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Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We applied an improved representational difference analysis (RDA), efficiency-monitored RDA (EM-RDA), to analyze the genetic alterations of scirrhous gastric cancer. Clinical samples of this cancer are difficult to analyze genetically because of the large number of normal cells in the stroma. The entire 3rd difference product obtained from EM-RDA was subcloned. This is equivalent to the scirrhous gastric cancer DNA with the normal gastric tissue DNA subtracted from it. The difference clones, which were confirmed by Southern blot as being derived from the cancer, were sequenced. As a result, two difference clones were identified as DNA fragments of the Epstein-Barr virus (EBV). The existence of EBV in the scirrhous gastric cancer cells was proved by EBV-encoded small RNA 1 in situ hybridization. EM-RDA made it possible to detect the first case of EBV-related gastric cancer in a young woman.
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PMID:Isolation of the Epstein-Barr virus in scirrhous gastric cancer by efficiency-monitored representational difference analysis. 1094 Aug 21

The relative contribution of tumour histology or molecular changes, compared with invasion pattern or stage, to prognostic assessment of gastric cancer was investigated in a series of 185 advanced (T2 to T4, stage IB to IV) cancers that had undergone intentionally curative surgery at Varese General Hospital. Survival analysis of the histological types considered in commonly used classifications, such as Lauren, Kubo, the World Health Organization (WHO) and related classifications, allowed separation of a small high-grade (Hg, 12 cases) group of adenosquamous, anaplastic and small cell endocrine carcinomas from a large cohesive group (C, 86 glandular or solid cancers) and from another large (87 cases) group of tumours with dissociated cells [29 diffuse (D) and 58 mixed (M) tumours]. Univariate and multivariate analysis showed the independent prognostic value of this C/M+D/Hg classification approach, which proved superior to other classifications and to cell dissociation at the growing front or angio, lympho and neuro-invasion. Expression of sialyl Lewis(c), the DUPAN-2 antigen, proved to be an independent predictor of worse survival among tumours beyond stage I, showing an exclusively or predominantly cohesive structure. Microsatellite instability (MSI) predicted favourable survival in purely cohesive tumours of intermediate (II) stage, especially of solid/medullary and lymphoid stroma/lympho-epithelioma-like structure, among which two distinct tumour subsets were characterised, one MSI-positive and the other Epstein-Barr virus positive. T2NOM0 (stage IB) tumours showed mostly favourable survival independently from histological type, invasive pattern, DUPAN-2 or MSI status. It is concluded that an appropriate histological evaluation, coupled with sialylated glycoproteins histochemistry and, for stage-II tumours, MSI tests may contribute significantly to prognostic assessment of tumours beyond stage I. However, the stage itself, with special reference to lymph-node metastases and invasion level beyond subserosa, remains the most important prognostic clue for gastric cancer.
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PMID:The role of histological investigation in prognostic evaluation of advanced gastric cancer. Analysis of histological structure and molecular changes compared with invasive pattern and stage. 1156 56

Large scale scanning of the human genome has become possible with the introduction of DNA microarray. The ability to survey the expression of up to 5000 to 50,000 genes in a single experiment provides significant new opportunities, as well as new challenge. It will be important to translate genomic scale information on cancer biology to functional or clinical application. This requires prioritization of hundreds of targets discovered, functional validation of these targets, as well as a thorough knowledge of the involvement of the candidate target genes in vivo in human tissue. We have developed a tissue array technology for genome scale expressional and clinical cancer research. This technology enables high-throughput molecular analysis of large number of specimens. Our tissue arrays are constructed by arranging the cylindrical biopsies of 2.0 mm diameter from 60 individual tumor tissues into a tissue array block, which is then sliced into 200 or more identical slides for probing RNA or protein targets. A single immunohistochemistry or in situ hybridization experiment provides information on all 60 specimens on the slides, while subsequent sections can be analyzed with other probes or antibodies. We produced gastric cancer tissue array slides with various kinds of subsets, including 600 subsequent cancer cases, 100 preneoplastic lesions, 60 metastatic lesions, 60 synchronous cancers, 60 metachronous cancers, 60 young age patients, and 120 familial cases. We searched the presence of Epstein-Barr virus in those cancer specimens. We also applied 10 antibodies in those samples and stratify the prognostic significance of these antibodies. Tissue array technology expand the scope of high-throughput molecular analysis of archival tissue specimens with multiple probes for specific genes or proteins for functional or clinical application.
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PMID:[Tissue array technology for translational research. From gene discovery to application]. 1170 21

Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC), which accounts for most lymphoepithelioma-like gastric carcinoma and 10% or less of ordinary gastric carcinoma, is found worldwide and is the most common EBV-associated neoplasm. The pathologic features of EBVaGC are male predominance, occurrence primarily in the proximal stomach, multiplicity, moderately or poorly differentiated histological type, and association with lymphocytic infiltration. Virologically, EBV in EBVaGC is monoclonal or oligoclonal in the intramucosal or early invasive stage, and invariably monoclonal in advanced carcinomas. Latency type of gene expression in EBV is the same as that in Burkitt lymphoma (latency type I). Thus, EBVaGC is a unique type of gastric carcinoma, which is derived from a single or a few EBV-infected epithelial cells. However, there are still some unanswered questions, such as the mechanism of EBV infection of epithelial cells, the primary target in the gastric epithelium, the molecular events underlying EBVaGC, and the interaction of EBV with cytokine genes in cancer cells, as well as the predisposing factors for EBVaGC. To develop an experimental model, we recently established a transplantable EBVaGC - in severe combined immunodeficiency (SCID) mice - which retains the original EBV and the same pattern of latency gene expression as the original carcinoma. The development of a new therapeutic approach using this model, such as a gene therapy specific to EBV-associated neoplasm, will make EBVaGC not only a pathologically but also a clinically distinct gastric carcinoma entity.
Gastric Cancer 1998 Mar
PMID:Epstein-Barr virus and gastric carcinoma. 1195 53

BACKGROUND: The developmental process of Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) has not been clearly demonstrated, especially in its relation to intestinal metaplasia and epithelial EBV infection.METHODS: Gastritis and intestinal metaplasia was histologically evaluated in non-neoplastic gastric mucosa that surrounded early carcinoma of EBVaGCs ( n = 23) and EBV-negative gastric carcinomas (GCs) (intestinal type, n = 139; diffuse type, n = 44). Helicobacter pylori infection was evaluated by immunohistochemistry. EBV infection in the gastric mucosa was examined by both RNA probe in situ hybridization (ISH) and polymerase chain reaction (PCR) for the BamHI-W region of EBV DNA, the latter of which was applied to the microdissected mucosa.RESULTS: Marked grade of atrophy and moderate to marked grade of lymphocytic infiltration were significantly more frequent in EBVaGCs (74% and 78%, respectively), compared to intestinal-type (49% and 12%)and diffuse-type (27% and 12%) of EBV-negative GCs. Only 13% of EBVaGCs were surrounded by intestinal metaplasia, in contrast to 41% of intestinal-type EBV-negative GCs. Immunohistochemistry revealed nearly the same frequencies of H. pylori infection (70%) in three types of GCs. RNA probe ISH for EBV-DNA failed to identify any positive cells in nonneoplastic mucosa, including intestinal metaplasia. Two of 118 microdissected samples of EBVaGC and 5 of 62 samples of EBV-negative GCs showed amplification of EBV-DNA, consisting of 3 pyloric and 4 fundic but no metaplastic gland samples.CONCLUSIONS: EBVaGC may develop from rare EBV-infected epithelial cells with severe atrophic gastritis, but the process is not directly related to intestinal metaplasia or H. pylori infection.
Gastric Cancer 1999 Aug
PMID:Atrophic gastritis, Epstein-Barr virus infection, and Epstein-Barr virus-associated gastric carcinoma. 1195 81

Acase of stomach carcinoma showing features of submucosal tumor is reported. The patient was a 50-year-old man presenting with hematemesis. Endoscopic examination was performed and revealed a submucosal tumor-like lesion with central ulceration in the fornix of the stomach. The biopsy specimen from this lesion showed poorly differentiated adenocarcinoma, and surgery was performed. The tumor, measuring 3.5 x 2.7 cm in size, invaded to the muscularis propria with proliferation of the interstitial connective tissue and lymphoid follicles consisting mainly of B lymphocytes in the submucosal layer. In situ hybridization of tumor tissue for Epstein-Barr virus (EBV)-encoded small RNA1 as target revealed negative results. In stomach carcinoma simulating submucosal tumor, as in this patient, preoperative diagnosis is important to plan treatment strategies.
Gastric Cancer 1999 Nov
PMID:Gastric carcinoma resembling submucosal tumor. 1195 95

Tumor invasion marks a critical point in cancer progression; it is a harbinger of morbidity and mortality. Thus, the cellular events that enable the invasive phenotype are under intense investigation. Epstein-Barr virus (EBV) is associated with a number of cancers, including Burkitt lymphoma (BL) and nasopharyngeal carcinoma (NPC) and is suspected to contribute to their tumorigenesis. On average, 8% of gastric carcinomas have been shown to carry this virus. To explore whether the presence of EBV in gastric carcinoma contributes to tumor progression in this predominantly invasive carcinoma, we examined a panel of 2 in vitro EBV-infected human gastric cancer cell line sublines and their mock-infected AGS parental control line. We found EBV infection caused a marked increase in transmigration of a Matrigel barrier (415% and 303%, p < 0.05, for the 2 infected lines). This correlated with increased motility of these sublines (233% and 140%, p < 0.05). As this pattern of increased motility leading to a more pronounced enhancement of invasion has been noted in other tumor cells, we explored the roles of autocrine signaling pathways previously implicated in carcinoma motility and invasion. Inhibitors to the epidermal growth factor receptor (EGFR) (PD153035), phospholipase C (PLC) (U73122), extracellular-signal regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) (PD089035) and PI-3 kinase (Wortmannin) were not informative. These data suggest that EBV increases migration of AGS cells by a mechanism independent of these autocrine growth factor-induced pathways. Instead, we found that the EBV-infected cells presented increased focal adhesion kinase (FAK) phosphorylation. These findings suggest a role for integrin-mediated signaling in promoting EBV-associated invasiveness.
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PMID:EBV-expressing AGS gastric carcinoma cell sublines present increased motility and invasiveness. 1211 96

We report the cases of 5 patients with gastric cancer with lymphoid stroma, aged from 40 to 66 years. The tumor was located in the upper and the middle third of stomach in four patients. Using in situ hybridization, the tumor was Epstein-Barr virus-positive in all patients whereas immunohistochemical analysis was negative. Four patients had total gastrectomy associated in two cases with splenectomy and caudal pancreatic resection. The last patient had subtotal gastrectomy. One patient was lost to follow-up. After a mean follow-up of 31 months, 4 patients are alive and free of local recurrence.
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PMID:[Gastric cancer with lymphoid stroma: a rare form associated with Epstein-Barr virus. Five cases]. 1212 67

Epstein-Barr virus (EBV), a gamma herpesvirus, has been associated with a variety of human malignancies such as Burkitt's lymphoma, Hodgkin's lymphoma, NPC, and gastric cancer. A controversy regarding the association of EBV with breast cancers has recently been reported in the literature. These reports have mainly used the DNA detection techniques of polymerase chain reaction and Southern blot hybridization, with the inherent lacunae associated with these techniques for signal localization. Our group has studied EBV association with breast cancer by using in situ hybridization for detecting nonpolyadenylated EBV RNA (EBERs), along with using protein localization technique of immunohistochemistry, studying the EBV nuclear antigen 1 (EBNA1) and the latent membrane proteins (LMP1 and LMP2A). This is the first article analyzing the expression of LMP2A in breast cancer cells. In all of our 43 female breast cancer cases under study, we failed to detect expression of any of the EBV viral gene products tested.
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PMID:Lack of expression of the Epstein-Barr Virus (EBV) gene products, EBERs, EBNA1, LMP1, and LMP2A, in breast cancer cells. 1221 80

Epidemiological and clinicopathological features of Epstein-Barr virus (EBV) associated gastric carcinoma was compared in India and Japan, two countries differing markedly in gastric cancer incidence. Using in situ hybridization assay, the presence of EBV-encoded small RNA (EBER) was examined in 215, and 2,011 gastric cancer cases in Kerala, India, and Japan, respectively. Ten cases (5%), all males, in the Indian series were EBER-positive. This frequency was similar to that in the Japanese series (6.2%). As was the case with Japanese series, the EBV-associated gastric carcinoma in the Indian series was observed most frequently in the middle part of the stomach (1 in antrum, 4 in middle part, 2 in cardia, and 3 unknown), and, histologically, the diffuse type Lauren's classification (8 cases) was more common than the intestinal type (2 cases). Virus subtyping by PCR-RFLP revealed that all of the 10 EBV strains isolated from the EBER-positive Indian cases were subtype A, and wild-type F for Bam HI F region. In Bam HI I region, 8 cases were type C and the remaining 2 cases were type D. In either series, there was no significant difference in the frequency of tumors with p53 overexpression between EBER-positive and -negative cases. However, the proportion of cells with p53 overexpression in EBER-negative tumors was significantly higher than that in EBER-positive tumors regardless of histological type in both series. In conclusion, the frequency and major clinicopathological features of EBV-associated gastric carcinoma in south India were similar to those observed in Japanese series although gastric cancer incidence in these two countries differs markedly.
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PMID:Epstein-Barr virus-associated gastric carcinoma in southern India: A comparison with a large-scale Japanese series. 1222 26


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