Development and validation of prognostic nomograms for adult with papillary renal cell carcinoma: A retrospective study.

OBJECTIVE: The aim of the study was to create two consensus nomograms for predicting Overall Survival (OS) and Cancer-Specific Survival (CSS) in adults with papillary Renal Cell Carcinoma (pRCC). METHODS: Using the Surveillance, Epidemiology, and End Results databases, a retrospective analysis of 1,074 adults with pRCC from 2004 to 2015 was performed. These patients were then randomly divided into two independent cohorts with a ratio of 7:3 (training cohort: 752; validation cohort: 322). In a retrospective analysis of 752 patients from the training cohort, independent prognostic variables affecting OS and CSS were found. R software was used to create prognostic nomograms based on the findings of Cox regression analysis. The performance of the nomograms was assessed using the Concordance Index (C-index), the Area Under Curve (AUC), a calibration curve, and Decision Curve Analysis (DCA). Data from the 107 postoperative pRCC patients at the Affiliated Hospital of Xuzhou Medical University were used for external validation of the nomogram. RESULTS: For OS and CSS, the C-indices and AUCs of the training cohort and the validation cohort indicated that the model had excellent discrimination. The DCA demonstrated that the model was clinically applicable, and the calibration curves in the internal and external validations showed that the model's accuracy was high. CONCLUSION: The authors developed and validated a prognostic nomogram that accurately predicted the 3-, 5-, and 8-year OS and CSS of adults with pRCC. Clinicians can use this knowledge to direct the clinical management and counseling of patients with pRCC.

Development and validation of prognostic nomograms for adult with papillary renal cell carcinoma: A retrospective study

Abstract Objective The aim of the study was to create two consensus nomograms for predicting Overall Survival (OS) and Cancer-Specific Survival (CSS) in adults with papillary Renal Cell Carcinoma (pRCC). Methods Using the Surveillance, Epidemiology, and End Results databases, a retrospective analysis of 1,074 adults with pRCC from 2004 to 2015 was performed. These patients were then randomly divided into two independent cohorts with a ratio of 7:3 (training cohort: 752; validation cohort: 322). In a retrospective analysis of 752 patients from the training cohort, independent prognostic variables affecting OS and CSS were found. R software was used to create prognostic nomograms based on the findings of Cox regression analysis. The performance of the nomograms was assessed using the Concordance Index (C-index), the Area Under Curve (AUC), a calibration curve, and Decision Curve Analysis (DCA). Data from the 107 postoperative pRCC patients at the Affiliated Hospital of Xuzhou Medical University were used for external validation of the nomogram. Results For OS and CSS, the C-indices and AUCs of the training cohort and the validation cohort indicated that the model had excellent discrimination. The DCA demonstrated that the model was clinically applicable, and the calibration curves in the internal and external validations showed that the model's accuracy was high. Conclusion The authors developed and validated a prognostic nomogram that accurately predicted the 3-, 5-, and 8-year OS and CSS of adults with pRCC. Clinicians can use this knowledge to direct the clinical management and counseling of patients with pRCC.

The addition of tislelizumab to gemcitabine and cisplatin chemotherapy increases thrombocytopenia in patients with urothelial carcinoma: A single-center study based on propensity score matching.

PURPOSE: Whether the addition of tislelizumab to gemcitabine and cisplatin (GC) chemotherapy increases the incidence of myelosuppression has not been well established. This study identified the risk factors for the development of myelosuppression in patients with urothelial carcinoma (UC) after receiving GC chemotherapy with or without tislelizumab. MATERIALS AND METHODS: We enrolled 192 UC patients who received GC with or without tislelizumab at the Affiliated Hospital of Xuzhou Medical University between July 2014 and November 2022. Patient baseline characteristics were included in the statistical analyses after adjusting for previously reported risk factors affecting survival using propensity score matching (1:1). Binary logistic regression analysis was used to identify the risk factors associated with posttreatment myelosuppression. RESULTS: A total of 192 patients were enrolled, of whom 96 were treated with tislelizumab plus gemcitabine and cisplatin (T + GC) and 96 with GC alone. The incidence of leukopenia, anemia, and thrombocytopenia of any grade was 50.0%, 70.8%, and 42.7%, respectively, in the T + GC group and 41.7%, 72.9%, and 20.8%, respectively, in the GC group. In multivariate analysis, patients aged over 70 years (OR = 2.486, 95% CI: 1.067-5.792, p = 0.035) and those who received T + GC (OR = 3.119, 95% CI: 1.576-6.173, p = 0.001) were more likely to develop thrombocytopenia. Patients aged over 70 years (OR = 3.213, 95% CI: 1.254-8.237, p = 0.015) were more likely to develop anemia, and patients with renal insufficiency (OR = 2.105, 95% CI: 1.035-4.280, p = 0.040) were more likely to develop leukopenia. Eventually, 99 (51.6%) patients with UC successfully completed all the treatment cycles. CONCLUSIONS: This study demonstrates that the addition of tislelizumab to GC chemotherapy led to a considerable increase in the occurrence of thrombocytopenia, whereas no significant changes were observed regarding anemia or leukopenia. It is crucial to fully inform patients at increased risk for myelosuppression of potential risks and closely monitor changes in their blood routines.

The efficacy and timing of adjuvant chemotherapy in upper tract urothelial carcinoma.

BACKGROUND: A recovery period between surgery and initiation of adjuvant chemotherapy (AC) is common in patients with upper tract urothelial carcinoma (UTUC), which can progress after a relatively long time. Therefore, the efficacy of AC initiated within 90 days after radical nephroureterectomy (RNU) was evaluated in UTUC patients at stage ≥pT2 (N0-3M0), in addition to the effect of delayed AC initiation on survival outcomes. METHODS: Clinical data for 428 UTUC patients diagnosed with transitional cell carcinoma with postoperatively confirmed pathological stages, muscle-invasive or greater-stage (pT2-4) disease, any nodal status, and metastasis-free (M0) disease were retrospectively analyzed. All patients who received AC were treated within 90 days after RNU and underwent at least 4 cycles of the AC procedure. Then, patients receiving AC were divided into the "within 45 days" and "45 to 90 days" groups according to the time interval between RNU and AC initiation. Their clinicopathological characteristics were evaluated and the survival outcomes of the 2 groups were compared. Any adverse events that occurred during the AC process were also recorded. RESULTS: A total of 428 patients were analyzed in the study, including 132 individuals who underwent the AC procedure with platinum in combination with gemcitabine within 90 days after RNU and 296 patients who failed to initiate AC within 90 days. The median age of all patients was 68 years (mean 67, range 28-90 years), and the median follow-up was 25 months (mean 36, range 1-129 months). There were no significant differences in age, sex, lymph node metastasis, tumor location, hydronephrosis status, hematuria status, cancer grade, or multifocality between the 2 groups. Individuals undergoing AC initiated within 90 days of RNU showed a significantly decreased mortality relative to those patients who did not receive AC. Shorter intervals between RNU and AC initiation within 45 days vs. 45-90 days did not improve patient OS and cancer-specific survival (CSS) and may have increased the incidence of adverse events. CONCLUSION: The present study data supported the finding that a platinum-based combination with gemcitabine regimen initiated postoperatively significantly improved OS and CSS in patients with UTUC at stages ≥pT2 (N0-3M0). Furthermore, no survival benefit was evident in patients who started AC within 45 days after RNU compared to those who received AC within 45 to 90 days.

Ureteroscopic Lithotripsy in Reverse Trendelenburg Position and Intraoperative Furosemide.

PURPOSE: Upward stone migration is a significant problem during ureteroscopic lithotripsy (URSL) for upper ureteral stone, especially in absence of a ureteral occlusion device. In this study, we evaluated the novel strategy of reverse Trendelenburg position (RTP) and intraoperative diuresis for URSL without ureteral occlusion devices to avoid upward migration. MATERIALS AND METHODS: From March 2018 to May 2020, a total of 119 URSLs were performed for upper ureteral stone (6-15 mm) with 67 procedures in RTP and 52 procedures in conventional lithotomy position (CLP). 20 mg of intravenous furosemide was administered prior to stone fragmentation with holmium laser only in RTP group. Patient demographics, stone side, stone size and operative characteristics were recorded and compared between the two groups. RESULTS: Patient data, stone side and size were similar in the two groups. All procedures were complete without conversion to open surgery and major complications. There was no significant difference in the mean operative time (47.9 ± 7.7 min vs 45.3 ± 7.0 min, P = .062) and mean hospital stay (3.9 ± 0.9 d vs 4.0 ± 1.0 d, P = .336) between the RTP and CLP group. Stone upward migration was significantly less in RTP group (3.0%, 2/67) than in CLP group (19.2%, 10/52) (P = .005). Stone-free rate at one month after initial treatment was 92.5% in RTP group and 73.1% in CLP group (P = .004). CONCLUSION: The strategy of placing the patient in RTP and intraoperative administration of intravenous furosemide is simple, feasible and cost-effective in preventing stone upward migration during URSL with holmium laser in absence of a ureteral occlusion device for upper ureteral stone.

How to Perform Intravesical Chemotherapy after Second TURBT for Non-Muscle-Invasive Bladder Cancer: A Single-Center Experience.

PURPOSE: The objective of this study aimed to explore whether the original IVC regimen should be continued after the second TURBT or whether the IVC induction phase should be restarted from the beginning. METHODS: A retrospective analysis was performed on 137 patients who underwent a second TURBT at the Affiliated Hospital of Xuzhou Medical University between April 2014 and June 2022. Based on the pathological findings, patients were divided into two groups: group A patients, who did not have a residual tumor on pathological examination after the second TURBT; and group B patients, who had residual tumor. Recurrence was determined using cystoscopy and imaging every three months. The endpoint was recurrence-free survival. RESULT: In the entire cohort, there was a statistically significant difference in the RFS between patients in the two IVC regimens (p = 0.029). The RFS of patients in group B1 was significantly lower than that of patients in group B2 (p = 0.009). There was no significant difference in RFS between the subgroups A1 and A2 (p = 0.560). Multivariate Cox regression analysis confirmed that the IVC regimen after a second TURBT (p = 0.012) and T stage after a second TURBT (p = 0.005) were both independent predictors for patient RFS. CONCLUSION: If the pathological findings of the second TURBT specimen is benign, patients can continue their previous treatment regimen without restarting an IVC induction phase. Unnecessary IVC can be avoided in these patients. In contrast, for patients with residual tumors in the second TURBT specimen, the need to restart the IVC induction phase should be emphasized to improve patient prognosis.

Tropism and transduction of oncolytic adenovirus vectors in prostate cancer therapy.

Oncolytic adenovirus has been applied in cancer therapy because of several advantages such as cost-effective production, high transduction efficiency and low toxicity. Recent efforts have been focused on the modification of oncolytic adenovirus by encoding transgenes within the viral genome to efficiently and selectively replicate within cancer cells, destroy cancerous cells, induce tumor cell apoptosis, and stimulate the recruitment of immune cells to the tumor site. Nevertheless, there are still big challenges for translational research of oncolytic virotherapy in clinical cancer management. Therefore, here we summarize current status on the design and application of oncolytic adenovirus vectors for prostate cancer therapy. In particular, we describe the main receptors associated with the tropism and transduction of oncolytic adenovirus vectors, and propose new directions in future studies for prostate cancer virotherapy.

The Tumor Suppressor Role of the Ras Association Domain Family 10.

The Ras association domain family 10(RASSF10), a tumor suppressor gene, is located on human chromosome 11p15.2, which is one of the members homologous to other N-terminal RASSF families obtained through structural prediction. RASSF10 plays an important role in inhibiting proliferation, invasion, and migration, inducing apoptosis, making cancer cells sensitive to docetaxel, and capturing G2/M phase. Some studies have found that RASSF10 may inhibit the occurrence and development of tumors by regulating Wnt/ß-catenin, P53, and MMP2. Methylation of tumor suppressor gene promoter is a key factor in the development and progression of many tumors. Various methylation detection methods confirmed that the methylation and downregulation of RASSF10 often occur in various tumors, such as gastric cancer, lung cancer, colon cancer, breast cancer, and leukemia. The status of RASSF10 methylation is positively correlated with tumor size, tumor type, and TNM stage. RASSF10 methylation can be used as a prognostic factor for overall survival and disease-free survival, and is also a sign of tumor diagnosis and sensitivity to docetaxel chemotherapy. In this review, we mainly elucidate the acknowledged structure and progress in the verified functions of RASSF10 and the probably relevant signaling pathways.

Microscopic hematuria predicts lower stage in patients with upper tract urothelial carcinoma.

BACKGROUND: The aim of this study was to assess the association between the severity of hema-turia (microscopic or gross) and the tumor stage and grade in a population of histopathologically confirmed upper tract urothelial carcinoma (UTUC) patients. PATIENTS AND METHODS: We conducted a multicenter, observational study of patients who were newly diagnosed with UTUC between January 2011 and December 2016. Demographic information, pathology, and the status of hematuria were retrospectively reviewed. The association between the severity of hematuria and the tumor stage and grade was evaluated using logistic regression. RESULTS: The UTUC patients presented with gross hematuria (GH, 76.7%), microscopic hematuria (MH, 11.1%), and no hematuria (12.2%) at the time of diagnosis. The pathological stages at diagnosis for those with MH were Ta in 5.1%, T1 in 47.5%, and ≥T2 in 47.5%. The stages at diagnosis for those with GH were Ta in 1.7%, T1 in 35.5%, and ≥T2 in 62.7%. On univariate and multivariate logistic regression analyses, after adjusting for clinical factors such as age, gender, and smoking history, GH was an independent risk factor for muscle-invasive UTUC (≥T2 disease) at diagnosis (OR 1.89, 95% CI 1.073-3.329; P=0.027). High-grade tumor was found in 47.8% of patients with GH and 39.0% of those with MH. The severity of hematuria was not associated with tumor grade. CONCLUSION: We are the first to report evidence that microscopic hematuria at presentation accurately predicts lower pathological stage in patients with newly diagnosed UTUC. Earlier detection of disease, before the development of GH, may influence the treatment decision and survival. The type of hematuria at the time of diagnosis does not impact the tumor grade.

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.

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.

[The effects of warm ischaemia time on renal function after laparoscopic partial nephrectomy in patients].

OBJECTIVE: To assess the effects of warm ischaemia time (WIT) on renalfunction after laparoscopic partial nephrectomy (LPN) for renal masses in patients. METHODS: From January 2010 to December 2012, 39 patients treated with LPN for a single T1 renal tumor were enrolled in this prospective study. There were 24 male and 15 female patients. Their age was (58 ± 10) years old, and their body mass index was (27 ± 3) kg/m(2). The mean operation time was (132 ± 12) minutes, and the mean WIT was (29 ± 8) minutes. Clinical parameters, the single glomerular filtration rates (sGFR) were compared before the operation and after 3 and 12 months in order to observer the effects on renal function and find the factors predicting the renal function impairment. RESULTS: There were significant differences between 3, 12 months after the operation ((26.8 ± 5.6) ml/min and (28.6 ± 5.6) ml/min, respectively) and preoperation ((31.9 ± 6.3) ml/min) in sGFR (F = 4.882 and 5.511, both P < 0.05). And there were significant negative correlations between the sGFR in 3 and 12 months after the operation and WIT (r = -0.569, P = 0.000 and r = -0.448, P = 0.004) . The preoperative sGFR (ß = 0.260, 95%CI:0.089-0.431) and WIT (ß = 0.369, 95%CI:0.189-0.555) were independent predictors for function decline of the operated kidney (both P < 0.05). The analysis showed that the effects of WIT within 30 minutes on renal function is relatively small. Longer WIT was associated with lower postoperative sGFR values (F = 22.128 and 20.552, both P = 0.000) . CONCLUSIONS: For the LPN operation, the longer of the WIT, the more serious of renal function damage. sGFR is an accurate measurement to assess the renal damage. Every effort should be made to minimise WIT during LPN, and the limit of 30 minutes should be not exceeded.

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.

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

BACKGROUND: Special 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. METHODS: 120 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. RESULTS: SATB1 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. CONCLUSIONS: These 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.

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

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.

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.

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.

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.

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.

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.