细胞色素P450 CYP1A1基因多态与鼻咽癌易感性的关联分析

Objective To investigate the association between CYP1A1 gene polymorphisms and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families through family-based association study. Methods A total of 457 Cantonese nuclear families, consisting of 2134 members, were recruited as subjects. Each family included two parents and at least one offspring with nasopharyngeal carcinoma. Two single nucleotide polymorphisms (SNP) in CYP1A1 named m1 (rs4646903) and m2 (rs1048943) , were genotyped by PCR-RFLP assay and verified by directly sequencing. The genotype data were analyzed with family-based association test (FBAT) software to check the linkage and association between the two genetic markers and susceptibility of nasopharyngeal carcinoma. Results FBAT analysis showed that the minor allele frequencies (MAF) of the two SN P were 0. 442 (C) and 0. 339 (G) respectively. For m1 polymorphism in CYP1A1 gene was not significantly associated with nasopharyngeal carcinoma in our study population whether stratified with VCA-IgA or not (without stratification : X2=2. 399, P=0. 301 ; with stratification : Iow-titer group (VCA-IgA<1 : 80), MAF=0. 457 (C), X2=1.221, P=0.543 ; high-titer group (VCA-IgA ≥1 : 80), MAF=0. 427 (C), X2=2. 832, P=0. 243). For m2 polymorphism, when VCA-IgA<1 : 80, the G allele showed decreased transmission under additive and dominant model (MAF=0. 347 (G) ; Zadditive=-2. 120,Padditive=0. 034;Zdominant=-2. 303,Pdominant=0.021)and a boundary P value was got with global statistic (X2=5. 394, P=0. 067). Haplotype TG (0. 057), constructed by ml and m2, might decrease nasophargneal carcinoma risk (Z=-2. 002,P=0. 045). A boundary P value was also got with global statistic (X2=7. 067 ,P=0. 070). Conclusion There was no statistical significance between ml polymorphism and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families. And this study showed that m2 polymorphism might associated with the decrease of nasopharyngeal carcinoma in Cantonese nuclear families.     

肿瘤生物治疗研究进展--2000年ASCO会议综述之二

今年的ASCO会议上肿瘤生物治疗(含基因治疗)领域的进展没有太大变化.如顾健人教授所言,我们已进入了一个比较理性的时代,大家都以一种更加务实、更加谨慎和更加深入的态度在积极地探索.一个值得注意的趋势是大家逐渐认同这样一种看法:肿瘤,特别是晚期肿瘤,是一种复杂的多因素疾病,在目前必须依赖于综合治疗,而生物治疗在多种手段的综合治疗中可以起到基础性作用.这种观点可以从大会所收集的100多份报告中明显地体现出来.现将报道较多的一些生物治疗领域的热点内容作以简单概括.     

分枝杆菌的质粒提取及电镜鉴定

经L型诱导的分枝杆菌,以稍加修改的碱性裂解法提取其质粒,从8株菌株中获得3个质粒,并经电子显微镜观察予以证实,它们的大小分别约为21kb、11kb和6.5kb。进一步的分析未能发现它们的存在与携带菌抗药性和菌落形态有明确的关系。     

肿瘤干细胞相关研究进展

近年来的研究表明,肿瘤干细胞(TSC)存在于多种肿瘤组织中,占肿瘤细胞总数的很少一部分,具有自我更新能力,能够分化为表型不一致的肿瘤细胞,并且对放化疗不敏感。当多数的肿瘤细胞被消灭后,TSC仍能使肿瘤复发。研究人员已经在血液系统肿瘤以及部分实体肿瘤中分离鉴定到了TSC的存在。这些研究将为人们制定新的治疗方案,研制有效的靶向治疗药物等提供新的突破口。     

"健康中国2020"卫生筹资总体方案阶段性目标预测与政策选择

以我国未来经济发展水平、人口规模和财政支出等数据为基础，对“健康中国2020”卫生筹资总体方案各项指标值进行预测．为我国卫生筹资改革提供清晰的阶段性目标。同时，对卫生筹资总体方案实现所面临的挑战等问题进行分析并提出政策建议。     

ASSOCIATION OF pIgR POLYMORPHISMS WITH NASOPHARYNGEAL CARCINOMA

Objective： Epstein-Barr virus （EBV） associated nasopharyngeal carcinoma （NPC） is an important squamous cell cancer endemic in southern China and Southeast Asia. pIgR （polymeric immunoglobulin receptor） gene plays central roles during immune responses and EBV inflammatory and therefore is a good candidate susceptibility gene for NPC. This study is to evaluated potential associations between pIgR gene and NPC susceptibility. Methods： Sequencing was used to identify multiple single nucleotide polymorphisms （SNPs） within the exon regions of pIgR in Guangdong population. Four SNPs were genotyped in 528 NPC patients and 408 normal individuals to perform case-control study. Results： There was no statistical difference in the allele frequencies of each SNP （P〉0.05）. After categorized into 2 groups by age of 45 y, in the group of age below 45 the minor allele T frequency of C888oT was 7%, whereas 4% in controls, with significant difference （P〈0.05）. The Odds Ratio （OR=1.84） also showed higher risk of NPC with individuals carried the minor alleles. Conclusion： The result has proved that SNP C8880T is associated with NPC susceptibility and pIgR gene might play a certain role in oncogenesis and development of NPC.     

鼻咽癌组织中EBV—BARFO基因序列的测定

目的：EB病毒（Epsterin-Barr virus,EBV)存在的变异影响到其生物学功能（如LMP1基因）。 BanHI A 区右向框0（BamHI Arightward fram0,BARF0)是在鼻咽癌（Nasopharyngeal Carcinoma,NPC)病人中检出率很高的一个EB病毒基因,对其 变异性的研究尚未报道,本研究是为了广东鼻咽癌组织中EBV－BARF0基因的序列及其变异。方法：应用PCR技术从20例鼻咽癌组织中,扩增EBV基因BARF0,并对它们的序列进行测定。 结果：与标准株B95－8相比,鼻咽癌纺织品 EBV－BARF0均是4个位点发生空变：160473（G→T）、160701(C→ A)、160707(C→T）、160701（C→A）、160707（G→C）,并导致相应的氨基酸的改变 ：2（A→Ser)、26（Leu→Phe)、78（Arg→Phe)、78（Arg→Ser)、80（Ala→Pao)。结论：由于EBV的BARF0基因在鼻咽癌细胞株及检组织中100％表达,在淋巴瘤组织及淋巴瘤细胞株中表达较低或不表达,本研究首次报道鼻咽癌组织中EBV－BARF0的序列分析,与B95－8相比存在变异,并导致了蛋白质的一级结构的改变,推测该基因 很可能在鼻咽癌变过程中起着重要的作用。     

鼻咽癌组织差异表达cDNA序列的克隆与鉴定

目的：分析鼻咽癌组织中的差异基因,寻找与鼻咽癌病理过程相关的新的癌基因的抑癌基因。方法：应用抑制性消减杂交法,构建了鼻咽组织与正常鼻咽组织的消减库;用差异筛选技术筛选出阳性克隆;用Southern blot和Northern blot杂交证实了阳性克隆的可靠性,用序列分析确定了阳性克隆的性质。结果：从消减库中获得了12个阳性克隆;序列分析表明,8个克隆与已知基因高度同源,2个为新的候选基因,2个新的候选基因在两个不同的消减库中确实存在差异,而其中的一个新基因在鼻咽癌组织和细胞系中下调表达。结论：抑制性消减杂交是分析相关基因的较好的方法,发现了两个与鼻咽癌病理过程有关的新的cDNA。     

鼻咽癌全基因组杂合性缺失分析

目的：分析鼻咽癌（nasopharyngeal carcinoma,NPS)全基因组染色体杂合性缺失（loss of heterozygosity,LOH),定位NPC发生高频率LOH的区域,为定位NPC相关基因提供分子遗传学依据。方法：用PCR微卫星多态性分析（335个位点）技术检测98例NPC肿瘤基因组DNA等位基因缺失。结果：在22对染色体中,19对染色体在所选取位点中有至少1个位点LOH频率≥30%,3对染色体（15号,20号和22号）无LOH频率大于30%的位点;在335个位点中,4个位点LOH频率≥60%,其中3个在3号染色体,1个在9号染色体;5个位点LOH频率介于50%-59%,其中3个在3号染色体,5号和11号染色体各1个位点;22个位点LOH频率介于40%-49%,52个位点LOH频率介于30%-39%,轼52个位点LOH频率低于30%,提示为背景缺失;LOH频率≥30%的位点主要集中于12个染色体臂,分布于：1p36-34,3p24-26,3p14-21,3q25-27,4q35-31,5q15-21和5q32-33,8p22-23,9p21-23和9q33-34,11p12-14,11q13-23,13q13-14和13q31-32,14q11-13,14q23-24,14q32。本研究新报道在染色体区带1p,5q和19q等发生高频率LOH,LOH精细图谱提示这些区域内可能存在与NPC相关的TSG。结论：NPC肿瘤细胞在多染色体区带发生高频率LOH是常见的分子事件,提示在这些缺失区,可能存在与NPC发生,发展过程中起重要作用的肿瘤抑制基因。