Clinical Reversal of Multidrug Resistance.
Reversal of drug resistance offers the hope of increasing the efficacy of conventional chemotherapy. We tested dexverapamil as a P-glycoprotein antagonist in combination with EPOCH chemotherapy in refractory non-Hodgkin's lymphoma. In a cross-over design, dexverapamil was added to EPOCH after disease stabilization or progression occurred. Objective responses were observed in 10 of 41 assessable patients. Biopsies for mdr-1 were obtained before EPOCH treatment and at the time of cross-over to dexverapamil. Levels of mdr-1 were low before EPOCH, but increased fourfold or more in 42% of patients in whom serial samples were obtained. Pharmacokinetic analysis revealed median peak concentrations of dexverapamil and its metabolite, nor-dexverapamil, of 1.66 µmol/l and 1.58 µmol/l, respectively. Since both are comparable antagonists, a median peak total reversing concentration of 3.24 µmol/l was achieved. Pharmacokinetic analysis of doxorubicin and etoposide levels confirmed a delay in the clearance of doxorubicin ranging from 5% to 24%; no change in the pharmacokinetics of etoposide was observed. This study provides sufficient rationale for testing dexverapamil in a randomized clinical trial.
RNAi Induced Inhibition of MRP1 Expression and Reversal of Drug Resistance in Human Promyelocytic HL60 Cell Line
Multidrug resistance (MDR) is a complex phenomenon in which many different genes regulating drug transport, cellular repair, detoxification and drug metabolism are involved. Nevertheless, in most drug resistant cell lines and cancer patients up-regulation of ABC-transporter genes such as MDR associated Protein (MRP1) gene could be at the basis of the drug resistance phenotype. We aimed to decre...متن کامل
Induction of apoptosis and reversal of permeability glycoprotein-mediated multidrug resistance of MCF-7/ADM by ginsenoside Rh2.
Multidrug resistance is a phenomenon that cancer cells develop a cross-resistant phenotype against several unrelated drugs, and permeability glycoprotein derived from the overexpression of multidrug resistance gene 1 has been taken as the most significant cause of multidrug resistance. In the present study, ginsenoside Rh2 was used to reverse permeability glycoprotein-mediated multidrug resista...متن کامل
We investigated the reversal effect of vitamin D on the multidrug-resistant leukemic Jurkat/ADR and K562/ADR cell lines and conducted a preliminary investigation of its reversal mechanism. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method was used to detect the reversal effect of vitamin D on multidrug-resistant cells. Real-time polymerase chain reaction was used to ...متن کامل
Molecular Investigation of Outer Membrane Channel Genes Among Multidrug Resistance Clinical Pseudomonas Aeruginosa Isolates
Background: Multidrug resistance Pseudomonas aeruginosa (MDRPA) is most important issue in healthcare setting. It can secrete many virulence effector proteins via its secretion system type (T1SS-T6SS). They are using them as conductor for delivering the effector proteins outside to begins harmful effect on host cell increasing pathogenicity, competition against other microorganism and nutrient ...متن کامل
Multidrug resistance is a serious obstacle encountered in cancer treatment. Since drug resistance in human cancer is mainly associated with overexpression of the multidrug resistance gene 1 (MDR1), the promoter of the human MDR1 gene may be a target for multidrug resistance reversion drug screening. In the present study, HEK293T cells were transfected with pGL3 reporter plasmids containing the ...متن کامل
Evaluation of Toxin and Antitoxin System in Acinetobacter Multidrug Resistance Bacteria Isolated From Clinical Specimens
Introduction: Acinetobacter baumannii is one of the most important nosocomial and community-acquired pathogens that is resistant to many antibiotics. Toxin-antitoxin systems are regulatory systems that maintain bacteria and serve as new targets for Antimicrobial therapies are considered. The prevalence and transcription of these systems in clinical isolates is still unknown. The aim of this stu...متن کامل