去唾液酸糖蛋白受体 2 基因在肝细胞性肝癌中的表达及意义

目的检测去唾液酸糖蛋白受体2（asialoglycoprotein receptor 2,ASGR2）基因在肝细胞性肝癌（hepatocellular carcinoma,HCC）中的表达水平,探讨ASGR2在HCC发生、发展中的作用和意义。方法以RT-PCR法检测55例HCC患者、55例非肝癌的其他肿瘤患者和33例非肿瘤的其他疾病对照患者外周血液中ASGR2基因的表达水平,并分析其意义。结果肝癌组和非肝癌的其他肿瘤组患者血液中ASGR2基因阳性表达率分别为85．5％、65．5％,两组差异有统计学意义（P〈0．05）,肝癌组和非肿瘤的其他疾病对照组ASGR2基因阳性表达率分别为85．5％、78．8％,两组差异无统计学意义（P〉0．05）,ASGR2基因在3组患者外周血液中的表达水平有明显差异（P〈0．05）。ASGR2基因的表达与HCC患者的性别、年龄、AFP、肝硬化、肿瘤家族史等临床病理特征均无统计学意义（P〉0．05）。结论ASGR2基因的表达水平可能与HCC发生、发展有关,检测ASGR2的水平有望作为HCC早期发病的预测指标。     

TACE联合索拉非尼治疗中晚期肝细胞性肝癌的临床研究

目的探讨经导管动脉化疗栓塞（transcatheterarterialchemoembolization,TACE）联合索拉非尼治疗中晚期肝细胞性肝癌（hepatocellularcarcinoma,HCC）的疗效及安全性。方法选择我院70例中晚期HCC患者,其中35例给予TACE联合索拉非尼治疗（观察组）,35例单纯行TACE治疗（对照组）。每4-8周根据实体瘤疗效评估标准（RECIST）行肿瘤应答评价,评估临床疗效及索拉非尼毒副反应,比较两组患者治疗后的中位生存期及中位疾病进展时间。结果观察组和对照组中位0s分别为14_8个月和8．2个月,差异有统计学意义（P〈0．05）,中位TIP分别为10．3个月和5．8个月,差异有统计学意义（P〈0．05）。观察组服用索拉非尼后有27例（77．1％）患者出现毒副反应,经对症治疗后好转。结论TACE联合索拉非尼治疗中晚期HCC疗效好,不良反应可耐受,有望成为中晚期HCC的一种治疗模式。     

tktl1在肝细胞肝癌中的表达及临床意义

目的：研究转酮醇酶样基因1（tktl1）在肝细胞肝癌（HCC）中的表达及其与临床病理的关系。方法：RT-PCR法检测转酮醇酶基因家族各成员（tkt、tktl1、tktl2）mRNA在42例HCC及癌旁组织中的表达并研究其与临床病理参数间的关系。结果：HCC组织中tktl1阳性表达率明显高于tkt和tktl2的阳性表达率（P〈0.05）。tktl1在HCC中的阳性表达率明显高于癌旁组织（P〈0.05）;而tkt和tktl2阳性表达率在肝癌及癌旁组织间无明显差异（P〉0.05）。 HCC中tktl1的高表达同肿瘤分化程度,静脉癌栓,CLIP评分有关（P〈0．05）,而与性别、年龄、肿瘤大小、肝内及淋巴转移、AFP水平无关（P〉0．05）。结论：tktl1与HCC的发生发展有关,影响肝癌的分化、转移及患者预后,有望成为HCC治疗的新靶点。     

E-钙黏蛋白和上皮细胞黏附分子在结节型肝细胞性肝癌大体形态亚型中的表达及相关性研究

目的分析结节型肝细胞性肝癌（hepatocellularcarcinoma,HCC）各形态亚型的生存情况,初步探讨E一钙黏蛋白（E—cadherin）和上皮细胞黏附分子（EpCAM）在结节型HCC各亚型中的表达及其相关性。方法选取2008年至2011年在我院手术切除、直径小于5am且经病理证实为结节型HCC的肿瘤组织,根据其大体形态划分为3个亚组：单个结节组（sN组）61例;单个结节伴有结外生长组（SNEG组）21例;多结节融合型组（CM组）18例。应用免疫组织化学sP法检测E—cadherin蛋白和EpCAM蛋白在结节型HCC各亚型中的表达情况,并初步探讨两者的相关性。采用Kaplan—Meier生存统计分析结节型HCC3种亚型的生存情况。结果结节型HCC中SN组的平均生存时间为（33．5±0．9）月,明显高于SNEG组（24．3＋2．6）月和CM组（29．3±2．6）月,SN组与SNEG组比较,差异有统计学意义（P〈0．01）。E—cadherin在SN组、SNEG组、CM组中的阳性表达率分别为40．98％（25／61）、9．52％（2／21）、27．78％（5／18）（P〈0．05）,其中SN组与SNEG组比较,差异有统计学意义（P〈0．05）。EpCAM在SN组、SNEG组、CM组中的阳性表达率分别为22．95％（14／61）、52．38％（11／21）、27．78％（5／18）（R0．05）,其中SN组与SNEG组比较,差异有统计学意义（P〈．0．05）。相关『生分析结果显示E．cadhefin与EpCAM两者的阳性表达呈负相关（r=-0．580,P〈0．01o结论结节型HCC中的SNEG有潜在的复发风险;E—cadhefin低表达与EpCAM高表达提示HCC患者术后预后不良,可作为评估预后的联合诊断指标。     

家族肿瘤史在肝炎与原发性肝癌关系中的作用

研究ＰＨＣ９２４例中家族肿瘤史对肝炎与ＰＨＣ关系的影响，结果表明：①合并ＨＢＶ感染的ＰＨＣ、乙肝组中有家族肿瘤史的患者均显著多于非乙肝组和无肝炎组（Ｐ＜０．０１～０．０５）。②乙肝组发病高峰年龄为３０～４９岁，显著高于其它两组（５０～５９，Ｐ＜０．０１）；乙肝组中有家族肿瘤史者发病高峰年龄为３０～３９岁，显著高于无家族肿瘤史者（４０～４９岁，Ｐ＜０．０１）。③肝炎后至发生临床肝癌时间乙肝组以５～９年居多，较非乙肝组１０～１４年居多提前一个年龄组（Ｐ＜０．０５），且有家族肿瘤史者比例显著高（Ｐ＜０．０５）。提示ＨＢＶ感染可促使ＰＨＣ的高发、早发，而家族肿瘤史则加速了这一进程。     

HBVDNA阳性肝癌患者血清HBeAg检测与肝细胞癌复发转移的关系

目的：研究HBVDNA阳性肝癌（HCC）患者血清HBeAg检测与肝细胞癌复发转移的关系。方法：HBVDNA阳性HCC肝切除术患者60例,HBVDNA阴性HCC肝切除术患者60例。60例HBVDNA阳性HCC患者中依据肿瘤病灶局限、肉眼以及镜下均无肝内播散和门静脉浸润的低侵袭组,共28例;肿瘤组织伴有多发性肝内播散和（或）门静脉主肝癌栓者为高侵袭组,共32例。检测患者术前及术后1周血清HBVDNA水平,观察肝功能变化并检测血清HBeAg水平。结果：HBVDNA阳性组与HBVDNA阴性组比较,60例HBVDNA阳性HCC患者中HBeAg阳性患者为48例,阳性率为80％,60例HBVDNA阴性HCC患者中HBeAg阳性患者为12例,阳性率为20％,（P〈0．05）。不同侵袭组HBeAg表达比较：32例高侵袭组中29例HBeAg检测阳性,阳性率为90．62％,28例低侵袭组中19例HBeAg检测阳性,阳性率为67．86％,（P〈0．05）。结论：早期肝癌患者血清HBVDNA和HBeAg可作为肝细胞癌复发转移监测指标。     

老年肝癌患者肝癌切除术后早期肠内营养支持治疗的临床价值

目的探讨老年肝癌患者肝癌切除术后早期肠内营养支持治疗的临床价值。方法将接受肝癌切除术治疗的76例老年肝癌患者随机分为观察组（38例）与对照组（38例）,观察组患者术后早期接受肠内营养治疗,对照组患者术后接受肠外营养治疗。结果①手术前,2组患者总胆红素（TBIL）、丙氨酸氨基转移酶（AIJT）、白蛋白（ALB）、拟胆碱酯酶（PCHE）、前白蛋白（PA）相比差异无统计学意义（P〉0．05）。手术后第7天,观察组TBIL、ALT显著低于对照组,ALB、PCHE、PA显著高于对照组（P〈0．05）。②手术前,两组患者CD4＋T细胞、CD8＋T细胞、CD4＋T细胞／CD8＋T细胞比值相比,差异无统计学意义（P〉0．05）。手术后第7天,观察组上述指标显著高于对照组（P〈0．05）。③观察组术后肺部感染、胆瘘发生率显著低于对照组（P〈0．05）。结论术后早期肠内营养支持治疗可以显著改善老年肝癌患者肝癌切除术后的营养状况及免疫力,降低并发症发生率。     

HBV感染与肝细胞肝癌生物学行为及VEGF的表达关系

[目的]探讨原发性肝细胞肝癌（HCC）中乙型肝炎病毒（HBV）的感染与肝癌生物学行为及其新生血管表达的关系。[方法]利用血清学指标检测56例HCC的HBV感染情况，并采用快速免疫组化MaxVisionTM法检测56例HCC组织中VEGF和CD105的表达并计数微血管密度（CD105-MVD）。[结果]HBV感染与肝癌的Edmondson分级、AFP值增高、门静脉癌栓形成、肝内转移相关，有统计学意义（P〈0．05）。38例HBV感染型HCC中VEGF的表达率为78．9％（30／38）．CD105-MVD值为45．40±4．45，18例非HBV感染型HCC中VEGF的表达率为50．0％（9／18），CD105-MVD值为35．30±3．21，差异均有统计学意义（P〈0．05）。[结论]HBV感染可能通过上调VEGF的表达，促进了肿瘤血管的生成．从而促进HCC的生长、浸润和转移。     

B-myb C-myc在肝细胞性肝癌中的表达及临床意义

目的：检测肝细胞性肝癌（hepatocellular carcinoma，HCC）中B—myb及C—myc蛋白的表达情况，探讨其在肝癌发生、发展及转移中的作用。方法：采用免疫组化法检测60例肝癌组织及60例癌旁肝组织中B-myb和C-myc的表达情况，结果：B—myb、C—myc在癌组织中的阳性率分别为56．67％和53．33％，而在癌旁组织中的阳性率分别为36．67％和35．00％．癌组织与癌旁组织比较差异有显著性（P〈0.05）。B—myb在肝癌组织中的表达与临床分期、肝外转移、术后复发肿瘤个数及包膜完整相关（P均〈0．05）；C—myc在肝癌组织中的表达与门静脉癌栓、肝外转移、术后复发、肿瘤分化程度及包膜完整相关（P均〈0．05）。B—myb与C—myc在癌组织中的表达正相关。结论：B-myb及C—myc蛋白的过表达．可促使肝癌细胞增殖，使肝癌细胞具有更强的侵袭力，与肝癌的发生、发展密切相关。     

VEGF和MMP-2表达与肝细胞肝癌复发和预后的关系

目的：研究血管内皮生长因子（VEGF）和基质金属蛋白酶2（MMP-2）在肝细胞肝癌（HCC）中的表达与HCC复发转移的关系。方法：按是否复发将93例肝癌患者分为复发组与未复发组，采用免疫组化方法检测两组标本中VEGF及MMP-2的表达情况，分析两者的表达与临床病理指标的关系。结果：VEGF与MMP-2在93例HCC中的阳性表达率分别为52．69％与67．74％，复发组（44例）的阳性表达率分别为68．18％（30／44）、88．64％（39／44）；未复发组（49例）的阳性表达率分别为36．78％（19／49）、48．98％（24/49），两组之间差异具有统计学意义（P〈0．05）。生存分析显示术后两年生存率MMP-2（＋）与（-）组分别为41．42％、63．36％，差异具有统计学意义（P〈0．05）；VEGF（＋）与（-）两年生存率分别为48．50％、52．21％，差异不具有统计学意义（P〉0．05）。结论：MMP-2表达高的肝癌，转移复发率高，预后差。     

WFDC-1基因在原发性肝癌组织中的表达及其临床意义

目的检测WFDC-1基因在肝癌和正常肝组织的表达差异并探讨其临床意义。方法采用荧光实时定量PCR（FQ-RT-PCR）法检测30例肝癌组织及相应远端正常肝组织WFDC-1mRNA的表达,分析其表达与肝癌患者临床特征的相关性。结果 WFDC-1mRNA在肝癌组织中的表达水平（0.050±0.026）明显低于远端正常肝组织（0.113±0.040）,两者差别有统计学意义（P〈0.05）。WFDC-1mRNA在肝癌中的表达水平与HBsAg水平有关,合并HBsAg阳性的肝细胞癌（HCC）中的表达低于HBsAg阴性HCC组（P〈0.05）,而与年龄、性别、肿瘤大小、临床分期、AFP及有无肝硬化无关（P〉0.05）。结论肝癌组织中WFDC-1基因表达水平明显低于相应正常肝组织,提示WFDC-1表达与降低肿瘤发生有一定的相关性,为潜在的抑癌基因。     

弥漫大Ｂ细胞淋巴瘤携带乙型肝炎病毒患者的临床特点

目的　分析弥漫大Ｂ细胞淋巴瘤（ＤＬＢＣＬ）携带乙型肝炎病毒患者的临床特点和预后。方法　回顾性分析１２０例ＤＬＢＣＬ患者,均采用ＣＨＯＰ类方案化疗,分析ＨＢｓＡｇ阳性与阴性患者的临床特点及总生存期。结果　１２０例ＤＬＢＣＬ患者中ＨＢｓＡｇ阳性４１例（３４.１７％）,ＨＢｓＡｇ阴性７９例（６５.８３％）;ＨＢｓＡｇ阳性组中位年龄为４３岁,阴性组为５５岁,两组年龄差异有统计学意义（Ｐ＝０.００９）。ＨＢｓＡｇ阳性组化疗引起肝功能损害发生率为３５.９０％,阴性组为２５.３２％,两组差异无统计学意义。全组中位生存期为６８.５０个月,３年生存率为５５.２０％,其中ＨＢｓＡｇ阳性组３年生存率为４４.７０％,中位生存期为２９.８０个月;ＨＢｓＡｇ阴性组３年生存率为６１.００％,中位生存期未达到,两组差异无统计学意义（χ^２＝１.２９１,Ｐ＝０.２６5）。ＨＢｓＡｇ阳性ＤＬＢＣＬ患者伴与不伴肝功能损害对总生存无显著影响。结论　ＤＬＢＣＬ携带乙型肝炎病毒患者的发病年龄较轻,但在中位生存期、３年生存率和化疗相关肝功能损害方面与非乙型肝炎携带者无显著差异。     

非霍奇金淋巴瘤与乙型肝炎病毒感染的关系

 【摘要】 目的 探讨非霍奇金淋巴瘤（ NHL）与乙肝病毒（HBV）之间的关系。方法　统计393例NHL患者的乙型肝炎表面抗原（HBsAg）阳性率,并与同期住院的大肠癌患者和门诊健康体检者作比较。结果　NHL患者的HBsAg阳性率高于大肠癌患者和健康体检者,分别为26.5 %（104／393）、14.5 %（155／1070）和8.8 %（47／534）（χ2=55.713,P＜0.001）;HBsAg阳性NHL患者中位年龄较HBsAg阴性患者年轻（中位年龄47岁∶52岁,t = -1.911,P＝0.021）; HBsAg阳性者中以B细胞型居多,为80.8 %（84／104）,T细胞型为15.4 %（16／104）（ χ2=39.152,P＜0.001）;而性别、分期、B症状等无差别。B细胞型NHL的HBsAg阳性率明显高于大肠癌患者和健康体检者,分别为29.6 %（84／284）、15.5 %（155／1070）和8.8 %（47／534）（Wald统计量分别为25.174和55.139,P＜0.001）;而T细胞型NHL的HBsAg阳性率（16.7 %）与大肠癌患者和健康体检者的差异无统计学意义。结论　NHL与HBV感染存在相关性,尤其是B细胞型NHL。     

VEGFR-2、PDGFR-β和c-MET在肝细胞癌中的表达及预后分析

目的 探讨血管内皮生长因子受体2（VEGFR-2）、血小板衍生生长因子受体β（PDGFR-β）和c-MET在肝细胞癌（HCC）中表达的临床意义及对预后的影响。方法 应用免疫组织化学法检测93例HCC组织中VEGFR-2、PDGFR-β和c-MET的表达,分析其与临床病理特征和预后的关系。结果 VEGFR-2、PDGFR-β和c-MET在HCC组织中的高表达率分别为86.0％、19.4％和80.6％。VEGFR-2表达与性别、HBsAg状态、分化程度、肝硬化有关（P＜0.05）,PDGFR-β表达与AFP、肿瘤数目、肝硬化有关（P＜0.05）,c-MET表达与临床病理特征无关。Cox多因素回归分析显示,65例服用索拉非尼患者的无进展生存期（PFS）与年龄（P=0.047）有关,总生存期（OS）与HBsAg（P=0.037）、AFP（P=0.015）和肿瘤大小（P=0.003）有关;PDGFR-β表达水平与OS相关（P=0.046）,c-MET与PFS相关（P=0.01）。结论 VEGFR-2在HCC合并肝硬化的患者中存在高表达,PDGFR-β高表达是HCC的预后不良指标,c-MET可能是HCC患者服用索拉非尼疗效的一个预测指标。     

Prevalence of antibody against non-A, non-B hepatitis virus in Japanese patients with hepatocellular carcinoma

Antibodies against a possible causative agent of non-A, non-B hepatitis, hepatitis C virus (HCV), in Japanese patients with hepatocellular carcinoma were analyzed using the enzyme-linked immunosorbent assay (ELISA) system from Ortho Diagnostic Systems, Japan. Fifty of 58 cases of hepatitis B virus surface antigen (HBsAg)-negative hepatocellular carcinoma were positive for the antibody (86%) and 8 of 42 cases of HBsAg-positive hepatocellular carcinoma were positive (19%). Among patients with HBsAg-negative hepatocellular carcinoma, the prevalence of the antibody was greater among those who had received a blood transfusion (97%) than among those with no history of transfusion (70%). Only 3 of 54 patients with cancers other than hepatocellular carcinoma were found to be antibody-positive (5.6%) and all three patients had a history of blood transfusion. These results show a close relationship between the presence of anti-HCV antibody and HBsAg-negative hepatocellular carcinoma in Japan.     

Alpha 1-antitrypsin levels and phenotypes and hepatitis B serology in liver cancer

Serum levels of alpha 1-antitrypsin (alpha 1 AT) were measured by radial immunodiffusion and phenotypes were determined by electrofocusing in acrylamide gel in 39 patients with hepatocellular carcinoma (HCC) positive for serum hepatitis B surface antigen (HBsAg), 41 patients with HCC negative for serum HBsAg, and 160 age- and sex-matched hospital controls. There was no difference between the control series and either of the two HCC groups with respect to alpha 1 AT phenotype pattern; also, there was no evidence of association between HCC and either the M2 allele or any of the alpha 1 AT deficiency phenotypes. However, HCC cases negative for HBsAg had significantly higher serum alpha 1 AT values (mean 665 +/- 26 mg 100 ml-1) than HCC cases positive for HBsAg (mean 571 +/- 23 mg 100 ml-1), who in turn, had significantly higher alpha 1 AT values than hospital controls (mean 434 +/- 13 mg 100 ml-1). These results indicate that in Greece, as in other high HCC incidence countries, genetically determined alpha 1 AT deficiency is not aetiologically important; the increase of serum alpha 1 AT is an important correlate of HCC with possible aetiologic significance and diagnostic potential and HBsAg-positive HCC and HBsAg-negative HCC are manifest differently as well as being aetiologically distinct.     

Prevalence of Antibody against Non-A, non-B Hepatitis Virus in Japanese Patients with Hepatocellular Carcinoma

Antibodies against a possible causative agent of non-A, non-B hepatitis, hepatitis C virus (HCV), in Japanese patients with hepatocellular carcinoma were analyzed using the enzyme-linked immunosorbent assay (ELISA) system from Ortho Diagnostic Systems, Japan. Fifty of 58 cases of hepatitis B virus surface antigen (HBsAg)-negative hepatocellular carcinoma were positive for the antibody (86%) and 8 of 42 cases of HBsAg-positive hepatocellular carcinoma were positive (19%). Among patients with HBsAg-negative hepatocellular carcinoma, the prevalence of the antibody was greater among those who had received a blood transfusion (97%) than among those with no history of transfusion (70%). Only 3 of 54 patients with cancers other than hepatocellular carcinoma were found to be antibody-positive (5.6%) and all three patients had a history of blood transfusion. These results show a close relationship between the presence of anti-HCV antibody and HBsAg-negative hepatocellular carcinoma in Japan.     

Blood Transfusion, Alcohol Consumption, and Cigarette Smoking in Causation of Hepatocellular Carcinoma: A Case-Control Study in Fukuoka, Japan

In the present study, we investigated the association between hepatocellular carcinoma (HCC) and hepatitis B virus infection (HBV), blood transfusion and drinking and smoking habits by comparing 124 HCC cases and 250 controls. We confirmed a very high relative risk (RR), i.e. 31.0 ( P <0.001), among persons who were positive for serum hepatitis B surface antigen (HBsAg). However, the prevalence of serum HBsAg positives among our cases was only 21%, about half of those reported earlier, indicating a role of other etiological factors. Those who have a history of blood transfusion showed a significantly elevated RR of 3.0 ( P <0.001) or 4.9 ( P <0.001), and most of them (85%) were non-carriers of HBV. Thus, the past history of blood transfusion is an important risk factor among the Japanese. Unidentified non-A, non-B hepatitis viruses in transfused blood probably play a significant role in causing HCC. We estimated that 15% of male HCCs were attributable to blood transfusion. A positive relationship between alcohol consumption and HCC was detected, particularly among HBsAg-negative subjects with no history of blood transfusion who had drunk heavily in their younger years. RR estimates were not great (e.g., heavy drinkers: 2.5), but a substantial proportion of HCC may be attributed to drinking because of common drinking habits among Japanese males. Smoking was also found to have a positive association, but the relationship at a young age was less clear, and further investigation is needed to clarify the etiological role of smoking.     

Blood transfusion, alcohol consumption, and cigarette smoking in causation of hepatocellular carcinoma: a case-control study in Fukuoka, Japan

In the present study, we investigated the association between hepatocellular carcinoma (HCC) and hepatitis B virus infection (HBV), blood transfusion and drinking and smoking habits by comparing 124 HCC cases and 250 controls. We confirmed a very high relative risk (RR), i.e. 31.0 (P less than 0.001), among persons who were positive for serum hepatitis B surface antigen (HBsAg). However, the prevalence of serum HBsAg positives among our cases was only 21%, about half of those reported earlier, indicating a role of other etiological factors. Those who have a history of blood transfusion showed a significantly elevated RR of 3.0 (P less than 0.001) or 4.9 (P less than 0.001), and most of them (85%) were non-carriers of HBV. Thus, the past history of blood transfusion is an important risk factor among the Japanese. Unidentified non-A, non-B hepatitis viruses in transfused blood probably play a significant role in causing HCC. We estimated that 15% of male HCCs were attributable to blood transfusion. A positive relationship between alcohol consumption and HCC was detected, particularly among HBsAg-negative subjects with no history of blood transfusion who had drunk heavily in their younger years. RR estimates were not great (e.g., heavy drinkers: 2.5), but a substantial proportion of HCC may be attributed to drinking because of common drinking habits among Japanese males. Smoking was also found to have a positive association, but the relationship at a young age was less clear, and further investigation is needed to clarify the etiological role of smoking.