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)

Ample evidence has been provided concerning the presence of tenascin in various histological subtypes of gastric cancer. However, conflict and discussion still persist regarding the correlation with different classification systems and prognostic impact. Therefore, we studied 203 adenocarcinomas of the stomach with special emphasis to the WHO-classification, Lauren's and Goseki's subtypes as well. The immunohistochemical ABC-method was applied using a monoclonal anti-human-tenascin antibody. 30% of all tumours showed a distinct staining reaction. Tubulo-papillary carcinomas (WHO) revealed a significantly stronger reactivity than signet-ring subtypes. Adenocarcinomas of intestinal type (Lauren) were significantly more positive than the diffuse types. Mucin-poor tumours (Goseki I+III) stained positive in a much higher degree compared to mucin-rich subtypes (Goseki II+IV). However, no correlation could been demonstrated regarding TNM-stage or prognosis.
Int J Mol Med 1999 Jul
PMID:Tenascin expression in gastric cancer with special emphasis on the WHO-, Lauren-, and Goseki-classifications. 1037 35

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.
Int J Mol Med 1999 Jul
PMID:Matrix metalloproteinase-1 expression is a prognostic factor for patients with advanced gastric cancer. 1037 41

For tumor progression, a cascade of linked sequential biological events is essential. We tried to test whether biological therapy can modulate specific biological phenotypes and increase the anti-tumor effect when combined with chemotherapy. Five human gastric cancer cell lines (YCC-1, YCC-2, YCC-3, YCC-7, AGS) were used in these studies. Pentosan polysulfate (PPS) as a heparin-binding growth factor inhibitor, Tranexamic acid as a plasmin inhibitor, Lovastatin as an adhesion inhibitor and Adriamycin as a chemotherapeutic agent were selected. The effects of each drug on colony formation and tumor cell proliferation were evaluated by soft agar assay and cell proliferation assay, respectively to test direct anti-tumor effect. The expression of uPA, PAI-1 was determined by ELISA, while MMPs activity was evaluated by zymography. PPS suppressed the colony-forming activity as much as Adriamycin did, but it showed only cytostatic effects in cell proliferation assay. Migration capacity using Boyden chamber assay was more closely correlated with adhesive capacity than uPA or MMP-2 expression. The motility inhibitory effect of Tranexamic acid was observed in the YCC-7 cell line, which expressed all the required biological phenotypes for migration. In AGS, with high cell motility and adhesiveness, the adhesion was inhibited by Lovastatin and most of the inhibitory effect was recovered by Mevalonate. When PPS was combined with Adriamycin on the Adriamycin-resistant, midkine (MK) gene expressing YCC-7 cell line, the growth inhibition rate increased up to 84%, while that for a single treatment of PPS or Adriamycin was 40% and 22%, respectively (p=0.001). When we combined Tranexamic acid and Adriamycin, we observed the synergistic effect in YCC-3 and YCC-7, while no combined effect was found in YCC-1. The combination of Lovastatin and Adriamycin did not show any combined effects in any of the cell lines. In conclusion, a synergistic anti-proliferative effect (chemo-sensitization) with combined chemo-biotherapy was found in cancer cells with specific biological target, MK. The anti-motility effect was the greatest when the gastric cancer cells expressed all the specific biological phenotypes.
Int J Mol Med 1999 Aug
PMID:Modulation of biological phenotypes for tumor growth and metastasis by target-specific biological inhibitors in gastric cancer. 1040 90

Tumor cells in abdominal lavage specimens from patients with gastric carcinoma strongly predict subsequent peritoneal metastasis and poor prognosis. Reverse transcription (RT)-polymerase chain reaction (PCR) detection of wild-type E-cadherin has been claimed to be superior to conventional cytology for the detection of patients who subsequently develop peritoneal metastases. The present study tested this hypothesis and determined whether or not the detection of mutated, tumor-specific E-cadherin messenger RNA in abdominal lavage specimens serve as a useful diagnostic tool. Preoperative lavage specimens from 52 patients with diffuse-type gastric carcinoma and from 5 patients with benign disease were analyzed by conventional cytology and by RT-PCR for amplification of E-cadherin. Tumor cells were detected by cytology in 8 (15.3%) of the 52 patients with gastric cancer. The E-cadherin was detected in all 57 samples by RT-PCR. Two of these had abnormal E-cadherin amplification products confirmed to be mutations by direct sequencing, which were identical in the primary tumors. These findings suggest that the detection of wild-type E-cadherin is not sufficiently tumor specific. Also, for diffuse gastric carcinomas with confirmed E-cadherin mutations, detection of mutant E-cadherin by RT-PCR is a potentially valuable method for tumor cell detection in lavage specimens.
Diagn Mol Pathol 1999 Jun
PMID:Rapid detection of mutated E-cadherin in peritoneal lavage specimens from patients with diffuse-type gastric carcinoma. 1047 80

The prognosis of advanced gastric cancer remains poor, given the frequent incidence of peritoneal metastasis. beta1-integrin is known to be associated with metastasis, though few reports have addressed the expression of beta1-integrin subunits in gastric cancer at primary and peritoneal lesions from the perspective of individual cases. We studied specimens from primary tumors from 50 patients and from metastatic peritoneal lesions from 27 patients with gastric carcinoma, including specimens from 22 metastatic lesions taken from the same patients whose primary tumors were sampled. Expression of beta1-integrin subunits, alpha2-alpha6beta1 integrins, was studied using an immunohistochemical method. alpha2beta1-integrin was significantly expressed on a larger proportion of tumor cells in peritoneal metastasis (70.4%) than in primary tumors (48%) (p<0.05), though alpha3beta1, alpha4beta1, alpha5beta1 and alpha6beta1-integrins did not demonstrate significant discrepancy. The expression of alpha2beta1-integrin in peritoneal lesions was significantly increased compared with its expression in the primary lesion in the same individual. In contrast, no relationship was found between the expression level of beta1 integrins and clinicopathological parameters. Peritoneal implantation of gastric carcinoma might be closely associated with alpha2beta1-integrin.
Int J Mol Med 2000 Jan
PMID:Increased expression of alpha2beta1-integrin in the peritoneal dissemination of human gastric carcinoma. 1060 69

Infection with Helicobacter pylori has been linked to numerous severe gastroduodenal diseases including peptic ulcer and gastric cancer. Several techniques have been used to measure the genetic heterogeneity of H. pylori at several different levels and to determine whether there is any correlation with severity of disease. The availability of two completed genome sequences from unrelated strains (J99 and 26,695) has allowed an analysis of the level of diversity from a large-scale yet detailed perspective. Although the two chromosomes are organized differently in a limited number of discrete regions, the genome size and gene order of these two "high-virulence" (cagA+ and vacA+) H. pylori isolates was found to be highly similar. The regions of organizational difference are associated with insertion sequences, DNA restriction/modification genes, repeat sequences, or a combination of the above. A significant level of variation at the nucleotide level is seen across the genome, providing an explanation for why the nucleotide-based typing techniques have such high discriminatory power among independent H. pylori isolates. This nucleotide variation together with the organizational rearrangements appears to have provided an over-estimation of the gene order diversity of H. pylori as assessed by pulse-field gel electrophoresis. Functional assignments are assigned to approximately only 60% of the gene products in each strain, with one-half of the remaining gene products of unknown function having homologues in other bacteria, while the remainder appear to be H. pylori-specific. Between 6% and 7% of the coding capacity of each strain are genes that are absent from the other strain, with almost one-half of these strain-specific genes located in a single hypervariable region called the plasticity zone. The majority of the strain-specific genes in each strain are also H. pylori-specific, with no homologues being identified in the public databases. Significantly, over one-half of the functionally assigned strain-specific genes in both H. pylori J99 and 26695 encode DNA restriction/modification enzymes. Analysis of the level of conservation between orthologues from the two strains indicates that the H. pylori specific genes have a lower level of conservation than those orthologues to which a putative function can be assigned. The plasticity zone represents one of several regions across each genome that is comprised of lower (G+C)% content DNA, some of which has been detected in self-replicating plasmids, suggesting that both horizontal transfer from other species and plasmid integration are responsible for the strain-specific diversity at this locus. These analyses have yielded results with important implications for understanding the genetic diversity of H. pylori and its associated diseases, and imply a need to reassess the respective roles of bacterial and host factors in H. pylori associated diseases.
J Mol Med (Berl) 1999 Dec
PMID:Analysis of the genetic diversity of Helicobacter pylori: the tale of two genomes. 1068 19

Retinoids exert wide-spectrum anti-tumor activities, which are mediated via the induction of growth arrest, differentiation or apoptosis. To determine whether the effects of retinoids are mediated by specific gene activation or repression, SC-M1 CL23 gastric cancer cells, pretreated with either vehicle alone or all-trans retinoic acid (10 microM) for 1 day, were analyzed using the technique of differential display. A novel retinoid-inducible gene 1 (RIG1) was isolated. The full-length RIG1 cDNA contained 768 base pairs and encoded a protein of 164 amino acids with a molecular weight of 18 kDa. The RIG1 gene was ubiquitously expressed in normal tissue, and its expression was positively associated with cellular density. Nucleotide sequence analysis demonstrated that the RIG1 gene was similar to a recently-isolated TIG3 gene, and displayed 54% nucleotide sequence homology with a type II tumor suppressor gene H-REV-107-1. RIG1 cDNA, however, contained an extra 32 base pairs located at its 5' end and revealed three base pair differences for the remaining sequences leading to two amino acids substitution between the two encoded proteins. All-trans retinoic acid increased the level of RIG1 mRNA in a time- and concentration-dependent manner in SC-M1 CL23 gastric cancer cells. This was not observed for the H-REV-107-1 gene. The RIG1 regulation was related to cellular retinoid sensitivity. Both retinoic acid receptor alpha- and retinoic acid receptor gamma-selective agonists increased RIG1 mRNA level, and the retinoid x receptor-selective agonist potentiated this regulation. In conclusion, the cDNA of a novel retinoid-inducible gene RIG1 has been cloned. This gene is regulated by retinoic acid through the heterodimer of retinoic acid receptor and retinoid x receptor.
Mol Cell Endocrinol 2000 Jan 25
PMID:Cloning and characterization of a novel retinoid-inducible gene 1(RIG1) deriving from human gastric cancer cells. 1068 48

The topographical organisation of the epithelium lining mucous membranes has been an intense point of research. One of the fundamental biological issues underpinning this and associated issues relates to the role and regulation of epithelial adhesion molecules. Adhesion between individual cells allows an intact layer to be formed, which is selectively permeable. In addition, the orchestrated regulation of multiple adhesion molecules allows the gradual transition from basal secretory cells to apical absorptive cells in the crypt-villus gradient. Moreover, it is becoming clear that no one class of adhesion molecule can sufficiently govern crypt architecture; however, the main cell-cell adhesion molecules are the cadherins and the related desmosomal cadherins. These latter molecules interact with the catenins, which bind directly or indirectly with cytoskeletal molecules such as Rho and Rac. In addition, other complex glycoproteins, such as the carcinoembryonic antigens, might contribute to adhesion, although their mechanisms of function are distinctly different. Integrins on the basal aspect of the cells also signal important morphoregulatory signals as a result of their binding to the extracellular maxtrix. The disruption of these physiological processes also provides a necessary and, in some cases, sufficient molecular mechanism for cancer invasion and metastasis, such as occurs in E-cadherin mutation positive familial gastric cancer.
Mol Pathol 1999 Aug
PMID:Cadherin adhesion in the intestinal crypt regulates morphogenesis, mitogenesis, motogenesis, and metaplasia formation. 1069 34

Gastrointestinal tract tumours are notorious for their difficulty in relation to conventional cytogenetic analysis. In particular, necrosis, the presence of stromal inflammatory and other cells, and poor attachment of tumour cells have led to problems with the quality and reliability of cytogenetic preparations, even with the recently developed fluorescence in situ hybridisation (FISH) technique. Furthermore, background autofluorescence masks the weak hybridisation signals in the nuclei. To overcome this problem, brief microwave treatment was applied for the identification of centromeres by in situ hybridisation in gastric cancer cells. Using this technique, a panel of 17 centromeric specific alpha-satellite probes was used to detect chromosomal instability in these cells. Lymphocyte controls and cancer cells subjected to irradiation achieved the hybridisation threshold in 30 minutes, providing a significant difference when compared with the non-irradiated samples (mean (SD) frequency of diploid cells 97% (2.1%) v 76% (4.6%), respectively). Therefore, this protocol of intermittent microwave treatment is recommended as a simple, rapid, and highly reproducible technique for application to various types of probe. It also gives well defined hybridisation signals and reduces background "noise".
Mol Pathol 1999 Dec
PMID:Amplification of FISH signals using intermittent microwave irradiation for analysis of chromosomal instability in gastric cancer. 1074 71

Microsatellite markers permit the analysis of microsatellite instability and loss of heterozygosity. Frequently, the allelotypes of microsatellites are interpreted in the presence of numerous bands in gels. The importance of different gel electrophoresis conditions in the interpretation of microsatellite patterns was tested. Microsatellite markers were used to amplify DNA from gastric cancer samples and adjacent gastric mucosa. Polymerase chain reaction (PCR) products were separated by electrophoresis through 7% polyacrylamide gels containing either 5.6 M urea and 32% formamide or 7 M urea. PCR reactions separated on urea/formamide gels resulted consistently in clear allele definition (one or two bands), whereas 7 M urea gels resulted in allele patterns that comprised multiple bands. Analysis of microsatellite abnormalities using nonformamide gels gave false negative results in just under a third of cases (four of 13). In conclusion, the interpretation of microsatellite alterations in cancer DNA is improved by using electrophoresis conditions that result in complete DNA denaturation, such as urea/formamide/acrylamide gel electrophoresis.
Mol Pathol 1999 Oct
PMID:Variability in the interpretation of microsatellite patterns with different electrophoretic conditions. 1074 82


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