平阳霉素诱导鼻咽癌患者外周血淋巴细胞染色体畸变的研究

本文分析了平阳霉素诱发的鼻咽癌患者外周血淋巴细胞染色体畸变率、断裂点的分布规律,并讨论其与EB病毒整合、原癌基因及脆性部位的关系。结果表明,鼻咽癌患者染色体畸变率明显高于对照。断裂点在1号染色体上的分布显著高于对照及预期值。断裂点与原癌基因及脆性位点的一致率显著高于对照。在鼻咽癌组所有断裂点中,1P~(32)和3P~(25)是二个高敏感点。由此看出,患者染色体诱发断裂点是非随机分布的,并优先发生在原癌基因和脆性位点     

Wilms’瘤患儿淋巴细胞染色体畸变、脆性部位和姐妹染色单体交换的观察

研究表明人类肿瘤细胞特异性染色体重排所涉及的断裂点(癌断裂点)与癌基因位点、染色体脆性部位具有高度一致性,提出脆性部位可能是人类肿瘤某些染色体重排的易发因素,并与癌基因激活有关。Wilms’瘤为小儿最常见恶性实体瘤,遗传因素对其发生可能起重要作用。本文对Wilms’瘤患儿外周血淋巴细胞染色体畸变率(Chromosome Aberration Rate,CAR)、脆性部位(Fragile Siets,Fra)及姐妹染色体单体交换(Sister Chromatid Exchanse,SCE)进行观察,探讨染色体变异与Wilms’瘤的关系及     

鼻咽癌患者染色体断裂点脆性部位与姐妹染色单体互换关系的研究

 本文通过对鼻咽癌患者染色体断裂点、脆性部位与姐妹染色单体互换关系的研究，认为鼻咽癌患者染色体畸变断裂点、脆性部位和SCE无论在发生频率，累及染色体组别，还是在发生部位上都有一定相关。基于它们都反映染色体脆性的良好指标，因此在人群中尤其在某些肿瘤高发区，癌高发家族中进行检测，可能有助于确定肿瘤的起因和易感性，对早期发现癌患者有一定参考价值。     

16例乳腺癌的细胞遗传学研究

本文对16例乳腺癌患者的肿瘤组织进行了染色体核型分析,其中12例进行了G带核型分析。结果表明乳腺癌细胞具有明显的染色体数目和结构异常。染色体数目以非整倍体为主,占81.48％。其中三倍体和四倍体数目范围最多见,其次为亚二倍体和超二倍体。染色体结构异常主要累及1,2,3,4,6和11号染色体。累及1号染色体的结构异常有6种类型,其断裂点在P~(13),q~(11—12),q~(21—22)。6号染色体异常的断裂点在6q~(22—24)。累及11号染色体的断裂点在11p~(13—15)和11q~(25)而累及3号染色体的断裂点在p~(25—26)。上述1,6,11和3号染色体的断裂点与细胞癌基因NRAS,SK,MYB,HRAS1,ETS和RAF1的定位相关。目前,许多实验表明癌基因的协同作用使正常细胞转化,本实验从细胞遗传学的角度为此理论提供了证据。     

普通型脆性部位与食管癌易感性的相关性

自Yunis(1983)首次报告了染色体脆性部位与肿瘤细胞染色体重排相关以来,大量研究结果表明,某些肿瘤患者的脆性部位、肿瘤相关断裂点及癌基因位点这三者在人类基因组中具有定位的相关性。本文对四川盐亭县食管癌患者的一级亲属的染色体畸变率(CAR)及脆性部位进行了检测,着重对普通型脆性部位(Common fragile sites,c-fra)与食管癌易感性的相关性作了探讨。材料与方法一、研究对象 4个食管癌高发家族(即连续两代以上有两名患者的家族)的一级亲属(父母、兄弟、姐妹、子女)15例(男13例、女2例),年龄16～84岁;4个食管癌低发家族     

22例急性白血病患者染色体脆性部位分析

对22例急性白血病患者和15例正常人外周血淋巴细胞染色体脆性部位进行了观察分析。实验结果表明:病人组的染色体结构畸变率和脆性部位检出率均显著高于正常对照组。经C显带定位的断点中检出脆性部位43种表达211次,有26种和癌断裂点对位,有8种与癌基因位点一致。以上结果提示脆性部位和染色体的断裂重排有相关性,在急性白血病的发病机理上可能起重要作用。     

喉癌及鼻腔鼻窦癌患者淋巴细胞染色体脆性部位的研究

用ＴＣ１９９培养基及原位显带的方法，对３７例喉癌、鼻腔鼻窦癌及２０例正常人染色体脆性部位进行分析。结果表明癌症患者脆性部位表达率显著高于正常人，且其表达的脆性部位与癌相关断裂点及癌基因位点密切相关。     

环境致癌物、脆性部位与肿瘤研究

近年来,脆性部位的研究方兴未艾。有学者认为脆性部位是由许多致突变物、致癌物作用的靶位点。脆性部位、染色体重排断裂点、癌基因三者之间密切相关,在肿瘤发生过程中起重要作用。但也有一些学者持不同看法。本文就环境致癌物、脆性部位与肿瘤研究的新进展作一综述,并概说目前对脆性部位分子基础的几种推测。     

鼻咽癌患者染色体断裂热点与SCE高发位点,脆性部位,原癌基因位…

采用在染色体标本上同是显示ＳＣＥ及Ｇ带带型的方法，对鼻咽癌患者染色体断裂热点与ＳＣＥ高发位点，染色体脆性部位及原癌基因位点之间的相关性进行了分析。结果表明：患者的ＳＣＥ频率，染色体畸变率均显著的高对照组，患者的染色断裂点和ＳＣＥ位点都主要分布在染色体的Ａ、Ｂ、Ｃ、Ｄ组浅带上，且两者所累及的染色体号存在着明显的相关，患者的１５个断裂热点与ＳＣＥ高发位点的一致率为５３．３３％，与脆性部位的一致率为８０     

肺癌的细胞遗传学初步研究

我们用细胞遗传学方法分析了6例肺癌患者原发肿瘤的G带染色体,结果表明:6例肿瘤均有染色体数目和结构异常;染色体数目分布范围广(从38—180),除一例染色体众数是亚二倍体外,其余各例均为高异倍体。结构方面:每例有3—4个标记染色体和各种异常染色体,其中1q等臂染色体是出现频率较多的标记染色体(4/6),1p等臂染色体亦在3例中可见,其次受累的染色体是3、5、9、11、13号等。 虽然1号染色体的变化与多种肿瘤有关,而在肺癌方面更似有明显的关系,其断裂点在1q~(11)或1p~(11),断裂后形成恒定的标记染色体。我们提出:1q~(11)和1p~(11)的断裂与肺癌的发生有一定的联系。     

鼻咽癌高发家系遗传学、EB病毒血清学分析

目的:分析鼻咽癌高发家系遗传因素、EB病毒感染在其病因学中的意义。方法:家系资料采用系谱分析及问卷调查,家系成员行外周血染色体脆性位点分析,免疫酶联法检测EB病毒VCA/IgA、EA/IgA。结果:患者一级亲属鼻咽癌检出率高达19.60%。家系成员与对照组染色体总畸变率分别为5.81%和4.93%(P>0.05),3p14、1p32、1q32等脆性位点表达率较高。家系成员EBVVCA/IgA阳性率为23.56%,显著高于人群(P<0.001)。结论:在鼻咽癌高发家系中,由血缘关系决定的遗传易感性和EB病毒感染是鼻咽癌发病的重要因素。     

血浆 EB病毒游离 DNA检测对监测鼻咽癌患者预后的意义

背景与目的:有报道 , 测定血浆中的 EB病毒游离 DNA( EBV-DNA)的拷贝数可作为诊断及监测鼻咽癌患者病情变化的手段之一.本研究旨在评价血浆 EBV-DNA检测在鼻咽癌患者预后监测上的价值, 并进一步与 VCA/IgA、 EA/IgA进行比较.方法:比较鼻咽癌放疗后 30例远处转移患者、 22例局部复发患者、 24例无 瘤生存者血浆中 EBV-DNA、 VCA/IgA、 EA/IgA水平.分别应用荧光定量 PCR方法检测血浆 EBV-DNA水平,免疫酶法检测 VCA/IgA、 EA/IgA;前瞻性观察 20例初诊鼻咽癌患者放疗前、放疗剂量达 40 Gy时及放疗结束时上述指标的变化. 结果:放疗后各组不同预后患者的血浆 EBV-DNA含量的中位数有显著性差异, 远处转移组为 135 100 copies/ml(四分线区域 5 525～ 1 003 750 copies/ml) >局部复发组的 20 500(四分线区域 0～ 58 500 copies/ml) > 无瘤生存组的 0 copy/ml(四分线区域 0～ 0 copy/ml), P均 < 0.05. 远处转移组的血浆 EBV-DNA水平高者较多, 当阳性标准为 1 000 000 copies/ml时,诊断远处转移组的敏感性为 27.3%,而诊断局部复发组的敏感性为 0.0%,特异性均为 100.0%.在初诊患者放疗前、放疗剂量达 40 Gy时及放疗结束时, EBV-DNA水平逐渐降低,平均含量分别为 32 050 copies/ml(四分线区域 3 880～ 317 750 copies/ml)、 0 copy/ml(四分线区域 0～ 14 375 copies/ml)、 0 copy/ml(四分线区域 0～ 2 940 copies/ml), P均 < 0.05, 而 VCA/IgA、 EA/IgA的水平未见明显变化. 结论: 血浆 EBV-DNA检测可用于监测鼻咽癌患者预后,其价值明显优于 VCA/IgA、 EA/IgA.     

Significance of cell-free epstein-barr virus DNA in monitoring prognosis of nasopharyngeal carcinoma

Objective It has been reported that cell-free Epstein-Barr virus (EBV-DNA) in plasma was useful in diagnosing and monitoring nasopharyngeal carcinoma (NPC). The current study was designed to evaluate the significance of EBV-DNA in monitoring the prognosis of nasopharyngeal carcinoma and comparing its significance with that of plasma VCA/lgA and EA/lgA levels. Methods E8V -DNA, VCA/lgA, and EA/lgA levels in plasma were determined in NPC patients with different prognosis after radiotherapy, including 30 distant metastatic patients, 22 local recurrence patients and 24 individuals with remission who had been followed-up for more than 2 years after treatment. EBV-DNA was determined using a real-time quantitative PCR system, and levels of VCA/lgA and EA/lgA were measured using standard immunofluorescence. In a cohort study, the indexes were determined after different radiation periods for the 20 new cases of nasopharyngeal carcinoma. Results The median plasma EBV-DNA concentration was 135,100 copies/ ml (interquartile range: 5,525-1,003 750) in metastatic group, 20,500 copies/ ml (interquartile range: 0 -58,500) in the local recurrence group and 0 copies/ml (interquartile range: 0-0) in the continuous remission group (P< 0.05). The levels of VCA/lgA and EA/lgA showed no significant differences among the different groups. The high level of EBV-DNA concentration in the metastatic group was more than that in the local recurrence group. A level of 1,000,000 copies/ml of EBV DNA was an indication of distant metastasis of the NPC patients with a sensitivity of 27.3%. However, the sensitivity was 0 in the local recurrence group. For the 20 new patients, EBV -DNA concentration gradually decreased during the radiation period. Before radiation there were 32,050 copies/ml (interquartile range: 3,880-317,750), 0 copies/ml (interquartile range: 0-14 375) after a 40 Gy radiation dose and 0 copies/ml (interquartile range: 0-2940) after the radiation was finished (P< 0.05). However, the levels of VCA/lgA and EA/lgA showed no significant difference. Conclusion Determination of plasma cell -free EBV -DNA level is more valuable than evaluation of VCA/lgA and EA/lgA for monitoring the prognosis of NPC patients.     

鼻咽癌分子遗传学研究进展

探讨鼻咽癌（nasopharyngeal carcinoma,NPC）发生发展的分子遗传学事件及其变异的NPC临床病理变化的影响。对原发性NPC进行杂合性缺失（loss of hetrozygosity,LOH)和比较基因组杂交（comparative genomic hybridization CGH)分析,观察到NPC发生高频率LOH的染色体主要位于1p、3p、9p、9q、11q、13q、14q、16q和19p,并定位了相应的LOH最小丢失区,并发现特定区域LOH与鼻咽癌临床病理有密切关系;LOH最化值高（FAL值）并伴随病人血清高滴度EBV／EA和EBV／VCA抗体的NPC,多表现为T3＋F4期、进展期TNM／Ⅲ Ⅳ期和远处淋巴结转移。NPC发生遗传物质扩增（gain）的染色体主要位于1q、2q、3q、6p、6q、7q、11.2、8q、11q13、12、15q、17q和20q,表明在这些区域可能存在与NPC发生发展相关的癌基因（oncogenes）活化,且1q,8q,18q的坟增和9p的丢失与晚期NPC有密切关系。正常鼻咽上皮和鼻咽上皮不典型生病变,3p区LOH的检出率分别高达74％和75％,表明3p区缺失是NPC发生过程中极早期分子事件。连锁分析表明HLA基因和细胞色素P4502E1酶基因可能是NPC的遗传易感基因,并定位了新的潜在NPC易感基因位点。应用cDNA微阵列技术,发现细胞周期蛋白、抗凋亡因子、某些癌基因／肿瘤抑制基因、生长促进因子、肿瘤发生生长因子和肿瘤血管生长因子等在NPC发生上调控表达;不同临床分析的NPC与正常鼻咽上皮间均存在差异表达。NPC发生遗传不稳定性（缺失和扩增）是常见的分子事件,遗传变异在NPC的发生、发展过程中起重要作用。通过LOH、CGH、连锁分析和微阵列分析确定NPC特异的分子标记物,能提供用于NPC早期诊断和预后判断的分子标记物,并将使我们建立独立于传统临床分期和分型的新的NPC分子分期的分子分型成为可能。     

Significance of Cell-Free Epstein-Barr Virus DNA in Monitoring Prognosis of Nasopharyngeal Carcinoma

Objective  It has been reported that cell-free Epstein-Barr virus (EBV-DNA) in plasma was useful in diagnosing and monitoring nasopharyngeal carcinoma (NPC). The current study was designed to evaluate the significance of EBV-DNA in monitoring the prognosis of nasopharyngeal carcinoma and comparing its significance with that of plasma VCA/lgA and EA/lgA levels. Methods  E8V -DNA, VCA/lgA, and EA/lgA levels in plasma were determined in NPC patients with different prognosis after radiotherapy, including 30 distant metastatic patients, 22 local recurrence patients and 24 individuals with remission who had been followed-up for more than 2 years after treatment. EBV-DNA was determined using a real-time quantitative PCR system, and levels of VCA/lgA and EA/lgA were measured using standard immunofluorescence. In a cohort study, the indexes were determined after different radiation periods for the 20 new cases of nasopharyngeal carcinoma. Results  The median plasma EBV-DNA concentration was 135,100 copies/ ml (interquartile range: 5,525-1,003 750) in metastatic group, 20,500 copies/ ml (interquartile range: 0 -58,500) in the local recurrence group and 0 copies/ml (interquartile range: 0-0) in the continuous remission group (P< 0.05). The levels of VCA/lgA and EA/lgA showed no significant differences among the different groups. The high level of EBV-DNA concentration in the metastatic group was more than that in the local recurrence group. A level of 1,000,000 copies/ml of EBV DNA was an indication of distant metastasis of the NPC patients with a sensitivity of 27.3%. However, the sensitivity was 0 in the local recurrence group. For the 20 new patients, EBV -DNA concentration gradually decreased during the radiation period. Before radiation there were 32,050 copies/ml (interquartile range: 3,880-317,750), 0 copies/ml (interquartile range: 0-14 375) after a 40 Gy radiation dose and 0 copies/ml (interquartile range: 0-2940) after the radiation was finished (P< 0.05). However, the levels of VCA/lgA and EA/lgA showed no significant difference. Conclusion  Determination of plasma cell -free EBV -DNA level is more valuable than evaluation of VCA/lgA and EA/lgA for monitoring the prognosis of NPC patients.     

鼻咽癌患者EB病毒与乙肝病毒双重感染的观察

目的：探讨鼻咽癌患者ＥＢ病毒和乙肝病毒感染的关系。方法检测５０５１健康康者和１２５例鼻咽癌患者的血清ＥＢＶ－ＩｇＡ／ＶＣＡ和ＨＢｓＡｇ。结果健康人群的ＥＢＶ－ＩｇＡ／ＶＣＡ和ＨＢｓＡｇ的阳性率分别为５．４％和１１．３％;健康人群ＥＢ病毒感染者的ＨＢｓＡｇ阳性率为９．７％;鼻咽癌患者的ＥＢＶ－ＩｇＡ／ＶＣＡ和ＨＢｓＡｇ的阳性率分别为９７．６％、２５．６％。鼻咽癌ＥＢ病毒、乙肝病毒双重感染率明显高于正     

Loss of heterozygosity on chromosome 14 in primary nasopharyngeal carcinoma

Multiple genetic alterations are believed to be involved in the pathogenesis of nasopharyngeal carcinomas (NPC). Loss of heterozygosity (LOH) of chromosomes 3p, 9p and 11q were previously reported in NPC. In order to further define the genetic alterations in NPC, 42 pairs of normal and tumor DNA of NPC were examined for LOH on chromosomes 5p, 5q, 6q, 14q, 15q, 16p, 16q, 17q using 16 polymorphic microsatellite markers. Frequent LOH (33%; 7 out of 21 cases) was observed in chromosome 14q at locus D14s81 (14q31). In order to define the common region of deletion, nine polymorphic microsatellite markers on 14q were examined for LOH in NPC. A common region of deletion was defined in NPC at chromosome 14q24.3-q32.1 flanked by two microsatellite markers D14s76 and D14s45. The common region of deletion (14q24.3-32.1) identified in NPC overlapped with the deleted regions of 14q reported in several human cancers. In 2 cases of NPC, the pattern of LOH revealed the presence of another commonly deleted region defined by loci D14s63 and D14s69 (mapped to 14q11.1-24.1) and located proximal to locus D14s76(14q24.3). This study suggests that multiple tumor suppressor genes present on chromosome 14q are involved in the pathogenesis of NPC.     

鼻咽癌误诊42例分析

目的　探讨鼻咽癌 (Nasopharyngealcarcinoma ,NPC)的误诊原因及对策。方法　对 42例误诊的NPC病人的临床资料作回顾性分析。结果　误诊率 15 .1%。误诊为慢性淋巴结炎 33例、中耳炎 3例、偏头痛 2例、颈淋巴结结核 2例、慢性鼻炎 2例。县乡级医院误诊占 6 9%,市级及以上医院误诊占 31%;非专科误诊占 73.8%,专科误诊占 2 6 .2 %。误诊后行颈部肿块手术的占 2 1.4%。结论　伴发病及继发病的干扰、对NPC生物学特性了解不清及隐匿性NPC为误诊的主要原因。推广纤维鼻咽镜检查及VCA IgA检测及鼻咽CT、MRI检查可减少误诊漏诊     

鼻咽癌HSP70表达与血清EB病毒IgA/VCA的关系及其临床意义

背景与目的:热休克蛋白(HSP)70在许多恶性肿瘤中均有表达,但在鼻咽癌组织中的表达与血清IgA/VCA滴度及预后的关系尚不清楚。本研究旨在检测鼻咽癌组织中HSP70的表达和含量水平,探讨HSP70表达与鼻咽癌患者血清EB病毒IgA/VCA滴度及预后的关系。方法:采用SP免疫组化法检测38例鼻咽癌组织中HSP70表达,ELISA法检测38例鼻咽癌组织中HSP70含量,免疫酶标法检测38例鼻咽癌患者血清IgA/VCA滴度。结果:HSP70在38例鼻咽癌组织中表达率为60.5%。在不同性别、年龄、T分期、N分期和临床分期鼻咽癌组织中HSP70表达率均无显著性差异(P>0.05)。HSP70表达和含量与血清EB病毒抗体IgA/VCA滴度呈正相关(P=0.001)。HSP70阳性组和阴性组患者的5年生存率分别为65.2%和80.0%,5年无瘤生存率分别为40.0%和78.6%(P=0.04)。结论:HSP70在临床Ⅱ、Ⅲ期鼻咽癌患者癌组织中的表达与患者的IgA/VCA滴度正相关,HSP70阳性患者常规治疗后预后较差。     

食管癌遗传病因的研究：Ⅴ.林县食管癌高癌家族成员淋巴...

The chromosome fragile sites of cultured peripheral lymphocytes from 40 members of 4 high risk cancer families and 10 members of 4 low risk cancer families in Linxian County were analysed. The results showed that 46 fragile sites in 7045 lymphocytes expression at 502 times (7.13%) were found in high risk cancer families and 8 fragile sites in 1053 lymphocytes expression at 26 times (2.47%) were found in low risk cancer families. There was a significant difference between the two groups (P less than 0.01). In 46 fragile sites carried by 40 members of high risk cancer families, 27 were common, 5 rare, 12 provisional and 2 new fragile sites. Among them, the fragile sites at 1p22-p36 and 4q21-q31 were detected in members of high risk cancer families and in patients with esophageal cancer, meanwhile, uniform breakpoint in chromosome deletion and rearrangement was also found in 4 esophageal cancer cell lines. Therefore, the author conjectures that these fragile sites at 1p13-p36 and 4q21-q31 may be fragile site-specific for high risk cancer families and patients with esophageal cancer, and they may be breakpoint-specific for esophageal cancer cells. These fragile sites may play an important role in esophageal carcinogenesis in high risk cancer families.