Research On Expression Of Vascular Endothelial Growth Factor In The Serum And Urine And Antisense VEGF Gene Therapy Of Bladder Cancer

BACKGROUND: Bladder cancer is the most common malignant tumors of urinary system, and its morbidity is increasing these years. Because of the inconvenience and invasion of cystoscopy in diagnosis and postoperative follow-up, some non-invasive means were done such as ultrosonic and urinary cytology. But these ways sometimes are not sensitive to the patients with bladder cancer in early stage or recurrence. Though the surgery and bladder instillation are effective to many patients, the recurrence and morbility are still high.There is no effective treatment for the patients with advanced bladder cancer. It is known that the growth and dissemination of solid tumors is depended on angiogenesis. A lot of angiogenic factors such as basic fibroblast growth factor, platelet-derived growth factor and VEGF affect the angiogenesis of tumors. Of these factors, VEGF is the most powerful facilitators angiogenesis identified to date, with affects on endothelial cell proliferation, motility, and vascular permeability. Recently the determing serum or urinary vascular endotheial growth factor was reported to be a possible marker in several types of human malignancies, such as renal cancer, epithelial ovarian cancer and transitional cell bladder cancer. Currently there are few published reports of expression of both of serum and urinary VEGF in bladder cancer. Inhibition of tumor angiogenesis is a suitable target for therapy has been proposed previously to be an important concept for antitumor treatment. Antisense VEGF gene therapy may reduce the VEGF produced by tumor cells and thus inhibit the bladder cancer growth. It may provide the basis for the development of antiangiogenic gene therapy of bladder cancer. We quantitated the preoperative and postoperative levels of VEGF in serum and urine of the patients with bladdr cancer and the controls using enzyme-linked immunoadsordent assay (ELISA). We discussed the possibility of VEGF as tumor markers. We also transfected with a eukaryotic expression vector bearing an antisense VEGF121 cDNA to observe the tumor cells' growthin vitro and nude mice. We discussed the value and possibility of antisense VEGF gene therapy in the treatment of bladder cancer in the future. Part Ⅰ Quantitation of VEGF in serum and urine of patients with bladder cancerOBJECTIVE To quantify the level of serum and urinary VEGF and study its potential as a tumor marker in bladder cancer. MATERIALS AND METHODS VEGF was measured by enzyme-linked immunosorbent assay kits (R&D System)in the serum and urine of 40 patients with bladder cancer ,including superficial and invasive tumors in 20 and 20,respectively, and 36 controls including benign urological condition or the healthy.15 cases were followed up 3 months later after bladder tumors were resected and 5 cases 6 months later because of recurrence. The experiment was performed strictly under the guide of the kit. The urinary VEGF were corrected by the creatinine concentration in urine. A morning mid stream urine specimen and blood from vein was collected.RESULTS VEGF was detectable in serum and urine in all of the patients. The mean levels of serum and urinary VEGF in patients with bladder cancer were 348.53±225.80 pg/mL and 576.54±390.50 ng/gCr respectively, which were both significantly higher than those in controls (123.89±50.19 pg/mL in serum and 60.08±36.26 ng/gCr in urine). The levels of serum and urinary VEGF both tended to increase correlating with the stages and grades of bladder cancer.Serum and urinary VEGF were markedly decreased 3 months later after tumors resection and increased 6 months later when tumors recurred .CONCLUSIONS The present study demonstrated that VEGF are highly expressed in the serum and urine by ELISA quantitative analysis, and confirmed their important role in bladder cancer. The levels of serum and urinary VEGF were correlated with tumor stage and grade. This result indicates that they may serve as markers for bladder cancer in the diagnosis and prognostic prediction.