BackgroundPrevious work has shown reduced expression levels of let-7 in lung tumors. But little is known about the expression or mechanisms of let-7a in prostate cancer. In this study, we used in vitro and in vivo approaches to investigate whether E2F2 and CCND2 are direct targets of let-7a, and if let-7a acts as a tumor suppressor in prostate cancer by down-regulating E2F2 and CCND2.Methodology/PrincipalFindings Real-time RT-PCR demonstrated that decreased levels of let-7a are present in resected prostate cancer samples and prostate cancer cell lines. Cellular proliferation was inhibited in PC3 cells and LNCaP cells after transfection with let-7a. Cell cycle analysis showed that let-7a induced cell cycle arrest at the G1/S phase. A dual-luciferase reporter assay demonstrated that the 3′UTR of E2F2 and CCND2 were directly bound to let-7a and western blotting analysis further indicated that let-7a down-regulated the expression of E2F2 and CCND2. Our xenograft models of prostate cancer confirmed the capability of let-7a to inhibit prostate tumor development in vivo.Conclusions/SignificanceThese findings help to unravel the anti-proliferative mechanisms of let-7a in prostate cancer. Let-7a may also be novel therapeutic candidate for prostate cancer given its ability to induce cell-cycle arrest and inhibit cell growth, especially in hormone-refractory prostate cancer.

The aim of the study was to objectively analyze the outcomes for minimally invasive percutaneous nephrolithotomy (MPCNL) vs standard percutaneous nephrolithotomy (PCNL) by systematic review and meta-analysis of published data. A systematic literature review was performed in November 2014 using the PUBMED, EMBASE and Cochrane Library databases to identify relevant studies. Only comparative studies investigating MPCNL vs PCNL were included. Effect sizes were estimated by pooled odds ratio (ORs) and mean differences (MDs). The analyzed outcomes were stone-free rate (SFR), blood loss, pain assessment, operative time, hospital stay and complications. We identified 8 trials with a total 749 patients. 353 patients were treated with MPCNL and 396 with PCNL. Meta-analysis of the data showed that there was no difference in SFR between MPCNL and PCNL (OR 1.06, 95% CI 0.71-1.58). Patients in the MPCNL group experienced less drop in hemoglobin (MD: -4.67 g/L, 95% CI -7.29 to -2.04), a lower incidence of blood transfusion (OR 0.18, 95% CI 0.06-0.54), less pain (visual analog score) (MD: -0.53, 95% CI -0.94 to -0.13) and shorter hospitalization (MD: -1.32 days, 95% CI -2.15 to -0.50). Operative time was longer in the MPCNL group (MD: 15.54 min, 95% CI 4.25-26.83). Postoperative fever and pyelocalyceal perforation did not differ between the groups (p = 0.38 and 0.44, respectively). Current evidence suggested that MPCNL was a safe and effective procedure with an SFR comparable to that of PCNL. MPCNL resulted in less bleeding, fewer transfusion, less pain and shorter hospitalization. Well-designed multicentric/international randomized, controlled trials are still needed.

Our experience with the Chinese MPCNL shows that it is safe and effective for managing all kinds of upper-tract calculi.