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The emergence and outgrowth of a population of tumour cells resistant to multiple drugs is a major problem in the chemotherapeutic treatment of cancer. We have used highly drug-resistant cell lines developed in vitro to study the molecular basis of multidrug resistance. In these cell lines high levels of resistance are frequently associated with(More)
The multidrug-resistant P-glycoprotein (Pgp), a M(r) 170,000 plasma membrane protein encoded by the mammalian multidrug resistance gene (MDR1), appears to function as an energy-dependent efflux pump. Many of the drugs that interact with Pgp are lipophilic and cationic at physiological pH. We tested the hypothesis that the synthetic gamma-emitting(More)
The complete nucleotide and primary structure (1276 amino acids) of a full length mdr cDNA capable of conferring a complete multidrug-resistant phenotype is presented. The deduced amino acid sequence suggests that mdr is a membrane glycoprotein which includes six pairs of transmembrane domains and a cluster of potentially N-linked glycosylation sites near(More)
Cytochalasin B (CB) induces a biphasic retraction is some cell types. The rapid response that peaks in 30 min leads to the "dendritic" condition. Replicating myogenic and fibrogenic cells, as well as postmitotic myoblasts and myotubes, participate in this reaction. This is followed by a slower phase that requires 40 h for stabilization and leads to the(More)
Resistance to multiple chemotherapeutic agents remains the major cause of failure in cancer chemotherapy. Multidrug resistant cell lines developed in vitro have provided a useful model for analyzing this phenomenon. We describe a complementary DNA, lambda DR11, which is present in normal cells and overexpressed in multidrug resistant cell lines. We have(More)
A potential therapeutic option for patients with Fanconi anemia is collection of peripheral blood stem cells prior to the development of severe pancytopenia. These hematopoietic cells potentially could be infused when symptomatic bone marrow failure develops, as autologous rescue after chemotherapy in the event of leukemic transformation, or as targets for(More)
A membrane glycoprotein, termed P-glycoprotein, has been shown to be responsible for cross-resistance to a broad range of structurally and functionally distinct cytotoxic agents. P-glycoprotein, encoded in humans by the mdrl gene, functions as an energy-dependent effiux pump to exclude these cytotoxic agents from the resistant ceil. In order to study the(More)
Recent studies have shown that tumor cells genetically modified by transduction of B7-1, a natural ligand for the T-cell costimulatory molecules CD28 and CTLA-4, are rejected in syngeneic hosts. In these reports, transformed cell lines and drug-selected cells have been used for vaccinations. To determine the effectiveness of B7-1-transduced primary acute(More)
The multidrug-resistant P-glycoprotein (Pgp), a M, 170,000 plasma membrane protein encoded by the mammalian multidrug resistance gene (MI)Kl), appears to function as an energy-dependent efflux pump. Many of the drugs that interact with Pgp are lipophilic and cationic at physio logical pH. We tested the hypothesis that the synthetic-/-emitting(More)
chondrial membrane potentials, final overall accumulation is inversely proportional to the level of P-glycoprotein expression. As with other P-glycoprotein transport substrates, [@mTc]Sestamibi efflux is energy dependent, and its accumulation is enhanced by traditional reversal agents. This transition metal complex is capable of inhibiting pho toaffinity(More)
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