Exocrine pancreas biomarkers

Hamack, L.J., Anderson, K.E., Zheng, W., Folsom, A.R., Sellers, T.A., and Kushi, L.H., Smoking, alcohol, coffee, and tea intake and incidence of cancer of the exocrine pancreas the Iowa women s health study. Cancer Epidemiol, Biomarkers Prev., 6, 1081-1086, 1997. 

The initial hazard identification of pancreatic toxicity in a prechnical study is always concerning because of the potentially serious human health risks, which may include fulminant, hfe-threatening cases of DIAP or a lifelong iUness, such as CP, type 1 diabetes, or pancreatic neoplasia. Because both the exocrine and the endocrine pancreas have enormous reserve capacities and there are limited sensitive and specific biomarkers to detect pancreatic injury in both animals and humans, there is always the concern that subclinical DIAP may initially go undetected in humans. Further, AP may progress until a threshold of severity is evident in minimally or asymptomatic healthy human volunteers exposed to drug candidates with unknown risks and/or in previously healthy patients that receive standard-of-care agents with marked... 

Case Study 2 Drug Candidate-Induced Micro vascular Injury at the Exocrine-Endocrine Interface in the Rat with Unsuccessful Confirmation of Toxicity In Vitro and No Pancreas-Specific Monitorable Biomarkers Identified... 

To further characterize the toxicity and investigate its possible mechanism, a 14-day time-course study in the rat was conducted to allow for the observation of the lesion development and progression (Brenneman et al., 2014). Light microscopic (i.e., histochemical and IHC with quantification) and ultrastructural (i.e., TEM) examination showed that the injury appeared to originate as degeneration and loss of endothelial cells in the capillaries at the exocrine-endocrine interface. This injury was not associated with any increases in traditional or exploratory serum biomarkers of exocrine injury nor any evidence of endocrine dysfunction as assessed via an OGTT however, it was associated with an increase in EMPs that was not pancreas specific. 

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