大鼠肝癌发生过程中胰岛素样生长因子-Ⅱ的表达及意义

目的:研究胰岛素样生长因子-Ⅱ(IGF-Ⅱ)在肝癌发生过程中的表达及意义.方法:采用二乙基亚硝胺(DEN)诱癌建立大鼠肝癌模型.应用放射免疫分析检测诱癌过程中血清IGF-Ⅱ浓度,应用免疫组织化学方法观察诱癌过程中大鼠肝组织IGF-Ⅱ的表达情况.结果:在大鼠肝癌的发生发展过程中,从肝细胞损伤期、增生-硬化期至癌变期3个阶段大鼠血清IGF-Ⅱ水平呈"高到低到高"的变化趋势;肝细胞损伤期嗜酸性变细胞中见IGF-Ⅱ阳性表达,癌变期癌灶中表达低于癌周增生灶、增生结节和非典型增生结节,而增生-硬化期阳性表达较少.结论:大鼠血清和肝中IGF-Ⅱ的高表达是肝癌发生发展过程中的早期及晚期事件,提示IGF-Ⅱ可能与肝细胞持续增殖及恶性转化有关.     

IGF-Ⅱ在肝癌Huh7细胞增殖、迁移与侵袭中的作用

目的:以胰岛素样生长因子Ⅱ(IGF-Ⅱ)为靶点,观察不同表达水平的IGF-Ⅱ对肝癌Huh7细胞生长增殖、侵袭和迁移的影响,探讨IGF-Ⅱ基因在肝癌发生发展过程中的作用,为肝癌的靶向治疗提供新的思路。方法:分别将构建好的IGF-Ⅱ基因过表达质粒pc DNA3.1(+)-IGF-Ⅱ和RNA干扰质粒p LVX-shRNA2-IGF-Ⅱ转染肝癌Huh7细胞,通过real-time PCR及Western blot检测IGF-Ⅱ的表达,采用CCK-8、平板克隆形成、细胞划痕、Transwell小室实验,检测过表达与抑制IGF-Ⅱ对肝癌Huh7细胞生长增殖、侵袭与迁移的影响。结果:过表达IGF-Ⅱ能促进肝癌细胞的生长增殖及侵袭迁移(P0.05),而抑制IGF-Ⅱ的表达得到相反的结果。结论:IGF-Ⅱ参与调控肝癌Huh7细胞的生物学行为,可能在肝细胞癌的发生发展中发挥重要作用。     

乳腺癌患者血清IGF-Ⅱ、TGF-α水平及三苯氧胺治疗后变化

我们检测34例乳腺癌患者血清胰岛素样生长因子-Ⅱ(IGF-Ⅱ)、转化生长因子-α(TGF-α)水平,并对12例雌激素受体阳性接受三苯氧胺治疗的患者进行动态观察,现将结果报告如下.     

胰岛素样生长因子及胰岛素样生长因子结合结白-3与胎儿生长发育的关系

目的探讨胰岛素样生长因子-Ⅰ、胰岛素样生长因子-Ⅱ、胰岛素样生长因子结合蛋白-3与胎儿生长发育的关系,为FGR的临床诊断和治疗提供理论依据和新思路。方法分别采集确诊FGR组、正常对照组和巨大儿组胎儿脐血标本,采用放射免疫测定其中胰岛素样生长因子-Ⅰ、胰岛素样生长因子-Ⅱ、胰岛素样生长因子结合蛋白-3的含量。结果 1.FGR组脐血清IGF-Ⅰ、IGF-Ⅱ、IGFBP-3水平下降,巨大儿组脐血清IGF-Ⅰ水平升高;2.新生儿脐血清IGF-Ⅰ、IGF-Ⅱ水平与新生儿出生体重、身长、胎盘重量呈明显正相关关系,脐血清IGF-Ⅰ水平与胎龄呈明显正相关关系,脐血清IGFBP-3水平与胎龄、新生儿出生体重、身长、胎盘重量呈明显正相关关系;3.脐血清IGF-Ⅰ与IG-FBP-3水平与产妇产前体重呈明显正相关关系,IGF-Ⅱ水平与产妇产前体重呈正相关关系。结沦脐血清IGF-Ⅰ、IGF-Ⅱ、IGFBP-3水平可作为预测胎儿和胎盘生长发育情况的参考指标,IGF-Ⅰ水平是其中最灵敏的指标;脐血清IGF-Ⅰ、IGF-Ⅱ、IGFBP-3水平的降低可能是导致FGR的重要原因之一;监测产妇产前体重可以间接反映胎儿血IGFs及IG-FBP-3水平,进而反映胎儿的生长发育状况。     

原发性肝癌患者血清IGF-Ⅱ水平与AFP、HA和PⅢP的关系

胰岛素样生长因子-Ⅱ(IGF-Ⅱ)是IGFS家族成员之一,在胚胎发育、组织修复、肿瘤生长及中枢神经系统中起着十分重要的作用[1].AFP早就被认为对原发性肝癌(PHC)患者诊断具有十分重要的临床价值[2].HA、PⅢP为早期诊断肝纤维化的两项重要检测指标[3].本文报告PHC患者血清IGF-Ⅱ水平与AFP、HA和PⅢP水平的关系,现报告如下:     

IGF-1和胰岛素对成骨细胞功能影响的研究进展

胰岛素样生长因子-1(IGF-1)是一类既具有促进细胞分化和增殖活性又具有胰岛素样作用的多肽.IGF-1与胰岛素原有60%的结构同源性.对小鼠、大鼠和人的成骨细胞的研究结果显示:IGF-1和胰岛素可通过促进骨祖细胞及成骨样细胞的增殖和分化等多种机制而发挥保护骨量的作用.IGF-1和胰岛素的作用受IGF结合蛋白(IGFBP)、激素和细胞因子的调节.     

TGF—αT —Ⅱ在乳腺癌患者围手术期的表达

胰岛素样生长因子(IGF-Ⅱ)和转化生长因子(TGF-α)是具有广泛生物学活性的多肽类生长因子,但在正常组织及肿瘤组织中的表达如何,研究报道不一。本文测定了乳腺癌患者血液、尿液及肿瘤组织IGF-Ⅱ和TGF-α水平,旨在探讨其在乳腺癌患者围手术期的表达及生物学意义。1材料和方法1.1研究对象21例女性,年龄40～71岁,均系本院手术后经病理诊断证实的乳腺癌患者。其中浸润型导管癌14例,乳腺髓样癌3例,乳腺低分化腺癌2例,导管浸润癌伴腺癌2例;正常对照组:30例,为我院查体健康的女性,年龄38～55岁。1.2标本采集及检测方法采集乳腺癌患者手术前血…     

胰岛素样生长因子-1对骨骼肌源性干细胞的促增殖效应

目的 观察胰岛素样生长因子-1(IGF-1)对骨骼肌源性干细胞(MDSCs)生长的影响.方法 采用连续预贴壁法从新生小鼠后肢肌分离培养MDSCs;用含2%胎牛血清的DMEM培养基促进其向骨骼肌细胞分化.免疫细胞化学SP法检测于细胞标志Sca-1和骨骼肌细胞标志肌节(α-sarcomeric)肌动蛋白的表达情况;采用四甲基偶氮唑盐(MTT)比色法检测IGF-1对MDSCs增殖的影响,并分析IGF-1效应与培养时间以及与IGF-1浓度之间的关系.结果 从新生小鼠后肢肌成功分离培养MDSCs,90%以上的MDSCs呈Sca-1阳性;在分化培养中MDSCs能够产生α-sarcomeric 肌动蛋白阳性的肌管;IGF-1对MDSCs促增殖作用随细胞培养时间的延长逐渐明显;随IGF-1浓度的增加而增加,并逐渐趋于饱和.结论 IGF-1对体外培养的MDSCs有促进增殖的作用.     

结直肠癌中IGF-Ⅱ、IGFBP-6的表达及意义

目的：观察胰岛素样生长因子（ insu1in-1ike growth factor,IGF）-Ⅱ及胰岛素样生长因子结合蛋白（ insu1in-1ike growth factor binding protein,IGFBP）-6在结直肠癌（ co1orecta1 cancer,CRC）组织中的表达及临床意义。方法采用免疫组化MaxVision法及RT-PCR法检测50例CRC组织和50例对应癌旁正常结直肠黏膜组织中IGF-Ⅱ及IGFBP-6的表达。结果（1）CRC组织中IGF-Ⅱ蛋白及mRNA表达量明显高于癌旁正常结直肠黏膜组织;CRC组织中IGFBP-6蛋白及mRNA表达量均明显低于癌旁正常结直肠黏膜组织;（2）IGF-Ⅱ和IGFBP-6表达与肿瘤浸润深度、有无淋巴结转移及Dukes分期有关（P<0.05）;IGF-Ⅱ及IGFBP-6表达与患者性别、年龄、肿瘤分化程度无关（ P>0.05）。结论 IGF-Ⅱ及IGFBP-6的蛋白表达及mRNA表达量与CRC临床病理特征有明显相关性。联合检测IGF-Ⅱ及IGFBP-6有可能作为CRC发生及预后的生物学指标,为CRC的诊断及治疗提供新的方案。     

IGF-Ⅱ及CT含量对正常人骨代谢的影响

目的:了解不同年龄不同性别正常人胰岛素样生长因子-Ⅱ(IGF-Ⅱ)及降钙素(CT)含量变化对 骨代谢的影响。方法:选择180例正常人按不同年龄不同性别分为5组;进行IGF-Ⅱ和CT血清含量的测定, 均采用放射免疫分析法。结果:正常人随年龄的增加,IGF-Ⅱ及CT浓度逐步下降,其中IGF-Ⅱ血清含量(27 ～39)岁组与(60～69)岁组和70岁以上组比较P<0.05～P<0.01;(40～49)岁组与70岁以上组比较P< 0.01;(50～59)岁组与70岁以上组比较P<0.01。CT血清含量(27～39)岁组与50岁以上各组比较P<0.05 ～P<0.01间;(40～49)岁组与50岁以上各组比较P<0.01。不同性别间的比较在50岁以上女性IGF-Ⅱ和 CT含量略低于男性,但无统计学差异(P>0.05)。结论:正常人随着增龄IGF-Ⅱ浓度逐步降低,对骨骼细胞 的增殖和调控能力下降,抑制性IGF结合蛋白增加;同时,CT浓度的下降不能抑制破骨细胞介导的骨质吸收; 而老年女性IGF-Ⅱ及CT含量低于男性与雌激素水平降低可能有关。因此,老年性骨质疏松症与IGF-Ⅱ及 CT含量的变化有关,它们不仅参与了骨代谢而且是骨质疏松疾病发生的启动因子。     

肝细胞癌组织中PEG10、SIAH2的表达及其意义

目的探讨遗传印记基因PEG10(paternally expressed gene 10,PEG10)与泛素连接酶SIAH2(seven in absentia homologs 2,SIAH2)在原发性肝细胞癌(hepatocellular carcinoma,HCC)组织中的表达及其临床意义。方法采用免疫组化SP法检测50例HCC和相应癌旁组织中PEG10、SIAH2蛋白的表达。结果 (1)PEG10和SIAH2在肝癌组织中的阳性率分别为84%和78%,高于相应癌旁组织中的阳性率8%和14%,差异有统计学意义(P<0.01)。(2)PEG10和SIAH2表达与肿瘤TNM分期有相关性(P<0.01),但与患者的年龄、性别、肿瘤大小、血清HbsAg、AFP水平、是否伴肝硬化无相关性(P>0.05)。(3)HCC中PEG10、SIAH2蛋白表达呈正相关(r=0.42,P<0.01)。结论 PEG10、SIAH2表达与HCC的发生、发展具有明显相关性。     

Clinical implications of telomerase activity in resected hepatocellular carcinoma.

This study investigated the relationship of telomerase activity to its clinical implications in hepatocellular carcinoma (HCC). Telomerase activity was quantatively examined by a non-radioisotope quantitative system based on a TRAP-eze (ONCOR) in 42 HCC nodules and 40 non-cancerous liver tissue adjacent to the HCC nodules, obtained by surgical resection. Telomerase activity was confirmed in 37 HCC nodules (88.1%), being more statistically intense in de-differentiated tumors (p<0.01). Telomerase activity was positive in 9 cases (22.5%) of non-cancerous liver tissue and its activation was closely associated with the biologically malignant potential of the tumor itself such as the histological grade, portal vascular invasion, and intrahepatic metastasis (p<0. 05). The disease-free survival rate with its activity was also statistically lower than that without its activity of the non-cancerous tissue (p<0.01). These results indicate that telomerase may be a useful marker of biological characteristics in HCC and may lead to more effective surgical procedures.     

p53, Ki-67, and serum alpha feto-protein as predictors of hepatocellular carcinoma recurrence in liver transplant patients.

Patients with hepatocellular carcinoma who undergo orthotopic liver transplantation (OLT) are at risk for post-transplant tumor recurrence. The aim of this study was to evaluate whether expression of p53 and Ki-67 in hepatocellular carcinoma lesions present in explanted liver tissue was associated with time to tumor recurrence after OLT. Subjects consisted of 20 consecutive patients who underwent OLT and were found to have hepatocellular carcinoma in the liver explant. Immunostaining for p53 and Ki-67 was performed by standard methods. The presence of nuclear immunostaining in >10% of the tumor tissue was considered positive. Time to recurrence of hepatocellular carcinoma after OLT was compared between patients with positive and negative immunostaining by the log rank test. Multivariate analysis was performed using a Cox regression model to control for potentially confounding clinical factors. Time to post-transplant hepatocellular carcinoma recurrence was significantly more rapid in p53+ (P=0.0007) and Ki-67+ cases (P=0.001). These associations remained significant in multivariate analysis. Furthermore, time to recurrent hepatocellular carcinoma was significantly shorter in patients with a serum alpha feto-protein (AFP) level >or=100 ng/ml at time of diagnosis, compared to those with an AFP level <100 ng/ml (P=0.003). In conclusion, expression of p53 and Ki-67 in hepatocellular carcinoma lesions, and a serum AFP level >or=100 ng/ml were associated with more rapid recurrence of hepatocellular carcinoma after OLT. Identification of patients at risk for early post-transplant recurrence could be used to guide surveillance and adjuvant treatment strategies.     

Hep par 1 antibody stain for the differential diagnosis of hepatocellular carcinoma: 676 tumors tested using tissue microarrays and conventional tissue sections.

A well-characterized positive marker for hepatocellular differentiation would be a useful tool for the diagnosis of hepatocellular carcinoma (HCC). The recently commercially available Hep Par 1 antibody (clone OCH1E5.2.10) has been reported to be a sensitive marker for HCC in paraffin embedded sections. Of non-hepatocellular tumors, occasional carcinomas have been reported to stain, most frequently gastric adenocarcinomas. This study further evaluated the staining of this antibody on a large number of neoplasms using tissue microarray technology as well as conventional tissue sections. Six hundred seventy-six tumors, including 19 cases of HCC, were tested. Eighteen of 19 cases of HCC were positive, 3 showing <5% staining. Two cases negative on the array showed focal staining when whole tissue sections from the same tumors were used. 16 of 34 cases of gastric carcinomas gave positive reactions, 4 of these showed less than 5% staining. Staining of gastric carcinomas was not limited to signet ring-type carcinomas or to areas of hepatoid differentiation. Only 1 of 11 cases of cholangiocarcinoma showed focal staining. We also noted several other tumors to stain occasionally, including adrenal cortical carcinoma (3/13), yolk sac tumor (2/9), colonic adenocarcinoma (8/106), lung carcinoma (3/52), ovarian carcinoma (5/48), and endocervical adenocarcinoma (1/5). We did not observe staining in pancreatic carcinoma (11), renal cell carcinoma (36), breast carcinoma (85), melanoma (25), or mesothelioma (5). This study supports Hep Par 1 as a useful marker in the differential diagnosis of HCC, but with significant limitations. Cautious use of this antibody in a panel with other positive (alpha fetoprotein, CD10, polyclonal carcinoembryonic antigen) and negative (epithelial membrane antigen, monoclonal carcinoembryonic antigen, CD15) markers of hepatocellular differentiation may aid in the accurate diagnosis of HCC.     

胰岛素样生长因子Ⅰ、胰岛素样生长因子Ⅰ受体在大肠癌中的表达及其意义

目的检测胰岛素样生长因子Ⅰ（IGF-Ⅰ）、胰岛素样生长因子Ⅰ受体（IGF-ⅠR）蛋白在大肠癌中的表达,并分析与临床病理学因素的关系．探讨两者在大肠癌发病机制中的相互作用及与患者预后的关系。方法选取不同类型的大肠癌组织48例（试验组）,其中男性25例,女性23例：年龄34～78岁,平均年龄53岁。任意选癌旁5cm以上的正常组织24例（正常对照组）。采用SABC法检测IGF-Ⅰ、IGF-ⅠR的表达。结果在48例大肠癌组织中,IGF-Ⅰ、IGF-ⅠR的阳性表达率分别为64．58％、58．33％,均显著高于癌旁正常组织中的16．67％、16．67％。IGF-Ⅰ、IGF-ⅠR在大肠癌组织中的表达与肿瘤的浸润程度、淋巴结转移、Dukes’分期有关。而与其他的病理因素及患者5年生存情况无关。IGF-Ⅰ和IGF-ⅠR在大肠癌组织中的表达呈明显相关性。结论IGF-Ⅰ、IGF-ⅠR可能相互协同作用参与大肠癌的浸润、转移,可作为反映大肠癌进展的重要生物学指标．但IGF-Ⅰ、IGF-ⅠR阳性表达与大肠癌患者的预后无明显相关性。     

表皮生长因子受体在肝细胞癌及胆管细胞癌中的表达

目的：比较表皮生长因子受体（ＥＧＦＲ） 在肝细胞癌及胆管细胞癌中表达的差异。方法：采用免疫组化及原位杂交方法检测９２ 例肝细胞癌及５０ 例胆管细胞癌组织中ＥＧＦＲ蛋白及ｍ ＲＮＡ的表达。结果：９２ 例肝细胞癌标本中,４２ 例ＥＧＦＲ 蛋白或ｍＲＮＡ阳性,占４５－７％ 。５０ 例胆管细胞癌中,３６ 例ＥＧＦＲ蛋白或ｍＲＮＡ 阳性,占７２－０ ％ 。结论：与肝细胞癌相比,胆管细胞癌的发生、发展与ＥＧＦＲ 表达增高的关系更加密切。     

Detection of telomerase in hepatocellular carcinomas using a PCR ELISA assay: comparison with hTR expression

BACKGROUND: While telomerase is undetectable in most normal somatic tissues, telomerase activation has been detected in many immortal cell lines and various cancers. AIM: To investigate telomerase expression in hepatocellular carcinoma, and to assess the expression of the RNA component of telomerase, hTR. METHODS: 39 hepatocellular carcinomas were studied using a telomerase polymerase chain reaction (PCR) enzyme linked immunosorbent assay, which does not require radioactive PCR amplification and yields a semiquantitative measurement. Expression of hTR was also assessed by a non-radioactive in situ hybridisation procedure. The correlations between these two markers and the clinicopathological data were analysed. RESULTS: Telomerase activity was detected in 23 of 39 hepatocellular carcinoma specimens (59%). Comparison of hepatocellular carcinoma with and without telomerase expression, or with high and low telomerase (10 cases v 13 cases), showed no differences in the principal clinicopathological data. Although median survival was lower in the group with detectable telomerase activity than in that with undetectable activity (510 v 720 days) the difference was not significant (log-rank test, p = 0.08). hTR expression was detected in 11 of 14 cases of hepatocellular carcinoma tested (78%) and in four of 12 samples of adjacent non-cancerous tissue (33%). Five tumours and four non-cancerous tissues were positive for hTR, whereas no telomerase activity was detected in these. CONCLUSIONS: The presence of telomerase activity in hepatocellular carcinomas is confirmed. No correlation was observed between clinicopathological data and telomerase expression in hepatocellular carcinoma, but survival seemed better in the absence of telomerase expression. hTR seems to be more widely expressed than telomerase.     

免疫评分在肝癌患者中的预后研究

目的　探讨免疫评分及PD-L1在肝癌组织的表达情况,分析肝癌患者的免疫评分与其临床病理特征及预后的关系。 方法　采用免疫组化检测免疫评分与PD-L1在61例肝癌患者中的表达,分析PD-L1、免疫评分与临床病理特征及预后之间的关系。 结果　肝癌中免疫评分较高的表达率为26.2%,较低的表达率为73.8%。统计分析发现免疫评分与AFP增高（P<0.05）及肝内复发（P>0.05）具有相关性;而与患者年龄、性别、肿瘤直径、分化程度、脉管癌栓等临床因素无相关性（P>0.05）。生存分析发现免疫评分较高患者的总生存期与无复发生存期显著高于免疫评分较低的患者（χ2=11.39,P<0.01;χ2=14.78,P<0.01）。肝癌组织PD-L1的阳性表达率为44.3%,对应癌旁低表达,具有统计学差异（χ2=7.313,P<0.01）。PD-L1阳性患者的总生存期与无复发生存期低于PD-L1阴性患者（χ2=5.598,P<0.05;χ2=10.90,P<0.01）。肝癌组织中PD-L1与免疫评分间具有负相关性（χ2=12.703,P<0.01）。 结论　免疫评分可作为患者预后的一个标志物,免疫评分高的患者预后较好,反之易早期复发且预后较差;肝癌组织PD-L1与免疫评分之间具有负相关性。     

Expression of carbonic anhydrase IX,PAX2 and PAX8 and their association with clinicopathologic characteristics in renal epithelial tumors北大核心CSCD

Objective: To study the expression of carbonic anhydrase IX (CAIX), PAX2 and PAX8 in different types of renal epithelial tumor and their association with clinicopathologic characteristics. Methods: Immunohistochemical study by EnVision method was performed in order to assess the expression of CAIX, PAX2 and PAX8 in 155 cases of renal cell carcinoma and 4 cases of metastatic clear cell renal cell carcinoma (CCRCC). Ninety-six cases of non-neoplastic renal parenchymal tissue adjacent to CCRCC, 8 cases of clear cell hepatocellular carcinoma and 2 cases of clear cell hidradenoma were used as controls. Results: CAIX was commonly expressed in CCRCC (94. 0%, 63/67), of which 77. 8% (49/63) showed strong positivity. CAIX was focally positive in papillary renal cell carcinoma, collecting duct carcinoma and urothelial carcinoma of renal pelvis. It was negative in chromophobe renal cell carcinoma, oncocytoma and adjacent non-neoplastic renal tissue. CAIX was also strongly expressed in the 4 cases of metastatic CCRCC. Focal expression of CAIX was demonstrated in the 8 cases of clear cell hepatocellular carcinoma and 2 cases of clear cell hidradenoma. The expression of CAIX in CCRCC did not correlate with tumor grading, clinical staging and presence of distal metastasis. On the other hand, PAX2 showed positive expression in different types of renal epithelial tumor, clear cell hepatocellular carcinoma and clear cell hidradenoma in various degrees. In contrast, PAX8 was commonly expressed in all types of renal epithelial tumor, with the exception of urothelial carcinoma of renal pelvis. PAX8 was not expressed in clear cell hepatocellular carcinoma and clear cell hidradenoma. Regarding diagnosis of CCRCC, CAIX demonstrated high sensitivity and specificity. PAX2 showed high specificity but low sensitivity. PAX8 was sensitive and specific in the diagnosis of renal epithelial tumor. Conclusions: CAIX is a useful immunohistochemical marker with high specificity and sensitivity in distinguishing CCRCC from other types of renal epithelial tumor and clear cell tumors of non-renal origin. PAX2 is a marker with high sensitivity and low specificity for diagnosis of renal epithelial tumors. PAX8 is typically expressed in renal epithelial tumors. The combined detection of CAIX, PAX2 and PAX8 is useful in the diagnosis and differential diagnosis of renal epithelial tumors.