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

H. pylori (Hp) -induced atrophic gastritis is a well-known risk factor for the development of gastric cancer. Whether Hp eradication can prevent or retard the progress of atrophy and metaplasia has been the topic of numerous studies but the subject remains controversial. Recently, the increased expression of ornithine decarboxylase (ODC), gastrin and cyclooxygenase (COX)-2 has been shown to be increased in premalignant lesions in gastric mucosa and to play an essential role in the malignant transformation. The aim of the study is to assess the effect of eradication therapy on atrophic gastritis and analyze the gene expression for ODC, COX-2 and gastrin in gastric mucosa after succesful eradication in patients with atrophic gastritis. Twenty patients with chronic atrophic gastritis including both corpus and antrum of the stomach were included in this study. Four antral mucosal biopsy specimens were obtained from antrum and four from corpus. The histopathologic evaluation of gastritis was based on Sydney classification of gastritis. All patients were Hp positive based on the [13C] urea breath test (UBT) and the presence of anti-Hp IgG and anti-CagA-antibodies detected by ELISA. The patients were then eradicated with triple therapy consiting of omeprazol (2 x 20 mg), amoxycillin (2 x 1 g) and clarithromycin (2 x 500 mg) for seven days and vitamin C 1 g/day for three months. In gastric mucosal samples obtained from the antrum and corpus before and after eradication, the mRNA expression for ODC, COX-2, and gastrin was assessed by reverse-transcription polymerase chain reaction (RT-PCR). In all patients the gastric secretory analysis was performed by measuring gastric acid output and serum gastrin levels. After triple therapy the successful eradication assessed by UBT was observed in 95% of patients. In 45% of patients the infection with CagA-positive Hp strain was observed. Three months after eradication a significant reduction in the gastric activity (neutrophilic infiltrate) and severity (mononuclear infiltrate) of gastritis was observed. The atrophy score improved in both antrum and corpus after eradication. The expression of COX-2 and ODC was significantly up-regulated in the gastric mucosa of patients with atrophic gastritis and significantly reduced after eradication therapy. In all successfully eradicated patients with atrophic gastritis a significant increase in gastric acid secretion and decrease in serum gastrin were observed. We conclude that: (1) Hp eradication leads to the decrease in ODC and COX-2 gene expression in the gastric mucosa, and this may be relevant for the prevention of the Hp-associated gastric carcinogenesis; and (2) gastric atrophy ameliorates upon successful Hp eradication therapy.
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PMID:Gene expression of ornithine decarboxylase, cyclooxygenase-2, and gastrin in atrophic gastric mucosa infected with Helicobacter pylori before and after eradication therapy. 1264 88

The cholecystokinin 2 receptor (CCK2R) increases proliferation of normal and neoplastic gastrointestinal cells and activates various mitogenic signaling pathways when stimulated by gastrin. To study the incidence of permanent activation of this receptor in tumorigenicity, a constitutively active mutant was generated by replacing residue Glu151 in the conserved E/DRY motif by Ala. Expression of the E151A-CCK2R mutant in NIH-3T3 cells causes ligand-independent activation of phospholipase C and ornithine decarboxylase, two enzymes critical for mitogenesis. Strikingly, the constitutive activity of this mutant was associated with dramatic alteration of NIH-3T3 cell morphology, enhanced cell proliferation and invasion. Moreover, injection of cells expressing E151A-CCK2R in nude mice resulted in the development of large and rapidly growing tumors. By contrast, none of these effects was observed with cells expressing the wild-type CCK2R, indicating that the tumorigenic properties of the E151A-CCK2R mutant is the result of its constitutive activation. To date, this is the first report that provides evidence for the high tumorigenic effect of a constitutively active CCK2R mutant, thus raising a potential role of the CCK2R in human cancer.
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PMID:High tumorigenic potential of a constitutively active mutant of the cholecystokinin 2 receptor. 1295 87


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