Acquired Immunodeficiency Syndrome ; complications ; pathology ; Antigens, CD34 ; metabolism ; Gastrectomy ; methods ; Humans ; Male ; Middle Aged ; Sarcoma, Kaposi ; metabolism ; pathology ; surgery ; virology ; Stomach ; pathology ; Stomach Neoplasms ; metabolism ; pathology ; surgery ; virology ; Vimentin ; metabolism

OBJECTIVETo evaluate the H. pylori and Epstein-Barr virus infection in cardiac and distal gastric adenocarcinoma tissues in residents in Cixian county, a high risk area of esophageal cancer in Hebei province, and to explore the putative role of H. pylori and Epstein-Barr virus infection in the carcinogenesis of adenocarcinoma at different subsites of stomach.

METHODSH. pylori and Epstein-Barr virus latent membrane protein 1 (EBV-LMP1) immunopositivities were determined by Elivision(TM) plus immunohistochemical staining in 190 gastric adenocarcinoma tissues including 144 cases of cardiac adenocarcinoma and 46 cases of distal gastric adenocarcinoma. The relationship between H. pylori and Epstein-Barr virus infection and the subsite, Laurén type as well as other clinicopathological features of gastric adenocarcinoma were analyzed.

RESULTSNo significant difference was found between the H. pylori detection rates in cardiac and distal gastric adenocarcinomas(56.9% vs. 65.2%, P > 0.05). The detection rate of H. pylori in intestinal type was significantly higher than that in the diffuse type distal gastric adenocarcinomas (71.8% vs. 28.6%, P < 0.05). No positive expression of EBV-LMP1 was found in the gastric adenocarcinomas in this study.

CONCLUSIONSNo significant differences in H. pylori and EBV-LMP1 infections were found between cardiac and distal gastric adenocarcinomas in Cixian county. H. pylori infection is related with the intestinal type of distal gastric adenocarcinoma.

Adenocarcinoma ; microbiology ; pathology ; virology ; Aged ; Cardia ; China ; Epstein-Barr Virus Infections ; pathology ; Female ; Helicobacter Infections ; pathology ; Helicobacter pylori ; isolation & purification ; Humans ; Male ; Middle Aged ; Stomach Neoplasms ; microbiology ; pathology ; virology ; Viral Matrix Proteins ; metabolism

OBJECTIVES: Research on how the risk of gastric cancer increases with Epstein-Barr virus (EBV) infection is lacking. In a systematic review that investigated studies published until September 2014, the authors did not calculate the summary odds ratio (SOR) due to heterogeneity across studies. Therefore, we include here additional studies published until October 2015 and conduct a meta-analysis with meta-regression that controls for the heterogeneity among studies. METHODS: Using the studies selected in the previously published systematic review, we formulated lists of references, cited articles, and related articles provided by PubMed. From the lists, only case-control studies that detected EBV in tissue samples were selected. In order to control for the heterogeneity among studies, subgroup analysis and meta-regression were performed. RESULTS: In the 33 case-control results with adjacent non-cancer tissue, the total number of test samples in the case and control groups was 5280 and 4962, respectively. In the 14 case-control results with normal tissue, the total number of test samples in case and control groups was 1393 and 945, respectively. Upon meta-regression, the type of control tissue was found to be a statistically significant variable with regard to heterogeneity. When the control tissue was normal tissue of healthy individuals, the SOR was 3.41 (95% CI, 1.78 to 6.51; I-squared, 65.5%). CONCLUSIONS: The results of the present study support the argument that EBV infection increases the risk of gastric cancer. In the future, age-matched and sex-matched case-control studies should be conducted.
Case-Control Studies ; DNA, Viral/analysis/metabolism ; Databases, Factual ; Epstein-Barr Virus Infections/*pathology/virology ; Herpesvirus 4, Human/genetics/isolation & purification/*pathogenicity ; Humans ; Odds Ratio ; Stomach Neoplasms/*pathology/virology

BACKGROUNDTo study the difference in gene expression between the EBV associated gastric carcinoma (EBVaGC) tissues. To explore the mechanism of gastric carcinoma pathogenesis initiated by EBV.

METHODSIn situ hybridization was used to study the frequencies of EBV small RNA expression in 155 cases of gastric carcinoma tissues. The expression levels of P53 protein and P21WAF1 protein were detected by immunohistochemistry in all gastric carcinoma tissues.

RESULTSThe expression of EBV small RNA was positive in 10 out of 155 cases (6.45%). The expression of P53 protein was weakly positive in 4 of the 10 cases. The expression level of P53 protein in EBVaGC was much lower than that in EBVnGC and was weakly positive in 30 of 145 cases with EBVnGC). P21WAF1 expression was detected in 7 of 10 cases with EBVaGC, but in 55 out of 145 cases with EBVaGC, P21WAF1 expression in EBVaGC was much higher than that in EBVnGC.

CONCLUSIONThere seems existing a special mechanism of pathogenesis in EBVaGC. In which P53 gene mutation may not play an important role.

Epstein-Barr Virus Infections ; metabolism ; pathology ; virology ; Herpesvirus 4, Human ; genetics ; physiology ; Host-Pathogen Interactions ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Proto-Oncogene Proteins c-met ; metabolism ; RNA, Viral ; genetics ; Stomach Neoplasms ; metabolism ; pathology ; virology ; Tumor Suppressor Protein p53 ; metabolism

OBJECTIVETo understand Epstein-Barr virus (EBV) infection of gastric carcinoma cells.

METHODSThe authors tested the infection of a signet ring cell line HSC-39 derived from human gastric carcinoma with Akata and P3HR-1 strains of EBV. Akata and P3HR-1 infected of EBV cell clones were isolated by a limiting dilution method.

RESULTSEBV-encoded small RNAs (EBERs) were expressed in the infected cells with each EBV strain by in situ hybridization. The EBV infected parental cells and most clones expressed EBNA1, but not EBNA2, latent membrane protein (LMP) 1 and LMP2A. Both EBV strains infected parental cells and clones presented type I latency. The uninfected HSC-39 cells were negative for CD21 expression; however, the Akata but not P3HR-1-infected clones were positive for CD21 expression at mRNA level.

CONCLUSIONThese results demonstrated that EBV infecting HSC-39 by CD21-independent pathway. This study also defined a signet ring cell line as a new target for EBV.

Carcinoma, Signet Ring Cell ; pathology ; virology ; Cell Line, Tumor ; Epstein-Barr Virus Nuclear Antigens ; analysis ; Herpesvirus 4, Human ; genetics ; physiology ; Humans ; RNA, Messenger ; RNA, Viral ; analysis ; Receptors, Complement 3d ; analysis ; genetics ; physiology ; Stomach Neoplasms ; pathology ; virology

OBJECTIVETo study Epstein-Barr virus infection and p16 protein abnormal expresson in carcinogenesis and progression of gastric adenocarcinomas (GAC).

METHODSImmunohistochemical staining SP method was used to detect the expression of LMP-1 and p16 in 97 cases of GAC.

RESULTSEBV LMP-1 and p16 protein were detected in 30.9% (30/97) and in 63.91% (62/97) cases of gastric adenocarcinomas respectively. There was no significant difference between EBV-positive and EBV-negative gastric carcinomas in sex, histologic type, depth of tumor invision, lymph node metastasis and clinical stages (P > 0.05); overexpression of p16 was associated with lymph node metastasis and clinical stages; no correlation was found between the expression of EBV LMP-1 and p16 protein.

CONCLUSION1. EBV play a role in carcinogensis of GAC. 2. P16 gene abnormality is frequently involved in GAC and might be one of the important prognostic factors. 3. EBV infection and p16 alteration are two independent roles in GAC carcinogenesis.

Adenocarcinoma ; genetics ; metabolism ; pathology ; virology ; Adult ; Aged ; Cyclin-Dependent Kinase Inhibitor p16 ; genetics ; metabolism ; Epstein-Barr Virus Infections ; genetics ; metabolism ; pathology ; virology ; Female ; Gene Expression Regulation, Neoplastic ; Herpesvirus 4, Human ; genetics ; metabolism ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Stomach Neoplasms ; genetics ; metabolism ; pathology ; virology ; Viral Matrix Proteins ; genetics ; metabolism

BACKGROUND AND OBJECTIVEEpstein-Barr virus (EBV) has been detected in about 10% of gastric carcinomas. However, the pathogenetic role of EBV in gastric carcinoma is uncertain. This study was to explore the correlation of Fas/FasL expression to the apoptosis of tumor cells and tumor-infiltrating lymphocytes (TIL) in EBV-associated gastric carcinoma (EBVaGC).

METHODSFas/FasL expression in 49 specimens of EBVaGC, 20 specimens of EBV-negative gastric carcinoma (EBVnGC) and 12 specimens of normal gastric mucosa was detected by immunohistochemistry. The apoptotic index (AI) of cells was determined by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL).

RESULTSThe positive rates of Fas were 91.7% in normal gastric mucosa and 76.8% in gastric carcinoma (P < 0.05); those of FasL were 16.7% in normal gastric mucosa and 58% in gastric carcinoma (P < 0.05). The positive rate of Fas was significantly lower in EBVaGC than in EBVnGC (71.4% vs. 90.0%, P < 0.05). The positive rate of FasL in EBVaGC was significantly higher than that in EBVnGC (63.2% vs. 45%, P < 0.05). The AI of EBVaGC cells was significantly lower than that of EBVnGC cells (P = 0.002). The number and AI of TIL in EBVaGC were higher than those in EBVnGC (P < 0.05). The AI of TIL was positively correlated with the level of FasL expression in tumor cells (r=0.237, P = 0.028).

CONCLUSIONUp-regulation of FasL expression and decrease of TIL apoptosis in EBVaGC may facilitate the escape of tumor cells from the host immunosurveillance, and it might contribute to the development and progression of carcinoma.

Adult ; Apoptosis ; Epstein-Barr Virus Infections ; Fas Ligand Protein ; metabolism ; Female ; Herpesvirus 4, Human ; isolation & purification ; Humans ; Immunohistochemistry ; Immunologic Surveillance ; In Situ Nick-End Labeling ; Lymphocytes, Tumor-Infiltrating ; pathology ; Male ; Middle Aged ; Stomach Neoplasms ; metabolism ; pathology ; virology ; Tumor Escape ; fas Receptor ; metabolism

OBJECTIVETo investigate the prevalence of Epstein-Barr virus (EBV)-associated gastric carcinomas in Guangzhou, their clinicopathologic features and related protein expressions including DNMT1, p16, and cyclin D1.

METHODA total of 676 cases of EBV-associated gastric carcinoma were included in the study. The presence of EBV-encoded small RNA1 (EBER1), a marker for EBV infection, was analyzed by in-situ hybridization using formalin-fixed and paraffin-embedded tumor samples. Expression of EBV-encoded proteins, DNMT1, p16 and cyclin D1 were detected by immunohistochemistry.

RESULTSForty-five of 676 gastric carcinomas showed EBER intranuclear positivity in all tumor cells. EBV involvement was significantly more frequent among the male than the female patients, especially in tumors of less differentiated types (diffuse type) and involving the upper stomach (P < 0.05). EBNA1 and LMP2A expression were detected in 42 (93.3%) and 24 (53.3%) cases, respectively. None expressed EBNA2, LMP1, and ZEBRA. Among 45 cases of EBV associated gastric carcinomas, DNMT1, p16 and cyclin D1 expression were seen in 35 (77.8%), 10 (22.2%), and 29 (64.4%) cases, respectively. In contrast, among 40 EBV negative gastric carcinomas, expression of the three proteins were 20 (50.0%), 25 (62.5%) and 12 (30.0%), respectively. The difference of expression of the three proteins between the two groups was significant (P < 0.05). Expression of p16 correlated with the depth of the tumor invasion. Correlated protein expression was seen between LMP2A and DNMT1, between DNMT1 and p16, and between p16 and cyclin D1 (P < 0.05).

CONCLUSIONSEBV associated gastric carcinoma accounts for 6.7% of gastric carcinomas in Guangzhou with the Latency I pattern in some cases and between Latency I and II in others. The correlated expression of LMP2A, DNMT1, p16 and cyclin D1 may contribute to the pathogenesis of EBV associated gastric carcinomas.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; China ; Cyclin D1 ; metabolism ; Cyclin-Dependent Kinase Inhibitor p16 ; metabolism ; DNA (Cytosine-5-)-Methyltransferase 1 ; DNA (Cytosine-5-)-Methyltransferases ; metabolism ; Epstein-Barr Virus Infections ; virology ; Epstein-Barr Virus Nuclear Antigens ; metabolism ; Female ; Herpesvirus 4, Human ; isolation & purification ; Humans ; Male ; Middle Aged ; Neoplasm Invasiveness ; RNA, Viral ; metabolism ; Sex Factors ; Stomach Neoplasms ; metabolism ; pathology ; virology ; Viral Matrix Proteins ; metabolism ; Young Adult

OBJECTIVETo study the effect of the adenovirus containing CD/TK fusion gene controlled by the human vascular endothelial growth factor (VEGF) promoter on apoptosis of human gastric carcinoma cells SGC-7901.

METHODSVEGF-expressing SGC-7901 cells were infected by the recombinant adenovirus Ad-VEGFP-CD/TK, and the infection efficiencies were observed with fluorescence microscopy. The toxic effect and intracellular calcium concentration induced by 5-fluorocytosine (5-FC) and ganciclovic (GCV) were determined by light microscopy, electron microscopy and flow cytometry.

RESULTSThe transfection efficiency of the recombinant adenovirus in SGC-7901 cells increased with the viral titer. At the multiplicity of infection (MOI) of 100, 5-FC and GCV could induce apoptosis of SGC-7901 cells within a given dose range in a dose- and time-dependent manner, and apoptotic changes of the cells were observed with electron microscopy. Apoptotic peak was also detected by flow cytometry. Cell cycle analysis revealed increased cell percentage in G(0)-G(1) phase and decreased percentage of cells in G(2)-M and S phases in response to treatment with the pro-drugs, which also induced marked elevation of intracellular calcium concentration in the infected cells.

CONCLUSIONSCD/TK fusion gene system driven by VECF promoter selectively induces apoptosis of VEGF-expressing SGC-7901 cells, the action of which is probably mediated by intracellular calcium variation.

Adenoviridae ; genetics ; physiology ; Animals ; Apoptosis ; drug effects ; genetics ; Calcium ; metabolism ; Cell Line, Tumor ; DNA ; metabolism ; DNA, Recombinant ; genetics ; Dose-Response Relationship, Drug ; Flucytosine ; pharmacology ; Ganciclovir ; pharmacology ; Genes, Transgenic, Suicide ; genetics ; Humans ; Microscopy, Electron ; Promoter Regions, Genetic ; genetics ; Stomach Neoplasms ; genetics ; metabolism ; pathology ; virology ; Vascular Endothelial Growth Factor A ; genetics

OBJECTIVETo study the regulatory effect of Helicobacter pylori CagA protein on gastrin promoter and the related signaling pathways as to further elucidate the mechanism of the development and progression of human gastric carcinoma.

METHODSAfter pcDNA3.1ZEO(-)/CagAand PGL/GP were identified by double restriction enzyme digestion, PCR and sequencing, the gastric cancer cell lines AGS and SGC-7901 cells were co-transfected with pcDNA3.1ZEO(-)/CagA and PGL/GP for 48 h. Alternatively, AGS and SGC-7901 cells were transfected by PGL/GP for 36 h later, and infected with Helicobacter pylori for additional 12 h. Meanwhile, the transfected and infected cells were treated using the JAK2 signaling pathway inhibitor AG490 and the ERK signaling pathway inhibitor U0126. The untreated cells and empty-vector-transfected cells were used as the control. Finally, luciferase activity was detected using the luciferase reporter assay system in transfected and infected cells. The levels of gastrin mRNA was determined by TaqMan® real-time quantitative PCR.

RESULTSAfter co-transfection with pcDNA3.1ZEO(-)/CagA and PGL/GP, the activities of luciferase were increased by 251.3, 106.1 and 2.4 times in AGS cells and 35.8, 22.7 and 13.4 times in SGC-7901 cells, respectively, as compared with that of the control, pcDNA3.1 ZEO(-)/CagA + PGL3/Basic and pcDNA3.1 ZEO(-) + PGL/GP groups. The activities of luciferase in PGL/GP transfection and HP infection group were also increased by 1673.2, 33.5, 1.4 times in AGS cells and 1180.2, 72.2 and 1.5 times in SGC-7901 cells, respectively, as compared with that of the control, PGL3/Basic + HP and PGL/GP groups. There were statistically significant differences between them (P < 0.05), which suggested that the transcription activity of gastrin promoter increased significantly. But after adding the inhibitor AG490 and U0126, respectively, the activities of luciferase were significantly decreased by 95.7% (U0126) and 33.0% (AG490) in co-transfected AGS cells and 94.8% (U0126) and 86.2% (AG490) in co-transfected SGC-7901 cells with pcDNA3.1ZEO(-)/CagA and PGL/GP (P < 0.05). In the PGL/GP transfection and HP infection group, the activities of luciferase were significantly decreased by 24.6% (U0126) and 25.8% (AG490) in AGS cells and 57.3% (U0126) and 14.1% (AG490) after adding the inhibitor AG490 and U0126, respectively (P < 0.05). The results showed that the gastrin promoter activities were significantly inhibited. The gastrin mRNA levels were 3.0 and 4.5 times higher in HP-infected AGS and SGC-7901 cells, respectively, than that in the control groups. In the cells transfected with pcDNA3.1ZEO(-)/CagA, the gastrin mRNA levels were raised 10.8 and 2.3 times (AGS cells) and 10.9 and 16.2 times (SGC-7901 cells), respectively, as compared with that of control and pcDNA3.1ZEO(-) groups. All of the differences were statistically significant (P < 0.05).

CONCLUSIONThese results suggest that CagA may activate the gastrin promoter and up-regulate the expression of gastrin gene, and CagA is one of the important proteins in regulating gastrin gene expression. The ERK/MAPK and JAK/STAT signaling pathways may be involved in the controlling of gastrin gene expression by CagA.

Antigens, Bacterial ; genetics ; metabolism ; Antineoplastic Agents ; pharmacology ; Bacterial Proteins ; genetics ; metabolism ; Butadienes ; pharmacology ; Cell Line, Tumor ; Enzyme Inhibitors ; pharmacology ; Gastrins ; biosynthesis ; genetics ; Gene Expression Regulation, Neoplastic ; Genetic Vectors ; Helicobacter Infections ; Helicobacter pylori ; isolation & purification ; Humans ; Nitriles ; pharmacology ; Promoter Regions, Genetic ; RNA, Messenger ; metabolism ; Stomach Neoplasms ; metabolism ; pathology ; virology ; Transfection ; Tyrphostins ; pharmacology ; Up-Regulation