Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Remote partial gastrectomy for benign disease is a premalignant condition. The overall risk of gastric stump cancer is approximately a twofold increase, but patients more than 20-25 years postoperatively may have a four- to fivefold increased risk, compared to the age- and sex-matched general population. The duration of postoperative interval is the most important risk factor. For the first 10 years after initial surgery, gastric cancer risk may be reduced due to the removal of the most cancer-prone distal part of the stomach, but thereafter there is a rapid increase of the relative risk. The etiology and precise mechanism of carcinogenesis is unknown, but the time relationship with surgery suggests that the anatomical alterations induced by the operation must be important. Hypochlorhydria, reflux, diminished gastrin production, bacterial proliferation, and nitrosation are the putative contributing factors. In addition, smoking appears to contribute to a generalized cancer mortality and decreased life expectancy after peptic ulcer surgery. Digestive tract cancers other than the gastric ones which show an increased risk after peptic ulcer surgery are pancreatic and biliary tract cancers. Premalignant and precursor lesions occur more frequently in the gastric remnant after peptic ulcer surgery and endoscopic bioptic screening can detect early stump cancers at a curable stage. Large-scale screening programs of post-gastrectomy patients are nevertheless not recommended, and surveillance appears not justified.
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PMID:Carcinogenesis after remote peptic ulcer surgery: the long-term prognosis of partial gastrectomy. 857 37

The brain-gut hormones, cholecystokinin (CCK) and gastrin, regulate the growth of gastrointestinal mucosa and tumor cells. In this study, reverse transcription-polymerase chain reaction (RT-PCR) was used to evaluate messenger RNA expression for CCK, gastrin, CCK-A receptor, and CCK-B/gastrin receptor in surgical specimens of gastric cancers and in normal antrum and body mucosa of the stomach. The CCK mRNA expression was detectable in 4/14 (29%) samples of gastric cancer and in 3/12 (25%) samples of antral mucosa. However, the gastrin mRNA expression was not detectable in any gastric cancer samples, although it was detectable in all the samples of antral mucosa. The CCK-A receptor mRNA expression was detectable in 5/14 (36%) samples of gastric cancer and in 7/12 (58%) body mucosa. Three cases out of 14 (21%) of gastric cancer expressed both CCK gene and CCK-A receptor gene. The CCK-B receptor mRNA expression was detectable in only 1/14 (7%) samples of gastric cancer, although it was detectable in 10/12 (83%) body mucosa of the stomach. These findings may suggest a greater role for CCK and CCK-A receptor than for gastrin and CCK-B receptor in gastric cancers.
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PMID:Evaluation of cholecystokinin, gastrin, CCK-A receptor, and CCK-B/gastrin receptor gene expressions in gastric cancer. 884 81

Gastrin is a well known endogenous stimulator of gastric acid. In addition, recent studies have revealed that gastrin has a growth promoting effect on gastric ECL cells. Indeed, development of ECL carcinoid tumor occurs almost exclusively in patients with hypergastrinemia such as autoimmune gastritis and Zollinger-Ellison syndrome with MEN type I. We have recently cloned human gastrin receptor gene, and by using it, we found that both gastric carcinoid tumor and endocrine cell carcinoma of the stomach express significant amount of gastrin receptor gene whereas none of gastric cancer tissue shows gastrin receptor gene expression. Thus, it is clear that gastrin plays important roles in the development of gastric carcinoid tumor as well as endocrine cell carcinoma of the stomach.
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PMID:[Gastrin and gastrin receptor]. 892 Jun 78

Five peptide fragments, based on the C-terminal sequence of bombesin (BN)-(6-14) or BN-(7-14), were selected as carriers for radicals doxorubicin (DOX) and 2-pyrrolino-DOX to create hybrid cytotoxic analogs. All these compounds had a reduced peptide bond (CH2-NH or CH2-N) between positions 13 (Phe or Leu) and 14 (Phe, Leu, or Tac) (Tac = thiazolidine-4-carboxylic acid). Three pseudononapeptide carriers contained N-terminal D-Phe or D-Tpi at position 6 (Tpi = 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid). Two pseudooctapeptides had Gln7 at the N terminus. The conjugation of N-(9-fluorenylmethoxycarbonyl) doxorubicin (N-Fmoc-DOX)-14-O-hemiglutarate to the peptide carriers at the N terminus resulted in cytotoxic hybrids of BN-like peptides containing DOX. These hybrids could then be converted to analogs with 2-pyrrolino-DOX by a reaction with 4-iodobutyraldehyde. The ability of the carriers and the conjugates to inhibit the binding of 125I-labeled [Tyr4]BN to receptors for BN/gastrin releasing peptide (GRP) on Swiss 3T3 cells was determined. Cytotoxic conjugates of pseudooctapeptide carrier analogs displayed the highest binding affinity (KD approximately 1 nM). The cytotoxic BN analogs and their corresponding cytotoxic radicals exerted similar inhibitory effects on the in vitro growth of CFPAC-1 human pancreatic cancer, DMS-53 human lung cancer, PC-3 human prostate cancer, and MKN-45 human gastric cancer cell lines that have receptors for BN/GRP. In DMS-53 cells, the activity of 2-pyrrolino-DOX and its conjugates was approximately 2500 times higher than that of DOX and its hybrids. These highly potent cytotoxic analogs of BN have been designed as targeted anti-tumor agents for the treatment of various cancers that possess receptors for BN/GRP.
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PMID:Design, synthesis, and in vitro evaluation of cytotoxic analogs of bombesin-like peptides containing doxorubicin or its intensely potent derivative, 2-pyrrolinodoxorubicin. 901 39

Helicobacter pylori affects gastric acid secretion via several mechanisms. One of these is by changing gastric regulatory physiology. The infection elevates plasma gastrin levels and decreases gastric mucosal expression of the inhibitory peptide somatostatin. These changes may be due to products of H. pylori itself or inflammatory cytokines released in H. pylori infection: acid secretion is inhibited less by a low intra-gastric pH, infusions of cholecystokinin and gastric distention in infected persons. Eradication of H. pylori rapidly decreases basal acid secretion and gastrin-releasing, peptide-stimulated acid secretion. There are now reports that maximally-stimulated acid secretion, a measure of the parietal cell mass, falls significantly six and 12 months after eradication of H. pylori from duodenal ulcer patients. This might be due to withdrawal of the trophic effect of gastrin. However H. pylori can also decrease gastric acid secretion, both through the mechanisms described in Dr. Cave's paper and by causing gastric mucosal atrophy with loss of parietal cells. The net effect on acid presumably depends on which mechanism predominates. The processes involved may be crucial determinants of clinical outcome. For example, infection with little atrophy and high acid secretion is associated with duodenal ulcers, while infection with atrophy and low acid secretion increases the risk of gastric cancer of the intestinal-type.
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PMID:Helicobacter pylori and hormones. 904 88

The histidine decarboxylase (HDC) gene is regulated transcriptionally by gastrin and phorbol 12-myristate 13-acetate (PMA) through a protein kinase C (PKC)-related pathway. To determine the role of AP-1 (fos/jun) in the regulation of the HDC promoter, gastric cancer (AGS-B) cells stably expressing the cholecystokinin-B/ gastrin receptor and the 1.8-kb human (h) HDC-luciferase (luc) construct were cotransfected with constructs expressing c-fos and c-jun. Overexpression of c-fos and c-jun activated the HDC promoter in a dose-dependent fashion in 1.8-kb hHDC-luc/AGS-B cells as well as in transfected F9 embryonal carcinoma cells, which lack endogenous AP-1 activity. PMA was unable to activate the HDC promoter in F9 cells, which were not transfected with c-fos and c-jun. Gastrin stimulation increased c-fos and c-jun mRNA abundance and AP-1-dependent transcriptional activity, as assessed by a reporter construct in which the CAT reporter gene is under the control of a 12-O-tetradecanoylphorbol-13-acetate response element multimer. Gastrin-stimulated HDC promoter activity was blocked by transfection of c-fos antisense and dominant negative c-jun expression constructs. Finally, overexpression of c-fos and c-jun activated the hHDC promoter through a downstream cis-acting element (gastrin response element), which does not bind AP-1. In conclusion, activation of AP-1 is essential for gastrin-stimulated HDC transcription, but the mechanism appears to be indirect.
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PMID:Gastrin regulates the human histidine decarboxylase promoter through an AP-1-dependent mechanism. 914 14

It is now widely recognized that H. pylori gastritis can produce marked alterations in gastric acid secretion. In subjects with an antral predominant gastritis there is increased release of gastrin and consequently increased acid secretion. Such subjects are at risk of developing duodenal ulcers. In other subjects the infection produces a marked body gastritis and this is associated with marked hyposecretion of acid or complete achlorhydria. These subjects have an increased risk of developing gastric cancer. Between these two ends of the disease spectrum lie the majority of H. pylori-infected subjects who have gastritis of both the antrum and body and no overall change in acid secretion. The reason why the infection exerts these divergent effects on gastric morphology and function remains unclear and is a challenge for ongoing research.
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PMID:Helicobacter pylori and acid secretion: where are we now? 916 Jan 98

This study evaluated the effect of gastric acid secretion and serum gastrin response on tumor differentiation for early gastric cancer according to patients' age. We investigated the association between serum gastrin levels, gastric acid secretion and the histologic types of 335 early gastric carcinomas limited to the mucosal and submucosal layers in comparison with 450 gastric and 197 duodenal ulcers. The preoperatively examined basal acid output, maximal acid output and peak acid output after administration of tetragastrin and serum gastrin levels before and after ingestion of a test meal were determined. Patients with differentiated cancer and duodenal ulcer showed a significant negative correlation between gastric acid secretion and age, while the former group also had a significant positive correlation between serum gastrin levels and age. On the other hand, patients with undifferentiated cancer did not show any such correlation between gastric acid and age, but showed a significant positive correlation between serum gastrin, integrated gastrin response and age. Patients with gastric ulcer did not show any such correlations. These data suggest that both low acid secretion and endogenous hypergastrinemia, especially in the elderly, may play an important role in differentiated and undifferentiated gastric carcinomas.
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PMID:Association between serum gastrin levels, gastric acid secretion and age in early gastric cancer. 927 31

Gastrin stimulates transcription of the human histidine decarboxylase (HDC) gene through binding to the G-protein-coupled cholecystokinin-B/gastrin receptor. We have explored the possibility that mitogen-activated protein kinase cascades play a role in mediating the effects of gastrin on transcription in a gastric cancer (AGS-B) cell line. Gastrin and phorbol 12-myristate 13-acetate (PMA) treatment of AGS-B cells was found to increase the phosphorylation of tyrosine residues of extracellular signal-regulated kinases (ERKs) 1 and 2 and increase ERK activity as determined by the in vitro phosphorylation of myelin basic protein. Reporter gene assays also demonstrated that gastrin and PMA stimulated Elk-1- and c-Myc-dependent transactivation, consistent with gastrin- and PMA-induced activation of ERKs. Overexpression of wild type ERK-1 and ERK-2 or activation of endogenous ERKs using activated MEK-1 (mitogen-activated protein kinase kinase or ERK kinase) overexpression stimulated HDC promoter activity in a dose-dependent fashion. Interruption of the ERK-related pathway using expression vectors for kinase-deficient ERKs or an ERK-specific phosphatase (PAC-1) blocked gastrin- and PMA-stimulated HDC promoter activity. In contrast, inhibition of the Jun kinase pathway using an interfering dominant negative SEK-1 (stress-activated protein kinase/ERK-1) mutant did not inhibit HDC promoter activity. Furthermore, whereas gastrin stimulated phosphorylation of Shc proteins and association with Grb2, activation of the HDC promoter was not influenced by expression of dominant negative Ras (N15 or N17) proteins. However, gastrin stimulated Raf-1 kinase activity, and activation of the HDC promoter was blocked by coexpression of a dominant negative Raf-1 construct. Overall, these data demonstrate that gastrin regulates HDC transcription in a Rafdependent, Ras-independent fashion predominantly through activation of the ERK-related pathway.
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PMID:Gastrin and phorbol 12-myristate 13-acetate regulate the human histidine decarboxylase promoter through Raf-dependent activation of extracellular signal-regulated kinase-related signaling pathways in gastric cancer cells. 934 Nov 40

Epidemiological studies have consistently shown an association between infection of Helicobacter pylori (Hp) and duodenal ulcer (DU) and gastric cancer. The mechanism of the ulcerogenic effect of Hp has been related to excessive gastrin release, gastric acid hypersecretion and gastric metaplasia in duodenum. The implication of Hp in gastric carcinogenesis has not been explained. In this study, mucosal expression of EGF and TGF alpha and luminal release of EGF as well as basal and pentagastrin-stimulated acid secretion and plasma gastrin levels have been determined in healthy subjects, gastric carcinoma and DU patients. It was found that Hp positive DU patients show excessive gastrin release and gastric acid secretion combined with increased expression and luminal release of EGF and TGF alpha. These changes returned to normal values two years after the eradication of Hp. Gastric cancer patients also showed increased expression of EGF and TGF alpha and highly increased plasma gastrin but their gastric acid secretion was markedly reduced possibly due to atrophy of oxyntic mucosa. This study indicates that overexpression of growth factors in gastric mucosa may be implicated in the pathogenesis of both duodenal ulcer and gastric cancer and that Hp positive hypochlorhydric and hypergastrinemic patients may be predisposed to development of gastric cancer.
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PMID:Gastric mucosal expression and luminal release of growth factors in gastric carcinoma and duodenal ulcer patients before and after eradication of Helicobacter pylori. 937 20


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