Cyclin D1与p21WAF1在鼻咽癌中的表达

目的探讨鼻咽上皮癌变过程中周期蛋白CyclinD1与抑癌基因p21（wild—type p53 activated fragment 1,p21wAF1）蛋白的表达及其意义。方法应用免疫组化方法检测47例鼻咽癌组织、21例癌旁上皮组织和14例正常鼻咽粘膜中Cyclin D1与p21WAF1蛋白表达。结果从鼻咽正常粘膜、癌旁粘膜上皮组织到癌组织,Cyclin D1表达阳性率逐渐增加,并且差异有显著意义（均为P〈0．05）。p21WAF1蛋白在以上组织中阳性率较高,且各组间差异无显著性。结论Cyclin D1、p21WAF1蛋白与鼻咽部上皮细胞恶性增生密切相关,p21wA兀蛋白表达可能与细胞周期调控的反馈机制有关。     

Cloning of a novel gene associated with human nasopharyngeal carcinoma

One EST N27741 with high expression in normal adult nasopharynx tissues but low expression in adult poorly differentiated squamous nasopharyngeal carcinoma has been selected out by the high-density cDNA array expression profiling technique. The differential expression has been confirmed by RT-PCR. One novel gene of 1096 bp has been cloned based on this EST. Bioinformatics analysis found that the new gene sequence contains a whole reading frame encoding 256 amino acids. There is a stop codon TAA in front of the 5′ end start codon, and a tailing signal AATAAA and poly A tail at the 3′ end. There is no homologous known gene found after searching by blasting this sequence to non-redundancy nucleotide database. Therefore it is considered a novel gene related to nasopharyngeal carcinoma.     

干扰长链非编码RNA Z38表达对鼻咽癌细胞增殖的影响

新型的长链非编码RNA Z38已证实高表达于肿瘤组织,低表达于癌旁组织,属于癌基因,但其功能和作用机制尚需深入分析。研究目的在于探讨稳定干扰长非编码RNA Z38对鼻咽癌细胞HNE1、5-8F功能和机制的影响。采用慢病毒包埋Z38-shRNA转染进人鼻咽癌细胞HNE1与5-8F,用嘌呤霉素筛选出稳定的干扰细胞系,利用相对实时荧光定量的方法检测干扰效率;使用MTT、和平板克隆集落形成实验验证其对HNE1、5-8F细胞增殖的抑制作用;Transwell检测细胞迁移的能力;采用Western Blot检测干扰Z38表达对抑癌因子P~(53)、P~(21)表达水平的影响。结果表明,慢病毒干扰鼻咽癌细胞显著降低了Z38基因表达水平,并且干扰Z38基因表达后使细胞增殖能力、细胞集落形成能力降低,穿过Transwell小室的细胞数降低,抑癌因子P~(53)、P~(21)表达量上调。由此推测,Z38基因可能为鼻咽癌细胞的癌基因之一。     

Protection of cottontop tamarins against Epstein-Barr virus-induced malignant lymphoma by a prototype subunit vaccine

Epstein-Barr (EB) virus is one of the five herpesviruses of man. Strong links between this agent and the chain of events causing two human cancers, endemic Burkitt's lymphoma and undifferentiated nasopharyngeal carcinoma, have long been evident (reviewed in ref. 1). Because of this, and because of the very high incidence of nasopharyngeal carcinoma in certain large populations, it was suggested in 1976 that a vaccine should be developed against EB virus to prevent infection and thereby reduce tumour incidence amongst those at risk. The virus-determined membrane antigen (MA) was proposed as immunogen because it was known to elicit naturally occurring virus-neutralizing antibodies in man and because analogous antigens had been shown to act as effective experimental vaccines for preventing the herpesvirus-induced lymphomas of Marek's disease in chickens. Progress has been achieved in defining, quantifying and preparing MA molecules, and in enhancing their immunogenicity; a sensitive assay for antibodies to MA has been elaborated. Here we report that isolated cell membranes expressing MA, or purified MA glycoprotein of relative molecular mass (Mr) 340,000 (gp340), have been used to vaccinate cottontop tamarins (Saguinus oedipus oedipus), and that animals receiving either preparation were protected against the effects of a 100% tumour-inducing challenge dose of EB virus.     

HLA DRB1＊1501和DQB1＊0602与新疆维吾尔、汉族HPV感染及宫颈癌发生的相关性

探讨HLADRB1＊1501和DQB1＊0602与新疆维吾尔、汉族妇女HPV感染及宫颈癌发生的相关性。PCR-SSP和PCR检测287例浸润性宫颈癌（维族192例,汉族95例）及297例正常宫颈组织（维族203例,汉族94例）中DRB1＊1501和HLADQB1＊0602的分布频率和HPV16DNA。维族HPV16阳性NILM组中DRB1＊1501基因频率高于HPV16阴性NILM组（OR,2．222;95％CI,1．107—4．461;P=0．023）,差异有统计学意义;在维族ISCC组及HPV16阳性ISCC组中DQB1＊0602基因频率均低于对照组（OR,0．484;95％CI,0．324～0．722;P=0．000;OR,0．552;95％CI,0．360～0．845;P=0．006）,差异有统计学意义;汉族ISCC组中DRBl。1501等位基因及DRB1＊1501～DQB1＊0602单体型均低于对照组（分别为OR,0．305;95％CI,0．115～0．813;P=0．013和OR,0．274;95％CI,0．086—0．874;P=0．021）,差异有统计学意义。携带DRB1＊1501等位基因为新疆维族妇女HPV16易感基因。DQB1＊0602基因可能是新疆维族妇女宫颈癌的保护基因,而DRB1＊1501基因及DRB1＊1501～DQB1＊0602单体型则可能是新疆汉族妇女宫颈癌的保护基因。     

Different amino acids at position 57 of the HLA-DQ beta chain associated with susceptibility and resistance to IgA deficiency

The human leukocyte antigens (HLA) are implicated in the genetic susceptibility to a large number of diseases. Some of the diseases associated with HLA class II are related to specific amino acids or epitopes of the domain of the HLA class II molecule that is distal to the membrane. In man, selective immunoglobulin A deficiency is the most common immunodeficiency, frequently resulting in recurrent sino-pulmonary infections and gastro-intestinal disorders. Associations have been described with HLA class I, and to a lesser extent with different class II alleles, which might indicate that they share some common feature. Here we study 95 IgA-D patients and find positive associations with three DR-DQ haplotypes and a strong negative association with a fourth haplotype. Comparison of the sequences of the polymorphic amino-terminal domain of the DQ beta chain showed that the three 'susceptibility' haplotypes all had a neutral alanine or valine at position 57. The 'protective' allele had the negatively charged aspartic acid at this position (Asp57). Codon 57 of the HLA-DQ beta chain has been implicated in the susceptibility to insulin-dependent diabetes mellitus. Our data suggest that the same amino acid position could possibly also influence susceptibility and resistance to selective immunoglobulin A deficiency.     

千伏级锥形束CT在摆位误差对鼻咽癌放疗剂量分布影响中的应用探讨

目的：探讨千伏级锥形束CT在鼻咽癌调强放射治疗中摆位误差的监测及分析鼻咽癌（NPC）调强放射治疗（IMRT）中误差对靶区和危及器官物理剂量学的影响。方法：随机抽取鼻咽癌患者5例。应用医科达Synergy肿瘤治疗系统IGRT-CBCT（Conebeam CT,CBCT）,每次照射钱获取X线容积图像（XVI）,将CBCT图像与计划CT图像靶中心匹配。获得x（左右）、y（头脚）、z（腹背）方向误差,并通过Pinnacle治疗计划系统研究误差在鼻咽癌放疗中对剂量分布的影响。结果：系统误差（均数）±随机误差（标准差）在x、y、z方向分别为（-0．55±1．14）mm、（-0．20±2．52）mm、（-0．56士1．18）mm,GTVnd总剂量变化范围0．29—11．54％,GTVnx为-0．27～0．54％,左晶体为-11．95～0．10％,右晶体为-18．27— -0．04％,脊髓为-0．15～8．35％,脑干为-5．50—6．15％。结论：鼻咽癌IMRT具有一定程度的摆位误差。在KV—CBCT系统下进行实时摆位误差纠正,可进一步降低摆位系统误差和随机误差,提高摆位精度。并提高靶区及周围器官所受计量的准确性。     

鼻咽癌定位分光系统荧光光谱信号扫描控制

利用激光诱导荧光技术开发了用于早期鼻咽癌药物荧光光谱诊断和定位系统,重点讨论系统中荧光光谱定位分光系统的组成及其荧光光谱信号的扫描控制方法.实验结果表明:系统不仅满足对荧光光谱信号分光精度和采集密度的要求,而且提高了信号的信噪比,为药物荧光光谱技术检测和定位早期鼻咽癌提供了可靠的技术支持.     

Functional epistasis on a common MHC haplotype associated with multiple sclerosis

Genes in the major histocompatibility complex (MHC) encode proteins important in activating antigen-specific immune responses. Alleles at adjacent MHC loci are often in strong linkage disequilibrium; however, little is known about the mechanisms responsible for this linkage disequilibrium. Here we report that the human MHC HLA-DR2 haplotype, which predisposes to multiple sclerosis, shows more extensive linkage disequilibrium than other common caucasian HLA haplotypes in the DR region and thus seems likely to have been maintained through positive selection. Characterization of two multiple-sclerosis-associated HLA-DR alleles at separate loci by a functional assay in humanized mice indicates that the linkage disequilibrium between the two alleles may be due to a functional epistatic interaction, whereby one allele modifies the T-cell response activated by the second allele through activation-induced cell death. This functional epistasis is associated with a milder form of multiple-sclerosis-like disease. Such epistatic interaction might prove to be an important general mechanism for modifying exuberant immune responses that are deleterious to the host and could also help to explain the strong linkage disequilibrium in this and perhaps other HLA haplotypes.     

妊娠相关性鼻咽癌预后研究进展

妊娠相关性鼻咽癌(Pregnancy-Associated Nasopharyngeal Cancer, PANPC)是一种更为罕见的、特殊类型的鼻咽癌(Nasopharyngeal Cancer, NPC),其治疗模式通常参照非妊娠相关的成人鼻咽癌治疗指南。妊娠期间体内代谢状态复杂,常规治疗模式下,妊娠相关性鼻咽癌患者的预后是否有别于非妊娠相关性鼻咽癌患者,其治疗策略是否应有所不同,目前关于妊娠相关性鼻咽癌患者预后的研究报道不多且结论不一,本文就此作归纳总结,以供临床参考。     

抑癌基因ING1在鼻咽癌中的表达及突变分析

本研究运用免疫组化技术、逆转录 - PCR( RT- PCR) ,PCR- SS-CP技术对鼻咽癌组织及鼻咽癌细胞系中 ING1的表达和突变进行检测 .结果发现 3 0例鼻咽癌标本中 ING1蛋白表达下调率为 70 % ( 2 1/ 3 0 ) ;ING1m RNA表达明显下调率为 4 6% ( 12 / 2 6) ,6例鼻咽癌细胞系中有 2例鼻咽癌细胞系表达明显下调 ,而 11例 ( 4 2 .5 % ) NPC组织及其它 4例细胞系表达与正常水平相当 ,另有 3例 ( 11.5 % )鼻咽癌组织过表达 ;单链构像多态性分析 ( SSCP)在鼻咽癌及鼻咽癌细胞系中均未发现突变 .结果表明ING1基因的转录及翻译表达水平与鼻咽癌的发生 /发展呈负相关 ,该基因的异常表达是鼻咽癌发生中的频发事件而与基因突变无关     

腺病毒介导人MDA-7/IL-24基因对人鼻咽癌细胞CNE的凋亡作用

mda-7(melanoma differentiaton-associated gene 7,黑色素瘤分化相关基因7),其表达产物又称 IL-24(Interleukin-24,白介素24),现有实验证明其对多种肿瘤细胞有明显的生长抑制和凋亡诱导作用,具有广泛的癌症治疗前景和预期.鼻咽癌作为中国南方多发的癌症,目前少有mda-7对其凋亡作用的研究,本实验利用腺病毒载体(复制缺陷型)构建搭载mda-7的重组病毒Ad-mda7及空病毒Ad-GFP,用HEK 293T细胞对病毒进行扩增,得到的重组病毒用于人鼻咽癌细胞CNE的凋亡研究.Hoechst 33258凋亡染色以及流式细胞仪PI染色检测结果表明:重组病毒Ad-mda7相比空病毒Ad-GFP以及PBS处理组,对CNE细胞有较明显的凋亡诱导作用.     

Monitoring p21 mRNA expression in living cell based on molecular beacon fluorescence increasing rate

Studying the expression level of mRNA in living cells will offer tremendous opportunities for advancement in cell biology research, disease diagnostics, and drug discovery. In this paper, a molecular beacon （MB） specific for the important tumor suppressor gene p21 has been designed and synthesized. The fluorescence signal was detected in real-time after the MB entered the cytoplasm of nasopharyngeal carcinoma cells. After injecting the p21MB into nasopharyngeal carcinoma cell and p33-transfected nasopharyngeal carcinoma cell, the consistent increase of fluorescent signal intensity was detected in both cell lines, and maximum fluorescence intensity achieved in about 15 min. In about 4 min following microinjection, the fluorescence increasing rate was significantly different between these two cell lines, which indicate the different p21 mRNA expression levels. The results obtained in the real-time detection were also validated by RT-PCR. Analysis of the initial fluorescence increasing rate can efficiently reduce the side effect of enzyme and improve the accuracy in living cell mRNA detection.     

微量元素多变量分析辅助诊断鼻咽癌

以鼻咽癌患才和对照组的64例样本的微量元素含量及其比值作为多元统计分析，建立判别方程、回归方程和主成分方程。应用所建立的方程对64个训练样本进行判别分类，分类准确率为94％。此方法可应用于临床作为鼻咽癌的辅助诊断。     

鼻咽癌定位分光系统光电信号处理技术初步研究

利用激光诱导荧光技术开发了用于早期鼻咽癌药物荧光光谱诊断和定位系统，文中重点讨论了系统重要组成部分之一的荧光光谱定位分光系统的组成及其光电信号的处理技术，其中包括荧光光谱信号的分光和处理技术．实验结果表明：系统不仅满足对荧光光谱信号分光精度和采集密度的要求，而且提高了信号的信噪比，为药物荧光光谱技术检测和定位早期鼻咽癌提供了可靠的技术支持．     

HIV in Africa (Communication arising): chemokine-receptor genes and AIDS risk

Schliekelman et al. have provided a model to quantify the speed at which HIV-resistance haplotypes can become enriched in a susceptible population through a delay in the onset of AIDS, permitting greater lifetime reproduction and the selection of AIDS-delaying haplotypes. But we question their conclusion that there could be a rapid evolution of resistance to AIDS onset in some African populations if the current HIV epidemic persists, as this depends on an untested assumption: that variant forms of the chemokine-receptor-5 (CCR5) gene impart selective advantages or disadvantages in Africa that are comparable to those reported for African Americans. Here we test this premise in a large Ugandan population, and find that CCR5 variants are not associated with HIV/AIDS disease risk in Africa--the origin and centre of the current AIDS pandemic. This gene may therefore not be subject to rapid evolutionary change as a result of the HIV epidemic in Africa.     

VEGF及其受体与鼻咽癌的关系

VEGF是新生血管形成的主要促进因子,鼻咽癌细胞的生长及转移与VEGF的产生及VEGFR的特异性激活密切相关。现综述近年来有关VEGF、VEGFR与鼻咽癌关系,以及VEGF、VEGFR抑制剂在鼻咽癌治疗中应用的研究进展。     

Polymorphism of human Ia antigens generated by reciprocal intergenic exchange between two DR beta loci

Class II molecules encoded by the human major histocompatibility complex (MHC) are involved in regulating T-cell response to antigens. The mechanisms for generating polymorphism in products of the MHC have been studied extensively for both the murine H-2 and the human HLA complex. Such studies indicate that point mutations plus selection have a major role in the generation of polymorphisms of class I and class II MHC genes. However, a non-reciprocal gene conversion mechanism has been proposed to explain several examples of clustered sequence variation in MHC genes. In all these examples, the proposed gene conversion event is unidirectional; that is, one of the two interacting genes acts as sequence donor and the other as sequence recipient. No examples of potential reciprocal genetic exchange (as occurs in the fungal system), in which the two interacting genes act as both donor and recipient of gene fragments, have been found in the MHC system or in other multigene families of higher organisms. We sequenced two different HLA-DR beta complementary DNAs from each of two different cells all expressing the same serologically defined determinant (DR2) but different T-cell-recognized (Dw) specificities (Dw12 and MN2). Sequence comparisons of these four cDNA clones (and two DR beta amino-acid sequences from the DR2-Dw2 subtype) suggest that new coding sequences for DR beta molecules in the DR2 haplotypes are potentially generated by reciprocal intergenic exchange.     

鼻咽癌旁原位癌的病理学研究

作者采用组织学、显微镜光度计和免疫组织化学的方法,描述了鼻咽癌旁原位癌的组织病理学特征及其在肿瘤组织发生和演进中的作用. 作者将鼻咽癌旁原位癌分为柱状和鳞状两型,比较了它们各自的组织学和细胞学特点. 本文认为:在浸润性鼻咽癌出现之前已经发生了一系列的改变,而原位癌则是癌症的组织发生和肿瘤演进过程中关键性的一步.已呈异型性改变的储备细胞或未分化中间细胞恶变为原位癌细胞;然后在未知因素的影响下,原位癌细胞呈侵袭性而形成浸润性鼻咽癌.