Verapamil Restoration of Daunorubicin Responsiveness in Daunorubicin-resistant Ehrlich Ascites Carcinoma

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Verapamil restoration of daunorubicin responsiveness in daunorubicin-resistant Ehrlich ascites carcinoma.

We have studied the influence of verapamil hydrochloride on the in vitro and in vivo effects of daunorubicin in Ehrlich ascites carcinoma. Daunorubicin-sensitive tumor was rendered resistant to daunorubicin by the continuous treatment of sequential generations of tumor-bearing BALB/c mice. The ability of daunorubicin to inhibit [(3)H]uridine and [(3)H]thymidine incorporation and the effect of d...

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Mechanisms of resistance to daunorubicin in Ehrlich ascites tumor cells.

Uptake and binding of daunorubicin were studied in a sensitive (EHR 2) and in a resistant (EHR 2/DNR+) subline of Ehrlich ascites tumor cells. At steady state, the celhmedium ratio of daunorubicin was about 10-fold higher in EHR 2 than in EHR 2/DNR + . The bindings of daunorubicin to cell homogenate of the two cell lines were equal when the concentration at equilibrium was below 0.7 fig/ml, whe...

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Enhancement by cyclosporin A of daunorubicin efficacy in Ehrlich ascites carcinoma and murine hepatoma 129.

Cyclosporin A abrogates pleiotropic drug resistance in certain experimental tumors. Its impact on drug-sensitive tumors has not been investigated. Our studies show that in drug-sensitive Ehrlich ascites carcinoma and hepatoma 129 cyclosporin A enhances daunorubicin inhibition of DNA synthesis in vitro and prolongs survival of host mice in vivo. Of particular interest is that cyclosporin A conve...

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Decreased DNA topoisomerase II in daunorubicin-resistant Ehrlich ascites tumor cells.

We have previously shown that the multidrug-resistant EHR2/DNR+ cells, which overexpress P-glycoprotein, accumulate only about 20-30% of daunorubicin at steady state compared to the sensitive cells. These cells have been thought to be a "pure" P-glycoprotein cell line. We now report that the EHR2/DNR+ cells exhibit decreased DNA topoisomerase II catalytic activity. We also found that the amount...

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Decreased DNA Topoisomerase II in Daunorubicin-resistant Ehrlich Ascites Tumor Cells1

We have previously shown that the multidrug-resistant EHR2/DNR+ cells, which overexpress P-glycoprotein, accumulate only about 20-30% of daunorubicin at steady state compared to the sensitive cells. These cells have been thought to be a "pure" P-glycoprotein cell line. We now report that the EHR2/DNR+ cells exhibit decreased DNA topoisomerase II catalytic activity. We also found that the amount...

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ژورنال

عنوان ژورنال: Journal of Clinical Investigation

سال: 1982

ISSN: 0021-9738

DOI: 10.1172/jci110702