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)

Twenty gastric carcinoma cases were studied for the detection of CD44 aberrant transcripts using a cDNA/PCR/blot-hybridization technique which can detect splice variants containing an aberrant exon 11 of the CD44 gene. All the tumor tissues as well as their metastatic foci demonstrated overexpression of CD44 splice variants of more than 1.0 kbp than corresponding normal gastric mucosas. Six out of nine (66.7%) well-differentiated or intestinal type gastric cancers overexpressed more than three aberrant transcripts, whereas ten out of eleven (90.9%) poorly differentiated or diffuse type cancers overexpressed single or two lower molecular weight variants. These results indicate that the detection of CD44 transcription variants can serve as a powerful tool for the diagnosis of gastric cancer. It is also suggested from the difference in variant expression pattern that well-differentiated type and poorly differentiated type gastric carcinomas have different genetic pathways.
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PMID:Expression of CD44 abnormal transcripts in human gastric carcinomas. 752 Mar 54

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

Knowing the differential expression of CD44 isoforms in intestinal- and diffuse-type gastric carcinomas, we used antibodies against the standard form of CD44 (CD44s) and the domain encoded by exon v6 (CD44v6) in 103 patients with primary gastric adenocarcinomas to explore the role of CD44 isoforms in metastases of both types of gastric cancer. Carcinomas of the intestinal type were more frequently CD44s and CD44v6 positive than carcinomas of the diffuse type (p = 0.034 for CD44s and p = 0.022 for CD44v6). The reactivity to these two antibodies did not correlate with histopathological and clinical prognostic factors in intestinal-type carcinoma. In contrast, expression of CD44v6 was associated with infiltrative tumor growth (p = 0.021), depth of invasion (p = 0.012), lymph node involvement (p = 0.005) and a higher incidence of distant metastasis (p = 0.069) in cancers of the diffuse type. CD44s-expressing diffuse-type tumors had a higher incidence of distant metastasis at presentation (p = 0.001), but expression of CD44s was not correlated with other clinicopathologic indices. For all cases, there was a nonsignificant association between CD44s expression and poor survival. Unexpectedly, there was also no significant difference in survival regarding expression of CD44v6 for all cases or the diffuse-type subset. This study showed the role of CD44v6 in invasion and metastases of diffuse-type gastric carcinoma and demonstrated the necessity of subclassifying tumor types when studying the clinical significance of CD44 in human cancers.
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PMID:Expression of CD44 and its clinical implication in diffuse-type and intestinal-type gastric adenocarcinomas. 753 3

The aim of this study was to compare the distribution of CD44 variants 5 and 6 in normal mucosa and gastric cancer and to determine their relationship with histoclinical Parameters of the disease. Experimental material included 112 paraffin blocks of various human gastric carcinomas. Both variants of CD44 were detected immunohistochemically with primary antibodies deriving from Bender Med. Systems. In normal gastric mucosa positive reactions with both antibodies were observed in surface epithelium, parietal cells, myocytes and vascular endothelia. They were also found in intestinal enterocytes, esophageal epithelium and myoepithelial. Additional reactivity with antibodies against variant 6 was observed in Paneth cells. In gastric cancer, variants 5 and 6 were demonstrated in 91% and 64% of cases respectively, without significant correlation with the tumor type. The occurrence of variant 6 correlated positively with tumor size (p = 0.081) and negatively with histological grading (p = 0.093). The relationship with metastases was insignificant.
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PMID:Immunohistochemical localization of CD44 variants 5 and 6 in human gastric mucosa and gastric cancer. 754 68

CD44 abnormal transcription in gastric carcinomas is overviewed. The overexpression of aberrant CD44 transcripts detected by RT-PCR/Southern blot hybridization method is a common genetic event in gastric carcinomas regardless of the histological type or clinicopathological stage. In addition, six out of nine (66.7%) well differentiated or intestinal type gastric cancers overexpressed more than three aberrant transcripts, whereas ten out of eleven (90.9%) poorly differentiated or diffuse type cancers overexpressed single or two lower molecular weight variants. These results indicate that the detection of CD44 transcription variants can serve as a powerful tool for the diagnosis of gastric cancer. It is also suggested from the difference in variant expression pattern that the well differentiated and the poorly differentiated type gastric carcinomas have different genetic pathways.
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PMID:[Abnormal transcription of cell adhesion molecule CD44 in human gastric carcinomas]. 763 9

Gastric cancer involves changes in multiple oncogenes and multiple suppressor genes, and it causes genetic instability. Aberrant expression and amplification of the c-met gene, inactivation of the p53 gene, and CD44 abnormal transcripts are common events of both well differentiated and poorly differentiated gastric cancers. Amplification of the cyclin E gene is also observed in gastric cancer regardless of histologic type. Decreased expression of the pic1 (p21) gene occurs independent of the p53 mutations. In addition, K-ras mutations, c-erbB-2 gene amplification, loss of heterozygosity (LOH) and mutations of the APC gene, LOH of the bcl-2 gene, and LOH at the DCC locus are preferentially associated with well differentiated gastric cancer. Moreover, LOH on chromosome 1q is involved in the progression of well differentiated cancer. Precancerous lesions, including hyperplastic polyp, intestinal metaplasia, and adenoma, share genetic changes found in well differentiated cancers. Conversely, genetic instability may be involved in the first step of stomach carcinogenesis of the poorly differentiated type. Reduction or loss of cadherin and catenins, K-sam gene amplification, and c-met gene amplification are necessary for the development and progression of poorly differentiated or scirrhous carcinoma. Interaction between cell-adhesion molecules in the c-met expressed tumor cells and hepatocyte growth factor from stromal cells is implicated in the morphogenesis of two types of gastric cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Molecular biology of gastric cancer. 767 88

Immunohistochemical screening of gastric adenocarcinomas from 42 different patients revealed variant CD44 expression in all specimens tested. Adenocarcinomas of the intestinal type were strongly positive for epitopes encoded by variant exons v5 and v6, whereas diffuse-type adenocarcinomas predominantly expressed only exon v5. Normal stomach mucosa was stained by an exon v5-specific monoclonal antibody within the foveolar proliferation zone and on mucoid surface epithelium. Areas of intestinal metaplasia reacted positively with monoclonal antibodies specific for exons v5 and v6. Analysis of RNA expression revealed dramatic differences between normal mucosa and adenocarcinomas. Whereas in normal epithelium only two CD44 variant RNAs containing exons v5 and/or v6 could be detected, intestinal-type tumors yielded a much more complex pattern of amplification products which hybridized to exons v5 and v6. A similar complex expression pattern of CD44 variants was observed in three cell lines established from intestinal-type tumors. In a sample of a diffuse-type tumor, expression of exon v5, but not v6, could be detected, confirming the data obtained with immunohistochemistry. These differences in variant exon v6 expression observed between diffuse-type and intestinal-type stomach adenocarcinomas establish variant CD44-specific antibodies as a tool in gastric cancer diagnosis and also support the theory of different origins for these tumor types.
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PMID:Differential expression of CD44 splice variants in intestinal- and diffuse-type human gastric carcinomas and normal gastric mucosa. 768 29

Gastrointestinal cancers involve genetic alterations in multiple oncogenes, multiple tumor suppressor genes, and multiple DNA repair genes. However, common and different genetic changes are observed in esophageal, gastric, and colorectal carcinomas, respectively. Inactivation of the p53 gene and expression of CD44 abnormal transcripts are common events that serve as a powerful tool for cancer diagnosis. Gene amplification of cyclin D is found preferentially in esophageal cancer, whereas gene amplification of cyclin E and c-met is frequently associated with gastric cancer. Mutations of the cyclin-dependent kinase inhibitor genes also occur in esophageal and gastric cancers. However, the scenario of multiple gene changes differs depending on the two histologic types of gastric cancer, because they may have different genetic pathways. Interestingly, the frequency of genetic instability is also quite different between the two types of gastric cancer. A new strategy of molecular diagnosis for gastrointestinal cancers, which started as routine work at Hiroshima City Medical Association Clinical Laboratory last August, may provide a new approach to cancer diagnosis for the next decade.
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PMID:Genetic alterations in human gastrointestinal cancers. The application to molecular diagnosis. 788 67

Alterations in the structure and function of oncogenes and tumor suppressor genes, as well as genetic instability at several other genetic foci may be responsible for stomach carcinogenesis. The particular combination of multiple gene changes found in gastric cancer differs depending on the two histological types, strongly indicating that different genetic pathways exist for well differentiated or intestinal type and poorly differentiated or diffuse type gastric cancers. In general, genetic instability, telomerase activity, CD44 abnormal transcripts, and p53 mutation, all of which are common events of two types of gastric cancer, may be involved mainly in the early stage of stomach carcinogenesis, whereas activation of oncogenes and overexpression of the epidermal growth factor-related growth factor system may chiefly confer progression on gastric cancer. A new strategy of molecular diagnosis of gastrointestinal cancer, which has been implemented as a routine service in the Hiroshima University Clinical Laboratory, may provide new opportunities for early cancer diagnosis and more accurate evaluation of prognosis or grade of malignancy.
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PMID:Molecular biological observations in gastric cancer. 865 14

A splice variant of CD44 (exon V4-V7) confers metastatic behavior in a rat carcinoma model; aberrant expression of splice variants has been detected on a variety of human tumor cell lines as well as primary and metastatic human tumors, including lymphomas, carcinomas (colon, thyroid, mamma, bladder), and glioma. We used enzyme-linked immunosorbent assay to determine the concentration of soluble CD44 in the serum samples of 10 normal individuals and 41 patients with various stages of gastric cancer. Soluble CD44S and its isoforms, V5 and V6, were present in the serum of normal individuals (288.53 +/- 18.33, 25.49 +/- 1.70, and 148.32 +/- 3.15 ng/ml, respectively). The concentrations of soluble CD44 V5 and V6 were elevated in patients with advanced gastric carcinoma (69.39 +/- 6.06 and 216.62 +/- 32.98 ng/ml, respectively). Serum CD44 V5 concentrations correlated with the extent of tumor invasion (T), the status of lymph node involvement (N), and distant metastasis (M) (TNM staging) (p < 0.05), whereas CD44S did not. These results suggest that detection of abnormal regulation of CD44 splicing could be helpful in gastric cancer diagnosis and disease evaluation.
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PMID:Soluble CD44 isoforms in serum as potential markers of metastatic gastric carcinoma. 874 47


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