Growth and molecular interactions between tamoxifen and. Clonality, apoptosis, and migration were measured using the plate clone formation assay, annexin vpropidium iodide pi staining, hoechst 33342 staining, and the woundhealing test. Combination assays using the chou talalay method were performed on three responsive gscs, gs102, gs224 and gs289, to evaluate synergy between the hdaci scriptaid or lbh589 and delta24rgd. Drug interactions were analyzed using the choutalalay method with compusyn software. The choutalalay method for drug combination is based on the. Dorothy chou in 2005 with purpose of promoting the pharmacodynamic research and simple computerized analytical simulation using the medianeffect principle of the massaction law 2,3 and its combination index theorem 3,4 has achieved its goals. Synergy determination with the choutalalay method the choutalalay method 18 to determine possible synergistic effects of selected kinase inhibitor combina. The effect of drugs on cell proliferation was determined by using mtt assay kit sigma, supplementary table s3 as per manufacturer instructions.
Synergistic enhancement of efficacy of platinum drugs with. Drug combination studies and their synergy quantification using the choutalalay method. The ic 50 50% inhibitory concentration values were calculated based on choutalalay method using compusyn software. First the ic 50 values of scriptaid, lbh589 and delta24rgd were determined by medianequation calculation and subsequently the combination assays were. The choutalalay method for drug combination is based on the medianeffect equation, derived from the massaction law principle, which is the unified theory that provides the common link between. How to interpret data from compusyn software combination index. The median effect principle and the combination index for quantitation of synergism and antagonism. The medianeffect equation derived from the massaction law principle at equilibriumsteady state via mathematical induction and deduction for different reaction sequences and mechanisms and different types of inhibition has been shown to be the unified theory for the michaelismenten equation, hill equation, hendersonhasselbalch equation, and scatchard equation. Synergistic combination of microtubule targeting anticancer. For the assessment of drug interactions, tests were performed comprising the individual drugs al one and in combination, followed by calculation of the combination indices ci using the choutalalay method with help of the compusyn software combosyn, inc. Synergistic and antagonistic drug interactions are important to consider when developing mixtures of anticancer or other types of drugs. Cytotoxic effects of the newlydeveloped chemotherapeutic.
To compare effects of different treatments, the students t. For this method to be applicable, each drug should show a doseeffect relationship, at least three data points are required for each single drug effect, and the linear correlation coefficient should be 0. The choutalalay method for drug combination is based on the medianeffect equation, derived from the massaction law principle, which is the unified theory that provides the common link between single entity and multiple entities, and first order and higher order dynamics. The choutalalay method for drug combination is based on the medianeffect equation, derived from the massaction law principle, which is the. Tingchao chou is the founder and president of pd science llc.
Both calcusyn and compusyn programs were written based on choutalalays combination index theorem. This method is entirely based on the physical, chemical and mathematical principles of the massaction law, i. Drug combination studies and their synergy quantification. This general equation encompasses the michaelismenten, hill, henderson. Hen dersonhasselbalch ph ionization, hill higher order ligand binding saturation, michaelis. The data revealed that 17aag shows a potent synergistic interaction ci 1 indicates an antagonistic effect. These information will be used in this registration of download and agreements but not for any commercial purposes. Boik, newman, and boik 2008 proposed the mixlow method as an alternative to the medianeffect method of chou and talalay 1984 for estimating. Frequently asked questions in drug combinations and the mass action law based answers. The choutalalay method for drug combination is based on the medianeffect. In analyzing our results, we employed the widely used chou and talalay method 4, 5 using commercially available software for the analysis. Drug combination studies and their synergy quantification using the.
Tingchao chou, 70 phd inducted into the society of. Their combined citations are counted only for the first article. Analyses can be saved in a fastcicompatible format or exported for use in graphpad prism. Choudrug combination studies and their synergy quantification using the choutalalay method cancer res. His 457 scientific articles have been cited in 26,292 papers in over 754 biomedical journals as of may 5, 2017.
Drug combination studies and their synergy quantification using the chou talalay method. Theoretical basis, experimental design, and computerized. Synergistic activity of hsp90 inhibitors and anticancer. Drug interactions were analyzed using choutalalay method to calculate the combination index ci. How to interpret data from compusyn software combination. A major limitation of the choutalalay method is its dependence on accurate and welldefined doseeffect curves, which are not always available. A computational approach for identifying synergistic drug. To calculate the combination indices ci, the compusyn software was used version 1. Have performed invitro assay with multipleray design to explore different. A measure of how much the dose of each drug in a synergistic combination may be reduced at a given effect level compared with the doses of each drug alone application of the choutalalay method 15 application of the choutalalay method scope of application since both the medianeffect equation of chou and the combinationindex equation of chou. The hdac inhibitors scriptaid and lbh589 combined with the.
A375, igr37 and 501mel parental and brafiresistant cells were seeded at a density of 0. There is a lot of information and misinformation online about the differences between these two types of foam. The ic 50s were determined for 3 biological replicates and are listed with their standard deviations. But to use it is very easy with the help of compusyn software. The choutalalay method to determine possible synergistic effects of selected kinase inhibitor combinations was used as described in. Given the poor prognosis of braf melanoma and the rapid rate at which resistance develops and tumors progress, there is an urgent need to. All data were presented as means standard deviation sd. Implementation of the choutalalay method for studying the. Based on these algorithms, computer software, compysyn, is used for. Quantitative determination of synergism or antagonism with the combination index theorem of choutalalay and automated compusyn simulation has been used for antiviral and anticancer drug combination studies in over 10,000 scientific papers. Also measured by the choutalalay combination index bliss 1939. Investigating antimalarial drug interactions of emetine. Over 98% of them have been 2drug combinations in vitro.
The choutalalay method was performed as described 16 and means were plotted with standard deviations. Design of antiviral cocktails with combination index. Determine the interaction of two drugs as synergy, additivity, or antagonism. Research paper in vitro cytotoxic activities of the oral. Kinase inhibitor library screening identifies synergistic. The dunlop process and the talalay process are the two main processes used to create latex foam.
Read more about drug combination studies and their synergy quantification using the choutalalay method. The ci was determined by choutalalay method and calcusyn software biosoft, ferguson, mo, usa. The following provides an overview of the isobologram and ci analyses. Ayers, and reuben lotan in journal of biopharmaceutical statistics 2007, 17 3, pp. In a population, is each individuals probability of death from drug a statistically independent of the probability of death from drug b. For combination studies, the choutalalay method is used to generate an faci plot and provide interpretations of synergy and antagonism. By using the compusyn software, attached are the graphs output from one of my. Software described in interaction index and different methods for determining drug interaction in combination therapy by j.
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