Ursolic acid activates the apoptosis of prostate cancer via ROCK/PTEN mediated mitochondrial translocation of cofilin-1.

Ursolic acid has various pharmacological activities, and can reduce blood fat as well as having antihepatic, antitumoral, anti-inflammatory and antiviral properties. However, the pro-apoptotic mechanism by which ursolic acid influences human prostate cancer requires additional study. The aim of the present study was to assess whether ursolic acid activates the apoptosis of prostate cancer and to investigate the mechanism by which the Rho-associated protein kinase 1 (ROCK1)/phosphatase and tensin homolog (PTEN) signaling pathway performs a role in ursolic acid-mediated cofilin-1 to induce apoptosis in human prostate cancer. Firstly, the present study determined the pro-apoptotic mechanism by which ursolic acid influences the cell proliferation and apoptosis of human prostate LNCaP cancer cells. Caspase-3/9 activities and ROCK1, PTEN, Cofilin-1 and cytochrome c protein expression levels were also analyzed. In the present study, it is reported that the pro-apoptotic mechanism of ursolic acid potently suppressed the cell proliferation of human prostate LNCaP cancer cells. The present study revealed that the mediation of ROCK1/PTEN-cofilin-1/cytochrome c protein expression activates caspase-3/9 activities which subsequently induced the apoptosis of human prostate cancer cells. In conclusion, these findings demonstrated that ursolic acid activates the apoptosis of prostate cancer via ROCK/PTEN mediated cofilin-1/cytochrome c which mediated caspase-3/9 activities.

Aurora-A regulates autophagy through the Akt pathway in human prostate cancer.

BACKGROUND: Aurora A kinase is frequently overexpressed in a variety of tumor types, including the prostate. However, the function of Aurora A in autophagy in prostate cancer has not been investigated. Here, we aimed to study the functioning mechanism and autophagy associated signaling pathways of Aurora A in prostate cancer. METHODS: To investigate the biological function of Aurora A, down-regulation of Aurora A was performed followed by functional testing assays. Immunohistochemistry was used to detect the expression of Aurora A in human prostate cancer specimens. CCK8, Transwell, flow cytometric analysis and measurement of tumor formation in nude mice were performed to test the effects of Aurora A down-regulation in vivo and in vitro. Signaling pathway analysis was performed by using Western blot. Autophagy activity was measured by monitoring the expression levels of LC3-II. RESULTS: Aurora A overexpression was significantly higher in human prostate cancer specimens than in BPH. Furthermore, Aurora A knockdown inhibited the proliferation of prostate cancer cells by suppressing the Akt pathway, indicating that Akt is a novel Aurora A substrate in prostate cancer. Additionally, Aurora A down-regulation prompts autophagy in prostate cancer cells. Most importantly, Aurora A ablation almost fully abrogates tumorigenesis in nude mice, suggesting that Aurora A is a key oncogenic effector in prostate cancer. CONCLUSIONS: Taken together, our data suggest that Aurora-A plays an important role in the suppression of autophagy by inhibiting the phosphorylation of Akt, which in turn prevents autophagy-induced apoptosis in prostate cancer.

Increased expression of ESCO1 is correlated with poor patient survival and its role in human bladder cancer.

There is increasing evidence suggesting that establishment of sister chromatid cohesion N-acetyltransferase 1 (ESCO1) was involved in tumorigenesis. However, its role in bladder cancer remains unclear. In this study, we aimed to study the clinical correlation and biological significance of ESCO1 in bladder cancer. Our results showed that ESCO1 was significantly over-expressed in bladder cancer tissues compared with that in adjacent normal tissues. And, increased ESCO1 expression was significantly associated with higher grade (P < 0.001), higher tumor stage (P = 0.014), and multifocality (P = 0.042). Kaplan-Meier analysis and Cox proportional hazards model were performed to determine the prognostic significance of ESCO1, and the results showed that ESCO1 is a useful prognostic marker for bladder cancer patients. Moreover, we found that ESCO1 knockdown inhibited the growth, migration, and invasion of bladder cancer cells. In conclusion, our findings indicated that ESCO1 may play an important role in human bladder cancer, and ESCO1 might serve as a novel target and prognosis factor for human bladder cancer.

Benign Prostatic Hyperplasia Treatment by Transurethral Enucleation of the Prostate Using a 2-µm Laser.

This study investigates the efficacy of benign prostatic hyperplasia (BPH) treatment by prostate transurethral enucleation using a 2-µm laser. A total of 107 patients with BPH were treated by prostate transurethral enucleation using a RevoLix 2-µm laser surgery system. Bleeding volume, operation time, catheterization time, voiding situation, maximum urinary flow rate, and hospital stay were observed. The mean operation time was 74 min ± 12 min (range 45 to 150 min), the mean follow-up period was 2 to 6 months, the mean catheter time was 5 days, and the mean peak urinary flow rate increased from 6.3 ± 0.6 to 17.5 ± 1.5 mL/s. The International Prostate Symptom Score and quality of life significantly declined (p < 0.01). No significant differences were observed in the hemoglobin and blood electrolytes before and after operation. Prostate transurethral enucleation using a 2-µm laser is safe and efficient for BPH treatment.

Application of two micron laser vaporesection combined with transurethral resection of the prostate in treatment of benign prostatic hyperplasia: analysis of 340 cases.

PURPOSE: To evaluate clinical efficacy and safety of two micron laser vaporesection combined with transurethral resection of the prostate (TURP) in treating benign prostatic hyperplasia (BPH). METHODS: In total, 340 BPH patients aged 62-86 years, were treated with two micron laser vaporesection plus TURP. Mean prostatic volume was measured as 38-182 ml. Operative time, intraoperative hemorrhage volume, time of postoperative bladder irrigation, time of indwelling urinary catheter and surgical complications were examined. International Prostate Symptom Score (IPSS), quality of life score (QOL), maximal urinary flow rate (Qmax) and post void residual urine volume (PVR) were analyzed. RESULTS: All cases underwent the surgery successfully. No transurethral resection syndrome was noted. Mean operative time was (72±15) min. Mean intra operative hemorrhage volume was (48.4±13.0) ml. Four patients were transfused with 2 U of suspended red blood cells. Time of postoperative bladder irrigation ranged from 0.5-2.5 d. Time of indwelling urinary catheter was 3-6 d. After removing urinary catheter, mild urinary irritation symptoms were noted in 19 cases. Ten patients developing urinary infection were recovered following anti-infection therapy. One with secondary urethral stenosis was healed after urethral dilatation for three times. Postoperative IPSS, QOL, Qmax and PVR were (6.0±2.0), (2.0±0.2), (18.5±1.6) ml/s and (11.0±4.0) ml, significantly improved compared with preoperative levels (all P<0.05). Fifty eight cases with normal sexual function retained sexual function postoperatively and had no retrograde ejaculation. CONCLUSIONS: Two micron laser vaporesection plus TURP is efficacious and safe in treating BPH with mild lower urinary tract symptoms and perioperative complications.

Oleanolic acid suppresses the proliferation of human bladder cancer by Akt/mTOR/S6K and ERK1/2 signaling.

Oleanolic acid has significant pharmacological activities, such as anti-tumor, regulating blood sugar level and liver protection, which are more effective compared with free aglyconeoleanolic acid. However, it is still unknown if oleanolic acid affects the proliferation of human bladder cancer. We utilized T24 cells to study the effect of oleanolic acid on the proliferation and apoptosis of human bladder cancer. In this study, we found that the anti-cancer effect of oleanolic acid significantly suppressed cell proliferation and increased apoptosis and caspase-3 activity of T24 cells. Furthermore, Akt, mTOR and S6K protein expression was greatly inhibited in T24 cells under oleanolic acid treatment. Meanwhile, ERK1/2 of phosphorylation protein expression was significantly promoted by oleanolic acid treatment. Taken together, we provided evidences that oleanolic acid was Akt/mTOR/S6K and ERK1/2 signaling-targeting anti-tumor agent. These findings represent new evidences that oleanolic acid suppresses the proliferation of human bladder cancer by Akt/mTOR/S6K and ERK1/2 signaling, and oleanolic acid may be used to prevent human bladder cancer.

Diagnosis and treatment of ureteral endometriosis: study of 23 cases.

PURPOSE: To describe our experience in the diagnosis and treatment of 23 patients with ureteral endometriosis. MATERIALS AND METHODS: We performed a retrospective analysis of 23 cases of ureteral endometriosis with histopathological results from 2002 to 2011. RESULTS: In patients with ureteral endometriosis, 23 cases were diagnosed by ultrasound, 21 by intravenous urography, 11 by retrograde urography, 16 by computed tomography, and 8 with magnetic resonance imaging. All cases were treated by operative treatment. The treatments included ureterolysis in 3 cases, partial ureteral resection and ureteroneocystostomy in 6 cases, partial ureteral resection and end-to-end ureteral anastomosis in 12 cases, and endoscopic resection of ureteral endometriosis lesion in 2 cases. All of the pathologic exam­ination results were endometriosis. CONCLUSION: Our findings suggest that surgery is an effective treatment option in most patients with ureteral endometriosis exhibiting mild or moderate to severe hydronephrosis. The type of technique depends on the location and depth of the lesion.

Long-term follow-up on the effects of sigmoid-rectal pouch for urinary diversion.

PURPOSE: The aim of this study was to investigate the long-term clinical effects of sigmoidrectal pouch for urinary diversion. MATERIALS AND METHODS: A total of 45 patients, including 40 males and 5 females, underwent sigmoid-rectal pouch procedure. The patients aged from 38 to 70 years with a mean age of 59 years. The postoperative follow-up ranged from 6 months to 19 years with an average of 6 years. Postoperative continence and voiding were analyzed, urinary reservoir pressure was measured and the complications of upper urinary tract were determined. The index of quality of life (QoL) in the International Prostate Symptom Score (IPSS) was used to evaluate the degree of satisfaction to urinate. RESULTS: Forty patients had slight incontinence in the early postoperative stage and could control urination well 30 days postoperatively. The volume of pouch was 270-600 mL with an average of 375 mL. The basic pressure during filling period was 6-20 cmH2O with an average 15 cmH2O, the maximum filling pressure was 15-30 cmH2O with an average 26 cmH2O. The compliance of sigmoid-rectal pouch was fine with an average of 30 (range 18-40) mL/ cmH2O. There were no severe complications such as hyperchloremic acidosis or retrograde pyelonephritis. Six patients had slight hydronephrosis. The index of QoL were 0-2 in 20 patients, 3 in five patients and 4 in two patients. CONCLUSION: The sigmoid-rectal pouch operation was simple and acceptable by surgeons and patients. It may be an ideal urinary diversion for patients with muscle-invasive bladder cancer, especially for patients on whom urethrectomy should be done.

Sodium butyrate induces growth inhibition and apoptosis in human prostate cancer DU145 cells by up-regulation of the expression of annexin A1.

BACKGROUND: Sodium butyrate, a histone deacetylase inhibitor, has emerged as a promising anticancer drug for multiple cancers. Recent studies have indicated that sodium butyrate could inhibit the progression of prostate cancer; however, the exact mechanism is still unclear. The aim of this study was to investigate the mechanism of sodium butyrate action in prostate cancer DU145 cells. METHODS: The inhibitory effects of NaB on cell growth were detected by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrrazolium bromide assay. Cell apoptosis was determined by flow cytometric analysis of DU145 cells stained with annexin V and PI. Hoechst 33258 and fluorescence microscopes were used to observe the nuclear morphology of DU145 cells after treatment with NaB. ANXA1 knockdown cells were established through transfection with ANXA1 siRNA. ANXA1 mRNA levels were measured by qRT-PCR. Bcl-2, Bax, ANXA1, ERK1/2 and pERK1/2 were detected by western blot. RESULTS: NaB significantly inhibited the growth and induction apoptosis of DU145 and PC3 cells in a dose-dependent manner. Expression of the anti-apoptosis gene Bcl-xl and Bcl-2 in DU145 cells are decreased and expression of the pro-apoptosis gene Bax and Bak increased after NaB treatment. Further studies have demonstrated that NaB up-regulated the expression of ANXA1 and that the tumor inhibition action of NaB was reduced markedly through knockdown of the ANXA1 gene in DU145 cells. Moreover, the siANXA1 cells showed that cell proliferation increased and cell apoptosis was induced by the inactivation of extracellular regulated kinase (ERK). CONCLUSION: Our results support a significant correlation between NaB functions and ANXA1 expression in prostate cancer, and pave the way for further studying the molecular mechanism of NaB actions in cancers.