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Abstract
Treatment of chronic lymphocytic leukemia (CLL) remains a challenge due to the frequency
of drug resistance amongst patients. Improving the delivery of chemotherapeutic agents
while reducing the expression of anti-apoptotic Heat Shock Proteins (HSPs) within
the cancer cells may facilitate in overcoming this drug resistance. We demonstrate
for the first time that sub-lethal doses of chemotherapeutic agents can be combined
with membrane fluidizing treatments to produce a significant increase in drug efficacy
and apoptosis in vitro. We show that fluidizers result in a transient decrease in
intracellular HSPs, resulting in increased tumor-cell sensitivity and a membrane-associated
induction of HSP gene expression.
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