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)

Exposure to N-nitroso-compounds and aromatic amines, xenobiotics which require an activation in order to exert their genotoxic potential, is causally associated with gastric cancer. We evaluated the capacity of microsome-containing fractions from human gastric mucosa to activate two model carcinogenic compounds. A 9,000 x g supernatant (S9) was obtained from gastric mucosal specimens and, for comparison, from human liver and aroclor-induced and non induced rat liver. The capacity of the S9 to activate N-nitrosopyrrolidine (NPY) and 2-aminofluorene (2AF) to mutagenic metabolites was tested in the Ames/Salmonella reversion assay, while dimethylnitrosamine (DMN) and aminopyrine (AP) demethylation activities were spectrophotometrically evaluated by using an enzymatic assay of the amount of formaldehyde released following the enzymatic demethylation of the corresponding substrates. Results indicate that human gastric S9 fractions may activate 2AF to a genotoxic derivative and are characterized by DMN and AP demethylase activities higher (p < 0.05) than those of human liver, when expressed in mg/protein (p < 0.05). Although the parameters evaluated can only be considered as a partial measure of the general activating capacity toward dietary and environmental procarcinogens, these results suggest that human gastric mucosa may be directly involved in the metabolic activation of these compounds to mutagenic/carcinogenic species.
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PMID:Direct involvement of human gastric mucosa in the activation of alimentary pro-carcinogens. 184 83

Nineteen gastric carcinomas with lymphoid stroma were selected from 554 surgical cases and examined pathologically and immunohistochemically using formaldehyde-fixed, paraffin embedded materials. Most showed ulcerative lesion and 15 cases located in fundic and cardiac gland regions. They were subdivided histologically into three groups, early (group I), localized (group II) and infiltrative tumors (group III), the number of cases being 2, 10 and 7, respectively. Lymph node metastases occurred in 3 cases in group II and 6 in group III, the latter showing a significantly higher incidence. The number of carcinoembryonic antigen and CA19-9 immunoreactive tumor cells was apparently smaller in gastric carcinomas with lymphoid stroma than in ordinary gastric carcinomas. Frequent presence of alpha 1-antichymotrypsin immunoreactivity characterized the tumor cells of gastric carcinoma with lymphoid cells. Stroma cells consisted of lymphocytes, plasma cells, granulocytes and histiocytes. Of these, the greatest number examined immunohistochemically was B cells and IgG cells, followed in descending order by T cells, IgA cells and IgM cells in the order given. A variable number of lysozyme immunoreactive histiocytes were also detected in all the cases. Gastric carcinoma with lymphoid stroma might be subclassified as a separate entity, although short term follow-up study did not demonstrate a favorable prognosis for this type of gastric cancer.
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PMID:Gastric carcinoma with lymphoid stroma: pathological and immunohistochemical analysis. 222 25

The expression of carbohydrate antigens in malignant and non-malignant gastric mucosa was studied immunohistochemically using the monoclonal antibody AH6 directed to Ley antigen, FH2 directed to Lex antigen, and FH6 directed to sialyl-Lex antigen. Formalin-fixed gastric tissue resected from 54 patients with gastric cancer and 20 patients with gastric ulcer were tested. The incidence of positive cases in gastric cancer patients with each antibody was as follows: AH6;85%, FH2;74%, FH6;74%. The Lex antigen was expressed in 81.5% of cases histologically classified as undifferentiated type, and 66.7% of cases classified as differentiated type. It was expressed in a higher incidence in early stage cancer (93.3%) than in advanced stage cancer (66.7%). Sialyl-Lex antigen was detected in more cases of differentiated type (88.9%) than in those of undifferentiated type (59.3%), whereas none of 8 early cancers of undifferentiated type expressed the antigen. The incidence of the expression of Ley antigen did not differ in relation to histological type or invasiveness. Lex and Ley antigens were detected in noncancerous gastric epithelium. Sialyl-Lex antigen was not detected in the normal fundic gland region. These results demonstrate that Lex antigen may be a differentiation-associated antigen, and sialyl-Lex antigen might be useful as a marker of differentiated cancer and an indication for invasion of undifferentiated cancer.
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PMID:Immunohistochemical study of carbohydrate antigen expression in gastric carcinoma. 266 6

Sixteen clones (RASK-1 to -16) of murine monoclonal antibodies were raised against ras Mr 21,000 protein (p21). The p21 produced by Escherichia coli with inserted v-Ki-ras genes was used as immunogen. RASK-1 was found to be specific for Ki-ras p21, whereas RASK-2 to -16 reacted with the p21s of Ki-, N-, and Ha-ras genes in both enzyme-linked immunosorbent and immunoblotting assays. Binding inhibition assays with biotinylated monoclonal antibodies by enzyme-linked immunosorbent assay showed that the monoclonal antibodies of the 16 clones included those binding to several mutually distinct sites on p21. The expressions of ras p21 in human stomach and thyroid tissues were examined with RASK-3, which reacted with all the Ki-, N-, and Ha-ras p21s immunohistochemically by the avidin-biotin peroxidase complex method. Formalin-fixed, paraffin-embedded tissues of 101 cases of stomach cancer, 53 cases of noncancerous stomach, 74 cases of cancer of the thyroid, and 59 cases of noncancerous thyroid were analyzed. In both the stomach and thyroid, cancer cells expressed p21 predominantly. Cells of cases with various noncancerous disorders as well as certain types of normal cells were also p21 positive. These findings suggest that precaution is required in use of p21 as a cancer marker. Expression of p21 was noted in moderately to well-differentiated stomach cancer, intestinal metaplasia, and atypical hyperplasia. This finding suggests that the appearance of p21 in stomach cancer may be initiated before cytological transformation.
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PMID:Preparation of anti-ras Mr 21,000 protein monoclonal antibodies and immunohistochemical analyses on expression of ras genes in human stomach and thyroid cancers. 304 40

Earlier epidemiological studies have shown that exposure to aluminium oxide and silicon carbide might carry with it an increased risk of lymphomas, stomach cancer, and non-malignant respiratory disease. To elucidate further this possible hazard, the cancer morbidity and the total mortality pattern was studied among 521 men manufacturing abrasive materials who had been exposed to aluminium oxide, silicon carbide, and formaldehyde. Total dust levels were in the range of 0.1-1.0 mg/m3. The cohort was followed up from 1958 until December 1983. No significant increase was found in total mortality, cancer mortality, or incidence of non-malignant respiratory diseases.
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PMID:Mortality and cancer incidence among workers in an abrasive manufacturing industry. 381 36

The prognostic value of overexpression of the p53-encoded protein was evaluated in 242 patients with gastric cancer. Formalin-fixed paraffin-embedded specimens of gastric adenocarcinomas were stained with the monoclonal antibody DO-7. 95 patients (39%) showed a high level of immunoreactivity (> or = 20% of cell nuclei staining positively), suggesting the presence of a mutation in the TP53 coding sequence. Overexpression of the p53 protein correlated significantly with stage of disease (P = 0.01), the presence of distant metastases (P = 0.04) and with the intestinal type of cancer (P = 0.04). No correlation between p53 overexpression and age, gender or the presence of the lymph node metastases was found. In univariate analysis, p53 immunoreactivity correlated significantly with survival (P = 0.0005). The median survival in the p53 high-level group was 19 months compared with 65 months in the p53 low-level group. In multivariate analyses, stage of disease and the presence of distant metastases emerged as independent prognostic factors, whereas p53 immunoreactivity did not (P = 0.08). The present results indicate that overexpression of the p53 protein is not an independent prognostic factor in patients with gastric cancer.
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PMID:Expression of p53 protein as a prognostic factor in patients with gastric cancer. 866 30

Levels of gastric juice nitrite, several urinary N-nitroso compounds, and other analytes were examined among nearly 600 residents in an area of Shandong, China, where precancerous gastric lesions are common and rates of stomach cancer are among the world's highest. Gastric juice nitrite levels were considerably higher among those with gastric juice pH values above 2.4 versus below 2.4. Nitrite was detected more often and at higher levels among persons with later stage gastric lesions, especially when gastric pH was high. Of those with intestinal metaplasia, 17.5% had detectable levels of gastric nitrite, while this analyte was detected in only 7.2% of those with less advanced lesions. Relative to those with undetectable nitrite, the odds of intestinal metaplasia increased from 1.5 (95% confidence interval = 0.6-4.1) to 4.1 (95% confidence interval = 1.8-9.3) among those with low and high nitrite concentrations, respectively. Urinary acetaldehyde and formaldehyde levels also tended to be higher among those with more advanced pathology, particularly dysplasia. However, urinary excretion levels of total N-nitroso compounds and several nitrosamino acids differed little among those with chronic atrophic gastritis and intestinal metaplasia and dysplasia, consistent with findings from recent studies in the United Kingdom, France, and Colombia. The data from this high-risk population suggest that elevated levels of gastric nitrite, especially in a high pH environment, are associated with advanced precancerous gastric lesions, although specific N-nitroso compounds were not implicated.
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PMID:Nitrite, N-nitroso compounds, and other analytes in physiological fluids in relation to precancerous gastric lesions. 877 Apr 66

Formalin-fixed and paraffin-embedded tissues are a valuable resource for diagnosis and research. PCR is one of the most powerful methods of retrospective analysis of the DNA present in fixed tissues. One major problem with the molecular analysis of tissue samples, however, is cellular heterogeneity, ie, the large variety of cell types usually present in these specimens can mask cell-specific genetic alterations associated with disease. Herein we describe a procedure for obtaining and analyzing single cells recovered from stained histologic tissue sections without risking contamination from neighboring cells. An ultraviolet laser microbeam was used to physically destroy the tissue surrounding the single cells of interest. These cells, now freed from adjacent cells, were then easily retrieved with a motorized, computer-controlled micromanipulator and molecularly characterized through the use of PCR-based microanalysis. This accurate microdissection technique, followed by DNA amplification and direct sequencing, revealed a novel mutation in the gene coding for the cell adhesion molecule E-cadherin in single tumor cells that was absent in the adjacent single epithelial cells of a patient with early gastric cancer of the diffuse type. In this form of malignancy, tumor cells lose homophilic cell-to-cell interactions and invade the connective tissue as single cells. E-cadherin gene mutations have previously been detected in advanced diffuse-type gastric cancer and gastric carcinoma cell lines. The present study suggests that E-cadherin gene mutations may be an early event in gastric tumorigenesis. The laser-based isolation and subsequent molecular characterization of individual cells, as described herein, allows for micrometer-sized precision and should prove useful in detecting the nucleic acid abnormalities that underlie cancer, infection, and genetic disease.
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PMID:Single-cell mutation analysis of tumors from stained histologic slides. 897 75

Gastric carcinogenesis is strongly associated with Helicobacter pylori infection, but the underlying genetic mechanisms are largely unknown. The aim of this study was to correlate chromosomal aberrations in gastric cancer to H. pylori status and its different strains, as well as to histological type and other clinico-pathological variables. DNA from 46 gastric cancers (male/female 35/11, age 27-85 years) was extracted from formaldehyde-fixed, paraffin-embedded material and tested for chromosomal gains and losses by comparative genomic hybridization (CGH). Chromosomal aberrations with frequencies of 20% or higher were considered to be non-random changes associated with gastric cancer. The mean number of chromosomal events per tumour was 9.7 (range 0-27), with a mean of 3.2 gains (range 0-16) and 6.5 losses (range 0-15). Gains were most frequently found at chromosomes 8q and 13q (24% and 26%, respectively). Losses were predominantly found on chromosome arms 2q, 9p, 12q, 14q, 15q, 16p, 16q, 17p, 17q, 19p, 19q, and 22q (22%, 30%, 43%, 22%, 33%, 50%, 28%, 50%, 39%, 33%, 39%, and 37%, respectively). Common regions of overlap narrowed down to 2q11-14, 8q23, 9p21, 12q24, 13q21-22, 14q24 and 15q11-15. The mean number of gains was higher in tumours with metastases than in localized tumours (4.1 vs. 1.9, p=0.04). Tumours with a loss at 17p showed a higher number of losses than tumours without a 17p loss (9. 5 vs. 4.7 on average, p<0.001). Neither H. pylori status (+, n=25; -, n=21) nor H. pylori strain was correlated to the total number of events or to any specific chromosomal aberration, nor were there differences between intestinal (n=30) and diffuse (n=15) cancers or any other clinico-pathological variable tested. In conclusion, a complex of chromosomal aberrations is involved in gastric cancer, but their pattern does not depend on H. pylori status or strain, nor on the histological type of the tumour. The exact biological meaning of these aberrations in carcinogenesis needs further clarification.
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PMID:Helicobacter pylori-related and -non-related gastric cancers do not differ with respect to chromosomal aberrations. 1105 12

Tumours from 45 patients with advanced gastric cancer were assessed by immunohistochemistry. Tissue sections were fixed in 10% buffered formaldehyde solution, embedded in paraffin and stained immunohistochemically with anti-human Ki-67 and PCNA antibodies. No correlation was found between Ki-67, PCNA protein expression, the age of patients and the localization of tumour. A significant, positive association was observed between the expression of Ki-67, PCNA and tumour differentiation and Lauren's classification. Also a strong correlation was found between lymph node involvement and the expression of Ki-67 protein. These data suggest that the expression of Ki-67, PCNA proteins were closely connected with the high grade of tumour malignancy.
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PMID:Evaluation of proliferating markers Ki-67, PCNA in gastric cancers. 1563 77


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