PamGene's Posters at the SOT 2012
During the Annual Meeting of the Society of Toxicology in March 2012 in San Francisco, two posters were presented of studies in which PamGene technology was used. One poster was presented by Peter Lord, on the subject of kinase activity profiling in investigative toxicology. The other poster covered a study on a possible alternative for rat uterotrophic assay for endocrine disruptors, by René Houtman. 
Kinase activity profiling in investigative toxicology

Peter Lord’s study shows that by monitoring signalling kinases with dynamic peptide microarrays, underlying mechanisms of toxic responses can be studied. The researchers extracted total protein from renal cell carcinoma and normal kidney tissues from patients treated with either sorafenib or sunitinib. Equal amounts of total protein were analysed for kinase activities on PamChip peptide microarrays.
Tumour tissue showed higher activity in phosphorylation profiles than healthy tissue of the same patient. Investigating both chemotherapeutics, similar profiles were found in tumour tissue, while clear differences were detected in the corresponding normal tissue. These are potentially linked to differences in toxicity between the drugs.
This novel molecular approach has a good potential application in clinical and preclinical toxicological research. Clearly it provides the means to study the dynamics of the adverse effect of pharmaceuticals, whether from cell lines or (animal or patient derived) tissues.
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Possible alternative for rat assays

The rat uterotrophic assay (RUA) is a widely accepted test to detect endocrine disruptors: chemicals that interfere with the female reproduction system. However, there is an increasing concern over the use of animals, which leads to the need for alternative in vitro approaches.
The poster of René Houtman shows the results of a possible alternative to the RUA. An estrogen receptor activity test was applied on a set of reference compounds that are established as positives or negatives in the rat uterotrophic assay (RUA). In this technique, compounds are profiled for their ability to modulate ERα activity, that is, receptor-coregulator binding. The researchers built a class-prediction model from the compound profiles to discriminate positive from negative endocrine disruptors. Using this model they were able to reproduce RUA compound classification accurately.
Houtman’s conclusion is that this technique may provide a simple and high throughput in vitro alternative to the uterotrophic assay. 
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