Shouzhen Chen

Grape Seed Proanthocyanidin Extract Ameliorates Diabetic Bladder Dysfunction via the Activation of the Nrf2 Pathway.

Diabetes Mellitus (DM)-induced bladder dysfunction is predominantly due to the long-term oxidative stress caused by hyperglycemia. Grape seed proanthocyanidin extract (GSPE) has been reported to possess a broad spectrum of pharmacological and therapeutic properties against oxidative stress. However, its protective effects against diabetic bladder dysfunction have not been clarified. This study focuses on the effects of GSPE on bladder dysfunction in diabetic rats induced by streptozotocin. After 8 weeks of GSPE administration, the bladder function of the diabetic rats was improved significantly, as indicated by both urodynamics analysis and histopathological manifestation. Moreover, the disordered activities of antioxidant enzymes (SOD and GSH-Px) and abnormal oxidative stress levels were partly reversed by treatment with GSPE. Furthermore, the level of apoptosis in the bladder caused by DM was decreased following the administration of GSPE according to the Terminal Deoxynucleotidyl Transferase (TdT)-mediated dUTP Nick-End Labeling (TUNEL) assay. Additionally, GSPE affected the expression of apoptosis-related proteins such as Bax, Bcl-2 and cleaved caspase-3. Furthermore, GSPE showed neuroprotective effects on the bladder of diabetic rats, as shown by the increased expression of nerve growth factor (NGF) and decreased expression of the precursor of nerve growth factor (proNGF). GSPE also activated nuclear erythroid2-related factor2 (Nrf2), which is a key antioxidative transcription factor, with the concomitant elevation of downstream hemeoxygenase-1 (HO-1). These findings suggested that GSPE could ameliorate diabetic bladder dysfunction and decrease the apoptosis of the bladder in diabetic rats, a finding that may be associated with its antioxidant activity and ability to activate the Nrf2 defense pathway.

Cannabinoid receptors 1 and 2 are associated with bladder dysfunction in an experimental diabetic rat model

To investigate diabetes‐associated changes in urinary bladder expression of cannabinoid receptors 1 and 2 (CB1 and CB2) and the functional role of CB agonists and antagonists in mediating phasic contractions of isolated bladder strips using a streptozotocin‐induced diabetic rat model.

Prognostic scores based on the preoperative plasma fibrinogen and serum albumin level as a prognostic factor in patients with upper urinary tract urothelial carcinoma

This study is to clarify the prognostic value of preoperative plasma fibrinogen and serum albumin level, as known as FA score, in a cohort of Chinese patients with upper urinary tract urothelial carcinoma (UTUC). We retrospectively evaluated clinicopathological data on 169 patients who underwent surgery between 2006 and 2013. The FA score was calculated based on cutoff values of 3.53g/L for fibrinogen and 43.56 g/L for albumin. Overall survival and cancer specific survival was assessed using the Kaplan-Meier method and the equivalences of the curves were tested by log-rank tests. The Cox proportional hazards regression model was applied in univariate and multivariate analyses. In univariate analysis, tumor size, tumor grade, pathological T stage and FA score were significantly associated with overall survival and cancer specific survival, and multivariate Cox proportional hazards regression analysis identified FA score (score 1: HR=3.486, 95%CI 1.358-8.948, p=0.009; HR=3.485, 95%CI 1.363-8.913, p=0.009, respectively; score 2: HR=5.509, 95%CI 2.144-14.158, p<0.001; HR=5.521, 95%CI 2.074-14.697, p=0.001, respectively) was an independent predictor for overall survival and cancer specific survival. The evaluation of preoperative FA score can be regarded as an independent prognostic factor for predicting overall survival and cancer specific survival in UTUC. The fibrinogen and albumin levels are low cost and easy accessibility in clinical practice.This study is to clarify the prognostic value of preoperative plasma fibrinogen and serum albumin level, as known as FA score, in a cohort of Chinese patients with upper urinary tract urothelial carcinoma (UTUC). We retrospectively evaluated clinicopathological data on 169 patients who underwent surgery between 2006 and 2013. The FA score was calculated based on cutoff values of 3.53g/L for fibrinogen and 43.56 g/L for albumin. Overall survival and cancer specific survival was assessed using the Kaplan-Meier method and the equivalences of the curves were tested by log-rank tests. The Cox proportional hazards regression model was applied in univariate and multivariate analyses. In univariate analysis, tumor size, tumor grade, pathological T stage and FA score were significantly associated with overall survival and cancer specific survival, and multivariate Cox proportional hazards regression analysis identified FA score (score 1: HR=3.486, 95%CI 1.358-8.948, p=0.009; HR=3.485, 95%CI 1.363-8.913, p=0.009, respectively; score 2: HR=5.509, 95%CI 2.144-14.158, p<0.001; HR=5.521, 95%CI 2.074-14.697, p=0.001, respectively) was an independent predictor for overall survival and cancer specific survival. The evaluation of preoperative FA score can be regarded as an independent prognostic factor for predicting overall survival and cancer specific survival in UTUC. The fibrinogen and albumin levels are low cost and easy accessibility in clinical practice.

Combination of Intravesical Chemotherapy and Bacillus Calmette-Guerin Versus Bacillus Calmette-Guerin Monotherapy in Intermediate- and High-risk Nonmuscle Invasive Bladder Cancer: A Systematic Review and Meta-analysis.

Abstract Urothelial carcinoma of the bladder has become a major cause of morbidity, mortality, and health-related costs. There is still no standard instillation therapy against bladder cancer. A meta-analysis was conducted to evaluate the efficacy and toxicity of adding chemotherapy to Bacillus Calmette–Guerin (BCG) in intermediate- and high-risk nonmuscle invasive bladder cancer (NMIBC). All randomized controlled trials (RCTs) that evaluated the efficacy of combination therapy and BCG monotherapy for intermediate- and high-risk NMIBC were comprehensively searched. Relevant databases, including PubMed, Embase, Cochrane Central Register of Controlled trials databases, and American Society of Clinical Oncology (http://www.asco.org/ASCO), the clinical trial registration website (ClinicalTrials.gov), and relevant trials from the references of selected studies were searched from initial state up to June 6, 2015. Random-effects model was used to estimate hazard ratios (HRs) statistics. All statistical analyses were performed by STATA (version 13.0, College Station, TX). Seven studies, including 1373 patients with intermediate- and high-risk NMIBC, were identified. For disease-free survival, the pooled HRs from all studies was 0.69 (95% confidence interval [CI], 0.48–1.00; P = 0.048). The disease-free survival benefit was more apparent among patients with intermediate-risk NMIBC (P = 0.002) or Ta/T1 with/without carcinoma in situ (P < 0.01). In subgroup analysis, a significant reduction in recurrence was found in studies that explored the influence of a perioperative single dose instillation compared with delayed BCG monotherapy (HR = 0.60; 95% CI, 0.38–0.92; P = 0.021). No significant difference was found for progression-free survival (HR = 0.78; 95% CI, 0.43–1.44; P = 0.435). Patients with intermediate- and high-risk NMIBC who underwent combination therapy achieved lower rates of recurrence than those who underwent BCG therapy alone. No difference in progression-free survival was found between the 2 different therapy schedules. Better efficacy for a perioperative single dose instillation compared with delayed BCG monotherapy was found in this meta-analysis.

Changes in alpha1-adrenoceptor and NGF/proNGF pathway: a possible mechanism in diabetic urethral dysfunction.

Objective: To investigate the changes in the α1-adrenoceptor and nerve growth factor (NGF)/NGF precursor (proNGF) pathway in the urethra after diabetes induction. Materials and Methods: Urethral relaxation function was determined by simultaneous recordings of intravesical pressure under isovolumetric conditions and urethral perfusion pressure (UPP) in diabetic rats. The expression of α1-adrenoceptor, NGF, proNGF, low-affinity p75 receptor for neurotrophins (p75NTR) and sortilin in the urethras was measured using real-time quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay and Western blotting. Results: In diabetic rats, the lowest urethral pressure (UPP nadir) during urethral relaxation was significantly higher. Intravenous administration of tamsulosin, an α1-adrenoceptor antagonist, significantly decreased the UPP nadir and baseline UPP in diabetic rats. RT-qPCR and Western blotting studies showed a statistically significant increase of α1a- and α1b-adrenoceptor in the urethras from the diabetic group (p < 0.05). The expression of NGF was significantly decreased in the urethras from the diabetic group while the expression of proNGF was significantly increased (p < 0.05). The p75NTR level in the urethras of diabetic rats was decreased compared with controls (p < 0.05) and there was no significant difference regarding sortilin between the two groups (p > 0.05). Conclusion: This study validated the diabetic urethral dysfunction and furthermore indicated that the increase in the expression of α1-adrenoceptor and changes in the NGF/proNGF pathway may be involved in diabetic urethral dysfunction.

Clinical characteristics and pathology of thyroid‑like follicular carcinoma of the kidney: Report of 3 cases and a literature review

Thyroid-like follicular carcinoma (TLFC) of the kidney is an extremely rare type of renal tumor, which has not been classified under a known subtype of renal cell carcinoma. It is histologically similar to the primary thyroid follicular carcinoma; however, the characteristics lack thyroid immunohistochemical markers. The aim of the present study was to illustrate the clinical characteristics of 3 new cases along with a review of the literature. The patients were compared with regards to gender, age, location and size of the tumor, imageology, morphology, immunohistochemistry and prognosis. According to the limited data, TLFC occurs mainly in young women and its clinical manifestations have no difference with other renal tumors. Its imageological features resemble a large spectrum of benign and malignant renal and extra-renal conditions, which should be eliminated in the diagnostic process. Confirmed diagnosis depends on the examination of pathology and immunohistochemistry. Surgical ablation is the preferred therapeutic method. Currently, TLFC has a relatively good prognosis; however, this conclusion requires further cases and long-term follow-ups. Improving the understanding of TLFC can help avoid misdiagnosis and prevent inappropriate treatment.

Pelvic Floor Reconstruction After Radical Prostatectomy: A Systematic Review and Meta-analysis of Different Surgical Techniques

Radical prostatectomy (RP) is the gold standard for the treatment of localized PCa. A meta-analysis was conducted to evaluate the effect of different techniques of pelvic floor reconstruction on urinary continence. A comprehensive search was made for trials that evaluated the efficacy of pelvic floor reconstruction. Relevant databases included PubMed, Embase, Cochrane, Ovid, Web of Science databases and relevant trials from the references. Random-effects model was used to estimate risk ratios (RRs) statistics. Pooled results of patients treated with posterior reconstruction (PR) demonstrated complete urinary continence improved at 1–4, 28–42, 90, 180 and 360 days following catheter removal. Anterior suspension (AS) was associated with improvement only at 28–42 days. The anterior reconstruction (AR) + PR was associated with urinary continence at 1–4, 90 and 180 days. AS + PR was not associated with any benefit. And PR improved social urinary continence at 7–14 and 28–42 days. No benefit was associated with AS. AR + PR had better outcomes at 90 and 180 days. AS + PR was significant improved at 28–42 and 90 days. Patients who underwent RP and PR had the least urinary incontinence. No significant benefit was observed after AS. AR + PR and AS + PR had little benefit in the post-operative period.

CCL17-CCR4 axis promotes metastasis via ERK/MMP13 pathway in bladder cancer: ZHAO et al.

As an important chemokine receptor, the role of CCR4 in the progression of bladder cancer (BC) remains unknown. In this study, we have shown that CCR4 expression was upregulated in bladder carcinoma tissues compared with adjacent nontumor tissues. Kaplan‐Meier survival analysis revealed that CCR4 expression was an independent prognostic risk factor in BC patients, and the addition of CCL17 induced CCR4 production and promoted migration and invasion of BC cells. In addition, CCR4 knockdown significantly attenuated the migratory and invasive capabilities of BC cells. Mechanistically, CCL17‐CCR4 axis is involved in ERK1/2 signaling and could mediate the migration and invasion of BC cells by regulating MMP13 activation. This study suggests that CCR4 might represent a promising prognostic biomarker and a potential therapeutic option for BC.

Primary Adenocarcinoma of the Ureter with Elevated CarbohydrateAntigen-19-9: A Case Report and Review of the Literature

Primary adenocarcinoma of the upper tract urothelial cell carcinomas (UTUCs) is rarely reported. We report a case of primary adenocarcinoma of the ureter with elevated carbohydrate antigen 19-9 (CA-19-9). A 44-year-old male was admitted to the hospital for severe right flank and hypogastrium pain for 7 days without visible or microscopic haematuria. The patient underwent radical nephroureterectomy followed by chemotherapy with gemcitabine/ carboplatin and inorelbine/Adriamycin (ADM)/5-fluoro-2,4 (1 h, 3 h) pyrimidinedione (5-FU) and radiotherapy, and the level of CA19-9 decreased to normal. Histopathology revealed adenocarcinoma. The patient died of tumor pelvic metastasis after 6 months. A review of the literature is also reported.

The role of c-Met in prognosis and clinicopathology of renal cell carcinoma: Results from a single-centre study and systematic review

BACKGROUND AND OBJECTIVES The c-Met proto-oncogene pathway plays an important role in the progression of various cancers. However, the effect of the c-Met pathway on renal cell carcinoma (RCC) remains controversial. We decided to clarify the role of c-Met in prognosis and clinicopathology of RCC. METHODS A total of 10 pairs of tumour and adjacent tissues were obtained from patients with primary RCC between 2013 and 2014 and tissue microarrays to assess c-Met expression in tumour tissues from 90 patients with RCC by Western blot and immunohistochemical staining. We also presented a meta-analysis to explore the correlation between c-Met and pathological grade and stage of RCC. The two-tailed Pearsons χ2 and Fischer exact tests were used to compare categorical variables. Multivariate analysis was performed using the multivariate Cox proportional hazards model. RESULTS C-Met protein levels were increased in 8 of 10 RCC tissue samples compared with their adjacent normal tissue and c-Met expression levels were positively associated with a high nuclear grade (P = 0.008) and pT stage (P = 0.002). Multivariate analysis showed that a high expression of c-Met was an independent predictor of disease-specific survival (P = 0.017). A meta-analysis found that increased c-Met expression in RCC tissues was closely correlated with high tumour grade (P<0.001) and high pT stage (P = 0.001). Most importantly, c-Met expression was significantly correlated with disease-specific survival (P<0.001). CONCLUSIONS Because c-Met is strongly associated with pathological grade, stage and disease-specific survival, c-Met levels may have potential to predict patient prognosis and to guide clinical diagnosis and treatment.