(based on the applicant's narrative) The overall objectives of this application are to conduct research aimed at improving the treatment of bladder cancer by developing methods to assess the risk of progression and monitor response to therapy in superficial and invasive bladder cancer. It is also aimed at developing methods for sensitive non-invasive detection of bladder tumors to be used in early detection and in monitoring of patients with superficial disease to decrease the morbidity involved with monitoring of recurrence. According to the applicants, the identification of markers must integrate multiple approaches that reflect the combination of cumulative genetic and molecular changes most likely involved in the heterogenous behavior of bladder cancer. Cooperative clinical studies will be conducted with other members of this network to evaluate promising diagnostic and prognostic markers. Clinical material will be shared as well as specific expertise of the applicants in immunological and molecular biology methods for tumor marker studies.
The first aim of the research will be to identify new monoclonal antibodies capable of detecting urinary shed antigens, metastasis-associated antigens and serum antigens for monitoring patients with advanced bladder cancer.
A second aim will be to evaluate cytologic markers for the detection and monitoring of bladder tumors in collaboration with the network members. Preliminary studies will also be conducted to assess the value of monoclonal antibodies recently developed by the applicants against urinary proteinsof bladder tumor patients. These studies will involve the evaluation of autocrine motility factor (AMF) and tumor collagenase stimulating factor (TCSF) in urine as potential markers for detection or prognosis.
A third aim will be to evaluate markers of risk assessment in studies conducted on tumor material and on exfoliated cells. Immunological and molecular biology techniques will be used to study antigens of bladder tumors, characterized by the applicants, p53 mutation and the implications of human papillomavirus in bladder tumors, on a cohort of patients with known clinical follow-up. Studies will also be conducted to design methods for multiparametric analyses of markers on exfoliated cells using image analysis. Finally, preliminary studies will be conducted to test possible immunological parameters predictive of response to BCG therapy, a commonly used intravesical form of treatment for superficial bladder tumors. These studies will primarily involve collaboration with the network members as a group or as individuals, to fully exploit the research capabilities of the group in determining the clinical usefulness of combination of markers in the management of human bladder cancer.
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