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The first formal qualification of safety biomarkers for regulatory decision making marks a milestone in the application of biomarkers to drug development. Following submission of drug toxicity studies and analyses of biomarker performance to the Food and Drug Administration (FDA) and European Medicines Agency (EMEA) by the Predictive Safety Testing(More)
The marriage of toxicology and genomics has created not only opportunities but also novel informatics challenges. As with the larger field of gene expression analysis, toxicogenomics faces the problems of probe annotation and data comparison across different array platforms. Toxicogenomics studies are generally built on standard toxicology studies(More)
The Critical Path Institute recently established the Predictive Safety Testing Consortium, a collaboration between several companies and the U.S. Food and Drug Administration, aimed at evaluating and qualifying biomarkers for a variety of toxicological endpoints. The Carcinogenicity Working Group of the Predictive Safety Testing Consortium has concentrated(More)
Biomarkers may be qualified using different qualification processes. A passive approach for qualification has been to accept the end of discussions in the scientific literature as an indication that a biomarker has been accepted. An active approach to qualification requires development of a comprehensive process by which a consensus may be reached about the(More)
Clinical proteomics has yielded some early positive results-the identification of potential disease biomarkers-indicating the promise for this analytical approach to improve the current state of the art in clinical practice. However, the inability to verify some candidate molecules in subsequent studies has led to skepticism among many clinicians and(More)
UNLABELLED Developing biomarkers for detecting acetaminophen (APAP) toxicity has been widely investigated. Recent studies of adults with APAP-induced liver injury have reported human serum microRNA-122 (miR-122) as a novel biomarker of APAP-induced liver injury. The goal of this study was to examine extracellular microRNAs (miRNAs) as potential biomarkers(More)
Epigallocatechin gallate (EGCG), the major flavonoid in green tea, is consumed via tea products and dietary supplements, and has been tested in clinical trials. However, EGCG can cause hepatotoxicity in humans and animals by unknown mechanisms. Here EGCG effects on rat liver mitochondria were examined. EGCG showed negligible effects on oxidative(More)
Carboxylesterase activity in the rat nasal mucosa plays an important role in the response of this tissue to certain toxic inhaled esters. We have examined this activity in extracts of both Fischer-344 rat and human nasal tissue using the substrate alpha-naphthyl butyrate, the same substrate as that used for histochemical analysis of this activity. We find(More)
The goal of this study was to compare and contrast the basal gene expression levels of the various enzymes involved in glutathione metabolism among tissues and genders of the rat, mouse and canine. The approach taken was to use Affymetrix GeneChip microarray data for rat, mouse and canine tissues, comparing intensity levels for individual probes between(More)
The tyrosine kinase inhibitor regorafenib was approved by regulatory agencies for cancer treatment, albeit with strong warnings of severe hepatotoxicity included in the product label. The basis of this toxicity is unknown; one possible mechanism, that of mitochondrial damage, was tested. In isolated rat liver mitochondria, regorafenib directly uncoupled(More)