A simple and effective method for bladder blood clot evacuation using hydrogen peroxide.

OBJECTIVE: Urinary retention caused by bladder clots can be frustrating because such blood clots are difficult to remove. We established a novel technique in which hydrogen peroxide is applied to evacuate bladder clots. METHODS: In this single-center retrospective study, we evaluated 31 patients with retention of blood clots in the bladder who underwent emergency evacuation using hydrogen peroxide. RESULTS: The patients comprised 17 men and 14 women with mean age of 61.2 years (range, 42-82 years). Hydrogen peroxide solution and a 20-Fr three-cavity Foley catheter with large-diameter side holes were used for manual bladder irrigation in all patients. The bladder blood clots were successfully removed in 27 patients. The remaining four patients could not tolerate the symptoms of urinary retention and had to resort to surgery. CONCLUSION: Hydrogen peroxide solution for manual bladder irrigation can improve the efficiency of bladder blood clot evacuation. This is a simple and effective option for managing bladder clot retention.

The clinical study of en bloc transurethral resection with 980 nm laser for treatment of primary non-muscle invasive bladder cancer.

OBJECTIVE: To elevate safety and efficacy of en bloc transurethral resection with 980 nm laser as treatment for primary non-muscle-invasive bladder cancer (NMIBC). METHODS: Total 84 cases were enrolled in this study. Among them, 36 and 48 cases underwent treatment using the 980 nm laser and the traditional TUR-BT procedure, respectively. The peri-operative characteristics (tumor size, tumor multiplicity, tumor grade, etc.) and intra-operative complications (obturator nerve reflex, bladder perforation, bladder irrigation, etc.) were recorded and compared between the two groups. RESULTS: There are no significant difference in baseline characteristics between laser and TUR-Bt treatment groups. Operation time also has no significant difference in two groups. Obturator nerve reflex and bladder perforation were noted in 6 patients and in 3 patients during TUR-Bt group, respectively. No obturator nerve reflex and bladder perforation were observed in the laser group. The patients who need bladder irrigation was lower in laser group than in TUR-Bt group. There were no significant differences in catheterization time and hospitalization time between two groups. No significant difference in the overall recurrence rate were observed among the two groups during the follow-up periods. CONCLUSION: En bloc transurethral resection using 980 nm laser is an effective and safe treatment option for non-muscle-invasive bladder cancer. Compared to the traditional TUR-Bt procedure, the procedure using 980 nm laser has fewer perioperative complications and similar oncological results.

Blockage of O-linked GlcNAcylation induces AMPK-dependent autophagy in bladder cancer cells.

BACKGROUND: High levels of the post-translational modification O-GlcNAcylation (O-GlcNAc) are found in multiple cancers, including bladder cancer. Autophagy, which can be induced by stress from post-translational modifications, plays a critical role in maintaining cellular homeostasis and regulating tumorigenesis. The impact of O-GlcNAcylation on autophagy in bladder cancer remains unclear. Here, we evaluate the change in autophagic activity in response to O-GlcNAcylation and explore the potential mechanisms. METHODS: O-GlcNAcylation levels in bladder cancer cells were altered through pharmacological or genetic manipulations: treating with 6-diazo-5-oxo-norleucine (DON) or thiamet-G (TG) or up- and downregulation of O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA). Autophagy was determined using fluorescence microscopy and western blotting. Co-immunoprecipitation (Co-IP) assays were performed to evaluate whether the autophagy regulator AMP-activated protein kinase (AMPK) was O-GlcNAc modified. RESULTS: Cellular autophagic flux was strikingly enhanced as a result of O-GlcNAcylation suppression, whereas it decreased at high O-GlcNAcylation levels. Phosphorylation of AMPK increased after the suppression of O-GlcNAcylation. We found that O-GlcNAcylation of AMPK suppressed the activity of this regulator, thereby inhibiting ULK1 activity and autophagy. CONCLUSION: We characterized a new function of O-GlcNAcylation in the suppression of autophagy via regulation of AMPK. GRAPHICAL ABSTRACT: Blockage of O-linked GlcNAcylation induces AMPK dependent autophagy in bladder cancer cells.

The status and characteristics of urinary stone composition in China.

OBJECTIVES: To explore characteristics of urinary stone composition in China, and determine the effects of gender, age, body mass index (BMI), stone location, and geographical region on stone composition. PATIENTS AND METHODS: We prospectively used Fourier-transform infrared spectroscopy to analyse stones from consecutive patients presenting with new-onset urolithiasis at 46 hospitals in seven geographical areas of China, between 1 June 2010 and 31 May 2015. Chi-squared tests and logistic regression analyses were used to determine associations between stone composition and gender, age, BMI, stone location, and geographical region. RESULTS: The most common stone constituents were: calcium oxalate (CaOx; 65.9%), carbapatite (15.6%), urate (12.4%), struvite (2.7%), and brushite (1.7%). CaOx and urate stones occurred more frequently in males, whereas carbapatite and struvite were more common in females (P < 0.01). CaOx and carbapatite were more common in those aged 30-50 and 20-40 years than in other groups. Brushite and struvite were most common amongst those aged <20 and >70 years. The detection rate of urate increased with age, whilst cystine decreased with age. Obese patients were more likely to have urate stones than carbapatite or brushite stones (P < 0.01). CaOx, carbapatite, brushite, and cystine stones were more frequently found in the kidney than other types, whereas urate and struvite were more frequent in the bladder (P < 0.01). Stone composition varied by geographical region. CONCLUSIONS: The most common stone composition was CaOx, followed by carbapatite, urate, struvite, and brushite. Stone composition differed significantly in patients grouped by gender, age, BMI, stone location, and geographical region.

Comparison of vaporization using 120-W GreenLight laser versus 2-micrometer continuous laser for treating benign prostatic hyperplasia: A 24-month follow-up study of a single center.

OBJECTIVE: To evaluate safety, efficacy, and long-term outcomes of photoselective vaporization of prostate using 120-W HPS GreenLight KTP laser and compare the results with those obtained with 2-micrometer continuous-wave (2 um CW) laser for treatment of patients with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: One group of 216 patients diagnosed with BPH underwent 120-W KTP laser vaporization of the prostate, while another group of 198 BPH patients underwent 2 um CW laser vaporization. The relevant pre-, peri-, and post-operative parameters were compared between the two therapy groups. Functional results in terms of improvement of International Prostate Symptom Score (IPSS), maximum flow rate (Qmax), and post-void residual (PVR) urine were assessed at 3, 6, 12, and 24 months. RESULTS: BPH was successfully treated with 120-W HPS KTP laser and 2 um CW laser in all patients. There were no significant difference between two patient groups in the baseline characteristics (such as PSA, IPSS, QoL, and Qmax). No major complications occurred intraoperatively (capsule perforation and TUR syndrome) or postoperatively (electric unbalance), and no blood transfusions were required in both groups. Average catheterization time was 1.9±1.3 days for the 120-W PVP and 2.2±1.9 days for the 2 um CW laser treatment. In addition, the hospitalization times were 3.8±1.2days (120-W PVP) and 4.8±1.5 days (2 um CW laser), respectively. The incidence of dysuria and urge incontinence was higher in the 2 um CW laser group (35/198, 24/198) than in the 120 W PVP group (15/216, 10/216). Dramatic improvement was observed in Qmax, IPSS, Qol, and PVR as compared with the respective pre-operative values. The degree of improvement during the follow-up period was comparable in both groups. No significant differences were observed in terms of re-operation rates, bladder neck stricture, and urethral stricture. CONCLUSIONS: Both 120-W HPS laser and 2 um CW laser vaporization present effective treatment options in patients with BPH, but 120-W PVP provides safer therapy with less post-operative complications within the 2-year follow-up period.

A multicenter observational study of the real-world use of docetaxel for metastatic castration-resistant prostate cancer in China.

AIM: To investigate the use of docetaxel for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in real-world clinical practice in China. METHODS: This single-arm, prospective, observational study was conducted at 32 study centers in China and included male patients aged ≥18 years with histologically confirmed prostate cancer who received ≥1 dose of docetaxel following failure of hormonal therapy (disease progression with serum testosterone <50 ng/dL). The primary aim was to investigate patterns of docetaxel treatment. RESULTS: Overall 403 patients were included between August 2011 and June 2016; patients initiated docetaxel after failure of first- (42.2% [170]), second- (31.0% [125]) and ≥third-line (12.7% [51]) hormonal therapy, estramustine (11.4% [46]) or other (2.7% [11]). The planned cycles of docetaxel therapy were completed by 30.8% of patients, and the mean (SD) number of cycles received was 4.4 (2.86). Median overall survival (mOS) was 22.4 (95% CI, 20.4-25.8) months and the prostate-specific antigen (PSA) response rate in patients with available data was 70.9% (168/237), with no differences in mOS and PSA response rates between treatment settings. Subgroup analysis revealed higher mOS in patients without visceral metastasis versus those with such metastases (22.9 vs. 17.4 months; P = 0.022). No new safety signals were observed and the most common adverse events associated with docetaxel were granulocytopenia (5%) and leukopenia (4.5%). CONCLUSION: Data from this study showed that around three-quarters of Chinese patients with mCRPC treated with docetaxel initiated treatment following first- or second-line hormonal therapy and no new safety signals were observed.

Flexible Ureterorenoscopy Management of Calyceal Diverticular Calculi.

OBJECTIVE: To introduce flexible ureterorenoscopy with holmium laser lithotripsy in the management of symptomatic caliceal diverticular calculi. MATERIALS AND METHODS: The records of 26 patients who underwent flexible ureterorenoscopy and lithotripsy with holmium laser to manage symptomatic caliceal diverticular calculi from January 2012 to June 2016 were retrospectively reviewed. RESULT: Flexible ureterorenoscopy lithotripsy was successfully placed in all 26 patients. Twenty-two cases accepted lithotripsy at the same time, and the success rate was 84.6%. The stone-free rate was 76.9%.The mean operative time was 48 ± 16 minutes. The mean hospital stay was 4.8 ± 1.6 days. There was no evidence of stone regrowth or recurrence at a mean follow-up of 11.5 months. CONCLUSION: Flexible ureterorenoscopy with holmium laser lithotripsy is safe and effective, and it can be offered as a first line therapy for symptomatic caliceal diverticular calculi.

[Low-concentration hydrogen peroxide solution for continuous bladder irrigation after transurethral resection of the prostate].

OBJECTIVE: To evaluate the effectiveness and safety of low-concentration hydrogen peroxide solution (HPS) for continuous bladder irrigation after transurethral resection of the prostate (TURP). METHODS: We retrospectively analyzed the clinical data about 148 cases of benign prostatic hyperplasia (BPH) treated by TURP from January 2013 to January 2016. Seventy-six of the patients received postoperative continuous bladder irrigation with 0.15% HPS (group A) and the other 72 with normal saline (group B). We compared the two groups of patients in their postoperative hemoglobin (Hb) levels, duration of bladder irrigation, frequency of catheter blockage, time of catheterization, and length of hospital stay. RESULTS: There were no statistically significant differences between the two groups of patients preoperatively in the prostate volume, International Prostate Symptoms Score, maximum urinary flow rate, postvoid residual urine, or levels of serum PSA and Hb (P > 0.05). At 48 hours after operation, a significantly less reduction was observed in the Hb level in group A than in group B (ï¼»3.38 ± 2.56ï¼½ vs ï¼»7.29 ± 6.58ï¼½ g/L, P < 0.01). The patients of group A, in comparison with those of group B, also showed remarkably shorter duration of postoperative bladder irrigation (ï¼»32.57 ± 5.99ï¼½ vs ï¼»46.10 ± 8.79ï¼½ h, P < 0.01), lower rate of catheter blockage (3.3% vs 11.8%, P < 0.01), shorter time of catheterization (ï¼»3.74 ± 0.79ï¼½ vs ï¼»4.79 ± 0.93ï¼½ d, P < 0.01), and fewer days of postoperative hospital stay (ï¼»4.22 ± 0.81ï¼½ vs ï¼»4.67 ± 0.88ï¼½ d, P < 0.01). CONCLUSIONS: Low-concentration HPS for continuous bladder irrigation after TURP can reduce blood loss, catheter blockage, bladder irrigation duration, catheterization time, and hospital stay, and therefore deserves a wide clinical application.

Combined inhibition of JAK1,2/Stat3­PD­L1 signaling pathway suppresses the immune escape of castration­resistant prostate cancer to NK cells in hypoxia.

Castration­resistant prostate cancer (CRPC) is difficult to treat in current clinical practice. Hypoxia is an important feature of the CRPC microenvironment and is closely associated with the progress of CRPC invasion. However, no research has been performed on the immune escape of CRPC from NK cells. The present study focused on this subject. Firstly, when the CRPC cell lines C4­2 and CWR22Rv1 were induced by hypoxia, the expression of the UL16 binding protein (ULBP) ligand family of natural killer (NK) group 2D (NKG2D; ULBP­1, ULBP­2 and ULBP­3) and MHC class I chain­related proteins A and B (MICA/MICB) decreased. NKG2D is the main activating receptor of NK cells. Tumor cells were then co­cultured with NK cells to conduct NK cell­mediated cytotoxicity experiments, which revealed the decreased immune cytolytic activity of NK cells on hypoxia­induced CRPC cells. In exploring the mechanism behind this observation, an increase in programmed death­ligand 1 (PD­L1) expression in CRPC cells induced by hypoxia was observed, while the addition of PD­L1 antibody effectively reversed the expression of NKG2D ligand and enhanced the cytotoxic effect of NK cells on CRPC cells. In the process of exploring the upstream regulatory factors of PD­L1, inhibition of the Janus kinase (JAK)1,2/signal transducer and activator of transcription 3 (Stat3) signaling pathway decreased the expression of PD­L1 in CRPC cells. Finally, it was observed that combined inhibition of JAK1,2/PD­L1 or Stat3/PD­L1 was more effective than inhibition of a single pathway in enhancing the immune cytolytic activity of NK cells. Taking these results together, it is thought that combined inhibition of the JAK1,2/PD­L1 and Stat3/PD­L1 signaling pathways may enhance the immune cytolytic activity of NK cells toward hypoxia­induced CRPC cells, which is expected to provide novel ideas and targets for the immunotherapy of CRPC.

ATM­JAK­PD­L1 signaling pathway inhibition decreases EMT and metastasis of androgen­independent prostate cancer.

Castration-resistant prostate cancer (CRPC), also known as androgen-independent prostate cancer, frequently develops local and distant metastases, the underlying mechanisms of which remain undetermined. In the present study, surgical specimens obtained from patients with clinical prostate cancer were investigated, and it was revealed that the expression levels of ataxia telangiectasia mutated kinase (ATM) were significantly enhanced in prostate cancer tissues isolated from patients with CRPC compared with from patients with hormone­dependent prostate cancer. CRPC C4­2 and CWR22Rv1 cells lines were subsequently selected to establish prostate cancer models, and ATM knockout cells were established via lentivirus infection. The results of the present study demonstrated that the migration and epithelial­mesenchymal transition (EMT) of ATM knockout cells were significantly decreased, which suggested that ATM is closely associated with CRPC cell migration and EMT. To further investigate the mechanisms underlying this process, programmed cell death 1 ligand 1 (PD­L1) expression was investigated in ATM knockout cells. In addition, inhibitors of Janus kinase (JAK) and signal transducer and activator of transcription 3 (STAT3; Stattic) were added to C4­2­Sc and CWR22Rv1­Sc cells, and the results demonstrated that PD­L1 expression was significantly decreased following the addition of JAK inhibitor 1; however, no significant change was observed following the addition of Stattic. Furthermore, a PD­L1 antibody and JAK inhibitor 1 were added to C4­2­Sc and CWR22Rv1­Sc cells, and it was revealed that cell migration ability was significantly decreased and the expression of EMT­associated markers was effectively reversed. The results of the present study suggested that via inhibition of the ATM­JAK­PD­L1 signaling pathway, EMT, metastasis and progression of CRPC may be effectively suppressed, which may represent a novel therapeutic approach for targeted therapy for patients with CRPC.

ELL2 regulates DNA non-homologous end joining (NHEJ) repair in prostate cancer cells.

ELL2 is an androgen-responsive gene that is expressed by prostate epithelial cells and is frequently down-regulated in prostate cancer. Deletion of Ell2 in the murine prostate induced murine prostatic intraepithelial neoplasia and ELL2 knockdown enhanced proliferation and migration in C4-2 prostate cancer cells. Here, knockdown of ELL2 sensitized prostate cancer cells to DNA damage and overexpression of ELL2 protected prostate cancer cells from DNA damage. Knockdown of ELL2 impaired non-homologous end joining repair but not homologous recombination repair. Transfected ELL2 co-immunoprecipitated with both Ku70 and Ku80 proteins. ELL2 could bind to and co-accumulate with Ku70/Ku80 proteins at sites of DNA damage. Knockdown of ELL2 dramatically inhibited Ku70 and Ku80 recruitment and retention at DNA double-strand break sites in prostate cancer cells. The impaired recruitment of Ku70 and Ku80 proteins to DNA damage sites upon ELL2 knockdown was rescued by re-expression of an ELL2 transgene insensitive to siELL2. This study suggests that ELL2 is required for efficient NHEJ repair via Ku70/Ku80 in prostate cancer cells.

Dual inhibition of BRD4 and PI3K-AKT by SF2523 suppresses human renal cell carcinoma cell growth.

Bromodomain-containing protein 4 (BRD4) and PI3K-AKT are both important for renal cell carcinoma (RCC) development and progression. SF2523 is a BRD4 and PI3K-AKT dual inhibitor. The present study demonstrated that SF2523 was cytotoxic and anti-proliferative to established RCC cell lines (786-O and A498) and primary human RCC cells. SF2523 induced activation of caspase and apoptosis in RCC cells. Further, SF2523 disrupted RCC cell cycle progression and inhibited cell migration in vitro. At the signaling level, SF2523 in-activated PI3K-AKT-mTOR, and downregulated BRD4-dependent proteins, Bcl-2 and Myc, in RCC cells. Remarkably, SF2523 was more efficient than Wortmannin (the PI3K inhibitor) and JQ1 (the BRD4 specific inhibitor) in killing RCC cells. In vivo, SF2523 administration at well-tolerated doses suppressed 786-O xenograft tumor growth in severe combined immunodeficient (SCID) mice. Together, our results suggest that concurrent blockage of BRD4 and PI3K-AKT signalings by SF2523 efficiently inhibits RCC cell growth in vitro and in vivo.

Suppression of STIM1 inhibits the migration and invasion of human prostate cancer cells and is associated with PI3K/Akt signaling inactivation.

Store-operated calcium entry (SOCE) plays an important role in the invasion and migration of cancer cells. Stromal-interacting molecule 1 (STIM1) is a critical component in the SOCE. STIM1 has been attracting more and more attention due to its oncogenic potential. STIM1 inhibition suppresses cell proliferation, migration and invasion in a variety of cancer models both in vitro and in vivo. However, the role of STIM1 in prostate carcinogenesis, in particular, in tumor migration and invasion is unclear. Herein, we downregulated STIM1 in prostate cancer cells by lentivirus-mediated short hairpin (shRNA), and then studied its impacts on cell migration and invasion. We found that migration and invasion of prostate cancer cells were significantly inhibited after the suppression of STIM1. Furthermore, we demonstrated that the PI3K/Akt signaling pathway was inactivated by STIM1 knockdown. The PI3K inhibitor LY294002 synergized with STIM1 knockdown to inhibit cell motility. Our results revealed that STIM1 may act as a novel regulator to promote migration and invasion of prostate cancer cells and is associated with the activation of the PI3K/Akt signaling pathway.

Transrectal real-time tissue elastography targeted biopsy coupled with peak strain index improves the detection of clinically important prostate cancer.

The focus of the present study was to evaluate transrectal real-time tissue elastography (RTE)-targeted two-core biopsy coupled with peak strain index for the detection of prostate cancer (PCa) and to compare this method with 10-core systematic biopsy. A total of 141 patients were enrolled for evaluation. The diagnostic value of peak strain index was assessed using a receiver operating characteristic curve. The cancer detection rates of the two approaches and corresponding positive cores and Gleason score were compared. The cancer detection rate per core in the RTE-targeted biopsy (44%) was higher compared with that in systematic biopsy (30%). The peak strain index value of PCa was higher compared with that of the benign lesion. PCa was detected with the highest sensitivity (87.5%) and specificity (85.5%) using the threshold value of a peak strain index of ≥5.97 with an area under the curve value of 0.95. When the Gleason score was ≥7, RTE-targeted biopsy coupled with peak strain index detected 95.6% of PCa cases, but 84.4% were detected using systematic biopsy. Peak strain index as a quantitative parameter may improve the differentiation of PCa from benign lesions in the prostate peripheral zone. Transrectal RTE-targeted biopsy coupled with peak strain index may enhance the detection of clinically significant PCa, particularly when combined with systematic biopsy.

Breviscapine (BVP) inhibits prostate cancer progression through damaging DNA by minichromosome maintenance protein-7 (MCM-7) modulation.

Naturally occurring compounds are reported as effective candidates for prevention and treatment of various cancers. Breviscapine (BVP) is a mixture of flavonoid glycosides, derived from the Chinese herbs. Previous researches have indicated that BVP has comprehensive pharmacological functions. However, little is known about whether BVP has preventive effects on human prostate cancer. Here, we attempted to explore if BVP inhibits human prostate cancer in vitro and in vivo in a comprehensive manner. We found that BVP triggered cytotoxicity in prostate cancer cell lines dose-dependently. BVP-induced DNA damage caused the cell cycle arrest and apoptosis and further induced cell death. High expression of MCM-7 was reduced in BVP-treated cancer cells and tumor tissues, and also the DNA damage response marker of γH2AX is down-regulated by BVP, associated with MCM-7 expression through regulating retinoblastoma protein (Rb) and checkpoint control proteins expression. Additionally, BVP induced apoptotic response in prostate cancer cells and tumors via activating Caspase-3 and PARP. In vivo studies indicated that BVP impeded tumor growth in xenograft animal models. In conclusion, our data indicates that breviscapine (BVP) can be further explored for its potential, which might be used in human prostate cancer therapeutics.

High expression of Rab25 contributes to malignant phenotypes and biochemical recurrence in patients with prostate cancer after radical prostatectomy.

BACKGROUND: Ras-related protein 25 (Rab25) functions either as an oncogene or a tumor suppressor with a cancer type-dependent manner. We aimed to investigate clinical significance of Rab25 in prostate cancer (PCa). METHODS: Quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry were respectively performed to detect Rab25 mRNA and protein expression in PCa and adjacent non-cancerous prostate tissues. Receiver-operating characteristic curve analysis was used to evaluate predictive diagnostic value of Rab25. Associations of Rab25 expression with various clinicopathological characteristics and biochemical recurrence-free survival of PCa patients were statistically evaluated. In vitro, PCa cell proliferation was assessed by CCK-8 assay, and the cell migration and invasion activities were evaluated by Transwell assay, following the transfection of Rab25 small interfering RNA. RESULTS: Ras-related protein 25 mRNA and protein expression in PCa tissues were both significantly higher than adjacent non-cancerous prostate tissues (both P < 0.001). The area under the curve of Rab25 immunoreactive score (IRS) was 0.896 (P < 0.001) with 74.0% sensitivity and 95.0% specificity. High Rab25 IRS was significantly associated with high Gleason score (P = 0.02) and distant metastasis (P = 0.01). PCa patients with high Rab25 IRS had shorter overall and biochemical recurrence-free survivals than those with low Rab25 IRS (both P < 0.001). Cox regression analysis identified Rab25 as an independent biomarker for both overall and biochemical recurrence-free survivals of PCa patients. By exploring its activities in vitro, Rab25 downregulation was found to inhibit PCa cell proliferation, migration and invasion. CONCLUSIONS: High expression of Rab25 may contribute to malignant progression and biochemical recurrence of PCa patients after radical prostatectomy.

microRNA-302c-3p inhibits renal cell carcinoma cell proliferation by targeting Grb2-associated binding 2 (Gab2).

The expression and biological function of Grb2-associated binding 2 (Gab2) in renal cell carcinoma (RCC) cells was tested here. We showed that Gab2 expression was significantly elevated in human RCC tissues and RCC cells. It was correlated with over-activation of Akt and downregulation of microRNA-302c-3p ("miR-302c-3p"), a putative Gab2-targeting microRNA. Knockdown of Gab2 inhibited Akt activation and 786-O RCC cell proliferation. Reversely, forced over-expression of Gab2 led to Akt hyper-activation to facilitate 786-O cell proliferation. Exogenous expression of miR-302c caused Gab2 downregulation, Akt inhibition and 786-O cell proliferation inhibition. On the other hand, miR-302c-3p depletion by expressing its anti-sense ("antagomiR-302c") led to Gab2 upregulation, Akt activation and increased 786-O cell proliferation. Significantly, miR-302c-3p failed to affect the proliferation of 786-O cells with shRNA-depleted Gab2. Together, we suggest that miR-302c-3p depletion in human RCC cells leads to Gab2 over-expression, Akt hyper-activation and cell proliferation.

Concurrent inhibition of mTORC1 and mTORC2 by WYE-687 inhibits renal cell carcinoma cell growth in vitro and in vivo.

Mammalian target of rapamycin (mTOR)in renal cell carcinoma (RCC) represents a valuable oncotarget for treatment. We here tested the potential anti-RCC activity by a novel mTOR kinase inhibitor WYE-687in vitro and in vivo.WYE-687 was cytotoxic and anti-proliferative to established RCC cell lines (786-O and A498) and primary human RCC cells. Yet, it was non-cytotoxic toHK-2 tubular epithelial cells.WYE-687 provoked caspase-dependent apoptosis in the RCC cells. At the molecular level, WYE-687 almost completely blocked mTORC1 (p-S6K1 and p-S6) and mTORC2 (p-Akt Ser 473) activation in both 786-Ocells and primary human RCC cells, where it downregulated both hypoxia-inducible factor (HIF)-1α and HIF-2α expression. Significantly, oral administration of WYE-687 potently suppressed786-O tumor xenograft growth in nude mice. mTORC1/2 activation and HIF-1α/2α expression were also remarkably downregulated in WYE-687-treated tumor tissues. Thus, our preclinical results imply that WYE-687 may have important translational value for the treatment of RCC.

The efficacy and safety of 2-µm continuous laser in the treatment of high-risk patients with benign prostatic hyperplasia.

Two-micrometer laser resection of prostate-tangerine technique dissects whole prostatic lobes off the surgical capsular, similar to peeling a tangerine. The present study aimed to evaluate the safety and efficacy of 2-µm continuous laser vaporization in the treatment of high-risk patients with benign prostatic hyperplasia (BPH) during the 24-month follow-up. The study included 248 patients with moderate to severe lower urinary tract symptoms who underwent 2-µm continuous laser vaporization of the prostate. All patients were accompanied with different degree comorbidities and 94 patients were taking oral anticoagulants. BPH was successfully treated with 2-µm continuous laser vaporization in all patients. Mean pre-operative prostate volume was 76 ± 25.3 ml and mean operative time was 49.8 ± 16.5 min. There were no major complications intra-operatively or postoperatively, and no blood transfusions were needed. About 20 patients (8.1%) needed bladder irrigation postoperatively. Average catheterization time was 2.0 ± 1.8 days (range 1-5 days). Four patients required reoperation due to enlarged prostates from residual adenoma. At 3-, 6-, 12-, and 24-month follow-ups, maximum urinary flow rates (Qmax) increased from 6.9 ± 1.7 to 19.1 ± 4.2, 19.5 ± 4.6, 19.4 ± 4.6, and 19.5 ± 4.1 ml/s, respectively. Mean International Prostate Symptom Scores (IPSS) decreased from 27.6 ± 5.1 (pre-operation) to 9.2 ± 2.6, 7.12 ± 1.42, 6.18 ± 1.32, and 6.25 ± 1.30 at 3-, 6-, 12-, and 24-month post-operation, respectively. Two-micrometer continuous laser vaporization is a safe and effective surgical endoscopic technique associated with low complication rate in BPH patients at high risk and those on anticoagulation therapy who have severe LUTS caused by BPH.

Chemical characterization, anti-benign prostatic hyperplasia effect and subchronic toxicity study of total flavonoid extract of Pteris multifida.

The decoction of Pteris multifida had been applied to attenuate symptoms of benign prostatic hyperplasia in Chinese folk medicine. In this study, the total flavonoid extract of Pteris multifida was processed at first. High performance liquor chromatography and tandem mass spectrometer assay revealed 10 flavonoids as key constituents of this extract. After 60-day administration, the total flavonoid extract (180 mg/kg, i. g.) decreased the prostate index in mice of benign prostatic hyperplasia apparently. Immunohistochemical assay revealed inhibition of vascular endothelial growth factor expression, together with activation of transforming growth factor-beta 1 expression in the prostatic samples after administration of the extract. A 90-day subchronic toxicity test was further undertaken in male Sprague-Dawley rats, and the no-observed-adverse-effect level for the extract was 200 mg/kg body weight/day. These results revealed that the total flavonoid extract of Pteris multifida exhibited positive effect with safety, which might be applied in treatment of benign prostatic hyperplasia.