p21-ras、p53和VEGF在甲状腺乳头状癌中的表达及意义

目的　研究原癌基因Ras、抑癌基因p5 3及血管内皮生长因子 (VEGF)在甲状腺乳头状癌中的表达及相关性。方法　应用免疫组织化学S P法对 4 0例甲状腺乳头状癌中p2 1 ras、p5 3及VEGF的表达进行研究。结果　甲状腺乳头状癌中存在p2 1 ras、p5 3及VEGF的过度表达 ;VEGF的表达与p2 1 ras、p5 3的表达显著相关 (P <0 .0 5 ) ;VEGF的表达与甲状腺乳头状癌淋巴结转移显著相关 (P <0 .0 5 )。结论　p2 1 ras、p5 3、VEGF在甲状腺乳头状癌的发生发展过程中起重要作用 ;VEGF的表达与p2 1 ras、p5 3表达显著相关 ,可能受其调控。     

rasP21在人乳腺良恶性病变中表达的研究

目的探讨ras基因在人乳腺癌及良性疾患组织中的表达情况及其与淋巴结转移等预后因素之间的关系。方法乳腺组织标本共万例，以昆抗人之panras单抗IgG2b及免疫组化方法检测ras基因在乳腺组织中的表达产物。结果rasP21位于胞浆；rasP21在乳腺癌中表达率为63．6％，而在所有良性乳腺疾患中仅1例阳性；rasP21表达与乳腺癌淋巴结转移正相关，且同一病人13对原发灶及淋巴结转移灶配对标本中有9对表达一致。结论rasP21的检测在评估乳腺癌淋巴转移及良恶性病变上有肯定意义，P21是评估乳腺癌患者预后有价值的生物学指标。     

p21 ras protein expression in benign and malignant

The ras oncogenes encode for GTP binding and GTPase active proteins of relative molecular mass 21 000 (p21^ras) which are involved in the transduction of stimuli for cell proliferation. There have been conflicting reports about the detection and significance of expression of p21^ras protein in human breast disease as determined by immunohistochemistry. The antibody Y13-259, which detects a single protein of M_r 21 000, has been applied immunohistochemically to frozen sections of normal, benign proliferative breast, fibroadenomas, and carcinomas. Uniform staining of normal breast epithelium and myoepithelium was found, with occasional stronger staining in areas of epithelial hyperplasia in benign breast disease. Contrary to previous reports, decreased expression, usually heterogeneous, was found in half of the carcinomas examined. Thirty per cent of the carcinomas exhibited heterogeneous staining stronger than that of normal breast, interpreted as increased expression of p21^ras protein. This did not relate to tumour grade or node status but showed a significant correlation with proliferation rate as determined by the monoclonal antibody Ki-67. This study confirms previous reports that p21^ras protein expression is a feature of normal cells, and has identified increased expression in 30 per cent of tumours associated with higher proliferation rates, which is a lower incidence than previously claimed when a different antibody was employed.     

大鼠单克隆抗体夹心ELISA法检测肝病病人血清中p21^ras蛋白

本文应用抗癌基因ｒａｓ表达产物Ｐ２１ｒａｓ蛋白的大鼠单克隆抗体建立的双抗体夹心ＥＬＩＳＡ法，检测了肝癌及癌病变前病人血清中ｐ２１ｒａｓ蛋白的浓度。所获阳性检出率分别为：慢性乙型肝炎为１３．０％（１２／９２），肝硬化为２７．８％（１０／３６）和肝癌为５０．０％（８／１６）。另外，对试验方法的敏感性、特异性及稳定性，以及检测Ｐ２１ｒａｓ蛋白与ＡＦＰ的关系进行了评价。结果表明，Ｐ２１ｒａｓ蛋白的过高表达发生在肝细胞癌变之前。提示在慢性乙型肝炎及肝硬化病人血清中检出Ｐ２１ｒａｓ蛋白，是预测肝细胞癌变的危险信号。     

B cell antigen receptor cross-linking induces tyrosine phosphorylation and membrane translocation of a multimeric Shc complex that is augmented by CD19 co-ligation

The SH2 domain-containing transforming Shc protein has been implicated in mitogenic signaling via several surface receptors through p21^ras. Following tyrosine phosphorylation by either receptor or non-receptor tyrosine kinases, Shc may interact with the adaptor protein Grb2, which is linked to Sos1, a guanine nucleotide exchange factor for human ras. Ligation of the antigen receptor complex on B cells (BCR) is known to activate various intracellular signaling pathways, which may accumulate in mitogenic responses. With respect to the initial steps, the activation of BCR-associated non-receptor tyrosine kinases appears to be indispensible. In this report we show that Shc proteins become tyrosine phosphorylated after BCR ligation on both transformed and normal human B cells. This is accompanied by the association of Shc with Grb2 proteins and a yet unidentified 145-kDa tyrosine phosphorylated protein. Subcellular fractionation revealed that this activation-induced multimeric Shc complex rapidly translocates towards the plasma membrane. Co-ligation of the BCR with the CD19 molecule results in a marked increase of these events, whereas CD19 cross-linking alone does not induce Shc tyrosine phosphorylation or translocation. Thus, in B cells the Shc complex may represent a molecular junction between the BCR and the mitogenic p21^ras cascade.     

慢性胰腺炎K—ras基因突变的临床病理学意义

目的：探讨慢性胰腺炎K－ras基因突变的临床病理学意义。方法：9例手术切除的慢性胰腺炎的石蜡标本,用微解剖法分离慢性胰腺炎的胰导管上皮粘液细胞增生灶,提取,扩增DNA,用ASO斑点杂交检测K－ras基因第12密码子的碱基序列。对9例接受手术治疗的病人进行长期随访,结果：9例慢性胰腺炎中4例有明显的胰导管上皮粘液细胞增生,其中2例被检出GAT型突变,分别占全组和有胰管上皮粘液细胞增生的22％和505,两个突变病例分别是接受了胰体尾切除和胰头十二指肠切除手术,术后分别随访17年和10年,没有发现任何恶变迹象,结构：慢性胰腺为可以检出K－ras基因突变,发生了K－ras基因突变的慢性胰腺炎上皮粘液细胞增生灶,未必一定发生为胰腺癌,胰液、粪便、末梢血液和尿液的检测,以及胰腺组织细针刺液检出K－ras基因突变,对胰腺癌的诊断有重要参考价值,但不应视为胰腺癌的确诊依据。     

癌基因c-myc和n-ras在妊娠滋养细胞疾病中表达的研究

为研究癌基因c-myc和n-ras在妊娠滋养细胞疾病(GTD)发生、发展中的作用,用地高辛标记的c-myc、n-ras裸核探针与54例石蜡包埋的GTD组织进行原位杂交.结果显示c-myc mRNA在葡萄胎、侵蚀性葡萄胎和绒癌组织中阳性表达率分别为44.4%、55.6%和83.3%,绒癌c-myc阳性表达率高于葡萄胎(P＜0.05).n-ras mRNA在葡萄胎、侵蚀性葡萄胎和绒癌组织中阳性表达率分别为88.9%、77.8%和44.4%,绒癌n-ras阳性表达率显著低于葡萄胎(P＜0.01)和侵蚀性葡萄胎(P＜0.05).Ⅲ～Ⅳ期妊娠滋养细胞瘤(GTT)组织中c-myc阳性表达率为90.9%,高于I期的45.5%(P＜0.05).c-myc和n-ras基因在GTT组织中共同表达率为47.2%.结果提示c-myc基因与GTD病变的发展及GTT临床分期有关,n-ras基因可能为GTT发生的早期事件,c-myc和n-ras基因在GTD癌变过程中起协同作用.     

细胞周期调节因子在原发和复发鼻咽癌的表达

【目的】探讨细胞周期调节因子在鼻咽癌复发中的作用。【方法】采用LsAB法同时检测69例患者原发和复发鼻咽癌组织中p53、MDM2、p21ras和p21WAF1蛋白的表达。【结果】复发癌与原发癌相比阳性表达率方面,p53蛋白(78%和80%)或MDM2蛋白(84%和83%)很相近,p21ras蛋白(73%和93%)或p21WAF1蛋白(52%和84%)明显下降;高表达率方面,p53蛋白(42%和51%)很相近,MDM2蛋白(57%和32%)明显升高,p21ras蛋白(16%和65%)或p21WAF1蛋白(17%和46%)明显下降。其中,MDM2蛋白表达水平在复发癌明显升高主要见于复发间期<34个月患者组（P<0.05),p21ras蛋白和p21WAF1蛋白表达水平在复发癌明显下降见于复发间期<34个月和≥34个月患者组（均<0.02以下)。【结论】原发鼻咽癌临床治愈后,p53蛋白和MDM2蛋白过度表达以及p21WAF1蛋白低表达或不表达可能仍然对鼻咽癌的复发起重要作用;MDM2蛋白表达水平显著升高和p21WAF1蛋白表达水平显著下降可能进一步加促鼻咽癌的复发过程。     

Tumor suppressor genes,growth factor genes,and oncogenes in hepatitis B virus-associated hepatocellular carcinoma

A series of changes in the genes that control hepatocyte growth, or interference with the protein products of these genes, appears to have an important role in the etiology of hepatocellular carcinoma (HCC). Mutations of the p53 tumor suppressor gene have been identified in 30-50% of HCC patients in some geographic areas. Abnormalities of the RB tumor suppressor gene have been found in 20-25% of HCCs, including 80-86% of HCCs with p53 mutations. Overexpression of transforming growth factor α (TGF-a), insulin-like growth factor II (IGF-II), and the oncogenes N-ras, c-myc, and c-fos have been found in high percentages of HCC patients. The cumulative effect of these changes may be more important than the order in which they occur. Some of these changes may explain the mechanism(s) by which the hepatitis B virus participates in the development of HCC. © 1994 Wiley-Liss, Inc.     

胃癌及癌前病变组织中雌激素受体和P21ras的表达及意义

目的 探讨雌激素受体（ＥＲ）和ｒａｓ原癌基因蛋白－Ｐ２ｒａｓ的表达在胃癌发生、发展中的作用及与胃癌生物学行为的关系。方法 采用免疫组化ＳＰ法。结果 ＥＲ在慢性浅表性胃炎（２０例）、异型增生（２１例）中均为阴性,胃癌（４０例）的表达阳性率为４０％,三组比较有显著性差异（Ｉ〈０．０５）。Ｐ２１＾ｒａｓ在慢性浅表性胃炎、异型增生、胃癌的表达阳性率分别为１０％、２３．８％、４７．５％,三组比较差异有显著性