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[Early stomach cancer in comparison with advanced stomach cancer. Results of a prospective study of diagnosis and 5-year survival of 131 patients with early stomach cancer and 795 patients with advanced stomach cancer].

A multicentre prospective observational study with 22 surgical and 14 pathological units in West-Germany gathered data from 1420 patients with gastric cancer between April 1982 and October 1989, 131 patients with early gastric cancer (EGC) and 795 patients with a resectable advanced gastric cancer (AGC) were selected for comparison. Patients with EGC were younger than those with AGC (49% vs 37% younger than 60 years) and symptoms of an ulcer were found twice in comparison to AGC (40.7% vs 23.7%). EGC in comparison to AGC were frequently multifocal (9.2% vs 3.0%) and located in the middle and lower part of the stomach (83.9% vs 56.8%). Five-year-survival rates of mucosa carcinoma was 84% and of submucosal carcinoma 69% (p = 0.0741). WHO-typing of EGC and AGC were identical. But according to Laurén's classification there were more intestinal types with EGC than with AGC (60.3% vs 51.5%) and less diffuse or mixed types with EGC than with AGC (33.6% vs 44.0%). Five-year-survival rates of diffuse and intestinal types of EGC showed no significant difference (p = 0.19). Extended lymph node dissection was done in only one third of EGC and AGC. Five-year-survival rates of 36 EGC patients with and 95 EGC patients without extended lymph node dissection were 85% versus 72% (p = 0.0916). These results are a hint that systematic lymphadenectomy may have a beneficial effect on survival.

Adult↗

[Epidemiological evaluation of the protective effect for dying of stomach cancer by screening programme for stomach cancer with applying a method of case-control study--a study of a efficient screening programme for stomach cancer].

An epidemiological evaluation of the protective effect for dying of stomach cancer by screening programme for stomach cancer was conducted with applying a method of case-control study. And also in order to carry out an efficient screening programme, the age groups who should be intensively recommended to receive screening and an optimal screening time interval since the last test were analyzed. 527 cases of men and 273 of women, dying of stomach cancer in the years 1981-1989 in the Awa region of Chiba prefecture, were identified from Chiba Cancer Registry. For each case, 3 controls were drawn at random from Awa living residents (about 162000 inhabitants at 1989 national census), with being matched strictly according to the district of residence, sex and born within 3 years of birth-year. For both cases and controls, the information about the screening history until the date of diagnosis of the case in each matched set was collected respectively from comparison with the screening certification. The results showed a relative risk of 0.417 (99% CI 0.284-0.612) in ever screened men compared with never screened and 0.480 (99% CI 0.280-0.823) in women. The significant reduction in risk was intensively observed on age groups 40-74 years among men and 50-69 years among women and the protective effect continued at most in the following three years since last screening. For an efficiency of screening programme, these age groups should be intensively recommended to receive screening and it is allowable that an optimal screening time interval since last negative test is at most 3 years for general attendance.

Adult↗

[The epidemiology of stomach carcinoma from the surgical viewpoint. The results of the German Stomach Carcinoma Study 1992. The German Stomach Carcinoma Study Group].

In a prospective multi-centre study data were collected on 1,999 patients (1273 men, 726 women; mean age 62.3 [19-99] years) with gastric carcinoma, admitted to one of 19 surgical departments in Germany between 1.4. 1986 to 30. 6. 1989. Previously treated patients as well as those with synchronous or metachronous tumours and carcinoma of the gastric stump had been excluded. The resection rate for gastric carcinoma was 82.7%, i.e. resection was no longer possible because of the advanced tumour stage in nearly 20%. The tumour was located in the upper third of the stomach in 30%, the antrum in 26.3%. An intestinal type of growth was present in 51.9%. An early carcinoma was diagnosed in 16.9% of operated patients; it had already metastasized to regional lymph nodes in 16.5%. Nearly 70% of patients with resectable tumours had metastases to the regional lymph-nodes, with distant metastases in 30%. An advanced tumour stage (UICC stage IIIB or IV) was present in 43%. Exclusively surgical treatment is not effective in these cases.

Adult↗

A tissue-engineered stomach as a replacement of the native stomach.

BACKGROUND: Despite recent advances in reconstruction techniques, total gastrectomy is still accompanied by various complications. As an alternative treatment, we propose a tissue-engineered stomach that replaces the mechanical and metabolic functions of a normal stomach. The objective of this study was to demonstrate the function of a tissue-engineered stomach as a replacement of the native stomach. METHODS: Tissue-engineered stomachs were formed in recipient rats from stomach epithelium organoid units isolated from neonatal donor rats. After 12 weeks, the animals underwent a second operation for replacement of the native stomachs. RESULTS: Tissue-engineered stomachs were successfully used as a substitute of the native stomach in a rat model. An upper gastrointestinal tract study revealed no evidence of bowel stenosis or obstruction at both anastomosis sites. Histologically, the tissue-engineered stomachs had well-developed vascularized tissue with a neomucosa continuously lining the lumen and stratified smooth muscle layers. Immunohistochemical staining for alpha-actin smooth muscle showed that the smooth muscle layers were arranged in a regular fashion. Scanning electron microscopy showed that the surface topography of the tissue-engineered stomachs resembled that of native stomachs. CONCLUSIONS: It has been demonstrated that a tissue-engineered stomach can replace a native stomach in a rat model. Replacement of the native stomach by a tissue-engineered stomach had beneficial effects on the formation of neomucosa and smooth muscle layers in the tissue-engineered stomach.

Animals↗

Effects of 5-methoxypsoralen (5-MOP) on arylamine N-acetyltransferase activity in the stomach and colon of rats and human stomach and colon tumor cell lines.

BACKGROUND: It has been shown that cytochrome P450 enzymes (CYPs) and acetyltransferase can be used as biomarkers of carcinogen-DNA adduct levels and human cancer susceptibility. The gastrointestinal tract is the portal of entry of foreign compounds and presents xenobiotic metabolizing N-acetyltransferase (NAT) and CYPs activities. 5-Methoxypsoralen (5-MOP) has been used in combination with UV radiation in skin photochemotherapy for decades. A number of studies have demonstrated that 5-MOP is inhibitory towards mouse and human CYP isoforms, but investigations on the direct effects on NAT activity in laboratory animals and human cancer cells are limited. The main objective of this study was to document the effects of 5-MOP on the modulation of NAT activities in the stomach and colon of rats and human stomach and colon tumor cell lines. MATERIALS AND METHODS: N-Acetylation of 2-aminofluorene (AF) to 2-acetylaminofluorene (AAF) by NAT in the stomach and colon of Sprague-Dawley (SD) rats and in human stomach (SC-M1) and colon (COLO 205) tumor cell lines was investigated. RESULTS: The data show that the metabolic activity of NAT in the rat colon was higher than that in the rat stomach, and the further metabolism of AAF was slower in the stomach than in the colon. 5-MOP increased the activity of NATand also increased the further metabolism of AAF at 24 h in the rat stomach. In the rat colon, no statistically significant changes caused by 5-MOP were observed in NAT activity, but 5-MOP increased the further metabolism of AAF at 24 to 72 h. 5-MOP decreased the activity of NAT only at 72-h incubation in SC-M1 cells. In COLO 205 cells, however, 5-MOP decreased the activity of NAT between 24 h and 72 h. The optimal concentrations of 5-MOP to induce decreased NAT activity in SC-M1 cells were 0.05 mM to 25 mM. In COLO 205 cells, the data indicate that the higher the concentrations of 5-MOP, the higher the acetylation of AF; a promotion effect of NAT activity occured at a higher dose (50 mM) of 5-MOP and an inhibition effect occured at lower doses (0.05-0.5 mM) of 5-MOP, while concentrations of 5-25 mM of 5-MOP showed no significant difference compared with the control regimen. CONCLUSION: The metabolic activity of NAT in the rat colon was higher than that in the rat stomach, and the results also showed a high degree of correspondence with SC-M1 cells and COLO 205 cells. 5-MOP more efficiently inhibited NAT activity in human stomach and colon tumor cell lines than in the stomach and colon of rats.

2-Acetylaminofluorene↗

Inductions of ornithine decarboxylase and DNA synthesis in rat stomach mucosa by glandular stomach carcinogens.

The inductions of ornithine decarboxylase (ODC) and DNA synthesis in the pyloric mucosa of the stomach of male F344 rats after oral administrations of chemicals were studied. The glandular stomach carcinogens N-methyl-N'-nitro-N-nitrosoguanidine, N-ethyl-N'-nitro-N-nitrosoguanidine, N-propyl-N'-nitro-N-nitrosoguanidine, 4-nitroquinoline 1-oxide and N-nitroso-N-methylurethane induced up to 100-fold increase in ODC activity in the pyloric mucosa of the stomach; the activity was maximal 24 hr after administration and returned to the control level after 48 to 72 hr. These compounds also induced 14- to 30-fold increase in DNA synthesis in the pyloric mucosa of the stomach; synthesis was maximal 16 to 24 hr after administration and returned to the control level after 144 hr. The non-gastric carcinogens 2-acetylaminofluorene, dimethylnitrosamine and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) did not induce ODC or DNA synthesis in the pyloric mucosa of the stomach. Ethyl alcohol also did not induce ODC or DNA synthesis in the pyloric mucosa of the stomach. These results and previous findings that stomach-tumor promoters such as NaCl, taurocholate, glyoxal, K2S2O5 and formaldehyde induced ODC and DNA synthesis in the pyloric mucosa of the stomach of F344 rats suggest that the inductions of ODC and DNA synthesis in the glandular stomach mucosa are markers of promotive activities of complete carcinogens and tumor promoters in the glandular stomach.

Animals↗

Stomach remodeling-associated changes of H+/K+-ATPase beta subunit expression in Xenopus laevis and H+/K+-ATPase-dependent acid secretion in tadpole stomach.

Through subtractive hybridization, H+/K+-ATPase beta subunit mRNA, highly expressed in the larval stomach of Xenopus laevis, was isolated. In situ hybridization demonstrated that the H+/K+-ATPase beta subunit mRNA was exclusively expressed in manicotto gland cells of the larval stomach, not in any other cell. Northern blot analysis showed that metamorphosis-associated changes of the H+/K+-ATPase beta subunit mRNA expression in the stomach were characterized by high expression in tadpoles, a considerably lower expression in metamorphosing tadpoles, and a re-increase of expression in froglets. Further in situ hybridization showed that the decrease of expression correlated with the degeneration of larval type epithelium in the manicotto gland, while the re-increase correlated with the differentiation of oxynticopeptic cells of the adult type stomach. Moreover, the H+/K+-ATPase beta subunit mRNA was expressed in adult epithelial primordia. Such changes were found in thyroid hormone-induced precocious metamorphosis. Based on studies using this ATPase as well as xP1 and PgC (pepsinogen C) as molecular markers, this study discusses a probable cell lineage involved in metamorphosis-associated stomach remodeling. The pH of luminal contents of the larval stomach was found to be lower than 2. In addition, the pH of an isolated stomach changed from 7.2 to lower than 4 after incubation in Ringer's solution, suggesting acid production from the larval stomach. This is the first demonstration of the H+/K+-ATPase-mediated acid production and secretion in the larval stomach of Xenopus laevis.

Animals↗

[Risk of surgical therapy of stomach cancer in Germany. Results of the German 1992 Stomach Cancer Study. German Stomach Cancer Study Group ('92)].

The German Gastric Cancer Study (GGCS '92) permits a representative pictures of the current situation in surgery for gastric carcinoma at university centers in Germany. The analysis of frequency of resection, complication rate and mortality provides a quality measure for anybody who performs surgical therapy for gastric carcinoma. The results of multivariate analyses will have therapeutic consequences.

Cause of Death↗

Identification of immunoreactive plasma and stomach ghrelin, and expression of stomach ghrelin mRNA in the bullfrog, Rana catesbeiana.

In this study, we established a radioimmunoassay (RIA) specific for ghrelin from the bullfrog Rana catesbeiana using a novel antibody raised against the C-terminal amino acid sequence of bullfrog ghrelin [13-28]. We also examined the distribution of ghrelin-producing cells in the stomachs of bullfrogs using this antibody and a cRNA probe specific for the bullfrog ghrelin gene. Ghrelin levels in plasma and stomach extracts were approximately 150 fmol/ml and 83-135 fmol/mg wet tissue, respectively. Reverse-phase high performance liquid chromatographic analysis, combined with bullfrog ghrelin RIA, revealed that ghrelin immunoreactivity in the stomach was composed of non-acylated ghrelin (des-acyl ghrelin) and several acylated forms of ghrelin bearing different fatty acid modifications, which could induce increases in intracellular Ca2+ in cells expressing the rat GH secretagogue receptor. In the stomach, the major storage form was acylated ghrelin. In bullfrog plasma, however, the majority of ghrelin immunoreactivity was des-acyl ghrelin and C-terminal fragments of frog ghrelin. Acylated ghrelin forms comprised only minor peaks. Ghrelin-immunopositive and ghrelin mRNA-expressing cells were observed within the mucosal layer of the stomach. Following starvation, significant increases in plasma ghrelin levels and stomach ghrelin mRNA levels were observed as early as 10 days after starvation. These results indicate that ghrelin is present in the stomach and plasma of the bullfrog, which can be detected with our novel antibody. Interestingly, the primary storage form of ghrelin in the stomach differed from the circulating form dominating in the plasma. Furthermore, increases in ghrelin levels in plasma and mRNA levels in the stomach after starvation suggest the possible involvement of ghrelin in energy homeostasis in the bullfrog.

Animals↗

Transforming gene from human stomach cancers and a noncancerous portion of stomach mucosa.

DNAs from 21 human stomach cancers, 16 metastatic stomach cancers to lymph nodes, and 21 apparently noncancerous specimens of stomach mucosae from a total of 26 patients with stomach cancer were tested for their ability to induce neoplastic transformation of NIH 3T3 cells on transfection by the calcium phosphate precipitation technique. Three samples of DNA were shown to have transforming activity; one was from a primary stomach cancer of one patient, the second was from a noncancerous portion of stomach mucosa of the same patient, and the third was from a lymph node metastasis of stomach cancer from another patient. These transformants were tumorigenic in nude mice, and DNAs from the cells could induce secondary transformants. A portion of the transforming gene from the stomach cancer of one patient, which contained the sequences expressed in the NIH 3T3 transformants, was cloned. The transforming gene did not have any homology with the transforming sequences reported previously. We have applied the term hst to this novel human transforming gene. The transforming gene, hst, was found to be present in all the primary and secondary transformants induced by the other two samples of DNA.

Adenocarcinoma↗

Immunolocalization of the ecto-ATPase and ecto-apyrase in chicken gizzard and stomach. Purification and N-terminal sequence of the stomach ecto-apyrase.

We have examined the in vivo localization of extracellular ecto-ATPase and ecto-apyrase (ATPDase) in adult chicken gizzard and stomach by immunofluorescence and laser scanning confocal microscopy. In chicken gizzard, the ecto-ATPase was distributed in discrete clusters restricted to the sarcolemma of the smooth muscle cells. Anti-ecto-apyrase antibody detected a single 80-kDa band (putative apyrase) in Western blots of both chicken gizzard membrane extracts and partially purified anion exchange fractions, but the antibody did not detect ecto-apyrase in immunolabeled gizzard cryosections. In adult chicken stomach, the ecto-apyrase was observed at the apical membrane of the glandular oxyntico-peptic cells as described in previous immunoperoxidase studies (Stout, J. G., R. S. Strobel, and T. L. Kirley (1995) Biochem. Mol. Biol. Int. 36, 529-535). However, ecto-ATPase was clustered in the sarcolemma of the organized layer of circular smooth muscle and in smooth muscle cells of the septa surrounding the glandular tissue, but not in the glandular cells containing the ecto-apyrase. The findings indicate compartmentalization of the two related extracellular nucleotide hydrolyzing enzymes and suggest differential functions that are specialized for different regions of the chicken stomach. We also partially purified the ecto-apyrase of chicken stomach, an 80-kDa membrane glycoprotein. Chicken stomach membranes were solubilized in digitonin, glycoproteins were separated from solubilized proteins by lectin chromatography, and nucleotide-binding glycoproteins were selected by immobilized Cibacron blue chromatography. Further purification by size exclusion and anion exchange chromatography yielded purification of 94-fold. The ATPase specific activity of the purified stomach ecto-apyrase was 75,000 micromol of Pi/mg of protein/h, and the purified preparation consisted of a major band (55% of total protein) at 80 kDa. The purified enzyme could be deglycosylated with peptide N-glycosidase-F to a core molecular mass of 54 kDa. The N-terminal sequence of the 80-kDa stomach ecto-apyrase band (which reacted with anti-ecto-ATPDase antibodies) was determined to be: MEYKGKVVAGLLTATWV. Immunological cross-reactivity data indicate that the stomach 80-kDa protein isolated is an ecto-apyrase and is related to both the chicken liver and oviduct ecto-ATPDase enzymes characterized earlier, as well as to the human lymphoid cell activation antigen, CD39.

Adenosine Triphosphatases↗