细胞因子与EB病毒在影响肿瘤发生、演进中的协同作用

研究表明,EB病毒与多种细胞因子相互作用直接影响了EB病毒相关性肿瘤的发生、演进过程,在此过程中EB病毒编码的潜伏膜蛋白1(LMP-1)可能是一个关键的调节点。本文就EB病毒及其相关的细胞因子在肿瘤发生、发展过程中的协同作用做一综述。     

Regression of Experimental Human Leukemias and Solid Tumors Induced by Epstein-Barr Virus-Immortalized B Cells

We previously have reported on an experimental athymic mouse model in which regression of human Burkitt's lymphoma is induced by either coinjection with or intratumor inoculation of Epstein-Barr virus (EBV)-immortalized human B cells. In the current study, we were interested in determining whether the powerful antitumor effects of EBV-immortalized B cells could be effective against a variety of human tumors grown in athymic mice, including acute lymphocytic leukemia, malignant melanoma, acute promyelocytic leukemia, neuroblastoma, lung carcinoma, colon adcnocarcinoma, Wilms tumor, Hodgkin's lymphoma, rhabdomyosarcoma and breast adenocarcinoma. We report here the results of experiments in nude mice that demonstrated the potent antitumor effect of EBV-immortalized B cells against human tumors derived from a variety of different tissues.     

不同类型淋巴瘤438例EB病毒分布特点

目的 探讨不同类型淋巴瘤中EB病毒(EBV)的分布特点.方法 选用免疫组织化学EnVision法标记ALK1、CD3、CD5、CD7、CD10、CD15、CD20、CD23、CD30、CD38、CD43、CD56、CD68、CD79、CD99、CyclinD1、EMA、TdT与EBV潜伏膜蛋白(LMP-1),原位杂交技术标记EBV编码的RNA(EBER).按照2008年WHO淋巴造血系统肿瘤分类标准对存档的438例淋巴瘤组织标本重新分类.结果 在B细胞非霍奇金淋巴瘤(B-NHL)、NK/T细胞淋巴瘤和霍奇金淋巴瘤(HL)中EBER阳性率分别是5.4％(14/261)、16.5％(19/115)和59.7％(37/62),LMP-1阳性率分别为5.4％(14/261)、5.2％(6/115)和59.7％(37/62).弥漫大B细胞淋巴瘤(DLBCL)患者中,EBER在60岁以上组中的阳性率(13.2％,7/53)明显高于60岁及以下组(1.2％,1/81)(P＜0.05);在NK/T细胞淋巴瘤中LMP-1蛋白表达与EBER表达具有不一致性,EBER阳性率明显高于LMP-1(P＜0.05);5例鼻型NK/T细胞淋巴瘤中全部表达EBER;在HL淋巴瘤中LMP-1蛋白表达与EBER表达具有一致性.结论 EBV感染与淋巴瘤类型相关,EBV在鼻型NK/T细胞淋巴瘤中表达率高,HL次之.鉴于EBER与LMP-1在HL中的一致性表达,出于经济学考虑,LMP-1可代替EBER用作EBV的检测.EBV可能在鼻型NK/T细胞淋巴瘤、HL等的发生、发展中有重要作用.     

Epstein-Barr virus at 50——future perspectives

The special November and December issues of the Chinese Journal of Cancer celebrate the 50th anniversary of the discovery of Epstein-Barr virus（EBV） with a series of reviews covering the association of the virus with various cancers, with special emphasis on the role of EBV in the pathogenesis of nasopharyngeal cancer（NPC）. The restricted geographic prevalence of NPC along with the tumor＇s consistent association with EBV infection has fascinated scientists and clinicians ever since it was first suggested in 1966. As in all cancers, NPC development reflects the complex interplay between host genes and environmental factors, but the essential role of EBV infection provides important insight into the etiology of this tumor. Indeed, it is this understanding that is now translating into exciting diagnostic and therapeutic opportunities.     

EB病毒与淋巴瘤

越来越多的研究发现,EB病毒(EBV)感染与淋巴瘤的发生、发展、治疗及预后有着密切关系.EBV阳性淋巴瘤的治疗主要以放化疗为基础,应用更昔洛韦、阿昔洛韦等核苷类抗病毒药物.近年新的治疗方法也不断涌现,如CDTO单克隆抗体、丁酸盐等,而预防EBV感染的惟一途径是接种抗病毒疫苗.EBV阳性淋巴瘤的标准治疗尚待进一步深入研究...     

山西省雁同地区鼻咽部淋巴瘤的特点及与EB病毒相关性

目的：探讨山西省雁同地区鼻咽部淋巴瘤的特点及其与EB病毒相关性。方法：用免疫组织化学(LSAB)法及EB病毒寡核苷酸探针(EBER)原住杂交，检测30例在当地生活10a以上的鼻咽部淋巴瘤肿瘤细胞的免疫表型及EBV感染情况，分析其特点及与EB病毒的关系。采用χ^2检验和t检验进行统计学处理。结果：经免疫组化证实，30例中，27例为T细胞性淋巴瘤(90％)。3例为B细胞性淋巴瘤(10％)，EBV-EBER原住杂交，T细胞性淋巴瘤均为阳性，B细胞性淋巴瘤均为阴性。结论：山西省雁同地区鼻咽部淋巴瘤患者绝大多数为T细胞性淋巴瘤。根据其细胞形态特点，来判断T细胞性淋巴瘤，与免疫组化对照符合率为76．6％(23／30)，正确率较高。可作为基层医院防止对鼻咽部淋巴瘤漏诊的一个方法。鼻咽部T细胞性淋巴瘤与EBV显著相关。     

Epstein-Barr Virus-Associated Hemophagocytic Syndrome

A virus-associated hemophagocytic syndrome (VAHS) is a non-neoplastic, generalized histiocytic proliferation with prominent hemophagocytosis associated with a systemic viral infection. Epstein-Barr virus (EBV) is one candidate for this association but serologic and molecular biologic studies have been lacking in many cases. Although VAHS is generally a benign process, EBV-associated hemophagocytic syndrome (EBV-AHS) is often fatal and has a relatively high mortality rate. Therefore, EBV-AHS must be distinguished from VAHS caused by other viruses. Recent evidence indicates that the pathophysiology in EBV-AHS appears to be mediated by the unrestricted release of cytokines produced by the EBV-infected T cells. Clinical and laboratory findings, the differential diagnosis, virology studies, pathophysiology, and treatment in EBV-AHS are reviewed.     

肺癌患者咽部、血液、癌组织EB病毒感染及其关系初探

目的:探讨肺癌患者咽部分泌物、血液及癌组织中EB病毒感染情况与肺癌的关系.方法:应用PCR技术和ELISA法对采自30例进展期肺癌患者的咽部分泌物、血液及新鲜肺癌组织标本进行EB病毒检测.结果:肺癌患者咽部分泌物EB病毒感染率低,差异无显著性(P＞0.05);血液EB病毒VCA-IgG抗体高于非癌胸疾病患者(P＜0.01);癌组织中EB病毒感染率为43.3%;不同病理类型肺癌EB病毒感染率差异无显著性;肺癌患者癌组织EB病毒感染率与血液EB病毒VCA-IgG抗体之间呈中度相关.结论:肺癌患者血液及癌组织中EB病毒感染存在增高现象,EB病毒长期感染与肺癌关系密切.     

六种抗EB病毒抗体检测在鼻咽癌血清学诊断中的比较

目的:评估EBNA1-IgA,EBNA1-IgG,Zta-IgA,Zta-IgG,VCA-p18-IgA和VCA-p18-IgG六种酶联免疫吸附检测(ELISA)在血清学诊断鼻咽癌中的应用,探讨哪种ELISA组合更有功效.方法:收集85例治疗前鼻咽癌患者和132例健康成人血清.应用六种EB病毒特异性重组融合蛋白ELISA,检测血清抗EB病毒的抗体水平.采用灵敏度、特异度、优势比等参数来评估它们在诊断鼻咽癌中的效率.结果:单独采用一种检测时,Zta-IgG和EBNA1-IgA的灵敏度与特异度均可达0.8106以上.Zta-IgG/EBNA1-IgG和Zta-IgG/EBNA1-IgA两种检测双阳性的特异度提高至0.9621以上.Zta-IgG/EBNA1-IgA/EBNA1-IgG或Zta-IgG/EBNA1-IgG/Zta-IgA三种检测均阳性者,其特异度不仅可达0.9824,优势比也明显升高(分别为206.4242和196.5000).85例患者血清中无1例同时呈Zta-IgG/EBNA1-IgA/EBNA1-IgG阴性者.结论:临床血清学诊断鼻咽癌,首选Zta-IgG或EBNA1-IgA.同时检测两种ELISA,宜采用Zta-IgG/EBNA1-IgA或Zta-IgG/EBNA1-IgG.三种ELISA同时检测,可以提高特异度.推荐Zta-IgG/EBNA1-IgA/EBNA1-IgG或Zta-IgG/EBNA1-IgG/Zta-IgA三项.     

EB病毒相关微小RNA与淋巴瘤调控机制的研究进展

EB病毒（EBV）与淋巴瘤的发生、发展密切相关,其发病机制仍不甚明了.微小RNA（miRNA）对EBV感染相关淋巴瘤的调控作用逐渐被认识,文章就EBV相关miRNA在淋巴瘤中发病机制的研究进展进行综述.     

Frequent association of Epstein-Barr virus in Japanese patients with Burkitt's lymphoma.

Seven Japanese patients with Burkitt's lymphoma (BL), residing in Hokkaido, were studied during the period, 1979-1991. Immunological analyses of their lymphoma cells showed all to express surface and/or cytoplasmic immunoglobulins. Chromosomal analysis was performed in five cases. Four of the five lymphomas had the chromosomal translocation, t(8;14), and one had t(2;8). Three patients had extremely high IgG antibody titers to Epstein-Barr virus (EBV) viral capsid antigen (VCA) and to EBV early antigens (EA). Two patients had positive antibodies to EA, and two others had normal antibody patterns comparable to those of EBV-seropositive age- and sex-matched healthy controls. Four of the seven lymphomas (57.1%) were positive for EBV-determined nuclear antigen (EBNA) by anticomplement immunofluorescence and/or EBV DNA using DNA-DNA reassociation kinetics, and/or Southern blot analysis. The frequency of EBV positivity in BL patients residing in Hokkaido was higher than that of cases previously reported in Japan. Three of the four EBV genome-positive BL patients responded well to chemotherapy, radiotherapy and/or surgical treatment, with no significant relapse being observed during the study period. In contrast, EBV genome-negative patients had poor prognoses despite having similar levels of clinical staging at the time of diagnosis.     

Epstein-Barr virus and gastric carcinoma

Received for publication on Jun. 1, 1998; accepted on Sept. 3, 1998     

V-val突变型EB病毒核抗原1的功能研究

背景与目的:EB病毒核抗原1(Epstein-Barr viral nuclear antigen 1,EBNA 1)对于维持EB病毒的潜伏感染有重要作用。V-val变异型的EBNA1与鼻咽癌有密切的相关性。本研究旨在比较原型和V-val变异型的EBNA1基因在上皮细胞中的功能的差异。方法:用PCR方法扩增出原型和V-val变异型EBNA1基因的全长并克隆到pGFP载体上,转染HEK293细胞,检测两种亚型的EBNA1蛋白的表达对细胞生物学性状的影响。以含有EB病毒增强子FR序列的荧光素酶载体作为报告基因,比较两种亚型的EBNA1基因对质粒的转录激活能力。结果:原型和V-val变异型EBNA1基因的表达对HEK293细胞的生长速度没有明显影响,但表达原型EBNA1的细胞的克隆形成能力明显低于V-val亚型。在裸鼠致瘤实验中,接种表达原型和V-val变异型EBNA1细胞的实验组均未见肿瘤形成。但是在瞬时转染实验中,表达V-val变异型EBNA1基因的HEK293细胞的荧光素酶活性明显高于原型EBNA1基因。结论:原型和变异型EBNA1均未发现有明显的转化细胞的能力,但是V-val变异型EBNA1蛋白与原型相比,其转录激活的功能明显增强。     

EBER Gene Expression in Epstein-Barr Virus-Associated Hematopoietic Neoplasms

Epstein-Barr virus encoded RNA's (EBER) are small RNA species found in cells latently infected by the virus. The physiological function of these molecules is currently a matter of speculation. Nonetheless, their presence in extremely high copy number has made it possible to reliably detect the Epstein-Barr virus by in-situ hybridization, in human tissues routinely fixed with formalin and embedded in paraffin. Such studies have enhanced our understanding of a number of hematologic malignancies, particularly Hodgkin's disease, angiocentric im-munoproliferative lesions and angio-immunoblastic lymphadenopathy. In addition, sequential EBER in-situ hybridization studies on lymphoid tissues should enable oncologists to monitor the development of lymphoproliferative disorders occurring in the setting of organ transplantation, AIDS and hereditary immunodeficiencies.     

成年人慢性活动性EB病毒感染相关T细胞淋巴瘤合并噬血细胞综合征一例并文献复习

目的:探讨慢性活动性EB病毒感染（CAEBV）患者的病理变化机制。方法:回顾性分析苏州弘慈血液病医院确诊的1例CAEBV相关T细胞淋巴瘤合并噬血细胞综合征患者的临床表现、实验室检查及诊治经过,并进行相关文献复习。结果:结合不同时期实验室、淋巴结活组织检查及骨髓等检测结果,患者初期表现为淋巴组织增殖性疾病,逐步转变成淋巴瘤,具有不同时期EB病毒相关淋巴细胞克隆表现的诊断结果。患者在不同时期接受相应方案治疗,但最终因合并噬血细胞综合征且病情进展迅速死亡。结论:CAEBV可能导致淋巴细胞由多克隆状态向单克隆逐步演变。     

Polyclonal Bence Jones Proteinuria Associated with Reactive Plasmacytosis

A 43 year old black male patient presented with progressive respiratory symptoms, fever and malaise of short duration accompanied by mild epistaxis. Physical examination revealed generalised lymphadenopathy and hepatosplenomegaly. Peripheral blood examination showed a striking plasmacytosis. Further investigation revealed Bence Jones proteinuria consisting of both kappa and lambda light chains. There was no monoclonal peak on serum electrophoresis and cytoplasmic immunoglobulin and gene rearrangement studies on the peripheral blood plasma cells demonstrated polyclonality. The possible role of Epstein-Barr virus in stimulating B cell proliferation in this case is discussed.     

涎腺淋巴上皮癌的治疗现状研究进展

涎腺淋巴上皮癌是一种伴有淋巴间质浸润的未分化癌,发病率低,其发病与EB病毒感染、免疫反应、良性淋巴上皮病变等因素有关。近年来研究证实,涎腺淋巴上皮癌是一种放射治疗敏感肿瘤,手术联合术后放射治疗为本病治疗的常用模式,获得了良好的局部控制率及无病生存率。     

血浆EB病毒DNA检测在鼻咽癌中的应用进展

EB病毒(Epstein-Barr virus,EBV)与鼻咽癌的发生、发展密切相关,采用PCR方法对鼻咽癌患者不同阶段的血浆EB病毒DNA (EBV DNA)进行定量检测可有效评估患者对治疗的反应,预测复发、转移的风险,治疗前的EBV DNA基线浓度与肿瘤负荷密切相关,而治疗后的EBV DNA含量与肿瘤复发转移关系更密切.EBV DNA定量检测有望成为一种新的肿瘤预后指标.本文就鼻咽癌患者不同时期的EBV DNA水平在诊断、分期、疗效评估和预后预测中的应用进行综述.     

EB病毒与乳腺癌的相关性研究进展

乳腺癌的病因尚未明确,已知的危险因素包括生殖因素、影响体内性激素水平因素和遗传易感因素,但这些因素也只能解释约50%腺癌病例。近年来有研究试图从病毒感染的角度探讨乳腺癌的病因,EB病毒（Epstein—Barrvirus,EBV）正是研究热点之一。但EBV与乳腺癌的关系仍存在着很大的争议。本文就EBV生物学特点、EBV与乳腺癌的相关性研究（包括癌组织中的EBV检测、血清学研究、细胞学实验和临床特点分析）作一综述,并提出目前存在的问题和今后研究的方向。