幽门螺杆菌阳性胃癌前病变上皮增殖状态及癌基因表达的研究

目的:探讨胃癌前病变——不完全结肠型肠化(ICM)和/或中度以上异型增生(Dys)的上皮增殖状态及癌基因蛋白表达在幽门螺杆菌(Hp)阳性、阴性患者之间有无差异。方法:对243例胃粘膜病变,如慢性浅表性胃炎(CSG)、慢性萎缩性胃炎(CAG),ICM和/或Dys及胃癌患者胃粘膜上皮分别用AgNOR染色及单克隆抗体免疫组织化学技术研究其增殖状态和ras P~(23)表达情况,Hp感染由CLO试验结合病理Warthin-Starry染色而确定,其中128例阳性,115例阴性。比较胃癌前病变中Hp阳性与阴性组间AgNOR数目和ras p~(-1)阳性表达率。结果:Hp阳性各胃粘膜病变AgNOR数目及ras p~(21)阳性表达率除浅表性胃炎外均显著高于阴性组(P<0.05或P<0.01)。胃癌前病变83例中Hp阳性40例,阴性43例。Hp阳性组AgNOR均数及ras p~2阳性表达率均显著高于阴性组(P<0.01或P<0.05)。同时发现Hp密度与AgNOR均数及ras p~2表达无关。结论:Hp阳性胃癌前病变具有更多恶性肿瘤的生物学行为。在此过程中,Hp可能作为促进剂激活ras基因,并促使胃粘膜上皮细胞过度增殖。胃癌的发生可能与一种特殊的Hp菌株感染有关。     

恶性浆膜腔积液脱落细胞中P21 ras蛋白表达状况及其意义

目的:检测浆膜腔积液脱落细胞P21 ras蛋白表达状况,探讨其对恶性浆膜腔积液的诊断价值.方法:将新鲜浆膜腔积液离心后收集脱落细胞,取部分细胞涂片进行常规细胞学诊断,据此将积液分为良性与恶性两组.对余下脱落细胞作"标准化"处理,包括去除红细胞、多聚甲醛固定、调整细胞浓度、制备细胞涂片,然后进行P21 ras蛋白免疫化学染色(SP法).结果:共108例浆膜腔积液,恶性53例,良性55例.39例恶性积液P21 fas蛋白免疫化学染色阳性(73.6%),且多为强阳性或阳性;12例良性积液P21 ras蛋白染色阳性(21.8%),且多为弱阳性或阳性,两组间阳性率(χ2=29.02,P＜0.001)及阳性强度(Uc=6.786,P＜0.001)的差异均有显著性统计学意义.P21 ras蛋白免疫化学染色诊断恶性积液的敏感度为73.6%,特异度为78.2%,诊断符合率达75.9%.结论:浆膜腔积液中脱落细胞P21 ras蛋白免疫化学染色在肿瘤细胞多为阳性,良性细胞多为阴性,对恶性体腔积液的诊断有较大的价值.     

ras基因突变与侵蚀性葡萄胎组织分化的关系研究

【目的】探讨ras 基因突变与侵蚀性葡萄胎组织分化之间的关系。【方法】采用聚合酶链反应—单链DNA 构象多态性分析法,对30 例侵蚀性葡萄胎石蜡包埋组织Haras 基因Exon Ⅰ突变情况进行了检测。【结果】侵蚀性葡萄胎组织分化Ⅰ级,Ⅱ级,Ⅲ级,Haras 基因第一外显子点突变率依次为15 .4 % ,40 .0 % ,71 .4 % ,经秩和检验,差异有显著性( P< 0 .01) 。【结论】ras 基因突变与侵蚀性葡萄胎恶性程度有关,恶性程度越高,ras 基因突变率越高;提示ras 基因突变对疾病预后有负影响。     

Analysis of N-ras gene mutation and p53 gene expression in human hepatocellular carcinomas

AIM:To study the relationship between N-ras gene mutation and p53 gene expression in the carcinogenesis and the development of human hepatocellular carcinomas (HCC).METHODS:The N-ras gene mutation and the p53 gene expression were analyzed in 29 cases of HCC by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and immunohistochemistry.RESULTS:Thirteen cases of HCCs were p53 positive (44.8%), which showed a rather high Cpercen-tage of p53 gene mutation in Guangxi. The aberrations at N-ras codon 2-37 were found in 79.31% of HCCs and 80.77% of adjacent non-tumorous liver tissues. More than 2 point mutations of N-ras gene were observed in 22 cases (75.86%). Twelve cases (41.37%) of HCCs showed both N-ras gene mutation and p53 gene expression.CONCLUSION:N-ras gene and p53 gene may be involved in the carcinogenesis and the development of HCC.That 38% of HCCs with N-ras gene mutation did not express p53 protein indicates that some other genes or factors may participate in the carcinogenesis and the development of HCC.     

ras和nm23的表达与胃癌转移的相关性研究

目的:观察nm23与ras在原发性胃癌中的表达水平与胃癌淋巴结转移的关系.方法:免疫组化和RT-PCR.结果:通过对80例原发性胃癌的研究表明nm23低表达者淋巴结转移率(90%)比nm23正常表达者高(40%,P<0.05).同时发现p21 ras阳性为65%,p21 ras阳性者淋巴结转移率高于p21 ras阴性者淋巴结转移率(78.5%对57.1%,p<0.05).肿瘤组织如同时具有nm23低表达和ras过表达则有更高的淋巴结转移率(94.12%),而nm23高表达和ras低表达者则淋巴结转移率更低(25%),ras-mRNA半定量分析说明ras的表达与淋巴结转移正相关,结论:nm23低表达和ras过表达在原发性胃癌淋巴结转移中起重要的联合作用.它们可以作为判断胃癌预后的一个生物学标志.     

亚硒酸钠对胃粘膜细胞非程序DNA合成、LPO和ras P21表达的影响

目的研究亚硒酸钠对甲基硝基亚硝基胍（ＭＮＮＧ）所致胃粘膜细胞损伤的防护作用．方法观察了亚硒酸钠对ＭＮＮＧ所致胃粘膜细胞非程序ＤＮＡ合成（ＵＤＳ）、脂质过氧化物（ＬＰＯ）和ｒａｓＰ２１表达的影响．结果胃粘膜细胞先用１０μｍｏｌ／Ｌ或１μｍｏｌ／Ｌ亚硒酸钠预处理４ｈ，再给ＭＮＮＧ组细胞的非程序ＤＮＡ合成水平（ｃｐｍ／×１０－６ｍｉｎ－１，１１６６±１５６或１５６６±１８７ｖｓ１８３８±２０５，Ｐ＜００１～００５），脂质过氧化物（２０ｄ，μｍｏｌ／Ｌ，４５±０６或４７±０６ｖｓ７４±０７，Ｐ＜００１）和ｒａｓＰ２１蛋白含量（２０ｄ，Ａ，０６８±００８或０８６±００７ｖｓ１０８±０１１，Ｐ＜００１～００５）均显著低于ＭＮＮＧ组．结论一定剂量亚硒酸钠对ＭＮＮＧ诱导的胃粘膜细胞损伤有防护作用．     

The Expression of Tumor Rejection Antigen on Rat Fetus Fibroblasts Transformed by the ras Oncogene

The expression of tumor rejection antigens (TRA) was analyzed on clones of rat fetus-derived fibroblasts, WFB, transformed or transfected by oncogenes. It was shown that a tumorigenic W14 clone, which is an activated H- ras transformant of parental WFB, expressed TRA in transplantation experiments using syngeneic WKA rats. The data also showed that W14 TRA was acquired in the event of cell transformation, since it was not detected on parental non-transformed WFB cells or Wmyc-4 clone which is a transfectant of WFB by mouse plasmacytoma-derived c- myc DNA. However, TRA was not expressed or at least was not detected on highly tumorigenic W31, another clone of H- ras transformants of parental WFB, in the transplantation experiments. We also assessed the level of expression of major histocompatibility antigens (MHC) class I molecules on these cells by using R4-8B1 Mab that reacts specifically with rat class I antigen. The data indicated that it was decreased on W14, W31, and Wmyc-4, but not on parental WFB. Although this molecule was weakly positive on W14 cells, W31 and Wmyc-4 showed even greater decreases. These data may indicate that the TRA expression and its recognition by syngeneic hosts are dependent upon the transformed clones, although their parental cell is the same. We discuss in detail this difference of expression and recognition of TRA in the context of the cell transforming process.     

子宫内膜癌前病变中K-ras与MTS1/p16基因的表达及意义

 目的　探讨K ras激活与MTS1/ p16基因突变 /缺失在子宫内膜癌中的发生发展关系。 方法　对子宫内膜癌及癌前病变组织K ras与MTS1/p16蛋白的免疫组化测定并用PCR技术对MTS1/ p16基因在子宫内膜癌中的纯合性缺失进行检测。结果　K ras、p16蛋白广泛存在于子宫内膜癌和癌前病变组织中 ,癌前病变K ras表达为 11.9% ,癌组为 6 2 .96 % (P <0 .0 5 ) ,而p16表达分别为 76 .5 9%与5 1.85 %。 13例 p16蛋白表达阴性子宫内膜癌PCR扩增 ,7例显示外显子 1缺失。K ras表达与细胞恶性程度呈正相关 ,p16表达则呈负相关。 结论　 (1)K ras基因激活与MTS1/ p16基因突变 /缺失导致细胞周期增殖失控 ,是内膜癌发生发展的一个重要环节 ;(2 )子宫内膜癌中p16基因外显子 1纯合子缺失可能是p16蛋白表达降低的机制之一 ;(3)动态观测内膜增生组织中的p2 1ras表达阳性者 ,对子宫内膜癌的早期发现可能有积极意义