Ru-Min Wen

SATB1 is overexpressed in metastatic prostate cancer and promotes prostate cancer cell growth and invasion.

BackgroundSpecial AT-rich sequence binding protein 1 (SATB1) is a nuclear factor that functions as the global chromatin organizer to regulate chromatin structure and gene expression gene expression. SATB1 has been shown to be abnormally expressed in various types of cancer. However, the expression and role of SATB1 in prostate cancer remain unclear.Methods120 cases of prostatic carcinoma and 60 cases of benign prostate hyperplasia were analyzed for SATB1 expression by immunohistochemistry. LNCaP, DU-145, and PC3 prostate cancer cells were examined for SATB1 expression by Western blot analysis. Cell proliferation and invasion was evaluated by CCK8 and transwell invasion assay, respectively.ResultsSATB1 staining was stronger in prostatic carcinomas with metastasis than in those without metastasis, but was absent in benign prostate hyperplasia. Furthermore, SATB1 expression was positively correlated with bone metastasis and the Gleason score. SATB1 overexpression promoted the proliferation and invasion of LNCaP cells while SATB1 knockdown inhibited the proliferation and invasion of DU-145 cells.ConclusionsThese findings provide novel insight into oncogenic role of SATB1 in prostate cancer, suggesting that SATB1 is a promising biomarker and therapeutic target for prostate cancer.

Inhibition of renal cancer cell growth by oncolytic adenovirus armed short hairpin RNA targeting hTERT gene

RNA interference (RNAi) has been proved to be a powerful tool for gene knockdown purpose and holds a great promise for the treatment of cancer. Our previous study demonstrated that the reduction of hTERT expression by means of chemically synthesized siRNAs and shRNAs expressed from plasmid resulted in proliferation inhibition in human renal carcinoma cells. In this study, we constructed a novel oncolytic adenovirus-based shRNA expression system, ZD55-hTERT, and to explore ZD55- hTERT–mediated RNAi for hTERT gene silencing. Our results showed that ZD55-hTERT could induce silencing of hTERT gene effectively, allow for efficient tumor-specific viral replication and induce the apoptosis of tumor cells effectively in vitro and in nude mice. We conclude that combining shRNA gene therapy and oncolytic virotherapy can enhance antitumor efficacy as a result of synergism between CRAd oncolysis and shRNA antitumor responses.

Potent antitumor efficacy of interleukin-18 delivered by conditionally replicative adenovirus vector in renal cell carcinoma-bearing nude mice via inhibition of angiogenesis.

It has been demonstrated that interleukin 18 (IL-18) exerts antitumor activity. In this study, we investigated whether oncolytic adenovirus-mediated gene transfer of IL-18 could induce strong antitumor activity. A tumor-selective replicating adenovirus expressing IL-18 (ZD55-IL-18) was constructed by insertion of an IL-18 expression cassette into the ZD55 vector, which is based on deletion of the adenoviral E1B 55-kDa gene. ZD55-IL-18 could express substantially more IL-18 than Ad-IL-18 because of replication of the vector. It has been shown that ZD55-IL-18 exerted a strong cytopathic effect and significant apoptosis in renal cell carcinoma. ZD55-IL-18 significantly decreased VEGF and CD34 expression in the tumor cells. Treatment of established tumors with ZD55-IL-18 showed much stronger antitumor activity than that induced by ZD55-EGFP or Ad-IL-18. These data indicated that oncolytic adenovirus expressing IL-18 could exert potential antitumor activity via inhibition of angiogenesis and offer a novel approach to cancer therapy.

Preoperative Neutrophil to Lymphocyte Ratio as a Prognostic Factor in Patients with Non-metastatic Renal Cell Carcinoma.

BACKGROUND The neutrophil-to-lymphocyte ratio (NLR) is a strong predictor of mortality in patients with colorectal, lung, gastric cancer, pancreatic and metastatic renal cell carcinoma. We here evaluated whether preoperative NLR is an independent prognostic factor for non-metastatic renal cell carcinoma (RCC). MATERIALS AND METHODS Data from 327 patients who underwent curative or palliative nephrectomy were evaluated retrospectively. In preoperative blood routine examination, neutrophils and lymphocytes were obtained. The predictive value of NLR for non-metastatic RCC was analyzed. RESULTS The NLR of 327 patients was 2.72±2.25. NLR <1.7 and NLR ≥1.7 were classified as low and high NLR groups, respectively. Chi-square test showed that the preoperative NLR was significantly correlated with the tumor size (P=0.025), but not with the histological subtype (P=0.095)and the pT stage (P=0.283). Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan-Meier method. Effects of NLR on OS (P=0.007) and DFS (P=0.011) were significant. To evaluate the independent prognostic significance of NLR, multivariate COX regression models were applied and identified increased NLR as an independent prognostic factor for OS (P=0.015), and DFS (P=0.019). CONCLUSIONS Regarding patient survival, an increased NLR represented an independent risk factor, which might reflect a higher risk for severe cardiovascular and other comorbidities. An elevated blood NLR may be a biomarker of poor OS and DFS in patients with non-metastatic RCC.

Comparison of two approaches to retroperitoneoscopic renal pedicle lymphatic disconnection for chyluria.

BACKGROUND AND PURPOSE The retroperitoneoscopic renal pedicle lymphatic disconnection has been performed mainly via a renal adipose (RA) capsule approach. In this study, we reported a novel technique via extra-adipose (EA) capsule approach and compared the two approaches for intractable chyluria. PATIENTS AND METHODS From December 2002 to March 2008, retroperitoneoscopic renal pedicle lymphatic disconnection was performed on 41 patients with 23 EA and 18 RA. The stripping of hilar vessels and ureterolympholysis were performed in both approaches, while the mobilization of the kidney was only performed in RA. Comparisons of the two approaches were conducted, including mean operative time, intraoperative blood loss, postoperative bed rest, and hospital stay, as well as operative outcome. RESULTS Patients were treated successfully without major complications. EA showed the same advantages as RA in terms of intraoperative blood loss (54.9±19.3 mL vs 59.3±26.5 mL, P>0.05), postoperative hospital stay (6.6±1.0 d vs 7.2±0.9 d, P>0.05). Chyluria disappeared in all patients immediately after the operations. EA was significantly superior to RA in operative time (78.9±18.3 min vs 101.8±20.6 min, P<0.05) and the postoperative bed rest time (20.7±1.7 h vs 72.0±0.0 h, P<0.05). No recurrence or nephroptosis was diagnosed in any patient within the follow-up of 21 to 84 months. CONCLUSIONS Retroperitoneoscopic renal pedicle lymphatic disconnection for chyluria is safe and efficacious. EA offers significantly shorter operative time and earlier return to postoperative ambulation.

Relationships among MTHFR a1298c Gene Polymorphisms and Methylation Status of Dact1 Gene in Transitional Cell Carcinomas

OBJECTIVES The purpose of this study was to determine the relationship between methylation status of the Dact1 gene and MTHFR a1298c polymorphic forms in transitional cell carcinoma tissues in a Chinese population. METHODS Polymorphisms of folate metabolism enzyme gene MTHFR were assessed by restrictive fragment length polymorphism (RFLP) methods and PCR-based DNA methylation analysis was used to determine the CpG island methylation status of the Dact1 gene. Associations between the methylation status of the Dact1 gene and clinical characteristics, as well as MTHFR a1298c polymorphisms, were analyzed. RESULTS aberrant methylation of the Dact1 gene was found in 68.3% of cancer tissues and 12.4% of normal tissues,. The methylation rate of the Dact1 gene in cancer tissues was significantly higher in patients with lymph node metastasis than in those without lymph node metastasis (46.3% vs. 17.2%, P = 0.018). No association was found between aberrant DNA methylation and selected factors including sex, age, tobacco smoking, alcohol consumption and green tea consumption. After adjusting for potential confounding variables, variant allele of MTHFR a1298c was found to be associated with methylation of the Dact1 gene. Compared with wild type CC, the odds ratio was 4.33 (95% CI: 1.06-10.59) for AC and 4.95 (95% CI: 1.18-12.74) for AA. The N stage in TNM staging and the occurrence of lymph node metastasis were associated with an MTHFR 1298 AAμAC genotype (P<0.05). CONCLUSION MTHFR 1298 AC and AA genotypes might help maintain a normal methylation status of the Dact1 gene, aberrant CpG island methylation of which is closely related to the genesis and progression of transitional cell carcinoma.

Retroperitoneoscopic Renal Pedicle Lymphatic Disconnection for Chyluria in Presence of Complex Renal Vasculature

OBJECTIVE To evaluate retroperitoneoscopic renal pedicle lymphatic disconnection (RRPLD) for chyluria in the setting of complex renal vasculature and compare those outcomes with the RRPLD outcomes of patients with normal renal vasculature. MATERIALS AND METHODS From December 2002 to December 2011, RRPLD was performed in 14 patients with complex renal vasculature and 64 patients with normal renal vasculature. Preoperative multislice spiral computed tomography angiography for renal vessels was done on 5 patients with complex vasculature. The demographic and perioperative data were collected to assess critical outcomes. RESULTS The abnormal vasculature was identified using preoperative multislice spiral computed tomography angiography in 5 patients and surgical exploration in 9 patients. RRPLD was successfully completed in all patients without conversion to open surgery or vascular injury. The mean operative time was significantly longer in those with complex renal vasculature than those with normal renal vasculature (105.4 ± 18.7 vs 84.5 ± 15.6 minutes; P = .000). The outcomes were similar in the 2 groups in terms of intraoperative blood loss (P = .060), mean hospital stay (P = .478), and intraoperative complications (P = .660). The occurrence of postoperative gross hematuria was significantly greater in those with complex renal vasculature than in those with normal renal vasculature (4 of 14 vs 2 of 64; P = .008). The event was resolved uneventfully. CONCLUSION Although it is technically challenging, RRPLD is feasible and safe for patients in the presence of complex renal vasculature. Preoperative evaluation of the renal vasculature with multislice spiral computed tomography angiography is beneficial for managing abnormal renal vessels.

Replication-competent adenovirus expressing TRAIL synergistically potentiates the antitumor effect of gemcitabine in bladder cancer cells

Replication-competent adenovirus armed with therapeutic tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene has been shown to sensitize cancer cells to chemotherapy and radiotherapy. However, the synergistic antitumor effect of replication-competent adenovirus expressing TRAIL and the cytotoxic chemotherapy in bladder cancer remains to be determined. Bladder cancer T24 cells or mouse tumor xenografts were infected with replication-competent adenovirus armed with human TRAIL (ZD55-TRAIL) alone or in combination with gemcitabine. The mRNA and protein levels of TRAIL were determined by “Reverse transcription polymerase chain reaction” and Western blotting, respectively. Cell viability was tested by CCK8 assay. Tumor growth in the mice was monitored every week by measuring tumor size. Cell apoptosis was detected by Annexin V-FITC staining and TUNEL assay. We found that adenovirus ZD55-TRAIL efficiently replicated both in cultured bladder cancer T24 cells and T24 mouse tumor xenograft as demonstrated by the overexpression of TRAIL and E1A. Gemcitabine did not affect the expression of TRAIL. In cultured T24 cells, ZD55-TRAIL enhanced the growth inhibitory effects of gemcitabine, accompanied by increased apoptosis. Similarly, ZD55-TRAIL synergistically enhanced the antitumor effect and induction of apoptosis following gemcitabine treatment in mouse T24 xenografts. In conclusion, replicative adenovirus armed with TRAIL synergistically potentiates the antitumor effect of gemcitabine in human bladder cancer. Our study provides the basis for the development of ZD55-TRAIL in combination with conventional chemotherapy for the treatment of bladder cancer.

Oncological Outcome of Primary and Secondary Muscle-Invasive Bladder Cancer: A Systematic Review and Meta-analysis.

Conflicting results of survival outcomes for primary and secondary muscle-invasive bladder cancer (MIBC) have been reported in previous studies. Primary MIBC is defined as presentation of muscle-invasive disease at initial diagnosis while secondary MIBC presumes that non-muscle invasive disease later progressed to MIBC. Due to the varying reports, we conducted a systematic review and meta-analysis to compare survival outcomes between the two groups. Relevant studies were retrieved from Medline, Embase, the Cochrane Library, and Scopus using a comprehensive search approach. Cancer-specific survival (CSS) was the outcome measure. A total of 14 studies involving 4,075 cases were included. Patients with secondary MIBC were significantly correlated with worse CSS in model I (pooled HR: 1.29, 95% CI: 1.07–1.56, P = 0.008). The results of sensitivity analyses indicated that the omission of any single study each time did not have a significant impact on the combined risk estimates. Egger’s test suggested no publication bias among these studies. The European Organization for Research and Treatment of Cancer (EORTC) risk score offers the possibility of stratifying the secondary MIBC patients into different risk groups. In high-risk NMIBC, timely radical cystectomy should be considered. Further study is required to assess the multimodal therapy in both high-risk NMIBC and secondary MIBC patients as well as to evaluate genetic and molecular drivers of tumor induction, promotion, and progression.

Closed technique for the creation of retroperitoneal working space for symptomatic renal cysts

Abstract Purpose: To evaluate the feasibility and safety of the closed technique (CT) with Veress needle for the creation of retroperitoneal working space (RWS) for the retroperitoneoscopic ablation of symptomatic renal cysts by comparison with the open technique (OT). Material and methods: In this series of 412 patients who underwent retroperitoneoscopic ablation of symptomatic renal cysts, RWS was created by OT in 231 patients and CT in 181 patients, respectively. The time to create RWS, operative time, and complications were analyzed. Results: Creation of RWS and retroperitoneoscopic cyst ablation were completed successfully in all cases. The time to create RWS by CT was significantly shorter than that by OT (6.4 ± 1.2 vs 9.6 ± 1.2 min, P < 0.01). The operative time was shorter with CT than with OT (50.5 ± 6.5 vs 52.5 ± 6.7 min, P < 0.01). Subcutaneous emphysema developed in five (2.16%) of 231 patients undergoing OT and one (0.55%) of 181 patients undergoing CT. Port-site gas leakage was observed in six patients undergoing OT. Conclusions: Our study shows that CT with Veress needle for the creation of RWS for symptomatic renal cysts is feasible and safe in experienced hands, reducing troublesome port-site gas leakage and subcutaneous emphysema.