Influence of Androgen Receptor Antagonist MDV3100 Therapy on Rats With Benign Prostatic Hyperplasia / 대한배뇨장애요실금학회지

Purpose@#To probe the effect and mechanism of androgen receptor antagonist MDV3100 on benign prostatic hyperplasia (BPH) of rats @*Methods@#BPH rat model was induced by testosterone propionate. Then antagomir-miR-21-3p or agomir-miR-21-3p was injected into rats before MDV3100 treatment. The prostate index was measured by weighing the wet weight of the rat prostate. The structural morphology of rat prostate was observed after hematoxylin & eosin staining. Immunohistochemistry was applied to evaluate the expression levels of Ki-6 and inflammatory cytokines (interleukin [IL]-6, IL-18, and tumor necrosis factor-α) in rat prostate tissues. Quantitative reverse transcription polymerase chain reaction was utilized for assessment of miR-21-3p expression, and Western blot for the performance of the phosphorylation levels of IKKα and p65. @*Results@#Injection of testosterone propionate caused increased prostate gland hyperplasia, heightened miR-21-3p level, and activated nuclear factor-kappa B (NF-κB) signaling pathway. Additionally, BPH was accompanied by inflammatory response, as evidenced by enhanced expressions of Ki-67 and inflammatory cytokines. MDV3100 exposure ameliorated BPH and suppressed miR-21-3p expression. Overexpression of miR-21-3p intensified BPH and inflammation level, while knockdown of miR-21-3p relieved BPH. The coeffect of miR-21-3p upregulation and MDV3100 subjection led to higher inflammatory response, elevated phosphorylation levels of IKKα and p65 than MDV3100 treatment alone. @*Conclusions@#Androgen receptor antagonist MDV3100 alleviates BPH and inflammatory response through miR-21-3p downregulation and NF-κB signaling pathway blockade.

Influence of Androgen Receptor Antagonist MDV3100 Therapy on Rats With Benign Prostatic Hyperplasia / 대한배뇨장애요실금학회지

Purpose@#To probe the effect and mechanism of androgen receptor antagonist MDV3100 on benign prostatic hyperplasia (BPH) of rats @*Methods@#BPH rat model was induced by testosterone propionate. Then antagomir-miR-21-3p or agomir-miR-21-3p was injected into rats before MDV3100 treatment. The prostate index was measured by weighing the wet weight of the rat prostate. The structural morphology of rat prostate was observed after hematoxylin & eosin staining. Immunohistochemistry was applied to evaluate the expression levels of Ki-6 and inflammatory cytokines (interleukin [IL]-6, IL-18, and tumor necrosis factor-α) in rat prostate tissues. Quantitative reverse transcription polymerase chain reaction was utilized for assessment of miR-21-3p expression, and Western blot for the performance of the phosphorylation levels of IKKα and p65. @*Results@#Injection of testosterone propionate caused increased prostate gland hyperplasia, heightened miR-21-3p level, and activated nuclear factor-kappa B (NF-κB) signaling pathway. Additionally, BPH was accompanied by inflammatory response, as evidenced by enhanced expressions of Ki-67 and inflammatory cytokines. MDV3100 exposure ameliorated BPH and suppressed miR-21-3p expression. Overexpression of miR-21-3p intensified BPH and inflammation level, while knockdown of miR-21-3p relieved BPH. The coeffect of miR-21-3p upregulation and MDV3100 subjection led to higher inflammatory response, elevated phosphorylation levels of IKKα and p65 than MDV3100 treatment alone. @*Conclusions@#Androgen receptor antagonist MDV3100 alleviates BPH and inflammatory response through miR-21-3p downregulation and NF-κB signaling pathway blockade.

Effect of silencing Notch1 gene on proliferation, apoptosis and Akt/mTOR pathyway inhibition in clear cell renal cell carcinoma / 中华泌尿外科杂志

Objective To investigate the effect of silencing Notch1 gene by RNA interference on the proliferation,apoptosis and Akt/mTOR signaling pathway in clear renal cell carcinoma.Methods The optimal segment targeting Notch1 gene was designed and transfected into 786-O cells by Lipofectamine TM2000.The Notch1 mRNA and protein were detected by RT-PCR and Western blot.The proliferation rate of 786-O cells was evaluated by MTT and the variation of apoptosis was measured by TUNEL.The protein expression level of apoptosis-related protein Bcl-2,caspase-3,caspase-9,and signaling pathway protein Akt,p-Akt,p-mTOR,p-P70S6K were detected by Western blott.Results Notchl mRNA and protein was markedly suppressed by the siRNA targeting Notch1.Treated with 0,40,60,80,100 and 120 nmol/L of Notch1 siRNA for 24 hours,cell proliferation rates were (98.51 ± 1.33) ％,(87.34 ± 2.26) ％,(64.72 ± 3.24)％,(57.68 ±3.32)％,(31.91 ± 1.85)％ and (19.27 ±2.73)％,and the difference was statistically significant (P ＜ 0.01).Treated with 0,40,80,and 120 nmol/L of Notchl siRNA for 24 hours,apoptosis rates were (7.6 ± 3.8) ％,(21.5 ± 4.8) ％,(32.3 ± 3.5) ％,and (46.3 ± 4.7％),the difference was statistically significant (P ＜ 0.05).Decreased expression of Akt signaling pathway proteins p-Akt,p-mTOR,p-70S6K and apoptosis-related protein Bcl-2,procaspase-3 was detected,but no change in the total protein of Akt.Conclusions Depletion of Notch1 gene could inhibit cell growth and induce apoptosis in 786-O cell line.It inhibits Akt/mTOR signaling pathway by dephosphorylated.

ImmunoCyt™ and cytology for diagnosis of bladder carcinoma: a meta analysis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Currently, cystoscopy and urine cytology are standard modalities in therapy monitoring and follow-up of bladder carcinoma (BC). Cystoscopy is an invasive and uncomfortable procedure while cytology has a limited value because it is operator-dependent and has low sensitivity. This study was to assess the accuracy of ImmunoCyt in detecting BC by comparing it with cytology using systemic analyses of studies published in both English and Chinese.</p><p><b>METHODS</b>Cochrane systematic evaluation was used to search through MEDLINE, EMBASE, Cochrane Library, CMCC, and CNKI for studies regarding ImmunoCyt and cytology for detection of BC. Data were extracted and analyzed by the software MetaDiSc 1.4.</p><p><b>RESULTS</b>In total 42 relevant studies were searched, of which 15 were enrolled and 12 491 patients were included. Heterogeneity, except for threshold effects, was found within these studies. A meta-analysis was performed using the random effect model. Pooled accuracy indicators like sensitivity, specificity, and diagnostic odds ratio of ImmunoCyt™ and cytology were 0.75 (0.73-0.77) vs. 0.45 (0.43-0.48), 0.73 (0.72-0.74) vs. 0.97 (0.96-0.97), and 10.97 (7.53-15.99) vs. 16.40 (10.57-25.46), respectively. The sensitivity of both was increased with the increase of tumor grade and stage. The area under summary receiver operating characteristics curve was 0.834 4 and 0.853 4 and the Q index 0.766 7 and 0.785 3 for ImmunoCyt and cytology, respectively. Combination of both can obviously improve the accuracy of diagnosis.</p><p><b>CONCLUSIONS</b>ImmunoCyt has a high sensitivity in detecting BC, but its specificity is low. As an important adjunct, ImmunoCyt™ can not replace cytology, but combined with cytology it could improve sensitivity with high specificity in the detection and postoperative monitoring of BC.</p>

Relationship between condition of hypoxia and prognosis in patients with renal clear cell carcinoma / 中华泌尿外科杂志

Objective To explore the relationship between condition of hypoxia and prognosis in patient with renal clear cell carcinoma (RCCC).Methods The expression of hypoxia-inducible factor-lo( HIF-1 α) protein in cancer tissue of 89 RCCC cases was examined by streptavidin-biotin complex immunohistochemistry.Clinical and pathological data and prognosis of 89 cases were analyzed retrospectively.There were 66 males and 23 females,with an average age of 57 years.The patients were divided into two groups,the chronic pulmonary disease (CPD) group ( 19 cases) and non CPD (NCPD) group (70 cases),with 46cases in clinical stage I,15 cases in stage Ⅱ,26 cases in stage Ⅲ,and 2 cases in stage Ⅳ.The relationship between survival time and clinicopathological variables including the presence of CPD,the positive rate of HIF-1α protein,smoking history and hemoglobin level were evaluated by the Kaplan-Meier method.And the Cox proportional hazards regression model was build to analyze the correlation between each variable and survival time.Results The 89 cases were followed up for a median time of 19 months (6 to 84 months).Twenty cases died,and 69 cases survived.Between the CPD group and NCPD group,clinical stage,hemoglobin level and the degree of expression of HIF-1 α were significantly different (P ＜ 0.05 ).The median survival time was 44 and 71 months in CPD group and NCPD group,respectively,and the difference was significant ( P ＜ 0.05 ).The median survival time was 43 and 70 months in Hb≤ 110 g/L group and Hb ＞ 110 g/L group,respectively,and the difference was significant ( P ＜ 0.05).The stronger the degree of expression of HIF-lα was,the shorter the overall survival was.And the difference was significant ( P ＜0.05 ).Associated with CPD,hemoglobin level,the expression of H1F-1α were independent factors affecting overall survival of the patients (P ＜0.05 ).CPD and HIF-1 α expression were positively related to disease-free survival time,and hemoglobin level was negatively related to disease-free survival time.Conclusions Systemic hypoxia caused by CPD may aggravate the hypoxie state in the organization of the patients with RCCC.The condition of hypoxia and prognosis in patient with RCCC is negatively correlated.

Urine bladder tumor antigen stat in bladder tumor diagnosis: a meta-analysis / 中华泌尿外科杂志

Objective To systematic review bladder tumor antigen(BTA) stat in the diagnosis of bladder cancer. Methods MEDLINE, EMBASE, Cochrane Library, CMCC and CNKI were searched for studies about BTA stat in the diagnosis of bladder cancer. The search strategy was made according to the Collaborative Review Group search strategy. Data were extracted by two reviewers using the designed extraction form. The software MetaDiScl. 4 was used to review management and data analysis. Results Seventy-one relevant studies were searched, of which 20 studies were included with 5929 patients involved and 51 studies were excluded. Heterogeneity (except for threshold effect) was found within these studies. A meta-analysis was performed using random effect model. Pooled accuracy indicators like sensitivity, specificity, positive likelihood ratio (LR), negative LR and diagnostic odds ratio (dOR) were 0. 64(95%CI 0. 62-0. 66), 0. 72(95%CI 0. 70-0. 73) , 2. 33(95% CI 2. 03-2. 68), 0. 48(95%CI 0.42 -0.55) and 5.12(95%CI 3. 88-6. 75), respectively. The sensitivity increased with tumor grades. The sensitivity of primary tumors was higher than the recurrent tumors. Area under curve (AUC) of SROC curve was 0. 7500 and Q* index was 0. 6934. Conclusions The performance of urine BTA stat is moderate in the diagnosis of bladder tumor. It can be an optional non-invasive test and an important adjunct test in preoperative detecting and postoperative monitoring of bladder tumor.

Meta-analysis of antibiotic prophylaxis use in transrectal prostatic biopsy / 中南大学学报(医学版)

ObjectiveTo determine whether antibiotic prophylaxis can reduce the risk of postoperative infective complications in men undergoing transrectal prostatic biopsy (TPB) who had sterile preoperative urine.MethodsMEDLINE, EMBASE, Cochrane Collaboration Reviews, Chinese Medical Current Contents (CMCC), and National Knowledge Infrastructure (CNKI) were searched for rando-mized controlled trials that compared the effect of antibiotic prophylaxis with placebo or active controls for men undergoing TPB with preoperative sterile urine. Two reviewers independently extracted the data of patient characteristics and outcomes based on a prospectively developed protocol.ResultsA total of 12 trials (3 placebo controlled, 3 non-treatment controlled, and 6 activly controlled) involving 1 987 patients, met the inclusion criteria. Prophylactic antibiotic use in patients at low risk undergoing TPB significantly decreased bacteriuria and middle degree fever incidence, but could not decrease the incidence of bacteremia. The relative risk for post-TPB bacteriuria, middle degree fever, and bacteremia were 0.32 (95% CI 0.23 to 0.46), 0.37 (95% CI 0.17 to 0.77), and 0.96 (95% CI 0.61 to 1.50), respectively. Effective antibiotic classes included quinolone, co-quinolone and nitroimidazole, and co-trimethoprim and sulfamethoxazole. Treatment protocols of any duration were effective.ConclusionAntibiotic prophylaxis obviously decreases the incidence of bacteriuria and middle degree fever but not bacteremia in men with preoperative sterile urine undergoing TPB. A significant decrease in bacteriuria incidence can be achieved with a range of antibiotic agents, including quinolones and co-quinolone and nitroimidazole. Treatment protocols of any duration are effective with no heterogeneity.