乳腺癌HSV—1,HSV—2与c—erbB—2关系的免疫组化研究

采用免疫组织化学Ｓ－Ｐ法检测５２例手术切除乳腺癌组织ｃ－ｅｒｂＢ－２蛋白和ＨＳＶ－１、ＨＳＶ－２表达情况。结果发现癌组织中ｃ－ｅｒｂＢ－２阳性３４例（６５．４％）；ＨＳＶ－１阳性３８例（７３．１％）；ＨＳＶ－２阳性１５例（２８．８％）。癌旁组织３２例，阳性分别为３例（９．４％）；１２例（３７．５％）；２例（６．３％）。乳腺癌中ｃ－ｅｒｂＢ－２阳性率明显高于癌旁组织。乳腺癌及癌旁的ＨＳＶ－１阳性率明     

Expression of the c-erbB-2-encoded oncoprotein and progesterone receptor in human meningiomas

The present study investigated the expression of c-erbB-2 in 59 meningiomas, including different histological subtypes and anaplastic variants, by immunocytochemistry and molecular biological techniques. Immunohistochemistry using the monoclonal antibody FWP-51 directed against c-erbB-2-encoded oncoprotein gp185 demonstrated variable degrees of immunoreactivity in all meningiomas. The intensity of immunostaining correlated with the degree of expression as assessed by Western analysis in 28 meningiomas using polyclonal antiserum 21N. There was no correlation between the degree of expression and histological variants. Immunoreactivity of all menigiomas was distinctly less intense, however, than that of the human breast cancer cell line SK-BR-3, and slightly lower than that of brain metastases of breast and ovarian carcinomas that served as positive controls for both methods. By Southern analysis all meningiomas showed a single copy of the c-erbB-2 gene. Non-neoplastic arachnoid cap cells also exhibited c-erbB-2 expression and the degree of immunoreactivity was comparable with the majority of meningiomas. These data argue against an overexpression of c-erbB-2 in meningiomas, but rather indicate a cell-type-specific constitutive expression of the c-erbB-2 gene product in meningiomas and their putative progenitor cells. Since a subgroup of meningiomas is known to express progesterone receptors (PR), gp185 immunoreactivity was compared to the hormone receptor status using monoclonal antibody KD68. Fifty-six percent meningiomas showed PR immunoreactivity, but there was no statistically significant correlation with the degree of gp185 expression.This study was supported by a grant of the Tumorzentrum Heidelberg/Mannheim (M.K., No. 10028060)     

转移相关基因nm23和P53及S100A4在晚期胃癌中的表达及与侵袭转移的相关性研究

目的探讨转移相关蛋白（nm23和P53及S100A4）在晚期胃癌转移发展过程中的意义。方法应用组织芯片和免疫组织化学方法研究nm23、P53和S100A4在74例胃癌患者的癌、癌旁、淋巴结转移、远处转移（肝脏、胰腺、卵巢等）组织中的表达。结果同癌旁组织相比，癌组织中P53和S100A4表达明显升高（P〈0．01），而nm23的表达明显降低（P〈0．05）；同癌组织相比，淋巴结中nm23的表达明显降低（P〈0．05）。远处转移组织S100A4表达明显升高（P〈0．01）。3者的阳性表达与胃癌的部分恶性生物学行为有关。癌组织中nm23^＋／P53^＋、P53^＋／S100A4^＋和nm23^＋／S100A4^＋的基因表型比例分别为48例（64．9％）、50例（67．6％）和39例（52．7％），其中P53^＋／S100A4^＋、nm23^＋／S100A4^＋和nm23^＋／P53^＋／S100A4^＋均与胃癌的高转移潜能相关。结论nm23和S100A4在肿瘤转移中发挥了重要作用；联合检测nm23、P53和S100A4的表达可用于评定胃癌的转移潜能。     

垂体腺瘤的分子病因学研究进展

垂体腺瘤是发生于垂体前叶的良性肿瘤，约占中枢神经系统肿瘤的10％-20％，而无功能微腺瘤占到成人尸检的23％左右。生理上根据免疫组化将垂体腺瘤按功能分为有激素分泌活性腺瘤（functioning pituitary adenoma，FPA）和非激素分泌活性腺瘤（non—functioning pituitary adenoma，NFPA）两大类。[第一段]     

重组人肿瘤坏死因子诱导HL－60白血病细胞分化及调控原癌基因表达的作用

采用２０～２００Ｕ／ｍｌ的重组人肿瘤坏死因子（ｒｈＴＮＦ－α）处理体外液相培养的人早幼粒白血病细胞珠ＨＬ－６０，观察到５０～２００Ｕ／ｍｌ的小剂量ＴＮＦ具有诱导其向单核－巨噬细胞途径分化及抑制其增殖的效应。采用细胞总ＲＮＡ打点杂交技术检测１～１００Ｕ／ｍｌＴＮＦ诱导ＨＬ－６０细胞早期（１２小时内）对其ｃ－ｍｙｃ，ｃ－ｆｏｓ原癌基因表达的影响，发现ＴＮＦ可抑制ｃ－ｍｙｃｍＲＮＡ水平及ｃ－ｆｏｓ短暂性表达增高。结果表明此小剂量ｒｈＴＮＦ－α具有诱导白血病细胞分化的效应及调控多癌基因表达的作用。     

三种癌基因蛋白产物在结肠癌的表达及意义

 用免疫组化方法检测4B例结肠良性病变和113例结肠癌中c－erbB－2、c－myc及P⁵³蛋白的表达。结果：三种癌基因蛋白产物在结肠癌中的表达显著高于结肠良性病变（P<0.01）。c－erbB－2、P⁵³蛋白表达与结肠癌淋巴结转移密切相关。P⁵³蛋白表达与结肠癌的分化程度有关。检测结肠癌组织中三种癌基因蛋白产物表达可作为结肠癌的诊断和判断预后的参考指标。     

玻璃纤维诱导的转化细胞活化癌基因的研究

用玻璃纤维处理BALB/C3T3细胞,使细胞发生转化,从转化细胞中抽提DNA用以转染NIH3T3细胞,结果被转染的细胞亦发生转化。用~(32)P标记的Ha-ras癌基因作探针,通过斑点杂交,征明玻璃纤维诱发的BALB/3T3转化细胞中,Ha—ras的原癌基因被激活。     

Why Are Human Cells Resistant to Malignant Cell Transformation in vitro?1

Transformation of human cells, both induced and spontaneous, is an extremely rare event, whereas rodent cells are relatively easily transformed when treated with a single carcinogenic agent. The present review addresses the question of why human cells are resistant to malignant transformation in vitro. To facilitate understanding of the problem, the process of transformation is divided operationally into two phases, i.e. phase I, immortalization; and phase II, malignant transformation. In human cells, one-phase transformation, i.e., the consecutive occurrence of phases I and II due to the action of a single carcinogenic agent, is observed only rarely. Once human cells are immortalized, however, malignant transformation by chemical carcinogens or oncogenes proceeds, suggesting that for human cells, phase I immortalization is a prerequisite for such transformation to take place. To date, about 20 papers have been published describing protocols for the two-phase transformation of a variety of human epithelial cells and fibroblasts. In most experiments, SV40, human papilloma viruses and their transforming genes are utilized for induction of phase I (immortalization) followed by the use of chemical carcinogens or activated oncogenes for induction of phase II (malignant transformation). Possible mechanisms that would render human cells refractory to transformation are discussed below.     

幽门螺杆菌感染诱导胃黏膜上皮细胞凋亡及端粒酶逆转录酶表达

目的研究幽门螺杆菌（Hp）根除前后胃黏膜上皮细胞凋亡和端粒酶逆转录酶（hTERT）表达及其与bcl-2、c-myc蛋白表达的关系。方法采用脱氧核糖核酸末端转移酶介导的缺口末端标记（TUNEL）技术及免疫组化染色方法检测39例却Hp性患者根除治疗及21例却阴性患者对症治疗前后胃黏膜上皮细胞凋亡、hTERT、bcl-2、c—myc蛋白表达的变化。结果治疗前却阳性者胃黏膜上皮细胞凋亡指数为16．2％，显著高于却阴性者（P〈0．05）；却阳性者hTERT、c—myc蛋白表达显著高于却阴性者（53．8％比23．8％；53．8％比28．6％，P〈0．05）。邯根除者治疗后胃黏膜上皮细胞凋亡、hTERT及bcl-2、c—myc蛋白表达与根除前相比均显著下降（16．9％比9．0％；59．3％比22．2％；59．3％比25．9％；59．3％比14．8％，P〈0．01），且与却阴性对照组相比差异无统计学意义（P〈0．05）；而邯未根治组及对照组上述指标均无显著变化。治疗前bcl-2、c—myc蛋白与hTERT呈显著正相关，秩相关系数r分别为0．269、0．474（P〈0．05）。结论却感染诱导细胞凋亡及hTERT过度表达，使胃黏膜不稳定性增加。根除却可纠正细胞凋亡失调，使hTERT表达下降或消失，从而降低胃癌发生的可能性。bcl-2及c—myc蛋白对hTERT表达可能具有调控作用。     

胃癌组织中Fas、FasL和P27表达的临床研究

目的 研究Fas、FasL、P27在胃癌组织中的表达，并探讨其生物学意义。方法 采用免疫组化SP法检测50例胃癌组织、癌旁交界组织、距肿瘤边缘5cm组织及10例正常胃粘膜中Fas、FasL的表达，并对正常胃粘膜和肿瘤组织中P27的表达进行检测。结果 胃癌组织、癌旁交界组织的Fas表达和P27的表达明显低于正常组织(P＜0．01)，而FasL表达明显高于正常组织。胃癌不同TNM分期、不同分化程度、淋巴结有无转移的Fas、FasL表达无显著性差异(P＞0．05)，而P27表达有显著性差异(P＜0．01，P＜0．05)。结论 Fas、FasL表达与胃癌形成有关，与胃癌进展无关，Fas/FasL系统可能在胃癌发生发展过程的免疫逃避中起重要作用；P27可能是一个预测胃癌预后的重要因素。