肝细胞癌mdm2基因表达及其与p53基因突变的关系

目的研究ｍｄｍ２基因在原发性肝细胞癌（ＨＣＣ）中的表达并探讨其与ｐ５３基因突变的关系．方法用银染ＰＣＲＳＳＣＰ法检测ｐ５３基因第５～８外显子的突变,原位杂交检测ｍｄｍ２基因ｍＲＮＡ的表达,ＳＡＢＣ法检测ｍｄｍ２蛋白的表达．结果３９３％（１１／２８）的病例有异常的电泳迁移率．ｐ５３基因突变与肿瘤的大小、分化及转移无关．原位杂交显示９例ＨＣＣ出现ｍｄｍ２基因ｍＲＮＡ增加,７例ＨＣＣ可检测到ｍｄｍ２蛋白表达,ｍｄｍ２基因表达与ＨＣＣ的大小、分化及是否转移无关．Ⅰ～Ⅱ级ＨＣＣ中ｍｄｍ２阳性表达率（１３３％）明显低于Ⅲ～Ⅳ级ＨＣＣ中的阳性表达率（５３８％）．１１例有ｐ５３基因突变的ＨＣＣ中,只有３例出现ｍｄｍ２基因表达,另外６例有ｍｄｍ２过表达的ＨＣＣ未见ｐ５３基因突变．ｐ５３基因突变的ＨＣＣ与ｐ５３基因无突变的ＨＣＣ相比,ｍｄｍ２基因表达阳性率无显著差别．结论ｐ５３基因突变和ｍｄｍ２基因表达在原发性ＨＣＣ的发病中起重要作用．ｍｄｍ２基因表达与ＨＣＣ的恶性程度相关．ｍｄｍ２基因表达与ｐ５３基因是否突变无关．     

Aflatoxin sufferer and p53 gene mutation in hepatocellular carcinoma

Ａｆｌａｔｏｘｉｎｓｕｆｅｒｅｒａｎｄｐ５３ｇｅｎｅｍｕｔａｔｉｏｎｉｎｈｅｐａｔｏｃｅｌｕｌａｒｃａｒｃｉｎｏｍａＤＥＮＧＺｈｕｏＬｉｎａｎｄＭＡＹｕｎＳｕｂｊｅｃｔｈｅａｄｉｎｇｓＡｆｌａｔｏｘｉｎＢ１;ｇｅｎｅｓ,ｐ５３;ｍｕｔａｔｉｏｎ;...     

肝细胞癌抑癌基因p53突变

目的分析重庆地区肝细胞癌ｐ５３基因突变谱．方法住院肝细胞癌患者２０例，皆经病理证实，长期在重庆地区居住，其中早期小肝癌４例，中期６例，晚期１０例．采用ＰＣＲ－ＳＳＣＰ，ＰＣＲ直接测序技术分析ｐ５３基因５，６，７和８外显子突变．结果ｐ５３基因总的突变率为４０％．其中外显子５和６各占１０％，外显子７占２０％，未发现外显子８的突变；测序证实外显子７为第２４９位密码子Ｇ→Ｔ的颠换突变．突变病例多为晚期肿瘤．结论重庆地区肝细胞癌存在明显的ｐ５３基因突变，反映了该地区肝癌与黄曲霉毒素和ＨＢＶ或ＨＣＶ病毒有关     

Codon 249 mutations of p53 gene in development of hepatocellular carcinoma

Ｃｏｄｏｎ２４９ｍｕｔａｔｉｏｎｓｏｆｐ５３ｇｅｎｅｉｎｄｅｖｅｌｏｐｍｅｎｔｏｆｈｅｐａｔｏｃｅｌｕｌａｒｃａｒｃｉｎｏｍａＰＥＮＧＸｉａｏＭｏｕ,ＰＥＮＧＷｅｎＷｅｉａｎｄＹＡＯＪｉＬｕＳｕｂｊｅｃｔｈｅａｄｉｎｇｓｌｉｖｅｒｎｅｏｐｌａ...     

原发性胃癌p53基因突变

目的 p53基因是当前抑癌基因研究中的热点之一。迄今,有关 p53基因异常与胃癌临床病理学参数如大体类型、临床分期、组织分化程度,浸润深度及淋巴结转移之间的关系尚无定论。Tumura 报告p53基因改变主要发生于异倍体瘤,国内尚无报道。本实验目的主要是分析中国人原发性胃癌 p53基因突变与这些病理参数,包括 DNA 倍体之间的关系。方法用聚合酶链式反应—单构象多态分析(PCR—SSCP)技术对20例原发性胃癌 p53基因外显子5—8突变进行检测。结果 8例(40%)发生了突变,其中2例发生在外显子7,4例发生在外显子8。0至Ⅲ期均有突变存在。66.7%(6/9)的异倍体瘤检测到了p53突变,而二倍体瘤中只有18.2%(2/11)发生了 p53突变。结论 p53基因突变与胃癌临床病理参数如大体类型、分期、组织分化程度、浸润深度及淋巴结转移之间无明显关系,而与胃癌 DNA 倍体改变有关。     

胰腺癌ras癌基因及p53抑癌基因表达的临床意义

目的研究ras癌基因及p53抑癌基因在在胰腺癌表达的临床意义．方法胰腺石蜡包埋标本55例，包括胰腺癌32例，癌切缘未受浸润的胰腺组织12例，急慢性胰腺炎7例，正常胰腺4例，标本均经病理学证实，用免疫组织化学ABC法对上述标本的ras癌基因及p53抑癌基因表达进行检测．结果在32例胰腺癌中，ras和p53基因的阳性表达率分别为71．9％和28．1％，高于胰腺炎和癌切缘组织（P＜0．05）ras，p53基因表达与患者性别、年龄、肿瘤所在部位及大小和初发症状无关（P＞0．05），p53基因表达与临床分期和病理分级相关（P＜0．05），p53基因表达阳性者其临床分期较晚期，细胞分化较差，而ras基因表达仅与病理分级有关（P＜0．05）．P53基因表达与癌肿可切除率相关（P＜0．05），凡癌肿能切除者多为p53基因表达阴性者.p53基因表达亦与淋巴结转移有关（P＜0．05），其表达阳性者多已有淋巴结转移．ras与p53基因表达之间存在正相关关系．结论ras与p53基因表达可以反映胰腺癌的生物学行为，对胰腺癌的诊断和治疗有一定指导意义．     

p53 point mutations in primary human gastric carcinomas

Summary p53 point mutations in primary gastric carcinomas were analyzed by performing cDNA deoxynucleotide sequencing of the gene. Out of 16,9 (56.3%) primary gastric carcinoma cases, including early cancer, showed one or more p53 point mutations in their open-reading frame, and 4 out of 9 cases had a p53 point mutation within highly conserved domains. The characteristics of the p53 mutation spectrum observed in primary tumors were (a) frequent mutation at an A:T pair (50%, 7 out of 14 mutations), (b) high transversion incidence (29%, 4 out of 14 mutations), (c) no transition at CpG, and (d) no G:C to T:A transversion. Our results suggest that p53 mutation is a common event in gastric carcinoma occurring from the early stage of progression with its specific mutation spectrum.Abbreviation PCR-SSCP polymerase chain reaction single-strand conformation polymorphism     

抑癌基因PTEN及p53在肝细胞肝癌中表达的免疫组化研究

为探讨肝细胞肝癌组织中抑癌基因PTEN及p53蛋白的表达情况及临床病理意义。应用免疫组织化学技术检测了41例肝细胞肝癌及其相应的癌旁组织中PTEN和p53蛋白的表达情况。41例癌旁组织PTEN全部阳性表达,肝细胞肝癌组织中PTEN阳性表达率39％,阳性信号显示于胞浆中。p53阳性表达率51％,PTEN蛋白在肝细胞肝癌组织中的阳性表达与组织分化程度明显相关,高分化癌的阳性率为73％,低分化癌阳性率27％。肝细胞肝癌细胞中存在较高比例的PTEN蛋白阴性表达,说明在肝细胞肝癌的发生发展中PTEN基因失活起着重要作用,它的阳性表达可能有一定的预后意义。     

Aflatoxin and p53 abnormality in duck hepatocellular carcinoma

Recent studies have revealed that a point mutation at codon 249 in the p53 gene predominates in hepatocellular carcinoma (HCC) cases from Southern Africa and China, where infection with hepatitis B virus (HBV) and contamination of aflatoxin B₁ in food are risk factors for HCC. This unique mutation from G to T at the third base in codon 249 observed in human HCC cases is suggested to be linked to aflatoxin exposure. Six ducks with HCC, five of which were fed a diet containing aflatoxin B₁ for 1–2 years, were analysed for the presence of point mutations at this codon of the p53 gene by polymerase chain reaction and direct nucleotide sequencing. None of the six ducks with HCC showed the change at this codon regardless of duck hepatitis B virus infection. This suggests that aflatoxin B₁ itself might not be involved in the unique mutation at codon 249 in hepatocar-cinogenesis, or that other factors coincident with aflatoxin may be responsible for this unique mutation.     

胃癌活检标本中p53基因突变的研究

目的探索胃癌癌变过程中抑癌基因p53的变异规律．方法用聚合酶链反应，单链构象多态性，银染方法，检测胃癌活检标本30例（男20例，女10例，平均年龄56．8岁）的p53基因突变．结果病理诊断为胃癌的标本中检出的30例p53基因外显子5～8的突变18例，阳性率为60％．其癌基因的扩增和重排多发生于胃癌进展期，而p53基因的点突变发生于癌变各期结论胃癌癌变是多基因异常累积所引起的渐进过程，基因改变的数目，肿瘤的恶变性表现密切相关     

The mutation of codon 249 in the p53 gene is not specific in Japanese hepatocellular carcinoma

ABSTRACT— Hepatocellular carcinoma samples obtained from 59 patients at surgical resection were examined for mutations of the third base at codon 249 of the p53 gene, using the polymerase chain reaction and oligonucleotide hybridization techniques. This point mutation, which is frequently observed in HCC cases from Southern Africa and Quidong in China, was not recognized in either 60 hepatocellular carcinomas or 53 noncancerous liver tissue samples from Japan. Thirty-four of 45 patients (75.6%) were positive for the hepatitis C virus, which was a higher rate than that for hepatitis B virus infection (9 of 55; 16.4%). The exposure to aflatoxin B1 was not considered to be remarkable. These results suggest that the point mutation of the third base at codon 249 is not common in Japanese patients, and it is suggested that numerous other factors affect the mutation of the p53 gene and the development of hepatocellular carcinoma.     

Codon 249 mutations of p53 gene in non-neoplastic liver tissues

Ｓｕｂｊｅｃｔｈｅａｄｉｎｇｓｌｉｖｅｒ;ｐ５３ｇｅｎｅ;ｃｏｄｏｎ２４９ｍｕｔａｔｉｏｎ;ｌｉｖｅｒｎｅｏｐｌａｓｍｓ;ｈｅｐａｔｉｔｉｓ,ｖｉｒａｌ;ｌｉｖｅｒｃｉｒｈｏｓｉｓ;ｐｏｌｙｍｅｒａｓｅｃｈａｉｎｒｅａｃｔｉｏｎＡｂｓｔｒａｃｔＡＩＭ...     

肝细胞癌肿瘤抑制基因p53过度表达及点突变的研究

目的检测重庆地区肝细胞癌 p53突变发生率,并进一步探讨 p53突变与肝细胞癌临床病理及相关危险因素的关系.方法应用一种敏感的 ARF 免疫组化和 PCR、银染 PCR-SSCP 方法检测本地区38例肝细胞癌(HCC)组织中肿瘤抑制基因p53的过度表达及点突变.结果 16例有P53蛋白过度表达(41.2%),7例有 p53基因249位密码子点突变(18.4%),2例249位密码子外第7外显子点突变.9例 p53基因有突变的肝癌中8例 P53蛋白阳性,两者符合率为88.9%.p53基因蛋白过度表达和点突变与 HCC 分化和转移有关.本组 HCC p53基因突变率与该地区黄曲霉素(AFB1)含量及乙型肝炎病毒(HBV)感染分布一致.结论该结果提示 p53基因突变与 AFB1和 HBV 等环境因素的协同作用有关,其中 AFB1主要与 p53基因249位密码子特异型突变有关,而 HBV 可能在散发型突变中发挥重要作用.     

Anal cancer in Chinese: human papillomavirus infection and altered expression of p53

ＡｎａｌｃａｎｃｅｒｉｎＣｈｉｎｅｓｅ：ｈｕｍａｎｐａｐｉｌｏｍａｖｉｒｕｓｉｎｆｅｃｔｉｏｎａｎｄａｌｔｅｒｅｄｅｘｐｒｅｓｓｉｏｎｏｆｐ５３ＬＡＩＭａｏＤｅ,ＬＵＯＭｉｎＪｉｅ,ＹＡＯＪｉａｎＥｒａｎｄＣＨＥＮＰｅｉＨｕｉＳｕｂｊｅｃｔ...     

Anal cancer in Chinese: human papillomavirus infection and altered expression of p53

AIM To detect the presence of HPV DNA and study the alteration of p53 expression in anal cancers in Chinese.METHODS HPV DNA was amplified by PCR. The amplified HPV DNA was classified by DBH. HPV antigen and p53 expression were respectively detected by immunohistochemistry.RESULTS HPV DNA was amplified only in one case of squamous cell carcinoma of the 72 Chinese anal cancers and further classified as HPV type 16. Others were all HPV negative. HPV antigen and p53 expression were also detected in this case. Positive stainings with anti-p53 antibody were seen in 61.2% anal cancers. There were no statistically significant differences between anal squamous cell carcinomas and adenocarcinomas and between anal adenocarcinomas and rectal adenocarcinomas. p53 protein expression was observed in the basal cells of squamous epithelium of condyloma acuminatum and morphologically normal squamous epithelium in 2 cases invaded by anal adenocarcinoma.CONCLUSION HPV infection was not associated with these cases of anal cancer. p53 alteration was a common event. Positive p53 immunostaining can not be regarded as a marker for differentiating benign from malignant lesions.     

肝细胞癌p53及nm23-H1 mRNA表达的意义

目的探讨ｐ５３,ｎｍ２３Ｈ１与原发性肝细胞癌（ＨＣＣ）发生发展的关系．方法运用原位分子杂交技术对４９例ＨＣＣ中ｐ５３和ｎｍ２３Ｈ１基因ｍＲＮＡ进行检测,并结合临床病理特征进行分析．结果ｐ５３ｍＲＮＡ杂交阳性２３例,占４６９％;ｐ５３ｍＲＮＡ过表达与肿瘤的肝内转移．包膜侵犯及Ｅｄｍｏｎｄｓｏｎ分级相关（Ｐ＜００５）;ｎｍ２３Ｈ１ｍＲＮＡ阳性表达２７例,占５５１％;ｎｍ２３Ｈ１ｍＲＮＡ表达与肿瘤肝内转移及ＴＮＭ分期呈负相关（Ｐ＜００５）;同时发现ｐ５３ｍＲＮＡ过表达和ｎｍ２３Ｈ１ｍＲＮＡ低表达在ＨＣＣ肝内转移中具有协同作用．结论ｐ５３和ｎｍ２３Ｈ１参与ＨＣＣ的发生发展,ｐ５３过表达及ｎｍ２３Ｈ１低表达提示ＨＣＣ肝内转移．     

肺鳞癌组织Mdm2蛋白表达p53基因突变相关性研究

目的探讨原发性肺鳞癌与Ｍｄｍ２蛋白表达、ｐ５３基因突变之间的相关性。方法采用ＳＰ免疫组织化学方法和银染聚合酶链式反应单链构象多态性（银染ＰＣＲＳＳＣＰ）方法检测手术切除、经病理证实的４５例原发性肺鳞癌组织及癌旁肺组织中Ｍｄｍ２蛋白表达和ｐ５３基因突变情况。结果免疫组织化学检测的４５例肺鳞癌组织Ｍｄｍ２蛋白阳性率为６２％（２８／４５）,２例癌旁肺组织中Ｍｄｍ２蛋白呈弱阳性表达,免疫组织化学方法结合银染ＰＣＲＳＳＣＰ检测４５例肺癌组织ｐ５３基因突变,阳性率为５１％（２３／４５）,４５例癌旁肺组织未检测到ｐ５３基因突变。（１）肺鳞癌与ｐ５３基因突变有明显相关性（Ｐ＜０．０５）。（２）肺鳞癌与Ｍｄｍ２基因产物过度表达有明显相关性（Ｐ＜０．０５）。（３）Ｍｄｍ２蛋白过度表达与ｐ５３基因突变复合存在和肺鳞癌淋巴转移（６６％,１０／１５）有明显相关性（Ｐ＜０．０５）。结论Ｍｄｍ２蛋白过度表达与ｐ５３基因突变是临床估计患者预后重要的分子生物学指标     

Effects of endotoxin on expression of ras, p53 and bcl-2 oncoprotein in hepatocarcinogenesis induced by thioacetamide in rats

Ｅｆｅｃｔｓｏｆｅｎｄｏｔｏｘｉｎｏｎｅｘｐｒｅｓｓｉｏｎｏｆｒａｓ，ｐ５３ａｎｄｂｃｌ２ｏｎｃｏｐｒｏｔｅｉｎｉｎｈｅｐａｔｏｃａｒｃｉｎｏｇｅｎｅｓｉｓｉｎｄｕｃｅｄｂｙｔｈｉｏａｃｅｔａｍｉｄｅｉｎｒａｔｓＹＡＮＧＪｉｎＭｉｎｇ１，ＨＡＮ...     

N-ras and p53 gene mutations in Japanese patients with myeloproliferative disorders

Alterations of the N-ras oncogene and p53 tumor suppressor gene have been demonstrated to play an important role in pathogenesis of hematological malignancies. We simultaneously investigated genetic lesions of both genes in bone marrow cells from 64 Japanese patients with myeloproliferative disorders (MPD), including polycythemia vera (PV), essential thrombocythemia (ET), and idiopathic myelofibrosis (MF), by direct sequencing analysis. No mutations of the N-ras gene were detected in any cases. Two patients, one with chronic neutrophilic leukemia derived from PV and one with acute mylogenous leukemia derived from ET, exhibited three mutations of the p53 gene. Among them, two were missense mutations in exon 5 or 7 and one was a deletion in exon 5. All samples in chronic phase or from MF were devoid of mutations in both genes. These data suggested that disruptions of both genes are extremely rare in MPD in chronic phase and that loss of functions in the p53 gene could be involved in progression of MPD such as PV and ET.