The main goals of the proposal are to characterize the phenotype and genotype of preneoplastic and early carcinogenic events in bladder cancer, and to establish a chemoprevention program to treat patients with recurrent bladder tumors. The proposed studies represent a cohesive approach to the analysis of the biology and treatment of preneoplastic lesions and superficial bladder tumors. It integrates the disciplines of urologic oncology, pathology, molecular and cellular biology, thus enhancing our ability to relate tumor biology to potential therapeutic intervention. Our objective is to translate basic and clinical research findings into clinical studies.
The specific aims are: #1 To define the phenotype and genotype of early carcinogenesis in bladder tumors using molecular genetic and immunohistochemical analyses. #2 To evaluate N-(4-hydroxyphenyl) retinamide (4-HPR) for its ability to prevent new tumor recurrences in patients with superficial bladder cancer in a chemoprevention trial. #3 To evaluate the biologic effect of 4-HPR on human benign and malignant urothelium using molecular genetic and immunohistochemical analyses of sequential biopsy and bladder lavage samples. To validate promising biomarkers as predictors of bladder cancer risk. #4 To develop an in vitro uroepithelial screening model in order to evaluate future chemopreventive agents and their effects on cellular growth characteristics, genotype and immunophenotype.
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