Independent association between prostate-specific antigen nadir and PSA progression-free survival in first-line abiraterone acetate treatment in castration-resistant prostate cancer patients: a pilot study.

Background: There is limited evidence regarding the correlation between prostate-specific antigen (PSA) kinetics and clinical outcomes. Therefore, after regulating other covariates, we studied patients with castration-resistant prostate cancer who received abiraterone acetate as the first-line treatment. In this study, we investigated whether time to PSA nadir was independently associated with PSA progression-free survival (PFS). Methods: As a retrospective cohort study, this study contained a total of 77 castration-resistant prostate cancer patients who received abiraterone acetate from October 2015 to April 2021 in a Chinese hospital. The dependent variable was PSA-PFS. The objective independent variable was time to PSA nadir (TTPN). Covariates involved in this study included age, duration of androgen deprivation therapy (ADT), PSA level at baseline, time of 50% PSA decline, time of PSA decline to nadir, Gleason score, bone metastasis, previous treatment, PSA decline <50% in 3 months, PSA to nadir in 3 months, PSA decline <90%, PSA decline <0.2 ng/mL, and PSA flare. Results: For the 77 subjects, their mean age was 72.70 ± 8.08 years. Fully calibrated linear regression findings indicated that PSA decline and kinetics were positively associated with PFS (months) after adjusting confounders (ß = 0.77, 95% CI: 0.11-1.44). A non-linear relationship was not detected between PSA decline or PSA kinetics and progression-free survival. Conclusion: According to the data of this study, there was a correlation between early PSA changes and patients treated with abiraterone acetate.

Real-world effectiveness and safety of goserelin 10.8-mg depot in Chinese patients with localized or locally advanced prostate cancer.

OBJECTIVE: Real-word data on long-acting luteinizing hormone-releasing hormone (LHRH) agonists in Chinese patients with prostate cancer are limited. This study aimed to determine the real-world effectiveness and safety of the LHRH agonist, goserelin, particularly the long-acting 10.8-mg depot formulation, and the follow-up patterns among Chinese prostate cancer patients. METHODS: This was a multicenter, prospective, observational study in hormone treatment-naïve patients with localized or locally advanced prostate cancer who were prescribed goserelin 10.8-mg depot every 12 weeks or 3.6-mg depot every 4 weeks with or without an anti-androgen. The patients had follow-up evaluations for 26 weeks. The primary outcome was the effectiveness of goserelin in reducing serum testosterone and prostate-specific antigen (PSA) levels. The secondary outcomes included testosterone and PSA levels, attainment of chemical castration (serum testosterone <50 ng/dL), and goserelin safety. The exploratory outcome was the monitoring pattern for serum testosterone and PSA. All analyses were descriptive. RESULTS: Between September 2017 and December 2019, a total of 294 eligible patients received ≥ 1 dose of goserelin; 287 patients (97.6%) were treated with goserelin 10.8-mg depot. At week 24 ± 2, the changes from baseline [standard deviation (95% confidence interval)] in serum testosterone (n = 99) and PSA (n = 131) were -401.0 ng/dL [308.4 ng/dL (-462.5, -339.5 ng/dL)] and -35.4 ng/mL [104.4 ng/mL (-53.5, -17.4 ng/mL)], respectively. Of 112 evaluable patients, 100 (90.2%) achieved a serum testosterone level < 50 ng/dL. Treatment-emergent adverse events (TEAEs) and severe TEAEs occurred in 37.1% and 10.2% of patients, respectively. The mean testing frequency (standard deviation) was 1.6 (1.5) for testosterone and 2.2 (1.6) for PSA. CONCLUSIONS: Goserelin 10.8-mg depot effectively achieved and maintained castration and was well-tolerated in Chinese patients with localized and locally advanced prostate cancer.

DOK7, a target of miR-299-5p, suppresses the progression of bladder cancer.

OBJECTIVE: Bladder cancer (BLCA) is the 6th most common malignancy in males. microRNA (miRNAs) can function as tumor suppressors or oncogenic factors, which are of significance in the progression of BLCA. This study explored the mechanisms by which miR-299-5p modulates DOK7 (Docking Protein 7) expression and the functional role of DOK7 in the progression of BLCA. METHODS: The expression of the DOK7 in BLCA patient samples was examined by RT-qPCR (Real-time quantitative polymerase chain reaction), Western blotting and Immunohistochemical (IHC) staining. The malignant phenotype of BLCA cells upon DOK7 overexpression or silencing was assessed by functional assays including cell count kit-9 (CCK8), colony formation and 5-ethynyl-2'-deoxyuridine (Edu) staining assays, as well as Transwell migration and invasion assays. The miRNA regulators of DOK7 were identified through bioinformatics prediction, and the biological role of miR-299-5p/DOK7 axis was validated by functional assays. The impact of miR-299-5p/DOK7 axis on Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway was further examined by Western blotting. RESULTS: DOX7 was significantly downregulated in BLCA tumor tissues compared with normal tissues. Ectopic DOK7 expression suppressed the proliferation, migration and invasion of BLCA cells. DOK7 overexpression also attenuated the tumorigenesis of BLCA cells in nude mice. miR-299-5p was a negative regulator of DOK7 expression in BLCA cells. miR-299-5p/DOK7 axis impaired the malignancy of BLCA cells through regulating the JAK signaling pathway. CONCLUSION: Our data indicate that miR-299-5p/DOK7 axis suppresses BLCA progression possibly by regulating the JAK signaling pathway.

Feasibility of apalutamide combined with androgen deprivation therapy and short-course low-dose prednisone in treating metastatic hormone-sensitive prostate cancer: a pilot randomized controlled trial.

Introduction: The role of prednisone in the prevention of androgen receptor antagonist-related rash and treatment for metastatic hormone-sensitive prostate cancer (mHSPC) is unclear. This pilot trial (ChiCTR2200060388) aimed to investigate the feasibility of apalutamide combined with androgen deprivation therapy (ADT) and short-course low-dose prednisone in the treatment of mHSPC. Methods: All patients received apalutamide and ADT and were randomly divided into two groups based on the administration of oral prednisone or not (control group). The primary endpoint was the incidence of rash. The secondary endpoint included the proportions of patients with a decline in PSA ≥50% from baseline, PSA ≥90% from baseline, and decreased to PSA ≤0.2 ng/mL. Results: Between June 2021 and March 2022, a total of 83 patients were enrolled (41 in the prednisone group and 42 in the control group). During the 6-month follow-up, the incidence of rash was significantly lower in the prednisone group compared with the control group (17.1% vs. 38.1%, P=0.049). There were no significant differences in the incidence of other adverse events, the number of patients who required dose adjustment (reduction, interruption, or discontinuation) of apalutamide due to rash, the number of patients with prostate-specific antigen (PSA) decreased by ≥50%, the number of patients with PSA decrease ≥90%, and the number of patients with PSA ≤0.2 ng/mL between the two groups. All patients with diabetes had stable glycemic control with no glucose-related adverse events. Discussion: In patients with mHSPC, the addition of short-course low-dose prednisolone to apalutamide plus ADT can reduce the incidence of rash without risk of other adverse events.

Polydatin protects against calcium oxalate crystal-induced renal injury through the cytoplasmic/mitochondrial reactive oxygen species-NLRP3 inflammasome pathway.

BACKGROUND: Oxidative stress and inflammatory responses are critical factors in calcium oxalate (CaOx) crystal-induced renal injury. Reactive oxygen species (ROS) are usually produced in the cytoplasm and mitochondria and trigger the priming and activation of the NLRP3 inflammasome, thereby regulating cytokines and inflammation. Polydatin is a plant rhizome extract with anti-inflammatory, antioxidant, and antitumor effects. However, it remains not clear whether and how these pathophysiological processes exists in CaOx crystal-induced renal inflammatory injury. METHODS: Here, we measured the expression of the NLRP3 inflammasome, IL-18, IL-1ß, intracellular and mitochondrial ROS (mtROS) levels and relevant morphological changes in treated renal tubular epithelial cells (TECs) and stone-forming rats. The study further explored the action of intracellular ROS and mtROS on these inflammatory damage, and the beneficial effects and pathway of polydatin. RESULTS: We verified that CaOx crystal-induced cytoplasmic ROS and mtROS upregulation promoted the priming and activation of the NLRP3 inflammasome, thereby stimulating IL-18/1ß maturation and activation. Polydatin can relieve oxidative stress and inflammatory damage by decreasing ROS. We further demonstrated that mtROS is the main target for polydatin to exert the NLRP3 inflammasome-regulating function. The inhibition of mtROS can effectively relieve the inflammatory damage to TECs and kidney caused by CaOx crystal. CONCLUSION: These findings provide new insight into the relationship between mitochondrial damage and inflammation in nephrolithiasis and show that polydatin-mediated anti-inflammatory and antioxidative protection is a therapeutic strategy for, but not limited to, crystalline nephropathy.

Comprehensive characterization of tumor microenvironment in colorectal cancer via molecular analysis.

Colorectal cancer (CRC) remains a challenging and deadly disease with high tumor microenvironment (TME) heterogeneity. Using an integrative multi-omics analysis and artificial intelligence-enabled spatial analysis of whole-slide images, we performed a comprehensive characterization of TME in colorectal cancer (CCCRC). CRC samples were classified into four CCCRC subtypes with distinct TME features, namely, C1 as the proliferative subtype with low immunogenicity; C2 as the immunosuppressed subtype with the terminally exhausted immune characteristics; C3 as the immune-excluded subtype with the distinct upregulation of stromal components and a lack of T cell infiltration in the tumor core; and C4 as the immunomodulatory subtype with the remarkable upregulation of anti-tumor immune components. The four CCCRC subtypes had distinct histopathologic and molecular characteristics, therapeutic efficacy, and prognosis. We found that the C1 subtype may be suitable for chemotherapy and cetuximab, the C2 subtype may benefit from a combination of chemotherapy and bevacizumab, the C3 subtype has increased sensitivity to the WNT pathway inhibitor WIKI4, and the C4 subtype is a potential candidate for immune checkpoint blockade treatment. Importantly, we established a simple gene classifier for accurate identification of each CCCRC subtype. Collectively our integrative analysis ultimately established a holistic framework to thoroughly dissect the TME of CRC, and the CCCRC classification system with high biological interpretability may contribute to biomarker discovery and future clinical trial design.

Dual-Ligand-Functionalized Liposomes Based on Glycyrrhetinic Acid and cRGD for Hepatocellular Carcinoma Targeting and Therapy.

Hepatocellular carcinoma (HCC) is one of the most common cancers, with high mortality. Chemotherapy is one of the main treatment options for HCC. However, the high toxicity and poor specificity of chemotherapeutic drugs have limited their clinical application. In this study, dual-ligand liposomes modified with glycyrrhetinic acid (GA) and cyclic arginine-glycine-aspartic acid (cRGD) (GA/cRGD-LP) were designed to target the GA receptor and αvß3 integrin, respectively. The aim was to develop a highly selective targeted drug delivery system and further enhance the antitumor efficiency of drugs by targeting both hepatic tumor cells and vasculature. A novel lipid conjugate (mGA-DOPE) by coupling dioleoylphosphatidyl ethanolamine (DOPE) with methyl glycyrrhetinic acid (mGA) was synthesized, and its structure was confirmed. The targeting efficiency of GA/cRGD-LP by in vitro cellular uptake and ex vivo imaging was assessed. GA- and cRGD-modified doxorubicin-loaded liposomes (GA/cRGD-LP-DOX) were prepared, and their cytotoxicity in HepG2 and antitumor activity were evaluated. The results showed that the average particle size of the GA/cRGD-LP-DOX was 114 ± 4.3 nm, and the zeta potential was -32.9 ± 2.0 mV. The transmission electron microscopy images showed that the shapes of our liposomes were spherical. cGA/cRGD-LP-DOX displayed an excellent cellular uptake in both HepG2 and human umbilical vein endothelial cells. In the in vivo study, pharmacokinetic parameters indicated that cGA/cRGD-LP can prolong the circulation time of DOX in the blood. GA/cRGD-LP-DOX showed greater inhibition of tumor growth for HepG2-bearing mice than either the single-ligand-modified liposomes or nontargeted liposomes. GA/cRGD-LP-DOX displayed higher liver tumor localization than that of single-ligand-modified liposomes or free DOX. GA/cRGD-LP is a promising drug delivery system for liver cancer targeting and therapy and is worthy of further study.

Systematic review and meta-analysis of therapeutic effects of pelvic restoration combined with anti-stress urinary incontinence surgery on pelvic floor dysfunction.

BACKGROUND: In recent years, pelvic restoration surgery is widely used in the diagnosis and treatment of stress urinary incontinence (SUI) as people pay more attention to postpartum pelvic floor dysfunction (PFD). The therapeutic effect of pelvic restoration combined with anti-SUI surgery remains undetermined. The evaluation indicators of the therapeutic effects include the incidence of postoperative obstruction, the incidence of postoperative defecation difficulties, and the quality of life score. METHODS: PubMed, Cochrane Library, and EMBASE were searched from the establishment of the database to April 2021 for randomized control trials (RCTs) of pelvic restoration and anti-SUI surgery, and the RevMan5.3 software provided by the Cochrane Collaboration was used for meta-analysis. RESULTS: A total of 6 documents (a total of 1,944 patients) were included, including 1,021 patients in the experimental group and 923 patients in the control group. The incidence of obstruction after pelvic restoration combined with anti-SUI surgery was statistically significant (OR =1.35, 95% CI, 0.95-1.92, P=0.10); there was a statistically significant difference in the incidence of postoperative dyspareunia (OR =1.58, 95% CI, 0.91-2.74, P=0.10). DISCUSSION: A total of 8 documents included in this meta-analysis confirmed that pelvic restoration combined with anti-SUI surgery for PFD can improve the prognosis and quality of life of patients.

Systematic review and meta-analysis of ureteral stent for risk factors of restenosis after laparoscopic pyeloplasty.

BACKGROUND: Laparoscopic pyeloplasty (LP) has been widely used to treat ureteropelvic junction obstruction (UPJO); however, no previous series of reports has focused on analyzing the factors that influence the complications and outcomes of LP. In this study, we analyzed the risk factors related to complications of LP, especially that of restenosis. The aim of this study is to perform meta-analysis of relevant comparative studies to analyze the risk factors of restenosis after LP treatment with ureteral stent as of 30 April 2021. METHODS: A systematic search was conducted in April 2021. The evaluation results included operation time (OT), intraoperative blood loss (IBL), anastomotic tension (AT), postoperative drainage (PD), and ectopic blood vessels (EBV). Relative risk (RR) and standardized mean difference (SMD) were extrapolated with a 95% confidence interval (CI). Subgroup analysis was performed based on research design and technology. RESULTS: After screening, 7 studies were included, incorporating a total of 979 patients with PUJO treated by LP. Analysis revealed the likelihood of risk factors as follows: OT [mean difference (MD) -3.16, 95% CI: -7.18 to 0.85; P=0.12], IBL (MD -3.16, 95% CI: -7.18 to 0.85; P=0.12), AT (RR 3.86, 95% CI: 2.96 to 5.02; P<0.00001), PD (MD 303.97, 95% CI: 219.49 to 388.44; P<0.00001), and EBV (RR 1.15, 95% CI: 0.78 to 1.68; P=0.49). The results indicated that high AT and increased PD are risk factors for postoperative ureteral restenosis. DISCUSSION: The results of the meta-analysis showed that among the factors related to the efficacy of LP in the treatment of ureteral stenosis, OT, IBL, AT, and EBV were not significantly correlated with postoperative restenosis. However, AT and PD are independent risk factors for postoperative restenosis of the ureter. Therefore, during the operation, the AT should be reduced, and the local injury is reduced to reduce the PD, thereby reducing the risk of restenosis.

Identification of potential autophagy-associated lncRNA in prostate cancer.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been linked to autophagy. It is urgent to identify and assess the hub autophagy-associated lncRNA in prostate cancer. METHODS: Differentially expressed lncRNAs associated with autophagy were identified in prostate cancer based on The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) data. An autophagy-mediated competing endogenous RNA network was constructed to screen for autophagy-associated lncRNA, and the preselected lncRNAs were further validated using Gene Expression Omnibus (GEO) datasets. Furthermore, a prognostic lncRNA signature was established and assessed. Additionally, Gene Set Enrichment Analysis (GSEA) revealed the underlying molecular mechanisms. RESULTS: Using a competing endogenous RNA network, 66 differentially expressed lncRNAs associated with autophagy were identified, and the differential expression of 7 lncRNAs were verified using the TCGA-PRAD, GSE21034, and GSE94767 datasets. Additionally, a lncRNA signature associated with autophagy, including MKNK1-AS1 and INE1, was identified as an independent indicator of survival with a C-index of 0.882. The GSEA analysis indicated that several autophagy-related signaling pathways were enriched in different risk groups. CONCLUSIONS: The lncRNAs associated with autophagy were identified, and a prediction model was developed that could be used as a prognostic predictor for prostate cancer, indicating the critical role of lncRNA in the regulation of prostate cancer autophagy regulation.

Systematic review and meta-analysis of the efficacy of tension-free vaginal tape on pelvic organ prolapse complicated by stress urinary incontinence.

BACKGROUND: Patients with pelvic organ prolapse combined with stress urinary incontinence (SUI) require pelvic floor repair and surgical treatment; however, there is currently no systematic evaluation of the treatment effect. METHODS: PubMed, Medline, Embase, Elsevier, The Cochrane Library, Web of science, and other databases were searched for randomized controlled trials (RCTs) published between January 2000 and December 2020 regarding tension-free vaginal tape (TVT) treatment of pelvic organ prolapse combined with SUI. Quality evaluation of the articles included in this study was conducted in accordance with the Cochrane Work Manual (5.3), and RevMan 5.3 software was used to conduct meta-analysis of the data extracted from literature meeting the requirements. RESULTS: A total of 10 articles were included, involving a total of 1,361 subjects, including 553 in the control group (a different surgical treatment) and 808 in the observation group (single TVT or TVT combined with pelvic floor repair). The bias evaluation results showed that all of the included literature was rated as level B, so there was no need for sensitivity analysis. The meta-analysis showed that the combined effect size of the clinical cure rate was {odds ratio (OR) [95% confidence interval (CI)]: 3.82 (1.39, 10.52); Z=2.59, P=0.010}, and the combined effect size of the clinical complication rate was [risk difference (RD) (95% CI): -0.09 (-0.16, -0.02); Z=2.38; P=0.02]. The results showed that the clinical cure rate of the observation group was significantly higher than that of the control group, while the clinical complication rate was significantly lower than that of the control group (P<0.05). DISCUSSION: TVT surgery or TVT combined with pelvic floor repair surgery can significantly improve the cure rate of patients with pelvic organ prolapse combined with SUI, and reduce the incidence of postoperative complications. Therefore, TVT is a suitable surgical method for the treatment of patients with pelvic organ prolapse combined with SUI.

[Correlation of Mycoplasma genitalium infection with semen parameters and sperm DNA integrity in male infertility patients].

OBJECTIVE: To analyze the relationship of Mycoplasma genitalium (MG) infection with routine semen parameters and sperm DNA integrity in male infertility patients. METHODS: Totally, 114 semen samples, 34 MG-positive and 80 MG-negative, were collected from male infertility patients and subjected to routine semen analysis with the computer-assisted sperm analysis system, Papanicolaou staining for observation of sperm morphology, and sperm chromatin diffusion (SCD) test for detection of sperm DNA integrity. Semen parameters and DNA integrity were compared between the MG-positive and MG-negative groups with SPSS 21.0 statistical software and the relationship between the semen parameters and DNA integrity analyzed by Pearson correlation analysis. RESULTS: The MG-positive samples, compared with the MG-negative ones, showed significantly decreased semen volume (ï¼»2.87 ± 0.37ï¼½ vs ï¼»3.86 ± 0.43ï¼½ ml, P < 0.01), sperm concentration (ï¼»29.05 ± 6.17ï¼½ vs ï¼»32.56 ± 5.97ï¼½ ×106/ml, P < 0.01), and percentages of progressively motile sperm (PMS) (ï¼»15.86 ± 2.79ï¼½% vs ï¼»23.65 ± 3.47ï¼½%, P < 0.01) and morphologically normal sperm (MNS) (ï¼»6.35 ± 2.06ï¼½% vs ï¼»7.14 ± 1.89ï¼½%, P < 0.05), increased proportions of non-halo sperm (ï¼»15.02 ± 3.52ï¼½% vs ï¼»9.72 ± 2.94ï¼½%, P <0.01) and small-halo sperm (ï¼»16.37 ± 5.26ï¼½% vs ï¼»11.07 ± 1.65ï¼½%, P < 0.01) and sperm DNA fragmentation index (DFI) (ï¼»31.39 ± 3.16ï¼½% vs ï¼»20.79 ± 3.59ï¼½%, P < 0.01), and reduced proportion of large-halo sperm (ï¼»54.75 ± 8.74ï¼½% vs ï¼»64.15 ± 9.76ï¼½%, P < 0.01). DFI was negatively correlated with the percentages of PMS (r = －0.516, P < 0.05) and MNS (r = －0.429, P < 0.05) in the MG-positive group, but not correlated with any of the routine semen parameters in the MG-negative patients (P > 0.05). CONCLUSIONS: MG infection may be an important factor affecting sperm quality in male infertility patients. Active prevention and treatment of MG infection can help prevent male infertility.

Impact of Diabetes Mellitus on Urinary Continence Recovery after Radical Prostatectomy: a Systematic Review and Meta-Analysis.

PURPOSE: To evaluate the impact of diabetes mellitus (DM) on the recovery of urinary continence (UC) after radical prostatectomy (RP). MATERIALS AND METHODS: A systematic review of English articles was performed in August 2019, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Trials were identified in a literature search of PubMed, Embase, Cochrane Library and Web of Science using appropriate search terms. All comparative studies reporting diabetes mellitus, study characteristics, and outcome data including the relationship between diabetes mellitus and urinary continence data were included. Continence rates at different time after RP were compared. Odds ratio (OR) was used for the comparison and all the results were presented with 95% confidence intervals (CIs). RESULTS: Seven cohort studies comprising with 5944 participants were included, the percentage of DM patients was 8.7%. The results showed that DM decreased urinary continence rates at 12 months after RP (OR 0.54, 95%CI 0.36 to 0.81, p = 0.003). The continence rates were not significantly different between DM and Non-DM groups at short-term (catheter removal, 3 months, 6 months) and long-term (>12 months). When stratified by the surgical approaches, the pooled results in patients who underwent robot -assisted radical prostatectomy (RARP) were similar to results of the overall analysis. CONCLUSION: DM has an adverse impact on the recovery of UC during the intermediate-term after RP. Well-designed trials with strict control of confounders are needed to make results more comparable.

Expression of CD44 and the survival in glioma: a meta-analysis.

BACKGROUND: Higher tumor expression of CD44, a marker of cancer stem cells (CSCs), is associated with poor overall survival (OS) in various cancers. However, the association between CD44 and poor OS remains inconsistent in glioma. We aimed to evaluate the potential predictive role of CD44 for prognosis of glioma patients in a meta-analysis. METHODS: Observational studies comparing OS of glioma patients according to the level of CD44 were identified through searching PubMed, Embase, and Cochrane's Library databases. Meta-analyses were performed with a random- or fixed-effect model according to the heterogeneity. Subgroup analyses were performed to evaluate the influences of study characteristics. RESULTS: Eleven retrospective cohort studies were included. Results showed that increased CD44 expression in tumor predicted poor OS in glioma patients (hazard ratio [HR]: 1.42, 95% confidence interval [CI]: 1.02-1.97, P=0.04). Subgroup analyses showed that higher tumor CD44 expression significantly predicted poor OS in patients with World Health Organization (WHO) stages II-III glioma (HR: 2.99, 95% CI: 1.53-5.89, P=0.002), but not in patients with glioblastoma (HR: 1.26, 95% CI: 0.76-2.08, P=0.47; P for subgroup difference = 0.03). Results were not statistically different between subgroups according to patient ethnicity, sample size, CD44 detection method, CD44 cutoff, HR estimation, univariate or multivariate analysis, or median follow-up durations (P-values for subgroup difference all >0.10). CONCLUSION: Higher tumor expression of CD44 may predict poor survival in patients with glioma, particularly in those with WHO stage II-III glioma.

miR-7-5p acts as a tumor suppressor in bladder cancer by regulating the hedgehog pathway factor Gli3.

Although important progresses have been made in the diagnosis and treatment of bladder cancer (BCa), the overall survival for patients with advanced BCa remains poor. It is necessary to uncover the molecular mechanism underlying the initiation and progression of bladder cancer. According to previous reports, mircoRNAs (miRNAs) can regulate tumorigenesis by targeting their downstream mRNAs. This study aims to explore and analyze a novel miRNA-mRNA axis which can regulate the progression of bladder cancer. Based on the microarray analysis, 182 mRNAs were found to be upregulated in BCa tissues. Gene oncology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that these upregulated mRNAs are related with hedgehog pathway. Gli3, an important factor of hedgehog pathway, belongs to these 182 upregulated mRNAs. Therefore, Gli3 was chosen to do further study. Kaplan-Meier analysis revealed that highly expressed Gli3 predicted unfavorable prognosis for patients with BCa. Results of functional experiments indicated the inhibitory effects of silenced Gli3 on cell proliferation, migration and EMT progress. Mechanically, Gli3 was the target mRNA of miR-7-5p in BCa cells. Finally, rescue assays were performed to validate the specific function of miR-7-5p/Gli3 axis in BCa progression. According to all data, we concluded that miR-7-5p acts as a tumor suppressor in BCa by downregulating Gli3.

Value of the Application of Neuroendoscope in the Treatment of Ventriculoperitoneal Shunt Blockage.

OBJECTIVE: To explore the value of the application of neuroendoscopy techniques in the treatment of ventriculoperitoneal (VP) shunt blockage. METHODS: Our study included 3 plans for revision surgeries for VP shunt blockage. In plan A, the choroid plexus or ependyma growing inside the ventricular catheter was completely removed. In plan B, the terminal part of the ventricular catheter was clipped and removed. In plan C, the ventricular catheter was carefully extracted with the aid of neuroendoscopy, and the tissues blocking the catheter were removed. The ventricular catheter was then reinserted into the lateral ventricle. RESULTS: The side holes of the tube may be blocked by cerebral tissue, granulation tissue, newly formed blood vessels, choroid plexus, or ependyma. Five patients successfully underwent plan A revision surgery, 8 patients underwent plan B revision surgery, and the remaining 22 patients underwent plan C revision surgery. After the operation, 34 patients experienced relief of symptoms of elevated intracranial pressure. In all patients, the shunt obstruction was resolved. CONCLUSIONS: Neuroendoscopy techniques can be used to reveal the various causes of shunt obstruction. Any attempt to extract the tube should be performed with the aid of a neuroendoscope. The 3 surgical revision strategies for a blocked catheter are described for the first time in the literature. These approaches can reduce the operation time, the incidence of intraventricular hemorrhage, and the risk of infection.

A phase 3, double-blind, randomized placebo-controlled efficacy and safety study of abiraterone acetate in chemotherapy-naïve patients with mCRPC in China, Malaysia, Thailand and Russia.

OBJECTIVE: This double-blind, placebo-controlled phase 3 study was designed to compare efficacy and safety of abiraterone acetate + prednisone (abiraterone) to prednisone alone in chemotherapy-naïve, asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer (mCRPC) patients from China, Malaysia, Thailand and Russia. METHODS: Adult chemotherapy-naïve patients with confirmed prostate adenocarcinoma, Eastern Cooperative Oncology Group (ECOG) performance status (PS) grade 0-1, ongoing androgen deprivation (serum testosterone <50 ng/dL) with prostate specific antigen (PSA) or radiographic progression were randomized to receive abiraterone acetate (1000 mg, QD) + prednisone (5 mg, BID) or placebo + prednisone (5 mg, BID), until disease progression, unacceptable toxicity or consent withdrawal. Primary endpoint was improvements in time to PSA progression (TTPP). RESULTS: Totally, 313 patients were randomized (abiraterone: n = 157; prednisone: n = 156); and baseline characteristics were balanced. At clinical cut-off (median follow-up time: 3.9 months), 80% patients received treatment (abiraterone: n = 138, prednisone: n = 112). Median time to PSA progression was not reached with abiraterone versus 3.8 months for prednisone, attaining 58% reduction in PSA progression risk (HR = 0.418; p < 0.0001). Abiraterone-treated patients had higher confirmed PSA response rate (50% vs. 21%; relative odds = 2.4; p < 0.0001) and were 5 times more likely to achieve radiographic response than prednisone-treated patients (22.9% vs. 4.8%, p = 0.0369). Median survival was not reached. Most common (≥10% abiraterone vs. prednisone-treated) adverse events: bone pain (7% vs. 14%), pain in extremity (6% vs. 12%), arthralgia (10% vs. 8%), back pain (7% vs. 11%), and hypertension (15% vs. 14%). CONCLUSION: Interim analysis confirmed favorable benefit-to-risk ratio of abiraterone in chemotherapy-naïve men with mCRPC, consistent with global study, thus supporting use of abiraterone in this patient population.

Long non-coding RNA CCAT2 promotes cell proliferation and invasion through regulating Wnt/ß-catenin signaling pathway in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a common urologic malignancy. Long non-coding RNA colon cancer-associated transcript 2 (CCAT2) has been suggested as serving pivotal roles in tumorigenesis. However, the clinical significance and biological role of CCAT2 in ccRCC remains elusive. The purpose of this study is to identify the function of CCAT2 in ccRCC and its possible molecular mechanism. Expression of CCAT2 was analyzed in 61 ccRCC tissues and two ccRCC cell lines (786-O and ACHN) by quantitative reverse transcription polymerase chain reaction. The functional roles of CCAT2 in ccRCC were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, colony formation assay, Transwell assay, and flow cytometric analysis. The influence of CCAT2 on tumorigenesis was monitored by in vivo mice xenograft model. The activation of Wnt/ß-catenin signaling pathway was evaluated by the TOP/FOP Wnt luciferase reporter assay and western blot assay. CCAT2 expression was markedly higher in ccRCC cell lines and tissues, being positively associated with tumor size and tumor stage in ccRCC patients. Patients with higher CCAT2 expression had a markedly poorer overall survival than did patients with low CCAT2 expression. Knocking down CCAT2 expression led to reduced cell proliferation and increased apoptosis of ccRCC cells in vitro as well as the activation of Wnt/ß-catenin signaling pathway, and CCAT2 overexpression remarkably enhanced these oncogenic properties. In vivo mice xenograft model also showed that knocking CCAT2 expression inhibited the growth of ccRCC xenografts. In conclusion, these results indicated that CCAT2 may play a critical role in ccRCC progression and will be further considered as a biomarker for predicting the survival of ccRCC patients and a potential therapeutic target for ccRCC intervention.

miR-143 Induces the Apoptosis of Prostate Cancer LNCap Cells by Suppressing Bcl-2 Expression.

BACKGROUND Prostate cancer has become a serious threat to the life of patients. microRNAs are small non-coding RNA molecules that regulate the growth and apoptosis of cells. We aimed to investigate the regulation and mechanism of microRNA (miR-143) in the proliferation and apoptosis of prostate cancer LNCap cells. MATERIAL AND METHODS miR-143 and control scramble miRNA were synthesized and respectively transfected into LNCap cells. The proliferation and apoptosis were detected by MTT assay, flow cytometry, and caspase-3 activity assay. The intracellular expression of Bcl-2 was determined by Western blot. Further, LNCap cells were transfected with small interfering RNA (siRNA) targeting Bcl-2 (siBcl-2) or plasmid expressing Bcl-2, followed by transfection of miR-143 or control miRNA. Bcl-2 expression was detected by Western blot, and cell apoptosis was measured by caspase-3 activity assay. RESULTS Transfection of miR-143 significantly inhibited the proliferation of LNCap cells (P=0.0073), increased the percentage of externalized phosphatidylserine (P=0.0042), activated the caspase-3 (P=0.0012), and decreased the expression of Bcl-2 (P=0.012) when compared with the control miRNA group. The expression of Bcl-2 was significantly reduced after siBcl-2 transfection. The apoptosis in the siBcl-2+miR-143 group was significantly increased compared with that in the miR-143 group (P=0.036), whereas there was no significant difference in the apoptosis between the siBcl-2+miRNA and miRNA groups. The expression of Bcl-2 was obviously higher after the transfection of Bcl-2-expressing plasmid. The apoptosis in Bcl-2+miR-143 group was significantly reduced compared with the miR-143 group (P=0.031), whereas no significant difference in the apoptosis was detected between the miRNA and Bcl-2+miRNA groups. CONCLUSIONS Transfection of miR-143 induces the apoptosis of prostate cancer LNCap cells by down-regulating Bcl-2 expression, suggesting that Bcl-2 might be a potential therapeutic target for prostate cancer.

[Microscopic spermatic vein ligation for the treatment of varicocele].

OBJECTIVE: To explore the effect of spermatic vein ligation under the microscope in the treatment of varicocele (VC). METHODS: A total of 120 VC patients received in our department from September 2011 to February 2015 were randomly divided into an experimental and a control group of equal number, the former treated by microscopic spermatic vein ligation and the latter by conventional open high ligation. Comparisons were made between the two groups of patients in the internal diameters of the spermatic vein during eupnea and Valsalva maneuver, the reflux time of the spermatic vein, blood flow parameters of the testicular artery, and semen quality before and at 3 months after surgery. RESULTS: At 3 months after surgery, the experimental group, as compared with the control, showed significantly decreased reflux time of the spermatic vein (ï¼»0.41 ± 0.10ï¼½ vs ï¼»1.08 ± 0.10ï¼½ s, P <0.05) and peak systolic velocity (9.26 ± 1.35 vs 10.64 ± 1.28, P <0.05) and resistance index (0.52 ± 0.03 vs 0.61 ± 0.03, P <0.05) of the testicular artery but markedly increased internal diameters of the spermatic vein during eupnea (ï¼»1.63 ± 0.07ï¼½ vs ï¼»1.59 ± 0.06ï¼½ mm, P <0.05) and Valsalva maneuver (ï¼»1.72 ± 0.05ï¼½ vs ï¼»1.68 ± 0.07ï¼½ mm, P <0.05), sperm concentration (ï¼»46.84 ± 5.24ï¼½ vs ï¼»35.35 ± 4.26ï¼½ ×106/ml, P <0.05), sperm motility (ï¼»63.75 ± 7.73ï¼½ vs ï¼»53.87 ± 6.46ï¼½ %, P <0.05), and total sperm count (ï¼»89.54 ± 7.95ï¼½ vs ï¼»75.24 ± 8.43ï¼½ ×106/ml, P <0.05). CONCLUSIONS: Microscopic spermatic vein ligation has a definite effect in the treatment of varicocele, which can significantly improve the testicular blood flow and semen quality of the patient.