Genetic Elements for Chemoprotection Against Cyclophosphamide
Annual rept 19-Aug 96-18-Aug 97
ILLINOIS UNIV AT CHICAGO CIRCLE
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Our goal is identification of genes that affect cellular response to alkylating agent cyclophospharmide CP expression modulation of such genes will protect cells from CP toxicity. Chemotherapeutic approach to advanced breast cancer treatment relies heavily on the use of CP. High dose CP therapy has to deal with several dangerous side effect, myelosuppression being the most serious. Autologous bone marrow transplantation ABMT or peripheral blood stem cell transplantation PBSCT is an effective adjunct therapy. This approach, however, has several serious drawbacks 1 initial myelosuppession with acute leukopenia and increased risk of infectious complications 2 possibile contamination with neoplastic cells increases with every consecutive round of transplantation 3 escalating costs of successive rounds of ABMTPBSCT. We will identify genetic elements which protect cells from toxic effects of CP these elements, when introduced in bone marrow in the course of the first round of ABMTPBSCT, would protect bone marrow from CP. ABMTPBSCT with CP-resistant bone marrow 1 will allow dose escalation without hematological complications 2 will reduce the risk of re-introduction of neoplastic cells and 3 will reduce the economic impact of the disease. Identification of genes involved in CP resistance will provide insights into mechanisms of this process.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research
- Organic Chemistry