The goal of this research is the development and evaluation of markers for the diagnosis, prognosis and management of patients with bladder cancer. A primary focus remains the analysis of aberrations of chromosome 9 as our preliminary studies suggest that these aberrations provide information of clinical utility. The rationale for our studies is that genetic events may be identified and markers developed which antedate detectable tumor recurrence, that offer insight into fundamental biological events of bladder cancer development and progression, and provide information on clinical course for patients with superficial transitional cell carcinoma. The goal will be met through four specific aims: l) Test the hypothesis that chromosome 9 aberrations detected in longitudinally collected bladder irrigation and tumor specimens have clinical utility in the diagnosis and prognosis of superficial bladder cancer by correlating aberrations of chromosome 9 and DNA ploidy with patient clinical course. Covariates will include cell cycle control proteins, stage, and grade in the index tumor. 2) Test the hypothesis that specific aberrations of chromosome 9 have prognostic utility in patients with superficial bladder cancer treated by intravesical therapy by correlating aberrations of chromosome 9 and DNA ploidy on specimens from patients following BCG intravesical therapy with recurrence and progression and determining whether chromosome 9 aberrations can serve as predictors of outcome or markers of response to other intravesical agents. 3) Assess the clinical utility of measurement of DNA ploidy and aberrations in chromosome 9 using fluorescence in situ hybridization in the longitudinal sampling of a well characterized population of patients with newly diagnosed superficial bladder tumors treated in a study with the polyamine synthesis inhibitor, difluoromethylomithine (DFMO) or placebo. Of particular interest is prediction of recurrence, time to recurrence, and the influence of DFMO on cell populations with chromosome 9 aberrations. 4) Characterize widespread changes in the urothelium of patients with bladder cancer by determining if aberrations in chromosome 9, 9p21 and DNA ploidy in bladder irrigation specimens reflect aberrations in tissues from tumorous and remote urothelium and determining whether other abnormalities on tumors (aberrations in p53, pRb, and epidermal growth factor receptor expression) are found in remote urothelium and in irrigation specimens, with or without cystoscopically evident tumors.
Showing the most recent 10 out of 22 publications
