p53蛋白在上皮性卵巢癌的表达及临床意义

目的:探讨抑癌基因p53蛋白在上皮性卵巢癌中的表达及预后的关系。方法:应用免疫组化方法检测72例上皮性卵巢癌p53蛋白的表达,研究其与预后的相关性。结果:上皮性卵巢癌中P53蛋白有一定的表达缺失,在G1、G2级组织表达率显著低于G3级;不同的临床分期中,Ⅰ、Ⅱ期阳性表达显著低于Ⅲ、Ⅳ期;在浆液性和粘液性两种组织类型无明显差异。p53(-)和p53(+)患者化疗的5年生存率分别为60.71%和27.27%,有显著差异(P<0.05)。结论:p53蛋白表达与肿瘤细胞的分期分化程度有关,与肿瘤组织学类型无关。p53蛋白表达可作为卵巢癌预后和化疗耐药的一个指标。     

p53、bcl-2和c-erbB-2在恶性卵巢上皮性肿瘤中的表达及临床意义

目的检测62例恶性卵巢上皮性肿瘤中p53、bcl-2和c-erbB-2的表达情况以探讨三种基因对恶性卵巢上皮性肿瘤的早期诊断及预后判断的意义。方法采用免疫组织化学方法检测p53、bcl-2 and c-erbB-2在恶性卵巢上皮性肿瘤中的表达及其与组织学分类，临床分期，腹水，淋巴结转移预后的关系。结果恶性卵巢上皮性肿瘤在p53、bcl-2 and c-erbB-2的表达阳性率分别52．23％，62．90％和45．16％与卵巢瘤组和正常组之间比较差异有显著性（P〈0．05）在晚期卵巢癌，腹水细胞阳性，有淋巴结转移组中p53、bcl-2 and c-erbB-2的表达阳性率显著增高组间比较差异有显著性（P〈0．05）。而其表达率与组织学类型无关（P〉0．05）。结论p53、bcl-2 and c-erbB-2多个基因表达提示恶性卵巢上皮性肿瘤预后差，D53、bcl-2和c-erbB-2的多个基因表达的预后判断明显优于其中某个单基因的表达监测。     

Survivin和p53蛋白在上皮性卵巢癌中的表达及临床意义

【目的】探讨Survivin、p53蛋白在上皮性卵巢癌中的表达及与临床分期、病理类型、组织学类型的关系。【方法】应用免疫组织化学染色SABC法及半定量分析的方法，检测30例正常卵巢组织标本和62例恶性卵巢肿瘤中Survivin和p53蛋白的表达，分析与卵巢癌组织学分类、临床分期、病理类型的关系。【结果】在卵巢癌组织中p53蛋白阳性表达率为54．84％（34／62），与正常对照组比较有显著差异（P〈O．01）；在卵巢癌组织Survivin蛋白阳性表达率为43．55％（27／62），与正常对照组比较有显著差异（P〈0．05）；p53和Survivin蛋白的表达与上皮性卵巢癌组织学分型无关（P〉0．05），与分化程度、临床分期有关（P〈0．05）；上皮性卵巢癌组织中Survivin蛋白的表达与p53蛋白表达呈正相关（P〈O．05）。【结论】①卵巢癌Survivin和p53蛋白表达与卵巢癌临床分期、病理分级存在一定内在联系；②Survivin和p53蛋白是卵巢癌临床重要生物学指标，参与卵巢癌的发生和发展，检测p53和Survivin蛋白表达对判断卵巢癌的恶性程度及预测预后有重要参考价值。     

P16、P53、HE4在卵巢浆液性肿瘤中的表达及意义

目的观察P16蛋白、P53蛋白、人附睾蛋白4(HE4)在卵巢浆液性肿瘤中的表达水平及其临床检测意义。方法回顾性选择河北省秦皇岛市妇幼保健院病理科2012年1月至2017年1月存档的53例浆液性卵巢癌石蜡标本作为观察组,选择50例良性上皮性卵巢肿瘤患者肿瘤组织作为良性组,选择50例已绝经子宫肌瘤正常卵巢组织作为对照组,均为手术切除后病理学检查证实;对三组病理组织的P16、P53、HE4蛋白的表达水平进行检测,同时分析上述3种指标与卵巢临床病理学特征之间的关系。结果 P16在观察组、良性组、对照组的阳性表达率分别为90.6%(48/53)、22.0%(11/50)、2.0%(1/50),P53在观察组、良性组、对照组的阳性表达率分别为50.9%(27/53)、8.0%(4/50)、0(0/50),HE4在观察组、良性组、对照组的阳性表达率分别为73.6%(39/53)、12.0%(6/50)、0(0/50)。观察组的P16、P53、HE4的表达水平均高于良性组和对照组(P0.05);观察组中,P16在临床分期晚期(Ⅲ/Ⅳ期)与早期(Ⅰ/Ⅱ期)、组织学分级高级与低级的阳性表达率差异均无统计学意义(P0.05),P53在组织学分级高级与低级的阳性表达差异具有统计学意义(P0.05),但在临床分期晚期(Ⅲ/Ⅳ期)与早期(Ⅰ/Ⅱ期)的阳性表达率差异均无统计学意义(P0.05),HE4在临床分期晚期(Ⅲ/Ⅳ期)与早期(Ⅰ/Ⅱ期)、组织学分级高级与低级的阳性表达率差异均具有统计学意义(P0.05)。结论 P16、P53在卵巢浆液性肿瘤中均有较高的阳性表达,但P53的阳性表达更多见于高级别卵巢浆液性癌中;HE4的表达与卵巢浆液性肿瘤的临床分期、组织学分级均有较大相关性,可为临床诊断和评估卵巢浆液性肿瘤预后提供参考。     

YKL-40在上皮性卵巢癌患者血清和组织中的表达及意义

目的:检测上皮性卵巢癌患者手术前后血清YKL-40水平及其在病理组织中YKL-40的表达,并分析其相关性,了解YKL-40在上皮性卵巢癌中的临床意义.方法:用酶联免疫吸附试验检测46例上皮性卵巢癌患者(上皮性卵巢癌组)术前及术后静脉血中YKL-40浓度,并以10例非卵巢病变住院妇女(正常对照组)及25例卵巢良性上皮性肿瘤患者(卵巢良性上皮性肿瘤组)作为对照.用免疫组化方法检测YKL-40在卵巢病变及正常组织中的表达情况.结果:正常对照组与卵巢良性上皮性肿瘤组YKL-40浓度差异无统计学意义(P=0.796),上皮性卵巢癌组(术前)与正常对照组、卵巢良性上皮性肿瘤组及上皮性卵巢癌组(术后)的血清YKL-40浓度差异均有统计学意义(P<0.001).上皮性卵巢癌组术前血清YKL-40浓度与患者的临床分期、CA125有相关性,与组织分级、组织学类型无相关性.YKL-40在正常卵巢组织中无表达,在卵巢良性和恶性上皮性肿瘤中的阳性表达率差异有统计学意义(P<0.005).在上皮性卵巢癌组中YKL-40阳性表达率与组织学分级、临床分期有关(P<0.05).结论:上皮性卵巢癌患者术前血清YKL-40浓度明显增高,手术治疗后YKL-40浓度明显下降,YKL-40在上皮性卵巢癌组织中其阳性表达率与组织分级和临床分期有关,提示检测YKL-40对上皮性卵巢癌恶性程度的判断有一定的临床意义.     

预防性切除双附件降低高级别浆液性卵巢癌风险的临床研究

正高级别浆液性卵巢癌是卵巢上皮性恶性肿瘤中最常见的组织学类型,约占70%,大多数患者发现时已是晚期阶段。高达20%的高级别浆液性卵巢癌患者携带基因BRCA1或2的突变,突变患者常常表现为明显的乳腺-卵巢肿瘤家族史[1]。BRCA1或2基因是肿瘤抑制基因,在染色体损伤的修复中     

抑制素和激活素在上皮性卵巢癌中的表达及其与卵巢癌发病机制的关系

目的：研究人表皮生长因子受体2（human epidermal growth factor receptor 2，HER-2/neu）在上皮性卵巢癌患者中的表达情况及其临床意义。方法：应用免疫组织化学SP法检测52例卵巢癌、10例交界性卵巢肿瘤、10例良性上皮性卵巢肿瘤中HER-2蛋白的表达情况。结果：（1）卵巢癌中的HER-2阳性表达率显著高于卵巢良性上皮性肿瘤及卵巢交界性肿瘤，差异有显著性(P=0.045)。（2）HER-2/neu蛋白在不同组织学类型、病理分级及临床分期卵巢癌中的表达差异无显著性(P>0.05)。（3）生存时间比较：HER-2/neu蛋白阳性组平均生存时间短于阴性组（16.9月与40.7月），经Log Rank检验，差异有显著性（P=0.005）。结论：HER-2/neu蛋白的过表达可能在卵巢癌的发生和发展中起一定作用，且与卵巢癌患者的不良预后相关，显著缩短患者术后生存时间，是卵巢上皮性癌患者的不良预后因素。     

p53 R2在上皮性卵巢肿瘤中的表达及临床意义

目的探讨核糖核苷酸还原酶小亚基（ p53 R2）在卵巢上皮性肿瘤中的表达及其临床病理意义。方法应用免疫组织化学方法检测66例上皮性卵巢癌组织,20例上皮性卵巢交界性肿瘤组织、36例上皮性卵巢良性肿瘤组织、20例卵巢组织中p53 R2蛋白的表达情况,并分析其与卵巢癌临床病理特征的关系。结果免疫组化检测结果显示,上皮性卵巢癌组织中p53 R2蛋白表达阳性率为72.7％（48/66）,交界性上皮性卵巢肿瘤中为50％（10/20）,卵巢上皮性良性肿瘤组织中为46％（15/36）,正常卵巢组织为5％（1/20）;低分化肿瘤组织中p53 R2蛋白表达阳性率显著高于中、高分化者（ P＜0.05）;并发肝转移的癌组织中p53 R2表达高于无肝转移组（ P＜0.01）;p53 R2蛋白表达与有无淋巴结转移无关（ P＞0.05）;p53 R2蛋白高表达者,术后生存时间短（ P＜0.05）。结论上皮性卵巢癌中p53 R2蛋白表达阳性率明显增高,并与卵巢癌病情进展有关,可望作为卵巢癌患者独立的预后指标。     

HER-2/neu在上皮性卵巢癌中的表达及其临床意义

目的：研究HER-2／neu在上皮性卵巢癌患者中的表达情况及其临床意义。方法：应用免疫组织化学SP法检测52例上皮性卵巢癌、10例卵巢交界性肿瘤、10例卵巢良性上皮性肿瘤中HER-2蛋白的表达情况。结果：上皮性卵巢癌中的HER-2阳性表达率显著高于卵巢良性上皮性肿瘤及卵巢交界性肿瘤，差异有显著性（P=0．045）。HER-2／neu蛋白在不同组织学类型、病理分级及临床分期上皮性卵巢癌中的表达差异无显著性（P〉0．05）。HER-2／neu蛋白阳性组平均生存时间短于阴性组（16．9个月vs40．7个月），经Log Rank检验，差异有显著性（P=0．005）。结论：HER-2／neu蛋白的过表达可能在上皮性卵巢癌的发生和发展中起一定作用，且与上皮性卵巢癌患者的不良预后相关．显著缩短患者术后生存时间。是上皮性卵巢癌患者的不良预后因素。[     

卵巢上皮性癌雌激素受体、孕激素受体的表达及与其预后的关系

目的研究雌激素受体(ER)、孕激素受体(PR)在卵巢上皮性癌中的表达情况,探讨其在卵巢癌发生中的作用以及与患者预后的关系。方法对68例卵巢上皮性癌组织、35例良性上皮肿瘤组织及10例正常卵巢组织采用免疫组化法测定其ER、PR表达情况,电话随访卵巢上皮性癌组3年复发情况,采用SPSS软件进行统计学分析。结果在研究的68例卵巢癌患者中,ER阳性者例数有43(63.24%),PR阳性者例数有45(66.18%),恶性组的两检测指标明显高于正常对照组、良性组,P0.05。ER、PR的阳性表达在卵巢上皮性癌各项临床病理特性的对比中,没有明显的统计学差异(P0.05)。结论本次研究实验结果表明,ER、PR阳性率在卵巢上皮性癌中明显增高,但与其临床病理类型、分期及分级没有明显关系。     

MDM2、p53在卵巢肿瘤组织及细胞系的表达和意义

目的　研究MDM 2 (murinedoubleminute 2 )和 p5 3在卵巢肿瘤组织、细胞系表达及与卵巢癌发生关系。 方法　①用细胞培养、蛋白质提取、Western免疫印迹法检测 17个卵巢癌细胞系MDM 2、p5 3蛋白表达。②用免疫组化SP法检测卵巢良性上皮性肿瘤、卵巢交界性上皮性肿瘤和卵巢癌中MDM 2、p5 3蛋白的表达。结果　① 17个卵巢癌细胞系MDM 2蛋白p90表达阳性率为 11 8% (2 / 17) ;p5 3的阳性表达率为 3 5 3 % (6/ 17) ,2例MDM 2表达阳性出现在野生型卵巢癌细胞株。②在卵巢良性上皮性肿瘤、卵巢交界性上皮性肿瘤和卵巢癌中MDM 2的阳性表达率分别为 :2 0 % (2 / 10 )、2 5 % (2 / 8)和 2 5 % (5 / 2 0 ) ;p5 3的阳性表达率分别为 2 0 % (2 / 10 )、3 7 5 % (3 / 8)和 60 % (12 / 2 0 )。 3组中 ,MDM 2阳性表达率无显著性差异 (P >0 0 5 ) ,而 p5 3在卵巢癌中的阳性表达率显著高于卵巢良性上皮性肿瘤和交界性上皮性肿瘤 (P <0 0 5 )。结论　p5 3的异常表达与卵巢肿瘤的恶性表型相关。在卵巢癌的发生发展过程中 ,p5 3的异常表达比MDM 2更有意义。MDM 2表达阳性可能在无 p5 3基因突变的卵巢癌细胞发生、发展过程中起一定作用     

Increased bcl-2 expression is associated with primary resistance to chemotherapy in human epithelial ovarian cancer.

OBJECTIVE: bcl-2, an anti-apoptotic factor, has a role in the pathogenesis of ovarian cancer as well as in resistance to chemotherapy. DESIGN AND METHODS: 20 benign, and 26 malignant epithelial ovarian tissues were analyzed for bcl-2 protein and mutant p53 by enzyme-immunoassay (EIA). Flowcytometric analysis was also performed. Patients of malignant group were followed up to monitor overall survival and primary resistance to chemotherapy. RESULTS: bcl-2 was significantly higher in malignant group than benign group (p < 0.001). A cutoff value was determined for bcl-2 (63.8 kU/g protein). At this cutoff, sensitivity is 80.7%, and specificity is 85%. Using chi square analysis, a significant correlation was found between bcl-2 and FIGO stage (p = 0.01), overall survival (p = 0.01), as well as primary resistance to chemotherapy (p = 0.03). By correlation coefficient analysis the relation between bcl-2 and synthetic phase fraction was highly significant (p = 0.002). Bcl-2, p53, and FIGO stage were significantly correlated to poor survival (p = 0.01) in univariate analysis. However, in multivariate analysis, only FIGO stage, and p53 were independent risk factors. CONCLUSION: EIA could be a useful tool for investigating the prognostic value of bcl-2, and its possible prediction of platinum resistance in epithelial ovarian cancer. This might help in selecting patients for future anti-bcl-2 therapy.     

PLK1和P53蛋白在卵巢上皮性癌中的表达及其意义

目的检测POLO样蛋白激酶1(PLK1)和P53蛋白在卵巢上皮性癌中的表达,探讨其与患者预后的关系。方法采用免疫组织化学SP法检测20例正常卵巢组织、19例卵巢良性上皮性肿瘤组织和52例卵巢上皮性癌组织中PLK1和P53蛋白的表达情况,分析其与卵巢癌临床病理指标的关系及二者在卵巢癌组织中表达的相关性,单因素和多因素Logistic回归分析影响卵巢癌患者预后的危险因素,Kaplan-Meier法分析PLK1和P53表达与卵巢癌患者预后的关系。结果 PLK1和P53在卵巢上皮性癌组织中的表达分别为38.5%和67.3%,显著高于良性肿瘤和正常卵巢组织(P<0.05)。在卵巢上皮性癌中,PLK1和P53异常高表达与临床分期和组织分化相关,临床分期越晚、组织分化越差的癌组织中PLK1和P53蛋白表达越高(P<0.05);PLK1蛋白的表达与P53蛋白的表达呈负相关(r=-0.629,P=0.000)。单因素Logistic回归分析显示PLK1、P53、临床分期、组织分化和淋巴结转移是影响卵巢癌患者预后的因素,多因素Logistic回归分析显示仅PLK1是影响卵巢癌患者预后的独立因素(OR=2.288,P=0.025,95%CI:0.105⁵0.050)。与其他患者相比,PLK1表达阳性同时P53表达阳性的卵巢癌患者,生存期最短(?2=17.246,P=0.037)。结论 PLK1和P53共同参与了卵巢癌的发生发展,PLK1可作为判断卵巢癌患者预后的标志物。     

Enzymatic mutation detection method evaluated for detection of p53 mutations in cDNA from breast cancers

BACKGROUND: Rapid, reproducible, and easily run methods with high sensitivity and specificity are required for mutation screening of clinical samples. We evaluated the Enzymatic Mutation Detection (EMD(TM)) method by analysis of archival cDNA from 203 breast cancer patients and comparison with results of cDNA-based sequencing of the tumor suppressor gene p53. METHODS: The EMD technology uses the T4 endonuclease VII, which cleaves double-stranded DNA at sites where a DNA mismatch is present because of mispairing or an insertion/deletion of nucleotides. The EMD analyses were carried out by dividing the p53 gene into two overlapping fragments that were analyzed separately. After PCR amplification, the fragments were hybridized with wild-type p53 and subsequently exposed to the EMD enzyme. Cleavage products were analyzed and scored using an ALF(TM) automated DNA sequencer and ALFwin Fragment Analyzer software (VER: 1.02). RESULTS: The EMD technique had sensitivities of 45% and 64% and specificities of 83% and 84% for the two fragments, respectively. Patients with EMD-positive, wild-type p53 tumors had a survival similar to that of patients with EMD-negative, wild-type p53 tumors. Node-positive patients with p53 mutated tumors according to sequencing had a statistically significantly worse overall survival than those with p53 wild-type tumors (P = 0.016), whereas this difference in survival was not detected when p53 status was determined with EMD (P = 0.47). CONCLUSIONS: EMD had insufficient sensitivity for consideration in screening for the p53 gene in this archival material. Sequencing must still be considered as the standard procedure.     

Sensitization of p53-mutated epithelial ovarian cancer to CD95-mediated apoptosis is synergistically induced by cisplatin pretreatment

Epithelial ovarian carcinoma (EOC) remains a highly lethal malignancy. Despite the progress in surgical and therapeutic strategies, resistance to chemotherapy is still a major concern. Cytotoxic therapies mediate killing of cancer cells by activating the intrinsic mitochondrial apoptotic pathway, and p53 status is a key factor in determining the efficacy of apoptotic signaling. The extrinsic (CD95) death receptor-dependent signaling pathway also contributes to the efficacy of cancer therapy. We previously showed that EOC are generally resistant to CD95-dependent apoptosis. In p53 wild-type EOC tumors, CD95-mediated apoptosis is impaired at the receptor level by the long form of cellular FLICE-inhibitory protein, whereas this mechanism does not account for resistance in tumors with mutated p53 (p53mu). In the present study, we examined both intrinsic and death receptor-dependent apoptotic signaling in p53mu OVCAR3 EOC cell line, showing that these cells are less susceptible to cisplatin treatment as compared with p53 wild-type EOC cells and also resist CD95-mediated apoptosis due to inefficient formation of the death-inducing signaling complex and weak mitochondrial signal amplification. However, pretreatment of OVCAR3 cells with clinically relevant cisplatin concentrations significantly improved receptor-dependent apoptotic signaling by up-modulating CD95 receptor expression and increasing death-inducing signaling complex formation efficiency. The synergy of cisplatin pretreatment and CD95 triggering in inducing cell death was also shown in p53mu tumor cells derived from ascitic fluid of advanced-stage EOC patients. These findings support the effectiveness of a combined therapeutic treatment able to sensitize cancer cells to apoptosis even when p53 is functionally inactivated.     

上皮性卵巢癌磷酸酶-张力蛋白和突变型P53表达的临床意义

目的 探讨磷酸酶-张力蛋白（PTEN）、突变型P53（mtP53）表达与上皮性卵巢癌病理学特征的关系及二者在卵巢癌发生、发展、转移中的相互作用，为预测诊断卵巢癌提供理论基础。方法 利用免疫组织化学技术分别检测32例正常卵巢者及31例卵巢良性肿瘤、74例上皮性卵巢癌患者PTEN、mtP53表达情况。结果 ①PTEN在上皮性卵巢癌表达缺失率及mtP53表达率分别高于对照组（P〈0．01）；②PTEN在浆液性囊腺癌表达缺失率高于粘液性囊腺癌（P〈0．05），晚期表达缺失率高于早期（P〈0．01），G3表达缺失率高于G1＋G2（P〈0．05）。③mtP53在粘液性囊腺癌中表达率高于浆液性囊腺癌（P〈0.05），晚期的阳性率高于早期（P〈0．01）；④PTEN蛋白表达与mtP53蛋白表达呈负相关（r=0．327，P〈0．01）。结论 PTEN表达缺失、mtP53表达在上皮性卵巢癌的发生发展和转移中有重要作用；PTEN、mtP53同时发生异常可作为评估卵巢癌恶性程度的重要生物学指标。     

k-ras、p16基因在卵巢上皮性肿瘤的表达及临床意义

目的　研究k ras、p16基因在卵巢上皮性肿瘤中的表达及其意义。方法　应用链霉菌抗生物 过氧化酶连接法检测 98例卵巢上皮癌石蜡块中的表达情况 ,应用kaplam meier法及多变量cox比例风险回归摸型 ,分析 2种蛋白表达与患者预后关系。结果　k ras蛋白表达率为 79 6% ,其表达与临床分期及病理类型有关 (P <0 0 1) ;p16蛋白表达率 60 2 % ,其表达与临床分期、癌瘤播散、淋巴转移及患者预后有关 (P <0 0 1) ;患者生存随访表明p16表达阳性者平均生存时间短于无表达者 ,k ras对生存预后影响不显著。结论　p16蛋白表达与卵巢上皮癌的恶性程度有显著相关性 ,并能判断其癌瘤播散、转移能力、估计患者的预后 ;k ras基因表达主要发生在早期或分化好的卵巢肿瘤中 ,可以作为卵巢肿瘤发生的启动基因。     

Ribozyme-mediated induction of apoptosis in human cancer cells by targeted repair of mutant p53 RNA.

A variety of mutations in the p53 tumor suppressor gene have been found in over half of human tumors. Thus, restoration of wild-type p53 activity by repair of mutant RNA has been previously suggested as an approach to cancer treatment. To explore the potential utility of RNA repair for cancer therapy, we developed a group I intron-based ribozyme that can replace mutant p53 RNA with a wild-type RNA sequence attached to the 3' end of the ribozyme by trans-splicing reaction. First, RNA mapping analysis demonstrated that the leader sequences upstream of the AUG start codon in the mutant p53 RNA appeared to be particularly accessible to the ribozymes. Then, the trans-splicing ribozyme specifically recognizing the most accessible sequence induced functional p53 activity, resulting in an 8- and a 2.6-fold induction of transactivation of p53-responsive promoters in two mutant p53-related ovarian cancer cell lines, SKOV3 cells and 2774 cells, respectively, by repairing defective p53 RNA. The repair efficiency of the mutant p53 RNA was almost 10% in 2774 cells. Moreover, the ribozyme activated the expression level of endogenous p21 and Bax genes in the cells. Furthermore, apoptosis was efficiently triggered in the human cancer cells transfected with the specific ribozyme. These results suggest that a trans-splicing ribozyme could be a potent anti-cancer agent that can revert the defective p53-related neoplastic phenotype.     

Adenovirus type 5 E1A gene therapy for ovarian clear cell carcinoma: a potential treatment strategy

Resistance of ovarian clear cell carcinoma (CCC) to platinum-based chemotherapy is associated with poor prognosis, and an effective treatment for advanced disease is urgently needed. HER2/neu is up-regulated more often in CCC than in other histologic types of epithelial ovarian cancer. The purpose of this study was to assess possible treatment for ovarian CCC with the anti-HER2 antibody trastuzumab or human adenovirus type 5 E1A. We treated 10 CCC cell lines with trastuzumab or E1A and assessed cell viability, proliferation, and colony formation and the expression of HER2 and wild-type p53 proteins and molecules downstream of those signaling pathways. HER2 protein was detected at various levels in all 10 cell lines by Western blotting and in 5 CCC cell lines by immunohistochemical staining; HER2 gene amplification was detected (by fluorescence in situ hybridization) in only one cell line (RMG-I). Trastuzumab did not inhibit proliferation in any of the four CCC cell lines tested (RMG-I, SKOV-2, OVTOKO, and OVSAYO). However, transfection with E1A (as compared with control vectors) reduced colony formation in all 10 CCC cell lines regardless of HER2 expression level. Infection of RMG-I and SMOV-2 cells with an adenoviral vector encoding E1A led to significant (P < 0.05) suppression of proliferation and enhancement of cell death; this effect required stabilization of p53 (but not p73) protein and was associated with the up-regulation of Bax and the cleavage of caspase-9. Other mechanisms, such as p53-independent apoptosis, may also be involved in E1A-mediated cell death in CCC. Finally, treatment with E1A prolonged survival in a CCC xenograft model (P < 0.001). E1A gene therapy, because of its ability to stabilize wild-type p53, is worth exploring as a treatment modality for women with ovarian CCC, which typically expresses wild-type p53.     

卵巢癌组织NFkB家族蛋白的表达和临床意义

目的　研究卵巢癌组织NFkB家族蛋白的表达及其临床意义。方法　采用免疫组化方法检测卵巢良性上皮性肿瘤、卵巢交界性上皮性肿瘤和卵巢癌中NFkB蛋白的表达。结果　在卵巢良性上皮性肿瘤、卵巢交界性上皮性肿瘤和卵巢癌中NFkB的阳性表达率分别为 3 3 3 %、3 7 5 %和 65 % ;在卵巢癌组织 ,p65核染色阳性与分化程度、淋巴结转移、临床分期及肿瘤大小明显相关 (P <0 0 5 )。结论　NFkB与卵巢癌的发生、发展有关 ;NFkB可望成为判断卵巢癌预后新的标志物。