Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Microsatellite instability (MIN) has been detected in many cancer types; however, recently we also observed it in the nonneoplastic but inflammatory setting of pancreatitis. Consequently, we sought to examine whether MIN was present in another inflammatory condition, ulcerative colitis (UC). MIN was found in 50% of UC patients whose colonic mucosa was negative for dysplasia, 46% of those with high-grade dysplasia, and 40% of those with cancer but in none of the ischemic or infectious colitis controls (P<0.03). Thus, UC patients may have MIN within mucosa that has no histological evidence of neoplastic change. MIN in this setting may reflect the inability of DNA repair mechanisms to compensate for the stress of chronic inflammation, and may be one mechanism for the heightened neoplastic risk in UC.
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PMID:Microsatellite instability in nonneoplastic mucosa from patients with chronic ulcerative colitis. 864 Aug 5

Of all the body systems, the gastrointestinal (GI) tract is the most exposed to proteinases. Proteolytic activity must thus be tightly regulated in the face of diverse environmental challenges, because unrestrained or excessive proteolysis leads to pathological GI conditions. The protease-activated receptor-2 (PAR-2) is expressed in numerous cell types within the GI tract, suggesting both multiple functions and numerous modes of receptor activation. Although best known as a pancreatic digestive enzyme, trypsin has also been found in other tissues and various cancers. Of interest, trypsin and PAR-2 act together in an autocrine loop that promotes proliferation, invasion and metastasis in neoplasia through various mechanisms. Trypsin and PAR-2 seem to act both directly and indirectly through activation of other proteinase cascades, including metalloproteinases. PAR-2 activation can participate in inflammatory reactions, be protective to mucosal surfaces, send or inhibit nociceptive messages, modify gut motility or secretory functions, and stimulate cell proliferation and motility. Several studies point to a role for the PARs in disease processes of the GI tract and pancreas ranging from inflammatory bowel disease, symptoms associated with irritable bowel syndrome, pain in pancreatitis, development of colon and other GI cancers, and even infectious colitis. Proteinases should not only be considered from the traditional view as digestive or degradative enzymes in the gut, but additionally as signalling molecules that actively participate in the spectrum of physiology and diseased states of the GI tract.
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PMID:Proteinase-activated receptor 2 (PAR-2) in gastrointestinal and pancreatic pathophysiology, inflammation and neoplasia. 1908 62