Epstein-Barr Virus and Human Cancer: Hokkaido University, July 4-6, 2001 (original) (raw)
Related papers
Medicina
Nasopharyngeal carcinoma (NPC) is an uncommon type of malignancy/cancer worldwide. However, NPC is an endemic disease in southeast Asia and southern China and the reasons behind the underlying for such changes are unclear. Even though the Epstein–Barr infection (EBV) has been suggested as an important reason for undistinguishable NPC, the EBV itself is not adequate to source this type of cancer. The risk factors, for example, genetic susceptibility, and environmental factors might be associated with EBV to undertake a part in the NPC carcinogenesis. Normal healthy people have a memory B cell pool where the EBV persists, and any disturbance of this connection leads to virus-associated B cell malignancies. Less is known about the relationship between EBV and epithelial cell tumors, especially the EBV-associated nasopharyngeal carcinoma (EBVaNPC) and EBV-associated gastric carcinoma (EBVaGC). Currently, it is believed that premalignant genetic changes in epithelial cells contribute to ...
Epstein-Barr virus genes and nasopharyngeal cancer
2006
widespread in all areas of the world, infecting over 95% of the adult population. EBV primarily infects and replicates in the stratified squamous epithelium of the oropharynx during acute infection. Besides, its well-known tropism for B cells, the targets of EBV infection may also include epithelial cells, T cells, and cells of the macrocytic, granulocytic, and natural killer lineages. Although most humans coexist with the virus without serious sequelae, a small proportion will develop tumors. Almost every undifferentiated nasopharyngeal carcinoma (NPC) is EBV positive, despite geographical origin. EBV-derived IL-10 which is considered to play a role in the establishment of latent infection by suppression of the host immune system, may contribute to the growth of the tumor and to immune evasion. Latent membrane protein-1 (LMP-1) has transforming ability and support to the concept that EBV is involved in the pathogenesis of NPC. The association of NPC with EBV has been firmly established however the evidence indicating a role for the virus in the pathogenesis is still unknown and controversial. The main question is how the EBV-infected cells can escape from the immune response. [Turk J Cancer 2006;36(3):97-107].
Epstein-Barr virus transcription in nasopharyngeal carcinoma
Journal of Virology, 1983
Sequences which encode Epstein-Barr virus (EBV) RNA in nasopharyngeal carcinoma (NPC) tissue have been identified. We utilized human biopsy material directly as well as NPC grown in nude mice. Total RNA was extracted from the tumor material and separated into polyadenylated and nonpolyadenylated fractions by oligodeoxythymidylate-cellulose chromatography. This material was used as template to construct 32P-labeled cDNA. The labeled cDNAs were hybridized to Southern blots of recombinant EBV DNA fragments. Three of the biopsies, F, 49, and 55, contained polyadenylated RNA homologous to the EBV BamHI fragments V and K, and EcoRI-DIJhet. These same fragments encode the most abundant polyribosomal RNAs in latently infected lymphoblastoid cell lines. The sequences which encoded nonpolyadenylated RNA in NPC tumor 49 were more extensive and included BamHI fragments C, V, B, E, and K, and EcoRI fragments DIJhet, E, F, and G1, a result that indicates selective polyadenylation in EBV RNA proce...
Epstein--Barr Virus Gene Expression in Nasopharyngeal Carcinoma
Journal of General Virology, 1988
Epstein-Barr virus (EBV), an agent with growth transforming potential for human B cells, is associated with certain B cell lymphomas in man and also with an epithelial tumour, undifferentiated nasopharyngeal carcinoma (NPC). Since B cell growth transformation is associated with the constitutive expression of a small number of EBV-coded latent proteins, the nuclear antigens EBNA 1, EBNA 2, EBNA 3 and EBNA-LP and the latent membrane protein (LMP), the present work sought to determine whether this same pattern of virus gene expression occurred in NPC. Tumour biopsies were taken from NPC patients from three areas of differing tumour incidence (Kenya, Algeria, Britain) and immediately snap-frozen, as were biopsies of non-EBV-related carcinomas for controls. Immunoblotting of PAGE-separated proteins with selected human sera identified 24 NPC biopsies clearly expressing EBNA 1. When the analysis was extended using selected human sera with antibodies against the other EBNAs, there was no detectable expression of EBNA 2, EBNA 3 or EBNA-LP in any of these 24 biopsies; their EBNA 2-negative status was confirmed using a monoclonal antibody (MAb) PE2 which was reactive in immunoblotting and in immunoprecipitation with EBNA 2A and EBNA 2B proteins. Similar experiments with two different LMP-specific MAbs, CS1 to 4 and S12, revealed heterogeneity between NPC biopsies; 9/24 biopsies were demonstrably LMP-positive, the degree of expression varying considerably between individual tumours in a manner which was not related to the level of EBNA 1 expression. None of the 24 NPC biopsies expressed detectable amounts of EBV lytic cycle antigens. A nude mouse-passaged NPC cell line, C15, likewise expressed EBNA 1 and LMP but none of the other EBV latent proteins nor lytic cycle antigens. This work identifies a novel type of EBV-cell interaction in NPC cells which is distinct from that seen in in vitro transformed B cell lines and from that seen to date in EBV-positive B cell lymphomas.
The differentiated form of nasopharyngeal carcinoma contains epstein-barr virus DNA
International Journal of Cancer, 1987
Immunologic studies of Epstein-Barr virus (EBV) have implicated EBV in undifferentiated and partially differentiated, non-keratinizing nasopharyngeal carcinoma (NPC). Patients with the well-differentiated, keratinizing form of NPC have EBV serologic patterns similar to those of control populations. In addition, viral DNA has not been detected in the differentiated tumors using viral cRNA probes to DNA immobilized on filters. In this study we have tested for EBV DNA using recombinant DNA probes to Southern blots of DNA from 33 NPC specimens. The 24 undifferentiated and 4 partially differentiated specimens generally contained a relatively high number of EBV genome equivalents, while the 5 well-differentiated NPC all contained detectable EBV, but at low copy number. The viral DNA from one of the well-differentiated specimens was cloned into a cormid vector. Five recombinant clones representing the fused viral termini were obtained, indicating the presence of episomal, intracellular DNA in the tumor. These findings indicate that all histologic subsets of NPC contain EBV DNA.
Expression of Epstein-Barr virus-encoded proteins in nasopharyngeal carcinoma
International Journal of Cancer, 1988
Expression of the Epstein-Barr virus (EBV) encoded nuclear antigens (EBNA I to 6) and membrane-associated protein (LMP) was investigated by immunoblotting in 83 nasopharyngeal carcinoma (NPC) biopsies and 25 other tumor and normal tissue specimens from the head and neck region. Fifty-eight of the 83 NPC biopsies were large enough to yield parallel data on virus D N A and viral expression. All 16 cases of clinically diagnosed and histologically confirmed NPCs from North Africa contained EBV D N A and expressed EBNA-I. O f 31 clinically diagnosed NPCs from China, 29 contained EBV D N A and 25 of these expressed EBNA-I. One control tissue biopsy from the oropharynx of NPC patients contained EBV DNA, but none expressed EBNA-I. The latent membrane protein (LMP) was detected in 22/31 of the Chinese and in 10/16 of the
Chinese journal of cancer, 2014
The interplay between host cell genetics and Epstein-Barr virus (EBV) infection contributes to the development of nasopharyngeal carcinoma (NPC). Understanding the host genetic and epigenetic alterations and the influence of EBV on cell signaling and host gene regulation will aid in understanding the molecular pathogenesis of NPC and provide useful biomarkers and targets for diagnosis and therapy. In this review, we provide an update of the oncogenes and tumor suppressor genes associated with NPC, as well as genes associated with NPC risk including those involved in carcinogen detoxification and DNA repair. We also describe the importance of host genetics that govern the human leukocyte antigen (HLA) complex and immune responses, and we describe the impact of EBV infection on host cell signaling changes and epigenetic regulation of gene expression. High-power genomic sequencing approaches are needed to elucidate the genetic basis for inherited susceptibility to NPC and to identify t...
Medical microbiology and immunology, 2018
Epstein-Barr virus (EBV) has been identified as a group 1 carcinogenic agent, particularly for nasopharyngeal carcinoma (NPC). The sequence diversity of EBV nuclear antigen 1 (EBNA1) reflects region-restricted polymorphisms, which may be associated with the development of certain malignancies. The aims of the present study were to evaluate EBV EBNA1 gene polymorphisms circulating in NPC, infectious mononucleosis, and isolates from patients with transplanted organs to determine if EBNA1 sequence specificities are useful as viral biomarkers for NPC. Forty biopsies of undifferentiated carcinoma of nasopharyngeal type (UCNT), 31 plasma samples from patients with mononucleosis syndrome, and 16 plasma samples from patients after renal transplantation were tested in this study. The EBNA1 gene was amplified by nested PCR. Further investigation included sequencing, phylogenetic, and statistical evaluations. Eighty-seven sequences were identified as one of the four EBNA1 subtypes, P-Ala, P-Th...