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)

E-cadherin (ECD) is one of subclasses of the cadherin family which plays a major role in the maintenance of intercellular adhesion in epithelial tissues. An immunohistochemical study of ECD expression was performed on gastric adenocarcinoma from 103 patients using our monoclonal antibody for human ECD (HECD-1). ECD was strongly expressed in normal gastric epithelium without exception; however, various staining patterns were observed in cancer tissues. The frequency of tumours with preserved ECD expression (Pre-type) and reduced ECD expression (Rd-type) was 42% and 58% respectively. Tumours with a high frequency of Rd-type expression particularly included: undifferentiated tumours (85%, 46/54), Borrmann's type 4 (90%, 9/10), tumours larger than 2.6 cm in diameter (65%, 53/81), tumours invading beyond the subserosa layer (78%, 46/59), and tumours with infiltrative growth (87%, 41/47). Furthermore, the frequency of Rd-type expression in cases with peritoneal dissemination (82%, 9/11) or lymph node metastasis (73%, 43/59) was significantly higher than that in cases without dissemination or metastasis. These results suggest that ECD might play a key role in the genesis of histological differentiation, and that the reduction of ECD expression may affect the mode of invasion and metastasis of human gastric cancer cells.
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PMID:Immunohistochemical evaluation of E-cadherin adhesion molecule expression in human gastric cancer. 151 46

The prerequisite for a curative resection of metastases is their restriction to the key organs, the liver and lungs, in the sense of a limited dissemination. For long-term prognosis, the type of primary tumor as well as the radical resection of lung and liver metastases is essential. To improve the process of surgical indication and therapy of tumors, clear definitions for the terms "tumor recurrence" and "metastases" have been agreed upon. Research and clinical investigation have led to a better understanding of tumor-regulating factors, some of which are briefly described: Metastasis promoting factors include the lack of E-cadherin, which leads to a local penetration of basal membranes by tumor cells; CD44 seems to play an important role in cell-cell and cell-matrix interactions, apparently increasing the metastatic potential of tumors and reducing the long-term survival of patients. High levels of urokinase in primary tumors are also associated with a poorer prognosis, as well as plasminogen inactivator inhibitor PAI II, which plays a crucial role in tumor growth. Positive findings in bone marrow aspirates of patients with different malignancies, stained for cytokeratin 18, either are associated with higher recurrence rates in colon and breast cancer or can be correlated to the prognosis of patients with gastric cancer. Technical aspects of surgery for hepatic, pulmonary and skeletal metastases are presented and discussed with respect to curative and palliative indications.
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PMID:Surgical treatment of tumor metastases: general considerations and results. 753 64

E-cadherin is a calcium dependent cell-cell adhesion molecule. In cancer tissue, detachment of the adhesion system is indispensable for invasion and metastasis of cancer cells. We have investigated mechanism of the dysfunction of E-cadherin-dependent cell-cell adhesion system in gastric carcinoma cells. Although the high expression of E-cadherin in a scirrhous gastric cancer cell line HSC-39, the function of E-cadherin was completely abolished. Western blotting of beta-catenin in HSC-39 cells demonstrated that a truncated beta-catenin was detected. The truncation was due to partial deletion of beta-catenin DNA. It was concluded that in HSC-39 loss of E-cadherin dependent cell-cell adhesion was due to mutation of beta-catenin gene.
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PMID:[Dysfunction of E-cadherin due to mutation of beta-catenin in a scirrhous gastric cancer cell line]. 762 93

E-cadherin, Ca(2+)-dependent intracellular adhesion molecule, is known to be an invasion suppressor gene. To elucidate the correlation between E-cadherin expression and invasion or metastasis in gastric cancer, we examined E-cadherin tissue status immunohistochemically. Ninety-eight primary gastric cancer, prepared by AMeX method, were retrospectively analyzed with anti-E-cadherin monoclonal antibody. In normal gastric epithelium, E-cadherin is expressed homogeneously with a typical membranous staining at cell-cell borders. Decreased and heterogeneous expression is found in 70 of 98 tumours. Tumours with decreased E-cadherin expression had a tendency to infiltrate more deeply in stomach wall, and metastasize in lymph nodes or peritoneal surface. More importantly, decreased E-cadherin expression correlates with shorter survival (z = 3.98, P = 0.00086). These results may indicate that E-cadherin tissue status is a powerful prognostic indicator in gastric cancer. The high malignant potential of tumours with decreased E-cadherin expression may be associated with high potential of lymph node metastasis and peritoneal dissemination.
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PMID:Decreased E-cadherin expression correlates with poor survival in patients with gastric cancer. 778 14

Detachment of cell-cell adhesion is indispensable for the first step of invasion and metastasis of cancer. This mechanism is frequently associated with the impairment of either E-cadherin expression or function. However, mechanisms of such abnormalities have not been fully elucidated. In this study, we demonstrated that the function of E-cadherin was completely abolished in the human gastric cancer cell line HSC-39, despite the high expression of E-cadherin, because of mutations in one of the E-cadherin-associated cytoplasmic proteins, beta-catenin. Although immunofluorescence staining of HSC-39 cells by using an anti-E-cadherin antibody (HECD-1) revealed the strong and uniform expression of E-cadherin on the cell surface, cell compaction and cell aggregation were not observed in this cell. Western blotting (immunoblotting) using HECD-1 exhibited a 120-kDa band which is equivalent to normal E-cadherin. Northern (RNA) blotting demonstrated a 4.7-kb band, the same as mature E-cadherin mRNA. Immunoprecipitation of metabolically labeled proteins with HECD-1 revealed three bands corresponding to E-cadherin, alpha-catenin, and gamma-catenin and a 79-kDa band which was apparently smaller than that of normal beta-catenin, indicating truncated beta-catenin. The 79-kDa band was immunologically identified as beta-catenin by using immunoblotting with anti-beta-catenin antibodies. Examination of beta-catenin mRNA by the reverse transcriptase-PCR method revealed a transcript which was shorter than that of normal beta-catenin. The sequencing of PCR product for beta-catenin confirmed deletion in 321 bases from nucleotides +82 to +402. Southern blotting of beta-catenin DNA disclosed mutation at the genomic level. Expression vectors of Beta-catenin were introduced into HSC-39 cells by transfection. In the obtained transfectants, E-cadherin-dependent cell-cell adhesiveness was recovered, as revealed by cell compaction, cell aggregation, and immunoflourescence staining. From these results, it was concluded that in HSC-39 cells, impaired cell-cell adhesion is due to mutations in beta-catenin which results in the dysfunction of E-cadherin.
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PMID:Loss of E-cadherin-dependent cell-cell adhesion due to mutation of the beta-catenin gene in a human cancer cell line, HSC-39. 786 12

Monoclonal antibodies were raised against human placental soluble E-cadherins and used in an immunoenzymometric assay to detect soluble E-cadherins in biological fluids. The E-cadherin assay was accurate enough to quantitate the concentration of soluble E-cadherin in the cell culture supernatants. Immunoreactive E-cadherins, identified as existing in the soluble form in normal serum, were shown to have apparent lower molecular mass (approximately 80 kDa) than intact molecules of E-cadherin. We found that the immunoreactive E-cadherin levels in the serum of the studied cancer patients were significantly elevated (mean +/- s.d. 3.80 +/- 2.36 micrograms ml-1, P < 0.0001) when compared with the normal levels (1.99 +/- 0.50 micrograms ml-1). We also found that serum E-cadherin levels in the 22 patients with gastric cancer (3.51 +/- 1.78 micrograms ml-1, P < 0.02) or the 11 patients with hepatocellular cancer (5.55 +/- 3.11 micrograms ml-1, P < 0.001) were significantly higher than those in the 26 diabetic patients (2.33 +/- 1.58 micrograms ml-1). Of the 54 cancer patients, 53.7% exhibited an elevated amount of soluble E-cadherin in serum. Thus, it is evident that soluble E-cadherin in circulation can be used as a prospective tumour marker that accurately reflects the progressive regeneration of E-cadherin at tumour sites, potentially induced by tumour-associated proteolytic degradation.
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PMID:Soluble E-cadherin fragments increased in circulation of cancer patients. 812 91

We established a peritoneal-metastatic model for scirrhous gastric carcinoma. Peritoneal metastasis had developed after intraperitoneal inoculation of OCUM-2MD3 cells in nude mice. This cell line was derived from a peritoneal-metastatic nodule at the mesenterium after orthotopic implantation of OCUM-2M cells which developed no peritoneal metastasis after intraperitoneal inoculation. The histologic findings of orthotopic-implanted tumor in the stomach show scirrhous type while those of subcutaneous-implanted tumor show medullary type. There might be factors, in OCUM-2MD3 cells, which are responsible for peritoneal metastasis. We next investigated the differences in the biological behavior of the original OCUM-2M and the derived variant OCUM-2MD3. Morphology and growth activity of the two cell lines were similar to each other. The specific chromosomes, add(6)(q13), del(7)(q21.2) and inv(11)(p13q21), were found in OCUM-2MD3 cells but not in OCUM-2M cells. While the oncogenes amplification by OCUM-2M cells was found in K-sam and c-myc, that by OCUM-2MD3 cells was found only in c-myc. The expression of E-cadherin by OCUM-2MD3 cells was decreased compared with that of OCUM-2M cells. Expression level of beta 1-integrin of OCUM-2MD3 cells were higher than that of OCUM-2M cells. The binding and invasion activity of OCUM-2MD3 cells were higher than those of OCUM-2M cells, and were decreased by anti-beta 1-integrin antibody. The invasion activity of OCUM-2MD3 cells was increased in the presence of peritoneal fibroblast. In this study, it was suggested that orthotopic implantation of cancer cells might have an effect on the acquisition of metastatic ability. beta 1-integrin and peritoneal fibroblasts might be correlated with peritoneal metastasis. This peritoneal-metastatic model should be useful for analysing the mechanism of peritoneal metastasis of human scirrhous gastric cancer.
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PMID:Peritoneal metastatic model for human scirrhous gastric carcinoma in nude mice. 852 16

There is a need to establish animal models which are suitable for investigation of human gastric cancer metastasis to the liver. To this end, a human gastric carcinoma line, AZ521 was injected into the spleens of nude mice. Cells from the few liver metastatic foci of injected AZ521 were expanded "in vitro" and subsequently injected into the spleens of nude mice. By repeating these procedures three times, we were able to obtain a cell line, designated as AZ-H3c, with high metastatic potential in nude mice. Liver metastasis developed in 15 of 21 (71%) animals injected with AZ-H3c, but only in 14% of those injected with parental AZ521. Further, AZ-H3c caused faster tumor development than did AZ521. However, the primary AZ-H3c tumors and liver metastatic AZ-H3c tumors showed essentially the same histological appearance. We also analyzed the cell surface expression of adhesion molecules. The data showed that the expression of VLA-1, VLA-2, VLA-3, VLA-4, VLA-5 was enhanced in AZ-H3c. In contrast, the expression of VLA-6, (alpha(v)beta3), E-cadherin, ICAM-1 and LFA-1 was reduced in this high-metastatic line. These results suggest that (beta1) integrins play an important role in the liver metastasis of human gastric carcinoma cells. Our high-metastatic line should be useful for studies aimed at the prevention of liver metastasis.
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PMID:Establishment and characterization of human gastric carcinoma lines with high metastatic potential in the liver: changes in integrin expression associated with the ability to metastasize in the liver of nude mice. 860 64

This study is a comparative analysis of the prevalence, absolute number and aggregation status of bone marrow micro-metastases (BMM) between breast (n=234) and gastric (n=102) cancer patients based on a standardized number of 1 X 10(6) bone marrow-derived cells per patient. Additionally, expression of the epithelial cell adhesion molecule E-cadherin was analyzed on disseminated tumor cells. A positive BMM status was demonstrated in 88/234 breast and 45/102 gastric cancer patients. The presence of CK18+ cells positively correlated with parameters of advanced tumor progression in breast, but not in gastric cancer. Interestingly, 25.2% of the node-negative patients already had micrometastatic cells in the bone marrow at diagnosis. Regarding the absolute number of CK18+ cells and the frequency of CK18+ cell clusters, no significant difference was found between the 2 tumor types. However, clusters consisting of more than 10 CK18+ cells (type II clusters) were present exclusively in breast cancer patients. Additionally, co-expression of CK18 and E-cadherin was detectable in 15/21 micrometastases-positive breast but in only 1/9 gastric cancer patients. While prevalence of micrometastatic cells in bone marrow is discussed as an early indicator for systemic disease, aggregation status and a certain antigen profile might be indicative for site-specific differences in the manifestation pattern of solid metastases.
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PMID:Comparative analyses of bone marrow micrometastases in breast and gastric cancer. 863 87

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


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