Abstract
Some "multidrug-resistant" (MDR) cell lines are not associated with a defect in drug accumulation or with the overexpression of P-glycoprotein. These cell lines are defined as "atypical MDR" (at-MDR) and they often express altered or mutated topoisomerase II. We investigated the ability of tumor necrosis factor to reverse at-MDR (in the human ovarian cancer cell line A2780 DX3) on the basis of its efficacy in potentiating in vitro topoisomerase II-targeted drugs, and because there is convincing evidence that the synergy is due to an increased number of topoisomerase-associated strand-breaks as well as to an increased level of extractable topoisomerase.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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DNA Damage
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DNA Topoisomerases, Type II / metabolism*
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Doxorubicin / pharmacology
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Doxorubicin / therapeutic use
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Drug Resistance / genetics
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Drug Resistance / physiology*
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Drug Synergism
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Etoposide / pharmacology
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Etoposide / therapeutic use
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Female
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Humans
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Mitoxantrone / pharmacology
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Mitoxantrone / therapeutic use
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Ovarian Neoplasms / drug therapy
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Ovarian Neoplasms / enzymology*
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Topoisomerase II Inhibitors
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Tumor Cells, Cultured / enzymology
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Tumor Necrosis Factor-alpha / pharmacology*
Substances
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Topoisomerase II Inhibitors
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Tumor Necrosis Factor-alpha
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Etoposide
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Doxorubicin
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Mitoxantrone
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DNA Topoisomerases, Type II