Epstein-Barr Virus-Related Lymphocyte Stimulation Inhibitor: A Possible Prognostic Tool for Undifferentiated Nasopharyngeal Carcinoma
Lakshmi S. KamarajuPascale LevineS K SundarD. V. AblashiAlberto FaggioniG. ArmstrongG. BertramG R Krueger
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It is demonstrated in this study that a serum factor, a lymphocyte stimulation inhibitor (LSI), which inhibits Epstein-Barr virus (EBV)-induced lymphocyte stimulation, is a potentially useful tool in the diagnosis and monitoring of nasopharyngeal carcinoma (NPC). In a study of 25 patients with undifferentiated NPC, 20 healthy controls, and 20 patients with other head and neck tumors, LSI was found only in the NPC patients with active disease. In a more complete study of 8 patients longitudinally followed up for at least 20 months, a comparison of LSI with antibodies to a variety of EBV antigens including viral capsid antigen, early antigen, and nuclear antigen indicated that LSI levels provided a reliable and sensitive indicator of disease activity that should be added to clinical markers currently in use as monitors of disease activity in NPC.BackgroundElevated levels of antibodies against antigens in the Epstein–Barr virus (EBV) lytic phase are important predictive markers for nasopharyngeal carcinoma (NPC) risk. Several lifestyle factors, including smoking, have also been associated with NPC risk. We hypothesized that some specific lifestyle factors induce transformation of EBV from the latent to the lytic stage and contribute to NPC occurrence.
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Epstein–Barr virus infection
Gammaherpesvirinae
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<i>Objectives:</i> To characterize the specific Epstein-Barr virus (EBV) polymorphisms from nasopharyngeal carcinoma (NPC) patients and healthy donors in Northern China, and to explore the relationship between the EBV genotypes and NPC. <i>Methods:</i> The genotypes of EBV strains were analyzed by the polymerase chain reaction and restriction fragment length polymorphism. <i>Results:</i> The predominant EBV type was A, C or F in both NPC and healthy individuals. The distributions of the EBV subtypes between NPC and healthy donors were not significantly different (p > 0.05). The frequency of type f strains in NPC was significantly lower in Northern China than in Southern China. <i>Conclusions:</i> No evidence of special EBV genotypes associated with NPC was found, suggesting that EBV strains derived from the NPC patients may reflect geographic distribution rather than being NPC restricted.
Gammaherpesvirinae
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Sera from 99 patients with nasopharyngeal carcinoma (NPC), 17 patients with diseases other than NPC and 24 healthy individuals were examined for their antibody activities to Epstein-Barr virus (EBV) DNase. Most of the sera from NPC patients showed high level of antibody activity even in the stage I of the disease. On the contrary, sera from healthy donors and patients with diseases other than NPC showed only very little or none of the activity. The results strongly suggest that the test for EBV DNase activity could be used for the early diagnosis of NPC.
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An Epstein-Barr virus (EBV) genome-positive epithelial hybrid cell line, NPC-KT, derived from the fusion of primary nasopharyngeal carcinoma cells with a human epithelial cell line of adenoid origin and a subline of EBV genome-positive Ramos cells, Ramos/NPC, converted after infection with NPC-KT EBV have been previously described (Takimoto et al., 1984; Takimoto et al., 1987). The NPC-KT cells produce virus (NPC virus) with both transforming and lytic properties. In this study, NPC-KT and Ramos/NPC cells were examined for the presence of the EBV receptor as measured by the capacity to absorb radio-labelled P3HR-1 and NPC viruses. It was determined that only P3HR-1 virus can attach to NPC-KT cells. Also, the relative concentration of NPC virus receptors on Ramos/NPC cells was found to be significantly reduced when compared to EBV genomenegative Ramos cells, whereas the relative concentration of receptors for P3HR-1 virus was similar to parental Ramos cells. The results suggest that there are differences at least in part of the receptors for P3HR-1 and NPC viruses.
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To observe the frequency of nasopharyngeal carcinoma (NPC) and its association with Epstein Barr Virus (EBV) infection.This study included consecutive cases of nasopharyngeal carcinoma, which were diagnosed in the Department of Pathology at the Aga Khan University Hospital, Karachi in the period of two years (1996-97).These tumors were initially evaluated on H&E stained sections. The tumors showing evidence of keratinization were excluded from the study. The Epstein Barr Virus was detected with the help of Polymerase chain reaction in formalin fixed, paraffin embedded tissue sections.During the study period, seventeen cases of nasopharyngeal carcinoma were diagnosed which comprised 0.3% of all malignant tumors. The age ranged from 5 years to 70 years with male to female ratio of 2.4:1. The NPC was more prevalent in adults (71%) as compared to children (29%) under 15 years. Six cases (35%) exhibited positive signal for Epstein Barr Virus.Nasopharyngeal carcinoma is an infrequent tumor. The prevalence of Epstein Barr virus infection in nasopharyngeal carcinoma is quite low as compared to other regions of the world.
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Despite the fact that most adult humans worldwide are latently infected by the Epstein-Barr virus (EBV), only a very small percentage of them will develop an EBV-associated malignancy. We do not know whether this situation reflects the existence of more sensitive individuals or of particularly tumorigenic EBV strains. We postulated that if highly tumorigenic EBV strains did exist, they would be preferentially found in consistently EBV-associated tumors, such as nasopharyngeal carcinoma (NPC), and differ significantly from the strains present in other, non-pathological sites of the same patients. To test this hypothesis, we compared the BNLF1 gene of the EBV strains present in tumors and in “reservoir lymphocytes” of 6 NPC-bearing patients from Tunisia. Our results show that all of these patients were infected by more than 1 (and up to 7) EBV strains. Moreover, lymphocytes and tumor cells from the same individual were systematically infected by different viral strains. The origin and biological significance of these multistrain infections are discussed. © 2001 Wiley-Liss, Inc.
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Cryosections of nasopharyngeal tissue from 9 patients suspected of having nasopharyngeal carcinoma (NPC) were examined for the presence of Epstein-Barr virus (EBV) markers in situ to assess virus infection in the nasopharynx. Viral DNA, EB nuclear antigen, and/or early antigens (EA.D and EA.R) were detected in 5 NPC specimens. EBV infection was not confined to the tumor areas of the biopsy specimens. Lymphoid cells and nontumor areas of these specimens contained EBV markers. In addition, nasopharyngeal tissues obtained from 3 of 4 patients in clinical remission for the disease showed evidence of EBV infection.
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Gene mapping of an Epstein-Barr virus (EBV) isolate derived from a nasopharyngeal carcinoma (NPC), designated NPC-EBV, has been performed. This isolate was rescued from an NPC epithelial hybrid cell line (NPC-KT), and used to transform cotton-top tamarin lymphocytes which, along with the epithelial NPC-KT cells, were used in the mapping studies. Using the BamHl and EcoRl restriction enzymes, we found that the NPC-EBV isolate did not contain the deletions observed in the genomes of the prototype HR-1 and B95–8 isolates, and may represent a 'more complete' virus genome. Polymorphism was observed in the βαmHI-X, T, H, and L regions as compared to the HR-1 and B95–8 isolates. The NPC-EBV DNA in the epithelial NPC-KT cells was compared to the NPC-EBV genome in three different cotton-top tamarin lymphoblastoid cell lines transformed with the isolate. The restriction patterns were the same with one exception; there were differences in the size of the BamHl N-J het regions. This finding is consistent with the idea that the BamHl N-J het region may be the switch point of EBV DNA from the linear to the episomal form. The NPC-EBV is the first NPC-derived isolate to be obtained from epithelial cells in vivo and maintained in epithelial cells in vitro, and will be useful for studying biological variability of EBV.
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Abstract It is important to know whether there are variants of Epstein‐Barr virus (EBV) with biological properties that are different from the prototype viruses that have been studied in detail, such as P3HR‐1 and B95‐8. We have studied an EBV isolate derived from a nasopharyngeal carcinoma (NPC) tumor, designated NPC‐EBV. We have examined the target B lymphocytes infected and growth‐transformed with NPC‐EBV as compared with two common EBV isolates, B95‐8 and AG876 EBV, for stage of maturation using antibodies to several immunoglobulin chains. Typing of the NPC‐EBV transformed lymphoblastoid cell lines revealed the predilection of the NPC‐EBV isolate to infect immature B lymphocytes. This was not the case for the B95‐8 and AG876 isolates. The reason for the predilection of NPC‐EBV for immature B lymphocytes remains to be explored further. However, these results may be important in understanding the pathophysiology of EBV‐associated diseases.
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