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)

Serological markers of gastritis, like pepsinogen A, pepsinogen C, gastrin, and Helicobacter pylori antibodies, can be used to explore the state of the gastric mucosa in populations with contrasting cancer risks. A decreasing pepsinogen A:C ratio and an increasing serum gastrin are known to reflect an increasing severity of atrophic corpus gastritis, which is a precursor of gastric cancer. In 723 subjects (without gastroduodenal surgery) from Japanese (n = 225) and Dutch (n = 498) working populations, which had a similar composition of age (mean 48 years), sex (male to female ratio 6:1), and type of occupation, fasting serum samples were analysed for IgG antibodies to H pylori, pepsinogen A, pepsinogen C, and gastrin in the same laboratory. H pylori infection was significantly more prevalent in the Japanese than in the Dutch (74.7% and 31.3%); as was a very low pepsinogen A, indicative of severe mucosal atrophy (4.4% and 1.6%). Among subjects with and without severe mucosal atrophy the H pylori seropositivity rate was similar. Between the Japanese and the Dutch there were significant differences in mean gastrin (31.8 and 13.4 pmol/l) and pepsinogen A:C ratio (1.7 and 2.9). These intercountry differences were as great for H pylori negative subjects (gastrin: 23.7 and 10.3 pmol/l, pepsinogen A:C ratio: 2.4 and 3.2) as for H pylori positive subjects (gastrin: 34.6 and 20.1 pmol/l, pepsinogen A:C ratio: 1.5 and 2.5). The intercountry difference in gastrin nearly disappeared after stratification into categories of pepsinogen A:C ratio. In conclusion, the intercountry differences in pepsinogen A:C ratio and gastrin reflect a higher prevalence of mild and severe mucosal atrophy of the corpus in the Japanese than in the Dutch, both among H pylori positive and negative subjects. Thus, these findings suggest that in the Japanese the development of atrophic gastritis is in part unrelated to H pylori.
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PMID:Seroepidemiology of gastritis in Japanese and Dutch working populations: evidence for the development of atrophic gastritis that is not related to Helicobacter pylori. 755 68

Gastrin plays a central role in the regulation of acid secretion. It is released by meals in quantities sufficient to explain meal-stimulated acid secretion. Gastrin stimulates acid secretion mainly by releasing histamine from the enterochromaffin-like (ECL) cell. Whether gastrin has any functional direct effect on the parietal cell remains to be shown. Gastrin stimulates not only the function but also the growth of the ECL cell, and long-term hypergastrinemia may lead to ECL cell carcinoids. The role of the ECL cell in human gastric carcinogenesis is controversial, but it seems wise to avoid long-term iatrogen hypergastrinemia especially in young persons. Interestingly, the oxyntic mucosal D cell, on which gastrin has a negative trophic effect, may play a role in gastric stump carcinoma, and thus hypogastrinemia may also dispose to gastric cancer.
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PMID:Gastrin-physiological and pathophysiological role: clinical consequences. 760 34

This investigation, conducted on 35 patients with advanced-stage gastric cancer, included 28 men and 7 women with a mean age of 50.1 years; also studied were 33 normal subjects as controls: 26 men and 7 women with a mean age of 45.8 years. Samples of blood and gastric juice were collected at fasting and in gastroscopy respectively. Substance P (SP), beta-endorphin (beta-EP), vasoactive intestinal peptide (VIP), motilin (MTL), gastrin (GT), and leu-enkephalin (LEK) of the sera and gastric juices were measured by radioimmunoassay kits. In the patients, SP and beta-EP of serum and gastric juice, and VIP, MTL and LEK of gastric juice, were higher than in the normal subjects (p < 0.01); gastrin of serum and gastric juice were decreased (p < 0.01). Serum and gastric juice SP, beta-EP levels correlated negatively with the gastrin (r = 0.462-0.519, p < 0.05). These data support the assumption that study of the peptides of serum and gastric juice can show a clinically significant change in gastric cancer patients.
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PMID:[Study on the peptides of serum and gastric juice in patients with gastric cancer]. 768 17

Although an association is suggested between gastric cancer and prior infection with Helicobacter pylori (HP), the role of HP in gastric carcinogenesis remains obscure. HP has potent urease activity and produces ammonia, a factor causing HP-related gastroduodenal mucosal lesions. In this study, rats were examined in an effort to determine effects of ammonia on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). After pretreatment with MNNG (83 mg/l) for 24 weeks, a solution of either 0.01% ammonia or plain tap water was administered to the animals as drinking water for an additional 24 weeks. The administration of the 0.01% ammonia solution significantly increased the incidence and number of cancers in the glandular stomach. The numbers of cases in which these cancers penetrated the muscle layer or deeper and of low-grade differentiated adenocarcinomas were significantly higher in rats receiving the ammonia solution. Continuing administration of ammonia accelerated cell proliferation in the gastric mucosa, but had no effect on the serum gastrin level. Therefore, gastric ammonia, which stimulates mucosal cell proliferation, appears to be an important promoter in carcinogenesis in rats and possibly in the HP-related gastric carcinogenesis in humans.
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PMID:Mechanism for ammonia-induced promotion of gastric carcinogenesis in rats. 769 14

A critical evaluation has been made of the available evidence in man of the effects of prolonged low acid states on the structure and function of the stomach. Various human models have been examined. 1. Ageing does not affect acid output from the normal male stomach, and there may be an increase in women. With progressive atrophy of the corpus mucosa, which is more frequent and rapid in patients with gastric ulcer, there is an associated loss of secretory function. Chronic gastritis and atrophy are the most important age-related changes, which in many cultures are hypothesized to develop via a prior Helicobacter pylori-related gastritis. However, H. pylori colonization of the mucosa decreases with increasing grades of gastric atrophy probably because intestinal metaplasia provides a hostile environment. Atrophy and intestinal metaplasia are associated with precancerous lesions and gastric cancer. Apparent hyperplasia of the gastric argyrophil endocrine cells is a common and spontaneous phenomenon in patients with atrophic gastritis, which in part may be related to the preferential loss of nonendocrine cells. 2. Pernicious anemia is associated with a complete lack of acid production, marked hypergastrinemia, and endocrine cell hyperplasia in the majority of patients. ECL-cell carcinoids and gastric cancer occur with a prevalence of 3-7%, and endoscopic surveillance in routine clinical practice is not warranted. 3. Gastric ECL-cell carcinoids are rare events that have been described in association with two diseases in man, pernicious anemia and Zollinger-Ellison syndrome as part of multiple endocrine neoplasia syndrome type I, and usually relate to marked hypergastrinemia and the presence of chronic atrophic gastritis with gastric antibodies or a genetic defect rather than the presence or absence of acid. Regression or disappearance of ECL-cell carcinoids, either spontaneously or after removal of the gastrin drive, has been recorded. Lymph node, and rarely hepatic, metastases are documented but death in these cases has been anecdotal. 4. Therapy with H2 antagonists may result in up to a twofold rise in serum gastrin levels but in man no endocrine cell hyperplasia has been recorded. However, the data for H2 antagonists on these aspects are very limited. There is no drug-related risk of gastric or esophageal cancer, although the incidence of the latter may be raised. Long-term treatment with omeprazole is associated with a two- to fourfold increase in gastrin levels over baseline values in one third of patients and apparent endocrine cell hyperplasia in 7% of cases overall.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pathophysiological effects of long-term acid suppression in man. 785 87

Previously, we have shown that a significant proportion of human gastric carcinomas of the diffuse type may be neuroendocrine tumors derived from the enterochromaffinlike (ECL) cell. The growth of the ECL cell is specifically regulated by gastrin, suggesting an important role of gastrin in human gastric carcinogenesis. However, patients with antral-resected stomachs have reduced plasma gastrin and despite that an increased risk of gastric cancer. Recently, it has been shown that gastrin has a negative trophic effect on the oxyntic D-cell of the rat. The present study evaluates whether gastric stump carcinomas are D-cell derived. Twenty gastric stump carcinomas that had developed from 20 to 53 years after antral resection were examined for neuroendocrine differentiation by neuron-specific enolase immunohistochemistry and for D-cell origin by somatostatin immunohistochemistry. Half the tumors were classified as gastric carcinomas of the intestinal type, while the other half initially was classified as gastric carcinomas of the diffuse type. One of these latter tumors could, however, be reclassified as carcinoid tumor by appearance in hematoxylin erythrosin saffron-stained sections as well as by neuron-specific enolase positivity. Interestingly, this tumor was also positive for somatostatin, suggesting D-cell origin. Three other tumors were positive for neuron-specific enolase, but they were negative for somatostatin. Nevertheless, this study suggests that some gastric stump carcinomas may be malignant neuroendocrine tumors derived from neuroendocrine cells and possibly from D-cells. Furthermore, this study may indicate an important role for hormones and neuroendocrine cells in human gastric carcinogenesis.
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PMID:Do neuroendocrine cells, particularly the D-cell, play a role in the development of gastric stump cancer? 786 15

Nude mice bearing xenografts of the gastrin-responsive human gastric carcinoma MKN45 cell line were treated for 4 to 5 weeks with bombesin/gastrin-releasing-peptide(GRP) antagonist (RC-3095), somatostatin analogues RC-160 and SMS 201-995, or the combination of RC-3095 and RC-160. Tumor volumes and weights were reduced significantly to a similar extent by RC-160 and SMS 201-995, administered by daily s.c. injections at a dose of 100 micrograms/day. Bombesin/GRP antagonist RC-3095, given s.c. at a dose of 20 micrograms/day, had the greatest inhibitory effect on tumor growth. The combination of RC-3095 with RC-160 did not further potentiate the suppression of tumor growth. Histologically, the number of mitotic cels decreased significantly in the groups treated with RC-160 or the combination of RC-3095 with RC-160. Serum gastrin levels were significantly diminished in all treated groups. Therapy with RC-160 or the combination also significantly decreased levels of serum growth hormone. Receptor assays on tumor membranes showed that bombesin was bound to 2 classes of receptor sites, one with high affinity and low capacity, the other with low affinity and high capacity. Binding sites for epidermal growth factor (EGF) were down-regulated in tumor cells after treatment with RC-3095, RC-160 or the combination of RC-3095 with RC-160. In studies in vitro, both RC-160 and RC-3095 significantly inhibited the proliferation of MKN45 cells in culture as measured by cell number. These data demonstrate, for the first time, that the growth of human gastric cancer in nude mice can be inhibited not only by somatostatin analogues, but also by administration of modern bombesin/GRP antagonists, such as RC-3095.
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PMID:Inhibition of growth of MKN45 human gastric-carcinoma xenografts in nude mice by treatment with bombesin/gastrin-releasing-peptide antagonist (RC-3095) and somatostatin analogue RC-160. 791 Jan 53

Binding of the radiolabeled bombesin analog [125I-Tyr4]bombesin to crude cell membranes of MKN45 human gastric cancer grown in nude mice was investigated in vitro. Scatchard analyses of multipoint binding data, performed by complete displacement method demonstrated the presence of two classes of [Tyr4]bombesin binding sites. The high-affinity binding sites had a mean dissociation constant (Kd1) of 2.75 nM with a mean maximal binding capacity (Bmax1) of 492 fmol/mg membrane protein, while the low-affinity binding sites showed a mean dissociation constant (Kd2) of 0.41 microM with a mean maximal binding capacity (Bmax2) of 41.4 pmol/mg membrane protein. Binding of [125(1)-Tyr4]bombesin was specific, reversible and linearly related to the protein concentration of tumor membrane. In displacement studies, the binding of radiolabeled [Tyr4]bombesin was inhibited in a dose-dependent manner by gastrin releasing peptide (GRP)(14-27) and two synthetic antagonists of bombesin/GRP, RC-3095 and RC-3950-II. Both antagonists exhibited high affinity in nearly the same concentration range as GRP(14-27). The presence of receptors for bombesin/GRP on human gastric cancer membranes suggests that bombesin-like peptides may play a role in growth of gastric cancer.
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PMID:Characterization of bombesin/gastrin-releasing peptide receptors in membranes of MKN45 human gastric cancer. 792 93

The stomachs from 40 patients operated on for gastric cancer and chronic ulcer were studied immunohistochemically using antibodies to CEA, galactosyl transferase, pepsinogens A and C, gastrin, alpha 1-antitrypsin. CEA and galactosyl transferase of the cancer parenchyma are shown to mark tumor progression. The ratio of alpha 1-antitrypsin to pepsinogens in gastric epithelium and cancer cells probably plays a role in ulcerogenesis of normal mucosa and tumor tissue. Gastrin in carcinoma tissue is both an ulcerogenesis factor and a marker of tumor progression, an unfavourable prognosis of gastric cancer.
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PMID:[Possible markers of the progression and ulcerogenesis of stomach cancer]. 798 72

The growth of the human gastric cancer cell line HGT-1 is regulated by a gastrin-like peptide through an autocrine process. In order to analyse the mechanism of action of this peptide, a study at different steps of the cell cycle was considered; so, a blocking of this cell line by thymidine or hydroxy-urea was studied by cytofluorimetry. In normal growth conditions in 10% FCS medium, 57% of the cells were in G0/G1 phase and 31% in S phase. A treatment with 2 mM hydroxy-urea followed by 4 hours in 10% FCS medium led to 85% of the cells in S phase. By successive treatments with thymidine and hydroxy-urea followed by 1 hour in 10% FCS medium, 2 peaks of S phase corresponding to 86% of the cells were observed; after 24 hours, cells were distributed as found for the unconfluent cell line, whatever the treatment. On the other hand, the thymidine kinase activity of unconfluent cells which was relatively elevated as compared to other cell lines (278 mU/mg protein), was increased by synchronisation with hydroxyurea followed by 1 hour in 10% SVF medium (338 mU/mg protein); after 8 hours in 10% FCS medium, this activity decreased at the value observed for cells treated with thymidine followed by 1 hour in 10% FCS medium (214 mU/mg protein). In conclusion, a synchronisation either by thymidine or by hydroxy-urea, led to a blocking of the HGT-1 cell line at different steps of the cell cycle, leading to a better knowledge of its autocrine growth regulation.
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PMID:[Study of S phase synchronization of the human gastric cancer line HGT-1]. 806 18


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