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)

In order to investigate the role of collagenase in cancer invasion and metastasis, two collagenase activities of interstitial collagenase and type IV collagen degrading enzyme (type IV collagenase) were determined in 40 cases of human stomach cancer tissue. Elevated cancers which are known to have a propensity to cause blood-borne metastases showed higher activities of both interstitial collagenase and type IV collagenase than flat or ulcerous type of cancer. Using the parameters of lymph node metastasis vs tumor size or vs depth of cancerous invasion into the stomach wall, classification of the cases was attempted according to the degree of malignancy. In the cases with marked lymph node metastases in spite of small tumor size and/or shallow cancerous invasion into the stomach wall, type IV collagenase activity was higher than that in the cases with lower malignancy (p less than 0.025, p less than 0.05, respectively). These results suggest that collagenase in stomach cancer tissue play an important role in the invasion and metastasis of cancer cells. Type IV collagenase activity in stomach cancer tissue could be one of the useful biological markers for the degree of malignancy.
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PMID:The collagenase activities, interstitial collagenase and type IV collagenase, in human stomach cancer: with special reference to local spreading and lymph node metastasis. 217 1

Activities of several proteinase-like peptidases have been determined in homogenates of malignant tissue, non-malignant tissue adjacent to the tumour (A-NM) and non-malignant tissue distant to the tumour (D-NM) from 17 patients undergoing surgery for histologically confirmed gastric malignancies. In homogenates of malignant tissues the activities of collagenase, cathepsin B, cathepsin (B+L), cathepsin H and cathepsin D were significantly higher than in D-NM tissues. By contrast, the levels of plasminogen activator were significantly lower in malignant tissues than in the D-NM tissues. Furthermore, the activities of collagenase-like and the cysteine-proteinase-like peptidases in the A-NM tissues were lower than in malignant tissues but higher than in the D-NM tissues. Separation of full-thickness non-malignant tissues into mucosal and seromuscular layers revealed significantly higher activities in the former. The elevated levels of these proteinase-like peptidases in homogenates of gastric cancer tissue suggests an important role for these enzymes in tumour invasion.
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PMID:Proteinase-like peptidase activities in malignant and non-malignant gastric tissue. 388 38

Four monoclonal antibodies (GC301, 302, 303, 304) produced by hybridomas obtained from mice immunized with NUGC3 were analyzed by serological assay (Mixed Hemadsorption Assay-MHA) and immunoperoxidase technique. GC301(IgG1) showed tumor restricted reactivity in serological analysis, but it reacted with fibrous interstitial tissues immunohistochemically. GC302(IgG1) was serologically reactive with epithelial tumors such as gastric cancers, colon cancers and gynecological cancers, but not with brain tumors, melanomas and other normal cells. In tissue sections, all gastric cancers, intestinal metaplasia, stomach of fetus and bile duct were stained, but brain and hepatocytes were not. These results indicate that the antigen detected by GC302 is not only differentiation antigen by which gastrointestinal tract could be divided into foregut and midgut origins, but also the new type of oncofetal antigen different from CEA. GC302 would be useful for preoperative detection of gastric cancer in lymph nodes, using radioimmunodetection scans. GC303(IgG1) and GC304(IgG1) were broadly reactive with various cells in serological assay. Immunohistochemically, GC304 reacted with submucosal connective tissue, which was inhibited by collagenase. The results obtained from GC301 and GC304 suggest the possibility of interaction between tumor cells and interstitial tissues.
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PMID:[Analysis of cell surface antigens of gastric cancer and preliminary study of clinical application by using mouse monoclonal antibodies produced against NUGC3]. 388 84

We examined the expression of E-cadherin and collagenase type IV in formalin-fixed, paraffin-embedded specimens of human gastric carcinoma by an in situ mRNA hybridization (ISH) technique. The ISH technique revealed intertumoral heterogeneity for expression of E-cadherin and collagenase among 12 cases of early gastric cancer and 13 cases of advanced gastric cancer. In the majority of the tumors, we found an inverse relationship between the reactivities of E-cadherin and collagenase type IV. Specifically, E-cadherin was expressed at higher levels in the center of the neoplasms than in their periphery, whereas collagenase type IV was expressed at a higher level in the periphery (invasive edge) than in the center. Advanced gastric cancers with high levels of expression for collagenase type IV in the periphery had a higher incidence of distant lymph node metastasis than those with low expression. The data show an inverse relationship between E-cadherin (involved in cell-to-cell adhesion) and collagenase type IV (involved in invasion) in different zones of human gastric carcinoma and suggest that the relative expression of these independent genes may be involved in local invasion and metastasis.
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PMID:Intratumoral heterogeneity and inverse correlation between expression of E-cadherin and collagenase type IV in human gastric carcinomas. 864 46

The requirement for well spread out chromosomes for the cytogenetic analysis of primary gastrointestinal tumors led us to develop new techniques. These techniques involved two main procedures: (1) preliminary incubation with culture medium in the presence of collagenase, Dispase, and colcemid, for 3 h, and (2) treatment with an extremely hypotonic solution (0.044M KCl) for 30 min. The techniques were applied to 11 gastrointestinal malignancies (including 1 early gastric cancer and 1 metastatic liver lesion of colon cancer) and significant increases (P < 0.01) in the number of metaphases of analyzable karyotypes were obtained, compared with a previous method in which the standard hypotonic molarity of KCL (0.075 M) was employed. The mean value for metaphase numbers of the analyzable karyotypes was 37.0 +/- 3.7% in the 5 gastric cancers and 44.7 +/- 4.8% in the 5 colon cancers and 1 metastatic lesion. These values were three times and more than twice, respectively, the values obtained by the previous method. A fluorescence in situ hybridization (FISH) study was carried out on one cologenic tumor, the alpha-satellite centromere-specific probe 17 being used. Deletion of the long arm of chromosome 17 was demonstrated. The method proposed here could yield a sufficient number of metaphases without the use of tissue culture that might cause alteration of karyotype. It can be employed with small biopsy specimens and in studies utilizing the FISH technique.
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PMID:Chromosome spreading techniques for primary gastrointestinal tumors. 884 70

The expression of matrix metalloproteinase-1 (MMP-1) gene and the presence of MMP-1 protein in gastric cancer were examined by in situ hybridization and immunohistochemistry. Expression of the interstitial collagenase (MMP-1) gene was detected within the stroma of the neoplastic glands, and infiltration of eosinophils was observed to be associated with regions of MMP-1 gene expression. The degree of eosinophilic infiltration correlated with the level of MMP-1 mRNA expression. Immunostaining showed localization of MMP-1 protein in the stromal cells, and additionally in the neoplastic glands. These findings indicate that the stromal cells may play an important role in the expression of MMP-1, and suggest a pathophysiological role for MMP-1 in the invasion and metastasis of gastric cancer.
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PMID:Expression of interstitial collagenase (matrix metalloproteinase-1) in gastric cancers. 919 33

Gastric cancer is classified into intestinal and diffuse types, which exhibit different biological behavior. Urokinase-type plasminogen activator (uPA), its receptor (uPAR) and matrix metalloproteinases (MMPs)-1 and -9 are considered to play important roles in cancer invasion and metastasis. We have already suggested a functional duality of these matrix-degrading enzymes/factors; they may also be involved in the matrix turnover (remodeling) or host immune/inflammatory reactions as far as they are expressed by host cells. We performed a retrospective study on the immuno-histochemical expression of these enzymes/factors in surgical specimens from patients with gastric cancer, including 26 with the diffuse and 78 with the intestinal type. We also evaluated macrophages since they are major sources of uPAR. The positivity rate for uPA in cancer cells was significantly lower in diffuse-type than in intestinal-type. Stromal expression was seen mainly along the invasive margin (tumor-host interface). The degree of stromal expression of uPAR and MMP-9 and the macrophage number were markedly decreased in diffuse-type compared with intestinal-type. Stromal expression of uPAR and macrophage number in intestinal-type were higher in patients without liver metastasis than in patients with liver metastasis, while uPA expression in cancer cells was more pronounced in patients with liver metastasis. Studies using frozen sections revealed that the expression of MMP-1, restricted to the stromal area, was more decreased in diffuse-type (18 patients) than in intestinal-type (21 patients). Our results show that the in situ expression of matrix-degrading enzymes/factors in gastric cancer is significantly more diminished in diffuse-type than in intestinal-type, suggesting a multifunctional aspect of the matrix-degradation process in cancer tissue.
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PMID:Differing expression of MMPs-1 and -9 and urokinase receptor between diffuse- and intestinal-type gastric carcinoma. 998 36

Proteolytic activity of cancer cells is an important factor in metastasis. This study examined the relationship between MMP-1 expression of gastric cancer cells and peritoneal metastasis. MMP-1 expression was found in 76/103 (75.2%) cases examined and was significantly associated with both peritoneal metastasis and lymph node metastasis (p<0.05, respectively). The prognosis of patients with MMP-1 positive tumor was significantly worse than that of patients with MMP-1 negative tumor (p<0.05). These findings suggested that MMP-1 might be a prognostic factor in case of advanced gastric cancer and might be useful in determining whether or not adjuvant therapy was indicated for patients at high risk of peritoneal recurrence.
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PMID:Matrix metalloproteinase-1 expression is a prognostic factor for patients with advanced gastric cancer. 1037 41

Human gastric mucous cells - gastric cancer cell lines mucin gene expression - TNFalpha - RT-PCR immunocytochemistry Little is known on the expression pattern of mucin genes in human gastric cancer cell lines in relation to mucin expression in normal gastric epithelial cells. Thus, the aim of this study was to compare gastric cancer cell lines and non-transformed epithelial cells in their expression of the different mucin genes, in order to use these cells as models for physiological MUC expression in human stomach. Human gastric mucous cell primary cultures which were obtained from surgical specimen by collagenase/pronase treatment and a panel of six human gastric cancer cells were screened for mRNA expression of the mucin genes MUC1, MUC2, MUC5AC, MUC5B, and MUC6. Mucin gene expression was analyzed by semi-quantitative RT-PCR, and by Western blotting and immunocytochemistry. Primary cultured human gastric mucous cells retained the stomach-specific pattern of mRNA expression found in gastric mucosal biopsies (MUC1, MUC5AC, MUC6), whereas any gastric cancer cell line exhibited an aberrant mucin gene expression. Mucin gene expression showed large variations in levels and patterns from cell line to cell line, but MUC2 was aberrantly expressed in all cancer cells. Immunocytochemistry confirmed aberrant MUC2 protein expression in cancer cells. The expression of the secretory mucin genes MUC2 and MUC5AC varied in relation to the length of cultivation of the cancer cell lines. Treatment of the gastric cancer cells with TNFalpha resulted in an enhanced mRNA expression of MUC1, MUC2, and MUC5AC (2-fold increase within 3 hours; p <0.05). In contrast, immunocytochemistry disclosed a decrease in MUC2 and MUC5AC staining intensity. Our results indicate that primary cultured human gastric mucous cells provide a physiological in vitro system for investigations of gastric mucin gene regulation. In gastric cancer cells marked changes in the mucin gene expression pattern are found with coexpression of non-gastric type mucins. Gastric mucin gene expression may be regulated by proinflammatory cytokines which could have implications in gastritis.
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PMID:Variation of human mucin gene expression in gastric cancer cell lines and gastric mucous cell primary cultures. 1060 60

Tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in plasma has been reported to be related to disease progression in patients with gastric cancer. However, the prognostic significance of plasma TIMP-1 concentrations has not been clarified. Concentrations of TIMP-1 protein were measured by enzyme-linked immuno-sorbent assay in plasma samples of 147 preoperative patients who subsequently underwent gastric resection, and prognosis was compared. The cut-off value of plasma TIMP-1 concentrations was defined as 112.5 ng/ml, referring to the TIMP-1 levels in patients with intramucosal gastric cancer. Twenty-nine out of 147 patients had higher plasma TIMP-1 levels than the cut off value. When the patients were divided into those with elevated values and those with normal TIMP-1, such parameters as age, serosal invasion, metastases to lymph nodes, peritoneum, and liver, lymphatic invasion, curability, and stage were significantly different between the two. By univariate analysis of the factors affecting survival, macroscopic type, histology, serosal invasion, metastasis to lymph node, peritoneum, and liver, vessel invasions, curability, and plasma TIMP-1 were significant. However, multivariate analysis revealed that TIMP-1 was the only significant factor. In patients with gastric cancer, plasma TIMP-1 seem to be an independent and most powerful prognosticator for the survival.
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PMID:Prognostic value of tissue inhibitor of matrix metalloproteinase-1 in plasma of patients with gastric cancer. 1076 26


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