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)

Helicobacter pylori causes chronic atrophic gastritis and intestinal type gastric cancer arises against a background of atrophic gastritis. Increased proliferation of epithelial cells is an important indicator of increased risk for gastric adenocarcinoma. We investigated gastric mucosal cell proliferation in H. pylori-associated gastritis and the effect of eradication therapy on this proliferation in 45 patients endoscopically diagnosed (31 with persistent eradication and 14 in whom H. pylori) recurred. H. pylori status was determined by culture and histology in biopsied specimens from the gastric antrum and corpus. Eradication of the infection was defined as reversal to negative on both tests. In vitro Ki-67 immunostaining of endoscopic biopsy specimens was used to measure mucosal cell proliferation in H. pylori-associated gastritis before and after therapy. The proliferative zone was defined as the distance of Ki-67-positive gastric epithelial cells between the highest and the lowest cells. In patients in whom H. pylori was eradicated, cell proliferation in both the antral and corpus mucosa had decreased 4 weeks after completion of the eradication therapy (P < 0.01, P < 0.001), and 6 months later, it had markedly decreased (P < 0.05, P < 0.05) and returned to normal. In patients in whom H. pylori recurred, only antral epithelial cell proliferation was reduced 4 weeks after eradication therapy, but when H. pylori recurred, determined by culture and histology, cell proliferation level was the same as that before eradication. These results suggest that H. pylori infection accelerates cell proliferation in gastric mucosa and may play a causal role in the chain of events leading to gastric carcinoma.
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PMID:Helicobacter pylori infection accelerates human gastric mucosal cell proliferation. 908 65

Increased epithelial cell proliferation is associated with an increased risk of gastric carcinoma. Helicobacter pylori infection is an established risk factor for gastric cancer and the organism has recently been classified as a group I carcinogen by an IARC working group. In this study, we describe differences in gastric epithelial cell proliferation between a H. pylori eradicated group (n = 21) and a not eradicated group (n = 8) after anti-H. pylori eradication therapy to show that increased cell proliferation is associated with H. pylori infection. H. pylori infection was determined by rapid urease test and immunohistochemical method with anti-H. pylori polyclonal antibody. Gastric epithelial cell proliferation was assessed using immunohistochemical method using Ki-67 monoclonal antibody. Ki-67 positive cells in H. pylori associated chronic active gastritis were observed in the glandular neck and the upper portion of foveolar epithelium. Patients who cleared their H. pylori infections showed a significant decrease of Ki-67 labeling index after therapy (0.73 +/- 0.10 vs. 0.48 +/- 0.08, p < 0.01). By contrast, Ki-67 labeling index before and after treatment in patients who remained positive for H. pylori showed no significant difference (0.78 +/- 0.08 vs 0.74 +/- 0.10, p > 0.05). These results indicate that H. pylori infection increases the proliferation of gastric foveolar epithelium, which is reduced by the eradication therapy. We suggest that anti-H. pylori eradication therapy can prevent mucosal cell proliferation to be closely associated with gastric carcinogenesis.
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PMID:Decreased gastric proliferation of foveolar epithelial cells after the eradication of Helicobacter pylori. 936

The combination effect of 5-fluorouracil (5-FU) and cisplatin was examined in terms of the proliferation, morphology and expression of Ki-67 antigen, and propidium iodide (PI) staining using four cultured human gastric cancer cell lines, and we assessed how such activity was affected by the exposure time and the timing of treatment. MKN-1, MKN-28, MKN-45 and MKN-74 cells were exposed to various concentrations of 5-FU for 72 h and cisplatin for 8 or 72 h. At IC50, MKN-28 cells were more sensitive to 5-FU than other cell lines, whereas MKN-1 and MKN-45 cells were more sensitive to cisplatin than other cell lines. The cell growth-inhibitory activity of cisplatin was found to be 'area under the curve' dependent. When 5-FU and cisplatin were combined simultaneously, the combination effect was higher than that of 5-FU or cisplatin alone. On the other hand, when cisplatin was applied before 5-FU, there was no potentiation of the cell growth-inhibitory activity by combination treatment. In 5-FU-treated MKN-74 cells, the size, morphology and PI staining of nuclei were almost the same as those of the untreated cells, and the expression of Ki-67 antigen was less than that of the untreated cells. In cisplatin-treated MKN-74 cells, the size of cells and nuclei was larger than that of the untreated cells and fragmentation of nuclei was observed. The expression of Ki-67 antigen was less than the untreated cells but more than that of 5-FU-treated cells. In the cells treated with 5-FU and cisplatin in combination, the above changes were an intermediate of those of 5-FU-treated cells and cisplatin-treated cells. In conclusion, the cell growth-inhibitory activity of 5-FU and cisplatin against gastric cancer cells was potentiated by the combined treatment with 5-FU and cisplatin simultaneously, but not with cisplatin followed by 5-FU.
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PMID:In vitro combination effect of 5-fluorouracil and cisplatin on the proliferation, morphology and expression of Ki-67 antigen in human gastric cancer cells. 943 43

We examined the relationship between apoptosis and the progression of human gastric carcinoma. Studies were conducted on a total of 88 surgically removed stomachs, comprising 26 minute (less than 5 mm in diameter), 29 early (limited to the mucosal and submucosal layer) and 33 advanced carcinomas. Apoptotic cells were visualized by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labelling (TUNEL). Serial sections were immunostained for p53 and Ki-67. The mean apoptotic indices (AI: percentage of TUNEL signal positive cells) of minute, early, and advanced carcinomas were 4.1 +/- 0.6, 3.8 +/- 1.2, and 4.0 +/- 1.2 in 46 well differentiated carcinomas, and 2.1 +/- 0.5, 2.7 +/- 0.9, and 2.2 +/- 1.1 in 42 poorly differentiated carcinomas, respectively. Similarly, the mean Ki-67 labelling indices (KI) were 39.2 +/- 7.8, 47.2 +/- 12.8, 52.6 +/- 13.1 in the former, and 35.0 +/- 9.3, 36.9 +/- 10.3, and 40.0 +/- 9.2 in the latter, respectively. Both mean AI and mean KI were significantly higher in well differentiated than in poorly differentiated carcinomas (P < 0.05). However, the value of mean AI did not differ among minute, early, and advanced carcinomas in either histological type, while KI increased gradually with tumour progression. The frequency of nuclear p53 expression did not differ among the three categories, implying that the gene mutation is an early event in gastric carcinogenesis. There was no statistical significance between nuclear p53 expression and mean AI. These results suggest that the progression of gastric cancer is defined by a gradual increase of proliferative activity and constant occurrence of apoptosis and that naturally occurring apoptosis is induced predominantly via a p53-gene-independent pathway.
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PMID:Frequent occurrence of apoptosis is an early event in the oncogenesis of human gastric carcinoma. 946 86

The expression of 67-KDa laminin receptor (LR) was investigated in a group of 75 patients who underwent curative gastrectomy for advanced gastric cancer, with special reference to the possible role in the tumor progression and in the overall survival. In 56 out of these 75 patients also the prognostic significance of proliferative activity was investigated using the monoclonal antibody Ki-67. The tumor LR expression and the Ki-67 labeling index (Ki-67 LI) were immunohistochemically determined in paraffin-embedded sections using the avidin-biotin immunoperoxidase method. The cumulative 5-years survival rate was 75.1% for patients without expression of LR, 52.6% for those with positive LR expression. Significant association between LR expression and depth of tumor invasion (p = 0.022) was found. By univariate analysis the presence of laminin receptor seemed to be associated with an higher risk of death (RR1.73-95% C.I. 0.71-4.20), but this effect disappeared after controlling for depth of tumor invasion. There was no significant relationship between the Ki-67 LI and wall invasion (p = 0.80) or nodal status (p = 0.73). The cumulative 5-year survival rates (95% CI) were 61.0% (35.3-79.2) in patients with Ki-67 index < 10%, 52.4% (29.7-70.9) with Ki-67 index = 10%-40%, 52.9% (27.6-73.0) with Ki-67 index > 40% and the differences were not statistically significant (p = 0.93). Also in multivariate analysis the proliferative activity did not independently affect survival (p = 0.98). An interaction between Ki-67 index and age was found and Ki-67 index > 40% was significantly associated with a poor prognosis in patients over 70 years old old (p = 0.002). In conclusion, tumor expression of laminin receptor could be correlated with gastric cancer aggressiveness, however its prognostic significance is already provided by depth of tumor invasion. The proliferative activity, determined with the monoclonal antibody Ki-67, does not seems to influence the survival except in elderly patients (> or = 70 years old).
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PMID:[Immunohistochemical study on the prognostic value of the expression of laminin and Ki-67 receptors in advanced gastric cancer]. 973 82

The prognostic value of the immunohistochemical expression of p53 protein, proliferating-cell nuclear antigen (PCNA) and Ki-67 antigen was evaluated in a series of 116 stage I-II gastric cancer patients. The staining for p53 protein (staining frequency and intensity) in malignant cells was expressed as a p53 index. Similarly, the staining frequency and intensity for PCNA and Ki-67 were evaluated. The p53 index was independent of the stage and differentiation grade, but significantly related to DNA ploidy, S-phase fraction and mitotic activity. A high p53 index was a sign of inferior survival, compared to a low or intermediate index. p53-negative tumours were also associated with poor survival. In a multivariate analysis, only the depth of tumour infiltration and the presence of nodal metastases were independent prognostic factors in stage I-II gastric cancer. PCNA expression and Ki-67 antigen expression were not related to the stage, ploidy, proliferative activity or p53 expression, and they had no impact on survival. The results indicate that p53 protein expression may be of prognostic significance in gastric cancer, while PCNA and Ki-67 antigen expression have no predictive value.
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PMID:Clinical relevance of p53 index and expression of proliferating cell nuclear antigen and Ki-67 in gastric cancer. 980 24

The human MAGE gene products are recognized by major histocompatibility complex-restricted cytotoxic T lymphocytes. We analyzed by RT-PCR the expression of MAGE-1, MAGE-2, MAGE-3 and HLA-A2 genes in 10 human gastric cancer cell lines and 46 human stomachs removed due to advanced gastric carcinomas. All the cell lines expressed MAGE genes, except for MKN-45 and -74 which lacked the expression of MAGE-1 and -3 genes in this study. Of the 46 gastric carcinomas, MAGE-1, -2 and -3 genes were expressed in 14 (30%), 10 (22%) and 26 (57%) cases, respectively, regardless of histological type. Normal gastric mucosa and intestinal metaplastic mucosa showed no expression of these genes. HLA-A2 gene expression was noted in 14 both normal and carcinoma cases. Simultaneous expression of MAGE-3 and HLA-A2 genes was noted in 7 cases. Mean apoptotic and Ki-67-labeling indices (AI and KI) of carcinoma cells were 2.3 +/- 0.5 and 48.1 +/- 6.0 in 7 cases, and 2.8 +/- 0.2 and 47.3 +/- 2.7 in the other 39 cases lacking the expression of MAGE-3 and/or HLA-A2 genes, respectively. The two-year survival rate did not differ between the two groups. Although this study confirmed the relatively higher expression of the MAGE gene family in human advanced gastric carcinomas, it might suggest that simultaneous expression of MAGE-3 and HLA-A2 genes does not necessarily imply the induction of cancer cell apoptosis by CTL.
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PMID:Expression of MAGE-1, MAGE-2 and MAGE-3 genes in human gastric carcinomas; lack of evidence for cytotoxic effects in cases with simultaneous expression of MAGE-3 and HLA-A2. 985 70

In various types of human malignant tumors, the presence or absence of expression of apoptosis-associated gene products (p53 protein and Bcl-2 protein) and the tumor proliferation activity-related factor (Ki-67) was assessed by immunohistochemical staining and the correlation between this expression and chemosensitivity to anticancer drugs was investigated. Study subjects comprised 55 preoperative patients with untreated malignant tumors (9 with esophageal cancer, 11 with stomach cancer, 11 with colon cancer, 13 with hepatic cancer and 11 with breast cancer). A chemosensitivity test was carried out with the histoculture drug response assay (HDRA) method using 4 drugs, mitomycin C (MMC), 5-fluorouracil (5-FU), doxorubicin hydrochloride (ADM), and cisplatin (CDDP). Immunohistochemical staining was used to assess expression of p53 protein, Bcl-2 protein and Ki-67. The tumor growth inhibition index (I.I.) of the 4 drugs was significantly lower in a group of the patients with p53 protein overexpression-type (mutant p53 protein positive expression-type) tumors than in a group with p53 protein negative expression-type tumors (p<0.05). No significant correlation was found between the expression of the Bcl-2 protein by and the I.I. of any drug studied in any type of cancer. A negative correlation was found between the labeling index (L.I.) for Ki-67 in all cases and I.I. for MMC and ADM and thus, chemosensitivity of the tumors with high growth activity was lower. Furthermore, a positive correlation existed between the L.I. for Ki-67 and that for p53 protein. The patients with p53 protein overexpression-type (mutant p53 protein positive) tumors showed low chemosensitivity. In addition, overexpression of p53 protein is suggested to be one of the factors involved in the lowered chemosensitivity of the tumors with high growth activity. Summarizing these findings, the p53 protein can play an important role in cancer therapy.
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PMID:Usefulness of p53 protein, Bcl-2 protein and Ki-67 as predictors of chemosensitivity of malignant tumors. 1020 14

In a patient with gastric cancer (GC) associated with one synchronous and three metachronous hepatic metastases (HM), who underwent four hepatectomies, we carried out histochemical investigations regarding cell proliferation, apoptosis, and angiogenesis in the GC and HM. Tissue samples were taken from the primary GC and four HM. Ki-67 immunostaining was performed to evaluate cell proliferation and determine the labeling index (Ki-67 LI; ie, the percentage of cancer cells with nuclei stained for Ki-67). Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) was performed to evaluate apoptosis and determine the apoptotic index (ie, the percentage of TUNEL-positive cells), and immunostaining for factor VIII-related antigen was performed to evaluate angiogenesis and measure microvessel density (MVD). The Ki-67 LI was 43.2% in the primary GC and 39.9% in the synchronous HM, and the LI increased with the number of resections of metachronous HM. The apoptotic index was 3.36% in the primary GC, and 5.30% in the synchronous HM, and the index decreased after further resections of the metachronous HM. The MVD was 35 in the primary GC, and 22 in the synchronous HM, and it increased with the number of resections of metachronous HM. The primary GC in this patient may have strongly influenced the growth of HM through effects on cell proliferation, apoptosis, and angiogenesis.
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PMID:Four resections for hepatic metastasis from gastric cancer: histochemical analysis of cell proliferation, apoptosis, and angiogenesis. 1068 Jun 71

The nuclear area (NA) of cancer cells have been reported to be a useful prognostic indicator in various tumors. However, this image analysis of cancer nucleus has only rarely been applied to gastric adenocarcinoma. Moreover, it remains to be shown what types of biological factors influence this nuclear feature. In this study, we analyzed the area of cancer nuclei in tumors from 97 patients with advanced gastric cancer (t3, n0, stage II) by using hematoxylin and eosin stained slides with a computer-assisted image-analysis system. The morphometric data were compared with clinicopathological and biological status of the tumors. The mean NA of 50 tumors with venous invasion (50 microm2) was significantly larger than that of 47 tumors without venous invasion (38 microm2, p<0.0001). There was a significant correlation between the NAs of cancer cells and the p53 labeling indices of tumors (p=0.0012) and Ki-67 labeling indices of tumors (p=0.0324). However, no significant correlation was detected between the NAs of cancer cells and other factors, such as, tumor size, DNA ploidy pattern, expression of vascular endothelial growth factor (VEGF), or microvessel density of tumors. The five-year survival rate of 49 patients with large nuclear area (NA > or =41 microm2, 63%) was significantly lower than that of 48 patients with small nuclear area (NA <41 microm2, 78%, p=0.043). Data from computerized morphometry are objective and can be obtained rapidly by conventional microscopic analysis. The NA of cancer cells in advanced gastric cancer appears to predict the ability to invade the microvessels in the gastric wall. This nuclear morphological feature strongly correlated with p53 accumulation in the nuclei of gastric adenocarcinoma.
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PMID:Nuclear accumulation of p53 protein in gastric cancer strongly correlates with enlargement of nuclear area of cancer cells. 1076 71


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