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Effects of quinidine and related compounds on cytotoxicity and cellular accumulation of vincristine and adriamycin in drug-resistant tumor cells.
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Quinidine, which has antiarrhythmic activity, greatly enhanced the cytotoxicity of vincristine (VCR) in tumor cells and especially in VCR-resistant sublines of P388 leukemia (P388/VCR) and human myelogenous leukemia. A nontoxic concentration of quinidine increased VCR cytotoxicity in these resistant
Adequate tumour quinidine levels for multidrug resistance modulation can be achieved in vivo.
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The multidrug resistance (MDR) phenotype can be reversed in vitro by a number of agents thought to interact with P-glycoprotein (P-gp). Although plasma levels, adequate for MDR modulation, can be achieved with certain modulators, concern has been expressed that tumour levels may be inadequate due to
Enabling P-glycoprotein inhibition in multidrug resistant cancer through the reverse targeting of a quinidine-PEG conjugate.
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Previously identified as a key mediator of multidrug resistance, the drug efflux behavior of P-glycoprotein (P-gp) remains a prominent challenge in cancer treatment. P-gp belongs to the ATP-binding cassette transporter family of membrane proteins, and modulates the efflux of many drugs at the cell
Lack of effect of treatment with human recombinant-tumour necrosis factor (HrTNF) on the binding of quinidine to alpha 1-acid glycoprotein (AGP).
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Tumour necrosis factor (TNF) is known to be a key mediator in the acute phase response and its administration has been shown to cause a five fold increase in serum alpha 1-acid glycoprotein (AGP) concentration in the rat. Since, in man, plasma AGP level determines the protein binding of many
Myc protein is differentially sensitive to quinidine in tumor versus immortalized breast epithelial cell lines.
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Quinidine regulates growth and differentiation in human breast tumor cells, but the immortalized mammary epithelial MCF-10A cell line is insensitive to quinidine. We found that a morphologically similar differentiation response was evoked by quinidine and c-myc antisense oligonucleotides in MCF-7
Amiodarone inhibits production of tumor necrosis factor-alpha by human mononuclear cells: a possible mechanism for its effect in heart failure.
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BACKGROUND
Recent studies suggest that cytokines such as tumor necrosis factor (TNF)-alpha and interleukins (ILs) are capable of modulating cardiovascular function and that drugs used in the treatment of heart failure have various modulatory effects on the production of cytokines. This study was
Antiarrhythmic agents and the risk of malignant neoplasm of liver and intrahepatic bile ducts.
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BACKGROUND
The objective of this study was to determine the association between the use of antiarrhythmic agents and the risk of malignant neoplasm of liver and intrahepatic bile ducts (MNLIHD).
METHODS
We used the research database of the Taiwan National Health Insurance Program to conduct a
Development of an intrinsic P-glycoprotein-mediated doxorubicin resistance in quiescent cell layers of large, multicellular prostate tumor spheroids.
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Growing multicellular prostate tumor spheroids develop quiescent cell subpopulations in central regions with features of intrinsic multicell-mediated drug resistance. Doxorubicin (dox) uptake was significantly reduced in large spheroids (diameter 400+/-70 microm), which consist predominantly of
Redox regulation of P-glycoprotein-mediated multidrug resistance in multicellular prostate tumor spheroids.
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Multicellular prostate tumor spheroids develop intrinsic P-glycoprotein (Pgp)-mediated multidrug resistance with the appearance of quiescent cell areas. We have investigated the effect of intracellular reactive oxygen species (ROS) on Pgp expression in large, quiescent and drug-resistant
An ATP-sensitive K(+) current that regulates progression through early G1 phase of the cell cycle in MCF-7 human breast cancer cells.
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Whole-cell recordings were used to identify in MCF-7 human breast cancer cells the ion current(s) required for progression through G1 phase of the cell cycle. Macroscopic current-voltage curves were fitted by the sum of three currents, including linear hyperpolarized, linear depolarized and
Identification of a multidrug resistance modulator with clinical potential by analysis of synergistic activity in vitro, toxicity in vivo and growth delay in a solid human tumour xenograft.
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Circumvention of multidrug resistance in vitro by resistance modulators is well documented but their clinical use may be limited by effects on normal tissues. We have compared four resistance modifiers, both in terms of modulation of doxorubicin sensitivity in vitro and toxicity in vivo, in order to
Metastatic breast cancer.
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Tamoxifen as adjuvant systemic treatment after first isolated locoregional recurrence of breast cancer has been shown to decrease the subsequent locoregional relapse rate, but it affects neither distant metastases nor survival. In metastatic disease, tamoxifen has not improved response when added to
The role of drug-drug interactions in prostate cancer treatment: Focus on abiraterone acetate/prednisone and enzalutamide.
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Elderly patients with cancer may have comorbidities, each requiring additional pharmacologic treatment. Therefore, the occurrence of pharmacokinetic (PK) and pharmacodynamic (PD) interactions is very likely, and the risk of adverse reactions (ADRs), due to the narrow therapeutic window of anticancer
A pilot study of amiodarone with infusional doxorubicin or vinblastine in refractory breast cancer.
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Increasing evidence suggests that P-glycoprotein (Pgp) expression can mediate drug resistance in refractory breast cancer. We studied 33 patients with refractory breast cancer enrolled in a pilot study of oral amiodarone as a Pgp antagonist given in combination with infusional doxorubicin or
Chemoresistance in breast tumors.
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Resistance to multiple chemotherapeutic agents is a common clinical problem in the treatment of cancer: such resistance may occur in primary therapy or be acquired during treatment. The most commonly used antineoplastic agents in the treatment of disseminated breast cancer are adriamycin,
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