MULTIDRUG RESISTANCE GENES--ANALYSIS AND APPLICATIONS

Project: Research project

Project Details

Description

The development of resistance to chemotherapeutic agents by
malignant cells remains a significant problem in successful cancer
therapy. In vitro analysis of a mechanism which simultaneously
conveys resistance to multiple chemotherapeutic agents has been
associated with amplification of a specific region of the genome.
The techniques of molecular biology, cell biology and recombinant
retroviral vectors will be utilized in characterizing this amplified
region and the genes overexpressed in multidrug resistant cell
lines. Molecular probes from this amplified region will be used to
advance our understanding the chemotherapeutic protocols of the
future. The practical application of multidrug resistance genes
transduced into hematopoetic stem cells will expand our
knowledge of hematopoesis and represents the first step towards
utilizing hematopoetic stem cells resistant to chemotherapeutic
agents as an integral component of chemotherapeutic regimens
and bone marrow transplantation. The specific aims of these studies will be: 1) characterization of
the cDNA clones to the gene(s) responsible for multidrug
resistance, 2) characterization of the protein(s) encoded by the
cDNA clones which are responsible for multidrug resistance, 3)
characterization of the mechanism of amplification of multidrug
resistance genes, 4) evaluation of children being treated for acute
lymphoblastic leukemia for the development of amplification of
multidrug resistance gene(s) and its relationship to
chemotherapeutic failures, 5) development of in vivo models for
the direct analysis of the development of multidrug resistance at
the molecular level, 6) construction of a retroviral vector
containing the gene responsible for multidrug resistance, and 7)
selection in vivo of hematopoetic stem cells carrying the
multidrug resistant gene to develop model systems for the
analysis of hematopoesis and protection of bone marrow from
chemotherapeutic agents.
StatusFinished
Effective start/end date7/1/876/30/92

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $75,972.00

ASJC

  • Medicine(all)

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