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)

A poorly differentiated medullary carcinoma of human stomach, designated HY-1, was successfully transplanted to nude mice by either the subcutaneous or intramuscular route for five generations. The transplanted tumor showed spontaneous lung metastases in nearly 100% of KSN and Balb/c female nude mice. There were over 20 visible lung metastatic nodules in KSN and Balb/c nude mice bearing tumors for over 80 days. Immunostaining of type IV collagen and electron microscopy revealed that tumor cells were often in direct contact with basement membrane (BM) of tumor blood vessels in the primary tumor tissue. At the site of contact between tumor cells and vascular BM, focal disappearance of the BM, disruption of endothelial cells and entry of tumor cell clusters into vascular lumen were observed. Immunostaining of 72 kDa gelatinase/type IV collagenase demonstrated that tumor cells expressed this enzyme in their cytoplasm. These results suggest that spontaneous metastasis of this tumor may be partly due to a marked tendency to vascular invasion involving the following sequential events: tumor cell contact with vascular BM, BM degradation possibly by 72 kDa gelatinases and endothelial disruption. This model could be a useful tool for understanding the mechanism of hematogenous metastasis of human gastric cancer.
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PMID:Establishment and characterization of a new spontaneous metastasis model of human gastric carcinoma in nude mice. 165 13

In order to study the role of both collagenases against type I and type IV collagen (type I and type IV collagenase) with regard to tumor invasion and metastasis, the activities of both collagenases in tissue homogenate in each 40 cases of stomach and lung cancers were investigated. The direct assay method of type IV collagenase in tissue was established through modification of Liotta's method. In stomach cancer, the part of advancing front of cancer showed the highest activity of type I collagenase. The adjacent mucosa to cancer also showed high activity of type IV collagenase. The cancer tissues that had the remarkable finding of vascular invasion of cancer cells showed high activity of type IV collagenase. In lung cancer, the correlation between the size of cancer mass and activity of type I collagenase was shown. Squamous cell carcinoma in comparison to adenocarcinoma had higher activity of type I collagenase and poor activity of type IV collagenase. These results suggested that the activity of type I collagenase might participate in local invasion and the activity of type IV collagenase might be associated with vascular invasion of cancer through disruption of basement membrane and they could be one of the useful biochemical tumor marker to represent the growth and metastatic pattern.
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PMID:[New direct assay method of type IV collagenase in tissue homogenate and biochemical role of collagenase against type I, and IV collagens to the invasion of the stomach and lung cancer]. 215 47

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

The mRNA localizations of gelatinase A(MMP-2) and type I carcinoma and non-neoplastic fibrous granulation tissue were compared. By in situ hybridization, gelatinase A was shown to be expressed in fibroblasts not only in cancer stroma but also in the "reactive fibrosis zone," which surrounds the invasive margin of cancer. In most cases, no accentuation of gelatinase A expression was observed in the invasive margin. This localization pattern of gelatinase A was essentially the same as that of type I procollagen. In gastric cancer associated with deep ulceration, gelatinase A was more abundantly expressed in fibroblastic cells in granulation tissue of the ulcer base than in cancer stroma. The same situation was found in non-neoplastic fibrous granulation tissue, in which fibroblasts abundantly expressed mRNAs for both gelatinase A and type I collagen. Scar tissue (old fibrotic lesion) showed diminished expression of mRNAs for both gelatinase A and type I procollagen. The localization patterns suggest another function of gelatinase A in cancer tissue as a turnover enzyme of the extracellular matrix.
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PMID:Similarities of in situ mRNA expression between gelatinase A (MMP-2) and type I procollagen in human gastrointestinal carcinoma: comparison with granulation tissue reaction. 759 60

The expression of integrin Alpha-6-subunit, laminin, type IV collagenase, type IV collagen and ras p21 were studied immunohistochemically in gastric cancer. The results showed that the expression of alpha 6 and laminin (LN) was often in continuous or interrupted linear pattern in the expanding type of gastric carcinoma (GC); while in the infiltrating type of GC, they were expressed either in interrupted spotty or fragmentary pattern, or almost lost. Suggesting that the interaction between the laminin receptor and its ligand may influence the mode of growth in GC. Intense expression of type IV collagenase was often found in GC cells, especially in the infiltrative type of GC and in those with lymph node metastasis, it can therefore be used as a marker for invasion and metastasis of GC cells. A positive correlation was found between the expression of type IV collagenase and ras p21 in GC. The expression of type IV collagen was similar to that of laminin, but in reverse proportion to the expression of type IV collagenase. These investigations provide a better understanding of the molecular pathological basis of tumor invasion and metastasis.
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PMID:[The relation between integrin, type IV collagenase and extracellular matrix in invasion and metastasis of gastric carcinoma]. 787 59

The extra-cellular matrix (ECM) related antigens, type IV collagen, laminin, M(r) 68,000 laminin receptor (LR), M(r) 72,000 type IV collagenase (MMP-2), its inhibitor TIMP-2, and alpha 2-macroglobulin expression have been immunohistochemically investigated in 100 cases of human gastric carcinoma with a 5-yr follow up. Basement membranes were inversely related to tumoral differentiation. At the early intramucosal stage of both intestinal and diffuse histological types, TIMP-2 was expressed by the majority of tumor cells (60/63%), whereas MMP-2+ and LR+ cells were in the minority (24/19%, 23/0%, respectively). At the early submucosal stage, TIMP-2+ cells moderately decreased in both histological types (49/49%), whereas a consistently higher number of both MMP-2+ and LR+ cells were detected only in the diffuse carcinomas (72%). In the advanced stage, the expression of TIMP-2 further declined (22/24%), although the other two antigens increased or maintained high levels of expression. AMG+ cells never exceeded 10% in either histological type at any stage. In the liver metastases, both MMP-2+ and LR+ cells were more numerous than in the primary tumor (P < 0.002 and P < 0.01). Patients who died from their primary tumor had higher percentages of LR+, MMP-2+, and AMG+ cells and lower percentages of TIMP-2+ cells with respect to survivors. We believe evaluation of ECM-related antigens, and especially TIMP-2, may help determine a confident prognosis for gastric cancer.
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PMID:Prognosis of gastric carcinoma revealed by interactions between tumor cells and basement membrane. 800 47

A one-step sandwich enzyme immunoassay (EIA) for human matrix metalloproteinase 2 (MMP-2, 72-kDa gelatinase/type IV collagenase, EC 3.4.24.24) was established with a pair of monoclonal antibodies prepared against the precursor form of MMP-2 (proMMP-2) purified from the conditioned medium of human skin fibroblasts or against a synthetic peptide corresponding to the N-terminal domain of proMMP-2. ProMMP-2 in samples was allowed to simultaneously react with both solid-phase and peroxidase-labeled antibodies. Sensitivity of this EIA system was 2.4 pg/assay (0.24 microgram/l) and linearity was obtained between 10 and 5,000 pg/assay (1.0-500 micrograms/l). The EIA system recognized both the free form of proMMP-2 and its complex form with TIMP-2 with the same degree of immunoreactivity. ProMMP-2 levels in human sera from patients in various disease states were analyzed. In sera from patients with hyperthyroidism (12), primary biliary cirrhosis (8) and hepatocellular carcinoma (11), 749 +/- 166, 716 +/- 135 and 686 +/- 236 micrograms/l of proMMP-2 were detected, respectively and these were significantly higher than that observed in 213 normal human sera (570 +/- 118 micrograms/l). In contrast, the levels in sera from 33 patients with osteoarthritis (449 +/- 72 micrograms/l), 45 with rheumatoid arthritis (408 +/- 139 micrograms/l), 13 with stomach cancer (427 +/- 103 micrograms/l) and 10 with pancreatic cancer (422 +/- 130 micrograms/l) were significantly lower than that found in normal sera. Immunoblot and gel filtration analyses showed that human sera contain several MMP-2 species in addition to proMMP-2 which exist in a complex form with TIMP-2.
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PMID:A one-step sandwich enzyme immunoassay for human matrix metalloproteinase 2 (72-kDa gelatinase/type IV collagenase) using monoclonal antibodies. 814 45

A one-step sandwich enzyme immunoassay system was developed with a pair of monoclonal antibodies against two individual oligopeptides prepared from the amino acid sequence of the human tissue inhibitor of metalloproteinases-2 (TIMP-2). The assay system consisting of two simultaneous immunoreactions used a solid phase monoclonal antibody and a horse-radish peroxidase-labeled monoclonal antibody. The system detected a free form of TIMP-2 and that complexed with active forms of matrix metalloproteinases (MMPs) giving a different sensitivity for each MMP but not TIMP-2 complexed with the precursor of 72 kDa gelatinase/type IV collagenase (MMP-2). The sensitivity of the system was 1.6 microgram/l (16 pg/assay) and linearity was obtained between 6.3 and 50 micrograms/l (63-500 pg/assay). TIMP-2 levels in the sera of 20 patients with rheumatoid arthritis (68 +/- 25 micrograms/l, mean +/- S.D.) and 13 patients with hepatocellular carcinoma (76 +/- 46 micrograms/l) were significantly higher (P < 0.05) than those of 18 normal subjects (5.6 +/- 7.4 micrograms/l). In contrast, the levels in the sera of 10 patients with gastric cancer (45 +/- 18 micrograms/l) and 7 patients with cancer of the uterus (36 +/- 13 micrograms/l) were significantly lower (P < 0.05 or P < 0.01) than those of normal subjects. Immunoreactivity analyses suggested that the precursor of MMP-2 in normal sera exists in a complexed form with TIMP-2 by interacting with the C-terminal domain of TIMP-2.
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PMID:A one-step sandwich enzyme immunoassay for tissue inhibitor of metalloproteinases-2 using monoclonal antibodies. 828 59

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

During the process of invasion, tumor cells must detach from the primary neoplasm and degrade host stroma. E-cadherin is responsible for the cell-cell adhesion and collagenase IV is the one of the matrix metalloproteinases. We determined whether the levels of mRNA for E-cadherin and collagenase IV were differently expressed within 12 cases of early and 13 cases of advanced gastric cancers using a rapid calorimetric in situ hybridization assay for mRNA. In 6 of 12 early cancers, we found a decreased expression of E-cadherin mRNA in the invasion edge compared to the main tumor. In advanced gastric cancers, 3 out of 13 cancers also exhibited this finding. Higher expression of the collagenase IV at the invasion edge of the tumor compared to the main tumor was observed in half of the early and advanced gastric cancer cases. Inverse expression levels of E-cadherin and collagenase IV mRNA were observed in 6 of 12 early cancers. However, only one of 13 advanced cancer cases expressed the same finding.
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PMID:[Comparative study of mRNA expression of E-cadherin and collagenase IV in early and advanced cancers]. 867 57


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