Virus de Epstein-Barr: más que una mononucleosis infecciosa / Epstein-Barr virus: more than infectious mononucleosis

El virus de Epstein-Barr (VEB) fue el primer virus asociado a neoplasias en humanos. Infecta el 95 % de la población mundial, y aunque usualmente es asintomático, puede causar mononucleosis infecciosa y se relaciona con más de 200.000 casos de neoplasias al año. De igual forma, se asocia con esclerosis múltiple y otras enfermedades autoinmunes. A pesar de ser catalogado como un virus oncogénico, solo un pequeño porcentaje de los individuos infectados desarrollan neoplasias asociadas a VEB. Su persistencia involucra la capacidad de alternar entre una serie de programas de latencia, y de reactivarse cuando tiene la necesidad de colonizar nuevas células B de memoria, con el fin de sostener una infección de por vida y poder transmitirse a nuevos hospederos. En esta revisión se presentan las generalidades del VEB, además de su asociación con varios tipos de neoplasias, como son el carcinoma nasofaríngeo, el carcinoma gástrico, el linfoma de Hodgkin y el linfoma de Burkitt, y la esclerosis múltiple. Adicionalmente, se describen los mecanismos fisiopatológicos de las diferentes entidades, algunos de ellos no completamente dilucidados

Epstein-Barr virus (EBV) was the first virus associated with human cancer. It infects 95% of the world's population, and although it is usually asymptomatic, it causes infectious mononucleosis. It is related to more than 200,000 cases of cancer per year, and is also associated with multiple sclerosis and other autoimmune diseases. Despite being classified as an oncogenic virus, only a small percentage of infected individuals develop EBV-associated cancer. Its persistence involves the ability to alternate between a series of latency programs, and the ability to reactivate itself when it needs to colonize new memory B cells, in order to sustain a lifelong infection and be able to transmit to new hosts. In this review, the general characteristics of EBV are presented, in addition to its association with various types of cancers, such as nasopharyngeal carcinoma, gastric carcinoma, Hodgkin's lymphoma and Burkitt's lymphoma, and multiple sclerosis. Additionally, the pathophysiological mechanisms of the different entities are described, some of them not completely elucidated yet

Association of plasma EBV-DNA copy number and cytokines with B symptoms in patients with extranodal natural killer/T-cell lymphoma, nasal type / 中华放射肿瘤学杂志

Objective:To investigate the association of plasma EBV-DNA copy number, serum cytokines and B symptoms in patients with extranodal natural killer/T-cell lymphoma, nasal type (ENKTL), unravel the mechanism and assess the prognostic value of clinical indicators.Methods:Clinical data of 173 newly-diagnosed ENKTL patients (116 male, 57 female; median age: 43, 4 to 71 years)were retrospectively analyzed. According to Ann Arbor stage, 126 cases were classified as stage I-II and 47 cases of stage Ⅲ-IV. The primary sites of tumors included nasal cavity (n=100), extranasal upper aerodigestive tract (extranasal UADT, n=34), and extra-upper aerodigestive tract (extra-UADT, n=39). Prior to treatment, 91 patients had B symptoms and 82 cases of without B symptoms. According to plasma EBV-DNA copy levels, all patients were divided into the negative group (n=36), low load group (<10 4 copies/ml, n=73) and high load group (≥10 4 copies/ml, n=64). Serum cytokines including IFN-γ, IL-2, IL-4, IL-6, IL-10 and TNF-α were detected. Correlation analysis was performed by Cochran-Armitage trend test and Spearman correlation analysis. Survival analysis was conducted using univariate and multivariate Cox regression hazard analysis and survival curves were derived from Kaplan-Meier survival analysis. Results:The incidence of B symptoms and fever showed a significant upward trend with the increasing plasma EBV-DNA copy levels. In addition, serum levels of IFN-γ, IL-6 and IL-10 cytokines were higher in patients with B symptoms than those without B symptoms (all P<0.05). Serum IFN-γ, IL-6, and IL-10 levels were also positively correlated with plasma EBV-DNA copy number. The occurrence of B symptoms was associated with high-risk clinical features including advanced stage, primary tumor invasion, regional lymph node involvement, and elevated pre-treatment LDH. Survival analysis showed that stage, B symptoms, plasma EBV-DNA, and the above serum cytokines affected the prognosis of overall survival (OS) and progression-free survival (PFS) (all P<0.05). However, multivariate analysis showed that the occurrence of B symptoms was not an independent prognostic factor of ENKTL patients. Conclusion:This exploratory study suggests that the incidence of B symptoms is associated with increasing levels of EBV-DNA copies and cytokines, and these indicators are also important factors influencing the prognosis of ENKTL patients.

Application of Flow Cytometry Combined Fluorescence in Situ Hybridization to Indentify the Lymphocyte Subtypies with Epstein-Barr Virus Infection / 中国实验血液学杂志

OBJECTIVE@#To establish the technique that take the advantages of flow cytometry combined fluorescence in situ hybridization (Flow-FISH) to identify the Epstein-Barr virus(EBV) infected lymphocyte subtypies in patients' peripheral blood sample.@*METHODS@#Peripheral Blood monocyte from 9 patients with EBV infection enrolled at Children's Hospital in Chongqing Medical University were isolated by Ficoll-paque centrifugal separation. The expressions of EBER1, EBER2 in cell were detected by qRT-PCR. The surface markers of cell were detected by Flow cytometry after staining with their antibodies. The cell was treated Fix-Permeabilization Buffer before hybridization with fluorescent labeled probe at 37 ℃ overnight. The cell status, surface markers and targeted mRNA are detected by flow cytometry and fluorescence microscope.@*RESULTS@#It was optimized that the Fix-Permeabilization Buffer and recipe with 0.2% Tween-20 were picked out as providing a good cell integrity and high resolution of surface markers. Hybridization with 20% formamide and 7% dextran sulfate at 37 ℃ overnight is the optimal hybridization condition as a good hybridization effect, a detectable cell integrity and a high resolution of cell markers under flow cytometry detection. Finally, upon the established Flow-FISH method, lymphocyte subpopulations of the EBV+ cells from cell lines and blood samples of patients were identified successfully.@*CONCLUSION@#A Flow-FISH technology is established, which can be applied in the identification of EBV infected cell subtypes. This research provides a foundmental for its application in clinical test in EBV+ related proliferative diseases.

Prevalence of Epstein-Barr virus infection in individuals with nasopharyngeal carcinoma in Malaysia: The first systematic review and meta-analysis

@#Epstein-Barr virus (EBV) was the first herpesvirus associated to human malignancies. Despite the well-known association between EBV and malignancies, the prevalence of EBV infection in Malaysians with malignancies is unknown. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) was used to conduct a systematic review and metaanalysis of published data in this study. Studies reporting the occurrence of EBV infection in Malaysian malignancy patients were searched in electronic databases like PubMed, Scopus, ScienceDirect, and Google Scholar without year or language constraints. The study protocol was filed in PROSPERO (CRD42021273769). A total of 21 studies were included, with 1,036 EBV infection cases among 2,078 malignancy patients. The random-effects model was used to produce summary estimates. The pooled prevalence of EBV infection in Malaysians with malignancy was 36.3% (95% CI, 20.3 – 56.2). When the prevalence estimates were stratified by malignancy type, nasopharyngeal carcinoma has the highest prevalence (90.5%), followed by lymphoma (23.4%), and gastric carcinoma (10.0%). Male patients had a higher cases prevalence and most patients were above the age of 40. In Malaysia, many malignancies are increasingly linked to EBV infection. Screening for EBV infection in malignancy patients is therefore important to determine disease recurrence and metastases.

Analysis of carcinogenic virus infection in HIV-infected patients / 上海预防医学

Objective To investigate the status of carcinogenic infection in people infected with HIV and those with negative HIV test results in VCT clinics. To analyze the epidemiological characteristics and provide scientific basis for more targeted disease prevention and control strategies. Methods The serum levels of Epstein-Barr virus （EBV）， human herpesvirus type 8 （HHV-8） and human T-lymphotropic virus type Ⅰ （HTLV-Ⅰ） antibodies were detected by ELISA method in 224 HIV-infected patients and 480 HIV-negative visitors treated in VCT clinics during the same period from 2014 to 2017， to compare the differences in the infection rates of this virus between HIV-infected and HIV-negative individuals and to systematically analyze the correlation between viral infections and high-risk sexual behavior. Results Among the 224 HIV-infected patients， 79 were positive for EBV antibody， with the infection rate of 35.27%； 151 were positive for HHV-8 antibody， with the infection rate of 67.41%； and 95 were positive for HTLV-Ⅰ， with the infection rate of 42.41%. A total of 480 HIV negative visitors were tested. 7 patients were positive for EBV antibody， with the infection rate of 1.46%. 26 patients were infected with positive HHV-8 antibody， with the infection rate of 5.41%. 9 patients had positive HTIV-Ⅰ antibody， with the infection rate of 1.86%. The infection rates of the three carcinogenic viruses in HIV-infected patients were all higher than those in HIV-negative groups， and the differences were statistically significant （ P <0.05）. Conclusion There is a high prevalence of three highly carcinogenic viruses in HIV-infected patients and serious co-infection. It is necessary to improve the education of safe sex among HIV-infected patients and people with high risk of infection in order to curb the epidemic of HIV and other infectious diseases.

Analysis of carcinogenic virus infection in HIV-infected patients / 上海预防医学

Objective To investigate the status of carcinogenic infection in people infected with HIV and those with negative HIV test results in VCT clinics. To analyze the epidemiological characteristics and provide scientific basis for more targeted disease prevention and control strategies. Methods The serum levels of Epstein-Barr virus （EBV）， human herpesvirus type 8 （HHV-8） and human T-lymphotropic virus type Ⅰ （HTLV-Ⅰ） antibodies were detected by ELISA method in 224 HIV-infected patients and 480 HIV-negative visitors treated in VCT clinics during the same period from 2014 to 2017， to compare the differences in the infection rates of this virus between HIV-infected and HIV-negative individuals and to systematically analyze the correlation between viral infections and high-risk sexual behavior. Results Among the 224 HIV-infected patients， 79 were positive for EBV antibody， with the infection rate of 35.27%； 151 were positive for HHV-8 antibody， with the infection rate of 67.41%； and 95 were positive for HTLV-Ⅰ， with the infection rate of 42.41%. A total of 480 HIV negative visitors were tested. 7 patients were positive for EBV antibody， with the infection rate of 1.46%. 26 patients were infected with positive HHV-8 antibody， with the infection rate of 5.41%. 9 patients had positive HTIV-Ⅰ antibody， with the infection rate of 1.86%. The infection rates of the three carcinogenic viruses in HIV-infected patients were all higher than those in HIV-negative groups， and the differences were statistically significant （ P <0.05）. Conclusion There is a high prevalence of three highly carcinogenic viruses in HIV-infected patients and serious co-infection. It is necessary to improve the education of safe sex among HIV-infected patients and people with high risk of infection in order to curb the epidemic of HIV and other infectious diseases.

Comparison of EB virus infection between short term and long term use of mycophenolate mofetil for prophylaxis of graft versus host disease after haploidentical hematopoietic stem cell transplantation / 中华内科杂志

Objective:To investigate the role of short-term use of mycophenolate mofetil (MMF) in EB viral infection and acute graft-versus host disease (GVHD) in patients receiving haploidentical hematopoietic stem cell transplantation (haplo-HSCT) .Method:Adult patients (≥14 years) who were diagnosed with hematological malignancies received haplo-HSCT in Peking University Institute of Hematology from May 2016 to December 2017 were retrospectively reviewed. The median age was 30 (14-60) years old. A total of 498 patients including 277 males and 221 females were enrolled. Donors' median age was 38 (8-66) years old. All patients were classified into long-term use of MMF ( n=199), which was defined as 500 mg every 12 hours from day 9 pre-transplant to 250 mg every 12 hours from day 30 after transplant then withdrawal on day 45 to 60 after transplant, and short-term use of MMF ( n=299), which was defined as 500 mg every 12 hour from day 9 pre-transplant then withdrawal till neutrophil engraftment. Kaplan-Meier model was used to analyze the cumulative incidence of EBV infection, and the Cox proportional regression model for multivariate analysis. Result:Characteristics including sex, age, disease types, mismatched HLA loci, donor-recipient relationship, donor-recipient blood type, donor age, and donor sex were comparable between two groups (all P＞0.05). According to once, the incidence of EBV viremia, defined as EBV＞10 3 copies/ml at least once, in short-term group and long-term group was 19.4% (58/299) and 27.6% (55/199) respectively ( P=0.046).Donor age and the duration of MMF prophylaxis (short-term group as reference) were associated with EBV viremia according to multivariate analysis [ HR=1.022(95% CI 1.006-1.038),1.600(95% CI 1.059-2.418); P=0.006 and 0.026, respectively]. The incidence of grade Ⅱ-Ⅳ and Ⅲ/Ⅳ acute GVHD in long-term and short-term group was 32.2% (64/199) versus 20.7% (62/299)( P=0.005) and 10.1% (20/199) versus 8.0% (24/299) ( P=0.427), respectively. Donor sex (female as reference) and duration of MMF prophylaxis (short-term group as reference) were associated with grade Ⅱ-Ⅳ acute GVHD [ HR=1.908(95% CI 1.079-3.373),1.752(95% CI 1.161-2.643); P=0.026 and 0.008, respectively].There were no statistical differences in the incidence of CMV viremia, refractory CMV viremia and hemorrhagic cystitis (all P＞0.05) between the two groups. Conclusion:Short-term use of MMF can reduce EBV viremia without increasing the development of acute GVHD in haplo-HSCT patients.

Role of EphA2 in pathogenesis of nasopharyngeal carcinoma and its potential as a therapeutic target / 中国肿瘤临床

The erythropoietin-producing hepatocellular receptor (Eph) and its ligand ephrin are the largest of the receptor tyrosine kinases (RTKs) family in humans. Since ephrin ligands and Eph receptors are membrane-bound proteins, binding and activation of Eph/ephrin intracellular signaling pathways can only occur via direct cell-cell interaction. Eph-ephrin complexes emanate bidirectional signals that affect cells expressing Eph and ephrin, respectively. Its repulsive signaling effects include retraction, which plays an important role in many physiological and pathological processes. EphA2 has been found to have a strong association with tumors and is most widely studied. EphA2 signal transduction in tumor cells may promote or inhibit tumor, depending on the tumor microenvironment. EphA2 "canonical" signaling involves ligand binding and kinase activity; thus EphA2 "noncanonical" signaling is ligand independent and lacks kinase activity. This review summarizes the pathogenesis of EphA2 in nasopharyngeal carcinoma (NPC), including ligand independent signal and EBV infection receptor, furthermore evaluates the prospect of its potential utilization as a target for cancer therapeutics. This may provide a new method for the prevention and treatment of NPC.

Research progress on posttransplant lymphoproliferative disease after lung transplantation / 器官移植

Posttransplant lymphoproliferative disease (PTLD) is a fatal complication after lung transplantation, which is intimately associated with age, immunosuppression level and Epstein-Barr virus (EBV) infection, etc. Reducing immunosuppression level, rituximab therapy and T cell immunotherapy are common treatments for PTLD. With the rapid development of lung transplantation in China, PTLD after lung transplantation has attracted widespread attention. This article reviews the risk factors, pathological types, clinical manifestations, diagnosis, treatment, prognosis and prevention of PTLD after lung transplantation, aiming to provide reference for early monitoring and management of the incidence and progression of PTLD.

Progress on biomarkers of EB virus-related posttransplant lymphoproliferative disease / 器官移植

Posttransplant lymphoproliferative disease (PTLD) is a series of heterogeneous lymphoproliferative diseases and a severe complication after solid organ transplantation in children. Over 70% of PTLD is associated with Epstein-Barr virus (EBV). EBV-related B-cell lymphoma is also the main malignant tumor after pediatric organ transplantation. EBV-related PTLD is still a challenge in pediatric solid organ transplantation, which is mainly caused by immune function damage induced by immune suppression after transplantation. However, the specific mechanism remains elusive. In recent years, biomarkers have been developed to guide the diagnosis and individualized treatment of EBV-related PTLD, which possesses excellent application prospect. In this article, research progresses on the incidence of EBV-related PTLD in solid organ transplantation and its biomarkers were reviewed, aiming to explore novel ideas for clinical diagnosis and treatment.

Mediastinitis as a complication of Epstein-Barr virus infection: a rare entity

Epstein-Barr virus (EBV) is a member of the herpes virus family that can infect humans. Common manifestations of Epstein-Barr virus infection include fever, lymphadenopathy and pharyngitis with some rare complications including mediastinitis, myocarditis, pancreatitis, acute kidney failure and neurological disorders. Clinical findings along with serological evidences are needed to diagnose the infection. Early investigation for EBV in febrile patients can expedite both diagnosis and treatment.

Genotypes of Epstein-Barr virus (EBV1/EBV2) in individuals with infectious mononucleosis in the metropolitan area of Belém, Brazil, between 2005 and 2016

Abstract Two types of Epstein Barr virus (EBV1/EBV2) have been shown to infect humans. Although their genomes are similar, the regions containing the EBNA genes differ. This study aimed to characterize the EBV genotypes of infectious mononucleosis (IM) cases in the metropolitan region of Belém, Brazil, from 2005 to 2016. A total of 8295 suspected cases with symptoms/signs of IM were investigated by infectious disease physicians at Evandro Chagas Institute, Health Care Service, from January 2005 to December 2016. Out of the total, 1645 (19.8%) samples had positive results for EBV by enzyme immunoassay and 251 (15.3%) were submitted to polymerase chain reaction (PCR) technique, using the EBNA3C region, in order to determine the type of EBV. Biochemical testing involving aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transferase were also performed. EBV type was identified by PCR in 30.3% (76/251) of individuals; of those, 71.1% (54/76) were classified as EBV1, 17.1% (13/76) as EBV2, and 11.8% (9/76) as EBV1+EBV2. The main symptoms/signs observed with EBV1 infection were cervical lymphadenopathy (64.8%, 35/54), fever (63%, 34/54), headache (20.4%, 11/54), arthralgia (20.4%, 11/54), and exanthema (18.5%, 10/54). EBV2 infection was detected in all but two age groups, with an average age of 24 years. The most common signs/symptoms of EBV2 were fever (76.9%, 10/13), average duration of 18 days, and lymphadenopathy (69.2%, 9/13). In contrast, EBV1+EBV2 coinfections were more frequent in those aged five years or less (20.0%, 2/10). The symptoms of EBV1+EBV2 coinfection included fever (66.7%, 6/9), and cervical lymphadenopathy and headache (33.3%, 3/9) each. The mean values of hepatic enzymes according to type of EBV was significantly different (p<0.05) in those EBV1 infected over 14 years of age. Thus, this pioneering study, using molecular methods, identified the EBV genotypes in 30.3% of the samples, with circulation of EBV1, EBV2, and EBV1+EBV2 co-infection in cases of infectious mononucleosis in the northern region of Brazil.

Advances in immunotherapy of extranodal NK/T cell lymphoma / 中华耳鼻咽喉头颈外科杂志

Extranodal NK/T-cell lymphoma (ENKTCL) is a relatively rare group of highly aggressive non-Hodgkin′s lymphoma (NHL). The disease has rapid clinical progress, high degree of malignancy and poor prognosis. Traditional chemoradiotherapy regimens have not shown good efficacy. In recent years, the immunotherapy of tumors has developed rapidly. At present, it has shown strong therapeutic activity in the treatment of various solid tumors such as non-small cell lung cancer, prostate cancer, melanoma and kidney cancer. Multiple tumor immunotherapy drugs have been approved by the US Food and Drug Administration (FDA) for clinical use. This article reviews recent novel immunotherapeutic regimens of ENKTCL, hoping to change the treatment modality of this malignant disease.

The value of plasma EBV DNA in monitoring the therapeutic effect of nasopharyngeal carcinoma / 中华放射肿瘤学杂志

Objective@#To investigate the clinical value of plasma EBV DNA in monitoring clinical efficacy in the treatment of nasopharyngeal carcinoma (NPC).@*Methods@#Clinical data of 799 patients initially diagnosed with NPC treated with radical intensity-modulated radiotherapy (IMRT) in our hospital from 2016 to 2017 were analyzed retrospectively. Prior to treatment, the correlation between plasma EBV DNA, clinical stage and tumor progression was analyzed. The relationship between EBV DNA and tumor progression was analyzed after radiotherapy and during follow-up.@*Results@#Before IMRT, the level of EBV DNA was positively correlated with both clinical stage and tumor progression (both P<0.001). At 6 to 8 weeks after IMRT, 19(2.3%) patients positive for plasma EBV DNA obtained the worst prognosis and 14 cases had tumor progression. At 6-8 weeks after IMRT, 9 patients were negative for EBV DNA and 3 cases had tumor progression. The tumor progression rate of patients with undetectable plasma EBV DNA at the end of IMRT was only 8.3%(64/772), and the progression-free survival rate significantly differed among three groups (all P<0.05). The sensitivity, specificity and accuracy rates of persistent positive plasma EBV DNA during follow-up were calculated as 77.6%, 100% and 98.1%, respectively.@*Conclusions@#The level of plasma EBV DNA in patients with NPC is correlated with tumor bearing and tumor progression prior to IMRT. At 6-8 weeks after IMRT, patients who are persistently positive for EBV DNA obtain the worst prognosis and should be given with appropriate adjuvant therapy. The correlation between persistent positive plasma EBV DNA during follow up and tumor progression yields a high accuracy rate, indicating that plasma EBV DNA is a reliable biomarker for monitoring the clinical efficacy after radical treatment for NPC patients.

Effects of Epstein-Barr Virus on Proliferation，Apoptosis and Lipid Metabolism of Gastric Cancer Cells / 中山大学学报(医学科学版)

@# 【Objective】To investigate the effects of Epstein-Barr virus（EBV）on proliferation，apoptosis and lipid metabolism of gastric cancer cells，revealing the pathogenesis and development of EBV-associated gastric carcinoma （EBVaGC）.【Methods】EBV-positive cell line AGS-EBV was established by co-culturing AGS and Akata. Then we compared proliferation，apoptosis and lipid metabolism level between AGS and AGS-EBV cells. CCK-8 assays and Annexin V PE/7-AAD assays were performed to determine the proliferation and apoptosis of gastric cancer cells. Oil-Red O staining and three kinds of kits were used to detect lipid contents including lipid droplets，free fatty acid，triacylglycerol and total cholesterol. Key enzymes of lipogenesis were measured by qRT-PCR.【Results】EBV promoted the proliferation of gastric cancer cell line AGS（F = 23.214，P = 0.001；P values of 24 h，48 h，72 h，96 h and 120 h were 0.007， 0.004，＜0.001，＜0.001 and ＜0.001，respectively），inhibited apoptosis（P values of late and total apoptotic rates were 0.032，< 0.001），and increased intracellular lipid droplets，free fatty acids（P < 0.001），triacylglycerol（P = 0.004） and total cholesterol（P < 0.001）probably via lipogenesis. 【Conclusions】EBV promotes proliferation，inhibits apoptosis， and enhances lipid metabolism of gastric cancer cells.

Early diagnosis and treatment of chronic active Epstein-Barr virus hepatitis / 中国实用内科杂志

Non-hepatotropic viruses such as Epstein-Barr virus(EBV) has high infection rate in the population with biological characteristics of infective-latent-activation. EBV-related diseases including infectious mononucleosis(IM), chronic active EBV infection(CAEBV), EBV-related tumors and other diseases are complex and diverse, and all these can lead to varying degrees of liver damage.CAEBV can induce hepatitis(chronic active Epstein-Barr virus hepatitis, CAEBVH) or even liver failure. The prognosis of the disease is poor and the mortality rate is high. Early identification, diagnosis, and multidisciplinary collaborative treatment of CAEBVH are key to improving the prognosis of patients. This article will review the diagnosis and treatment progress of CAEBVH, and provide references for clinicians to diagnose and treat CAEBVH.

Association between lncRNAH19 polymorphisms and susceptibility to gastric carcinoma and EBV-associated gastric carcinoma in Han population in Qingdao / 中国肿瘤生物治疗杂志

@# Objective: To evaluate the potential associations between the single nucleotide polymorphisms (SNPs) of lncRNA H19 genes and the susceptibility to gastric cancer (GC), especially to EBV-associated gastric cancer (EBVaGC) in Han population in Qingdao. Methods: 225 cases of pathologically confirmed fresh gastric cancer tissues or paraffin embedded gastric cancer tissues during January 2015 and October 2018 were collected from Affiliated Hospital of Qingdao University, as GC group; in the meanwhile, 200 healthy people underwent physical examination at Outpatient were collected as control. The 225 cases of cancer tissues were assigned into two groups according to the transcription result of EBV-encoded small molecule non-polyadenylation (EBER 1) by In situ hybridization: EBVaGC group (70 cases) and EBVnGC group (155 cases). DNA was extracted from the tissues of two groups and peripheral blood of healthy participants.According to the general setting of HaploView software (MAF>0.05, r2>0.8), four TagSNPs (rs217727, rs2735971, rs2839698 and rs3741216) of H19 were screened. Genotyping of each SNP locus was carried out by using Taq-Man MGB allele typing kit, and the gene polymorphisms were examined. Results: H19 SNPs of collected tissue samples were in accordance with the HardyWeinberg equilibrium. Compared with control group, patients carrying TT genotype of H19 rs217727 loci had significantly increased susceptibility to gastric cancer (χ2=9.073, P=0.003, OR=1.999, 95% CI=1.271-3.143), so did the T allele (χ2=13.475, P=0.001, OR= 1.661, 95% CI=1.266-2.180). In contrast, patients carrying TC and CC genotype of rs2839698 loci had significantly increased susceptibility to gastric cancer (χ2=9.407, P=0.002; χ2=6.517, P=0.011), and patients carrying C allele had obviously increased susceptibility to GC (χ2=6.163, P=0.013, OR=1.417, 95%CI=1.076-1.867; χ2=9.542, P=0.02, OR=2.070, 95%CI=1.298-3.302).As for the rs2735971 and rs3741216, there was no significant difference between the GC group and the control group (all P>0.05). The distribution of 4 H19 SNPs showed no statistical difference in both EBVaGC group and EBVnGC group (all P>0.05). Conclusion: There was an association between H19 gene polymorphism (rs217727 and rs2839698) and gastric carcinoma; patients carrying the TT genotype of rs217727 and C allele of rs2839698 may increase the risk of gastric carcinoma. No significant association was observed between H19 SNP polymorphism and risk of EBVaGC.

Epstein-Barr virus BZLF1 promotes the growth of gastric cancer cells through activa-tion of the PI3K/AKT signaling pathway / 中国肿瘤临床

Objective: To explore the effect of the Epstein-Barr virus (EBV) BZLF1 gene on the biological behavior of EBV-negative gas-tric cancer cells and the underlying molecular mechanism. Methods: Lentiviral overexpressing BZLF1 was used to infect AGS and HGC27 gastric cancer cell lines. And the cell proliferation, apoptosis and migration invasive ability, and expression changes of cell sig-naling pathway were detected by CCK8 assay, apoptosis detection, migration and invasion assay, as well as western blot. HGC27 cells overexpressing BZLF1 were injected into the dorsal of NOD/SCID mice to construct xenografts, and the effect of BZLF1 on tumor growth was observed. Results: The expression of BZLF1 protein was significantly up-regulated in AGS-BZLF1 and HGC27-BZLF1 infected by over-expressing BZLF1 lentivirus. The cell proliferation in vitro and the tumorigenic ability in mice were significantly increased (P<0.05). Apoptosis was inhibited by BZLF1 protein, and the apoptotic rate of AGS-BZLF1 and HGC27-BZLF1 was (2.40±0.14)% and (3.90± 0.14)%, which was significantly lower than (5.75±0.35)% and (9.70 ± 0.42)% of AGS and HGC cells (P<0.05); however, there was no sig-nificant change in cell migration and invasion ability. In-depth molecular mechanism studies found that PI3K/AKT signaling pathway was significantly activated with enhanced pAKT and pS6 expression. After blocking the PI3K/AKT signaling pathway with BEZ235 inhibi-tor, the growth of HGC27-BZLF1 and AGS-BZLF1 cells was inhibited. Conclusions: EBV BZLF1 may promote the growth of gastric cancer cells by activating the PI3K/AKT signaling pathway and targeting PI3K/AKT pathway inhibitors, and serve as a promising treatment op-tion for EBV-associated gastric carcinoma.

Advances in DNA test for non-neoplastic Epstein-Barr virus associated diseases in children / 国际儿科学杂志

Epstein-Barr ( EB) virus is wildly spreaded in human and associated with many diseases. EBV-DNA load measurement by PCR has been shown to play an important role in the diagnosis of these disea-ses, a method to monitor patients and a prognosis factor of the outcome in many EBV-associated diseases. This review focuses on the development of the EBV-DNA detection technique and the advances of clinical use in sev-eral non-neoplastic EBV-associated diseases in children.