UMLS:C0024623 - FACTA Search

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Query: UMLS:C0024623 (gastric cancer)
36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The major obstacle towards improved survival from gastric cancer is in the development of metastatic disease. Techniques in cellular and molecular biology have now advanced to the point to allow an examination of specific biomolecules in processes related to gastric cancer cell invasion through the basement membrane of blood vessels or lymphatics (eg, the first step in developing metastatic disease). Identification of such biomolecules in primary gastric cancer has been enhanced by the establishment of primary human gastric cancer cell lines. These cell lines, named SK-GT for Sloan-Kettering gastric tumor, have provided the basis for a detailed analysis of the invasive phenotype of gastric cancer cells and has resulted in the identification of potentially important prognostic biomarkers. These molecular studies have revealed that in gastric cancer cells there exists a series of integrated biomolecules that are intimately involved in processes related to tumor cell invasion. Included among these are proteins associated with attachment to the basement membrane (ie, laminin receptor) as well as with proteolysis of the basement membrane (ie, matrix metalloproteinase-2, MMP-2). These factors, as well as others, have been clinically evaluated for their prognostic significance in patients with resected, primary gastric cancer. These clinical studies indicate that overexpression of factors associated with the invasion of gastric cancer cells through the basement membrane, including E-cadherin, MMP-2, plasminogen activator inhibitor-1 (PAI-1), and tissue inhibitor metalloproteinase-2 (TIMP-2), can be predictive of tumor recurrence and overall survival in patients with this disease.
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PMID:Invasion and metastases in gastric cancer: in vitro and in vivo models with clinical correlations. 865 15

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

Changes in the expression and function of adhesion molecules on the surface of cancer cells are important characteristics in the development of gastrointestinal malignancies and might be used in the future as prognostic factors or as new targets for diagnostic and therapeutic approaches. In esophageal cancer a down-regulation of the E-cadherin receptor and the cytoplasmic protein alpha-catenin is associated with tumor dedifferentiation, infiltrative growth and lymph-node metastasis. In gastric cancer a reduction of E-cadherin expression due to gene mutations is restricted to diffuse-type tumors while the occurrence of the CD44-standard and the CD44-9v isoform is significantly related to a higher tumor-induced mortality and a shorter survival time. The CD44-6v isoform is predominantly expressed by intestinal-type gastric carcinomas, giving these tumor cells the ability to perform lymph-node metastasis. In pancreatic cancer the expression of integrin adhesion receptors is significantly altered during the malignant transformation while a loss of the E-cadherin receptor can generate dedifferentiation and invasiveness of pancreas carcinoma cells. There is increasing evidence that integrin receptors as well as different isoforms of the CD44 receptor are altered following the malignant transformation of colonic mucosa into adenomas and invasive carcinomas. The expression of the CD44-6v isoform seems to be associated with an adverse prognosis in colorectal cancer due to the development of tumor metastases. A strong correlation has been observed between the expression of the 67-kDa laminin receptor and the degree of differentiation, the invasive phenotype and the metastatic abilities af colorectal cancer cells. Analyzing the expression of the E-cadherin receptor showed that this receptor may serve as an independent prognostic marker in Dukes' stage B colorectal cancer to identify patients with poor prognosis and designate them for intensive adjuvant therapy and clinical observation after curative surgical tumor treatment.
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PMID:Adhesion receptors in malignant transformation and dissemination of gastrointestinal tumors. 877 62

In order to understand the expression and modulation of adhesion molecules (AMs) on the surface of different gastric cancers, we studied 4 gastric-cancer cell lines including SC-M1, KATO-III, AGS and AZ-521. The expression of E-cadherin, integrins (beta1, beta2 and beta3), ICAMs (1 and 2), and CD11 (a, b and c) on the cells was detected by flow cytometry. We found that E-cadherin was only expressed on SC-M1 and KATO-III. CD29 (beta1 integrin) could be found in cells of all 4 lines. CD54 (ICAM- 1) could not be detected in AZ-521. In contrast, CD18 (beta2 integrin), CD61 (beta3 integrin), ICAM-2, CD11a, CD11b and CD11c were all absent from these cells. Heat-shock treatment (42.5 degrees C, 60 min) enhanced the expression of E-cadherin, CD29 and CD54 on SC-M1, and of CD29 on AGS. In addition, TNF-alpha (50U/ml) and IL-1beta (10U/ml) modulated the expression of these AMs, like heat-shock treatment. The increment of these adhesion molecules caused by heat shock, TNF-alpha and IL-1beta stimulation on SC-M1 was also confirmed by Western blot analysis. Functionally, these treatments increased the binding between normal human mononuclear cells and SC-Ml cells. The heat-shock treatment could induce a significant amount of TNF-alpha and IL-1beta release from SC-M1 and KATO-III, but seemed irrelevant to the expression of AMs. These results suggest that limited adhesion molecules were expressed on the surface of different gastric cancer cells. Heat shock, IL-1beta and TNF-alpha may selectively modulate the expression of these 3 molecules on some of the cells, and this is probably related to their antitumor effect.
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PMID:Heat shock and cytokines modulate the expression of adhesion molecules on different human gastric-cancer cell lines. 878 60

Aberrant tyrosine phosphorylation of beta-catenin inactivates the E-cadherin-mediated cell adhesion and invasion suppressor system in cancer cells. Elucidation of the association between beta-catenin and c-erbB-2 protein prompted us to investigate whether interference with this interaction can change the invasive phenotype. In a human gastric cancer cell line, TMK-1, N-terminally deleted beta-catenin, which binds to c-erbB-2 but not to cadherin, inhibited the association between endogenous beta-catenin and c-erbB-2 protein, and suppressed the tyrosine phosphorylation of beta-catenin. Cells expressing truncated beta-catenin exhibited markedly reduced invasiveness in vitro and peritoneal metastasis in vivo, and developed an epithelial morphology. These results suggest that tyrosine phosphorylation of beta-catenin regulated by c-erbB-2 protein may play an important role in the invasion, metastasis and morphogenesis of cancer cells and that inhibition of the aberrant tyrosine phosphorylation of beta-catenin effectively prevents invasion and metastasis of cancer cells.
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PMID:Dominant negative inhibition of the association between beta-catenin and c-erbB-2 by N-terminally deleted beta-catenin suppresses the invasion and metastasis of cancer cells. 880 77

Adhesion receptors on the surface of cancer cells play an important role in tumor cell migration, invasion, and metastasis. A number of specific cell surface-associated molecules that mediate cell-matrix and cell-cell interactions have been characterized, including the family of integrin receptors, the cadherins, the immunoglobulin (IgG) superfamily, a 67-kDa laminin-binding protein, and the CD44 receptor. Changes in the expression and function of these adhesion molecules are important characteristics in the development of gastrointestinal malignancies and might be used in the future as prognostic factors or as new targets in diagnosis and therapy. In esophageal cancer a downregulation of the E-cadherin receptor and the cytoplasmic protein alpha-catenin is associated with tumor dedifferentiation, infiltrative growth, and lymph node metastasis. In gastric cancer a reduction of E-cadherin expression due to gene mutations is restricted to diffuse-type tumors. The occurrence of the CD44 standard and the CD44-9v isoform on the surface of gastric cancer cells is significantly related to a higher tumor-induced mortality and a shorter survival time. The CD44-6v isoform is predominantly expressed by intestinal-type gastric carcinomas giving these tumor cells the ability to metastasize in the lymph nodes. In pancreatic cancer the expression of integrin adhesion receptors is significantly altered during the malignant transformation of the pancreatic tissue while a loss of the E-cadherin receptor can generate dedifferentiation and invasiveness of pancreas carcinoma cells. There is increasing evidence that integrin receptors and different isoforms of the CD44 receptor are altered following the malignant transformation of colonic mucosa into adenomas and invasive carcinomas and thus influencing in their metastatic potential. The expression of the CD44-6v isoform seems to be associated with an adverse prognosis in colorectal cancer due to the development of tumor metastases. A strong correlation could be observed between the expression of the 67-kDa laminin receptor and the degree of differentiation, the invasive phenotype, and the metastatic abilities of colorectal cancer cells. Analyzing the expression of the E-cadherin receptor in colorectal carcinomas it has been shown that this receptor may serve as an independent prognostic marker in Dukes' stage Colon cancer to identify patients with poor prognosis and designate them for adjuvant therapy after curative surgical treatment.
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PMID:Adhesion receptors in malignant transformation and dissemination of gastrointestinal tumors. 889 33

Preoperative staging of gastric cancer is difficult. Several molecular markers associated with initiation and progression of cancer seem promising for obtaining preoperative prognostic information. To investigate whether these markers are indicative especially for the presence of lymph node metastases in patients with gastric cancer, we have examined primary tumour specimens from 105 patients with primary adenocarcinoma of the stomach entered in a surgical trial. In this trial, lymph node status was determined by strictly quality-controlled lymph node dissection and examination. The selected markers were growth regulators (p53, Rb and myc), metastasis-suppressor gene product (nm23), adhesion molecules (Ep-CAM, E-cadherin, CD44v5 and CD44v6) and urokinase-type plasminogen activator (u-PA). Also, the amount of eosinophilic and lymphocytic infiltrates available post-operatively was analysed with respect to its prognostic value for lymph node status. Moreover, the association of these parameters with survival and disease-free period (DFP) was evaluated. Of all molecular markers investigated, only Rb expression had a significant association with the presence of lymph node metastasis in both univariate and multivariate analysis. For curative resectability, a significant association was found with Rb and E-cadherin expression, while in multivariate analysis Rb and myc were selected as the combination with additional independent prognostic value, and E-cadherin had no additional independent value. For overall survival in univariate analysis, the amount of both eosinophilic and lymphocytic infiltrates and Rb and myc expression were of significant prognostic value. Only the amount of lymphocytic infiltrate had a prognostic significance for DFP. In stepwise multivariate analysis, TNM stage (I + II) and marked lymphocytic infiltrate were associated with better overall survival and longer DFP. We conclude that, if these results are confirmed in a larger series of patients, molecular markers can provide useful prognostic information.
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PMID:Expression of oncoproteins and the amount of eosinophilic and lymphocytic infiltrates can be used as prognostic factors in gastric cancer. Dutch Gastric Cancer Group (DGCG). 895 93

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

The E-cadherin-mediated cell adhesion system acts as an "invasion suppressor" system, which is widely considered to be inactivated when the expression of E-cadherin is reduced and/or heterogeneous. To further investigate the molecular mechanisms responsible for dysfunction of this system in cancers, we examined human carcinoma cell lines lacking tight cell-cell adhesion. In KATO-III, established from stomach cancer, a point mutation of the E-cadherin gene resulted in a mRNA splicing error and markedly reduced E-cadherin expression. In another stomach cancer cell line, MKN 45, an 18-bp deletion of the E-cadherin gene caused a mRNA splicing error and a 4-amino-acid deletion, which was considered to alter the conformation around the key Ca(2+)-binding motif. In these two cell lines, the wild-type allele of the E-cadherin locus, which was assigned to chromosome 16q, was lost. Also in vivo, we found mutation of E-cadherin in breast cancers, where allele loss on chromosome 16 has frequently been reported. Thus, dysfunction of E-cadherin could be caused by a combination of the loss of one allele and a mutation in the remaining allele. Homologous deletion of part of the alpha-catenin gene, resulting in markedly reduced expression, was observed in a human lung cancer cell line, PC9. Recently, we also found mutations of beta-catenin in human carcinoma cell lines. These findings indicate the possible involvement of genetic abnormalities of various components in inactivation of the E-cadherin-mediated "invasion suppressor system" in cancers.
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PMID:Alterations of the cadherin-catenin cell adhesion system in cancers. 898 63

The concentrations of the soluble adhesion molecules E-cadherin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were investigated in 45 patients with gastric cancer before treatment and their correlation with clinical, histological and routine laboratory parameters was examined. Data were collected on tumour stage at presentation, presence and sites of metastatic disease, tumour pathology, survival and results of routine laboratory tests. Serum concentrations of ICAM-1 and VCAM-1 were significantly elevated in the patients with gastric cancer in comparison with the group of healthy subjects (P < 0.00001 and P < 0.0001 respectively). Increased serum concentrations of VCAM-1 were associated with locally advanced and metastatic disease whereas ICAM-1 was significantly elevated both in local and in advanced/metastatic disease. Soluble E-cadherin and E-selectin concentrations did not show any significant elevation in gastric cancer patients. Concentrations of soluble adhesion molecules showed significant correlation with each other (except E-selectin and VCAM-1) and with alkaline phosphatase. Soluble ICAM-1 and VCAM-1 were significantly associated with an elevated total white cell count. Patients with elevated VCAM-1 had significantly poorer survival in comparison with patients with normal serum levels (P = 0.0361).
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PMID:Circulating soluble adhesion molecules E-cadherin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in patients with gastric cancer. 940 Sep 33

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