The elucidation of the complex molecular and physiological events that characterize the differences between normal cells and cancer cells is under intense investigation both at the research level and in clinical practice. A large number of studies have been reported with DNA, RNA and protein-based technologies, however, few studies have been performed to characterize cancer at the biochemical level.

It is by gaining this type of mechanistic understanding of a disease that researcher will unlock the keys to discovering new diagnostics. This webcast presentation will provide an overview of a study undertaken to better understand and profile the biochemicals changes associated with prostate cancer aggressiveness. Using metabolomics, a global biochemical profiling technology, tissue, urine and plasma samples were analyzed enabling researchers to identify a series of biochemicals (including sarcosine) that are key potential predictors of cancer aggressiveness. (Nature, 12 February 2009)

Listeners will learn about this study as well as how the underlying technology that fueled this discovery is being applied in hundreds of other areas – like diabetes, drug safety research and even to gain a better of understanding of consumer goods products.

Drug-induced nephrotoxicity is a major concern, since many pharmacological compounds are filtered through the kidneys for excretion into urine. To discover biochemical biomarkers useful for early identification of nephrotoxicity, metabolomic experiments were performed on Sprague-Dawley Crl:CD (SD) rats treated with the nephrotoxins gentamicin, cisplatin, or tobramycin.

Using a combination of gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS), a global, nontargeted metabolomics analysis was performed on urine and kidney samples collected after one, five, and twenty-eight dosing days. Increases in polyamines and amino acids were observed in urine from drug-treated rats after a single dose, and prior to observable histological kidney damage and conventional clinical chemistry indications of nephrotoxicity.

Thus, these metabolites are potential biomarkers for the early detection of drug-induced nephrotoxicity. Upon prolonged dosing, nephrotoxin-induced changes included a progressive loss of amino acids in urine, concomitant with a decrease in amino acids and nucleosides in kidney tissue. A nephrotoxicity prediction model, based on the levels of branched-chain amino acids in urine, distinguished nephrotoxin-treated samples from vehicle-control samples, with 100%, 93%, and 70% accuracy at day 28, day 5, and day 1, respectively. Thus, this panel of biomarkers may provide a noninvasive method to detect kidney injury long before the onset of histopathological kidney damage.

This publication appears in Toxicological Pathology, Vol. 37, No. 3, 280-292 (2009).

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