Displaying publications 21 - 40 of 48 in total

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  1. Peh SC
    Histopathology, 2001 May;38(5):458-65.
    PMID: 11422484
    AIMS: The pattern of malignant lymphoma is known to vary in different populations. This study aims to elucidate the effect of ethnicity on subtype frequency of non-Hodgkin's lymphoma and EBV association rate.

    METHODS AND RESULTS: A total of 232 reconfirmed lymphoma cases in Malaysian patients were retrieved from the archives in the Department of Pathology, University Hospital, Kuala Lumpur. There were 24 (10%) Hodgkin's and 208 (90%) non-Hodgkin's lymphomas, 173 of the latter were in adult group (aged > or = 15 years). The ethnic composition were 41 Malays, 107 Chinese, 21 Indians and four none of the above. A male : female ratio of 2.4 : 1 was observed. Complete immunohistochemical studies in 158 cases revealed 36 (23%) T-cell, 121 (76%) B-cell and one (1%) null-cell phenotype. Seventy-five percent of the T-cell lymphomas were peripheral T/NK-cell types. Among the classifiable lesions, low-grade/indolent lymphomas constituted 17%: 2% were the lymphocytic subtype and 10% were follicular lymphomas. Approximately one-third of the follicular lymphomas occurred in Indian patients. The largest group of high-grade lymphoma was diffuse large B-cell type (46%), followed by peripheral T/NK-cell (18%). A predominance of NK/T-cell lymphomas occurred in Chinese (5/7), and all were EBV associated. Burkitt's lymphoma accounted for 5% (eight cases), all were Chinese males, with a 38% EBV-association rate. The frequency of EBV-associated B-cell lymphoma is three times more common in Chinese than Malays. The EBV positivity rate among lymphomas in ethnic Malay, Chinese and Indian patients was 5%, 15% and 22%, respectively, and in T- and B-cell lymphomas was 36% and 7%, respectively.

    CONCLUSIONS: This Malaysian series reveals differences in the subtype frequencies of non-Hodgkin's lymphomas and EBV association rate amongst patients of various ethnic groups residing in the same environment.

    Matched MeSH terms: Epstein-Barr Virus Infections/ethnology*; Epstein-Barr Virus Infections/virology
  2. Tan LP, Tan GW, Sivanesan VM, Goh SL, Ng XJ, Lim CS, et al.
    Int J Cancer, 2020 04 15;146(8):2336-2347.
    PMID: 31469434 DOI: 10.1002/ijc.32656
    Nasopharyngeal carcinoma (NPC) is originated from the epithelial cells of nasopharynx, Epstein-Barr virus (EBV)-associated and has the highest incidence and mortality rates in Southeast Asia. Late presentation is a common issue and early detection could be the key to reduce the disease burden. Sensitivity of plasma EBV DNA, an established NPC biomarker, for Stage I NPC is controversial. Most newly reported NPC biomarkers have neither been externally validated nor compared to the established ones. This causes difficulty in planning for cost-effective early detection strategies. Our study systematically evaluated six established and four new biomarkers in NPC cases, population controls and hospital controls. We showed that BamHI-W 76 bp remains the most sensitive plasma biomarker, with 96.7% (29/30), 96.7% (58/60) and 97.4% (226/232) sensitivity to detect Stage I, early stage and all NPC, respectively. Its specificity was 94.2% (113/120) against population controls and 90.4% (113/125) against hospital controls. Diagnostic accuracy of BamHI-W 121 bp and ebv-miR-BART7-3p were validated. Hsa-miR-29a-3p and hsa-miR-103a-3p were not, possibly due to lower number of advanced stage NPC cases included in this subset. Decision tree modeling suggested that combination of BamHI-W 76 bp and VCA IgA or EA IgG may increase the specificity or sensitivity to detect NPC. EBNA1 99 bp could identify NPC patients with poor prognosis in early and advanced stage NPC. Our findings provided evidence for improvement in NPC screening strategies, covering considerations of opportunistic screening, combining biomarkers to increase sensitivity or specificity and testing biomarkers from single sampled specimen to avoid logistic problems of resampling.
    Matched MeSH terms: Epstein-Barr Virus Infections/blood; Epstein-Barr Virus Infections/virology
  3. Wong KK, Prepageran N, Peh SC
    Pathology, 2009 Feb;41(2):133-9.
    PMID: 18972319 DOI: 10.1080/00313020802436790
    AIMS: To stratify upper aerodigestive tract (UAT) diffuse large B-cell lymphoma (DLBCL) into prognostic subgroups by immunohistochemical staining (IHC) method, and to evaluate the association rate of UAT DLBCL with Epstein-Barr virus (EBV).

    METHODS: Using a panel of antibodies to CD10, Bcl-6, MUM1 and CD138, consecutive cases of primary UAT DLBCL were stratified into subgroups of germinal centre B-cell-like (GCB) and non-GCB, phenotype profile patterns A, B and C, as proposed by Hans et al. and Chang et al., respectively. EBER in situ hybridisation technique was applied for the detection of EBV in the tumours.

    RESULTS: In this series of 32 cases of UAT DLBCL, 34% (11/32) were GCB, and 66% (21/32) were non-GCB types; 59% (19/32) had combined patterns A and B, and 41% (13/32) had pattern C. Statistical analysis revealed no significant difference in the occurrence of these prognostic subgroups in the UAT when compared with series of de novo DLBCL from all sites. There was also no site difference in phenotype protein expressions, with the exception of MUM1. EBER in situ hybridisation stain demonstrated only one EBV infected case.

    CONCLUSIONS: Prognostic subgroup distribution of UAT DLBCL is similar to de novo DLBCL from all sites, and EBV association is very infrequent.

    Matched MeSH terms: Epstein-Barr Virus Infections/complications; Epstein-Barr Virus Infections/epidemiology
  4. Setoh JWS, Ho CKM, Yung CF, Tam C, Yelen, Tee NWS
    Pediatr Infect Dis J, 2019 12;38(12):1173-1176.
    PMID: 31738332 DOI: 10.1097/INF.0000000000002484
    BACKGROUND: Epstein-Barr virus (EBV) spreads through bodily fluids, especially saliva, and can cause infectious mononucleosis. EBV immunity and infection status can be assessed by testing EBV viral capsid antigen and nuclear antigen (EBNA) antibodies in blood. In this study, we investigated the seroprevalence and force of infection (FOI) of EBV antibodies among children and young people in 3 ethnic groups in Singapore.

    METHODS: Eight hundred ninety-six residual serum samples at a tertiary hospital were tested for viral capsid antigen (IgG and IgM) and EBNA IgG antibodies using Abbott Architect assays. We calculated the EBV seroprevalence using catalytic models to estimate the EBV force of infection from age-stratified seroprevalence data, both overall and by ethnic group.

    RESULTS: Overall seropositivity was 68.3% (n = 612). Seropositivity was higher in Malays (81.8%) compared with both Chinese (64.2%) and Indians (58.4%). EBV FOI was consistently higher in Malays, with an estimated annual rate of seroconversion of 25% in children 1 year, of age compared with 14% among Chinese and Indians at the same age.

    CONCLUSIONS: The seroprevalence patterns of EBV antibodies in the Chinese and Indian, but not Malay children in Singapore by 19 years of age resemble those previously reported in developed countries. Ideally, any future EBV vaccination strategy would need to target infants <1 year of age for maximum population benefit.

    Matched MeSH terms: Epstein-Barr Virus Infections/ethnology*; Epstein-Barr Virus Infections/immunology
  5. Yap YY, Hassan S, Chan M, Choo PK, Ravichandran M
    Otolaryngol Head Neck Surg, 2007 Jun;136(6):986-91.
    PMID: 17547993
    OBJECTIVES: This study examines the presence of Epstein-Barr virus (EBV) in nasopharyngeal carcinoma (NPC) by using polymerase chain reaction (PCR).

    STUDY DESIGN: Eighty-six postnasal biopsy samples and 71 fine-needle aspirate samples of neck masses were obtained from patients who were clinically suspect for NPC. Genomic DNA was extracted from the samples, and EBNA1, EBNA2, and LMP genes of EBV were detected by PCR. PCR results were compared with NPC histopathology findings.

    RESULTS: The sensitivity of PCR to detect EBNA1 (97.14%), EBNA2 (88.57%), and LMP (91.43%) genes of EBV in nasopharyngeal biopsy samples were higher than those in fine-needle aspirate samples.

    CONCLUSION: Detection of EBV by PCR in tissue obtained from nasopharyngeal biopsy and fine-needle aspirate samples of neck masses is a relatively inexpensive, reliable, and accurate method of diagnosing NPC. Detection of EBV genes is on par with histopathological examination (HPE) and superior to fine-needle aspirate cytology.

    SIGNIFICANCE: PCR is an ideal tool for suggesting NPC and guiding the diagnostic workup in occult primary tumors, facilitating earlier diagnosis and reducing morbidity and mortality.

    Matched MeSH terms: Epstein-Barr Virus Infections/diagnosis*; Epstein-Barr Virus Infections/pathology; Epstein-Barr Virus Infections/virology
  6. Kim LH, Peh SC, Poppema S
    Hum Pathol, 2006 Jan;37(1):92-100.
    PMID: 16360421
    Deregulation of several genes involved in cell cycle control has been reported in classic Hodgkin lymphoma (cHL). This study aimed to investigate the expression of tumor suppressor proteins (P16(INK4A), retinoblastoma protein, and p53) in cHL in relation to the proliferation and apoptosis of Hodgkin/Reed-Sternberg (H/RS) cells, correlating with the status of Epstein-Barr virus (EBV). A total of 66 cHL cases and 10 nonneoplastic reactive lymphoid tissues were retrieved from the archives. Immunohistochemistry technique was used for the detection of protein expression. Presence of EBV infection was detected by EBV early RNA in situ hybridization. p16(INK4A) gene deletion status was assessed by fluorescence in situ hybridization technique. Expression of P16(INK4A) was observed in 49.2% of the cases, whereas positive retinoblastoma protein and p53 expressions in the H/RS cells were detected in 89.1% and 81.5% of the cases, respectively. Epstein-Barr virus positivity was detected in 53.0% of the cases. Proliferation marker, Ki-67 expression, was observed in 86.7% of the cases. There was no significant correlation between the expression of the various tumor suppressor proteins and Ki-67. Retinoblastoma protein and p53 were also not associated with the presence of EBV. An inverse relationship was observed between the expression of P16(INK4A) and the presence of EBV. There were no significant homozygous or hemizygous deletions of the p16(INK4A) gene. However, an aberrant copy number of chromosome 9 with the loss of one or more p16(INK4A) loci was detected in all cases assessable by fluorescence in situ hybridization. Loss of function of one or more tumor suppressor proteins may be involved in defective cell regulation of H/RS cells. Epstein-Barr virus may have a role in inhibiting P16(INK4A) expression, thus resulting in a perturbed p16(INK4A)-Rb cell cycle checkpoint.
    Matched MeSH terms: Epstein-Barr Virus Infections/metabolism*; Epstein-Barr Virus Infections/pathology; Epstein-Barr Virus Infections/virology
  7. Peh SC, Kim LH, Thanaletchimy N, Chai SP, Poppema S
    Malays J Pathol, 2000 Jun;22(1):13-20.
    PMID: 16329532
    Lymphoma is a relatively common group of neoplasms diagnosed in hospital practice. This study aims to elucidate the pattern of this disease encountered in a public service hospital of the Ministry of Health, Malaysia.
    Matched MeSH terms: Epstein-Barr Virus Infections/complications; Epstein-Barr Virus Infections/ethnology; Epstein-Barr Virus Infections/pathology
  8. Hoe SL, Lee ES, Khoo AS, Peh SC
    Pathology, 2009;41(6):561-5.
    PMID: 19900105
    AIMS: Nasopharyngeal carcinoma (NPC) is a common malignancy among men in Malaysia. To determine the role of p53 in NPC, we screened for p53 mutations and evaluated the protein expression levels in samples from local patients with NPC.

    METHODS: Fifty-three formalin-fixed, paraffin-embedded nasopharyngeal carcinoma tissue blocks were chosen for this study. The presence of Epstein-Barr virus (EBV) was determined by in situ hybridisation using an EBER probe. p53 protein expression was detected using immunohistochemistry. Simultaneously, amplifications by PCR were performed for p53 exons 5 to 8, followed by mutation screening via single strand conformation polymorphism (SSCP). Sequencing of all the four exons was performed in five samples with mobility shift. To rule out false negative results by SSCP, 13 samples with p53 overexpression and five samples with low p53 expression were randomly selected and sequenced.

    RESULTS: There was no mutation found in exons 5 to 8 in all the samples despite 46 (87%) of them having high p53 levels. EBV was detected in 51 (96%) out of 53 samples. There was no statistically significant association between p53 expression level and EBV presence.

    CONCLUSIONS: High-intensity staining for p53 by immunohistochemistry was common in our series of NPC tissue samples but was not associated with 'hot spot' mutations of exons 5-8 of the gene. We did not find a significant relationship between the expression level of p53 and presence of EBV. Our study confirms that mutation of the DNA-binding domain of p53 is rare in NPC.

    Matched MeSH terms: Epstein-Barr Virus Infections/complications; Epstein-Barr Virus Infections/genetics; Epstein-Barr Virus Infections/pathology
  9. Che Ismail Che Noh, Fox, Anthony William
    MyJurnal
    Ebola virus disease (EVD) is an emerging and remerging zoonosis associated with high fatality rate, mainly caused by the Zaire Ebola virus (ZEBOV) and Sudan Ebola virus (SEBOV) strains. Approximately 20 epidemics of EVD have been documented mainly in Central African countries since 1976. Currently, there are no therapeutics agents and vaccines yet approved for EVD. However, several promising therapeutics and vaccines candidates are actively undergoing various phase of clinical development. This study aims to study the EVD dynamics and evaluate the potential impacts of vaccines and other preventive measures on EVD transmission control and significance of medical intervention on outcome of the disease. An initial branch chain model of EVD dynamics was built based on data obtained from previous study. Different epidemiological scenarios for EVD with impacts of intervention were simulated using Berkeley-Madonna Version 8.3.18 software. Every reduction in the exposure rate of EBV infection by 10% produces two- to five-fold improvement in protection against EVD. Transmission control is optimum when the rate of exposure to EBV infection is reduced below 1%. Optimal control of EVD transmission can be achieved through strategic implementation of successful vaccination programme, and other preventive measures as well as rapid delivery of supportive medical care.
    Matched MeSH terms: Epstein-Barr Virus Infections
  10. Bruce JP, To KF, Lui VWY, Chung GTY, Chan YY, Tsang CM, et al.
    Nat Commun, 2021 07 07;12(1):4193.
    PMID: 34234122 DOI: 10.1038/s41467-021-24348-6
    Interplay between EBV infection and acquired genetic alterations during nasopharyngeal carcinoma (NPC) development remains vague. Here we report a comprehensive genomic analysis of 70 NPCs, combining whole-genome sequencing (WGS) of microdissected tumor cells with EBV oncogene expression to reveal multiple aspects of cellular-viral co-operation in tumorigenesis. Genomic aberrations along with EBV-encoded LMP1 expression underpin constitutive NF-κB activation in 90% of NPCs. A similar spectrum of somatic aberrations and viral gene expression undermine innate immunity in 79% of cases and adaptive immunity in 47% of cases; mechanisms by which NPC may evade immune surveillance despite its pro-inflammatory phenotype. Additionally, genomic changes impairing TGFBR2 promote oncogenesis and stabilize EBV infection in tumor cells. Fine-mapping of CDKN2A/CDKN2B deletion breakpoints reveals homozygous MTAP deletions in 32-34% of NPCs that confer marked sensitivity to MAT2A inhibition. Our work concludes that NPC is a homogeneously NF-κB-driven and immune-protected, yet potentially druggable, cancer.
    Matched MeSH terms: Epstein-Barr Virus Infections/genetics; Epstein-Barr Virus Infections/immunology*; Epstein-Barr Virus Infections/therapy; Epstein-Barr Virus Infections/virology
  11. Abdulamir AS, Hafidh RR, Abdulmuhaimen N, Abubakar F, Abbas KA
    BMC Public Health, 2008;8:400.
    PMID: 19055849 DOI: 10.1186/1471-2458-8-400
    Nasopharyngeal carcinoma (NPC) and other head and neck cancer (HNCA) types show a great epidemiological variation in different regions of the world. NPC has multifactorial etiology and many interacting risk factors are involved in NPC development mainly Epstein Barr virus (EBV). There is a need to scrutinize the complicated network of risk factors affecting NPC and how far they are different from that of other HNCA types.
    Matched MeSH terms: Epstein-Barr Virus Infections/immunology; Epstein-Barr Virus Infections/epidemiology*
  12. Vockerodt M, Vrzalikova K, Ibrahim M, Nagy E, Margielewska S, Hollows R, et al.
    J Pathol, 2019 06;248(2):142-154.
    PMID: 30666658 DOI: 10.1002/path.5237
    The Epstein-Barr virus (EBV) is found almost exclusively in the activated B-cell (ABC) subtype of diffuse large B-cell lymphoma (DLBCL), yet its contribution to this tumour remains poorly understood. We have focused on the EBV-encoded latent membrane protein-1 (LMP1), a constitutively activated CD40 homologue expressed in almost all EBV-positive DLBCLs and which can disrupt germinal centre (GC) formation and drive lymphomagenesis in mice. Comparison of the transcriptional changes that follow LMP1 expression with those that follow transient CD40 signalling in human GC B cells enabled us to define pathogenic targets of LMP1 aberrantly expressed in ABC-DLBCL. These included the down-regulation of S1PR2, a sphingosine-1-phosphate (S1P) receptor that is transcriptionally down-regulated in ABC-DLBCL, and when genetically ablated leads to DLBCL in mice. Consistent with this, we found that LMP1-expressing primary ABC-DLBCLs were significantly more likely to lack S1PR2 expression than were LMP1-negative tumours. Furthermore, we showed that the down-regulation of S1PR2 by LMP1 drives a signalling loop leading to constitutive activation of the phosphatidylinositol-3-kinase (PI3-K) pathway. Finally, core LMP1-PI3-K targets were enriched for lymphoma-related transcription factors and genes associated with shorter overall survival in patients with ABC-DLBCL. Our data identify a novel function for LMP1 in aggressive DLBCL. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
    Matched MeSH terms: Epstein-Barr Virus Infections/mortality; Epstein-Barr Virus Infections/virology*
  13. Bu W, Joyce MG, Nguyen H, Banh DV, Aguilar F, Tariq Z, et al.
    Immunity, 2019 05 21;50(5):1305-1316.e6.
    PMID: 30979688 DOI: 10.1016/j.immuni.2019.03.010
    Epstein-Barr virus (EBV) causes infectious mononucleosis and is associated with epithelial-cell cancers and B cell lymphomas. An effective EBV vaccine is not available. We found that antibodies to the EBV glycoprotein gH/gL complex were the principal components in human plasma that neutralized infection of epithelial cells and that antibodies to gH/gL and gp42 contributed to B cell neutralization. Immunization of mice and nonhuman primates with nanoparticle vaccines that displayed components of the viral-fusion machinery EBV gH/gL or gH/gL/gp42 elicited antibodies that potently neutralized both epithelial-cell and B cell infection. Immune serum from nonhuman primates inhibited EBV-glycoprotein-mediated fusion of epithelial cells and B cells and targeted an epitope critical for virus-cell fusion. Therefore, unlike the leading EBV gp350 vaccine candidate, which only protects B cells from infection, these EBV nanoparticle vaccines elicit antibodies that inhibit the virus-fusion apparatus and provide cell-type-independent protection from virus infection.
    Matched MeSH terms: Epstein-Barr Virus Infections/immunology; Epstein-Barr Virus Infections/prevention & control*
  14. Peh SC, Kim LH, Poppema S
    Pathology, 2002 Oct;34(5):446-50.
    PMID: 12408344
    AIMS: Epstein-Barr virus (EBV) is associated with many human malignancies. It is implicated in a pathogenetic role in some of these tumours. Two subtypes, type A and B have been identified on the basis of DNA sequence divergence in the nuclear protein genes (EBNA) 2, 3, 4 and 6. They differ in their transforming efficiency and prevalence pattern in different geographical locations. We aimed to identify the virus subtype infection pattern in our EBV-associated diseases.

    METHODS: Paraffin-embedded tissue from 38 lymphomas (17 Hodgkin's, 14 Burkitt's, four T cell and 3 B cell non-Hodgkin's lymphomas) and 14 nasopharyngeal carcinomas (NPC) were studied, with 12 reactive lymph nodes and tonsils as normal control. EBER in situ hybridisation was performed to confirm EBV association in the tumour cells. A nested polymerase chain reaction (PCR) protocol was employed using two pairs of consensus primers which flanked a 105-bp deletion in the type A virus. U2 region encoding for EBNA-2 was chosen as the target of amplification, with cell lines B95.8 and AG876 serving as positive controls for types A and B virus, respectively.

    RESULTS: All cases showed presence of type A virus, consistently detected with nested PCR protocol but not with single step PCR. There was no type B virus or mix infections detected.

    CONCLUSIONS: Nested PCR technique has successfully increased the sensitivity of EBV subtype detection, and type A virus is the prevalent strain associated with human diseases in Malaysia.

    Matched MeSH terms: Epstein-Barr Virus Infections/complications*; Epstein-Barr Virus Infections/pathology
  15. Lim CS, Krishnan G, Sam CK, Ng CC
    Clin Chim Acta, 2013 Jan 16;415:158-61.
    PMID: 23043757 DOI: 10.1016/j.cca.2012.08.031
    Because blocking agent occupies most binding surface of a solid phase, its ability to prevent nonspecific binding determines the signal-to-noise ratio (SNR) and reliability of an enzyme-linked immunosorbent assay (ELISA).
    Matched MeSH terms: Epstein-Barr Virus Infections/diagnosis*; Epstein-Barr Virus Infections/immunology
  16. Tan GW, Sivanesan VM, Abdul Rahman FI, Hassan F, Hasbullah HH, Ng CC, et al.
    Int J Cancer, 2019 Oct 15;145(8):2260-2266.
    PMID: 30698824 DOI: 10.1002/ijc.32173
    Nasopharyngeal carcinoma (NPC) is an epithelial cancer of the nasopharynx which is highly associated with Epstein-Barr virus (EBV). Worldwide, most of the top 20 countries with the highest incidence and mortality rates of NPC are low- and middle-income countries. Many studies had demonstrated that EBV could be detected in the tissue, serum and plasma of NPC patients. In this study, we explored the potential of assays based on non-invasive nasal washings (NW) as a diagnostic and prognostic tool for NPC. A total of 128 patients were evaluated for NW EBV DNA loads and a subset of these samples were also tested for 27 EBV and human miRNAs shortlisted from literature. EBV DNA and seven miRNAs showed area under the receiver operating characteristic curve (AUC) values of more than 0.7, suggestive of their potential utility to detect NPC. Logistic regression analyses suggested that combination of two NW assays that test for EBNA-1 and hsa-miR-21 had the best performance in detecting NPC. The trend of NW EBV DNA load matched with clinical outcome of 71.4% (10 out of 14) NPC patients being followed-up. In summary, the non-invasive NW testing panel may be particularly useful for NPC screening in remote areas where healthcare facilities and otolaryngologists are lacking, and may encourage frequent testing of individuals in the high risk groups who are reluctant to have their blood tested. However, further validation in an independent cohort is required to strengthen the utility of this testing panel as a non-invasive detection tool for NPC.
    Matched MeSH terms: Epstein-Barr Virus Infections/diagnosis*; Epstein-Barr Virus Infections/virology
  17. Lung RW, Hau PM, Yu KH, Yip KY, Tong JH, Chak WP, et al.
    J Pathol, 2018 Apr;244(4):394-407.
    PMID: 29230817 DOI: 10.1002/path.5018
    Nasopharyngeal carcinoma (NPC) is a highly invasive epithelial malignancy that is prevalent in southern China and Southeast Asia. It is consistently associated with latent Epstein-Barr virus (EBV) infection. In NPC, miR-BARTs, the EBV-encoded miRNAs derived from BamH1-A rightward transcripts, are abundantly expressed and contribute to cancer development by targeting various cellular and viral genes. In this study, we establish a comprehensive transcriptional profile of EBV-encoded miRNAs in a panel of NPC patient-derived xenografts and an EBV-positive NPC cell line by small RNA sequencing. Among the 40 miR-BARTs, predominant expression of 22 miRNAs was consistently detected in these tumors. Among the abundantly expressed EBV-miRNAs, BART5-5p, BART7-3p, BART9-3p, and BART14-3p could negatively regulate the expression of a key DNA double-strand break (DSB) repair gene, ataxia telangiectasia mutated (ATM), by binding to multiple sites on its 3'-UTR. Notably, the expression of these four miR-BARTs represented more than 10% of all EBV-encoded miRNAs in tumor cells, while downregulation of ATM expression was commonly detected in all of our tested sequenced samples. In addition, downregulation of ATM was also observed in primary NPC tissues in both qRT-PCR (16 NP and 45 NPC cases) and immunohistochemical staining (35 NP and 46 NPC cases) analysis. Modulation of ATM expression by BART5-5p, BART7-3p, BART9-3p, and BART14-3p was demonstrated in the transient transfection assays. These findings suggest that EBV uses miRNA machinery as a key mechanism to control the ATM signaling pathway in NPC cells. By suppressing these endogenous miR-BARTs in EBV-positive NPC cells, we further demonstrated the novel function of miR-BARTs in inhibiting Zta-induced lytic reactivation. These findings imply that the four viral miRNAs work co-operatively to modulate ATM activity in response to DNA damage and to maintain viral latency, contributing to the tumorigenesis of NPC. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
    Matched MeSH terms: Epstein-Barr Virus Infections/diagnosis; Epstein-Barr Virus Infections/virology*
  18. Tan EL, Peh SC, Sam CK
    J Med Virol, 2003 Feb;69(2):251-7.
    PMID: 12683415
    Nasopharyngeal carcinoma, a malignancy associated closely with Epstein-Barr virus (EBV), is prevalent among Chinese of Southern China origin. Epidemiological studies indicate a high prevalence of EBV in Asia with viral isolates having typical characteristics of the putative viral oncogene, latent membrane protein 1 (LMP-1), such as the loss of the Xho1 restriction site in Exon 1 and the 30-bp deletion in Exon 3. The EBV LMP-1 gene from throat washings of 120 nasopharyngeal carcinoma patients and 14 healthy individuals were analyzed. Similar analyses were also carried out on 30 and 12 postnasal space biopsies from nasopharyngeal carcinoma patients and healthy individuals, respectively. The 30-bp deletion was detected in 20% of nasopharyngeal carcinoma throat washes and in 100% of nasopharyngeal carcinoma postnasal space biopsies. Interestingly, 16% of the nasopharyngeal carcinoma biopsies possessed both the deleted and the undeleted variants, suggestive of dual infections. The notion of dual infections in nasopharyngeal carcinoma was further supported by the coexistence of both "F" and "f" (BamH1F region) EBV variants in 11% of the nasopharyngeal carcinoma biopsies. All of the throat washes and biopsies from the healthy controls showed the undeleted variant. The loss of the Xho1 restriction site was found with higher frequency both in throat washes and biopsies from patients with nasopharyngeal carcinoma. The discrepancy in the frequency of the 30-bp deletion between throat washes (20%) and postnasal space biopsies (100%) was an indication that this deletion is specific for viral isolates from primary tumour sites.
    Matched MeSH terms: Epstein-Barr Virus Infections/epidemiology; Epstein-Barr Virus Infections/virology
  19. Mohamed G, Vrzalikova K, Cader FZ, Vockerodt M, Nagy E, Flodr P, et al.
    J Gen Virol, 2014 Sep;95(Pt 9):1861-1869.
    PMID: 24893782 DOI: 10.1099/vir.0.066712-0
    The relationship between Epstein-Barr virus (EBV) and the germinal centre (GC) of the asymptomatic host remains an enigma. The occasional appearance of EBV-positive germinal centres in some patients, particularly those with a history of immunosuppression, suggests that EBV numbers in the GC are subject to immune control. The relationship, if any, between lymphoid hyperplasia with EBV-positive germinal centres and subsequent or concurrent lymphomagenesis remains to be clarified. As far as the development of EBV-associated Hodgkin's lymphoma is concerned, the suppression of virus replication, mediated by LMP1 on the one hand, and the loss of B-cell receptor signalling on the other, appears to be an important pathogenic mechanism. A further important emerging concept is that alterations in the microenvironment of the EBV-infected B-cell may be important for lymphomagenesis.
    Matched MeSH terms: Epstein-Barr Virus Infections/virology
  20. Yee PH, Sim SP
    J Biomed Sci, 2010;17:77.
    PMID: 20858288 DOI: 10.1186/1423-0127-17-77
    Nasopharyngeal carcinoma (NPC) is commonly found in Southern China and South East Asia. Epstein-Barr virus (EBV) infection is well associated with NPC and has been implicated in its pathogenesis. Moreover, various chromosome rearrangements were reported in NPC. However, the underlying mechanism of chromosome rearrangement remains unclear. Furthermore, the relationship between EBV and chromosome rearrangement with respect to the pathogenesis of NPC has not been established. We hypothesize that during virus- or stress-induced apoptosis, chromosomes are initially cleaved at the base of the chromatin loop domain structure. Upon DNA repair, cell may survive with rearranged chromosomes.
    Matched MeSH terms: Epstein-Barr Virus Infections/genetics
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