人类巨细胞病毒与胶质瘤的关系

人类巨细胞病毒属β-疱疹病毒亚科,在人群中普遍存在.研究发现,胶质瘤组织存在人类巨细胞病毒;神经干细胞、胶质细胞易感染人类巨细胞病毒;人类巨细胞病毒可诱导细胞恶性转化和关键性细胞调控通路功能障碍,如产生免疫耐受、出现基因突变、细胞周期调控异常、细胞凋亡异常、新生血管形成,有一定致瘤性.因此,人们推测人类巨细胞病毒在胶质瘤发生、发展中可能存在作用.     

抗人巨细胞病毒免疫球蛋白G在脑胶质瘤的表达及与预后的相关性

目的:探讨抗人巨细胞病毒免疫球蛋白G（HCMV IgG）水平在脑胶质瘤的表达及与预后的相关性。方法:选择2013年1月至2017年8月在我院就诊并接受手术切除的脑胶质瘤患者作为研究对象,入组后测定患者抗HCMV IgG水平,观察抗HCMV IgG表达及水平与脑胶质瘤患者特征与预后的相关性。结果:患者抗HCMV IgG阳性表达率为76.17％。抗HCMV IgG与年龄、性别、肿瘤部位、肿瘤大小、病程、KPS评分等均无相关性（P＞0.05）,与肿瘤分级存在正相关（P＜0.05）。肿瘤分级、手术方式、替莫唑胺疗程和抗HCMV IgG表达是影响患者1年死亡率的独立预后因素（P均＜0.05）。对IgG阳性患者进一步分析显示,抗HCMV IgG＜10 U/ml患者生存期低于10～29 U/ml和≥30 U/ml患者（P＜0.05）,抗HCMV IgG≥30 U/ml患者生存期高于10～29 U/ml患者但差异无统计学意义（P＞0.05）。结论:抗HCMV IgG表达与胶质瘤恶性程度呈正相关,与生存期呈负相关,抗HCMV IgG低表达患者具有更差的预后,应引起临床关注。     

胶质瘤耐药的分子机制

恶性胶质瘤手术后化疗效果不佳，除了血-脑屏障对药物进入脑组织的阻止作用外．肿瘤细胞本身对抗肿瘤药的耐药性也是化疗失败的重要原因，体内外研究发现肿瘤耐药的分子机制很复杂，包括靶基因突变、靶基因扩增、DNA损伤修复能力差异、药物进入肿瘤细胞内浓度减少等一近年来，分子生物学研究发现，肿瘤细胞内某些基因如：MDR、MGMT、卡复苷酸切除修复（NER）、谷光甘肽-S-转移酶（GST）、蛋白激酶C（PKC）、错配修复（MMR）等的表达与否与其耐药密切相关，且对其研究有了很多新的进展。     

人巨细胞病毒（HCMV）与宫颈癌关系的研究

近年来,宫颈癌的病毒病因研究已成为宫颈癌病因研究的热点,继发现HPV与宫颈癌相关之后,人们又发现HCMV感染可能与宫颈癌的发生有关,为了进一步探讨HCMV与宫颈癌的关系,我们对宜颈疾患病人宫颈活检组织DNA进行了HCMV DNA检测,现将结果报告如下: 材料和方法一、标本采取标本为87例宫颈炎患者和54例宫颈癌患者,取宫颈活检组织,分为2份,1份10％福尔马林固定,常规组织学切片,进行     

EB病毒肿瘤相关分子机制研究进展

Epstein－Bars病理（EBV）是一种全球性分布、人群感染率颇高的DNA病毒。它能在体外特异性地感染B淋巴细胞，受染细胞可获得长期生存和增殖的能力而达到“永生化”。EBV除直接导致传染性单核细胞增多症及一些免疫缺陷者淋巴组织增生性疾病的病原体之外，它还与一些人类肿瘤如Burkitt淋巴瘤、低分化鼻咽癌及其他一些恶性淋巴瘤密切相关。EBV作为一种潜在致瘤可能的病毒正日益受到重视。近年来随着分子生物学技术的发展，EBV的遗传学特点和致病机制的认识也正渐趋深人。本文试从分子水平对这方面的研究作一综述。一、EBV的肿日相关性…     

EB病毒与鼻咽癌相关的分子机制研究进展

全文着重讨论EB病毒与鼻咽癌组织学类型及肿瘤细胞表型的关系，肿瘤组织淋巴间质的可能作用。     

大肠癌人巨细胞病毒感染与p53基因突变的相关性

尽管人巨细胞病毒（ＨＣＭＶ）感染与人类肿瘤的关系还不十分清楚,但ＨＣＭＶ感染可导致原癌基因（如ｍｙｃ基因）的表达、生长因子转录、白细胞介素合成增加,酪氨酸羟化酶、多巴胺－β－羟化酶表达减少等。还有实验证实,神经胚细胞瘤体外培养中感染ＨＣＭＶ后,增加了...     

人巨细胞病毒的癌基因mtr Ⅱ在霍奇金淋巴瘤中作用的研究进展

人巨细胞病毒（HCMV）是一种重要的肿瘤DNA病毒，在多种肿瘤致瘤中均发现与HCMV感染有关，HCMV致瘤可能是癌基因mtrⅡ通过改变抑癌基因的细胞调控机制诱导细胞恶性转化，霍奇金病（HD）中存在HCMV的感染，因此癌基因mtrⅡ可能参与了HD的发病，其机制不清，值得进一步研究。     

胶质瘤放射敏感性的分子机制研究进展

 引言对放疗敏感性分子机制方面的研究 ,可使我们不断发现新的靶基因 ,通过相应的干预措施 ,在增强放疗对肿瘤细胞杀伤作用的同时 ,减少正常组织的放射损伤 ,从而更有效的控制肿瘤。这方面的研究内容主要是寻找与放射诱导的DNA修复、放射性细胞凋亡相关的调控基因。近年来发现的与放疗敏感性密切相关的蛋白或分子 ,如细胞膜上的生长因子受体以及与信号传导、细胞周期调控有关的蛋白或基因 ,加上一些与放疗反应相关的胞外或组织因素如缺氧和血管生成情况等 ,为更好地发挥放疗在肿瘤综合治疗中的作用提供了实验理论依据[1 ] ,现将目前研究较多的相关基因综述如下 :1　ATM (Ataxia telangiectasiaMutated)基因ATM基因的命名取意于“在共济失调—毛细血管扩张症中发生突变的基因”。共济失调—毛细血管扩张症 (A T)是一种少见的基因突变性疾病 ,主要症状表现为由于神经变性引起的小脑共济失调、眼球和面部的血管扩张以及由于细胞、体液免疫缺陷引起的反复感染。除此之外 ,人们还发现本病患者的细胞对放射线高度敏感 ,且易于发生肿瘤。通过研究证实此病的发生是由于病人染色体 1 1 q2 2 2 3上的一个基因突变...     

Sensitive detection of human cytomegalovirus in tumors and peripheral blood of patients diagnosed with glioblastoma

Human cytomegalovirus (HCMV) has been described to be associated with several human malignancies, though the frequency of detection remains controversial. It is unclear whether HCMV plays an active role in malignant tumor progression or becomes reactivated under pathologic conditions that result in chronic inflammation or immunosuppression. In this study, we report on the investigation of detecting HCMV in the tumors and peripheral blood of patients with newly diagnosed glioblastoma multiforme (GBM). Using immunohistochemistry, in situ hybridization, and polymerase chain reaction amplification of viral DNA, the detection of HCMV was investigated in tumor and blood specimens from patients with GBM as well as in the peripheral blood of normal volunteers and patients undergoing craniotomy for diagnoses other than GBM. We found that a high percentage (>90%) of GBM tumors, not surrounding normal brain, are associated with HCMV nucleic acids and proteins. Furthermore, a significant proportion of patients (80%) with newly diagnosed GBM have detectable HCMV DNA in their peripheral blood, while sero-positive normal donors and other surgical patients did not exhibit detectable virus, suggesting either a systemic reactivation of HCMV within patients with GBM or shedding of viral DNA from infected tumor cells into the periphery. These results confirm the association of HCMV with malignant gliomas and demonstrate that subclinical HCMV viremia (presence of viral DNA in blood without clinical symptoms of infection) is a previously unrecognized disease spectrum in patients with GBM.     

HCMV pp65蛋白在脑胶质瘤组织中的表达及临床意义

目的:探讨人巨细胞病毒（HCMV）pp65蛋白在脑胶质瘤组织中的表达及其与肿瘤级别和预后的相关性分析。方法:采用免疫组化方法检测HCMV pp65蛋白在不同级别脑胶质瘤组织中的表达情况,并通过统计学方法分析蛋白表达情况和患者预后的关系。结果:在89例脑胶质瘤组织中,60例（67.4%）在细胞核和（或）细胞质中出现HCMV pp65蛋白阳性表达,其中18例（56.3%）为Ⅱ级星形细胞瘤、20例（64.5%）为Ⅲ级星形细胞瘤以及22例（84.6%）为胶质母细胞瘤。在10例对照脑组织标本中没有发现HCMV pp65蛋白阳性表达。我们同时发现在不同级别脑胶质瘤组织中HCMV pp65蛋白表达差异性没有统计学意义,HCMV pp65蛋白表达水平与胶质瘤患者的无进展生存期（PFS）无相关性。结论:HCMV pp65蛋白在脑胶质瘤组织中高表达,为理解胶质瘤的形成和进展机制提供理论依据。     

Molecular classification of human gliomas using matrix-based comparative genomic hybridization

Gliomas are the most frequent primary brain tumors and comprise a group of morphologically, biologically and clinically heterogeneous neoplasms. The different glioma types are associated with distinct genetic aberrations, which may provide useful information for tumor classification as well as prediction of prognosis and response to therapy. To facilitate the molecular classification of gliomas, we established a genomic microarray that consists of bacterial artificial chromosome (BAC) and P1-derived artificial chromosome (PAC) clones representing tumor suppressor genes, proto-oncogenes and chromosomal regions frequently gained or lost in gliomas. In addition, reference clones distributed evenly throughout the genome in approximately 15 Mbp intervals were spotted on the microarray. These customized microarrays were used for matrix-based comparative genomic hybridization (matrix CGH) analysis of 70 gliomas. Matrix CGH findings were validated by molecular genetic analyses of candidate genes, loss of heterozygosity studies and chromosomal CGH. Our results indicate that matrix CGH allows for the sensitive and specific detection of gene amplifications as well as low-level copy number gains and losses in clinical glioma samples. Furthermore, molecular classification based on matrix CGH data closely paralleled histological classification and was able to distinguish with few exceptions between diffuse astrocytomas and oligodendrogliomas, anaplastic astrocytomas and anaplastic oligodendrogliomas, anaplastic oligodendrogliomas and glioblastomas, as well as primary and secondary glioblastomas. Thus, matrix CGH is a powerful technique that allows for an automated genomic profiling of gliomas and represents a promising new tool for their molecular classification.     

SU11274抑制人子宫内膜癌细胞增殖的分子机制

目的:探索HGF/c-met传导通路抑制剂SU11274抑制子宫内膜癌细胞增殖的分子机制。方法:使用不同浓度SU11274（0.5 μmol/L、1.0 μmol/L、1.5 μmol/L）作用ishikawa 和HEC-1B 两种细胞株1小时后，加入40 ng/ml的HGF，继续培养48小时，然后使用RT-PCR检测c-met、Survivin、XIAP水平以及Western blot检测细胞中Survivin、XIAP蛋白表达水平。结果:ishikawa细胞c-met低表达，而HEC-1B细胞c-met明显高表达，HEC-1B细胞中c-met mRNA表达量为ishikawa中的2.5倍。SU11274可以使HEC-1B、ishikawa细胞的Survivin、XIAP蛋白表达下调，呈现剂量依赖性，并且在HEC-1B细胞中，该下调作用明显强于ishikawa细胞（P<0.05）。结论:SU11274可以通过下调HGF/c-met传导通路中Survivin、XIAP的表达来抑制人子宫内膜癌细胞增殖。     

Consensus on the role of human cytomegalovirus in glioblastoma

The human cytomegalovirus (HCMV) and glioma symposium was convened on April 17, 2011 in Washington, DC, and was attended by oncologists and virologists involved in studying the relationship between HCMV and gliomas. The purpose of the meeting was to reach a consensus on the role of HCMV in the pathology of gliomas and to clarify directions for future research. First, the group summarized data that describe how HCMV biology overlaps with the key pathways of cancer. Then, on the basis of published data and ongoing research, a consensus was reached that there is sufficient evidence to conclude that HCMV sequences and viral gene expression exist in most, if not all, malignant gliomas, that HCMV could modulate the malignant phenotype in glioblastomas by interacting with key signaling pathways; and that HCMV could serve as a novel target for a variety of therapeutic strategies. In summary, existing evidence supports an oncomodulatory role for HCMV in malignant gliomas, but future studies need to focus on determining the role of HCMV as a glioma-initiating event.     

弥漫性较低级别胶质瘤的整合性分子病理分型研究进展*

弥漫性较低级别胶质瘤包含WHOⅡ级和Ⅲ级的星形细胞瘤、少突胶质细胞瘤和少突星形细胞瘤,其临床表现具有高度可变性,目前的组织病理学无法准确地预测其预后。近年来,胶质瘤分子病理取得了重大进展,已经发现一系列与胶质瘤临床特征和预后密切相关的分子标志物如异柠檬酸脱氢酶（isocitrate dehydrogenase ,IDH ）突变、染色体1p/ 19q 共缺失、ATRX 基因突变、TERT启动子突变、MGMT 启动子甲基化等。在此基础上,结合这些分子标志物对弥漫性较低级别胶质瘤进行整合性分子病理分型的研究相继开展,且这些研究的结果一致表明,整合性分子病理分型能够更好地预测弥漫性较低级别胶质瘤的预后和指导治疗。本研究对弥漫性较低级别胶质瘤的整合性分子病理分型研究进展进行综述。      

Editor's choice: Human cytomegalovirus infection in tumor cells of the nervous system is not detectable with standardized pathologico-virological diagnostics

Background

Experimental findings have suggested that human cytomegalovirus (HCMV) infection of tumor cells may exert oncomodulatory effects that enhance tumor malignancy. However, controversial findings have been published on the presence of HCMV in malignant tumors. Here, we present the first study that systematically investigates HCMV infection in human nervous system tumors by highly sensitive immunohistochemistry in correlation with the HCMV serostatus of the patients.

Methods

Immunohistochemical and quantitative PCR-based methods to detect different HCMV antigens and genomic HCMV DNA were optimized prior to the investigation of pathological samples. Moreover, the pathological results were matched with the HCMV serostatus of the patients.

Results

HCMV immediate-early, late, and pp65 antigens could be detected in single cells from HCMV strain Hi91-infected UKF-NB-4 neuroblastoma cells after 1:1024 dilution with noninfected UKF-NB-4 cells. Genomic HCMV DNA could be detected in copy numbers as low as 430 copies/mL. However, we did not detect HCMV in tumors from a cohort of 123 glioblastoma, medulloblastoma, or neuroblastoma patients. Notably, we detected nonspecifically positive staining in tumor tissues of HCMV seropositive and seronegative glioblastoma patients. The HCMV serostatus of 67 glioblastoma patients matched the general epidemiological prevalence data for Western countries (72% of female and 57% of male glioblastoma patients were HCMV seropositive). Median survival was not significantly different in HCMV seropositive versus seronegative glioblastoma patients.

Conclusions

The prevalence of HCMV-infected tumor cells may be much lower than previously reported based on highly sensitive detection methods.     

Alteration of c-fos gene methylation in human gliomas

In an attempt to find a common DNA alteration occurring in human glioma, we examined DNA methylation in 34 gliomas of various pathological grades and compared them with those in normal cerebral subcortex DNA. The total methylated cytosine levels in the genome did not differ appreciably between the tumors and the normal tissues; however, the degree of DNA methylation in several proto-oncogenes and suppressor oncogenes showed some alterations. Among them, the c-fos gene demonstrated deviation from that of normal tissues in all cases examined, suggesting that the alteration of c-fos gene methylation plays a role in the early steps of human glioma development. © 1996 Wiley-Liss, Inc.     

The roles of CD147 in the progression of gliomas

Gliomas are characterized by their invasiveness, angiogenesis, glycolysis and poor prognosis. Determining how to inhibit angiogenesis and glycolysis and induce cell death in gliomas is essential to the development of an effective therapy. CD147, a highly glycosylated transmembrane glycoprotein with two Ig-like extracellular domains that belongs to the immunoglobulin superfamily, plays an important role in the regulation of tumor invasiveness, angiogenesis and glycolysis by inducing the secretion of matrix metalloproteinases and vascular endothelial growth factor and by interacting with monocarboxylate transporters. In this review, we first summarize the roles played by CD147 in gliomas and then propose that CD147 may be a complementary prognostic biomarker and a possible therapeutic target for glioma treatment.