IGF-1及IGFBP-3在子宫内膜癌组织中的表达及意义

目的:探讨胰岛素样生长因子-1( IGF-1)和胰岛素样生长因子结合蛋白-3(IGFBP-3)在子宫内膜癌组织中的表达及临床意义.方法:38例子宫内膜癌患者为实验组,30例因子宫肌瘤手术患者(术后病理证实正常子宫内膜组织)为对照组.采用酶联免疫吸附法检测血清IGF-1及IGFBP-3水平,应用荧光PCR法检测IGF-1及IGFBP-3在内膜组织中基因及其产物表达.结果:子宫内膜癌组织IGF-1 mRNA(2.106±4.943)表达水平高于对照组(0.388±0.501),两者差异有统计学意义(P＜0.05);而IGFBP-3 mRNA (0.690±0.564)表达水平低于对照组(1.306±1.393),两者差异有统计学意义(P＜0.05).实验组中IGF-1 (76.958±95.600μg/L)在血清的表达水平高于对照组(28.474±11.744 μg/L),实验组IGFBP-3血清表达水平(27.260±13.284 μg/L)低于对照组(47.650±25.979 μg/L),差异均有统计学意义(P ＜0.05).结论: IGF-1、IGFBP-3与子宫内膜癌发生有关.检测血清IGF-1、IGFBP-3有助于发现子宫内膜癌高危人群,探索是否可作为其筛查及预后判断指标.     

SRC-3、IGF-1在子宫肌瘤组织中的表达及意义

目的:研究SRC-3、IGF-1蛋白及基因在子宫肌瘤中的表达,探讨其与子宫肌瘤发生发展的关系。方法:采用免疫组织化学SP法、RT-PCR和Western blot分别从细胞、基因及蛋白水平检测SRC-3和IGF-1在子宫肌瘤及瘤旁正常组织中的表达。结果:SRC-3蛋白的阳性表达主要定位于细胞胞浆中,少数位于细胞核。IGF-1蛋白的阳性表达定位于细胞胞浆中。SRC-3、IGF-1蛋白在子宫肌瘤中的阳性表达率(67.65%,80.88%)均显著高于瘤旁正常组织(16.18%,27.94%)(P均<0.05)。SRC-3 mRNA、IGF-1 mR-NA在子宫肌瘤中的表达水平均显著高于瘤旁正常组织(P均<0.05)。子宫肌瘤中SRC-3蛋白的表达与IGF-1蛋白的表达呈正相关(r=0.303,P<0.05)。结论:SRC-3、IGF-1与子宫肌瘤的发生发展有关。SRC-3可能参与调节IGF-1介导的信号传导通路,促进子宫肌瘤的发生发展,有望为子宫肌瘤的临床治疗提供新的研究方向。     

STAT3、cyclinD1、cyclinB1在卵巢上皮性癌的表达及意义

目的:研究STAT3及其下游基因cyclinD1、cyclinB1在卵巢上皮性癌的表达及意义。方法:用Westernblot和RT-PCR方法检测32例卵巢上皮性癌组织和12例正常卵巢组织中STAT3及其下游基因cyclinD1、cyclinB1的表达。结果:STAT3在卵巢癌和正常卵巢组织的蛋白表达阳性率分别为90.6%(29/32)和16.7%(2/12)。卵巢癌组STAT3表达明显高于正常卵巢组,差异有统计学意义(P<0.01);STAT3及其下游基因cyclinD1、cyclinB1mRNA在卵巢癌组织的阳性表达率分别为93.75%、87.5%、71.88%,与正常卵巢组阳性率的差异有统计学意义(P<0.05)。结论:卵巢上皮性癌中STAT3表达升高及活化可能促进了抗凋亡基因cyclinD1、cyclinB1表达,刺激细胞持续异常增殖,导致肿瘤发生。     

血管内皮生长因子在卵巢上皮性肿瘤的表达及其意义

体外研究表明,血管内皮生长因子(vascular endothelial growth factor, VEGF)是内皮细胞选择性有丝分裂原和血管渗透性诱导剂,与实体肿瘤的发生、发展及腹水形成等密切相关。我们应用免疫组化技术对VEGF在卵巢上皮性肿瘤中的表达进行研究,并结合卵巢癌的病理分级、临床分期、腹水量进行比较,探讨VEGF在卵巢癌发生发展中的作用。１ 资料与方法１．１ 病例资料 ７４份卵巢上皮性肿瘤标本为河南医科大学第一附属医院病理科１９９４至１９９８年的存档蜡块,标本均经１０％福尔马林固定,石蜡包埋,切片厚度为４μｍ。７４例卵巢上皮…     

胰岛素样生长因子1及胰岛素样生长因子结合蛋白3与胎儿生长发育的关系

目的:探讨胰岛素样生长因子1（IGF-1）及胰岛素样生长因子结合蛋白3（IGFBP-3）与胎儿生长发育的关系。方法:应用酶联免疫吸附试验（LISA）测定26例正常妊娠（正常组）,42例妊娠期糖尿病（GDM组）,20例胎儿宫内发育迟缓（IUGR组）孕妇足月剖宫产分娩时,母血与脐血中IGF-1及IGFBP-3的水平,同时记录3组孕妇的新生儿出生体重。结果:（1）母血IGF-1及IGFBP-3的水平正常组分别为18 6.81μg/L、22.82μg/L,GDM组为283.35μg/L、28.29μg/L,IUGR组为220.64μg/L、25.23μg/L,3组间 IGF-IN IGFBP.3水平差异均无显著性（P>0.05）;（2）脐血IGF-1及IGFBP-3的水平正常组分别为62.54μg/L、8.56μg/L,GDM组分别为83.74μg/L、10.21μg/L,IUGR组为37.94μg/L、7.82μg/L,分别进行3组间两两比较,3组IGF-1及IGFBP-3的差异均有显著性（P<0.01）;（3）新生儿平均出生体重正常组为3.22±0.32kg,GDM组为3.76±0.43kg,IUGR组为2.41±0.17kg,3组间两两比较,差异均有显著性（P<0.01）;（4）3组脐血IGF-1及IGFBP-3水平与新生儿出生体重均有显著性正相关（P<0.01）;（5）3组母血及脐血的IGF-1与IGFBP-3均呈显著性正相关（P<0.01）。结论:来自胎儿循环的IGF-1、IGFBP-3对胎儿的生长发育有重要的调节作用,可能参与巨大儿及IUGR的病     

EGFR、VEGF及LRP mRNA在卵巢上皮性癌组织中的表达及其意义

目的:探讨表皮生长因子受体(epidermal growth factor receptor,EGFR)、血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)和肺耐药蛋白(lung resistanceprotein,LRP)mRNA在卵巢癌的表达及意义。方法:用逆转录聚合酶链反应(RT-PCR)技术检测15例正常卵巢、13例卵巢良性肿瘤及51例卵巢上皮癌组织中EGFR mRNA、VEGF mRNA和LRP mRNA的表达,并分析它们的相关性。结果:卵巢上皮癌组织中EG-FR、VEGF和LRP阳性表达率显著高于正常卵巢及卵巢良性肿瘤组织(P<0.05);EGFRmRNA表达与卵巢上皮癌手术病理分期有关,Ⅲ~Ⅳ期的阳性表达率及表达强度高于Ⅰ~Ⅱ期(P<0.05);VEGF mRNA表达与卵巢上皮癌手术病理分期及淋巴结转移有关,Ⅲ~Ⅳ期和有淋巴结转移组的表达强度分别高于Ⅰ~Ⅱ期和无淋巴结转移组(P<0.05);LRP mRNA表达与卵巢上皮癌患者年龄、临床分期、分化程度、病理类型及淋巴结转移等临床病理参数无关(P>0.05);EGFR和VEGF基因之间(r=0.460,P<0.05)、EGFR和LRP基因之间表达显著相关(r=0.749,P<0.01)。结论:EGFR与卵巢癌血管生成和化疗耐药产生有关,可能参与了卵巢癌的发生发展,检测卵巢癌EGFR、VEGF和LRP可能对靶向化疗有指导作用。     

Dickkopf-1、LRP-5和LRP-6基因在卵巢上皮性癌中的表达及意义

目的 探讨Dickkopf-1(DKK-1)、低密度脂蛋白受体相关蛋白-5(LRP-5)和低密度脂蛋白受体相关蛋白-6(LRP-6)在卵巢上皮性癌中的表达和临床意义.方法 2002年1月至2008年4月在中国医科大学附属盛京医院采用RT-PCR的方法检测56例卵巢上皮性癌、35例卵巢上皮性良性肿瘤和12例正常卵巢组织中DKK-1mRNA、LRP-5mRNA和LRP-6mRNA的表达情况,分析3种基因与各临床病理参数的关系及其在癌组织中的表达相关性.结果 DKK-1mRNA,LRP-5mRNA和LRP-6mRNA在卵巢上皮性癌组织中的表达强度分别为0.90±0.32,0.71±0.27,0.80±0.28;明显高于卵巢上皮性良性肿瘤组织0.58±0.23,0.58±0.29,0.54±0.22和正常卵巢组织0.36 ±0.29,0.40±0.25,0.32 ±0.27(P均<0.0001).DKK-1 mRNA、LRP-5mRNA和LRP-6mRNA表达强度与临床分期(P=O.003～0.020)和病理分级(P=0.000～0.028)密切相关.DKK-1mRNA与LRP-5mRNA和LRP-6mRNA在卵巢上皮性癌中的表达强度存在统计学相关性(r=0.341,P<0.0001;r=0.815,P<0.0001).结论 DKK-1、LRP-5和LRP-6 mRNA在卵巢上皮性癌中表达增强,其表达强度存在相关联系.DKK-1、LRP-5和LRP-6在卵巢上皮性癌的发生、发展过程中起重要作用.     

AQP4,5在卵巢上皮性肿瘤的表达及意义

目的:探讨水通道蛋白4,5(AQP4,5)在卵巢上皮性肿瘤的表达及意义。方法:原位杂交和免疫组化染色检测AQP4 mRNA及蛋白在10例正常卵巢组织、15例卵巢良性上皮性肿瘤、15例卵巢交界性上皮性肿瘤及50例卵巢恶性上皮性肿瘤的分布和表达。结果:AQP4,5 mRNA及蛋白主要于交界性及恶性上皮性肿瘤细胞的胞质和胞膜表达。AQP4,5在恶性及交界性上皮性肿瘤的表达量明显高于良性上皮性肿瘤及正常卵巢组织(P0.05),良性上皮性肿瘤与正常卵巢组织间的表达差异无统计学意义(P0.05)。卵巢癌有腹水者AQP4,5表达量明显高于无腹水者(P0.05)。组织学分级为G2、G3的卵巢癌组织中AQP4,5表达高于G1;Ⅲ、Ⅳ期卵巢癌AQP4表达明显高于Ⅰ、Ⅱ期(P0.05);伴淋巴转移者AQP4明显高于无淋巴转移者(P0.05)。AQP4,5蛋白及mR-NA表达有相关性(P0.05,r=0.487)。结论:AQP4,5高表达可能通过增加肿瘤细胞对水的通透性,在卵巢上皮性肿瘤的发生及进展中起重要作用,并且可能参与卵巢癌腹水的形成。     

血管内皮生长因子及其受体在卵巢上皮性癌组织中的表达

目的研究血管内皮生长因子(VEGF)及其受体(FLT1、FLK1)mRNA在卵巢上皮性癌组织中的表达及与临床病理因素的相关性。方法采用逆转录聚合酶链反应技术检测70例卵巢上皮性癌及22例卵巢良性肿瘤病变组织标本中VEGFmRNA及其受体FLT1mRNA及FLK1mRNA的表达。结果在良、恶性卵巢组织中均检测到VEGF121mRNA、165mRNA的表达,在卵巢上皮性癌组织中表达水平分别为(0.452±0.134,0.301±0.096)高于良性卵巢肿瘤[0.195±0.066(P=0.000),0.204±0.059(P=0.001)];在卵巢上皮性癌组织中,VEGF121mRNA表达高于VEGF165mRNA(P=0.000),而在良性卵巢肿瘤组织中两者表达水平差异无显著性(P=0.667)。FLT1mRNA、FLK1mRNA在部分卵巢上皮性癌组织中表达,分别为38.6%(27/70)和25.7%(18/70),而在良性卵巢肿瘤组织中未见表达。卵巢癌组织中VEGF121、VEGF165、FLT1、FLK1之mRNA表达与患者年龄、肿瘤体积、淋巴结转移、肿瘤分期之间无明显相关性。结论VEGF121、165及其受体FLT1、FLK1在卵巢上皮性癌的血管生成中起重要作用。     

Serum insulin-like growth factor (IGF)-I,IGF binding protein (IGFBP)-3, leptin concentrations and insulin resistance in benign and malignant epithelial ovarian tumors in postmenopausal women

Aims. The aims of the present study were to determine the serum concentrations of insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3) and leptin and insulin resistance in benign and malignant epithelial ovarian tumors, and to discuss the use of these markers in benign–malignant tumor differentiation.

Methods. Forty-seven postmenopausal women with ovarian tumor and 31 age-matched, postmenopausal, healthy controls were included in this study. Insulin resistance index by homeostasis model assessment (HOMA score) and fasting blood glucose (FBG), serum IGF-I, IGFBP-3, leptin and CA-125 concentrations were determined in all patients preoperatively. The results were evaluated according to postoperative histopathology results.

Results. According to postoperative histopathology results, the patients were divided into malignant (n = 23), benign (n = 24) and control (n = 31) groups. There were no differences among the groups in relation to age, body mass index, FBG and HOMA score (p > 0.05). Serum concentrations of CA-125 were elevated in the malignant group compared with the benign ovarian tumor and control groups (p < 0.05). In contrast, serum IGF-I concentrations were significantly decreased in patients with malignant and benign ovarian tumors compared with controls (p < 0.05). Serum IGFBP-3 concentrations were also found to be lower in women with malignant ovarian tumors than in women with benign tumors (p < 0.05). Serum leptin did not differ among patients with malignant–benign tumors and controls (p > 0.05).

Conclusion. Serum leptin and HOMA score have not been found to be valid indicators in ovarian tumors. However, the present data suggest that low concentrations of IGF-I and IGFBP-3 could be a reliable marker to differentiate benign from malignant ovarian tumors. Further experimental studies are warranted to understand the impact of the IGF-I system in ovarian carcinogenesis.     

Evaluation of the insulin-like growth factors (IGF) IGF-I and IGF binding protein 3 in patients at high risk for breast cancer

Our data suggest that serum concentrations of insulin-like growth factor I and insulin-like growth factor binding protein 3 do not correlate with breast cancer development.     

Maternal insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and IGF BP-3 and the hypertensive disorders of pregnancy

Objective.?To investigate the relationship between levels of insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and insulin-like growth factor binding protein 3 (IGFBP-3) in antenatal maternal serum and gestational hypertension and pre-eclampsia (PET).

Methods.?Prospective cohort study of 1650 low-risk Caucasian women in a University teaching hospital in London. Statistical analysis was performed using commercial software (SPSS for Windows, version 6.1, SPSS, Chicago, IL), with P?<?0.05 as significant. Maternal IGF 1, IGF 2 and IGF BP-3 were assessed on maternal blood at booking. Blood pressure was checked at each visit in conjunction with urine analysis. The Davey & MacGillivray 1988 classification system was used in making the diagnosis of PET.

Results.?There was no significant correlation between maternal IGF-1 or IGFBP-3 levels and gestational hypertension or PET. However, a significant positive correlation does exist between maternal IGF-2 levels and PET.

Conclusions.?Maternal IGF-2 has a significant positive correlation with PET.     

胰岛素样生长因子1受体与卵巢癌SKOV3细胞顺铂耐药相关性的研究

目的:探讨胰岛素样生长因子1受体(IGF-1R)与卵巢癌SKOV3细胞顺铂耐药的相关性。方法:建立人卵巢癌细胞系SKOV3异种移植瘤模型,其中部分用顺铂处理;由此模型获得细胞分为SKOV3-P组(未化疗组)和SKOV3-R组(化疗组)。采用免疫细胞化学法和流式细胞术检测瘤细胞中IGF-1和IGF-1R的表达差异;MTT法和流式细胞术分别检测不同浓度顺铂(0、1、5、10、15、20μg/ml)和IGF-1R抑制剂NVP-AEW541(0、1、5、10、20μmol/L)单独及联合应用对瘤细胞的增殖及凋亡的影响。结果:SKOV3-P组、SK-OV3-R组细胞中均表达IGF-1和IGF-1R,且SKOV3-R组细胞的表达均显著高于SKOV3-P组细胞(P<0.05);NVP-AEW541对SKOV3-P组、SKOV3-R组细胞均表现增殖抑制,呈现剂量-时间依赖关系;NVP-AEW541联合顺铂作用瘤细胞时抑制作用显著增强,移植瘤细胞的顺铂敏感性显著增加(P<0.05);流式细胞术检测联合用药组细胞(10μmol/LNVP-AEW541+10μg/ml顺铂)凋亡率明显高于对照组和单独用药组(10μmol/L NVP-AEW541),且SKOV3-P组细胞的抑制率和凋亡率均显著高于SKOV3-R组细胞(P<0.05)。结论:IGF-1R参与了化疗耐药过程,通过NVP-AEW541抑制IGF-1R可能逆转卵巢癌细胞的顺铂耐药。     

VEGF和SDF-1/CXCR4在促进卵巢癌细胞侵袭与增殖中的相关作用

目的:研究血管内皮生长因子(VEGF)和趋化因子受体(Cys-X-Cysreceptor4,CXCR4)/配体基质细胞衍生因子-1(stromalcell-derivedfactor1,SDF-1)在卵巢上皮性癌细胞中的表达及其在促进卵巢癌细胞侵袭和增殖中的相关作用,进而探讨SDF-1/CX-CR4信号参与卵巢癌发生发展的相关机制。方法:(1)用Real-timeRT-PCR检测卵巢癌细胞株SKOV3中VEGF及其单克隆抗体anti-VEGF作用前后SDF-1/CXCR4mRNA表达水平的变化;(2)通过transwell小室体外侵袭实验检测VEGF和SDF-1以及anti-VEGF和CXCR4特异性抗体(AMD3100)对SKOV3细胞趋化活性的影响;(3)用MTT法测定VEGF和SDF-1以及anti-VEGF和AMD3100作用前后SKOV3细胞增殖率的变化。结果:(1)VEGF可以上调SDF-1和CXCR4的表达且有明显的剂量依赖性。(2)VEGF和SDF-1均有促进卵巢癌细胞侵袭的作用。VEGF的促侵袭作用具有一定的剂量依赖性且可以被40μg/mlanti-VEGF阻断,SDF-1的作用没有明显剂量依赖性;CXCR4的特异性受体抑制剂AMD3100有阻断VEGF和SDF-1的促侵袭作用。(3)VEGF和SDF-1均有促进卵巢癌细胞增殖的作用。VEGF的作用具有剂量依赖性,其效应可被anti-VEGF阻断,但不被AMD3100阻断,SDF-1的促增殖作用无明显剂量依赖性,其效应可被AMD3100阻断。结论:VEGF和SDF-1对卵巢癌细胞的侵袭和增殖有直接促进作用,并且VEGF可以上调SDF-1/CXCR4的表达。两者与卵巢癌的发生和生物学行为关系密切并协同促进卵巢癌细胞的转移。     

14-3-3γ在人卵巢上皮性癌中的表达检测

目的:检测14-3-3γ在卵巢上皮性癌组织的表达,探讨在卵巢上皮性癌发病机理中14-3-3γ蛋白家族的作用机制。方法:应用实时荧光定量PCR方法检测14-3-3γ在15例正常卵巢组织和52例卵巢上皮性癌组织中的表达差异,应用原位杂交方法检测14-3-3γ mRNA在正常卵巢组织和卵巢上皮性癌组织中的定位。结果:实时荧光定量PCR结果经过Mann-Whitney U检验,表明卵巢癌组的14-3-3γ mRNA水平显著高于正常卵巢组。14-3-3γ mRNA定位于卵巢癌细胞中,在正常卵巢组织中没有明显信号出现。结论:在人上皮性卵巢癌中,14-3-3γ转录上调,14-3-3γ mRNA定位于癌细胞。由此推测,14-3-3γ可能参与了人上皮性卵巢癌的发生。     

Gene expression patterns of insulin-like growth factor 1, 2 (IGF-1, IGF-2) and insulin-like growth factor binding protein 3 (IGFBP-3) in human placenta from preterm deliveries: influence of additional factors

Objective

To compare patterns of human placental gene expression of IGF from pregnancies that ended with preterm delivery vs. full term pregnancies as controls.

Study design

Real-time PCR was used to assess gene expression of IGF in human placental samples from 104 preterm and 140 full term pregnancies.

Results

In the preterm delivery group, the proportion of smokers was significantly higher than in the control group. A history of preterm delivery was more common in the preterm delivery group compared to the control group. In the preterm delivery group, placental samples showed an underexpression of the IGF-1 gene compared to controls. In cases of male fetal gender an overexpression of both the IGF-2 and the IGFBP-3 genes was observed.

Conclusion

Among environmental factors influencing preterm delivery, smoking was the most significant in our study. In the majority of cases, preterm delivery was induced by intrauterine infection leading to a decreased activity of the IGF system. This mechanism may also play a role in the development of neurological sequelae and in decreased tolerance to fetal distress. The overexpression of the IGF-2 gene observed in the placenta with male fetal gender can be explained by its physiological role in the development of the male phenotype.     

Maternal serum IGF-I, IGFBP-1 and IGFBP-3 at 11-13 weeks in trisomy 21 and trisomy 18 pregnancies

Objective

To investigate the possible value of maternal serum concentration of insulin-like growth factor-I (IGF-I), IGF binding protein-1 (IGFBP-1) and IGFBP-3 in first-trimester screening for fetal aneuploidies.

Study design

Maternal serum concentrations of IGF-I, IGFBP-1 and IGFBP-3 at 11-13 weeks of gestation were measured and compared in 30 trisomy 21, 30 trisomy 18 and 120 euploid pregnancies.

Results

The median multiple of the normal median (MoM) values of maternal serum IGF-I, IGFBP-1 and IGFBP-3 in trisomy 21, trisomy 18 and euploid pregnancies were not significantly different (IGF-I: 1.10, 1.14 and 1.0 MoM, respectively; IGFBP-1: 1.10, 1.01 and 1.0 MoM; IGFBP-3: 0.90, 1.16 and 0.98 MoM).

Conclusion

Measurement of maternal serum IGF-I, IGFBP-1 and IGFBP-3 at 11-13 weeks of gestation is unlikely to be useful in screening for trisomies 21 and 18.