Entremed (ENMD)

[C_Peptide]

Thx George. The PPAR-gamma story commands attention.

I am particularly impressed with the central role described for PPAR-gamma in the endothelial cells of tumors. When you add that to the recent safety concerns for the thiazolidinediones, or "glitazones", like Avandia, and the animal studies showing CARCINOGENESIS [1] with PPAR-gamma agonists, I would now think long and hard before prescribing a PPAR-gamma agonist for a diabetic [2].

If I were a reviewer of the paper, I would insist that the authors double-check, and clearly state, that the chronic pancreatitis patients, and the pancreatic cancer patients from whom surgical specimens were obtained, and who may be diabetic from pancreatic dysfunction or resection, were not taking a "glitazone", which would obviously be expected to produce the immunohistochemical results shown.

The reference [1] below states: "Mechanistic data to explain MOA for tumor formation [from PPAR agonists] is not available." It appears that mechanistic data is now available.

References:
1. El-Hage, J. Preclinical and Clinical Safety Assessments for PPAR-gamma Agonists http://www.fda.gov/cder/present/DIA2004/Elhage.ppt
2. Wikipedia: Rosiglitazone http://en.wikipedia.org/wiki/Avandia

Best Regards,
C. Peptide