不同临床分期肝癌患者抗AFPTh1和Tc1应答反应研究

目的:研究CD4(Th1)和CD8(Tc1)T细胞对肝癌患者的AFP的应答反应及其与临床特征的相关性,为其早期诊断与预防提供新策略。方法:研究对象为62例HCC患者,30例肝硬化患者及30例健康志愿者;重点分析CD4 T细胞和CD8 T细胞对HCC患者的AFP-衍生肽的反应;用胞内细胞因子检测法对IFN-γ进行检测。结果:抗AFP的Tc1反应检测阳性结果在对照组为28.5%,在OkudaⅠ期的肝癌患者中为25.0%,在Ⅱ或Ⅲ期的HCC患者中为31.6%。抗AFP Th1阳性反应仅在HCC患者中检测到。抗AFP Th1阳性反应在44.4%的Child-Pugh A级的HCC患者中检测到,但是在Child-Pugh B或C级中仅15.4%。Tc1型反应在Child-Pugh A级肝功的患者中为16.7%,在Child-Pugh B或C级患者中为46.2%。结论:抗AFP Th1应答更多出现在早期肝硬化的HCC的患者中,而抗AFP Tc1应答更可能出现在晚期肝硬化患者中,这些结论为抗肝癌疫苗药物设计提供了理论基础。     

胃肝样腺癌的临床病理特征

目的探讨胃肝样腺癌（hepatoid adenocarcinoma of the stomach,HAS）的临床病理学特点、发生机制和免疫组化特征,以提高诊断水平。方法收集并分析5例胃肝样腺癌的临床特征和病理资料,采用HE染色、免疫组化方法,并复习文献。结果组织学胃肝样腺癌具有管状腺癌、粘液性癌和肝样分化腺癌的移行过渡,肿瘤细胞呈小梁状、巢团状,间质为丰富的血窦。免疫表型胃肝样腺癌AAT（5／5）、ACT（5／5）、CEA（5／5）、AFP（4／5）均为阳性,Heppar1灶性阳性（2／5）。结论胃肝样腺癌是一种少见的高度恶性、侵袭性强的特殊类型胃癌,组织学呈肝细胞样腺癌,免疫表型AFP、AAT和ACT阳性有助诊断。     

原发性肝癌MRI检查图像特征分析及联合血清AFP、TK1、DKK1的诊断价值研究

摘要 目的：研究原发性肝癌（PHC）磁共振成像（MRI）检查图像特征及其联合血清甲胎蛋白（AFP）、胸苷激酶1（TK1）、Dickkopf相关蛋白1（DKK1）的诊断价值。方法：将我院从2017年1月～2020年1月收治的PHC患者76例纳入研究,记作观察组。另取同期我院收治的70例良性肝病患者记作对照组。对所有受试者均进行MRI扫描,比较两组MRI图像特征。检测并对比两组血清AFP、TK1、DKK1水平的差异。通过受试者工作特征（ROC）曲线分析MRI及上述各项血清学指标诊断PHC的效能。结果：PHC患者T1WI主要表现为均匀低或稍低信号,T2WI主要表现为不均匀高信号,DWI均表现为均匀高信号。观察组血清AFP、TK1、DKK1水平均高于对照组（均P＜0.05）。经ROC曲线分析可得：MRI检查联合血清AFP、TK1、DKK1诊断PHC的曲线下面积、灵敏度、特异度、准确度均高于上述各项检查方式单独诊断。结论：PHC患者MRI图像特征如下：T1WI主要表现为均匀低或稍低信号,T2WI主要表现为不均匀高信号,DWI均表现为均匀高信号。此外,MRI检查联合血清AFP、TK1、DKK1诊断PHC的效能较高,具有一定的临床应用价值。     

A DNA vaccine against chimeric AFP enhanced by HSP70 suppresses growth of hepatocellular carcinoma

Alpha-Fetoprotein (AFP) is produced principally in fetal liver, gastrointestinal tract and the yolk sac which is temporarily present during embryonic development. AFP is overexpressed in the majority of Hepatocellular Carcinoma (HCC) and thus offers an attractive target for immunotherapy against this neoplasm. Here, we report that anti-HCC effects were achieved in a therapeutic setting with a DNA vaccine encoding mouse AFP and co-expressing Heat Shock Protein 70 (HSP70) gene. We also demonstrated that this vaccine elicited a marked and highly effective AFP specific CTL response against AFP-positive target cells. This vaccine also induced the prolongation of life span in mice bearing the tumor and the eradication of HCC. It is anticipated that vaccine strategies such as this may contribute to the effective future treatment of Hepatocellular Carcinoma. Ying-hua Lan and Yong-guo Li contributed equally to this work.     

Alpha-fetoprotein (AFP)-derived peptides as epitopes for hepatoma immunotherapy: a commentary

The various immunological roles of human alpha-fetoprotein (HAFP), and its correlation with hepatomas, that is, hepatocellular carcinomas (HCCs), are not often addressed together in biomedical reports considering that HAFP is an established biomarker for hepatomas. Studies reporting measurement of HAFP serum levels in hepatoma patients in basic/clinical research settings has greatly increased over the years. Recent reports have now expanded our base knowledge in the mounting of an immune response against AFP, a self antigen, during hepatoma tumorigenesis. Advances in the detection and identification of AFP-derived peptide epitopes are opening new vistas of knowledge regarding the immunological role of AFP-peptides as T cell stimulating antigens in the course of hepatoma growth and progression. The present commentary addresses HAFP-derived peptides as immunologic responders in HCC and their use in the study and generation of AFP-peptide sensitized T cells directed against hepatoma cells. Attempts were further made to relate the AFP-derived peptide epitopes to T cell activities during the course of hepatoma immunotherapies and to profile the traits and properties of the peptides themselves. Hence, the present commentary was divided into two sections; (1) the characterization, properties, and traits of AFP peptide epitopes, and (2) the use of AFP-derived peptides in the therapeutic induction of T cells primed against hepatoma cells using both in vivo and in vitro models.     

超声造影定量分析联合血清AFP、VEGFR-2、sTim-3对原发性肝癌TACE治疗疗效的预测价值

摘要 目的：探讨超声造影定量分析联合血清甲胎蛋白（AFP）、血管内皮生长因子受体-2（VEGFR-2）、可溶性T细胞免疫球蛋白粘蛋白分子3（sTim-3）对原发性肝癌肝动脉化疗栓塞（TACE）治疗疗效的预测价值。方法：选择2020年1月至2022年10月海军军医大学第二附属医院收治的原发性肝癌患者94例。行TACE治疗2个月,采用改良的实体瘤疗效评价标准评估患者疗效,根据不同疗效分为疗效不良组（n=32）和疗效良好组（n=62）。所有患者均行超声造影检查,比较两组超声造影定量分析参数、治疗前血清AFP、VEGFR-2、sTim-3水平,采用受试者工作特征（ROC）曲线分析超声造影定量分析参数联合血清AFP、VEGFR-2、sTim-3对原发性肝癌TACE治疗疗效的预测价值。结果：经TACE治疗,62例患者疗效良好、32例患者疗效不良,治疗有效率为65.96%。疗效良好组术前超声造影达峰时间、等增强开始时间显著长于疗效不良组（P<0.05）。疗效良好组术前血清AFP、VEGFR-2、sTim-3水平显著低于疗效不良组（P<0.05）。ROC曲线分析结果显示,超声造影定量分析联合血清AFP、VEGFR-2、sTim-3对原发性肝癌TACE治疗疗效预测的曲线下面积（AUC）为0.950,灵敏度为84.85%,特异度为82.12%,高于各指标单独检测。结论：超声造影定量分析参数、血清AFP、VEGFR-2、sTim-3水平可预测原发性肝癌患者TACE治疗的疗效,且联合诊断的预测效能更高。     

Detection of squalene in alpha-fetoprotein and fetal serum albumin from bovine

Alpha-fetoprotein and fetal serum albumin have been simultaneously purified from fetal bovine serum by mild procedures utilizing ammonium sulfate, hydrophobic interaction, immobilized metal (nickel) affinity chromatography, and isoelectric focusing. The lipidic extract from each protein was analyzed by gas chromatography and the peak appearing just after the arachidonic acid was identified as squalene by gas chromatography-mass spectrometry. This isoprenoid was not detected formerly in these proteins from human, rat, bovine, and pig. Until recently, in the analysis of the fatty acid composition of the alpha-fetoprotein and serum albumin from mammals, a peak has been assigned in the last part of the chromatographic profile, after arachidonic acid, to docosahexaenoic acid. In the present work, it was found that the peak corresponds to squalene instead of docosahexaenoic acid. Furthermore, we conclude that bovine alpha-fetoprotein and fetal serum albumin carry squalene, but not docosahexaenoic acid. These results agree with others obtained analyzing the same proteins from chick embryo.     

Review and proposed action of alpha-fetoprotein growth inhibitory peptides as estrogen and cytoskeleton-associated factors

The (H) human growth-promoting factor, alpha-fetoprotein (AFP), has been reported to possess a growth inhibitory motif as an occult epitope in the compactly folded circulating form of the protein. Intermediate unfolded forms of the human HAFP molecule induced by stress, shock, and high ligand concentrations have revealed the presence of an encrypted growth-suppressive segment on the third domain of HAFP. A purified linear synthetic 34-mer segment termed the "growth inhibitory peptide" (GIP) exhibits various oligomeric forms with complex aggregation behaviors, in which dominant trimeric forms were found to be suppressive in assays of estrogen-induced growth. While several amino acid analogs of the cysteines of the GIP retained inhibitory activity, heavy metal binding and pre-incubation of the peptides with a variety of cations and hormone ligands were found to influence the outcomes of growth bioassays. Smaller segments of the original 34-mer were each found to display growth activities of their own, with the middle segment (P149b) also showing hydrophobic dye-binding properties. Studies of amino acid sequence identity further revealed that the GIP sequences displayed identity/similarity matches to both cytoplasmic and nucleus-cytoskeleton-associated proteins, and experimental evidence served to support these findings. That is, the peptide was capable of modulating tubulin polymerization, cell shape, and cell-surface aggregation phenomena reminiscent of a microtubule-associated protein. Immunofluorescence studies further pinpointed the localization of the GIP to cytoplasmic regions of high cytoskeletal density in the cell. Because of the involvement of the GIP in experimental models of the estrogen receptor/cytoskeleton, a mechanism of action is forwarded in which the linear GIP is proposed to be a G-coupled receptor binding ligand that is translocated across the plasma membrane via receptor-mediated endocytosis. Thus, it was predicted that the linear GIP and possibly its peptidic segments serve as decoy ligands to cell-surface receptors in order to gain access to the cytoplasmic compartment of the cell.     

视黄酸和亚硒酸钠对肝癌细胞某些表型逆转的加和作用

 人肝癌细胞株SMMC-7721经1μmol/L视黄酸和或2.5μmol/L亚硒酸钠处理后,膜上纤维连接蛋白沉着量逐日上升,且较相应天数的对照组细胞增加,而甲胎蛋白分泌量和~3H-TdR参入率被明显抑制。视黄酸和亚硒酸钠同时处理的联合组作用强度接近于两者单独使用时作用强度的加和。对以上结果和视黄酸及亚硒酸钠使肝癌细胞接触抑制恢复及表型逆转的关系作了讨论。     

以化脓性肝脓肿为初始表现的原发性肝癌的临床特点及诊治体会

目的：探讨以化脓性肝脓肿（PLA）为初始表现的原发性肝癌（PLC）的临床特点,总结诊治体会。方法：回顾性分析哈尔滨医科大学附属第一医院肝脏外科2007年6月至2012年6月收治的10例以PLA为初始表现的PLC患者以及269例同期收入院的PLA患者的临床资料。结果：以PLA为初始表现的PLC患者可表现为发热、寒战、右上腹痛、恶心、呕吐、腹泻、体重减轻以及黄疸等。实验室检查显示以PLA为初始表现的PLC患者甲胎蛋白（AFP）和糖类抗原19-9（CA19—9）升高的比例显著高于PLA患者,但其他实验室检查的差异无统计学意义。患者除静脉抗生素治疗外均接受了有创治疗,生存时间最长为13个月,最短仅为2个月。结论：对于AFP及CA199升高的PLA患者要警惕伴发PLC的可能。肝脏增强CT检查对AFP及CA199正常的此类患者有较大的诊断价值。早期准确诊断,把握手术时机是提高此类患者预后的根本。