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)

We evaluated the significance of aberrant DNA methyltransferase expression in human carcinogenesis by examining 32 colorectal and 34 stomach cancers. Levels of mRNAs encoding DNA methyltransferases were measured by reverse transcription, followed by real-time quantitative detection of PCR products. The DNA methylation state of CpG islands and peri-centromeric satellite regions was examined by bisulfite modification and Southern blotting, respectively. The average level of mRNA for DNMT1 and DNMT3b in colorectal and stomach cancers was significantly higher than in corresponding non-cancerous mucosae, whereas the average level of mRNA for DNMT2 was significantly lower in colorectal and stomach cancers than in non-cancerous tissue. Over-expression of DNMT3b in stomach cancer was significantly higher in cases with lymph node metastasis than in cases without. DNA hypermethylation on the p16, human Mut L homologue-1 and thrombospondin-1 genes and the methylated in tumor (MINT) 1, 2, 12, 25 and 31 clones was found in 23%, 27%, 9%, 23%, 20%, 23%, 20% and 10% of the colon cancers and in 9%, 19%, 30%, 25%, 34%, 19%, 81% and 3% of the stomach cancers, respectively. Criteria for identification of the CpG island methylator phenotype (CIMP) were met in 23% of colorectal cancers and 31% of stomach cancers. DNA hypomethylation on satellites 2 and 3 was detected in 0% and 8% of colorectal and stomach cancers, respectively. Over-expression of DNMT1 mRNA was significantly associated with CIMP, whereas the level of DNMT3b mRNA was not associated with CIMP or DNA hypomethylation of peri-centromeric satellite regions. These data suggest that both over-expression of the maintenance DNA methyltransferase DNMT1 and over-expression of a newly identified de novo DNA methyltransferase, DNMT3b, are involved in human carcinogenesis, probably at different stages and through different mechanisms.
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PMID:DNA methyltransferase expression and DNA methylation of CPG islands and peri-centromeric satellite regions in human colorectal and stomach cancers. 1114 46

To study the suppression effect of light rare earth elements (RE) on proliferation of two cancer cell lines. Two cancer cell lines PAMC82 and K562 were used to examine their colony-forming ability in soft agar, microtubule structure, calmodulin levels and regulation of some gene expressions by Northern blot analysis with and without treatment by RE. The results showed that on soft agar culture the colony-forming ability of human gastric cancer cell line PAMC82 treated by RE chloride decreased and the PAMC82 cell microtubule abnormal structure became normal. The calmodulin (CaM) levels decreased in human leukemia cells (K562) treated with cerium chloride and neodymium chloride. The Northern blot analysis revealed marked up-regulation of p53, p16(MTS1), p21 (WAF1) gene expressions in PAMC82 cells treated with lanthanum chloride and cerium chloride, as compared to control PAMC82 cells. The light rare earth elements studied have certain suppression effects on proliferation of cancer cells. This effect might be related to the decrease of calmodulin and up-regulation of some gene expressions in cancer cells.
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PMID:The suppression effect of light rare earth elements on proliferation of two cancer cell lines. 1135 62

CDKN2A is thought to be the main candidate gene for melanoma susceptibility. Deletion or mutations in the CDKN2A gene may produce an imbalance between functional p16 and cyclin D, causing abnormal cell growth. We here describe a novel mutation consisting of a 1 bp deletion at nucleotide position 201 (codon 67) (CACGGcGCG) resulting in a truncated protein (stop codon 145). The patient, a female subject from a melanoma-prone family, presented at the age of 47 years with a superficial spreading melanoma of the trunk. Her father had colon cancer at the age of 43 years and melanoma at 63 years, her uncle suffered from gastric cancer, and her grandfather had laryngeal cancer.
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PMID:CDKN2A novel mutation in a patient from a melanoma-prone family. 1159 80

AIM:To investigate the expression of multiple genes and the behavior of cellular biology in gastric cancer (GC) and other gastric mucosal lesions and their relations to Helicobacter pylori (H. pylori) infection, tumor staging and histological subtypes.METHODS:Three hundred and twenty seven specimens of gastric mucosa obtained via endoscopy or surgical resection, and ABC immunohistochemical staining were used to detect the expression of p53, p16, Bcl-2 and COX-2 proteins.H. pylori was determined by rapid urea test combined with patholo-gical staining or 14 Curea breath test. Cellular image analysis was performed in 66 patients with intestinal metaplasia (IM) and/or dysplasia (Dys). In 30 of them, both cancer and the paracancerous tissues were obtained at the time of surgery. Histolo-gical pattern, tumor staging, lymph node metastasis, grading of differentiation and other clinical data were studied in the medical records.RESULTS:p16 expression of IM or Dys was significantly lower in positive H. pylori chronic atrophic gastritis (CAG) than those with negative H. pylori (CAG: 54.8% vs 88.0%, IM:34.4% vs 69.6%, Dys: 23.8% vs 53.6%, all P < 0.05), Bcl-2 or COX-2 expression of IM or Dys in positive H. pylori cases was signi-ficantly higher than that without H. pylori (Bcl-2: 68.8% vs 23.9%, 90.5% vs 60.7%; COX-2: 50.0% vs 10.8%, 61.8% vs 17.8%; all P <0.05). The mean number of most parame-ters of cellular image analysis in positive H. pylori group was significantly higher than that in negative H. pylori group (Ellipser: 53 plus minus 14, 40 plus minus 12&mgr;m, Area(1): 748 plus minus 572, 302 plus minus 202&mgr;m(2), Area(2): 3050 plus minus 1661, 1681 plus minus 1990&mgr;m(2), all P< 0.05; Ellipseb: 79 plus minus 23, 58 plus minus 15&mgr;m, Ratio-1: 22% plus minus5%,13% plus minus4%,Ratio-2:79% plus minus17%,53% plus minus20%,all P<0.01). There was significant correl-ation between Bcl-2 and histologic pattern of gastric carcinoma, and between COX-2 and tumor staging or lymph node metasta sis (Bcl-2: 75.0% vs16.7%; COX-2: 76.0% vs 20.0%, 79.2% vs 16.7%; all P< 0.05).CONCLUSION:p16, Bcl-2, and COX-2 but not p53 gene may play a role in the early genesis/progression of gastric carcinoma and are associated with H. pylori infection. p53 gene is relatively late event in gastric tumorigenesis and mainly relates to its progression. There is more cellular-biological behavior of malignant tumor in gastric mucosal lesions with H. pylori infec-tion. Aberrant Bcl-2 protein expression appears to be preferentially associated with the intestinal type cancer. COX-2 seems to be related to tumor staging and lymph node metastasis.
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PMID:Multiple genetic alterations and behavior of cellular biology in gastric cancer and other gastric mucosal lesions:H.pylori infection, histological types and staging. 1181 7

Silencing of tumor suppressor and tumor-related genes by hypermethylation at promoter CpG islands is one of the major events in human tumorigenesis. Promoter methylation is also present in nonneoplastic cells as an age-related tissue-specific phenomenon that precedes the development of neoplasia. To clarify the significance of promoter methylation in nonneoplastic gastric epithelia as a precancerous signal, we investigated promoter methylation status of E-cadherin, hMLH1, and p16 genes in nonneoplastic cells of various organs obtained at autopsy, and compared the results with those of nonneoplastic epithelia of a cancerous stomach. Methylation of these genes was not seen in nonneoplastic cells of organs from people who were 22 years and younger (0%, 0 of 6). In contrast, E-cadherin and p16 were methylated in nonneoplastic gastric epithelia of persons who were 45 years or older. The numbers were 86% (12 of 14) and 29% (4 of 14), respectively. E-cadherin methylation occurred preferentially in the intestines, whereas p16 methylation was almost restricted to the stomach. For samples obtained from patients with stomach cancer, methylation was frequently observed in both neoplastic and corresponding nonneoplastic gastric epithelia: 47% (44 of 94) and 67% (63 of 94) for E-cadherin, 32% (30 of 94) and 24% (23 of 94) for hMLH1, and 22% (21 of 94) and 44% (41 of 94) for p16, respectively. hMLH1 methylation was not seen in nonneoplastic gastric epithelia from autopsy samples but occurred significantly in samples from nonneoplastic tissues of individuals with stomach cancer. Therefore, detection of hMLH1 methylation in nonneoplastic gastric epithelia may be useful for screening patients who may be at risk of developing gastric cancer.
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PMID:Promoter methylation status of E-cadherin, hMLH1, and p16 genes in nonneoplastic gastric epithelia. 1281 44

Gastric cancer of youth is predominantly a disease of women, usually of the signet-ring cell subtype, with a predilection for metastasizing to the ovaries. The metastatic ovarian tumor is named a Krukenberg tumor. However, the characteristic genetic alterations between the primary gastric cancer and its metastatic ovarian tumor have not been studied. We used laser capture microdissection to procure tissues from 7 patients with gastric cancer who had ovarian metastases (Krukenberg tumor) and tissues from 14 patients with gastric cancer without ovarian metastases. Loss of heterozygosity (LOH) analysis was performed by use of 16 polymorphic markers, which are mapped to the FHIT, APC, p16, BRCA2, E-cadherin, p53, BRCA1, and DPC4 loci. Immunohistochemical staining with anti-Fhit antibody was performed in 7 Krukenberg tumors and 92 gastric cancers without ovarian metastases. LOH at the FHIT locus was observed in six (85.7%) of the seven Krukenberg tumors. In contrast, the gastric cancers without ovarian metastases showed a lower frequency (28.6%, 4/14) of LOH at the FHIT locus (p < 0.05, odds ratio = 1/15). Anti-Fhit antibody showed that expression of Fhit was lost in each of the 7 (100%) Krukenberg tumors but in only 41 (44.6%) of the 92 patients who had gastric cancer without ovarian metastases (p < 0.05; odds ratio = 1/18.614). Further analysis showed that loss of Fhit expression is highly associated with signet-ring cell type gastric cancer (p < 0.0001, odds ratio = 62.5) but is not correlated with prognosis. Alteration of the FHIT gene is a characteristic of signet-ring cell type gastric cancer and Krukenberg tumor.
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PMID:Preferential loss of Fhit expression in signet-ring cell and Krukenberg subtypes of gastric cancer. 1221 81

Promoter hypermethylation is an alternative mechanism of gene silencing in human cancers including gastric cancer. While intestinal metaplasia (IM) is generally regarded as a precancerous lesion of the stomach, our study examines the presence of gene promoter hypermethylation in IM of patients with and without gastric cancer. We examined 31 samples of gastric cancer, 36 gastric IM (21 associated with gastric cancer and 15 from noncancer patients) and 10 normal gastric biopsies. Tissues containing foci of IM were carefully microdissected from paraffin-embedded section. Bisulfite-modified DNA was examined for gene promoter hypermethylation in DAP-kinase, E-cadherin, GSTP1, p14, p15, p16, RASSF1A and hMLH1 by methylation-specific-PCR. None of the control gastric tissues had hypermethylation detected, but gene promoter hypermethylation was frequently detected in gastric cancer and IM. The mean number of methylated genes in cancer and IM was 3.0 and 1.4, respectively (p < 0.0001). Methylation in IM from cancer patients was all associated with concurrent methylation in the corresponding tumor samples. The numbers of methylated genes were similar in IM obtained from cancer and noncancer patients. By examining the methylation patterns of these genes, 3 differential methylation patterns were recognized: hypermethylation was more frequent in cancer than in IM (DAP-kinase, p14, p15 and p16); comparable frequencies of methylation in cancer and IM (E-cadherin and hMLH1); and no methylation (GSTP1). Aberrant methylation in tumor-related genes is frequently detected in gastric IM of both cancer and noncancer patients, suggesting their early involvement in the multistep progression of gastric carcinogenesis.
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PMID:Promoter hypermethylation of tumor-related genes in gastric intestinal metaplasia of patients with and without gastric cancer. 1244 5

The objective of this study was to investigate the contribution of p16 inactivation in gastric cancer and to compare it with p53. A cohort of 34 primary GCs were analyzed for p16 mutations and transcriptional silencing of the gene due to hypermethylation of the promoter. SSCP analysis and direct sequencing of exons 1 and 2 of the p16 gene were performed to detect any structural alterations. The methylation specific PCR (MSP) assay was applied to reveal hypermethylation of the 'CpG' island in the regulatory region using specific primer pairs for methylated and unmethylated nucleotides after a chemical reaction converting cytosines into uracile when unmethylated. SSCP and direct sequencing analysis did not detect any p16 mutations. The MSP assay showed 4 MSP(+) variants (11.8%). Three MSP(+) were stage III-IV disease and 1 MSP(+) was detected in an early stage disease (IB). All MSP(+) were diffuse type adenocarcinomas. The MSP(+) samples were different from previously reported samples harboring p53 mutations in the same cohort. These data increase the number of gastric cancers showing alterations of either p53 or p16 to 29.4% (10/34). Functional inactivation by hypermethylation of the p16 locus and p53 mutations could play a significant, complementary role in the pathogenesis of sporadic gastric cancer.
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PMID:P16 hypermethylation contributes to the characterization of gene inactivation profiles in primary gastric cancer. 1246 65

The stomach is one of the organs whose epithelial cells frequently undergo aberrant methylation of CpG islands. To date, several reports on the methylation of various genes in gastric cancer (GC) have been published. However, most of these studies have focused on cancer tissues or a single gene only and gave no information about the methylation status of specific genes in the premalignant stages or the concurrent methylation of other genes in specific lesions. We attempted to investigate methylation of multiple genes in a large sample collection of GC (n = 80), gastric adenoma (GA) (n = 79), intestinal metaplasia (IM) (n = 57), and chronic gastritis (CG) (n = 74). We determined the methylation frequency of 12 genes, including APC, COX-2, DAP-kinase, E-cadherin, GSTP1, hMLH1, MGMT, p16, p14, RASSF1A, THBS1, and TIMP3, by methylation-specific PCR. Five different classes of methylation behaviors were found: (a). genes methylated in GC only (GSTP1 and RASSF1A), (b). genes showing low methylation frequency (<12%) in CG, IM, and gastric adenoma (GA) but significantly higher methylation frequency in GC (COX-2, hMLH1, p16), (c). a gene with low and similar methylation frequency (8.8-21.3%) in four-step lesions (MGMT), (d). genes with high and similar methylation frequency (53-85%) in four-step lesions (APC and E-cadherin), and (e). genes showing an increasing tendency with or without fluctuation of the methylation frequency along the progression (DAP-kinase, p14, THBS1, and TIMP-3). The average number of methylated genes was 2.7, 3.6, 3.4, and 5.2 per 12 tested genes in CG, IM, GA, and GC, respectively. Aberrant methylation at multiple loci in the same lesions suggests an overall deregulation of the methylation control, which occurs early in multistep gastric carcinogenesis. Our results suggest that tumor-suppressor genes show a gene-type specific methylation profile along the multistep carcinogenesis and that aberrant CpG island methylation tend to accumulate along the multistep carcinogenesis.
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PMID:Profile of aberrant CpG island methylation along multistep gastric carcinogenesis. 1269 55

To date, several reports on methylation of various genes in gastric cancer (GC) have been published. However, most of these studies focused on cancer tissues or a single gene only and gave no information about the methylation status of specific genes in the premalignant stages or about the concurrent methylation of other genes in specific lesions. We attempted to investigate methylation of multiple genes in a large sample collection of GC (n = 80), gastric adenoma (GA) (n = 79), intestinal metaplasia (IM) (n = 57), and chronic gastritis (CG) (n = 74). We determined the methylation frequency of 12 genes, including APC, COX-2, DAP-kinase, E-cadherin, GSTP1, hMLH1, MGMT, p16, p14, RASSF1A, THBS1, and TIMP3 by methylation-specific PCR. Five different classes of methylation behaviors were found: (1) genes methylated in GC only (GSTP1 and RASSF1A); (2) genes showing low methylation frequency (<12%) in CG, IM, and GA, but significantly higher methylation frequency in GC (COX-2, hMLH1, and p16); (3) a gene with low and similar methylation frequency (8.8-21.3%) in four-step lesions (MGMT); (4) genes with high and similar methylation frequency (53-85%) in four-step lesions (APC and E-cadherin); and (5) genes showing an increasing tendency with or without fluctuation of the methylation frequency along the progression (DAP-kinase, p14, THBS1, and TIMP3). The average number of methylated genes was 2.7, 3.6, 3.4, and 5.2 per 12 tested genes in CG, IM, GA, and GC, respectively. Our results suggest that tumor suppressor genes show a gene type-specific methylation profile and that aberrant CpG island methylation tends to accumulate along the pathway of multistep carcinogenesis.
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PMID:Profile of aberrant CpG island methylation along the multistep pathway of gastric carcinogenesis. 1274 73


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