Shiyu Tong

miR-150 Modulates Cisplatin Chemosensitivity and Invasiveness of Muscle-Invasive Bladder Cancer Cells via Targeting PDCD4 In Vitro

Background Chemotherapeutic insensitivity and tumor cell invasiveness are major obstacles to effectively treating muscle-invasive bladder cancer (MIBC). Recent reports show that microRNAs (miRNAs) play an important role in the chemotherapeutic response and disease progression of MIBC. Therefore, here we investigated the role of miR-150 in MIBC cells in vitro. Material/Methods miR-150 expression was quantified by qRT-PCR in two MIBC cell lines (5637 and T24). After successful miR-150 inhibition by transfection, MTS and transwell assays were used to assess the MIBC’s cisplatin sensitivity and cell invasiveness, respectively. The TargetScan database and a luciferase reporter system were used to identify whether the programmed cell death 4 protein (PDCD4) is a direct target of miR-150 in MIBC cells. Results miR-150 expression was found to be significantly increased in both MIBC cell lines, and treatment with a miR-150 inhibitor significantly sensitized MIBC cells to cisplatin and inhibited MIBC cell invasiveness. PDCD4 was identified as a direct target of miR-150 in MIBC cells, and increased PDCD4 expression via transfection with the pLEX-PDCD4 plasmid efficiently sensitized MIBC cells to cisplatin chemotherapy and inhibited MIBC cell invasiveness. Conclusions This study provides novel evidence that miR-150 functions as a tumor promoter in reducing chemosensitivity and promoting invasiveness of MIBC cells via targeting PDCD4. Thus, modulation of the miR-150-PDCD4 axis shows promise as a therapeutic strategy for MIBC.

Off-Clamp Versus Complete Hilar Control Partial Nephrectomy for Renal Cell Carcinoma: A Systematic Review and Meta-Analysis

OBJECTIVE To evaluate the safety, efficacy, and potential advantages of off-clamp partial nephrectomy (OFF-PN) compared with on-clamp partial nephrectomy (ON-PN). METHODS Relevant studies comparing the safety and efficacy of OFF-PN to ON-PN were identified through a literature search using MEDLINE, EMBASE, and the Cochrane Library. The outcome measures included baseline characteristics, primary outcomes, and secondary outcomes. RESULTS Ten retrospective studies (728 cases and 1267 controls) were included. No significant differences between the two groups were detected in any of the baseline variables (age: p=0.19; sex: p=0.49; BMI: p=0.29; tumor size: p=0.44, pre-eGFR: p=0.78) except for tumor location (p<0.001). The OFF-PN group had a higher blood transfusion rate (odds ratio [OR] 1.54, 95% confidence interval [CI] 10.7-2.21, p=0.02), a lower postoperative complication rate (OR 0.61, 95% CI 0.44-0.83, p=0.002), and a lower positive margin rate (OR 0.49, 95% CI 0.26-0.90, p=0.02) than ON-PN. OFF-PN offered a better preservation of renal function than ON-PN (p=0.005). No significant differences were detected between the two groups in other outcomes of interest. In sensitivity analysis, there was no change in the significance of any of the outcomes except for postoperative complication rate (OR 0.91, 95% CI 0.53-1.5, p=0.73) and positive margin rate (OR 0.55, 95% CI 0.25-1.23, p=0.15). CONCLUSIONS This meta-analysis suggests that with appropriate patient selection, OFF-PN offer comparable perioperative safety, equivalent oncologic outcomes, and superior long-term renal function preservation when compared with ON-PN for renal cell carcinoma. Given the inherent limitations of the included studies, future well-designed randomized controlled trials are required to confirm our findings.

miR-101 Suppresses Vascular Endothelial Growth Factor C That Inhibits Migration and Invasion and Enhances Cisplatin Chemosensitivity of Bladder Cancer Cells

Background The microRNA miR-101 is downregulated in several cancers, including bladder cancer. However, miR-101’s role in the invasion, metastasis, and chemosensitivity of bladder cancer cells remains unclear. This study was conducted to determine miR-101’s role on the lymphangiogenic molecule vascular endothelial growth factor C (VEGF-C) and their effects upon bladder cancer cell migration, invasion, and chemosensitivity to cisplatin. Methods Two bladder cancer cell lines (T24 and 5637) and the tool cell line 293T were employed here. Bladder cancer cells were transfected with either a miR-101 overexpression vector or a scrambled-sequence lentivirus, both of which exhibited a high transfection efficiency. Non-transfection was used as a mock negative control. Wound healing and Transwell assays were performed to measure cell migration and invasiveness. A luciferase reporter assay was performed to validate miR-101’s interaction with VEGF-C’s 3′ untranslated region followed by RT-PCR and Western blot confirmation. An MTS assay was used to evaluate the cisplatin sensitivity of the cell lines. Results miR-101 overexpression significantly inhibited the migration and invasiveness while significantly enhancing cisplatin sensitivity. miR-101 negatively regulated VEGF-C protein expression, and VEGF-C overexpression rescued the effects of miR-101 overexpression, indicating that miR-101 negatively regulates VEGF-C protein expression post-transcriptionally. miR-101 and VEGF-C interference independently enhanced cisplatin cytotoxicity in bladder cancer cells. Conclusions miR-101 suppresses VEGF-C expression, inhibits cell migration and invasion, and increases cisplatin sensitivity in bladder cancer cells. This study provides new insight into miR-101’s role in bladder cancer and shows miR-101’s promise as a potential molecular target for bladder cancer.

The Prognostic Role of Ki-67/MIB-1 in Upper Urinary-Tract Urothelial Carcinomas: A Systematic Review and Meta-Analysis

BACKGROUND Upper urinary-tract urothelial carcinomas (UTUC) constitute 5% of urothelial malignancies. Prognostic biomarkers would allow lower risk surgical approaches for less aggressive UTUCs. One biomarker-Ki-67/mindbomb E3 ubiquitin protein ligase 1 (Ki-67/MIB-1)-shows promise in UTUC, but there have been conflicting findings regarding its prognostic role. The systematic review and meta-analysis aim to determine the prognostic value of Ki-67/MIB-1 in UTUC in terms of UTUC-specific mortality rate, 5-year disease-free survival, and 5-year overall survival (including disease-specific survival). METHODS A systematic review of the current literature produced 654 records. A total of 13 studies consisting of 1030 patients were finally included in the meta-analysis. Hazard ratios (HRs) with 95% confidence intervals (CI) were extracted or estimated. The individual HR estimates were combined into a pooled HR using a fixed-effects model that summed homogeneity of the individual true HRs. RESULTS Patients with Ki-67/MIB-1 overexpression displayed significantly higher UTUC-specific mortality rate (pooled HR: 2.14, 95% CI: 1.73-2.64; p<0.00001), significantly reduced 5-year disease-free survival (pooled HR: 2.27, 95% CI: 1.79-2.92; p<0.00001), and significantly reduced 5-year overall survival (pooled HR=1.77; 95% CI: 1.39-2.23 p<0.00001). There was significant heterogeneity detected in the UTUC-specific mortality rate meta-analysis (I(2)=63%) and the 5-year disease-free survival meta-analysis (I(2)=65%), but there was no significant heterogeneity detected in the 5-year overall survival meta-analysis (I(2)=0%). Eggers testing showed that none of the outcomes were influenced by publication bias (p>0.05). CONCLUSIONS Ki-67/MIB-1 overexpression shows promise as a prognostic biomarker for UTUC patients and requires further investigation.

Epidermal Growth Factor Receptor and Ki-67 as Predictive Biomarkers Identify Patients Who Will Be More Sensitive to Intravesical Instillations for the Prevention of Bladder Cancer Recurrence after Radical Nephroureterectomy

Background To date, prophylactic intravesical chemotherapy after radical nephroureterectomy is one of the few available treatments that effectively prevent secondary bladder cancer. However, treating all patients with prophylactic intravesical chemotherapy is excessive for patients who are at a low risk or insensitive to the treatment. Thus, to guide individualized clinical treatment, in addition to identifying patients who are at risk of bladder cancer recurrence, it is equally necessary to identify the patients who will benefit the most from prophylactic, postoperative intravesical instillation therapy. Methods Epidermal growth factor receptor (EGFR) and Ki-67 expression levels were measured using immunohistochemical staining samples from 320 patients with upper urinary tract urothelial carcinoma (UTUC) from 2004 to 2012. Although no patients received intravesical chemotherapy after RNU before 2008, this method began to be used in 2008 to prevent bladder cancer recurrence. To identify the patients who would most benefit from intravesical chemotherapy, we assessed biological interactions between intravesical chemotherapy and clinicopathological factors or biomarkers. Results The incidence rates of bladder UTUC recurrence decreased after intravesical chemotherapy, and the decrease was greater in patients with low Ki-67 levels, negative EGFR staining and preoperative positive urine cytology. Biological interactions were observed between intravesical chemotherapy, low-level Ki-67 and EGFR negativity. The multivariate analysis showed that after balancing a variety of factors, intravesical chemotherapy is a protective factor for preventing intravesical recurrence in the negative EGFR, low-level Ki-67 and preoperative positive urine cytology sub-groups but not in their corresponding sub-groups. Additionally, the multivariate analysis revealed that preoperative positive urine cytology and Ki-67 were not but that EGFR positivity was an independent risk factor for recurrence after intravesical chemotherapy. Conclusions Patients with low Ki-67 levels, negative EGFR staining and preoperative positive urine cytology appear to be more sensitive to intravesical instillations for bladder recurrence prevention after RNU.

The use of self-retaining barbed suture preserves superior renal function during laparoscopic partial nephrectomy: a PADUA score matched comparison.

INTRODUCTION To evaluate the efficacy and safety of self-retaining barbed suture (SRBS) application during laparoscopic partial nephrectomy (LPN), by assessing perioperative outcomes. MATERIALS AND METHODS Data from consecutive patients who underwent retroperitoneal LPN from January 2008 to December 2013 were retrospectively collected. Patients were divided into two groups according to suture techniques for renorrhaphy: the sliding clip technique and SRBS. The SRBS cases (Group 2 [G2]) were 1:1 matched with cases in the sliding clip group (Group 1 [G1]) for the PADUA score. Patient characteristics, perioperative outcomes, and renal function changes were compared between the groups. RESULTS In total, 41 patients in G1 and 41 patients in G2 successfully underwent LPN. Patient characteristics, operative time, and complication rate were similar for both groups. Mean warm ischemia time was significantly shorter for the SRBS group (G1 versus G2, 27.5 versus 20.7 minutes; P<.05). The estimated blood loss was similar in both groups. An improved early affected renal function recovery was observed in the SRBS group (percentage of glomerular filtration rate reduction for G1 versus G2, 29% versus 20.8%; P<.05). CONCLUSIONS The SRBS application offers an effective and safe renal parenchyma repair. In addition, SRBS appears to significantly minimize the warm ischemia injury and results in superior short-term renal function preservation.

Extraperitoneal and transperitoneal laparoscopic partial cystectomy for benign non-urothelial bladder tumors: an initial experience.

Objective: This study presents our initial experience with extraperitoneal and transperitoneal laparoscopic partial cystectomy (LPC) in the treatment of benign non-urothelial bladder tumors. Methods: Eleven patients with benign non-urothelial bladder tumors underwent extraperitoneal or transperitoneal LPC. The five cases with tumors located on the anterior/anterolateral bladder wall received the extraperitoneal approach. The six cases with tumors located around the bladder dome or over the posterior bladder wall received the transperitoneal approach. Key perioperative parameters were recorded. Results: All patients underwent laparoscopic resection smoothly without requiring a conversion to a traditional open procedure, and no patient displayed perioperative complications. Pathology showed benign non-urothelial bladder tumors with normal margins in all eleven patients, including five leiomyoma cases, three pheochromocytoma cases, two paraganglioma cases and one inflammatory fibrous histiocytoma case. Follow-up cystoscopy and imaging studies in all eleven patients (mean follow-up period 32 months) revealed neither residual nor local recurrence. Conclusions: LPC is safe and feasible in select patients with benign non-urothelial bladder tumors and yields satisfactory oncological and functional results. Extraperitoneal LPC should be preferred for lesions located on the anterior/anterolateral bladder wall, while transperitoneal LPC should be preferred for lesions around the bladder dome or over the posterior bladder wall.

Resveratrol suppresses the epithelial-to-mesenchymal transition in PC-3 cells by down-regulating the PI3K/AKT signaling pathway

ABSTRACT Resveratrol possesses a wide spectrum of pharmacological properties and has been an ideal alternative drug for the treatment of different cancers, including prostate cancer. However, the mechanisms by which resveratrol inhibits the growth of prostate cancer are still not fully elucidated. To understand the effect of resveratrol on the apoptosis and the epithelial-to-mesenchymal transition (EMT) of prostate cancer as well as its related mechanism, we investigated the potential use of resveratrol in PC-3 prostate cancer cells in vitro using real-time PCR, fluorescence-activated cell sorting, Western blotting, etc. Resveratrol suppresses the PC-3 prostate cancer cell growth and induces apoptosis. Resveratrol also influences the expression of EMT-related proteins (increased E-cadherin and decreased Vimentin expression). Finally, resveratrol also suppressed Akt phosphorylation in PC-3 cells. This study indicates that resveratrol may be a potential anti-cancer treatment for prostate cancer; moreover, it provides new evidence that resveratrol suppresses prostate cancer growth and metastasis.

A preoperative marker panel for the prediction of residual tumor and the decision making for repeat transurethral resection.

OBJECTIVE To assess the ability of a combined preoperative marker panel to identify patients with residual non-muscle-invasive bladder cancer who might benefit from repeat transurethral resection (reTUR). METHODS Ki67, p53, vascular endothelial growth factor-C, E-cadherin, and survivin expressions were evaluated by immunohistochemical staining of surgical specimens from 72 patients who underwent reTUR. Related clinical and molecular markers were analyzed by univariate analyses to develop a marker panel. The predictive value of the marker panel was calculated by receiver operating characteristic curves. RESULTS Univariate analyses identified tumor size, number of tumors, p53 expression, E-cadherin expression, and the number of altered markers as risk factors for residual tumor (P = 0.03, 0.05, 0.06, 0.024, and 0.005, respectively). After adjusting for the effects of tumor stage and grade, multivariate analyses identified the number of altered markers as a risk factor for residual tumor (P = 0.004). The addition of tumor size, E-cadherin, and the number of altered markers to the base model (based on tumor stage and tumor grade) increased its discrimination for predicting residual tumor (5%, 6%, and 10%, respectively). CONCLUSION Some clinical and molecular markers could improve the accuracy of residual tumor prediction at reTUR. Such a marker panel may help to identify patients with non-muscle-invasive bladder cancer who have residual tumor after first TUR and who may therefore benefit from reTUR.