We represent insurers, corporate/commercial entities, banks and financial companies, and individuals. In summary, our toxicogenomic model is particularly useful for predicting the future onset of proximal tubular injury. With offices also in Ottawa, London, Kitchener & Barrie, we are dedicated to litigation & advocacy, with a strong focus on insurance defence & insurance coverage litigation. The genes included in our model were primarily involved in DNA replication, cell cycle control, apoptosis, and responses to oxidative stress and chemical stimuli. We also found that the prediction accuracy of the optimized model was substantially higher than that produced by any of the single genomic biomarkers or histopathology. Thum T, Erpenbeck VJ, Moeller J, Hohlfeld JM, Krug N, Borlak J. The model was evaluated using a five-fold cross validation, and achieved a sensitivity of 93% and selectivity of 90% with 19 probes. The stained arrays were scanned at 532 nm using an Affymetrix GeneChip Scanner 3000. We identified genomic biomarkers for use in future onset prediction using the gene expression profiles determined on day 1, when most of the nephrotoxicants had yet to produce detectable histopathological changes. Filter-type gene selection and linear classification algorithms were employed to discriminate future onset of proximal tubular injury. Gene expression profiles were generated from kidney total RNA using Affymetrix DNA microarrays. Animals were exposed to three different doses (low, middle, and high) of each compound, and kidney tissue was collected at 3, 6, 9, and 24 h after single dosing, and on days 4, 8, 15, and 29 after repeated dosing. Male Sprague-Dawley rats were dosed orally or intravenously once daily. In total, 41 nephrotoxic and nonnephrotoxic compounds were used for the present analysis. The specific aim of the present study was to develop a model for use in predicting the future onset of drug-induced proximal tubular injury following repeated dosing with various nephrotoxicants. Toxicogenomics is now a generally accepted tool for identifying chemicals with potential safety problems. Drug-induced renal tubular injury is a major concern in the preclinical safety evaluation of drug candidates.
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