Preliminary Study of Oxidative Stress in Human Hepatocellular Carcinoma and Adjacent Normal Liver Tissues

OBJECTIVE The antioxidative system in human hepatocellular carcinoma was investigated. METHODS The activities of cytosolic catalase (CAT), superoxide dismu-tase, glutathione peroxidase (GSH-Px), glutathione S-tranferase and levels of reduced glutathione, total protein thiols and malondialdehyde were assayed in 10 cases of hepatocellular carcinoma and adjacent normal liver. RESULTS Hepatoma tissues showed higher activities of CAT, GSH -Px and lower content of total antioxidative capacity compared to adjacent normal liver tissue (P<0.05). CONCLUSION These findings suggest that the antioxidative defense-related enzymes and antioxidants are largely regulated in hepatoma cells. However, the mechanism which is not clear requires further investigation.

Hepatitis D and hepatocellular carcinoma

Hepatitis D virus(HDV) is a defective circular shape single stranded HDV RNA virus with two types of viral proteins,small and large hepatitis D antigens,surrounded by hepatitis B surface antigen.Superinfection with HDV in chronic hepatitis B is associated with a more threatening form of liver disease leading to rapid progression to cirrhosis.In spite of some controversy in the epidemiological studies,HDV infection does increase the risk of hepatocellular carcinoma(HCC) compared to hepatitis B virus(HBV) monoinfection.Hepatic decompensation,rather than development of HCC,is the first usual clinical endpoint during the course of HDV infection.Oxidative stress as a result of severe necroinflammation may progress to HCC.The large hepatitis D antigen is a regulator of various cellular functions and an activator of signal transducer and activator of transcription(STAT)3 and the nuclear factor kappa B pathway.Another proposed epigenetic mechanism by which HCC may form is the aberrant silencing of tumor suppressor genes by DNA Methyltransferases.HDV antigens have also been associated with increased histone H3 acetylation of the clusterin promoter.This enhances the expression of clusterin in infected cells,increasing cell survival potential.Any contribution of HBV DNA integration with chromosomes of infected hepatocytes is not clear at this stage.The targeted inhibition of STAT3 and cyclophilin,and augmentation of peroxisome proliferatoractivated receptor γ have a potential therapeutic role in HCC.

Responsibility of hepatitis C virus in the development of hepatocellular carcinoma:From molecular alterations to possible solutions

There are several causes of hepatocellular carcinoma(HCC), but certainly the hepatitis C virus(HCV) is one of the most common. The HCV is able to contribute, both directly and indirectly, to the development of HCC. Determining early HCV clearance before an advanced liver disease develops, is absolutely necessary as this prevents the initiation of the cascade of events induced by HCV that may result in the development of HCC. The early treatment of the infection and the clearance of HCV represents today, in the age of the direct antiviral agents(DAAs), an extraordinary opportunity for true prevention of the development of HCV-related HCC.

Serum manganese superoxide dismutase and thioredoxin are potential prognostic markers for hepatitis C virus-related hepatocellular carcinoma

AIM:To evaluate the clinical significance of oxidative stress markers in patients with hepatitis C virus(HCV)related hepatocellular carcinoma(HCC).METHODS:Sixty-four consecutive patients who were admitted to Kagoshima University Medical and Dental Hospital were enrolled in this retrospective study.All patients had chronic liver disease(CLD) due to infection with HCV.Thirty patients with HCV-related HCC,34 with HCV-related CLD without HCC(non-HCC),and 20 healthy volunteers(HVs) were enrolled.Possible associations between serum manganese superoxide dismutase(MnSOD) and thioredoxin(TRX) levels and clinical parameters or patient prognosis were analyzed over a mean follow-up period of 31.7 mo.RESULTS:The serum MnSOD levels were significantly higher in patients with HCV-related HCC than in patients without HCC(P = 0.03) or HVs(P < 0.001).Similarly,serum TRX levels were also significantly higher in patients with HCV-related HCC than in patients without HCC(P = 0.04) or HVs(P < 0.01).However,serum levels of MnSOD and TRX were not correlated in patients with HCC.Among patients with HCC,the overall survival rate(OSR) was lower in patients with MnSOD levels ≥ 110 ng/mL than in patients with levels < 110 ng/mL(P = 0.01),and the OSR tended to be lower in patients with TRX levels < 80 ng/mL(P = 0.05).In addition,patient prognosis with HCC was poorest with serum MnSOD levels ≥ 110 ng/mL and serum TRX levels < 80 ng/mL.Furthermore,a multivariate analysis using a Cox proportional hazard model and serum levels of five factors(MnSOD,prothrombin time,serum albumin,serum α-fetoprotein(AFP),and serum des-γ-carboxy prothrombin) revealed that MnSOD levels ≥ 110 ng/mL(risk ratio:4.12,95% confidential interval:1.22-13.88,P = 0.02) and AFP levels ≥ 40 ng/mL(risk ratio:6.75;95% confidential interval:1.70-26.85,P < 0.01) were independent risk factors associated with a poor patient prognosis.CONCLUSION:Serum MnSOD and TRX levels are potential clinical biomarkers that predict patient prognosis in HCV-related HCC.

Therapeutic effect of hydrogen peroxide via altered expression of glutathione S-transferase and peroxiredoxin-2 in hepatocellular carcinoma

Background:Hepatocellular carcinoma(HCC)has a high incidence and mortality that epitomizes one of the prominent causes of cancer-related death globally.Novel therapeutic approaches are therefore required.Reactive oxygen species(ROS)are necessary for maintaining cell cycle.Although ROS is involved in HCC progression,hydrogen peroxide(H2O2)has anti-proliferative effect on HCC.Method:HCC Huh-7 cells were cultured and incubated with various concentrations of H2O2.Paraoxonase activity,levels of malondialdehyde,glutathione and protein oxidation were measured in treated and untreated Huh-7 cells.Furthermore,untreated and treated Huh-7 cells were subjected to two dimensional gel electrophoresis and identified protein spots which were differentially expressed by LC-MS/MS analysis.q RT-PCR was performed to validate the identified proteins.Results:H2O2 depleted glutathione(GSH)with the concomitant up-regulation of GSTP1 and Prx2.H2O2 also increased malondialdehyde and protein oxidation,decreased the activity of paraoxonase in Huh-7 cells.Conclusion:H2O2 could be used as a novel therapeutic agent that might be beneficial in inducing cell cytotoxicity and hence suppress HCC proliferation.

Acylcarnitine: Useful biomarker for early diagnosis of hepatocellular carcinoma in non-steatohepatitis patients

BACKGROUND Early diagnosis of hepatocellular carcinoma(HCC)is necessary to improve the prognosis of patients.However,the currently available tumor biomarkers are insufficient for the early detection of HCC.Acylcarnitine is essential in fatty acid metabolic pathways.A recent study reported that a high level of acylcarnitine may serve as a useful biomarker for the early diagnosis of HCC in steatohepatitis(SH)patients.In contrast,another study reported that the level of acetylcarnitine(AC2)-one of the acylcarnitine species-in non-SH patients with HCC was decreased vs that reported in those without HCC.AIM To investigate the usefulness of acylcarnitine as a biomarker for the early diagnosis of HCC in non-SH patients.METHODS Thirty-three non-SH patients(14 with HCC and 19 without HCC)were enrolled in this study.Blood samples were obtained from patients at the time of admission.The levels of acylcarnitine and AC2 in the serum were determined through tandem mass spectrometry.The levels of vascular endothelial growth factor(VEGF)and VEGF receptor 2(VEGFR-2)were determined by enzymelinked immunosorbent assay.Univariate and multivariate analyses were used to determine early diagnostic factors of HCC.RESULTS The level of acylcarnitine was significantly lower in non-SH patients with HCC vs those without HCC(P<0.05).In contrast,the level of lens culinaris agglutininreactive fraction ofα-fetoprotein(AFP)-AFP-L3%-was significantly higher in non-SH patients with HCC vs those without HCC(P<0.05).However,the levels of total carnitine,free carnitine,AFP,des-γ-carboxy prothrombin,VEGF,and VEGFR-2 were not different between patients with and without HCC.The multivariate analysis showed that a low level of acylcarnitine was the only independent factor for the early diagnosis of HCC.The patients with a low level of AC2 had a significantly higher level of VEGF vs those with a high level of AC2(P<0.05).CONCLUSION The metabolic pathways of fatty acids may differ between SH HCC and non-SH HCC.Further studies are warranted to investigate these differences.

Serum metabolome profiles characterized by patients with hepatocellular carcinoma associated with hepatitis B and C

AIM: To clarify the characteristics of metabolite profiles in virus-related hepatocellular carcinoma (HCC) patients using serum metabolome analysis.METHODS: The serum levels of low-molecular-weight metabolites in 68 patients with HCC were quantified using capillary electrophoresis chromatography and mass spectrometry. Thirty and 38 of the patients suffered from hepatitis B virus-related HCC (HCC-B) and hepatitis C virus-related HCC (HCC-C), respectively.RESULTS: The main metabolites characteristic of HCC were those associated with glutathione metabolism, notably 13 &#x003b3;-glutamyl peptides, which are by-products of glutathione induction. Two major profiles, i.e., concentration patterns, of metabolites were identified in HCC patients, and these were classified into two groups: an HCC-B group and an HCC-C group including some of the HCC-B cases. The receiver operating characteristic curve for the multiple logistic regression model discriminating HCC-B from HCC-C incorporating the concentrations of glutamic acid, methionine and &#x003b3;-glutamyl-glycine-glycine showed a highly significant area under the curve value of 0.94 (95%CI: 0.89-1.0, P &#x0003c; 0.0001).CONCLUSION: The serum levels of &#x003b3;-glutamyl peptides, as well as their concentration patterns, contribute to the development of potential biomarkers for virus-related HCC. The difference in metabolite profiles between HCC-B and HCC-C may reflect the respective metabolic reactions that underlie the different pathogeneses of these two types of HCC.

基于机器学习方法构建线粒体氧化应激相关肝细胞癌预后风险模型

肝癌是常见的恶性肿瘤之一,晚期肝癌的预后极差。鉴于线粒体氧化应激在肝癌发生发展中的重要作用,选用线粒体氧化应激相关基因构建肝细胞癌(hepatocellular carcinoma,HCC)预后风险模型。首先,结合单因素Cox回归分析与支持向量机、随机森林分析、LASSO回归分析3种机器学习方法筛选预后关键基因,并基于多因素Cox回归分析构建模型;其次,在数据库中对模型的预后价值进行验证;再次,利用基因富集分析探讨高低风险组间预后差异的可能机制,并比较两组间的免疫微环境及治疗反应;最后,使用实时荧光定量逆转录PCR(reverse transcription quantitative real-time PCR;RT-qPCR)验证关键基因在HCC组织中的表达。结果共筛选出PDE2A、TREM2、BMP6、NQO1、CPS1、EPO、MAPT、G6PD、SFN、HMOX1十个基因。与低风险组比较,高风险组HCC患者预后较差(P<0.0001)。富集分析表明,过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptor,PPAR)信号通路等在高低风险组间存在显著差异。肿瘤免疫分析表明,肿瘤免疫浸润、免疫检查点相关基因、免疫治疗反应等在高低风险组间也存在显著差异。RT-qPCR的验证结果表明,相比正常肝组织,HCC组织中CPS1、PDE2A、BMP6的表达显著降低(P<0.05),而G6PD、SFN的表达显著升高(P<0.05)。总之,本研究建立的线粒体氧化应激相关HCC预后风险模型具有良好的预测效能及准确度,可用于HCC的精准治疗,有较高的临床应用价值。

Psychosocial stress and liver disease status

"Psychosocial stress" is an increasingly common concept in the challenging and highly-demanding modern society of today. Organic response to stress implicates two major components of the stress system, namely the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Stress is anamnestically reported by patients during the course of disease, usually accompanied by a decline in their overall health status. As the mechanisms involving glucocorticoids and catecholamines have been deciphered, and their actions on immune cell function deeper understood, it has become clear that stress has an impact on hepatic inflam-matory response. An increasing number of articles have approached the link between psychosocial stress and the negative evolution of hepatic diseases. This article reviews a number of studies on both human populations and animal models performed in recent years, all linking stress, mainly of psychosocial nature, and the evolution of three important liver-related pathological entities: viral hepatitis, cirrhosis and hepatocellular carcinoma.

紫檀芪通过调控氧化应激和NLRP3炎症小体抑制肝癌增殖迁移

目的探讨紫檀芪(PTE)对肝细胞癌(HCC)的增殖和迁移能力的影响及其可能的机制。方法培养人HCC细胞Hep3B、HepG2、Bel-7404、Bel-7402及永生化人肝细胞LO2,观察PTE对细胞生长能力的影响。MTT、平板克隆、EdU实验和Western-blot实验观察PTE对细胞增殖能力的影响。细胞划痕实验、Transwell实验和Western-blot实验检测细胞迁移能力的改变。应用过氧化氢(H_(2)O_(2))、白细胞介素1β(IL-1β)和IL-18试剂盒分别检测H_(2)O_(2)、IL-1β和IL-18的表达水平。采用2,7-双乙酸二氯荧光素(DCFH-DA)荧光探针孵育细胞,应用荧光酶标仪法检测ROS的表达水平。qRT-PCR和/或Western-blot实验检测NOX4、NLRP3、ASC、Caspase-1和IL-1β的表达水平。免疫荧光染色方法检测NLRP3炎症小体的组装效应。结果MTT、单克隆形成、EdU和Western-blot实验结果表明,PTE抑制HCC的增殖能力(P<0.01)。划痕实验、Transwell和Western-blot实验结果表明,PTE显著降低HCC的迁移能力(P<0.01)。PTE抑制Hep3B细胞中NOX4、ROS和H_(2)O_(2)的水平,且结果呈剂量依赖性(P<0.01);予抗氧化剂NAC或NOX4抑制剂VAS2870处理后,细胞中ROS和H_(2)O_(2)水平进一步被抑制(P<0.01)。PTE呈剂量依赖性抑制Hep3B细胞中NLRP3炎症小体复合物组分NLRP3、ASC、Caspase-1及IL-1β的含量(P<0.01);予LPS或H_(2)O_(2)刺激后,Hep3B细胞中NLRP3、ASC、Caspase-1、IL-1β和IL-18的表达水平增加(P<0.01),但上述结果可被PTE抑制(P<0.01)。免疫荧光结果表明,PTE抑制LPS诱导Hep3B细胞内NLRP3炎症小体的组装活化水平。MTT和Transwell实验结果表明,予LPS或H_(2)O_(2)刺激后Hep3B细胞增殖和迁移能力明显增加(P<0.05),但上述结果可被PTE抑制(P<0.05)。结论PTE通过抑制氧化应激和NLRP3炎症小体进而抑制HCC的增殖和迁移。

基于氧化应激基因构建肝细胞癌预后模型及潜在中药预测分析

目的肝细胞癌(hepatocellular carcinoma,HCC)是一种具有高侵袭性、诊断延迟和不良预后的肿瘤。本研究旨在构建一个基于氧化应激基因的HCC预后模型,并探索与该模型相关的中药成分。方法研究使用癌症基因组图谱(the cancer genome atlas,TCGA)和基因表达集(gene expression omnibus,GEO)中的数据集,鉴定与氧化应激相关的差异表达基因。通过单变量和多变量Cox回归以及Lasso回归分析,构建一个用于预测HCC患者预后的模型。利用Coremine Medicine数据库预测模型基因潜在的相关中药成分,并进行归经和性味聚类以及分子对接分析。验证试验:采用MTT法检测预测中药马钱子和龙葵水提液对Hep3B细胞增殖的影响;使用Western blot检测马钱子和龙葵水提液对细胞中SCL7A11蛋白水平的调控。结果在氧化应激相关基因中,EZH2和SLC7A11基因可用于构建预后模型。预测模型模型基因相关的中药主要归肝经、味苦和性寒。分子对接分析表明,龙葵中的5'-甲氧基松脂素和马钱子中的马钱子碱N-氧化物分别与SLC7A11的247号丙氨酸(Affinity=-11.0)和198号赖氨酸(Affinity=-10.2)具有较强的结合能力。实验证实,马钱子和龙葵水提取物对Hep3B细胞增殖呈浓度和时间依赖性抑制作用,并减少了Hep3B细胞中SLC7A11蛋白的表达。结论本研究成功构建了一个基于氧化应激基因的个体化HCC预后模型,并预测了与模型基因相关的潜在中药成分。

岩藻多糖对高尿酸诱导HepG2细胞凋亡影响及机制

目的探讨岩藻多糖(Fucoidan)对高浓度尿酸(UA)诱导的人肝癌细胞(HepG2)线粒体凋亡的影响及机制。方法HepG2细胞随机分为对照组(加无药物培养液)、UA模型组(加入0.2 g/L UA溶液)、白黎芦醇组(Res组,用1μmol/L白藜芦醇溶液预处理24 h后加入0.2 g/L UA溶液)、F1组(加入0.2 g/L UA+20 mg/L Fucoidan溶液处理)、F2组(加入0.2 g/L UA+40 mg/L Fucoidan溶液处理)、F1+EX527组(加入0.2 g/L UA+20 mg/L Fucoidan+1μmol/L EX527溶液处理)、F2+EX527组(加入0.2 g/L UA+40 mg/L Fucoidan+1μmol/L EX527溶液处理)。各组加入相应药物处理24 h后,应用CCK8实验检测HepG2细胞活力,ELISA实验检测细胞上清液丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)水平及细胞内超氧化物歧化酶(SOD)、还原型谷胱甘肽(GSH)和丙二醛(MDA)水平;荧光显微镜检测活性氧(ROS)和线粒体膜电位,流式细胞仪测定细胞凋亡率,Western blot方法检测Sirt1蛋白表达。结果与对照组相比,UA模型组HepG2细胞活力降低(F=295.200,P<0.01),细胞上清液ALT和AST水平升高(F=204.300、9.511,P<0.01),细胞内SOD和GSH水平降低(F=47.880、8.261,P<0.01),MDA含量增加(F=132.400,P<0.01),ROS生成增加(F=23.720,P<0.05),Sirt1蛋白表达下调(F=64.520,P<0.01),细胞凋亡率明显升高(F=19.200,P<0.01);与UA模型组相比,Res组、F1组和F2组HepG2细胞生存率增加,ALT和AST水平降低,细胞内SOD和GSH水平增加,MDA含量降低,差异均有显著性(P<0.01);与UA模型组相比,F2组细胞内ROS生成减少,线粒体膜电位下降,Sirt1蛋白表达上调,细胞凋亡率下降,差异有显著性(P<0.05)。加入Sirt1抑制剂EX527能显著逆转Fucoidan的抗氧化和抗凋亡作用,差异有显著性(P<0.05)。结论Fucoidan通过上调Sirt1蛋白表达抑制线粒体氧化应激,逆转UA诱导的HepG2细胞线粒体凋亡。

Antioxidant and anti-inflammatory agents in chronic liver diseases:Molecular mechanisms and therapy

Chronic liver disease(CLD)is a continuous process that causes a reduction of liver function lasting more than six months.CLD includes alcoholic liver disease(ALD),non-alcoholic fatty liver disease(NAFLD),chronic viral infection,and autoimmune hepatitis,which can lead to liver fibrosis,cirrhosis,and cancer.Liver inflammation and oxidative stress are commonly associated with the development and progression of CLD.Molecular signaling pathways such as AMPactivated protein kinase(AMPK),C-Jun N-terminal kinase,and peroxisome proliferator-activated receptors(PPARs)are implicated in the pathogenesis of CLD.Therefore,antioxidant and anti-inflammatory agents from natural products are new potent therapies for ALD,NAFLD,and hepatocellular carcinoma(HCC).In this review,we summarize some powerful products that can be potential applied in all the stages of CLD,from ALD/NAFLD to HCC.The selected agents such asβ-sitosterol,curcumin,genistein,and silymarin can regulate the activation of several important molecules,including AMPK,Farnesoid X receptor,nuclear factor erythroid 2-related factor-2,PPARs,phosphatidylinositol-3-kinase,and lysyl oxidase-like proteins.In addition,clinical trials are undergoing to evaluate their efficacy and safety.

基于氧化应激的固态发酵白酒抑制肝癌HepG2细胞增殖

探究固态酿造浓香型白酒(NX)和酱香型白酒(JX)抑制肝癌细胞HepG2增殖的作用机制。采用细胞计数试剂盒8(CCK8)法评价细胞增殖,用试剂盒检测乙醇脱氢酶(ADH)、过氧化氢酶(CAT)、黄嘌呤氧化酶(XOD)的酶活以及活性氧(ROS)和一氧化氮(NO)的含量评价HepG2氧化应激酶的水平,采用实时定量PCR检测氧化应激关键基因核因子E2相关因子2(NRF2)及其下游基因醌氧化还原酶(NQO1)的表达。结果:100 mmol/L乙醇(ETOH)浓度时NX和JX均能显著抑制HepG2的增殖,抑制率达15%;JX(6.25~100 mmol/L ETOH)显著上调HepG2细胞内XOD和CAT的活力。ROS检测发现在12.5 mmol/L ETOH时其含量达到峰值,且受JX影响较大。NX(6.25~100 mmol/L ETOH)较JX显著促进NO的生成。NX和JX(100 mmol/L ETOH)均可显著抑制HepG2胞内NRF2及其下游基因HQO-1的表达。用抗氧化剂N-乙酰-L-半胱氨酸(NAC)抑制氧化应激反应后,NX和JX抑制HepG2增殖的作用均消失,同时也阻断其对NRF2和HQO-1表达的调控。结论:NX和JX均通过促进氧化应激抑制肝癌HepG2细胞的增殖。

原发性肝癌一氧化氮及一氧化氮合酶的研究

探讨一氧化氮 (Nitricoxide,NO)及诱导型一氧化氮合酶 (induciblenitricoxidesynthase ,iNOS)与原发性肝癌 (HCC)间的关系 ,用Griess反应测定 16 2例患者的血浆亚硝酸盐 /硝酸盐 (NO-2 /NO-3 )水平 ,其中HCC82例 ,非HCC80例 ,健康对照 36名。用免疫组化法检查组织中iNOS的含量 ,取正常肝脏组织 2 0例作对照 ,慢性肝炎 (CH)和肝硬化 (LC)的肝脏组织各 40例 ,HCC组织 48例。结果显示 ,正常人血浆NO-2 /NO-3 含量为 16 .8±4.9μmol/L,有HCC的CH(6 3 .4± 18.2 μmol)和LC(42 .2± 11.5 μmol/L)明显高于非HCC的患者 (CH :2 8.5±8.7μmol/L;LC :2 4.7± 6 .2 μmol/L .P <0 .0 1) ,患CH的HCC患者血浆NO-2 /NO-3 水平明显高于LC基础上的HCC患者 (P <0 .0 5 )。正常肝组织iNOS阴性 ,LC有 2 5例 (6 2 .5 % )阳性 ,CH 36例 (90 % )阳性 ,HCC 46例 (95 8% )阳性 ;且CH (P <0 .0 2 5 )及HCC(P <0 .0 0 1)的表达水平明显高于LC。提示HCC患者有NO分泌的增加 。

人体肝癌和正常肝脏细胞内硒与氧化应激机制的初步探讨

目的 探讨微量元素硒和氧化应激水平在肝癌发展中的作用。方法 采集了数例肝癌晚期切除样品及其癌旁正常组织 ,测定了正常肝脏组织和癌组织不同细胞器中硒的含量以及超氧化物歧化酶 (SOD)、谷胱甘肽过氧化物酶 (GSH -Px)、硫氧还蛋白还原酶 (TrxR)活性及谷胱甘肽 (GSH)和蛋白总巯基的含量。结果 Se在肝癌溶酶体 (P <0 0 5 )、微粒体 (P <0 0 5 )、细胞质中的含量高于正常肝组织 ,几种抗氧化酶酶的活性和巯基含量均高于正常肝。癌细胞中的Se含量要明显高于相应的癌旁周围正常肝细胞 ,尤其是细胞核、线粒体和细胞质。癌细胞线粒体、细胞质中几种抗氧化酶的活性以及巯基含量均高于相应的癌旁正常肝细胞。结论 癌细胞代谢旺盛 ,摄取更多的营养物质 ,从而造成周围正常细胞营养素的缺乏 ,抗氧化能力的下降 。

端粒酶反转录酶基因在肝细胞癌中的表达及其意义

目的研究肝细胞癌中端粒酶反转录酶（human telomerase reverse transcriptase,hTERT）基因的表达及其临床意义。方法采用原位杂交方法分别对肝细胞癌及肝炎后肝硬化组织中hTERTmRNA进行检测。结果肝癌中hTERTmRNA表达阳性率明显高于肝硬化组织,差别有统计学意义（P〈0.01）;中、低分化的肝癌hTERT mRNA阳性强度高于高分化者,差别有统计学意义（P〈0.05）;肝癌中hTERTmRNA表达阴性组患者术后3年生存率高于阳性组患者,差别有统计学意义（P〈0.05）;hTERTmRNA表达弱阳性的肝癌患者生存时间较强阳性者延长,差别有统计学意义（P〈0.05）。结论hTERTmRNA阳性表达普遍存在于肝癌组织中,通过检测肝癌中hTERTmRNA表达情况可用来作为肝癌诊断及预后估计的新标志物。

晚期人肝癌和癌旁组织中抗氧化酶及相关指标的测定及其意义

目的:研究肝癌晚期切除样品及其癌旁正常组织抗氧化酶及相关指标,探讨氧化应激反应水平在肝癌发展中的作用。方法:测定癌组织和癌旁正常组织中过氧化氢酶(CAT)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、谷胱甘肽硫转移酶(GST)活性及谷胱甘肽(GSH)、蛋白总巯基、脂质过氧化产物丙二醛(MDA)和总抗氧化能力(T-AOC)的含量(P<0.05)。结果:肝癌组织CAT和GSH-Px的活性显著高于相应的周围正常肝组织。癌旁组织的T-AOC含量则高于肝癌组织。结论:晚期肝癌组织中,体内抗氧化系统有显著改变。

氧化应激在肝细胞癌中的研究进展

肝细胞癌(HCC)是消化系统常见恶性肿瘤之一,数条涉及增殖和凋亡调节的分子通路参与了HCC的形成,但相关机制目前尚未完全明确。近年研究发现,环境或细胞线粒体功能障碍等因素造成的氧化应激参与了HCC的形成。本文就氧化应激在HCC中的研究进展作一综述。

肝癌和肝硬化患者血清一氧化氮水平探讨

目的 :探讨一氧化氮 (NO)与肝癌及其合并症、肝硬化、肝功能分级及肝硬化并发症的关系。方法 :应用化学比色法检测34例肝癌患者 ,45例肝硬化患者及20例正常人血清NO水平。结果 :肝癌组血清NO显著高于肝硬化组及正常对照组 ;肝癌合并代偿期肝硬化血清NO高于合并慢性肝炎者 ;肝硬化组血清NO与正常对照组比较 ,差异有显著性 ;并且随肝功能Child -Pugh分级的增加而升高 ,A级与对照组比较无差异 ,B级与A级、B级与C级比较 ,差异有显著性。并发肝肾综合征、食管胃底静脉曲张破裂出血者较无并发症肝硬化者NO明显升高。结论 :内源性NO在肝癌及肝硬化时合成增加 ,且与肝癌合并症、肝硬化病情严重程度及并发症的发生密切相关。