甲胎蛋白靶向USPIO分子探针在肝癌特异性磁共振成像中的价值

目的 探讨甲胎蛋白(AFP)靶向超小型超顺磁性氧化铁(AFP-USPIO)分子探针在肝细胞癌(HCC)主动靶向特异性成像方面的价值.方法 表面修饰的USPIO连接抗AFP抗体后构建AFP-USPIO靶向分子探针.实验分为AFP-USP1O组(靶向组)和USPIO组(非靶向组).将铁浓度为100 μg/ml的AFP-USPIO及USPIO,按照150μl、100 μl、50 μl的剂量分别与HepG2细胞孵育4h 后行体外磁共振成像,并测量T2WI信噪比(SNR).构建原位肝癌动物模型并随机分为两组(每组5只),分别于尾静脉注射AFP-USPIO或USPIO,注射剂量20μmol/kg.注射前及注射后1h进行磁共振成像,测量T2WI肝脏肿瘤与周围肝组织的对比噪声比(CNR),计算增强前后及两组之间CNR 的差异.普鲁士蓝铁染色验证SNR、CNR变化与细胞及组织铁含量的关系.结果 细胞学实验显示两组体外磁共振SNR均随AFP-USPIO或USPIO剂量的增加而下降,3种剂量间(P＜0.05)以及同一剂量时两组间SNR差异均具有统计学意义(P＜0.05).普鲁士蓝染色结果显示靶向组细胞内铁颗粒随剂量的增加而增多,并与SNR呈负相关关系(P=0.00,r=-0.926),而非靶向组铁染色的细胞数则明显降低.在注射AFP-USP1O前后,大鼠肝脏肿瘤的CNR分别为2.05±0.88和0.96±0.31,差异有统计学意义(P=0.028,t=3.380);而注射USPIO前后肝脏肿瘤的CNR分别为2.25±1.50和2.57±1.49,差异无统计学意义(P=0.275,t=1.263).靶向与非靶向组,肿瘤强化后的CNR差异也具有统计学意义(P=0.042,t=3.487).病理结果显示靶向组肿瘤组织内见大量铁染色颗粒,而非靶向组铁染色颗粒则明显减少.结论 AFP-USPIO分子探针对HepG2细胞及大鼠模型原位肝癌具有良好的主动靶向作用,可实现肝癌的特异性成像和诊断.     

肝癌患者外周血甲胎蛋白mRNA表达与术后生存和转移的相关性研究

目的 探讨肝癌患者外周血甲胎蛋白(AFP)mRNA的表达与术后生存和转移的关系.方法 收集2005年1月至2006年12月经过根治性手术切除的肝癌患者66例.提取外周血细胞总RNA,巢式PCR检测AFP mRNA的表达.术后随访60个月.结果 肝癌患者外周血AFPmRNA表达率为40.91％(27/66).肝癌患者外周血AFP mRNA的表达与有无微血管入侵和转移密切相关(P＜ 0.05或＜0.01),而与患者的性别、年龄、有无HBV感染、有无肝硬化、AFP浓度、肿瘤大小及数量、Edmondson分级无相关性(P＞0.05).AFP mRNA阳性肝癌患者术后1、2、≥3年的生存率分别是66.7％(18/27)、38.9％(7/18)、28.6％(2/7),AFP mRNA阴性肝癌患者分别为84.6％(33/39)、60.6％(20/33)、45.0％(9/20),两者比较差异有统计学意义(P＜0.01).结论 肝癌患者外周血AFPmRNA的检测可以提示肿瘤早期的微小转移,可以用来作为术后复发的预测指标.     

Screening is associated with a lower risk of hepatocellular carcinoma-related mortality in patients with chronic hepatitis B

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超声造影肝脏影像报告与数据系统在甲胎蛋白阴性肝细胞癌高危患者中的应用

目的 研究超声造影肝脏影像报告与数据系统2017版（CEUS LI-RADS v2017）在甲胎蛋白（AFP）阴性的肝细胞癌（HCC）高危患者肝局灶性病变中的应用价值。方法 回顾性分析2018年1月至2021年10月在我院行CEUS检查的AFP阴性HCC高危患者108例（134个结节）,采用CEUS LI-RADS v2017对结节进行分类,以组织病理学结果或增强影像学检查和随访结果为金标准,计算CEUS LI-RADS对AFP阴性患者HCC和肝内其他恶性肿瘤（OM）的诊断敏感性、特异性、阳性预测值、阴性预测值、准确率、受试者工作特征曲线下面积（AUC）。结果 AFP阴性HCC较OM小（P＜0.001）。CEUS LR-5类、LR-4类、LR-3类对AFP阴性HCC的阳性预测值分别为88.37%、47.06%、12.9%。LR-5类诊断AFP阴性HCC的敏感性、特异性、准确率和AUC分别为73.07%、 93.90%、85.82%和0.87。LR-M类诊断OM的敏感性、特异性、阳性预测值、阴性预测值、准确率和AUC分别为90.91%、97.32%、86.96%、98.20%、96.27%和0.94。结论AFP阴性HCC较OM小,CEUS LI-RADS v2017对AFP阴性HCC诊断特异性较高而敏感性较低,对OM有较好的诊断价值。     

SERUM ALPHA-FETOPROTEIN LEVELS IN EXTRAHEPATIC BILIARY ATRESIA, IDIOPATHIC NEONATAL HEPATITIS AND ALPHA-1-ANTITRYPSIN DEFICIENCY (PiZ)

Abstract. Serum alpha-fetoprotein levels were measured using a sensitive radioimmunoassay in 77 infants presenting with persistent conjugated hyperbilirubinaemia. A broad range of alpha-fetoprotein concentrations occurred in both the 23 infants with extrahepatic biliary atresia and the 35 with idiopathic neonatal hepatitis but the 13 with alpha-1-antitrypsin deficiency had uniformly low levels. High alpha-fetoprotein concentrations (above 10 000 μg/I) favoured the diagnosis of neonatal hepatitis especially in the first ten weeks of life, but the overlap between neonatal hepatitis and extrahepatic biliary atresia was large and alpha-fetoprotein determination cannot be recommended as a reliable method for distinguishing the two conditions. Serial alpha-fetoprotein values showed no consistent relationship with standard liver function tests and gave no guide to prognosis. There was an association between alpha-fetoprotein production and needle biopsy evidence of hepatic giant cell transformation. The uniformly low alpha-fetoprotein levels in alpha-1-antitrypsin deficient infants with neonatal hepatitis is a new observation and possible mechanisms for disordered glycoprotein release are discussed.     

Evaluation of alpha-fetoprotein in early infancy.

Serum AFP concentrations of normal subjects were statistically analyzed in order to obtain the normal ranges in early infancy. The 95% prediction band would seem to offer a convenient means of evaluating serum AFP in the age range 0-300 days of life. Some illustrative cases, whose AFP values were formerly considered to be abnormally high but later proved to be within normal range, are presented.     

AFP gene expression after acute diethylnitrosamine intoxication is not Afr2 regulated

The level of alpha-fetoprotein (AFP) gene expression during liver regeneration in mice is regulated by the Afr2 gene. C3H/HeJ mice express 10-fold higher levels of AFP than C57BL/6J mice. We show that AFP gene expression is not Afr2 regulated after intoxication with the carcinogen diethylnitrosamine (DEN). Peak levels of AFP gene expression of the 2 strains were identical, although reached at different times following treatment. Analysis of the expression of AFP derived transgenes not subject to Afr2 regulation and genetic analyses showed that the difference in timing of peak AFP gene expression after DEN intoxication was independent of Afr2 regulation.     

肝细胞癌新型靶向基因治疗体系的构建及应用研究

构建肝细胞癌(HCC)新型靶向基因治疗体系,并以存活素(survivin)基因为靶点,探讨该体系体外杀伤肝癌细胞的作用。构建由巨细胞病毒(CMV)增强子和甲胎蛋白(AFP)启动子构成的融合启动子(AV)驱动的pcD-NA3.1(-)AV质粒,及含绿色荧光蛋白(GFP)的pcDNA3.1(-)AVGFP和含siRNA-survivin的pcDNA3.1(-)AV-siRNA-survivin质粒,以磷酸钙纳米为载体,导入HepG2、SMMC-7721和Hela细胞中,观察转染效率及体外对肝癌细胞的杀伤效应,并采用流式细胞技术(FCM)检测细胞凋亡率。结果显示:AV启动子可特异性驱动下游基因在HepG2细胞表达。此外,pcDNA3.1(-)AVsiRNA-survivin在HepG2细胞中可有效沉默survivin的mRNA和蛋白表达,并诱导68.8%的细胞死亡,而在Hela和SMMC-7721细胞中无显著作用。生长曲线结果显示,转染了pcD-NA3.1(-)AVsiRNA-survivin的HepG2细胞的生长显著受抑(P<0.05)。结果表明,该新型靶向基因治疗体系可高选择性作用于肝癌细胞,可为临床肝癌的基因治疗提供新的研究思路。     

甲胎蛋白异质体测定对原发性肝癌诊断的作用

目的探讨微量离心柱法测定甲胎蛋白异质体(AFP—L3)在良性肝病及原发性肝癌预警中的作用。方法以装有耦联小扁豆凝集素(LCA)的微量离心柱分离慢性肝炎组、肝硬化组、原发性肝癌组共52例的患者血清甲胎蛋白异质体,用化学发光方法检测分离前AFP和分离后AFP(AFP-L3),计算AFP-L3在AFP中的含量比例[AFP-L3(%)]。结果原发性肝癌组AFP-L3(%)均值、阳性率与慢性肝炎、肝硬化组相比均显著增加(P<0.001)。肝癌术后AFP-L3(%)含量比例显著下降(P<0.001)。结论微量离心柱法测定AFP-L3对肝癌和良性肝病的诊断具有重要意义。     

Nitric Oxide is a Potential Diagnostic Marker for Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common cancer in men and the seventh most common in women. This cancer varies widely in incidence throughout the world, with rising incidence in Egypt. HCC is considered the second most frequent cause of cancer incidence and mortality among men in Egypt. This study aimed to estimate the serum levels of nitric oxide (NO) and glutathione reductase in order to evaluate their role as oxidative status markers in HCC development and progression. For this purpose, serum levels of these parameters were assessed in 50 HCC patients, and 30 cirrhotic patients in addition to 15 healthy subjects as a control group. In the present study, glutathione reductase activity showed a significant increase in HCC as compared to the control group (P= 0.019). On the other hand, no significant difference was observed between the cirrhotic and HCC patients (P= 0.492). Serum NO was significantly higher in patients with HCC than in cirrhotic patients (P= 0.001) or the control group (P= 0.001), with a sensitivity of (74%) and specificity of (88.89%) at a cut-off level of 614.1 μmol/l. While AFP, alpha-fetoprotein, at a cutoff level of 200 ng/ml had a sensitivity of (52%), the specificity was (100%). Indeed, nitric oxide was high in 62.5% of AFP-negative HCC patients. In conclusion, glutathione reductase has no role in HCC diagnosis. However, nitric oxide is a potential diagnostic marker for HCC. The simultaneous determination of serum nitric oxide and AFP gave significant improvement in the detection of HCC patients compared to that of AFP alone.