The Experts below are selected from a list of 58035 Experts worldwide ranked by ideXlab platform
Al Harris - One of the best experts on this subject based on the ideXlab platform.
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Reversal of acquired resistance to adriamycin in CHO Cells by tamoxifen and 4-hydroxy tamoxifen: role of drug interaction with alpha 1 acid glycoprotein
British Journal of Cancer, 1990Co-Authors: M Chatterjee, Al HarrisAbstract:Tamoxifen and 4-OH tamoxifen were used to reverse multidrug resistance (MDR) in CHO Cells with acquired resistance to adriamycin (CHO-Adrr). Because alpha 1 acid glycoprotein (AAG) can bind a range of calcium channel blockers that also reverse MDR and rises in malignancy, its interactions with tamoxifen and 4-OH tamoxifen were also studied. Tamoxifen decreased the IC50 of 10 microM adriamycin 4.8-fold in the parent CHO-K1 Cell Line and 16-fold in CHO-Adrr. Similarly 4-OH tamoxifen decreased the IC50 3-fold in the parent Cells, but 13-fold in the resistant Cells. Tamoxifen and 4-OH tamoxifen were similarly potent in reversing MDR, although their anti-oestrogen potency differs 100-fold. AAG was added in increasing concentrations to the combination of adriamycin and tamoxifen. As AAG concentrations increased from 0.5 to 2 mg ml-1 (the range found in vivo) the effect of tamoxifen on reversing MDR was gradually decreased. At the highest AAG concentrations, there was complete reversal of the effects of both tamoxifen and 4-OH tamoxifen. AAG was found to bind 3H-tamoxifen in a non-saturable non-specific manner, in contrast to the binding of tamoxifen to albumin. Thus the use of tamoxifen as a reversal agent for MDR in vivo may be impaired by high binding to AAG. However, at the lower range of normal values of AAG, there was still an effect of 10 microM tamoxifen. It may be desirable to select patients for modifier studies based on AAG plasma levels.
M Chatterjee - One of the best experts on this subject based on the ideXlab platform.
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Reversal of acquired resistance to adriamycin in CHO Cells by tamoxifen and 4-hydroxy tamoxifen: role of drug interaction with alpha 1 acid glycoprotein
British Journal of Cancer, 1990Co-Authors: M Chatterjee, Al HarrisAbstract:Tamoxifen and 4-OH tamoxifen were used to reverse multidrug resistance (MDR) in CHO Cells with acquired resistance to adriamycin (CHO-Adrr). Because alpha 1 acid glycoprotein (AAG) can bind a range of calcium channel blockers that also reverse MDR and rises in malignancy, its interactions with tamoxifen and 4-OH tamoxifen were also studied. Tamoxifen decreased the IC50 of 10 microM adriamycin 4.8-fold in the parent CHO-K1 Cell Line and 16-fold in CHO-Adrr. Similarly 4-OH tamoxifen decreased the IC50 3-fold in the parent Cells, but 13-fold in the resistant Cells. Tamoxifen and 4-OH tamoxifen were similarly potent in reversing MDR, although their anti-oestrogen potency differs 100-fold. AAG was added in increasing concentrations to the combination of adriamycin and tamoxifen. As AAG concentrations increased from 0.5 to 2 mg ml-1 (the range found in vivo) the effect of tamoxifen on reversing MDR was gradually decreased. At the highest AAG concentrations, there was complete reversal of the effects of both tamoxifen and 4-OH tamoxifen. AAG was found to bind 3H-tamoxifen in a non-saturable non-specific manner, in contrast to the binding of tamoxifen to albumin. Thus the use of tamoxifen as a reversal agent for MDR in vivo may be impaired by high binding to AAG. However, at the lower range of normal values of AAG, there was still an effect of 10 microM tamoxifen. It may be desirable to select patients for modifier studies based on AAG plasma levels.
Bruce D. Walker - One of the best experts on this subject based on the ideXlab platform.
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inhibition of herg channels stably expressed in a mammalian Cell Line by the antianginal agent perhexiLine maleate
British Journal of Pharmacology, 1999Co-Authors: Stella M Valenzuela, C B Singleton, Jane A Bursill, Kenneth R Wyse, Samuel N Breit, Bruce D. Walker, Terence J CampbellAbstract:PerhexiLine has been used as an anti-anginal agent for over 25 years, and is known to cause QT prolongation and torsades de pointes. We hypothesized that the Cellular basis for these effects was blockade of IKr. A stable transfection of HERG into a CHO-K1 Cell Line produced a delayed rectifier, potassium channel with similar properties to those reported for transient expression in Xenopus oocytes. PerhexiLine caused voltage- and frequency-dependent block of HERG (IC50 7.8 μM). The rate of inactivation was increased and there was a 10 mV hyperpolarizing shift in the voltage-dependence of steady-state inactivation, suggestive of binding to the inactivated state. In conclusion, perhexiLine potently inhibits transfected HERG channels and this is the probable mechanism for QT prolongation and torsades de pointes. Channel blockade shows greatest affinity for the inactivated state. British Journal of Pharmacology (1999) 127, 243–251; doi:10.1038/sj.bjp.0702502
Zachary Coker - One of the best experts on this subject based on the ideXlab platform.
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Investigation of superparamagnetic (Fe3O4) nanoparticles and magnetic field exposures on CHO-K1 Cell Line
Optical Interactions with Tissue and Cells XXVII, 2016Co-Authors: Zachary Coker, Larry E. Estlack, Saber M. Hussain, Tae-youl Choi, Bennett L. IbeyAbstract:Rapid development in nanomaterial synthesis and functionalization has led to advanced studies in actuation and manipulation of Cellular functions for biomedical applications. Often these actuation techniques employ externally applied magnetic fields to manipulate magnetic nanomaterials inside Cell bodies in order to drive or trigger desired effects. While Cellular interactions with low-frequency magnetic fields and nanoparticles have been extensively studied, the fundamental mechanisms behind these interactions remain poorly understood. Additionally, modern investigations on these concurrent exposure conditions have been limited in scope, and difficult to reproduce. This study presents an easily reproducible method of investigating the biological impact of concurrent magnetic field and nanoparticle exposure conditions using an in-vitro CHO-K1 Cell Line model, with the purpose of establishing grounds for in-depth fundamental studies of the mechanisms driving Cellular-level interactions. Cells were cultured under various nanoparticle and magnetic field exposure conditions from 0 to 500 μg/ml nanoparticle concentrations, and DC, 50 Hz, or 100 Hz magnetic fields with 2.0 mT flux density. Cells were then observed by confocal fluorescence microscopy, and subject to biological assays to determine the effects of concurrent extreme-low frequency magnetic field and nanoparticle exposures on Cellnanoparticle interactions, such as particle uptake and Cell viability by MTT assay. Current results indicate little to no variation in effect on Cell cultures based on magnetic field parameters alone; however, it is clear that deleterious synergistic effects of concurrent exposure conditions exist based on a significant decrease in Cell viability when exposed to high concentrations of nanoparticles and concurrent magnetic field.
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Deleterious synergistic effects of concurrent magnetic field and superparamagnetic (Fe3O4) nanoparticle exposures on CHO·K1 Cell Line
2015Co-Authors: Zachary CokerAbstract:While many investigations have been performed to establish a better understanding of the effects that magnetic fields and nanoparticles have on Cells, the fundamental mechanisms behind the interactions are still yet unknown, and investigations on concurrent exposure are quite limited in scope. This study was therefore established to investigate the biological impact of concurrent exposure to magnetic nanoparticles and extremely-low frequency magnetic fields using an in-vitro CHO-K1 Cell Line model, in an easily reproducible manner to establish grounds for further in-depth mechanistic, proteomic, and genomic studies. Cells were cultured and exposed to 10nm Fe3O4 nanoparticles, and DC or low frequency (0Hz, 50Hz, and 100Hz) 2.0mT magnetic fields produced by a Helmholtz coil pair. The Cells were then observed under confocal fluorescence microscopy, and subject to MTT biological assay to determine the synergistic effects of these concurrent exposures. No effects were observed on Cell morphology or microtubule network; however, Cell viability was observed to decrease more drastically under the combined effects of magnetic field and nanoparticle exposures, as compared to independent exposures alone. It was concluded that no significant difference was observed between the types of magnetic fields, and their effects on the nanoparticle exposed Cells, but quite clearly there are deleterious synergistic effects of these concurrent magnetic field and nanoparticle exposure conditions.
Peter E. Bryant - One of the best experts on this subject based on the ideXlab platform.
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Elevated levels of DNA double-strand breaks (dsb) in restriction endonuclease-treated xrs5 Cells correlate with the reduced capacity to repair dsb
Mutation Research DNA Repair, 1991Co-Authors: Nina D. Costa, Peter E. BryantAbstract:Recently we have reported the kinetics of DNA double-strand breaks (dsb) induced in electroporated mammalian (CHO) Cells that had been treated with the restriction endonuclease PvuII, as measured by the filter elution assay at the non-denaturing pH of 9.6. A gradual accumulation of dsb was observed over a 24-h incubation period following the restriction endonuclease (RE) treatment and this was attributed to a competition between incision of the DNA by PvuII and dsb repair. In order to test this ‘competition’ hypothesis we have carried out similar experiments in the radiosensitive xrs5 mutant Cell Line, which has been shown to be deficient in dsb repair.The levels of dsb monitored to be 3–4 times non-denaturing filter elution assay in the xrs5 Cell Line treated with PvuII was found to be 3–4 times higher than that found for the wild-type CHO K1 Cell Line. Levels of dsb were also significantly raised in xrs5 Cells treated with BAMHI, as compared with the background levels observed in the CHO Line. These data lend strong support to the competition hypothesis of simultaneous incision and repair of RE-induced dsb.
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Enhanced mutability at the tk locus in the radiosensitive double-strand break repair mutant xrs5.
Mutation Research Fundamental and Molecular Mechanisms of Mutagenesis, 1990Co-Authors: Taha A.k. Mussa, Baldev Singh, Peter E. BryantAbstract:Abstract The thymidine kinase locus (tk) has been utilised as the target locus to measure the induced mutation frequency following X-irradiation in the X-ray-sensitive xrs5 mutant and its parent CHO K1 Line of Chinese hamster Cells. Mutations of tk − Cells were measured by plating Cells in selective medium containing trifluorothymidine after a post-irradiation expression time of 4 days. Our results show that the mutation frequency was 3–4 times higher in the xrs5 mutant than in the CHo K1 Cell Line. This enhanced mutation frequency in xrs5 is though to result from the deficiency in DNA double-strand repair in this Cell Line which also results in the enhanced Cell killing and higher frequencies of chromosomal aberrations in respnose to X-irradiation. The findings of the present study suggest that DNA double-strand break is a critical lesion leading to mutations in irradiated Cells.