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)

The presence of high levels of aberrant DNA methylation in gastric mucosae correlates with risk of gastric cancer. Some gastric cancers are known to have methylation of multiple CpG islands (CGI), which is referred to as the CGI methylator phenotype (CIMP). In the present study, we aimed to clarify the possible association between the CIMP in cancers and high methylation levels in their background mucosae by accurate quantitative methylation analysis of 14 carefully selected promoter CGI. Methylation levels were measured in 66 cancers and their background mucosae, along with 19 normal mucosae of healthy volunteers. Methylation in cancers was classified as absent (methylation level = 0%) or positive. The number of methylated CGI in a cancer showed a continuous distribution, and cancers were classified as CIMP high (21 cases), CIMP low (30 cases), or CIMP negative (15 cases). CIMP-high gastric cancer patients had significantly better survival rates than CIMP-negative patients. Of the Epstein-Barr virus-positive gastric cancers studied, eight out of nine presented as CIMP high. Methylation in background mucosae showed a unimodal distribution, and was assessed by their degree. The gastric mucosae of cancer patients showed higher levels than normal gastric mucosae of healthy volunteers. Finally, the CIMP-high, CIMP-low, and CIMP-negative statuses in cancers were not associated with methylation levels of individual genes and their means in the background mucosae. These showed that the CIMP statuses in gastric cancers had no association with methylation levels in the background gastric mucosae.
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PMID:Lack of association between CpG island methylator phenotype in human gastric cancers and methylation in their background non-cancerous gastric mucosae. 1790 Feb 60

Among 185 cases of gastric cancer and 200 controls in Linxian, China, Epstein-Barr virus (EBV) seropositivity was not associated with increased risk of gastric cancer. High EBV nuclear antigen titres were associated with longer survival in cardia cancer cases, possibly due to chance.
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PMID:Epstein-Barr virus serology and gastric cancer incidence and survival. 1798 41

Here we report the case of a patient with advanced gastric cancer with esophageal invasion who was treated with chemotherapy using S-1 and cisplatin (CDDP) preoperatively. The patient was a 72-year-old woman who was diagnosed with advanced gastric cancer (T3N2M0) with esophageal invasion. S-1 was orally administered at 80 mg/day (60 mg/m(2) per day) on days 1-14 and CDDP was infused at 80 mg/day (60 mg/m(2) per day) on day 8, followed by a 1-week rest. Marked reductions in the sizes of the primary tumor and metastatic lymph nodes around the stomach were observed after two cycles of the therapy. Adverse reactions occurring during the therapy were only grade 2 gastrointestinal disorder and grade 1 leukocytopenia. Radiological and endoscopic examinations before surgery showed that a partial response (PR) had been achieved. The patient underwent curative surgery consisting of total gastrectomy, D2 lymph node dissection, and splenectomy. Her postoperative course was uneventful, without surgical complications. No gastric cancer cells were detected in the primary lesion or lymph nodes by immunohistochemical staining with cytokeratin, confirming a histological complete response (CR). As Epstein-Barr virus-encoded small RNA (EBER) had been detected by in-situ hybridization in the gastric cancer cells of a biopsy specimen, this tumor was diagnosed as an Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC), which was effectively treated with S-1 and cisplatin chemotherapy.
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PMID:Complete response of a patient with advanced gastric cancer, showing Epstein-Barr virus infection, to preoperative chemotherapy with S-1 and cisplatin. 1807 68

Gastric cancer cells often show altered Ras signaling, though the underlying molecular mechanism is not fully understood. We examined the expression profile of eight ras-association domain family (RASSF) genes plus MST1/2 and found that RASSF2A is the most frequently downregulated in gastric cancer. RASSF2A was completely silenced in 6 of 10 gastric cancer cell lines as a result of promoter methylation, and expression was restored by treating the cells with 5-aza-2'-deoxycytidine. Introduction of RASSF2A into non-expressing cell lines suppressed colony formation and induced apoptosis. These effects were associated with the cytoplasmic localization of RASSF2A and morphological changes to the cells. Complementary DNA microarray analysis revealed that RASSF2A suppresses the expression of inflammatory cytokines, which may in turn suppress angiogenesis and invasion. In primary gastric cancers, aberrant methylation of RASSF2A was detected in 23 of 78 (29.5%) cases, and methylation correlated significantly with an absence of the lymphatic invasion, absence of venous invasion, absence of lymph node metastasis, less advanced stages, Epstein-Barr virus, absence of p53 mutations and the presence of the CpG island methylator phenotype-high. These results suggest that epigenetic inactivation of RASSF2A is required for tumorigenesis in a subset of gastric cancers.
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PMID:Cytoplasmic RASSF2A is a proapoptotic mediator whose expression is epigenetically silenced in gastric cancer. 1831 Jun 59

The association of Helicobacter pylori (H. pylori) with gastric cancer is thus far the best understood model to comprehend the causal relationship between a microbial pathogen and cancer in the human gastrointestinal tract. Besides H. pylori, a variety of other pathogens are now being recognized as potential carcinogens in different settings of human cancer. In this context, viral causes of human cancers are central to the issue since these account for 10-20% of cancers worldwide. In the case of H. pylori and gastric cancer, as well as the human papillomavirus and anal cancer, the causal relationship between the infectious agent and the related cancer in the gastrointestinal tract has been clearly confirmed by epidemiological and experimental studies. Similarly, Epstein-Barr virus and the oncogenic JC virus are being suggested as possible causative agents for cancers in the upper and lower gastrointestinal tract. This review discusses various viral and microbial pathogens and their oncogenic properties in the evolution of gastrointestinal carcinogenesis and summarizes the available experimental data make a convincing agreement favoring the associations between infectious agents and specific human cancers.
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PMID:The role of viral and bacterial pathogens in gastrointestinal cancer. 1833 78

Gastric cancer is the most common cancer in Japan and infection with Epstein-Barr virus (EBV) is responsible for about 10% of gastric cancers worldwide. Although EBV infection may be involved at an early stage of gastric carcinogenesis, the mechanisms underlying its involvement remain unknown. To investigate the role of EBV in gastric carcinogenesis, we performed proteomic analyses of an EBV-infected gastric carcinoma cell line NU-GC-3 (EBV(+)) and its uninfected control (EBV(-)). 2-DE was combined with MS to identify differentially expressed proteins. We found that EBV infection upregulated one of the phosphorylated heat shock protein 27 kDa (HSP27). The phosphorylated HSP27 isoform which increased in EBV(+) cells can be induced by both heat shock and arsenite. The increase of phosphorylated HSP27 in EBV(+) cells was reduced by treatment with the phosphoinositide 3-kinase (PI3K) inhibitors (LY294002 and wortmannin). In addition, we found increased levels of phosphorylated Akt in EBV(+) cells. These findings suggest that EBV infection upregulates the phosphorylation of HSP27 via the PI3K/Akt pathway. Thus, activation of the PI3K/Akt pathway may contribute to the establishment of a malignant phenotype in EBV-infected gastric carcinomas.
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PMID:Epstein-Barr virus upregulates phosphorylated heat shock protein 27 kDa in carcinoma cells using the phosphoinositide 3-kinase/Akt pathway. 1860 70

Epstein-Barr virus (EBV)-associated gastric carcinoma (GC) is the monoclonal growth of EBV-infected epithelial cells, and the entity was recognized only recently. EBV-associated GC is distributed worldwide and more than 90,000 patients are estimated to develop GC annually in association with EBV (10% of total GC). EBV-associated GC occurs in two forms in terms of the histological features, i.e., lymphoepithelioma-like GC and ordinary type of GC. Both share characteristic clinicopathological features, such as the preferential occurrence as multiple cancer and remnant stomach cancer. While the expression of EBV-latent genes is restricted to several in the infected cells (Latency I), EBV-associated GC shows gastric cell phenotype, resistance to apoptosis, and the production of immunomodulator molecules. Recently, global and non-random CpG island methylation of the promoter region of many cancer-related genes has been demonstrated with their decreased expression, such as p16 INK4A, p73 and E-cadherin. This abnormality is accompanied by methylation of the EBV genome itself, suggesting a process of virus-driven hypermethylation in the development of neoplastic cells. Further studies are necessary to determine the precise sequence of EBV infection, methylation, transformation and selection of the predominant clone within the stomach mucosa. Future studies are also desirable for the target and strategy of therapy, such as initiating viral replication or reversing the DNA methylation of cellular genes.
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PMID:Epstein-Barr virus and gastric carcinoma--viral carcinogenesis through epigenetic mechanisms. 1878 28

While Epstein Barr virus (EBV) is associated with about 10% of gastric carcinomas worldwide, the role of the virus in the tumorigenesis of EBV-associated gastric carcinoma (EBVaGC) is unclear. Previously, we reported that a gastric cancer cell line, SNU-719, that is naturally infected with EBV closely resembles EBVaGC. Here, we attempted to eliminate the EBV genome from SNU-719 cells to ascertain the influence of EBV in EBVaGC. Southern blotting and fluorescence in situ hybridization (FISH) showed that EBV genomes were maintained as episomes in SNU-719 cells. To remove EBV episomes, SNU-719 cells were first cultured in a hydroxyurea (HU)-containing medium for up to 6 months. Real-time polymerase chain reaction and FISH results revealed no evidence of HU-mediated EBV genome reduction, although cell growth was reduced by acute HU treatment in dose- and time-dependent manners. Two small interfering RNAs against Epstein Barr nuclear antigen 1 (EBNA1) abrogated over 90% of the ectopic EBNA1 expression in HeLa cells, but only 40% of endogenous EBNA1 expression in SNU-719 cells. Together, our data suggest that maintenance of latent EBV infection is essential for the viability of EBVaGC cells, avoiding elimination of EBV episomes from the cells.
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PMID:Maintenance of the viral episome is essential for the cell survival of an Epstein-Barr virus positive gastric carcinoma cell line. 1947 75

A 73-year-old woman with rheumatoid arthritis had been treated with weekly low-dose methotrexate (MTX) for 5 years. She suffered from epigastric discomfort. Endoscopic examination revealed a tumor resembling advanced gastric cancer. Biopsy specimens showed atypical lymphoid cell infiltration. Immunohistological studies showed that these cells were positive for CD30 and CD79a, but not for CD15 or CD20. In situ hybridization identified Epstein-Barr virus latency-associated RNA expression in these cells. Clonally rearranged immunoglobulin heavy chain JH gene was not detected by Southern blot analysis. She was diagnosed with Epstein-Barr virus-associated polymorphic lymphoproliferative disorder (LPD) due to immunodeficiency caused by MTX administration. Cessation of MTX therapy led to complete regression of the tumor. To our knowledge, this is the first case of spontaneous remission of MTX-associated gastric LPD after discontinuation of MTX therapy. Increased awareness is needed on the possible occurrence of LPD resembling gastric cancer in rheumatoid arthritis patients treated with MTX.
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PMID:Reversible methotrexate-associated lymphoproliferative disorder resembling advanced gastric cancer in a patient with rheumatoid arthritis. 1974 1

Undifferentiated gastric carcinoma with lymphoid stroma is a histological type of gastric cancer with favourable prognosis, microscopically characterised by nests of neoplastic epithelial cells intermingled with a dense lymphoid proliferation. Various studies have shown a close relationship between undifferentiated gastric carcinoma with lymphoid stroma and Epstein-Barr virus infection; the presence of viral DNA in tumour cell nuclei has been demonstrated using polymerase chain reaction and Epstein-Barr virus-encoded small RNA in neoplastic cell nuclei have been found using in situ hybridization. We describe two cases of undifferentiated gastric carcinoma with lymphoid stroma, one infiltrating the submucosa of the gastric body and the other invading the muscularis propria of the antrum. No lymph node neoplastic invasion was documented in either case. Epstein-Barr virus was detected in the neoplastic cell nuclei in both cases with in situ hybridization.
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PMID:Undifferentiated gastric carcinoma with lymphoid stroma (lymphoepithelioma-like carcinoma/medullary carcinoma). 1977 67


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