Effect Of Epstein-Barr Virus Infection Research Articles

Effect of Epstein-Barr Virus Infection on the Treatment of Gastric Cancer in Tumor Immunotherapy

Gastric cancer is one of the biggest medical problems in the world today, and it is also a huge medical challenge for human beings. The main challenge is the complexity of the limitations of gastric cancer itself. At present, the efficacy of single-drug immune checkpoint inhibitors in treatment is not clear. It can be found in previous cases that Epstein-Barr virus positive gastric cancer patients have significantly higher response to PD-1 antibodies than the overall patients, from which it can be found that EBV infection can play an important role in gastric cancer immunotherapy. The purpose of this study was to investigate the effect of Epstein-Barr virus infection on gastric cancer and analyze specific clinical cases. The results showed that patients infected with Epstein-Barr virus had obvious advantages in the treatment of gastric cancer, which was significantly correlated with the expression of PD-L1 and EBV (+). This study highlights the potential benefits of Epstein-Barr virus infection in the treatment of gastric cancer, providing new insights into the development of future immunotherapy strategies. These findings will help to improve the treatment of gastric cancer patients, as well as to better understand the immune properties of gastric cancer and develop related vaccines. The significance of this study is that it provides a solid foundation for innovation in the treatment of gastric cancer.

Influence of Epstein-Barr virus infection on developing multiple sclerosis

Multiple sclerosis (MS) is the most common inflammatory-demyelinating disease. MS leads to the multifocal damage of the central nervous system, which causes the gradual deterioration of sensory, motor and cognitive functions. The etiology of this disease is not fully understood, but genetic and environmental factors (including the EBV infection) are suspected. In this review, we would like to summarize the state of knowledge over the effect of Epstein-Barr virus infection on developing multiple sclerosis.
 Infectious mononucleosis (IM) which is caused by EBV and MS have similar epidemiology: both diseases mainly affect people at a young age, geographical prevalence is also identical. There are many theories that explain the mechanism of the EBV involvement in the development of MS including: the migration of EBV-infected B cells into the Central Nervous System, the theory of molecular mimicry, the induction of αB-crystallin by EBV in lymphoid cells or cooperation of the EBV and other viruses in the development of MS. Observations by physicians from around the world suggest that EBV infection is a strong factor in the development of multiple sclerosis. Epstein-Barr virus is prevalent in the population. There are a lot of evidences that suggest its involvement in the development of multiple sclerosis. Prevention of EBV infection could potentially reduce the amount of cases of MS. However, more researches are needed to clearly confirm the involvement of EBV in the etiopathogenesis of developing MS.

Indication of Neurodegenerative Cascade Initiation by Amyloid-like Aggregate-Forming EBV Proteins and Peptide in Alzheimer's Disease.

The neurotropic potential of the Epstein-Barr virus (EBV) was demonstrated quite recently; however, the mechanistic details are yet to be explored. Therefore, the effects of EBV infection in the neural milieu remain underexplored. Previous reports have suggested the potential role of virus-derived peptides in seeding the amyloid-β aggregation cascade, which lies at the center of Alzheimer's disease (AD) pathophysiology. However, no such study has been undertaken to explore the role of EBV peptides in AD. In our research, ∼100 EBV proteins were analyzed for their aggregation proclivity in silico using bioinformatic tools, followed by the prediction of 20S proteasomal cleavage sites using online algorithms NetChop ver. 3.1 and Pcleavage, thereby mimicking the cellular proteasomal cleavage activity generating short antigenic peptides of viral origin. Our study reports a high aggregate-forming tendency of a 12-amino-acid-long (146SYKHVFLSAFVY157) peptide derived from EBV glycoprotein M (EBV-gM). The in vitro analysis of aggregate formation done using Congo red and Thioflavin-S assays demonstrated dose- and time-dependent kinetics. Thereafter, Raman spectroscopy was used to validate the formation of secondary structures (α helix, β sheets) in the aggregates. Additionally, cytotoxicity assay revealed that even a low concentration of these aggregates has a lethal effect on neuroblastoma cells. The findings of this study provide insights into the mechanistic role of EBV in AD and open up new avenues to explore in the future.

Effects of Epstein-Barr Virus Infection on the Response of Human Breast Cancer Cells to Nicotine.

The purpose of our study was to test whether EBV infection affects the response of human breast cancer cells to nicotine. In addition, the underlying signaling mechanisms were evaluated. EBV-infected MDA-MB-231 and LMP1-transfected MDA-MB-231 breast cancer cells were established. Reverse transcription-polymerase chain reaction and western blotting were performed to evaluate nicotine receptor expression. To verify the functional role and underlying signaling mechanism of nicotine receptor expression induced by EBV infection, morphologic analysis, and proliferation and inhibition assays were performed. Both EBV infection and LMP1 transfection increased cell proliferation and induced the up-regulation of α9-nAChR expression. Additionally, nicotine treatment induced tumorigenic activity in both EBV-infected and LMP1-transfected MDA-MB-231 breast cancer cells. Western blot and inhibitor assays showed that the nicotine-induced signaling was mediated through MAPK/ERK and AKT signaling pathways in EBV-infected and LMP1-transfected breast cancer cells, respectively. These results suggest that EBV infection and EBV-related LMP1 may act as potential molecular targets for breast cancer risk associated with nicotine, and provide a novel insight into the mechanism of nicotine stimulation in EBV-positive breast cancer cells.

Effects of Epstein-Barr Virus Infection on the Risk and Prognosis of Primary Laryngeal Squamous Cell Carcinoma: A Hospital-Based Case-Control Study in Taiwan.

Simple SummaryEpstein–Barr virus DNA positivity, age ≥ 55 years, cigarette smoking, and high BCL-2, B2M, and CD161 expression were identified as independent risk factors for primary laryngeal squamous cell carcinoma. A high EBER signal and low CD3 expression significantly and independently predicted local recurrence and disease-free survival within five years. The information obtained in this study improves our understanding of viral infections in laryngeal cancer, and may guide future prevention, treatment, and follow-up strategies. Mounting molecular evidence supports Epstein–Barr virus (EBV) involvement in the pathogenesis of laryngeal squamous cell carcinoma (LSCC); however, the epidemiological data are inconsistent. In this retrospective case-control study, we aimed to determine whether EBV infection underlies the risk and prognosis of LSCC. The prevalence of EBV infection, as analyzed using an EBV DNA polymerase chain reaction assay, was significantly higher in 42 Taiwanese patients with newly diagnosed primary LSCC, compared to 39 age- and sex-matched control patients without cancer (48% vs. 19%). Furthermore, most of the EBER signals detected using in situ hybridization were localized to the nuclei of tumor-infiltrating lymphocytes. In multivariate analysis, EBV DNA positivity, age ≥ 55 years, cigarette smoking, and high BCL-2, B2M, and CD161 expression (assessed using immunohistochemistry) were identified as independent risk factors for LSCC. Furthermore, five-year local recurrence and disease-free survival rates were 34% and 58%, respectively, with a high EBER signal and low CD3 expression independently predicting five-year local recurrence and disease-free survival. Our comprehensive profiling data accurately identified patients at risk for LSCC development, local recurrence, or disease-free survival. The information obtained in this study improves our understanding of EBV infection in LSCC, and may guide precision medicine for patients with LSCC.

Epstein–Barr virus and multiple sclerosis

Multiple sclerosis (MS) is a chronic inflammation of the central nervous system, a characteristic feature of which is the gradual development of focal and irreversible demyelination of the membranes of nerve structures in the spinal cord and brain, which leads to a gradual accumulation of neurological deficit and disability.Aim – substantiation of the role of Epstein–Barr virus infection in the etiology and pathogenesis of MS based on the analysis of modern literary sources.Herpes gamma viruses remain one of the most important suspects in the etiology of MS, including Epstein–Barr virus (EBV), which causes a lifelong infectious process in the human body. Human gammaherpesvirus 4 (HHV-4) can realize its pathogenic potential by performing lytic replication or lead to a delay in replication or reactivation of infection in both epithelial cells and B lymphocytes.Taking into account current data on the biological properties of EBV and analyzing the role of this herpes virus in the pathogenesis of neurodegenerative diseases, this review was generated. Due to its molecular structure, EBV has specific biological properties, among which one of the most important is its tropism for the host’s immune tissue, in particular, B-lymphocytes, which obviously determines the life-long persistence of the virus. Thus, forming a latent process in the human body due to replicative cycles in B cells, EBV, on the one hand, controls the primary response of B lymphocytes, which leads to a deficiency of both humoral and cellular immunity factors. On the other hand, it contributes to the persistence of HHV-4 and the development of an infectious process constant with periods of reactivation.With this in mind, an important detail that may link EBV infection with MS is that the development of the clinical picture and its course bears some similarity to natural HHV-4 infection, probably following the biological cycle of the virus over a certain period of time. Therefore, based on the found indirect relationship between EBV infection and MS, as well as on the indicated immunological and genetic mechanisms that are involved in neuroinflammatory processes, it is impossible not to take into account the role of herpes viruses in the development of the disease. But why, among a large population of HHV-4 carriers, only a small percentage develop EBV-associated MS remains to be seen.Analyzing the conducted studies in which different results were obtained on the effect of EBV infection on different periods of MS development (by initiating the triggering or maintaining the inflammatory process or participating in its progression), it has now become clear that if the etiological role of EBV in this disease is present, then the course of the disease is not may not be related to HHV-4 biological cycles.Conclusions. Currently, a direct connection is established between EBV infection and the development of MS. However, it is also impossible to refute and even more so to reject the role of human gammaherpesvirus 4 in the pathogenesis of multiple sclerosis.

Effects of Epstein-Barr Virus Infection on CD19+ B Lymphocytes in Patients with Immunorelated Pancytopenia.

Objectives To explore effects of Epstein-Barr virus (EBV) infection on CD19+ B lymphocytes in patients with immunorelated pancytopenia (IRP). Methods An enzyme-linked immunosorbent assay (ELISA) in vitro diagnostic kit was used to detect EBV capsid antigen- (CA-) IgG and VCA-IgM antibodies in the serum. We analyzed the EBV-DNA copies of CD19+ B lymphocyte by using real-time quantitative polymerase chain reaction (RT-qPCR). CD21, CD23, CD5, CD80, and CD86 receptors on the surfaces of CD19+ B cells were detected by flow cytometry (FCM). The correlation between these receptors and EBV-DNA copies were evaluated. Results The results revealed that the positive rate of EBVCA-IgM and CD19+ B lymphocyte EBV-DNA copy in the IRP group were significantly higher than those in the control group (P < 0.05). CD19+ B lymphocyte EBV-DNA copies were also more abundant in IRP patients than in control subjects (P < 0.05). CD19+ B lymphocyte EBV-DNA copies were also more abundant in IRP patients than in control subjects (P < 0.05). CD19+ B lymphocyte EBV-DNA copies were also more abundant in IRP patients than in control subjects (Conclusions EBV infection may activate CD19+ B lymphocytes and further disrupt bone marrow hematopoiesis in IRP patients.

Autoimmune and lymphoproliferative malignant diseases associated with Epstein-Barr viral infection

Currently, in medical practice, there is a high interest in diseases caused by herpes viruses, among them the Epstein-Barr virus (EBV) occupies the leading place. Almost 90% of the worlds population over the age of 40 are infected with VEB. In patients of the first two years, the proportion of asymptomatic carriage reaches 90%, and at the age of 2-10 30-50%. The article considers current data on the impact of EBV on cellular and humoral immunity, its connection with autoimmune and lymphoproliferative diseases. EBV has been shown to play a significant role in the onset of oncological diseases such as Hodgkins lymphoma, Burkitts lymphoma, nasopharyngeal carcinomas, as well as autoimmune diseases systemic lupus erythematosus, rheumatoid arthritis, Sjogrenʼs syndrome, autoimmune hepatitis, lymphoid interstitial hepatitis, lymphoid interstitial syndrome. The results of studies over the past 5 years of cases of activation of autoimmune processes associated with EBV infection, as well as predisposing factors underlying these manifestations, are presented. Due to the fact that the autoimmune effect of EBV infection is manifested in various organs and tissues, this problem is multidisciplinary, affecting such fields of medicine as pediatrics, infectious diseases, endocrinology, oncology, gynecology, ophthalmology, gastroenterology, etc.

Effect of Epstein-Barr virus infection on children suffered from juvenile idiopathic arthritis

Objective To study the effect of Epstein-Barr virus(EBV) infection on the children suffered from juvenile idiopathic arthritis(JIA). Methods The clinical and laboratory data of 167 children suffered from JIA were retrospectively analyzed.These children were divided into 2 groups according to if they had complications or not (such as organ involved, infection, etc). The differences about the history, laboratory tests of 2 groups of EBV infected and non-infected group were respectively analyzed. Results In the group of the 132 cases of JIA children with no complications, there were significant differences between EBV infected group and the non-infected group in onset age, erythrocyte sedimentation rate[21.00(9.00, 46.50) mm/1 h vs9.00(3.00, 24.00) mm/1 h], CD8%[(26.88±6.72)% vs (22.79±6.61)%], CD4%/CD8%[1.40(1.20, 1.75) vs 1.60(1.30, 2.00) ], IgA[1.70(0.88, 2.74) g/L vs 0.66(0.33, 1.14) g/L], IgG[11.40(9.73, 14.30) g/L vs 9.46(7.71, 11.90) g/L], IgE[8.41(23.93, 151.42)×103 IU/L vs 22.80(8.55, 69.75)×103 IU/L](all P<0.05). In the 35 cases with complications, there were significant differences between EBV infected group and the non-infected group in age of onset[(83.82±44.13)months vs (33.88±16.36) months], CD4%/CD8%[(1.32±0.41) vs (1.71±0.38)] and IgA[(1.50±1.04) g/L vs (0.47±0.27) g/L] and IgA (all P<0.05). Conclusions The pathogenesis of JIA is not very clear so far, EBV infection may be involved in the occurrence and development process, the children occurred JIA with EBV infection, the inflammatory reaction maybe more obvious and more difficult to control.The immune disorders maybe more significant.After all, EBV infection has a certain impact on JIA, but the specific impacts and mechanisms need to be further studied. Key words: Juvenile idiopathic arthritis; Epstein-Barr virus; Child

Effect of Epstein-Barr virus infection on predisposition and postradiotherapeutic prognostic value among Libyan patients with nasopharyngeal cancer

Abstract Libya is one of the North African countries with an endemic of nasopharyngeal carcinoma, particularly in the northern part of Libya as compared with its southern part. The clinical and histopathological presentation reveals no uniquely specific pattern of appearance; however, there is high deficiency in the data that confirm the possible predisposing factors that may play a role in the development of this common variety of head and neck cancer in this country, and whether these factors affect the patients’ response to treatment. This study was conducted to determine the role of the Epstein-Barr virus (EBV) in the risk for nasopharyngeal cancer in the Libyan population; the results were correlated with radiotherapy response and improvement in the post-therapeutic prognostic value. Sixteen patients aged 9–80 years presented at the ENT Department, Althowra Central Teaching Hospital, Albyda, Libya, from September 2005 to January 2014 with variable patterns of clinical presentation suggestive of nasopharyngeal carcinoma. All patients were evaluated radiologically and endoscopically. The diagnosis was confirmed by biopsy and further histopathological assessment. For all patients, serological elucidation for IgG and IgM anti-EBV antibodies was carried out, and the results were correlated with age at incidence, sex of the patient, pattern of clinical presentation, pattern of histopathological presentation, response to radiotherapy, rate of recurrence, and 5-year survival. In all, 88% of patients showed a significant increase in serum IgG against viral capsid antigen of EBV; 83% of the cases presented with cervical masses and unilateral otitis media with effusion; 86% of cases showed lymphoepithelioma as histopathological pattern. All patients with lymphoepithelioma showed significant response to concomitant radiochemotherapy (100%) with high survival rate exceeding 5 years. The EBV infection can be considered one of the main predisposing factors to nasopharyngeal carcinoma in the Libyan population. It was noted from this study that the induction of cancer by EBV is mainly by chronic infection rather than by acute infection; this was confirmed by significant elevation in serum IgG rather than IgM. In addition, it was postulated that the EBV infection is most likely associated with the lymphoepithelioma variety of histopathology rather than with the well-differentiated type, and as it was elucidated through this study that the association of the cancer with EBV infection increased the sensitivity of the tumor to concomitant radiochemotherpy, thus improving the 5-year survival after treatment.

Effects of Epstein-Barr virus infection on the development of multiple myeloma after liver transplantation

Reduced cellular immune function in patients after liver transplantation easily results in many types of viral infections, such as Epstein-Barr virus. Epstein-Barr virus is a Γ-herpesvirus and is related to many malignant diseases, especially epithelial and lymph tumors. The abnormal interaction of cluster of differentiation 40 with cluster of differentiation 40 ligand and expression of cluster of differentiation 40 ligand are considered closely related to the development of myeloma cells. This study explored the influence and mechanism of Epstein-Barr virus infection on the phenotype and biological behavior of myeloma cells after liver transplantation. Flow cytometry was used to detect coexpression of cluster of differentiation 40 and cluster of differentiation 40 ligand in 10 samples of freshly isolated multiple myeloma cells. Cluster of differentiation 40 and cluster of differentiation 40 ligand were coexpressed in sample Nos. 5, 8, 9, and 10, particularly in sample No. 5. Western blot analysis was used to detect the expression of the Epstein-Barr virus antigens latent membrane protein 1 and Epstein-Barr virus nuclear antigen 2 in the multiple myeloma cell line RPMI 8226 infected with Epstein-Barr virus. The antigen expression indicated that Epstein-Barr virus can infect multiple myeloma virus cells in vitro. Reverse transcription-polymerase chain reaction revealed upregulated expression of cluster of differentiation 40 ligand on the infected RPMI 8226 cells, which may be involved in the anti-apoptosis activity of the infected cells. Confocal microscopy showed that pairs of molecules of cluster of differentiation 40, cluster of differentiation 40 ligand, and latent membrane protein 1 were colocalized on the surface of the infected cells. CXC chemokine receptor 4 was upregulated on the RPMI 8226 cells after Epstein-Barr virus infection. The migratory ability of the infected cells improved in the presence of the chemokine stromal cell-derived factor-1α. Anti-apoptosis and migration are known important biological characteristics of malignant cells. Our results indicate the involvement of Epstein-Barr virus in the origin and development of multiple myeloma. The risk of multiple myeloma increases when Epstein-Barr virus infects B cells in the germinal center, which may result in an anti-apoptosis effect of B cells and an improved ability to migrate from the germinal center to peripheral blood.

Abstract 2037: Cyclin D1 overexpression supports stable EBV infection in nasopharyngeal epithelial cells

Abstract Poorly or undifferentiated nasopharyngeal carcinoma (NPC) is regularly associated with Epstein-Barr virus (EBV) infection. EBV infection of premalignant nasopharyngeal epithelial cells has been postulated to play an important role in the pathogenesis of nasopharyngeal carcinoma. We have previously reported that genetic alterations could be detected in premalignant nasopharyngeal epithelial tissues. It is not clear if these genetic alterations may associate with the establishment of EBV infection. In this study, we have examined the role of cyclin D1 in supporting EBV infection in nasopharyngeal epithelial cells. While cyclin D1 is commonly expressed in nasopharyngeal carcinoma tissues we found that overexpression of cycline D1 is readily detected in dysplastic nasopharyngeal epithelial closely associated with EBV infection. Furthermore, using a panel of immortalized nasopharyngeal epithelial cells, we demonstrated that overexpression of cyclin D1 or CKD4 supports EBV infection and result in the establishment of stable EBV infected nasopharyngeal cell lines. We also observed that EBV infection induced growth inhibition and senescence in nasopharyngeal epithelial cells, which may be the underlying reason for low detection rate of EBV infection in healthy nasopharyngeal epithelial tissues. However, cyclin D1 overexpression suppressed senescence and differentiation in the immortalized nasopharyngeal epithelial cells, suggesting cyclin D1 may play an important role in supporting EBV infection in these cells. We postulated that the altered expression of cyclin D1 or CDK4 in premalignant nasopharyngeal epithelial cells may over-ride the growth suppression effects of EBV infection and support EBV latent infection in premalignant nasopharyngeal epithelial cells. Acknowledgement: This study is sponsored by grant support received from the Hong Kong Research Grant Council (Grant number: GRF780911 and AoE /M-06/08) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2037. doi:1538-7445.AM2012-2037

Contribution of Epstein-Barr virus infection to chemoresistance of gastric carcinoma cells to 5-fluorouracil

Although Epstein-Barr virus (EBV) is associated with 6-16% of the gastric carcinoma (GC) cases, the effect of EBV infection on the tumorigenesis process and the responsiveness to chemotherapy remain unclear. We compared chemosensitivity of the EBV-positive GC (AGSEBV) and EBV-negative GC (AGS) cells to 5-fluorouracil (5-FU). Although 5-FU inhibited the growth of both cell lines in a dose- and time-dependent manner, the sensitivity of EBV-positive GC cells to 5-FU was lower than that of EBV-negative GC cells. The cleavage of PARP and caspase-3 was also lower in AGS-EBV cells than in AGS cells following 5-FU treatment. Both the level of Bcl-2 expression and the ratio of Bcl-2/Bax were higher in AGS-EBV than in AGS cells not only at basal state but also following 5-FU treatment. Moreover, p53 and p21 expression was enhanced further by 5-FU in AGS than in AGS-EBV cells. Immunofluorescence assay and Western blot showed that 5-FU induced the expression of EBV-lytic genes including BZLF1, BRLF1, BMRF1 and BHRF1. Our results suggest that latent and lytic EBV infection contributes to the chemoresistance to 5-FU in gastric carcinoma by modulating apoptosis related cellular genes.

NOLC1, an Enhancer of Nasopharyngeal Carcinoma Progression, Is Essential for TP53 to Regulate MDM2 Expression

Nasopharyngeal carcinoma (NPC) is one of the most common cancers among Chinese living in South China, Singapore, and Taiwan. At present, its etiological factors are not well defined. To identify which genetic alterations might be involved in NPC pathogenesis, we identified genes that were differentially expressed in NPC cell lines and normal nasomucosal cells using subtractive hybridization and microarray analysis. Most NPC cell lines and biopsy specimens were found to have higher expression levels of the gene encoding nucleolar and coiled-body phosphoprotein 1 (NOLC1) as compared with normal cells. Severe combined immunodeficiency mice bearing NPC xenografts derived from NOLC1-short hairpin-RNA-transfected animals were found to have 82% lower levels of tumor growth than control mice as well as marked tumor cell apoptosis. Measuring the expression levels of genes related to cell growth, apoptosis, and angiogenesis, we found that the MDM2 gene was down-regulated in the transfectants. Both co-transfection and chromatin immunoprecipitation experiments showed that tumor protein 53-regulated expression of the MDM2 gene requires co-activation of NOLC1. These findings suggest that NOLC1 plays a role in the regulation of tumorigenesis of NPC and demonstrate that both NOLC1 and tumor protein 53 work together synergistically to activate the MDM2 promoter in NPC cells.

Epstein-Barr virus induces an oxidative stress during the early stages of infection in B lymphocytes, epithelial, and lymphoblastoid cell lines

The study investigates the direct effect of Epstein-Barr virus infection on the oxidative profile of in vitro cultivated human cells. For this purpose, a panel of human EBV target cells presenting heterogeneity in their cellular and culture types (epithelial cells or lymphocytes; primary culture or continuous cell culture) was selected. These cells are purified human B lymphocytes, DG75, 293, and HepG2 cell lines. The oxidative stress was evaluated during the early stages of infection (2, 12, and 24 h) by measuring malondialdehyde, the end product of the lipid peroxidation, as well as the activities of two antioxidant enzymes: catalase and superoxide dismutase. The obtained results were compared with those of the untreated cells and the K562 cell line which has no interaction with EBV. The incubation of the different target cells with EBV induced an oxidative stress in the purified B lymphocytes, DG75, and 293, but not in HepG2 and K562. This oxidative stress was highlighted by an increase in MDA level (P < 0.05), which began 2 h after the addition of the virus and persisted after 12 and 24 h. Simultaneously, a decrease in catalase and superoxide dismutase activities was observed (P < 0.05), suggesting an alteration of the molecular mechanisms promoting cellular resistance to reactive oxygen species (ROS). The efficiency of EBV infection, assessed by viral DNA PCR amplification, was confirmed in 293 and DG75 but not in HepG2, which was in total concordance with their oxidative profiles. In conclusion, the EBV infection of B and epithelial cells leads to the establishment of an oxidative stress which can play a key role during the viral transformation.

Effect of Epstein-Barr Virus Infection on Response to Chemotherapy and Survival in Hodgkin's Disease

AbstractWe have analyzed paraffin sections from 190 patients with histologically confirmed Hodgkin's disease (HD) for the presence of Epstein-Barr virus (EBV) using in situ hybridization to detect the EBV-encoded Epstein-Barr virus early RNAs (EBERs) and immunohistochemistry to identify latent membrane protein-1 (LMP1) expression. EBV was present in the tumor cells in 51 HD cases (27%) and was mainly confined to the mixed cellularity and nodular sclerosis subtypes. There was no difference between EBV-positive and EBV-negative HD patients with regard to age, clinical stage, presentation, and the number of alternating chemotherapy cycles of ChIVPP and PABIOE received. The complete remission rate after study chemotherapy was 80% in EBV-positive patients versus 69% in EBV-negative patients (P = .05). The 2-year failure-free survival rate was significantly better for EBV-positive patients when compared with the EBV-negative HD group (P = .02). Although 2-year and 5-year overall survival rates were better for EBV-positive HD patients, the differences were not statistically significant (P = .18 andP = .40, respectively). In conclusion, the results confirm the favorable prognostic value of EBV in the tumor cells of HD patients and suggest important differences in response to chemotherapy between EBV-positive and EBV-negative patients.

Effect of Epstein-Barr Virus Infection on Response to Chemotherapy and Survival in Hodgkin’s Disease

We have analyzed paraffin sections from 190 patients with histologically confirmed Hodgkin’s disease (HD) for the presence of Epstein-Barr virus (EBV) using in situ hybridization to detect the EBV-encoded Epstein-Barr virus early RNAs (EBERs) and immunohistochemistry to identify latent membrane protein-1 (LMP1) expression. EBV was present in the tumor cells in 51 HD cases (27%) and was mainly confined to the mixed cellularity and nodular sclerosis subtypes. There was no difference between EBV-positive and EBV-negative HD patients with regard to age, clinical stage, presentation, and the number of alternating chemotherapy cycles of ChIVPP and PABIOE received. The complete remission rate after study chemotherapy was 80% in EBV-positive patients versus 69% in EBV-negative patients (P = .05). The 2-year failure-free survival rate was significantly better for EBV-positive patients when compared with the EBV-negative HD group (P = .02). Although 2-year and 5-year overall survival rates were better for EBV-positive HD patients, the differences were not statistically significant (P = .18 andP = .40, respectively). In conclusion, the results confirm the favorable prognostic value of EBV in the tumor cells of HD patients and suggest important differences in response to chemotherapy between EBV-positive and EBV-negative patients.

A Case of Type I Diabetes Mellitus Caused by the Suspected Effects of Epstein-Barr Virus Infection

A Case of Type I Diabetes Mellitus Caused by the Suspected Effects of Epstein-Barr Virus Infection

Lymphocyte transformation induced by autologous cells. VIII. Impaired autologous mixed lymphocyte reactivity in patients with acute infectious mononucleosis.

The autologous mixed lymphocyte reaction (MLR) is severely impaired in patients with acute infectious mononucleosis. Reactivity returned during the course of convalescence. The allogeneic MLR was not impaired in these patients. B cells from patients with infectious mononucleosis do not stimulate autologous T-cell proliferation, and this observation appears to explain the cellular basis of the impaired autologous MLR in infection. Two explanations for the B-cell defect were considered: (a) the influence of serum factors on B-cell function and (b) the effect of Epstein-Barr virus infection.