Accession Number : ADA333236

Title :   Genetic Elements for Chemoprotection Against Cyclophosphamide

Descriptive Note : Annual rept 19-Aug 96-18-Aug 97

Corporate Author : ILLINOIS UNIV AT CHICAGO CIRCLE

Personal Author(s) : Levenson, Victor

PDF Url : ADA333236

Report Date : SEP 1997

Pagination or Media Count : 17

Abstract : 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 ABMT/PBSCT. 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 ABMT/PBSCT, would protect bone marrow from CP. ABMT/PBSCT 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.

Descriptors :   *GENETICS, *CYCLOPHOSPHAMIDE, *BREAST CANCER, TOXICITY, IDENTIFICATION, DOSAGE, ALKYLATION, GENES, MODULATION, TRANSPLANTATION, BONE MARROW, CHEMOTHERAPY, CHEMOTHERAPEUTIC AGENTS, NITROGEN HETEROCYCLIC COMPOUNDS.

Subject Categories : Genetic Engineering and Molecular Biology
      Medicine and Medical Research
      Pharmacology
      Organic Chemistry

Distribution Statement : APPROVED FOR PUBLIC RELEASE