IPSS of at least 3 points. Of the patients with moderate to severe LUTS at baseline and IPSS scores available at baseline and at week 48 (n = 194), 86.6% achieved a total IPSS reduction of at least 3 points. CONCLUSIONS: The vast majority of Chinese patients with locally advanced or metastatic prostate cancer scheduled to receive triptorelin as part of their standard treatment have severe or moderate LUTS. Triptorelin therapy resulted in sustained improvement of LUTS in these patients.

A Panel of Biomarkers for Diagnosis of Prostate Cancer Using Urine Samples.

BACKGROUND/AIM: Prostate cancer (PCa) diagnosis using patient urine samples represents a non-invasive and more convenient method than the conventional biopsy and prostate-specific antigen (PSA) test. This study intended to identify a biomarker panel to distinguish PCa from benign prostate using urine samples. MATERIALS AND METHODS: We identified six biomarkers with differential gene expression in 154 PCa and benign prostate specimens. We then determined mRNA expression signature and the diagnostic performance of the 6-biomarker panel in 156 urine samples from patients with PCa and benign disease. RESULTS: The 6-biomarker panel distinguished PCa from benign prostate cases with sensitivity of 80.6%, specificity of 62.9% and area under the curve (AUC) of 0.803 (p<0.0001), whereas serum PSA at 4 ng/ml cutoff had sensitivity of 95.5%, specificity of 20.2% and AUC of 0.521 (p<0.0001). CONCLUSION: The 6-biomarker panel for use in urine samples was able to distinguish PCa from benign prostate with higher specificity and accuracy than PSA and may be useful in clinical settings.

Modified Mechanical Percussion for Upper Urinary Tract Stone Fragments After Extracorporeal Shock Wave Lithotripsy: A Prospective Multicenter Randomized Controlled Trial.

OBJECTIVE: To investigate the effectiveness of modified mechanical percussion for eliminating upper urinary tract stone fragments after extracorporeal shock wave lithotripsy. MATERIALS AND METHODS: We assigned patients aged 18-60 years with upper urinary tract calculi to the modified mechanical percussion (trial) or observation (control) group. Kidney-ureter-bladder radiography and ultrasound were used for diagnostic evaluation. The primary outcome was the stone-expulsion rate (SER) at 6 hours. The first stone-expulsion time, the SER at 3, 12, and 24 hours, the stone-free rate, additional interventions, and adverse events (AEs) were recorded. RESULTS: A total of 120 patients underwent randomization: 60 for each group. The mean first stone-expulsion time in the trial and control groups was 6.75 and 13.58 hours, respectively (P = .001). The SERs at 3, 6, and 12 hours in the trial group were 51.8%, 75.4%, and 76.8%, respectively, which were higher than the control group (all P <.05). Among patients who expelled fragments within 6 hours, the stone-free rates were improved at 1 week (P = .002) and at 2 weeks (P = .000). Patients needed fewer additional interventions in the trial group (P = .035). AEs occurred in 42.9% (24 of 56) and 67.9% (38 of 56) of the patients in the trial and control groups, respectively (P = .008). Age, gender, stone size and location, and SER at 24 hours did not differ significantly among the groups. CONCLUSION: Modified mechanical percussion significantly improved SERs and accelerated stone passage after shock wave lithotripsy, resulting in a stone-free status with a lower risk of AEs and reduced need for additional interventions.

Efficacy and Safety of Tamsulosin in Medical Expulsive Therapy for Distal Ureteral Stones with Renal Colic: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial.

BACKGROUND: Recent large high-quality trials have questioned the clinical effectiveness of medical expulsive therapy using tamsulosin for ureteral stones. OBJECTIVE: To evaluate the efficacy and safety of tamsulosin for distal ureteral stones compared with placebo. DESIGN, SETTING, AND PARTICIPANTS: We conducted a double-blind, placebo-controlled study of 3296 patients with distal ureteral stones, across 30 centers, to evaluate the efficacy and safety of tamsulosin. INTERVENTION: Participants were randomly assigned (1:1) into tamsulosin (0.4mg) or placebo groups for 4 wk. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end point of analysis was the overall stone expulsion rate, defined as stone expulsion, confirmed by negative findings on computed tomography, over a 28-d surveillance period. Secondary end points included time to stone expulsion, use of analgesics, and incidence of adverse events. RESULTS AND LIMITATIONS: Among 3450 patients randomized between September 1, 2011, and August 31, 2013, 3296 (96%) were included in the primary analysis. Tamsulosin benefits from a higher stone expulsion rate than the placebo (86% vs 79%; p<0.001) for distal ureteral stones. Subgroup analysis identified a specific benefit of tamsulosin for the treatment of large distal ureteral stones (>5mm). Considering the secondary end points, tamsulosin-treated patients reported a shorter time to expulsion (p<0.001), required lower use of analgesics compared with placebo (p<0.001), and significantly relieved renal colic (p<0.001). No differences in the incidence of adverse events were identified between the two groups. CONCLUSIONS: Our data suggest that tamsulosin use benefits distal ureteral stones in facilitating stone passage and relieving renal colic. Subgroup analyses find that tamsulosin provides a superior expulsion rate for stones >5mm, but no effect for stones ≤5mm. PATIENT SUMMARY: In this report, we looked at the efficacy and safety of tamsulosin for the treatment of distal ureteral stones. We find that tamsulosin significantly facilitates the passage of distal ureteral stones and relieves renal colic.

HMGB1-mediated autophagy confers resistance to gemcitabine in hormone-independent prostate cancer cells.

As a main treatment of prostate cancer, castration therapy has been widely applied in the clinic. However, the therapeutic strategy for hormone-independent prostate cancer (HIPC) was not satisfied. Gemcitabine is an important chemotherapeutic agent that has been approved for the treatment of numerous human solid tumors, including HIPC, whereas the gemcitabine resistance has become a serious problem in clinical chemotherapy. In the present study, the mechanisms of resistance to gemcitabine were investigated in HIPC cell lines. The results demonstrated that the autophagy markers were induced significantly in HIPC cells subsequent to gemcitabine treatment. Meanwhile, administration of gemcitabine to HIPC cells increased the expression of high mobility group box1 (HMGB1). Furthermore, the gemcitabine-induced autophagy response was attenuated in stable HIPC cells harboring HMGB1 shRNA. Notably, the HIPC cells stably transfected with HMGB1 shRNA or treated with autophagy inhibitors were more sensitive to gemcitabine compared with the control group. These data suggested that inhibition of HMGB1 increased the sensitivity to gemcitabine by decreasing autophagy response in HIPC cells. Overall, the present findings demonstrate a new mechanism for the resistance to gemcitabine in HIPC cell lines.

Knocking down glycoprotein nonmetastatic melanoma protein B suppresses the proliferation, migration, and invasion in bladder cancer cells.

Glycoprotein nonmetastatic melanoma protein B is a type 1 transmembrane protein that has been recently found to play a role in cancer cell proliferation, angiogenesis, and invasion. Due to its potential responsibility in cancer aggressiveness, the main objective of this work was to investigate its expression in bladder cancer and the biological functions in bladder cancer cells. Using immunohistochemistry, western blot, and reverse transcription polymerase chain reaction, we analyzed the expression of glycoprotein nonmetastatic melanoma protein B in bladder cancer tissues and bladder cancer cell lines. The effects of glycoprotein nonmetastatic melanoma protein B on proliferation, migration, and invasion were tested after knocking down the glycoprotein nonmetastatic melanoma protein B in bladder cancer cells with small interfering RNAs by CCK-8, Transwell, and Matrigel assays. Our results showed that glycoprotein nonmetastatic melanoma protein B protein was highly expressed in the bladder cancer tissues and cell lines. Downregulating glycoprotein nonmetastatic melanoma protein B could suppress the proliferation, migration, and invasion in bladder cancer cells. Glycoprotein nonmetastatic melanoma protein B expression was related to the poor differentiation and recurrence by immunohistochemistry analysis. The survival analysis also showed that glycoprotein nonmetastatic melanoma protein B was related to the patient prognosis. In conclusion, Glycoprotein nonmetastatic melanoma protein B protein was highly expressed in the bladder cancer, which was related to the poor prognosis in bladder cancer patients. Glycoprotein nonmetastatic melanoma protein B promoted the proliferation, migration, and invasion in bladder cancer cells.

Prospective Study of CRMP4 Promoter Methylation in Prostate Biopsies as a Predictor For Lymph Node Metastases.

Background: For patients with prostate cancer (PCa), the presence of pelvic lymph node metastasis (LNM) is a strong predictor of poor outcome. However, the approaches with promising sensitivity and specificity to detect LNM are still lacking. We investigated the value of collapsin response mediator protein 4 (CRMP4) promoter methylation in biopsies as a predictor for LNM. Methods: CRMP4 promoter methylation at two previously identified CpG sites was determined in 80 case-matched biopsy samples (the training set) using bisulfite pyrosequencing. The predictive cutoff value was independently validated using cohort I of 339 PCa patients (Southern China) and cohort II of 328 case patients (Germany, across China). Mann-Whitney U test, the receiver operating characteristic curve, McNemar's test, and logistic regression were used to assess data. All statistical tests were two-sided. Results: In the training set, CRMP4 promoter methylation (≥15.0% methylated) was statistically significantly associated with LNM (P < 001). Successful validations were achieved in both cohorts I and II (sensitivity = 92.3%, 95% confidence interval [CI] = 79.3 to 97.9, and sensitivity = 92.2%, 95% CI = 81.1 to 97.8, respectively; specificity = 92.7%, 95% CI = 80.2 to 99.1, and specificity = 91.3%, 95% CI = 87.4 to 94.4, respectively). The sensitivity of CRMP4 promoter methylation is superior to conventional MRI (cohort I: 92.3% vs 26.2%, P < 001; cohort II: 92.2% vs 33.3%, P < 001). CRMP4 promoter methylation is an independent predictor of LNM (cohort I: hazard ratio [HR] = 8.35, 95% CI = 5.64 to 12.35, P < 001; cohort II: HR = 12.46, 95% CI = 5.82 to 26.70, P < 001) in a multivariable analysis model. Conclusion: CRMP4 promoter methylation in diagnostic biopsies could be a robust biomarker for LNM in PCa.

Psychological burden, sexual satisfaction and erectile function in men whose partners experience recurrent pregnancy loss in China: a cross-sectional study.

BACKGROUND: The aim of this study was to elucidate recurrent pregnancy loss (RPL)-associated psychosocial effects and sexual functions of Chinese men whose partners experience a history of RPL. METHODS: Questionnaire data from a total of 236 men whose partners experience RPL(RPL group) and another 236 non-RPL male volunteers(control group) were analyzed. The self-administered questionnaires included anxiety and depression measures (SAS & SDS), the Index of Sexual Satisfaction (ISS) and the International Index of Erectile Function (IIEF-5) for evaluating psychological burden, sexual satisfaction and erectile function, respectively. RESULTS: The mean age of the RPL group and control group was 29.8 ± 8.6 and 28.2 ± 7.3, respectively. The incidence of erectile dysfunction was significantly higher in the RPL group than in the control group (19.07 % vs. 7.63 %, P < 0.001). Anxiety and depression were also more prevalent in RPL group than in the control group (anxiety: 36.90 % vs. 19.08 %, P < 0.001; depression: 26.30 % vs. 7.63 %, P < 0.001). Furthermore, after adjusting for age in the RPL group, negative relationships were observed between the IIEF-5 score and anxiety and depression (P < 0.001), and a positive correlation was found between the ISS and anxiety and depression (P < 0.001). In addition, history of RPL, anxiety and depressive symptoms were significantly associated with a higher risk of ED. CONCLUSIONS: Psychological functioning, sexual satisfaction and erectile function are impaired in infertile men with RPL partners. These men should be targeted for psychological consultation.

Multiple advanced surgical techniques to treat acquired seminal duct obstruction.

The aim of this study was to evaluate the outcomes of multiple advanced surgical treatments (i.e. microsurgery, laparoscopic surgery and endoscopic surgery) for acquired obstructive azoospermia. We analyzed the surgical outcomes of 51 patients with suspected acquired obstructive azoospermia consecutively who enrolled at our center between January 2009 and May 2013. Modified vasoepididymostomy, laparoscopically assisted vasovasostomy and transurethral incision of the ejaculatory duct with holmium laser were chosen and performed based on the different obstruction sites. The mean postoperative follow-up time was 22 months (range: 9 months to 52 months). Semen analyses were initiated at four postoperative weeks, followed by trimonthly (months 3, 6, 9 and 12) semen analyses, until no sperm was found at 12 months or until pregnancy was achieved. Patency was defined as >10,000 sperm ml⁻¹ of semen. The obstruction sites, postoperative patency and natural pregnancy rate were recorded. Of 51 patients, 47 underwent bilateral or unilateral surgical reconstruction; the other four patients were unable to be treated with surgical reconstruction because of pelvic vas or intratesticular tubules obstruction. The reconstruction rate was 92.2% (47/51), and the patency rate and natural pregnancy rate were 89.4% (42/47) and 38.1% (16/42), respectively. No severe complications were observed. Using multiple advanced surgical techniques, more extensive range of seminal duct obstruction was accessible and correctable; thus, a favorable patency and pregnancy rate can be achieved.

[Neutral alpha-glucosidase activity is correlated with the location of epididymal obstruction in azoospermia men].

OBJECTIVE: To evaluate the correlation of neutral alpha-glucosidase in seminal plasma with the location of epididymal obstruction in azoospermia men. METHODS: We detected neutral alpha-glucosidase activity in the seminal plasma of 59 men with obstructive azoospermia followed by determining the location of epididymal obstruction by scrotal exploratory surgery. Then we analyzed the correlation between neutral alpha-glucosidase and the location of epididymal obstructive azoospermia. RESULTS: Among the total number of patients, there were 25 cases of bilateral cauda epididymal obstruction, 15 bilateral corpus, 12 bilateral caput, 4 unilateral caput-opposite cauda, and 3 unilateral corpus-opposite cauda. The neutral alpha-glucosidase levels in the seminal plasma of bilateral cauda, corpus and capus epididymal obstructions were (4.1 +/- 1.9), (13.8 +/- 4.4) and (46.8 +/- 19.3) mU per ejaculate, respectively, with statistically significant differences among the three groups (P < 0.05). CONCLUSION: Neutral alpha-glucosidase activity is significantly correlated with the location of epididymal obstruction in azoospermia men, which helps to locate epididymal obstruction, evaluate surgical prognosis and reduce the time of scrotal exploratory surgery.

Imaging of partial right double vena cava with ureter crossing through its split, confirmed at surgery.

A complex development process occurs during the embryogenesis of the inferior vena cava (IVC), such as the formation of several anastomoses between three paired embryonic veins, which may result in a wide range of congenital abnormalities of the IVC. We report a case, not described before, of partial double right IVC with a circumcaval ureter crossing through the divide in the IVC.

A multicentre, prospective, randomized trial: comparative efficacy of tamsulosin and nifedipine in medical expulsive therapy for distal ureteric stones with renal colic.

OBJECTIVE: • To determine the comparative efficacy of tamsulosin and nifedipine in medical expulsive therapy (MET) for distal ureteric stones with renal colic. PATIENTS AND METHODS: • We evaluated the comparative efficacy of tamsulosin and nifedipine in MET in a prospective randomized trial of 3189 outpatients from 10 centres in China. • Eligible patients randomly received tamsulosin or nifedipine. Efficacies of the two agents in MET were compared at 4 weeks. • The primary endpoint was overall stone-expulsion rate. • Secondary endpoints were stone-expulsion time, rate of pain relief therapy, mean analgesic consumption for renal colic recurrence, and side-effects incidence. RESULTS: • Stone-expulsion rates in the tamsulosin group (group 1) were greater than those in the nifedipine group (group 2; P < 0.01). • There was a significant variation in stone-expulsion rates and times between groups 1 and 2 (P < 0.01); with improvements in stone-expulsion rate and time significantly better in group 1 than in group 2. • There was a significant variation in the rate of pain relief therapy for renal colic recurrence between groups 1 and 2 (P < 0.01); patients in group 1 required significantly less analgesics than those in group 2 (P < 0.01). • There were no statistically significant differences in side-effects incidence between the groups. CONCLUSIONS: • Administration of tamsulosin and nifedipine in MET was determined to be safe and effective for distal ureteric stones with renal colic. • Tamsulosin was significantly better than nifedipine in relieving renal colic and facilitating ureteric stone expulsion.

[Comparative study of pneumatic lithotripsy and holmium laser lithotripsy for ureteral stones].

OBJECTIVE: To compare the efficacy and safety of endoscopic laser lithotripsy (LL) and endoscopic pneumatic lithotripsy (PL) for ureteral stones. METHODS: We retrospectively analyzed the clinical data of 415 patients with ureteral calculi treated with endoscopic laser lithotripsy (n = 214 ) and pnumatic lithotripsy (n = 201 ). RESULTS: The overall successful fragmentation rate of all ureteral stones in a single session of the LL group was higher than that of the PL group (95% vs. 69%, P < 0.01). The average stonefree time of the LL group was shorter than that of the PL group (18 days vs. 31 days, P < 0.01). No complications such as perforation during the operation were observed in the LL group whereas 3 perforations occurred in the PL group. CONCLUSION: LL has its advantage over PL in its better clinical effect for the stone fragmentation and low complication rate and is an effective and safe treatment for ureteral stones.

[Nine cases of laparoscopic retroperitoneal lymph node dissection].

OBJECTIVE: To assess the effects of laparoscopic retroperitoneal lymph node dissection in the treatment of stage I nonseminomatous testicular cancer. METHODS: From January 2001 to May 2002, laparoscopic retroperitoneal lymph node dissection was performed on 9 patients with stage I nonseminomatous testicular cancer. RESULTS: The procedure was successful in all patients. The mean operation time was 260 minutes. None of the patients required blood transfusion and had major complications intraoperatively or postoperatively. The average period of hospitalization after the operation was 5.5 days. With a mean following-up of 9 months, retroperitoneal recurrence was not seen. CONCLUSIONS: Laparoscopic retroperitoneal lymph node dissection is feasible for stage I nonseminomatous testicular cancer and its procedure is safe, effective and minimally invasive.