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Korean J Urol Oncol > Volume 1(4); 2003 > Article
The Korean Journal of Urological Oncology 2003;1(4): 365-370.
N-butyl-N-(4-hydroxybutyl) Nitrosamine 유도 백서 방광암 초기 발암 과정에서 Vascular Endothelial Growth Factor(VEGF)의 발현과 신생혈관 형성
김정현, 이상욱, 박인애, 이은식
1강원대학교 의과대학 비뇨기과학교실, 서울대학교 의과대학 비뇨기과학교실, 2병리학교실
Vascular Endothelial Growth Factor (VEGF) Expression and Angiogenesis in BBN-induced Rat Bladder Carcinogenesis
Jeong Hyun Kim , Sangwook Lee , In Ae Park , Eunsik Lee
1Department of Urology, Kangwon National University, College of Medicine, Chuncheon, Departments of Urology, and 2Pathology, Seoul National University, College of Medicine, Seoul, Korea
Published online: December 30, 2003.
Angiogenesis is the process by which tumors induce a blood supply from their surrounding tissues and it has been shown to be necessary for tumor growth. The aim of the study was to investigate the expression of vascular endothelial growth factor (VEGF), one of the proangiogenic factors, and its relationship in angiogenesis in rat bladder cancer induced by N-Butyl-N-4-hydroxybutyl-nitrosamine (BBN).
Materials and Methods:
Eight-week old Fisher 344 female rats were given 0.05% BBN diluted in drinking water for 8 weeks and sacrificed at 24 weeks of experiment. The urinary bladders were examined grossly and microscopically and routinely embedded in paraffin. Expressions of VEGF and microvessel density (MVD) were analyzed immunohistochemically. MVD was evaluated in the hotspot area of the submucosal tissue beneath the urothelial lesion.
Histopathologic findings of rat bladder cancer induced by BBN were very similar to human bladder cancer. Nineteen hyperplasia (H), 30 non-infiltrating tumors (compatible with human Ta tumor, NITCC) and 11 infiltrating tumors (compatible with human T1 tumors, ITCC) were found in experimental group and normal urothelium in controls. VEGF was expressed in 100% of H, 77% of NITCC and 55% of ITCC (p<0.05). The mean MVD was 8.4 in normal urothelium, 12.5 in H, 23.8 in NITCC and 25.2 in ITCC (p<0.05).
Our study showed that in the early stage of bladder carcinogenesis VEGF expression was increased and preceded the neovascularization. These results suggest that VEGF might contribute to carcinogenesis by angiogenesis in bladder cancer. (Korean J Uro-Oncol 2003;1:365-370)
Key Words: Bladder neoplasms; Carcinogenesis; Angiogenesis; Vascular endothelial growth factor
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