Non-invasive Urine Test for Molecular Classification of Clinical Significance in Newly Diagnosed Prostate Cancer Patients.

Objective: To avoid over-treatment of low-risk prostate cancer patients, it is important to identify clinically significant and insignificant cancer for treatment decision-making. However, no accurate test is currently available. Methods: To address this unmet medical need, we developed a novel gene classifier to distinguish clinically significant and insignificant cancer, which were classified based on the National Comprehensive Cancer Network risk stratification guidelines. A non-invasive urine test was developed using quantitative mRNA expression data of 24 genes in the classifier with an algorithm to stratify the clinical significance of the cancer. Two independent, multicenter, retrospective and prospective studies were conducted to assess the diagnostic performance of the 24-Gene Classifier and the current clinicopathological measures by univariate and multivariate logistic regression and discriminant analysis. In addition, assessments were performed in various Gleason grades/ISUP Grade Groups. Results: The results showed high diagnostic accuracy of the 24-Gene Classifier with an AUC of 0.917 (95% CI 0.892-0.942) in the retrospective cohort (n = 520), AUC of 0.959 (95% CI 0.935-0.983) in the prospective cohort (n = 207), and AUC of 0.930 (95% 0.912-CI 0.947) in the combination cohort (n = 727). Univariate and multivariate analysis showed that the 24-Gene Classifier was more accurate than cancer stage, Gleason score, and PSA, especially in the low/intermediate-grade/ISUP Grade Group 1-3 cancer subgroups. Conclusions: The 24-Gene Classifier urine test is an accurate and non-invasive liquid biopsy method for identifying clinically significant prostate cancer in newly diagnosed cancer patients. It has the potential to improve prostate cancer treatment decisions and active surveillance.

Total Glucosides of Paeony Alleviate Cell Apoptosis and Inflammation by Targeting the Long Noncoding RNA XIST/MicroRNA-124-3p/ITGB1 Axis in Renal Ischemia/Reperfusion Injury.

OBJECTIVE: Renal ischemia/reperfusion injury (RI/RI) is the main cause of acute kidney injury. Total glucosides of paeony (TGP) are a traditional Chinese medicine. This study was aimed at exploring the role of TGP in RI/RI and its underlying mechanism of action. METHODS: Rat RI/RI models were constructed by surgical operation. Serum creatinine (Scr) and blood urea nitrogen (BUN) were used to evaluate renal function. The levels of proinflammatory cytokines were detected by ELISA. RI/RI was simulated by hypoxia/reoxygenation (H/R) treatment in renal cells in vitro. The lncRNA XIST (XIST) expression was analyzed by qRT-PCR. Then, the viability and apoptosis of renal cells were detected by MTT and flow cytometry assay. Additionally, dual-luciferase reporter assay was used to determine the interactions among XIST, microRNA-124-3p (miR-124-3p), and ITGB1. RESULTS: TGP improved renal function and inhibited inflammatory responses after RI/RI. XIST expression was highly expressed in rat RI/RI models and H/R-treated renal cells, whereas treatment with TGP downregulated the XIST expression. Additionally, TGP increased viability and attenuated apoptosis and inflammation of H/R-treated renal cells via inhibiting XIST. Moreover, XIST was competitively bound to miR-124-3p, and ITGB1 was a target of miR-124-3p. miR-124-3p overexpression or ITGB1 inhibition rescued the reduction effect on viability and mitigated the promoting effects on cell apoptosis and inflammation caused by XIST overexpression in H/R-treated renal cells. CONCLUSIONS: In vivo, TGP attenuated renal dysfunction and inflammation in RI/RI rats. In vitro, TGP inhibited XIST expression to modulate the miR-124-3p/ITGB1 axis, alleviating the apoptosis and inflammation of H/R-treated renal cells.

[Value of suprapubic cystostomy in bipolar transurethral resection of the prostate for benign prostatic hyperplasia below 80 gram].

OBJECTIVE: To investigate the perioperative benefit of suprapubic cystostomy in bipolar transurethral resection of the prostate (B-TURP) for treatment of benign prostatic hyperplasia (BPH) below 80 g. METHODS: This retrospective study was conducted in patients undergoing B-TURP for BPH below 80 g, who were stratified with respect of suprapubic cystostomy in B-TURP. The end points including the safety, efficiency, complications and nursing care were compared between the two groups. RESULTS: A total of 585 patients were enrolled, including 366 in cystostomy group and 219 in non-cystostomy group. The two groups showed similar postoperative reduction of serum sodium (0.06 vs 0.54 mmol/L, P>0.05), hematocrict (2.44% vs 2.89%, P>0.05), and blood hemoglobin concentration (9.62 vs 10.42 g/L, P>0.05), with comparable weight of resected prostate (42.50 vs 43.76 g, P>0.05). The operation time was significantly longer in cystostomy group than in non-cystostomy group (90.75 vs 76.28 min, P<0.05), but the rate of blood transfusion and incidences of postoperative fever and catheter blocking were comparable between the two groups. Compared with the non-cystostomy group, cystostomy group had significantly longer time for bladder washing (3.15 vs 2.57 days, P<0.05), catheter indwelling time (5.19 vs 4.15 days, P<0.05), and hospital stay after the operation (7.36 vs 5.65 days, P<0.05). CONCLUSIONS: In B-TURP for BPH below the weight of 80 g, suprapubic cystostomy is associated with a longer time for operation, bladder washing, catheter indwelling and postoperative hospital stay, and thus provides no obvious benefits for the patients.

Norcantharidin inhibits pre-replicative complexes assembly of HepG2 cells.

Norcantharidin (NCTD) is currently used for anticancer therapy but the exact mechanism of action remains unknown. Pre-replicative complexes (pre-RCs) are essential for cell DNA replication and highly related to malignant proliferation. Here, we examined the inhibitory effect of NCTD on pre-RC components in HepG2 cells. We showed that NCTD induced degradation of Cdc6 and Mcm2 in a dose-dependent manner. Under 100 µM NCTD concentration, about 70% of Cdc6 and 50% of Mcm2 were degraded. In addition, the nuclear translocation of Mcm6 was inhibited by NCTD. Further studies aiming at G1 synchronous cells showed that, NCTD reduced the chromatin-bound Cdc6, Mcm2 and Mcm6. Moreover, the cells were blocked from entering the S phase and accumulated at the G1 phase when released synchronously into the cell cycle. Consistently, the DNA replication was inhibited by NCTD. Finally, the combination NCTD with Cdc6 depletion lead to more severe cytotoxicity (88%) than NCTD (52%) and Cdc6 depletion (39%) alone. A synergic cytotoxicity was observed between Cdc6 depletion and NCTD. In conclusion, our results demonstrate that NCTD inhibits pre-RC assembly; subsequently blocks the G1 to S transition; and inhibits DNA replication in HepG2 cells. Pre-RCs are an intriguing target for cancer therapy, which merits further investigations for anticancer development.

The association of tea consumption with bladder cancer risk: a meta-analysis.

The association between tea consumption and bladder cancer has been confirmed in several animal studies, but one epidemiological study in 2001 showed no association between them. In order to provide an accurate assessment of this, we conducted a meta-analysis on tea consumption and bladder cancer risk. Studies were identified by a literature search in PubMed from January 1980 to March 2012 and the reference lists of relevant studies. Random effect models were used to calculate summary relative risk estimates (RR) and their corresponding 95% confidence intervals (CI) based on high contrast to low intake values. Twenty-four publications (6 cohort studies and 18 case-control studies) based on consumption of overall tea, black tea, and green tea to bladder cancer risk were included in this analysis. For overall tea, the summary RR indicated no association between tea consumption and bladder cancer (RR= 1.09, 95%CI: 0.85-1.40). In subgroup analyses, we found a moderate increase of bladder cancer risk in smoking group (RR= 1.77, 95%CI: 1.04-3.01). In the black tea group, no statistically significant association was observed (RR= 0.84, 95%CI: 0.70-1.01). Interestingly, in the subgroup of sex, a protective effect was observed between tea consumption and bladder cancer risk in female (RR= 0.61, 95%CI: 0.38- 0.98). For green tea group, there was no relationship associated with bladder cancer risk (RR= 1.03, 95%CI: 0.82- 1.31). In conclusion, our data suggest that high overall tea intake in smokers increased the risk of bladder cancer, and high black tea intake in female may reduce the risk of bladder cancer.