Cross-species gene expression analysis of species specific differences in the preclinical assessment of pharmaceutical compounds

Animals are frequently used as model systems for determination of safety and efficacy in pharmaceutical research and development. However, significant quantitative and qualitative differences exist between humans and the animal models used in research. This is as a result of genetic variation between human and the laboratory animal. Therefore the development of a system that would allow the assessment of all molecular differences between species after drug exposure would have a significant impact on drug evaluation for toxicity and efficacy. Here we describe a cross-species microarray methodology that identifies and selects orthologous probes after cross-species sequence comparison to develop an orthologous cross-species gene expression analysis tool. The assumptions made by the use of this orthologous gene expression strategy for cross-species extrapolation is that; conserved changes in gene expression equate to conserved pharmacodynamic endpoints. This assumption is supported by the fact that evolution and selection have maintained the structure and function of many biochemical pathways over time, resulting in the conservation of many important processes. We demonstrate this cross-species methodology by investigating species specific differences of the peroxisome proliferatoractivator receptor (PPAR) a response in rat and human

On-a-chip genotoxicity assay-application to high-throughput screening biochips

Times Cited: 0 Piron, R Rougier, N Vaudry, R Corlu, A Glaise, D Joly, P Le Pioufle, B 8th International Conference on Miniaturized Systems for Chemistry and Life Sciences Sep 26-30, 2004 Malmo, SWEDEN VINNIVA, Crafoord Fdn, Swedish Fdn Strateg Res, MCPT, Micralyne, SAMSUNG, Micro Plastab, GYROS, Lung Univ, Erysave AB, ATS Med, Silex Microsyst, Johnson &Johnson, Caliper Life Sci, MicroFluid Syst Inc, Analyt Chem, Sci AAAS, Lab Chip, Journal Separat SciInternational audienceWe present a cell array biochip dedicated to toxicological and high-throughput drug screening applications, on which are performed genotoxity analysis using micronucleus test. This cell biochip is an array of microwells optimized for living cell culture (Fig.1-a). Topographical aspects are exploited in order to control the distribution and the positioning of the cells on the biochip [1,2]. Such a miniaturized cell-based device is of great interest, in terms of cost and time, for pharmacological applications [3]

On-a-chip genotoxicity assay-application to high-throughput screening biochips

Times Cited: 0 Piron, R Rougier, N Vaudry, R Corlu, A Glaise, D Joly, P Le Pioufle, B 8th International Conference on Miniaturized Systems for Chemistry and Life Sciences Sep 26-30, 2004 Malmo, SWEDEN VINNIVA, Crafoord Fdn, Swedish Fdn Strateg Res, MCPT, Micralyne, SAMSUNG, Micro Plastab, GYROS, Lung Univ, Erysave AB, ATS Med, Silex Microsyst, Johnson &Johnson, Caliper Life Sci, MicroFluid Syst Inc, Analyt Chem, Sci AAAS, Lab Chip, Journal Separat SciInternational audienceWe present a cell array biochip dedicated to toxicological and high-throughput drug screening applications, on which are performed genotoxity analysis using micronucleus test. This cell biochip is an array of microwells optimized for living cell culture (Fig.1-a). Topographical aspects are exploited in order to control the distribution and the positioning of the cells on the biochip [1,2]. Such a miniaturized cell-based device is of great interest, in terms of cost and time, for pharmacological applications [3]

On-a-chip genotoxicity assay-application to high-throughput screening biochips

Times Cited: 0 Piron, R Rougier, N Vaudry, R Corlu, A Glaise, D Joly, P Le Pioufle, B 8th International Conference on Miniaturized Systems for Chemistry and Life Sciences Sep 26-30, 2004 Malmo, SWEDEN VINNIVA, Crafoord Fdn, Swedish Fdn Strateg Res, MCPT, Micralyne, SAMSUNG, Micro Plastab, GYROS, Lung Univ, Erysave AB, ATS Med, Silex Microsyst, Johnson &Johnson, Caliper Life Sci, MicroFluid Syst Inc, Analyt Chem, Sci AAAS, Lab Chip, Journal Separat SciInternational audienceWe present a cell array biochip dedicated to toxicological and high-throughput drug screening applications, on which are performed genotoxity analysis using micronucleus test. This cell biochip is an array of microwells optimized for living cell culture (Fig.1-a). Topographical aspects are exploited in order to control the distribution and the positioning of the cells on the biochip [1,2]. Such a miniaturized cell-based device is of great interest, in terms of cost and time, for pharmacological applications [3]