Zhenqiang Fang

Bladder Regeneration by Collagen Scaffolds With Collagen Binding Human Basic Fibroblast Growth Factor

PURPOSE Studies show that basic fibroblast growth factor can promote bladder regeneration. However, the lack of targeting delivery approaches limits its clinical application. We investigated a collagen based targeting system for bladder regeneration. A collagen binding domain was added to the native basic fibroblast growth factor N-terminal to allow it to bind to collagen. MATERIALS AND METHODS Sprague-Dawley rats underwent partial cystectomy. Collagen scaffolds loaded with collagen binding domain basic fibroblast growth factor, native basic fibroblast growth factor or phosphate buffered saline were grafted to the remaining host bladders, respectively. At days 30 and 90 reconstructed bladders were evaluated by histological analysis and urodynamics. RESULTS This targeting basic fibroblast growth factor delivery system induced satisfying bladder histological structures. It promoted more vascularization and smooth muscle cell ingrowth. Urodynamics revealed well accommodated bladder tissue with volume capacity and compliance. CONCLUSIONS Results show that the targeting delivery system consisting of collagen binding domain basic fibroblast growth factor and collagen membranes induced better bladder regeneration at the injury site. Thus, this targeting delivery system may be an effective strategy for bladder regeneration with potential clinical applications.

XRCC1 Arg194Trp and Arg280His polymorphisms increase bladder cancer risk in Asian population: evidence from a meta-analysis.

Background A lot of studies have investigated the correlation between x-ray cross complementing group 1 (XRCC1) polymorphisms and bladder cancer risk, but the results in Asian population were still inconclusive. We conducted a meta-analysis to ascertain the association of XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphisms with bladder cancer risk in Asian population. Methodology/Principal findings The association strength was measured with odds ratios (ORs) and 95% confidence intervals (95% CIs). A total of 9 eligible studies, conducted in China, India and Japan, were identified. We observed a significant increased risk of bladder cancer in dominant model (OR = 1.199, 95% CI: 1.021,1.408, Pheterogeneity = 0.372), allele comparison (OR = 1.200, 95% CI: 1.057,1.362, Pheterogeneity = 0.107) of Arg194Trp, heterozygote comparison (OR = 1.869, 95% CI: 1.205,2.898, Pheterogeneity = 0.011) and dominant model (OR = 1.748, 95% CI: 1.054,2.900, Pheterogeneity = 0.01) of Arg280His. Pooled results estimated from adjusted ORs further validated these findings. No publication bias was detected. Subgroup analyses found that significant increased risk was only found among community-based studies not hospital-based studies. There was no evidence of publication bias. Conclusion This is the first meta-analysis conducted in Asian investigating the correlation between XRCC1 polymorphisms and susceptibility to bladder cancer. Our meta-analysis shows that XRCC1 Arg194Trp and Arg280His polymorphisms are associated with a significantly increased risk of bladder cancer in Asian population.

Total Retroperitoneal Laparoscopic Nephroureterectomy with Bladder-Cuff Resection for Upper Urinary Tract Transitional Cell Carcinoma

ABSTRACT Background: Open nephroureterectomy (ONU) and bladder cuff resection (ONU-BCR) has been the gold standard of surgical treatment for upper urinary tract transitional cell carcinoma (UUT-TCC). The aim of this study is to introduce a modified total retroperitoneal laparoscopic nephroureterectomy (LNU) with bladder-cuff resection (LNU-BCR) method for treating UUT-TCC and compare its clinical efficacy with ONU-BCR. Methods: Sixty-five patients with UUT-TCC, who underwent ONU-BCR (n = 36) or LNU-BCR (n = 29) between January 2008 and June 2012, were analyzed in this retrospective study. Perioperative data as well as incidence of disease recurrence at the primary site or distant metastasis was compared in patients with at least 6 months follow-up. Results: As compared with patients with ONU-BCR, the patients with LNU-BCR had significantly shorter operative time, lower estimated blood loss, shorter time to oral intake, lower analgesic dose, shorter duration of analgesic use, shorter duration of incision drainage tube, shorter time to ambulation out of bed and reduced postoperative hospital stay (all, p < .05). No significant difference in postoperative complications or incidence of bladder carcinoma recurrence and distant metastasis during the follow-up period was observed. Conclusions: The modified LNU-BCR represents an effective and safe alternative technique to ONU-BCR with the advantages of reduced invasiveness, bleeding and hospitalization.

Association of Vitamin E Intake with Reduced Risk of Kidney Cancer: A Meta-Analysis of Observational Studies

Background Several observational studies suggested that vitamin E intake is related to the risk of kidney cancer; however, the results of published studies are inconsistent. Material/Methods A meta-analysis was performed to assess the relationship between vitamin E intake and the risk of kidney cancer by searching PubMed and Medline through August 2015. We computed pooled relative risks (RR) and 95%CI of kidney cancer for the highest versus lowest level of vitamin E intake. Results A total of 13 observational studies (7 case-control and 6 cohort) were included. The pooled RR (95%CI) of kidney cancer for the highest vs. the lowest level of vitamin E intake was 0.81 (0.69–0.94). In subgroup-analysis, this study found an inverse relationship between vitamin E intake and kidney cancer risk, which was not significantly modified by study design, study population, or sex distribution except in the cohort studies. Conclusions Results of the present study suggest an inverse relationship between vitamin E intake and kidney cancer risk. However, additional well designed cohort studies and randomized controlled trials that focus on the relationship between vitamin E intake and kidney cancer risk are needed.

Suture-free Technique of Extravesical Ureteroneocystostomy With Ring Pin Stapler: Experimental Study of Canines. I. Preliminary Results

OBJECTIVES To compare the mechanical and sutured ureteroneocystostomy in a canine model. METHODS In 18 dogs, extravesical ureteroneocystostomy on 1 side was randomly assigned to end-to-side anastomosis performed with a titanium ring-pin stapler or interrupted absorbable sutures. To create the antireflux tunnel, the longitudinal line of the muscle layer was closed over the implanted ureter with titanium clips or sutures. At 3 months postoperatively, renal ultrasonography, intravenous urography, ascending cystography, the Whitaker test, and the macroscopic and microscopic results were assessed. RESULTS The ureteroneocystostomy with the ring pin stapler and the antireflux tunnel construction with titanium clips had a 100% technical success rate. Compared with manual suturing anastomosis, the suture-free technique took a significantly shorter time and resulted in slightly, but not significantly, less ureteral obstruction after 3 months. One dog in group 2 had evidence of ureteral dilation and hydronephrosis compared with the normal contralateral side. No signs of stone formation, urinary cyst, or fistulas were found after either closure method. None of the 18 dogs demonstrated vesicoureteral reflux. Histologic examination showed no signs of acute inflammation or marked fibrosis in any of the 18 specimens. Moreover, the intrapelvic pressure in group 1 was approximately similar to that of the normal contralateral side. CONCLUSIONS Ureteroneocystostomy performed with a titanium ring-pin stapler is feasible and faster than using conventional sutures. This suture-free technique is simple and safe, with possibly lower complication rates than a nonstented suture technique. Additional studies with a longer follow-up duration are needed to confirm these results.

Long noncoding RNA PVT1 inhibits renal cancer cell apoptosis by up-regulating Mcl-1

Long non-coding RNA plasmacytoma variant translocation 1 (PVT1) is up-regulated in various human cancers, and our results indicated that PVT1 was up-regulated in clear cell renal cell carcinoma tissues. The Cancer Genome Atlas cohort analysis revealed that in clear cell renal cell carcinoma, higher PVT1 expression correlated with advanced TNM stage, histological grade, and poor survival. PVT1 knockdown promoted apoptosis, inhibited renal cancer cell proliferation, decreased Mcl-1, and increased cleaved caspase-3 and cleaved PARP. PVT1 increased Mcl-1 mRNA levels in renal cancer cells by promoting mRNA stability without influencing its transcription. in vitro, the enhanced apoptosis arising from PVT1 suppression was attenuated by overexpressing Mcl-1. In addition, in vivo experiments showed that PVT1 knockdown repressed xenograft tumor growth, while Mcl-1 overexpression partially rescued xenograft tumor growth. These results indicate the PVT1/Mcl-1 pathway inhibits renal cancer cell apoptosis in vitro and in vivo. PVT1 may thus serve as a novel biomarker, and the PVT1/Mcl-1 pathway may be a useful therapeutic target for clear cell renal cell carcinoma.

De Novo Mutations Contribute to the Development of Clear-Cell Renal-Cell Carcinoma in a 5-Year-Old Girl

Clear-cell renal-cell carcinoma (ccRCC) rarely occurs in children, especially in pediatrics reported worldwide. This case is the first worldwide report of ccRCC in a 5year-old girl. It is difficult to distinguish the diagnosis between Wilms tumor and renal-cell carcinoma by using enhanced computed tomography and ultrasound. The purpose of the present report was to discuss the clinical manifestation, pathologic features, and genetic basis for pediatric ccRCC. The present report will play an effective role in guiding clinical practice on the diagnosis of ccRCC.

MicroRNA-34a Attenuates Paclitaxel Resistance in Prostate Cancer Cells via Direct Suppression of JAG1/Notch1 Axis

Background/Aims: Treatment options for metastatic castrate-resistant prostate cancer (mCRPC) are limited and typically centered on paclitaxel-based chemotherapy. In this study, we aimed to evaluate whether miR-34a attenuates chemoresistance to paclitaxel by regulating target genes associated with drug resistance. Methods: We used data from The Cancer Genome Atlas to compare miR-34a expression levels in prostate cancer (PC) tissues with normal prostate tissues. The effects of miR-34a inhibition and overexpression on PC proliferation were evaluated in vitro via Cell Counting Kit-8 (CCK-8) proliferation, colony formation, apoptosis, and cell-cycle assays. A luciferase reporter assay was employed to identify the interactions between miR-34a and specific target genes. To determine the effects of up-regulation of miR-34a on tumor growth and chemo-resistance in vivo, we injected PC cells overexpressing miR-34a into nude mice subcutaneously and evaluated the rate of tumor growth during paclitaxel treatment. We examined changes in the expression levels of miR-34a target genes JAG1 and Notch1 and their downstream genes via miR-34a transfection by quantitative reverse transcription PCR (qRT-PCR) and western blot assay. Results: miR-34a served as an independent predictor of reduced patient survival. MiR-34a was down-regulated in PC-3PR cells compared with PC-3 cells. The CCK-8 assay showed that miR-34a overexpression resulted in increased sensitivity to paclitaxel while miR-34a down-regulation resulted in chemoresistance to paclitaxel in vitro. A study of gain and loss in a series of functional assays revealed that PC cells expressing miR-34a were chemosensitive. Furthermore, the overexpression of miR-34a increased the sensitivity of PC-3PR cells to chemotherapy in vivo. The luciferase reporter assay confirmed that JAG1 and Notch1 were directly targeted by miR-34a. Interestingly, western blot analysis and qRT-PCR confirmed that miR-34a inhibited the Notch1 signaling pathway. We found that miR-34a increased the chemosensitivity of PC-3PR cells by directly repressing the TCF1/ LEF1 axis. Conclusion: Our results showed that miR-34a is involved in the development of chemosensitivity to paclitaxel. By regulating the JAG1/Notch1 axis, miR-34a or its target genes JAG1 or Notch1 might serve as potential predictive biomarkers of response to paclitaxel-based chemotherapy and/or therapeutic targets that will help to overcome chemoresistance at the mCRPC stage.

MicroRNA-34a Attenuates Metastasis and Chemoresistance of Bladder Cancer Cells by Targeting the TCF1/LEF1 Axis

Background/Aims: Chemoresistance is largely responsible for relapses of bladder cancer during clinical therapy. However, the molecular mechanisms involved in the chemoresistance of bladder cancer are unclear. Growing evidence supports the theory that microRNAs (miRNAs) play an important role in chemotherapeutic drug resistance because they are downregulated in many malignancies that have been implicated in the regulation of diverse processes in cancer cells. More specifically, the extent and precise mechanism of the involvement of miR-34as in chemoresistance to epirubicin (EPI) in the treatment of bladder cancer remains unclear. Methods: In this study, real-time quantitative polymerase chain reaction (PCR) was used to analyze the expression of miR-34a in bladder cancer cell line BIU87 and its EPI chemoresistant cell line BIU87/ADR. The miR-34a profiles in bladder cancer tissues were obtained from The Cancer Genome Atlas database. The effect of miR-34a on chemosensitivity was evaluated by cell viability assays, colony formation assays, and in vivo experimentation. Apoptosis and the cell cycle were examined by flow cytometry. A luciferase reporter assay was used to assess the target genes of miR-34a. Western blot and qPCR were used to analyze the expression of target proteins and downstream molecules. Results: The downregulation of miR-34a in bladder cancer serves as an independent predictor of reduced patient survival. The CCK-8 assay showed that miR-34a overexpression resulted in increased sensitivity to EPI, while miR-34a downregulation resulted in chemoresistance to EPI in vitro. Moreover, it was found that miR-34a increased the sensitivity of BIU87/ADR cells to chemotherapy in vivo. The luciferase reporter assay ascertained that TCF1 and LEF1 are direct target genes of miR-34a. It was found that miR-34a increased chemosensitivity in BIU87/ADR cells by inhibiting the TCF1/LEF1 axis. Conclusions: The results of this study indicate that miR-34a contributes to the chemosensitivity of BIU87/ADR by inhibiting the TCF1/LEF1 axis. Consequently, miR-34a is a determinant of BIU87 chemosensitivity and may therefore serve as a potential therapeutic target in bladder cancer treatment.