Tesis sobre el tema "Epstein-Barr Virus Burkitt's Lymphoma"
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MUNDO, LUCIA. "Infectious agents and cancer: A look into EBV pathways involved in the transition from infection to lymphomagenesis". Doctoral thesis, Università di Siena, 2017. http://hdl.handle.net/11365/1012697.
Texto completoDonati, Daria. "Malaria, B lymphocytes and Epstein-Barr virus : emerging concepts on Burkitt's lymphoma pathogenesis /". Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-403-1/.
Texto completoKaymaz, Yasin. "Genomic and Transcriptomic Investigation of Endemic Burkitt Lymphoma and Epstein Barr Virus". eScholarship@UMMS, 2017. https://escholarship.umassmed.edu/gsbs_diss/914.
Texto completoKaymaz, Yasin. "Genomic and Transcriptomic Investigation of Endemic Burkitt Lymphoma and Epstein Barr Virus". eScholarship@UMMS, 2007. http://escholarship.umassmed.edu/gsbs_diss/914.
Texto completoAmoroso, Richard Benjamin Couture. "Studies on the expression and function of Epstein-Barr virus encoded microRNAs in Burkitt lymphoma". Thesis, University of Birmingham, 2013. http://etheses.bham.ac.uk//id/eprint/3694/.
Texto completoBoyce, Andrew John. "Epstein-Barr virus genome loss from endemic Burkitt lymphoma and its effect on cell phenotype". Thesis, University of Birmingham, 2009. http://etheses.bham.ac.uk//id/eprint/4731/.
Texto completoLeung, Yuen-ying y 梁婉瑩. "Effects of histone deacetylase and proteasome inhibitors on Epstein-barr virus-positive Burkitt lymphoma and lymphoblastoid cells". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/207474.
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Paediatrics and Adolescent Medicine
Master
Master of Philosophy
Rao, Sieta Padmaja. "Zebularine reactivates silenced E-cadherin but unlike 5-Azacytidine does not induce switching from latent to lytic Epstein-Barr virus infection in Burkitt's lymphoma Akata cells /". [S.l.] : [s.n.], 2008. http://opac.nebis.ch/cgi-bin/showAbstract.pl?sys=000253262.
Texto completoImreh, Marta P. "Modulation of cellular and viral functions in Epstein-Barr virus infected cells /". Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-171-3.
Texto completoCherdoud-Chelouah, Sonia. "Rôle fonctionnel de la protéine de latence EBNA-LP exprimée dans les cellules de lymphome de Burkitt infectées par la souche P3HR1 du virus d’Epstein-Barr". Thesis, Paris 11, 2012. http://www.theses.fr/2012PA11T023.
Texto completoOur group has previously shown that Burkitt’s lymphoma (BL) cells infected by the P3HR1 variant of Epstein-Barr virus (EBV) are more resistant to apoptotsis than EBV (-) BL cells or cells infected by wild-type EBV. The genome of the P3HR1 variant carries a deletion responsible for the expression of a truncated form of EBNA-LP (tEBNA-LP). We studied the functional role of tEBNA-LP in BL cells infected by the P3HR1 variant. A proteomic study allow us to identify cellular and viral partners of tEBNA-LP. These results confirmed the interaction between tEBNA-LP and PP2A, already established by our group, and showed that tEBNA-LP can form complexes with other proteins involved in many cellular processes including apoptosis and regulation of transcription. We have then demonstrated by a transcriptomic study, the transcriptional regulatory role of both forms of EBNA-LP stably expressed in EBV(-) BL cell lines. Indeed, we showed that both forms of EBNA-LP can regulate the expression of cellular genes independently of viral context. Some of these genes are common to both forms of EBNA-LP, others are specific to each form. We found that Y1Y2 domaine of EBNA-LP is essential to overexpression of the cellular gene encoding ID1 protein which is involved in LMP1 stabilization and cellular mmortalization. We also noted that some genes are similarly regulated in the presence of EBNA-LP alone or in the presence of viral genome. Finally, to better undertand the mecanisms of resistance to apoptosis in BL cell lines infected by the P3HR1 variant we extended our transcriptomic analysis to cell lines treated or not with an apoptosis inducer, cycloheximide. Our preliminary results show that TNF receptors signaling pathways (TNFR1 and 2) are rapidly and strongly induced in sensitive cell lines while being weakly and belatedly induced in the resistant cell lines. This study also shows that the JNK signaling pathway is probably activated very early in the sensitive cells in contrast to resistant cell lines
Movassagh, Mercedeh J. "Comprehensive Computational Assessment And Evaluation of Epstein Barr virus (EBV) Variations, miRNAs, And EBERs in eBL, AML And Across Cancers". eScholarship@UMMS, 2019. https://escholarship.umassmed.edu/gsbs_diss/1022.
Texto completoKiss, Csaba. "Analysis of viral and cellular gene expression patterns in cells latently infected with EBV by suppression subtractive hybridization /". Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-707-x.
Texto completoSompallae, Ramakrishna Rao. "In silico analysis of pathways targeted by EBV infection and malignant transformation". Stockholm : Karolinska institutet, 2009. http://diss.kib.ki.se/2009/978-91-7409-693-4/.
Texto completoCoy, Joanna Lucy. "Epstein Barr nuclear antigen 1 induced lymphoma in transgenic mice". Thesis, University of Glasgow, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.241746.
Texto completoCALENDER, ALAIN. "Pathogenese des lymphomes malins non hodgkiniens : donnees generales et contribution experimentale centree sur la biologie cellulaire et moleculaire du lymphome de burkitt et des lymphomes folliculaires". Lyon 1, 1991. http://www.theses.fr/1991LYO1M040.
Texto completoPeh, Suat-Cheng. "The pattern of Epstein-Barr virus infections in lymphoma of Malaysians". Thesis, University of Leicester, 2002. http://hdl.handle.net/2381/29407.
Texto completoPatton, John Thomas Jr. "Identifying and Targeting Immune Escape Mechanisms in Epstein-Barr Virus-Driven Lymphoproliferative Disease". The Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1461074032.
Texto completoIto, Yoshinori, Jun-ichi Kawada y Hiroshi Kimura. "EPSTEIN-BARR VIRUS-ASSOCIATED LYMPHOID MALIGNANCIES : THE EXPANDING SPECTRUM OF HEMATOPOIETIC NEOPLASMS". Nagoya University School of Medicine, 2013. http://hdl.handle.net/2237/18466.
Texto completoShen, Lijun y 沈立軍. "Immune escape mechanisms in EBV-associated nasal NK/T-Cell lymphoma". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2002. http://hub.hku.hk/bib/B31244713.
Texto completoHinke, Juliane Elisabeth [Verfasser] y Judith [Akademischer Betreuer] Dierlamm. "Die Integration des Epstein-Barr-Virus : Zytogenetische Lokalisation viraler Integrationsloki in EBV-positiven Zelllinien des Burkitt-Lymphoms / Juliane Elisabeth Hinke. Betreuer: Judith Dierlamm". Hamburg : Staats- und Universitätsbibliothek Hamburg, 2013. http://d-nb.info/1031280324/34.
Texto completoBaarle, Debbie van. "Viro-immunological studies on the role of Epstein-Barr virus in the development of AIDS-related non-Hodgkin's lymphoma". [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2000. http://dare.uva.nl/document/57552.
Texto completoTao, Qian. "Cellular localization and gene expression of epstein-barr virus in non-neoplastic nasal mucosa and nasal lymphoma /". Hong Kong : University of Hong Kong, 1996. http://sunzi.lib.hku.hk/hkuto/record.jsp?B17538828.
Texto completoKinch, Amelie. "Posttransplant Lymphoproliferative Disorders : Studies of Epstein-Barr Virus, Regulatory T Cells and Tumor Origin". Doctoral thesis, Uppsala universitet, Infektionssjukdomar, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-234130.
Texto completoDavies, Gillian Lucy. "Investigation into the contribution of the Epstein Barr virus nuclear antigen 1 to the pathogenesis of Hodgkin's lymphoma". Thesis, Birmingham City University, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.479110.
Texto completoDuc, Touyana. "Caractérisation moléculaire et sérologique de l'infection à Epstein-Barr virus chez les patients porteurs du VIH souffrant d'un lymphome". Thesis, Université Grenoble Alpes (ComUE), 2016. http://www.theses.fr/2016GREAV074.
Texto completoIn 2016, malignant lymphoproliférations [non Hodgkin's (NHL) and Hodgkin's lymphomas (HL)] remain a major concern in patients living with HIV (PLHIV), that each year 1-6% of these patients develop lymphomas. Lymphomas are the major cause of mortality in this population.Epstein-Bar Virus (EBV), long known for his immortalizing B cells power and oncogenic properties of some of its proteins, emerges as a cofactor favoring lymphoproliferations, more or less important, depending on the type of lymphoproliferation.One of the outstanding questions is whether the molecular and/or serological characterizations of EBV infection may help to better understand the pathophysiology of these diseases and better manage patients suffering from HIV-associated lymphomas.This dissertation under joint supervision between the University Grenoble Alpes and Irkutsk State Medical University aims to answer this question.The literature review of this thesis summarizes: (i) the role of EBV in LNH development in PLHIV (article published in Russian journal “Siberian Medical Journal” in 2015) and the current knowledge on the epidemiology and pathophysiology of Hodgkin's lymphoma (non published in French); (ii) published studies on the EBV viral load and serological evolutions in PLHIV.The experiments consist of three articles. The first article published in Journal of Clinical Microbiology in 2016, reports the demonstration that the application of international standard EBV developed by WHO can improve the quantification of EBV viral load in whole blood. The second study (in writing for publication) contains preliminary results of French National Agency for Research of HIV and hepatitis cohort study investigating PLHIV suffering from Hodgkin's lymphoma. The study focuses on whether the EBV viral load and serology of newly diagnosed lymphoma could provide prognostic information for this disease, as has been described in HIV-negative patients with HL. Our preliminary results don’t support this hypothesis; than EBV markers don’t can be used for best management of HL in PLHIV. The third study published in Russian Journal “HIV infection and Immunosuppressive disorders” (2015) describes the epidemiology of HIV-associated lymphoma in Irkutsk Oblast. The article shows that non-Hodgkin lymphoma incidence rates in PLHIV during 2007-2014 are probably due to HIV epidemic non-controlled in this Russian region
Huang, Yen-Lin. "Analyse des altérations oncogéniques associées aux lymphomes NK/T de type nasal". Thesis, Paris Est, 2009. http://www.theses.fr/2009PEST0052.
Texto completoIn Western countries, mature natural killer (NK)- and T-cell lymphomas account for 15% to 20% of aggressive lymphomas and around 10 % of all non-Hodgkin lymphomas. This number is higher in Asia, with 25% in Japan and 39% in Taiwan. Among those T- and NK-cell lymphomas with primary extranodal presentation, extranodal NK/T-cell lymphoma of nasal type (nasal NKTCL) is one of the most common entities in Asian, Central and South American populations. It classically arises in the nasal region showing a predilection for young adults with male predominance. This tumor morphologically exhibits an angiocentric and angio destructive growth pattern, admixed with polymorphous non-neoplastic infiltrates. Most tumor cells have a cytoplasmic CD3+, CD5-, CD56+, CD4-/CD8- phenotype with expression of cytotoxic granule-associated proteins and without rearrangement of T-cell receptors genes. Killer immunoglobulin-like receptors have been reproted to be expressed in a subset of this lymphoma and its expression might be associated with prognosis. Epstein-Barr virus is present in virtually all neoplastic cells in its clonal episomal form with type II latency program, implying a role in oncogenesis. Although the results were variable between different studies, methylations of TP73 (p73) and CDKN2A (p16) and mutations of FAS and TP53 (p53) were frequently found in nasal NKTCL. Genomic alterations have also been reported in nasal NKTCL with frequent deletion in chromosome 6q. A very recent study also identified both methylations and mutations of three putative tumor suppressor genes PRDM, ATG5, and AIM1 mapping to del6q21 in nasal NKTCL cell times. We performed integrative gene expression profiling and array-based comparative genomic hybridization analyses of nasal NKTCL tumors as well as tumour-derived cell lines, compared to that of normal NK cells and peripheral T-cell lymphomas, not otherwise specified (PTCL, NOS). We identified the distinctive molecular signature of nasal NKTCL with high transcript levels for NK-cell markers ans cytotoxic molecules, especially granzyme H in nasal NKTCL compared to PTCL, NOS. By immunohistochemistry, we validated expression of grnzyme H which appears a novel sensitive biomarker of nasal NKTCL. Compared to normal NK cells, nasal NKTCL tumors were closer to activated than resting cells and overexpressed several genes related to vascular biology, EBV-induced genes and PDGFRA. Notably, we confirmed the expression of PDGFRa and its phosphorylated form at the protein level, and in vitro the MEC04, nasal NKTCL-cell line, was sensitive to imatinib mesylate. Deregulation of the AKT, JAK-STAT and NF-kB pathways suggested by bioinformatical analysis, was corroborated by nuclear expression of phosphorylated AKT, STAT3 and RelA in nasal NKTCL, and several deregulated genes in these pathways mapped to regions of recurrent copy number aberrations (AKT3 (1q44), IL6R (1q21.3), CCL2 (17q12), TNFRSF21 (6p12.3)). In addition to constitutive activation of STAT3 as confirmed by the demonstration of phosphorylated STAT3 in the nuclei of neoplastic nasal NKTCL cells, growth inhibition and cell death of nasal NKTCL cells induced by STAT3 inhibition implied the role of STAT3 in the nasal NK/T-cell lymphomagenesis. Integrative analysis and qRT-PCR analysis also evidenced deregulation of another tumor suppressor HACE1 in the frequently deleed 6q21 region. Although the exact mechanism of activation of several pathways as well as that of HACE1 deregulation remains to be determined, our studies highlight emerging oncogenic pathways in nasal NKTCL and identify novel diagnostic and therapeutic targets. The ongoing investigation of microRNA expression profiling might shed light in a better understanding of the pathogenesis of nasal NKTCL and especially of the activation of oncogenic pathways. Connectivity map analysis may also help to depict other targeted therapies useful to improve the prognosis of this agressive lymphoma
Pujals, Anaïs. "Etude des mécanismes de résistance à l’apoptose induits par le virus d’Epstein-Barr et mise en place de nouvelles stratégies thérapeutiques pour le traitement des lymphomes B". Thesis, Paris 11, 2012. http://www.theses.fr/2012PA11T054/document.
Texto completo- Résumé en anglais : Our team is working on the mechanisms of apoptosis induced by nutlin-3, a small molecule which binds to MDM2 and activates p53, in different lymphomas associated with Epstein-Barr virus such as Burkitt lymphoma (BL) or Post-transplant lymphoproliferative disorder (PTLD). Our results show that nutlin-3 strongly induce apoptosis in EBV (-) cells whereas EBV (+) latency III cells are much more resistant. The aim of my PhD project was to study the mechanisms involved in the resistance of EBV (+) latency III cells to apoptosis and to develop new therapeutic strategies to bypass these mechanisms. A transcriptomic analysis was realized after treatment with nutlin-3 of two cell lines which only differs by their EBV status. Based on the results obtained, a study was performed which allow us to show that: 1) autophagy is induced after nutlin-3 treatment in EBV (+) latency III cells; 2) these cells strongly expressed beclin-1 and present a constitutively high level of autophagy; 3) autophagy is involved in the resistance of apoptosis observed in these cells. Furthermore, our results demonstrate that Bcl-2 also contributes to the resistance of EBV (+) latency III cells and that treatment with ABT-737, a Bcl-2 inhibitor, restores their susceptibility to nutlin-3 treatment. We thus assessed the efficiency of this compound in vivo, in monotherapy or associated with conventional treatments (Cyclophosphamide for BL and Rituximab for PTLD). Results obtained during these pre-clinical studies show that: 1) ABT-737 reduces tumor growth and increase the overall survival of mice xenografted with a lymphoblastoïd cell line (LCL, used as a model for PTLD studies) but has no effects on mice xenografed with BL cell lines; 2) the association ABT-737/Cyclophosphamide reduces tumor growth during treatment but doesn’t improve the overall survival of mice xenografed with BL cell lines; 3) the association ABT-737/Rituximab is very efficient and induces 70% of complete remission in mice xenografted with LCL
Delecluse, Henri-Jacques. "L'intégration dans le génome cellulaire comme mode de persistance lors de la latence virale : l'exemple des herpèsvirus d'Epstein-Barr et de Marek". Lyon 1, 1995. http://www.theses.fr/1995LYO1T130.
Texto completoWinter, Sarah. "Identification and characterization of new genetic defects involved in Epstein-Barr virus immune response and T-cell proliferation Loss of RASGRP1 in humans impairs T-cell expansion leading to Epstein-Barr virus susceptibility RASGRP1 is a negative factor of EOMES expression in T cells in association with an exhausted phenotype IL-27RA deficiency in humans, a new cause of susceptibility to Epstein-Barr virus infection Association of bi-allelic loss-of-function mutations in PIK3CD and TNFRSF9 causes fatal chronic active Epstein-Barr virus infection with T-cell lymphoproliferation". Thesis, Sorbonne Paris Cité, 2018. http://www.theses.fr/2018USPCB180.
Texto completoEpstein-Barr virus (EBV) is a gamma-herpes virus that infects 90% of humans without any symptoms in most cases. Some individuals, mostly adolescents, can develop infectious mononucleosis. In immunocompromised individuals, EBV can lead to lymphoproliferative disorders, lymphomas or virus-associated hemophagocytic syndrome. In the past 30 years, several primary immunodeficiencies associated with a high risk to develop EBV-associated disorders have been identified, including SAP, XIAP, ITK, MAGT1, CTPS1, CD27 or CD70 deficiencies. Their characterization has highlighted specific pathways required for efficient immunity to EBV. The objective of this work was to identify new genetic defects associated to a peculiar susceptibility to EBV infection. In two consanguineous families 3 patients developed EBV-associated B cell lymphomas and other EBV-associated lymphoproliferative disorders. By while exome sequencing (WES) we identified two homozygous mutations in RASGRP1 leading to a premature stop codon (A638GfsX16 and S314X). Immunologically these patients presented with CD4+ lymphopenia, low number of naïve T cells and absence of MAIT and iNKT cells. RASGRP1 codes for a diacylglycerol-regulated exchange factor preferentially expressed in T and NK cells, which acts as an activator of the small G protein RAS and the downstream RAF-MEK-ERK kinases cascade (or MAP kinases pathway). Analysis of patients' T cells or control T cells in which RASGRP1 expression was downregulated by short-hairpin RNA technique has highlighted the crucial role of RASGRP1 in T cell proliferation and in the expression of genes known to be involved in cell proliferation or replication such as CTPS1, PCNA or RECQL4. Furthermore, RASGRP1 seems to be a negative regulator of the transcription factor EOMES involved in T cell differentiation. EOMES was found overexpressed in T cells in the absence of RASGRP1. This might explain the skewed effector-memory and exhausted phenotype observed in RASGRP1-deficient patients. In another large consanguineous family two patients developed symptomatic EBV primary infection requiring for one or them anti-CD20 and corticosteroids treatment. Homozygous nonsense mutation leading to a premature stop codon in IL-27RA (G96X) was identified by exome sequencing. No protein expression could be detected in patients' cells. IL-27RA codes for the subunit of IL-27 receptor involved T cell proliferation and Th1 CD4+ development through JAKs/STATs pathway. Stimulation of patients' T cells with IL-27 led to absent JAK/STAT activation pathway and did not enhance their proliferation after anti-CD3 stimulation (contrary to healthy control T cells). Furthermore, Th1 functional defect was found in one patient. These results demonstrate that IL-27RA pathway is deficient is these two patients and that this genetic defect causes their immunodeficiency. Characterization of these two new primary immunodeficiencies associated with a high susceptibility to EBV infection has confirmed the crucial role of T cell proliferation and activation in EBV immune response but has also highlighted new pathways involved in T cell expansion
Pujals, Anaïs. "Etude des mécanismes de résistance à l'apoptose induits par le virus d'Epstein-Barr et mise en place de nouvelles stratégies thérapeutiques pour le traitement des lymphomes B". Phd thesis, Université Paris Sud - Paris XI, 2012. http://tel.archives-ouvertes.fr/tel-00767146.
Texto completoKlibi, Manel. "Remaniement nucléaire dans les lymphocytes B provoqué par les virus EBV et VIH-1". Thesis, Paris 11, 2013. http://www.theses.fr/2013PA11T090/document.
Texto completoEighty percent of Burkitt's lymphomas (BL) cases bear translocation t(8;14)(q24;q32). Thistranslocation is the initial event in malignant transformation of normal B-cell and derives from nonhomologousend joining of the oncogene CMYC to the immunoglobulin heavy chain locus IGH duringSomatic Hypermutation (SHM) of IGH. The probability of this translocation is inversely proportionalto the distance between the loci of involved chromosomes. The translocation t(8;14)(q24;q32) occursduring normal development of B-lymphocytes and more probable in patients infected with Epstein-Barr virus (EBV) and the human immunodeficiency virus (HIV-1).The subject of this study was to determine the possible origin of the translocation t(8;14)(q24;q32) inhuman normal B-lymphocytes. We followed the dynamics of the nuclear localization of IGH andCMYC genes in activated B-lymphocytes. We payed particular attention to the impact of EBV andHIV-1 viruses on dynamics of both IGH and CMYC. We applied Fluorescence in situ hybridization(FISH) for detection of CMYC (8q24) and IGH (14q32). In naïve B-cells CMYC is mainly localized inthe periphery of nucleus, whereas IGH is preferentially localized in the nuclear centre, i.e. these lociare distanced by a radius of cell nucleus. Activated B-lymphocytes displayed dramatic increase ofnumber of cells with colocalized IGH and CMYC. Close physical proximity of CMYC to IGH duringSHM amplifies the probability of occurance of translocation t(8;14)(q24;q32) in human Blymphocytes.Interestingly, we observed even more pronounced impact of EBVand HIV-1onproximity of IGH and CMYC. Finaly, among the molecules of HIV-1 we revealed those which possessthe most regulative role on dynamics of both IGH and CMYC. Our results suggest about twoindependent mechanisms of IGH and CMYC dynamics: the first is appropriate for normal developmentof B-lymphocytes and the second depends on virus and viral molecules, such as transactivator of viraltranscription HIV Tat
Schreck, Sabine. "Tumour cell induced leukocyte migration in Hodgkin Lymphoma (HL) : prognostic impact of T-cell subsets, B-cells and Epstein-Barr virus (EBV)-infection in HL". kostenfrei, 2008. http://d-nb.info/989353001/34.
Texto completoKriel, Raymond Frank. "An investigation of Epstein-Barr Virus (EBV) latency type and MYC gene aberrations in plasmablastic lymphoma diagnosed at Groote Schuur Hospital, Cape Town, South Africa". Master's thesis, Faculty of Health Sciences, 2020. http://hdl.handle.net/11427/32714.
Texto completoDavid, Amandine. "Coopération de voies oncogéniques dans la lymphomagenèse B dépendante de MYC : rôle de NF-kB". Limoges, 2014. https://aurore.unilim.fr/theses/nxfile/default/433795c0-3079-41a8-a828-9bc555d10da9/blobholder:0/2014LIMO310D.pdf.
Texto completoSCHUSTER, LAZARUS CATHERINE. "Interaction de steroides glucocorticoides et antiglucocorticoides au cours du mecanisme d'induction des antigenes precoces du virus d'epstein-barr dans des cellules de lymphome de burkitt". Université Louis Pasteur (Strasbourg) (1971-2008), 1991. http://www.theses.fr/1991STR13183.
Texto completoAyoubian, Mohammad Hiresh [Verfasser] y Eckart [Akademischer Betreuer] Meese. "Differential loading of the Argonaute complex in Epstein-Barr Virus (EBV)-infected cell lines derived from diffuse large B-cell lymphoma (DLBCL) / Mohammad Hiresh Ayoubian ; Betreuer: Eckart Meese". Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2018. http://d-nb.info/1173703217/34.
Texto completoMayrink, Graziela Toledo Costa. "Expressão do vírus Epstein-Barr em células tumorais do Linfoma de Hodgkin Clássico: correlação com fatores desfavoráveis e sobrevida". Universidade Federal de Juiz de Fora (UFJF), 2016. https://repositorio.ufjf.br/jspui/handle/ufjf/4795.
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Introdução: A associação entre Linfoma de Hodgkin clássico e o status tumoral do vírus Epstein- Barr é bem definida. Entretanto, a expressão da positividade do vírus Epstein-Barr nas células de Reed-Sternberg/Hodgkin e o impacto dessa relação na sobrevida do Linfoma de Hodgkin clássico permanecem controversos e apresentam resultados conflitantes em estudos de diversas regiões do mundo. Considera-se essencial o entendimento fisiopatogênico desse vírus no prognóstico dos pacientes com Linfoma de Hodgkin clássico. Objetivo: Correlacionar o status do vírus Epstein Barr com os fatores de risco desfavoráveis e fatores prognósticos do Linfoma de Hodgkin clássico em uma população brasileira. Métodos: A positividade do vírus Epstein-Barr foi determinada pelo método de Hibridização in situ para o ácido ribonucleico viral e pela imuno-histoquímica para proteína de membrana latente viral 1. A revisão histopatológica das amostras e a análise dos testes de identificação foram realizadas por uma hematopatologista experiente. Avaliou-se o impacto prognóstico do status do vírus Epstein-Barr em 29 pacientes com Linfoma de Hodgkin clássico. Os fatores prognósticos do Escore Prognóstico Internacional para estadio avançado e os fatores de risco desfavoráveis instituídos pelo Grupo Alemão de Estudos em Hodgkin para estadio limitado foram correlacionados com o status viral nas células tumorais. Para as associações entre presença do vírus Epstein-Barr e outras variáveis categóricas, aplicaram-se os testes de Qui-quadrado ou exato de Fisher. A Sobrevida Global e a Sobrevida Livre de Eventos foram analisadas pelo método de Kaplain-Meier e Modelo de Regressão Proporcional de Cox. Resultados: A média de idade ao diagnóstico foi 33 anos. O status do vírus Epstein-Barr nas células tumorais foi positivo em 37,9%. As células tumorais positivas para o vírus foram mais frequentes em pacientes com idade maior que 45 anos, sem diferença estatística. O subtipo celularidade mista foi o mais frequente (p = 0,02) e o tamanho de efeito desse teste foi de moderada magnitude. Na análise univariada, as sobrevidas Livre de Eventos e Global não apresentaram significância estatística para idade, sexo, estadio clínico, hemoglobina, leucocitose, linfocitopenia, albumina, envolvimento nodal, sintomas B, doença extranodal e doença Bulky entre os pacientes positivos e negativos para o vírus Epstein-Barr (p > 0,05). Os pacientes positivos apresentaram maior Sobrevida Livre de Eventos quando comparados aos pacientes negativos, embora a diferença não apresentasse significância (p = 0,07). Na análise multivariada, a positividade ao vírus Epstein-Barr não demonstrou fator prognóstico significante. Conclusões: Apesar do status do vírus Epstein-Barr nas células tumorais não ter revelado associação com fatores prognósticos adversos e não ter influenciado a Sobrevida Global e a Sobrevida Livre de Eventos, observou-se uma associação positiva entre a presença desse vírus e o subtipo celularidade mista, demonstrando uma relação com o subtipo histológico de pior prognóstico.
Introduction: The association between classical Hodgkin’s Lymphoma and tumor Epstein-Barr virus status is well established. However, the expression of Epstein-Barr virus presence in Hodgkin/Reed-Sternberg cells and its prognosis remains controversial and presentes conflicting results in studies worldwide. Understanding the pathophysiological role of this virus in the prognosis of patients with classical Hodgkin’s Lymphoma is essential. Objective: The aim of this study is to correlate the clinical outcome with Epstein-Barr virus status in a Brazilian population. Methods: Epstein-Barr virus positivity was determined by in situ hybridization for Epstein-Barr virus-encoded ribonucleic acid and immunohistochemistry for viral latent membrane protein-1. The histopathology review and the analysis of identification tests were performed by an hematopathologist expert. The prognostic impact of Epstein-Barr virus status in 29 patients with classical Hodgkin’s Lymphoma was evaluated. Prognostic factors from International Prognostic Score to advanced stage and risk factors from German Hodgkin Study Group to limited stage were correlated with tumor cells Epstein-Barr virus status. In order to determine associations between the presence of Epstein-Barr virus and other categorical variables, Chi-square or Fisher's exact tests were applied. Overall and event-free survivals were analyzed with Kaplan-Meier method and Cox proportional hazards regression models. Results: The mean age at diagnosis was 33 years. Tumor cells Epstein-Barr virus status was positive in 37.9%. Epstein-Barr virus-positive classical Hodgkin’s Lymphoma was more frequent in patients older than 45 years, with no statistical difference. Mixed cellularity histological subtype was more common in Epstein-Barr virus-related tumor cells (p = 0.02) and its effect-size index was medium. Univariate analysis, event-free survival and overall survival were not significantly associated to age, sex, clinical stage, hemoglobin, leukocytes, lymphocytes, albumin, nodal involvement, B symptoms, extranodal disease and Bulky disease in Epstein-Barr virus-positive and negative patients (p > 0.05). Epstein-Barr virus-positive patients had longer event free survival when compared to Epstein-Barr virus-negative ones, even though the difference was not statistically significant (p = 0.07). In multivariate analysis, Epstein Barr virus positivity was not a significant prognostic factor. Conclusions: Although the Epstein-Barr virus status in tumor cells was not associated with adverse prognostic factors and did not influence the overall and event-free survivals, a positive association between the presence of Epstein-Barr virus and Mixed-cellularity subtype was noticed.
Bahri, Racha. "Séquençage du génome complet du virus d’Epstein-Barr dans des prélèvements issus de lymphomes T angio-immunoblastiques". Thesis, Limoges, 2017. http://www.theses.fr/2017LIMO0106.
Texto completoMore than 90% of the world's population is infected by Epstein-Barr virus (EBV), a human herpesvirus. EBV is thought to be implicated in the pathogenesis of several human malignancies including epithelial tumors such as nasopharyngeal and gastric carcinomas as well as lymphoproliferative diseases such as Burkitt's lymphoma, NK/T lymphomas and some Hodgkin lymphomas. In angioimmunoblastic T-cell lymphoma (AITL), a peripheral neoplasm of follicular helper T (TFH) cells, a recurrent finding is the presence of EBV-positive B lymphocytes at the beginning of the disease. However, whether this EBV infection of B cells plays a role in AITL pathogenesis remains unclear. In this context, our work aimed to determine if the EBV associated with the AITL presented an oncogenic profile allowing us to consider its role in this pathology. To do this, we sequenced the whole EBV genomes in AIL samples and compared the results to those obtained for other lymphomas (B, NK / T) as well as to previously published sequences. Sequencing was first performed on 7 EBV-positive cell lines to validate the technique, and then was applied to lymphadenopathy specimens from 40 patients with lymphoproliferative disease, of whom 20 had AITL. Enrichment of the viral genome was performed by capture using specific EBV genome probes. The libraries were synthesized and sequenced on Illumina MiSeq and NextSeq platforms. In a second step, we performed de novo assembly and determined the sequence of the virus in each sample. The data obtained were analyzed bioinformatically. Interestingly, the virus was found to be clonal or quasi-clonal in AITL, while B cells were in some cases polyclonal. In addition, the mutational pattern was similar to other EBV-associated lymphomas, especially at the level of the target epitopes of immune cells suggesting a process of selection of the viral strain identical to that of a clone tumor associated with EBV. This could play an important role in the virus escape from the immune system in this context. The presence of polyclonal B cells with clonal EBV in a clonal tumor T cell compartment could be a dual tumor selection; or that is endogenous T and exogenous clonal EBV, and could therefore suggest the existence of a cross-talk between B-T cells
Hamdi, Leila. "Recherche de facteurs de risque immunologiques associés au lymphome hodgkinien de l’enfant". Thesis, Paris 11, 2013. http://www.theses.fr/2013PA114844/document.
Texto completoHodgkin’s Lymphoma (HL) is one of the most frequent lymphomas occurring in childhood. In young children, there is a high predominance in boys and frequent association with Epstein-Barr Virus (EBV). Cohort studies have shown that patients affected by several immune deficiency syndromes - e.g. X-linked lymphoproliferative syndrome (XLP), functional deficit of Fas/FasL pathway and common variable immunodeficiency (CVID) - are risk factors of HL. We intend to search for qualitative and quantitative immune deficiencies as susceptibility factors to child's HL in a prospective study related to Euronet –PHL C1 protocol. Eighty-three patients at diagnosis of HL have been analysed. Median age of the study population is 13 years, (5-18 years). Gender-ratio M/F is 1.1 with a larger male predominance before the age of 10 (gender-ratio of 3). The search for a defect of NKT population that would be suggesting of XLP was negative in all patients. A moderate expansion of circulating TCRαβ+ double negative cells (DNT) has been detected in 5 patients. This expansion has been further explored in the hypothesis of a defect of Fas/FasL pathway by plasmatic quantification of Fas ligand and Il-10. This led to the exclusionof the diagnosis of ALPS. An unexpected high frequency of B-cell lymphopenia has been detected in 31 out of 83 patients (37%). Peripheral B cell lymphopenia was associated with the following poor prognostic factors: advanced stages (p<0.04), low hemoglobin (p<0.06) and B symptoms (p<0.01). B-cell lymphopenia was not statistically correlated with morphology (subtype, amount of tumor cells and necrosis). Remarkably, B-lymphocytic counts were significantly higher in patients with in situ EBV (<0.05).Only a B lymphopenia with low IgG level suggesting DICV was detected. We extended the analysis to all the 395 patients included in the protocol EURONET, so we identified 4 patients with CVID. These cases will be further explored by molecular analyses. In parallel, the specific T-cells response against EBV was studied by flow cytometry in 15 patients and ELISPOT assay in 9 patients with HL. Flow cytometry , suggested a decrease in production of IL-2 by CD4 T cells in patients with high EBV viral load in response to EBV latent and lytic-cycle peptides and autologous lymphoblatoid cells lines compared to controls or patients with LH-EBV-. The ELISPOT-IFNγ assay was used to determine the frequency of T cells that produced IFNγ in response to peptides. One patient demonstrated inappropriate EBV-specific T-cell IFNγ production (<10 IFNγ secreted T cells and >1,000 EBV copies per 250000 PBMCs). These cases will be further explored by molecular analyses.Our findings confirm the known epidemiological data of HL now mainly associated to NS subtype in children and adolescents and EBV status in HL at this age. We show that peripheral B cell lymphopenia in paediatric and adolescent HL patients is frequent and associated with poor prognosis factors. We confirm the association between CVID and HL
Tanaka, Paula Yurie. "Detecção do vírus de Epstein-Barr (EBV), expressão de FOXP3 e avaliação da carga viral para EBV como marcadores prognósticos nos linfomas relacionados à AIDS". Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/5/5167/tde-30102012-133435/.
Texto completoIntroduction: Patients with HIV infection have increased risk for development of non-Hodgkins lymphoma compared to general population. Among mechanisms that could be related to this disease is the reactivation of Epstein-Barr virus infection secondary to immunosuppression. The role of immune system in development of tumors was reported a long time ago, and balance of this system is maintained by regulatory T cells; FOXP3 transcription factor is the main regulator and marker of these cells. In this study we evaluated the presence of EBER and FOXP3 in diagnostic samples, and also viral load of Epstein-Barr virus in patients with Aids-related lymphoma to evaluate and correlate the results as prognostic markers in this population. Methods: Prospective analysis of viral load of Epstein-Barr virus in plasma and peripheral blood mononuclear cells from 15 patients with Aids-related lymphoma treated at Instituto de Infectologia Emílio Ribas and Hospital das Clínicas/Instituto do Câncer do Estado de São Paulo da Faculdade de Medicina da Universidade de São Paulo. Viral load measures were performed by real time polymerase chain reaction at diagnosis of lymphoma, completion of treatment and three months afterwards. Two control groups composed by 26 HIV-positive patients in use of HAART and without diagnosis of lymphoma or opportunistic infection and 30 healthy persons were also analyzed for viral load comparison. Biopsy samples performed to lymphoma diagnosis were submitted to immunohistochemistry for FOXP3 and in situ hybridization to EBER. Results: 13 patients were male and two females, 14 were treated with chemotherapy and one with radiotherapy of central nervous system. Nine of 15 patients (60%) completed treatment achieving complete remission. Median viral load of Epstein-Barr virus before treatment was 13 copies/106 in peripheral blood mononuclear cells (1-1472 copies/106) and 70 copies/mL (0-24900 copies/mL) in plasma. After treatment it was 0,5/106 (0-109,5) and not detectable in plasma, with significant decrease of viral load in peripheral blood mononuclear cells (p=0,022) and in plasma (p=0,003) after treatment compared to diagnosis. In patients with complete remission, viral load decreased in the majority of cases. In situ hybridization for EBER was positive in 7/15 (46,7%), and significant higher in the group of patients with Aids-related lymphoma with more than one extra nodal site (p=0,041) and CD4 T-cells <100 cells/L (p=0,026). FOXP3 expression was negative in 15/15 (100%) of patients with ARL. Conclusions: EBER expression was positive in 7/15 (46,7%) of patients with Aids-related lymphoma and significantly higher in patients with advanced stages of lymphoma and higher degree of immunosuppression. Significant decrease in median viral load of Epstein-Barr virus was observed in peripheral blood mononuclear cells (p=0,022) and plasma (p=0,003) after lymphoma treatment compared to diagnosis in patients that achieved complete remission, what could be considered a prognostic marker of response to therapy
Barel, Monique. "Structure et fonctions de gp 140 : le recepteur pour le fragment c3d du troisieme composant du complement et pour le virus d'epstein-barr present a la surface des lymphocytes b humains". Paris 6, 1987. http://www.theses.fr/1987PA066143.
Texto completoBouzid, Makhlouf. "Polymorphisme génétique du virus d'Epstein-Barr en Afrique du Nord : étude dans le carcinome du rhinopharynx, la maladie de Hodgkin et les lymphomes malins non-Hodgkiniens". Université Joseph Fourier (Grenoble), 1998. http://www.theses.fr/1998GRE10111.
Texto completoSouza, Eni Maria de [UNIFESP]. "Avaliação da expressão do vírus de Epstein-Barr e metaloproteinase 9 nas células de Hodgkin-Reed-Sternberg e correlação com os parâmetros clínicos e evolutivos em pacientes com Linfoma de Hodgkin clássico no Brasil". Universidade Federal de São Paulo (UNIFESP), 2010. http://repositorio.unifesp.br/handle/11600/9024.
Texto completoO Linfoma de Hodgkin clássico (LHC) é caracterizado pela presença de uma pequena população de células grandes mono ou multinucleadas, denominadas células de Hodgkin-Reed-Sternberg (HRS), circundadas por uma grande massa inflamatória de células não neoplásicas. O vírus Epstein-Barr (EBV) está associado ao Linfoma de Hodgkin em cerca de 50% dos casos. O diagnóstico do LH EBV relacionado é possível por meio da identificação de proteínas virais nas células HRS. Os métodos considerados ideais para essa identificação são as reações de imuno-histoquímica utilizando anticorpos antiproteína latente de membrana (LMP1) e hibridação in situ com uma sonda para o RNA viral (EBER). A LMP-1 é considerada um oncogene clássico. Foi demonstrado que a LMP-1 pode controlar a expressão do gene da metaloproteinase 9 (MMP-9), em linhagem de células C33A. A MMP-9 é um membro da família das endopeptidases que facilita a invasão tumoral e metástases pela degradação do estroma extracelular. Objetivos: avaliar se a expressão da MMP-9 está relacionada ao status do EBV no tumor e se houve impacto na sobrevida livre de eventos (SLE) e sobrevida global (SG) em pacientes com LHC. Casuística e Métodos: foram examinados 97 pacientes com LHC. Todos os pacientes foram submetidos a protocolos de tratamentos equivalentes (MOPPABV ou ABVD). O diagnóstico histopatológico foi revisto e o subtipo classificado de acordo com a OMS. Reações de imuno-histoquímica para LMP-1 e MMP-9 e hibridação in situ para EBER foram realizadas. Resultados: A presença do EBV foi identificada em 52,5% dos casos. Houve uma maior prevalência do subtipo histológico celularidade mista em pacientes EBV positivos (P = 0,005). Não houve diferença na positividade do EBV em relação à faixa etária, sexo, estádio da doença ou pela presença de sintomas B. A presença do EBV no LHC não influenciou a SLE (P = 0,38) ou a SG (P = 0,80) com uma mediana de acompanhamento de 71 meses. A expressão da MMP-9 ocorreu em 87,6% dos casos estudados. Não houve diferença de casos positivos e negativos em relação ao status do EBV (P = 0,59). Quando avaliada a intensidade da expressão da MMP-9 nos casos positivos também não observamos correlação com a presença do EBV (P = 0,62). Não houve diferença entre o resultado da MMP-9 e os parâmetros: subtipo histológico, estádio, presença de sintomas B, idade e sexo. Não houve influência da MMP-9 na SLE (P = 0,98) e SG (P = 0,60). Conclusões: Demonstramos que a prevalência do LH relacionado ao EBV na população estudada é de 52,5%, e que a presença do vírus não altera a evolução clínica, SLE e SG de pacientes tratados uniformemente. Concluímos ainda que a MMP-9 é fortemente expressa nas células HRS. Não há correlação entre a expressão de MMP-9 e o status do EBV. Nem a SG nem a SLE foram influenciadas pela expressão dessa enzima.
Clinical and histological features of classical Hodgkin lymphoma (cHL) are primarily due to the effects of cytokines, enzymes and chemokines produced by Hodgkin-Reed-Sternberg (HRS) cells and their surrounding inflammatory cells in response to signals triggered by etiological factors such as Epstein-Barr virus (EBV). Matrix metalloproteinase-9 (MMP-9) has been associated with poorer survival in patients with aggressive non-Hodgkin lymphomas. In EBV-related cancers the expression of viral latent membrane protein 1 (LMP1) correlates with an increased MMP-9 expression. In this study, we evaluated the prognostic relevance of MMP-9 expression and EBV status in HRS cells in patients with cHL in Brazil. Material and Methods: We selected 97 patients with cHL. Patients were included if they had: 1) > 18 years, 2) Undergone similar chemotherapy protocols, 3) Paraffin blocks available for review and for EBV and MMP-9 detection and 4) Clinical, epidemiological and laboratorial parameters available. Results: EBV was detected in 52.5% of all cases. MMP-9 expression positivity was found in 87.6% of all cases. There was no correlation between MMP-9 expression and EBV status. Response to treatment and relapse rate were independent of MMP-9 expression and EBV status. When stratified according to chemotherapy protocol used or disease stage, we still did not find any difference. MMP-9 positivity did not influence overall survival and event free survival. Conclusion: MMP-9 are expressed in the majority of HRS cells and did not correlated with EBV status or survival. The consistent MMP-9 expression in HRS cells makes this enzyme a potential target for therapy.
TEDE
BV UNIFESP: Teses e dissertações
Baecklund, Eva. "Associations Between Rheumatoid Arthritis and Malignant Lymphomas". Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-5928.
Texto completoLiang, Chih-Lung y 梁熾龍. "Regulation of Epstein-Barr Virus Gene Promoters in Type I Burkitt's Lymphoma Cells". Thesis, 2000. http://ndltd.ncl.edu.tw/handle/84968235770041886428.
Texto completo國立陽明大學
微生物暨免疫學研究所
89
Abstract Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus associated with many diseases including Burkitt掇 lymphoma (BL). In BL cells, EBV remains in a latent stage and can be induced to enter into lytic cycle by TGF-b. However, the mechanism of TGF-b-induced activation is not understood. In EBV-infected BL cells, the viral gene expression is limited only to oncogenic EBV-encoded nuclear antigen 1 (EBNA 1) gene, which is directed from a latent promoter Qp. EBV lytic cycle can be induced upon activation of a promoter Zp of BZLF 1 gene, which encodes Zta, a latent-to-lytic switching protein. By examining the regulation of both Qp and Zp in EBV latently infected BL cells by TGF-b here we present a functional analysis of TGF-b-induced lytic cycle of EBV. Yeast one-hybrid screen analysis revealed that Smad4 binds the -50 to -37 sequence of Qp. Sequence analysis also reveals a Smad4 binding element (SBE) located between -49 and -45 of Qp. Transient expression of Qp reporter construct in two EBV(+) BL cell lines, Rael and WW2, showed that Qp activity is repressed in response to the TGF-b reatment. This repression involves the interaction of Smad3/Smad4 complex and a transcriptional repressor, TGIF, as determined by co-immunoprecipitation and co-transfection with Qp and its SBE-site-specific mutant construct. In contrast, co-transfection experiments indicated that Zp is synergistically activated by Smad3/Smad4 and c-Jun/c-Fos, specifically in response to TGF-b treatment. TGF-b treatment of Rael cells results in a production of infectious EBV, which infects EBV(-) CA46 cells in vitro. These results suggest a mechanism of TGF-b induction of EBV lytic cycle through interaction of TGF-b effectors with the key viral genes and also suggest a role of TGF-b in EBV-associated diseases. Furthermore, yeast one 臿ybrid screen analysis using the ?0 to ?0 of Qp as the bait, a cDNA clone coding for a cellular transcriptional factor, HIV-EP2 was identified. However, the role of HIV-EP2 in Qp activity requires further investigation.
Pinkert-Leetsch, Diana. "Funktionelle Analysen deregulierter Signalwege transformierter B-Lymphozyten - Das Epstein-Barr-Virus-Onkogen LMP1". Doctoral thesis, 2007. http://hdl.handle.net/11858/00-1735-0000-0006-AC5E-2.
Texto completoLo, San-Ren y 羅聖能. "Survival factor interference in Epstein-Barr virus-positive Burkitt’s lymphomas". Thesis, 2004. http://ndltd.ncl.edu.tw/handle/8rk4x9.
Texto completo國立成功大學
生物化學研究所
92
Epstein-Barr virus (EBV), a world-wide human herpes virus, is highly associated with an increasing number of tumors and lymphoid diseases, such as Burkitt’s lymphoma (BL), nasopharyngeal carcinoma (NPC), Hodgkin’s disease, and infectious mononucleosis, and is able to establish life-long persistent infection. The EBV induced pathogenesis is strongly associated with viral proteins that contribute to cell immortalization and immune evasion. Previous studies have shown that disruptions of these viral proteins result in inhibitions of viral replication or transforming abilities, suggesting that these proteins are potential candidates as therapeutic targets. EBV nuclear antigen 1 (EBNA1) is required for maintenance of latent EBV infection and is essential for EBV-associated malignancies. It has been shown that disruption of EBNA1 causes apoptosis in EBV-positive BL cells, suggesting that EBNA1 serves as a survival factor in these cells. EBNA1 may, therefore, play a pivotal role in the onset, progression or maintenance of BL. Efficient inhibition of EBNA1’s function would likely prove useful in the therapy of EBV associated malignancies. Using an effective DNA vector-based siRNA expression system and efficient active siRNA screening strategy, we have identified two extremely potent siRNA molecules that can effectively trigger sequence-specific inhibition of EBNA1 expression. Transient co-transfection of target and siRNA-expression vectors into BHK and HEK293 cells caused a more than 90% reduction in EBNA1 production in both western blot and immunohistochemistry. It was further confirmed by fluorescent image that EGFP-carry cells as siRNA-expressing cells showed no EBNA1 detected by immunostaining. In addition, EBNA1 can transactivate promoter transcription in an orip-dependent way BHK and HEK293 cells. When we co-transfect siRNA-expressing vectors and reporter plamids into EBNA1 stable line, siA1-3 also inhibits reporter activity about 50%. Furthermore, we have successfully developed two viral vector, adenoviral and retroviral vectors, expect to achieve the best transfection efficiency.
Chang, Kung-Chao y 張孔昭. "The Role of Epstein-Barr Virus in Pathogenesis of Hodgkin Lymphoma". Thesis, 2009. http://ndltd.ncl.edu.tw/handle/74949272896376841533.
Texto completo國立成功大學
臨床醫學研究所
97
Hodgkin lymphoma (HL) is one of the most important human malignancies. It has been recognized since 1832 by Dr. Thomas Hodgkin, an English pathologist, and thereafter referred to as Hodgkin “disease” for more than 150 years. In contrast to other human lymphomas, in which the tumor cells are the main populations of the tumor constituents, the tumor cells of HL, called “Hodgkin (H)/Reed-Sternberg (RS)” cells, account usually for less than 10% of tumor bulk against an inflammatory background. The enigmatic RS cells are unique in their abundant cytoplasm and characteristic bilobed nuclei with eosinophilic prominent nucleoli, imparting an “owl-eye” appearance. The viral inclusion-like morphology puzzled pathologists and led to the finding of HL association with Epstein-Barr virus (EBV). The association of HL with EBV, however, is variable in different geographic regions. My thesis is therefore designed to explore the association of HL with EBV at different time period. Furthermore, the enigmatic pathogenesis of RS cells is investigated, especially its potential association with EBV. In my first period of study, we tried to clarify the EBV association with HL in Taiwan and Vietnam, a country popular for EBV infection. By comparing pathologic features and EBV status detected by in situ hybridization in 99 HL cases diagnosed between 1996-2007 with 74 HL diagnosed from 1982-1995, we found that EBV association rate in Taiwan HL was about 50% and more frequently found in old patients with non-nodular sclerosis type. There were an increased frequency of nodular sclerosis subtype, decreased frequency of the mixed cellularity subtype, and significant decrease in EBV positivity rates among the nodular sclerosis and lymphocyte depleted subtypes in the period of 1996-2007, as compared to that of 1982-1995, that is, there were shifts in the frequency of histologic subtype and EBV association of HL in Taiwan over the last decade, with a trend closer to that seen in Western countries and Japan. Interestingly, the association rate of EBV in Vietnamese childish HL cases is nearly 100%, including nodular lymphocyte-predominant (NLP) subtype, which always shows no association with EBV in Western HL cases. The high incidence of EBV in these cases of HL is correlated with an earlier mean age of presentation of primary EBV infection, i.e. infectious mononucleosis, at 5.3 years old, in this patient population, compared to an average of 15-19 years old reported in developed countries. Our study demonstrates that in an area with an earlier mean age of onset of EBV infection, nearly all cases of pediatric HL, including all histological patterns, may be related to EBV infection. It implies an important role for environmental factors in the pathogenesis of HL. In the second stage of study, we tried to investigate the mechanism underlying the characteristic multinucleated RS cells. Since endoplasmic reticulum (ER) stress has been found to induce aberrant, cytoplasmic cyclin A expression, which will interact with Cdk2 to induce centrosome overduplication, leading to nuclear hyperdiploidy, we tested whether the aberrant expression of cyclin A is related to the RS morphology of HL cells. We found, by immunohistochemistry on 34 cases of HL, that aberrantly cytoplasmic expression of cyclin A, a cell cycle regulator, was associated with RS cell morphogenesis in both EBV-positive and -negative HL cases. In vitro, EBV-LMP1 induced cytoplasmic expression of cyclin A with an increase of multinucleated cell morphology in an EBV-negative HL cell line, L-428. Therefore, the aberrant expression of cyclin A is commonly associated with RS cell morphology in HL, probably through LMP1 signaling or other similar mechanisms in EBV-negative cases. We also demonstrate for the first time that the majority of HL cases expressed survival (GRP78 and XBP1) but not death (CHOP and ASK1) signals of endoplasmic reticulum (ER) stress in all histologic subtypes of HL and in both EBV-positive and –negative cases at a similar level. LMP1 transfection increased expression of GRP78 and XBP1 in L-428 cell line. Although, expression of ER signals did not bear prognostic significance, it may rescue HL cells from stress-induced cell death. Thus, surviving ER stress may be involved in the pathogenesis of HL. My PhD study therefore successfully finished the epidemiology of the association of EBV with HL in Taiwan and in Vietnam, and proposed a theory or mechanism to explain the characteristic RS morphology of HL.
Naidoo, Sharlene. "Laboratory diagnosis of Epstein Barr Virus in diffuse large B cell lymphoma". Thesis, 2017. https://hdl.handle.net/10539/24731.
Texto completoAims and objectives The study design aimed to assess and validate various laboratory techniques in the detection of EBV in HIV positive patients with diffuse large B cell lymphoma. The sensitivity and specificity of each technique was determined, as was the presence of an asymptomatic (latent) or lytic phase infection and the viral strain. DLBL samples occurring in HIV seropositive patients were used as a vehicle for these laboratory procedures which included chromogenic in situ hybridisation (EBER), immunohistochemistry (EBNA 2, LMP 1), real time PCR, (EBNA 1, LMP 2 and BZLF 1) and nested PCR (EBNA 2). Materials and Methods 46 cases of previously diagnosed DLBL from HIV positive individuals were identified and retrieved from the archives of the Department of Anatomical Pathology of the University of Witwatersrand and NHLS. All in-situ hybridisation, immunohistochemical and PCR laboratory procedures were carried out in accordance with the Standard Operating Procedures of the Anatomical Pathology Molecular Laboratory, using appropriate negative and positive controls throughout. Ethical clearance was obtained (M140273). Results/Conclusion A 20% frequency of EBV in HIV positive DLBL cases was established. All EBV infections were found to be in the lytic phase, with an almost equal distribution of latency patterns II and III and an equal distribution of EBV strains 1 and 2. EBER in situ hybridisation was confirmed to be the most sensitive and reliable method of viral detection, and the presence of the BZLF 1 gene determined by real time PCR was found to be a reliable indicator of a lytic infection.
LG2018
Niller, Hans Helmut [Verfasser]. "Wie verursacht das Epstein-Barr-Virus Tumore? : ein neues molekulares Modell der Entstehung des Burkitt-Lymphoms / vorgelegt von Hans Helmut Niller". 2003. http://d-nb.info/1001962540/34.
Texto completo