脑胶质瘤c—myc癌基因重排与MDR1基因的变化

作者对２２例胶质瘤ｃ－ｍｙｃ癌基因和ＭＤＲ１基因Ｓｏｕｔｈｅｒｎ分析发现有５例胶质瘤ｃ－ｍｙｃ癌基因发生基因重排，其中２例伴有重排序列的扩增。这些标本同时出现ＭＤＲ１基因限制片段拷贝量的倍增（ＥｃｏＲＩ，６．６ｋｂ），其倍增是脑组织２￣２８倍。这一分子事件不仅反映ｃ－ｍｙｃ癌基因与脑胶质瘤的恶性程度和预后关系密切，而且也与胶质瘤的耐药性有关。     

二甲基甲酰胺对胶质瘤细胞基因蛋白水平表达的影响

目的：观察诱导分化剂二甲基甲酰胺（ＤＭＦ）地胶质瘤细胞Ｃ６的增殖抑制作用,探讨作用机理中ＤＭＦ对ｃ－ｍｙｃ、ｐ１６基因蛋白水平表达的影响。方法：「＾３Ｈ」－Ｔ掺入法测增殖抑制率;免疫组化ＳＰ法测Ｃ－ｍｙｃ、ｐ１６基因蛋白水平的表达。结果：应用二甲基甲酰胺后,胶质瘤细胞ＣＰＭ值降低,ＤＮＡ合成总量减少。Ｃ－ｍｙｃ基因胞浆阳性表达下降,ｐ１６基因胞浆阳性表达升高。结论：二甲基酰胺对胶质瘤细胞增殖存在剂量依赖性抑制,作用机理与降低了癌基因Ｃ－ｍｙｃ对Ｃ６细胞恶性增殖的转录调节作用、增强了抑制基因ｐ１６活性有关。     

差异竞争性PCR定量扩增胃癌及转移灶癌基因HER2和C-myc

目的 介绍差异竞争性多聚酶链反应（ｄｉｆｆｅｒｅｎｔｉａｌｌｙ ｃｏｍｐｅｔｉｔｉｖｅ ＰＣＲ，ＤＣ－ＰＣＲ），并分析癌基因ＨＥＲ２和Ｃ－ｍｙｃ变异与胃癌生物学行为的关系。方法 用ＤＣ－ＰＣＲ定量检测胃原发癌、癌旁、转移淋巴结及远处脏器转移癌中ＨＥＲ２和Ｃ－ｍｙｃ扩增。结果 ＨＥＲ２扩增频率在近端胃癌组中高于远端胃癌组（分别是８４．６％和２６．３％，Ｐ〈０．０５），侵及浆膜组明显高于未侵及浆膜组（     

男性乳腺癌癌基因与抗癌基因表达的初步研究

本文观察了１２例男性乳腺癌的癌基因与抗癌基因产物的表达。１２例中ｃ－ｍｙｃ阳性６例，ＥＧＦＲ阳性６例，ｃ－ｅｒｂＢ－２阳性４例，Ｎ－ｒａｓ阳性２例，Ｒｂ阳性５例，ｐ５３阳性３例。上述癌基因与抗癌基因产物中，全部阳性的１例，全部阴性的４例。此外还作了ＣａｔｈｅｐｓｉｎＤ、ＥＲ、ＰＲ、ＡＲ、ＰＣＮＡ与ＡｇＮＯＲ检测，ｃ－ｅｒｂＢ－２或ｐ５３阳性的病例，ＣａｔｈｅｐｓｉｎＤ均阳性。     

Bcl-2基因重排在恶性淋巴瘤微小残留病变检测中的应用

目的建立敏感的检测淋巴瘤微小残留病变（ＭＲＤ）的方法,探索Ｂｃｌ２基因重排在恶性淋巴瘤的分期、化疗疗效和预后评估中的意义。方法多聚酶链反应（ＰＣＲ）检测Ｂｃｌ２／ＪＨ基因重排,系列稀释试验检测该方法的敏感性。结果９种恶性淋巴瘤细胞系中,ＳｕＤＨＬ４,ＳｕＤＨＬ６有Ｂｃｌ２／ＪＨ基因重排,系列稀释试验检测该方法的敏感度达１∶１０５。滤泡性淋巴瘤（ＦＮＨＬ）患者１６例中,４例外周血和骨髓中同时检出Ｂｃｌ２（ＭＢＲ）／ＪＨ基因重排,化疗达ＣＲ后仍存在。结论多聚酶链反应检测Ｂｃｌ２／ＪＨ基因重排,是检测滤泡性淋巴瘤患者微小残留病变的一个快速、有效、敏感的方法,对疾病的分期、疗效和预后评估有一定的临床应用价值。     

人食管癌中癌基因与预后

人食管癌中癌基因与预后祝淑钗食管癌的发生可能与癌基因ｃｅｒｂＢ、ｃｍｙｃ、ｉｎｔ２、ｈｓｔ１、ｃｙｃｌｉｎＤ１的扩增和抑癌基因ｐ５３、Ｒｂ、ＡＰＣ／ＭＣＣ纯合子的丢失、突变有关系。近两年的研究显示，ｃｙｃｌｉｎＤ１基因扩增和相关蛋白的过度表达...     

p53和c—myc异常表达与膀胱癌多药耐药性

为探讨ｐ５３和ｃ－ｍｙｃ基因异常表达与膀胱癌多药耐药性（ＭＤＲ）的关系，应用ＡＢＣ免疫组织化学方法检测６７例膀胱癌癌细胞中ｐ５３和ｃ－ｍｙｃ的表达产物及多药耐药基因（ｍｄｒ－１）产物Ｐ－ｇｐ。结果显示ｐ５３突变蛋白蓄积的膀胱癌中Ｐ－ｇｐ阳性表达率９２．３％；ｐ５３阴性者Ｐ－ｇｐ阳性率为３６．６％。Ｐ－ｇｐ表达与ｐ５３突变蛋白蓄积呈显著正相关（ｒ＝０．６４，Ｐ＜０．０５）；而ｃ－ｍｙｃ和ｍｄｒ－１的表达无明显相关。提示：ｐ５３异常表达可增加ｍｄｒ－１基因的表达，使膀胱癌细胞获得ＭＤＲ表型     

非霍奇金淋巴瘤bcl-2/IgH基因重排及在微小残留病变检测中的应用

目的：探索ｂｃｌ－２基因质重排在非霍奇金淋巴瘤（ＮＨＬ）的发生及演变中的作用，以ｂｃｌ－２／ＩｇＨ重排为克隆标志，建立敏感的检测淋巴瘤微小残留病变的方法。方法；多聚酶链反应（ＰＣＲ）检测ｂｃｌ－２／ＩｇＨ基因重排，系列稀释试验检测该方法的灵敏度。结果：９例恶性淋巴瘤细胞系中，Ｓｕ－ＤＨＬ－４，Ｓｕ－ＤＨＬ－６有ｂｃｌ－２／ＩｇＨ基因重排，系列稀释试验检测该方法的灵敏度为１：１０＾５。２９例ＮＨＬ石     

人类成纤维的体外细胞转化结合基因突变试验法

以人类成纤维细胞体外转化体系为模型研究致癌多步骤机制黄吉武，ＭｃＣｏｒｍｉｃｋＪＪ（西安医科大学预防医学系毒理室西安７１００６１美国密执安州立大学致癌研究室）以ｖ─ｍｙｃ癌基因转染正常人成纤维细胞建立永生化的近二倍体细胞株ＭＳＵ─１．１。该株具有由４...     

多重癌基因改变在良,恶性卵巢等妇科肿瘤的比较研究

应用Ｓｏｔｈｅｒｎ印迹杂交技术，在１８例良，恶性卵巢疾病患者的瘤组织和同源正常组织中，比较研究了Ｃ－ｍｙｃ，Ｃ－Ｈａ－ｒａｓＩ和Ｃ－ｅｒｂＢ－２癌基因的改变。在１１例卵巢癌患者中４例出现Ｃ－ｍｙｃ基因的扩增，重排或等位基因缺失，这些患者的肿瘤均已有浸润与转移，在有Ｃ－ｅｒｂＢ－２基因印迹杂交资料的６例卵巢癌患者中，２例晚期患者出现重排，其中１例伴有扩增，这是首次在人卵巢癌报告Ｃ－ｅｒｂＢ－２基因的     

Simultaneous presence of herpes simplex and human papilloma virus sequences in human genital tumors

Herpes simplex virus (HSV) and human papillomavirus (HPV) sequences were analyzed in tumors of the female lower genital tract, by probing DNA from 13 intraepithelial and 30 invasive neoplastic lesions with radiolabelled HPV-16 and HPV-18 DNA as well as cloned fragments of HSV-2 DNA. Careful removal of stromal tissue from the pathological specimens allowed authentic tumor DNA to be processed. Normal genital tissue obtained from the patients and genital condylomata were included as internal controls. The presence of HPV-16 or 18 DNA was detected in 12/13 (92.3%) intraepithelial neoplasms and in 16/30 (53.3%) invasive carcinomas. No significant difference was detected in titer or frequency of antibodies to HPV group-specific antigen in sera from patients and controls. Hybridization to BgIII N fragment of HSV-2 DNA was detected in 4/13 (30.8%) intraepithelial neoplasms and 4/30 (13.3%) invasive carcinomas but in none of the control tissues. All the 8 samples harboring HSV-2 homologous sequences were also positive for HPV, supporting the hypothesis of a synergistic association between the 2 viruses. The hybridization analyses performed to study c-myc involvement in genital oncogenesis did not reveal c-myc amplification in either invasive or pre-invasive lesions.     

Genetic alterations of c-myc, c-erbB-2, and c-Ha-ras protooncogenes and clinical associations in human breast carcinomas

We have analyzed genomic DNA sequences from 125 prospectively collected single unilateral primary breast carcinoma samples for the presence of alterations of c-myc, c-erbB-1, c-erbB-2, c-Ki-ras and c-Ha-ras protooncogenes. Amplification of the c-myc gene was found in 18% of the samples, and in one sample a non-germ line c-myc related DNA fragment or rearrangement was detected. We have found a significant association (P = 0.0010) between amplified c-myc gene and inflammatory carcinoma, a particularly aggressive breast cancer. The c-erbB-2 gene was amplified in 22% of the tumor samples and a rearrangement was observed once. Alteration of the c-erbB-2 gene was significantly linked to histological grade III tumors (P = 0.005) and the absence of estrogen and progesterone receptors (P = 0.036). No amplifications were observed for c-erbB-1, c-Ki-ras, and c-Ha-ras genes. About 40% of breast carcinomas contain either amplified c-myc or c-erbB-2 protooncogenes, whereas simultaneous amplification of both was seen in only one sample, suggesting the involvement of two distinct molecular mechanisms in breast cancer. Comparison of DNA from peripheral blood and tumor samples indicated loss of one c-Ha-ras allele in 29% of patients heterozygous for this polymorphism. A significant correlation (P = 0.016) between c-Ha-ras locus (11p14) allele loss and patient survival was found. These data suggest that 11p14 allelic loss plays a role in the evolution of human breast cancer, amplification of c-erbB-2 gene is associated with increasing stage of malignancy, and alteration of the c-myc gene in inflammatory breast carcinoma may contribute to the rapid progression of this human tumor subtype.     

41例人脑胶质瘤组织中p53基因突变的研究

背景与目的:p53抑癌基因在细胞周期的调控、维持细胞基因组的完整性、诱导细胞分化和凋亡中起着重要作用。胶质瘤尤其是星形细胞肿瘤中,经常发生p53基因突变。本研究探讨人脑胶质瘤中p53突变及与胶质瘤发生发展的相关性。方法:应用聚合酶链反应-单链构象多态性分析(polymerase chainreaction-single-strand conformation polymorphism,PCR-SSCP)及DNA测序技术对41例不同类型人脑胶质瘤p53基因突变进行检测。结果:通过PCR-SSCP检测发现在41例人脑胶质瘤组织中有17例(41.5%)呈现p53基因的单链构象多态性改变,均位于5～8外显子,突变例数依次为7(41.2%)、1(5.9%)、4(23.5%)、5(29.4%)。Ⅲ、Ⅳ级胶质瘤中p53基因突变率明显高于Ⅰ、Ⅱ级肿瘤(58.3%vs.17.6%,P<0.01);DNA序列分析显示,17例PCR-SSCP检测阳性的肿瘤p53基因相应外显子均存在基因点突变或缺失,其中错义突变13例,占76.5%;同义突变2例,占11.8%;移码突变2例,占11.8%;碱基突变以G→A或A→G最多,占55.6%。结论:胶质瘤中p53突变多发生于第5、8外显子,基因突变类型以错义突变为主,该基因的突变与胶质瘤的发生及恶性进展过程相关。     

分化相关基因MIBP1的表达与人脑胶质瘤恶性程度的关系

目的:应用荧光定量实时PCR技术检测与肿瘤分化相关的基因MIBP1(c-myc内含子结合蛋白1)在不同恶性程度的人脑胶质瘤中的表达。方法:收集病理确诊的30例不同恶性程度胶质瘤以及5例正常脑组织手术标本,抽提RNA,应用荧光定量PCR技术检测MIBP1基因在人脑胶质瘤中的表达,并分析该基因在不同级别胶质瘤中的表达情况。结果:荧光定量PCR系统稳定,WHOⅣ级胶质瘤与正常对照及Ⅱ级胶质瘤比较有显著性差异,多形性胶质母细胞瘤MIBP1基因表达明显降低。2例自身对照标本分析,Ⅳ级肿瘤中表达亦降低。结论:c-myc调控基因MIBP1在高度恶性胶质瘤中表达受抑制,提示该基因的下调可能为癌变的晚期事件。MIBP1基因可能有抑癌作用。     

myc family DNA amplification in small cell lung cancer patients' tumors and corresponding cell lines

Tumor specimens procured from 38 different small cell lung cancer patients were studied for DNA amplification of the myc family of protooncogenes (c-myc, N-myc, and L-myc). Six of the 38 specimens (16%) had 4-fold or greater myc family DNA amplification (N-myc in 4 and L-myc in 2). All 6 tumors with amplification came from patients who had received combination chemotherapy. The myc family gene copy number of the DNA prepared from 9 tumor cell lines established from these 38 patients was similar to the myc family gene copy number in the DNA prepared from fresh tumor specimens from these same patients. myc family DNA amplification is present in 16% of small cell lung cancer patients' tumors and the amplification pattern in the tumor cell lines is representative of the fresh tumors obtained from the same patients.     

Genomic rearrangement of the c-myc proto-oncogene in non-AIDS-related lymphoma in Japan

Southern blot analysis was employed to analyze the structural alterations of the c-myc oncogene in genomic DNA derived from tumor specimens of 35 adults with pathologically classified and immunophenotyped non-AIDS-related, non-Hodgkin's lymphoma in Japan. In this study, seven cases (20%), including one peripheral T-cell lymphoma and six B-cell lymphomas of various histological types, were demonstrated to have additional c-myc fragments. An interesting feature is that c-myc rearrangements were found in three out of eight primary gastrointestinal lymphomas. Analyses with several restriction enzymes revealed that the breakpoints in these cases were clustered in a region spanning the first exon, first intron and nearby 5'-flanking sequences of the c-myc gene, suggesting that the alteration of this region may represent an important molecular event in activating the oncogenic potential of the c-myc gene.     

Concurrent activation of c-myc and inactivation of bcl-2 by chromosomal translocation in a lymphoblastic lymphoma cell line

We have characterized a chromosomal translocation in a cell line (SU-DUL5) established from a patient with lymphoblastic lymphoma in which the c-myc gene on chromosome 8 was juxtaposed to a t(14;18). Cytogenetic analysis of this cell line showed 14q+, 18q-, and 8p+q+ marker chromosomes in the absence of t(14;18). Genomic Southern blot analysis showed juxtaposition of the immunoglobulin heavy chain joining region (JH) with chromosome 18 near the minor breakpoint cluster region (mcr) of the bcl-2 gene. There was also a rearranged c-myc gene detectable with a 5' c-myc probe. Molecular cloning studies showed that the c-myc gene was joined to chromosome 18 DNA. Nucleotide sequence analysis of cloned breakpoint DNA revealed that the crossover between chromosomes 8 and 18 occurred at the 3' end of the bcl-2 gene resulting in replacement of the bcl-2 gene on the 14q+ chromosome with the c-myc gene. As a result of this translocation the SU-DUL5 cell line contains no detectable bcl-2 mRNA or protein but has abundant levels of c-myc mRNA. Our data suggest that bcl-2 inactivation occurred simultaneously with c-myc translocation in a B cell lymphoblastic lymphoma.     

Association of Ki-ras with amplified DNA sequences, detected in human ovarian carcinomas by a modified in-gel renaturation assay

A modified in-gel DNA renaturation technique, which detects DNA sequences amplified greater than 7-fold in human DNA, was used to analyze gene amplification in surgical specimens of primary and metastatic ovarian carcinomas. Amplified DNA sequences were detected in two of eight tumors. Hybridization of these samples with different oncogene probes revealed that both tumors contained an amplified Ki-ras gene, which in one case was coamplified with c-myc. In one of the tumors, Ki-ras was found to be amplified in both the primary tumor and three different metastatic nodules. No mutations at codons 12 or 61 of Ki-ras were detected in these tumors. No additional cases of Ki-ras or c-myc amplification were detected by Southern hybridization in the tumors that were found to be amplification negative by modified in-gel renaturation assays. These results indicate that gene amplification in ovarian carcinomas is likely to involve the Ki-ras oncogene.