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.

AbstractsPurpose: To determine whether minimally invasive PCNL (MPCNL) is as safe and effective in the management of complex renal caliceal stones as it is for simple renal stones. Patients and Methods: We retrospectively reviewed 5761(41.2%) simple caliceal stones (isolated renal pelvis including isolated calix) and 8223 (58.8%) complex caliceal stones (renal pelvis accompanying two calices at least) that were managed by MPCNL between 1992 nd 2011. The safety, efficacy, and outcome were compared and analyzed. Results: Stone burden was larger in complex caliceal stones (1763.0 vs 1018.6 mm 2 , P < 0.05). Patients with simple stones had significantly shorter operative time, less frequency of multiple percutaneous accesses, and less hemoglobin drop. They also had a higher initial stone-free rate (SFR) (77.6% vs 66.4%) after a single session of MPCNL (P < 0.05). The differences diminished in the final SFR (86.7% vs 86.1%) after relook and/or auxiliary procedures (P > 0.05). The complication rate (17.9% vs 19.0%) and blood transfusion rate (grade II) (2.2% vs 3.2%) were similar in both groups (P > 0.05). Both groups had a low rate of high Clavien grade complications. Renal vascular embolizations (grade III), however, were significantly higher in patients with complex caliceal stones (P < 0.05). Conclusions: MPCNL is a safe and effective treatment option for patients with complex caliceal stones except there is a slightly higher frequency rate of embolization. There was a higher initial SFR in simple stones, but this difference diminished with secondary procedures.

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In recent years, the RNA-binding protein quaking 5 (QKI-5) has been recognized as a novel tumor suppressor in many cancers. To date, no studies have examined the role of QKI-5 in prostate cancer. The present study was designed to elucidate the correlation of QKI-5 expression with the clinical pathological features and prognosis of prostate cancer. In an overwhelming majority of the 184 cases of prostate cancer samples analyzed, the QKI-5 expression was significantly decreased, which was largely due to the high promoter methylation levels. Using lentiviral vectors, we established two stable prostate cancer cell lines with altered QKI-5 expression, including a QKI-5 overexpressing PC3 cell line and a DU145 cell line with knocked-down QKI-5 expression. The effects of the lentiviral-mediated QKI-5 knockdown on the PC3 cells and DU145 cells were assessed by cell growth curves, flow cytometry (FCM), and an invasion assay. The PC3 cells were transplanted into nude mice, and then, the tumor growth curves and TUNEL staining were determined. These results demonstrated that QKI-5 was highly expressed in benign prostatic hyperplasia (BPH) tissues but not in carcinomatous tissues and that QKI-5 effectively inhibited prostate cancer cell proliferation in vitro and in vivo. In addition, the decrease in QKI-5 expression was closely correlated with the prostate cancer Gleason score, poor differentiation, degree of invasion, lymph node metastasis, distant metastasis, TNM grading, and poor survival. These results indicate that the QKI-5 expression may be a novel, independent factor in the prognosis of prostate cancer patients.

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Patients with a solitary kidney suffering from stones larger than 2 cm in size who undergo MPCNL had a higher SFR than RIRS. The complications were comparable in both groups. Even though RIRS patients spent less time in hospital, this procedure might not be an effective treatment as MPCNL in solitary kidneys with larger and multiple stones.