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epstein-barr virus-positive follicular lymphoma.epstein-barr virus (ebv) -associated follicular lymphoma is only rarely reported. herein, we report the largest series analyzing prevalence and clinicopathologic characteristics of ebv-associated follicular lymphoma occurring in unselected cases. out of 382 analyzed cases, 10 ebv-positive follicular lymphomas were identified (prevalence=2.6%, 95% confidence interval 1.3-4.0%). all ebv-positive follicular lymphomas showed ebv-encoded small rna-positive lymphoma cells present in a follicular distr ...201727982024
immunotherapy against cancer-related viruses.approximately 12% of all cancers worldwide are associated with viral infections. to date, eight viruses have been shown to contribute to the development of human cancers, including epstein-barr virus (ebv), hepatitis b and c viruses, and human papilloma virus, among others. these dna and rna viruses produce oncogenic effects through distinct mechanisms. first, viruses may induce sustained disorders of host cell growth and survival through the genes they express, or may induce dna damage response ...201728008927
tonsillar cd56brightnkg2a+ nk cells restrict primary epstein-barr virus infection in b cells via ifn-γ.natural killer (nk) cells constitute the first line of defense against viruses and cancers cells. epstein-barr virus (ebv) was the first human virus to be directly implicated in carcinogenesis, and ebv infection is associated with a broad spectrum of b cell lymphomas. how nk cells restrict ebv-associated oncogenesis is not understood. here, we investigated the efficacies and mechanisms of distinct nk cell subsets from tonsils, the portal of entry of ebv, in limiting ebv infection in naïve, germi ...201728008151
quantitative multi-target rna profiling in epstein-barr virus infected tumor cells.epstein-barr virus (ebv) is etiologically linked to multiple acute, chronic and malignant diseases. detection of ebv-rna transcripts in tissues or biofluids besides ebv-dna can help in diagnosing ebv related syndromes. sensitive ebv transcription profiling yields new insights on its pathogenic role and may be useful for monitoring virus targeted therapy. here we describe a multi-gene quantitative rt-pcr profiling method that simultaneously detects a broad spectrum (n=16) of crucial latent and ly ...201727993616
b-cell posttransplant lymphoproliferative disorder isolated to the central nervous system is epstein-barr virus positive and lacks p53 and myc expression by immunohistochemistry.in this retrospective study from one institution, we performed a clinicopathological study of a cohort of patients with posttransplant lymphoproliferative disorder (ptld) confined to the central nervous system. we also identified a comparison cohort of patients with de novo primary diffuse large b-cell lymphoma of the central nervous system. we performed a detailed morphologic review, evaluated epstein-barr virus (ebv) by in situ hybridization, and interpreted a panel of immunohistochemical stai ...201727993575
restricted tet2 expression in germinal center type b cells promotes stringent epstein-barr virus latency.epstein-barr virus (ebv) latently infects normal b cells and contributes to the development of certain human lymphomas. newly infected b cells support a highly transforming form (type iii) of viral latency; however, long-term ebv infection in immunocompetent hosts is limited to b cells with a more restricted form of latency (type i) in which most viral gene expression is silenced by promoter dna methylation. how ebv converts latency type is unclear, although it is known that type i latency is as ...201728003489
ebi2 overexpression in mice leads to b1 b-cell expansion and chronic lymphocytic leukemia-like b-cell malignancies.human and mouse chronic lymphocytic leukemia (cll) develops from cd5(+) b cells that in mice and macaques are known to define the distinct b1a b-cell lineage. b1a cells are characterized by lack of germinal center (gc) development, and the b1a cell population is increased in mice with reduced gc formation. as a major mediator of follicular b-cell migration, the g protein-coupled receptor epstein-barr virus-induced gene 2 (ebi2 or gpr183) directs b-cell migration in the lymphoid follicles in resp ...201728003273
chronic airway inflammation provides a unique environment for b cell activation and antibody production.b cells play many roles in health and disease. however, little is known about the mechanisms that drive b cell responses in the airways, especially in humans. chronic rhinosinusitis (crs) is an inflammatory disease of the upper airways that affects 10% of europeans and americans. a subset of crs patients develop nasal polyps (nps), which are characterized by type 2 inflammation, eosinophils and group 2 innate lymphoid cells (ilc2s). we have reported that np contain elevated levels of b cells and ...201728000955
prognostication of serial post-intensity-modulated radiation therapy undetectable plasma ebv dna for nasopharyngeal carcinoma.plasma epstein-barr virus (ebv) dna titers have been used to monitor treatment response and provide prognostic information on survival for nasopharyngeal carcinoma (npc). however, the long-term prognostic role of pretreatment and posttreatment titers after radical contemporaneous radiation therapy remains uncertain. we recruited 260 evaluable patients with non-metastatic npc treated with radical intensity-modulated radiation therapy (imrt) with or without adjunct chemotherapy. plasma ebv dna tit ...201728029657
performance of the real-q ebv quantification kit for epstein-barr virus dna quantification in whole blood.there has been increasing interest in standardized and quantitative epstein-barr virus (ebv) dna testing for the management of ebv disease. we evaluated the performance of the real-q ebv quantification kit (biosewoom, korea) in whole blood (wb). nucleic acid extraction and real-time pcr were performed by using the magna pure 96 (roche diagnostics, germany) and 7500 fast real-time pcr system (applied biosystems, usa), respectively. assay sensitivity, linearity, and conversion factor were determin ...201728029001
prognostic significance of epstein-barr virus (ebv) infection in hodgkin lymphoma patients.the prognostic significance of epstein-barr virus (ebv) infection in hodgkin lymphoma (hl) is still controversial. in this work we sought to examine the prognostic differences between ebv-positive and -negative hl through a series of 131 cases from tunisia.201728034523
association between human herpesvirus & human endogenous retrovirus and ms onset & progression.this review discusses the role of epstein-barr virus (ebv), human herpesvirus 6 (hhv6) and human endogenous retroviruses (hervs) in the onset and progression of multiple sclerosis (ms). although ebv has been established as one of the causal factors in ms onset, its role in ms progression is still uncertain. moreover, interactions between ebv and other risk factor on ms development still need more investment. with less consistent evidence than ebv, hhv6 has also been implicated in the pathogenesi ...201728017222
human herpes virus 8/epstein-barr virus-copositive, plasmablastic microlymphoma arising in multicentric castleman's disease of an immunocompetent patient. 201728013535
combined immunodeficiency and epstein-barr virus-induced b cell malignancy in humans with inherited cd70 deficiency.in this study, we describe four patients from two unrelated families of different ethnicities with a primary immunodeficiency, predominantly manifesting as susceptibility to epstein-barr virus (ebv)-related diseases. three patients presented with ebv-associated hodgkin's lymphoma and hypogammaglobulinemia; one also had severe varicella infection. the fourth had viral encephalitis during infancy. homozygous frameshift or in-frame deletions in cd70 in these patients abolished either cd70 surface e ...201728011864
inherited cd70 deficiency in humans reveals a critical role for the cd70-cd27 pathway in immunity to epstein-barr virus infection.epstein-barr virus (ebv) infection in humans is a major trigger of malignant and nonmalignant b cell proliferations. cd27 is a co-stimulatory molecule of t cells, and inherited cd27 deficiency is characterized by high susceptibility to ebv infection, though the underlying pathological mechanisms have not yet been identified. in this study, we report a patient suffering from recurrent ebv-induced b cell proliferations including hodgkin's lymphoma because of a deficiency in cd70, the ligand of cd2 ...201728011863
prognostic differences: epstein-barr virus-associated primary leiomyosarcoma of the spine versus spinal leiomyosarcoma metastases.the authors studied 6 cases of osseous leiomyosarcoma of the spine. two of these cases were of immunocompromised human immunodeficiency virus (hiv)-positive patients with epstein-barr virus (ebv)-associated primary vertebral leiomyosarcomas. the remaining 4 cases were of patients with leiomyosarcoma metastases to the spine.201728011357
what should be done in inflammatory bowel disease patients with prior malignancy?treatment of inflammatory bowel disease (ibd) in patients with prior malignancy is challenging because therapeutic immunosuppression required for controlling ibd activity may increase the risk of cancer recurrence. key messages: contrary to the observations in the post-transplant population, retrospective observational studies of ibd patients with prior malignancy have not demonstrated that immunosuppressive drugs increased significantly the risk of new or recurrent cancer. however, these studie ...201728147366
ebi3 regulates the nk cell response to mouse cytomegalovirus infection.natural killer (nk) cells are key mediators in the control of cytomegalovirus infection. here, we show that epstein-barr virus-induced 3 (ebi3) is expressed by human nk cells after nkg2d or il-12 plus il-18 stimulation and by mouse nk cells during mouse cytomegalovirus (mcmv) infection. the induction of ebi3 protein expression in mouse nk cells is a late activation event. thus, early activation events of nk cells, such as ifnγ production and cd69 expression, were not affected in ebi3-deficient ( ...201728143936
an unusual case of epstein-barr virus-positive large b-cell lymphoma lacking various b-cell markers.epstein-barr virus (ebv) is associated with b-cell lymphoma in various conditions, such as immunodeficiency and chronic inflammation. we report an unusual case of ebv-positive diffuse large b-cell lymphoma (dlbcl) lacking the expression of many b-cell markers.201728143608
lymphoepithelial carcinoma in parotid gland related to ebv infection: a case report.lymphoepithelial carcinoma commonly occurs at the nasopharynx and rarely occurs at other sites in the head and neck region. it is well known to occur at limited patients of local area as asia or arctic circle. related to this point, it is pointed out that this tumor has strong relation with epstein-barr virus (ebv) infection. in this time, we experienced to treat lymphoepithelial carcinoma with metastatic cervical lymph nodes occurring at parotid gland. the morbidity ratio of this tumor is less ...201728139343
comprehensive transcriptome and mutational profiling of endemic burkitt lymphoma reveals ebv type-specific differences.endemic burkitt lymphoma (ebl) is the most common pediatric cancer in malaria-endemic equatorial africa and nearly always contains epstein-barr virus (ebv), unlike sporadic burkitt lymphoma (sbl) that occurs with a lower incidence in developed countries. given these differences and the variable clinical presentation and outcomes, we sought to further understand pathogenesis by investigating transcriptomes using rna sequencing (rnaseq) from multiple primary ebl tumors compared to sbl tumors. with ...201728137761
how to use … the monospot and other heterophile antibody tests.epstein-barr virus (ebv) is a highly prevalent virus, transmitted via saliva, which often causes asymptomatic infection in children but frequently results in infectious mononucleosis in adolescents. heterophile antibody tests, including the monospot test, are red cell or latex agglutination assays, which detect antired cell antibodies produced as part of a polyclonal antibody response occurring during ebv infection. heterophile antibody tests are rapid, cheap and specific tests that can be perfo ...201728130396
efficient evaluation of humoral immune responses by the use of serum pools.collection and testing of individual serum samples are often used in research to gain knowledge about e.g. the humoral response against bacteria or virus. this is a valid but time-consuming method and might be a waste of valuable serum samples for inefficient research. so far, no study has considered using serum pools as a quick and efficient screening method to confirm or deny hypotheses.201728130033
vaccination to improve the persistence of cd19car gene-modified t cells in relapsed pediatric acute lymphoblastic leukemia.trials with second generation cd19 chimeric antigen receptors (car) t-cells report unprecedented responses but are associated with risk of cytokine release syndrome (crs). instead, we studied the use of donor epstein-barr virus-specific t-cells (ebv ctl) transduced with a first generation cd19car, relying on the endogenous t-cell receptor for proliferation. we conducted a multi-center phase i/ii study of donor cd19car transduced ebv ctl in pediatric acute lymphoblastic leukaemia (all). patients ...201728126984
clinicopathological study of 30 cases of peripheral t-cell lymphoma with hodgkin and reed-sternberg-like b-cells from japan.the presence of hodgkin and reed-sternberg (hrs)-like b-cells in peripheral t-cell lymphoma (ptcl) is rare and its clinicopathological features still remain unclear. here, we describe 30 cases of ptcl with hrs-like b-cells from japan. twenty-three cases (77%) presented evidence of follicular t-helper phenotype (tfh) derivation: 12 were angioimmunoblastic t-cell lymphoma and 11 ptcl with tfh phenotype (ptcl-tfh). the remaining seven cases were diagnosed as ptcl, not otherwise specified (ptcl-nos) ...201728125450
epstein-barr virus induced gene 2 (ebi2) mediates allergen-induced, leukocyte migration into airways.background leukocyte recruitment to sites of allergic inflammation depends on the local production of priming cytokines, chemokines, and potentially other mediators as well. previously, we showed that eosinophils (eos) express numerous orphan g-protein coupled receptors (gprs) including ebi2. despite its contribution to inflammatory diseases, the role of ebi2 in pulmonary eosinophilia is unknown. objectives to determine whether oxysterol ligands for ebi2 are increased in asthma exacerbation and ...201728125291
lentivirus-mediated rnai knockdown of lmp2a inhibits the growth of the epstein-barr-associated gastric carcinoma cell line gt38 in vitro.in this study, lentivirus-mediated rna interference (rnai) was applied to inhibit latent membrane protein 2a (lmp2a) gene expression, in order to explore the effects of lmp2a silencing on the growth of an epstein-barr virus-associated gastric carcinoma (ebvagc) cell line in vitro. lentivirus-mediated rnai technology was employed to specifically knock down the lmp2a gene in the ebv-positive gastric carcinoma cell line gt38. after infection, reverse transcription-quantitative polymerase chain reac ...201728123488
parvovirus expresses a small noncoding rna that plays an essential role in virus replication.human bocavirus 1 (hbov1) belongs to the species primate bocaparvovirus of the genus bocaparvovirus of the parvoviridae family. hbov1 causes acute respiratory tract infections in young children and has a selective tropism for the apical surface of well-differentiated human airway epithelia (hae). in this study, we identified an additional hbov1 gene, bocavirus-transcribed small noncoding rna (bocasr), within the 3' noncoding region (nucleotides [nt] 5199 to 5338) of the viral genome of positive ...201728122984
high level of viral microrna-bart20-5p expression is associated with worse survival of patients with epstein-barr virus-associated gastric cancer.this study analyzed the relationship between several epstein-barr virus (ebv) microrna (mirna) expression profiles and the clinicopathologic features of patients with ebv-associated gastric cancer. the mirna expression was examined in 59 tumor and 39 paired normal mucosal tissues from available formalin-fixed paraffin embedded tissue samples. the expression levels of mir-bamhi fragment a rightward transcript (bart)1-5p, mir-bart4-5p, and mir-bart20-5p were determined using a quantitative real-ti ...201728122341
the association between circulating tumor cells and epstein-barr virus activation in patients with nasopharyngeal carcinoma.circulating tumor cells (ctcs) and microemboli (ctm) are attracting increasing attention in medical biology and clinical practice. however, the clinical relevance of ctcs in nasopharyngeal carcinoma (npc) has not yet been ascertained, and no study has focused on the influence of epstein-barr virus (ebv) status on ctcs in npc patients. these issues were therefore examined.201728121221
regulatory t cell effect on cd8(+) t cell responses to human herpesvirus 8 infection and development of kaposi's sarcoma.we assessed cd8(+) t cell reactivity to human herpesvirus 8 (hhv-8; kaposi's sarcoma [ks]-associated herpesvirus) and the role of cd4(+)cd25(hi)foxp3(+) regulatory t cells (treg) in hhv-8- and hiv-coinfected participants of the multicenter aids cohort study who did or did not develop ks. there were similarly low cd8(+) t cell interferon-γ responses to mhc class i-restricted epitopes of hhv-8 lytic and latent proteins over 5.7 years before ks in participants who developed ks compared to those who ...201728121161
clinicopathological analysis of 12 patients with epstein-barr virus-positive primary intestinal t/natural killer-cell lymphoma (ebv(+) itnkl).epstein-barr virus-positive (ebv(+) ) intestinal t/natural killer (nk) cell lymphoma (itnkl) is an uncommon tumour with an extremely aggressive clinical behaviour. however, the clinicopathological characteristics of this tumour, including t cell receptor (tcr) phenotype and the patient's background, remain unknown. the aim of this study was to elucidate the detailed clinicopathological profile of ebv(+) itnkl.201728120384
atraumatic splenic rupture secondary to epstein-barr virus infection.we present a case report of atraumatic splenic rupture secondary to epstein-barr virus (ebv) infection. a woman aged 36 years presented to a london teaching hospital's accident and emergency department with severe abdominal pain following a 6-day history of diarrhoea and vomiting, which had been under review by her gp. a ct scan demonstrated free intraperitoneal fluid and abnormal appearance of her spleen. blood tests demonstrated ebv infection with positive serology and leucocytosis. she underw ...201728119438
molecular classification of gastric cancer.gastric cancer is among the most common cancers worldwide. despite declining incidences, the prognosis remains dismal in western countries and is better in asian countries with national cancer screening programs. complete endoscopic or surgical resection of the primary tumor with or without lymphadenectomy offers the only chance of cure in the early stage of the disease. survival of more locally advanced gastric cancers was improved by the introduction of perioperative, adjuvant and palliative c ...201728118758
epstein-barr virus gene expression and latency pattern in gastric carcinomas: a systematic review.a systematic review of literature was conducted to identify all published reports regarding the expression of epstein-barr virus (ebv) proteins/transcripts and ebv latency patterns in ebv-associated gastric carcinomas (ebvagc).201728118740
a simple red blood cell lysis method for the establishment of b lymphoblastoid cell lines.a number of methods exist for the transformation of b lymphocytes by the epstein barr virus in vitro into immortalized cell lines. we have developed a new method with a powerful and simple strategy for the establishment of b-lcls, the red blood cell lysis method. this method simplified the pbmc separation procedure with red blood cell removal, and used as little as 0.5 ml of whole blood for establishing ebv-immortalized cell lines, which can proliferate to large cell numbers in a relatively shor ...201728117797
a rare presentation of isolated cns posttransplantation lymphoproliferative disorder.posttransplantation lymphoproliferative disorder (ptld) is a recognized and extremely morbid complication of solid organ transplantation, but central nervous system involvement, particularly in isolation, is rare. there are no standardized treatment strategies for ptld, though commonly used strategies include reduction of immunosuppression, chemotherapy, rituximab, radiation, and surgery. we present a case of an unusual morphologic variant of primary central nervous system ptld with successful r ...201728116196
a supporting role of chinese national immortalized cell bank in life science research.a biorepository of human samples is essential to support the research of life science. lymphoblastoid b cell line (lcl), which is easy to be prepared and can reproduce indefinitely, is a convenient form of sample preservation. lcls are established from human b cells transformed by epstein-barr virus (ebv). chinese national immortalized cell bank has preserved human lcls from different ethnic groups in china. as there are many studies on the nature of lcls and public available resources with geno ...201728115308
hpv and systemic lupus erythematosus: a mosaic of potential crossreactions.etiology, pathogenesis, and immunology of systemic lupus erythematosus (sle) form a complex, still undeciphered picture that recently has been further made complicated by a new factor of morbidity: human papillomaviruses (hpvs). indeed, a prevalence of hpv infections has been reported among sle patients. searching for molecular mechanisms that might underlie and explain the relationship between hpv infection and sle, we explored the hypothesis that immune responses following hpv infection may cr ...201728111707
[current events in immunotherapy for upper aerodigestive tract cancer].head and neck (hn) carcinomas (mostly represented by squamous cell carcinomas [scc]) still have a poor prognosis, which could be dramatically improved with immunotherapy. tumor's microenvironment changes, caused by many endogenous or exogenous events, can correlate with prognosis and therapeutic response. here, we review recent data regarding hnscc, nasopharyngeal carcinomas (npc) and salivary gland malignant tumors, all three being potential target of immunotherapies. about half of hnscc exhibi ...201728111039
an epstein-barr virus susceptible immature t-cell line, will4, established from a patient with t-lymphoblastic lymphoma bearing cd21 and a clonal ebv genome.we managed a patient with an epstein-barr virus-associated t-cell lymphoblastic lymphoma. mediastinal tumor cells at initial admission were positive for cd4, cd8, and tdt. interestingly, a lymph node at necropsy was compatible for a cd4-positive peripheral t-cell lymphoma without cd8 and tdt expression, suggesting a different phenotype from the mediastinal tumor. tumor cells in pleural effusion continued to proliferate in in vitro and were designated as will4. will4 cells were positive for cd3, ...201728110206
human immunity against ebv-lessons from the clinic.the mammalian immune system has evolved over many millennia to be best equipped to protect the host from pathogen infection. in many cases, host and pathogen have coevolved, each acquiring sophisticated ways of inducing or protecting from disease. epstein-barr virus (ebv) is a human herpes virus that infects >90% of individuals. despite its ubiquity, infection by ebv is often subclinical; this invariably reflects the necessity of the virus to preserve its host, balanced with sophisticated host i ...201728108590
epstein-barr-virus-related mucocutaneous ulceration that mimics oral squamous cell carcinoma: the importance of recognising this new condition.we report a case and present a literature search of the relatively newly reported condition of epstein barr virus (ebv)-related mucocutaneous ulceration. ebv-related mucocutaneous ulcers clinically present as oral squamous cell carcinoma (oscc) in immunocompromised elderly patients but usually resolve by stopping or modifying the medication. as the two conditions can present in a similar way, and the management of each is totally different, this case highlights the importance of recognising this ...201728108051
epstein-barr virus in the pathogenesis of oral cancers.epstein-barr virus (ebv) is a ubiquitous gammaherpesvirus that establishes a lifelong persistent infection in the oral cavity and is intermittently shed in the saliva. ebv exhibits a biphasic life cycle, supported by its dual tropism for b lymphocytes and epithelial cells, which allows the virus to be transmitted within oral lymphoid tissues. while infection is often benign, ebv is associated with a number of lymphomas and carcinomas that arise in the oral cavity and at other anatomical sites. i ...201728190296
mutation analysis of tumor necrosis factor alpha-induced protein 3 gene in hodgkin lymphoma.survival and proliferation of hodgkin and reed-sternberg (hrs) cells, the malignant cells of classical hodgkin lymphoma (chl), are dependent on constitutive activation of nuclear factor kb (nf-κb). a20, encoded by tnf alpha-induced protein 3 (tnfaip3), one of the inhibitors of nf-kb, was found to be inactivated by deletions and/or point mutations in chl.201728189285
alice in wonderland syndrome: a real life version of lewis carroll's novel.alice in wonderland syndrome was originally coined by dr. john todd in 1955. the syndrome is named after the sensations experienced by the character alice in lewis carroll's novel alice's adventures in wonderland. alice in wonderland syndrome consists of metamorphopsia (seeing something in a distorted fashion), bizarre distortions of their body image, and bizarre perceptual distortions of form, size, movement or color. additionally, patients with alice in wonderland syndrome can experience audit ...201728189272
pd1 blockade with pembrolizumab is highly effective in relapsed or refractory nk/t-cell lymphoma failing l-asparaginase.natural killer (nk)/t-cell lymphomas failing l-asparaginse-regimens have no known salvage and are almost invariably fatal. seven male nk/t-cell lymphoma patients (age: 49, 31-68, years) failing 2 (1-5) regimens (including l-asparaginase-regimens, and allogeneic hematopoietic stem cell transplantation, hsct, in 2 cases), were treated with the anti-programmed-death-1 (pd1) antibody pembrolizumab. all patients responded, according to various clinical, radiologic (positron emission tomography), morp ...201728188133
epstein-barr virus particles induce centrosome amplification and chromosomal instability.infections with epstein-barr virus (ebv) are associated with cancer development, and ebv lytic replication (the process that generates virus progeny) is a strong risk factor for some cancer types. here we report that ebv infection of b-lymphocytes (in vitro and in a mouse model) leads to an increased rate of centrosome amplification, associated with chromosomal instability. this effect can be reproduced with virus-like particles devoid of ebv dna, but not with defective virus-like particles that ...201728186092
epstein-barr virus-associated gastric cancer reveals intratumoral heterogeneity of pik3ca mutations. 201728184407
serum proteomic-based analysis identifying autoantibodies against prdx2 and prdx3 as potential diagnostic biomarkers in nasopharyngeal carcinoma.nasopharyngeal carcinoma (npc) is a major head and neck cancer with high occurrence in southeast asia and southern china. we aimed to identify autoantibodies that may contribute to early detection of npc.201728184180
next-generation sequencing of mirnas in clinical samples of epstein-barr virus-associated b-cell lymphomas.epstein-barr virus (ebv) encodes 49 micrornas (mirnas) in the bart and bhrf1 regions of its genome. although expression profiles of ebv-encoded mirnas have been reported for ebv-positive cell lines and nasopharyngeal carcinoma, to date there is little information about total mirna expression, including cellular and viral mirnas, in the primary tumors of ebv-associated b-lymphoproliferative disorders. in this study, next-generation sequencing and quantitative real-time reverse transcription-pcr w ...201728181423
the prognostic value and pathobiological significance of glasgow microenvironment score in gastric cancer.to evaluate the prognostic value and pathobiological significance of glasgow microenvironment score (gms), a parameter based on tumor stroma percentage and inflammatory cell infiltration, in gastric cancer.201728180998
"hemophagocytic lymphohistiocytosis after ebv reactivation and ibrutinib treatment in relapsed/refractory chronic lymphocytic leukemia".hemophagocytic lymphohistiocytosis (hlh) is a rare syndrome characterized by ineffective t-cell and nk response. we report the clinical course of a patient with relapsed cll who developed acute symptoms soon after starting ibrutinib. hyperpyrexia, splenomegaly, hyperferritinemia, hypertriglyceridemia, cytopenias, and a typical cytokine pattern, i.e. high interleukin (il)-6, il10 and il18, were consistent with a diagnosis of hlh. coexistent epstein barr virus reactivation was documented. ibrutini ...201728180067
differentiation-dependent lmp1 expression is required for efficient lytic epstein-barr virus reactivation in epithelial cells.epstein-barr virus (ebv)-associated diseases of epithelial cells, including tumors that have latent infection, such as nasopharyngeal carcinoma (npc), and oral hairy leukoplakia (ohl) lesions that have lytic infection, frequently express the viral latent membrane protein 1 (lmp1). in lytically infected cells, lmp1 expression is activated by the brlf1 (r) immediate early (ie) protein. however, the mechanisms by which lmp1 expression is normally regulated in epithelial cells remain poorly understo ...201728179525
epstein-barr virus is associated with periodontal diseases: a meta-analysis based on 21 case-control studies.some controversies still exist between the detection of epstein-barr virus (ebv)'s dna and risks of periodontal diseases. hence, a comprehensive meta-analysis on all available literatures was performed to clarify the relationship between ebv and preidontitis.a comprehensive search was conducted within the pubmed, embase, and wanfang databases up to october 10th, 2016 according to inclusion and exclusion criteria and finally 21 case-control literatures were obtained. the outcomes including odds r ...201728178139
[expression of long non-coding rna snhg8 in epstein-barr virus-related gastric cancer and clinical outcome].objective: to investigate the expression of long non-coding rna (lncrna) snhg8 in eb virus related gastric cancer and their correlation prognosis. methods: the expression of snhg8 in 93 gastric cancers and 93 cancer-free controls, matched by age and sex, were determined by real-time pcr. eb virus expression was detected by eber in situ hybridization. results: forty-one gastric cancers were eb virus associated. for all gastric cancers, snhg8 expression was 14 times higher (p=0.001) than that in n ...201728173665
clinical value of the epstein-barr virus and p16 status in patients with nasopharyngeal carcinoma: a single-centre study in japan.the clinical significance of the epstein-barr virus (ebv) status and p16 expression was unknown in nasopharyngeal carcinoma (npc).201728171876
lymphomatoid granulomatosis with pulmonary and gastrointestinal involvement.we present a rare case of grade ii lymphomatoid granulomatosis (lyg) with pulmonary and gastrointestinal involvement. lyg is considered an epstein-barr virus-driven lymphoproliferative disorder that often presents with multiple nodular lesions in the lungs and sometimes involvement of skin and the central nervous system. although the aetiology is unknown, it is associated with the use of immunosuppressives. involvement of other organ systems is very rare. we successfully treated our patients wit ...201728167690
belatacept after kidney transplantation in adolescents: a retrospective study.regardless of recipient age at kidney transplantation (ktx), patients are at greatest risk for graft loss in adolescence, partly due to nonadherence to an oral immunosuppressive regimen. belatacept, a non-nephrotoxic, first-in-class immunosuppressant that inhibits costimulation of t cells requires intravenous application only every 4 weeks, potentially leading to better adherence. however, it is only approved for use in adults. we report here the findings of the first study of belatacept in adol ...201728166398
multiple sclerosis-associated retrovirus, epstein-barr virus, and vitamin d status in patients with relapsing remitting multiple sclerosis.the relationship between infections and autoimmune diseases is complex and there are several reports highlighting the role of human endogenous retroviruses (hervs) in these patients. the levels of multiple sclerosis-associated retrovirus (msrv)-type dna of env gene was measured in peripheral blood mononuclear cells from 52 patients with relapsing-remitting multiple sclerosis (rrms) and 40 healthy controls using specific quantitative pcr (qpcr) analysis. furthermore, we analyzed the status of her ...201728165135
thiopurines and methotrexate use in ibd patients in a biologic era.although we have been living in the era of biologic therapy for several decades, the use of immunomodulators (primarily thiopurines [azathioprine and mercaptopurine] and less so methotrexate) still remains an important component of the inflammatory bowel disease (ibd) pharmaceutical arsenal. thiopurines as monotherapy exert corticosteroid-sparing effects and can maintain long-term remission in a considerable proportion of patients who have frequent relapses and are or have become mesalazine and/ ...201728160250
methyl-dependent and spatial-specific dna recognition by the orthologous transcription factors human ap-1 and epstein-barr virus zta. 201728158710
pattern and significance of asymptomatic elevation of liver enzymes in mycoplasma pneumonia in children.mycoplasma infection is on the rise in recent times. it usually infects any system, including liver. this study aims to show the significance of elevated liver enzymes in mycoplasma pneumonia and to have a look at future prospects. this is a single-center retrospective study involving 105 children serologically positive for mycoplasma igm and igg antibodies and 50 with community-acquired pneumonia caused by organisms other than mycoplasma and epstein-barr virus from june 2015 to june 2016 and al ...201728155329
regulatory network analysis of epstein-barr virus identifies functional modules and hub genes involved in infectious mononucleosis.epstein-barr virus (ebv) is the most common cause of infectious mononucleosis (im) and establishes lifetime infection associated with a variety of cancers and autoimmune diseases. the aim of this study was to develop an integrative gene regulatory network (grn) approach and overlying gene expression data to identify the representative subnetworks for im and ebv latent infection (li). after identifying differentially expressed genes (degs) in both im and li gene expression profiles, functional an ...201728155194
rituximab in the treatment of ocular cicatricial pemphigoid: a retrospective cohort study.the purpose was to evaluate the effectiveness and safety of rituximab (rtx) for the treatment of patients with aggressive ocular cicatricial pemphigoid (ocp).201728154932
epstein-barr virus-positive mucocutaneous ulcer. 201728088274
familial outbreak of eruptive pseudoangiomatosis with dermoscopic and histopathologic correlation. 201728087016
[gastric tumors and tumor precursors].gastric cancer is the fifth (men) and sixth (women) most common cause of cancer-related death in germany. despite a declining incidence of distal gastric cancer, the prognosis remains dismal: the 5‑year survival rate ranges between 35% for women and 31% for men. the majority are adenocarcinomas, which occur sporadically, familial or hereditary. adenomas and intraepithelial neoplasms are considered as precursor lesions. recently, whole genome sequencing and comprehensive molecular profiling descr ...201728084526
hhv8-related lymphoid proliferations: a broad spectrum of lesions from reactive lymphoid hyperplasia to overt lymphoma.human herpesvirus 8 (hhv8)-associated lymphoid proliferations are uncommon and poorly characterized disorders mainly affecting immunosuppressed patients, especially with hiv infection. they encompass different diseases with overlapping features that complicate their classification. in addition, the role of hhv8 in reactive lymphoid hyperplasia is not well known. to analyze the clinicopathological spectrum of these lesions, we have reviewed 66 biopsies of 61 patients with hhv8 infection. all case ...201728084335
carcinoma-risk variant of ebna1 deregulates epstein-barr virus episomal latency.epstein-barr virus (ebv) latent infection is a causative co-factor for endemic nasopharyngeal carcinoma (npc). npc-associated variants have been identified in ebv-encoded nuclear antigen ebna1. here, we solve the x-ray crystal structure of an npc-derived ebna1 dna binding domain (dbd) and show that variant amino acids are found on the surface away from the dna binding interface. we show that npc-derived ebna1 is compromised for dna replication and episome maintenance functions. recombinant virus ...201728077791
latent membrane protein 1 (lmp1) and lmp2a collaborate to promote epstein-barr virus-induced b cell lymphomas in a cord blood-humanized mouse model but are not essential.epstein-barr virus (ebv) infection is associated with b cell lymphomas in humans. the ability of ebv to convert human b cells into long-lived lymphoblastoid cell lines (lcls) in vitro requires the collaborative effects of ebna2 (which hijacks notch signaling), latent membrane protein 1 (lmp1) (which mimics cd40 signaling), and ebv-encoded nuclear antigen 3a (ebna3a) and ebna3c (which inhibit oncogene-induced senescence and apoptosis). however, we recently showed that an lmp1-deleted ebv mutant i ...201728077657
the global incidence of lip, oral cavity, and pharyngeal cancers by subsite in 2012.by using data from the international agency for research on cancer publication cancer incidence in 5 continents and globocan, this report provides the first consolidated global estimation of the subsite distribution of new cases of lip, oral cavity, and pharyngeal cancers by country, sex, and age for the year 2012. major geographically based, sex-based, and age-based variations in the incidence of lip, oral cavity, and pharyngeal cancers by subsite were observed. lip cancers were highly frequent ...201728076666
[paraffin-embedded tissue fragment suspension: a novel method for quality control preparation in in-situ hybridization for epstein-barr virus encoded rna]. 201728072979
nanoparticle exposure reactivates latent herpesvirus and restores a signature of acute infection.inhalation of environmental (nano) particles (np) as well as persistent herpesvirus-infection are potentially associated with chronic lung disease and as both are omnipresent in human society a coincidence of these two factors is highly likely. we hypothesized that np-exposure of persistently herpesvirus-infected cells as a second hit might disrupt immune control of viral latency, provoke reactivation of latent virus and eventually lead to an inflammatory response and tissue damage.201728069010
the autoimmune risk gene zmiz1 is a vitamin d responsive marker of a molecular phenotype of multiple sclerosis.multiple sclerosis (ms) is a neurological condition driven in part by immune cells from the peripheral circulation, the targets for current successful therapies. the autoimmune and ms risk gene zmiz1 is underexpressed in blood in people with ms. we show that, from three independent sets of transcriptomic data, expression of zmiz1 is tightly correlated with that of hundreds of other genes. further we show expression is partially heritable (heritability 0.26), relatively stable over time, predomin ...201728063629
chaetocin reactivates the lytic replication of epstein-barr virus from latency via reactive oxygen species.oxidative stress, regarded as a negative effect of free radicals in vivo, takes place when organisms suffer from harmful stimuli. some viruses can induce the release of reactive oxygen species (ros) in infected cells, which may be closely related with their pathogenicity. in this report, chaetocin, a fungal metabolite reported to have antimicrobial and cytostatic activity, was studied for its effect on the activation of latent epstein-barr virus (ebv) in b95-8 cells. we found that chaetocin rema ...201728063010
inkt and memory b-cell alterations in hhv-8 multicentric castleman disease.human herpesvirus 8 (hhv-8) is the causative agent of kaposi sarcoma (ks) and multicentric castleman disease (mcd), a life-threatening, virally induced b-cell lymphoproliferative disorder. hhv-8 is a b-lymphotropic γ-herpesvirus closely related to the epstein-barr virus (ebv). invariant natural killer t (inkt) cells are innate-like t cells that play a role in antiviral immunity, specifically in controlling viral replication in ebv-infected b cells. decline of inkt cells is associated with age or ...201728060720
virus-associated neoplasms of the nasopharynx and sinonasal tract: diagnostic problems.a significant fraction of nasopharyngeal and sinonasal tumors are associated with epstein-barr virus (ebv) or human papillomavirus (hpv). nasopharyngeal carcinoma (npc) and extranodal nk/t-cell lymphoma harbor ebv in practically all cases, although a small proportion of cases of the former harbor hpv. sinonasal inverted papillomas harbor hpv in about 25% of cases. sinonasal squamous cell carcinomas harbor transcriptionally active hpv in about 20% of cases, and limited data suggest that this subs ...201728060369
identification of distinct subgroups of ebv-positive post-transplant diffuse large b-cell lymphoma.post-transplantation lymphoproliferative disorder is an aggressive complication of transplantation, most frequently of diffuse large b-cell lymphoma morphology and associated with epstein-barr virus (ebv) infection/reactivation. in this study the microenvironment of ebv(+) (n=23) and ebv(-) (n=9) post-transplant non-germinal center b-cell diffuse large b-cell lymphoma was characterized. of ebv(+) cases somatic hypermutation analysis, gene expression profiling, and extensive phenotyping were perf ...201728059091
structural basis for the regulation of nuclear import of epstein-barr virus nuclear antigen 1 (ebna1) by phosphorylation of the nuclear localization signal.epstein-barr virus (ebv) nuclear antigen 1 (ebna1) is expressed in every ebv-positive tumor and is essential for the maintenance, replication, and transcription of the ebv genome in the nucleus of host cells. ebna1 is a serine phosphoprotein, and it has been shown that phosphorylation of s385 in the nuclear localization signal (nls) of ebna1 increases the binding affinity to the nuclear import adaptor importin-α1 as well as importin-α5, and stimulates nuclear import of ebna1. to gain insights in ...201728104399
clinical impact of serum survivin positivity and tissue expression of ebv-encoded rna in diffuse large b-cell lymphoma patients treated with rituximab-chop.survivin is an inhibitor of apoptosis and is upregulated by epstein-barr virus (ebv) latent genes. given the frequent association of ebv with lymphoid malignancies, survivin is expected to have prognostic value in diffuse large b-cell lymphoma (dlbcl). thus, we measured the pretreatment serum level of survivin in dlbcl patients and analyzed its association with survival outcome and ebv status, as represented by ebv-encoded rna (eber) in dlbcl. pretreatment serum survivin level was measured in pa ...201728099151
exome and genome sequencing of nasopharynx cancer identifies nf-κb pathway activating mutations.nasopharyngeal carcinoma (npc) is an aggressive head and neck cancer characterized by epstein-barr virus (ebv) infection and dense lymphocyte infiltration. the scarcity of npc genomic data hinders the understanding of npc biology, disease progression and rational therapy design. here we performed whole-exome sequencing (wes) on 111 micro-dissected ebv-positive npcs, with 15 cases subjected to further whole-genome sequencing (wgs), to determine its mutational landscape. we identified enrichment f ...201728098136
burkitt lymphoma in adolescents and young adults: management challenges.about one-half of all burkitt lymphoma (bl) patients are younger than 40 years, and one-third belong to the adolescent and young adult (aya) subset, defined by an age between 15 and 25-40 years, based on selection criteria used in different reports. bl is an aggressive b-cell neoplasm displaying highly characteristic clinico-diagnostic features, the biologic hallmark of which is a translocation involving immunoglobulin and c-myc genes. it presents as sporadic, endemic, or epidemic disease. endem ...201728096698
semisynthesis of (-)-rutamarin derivatives and their inhibitory activity on epstein-barr virus lytic replication.(+)-rutamarin inhibits ebv lytic dna replication with an ic50 of 7.0 μm. (-)-chalepin, a (-)-rutamarin derivative, was isolated from the whole plant of ruta graveolens and used as a precursor of (-)-rutamarin. altogether, 28 (-)-rutamarin derivatives were synthesized starting from (-)-chalepin. of these, 16 compounds (2a-e, 3b-e, 3g, 4f, 4k, 4m-p) were found to be more potent against ebv lytic dna replication than (-)-chalepin. compounds 4m, 4n, and 4p exhibited ic50 values of 1.5, 0.32, and 0.8 ...201728093914
subacute demyelinating polyradiculoneuropathy complicating epstein-barr virus infection in gata2 haploinsufficiency.autosomal dominant haploinsufficiency of gata2 causes monocytopenia and natural killer cell lymphopenia, resulting in predisposition to mycobacterial, fungal, and viral infections.201728093780
the most important questions in cancer research and clinical oncology : question 1. could the vertical transmission of human papilloma virus (hpv) infection account for the cause, characteristics, and epidemiology of hpv-positive oropharyngeal carcinoma, non-smoking east asian female lung adenocarcinoma, and/or east asian triple-negative breast carcinoma?specific research foci: (1) mouse models of gamma-herpes virus-68 (γhv-68) and polyomavirus (pyv) infections during neonatal versus adult life. (2) for human papilloma virus (hpv)-positive oropharyngeal carcinoma (opc)-(a) asking the question: is oral sex a powerful carcinogen? (b) examining the evidence for the vertical transmission of hpv infection. (c) examining the relationship between hpv and epstein-barr virus (ebv) infections and nasopharyngeal cancer (npc) in west european, east european ...201728093081
comprehensive assessment of peripheral blood tcrβ repertoire in infectious mononucleosis and chronic active ebv infection patients.epstein-barr virus (ebv) primary infection is usually asymptomatic, but it sometimes progresses to infectious mononucleosis (im). occasionally, some people develop chronic active ebv infection (caebv) with underlying immunodeficiency, which belongs to a continuous spectrum of ebv-associated lymphoproliferative disorders (ebv(+) lpd) with heterogeneous clinical presentations and high mortality. it has been well established that t cell-mediated immune response plays a critical role in the disease ...201728091735
gastrointestinal post-transplant lymphoproliferative disorder with rapidly forming characteristic lesions after cord blood transplantation: a report of two cases.epstein-barr virus (ebv)-related post-transplant lymphoproliferative disorder (ptld) frequently involves the gastrointestinal tract, but the endoscopic characteristics of this condition have not been discussed in detail. we report two cases of ebv-related ptld involving rapidly forming characteristic lesions. case 1 was a 60-year-old man with acute myeloid leukemia who underwent cord blood transplantation (cbt) after which he initially achieved complete remission (cr). he developed nausea and vo ...201728090016
epstein-barr virus and renal transplantation.epstein-barr virus (ebv) is a gamma herpesvirus associated with diseases ranging from asymptomatic viremia to post-transplant malignancies in kidney transplant recipients. ebv specifically is associated with post-transplantation lymphoproliferative disorder (ptld), in kidney transplant recipients, with increased risk in ebv seronegative patients with ebv seropositive donors on intensified immunosuppression. the diagnosis of ptld relies on clinical suspicion plus tissue biopsy with polymerase cha ...201728089555
activation of atr-chk1 pathway facilitates ebv-mediated transformation of primary tonsillar b-cells.primary infection of the immunocompromised host with the oncovirus epstein-barr virus (ebv) that targets mainly b-cells is associated with an increased risk for ebv-associated tumors. the early events subsequent to primary infection with potential for b-cell transformation are poorly studied. here, we modeled in vitro the primary infection by using b-cells isolated from tonsils, the portal of entry of ebv, since species specificity of ebv hampers modeling in experimental animals. increasing evid ...201728031537
epstein-barr virus ebna2 directs doxorubicin resistance of b cell lymphoma through ccl3 and ccl4-mediated activation of nf-κb and btk.epstein-barr virus (ebv)-encoded nuclear antigen, ebna2, expressed in ebv-infected b lymphocytes is critical for lymphoblastoid cell growth. microarray profiling and cytokine array screening revealed that ebna2 is associated with upregulation of the chemokines ccl3 and ccl4 in lymphoma cells. depletion or inactivation of ccl3 or ccl4 sensitized dlbcl cells to doxorubicin. our results indicate that ebv influences cell survival via an autocrine mechanism whereby ebna2 increases ccl3 and ccl4, whic ...201728036258
comparative analysis of 22 epstein-barr virus genomes from diseased and healthy individuals.epstein-barr virus (ebv) infects most of the world's population and is causally associated with several human cancers, but little is known about how ebv genetic variations might influence ebv-associated diseases and their geographical patterns. in the present study, 22 ebv whole-genome sequences from diseased and healthy individuals were analysed to explore ebv sequence variations at the whole-genome level. we found that the 22 ebv genomes were generally highly similar to each other at the genom ...201728036243
inhibition of epstein-barr virus reactivation by the flavonoid apigenin.lytic reactivation of ebv has been reported to play an important role in human diseases, including npc carcinogenesis. inhibition of ebv reactivation is considered to be of great benefit in the treatment of virus-associated diseases. for this purpose, we screened for inhibitory compounds and found that apigenin, a flavonoid, seemed to have the ability to inhibit ebv reactivation.201728056971
therapeutic vaccine targeting epstein-barr virus latent protein, lmp1, suppresses lmp1-expressing tumor growth and metastasis in vivo.in endemic area, nasopharyngeal carcinoma (npc) tumor cells harbor ebv latent infection and expresses viral antigens such as ebna1, lmp1 and lmp2. in this study, we established a npc-mimicry animal model and assessed the therapeutic potential of lmp1 vaccine.201728056887
high levels of ebv-encoded rna 1 (eber1) trigger interferon and inflammation-related genes in keratinocytes expressing hpv16 e6/e7.different types of cells infected with epstein-barr virus (ebv) can release exosomes containing viral components that functionally affect neighboring cells. previously, we found that ebv was localized mostly in infiltrating lymphocytes within the stromal layer of cervical lesions. in this study, we aimed to determine effects of exosome-transferred ebv-encoded rnas (ebers) on keratinocytes expressing human papillomavirus (hpv) 16 e6/e7 (donori-hpv16 hfks). lipid transfection of in vitro-transcrib ...201728056059
epstein-barr virus-encoded latent membrane protein 1 upregulates glucose transporter 1 transcription via the mtorc1/nf-κb signaling pathways.accumulating evidence indicates that oncogenic viral protein plays a crucial role in activating aerobic glycolysis during tumorigenesis, but the underlying mechanisms are largely undefined. epstein-barr virus (ebv)-encoded latent membrane protein 1 (lmp1) is a transmembrane protein with potent cell signaling properties and has tumorigenic transformation property. activation of nf-κb is a major signaling pathway mediating many downstream transformation properties of lmp1. here we report that acti ...201728053105
ebi2 expression and function: robust in memory lymphocytes and increased by natalizumab in multiple sclerosis.the interaction between oxysterols and the g protein-coupled receptor epstein-barr virus-induced gene 2 (ebi2) fine-tunes immune cell migration, a mechanism efficiently targeted by several disease-modifying treatments developed to treat multiple sclerosis (ms), such as natalizumab. we previously showed that memory cd4(+) t lymphocytes migrate specifically in response to 7α,25-dihydroxycholesterol (7α,25-ohc) via ebi2 in the ms murine model experimental autoimmune encephalomyelitis. however, the ...201728052250
the biological properties of different epstein-barr virus strains explain their association with various types of cancers.the epstein-barr virus (ebv) is etiologically associated with the development of multiple types of tumors, but it is unclear whether this diversity is due to infection with different ebv strains. we report a comparative characterization of snu719, gp202, and yccel1, three ebv strains that were isolated from gastric carcinomas, m81, a virus isolated in a nasopharyngeal carcinoma and several well-characterized laboratory type a strains. we found that b95-8, akata and gp202 induced cell growth more ...201728052012
mesenchymal stem cells ameliorate b-cell-mediated immune responses and increase il-10-expressing regulatory b cells in an ebi3-dependent manner.effector b cells are central contributors to the development of autoimmune disease by activating autoreactive t cells, producing pro-inflammatory cytokines and organizing ectopic lymphoid tissue. conversely, il-10-producing regulatory b (breg) cells have pivotal roles in maintaining immunological tolerance and restraining excessive inflammation in autoinflammatory disease. thus, regulating the equilibrium between antibody-producing effector b cells and breg cells is critical for the treatment of ...201728042143
human herpesviruses as copathogens of hiv infection, their role in hiv transmission, and disease progression.of eight human herpesviruses (hhvs), often, only herpes simplex virus types 1 (hsv-1) and 2 (hsv-2) find mention in medical literature as both of these viruses are commonly associated with genital lesions and oral ulcers, commonly known as cold sores. however, role of human herpesviruses as copathogens and in aggravation and in the transmission of other human diseases, especially the acquired immunodeficiency syndrome (hiv/aids) has only very recently been recognized. therefore, screening and tr ...201727013807
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