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.

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.

Research progress on the role and mechanism of miR-155 in the development of oral squamous cell carcinoma / 口腔疾病防治

@#Oral squamous cell carcinoma (OSCC) is the most common oral cancer. Previous studies have found significantly high miR-155 expression in OSCC. However, the mechanism by which miR-155 plays a role in OSCC oncogenesis is not yet clear. This article reviews the function of the relationship between miR-155 and tumors and the potential role of miR-155 in the development of OSCC. A literature review showed that mir-155, as a small carcinogenic RNA, can inhibit CDC73, BCL6, P27Kip1 and other target genes that play a role in cancer inhibition; promote the proliferation, migration and invasion of OSCC cells; and inhibit apoptosis. miR-155 can also be combined with biological factors (Epstein-Barr virus, human papillomavirus) to promote the development of OSCC.

Expression and clinical significance of PD-1/PD-Ls in EBV-positive T/NK lymphoprolif-erative disorders / 中国肿瘤临床

Objective: To investigate the expression and clinical significance of programmed death-ligand 1 (PD-L1), programmed death-ligand 2 (PD-L2), and their receptor programmed cell death protein 1 (PD-1) in EBV-positive T/NK lymphoproliferative disease [Epstein-Barr virus-positive T/natural killer (NK)-cell lymphoproliferative disease, EBV(+)-T/NK-LPD]. Methods: The pathological paraffin-embedded tissues of 17 patients with EBV(+)-T/NK-LPD from the First Affiliated Hospital of Zhengzhou University from January 2013 to December 2017 were collected. These patients include 12 males and 5 females, aged 10-82 years old, the average age being 29 years, 4 people in gradeⅠ, 7 in gradeⅡ, 3 in gradeⅢ, and 3 people with hydroa vacciniforme-like lymphoproliferative disorders. Immunohistochemical SP method was used to detect the expression of PD-1, PD-L1, and PD-L2 in human EBV(+)-T/NK-LPD tissues. The relationship between PD-1, PD-L1, PD-L2 expression, and clinicopathological parameters, pathological grades and prognosis were analyzed by Fisher's exact probabilities and Spearman rank correlation. Result: After statistical analysis, the results showed that in 17 cases of tissue samples, there were 12 cases with positive PD-1 expression, 6 cases with positive PD-L1 expression and 5 cases with positive PD-L2 expression. There was no significant correlation between PD-1 and PD-L2 expression and prognosis (P>0.05). PD-L1 expression showed a positive correlation with prognosis (P<0.05). There was no significant correlation between the expression of PD-L1 and PD-L2 with age, sex, as well as LDH and Ki-67 levels (P>0.05). Moreover, there was no significant correlation of PD-1 and PD-L2 expression with pathological grade (r=0.141, r=-0.149, both P>0.05). However, there was a negative correlation between the PD-L1 expression and pathological grade (r=-0.563), and the correlation between the PD-L1 ex-pression and pathological grade was statistically significant (P<0.05). Conclusions: PD-1, PD-L1, and PD-L2 are abnormally expressed in the pathological tissues of EBV(+)-T/NK-LPD. Although there was no significant correlation between the expression of PD-1 and prognosis or pathological grade, it was significantly higher in EBV+T/NK-LPD. PD-1/PD-Ls associated signaling pathway is expected to be a potential new target for EBV(+)-T/NK-LPD immunotherapy.

Presencia del marcador lmp-1 del virus epstein-barr en linfomas de caninos / Presence of lmp-1 protein of epstein-barr virus in lymphomas of canine origin

RESUMEN El virus Epstein-Barr (EBV) es un virus de alta prevalencia en humanos que se asocia con tumores de la línea linfoide B. En caninos se dispone de pocos reportes sobre la presencia del EBV y su rol en esta especie. El objetivo del presente estudio fue determinar la presencia de la proteína latente de membrana del EBV (LMP-1) en tejidos obtenidos de 20 linfomas de caninos cuyo diagnóstico se había realizado durante un periodo de 10 años, entre 2004 y 2014. Los linfomas se reclasificaron mediante las nuevas clasificaciones histopatológicas para linfomas y se sometieron a inmunohistoquímica (IHQ) con los anticuerpos anti-CD79a, anti-CD3, anticuerpos específicos para linfocitos B y T, además de un anti-LMP-1 como marcador de la presencia del EBV. Se encontró que el linfoma más común fue el linfoma nodal de zona T con un 75% de los casos. Al realizar la inmunomarcación se encontraron 18 casos positivos a CD3, 2 casos positivos a CD79a y 6 casos positivos a LMP-1, lo que representa el 30% de positividad del EBV en linfomas. El análisis Ji cuadrado demostró significancia estadística entre la presencia del virus y la presencia del linfoma lo que sugiere, no solamente que el virus está circulando en la población canina, sino que además puede tener relación con la ocurrencia de esta neoplasia. Con relación a las variables demográficas, sólo en la raza Golden Retriever se demostró relación con la presencia del linfoma, pero no con la presencia del virus.

ABSTRACT Epstein Barr virus (EBV) is a human high prevalent virus associated with lymphoid B cells tumors development. In canines, few reports have been published regarding the presence of the virus in dogs but its role in this species remains unclear. The aim of this study was to determine the presence of LMP-1 protein of EBV in 20 canine lymphomas tissues which were previously diagnosed in a period of time between 2004 -2014. Lymphomas were reclassified in accordance with the new histopathological classifications for lymphomas and were stained by IHQ with anti-CD79a, anti-CD3 and anti-LMP-1; in addition, specific antibodies for B lymphocytes, T lymphocytes and EBV biomarker, respectively. It was found that the most common lymphoma was T-zone lymphoma in 75% of the cases of the study. The distribution of the cases regarding the immunostaining was: 18 positive cases with anti-CD3, 2 positive cases with anti-CD79a and 6 positive cases with anti- LMP-1. Positive cases of LMP-1 as a biomarker of the presence of EBV corresponded to the 30% of the cases of the study. Chi-square test showed statistical significance between the presence of the virus and the presence of lymphomas, which suggests not only that the virus is circulating in the canine population but also that could have implications in the development of the disease. Regarding demographic parameters, only the Golden Retriever breed showed a relationship with the presence of lymphoma, but not with the presence of the virus.

Characteristic analysis of aggressive non-Hodgkin's lymphoma complicated by autoim-mune hemolytic anemia / 中国肿瘤临床

Objective:To explore the clinical characteristics and laboratory data of aggressive non-Hodgkin's lymphoma(NHL)compli-cated by autoimmune hemolytic anemia(AIHA).Methods:Data of six patients with aggressive NHL complicated by AIHA treated at the Second Affiliated Hospital of Suzhou University between September 2013 and July 2016 were reviewed retrospectively. The onset symptoms,disease progression,therapy,and prognostic factors were analyzed.Results:From September 2013 to July 2016,155 pa-tients with aggressive NHL were treated in our hospital.Six of them were complicated by AIHA(3.9%),with three males and three fe-males,aged from 62 to 74.The median age was 67 years.The first clinical symptoms included the following:five presented with lymph-adenectasis,three had fever,and one presented with multiple bone destruction and bone pain,all complicated by progressive hemo-globin decrease.Histological examination of the six patients revealed three cases with diffuse large B-cell lymphoma(DLBCL),including one case with positive Bcl-2,Bcl-6,and C-myc,and one case with positive CD5;one case was peripheral T-cell lymphoma-not other-wise specified(PTCL-NOS);and two cases with angioimmunoblastic T-cell lymphoma(AITCL).Epstein-Barr virus(EBV)-mRNA(EBER) was detected by chromogenic in situ hybridization(CISH).Up to 100%(5/5)cases were EBER-positive.Eastern Cooperative Oncology Group scores of the six patients were three to four.All six cases were in the Ann-Arbor stagesⅢ-Ⅳand International Prognostic Index score 4-5.All cases belonged to the high risk group.At the time when lymphoma was confirmed by pathology,the median level of he-moglobin was 56(34-79)g/L.The median ratio of reticulocytes was 6.7(0.2-21.0)%.The positive rate of Coombs test was 100%.All cas-es showed autoantibodies against C3(1:64-1:2 048).Four cases showed antoantibodies against G antigen(±~1:16).The plasma con-centration of EBV DNA of three patients was detected and all increased.Except that 1 case gave up treatment,five patients received the chemotherapy with CHOP or R-CHOP.Four patients received prednisone between chemotherapy intermittent period.Two cases showed sustained complete response(CR).The overall survival(OS)was 20 and 14 months.Another patient with DLBCL and one pa-tient with PTCL-NOS died from secondary severe pulmonary infection and heart failure during the myelosuppression.The OS times were 1.5 and 2 months,respectively.One patient with AITCL died in the disease progression after four cycles of chemotherapy.The OS was 4.5 months.Conclusion:Aggressive NHL complicated by AIHA is common in older patients with poor prognosis.The incidence rate of EBV infection was high,and hemolysis is rapid and serious.The patients'tolerance to chemotherapy was poor.Early diagnosis and effective chemotherapy may improve patients'prognosis.

Characteristic analysis of aggressive non-Hodgkin's lymphoma complicated by autoim-mune hemolytic anemia / 中国肿瘤临床

Objective:To explore the clinical characteristics and laboratory data of aggressive non-Hodgkin's lymphoma(NHL)compli-cated by autoimmune hemolytic anemia(AIHA).Methods:Data of six patients with aggressive NHL complicated by AIHA treated at the Second Affiliated Hospital of Suzhou University between September 2013 and July 2016 were reviewed retrospectively. The onset symptoms,disease progression,therapy,and prognostic factors were analyzed.Results:From September 2013 to July 2016,155 pa-tients with aggressive NHL were treated in our hospital.Six of them were complicated by AIHA(3.9%),with three males and three fe-males,aged from 62 to 74.The median age was 67 years.The first clinical symptoms included the following:five presented with lymph-adenectasis,three had fever,and one presented with multiple bone destruction and bone pain,all complicated by progressive hemo-globin decrease.Histological examination of the six patients revealed three cases with diffuse large B-cell lymphoma(DLBCL),including one case with positive Bcl-2,Bcl-6,and C-myc,and one case with positive CD5;one case was peripheral T-cell lymphoma-not other-wise specified(PTCL-NOS);and two cases with angioimmunoblastic T-cell lymphoma(AITCL).Epstein-Barr virus(EBV)-mRNA(EBER) was detected by chromogenic in situ hybridization(CISH).Up to 100%(5/5)cases were EBER-positive.Eastern Cooperative Oncology Group scores of the six patients were three to four.All six cases were in the Ann-Arbor stagesⅢ-Ⅳand International Prognostic Index score 4-5.All cases belonged to the high risk group.At the time when lymphoma was confirmed by pathology,the median level of he-moglobin was 56(34-79)g/L.The median ratio of reticulocytes was 6.7(0.2-21.0)%.The positive rate of Coombs test was 100%.All cas-es showed autoantibodies against C3(1:64-1:2 048).Four cases showed antoantibodies against G antigen(±~1:16).The plasma con-centration of EBV DNA of three patients was detected and all increased.Except that 1 case gave up treatment,five patients received the chemotherapy with CHOP or R-CHOP.Four patients received prednisone between chemotherapy intermittent period.Two cases showed sustained complete response(CR).The overall survival(OS)was 20 and 14 months.Another patient with DLBCL and one pa-tient with PTCL-NOS died from secondary severe pulmonary infection and heart failure during the myelosuppression.The OS times were 1.5 and 2 months,respectively.One patient with AITCL died in the disease progression after four cycles of chemotherapy.The OS was 4.5 months.Conclusion:Aggressive NHL complicated by AIHA is common in older patients with poor prognosis.The incidence rate of EBV infection was high,and hemolysis is rapid and serious.The patients'tolerance to chemotherapy was poor.Early diagnosis and effective chemotherapy may improve patients'prognosis.

Value of Detecting Peripheral Blood Cell Morphology Combined with EBV-DNA Quantity in the Initial Diagnosis for Infants Patients with Infectious Mononucleosis / 现代检验医学杂志

Objective To evaluate the value of detecting abnormal lymphocyte morphology in peripheral blood and Epstein Barr Virus(EBV)DNA quantity through real-time quantitative PCR (RT-qPCR)in the initial diagnosis for infants patients with infectious mononucleosis (IM).Methods From Jan.2013 to Dec.2014 212 infants patients with IM were analysed ret-rospectively,which were all in-patients in the hospital.The abnormal lymphocyte morphology in peripheral blood and Epstein Barr Virus (EBV)DNA quantity were both detected in the initial fever period and a week later.The latter was detected by real-time quantitative PCR (RT-qPCR),combined with all the symptoms were all analysed comprehensively.The percentage of abnormal lymphocyte more than 10% was positive,and the EBV-DNA quantity more than 1.0×103 copy per ml was posi-tive,too.Results Of all the infants patients,in the initial fever period,82 patients had more than 10% positive abnormal lymphocyte and 100 patients had positive EBV-DNA quantity.But a week later,156 patients had more than 10% positive ab-normal lymphocyte,the maximum abnormal lymphocyte was 56%.And 180 patients had positive EBV-DNA quantity.When both abnormal lymphocyte morphology in peripheral blood and Epstein Barr Virus (EBV)DNA quantity were detected,in the initial fever period,125 patients were positive,it rose significantly more than that of abnormal lymphocyte morphology in peripheral blood (χ2=17.45,P0.05).Conclusion The detecting of peripheral blood cell morphology combined with EBV-DNA quantity are very important in the initial diagnosis for infants patients with infectious mononucleosis.Including all the symp-toms,they could improve the diagnosis timely and accurately.

Evaluation of Real-time PCR Kits for Epstein-Barr Virus DNA Assays

BACKGROUND: Epstein-Barr virus (EBV) is known to be the causative agent of infectious mononucleosis and EBV-related malignancies. In this study, we compared the results of three real-time PCR kits for EBV DNA assays. METHODS: A total of 300 whole blood samples submitted for quantitative EBV PCR between January 2013 and September 2014 at Severance Hospital were included. The samples were tested by using the Artus EBV RG PCR Kit (Qiagen, Germany), AccuPower EBV Quantitative PCR Kit (Bioneer, Korea), and Real-Q EBV Kit (BioSewoom, Korea). Samples with discordant results between the three kits were confirmed by direct sequencing. RESULTS: The result concordance rate and kappa coefficient (K) were 86.3% and 0.69 for Artus-AccuPower, 93.3% and 0.85 for Artus-Real-Q, and 92.3% and 0.83 for AccuPower-Real-Q, respectively. The correlations between the three kits were found to be significant, with a correlation coefficient of r=0.854 for Artus-AccuPower, -0.802 for Artus-Real-Q, and -0.977 for AccuPower-Real-Q, respectively (P<0.0001). If the real-time PCR concordant results of 258 samples and the direct sequencing results of 42 real-time PCR discordant samples were assumed to be true, the sensitivity/specificity values were 0.921/0.976 for Artus, 0.902/0.965 for AccuPower, and 0.967/1.000 for Real-Q. CONCLUSIONS: The three real-time PCR kits showed excellent sensitivities and specificities. All these kits would be acceptable for clinical and therapeutic management of EBV. However, some discordant results between the kits indicate the need for caution in clinical diagnosis and staging. Further implementation of standardized methodology would be needed for EBV DNA assays.

Leucoplasia pilosa bucal: presentación de caso clínico / Bucal hairy leukoplakia: a case report

Se presenta caso clínico de paciente con lesiones blanquecinas en bordes laterales de lengua de 1 año de evolución aproximadamente; clínicamente asintomático, sin hábitos tóxicos ni antecedentes médicos de importancia. Actualmente bajo tratamiento ortodóntico, en donde el especialista lo alerta sobre la importancia de interconsultar con el Patólogo Bucal. Luego de una exhaustiva historia clínica, se toma muestra de la lesión y el examen histopatológico arrojó: hiperplasia epitelial exofítica, paraqueratosis excesiva y células superficiales en forma de globo con típica fragmentación nuclear, indicativo de inclusión viral (Cuerpos de Cowdry). Con estos hallazgos, la correlación con las características clínicas de la lesión y los exámenes serológicos (positivo para VIH), se llega a un diagnóstico conclusivo de Leucoplasia Pilosa Bucal (LPB). Se remitió el paciente al Instituto Anzoatiguense de la Salud (SALUDANZ), entidad encargada de problemas de Salud Pública en el Edo. Anzoátegui. La Leucoplasia Pilosa Bucal (LPB) se presenta comúnmente en pacientes VIH+ y representa un factor informativo y predictivo para el odontólogo, estomatólogo y cualquier especialista de la rama de la salud, en cuanto al tratamiento, diagnóstico y pronóstico bucal y sistémico del paciente.

We report the clinical case of a patient with whitish lesions on lateral tongue edges with 1 year of evolution approximately, clinically asymptomatic, without toxic habits or important medical history. The patient was in orthodontic treatment, when the specialist warns the importance of Bucal Pathologist review. After a thorough medical history, biopsy was taken and histopathological examination showed: exophytic epithelial hyperplasia, excessive parakeratosis and superficial balloon cells with typical nuclear fragmentation, indicative of viral inclusion (Cowdry Body´s). With these findings and correlation with lesion clinical features and serological tests (HIV positive), the final diagnosis was Bucal Hairy leukoplakia (OHL). The patient was referred Anzoatiguense Health Institute (Saludanz), entity responsible of public health problems in the Anzoátegui State, Venezuela. The Bucal Hairy Leukoplakia (OHL) occurs commonly in HIV patients and represents an informative and predictive factor for the dentist, stomatologist and any health branch specialist for treatment, diagnosis and prognosis of the patient.

Lytic replication of Epstein-Barr virus in human peripheral T-lymphocytes

Background: There are few reports about the interactions of EBV with peripheral T-cells, especially during the early phase of infection. Objective: Demonstrate the capability of EBV to infect and replicate in human peripheral T-cells in vitro. Methods: After treating with EBV, the susceptibility of in vitro EBV infection into T-cells was confirmed using electron microscopy, the expression of EBV mRNA using RT-PCR, and the expression of EBV proteins using Western blot analysis. The expression of CD19 and CD21 mRNA was determined using RT-PCR. The induction of cell death was measured using trypan blue exclusion assay. Results: The susceptibility of in vitro EBV infection was confirmed by the presence of virus particles in the cytoplasm. The entering to lytic infection was confirmed by detection the expression of EBV lytic (BZLF1) mRNA, and the expression of late lytic proteins (VCA and gp350/220). The expression of CD19 and CD21 were not observed using RT-PCR. The interactions of EBV with T-cells leaded to induction of T-cell death. Conclusion: Peripheral T-cells are a direct target of EBV infection. At the beginning of infection by EBV, EBV infection of T-cells leads to the entering into lytic virus replication. EBV binds to these cells through a receptor distinct from the CD21.

A case of concomitant epstein-barr virus-induced hepatitis on chronic autoimmune hepatitis / 대한내과학회지

Autoimmune hepatitis (AIH), a rare cause of chronic liver disease in Korea, is a chronic, predominantly periportal hepatitis characterized by hypergammaglobulinemia, tissue autoantibodies, and responsiveness to immunosuppressive therapy. Here we report a rare case of Epstein-Barr virus (EBV) hepatitis in the presence of a previous diagnosis of AIH. A 25-year-old woman was admitted to the hospital with fever and myalgias. Laboratory data showed elevated aminotransferases, hypergammaglobulinemia, increased anti-nuclear antibody (ANA) titer, positive anti-smooth muscle antibody (ASMA) test, negative anti-mitochondrial antibody (AMA) test, and negative antibody against liver kidney microsome-1 (anti-LKM-1) test. Serologic viral markers of EBV indicated a recent EBV infection. Liver biopsy was performed to search for evidence of accompanying autoimmune liver disease. Liver biopsy findings were consistent with chronic active hepatitis. In-situ hybridization performed on the liver tissue confirmed the presence of EBV DNA. The patient has been treated with prednisolone and has shown subsequent improvement in clinical symptoms and liver function tests.

Quantifing the Circulating Epstein-Barr Virus (EBV) DNA to Monitor a Case of Aggressive Natural Killer Cell Leukemia / 대한혈액학회지

Epstein-Barr virus (EBV) infection is associated with various lymphoproliferative diseases, including Hodgkin lymphoma, extranodal NK/T cell lymphoma, aggressive NK cell leukemia, Burkitt lymphoma and post-transplant lymphoproliferative disorder. In the recent studies, the plasma EBV-DNA levels in patients with EBV-associated lymphoproliferative disease appeared to be correlated with the therapeutic response. Aggressive NK cell leukemia (ANKL) is a fatal disease that's characterized by high fever, lymphadenopathy, hepatosplenomegaly and frequent hemophagocytosis. No serological tumor marker for this malignancy has yet been identified for monitoring the disease and predicting the outcome. We experienced a case of aggressive natural killer cell leukemia in a 48-year-old man, and we serially monitored the plasma EBV DNA load by performing real time quantitative PCR assay. Serial measurements of the plasma EBV DNA level during therapy showed a close correlation between the clinical response and the changes in the plasma EBV DNA titers.

The Comparative and Functional Study between Two Construction Methods of shRNA Expression Vector Targeted LMP1 Gene Encoded by EBV / 中国病毒学

To look for a more stable and convenient way of constructing short hairpin RNA expression vectors targeting the latent membrane protein-1(LMP-1) encoded by Epstein-Barr virus(pshLMP1), and to study the inhibition function of pshLMP1 expression vectors in HNE1 cells, we designed the pshLMP1 expression cassette and pshLMP1 expression vectors by both the annealing method and PCR method and then co-transfected with pEGFP-N1-1158 into HNE1 cells to observe the mRNA and protein levels of LMP-1 genes by green fluorescence analysis, RT-PCR and western blot. pshLMP1 expression vectors were successfully obtained by both methods but better cloning efficiency was achieved and fewer deletions and mutations of nucleotides were achieved with the PCR method. Furthermore, the mRNA and protein levels of LMP-1 genes were down-regulated by pshLMP1 expression vectors. According to our research, we found that the PCR method provides a more efficient way to construct pshLMP1 expression vectors which have the ability to inhibit the function of LMP-1 genes expressed in HNE1 cells, and also provides a novel application of RNA interference technology against-EBV.

Association of Epstein-Barr Virus and Head and Neck Cancer in an Endemic Area / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: A number of reports have suggested that Epstein-Barr virus (EBV) is associated with different forms of head and neck cancers (HNC) such as nasopharyngeal carcinoma, NK/T cell lymphoma and Burkitt's lymphoma. We evaluated the association of EBV with HNC as a causative factor in an endemic area of the virus. SUBJECTS AND METHOD: Fresh specimens of HNC were obtained from 72 new patients between August 2003 and January 2005. In situ hybridization for EBER was performed with immunohistochemical staining of p53, Bcl-2 and LMP-1 and serologic tests on anti-viral capsid antigen(VCA) and anti-early antigen (EA)-D. The results of EBV positivity were analyzed according to tumor TNM stages, sites, pathology and smoking status. A correlation between EBV positivity and p53, Bcl-2, LMP-1 positive staining was investigated. RESULTS: Nine (12%) of the total 72 patients showed EBV positivity of tumor, depending mainly on pathology and sites, but not tumor staging, age, sex or smoking status : NPC (3), NK/T cell lymphoma (5), lymphoephithelial carcinoma of the parotid gland (1). All patients had sero-positivity of anti-VCA IgG but not anti-VCA IgM and anti-EA-D. There was a relationship between the presence of EBV, its oncoprotein (LMP-1) and oncogene (Bcl-2). CONCLUSION: Overall, the incidence of EBV positivity of HNC in an endemic area is not significantly different from the prior reports about non-endemic area. The association between EBV and LMP-1 or Bcl-2 may be helpful for understanding the role of viral oncogenes in the HNC.

Bone Marrow Fibrin-Ring Granuloma: Review of 24 Cases / 대한진단검사의학회지

BACKGROUND: Fibrin-ring granuloma (FRG), which can be found in bone marrow or the liver, is a subtype of epithelioid granuloma characterized by a central fat vacuole and annular peripheral fibrinoid materials. FRG has been proven to be associated with many etiologies such as several infectious organisms (Coxiella burnett; Epstein-Barr Virus, EBV; cytomegalovirus, CMV; and hepatitis A virus), allopurinol induced hepatitis, Hodgkin's lymphoma, and peripheral T-cell lymphoma. METHODS: We retrospectively reviewed 24 patients diagnosed with FRG by bone marrow biopsy at a single institute between 1995 and 2004. We reviewed clinical symptoms and laboratory findings of the patients, classified them by etiology, and compared prognosis of each group. RESULTS: The most common cause of FRG was acute or chronic EBV infection. Chronic or acute EBV infection was associated with 41.4% of patients (10/24). Of the remaining patients, 33.3% (8/24) were leukemia or lymphoma patients after chemotherapy, 4.2% (1/24) was a patient with hepatic failure, and 20.8% (5/24) were diagnosed as fever of unknown origin. The most common symptom and clinical finding were fever and cytopenia. EBV-associated group comprised chronic active EBV infection, EBV-associated hemophagocytic histiocytosis, acute EBV infection, EBV-associated lymphoproliferative disease, and Langerhans' cell histiocytosis. The EBV-associated group showed a lower survival probability compared with the non-EBV group (P<0.05). CONCLUSIONS: Patients with bone marrow fibrin ring granuloma accompanied by fever require an active workup to find out the cause of infectious agents including EBV infection particularly due to their poor prognosis.

Epstein-Barr Virus in Human Malignancy: A Special Reference to Epstein-Barr Virus associated Gastric Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

Epstein-Bar virus (EBV), a human herpesvirus, establishes a life-long persistent infection in 90~95% of human adult population worldwide. EBV is the etiologic agent of infectious mononucleosis, and EBV is associated with a variety of human malignancy including lymphoma and gastric carcinoma. Recently, EBV has been classified as group 1 carcinogen by the WHO International Agency for Research on Cancer. Evidence is presented which suggests that failures of the EBV-specific immunity may play a role in the pathogenesis of EBV-associated malignancy. At present, the precise mechanisms by which EBV transforms B lymphocytes have been disclosed. Encouragingly, they have had enough success so far to keep them enthusiastic about novel therapeutic trial in the field of EBV-associated lymphoma. However, information on EBV-associated gastric carcinoma is still at dawn. This article reviews EBV biology, immunological response of EBV infection, unique oncogenic property of EBV, peculiarity of EBV-associated gastric carcinoma, and lastly, EBV-targeted therapy and vaccination.

Clinical Significance of Epstein-Barr Virus Expression in Breast Cancer / 한국유방암학회지

PURPOSE: Epstein-Barr Virus (EBV) is well understood as an oncogenic virus in human tumors. Its association with breast cancers has been reported but is still in controversy. So we have examined the expression of EBV in breast cancers and evaluated the relationship between the well-known prognositc factors of breast cancer and EBV expression. METHODS: A retrospective study was conducted with patients who had been re-evaluated to confirm the diagnosis based on immunohistochemical analysis with EBNA-2 expression, between January 1991 and December 2002. The cases were assigned to the positive lesion that displayed 10% or more of immunoreactive cells. RESULTS: The expressions of EBNA-2(Ebstein Barr virus nuclear antigen - 2) were noted in 26 (21.1%) out of 123 cases of breast cancer patients and 4 (20%) out of 20 cases in a control group of benign tumors. The expression of EBV in breast cancers and that of a control group were not different significantly. But, the correlation between the expression of EBNA-2 and ER status was noted statistically significant (P=0.040). CONCLUSION: Judging from the results of our study, EBV infection detected in breast cancer seems to be latent and the association of EBV to breast cancer is less likely related.