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undergo ABMT during the course of their treatment; 2) They are 
not usually cured by current therapy; and 3) Taxol and 
adriamycin are MDR-responsive drugs often given to these patients 
following relapse with other agents. 
Patients with metastatic cancer will be studied in our first 
protocol. Breast cancer patients with metastatic disease are 
initially treated with cyclophosphamide, 5-FU, and either 
methotrexate or adriamycin. They often relapse, and are then 
treated with high-dose chemotherapy such as platinum, 
cyclophosphamide, and thiotepa, but require ABMT to allow this 
regimen to be tolerated. We propose to transduce the bone marrow 
of these patients with MDR at this time. We will measure MDR 
gene transduction by PCR analysis and Southern blotting and MDR 
expression by measuring MDR mRNA and protein. Potential toxic 
effects will also be evaluated. We will also evaluate the 
potential marrow-protective effect of MDR gene transduction in 
patients who subsequently receive taxol. If the MDR gene is 
protective, bone marrow toxicity as reflected by decreased WBC 
and platelet counts and decreased bone marrow cellularity should 
be less severe than in patients not transduced with the MDR gene. 
Our protocol in patients with advanced cancer has two primary 
goals. In all patients undergoing ABMT and MDR gene 
transduction, we will evaluate: 1) The transfer and expression 
of the MDR gene and its stability in bone marrow cells over time 
(see below) ; and 2) Any toxicity from the transduction 
procedure. We will also have the opportunity to test the effect 
of MDR transduction on marrow toxicity in those patients 
subsequently treated with taxol in enriching the marrow for MDR- 
transduced cells and in decreasing marrow toxicity. 
Patients with advanced ovarian cancer undergoing ABMT and high- 
dose chemotherapy will also be eligible for this protocol. These 
patients are less likely to have marrow tumor infiltration. In 
addition, taxol has been shown to be an effective agent in the 
treatment of these patients. 
Patients with high-grade brain tumors undergoing ABMT and high- 
dose chemotherapy will also be eligible to enter this protocol. 
It should be noted that this initial protocol is designed 
primarily to assess the transfer and expression of the MDR gene 
and its safety. However, patients with advanced breast and 
ovarian cancer have a strong possibility of being treated with 
MDR-responsive agents such as taxol following marrow 
transduction. Treated patients should provide information on 
whether the added MDR gene can prevent or decrease bone marrow 
toxicity by enriching for cells resistant to these drugs. If MDR 
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