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Epstein-Barr Virus (epstein-barr + virus)
Terms modified by Epstein-Barr Virus Selected AbstractsEpstein-Barr virus infection and risk of lymphoma: Immunoblot analysis of antibody responses against EBV-related proteins in a large series of lymphoma subjects and matched controlsINTERNATIONAL JOURNAL OF CANCER, Issue 8 2007Silvia de Sanjosé Abstract Epstein-Barr Virus (EBV) is consistently associated with distinct lymphoproliferative malignancies and aberrant EBV antibody patterns are found in most EBV cancer patients. We evaluate the detection of an abnormal reactive serological pattern to EBV (ab_EBV) infection and the risk of lymphoma in a multicentric case,control study. Serum samples were collected at study entry from 1,085 incident lymphoma cases from Spain, France, Germany, Czech Republic, Italy and 1,153 age, sex and country matched controls. EBV immunoglobulin G (IgG) serostatus was evaluated through a peptide-based ELISA combining immunodominant epitopes of EBNA1 (BKRF1) and VCA-p18 (BFRF3). Further, immunoblot analysis was performed to evaluate distinct antibody diversity patterns to EBV early antigens (EA), besides EBNA1, VCA-p18, VCA-p40 (BdRF1) and Zebra (BZLF1). Patients with chronic active EBV infection and aberrant EBV activity were characterized as having an abnormal reactive pattern (ab_EBV). Ab_EBV was observed in 20.9% of 2,238 included subjects with an increased proportion of cases presenting ab_EBV as compared to the control population (23.9% vs. 18.0% p = 0.001). Ab_EBV positivity was a risk factor for all lymphomas combined (odds ratio [OR] = 1.42, 95% confidence interval [CI]=1.15,1.74), and specifically for chronic lymphocytic leukaemia (OR = 2.96, 95%CI = 2.22,3.95). Lower levels of ab_EBV were observed for follicular lymphoma (OR = 0.38, 95%CI = 0.15,0.98). EBV may be involved in a larger subset of lymphomas among clinically immunocompetent subjects than previously thought, probably explained by an underlying loss of immune control of EBV latent infection. Ab_EBV is a useful tool to explore EBV imbalances preceeding or paralleling possible EBV associated oncogenic events. © 2007 Wiley-Liss, Inc. [source] Role of Cytomegalovirus, Epstein-Barr Virus, and Human Herpes Virus-8 in Benign Lymphoepithelial Cysts of the Parotid GlandTHE LARYNGOSCOPE, Issue 8 2004Thomas L. Yen MD Abstract Objective: To provide background and evaluate the role of herpesviruses in benign lymphoepithelial cysts (BLC) of the parotid gland. Study Design: Case series derived from review of pathology specimens. Methods: Radiolabeled polymerase chain reaction (PCR) analysis was used to detect for the presence of cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human herpes virus 8 (HHV-8) DNA sequences in 14 paraffin embedded specimens and 1 freshly aspirated BLC specimen. Thirteen normal parotid tissue specimens obtained from paraffin embedded blocks were used as a control group. Results: CMV was detected with nearly equal frequency between the two groups (23% of normal vs. 20% in BLC). HHV-8 was found in 13% of the BLC group and in none of the normal group (P = .4841). There was significant difference in EBV detection between the normal (0%) and the BLC (33%) groups (P = .0437). Conclusion: CMV and HHV-8 does not appear to be associated with BLCs. Although EBV is found more frequently in BLC than in normal parotid controls, further studies are needed to elucidate the role of this virus in BLC pathogenesis. [source] Epstein-Barr Virus in Head and Neck Cancer Assessed by Quantitative Polymerase Chain ReactionTHE LARYNGOSCOPE, Issue 6 2004David Goldenberg MD Abstract Objectives/Hypothesis: Epstein-Barr virus (EBV) has classically been associated with nasopharyngeal carcinoma and Burkitt's lymphoma. Recently, multiple studies have been published linking EBV with oral squamous cell carcinoma and, to a lesser extent, hypopharyngeal and laryngeal tumors. Using a sensitive method of detection, the authors sought to analyze the presence and quantity of EBV DNA in a large cohort of head and neck cancers. Study Design: Retrospective cohort study. Methods: Three hundred head and neck cancer samples exclusive of nasopharyngeal carcinoma were examined for the presence of EBV using quantitative polymerase chain reaction. Eighty-four tumor samples from the larynx, 30 from the hypopharynx, 73 from the oropharynx, and 113 from the oral cavity were analyzed for EBV quantity, which was expressed as the number of viral copies per cell genome. Representative samples, which contained the highest EBV DNA levels, were examined using in situ hybridization. Results were correlated with tumor grade and site and tobacco and alcohol exposure. Results: Three of 300 (1%) tumor samples were overtly positive for EBV DNA (defined as >0.1 copies of viral DNA/cell genome). Five of 300 (2%) tumor samples showed low levels (defined as >0.01 and <0.1 copies of viral DNA/cell genome), and 68 of 300 tumor samples (23%) showed trace levels (defined as < 0.01 copies of viral DNA/cell genome) of EBV DNA. No correlation was found between EBV positivity and tobacco exposure, alcohol exposure, or tumor grade. Conclusion: In the overwhelming majority of head and neck cancers in this North American cohort, EBV did not appear to contribute to growth of a dominant clonal population with integrated EBV genome and was unlikely to be a genetic etiological agent in tumor development. The low quantities of EBV detected in a minority of head and neck cancers may be related to the presence of EBV genome in rare lymphoid or epithelial cells adjacent to the primary head and neck cancer. [source] Epstein-Barr Virus (EBV) Latent Membrane Protein 1 Induces Interleukin-8 through the Nuclear Factor-,B Signaling Pathway in EBV-Infected Nasopharyngeal Carcinoma Cell LineTHE LARYNGOSCOPE, Issue 5 2004Qingchun Ren MD Abstract Background/Objectives: Nasopharyngeal carcinoma (NPC) is a highly invasive and metastatic malignant tumor and is associated with Epstein-Barr virus (EBV) infection that exhibits type II latency. Angiogenesis is essential for tumor growth, invasion, and metastasis. Our previous studies have indicated that interleukin (IL)-8 was over-expressed in many NPC tissues and was found to be significantly correlated with angiogenesis by immunohistochemistry. Study Design: In vitro design. Methods: The influence of the EBV genome for IL-8 gene expression was studied using the EBV,genome-positive and -negative epithelial/NPC hybrid cell line NPC-KT. The EBV-positive and -negative clones were selected by polymerase chain reaction and in situ hybridization. Results: EBV-positive clones expressed abundant IL-8 mRNA compared with EBV-negative clones. This result indicated that over-expression of IL-8 depended on the presence of EBV genomes in NPC-KT cells. Two encoded genes, latent membrane protein (LMP)1 and EBV-encoded small RNAs (EBERs), expressed in NPC were transfected in EBV-negative NPC-KT cells. LMP1 transactivated the IL-8 promoter, whereas EBERs did not. Moreover, the nuclear factor (NF)- ,B binding site in the IL-8 promoter was essential for the response to LMP1, and the activator protein (AP)-1 binding site played only a partial role. Conclusions: LMP1 induces IL-8 mainly through the activation of NF-,B and partly through AP-1 in NPC model cell lines, NPC-KT, and this suggests that LMP1 plays an important role in the angiogenesis of NPC. [source] Adenotonsillar Hypertrophy and Epstein-Barr Virus in Pediatric Organ Transplant Recipients,THE LARYNGOSCOPE, Issue 6 2001Nina L. Shapiro MD Abstract Objectives/Hypothesis Epstein-Barr virus,related (EBV-related) lymphoid hyperplasia of the tonsils and adenoids is a precursor to post-transplantation lymphoproliferative disorder (PTLD). The incidence of post-transplantation adenotonsillar hypertrophy, a potential early sign of PTLD or EBV-related lymphoid hyperplasia, is not known. We sought to identify potential risk factors for adenotonsillar hypertrophy manifested as EBV-related hyperplasia and early PTLD in the pediatric solid organ transplant population. Study Design Cross-sectional analysis. Methods We developed a 65-point questionnaire concerning obstructive sleep disorder and upper respiratory tract infections and an 8-point focused physical examination, to identify prevalence of and risk factors for adenotonsillar hypertrophy in the pediatric transplant population. We evaluated 120 pediatric solid organ transplant recipients by parental questionnaire and focused adenotonsillar physical examination. Results Of the 120 patients, 62 had undergone liver transplantation and 58 had undergone kidney transplantation. Overall, the mean questionnaire score was 8.36 (range, 0,40) and the mean physical examination score was 3.86 (range, 1,8). Patients whose EBV serological test result was negative at the time of transplant had higher scores for both the questionnaire (mean score, 10.24) and the physical examination (mean score, 4.56) than those whose EBV serological test result was positive at the time of transplantation (scores of 7.38 and 3.30 for questionnaire and physical examination, respectively). The difference in examination scores was statistically significant (P <.003). Conclusions Epstein-Barr virus seronegativity at the time of organ transplantation is a known risk factor for PTLD, with associated risk of developing EBV-related lymphoid hyperplasia. Our results indicate a higher incidence of symptoms and signs consistent with adenotonsillar hypertrophy in the EBV seronegative population. Adenotonsillar hypertrophy may be a precursor to EBV-related lymphoid hyperplasia and PTLD and must be identified in this patient population. [source] Immunohistochemical Absence of CD21 Membrane Receptor in Nasopharyngeal Carcinoma Cells Infected by Epstein-Barr Virus in Spanish Patients ,THE LARYNGOSCOPE, Issue 12 2000Javier S. Burgos PhD Abstract Objectives/Hypothesis The aim of this study was to analyze the relevance of the CD21 membrane receptor in nasopharyngeal carcinoma (NPC). CD21 is implicated in the introduction of the Epstein-Barr virus (EBV) genome into epithelial cells and B lymphocytes. Study Design Immunohistochemical analysis of CD21 in NPC. Methods Paraffin-embedded samples of NPC of different histological types with demonstrated presence of EBV were analyzed for CD21 expression using immunohistochemistry. Results We detected EBV by non-isotopic in situ hybridization (NISH) and nested polymerase chain reaction (PCR) in 100% of samples, regardless of histological type, supporting the previous view that all the types of NPC are variants of an EBV-associated malignancy. CD21 was not detected in NPC, and this absence was a typical feature in our data group. Conclusions The loss of the CD21 membrane receptor could be one of the immunophenotypical changes of the neoplastic cells that occur in the evolution of the NPC malignancy. [source] Epstein-Barr Virus and Posttransplant Lymphoproliferative Disorder in Solid Organ Transplant RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2009U. Allen First page of article [source] Risk Factors for Rejection and Infection in Pediatric Liver TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2008R. W. Shepherd Rejection and infection are important adverse events after pediatric liver transplantation, not previously subject to concurrent risk analysis. Of 2291 children (<18 years), rejection occurred at least once in 46%, serious bacterial/fungal or viral infections in 52%. Infection caused more deaths than rejection (5.5% vs. 0.6% of patients, p < 0.001). Early rejection (<6 month) did not contribute to mortality or graft failure. Recurrent/chronic rejection was a risk in graft failure, but led to retransplant in only 1.6% of first grafts. Multivariate predictors of bacterial/fungal infection included recipient age (highest in infants), race, donor organ variants, bilirubin, anhepatic time, cyclosporin (vs. tacrolimus) and era of transplant (before 2002 vs. after 2002); serious viral infection predictors included donor organ variants, rejection, Epstein-Barr Virus (EBV) naivety and era; for rejection, predictors included age (lowest in infants), primary diagnosis, donor-recipient blood type mismatch, the use of cyclosporin (vs. tacrolimus), no induction and era. In pediatric liver transplantation, infection risk far exceeds that of rejection, which causes limited harm to the patient or graft, particularly in infants. Aggressive infection control, attention to modifiable factors such as pretransplant nutrition and donor organ options and rigorous age-specific review of the risk/benefit of choice and intensity of immunosuppressive regimes is warranted. [source] Reed-Sternberg cells in atypical primary EBV infectionACTA PAEDIATRICA, Issue 2 2001M Bitsori The presence of Epstein-Barr virus (EBV) in the Hodgkin's/Reed-Sternberg (HRS) cells of a significant proportion of cases of Hodgkin's lymphoma (HL) is a matter of consideration when a case of presumptive HL has to be differentiated from infectious mononucleosis (IM). A 15-y-old boy was admitted with a presumptive diagnosis of extranodal HL, based on the biopsy of a painless ulcer on the right mandibular alveolar crest. Histologic examination of the lesion was consistent with mixed cellularity HL. The patient additionally presented with hepatosplenomegaly and regional lymphadenopathy. Serology for EBV was indicative of acute infection. Histological examination of regional lymphoid tissue was consistent with immunologic activation due to primary EBV infection. The patient was left untreated, under close observation. All clinical findings resolved within 3 mo and EBV viral capsid antigen (VCA) IgM antibodies converted to negative after 6 mo. A 3-y follow-up period was uneventful. [source] A new look at viruses in type 1 diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 1 2003Hee-Sook Jun Abstract Type 1 diabetes (T1D) results from the destruction of pancreatic beta cells. Genetic factors are believed to be a major component for the development of T1D, but the concordance rate for the development of diabetes in identical twins is only about 40%, suggesting that nongenetic factors play an important role in the expression of the disease. Viruses are one environmental factor that is implicated in the pathogenesis of T1D. To date, 14 different viruses have been reported to be associated with the development of T1D in humans and animal models. Viruses may be involved in the pathogenesis of T1D in at least two distinct ways: by inducing beta cell-specific autoimmunity, with or without infection of the beta cells, [e.g. Kilham rat virus (KRV)] and by cytolytic infection and destruction of the beta cells (e.g. encephalomyocarditis virus in mice). With respect to virus-mediated autoimmunity, retrovirus, reovirus, KRV, bovine viral diarrhoea-mucosal disease virus, mumps virus, rubella virus, cytomegalovirus and Epstein-Barr virus (EBV) are discussed. With respect to the destruction of beta cells by cytolytic infection, encephalomyocarditis virus, mengovirus and Coxsackie B viruses are discussed. In addition, a review of transgenic animal models for virus-induced autoimmune diabetes is included, particularly with regard to lymphocytic choriomeningitis virus, influenza viral proteins and the Epstein-Barr viral receptor. Finally, the prevention of autoimmune diabetes by infection of viruses such as lymphocytic choriomeningitis virus is discussed. Copyright © 2002 John Wiley & Sons, Ltd. [source] Increased expression of microRNA-155 in Epstein-Barr virus transformed lymphoblastoid cell linesGENES, CHROMOSOMES AND CANCER, Issue 1 2006Jinmai Jiang First page of article [source] Use of combined molecular biomarkers for prediction of clinical outcomes in locally advanced tonsillar cancers treated with chemoradiotherapy aloneHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 1 2009Yih-Lin Chung MD Abstract Background. Environmental exposures to tobacco, alcohol, human papillomavirus (HPV) and/or Epstein-Barr virus (EBV), all of which can perturb multiple cell cycle proteins or tumor suppressors, have been implicated in the pathogenesis of different subsets of head and neck cancers. The aim of this study was to investigate to which extent the virus infection by itself, and/or the altered cell cycle proteins, contributes to prognosis in locally advanced tonsillar squamous cell carcinomas (TSCCs) treated with concurrent chemoradiotherapy (CCRT) alone. Methods. Serial tumor tissue arrays from archival samples were tested for the presence of HPV genome integration or EBV episome by means of DNA sequencing, real-time polymerase chain reaction (PCR), and in situ hybridization. Alterations of cell cycle proteins (p53, pRb, and p21) were evaluated by immunohistochemical staining. The association of viral presence with altered cell cycle proteins was correlated to clinical outcomes. Results. Of the 46 patients with the same T2N2bM0 stage IVA among consecutive patients with TSCC, 23 (50%) had integrated HPV DNA and only 1 (2%) had EBV episome. The HPV types detected were almost all HPV-16. A reduced expression pattern of p53, pRb, and p21 was noted in HPV-positive tumors, and the incremental number of alterations in the 3 proteins was significantly associated with HPV-negative tumors. The presence or absence of HPV together with the number of altered expression of the 3 cell cycle markers resulted in further identification of 4 biologically and clinically distinct subgroups with different outcomes after CCRT. Conclusions. Use of combined biomarkers of oncogenic HPV and tumor suppressors of p53, pRb, and p21 in advanced TSCC provides prognostic molecular classification superior to the TNM stage system and identifies low-risk patients for organ preservation by CCRT alone and high-risk patients who might benefit from planned tonsillectomy and neck dissection before or after CCRT. © 2008 Wiley Periodicals, Inc. Head Neck, 2009 [source] Upregulation of discoidin domain receptor 2 in nasopharyngeal carcinoma,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 4 2008Huey-Huey Chua PhD Abstract Background. Nasopharyngeal carcinoma (NPC) is associated with Epstein-Barr virus (EBV) and has high metastatic potential. Discoidin domain receptors (DDR1, DDR2) are receptor-type tyrosine kinases activated by collagen. Their ability to induce expression of matrix metalloproteinase is related with tumor invasion. Therefore, we aim to investigate DDRs gene expression and its regulation in NPC. Methods and Results. By use of real-time quantitative polymerase chain reaction (Q-PCR), DDR2 gene expression but not DDR1 was significantly higher in primary and metastatic NPC. DDR2 was predominantly distributed in NPC tumor cells rather than in infiltrating lymphocytes. EBV Z-transactivator (Zta) transfection may distinctly elevate DDR2 level. Furthermore, data from reporter assay indicate that Zta could transactivate DDR2 promoter activity, suggesting the possible upregulation mechanism. Conclusion. DDR2 was differentially upregulated in NPC and modulated by EBV Zta protein. DDR2 may play a role in NPC invasion and serve as a diagnostic and therapeutic target. © 2007 Wiley Periodicals, Inc. Head Neck, 2008 [source] Epstein-Barr virus (EBV) serology for predicting distant metastases in a white juvenile patient with nasopharyngeal carcinoma and no clinical response to EBV lytic induction therapyHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 11 2006Servi J. C. Stevens PhD Abstract Background. We describe a case of a 16-year-old white girl with Epstein-Barr virus (EBV)-positive nasopharyngeal carcinoma (NPC). Methods. At diagnosis, the patient had characteristic immunoglobulin (Ig)A and IgG responses to EBNA1, viral capsid antigen (VCA)-p18, and early antigens (EAs), with no detectable EBV DNA in her blood. Combined chemotherapy and radiotherapy resulted in complete remission. Eighteen months later, the patient's IgA responses to EBNA1 and p18 and both IgA and IgG anti-EA increased, without apparent recurrence. Five months later, lung metastases were found. She underwent surgical removal of the lung metastases and conventional chemotherapy, but had intraabdominal lymph node metastasis and mediastinal lesions develop. The patient was then treated with a novel treatment consisting of 5-fluorouracil plus valproic acid and subsequent valganciclovir to induce lytic EBV replication. This resulted in the first detectable EBV DNA levels in the blood but did not result in clinical response. Results. The patient's disease progressed, and the patient declined further cancer treatment and died. Conclusion. In contrast to EBV DNA load, EBV serology was useful in predicting distant NPC metastasis after initial complete remission in this patient. © 2006 Wiley Periodicals, Inc. Head Neck, 2006 [source] In vivo real-time diagnosis of nasopharyngeal carcinoma in situ by contact rhinoscopyHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 11 2005Martin Wai Pak FRCSEd(ORL) Abstract Background. Nasopharyngeal dysplasia or nasopharyngeal carcinoma in situ (NPCIS) lesions have rarely been reported. Timely diagnosis of the preinvasive lesion may improve prognosis. Contact endoscopy has been documented to accurately differentiate normal cells of the nasopharynx from malignant cells and allows a real-time diagnosis of primary and recurrent nasopharyngeal carcinoma (NPC) in a clinical setting. However, the role of contact endoscopy in the diagnosis of NPCIS is unknown. Methods. The superficial cells of the nasopharynx in a patient with NPCIS were examined in vivo under local anaesthesia by use of a contact rhinoscope. The contact endoscopic findings were correlated with the histologic findings of the biopsy. Results. The atypical cells of the lesion were magnified and visualized under contact endoscopy. Histopathologic analysis of the biopsied tissue confirmed the presence of NPCIS staining positively for Epstein-Barr virus (EBV),encoded RNA (EBER). No cell-free EBV DNA was detected in the sera of the patient. Conclusions. Contact endoscopy can accurately identify the atypical cells of a tiny preinvasive lesion in the nasopharynx in a clinical setting, which may not be evident in routine imaging examination. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX,XXX, 2005 [source] Clinical relevance of three subtypes of primary sinonasal lymphoma characterized by immunophenotypic analysisHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 7 2004Gwi Eon Kim MD Abstract Background. The purpose of this study was to investigate the clinical relevance of subtypes categorized by immunophenotypic analysis in primary sinonasal lymphomas. Methods. Eighty patients with localized non-Hodgkin's lymphoma involving the nasal cavity and/or paranasal sinuses were divided into three subtypes on the basis of their immunohistochemical findings: (A) B-cell lymphoma (n = 19), (B) T-cell lymphoma (n = 27), and (C) natural killer (NK)/T-cell lymphoma (n = 34). The clinicopathologic profiles, immunophenotypic data, patterns of treatment failure, and survival data among the three patient groups were retrospectively compared. Results. The nasal cavity was the predominant site of involvement in T-cell and NK/T-cell lymphoma, whereas sinus involvement without nasal disease was common in B-cell lymphoma. Systemic B symptoms were frequently observed in NK/T-cell lymphoma. Almost all patients with NK/T-cell lymphoma showed a strong association with the Epstein-Barr virus by in situ hybridization studies. Sixty-five patients (81%) patients achieved complete remission after initial treatment, but 36 (55%) of these subsequently experienced treatment failure. Although there were no significant differences in locoregional failure rates among the patients of the three groups, distant failure was far more common in B-cell or NK/T-cell lymphoma than in T-cell lymphoma (p = .005). Most B-cell lymphoma cases showed a predilection for sites of systemic failure in the nodal and extranodal sites below the diaphragm, such as the paraaortic lymph nodes or the gastrointestinal (GI) tract, whereas patients with NK/T-cell lymphoma showed an increased risk of systemic dissemination to the skin, testes, or GI tract, including the development of hemophagocytic syndrome. The 5-year actuarial and disease-free survival rates for all patients were 57% and 51%, respectively. Of the three subtypes of primary sinonasal lymphomas, T-cell lymphoma seemed to carry the most favorable prognosis and NK/T-cell lymphoma the worst. (The 5-year actuarial survival rate was 57% for B-cell lymphoma, 80% for T-cell lymphoma, 37% for NK/T-cell lymphoma; p = .02, log-rank.) By univariate and multivariate analyses, immunophenotype was identified as the most important prognostic factor. Conclusions. Our data indicate that the three subtypes of primary sinonasal lymphomas classified by immunohistochemical studies exhibit different clinical profiles, different patterns of failure, and different treatment outcomes. Given these observations, it is concluded that the recognition of these distinct subsets, diagnosed on the basis of immunophenotypic study, is very important and clinically relevant in predicting their potential behavior and prognosis. © 2004 Wiley Periodicals, Inc. Head Neck26: 584,593, 2004 [source] Epstein-Barr virus infection in immortalized nasopharyngeal epithelial cells: Regulation of infection and phenotypic characterizationINTERNATIONAL JOURNAL OF CANCER, Issue 7 2010Chi Man Tsang Abstract Epstein-Barr virus (EBV) infection has been postulated to be an early event involved in the pathogenesis of nasopharyngeal carcinomas (NPC). The lack of representative premalignant nasopharyngeal epithelial cell system for EBV infection has hampered research investigation into the regulation and involvement of EBV infection in NPC pathogenesis. We have compared the efficiency of EBV infection in nasopharyngeal epithelial cells with different biological properties including immortalized, primary and cancerous nasopharyngeal epithelial cells. EBV infection could be achieved in all the nasopharyngeal epithelial cells examined with variable infection rate. TGF-, effectively enhanced EBV infection into nasopharyngeal epithelial cells both in the immortalized and primary nasopharyngeal epithelial cells. Stable infection of EBV was achieved in a telomerase-immortalized nasopharyngeal epithelial cell line, NP460hTert. The expression pattern of EBV-encoded genes and biological properties of this EBV infected cell line on long-term propagation were monitored. The EBV-infected nasopharyngeal epithelial cells acquired anchorage-independent growth and exhibited invasive growth properties on prolonged propagation. A distinguished feature of this EBV-infected nasopharyngeal epithelial cell model was its enhanced ability to survive under growth factor and nutrient starvation. This was evidenced by the suppressed activation of apoptotic markers and sustained activation of pAkt of EBV-infected cells compared to control cells under nutrient starvation. Examination of cytokine profiles of EBV-infected NP460hTert cells to nutrient and growth factor deprivation revealed upregulation of expression of MCP-1 and GRO-,. The establishment of a stable EBV infection model of premalignant nasopharyngeal epithelial cells will facilitate research investigation into the pathogenic role of EBV in NPC development. [source] Cancer patterns in nasopharyngeal carcinoma multiplex families in TaiwanINTERNATIONAL JOURNAL OF CANCER, Issue 7 2009Kelly J. Yu Abstract Genetic and environmental factors have been implicated in the etiology of nasopharyngeal carcinoma (NPC), a tumor known to be closely associated with Epstein-Barr virus (EBV) infection. Studies have reported familial aggregation of NPC and have suggested the possible aggregation of NPC and other cancers. We evaluated familial aggregation of cancer in 358 high-risk families with two or more NPC cases enrolled in a NPC genetics study in Taiwan. Participants were linked to the Taiwan National Cancer Registry to identify incident cancers diagnosed after study enrollment (started in 1996) and before December 31, 2005, or death. In total, 2,870 individuals from the NPC Multiplex Family Study contributed 15,151 person-years over an average of 5.3 years of follow-up. One hundred ten incident cancers were identified. Multiple-primary standardized incidence ratios (MP-SIRs) were computed to evaluate overall cancer risk associated with infectious agents and with other tumors. The overall MP-SIR was 1.3 (95% CI: 1.1,1.6), which was largely explained by an excess in NPC (MP-SIR = 15; 95% CI: 10,23). Exclusion of incident NPC diagnoses led to an overall MP-SIR of 1.0 (95% CI: 0.83,1.3). Similarly, the observed excess risk of cancers associated with infectious agents (MP-SIR = 2.0; 95% CI: 1.5,2.6) was driven by the excess in NPC; exclusion of NPC cases led to a reduced MP-SIR that did not differ from 1.0. Analysis of the largest NPC multiplex family study to date confirms the presence of coaggregation of NPC within families in Taiwan but does not provide evidence for a broader familial syndrome involving NPC and other tumors. © 2008 Wiley-Liss, Inc. [source] Expression of RANTES and MCP-1 in epithelial cells is regulated via LMP1 and CD40INTERNATIONAL JOURNAL OF CANCER, Issue 12 2007Maike Buettner Abstract Epstein-Barr virus (EBV)-associated undifferentiated nasopharyngeal carcinoma (NPC) is characterized by a prominent nonneoplastic lymphoid stroma. The functional role of these inflammatory cells and the mechanism of their recruitment are not fully understood. In B-cells, the EBV-encoded latent membrane protein 1 (LMP1) can induce the expression of chemokines in an NF-,B dependent manner. We now show that LMP1 can induce the expression of RANTES and MCP-1 in an epithelial cell line, and that this effect is partially reversible by an inhibitor of NF-,B. Since tumor cells of virtually all NPCs show CD40 expression while many cases are LMP1-negative at the protein level, we also investigated the effect of CD40 signaling and demonstrate that CD40 stimulation can transiently induce RANTES and MCP-1 expression in LMP1-negative epithelial cells. In in situ hybridization only rare tumor cells showed expression of these chemokines unrelated to LMP1 expression, a pattern consistent with transient induction through CD40 signaling. Since RANTES and MCP-1 were also detected in the neoplastic cells of oral squamous cell carcinomas lacking a lymphoid stroma it remains uncertain to what extent these CC chemokines contribute to the attraction of inflammatory cells into the NPC microenvironment. © 2007 Wiley-Liss, Inc. [source] In vitro Epstein-Barr virus-immortalized lymphoma cell line carrying t(9;14)(p13;q32) chromosome abnormality, derived from splenic lymphoma with villous lymphocytesINTERNATIONAL JOURNAL OF CANCER, Issue 2 2006Masanori Daibata Abstract We herein describe splenic lymphoma with villous lymphocytes (SLVL) carrying t(9;14)(p13;q32). The t(9;14)(p13;q32) is a rare reciprocal chromosome translocation found in a subset of B-cell malignancies, mainly in low-grade non-Hodgkin's lymphomas. In t(9;14)(p13;q32), PAX-5 gene on 9p13 is involved with the immunoglobulin heavy-chain gene on 14q32. It has been thought that the deregulated expression of PAX-5 as a result of t(9;14)(p13;q32) may contribute to abnormal cell proliferation. Although continuous cell lines are invaluable tools for studying lymphomagenesis in the t(9;14)(p13;q32)-bearing lymphomas, establishment of such cell lines is extremely difficult since they are usually mature B-cell malignancies. In an attempt to transform the SLVL cells into a proliferating cell line, we examined the responses of the cells to infection by Epstein-Barr virus (EBV). SLVL cells were found to be susceptible to immortalization by EBV, resulting in a permanent cell line. The cell line, designated SL-15, possessed the t(9;14)(p13;q32). Genotype analysis and immunophenotype profiles confirmed that the cell line arose from the primary lymphoma cells. The cells had characteristic cytoplasmic villi. SL-15 cells has been growing over 2 years equivalent to 350,400 population doubling levels without proliferative crisis that is often observed in EBV-positive lymphoblastoid cell lines. Furthermore, SL-15 cells, when inoculated into nude mice, formed t(9;14)(p13;q32)-bearing tumors with cytoplasmic villi. The validated SLVL-derived cell line provide a useful model system to study molecular biology of t(9;14)(p13;q32)-bearing B-cell malignancies as well as lymphomagenesis of SLVL in vitro and in vivo. © 2005 Wiley-Liss, Inc. [source] Phenotypic alterations induced by the Hong Kong-prevalent Epstein-Barr virus-encoded LMP1 variant (2117-LMP1) in nasopharyngeal epithelial cellsINTERNATIONAL JOURNAL OF CANCER, Issue 6 2004Angela Kwok Fung Lo Abstract Epstein-Barr virus (EBV) is closely associated with nasopharyngeal carcinoma (NPC), a common cancer in Hong Kong. The EBV-encoded LMP1 protein is believed to play an important role in cell transformation. We have previously identified a prevalent LMP1 variant (2117-LMP1) that is expressed in 86% of primary NPC in Hong Kong. In this study, the biologic phenotypes induced by 2117-LMP1 were compared with those of the prototypic B95.8-LMP1 in an immortalized nasopharyngeal epithelial cell line, NP69. The 2117-LMP1 could induce cell proliferation and resistance to apoptosis induced by growth factor deprivation. Expression of 2117-LMP1 also suppressed expression of p16, p21 and Bax but induced expression of CDK2 and A20. Compared with B95.8-LMP1, 2117-LMP1 could induce a higher migration ability in NP69 cells but was less efficient in inducing morphologic changes, anchorage-independent growth and cell invasion. Relatively weaker ability of 2117-LMP1 than B95.8-LMP1 in upregulation of vimentin, VEGF and MMP9 as well as in downregulation of E-cadherin was observed. 2117-LMP1 could activate higher level of NF-,B activity in HEK 293 cells than B95.8-LMP1. The present study supports a role of 2117-LMP1 in NPC development by enhancing cell proliferation, cell death inhibition and migration in premalignant nasopharyngeal epithelial cells. Furthermore, our study reveals significant functional differences between 2117-LMP1 and the prototypic B95.8-LMP1. Our results provide insights into the pathologic significance of this prevalent LMP1 variant, 2117-LMP1, in the development of NPC in the Hong Kong population. © 2004 Wiley-Liss, Inc. [source] Lymphoproliferative disorders in autoimmune diseases in Japan: Analysis of clinicopathological features and Epstein-Barr virus infectionINTERNATIONAL JOURNAL OF CANCER, Issue 3 2004Yoshihiko Hoshida Abstract Lymphoproliferative disorders (LPD) occasionally develop in individuals with immune deficiencies such as immunosuppressive conditions and autoimmune diseases (AID). In our study, the clinicopathologic features and virus status were analyzed in 53 cases with LPD developing in rheumatoid arthritis (RA) and other AID. AID in only 4 of 53 patients had been treated with some sort of immunosuppressive therapy, including methotrexate. Median age at the diagnosis of LPD in AID was 60 years old with marked female predominance (M/F = 0.4). The median interval between the onset of AID and LPD development was 45 months, and longer in RA patients than in other AID (p < 0.01). The primary site of lymphoma was nodal in 21 cases and extra-nodal in 24, with clinical Stage I in 17, II in 5, III in 13, and IV in 13. Immunohistochemistry showed that 39 cases were B cell type, 10 were T cell type and 4 were Hodgkin lymphoma (HL). Then majority of B cell cases were diffuse large B cell lymphomas, and 2 were diffuse polymorphic type. EBER-1 in situ hybridization for Epstein-Barr virus (EBV) showed positive signals in tumor cells in 16 of 53 (30.2%) cases. The EBV-positive rate in T cell LPD (70%) was much higher than that in B cell LPD (12.8%) (p < 0.01). All 4 cases of HL were EBV-positive. Immunohistochemistry showed a latency II pattern of EBV infection (LMP-1+ and EBNA-2,). Five-year overall survival rate was 33%. Multivariate analysis showed that only type of AID was an independent factor for survival of patients, i.e., LPD in RA showed the most favorable prognosis. In conclusion, LPD in AID generally shared common features with sporadic LPD except for a much higher EBV-positive rate in T cell LPD. © 2003 Wiley-Liss, Inc. [source] Identification and prevalence of CD8+ T-cell responses directed against Epstein-Barr virus-encoded latent membrane protein 1 and latent membrane protein 2INTERNATIONAL JOURNAL OF CANCER, Issue 1 2002Pauline Meij Abstract Epstein-Barr virus (EBV) is associated with several human malignancies that each show different viral gene expression profiles. In malignancies such as Hodgkin's disease and nasopharyngeal carcinoma only Epstein-Barr nuclear antigen 1 (EBNA1) and varying levels of latent membrane proteins 1 and 2 (LMP1 and -2) are expressed. Since endogenously expressed EBNA1 is protected from CTL recognition, LMP1 and LMP2 are the most likely target antigens for anti-tumor immunotherapy. Therefore, we sought to identify in a systematic way CD8+ T-cell responses directed against eptitopes derived from LMP1 and LMP2. Using IFN,-ELISPOT assays of interferon-, release, peripheral blood mononuclear cells (PBMC) of healthy donors were screened with peptide panels (15 mer overlapping by 10) spanning the LMP1 and LMP2 sequences of the prototype EBV strain B95.8. When positive responses were found, CD4+ or CD8+ T cells were depleted from donor PBMC to determine the origin of the responder population. We detected CD8+ T-cell responses to LMP1 in 9/50(18%) donors and to LMP2 in 15/28 (54%) donors. In addition to the already described epitopes, 3 new LMP1- and 5 new LMP2-derived CD8+ epitopes were identified. In most donors LMP1- and LMP2-specific CD8+ precursor frequencies were low compared with precursors against immunodominant EBV epitopes from latent (EBNA3A, -3B and -3C) and lytic cycle antigens. These results demonstrate that CD8+ memory T cell responses to LMP1 and especially to LMP2 do exist in Caucasians, albeit at low levels and could potentially be exploited for therapeutic use. © 2002 Wiley-Liss, Inc. [source] Hydroa vacciniforme-like Epstein-Barr virus-associated monoclonal T-lymphoproliferative disorder in a childINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 10 2007Yu-Hung Wu MD Hydroa vacciniforme (HV) is a chronic photosensitivity disorder induced by ultraviolet radiation. Hydroa vacciniforme-like lymphoma is a rare cutaneous T-cell lymphoma occurring mainly in childhood. Recent studies have demonstrated an association between chronic latent Epstein-Barr virus (EBV) infection and both the benign skin disorder and the lymphoma. The authors report a 6-year-old boy with chronic EBV infection, HV-like skin eruptions, and chronic hepatitis. Histopathologic examination of a skin biopsy specimen demonstrated epidermal ballooning degeneration and dense superficial and deep perivascular and periappendageal lymphoid cell infiltrates extending to the fat lobules. Some blood vessels in the deep plexus were infiltrated by predominantly CD4+ and TIA-1+ cytotoxic T cells. The EBV genomes were found within tissue from three skin biopsies and peripheral blood cells. Monoclonal T-cell receptor gene rearrangement was present in skin biopsy specimens. Although no lymphoma has been found during 2 years of follow-up treatment, the possibility of lymphoma developing out of the current smoldering stage is of concern. The clinical manifestations of lymphoproliferative disorder and chronic active EBV infection are discussed. [source] Etiopathogenic role of HLA-B27 alleles in ankylosing spondylitisINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 3 2005Nurullah AKKOC Abstract HLA-B27 is the major genetic susceptibility factor for ankylosing spondylitis (AS). However, its precise role in the pathogenesis of AS still remains unclear, even though its gene has been cloned and sequenced, and its crystallographic structure has been defined. Arthritogenic peptide and molecular mimicry hypotheses propose mechanisms related to an antigen-presenting function of HLA-B27 to be responsible for disease development. However, peculiar aspects of its immunobiology, such as its misfolding and heavy chain dimerization raise the possibility of involvement of pathogenic mechanisms unrelated to its physiological function. Moreover, HLA-B27 is not a single allele, but a family of 31 different alleles, named HLA-B*2701 to HLA-B*2727. Studies worldwide indicate that the relatively common alleles (subtypes) HLA-B*2705, B*2704, and B*2702 are strongly associated with AS, whereas HLA-B*2706 which is prevalent in South-east Asia and HLA-B*2709 which is prevalent on the Italian island of Sardinia, seem to lack such an association. The distinction between the disease-associated subtypes and those that are not associated, may provide clues to the actual role of HLA-B27 in disease pathogenesis. B*2706 differs from B*2704 by only two residues, and B*2709 differs from B*2705 by only one residue. Moreover, both B*2706 and B*2709 bind an endogenous peptide (derived from vasoactive intestinal peptide type 1 receptor) and also an exogenous peptide (latent membrane protein 2 of Epstein-Barr virus) but in two drastically diverse conformations. These recent X-ray diffraction studies of individual peptides in the context of different HLA-B27 alleles broaden our perception of the possible pathogenetic role of this molecule in the development of AS and related spondyloarthopathies. In summary, the pathogenetic role of HLA-B27 in AS seem to be quite heterogenous, and cannot be explained by a single mechanism, and new ideas have been raised based on the aberrant immunobiologic features of HLA-B27. [source] Post-transplant EBV-negative anaplastic large-cell lymphoma with dual rearrangement: a propos of two cases and review of the literatureJOURNAL OF CUTANEOUS PATHOLOGY, Issue 2007Cynthia M. Magro Background:, Post-transplant lymphoproliferative disease (PTLD) is a recognized complication of the immunosuppressive regimens associated with solid organ transplantation. The vast majority of these lesions represent monomorphic B-cell lymphoproliferative disease. Rarely, however, T-cell malignancies may emerge, the commonest being anaplastic large-cell lymphoma (ALCL). Materials and methods:, We describe two patients who developed a post-transplant ALCL several years after transplantation. Comprehensive phenotypic and molecular studies were conducted. The technique of capillary gel electrophoresis was employed. Results:, One patient died of unrelated causes, while the other patient did achieve clinical remission. The neoplastic cell populace was composed of CD4-positive cytotoxic T cells exhibiting CD30 positivity. There were very few B cells. Striking and prominent clonally restricted infiltrates were identified whereby there was both a heavy chain and T-cell beta gene rearrangement. There was no evidence of lytic Epstein-Barr virus (EBV) infection. Conclusion:, T-cell-associated PTLD does not appear to be directly attributable to EBV infection. Iatrogenic immune dysregulation may result in excessive T-cell proliferation to various antigenic stimuli, hence resembling other drug-associated cell lymphoproliferative conditions such as angioimmunoblastic lymphadenopathy. The dual rearrangement may have some implications regarding the cell of origin. [source] Lymphoepithelioma-Like Carcinoma of the Skin: A Case ReportJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2005T. Mitsuhashi Lymphoepithelioma-like carcinoma of the skin is a rare tumor with a microscopic resemblance to lymphoepitheliomatous carcinoma of the nasopharynx. We present a 93-year-old man with papules on the left auricle to the cheek that were gradually enlarged. By the time of a biopsy, it grew to a 5.0 × 3.0 × 2.8 cm dark red mass, and necrotic debris was attached to the surface. Histologically, a relatively well-demarcated, dermal-hypodermic multiple lobules were composed of irregular islands of atypical epithelial cells. The uniform tumor cells had moderate amounts of lightly eosinophilic cytoplasm and vesicular nuclei with one or two prominent nucleoli. A dense lymphocytic infiltrate was present within the neoplastic islands, obscuring the epithelial component. The neoplastic cells were unconnected to the overlying epidermis. Neither squamous nor glandular differentiation was present. Immunohistochemically, the neoplastic cells were positive for epithelial membrane antigen and cytokeratin, and negative for latent membrane protein 1. No Epstein-Barr virus-encoded RNA (EBER) was detected by in situ hybridization. The negativity for Epstein-Barr virus may be a help in the differential diagnosis from metastatic undifferentiated nasopharyngeal carcinoma, which is uniformly positive for EBER. [source] Atypical imaging appearance of toxoplasmosis in an HIV patient as a butterfly lesionJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 4 2009Vinika V. Chaudhari MD Abstract In acquired immunodeficiency syndrome (AIDS) patients, differentiating toxoplasmosis and primary central nervous system (CNS) lymphoma remains a clinical and radiographic dilemma. The presence of butterfly lesions crossing the corpus callosum is customarily used to exclude the possibility of toxoplasmosis. We present an AIDS patient who had Epstein-Barr virus (EBV) polymerase chain reaction (PCR) -positive cerebrospinal fluid studies with a butterfly toxoplasmosis lesion confirmed by multiple methods signifying the importance of including toxoplasmosis in the differential diagnosis of butterfly lesions. J. Magn. Reson. Imaging 2009;30:873,875. © 2009 Wiley-Liss, Inc. [source] Expression of Epstein-Barr virus-encoded LMP1 and hTERT extends the life span and immortalizes primary cultures of nasopharyngeal epithelial cells,JOURNAL OF MEDICAL VIROLOGY, Issue 10 2010Yim-Ling Yip Abstract Cell immortalization is regarded as an early and pre-requisite step in tumor development. Defining the specific genetic events involved in cell immortalization may provide insights into the early events of carcinogenesis. Nasopharyngeal carcinoma is common among the Southern Chinese population. Epstein-Barr virus (EBV) infection is associated closely with nasopharyngeal carcinoma. The involvement of LMP1 (an EBV-encoded oncogene) has been implicated in the pathogenesis of nasopharyngeal carcinoma. In this study, LMP1 expression, in combination with ectopic expression of hTERT (catalytic unit of human telomerase), was shown to extend the life span of primary cultures of nasopharyngeal epithelial cells and facilitate the immortalization of one of the cell lines (NP446). This is the first report on the successful immortalization of nasopharyngeal epithelial cells involving LMP1. The events associated with the immortalization of nasopharyngeal epithelial cells by LMP1/hTERT were characterized. Expression of c-Myc, Bmi-1, and Id-1 were upregulated at an early stage of immortalization. At a later stage of immortalization, downregulation of p21 and p16 expression were observed. Upregulation of EGFR expression and activation of MAPK signaling pathway were observed in LMP1/hTERT -immortalized nasopharyngeal epithelial cells. The LMP1/hTERT -immortalized NP446 cells were non-tumorigenic in immunosuppressed nude mice and retained anchorage-dependent growth, suggesting that additional events are required for tumorigenic transformation. The ability of the EBV-encoded LMP1, in the presence of hTERT expression, to extend the life span and immortalize primary cultures of nasopharyngeal epithelial cells supports the involvement of EBV infection and its viral products in the early stage of pathogenesis of nasopharyngeal carcinoma. J. Med. Virol. 82:1711,1723, 2010. © 2010 Wiley-Liss, Inc. [source] Distribution patterns of ,- and ,-herpesviruses within Waldeyer's ring organsJOURNAL OF MEDICAL VIROLOGY, Issue 8 2007Christoph Berger Abstract The Waldeyer's ring designates a functional unit of lymphoid tissue within the pharynx including the adenoids and tonsils. To gain insight into distribution patterns of ,- and ,-human herpesviruses (HHVs) and their potential mutual influences at their natural portal of entry, quantitative polymerase chain reaction (qPCR) assays were applied to adenoids and tonsils obtained from 30 children. DNA of Epstein-Barr virus (EBV), cytomegalovirus (CMV), HHV-6, HHV-7, and HHV-8 was detected in adenoids, tonsils, or both of 24 (80%), 19 (63%), 23 (77%), 23 (77%), and 0 (0%) children, respectively. EBV, CMV, HHV-6, and -7 localized in both adenoids and tonsils from 92%, 37%, 52%, and 70% of children, respectively, with the virus detectable by qPCR. The amount of EBV was 2,10-fold higher than of other HHVs and correlated in autologous organs (P,=,0.01) as did the amount of HHV-7 (P,=,0.002). The amount of CMV correlated with the HHV-6 amount in adenoids (P,=,0.028) and tonsils (P,=,0.007), and with the amount of HHV-7 in adenoids (P,<,0.01). Levels of HHV-6 DNA were lower in adenoids with detectable CMV DNA than in adenoids without detectable CMV DNA (P,=,0.0062). Inversely, CMV and HHV-7 levels were higher in adenoids with than in adenoids without detectable EBV DNA (P,=,0.019 and P,=,0.039, respectively).Thus, ,- and ,-HHV exhibit distinct distribution behaviors in Waldeyer's ring organs and seem to interact. This may be of medical importance in immunocompromised hosts who are likely to reactivate HHVs causing severe morbidity and death. J. Med. Virol. 79: 1147,1152, 2007. © 2007 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||||||||||||||||||||