| BackgroundRenal cell carcinoma (RCC) is one of the most common malignant tumors of the urinary system, and its incidence is increasing in recent years. But its pathogenesis has not been yet fully elucidated. Oxidative stress has been implicated in the carcinogenic process, which is mainly due to oncogenic DNA damages. In addition, enhanced production of reactive oxygen species (ROS) has been linked to disease progression by promoting survivability, proliferation, and even horizontal cell growth. Noticeable, elevated ROS production can already be observed in premalignant lesions. Endogenous antioxidants are found at reduced levels from tumor patients, which is in line with observations of increased ROS levels in tumor cells of more aggressive phenotypes. There is growing evidence suggesting that during tumor growth important changes appear in the cellular redox homeostasis. It is believed that renal cell carcinoma (RCC) of the clear cell type also belongs to tumors in which signifiant changes occur in cellular redox balance. Thus, in RCC marked oxidative alterations of lipids, proteins and DNA have been found. Higher GCLC levels were associated with lower presence of intracellular ROS and interestingly also lower rates of cell proliferation. Glutamate-L-cysteine ligase (GCL) catalyzes the rate-limiting step of glutathione [L-g-glutamyl-cysteinyl-glycine(GSH)] synthesis, the key cellular antioxidant. Higher GCLC levels were associated with lower presence of intracellular ROS and interestingly also lower rates of cell proliferation.ObjectiveIn this study, we detect the gene and protein expression of GCLc and GCLm in renal tissues through quantitative real-time PCR and western blotting, and analyze the GCL activity between clear cell renal cell carcinoma and control groups. Through experiments in vitro, we aim to do the preliminary investigations on the biological functions of GCL in the pathogenic mechanism of RCC.MethodsThe hematologic indexes of the blood, the biochemical parameters and coagulation markers were analyzed in clear cell renal cell carcinoma and healthy control groups. Semi-quantative real time-PCR (qRT-PCR) was used to assay the mRNA expression of GCLc and GCLm subunit in clear cell renal cell carcinoma and control para-carcinoma tissue groups. Protein contents of GCLc and GCLm subunit in clear cell renal cell carcinoma and control para-carcinoma tissue groups were determined by Western blotting. GCL activity was determined by a fluorescence assay.Data was analyzed through SPSS13.0Software. Difference analysis was done using Student’s two-tailed t-tests. p<0.05indicate the differences. Data are expressed as mean±S.E.ResultsThe results indicated that the mRNA expression of GCLc and GCLm subunit in clear cell renal cell carcinoma has a significant decrease compared with control para-carcinoma tissue groups through Semi-quantative real time-PCR (GCLc: CCRCC group1±0.028, Control groups3.74±0.545; p<0.01)(GCLm:CCRCC group1±0.05, Control groups3.07±0.571;p<0.01). Through Western blotting, the results indicated that the protein contents of GCLC and GCLM subunit in clear cell renal cell carcinoma has a significant decline compared with control para-carcinoma tissue groups (GCLc:CCRCC group0.983±0.022, Control groups1.248±0.076; p <0.05)(GCLm:CCRCC group1.103±0.014, Control groups1.306±0.033; p<0.05). The analysis of GCL activity indicated that GCL activity in clear cell renal cell carcinoma was improved compared with control groups (CCRCC group:342±85mmol/min/mg protein; Control groups:98±21mmol/min/mg protein;p <0.01)ConclusionsThe mRNA expression and protein content of GCLC and GCLM in clear cell renal cell carcinoma was decreased. Perhaps, expression of GSH in tumor cells of renal cell carcinoma was regulated by gene expression of glutamine cysteine ligase and the change of protein content, thus affect the oxidation state, the proliferation and differentiation of tumor cells. The GCL enzyme activity in cells of renal clear cell carcinoma increased significantly. The result may be implied that change of enzyme content in tumor cells need higher enzyme activity to regulate the equilibrium of cell oxidation state. The results show that glutamine cysteine ligase may be as an indicator for treatment and judging the prognosis of patients with renal cell carcinoma. BackgroundBladder transitional cell carcinoma (BTCC) is the ninth most common urologic tumor in worldwide. The morbidity rate is increasing with the change of circumstance and the prolonged life. In China, BTCC is the most common urologic tumor for its highest morbidity and mortality. Though BTCC have not specific incident age, even can appear in infants, it really show a tendency of onset after age of30’s. furthermore, the morbidity and mortality show directly correlation with age.The carcinogenesis of bladder cancer is a long process covered multi-factor and multi-step. During the carcinogenesis, genetic factors and environmental factors exist comprehensive cross-talk. Currently, most people accept smoking and chemical materials can lead to carcinogenesis.The initial change during carcinogenesis is from DNA, the most common manner is DNA mutation. Proto-oncogene change to oncogene by mutation, then the cellular division become endless and cause carcinogenesis at last.Currently radical cystectomy with bilateral pelvic Lymphadenectomy followed with urinary diversion is the primary treatment modality in individuals with muscle-invasive bladder cancer. Among the different techniques of urinary diversion, Neobladder become the most popular technique these years. The superiority of neobladder mainly reflected by excellent life quality after operation and satisfied urinary control. Though with these superiorities, few patients would followed incontinence and ureterostenosis as well as long time catherization, these factors do decrease the life quality of these patients. Urodynamics is one kind of science that reflect the functional urethra by picture and data based on electrophysiology, fluid mechanics, sensor technology. There are very few reports about the urinary control after the procedure of neobladder, thus the clinical effectiveness still need further research in China. From Aug.2009, we perform urodynamic researchs on46patients that received neobladder. Our research covered filling cystometry, pressure-flow study, urethral pressure, etc. meanwhile, aimed to decrease the incidence of vesicoureteral reflux, residual urine, incontinence, enuresis, we further analyzed the perioperative complications, life quality score, urinary control and some others factors focused on the neobladder.Current research will offer further evidences for the improvemwnt of orthotopic continent ileal N-bladder reconstruction by comprehensively analyze the complications, urodynamic features and life quality.ObjectiveRadical cystectomy is the method of choice in management of muscle invasive, organ-confined tumors of the bladder (T2-T4, NO-Nx). The most frequent continent orthotopic urinary diversion after radical cystectomy is the ileal neobladder. To retrospectively review our clinical experience with a single series of46patients who underwent orthotopic continent ileal N-bladder replacement after radical cystectomy during a12-month period. Data are concerning the changes in complications,urodynamic characteristics functional outcomes and quality of life. The object of this study is to evaluate the urodynamic and functional characteristics of46patients and to provide proof for this technique’s improvement.MethodsThe study included46consecutive Chinese patients with orthotopic continent ileal N-bladder replacement after radical cystectomy created using the modified technique described previously. We examined the complications.urodynamic characteristics functional outcomes and quality of life.Complications, functional outcomes and health-related quality of life (HRQL, using the Short-Form36instrument)were evaluated in46patients with a mean follow-up of12months. Urodynamics were obtained a mean of11months (range3to24) after construction of the neobladder and it was performed in all patients to determine neobladder capacity, filling and voiding pressures,urethral pressure profile,peak and mean urinary flow and postvoid residual urine. All perioperative and longterm complications were recorded. The voiding pattern, frequency of micturition and continence were assessed, and a complete urodynamic profile recorded. A total of46patients completed by mail the SF-36, a validated quality-of-life survey. Completed surveys were then analyzed into physical (PCS) and mental (MCS) component quality-of-life scores per published protocols. Results were then compared with published age-based norms.ResultsThere were23early complications in46patients, including wound infection, ileus, and pyelonephritis etc, although open surgical intervention was required in only nine (6.5%). with9late complications including uretero-intestinal stricture in four and entero-urethral stricture in five. All patients could void spontaneously, the mean maximum cystometric pouch capacity was546ml(range from366ml to784ml). The neobladders demonstrated good compliance for the storage of urine, with a mean basal pressure of less than15cm. water at volumes of less than400cc and of22.4cm. water (range1to72) at100%capacity.The mean maximum flow rate, voided volume and postvoid residualwere19.6mL/s and42mL.The mean maximum flow rate, voided volume and postvoid residualwere18.6mL/s,345.3mL and24.5mL respectively. Daytime and nighttime continence were achieved in95.6%and58.6%respectively. Upper tract surveillance with computed tomography,renal ultrasound and serum creatinine estimation has shown4right ureteral strictures but no significant upper tract deterioration or ureteral recurrence.significant reflux was not observed during video urodynamics unless the reservoir was overfilled. During voiding.by outlet relaxation and straining if necessary. Ulike a normal bladder, no isolated intravesical pressure increase occurred. Through interviews and questionnaires we can find the neobladder’function attain stable at6months after its reconstruction. The HRQL survey after surgery showed no significant differences scores between the46patients with a ileal neobladder and an age-matched control population in chinese. Knowledge of the pathogenesis and identification of risk factors implies that prevention through proper design of the neobladder, meticulous surgical technique, and patient selection is paramount.ConclusionsIn this study, we found that orthotopic global neobladder reconstruction offers similar storage and voiding functions to normal bladder. We conclude that an orthotopic continent ileal N-bladder constructed shorter ileum than other similar operations. The urodynamics results and quality of life outcome proves that it has an adequate capacity at low pressures with a satisfactory continence rate. Our data suggest that although it is not a complication-free procedure, we advocate its use when possible. |
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