Malnutrition in pancreatic ductal adenocarcinoma (PDA): dietary pancreatic enzymes improve short-term health but stimulate tumor growth.

Malnutrition in pancreatic ductal adenocarcinoma (PDA): dietary pancreatic enzymes improve short-term health but stimulate tumor growth. Am J Pathol. 2017 Dec 14;: Authors: Zolghadri Y, Choudhuri SP, Ocal O, Ghalehsoukhteh SL, Berhe F, Hale MA, Wilkie TM Abstract Pancreatic ductal adenocarcinoma (PDA) is a deadly cancer that resists efforts to identify better chemotherapeutics. PDA is associated with chronic pancreatitis and acinar cell dedifferentiation. This reduces enzyme production by the exocrine pancreas, resulting in digestive insufficiencies. Malabsorption of partially digested food can cause bloating, overfilled intestines, abdominal pain, excessive feces, steatorrhea, and malnutrition. These maladies affect quality of life and restrict treatment options for pancreatitis and PDA. Here, we characterize the health benefits and risks of dietary pancreatic enzymes in three mouse models of PDA-KC, KCR8-16, and KIC. KC expresses oncogenic KrasG12D in pancreatic tissue whereas KCR8-16 also has deletions of the Rgs8 and Rgs16 genes. Rgs proteins inhibit the release of digestive enzymes evoked by G-protein coupled receptor agonists. KC and KCR8-16 mice developed dedifferentiated exocrine pancreata within two months of age, and became malnourished, underweight, hypoglycemic, and hypothermic. KC mice adapted but KCR8-16 rapidly transitioned to starvation after mild metabolic challenges. Dietary pancreatic enzyme supplements reversed th...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research