Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review was designed to show the role of expression of cyclooxygenase (COX)-1 and COX-2 in the cancerogenesis of esophagus, stomach and colon. Unlike COX-1, which is expressed in the normal esophago-gastro-colonic mucosa, COX-2 was found to be expressed mainly in the pre-cancer changes in the mucosa including Barrett's esophagus, Helicobacter pylori (H. pylori)-induced gastritis and inflammatory changes in colonic mucosa. In Barrett's esophagus, prostaglandins (PGs) derived from upregulated COX-2 contribute to the progression of low-grade to high-grade dysplasia and finally to cancer. In chronic gastritis induced by chronic H. pylori infection, overexpression of COX-2 is probably induced by inflammatory cytokines, growth factors, especially gastrin and reactive oxygen species leading to mutagenesis and subsequent metaplasia, dysplasia and cancer formation. The imbalance between cell proliferation and apoptosis caused mainly by products of COX-2 leads to cancerogenesis. Similarly, in colorectal cancer the overexpression of COX-2, possibly induced by the action of growth promoting factors including progastrin and gastrin and overexpression of survivin contribute to the colorectal cancerogenesis that could be, at least in part, amended by the treatment with specific COX-2 inhibitors. We conclude that: 1) COX-2-derived PGs play a key role in the tumorigenesis in the gastrointestinal tract; 2) The tumor-promoting effect of PGs may be attributed to their ability to stimulate cell proliferation and migration, to inhibit the apoptosis and to increase angiogenesis and invasiveness; 3) In accordance to the proposed major role of COX-2 in cancerogenesis, selective COX-2 inhibitors have been shown in numerous studies to exhibit strong chemopreventive effect on the development of gastrointestinal cancers.
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PMID:Prostaglandins as mediators of COX-2 derived carcinogenesis in gastrointestinal tract. 1624 89

Nonsteroidal anti-inflammatory drugs (NSAIDs) are valuable agents; however, their use has been limited by their association with mucosal damage in the upper gastrointestinal tract. NSAIDs inhibit cyclooxygenase and consequently block the synthesis of prostaglandins, which have cytoprotective effects in gastric mucosa; these effects on prostaglandins have been thought to be major cause of NSAID-induced ulceration. However, studies indicate that additional NSAID-related mechanisms are involved in formation of gastric lesions. Here, we used a toxicoproteomic approach to understand cellular processes that are affected by NSAIDs in mouse stomach tissue during ulcer formation. We used fluorogenic derivatization-liquid chromatography-tandem mass spectrometry (FD-LC-MS/MS)-which consists of fluorogenic derivatization, separation and fluorescence detection by LC, and identification by LC-tandem mass spectrometry-in this proteomic analysis of pyrolic stomach from control and diclofenac (Dic)-treated mice. FD-LC-MS/MS results were highly sensitive; 10 differentially expressed proteins were identified, and all 10 were more highly expressed in Dic-treated mice than in control mice. Specifically, expression levels of 78 kDa glucose-regulated protein (GRP78), heat shock protein beta-1 (HSP27), and gastrin were more than 3-fold higher in Dic-treated mice than in control mice. This study represents a first step to ascertain the precise actors of early NSAID-induced ulceration.
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PMID:Toxicoproteomic analysis of a mouse model of nonsteroidal anti-inflammatory drug-induced gastric ulcers. 2242 77

Refractory peptic ulcers are defined as ulcers that do not heal completely after 8 to 12 weeks of standard anti-secretory drug treatment. The most common causes of refractory ulcers are persistent Helicobacter pylori infection and use of nonsteroidal anti-inflammatory drugs (NSAIDs). Simultaneous use of two or more H. pylori diagnostic methods are recommended for increased sensitivity. Serologic tests may be useful for patients currently taking proton pump inhibitors (PPIs) or for suspected false negative results, as they are not affected by PPI use. NSAID use should be discontinued when possible. Platelet cyclooxygenase activity tests can confirm surreptitious use of NSAIDs or aspirin. Cigarette smoking can delay ulcer healing. Therefore, patients who smoke should be encouraged to quit. Zollinger-Ellison syndrome (ZES) is a rare but important cause of refractory gastroduodenal ulcers. Fasting plasma gastrin levels should be checked if ZES is suspected. If an ulcer is refractory despite a full course of standard PPI treatment, the dose should be doubled and administration of another type of PPI considered.
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PMID:Diagnostic and Treatment Approaches for Refractory Peptic Ulcers. 2624 Aug


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