七种癌-睾丸抗原基因在广西肝细胞癌中的表达

广西是肝细胞癌(Hepatocellular carcinoma，HCC)的高发区，其死亡率极高。尽管目前已建立了许多治疗的方法，但五年的生存率仍很低。因此急需寻求新的治疗方法，而免疫治疗正是其中新方法之一，但开展免疫治疗的前提是特异性肿瘤抗原的存在。目前己发现了众多的肿瘤相关抗原，其中一类为癌-睾丸抗原(Cancer-Testis Antigen，CTA)，     

NY-ESO-1和LAGE-1癌症-睾丸抗原在肝细胞癌的表达

目的　检测NY- ESO -1和LAGE- 1癌症睾丸抗原在肝细胞癌中的表达,探讨其作为肝细胞癌免疫治疗靶标的可行性及其与肝癌生物学行为的关系。方法　逆转录聚合酶链反应(RT -PCR)和免疫组织化学EnVision二步法检测30例肝细胞癌新鲜标本NY ESO -1和LAGE -1的表达;另将191例肝癌石蜡组织制成芯片观察NY- ESO- 1蛋白在肝癌中的分布和表达。结果NY- ESO -1和LAGE -1基因mRNA在肝癌中的阳性表达率分别是33. 3% (10 /30)和16. 7% (5 /30),至少表达1种基因mRNA者为36 7% (11 /30);NY- ESO -1蛋白主要分布在肝癌细胞胞质,有效标本中NY ESO 1表达13 8% (24 /174),小肝癌、中晚期肝癌、发生转移肝癌中的阳性表达率逐渐升高,分别为6 8% (3 /44)、16 2% (21 /130)、23 1% (12 /52),不发生转移的肝癌仅为9 8% ( 12 /122 ),其中转移组与无转移组之间比较差异有统计学意义(P<0 .05),全部病例癌组织与癌旁组织比较差异有统计学意义(P<0 .01)。NY- ESO-1蛋白的阳性表达与肿瘤大小无关,所有癌旁肝组织均未见NY -ESO -1和LAGE -1的mRNA和蛋白的表达。结论　NY -ESO- 1 /LAGE- 1在肝细胞癌组织中的特异性表达提示其可作为肝细胞癌特异性免疫治疗潜在的靶标;NY -ESO -1在肝癌早期出现,随病情进展表达率逐步增高,转移患者最高,提示N     

癌-睾丸抗原GAGE与肿瘤

肿瘤是严重威胁人类健康的疾病之一, 其诊断和治疗一直是人们关注的焦点.近年来, 肿瘤的发病率和死亡率呈明显上升趋势, 传统的治疗方法仍存在各种问题, 故寻找新的诊疗手段已势在必行.目前, 肿瘤免疫治疗已经成为该研究领域的热点之一.     

癌-睾丸抗原基因在神经胶质瘤干细胞中的表达

背景：癌-睾丸抗原基因在胶质瘤干细胞表达还不甚清楚。 目的：检测癌-睾丸抗原基因在神经胶质瘤干细胞中的表达。 方法：通过神经球培养的方法而分离干细胞。以半定量PCR及实时荧光定量PCR检测癌-睾丸抗原基因在母细胞、干细胞与分化细胞中的表达。 结果与结论：以神经球培养方式从胶质瘤细胞系中可分离出肿瘤球,将肿瘤球培养在含血清的培养基中,它的形态呈贴壁分化,且与母细胞没有区别。半定量PCR及实时荧光定量PCR检测发现与母细胞和分化细胞相比,癌-睾丸抗原基因在干细胞中的表达最高。提示癌-睾丸抗原基因可能为肿瘤干细胞的表面抗原。     

癌/睾丸抗原基因研究进展

癌/睾丸抗原(Cancer/Testis Antigen,CTA)基因在正常睾丸组织的生殖细胞和多种不同组织类型的癌细胞中特异表达,在其它正常组织不表达或表达水平较低,并且在癌症患者中有抗原性免疫反应,认为是一类理想的肿瘤疫苗靶分子.现已发现90个癌/睾丸抗原基因,分属于45个基因家族.本文综述了CTA基因的特性及其应用基础研究进展.     

癌/睾丸抗原胎盘特异性蛋白1在肿瘤中的研究进展

胎盘特异性蛋白1(placenta specific protein 1,PLAC1)属于癌/睾丸抗原(cancer/testis antigen,CTA),限制性表达于胎盘组织、睾丸及部分肿瘤中.PLAC1高表达于多种实体肿瘤如乳腺癌、结直肠癌与肺癌等,且与肿瘤细胞的增殖、侵袭、转移以及较差的临床预后相关.其促肿瘤机...     

鳞状细胞癌抗原及其在肿瘤诊断中的应用

鳞状细胞癌抗原(squamous cell carcinoma antigen, SCC Ag)最初于1977年从宫颈鳞癌组织中分离得到,并命名为TA-4,它是一组肿瘤相关蛋白,其血清水平检测广泛应用于多种鳞癌的诊断和管理.     

癌-睾丸抗原SSX-2抗原肽的鉴定及功能分析

SSX基因又称滑膜肉瘤X断裂点基因（Synovial Sarcoma Xbreakpoint，SSX），是个多成员的基因家族，其中一些成员编码的产物被认为是癌-睾丸抗原（Cancer-Testis Antigen，CTA）。CTA是一类可在多种肿瘤组织中表达，而在睾丸以外的其它正常组织中几乎不表达的抗原。因此，CTA非常适用于肿瘤免疫治疗。目前对SSX基因家族中的SSX-2抗原的研究显示，SSX-2抗原分子作为肿瘤免疫治疗的靶物质有着潜在的应用前景。现将其研究进展综述如下。     

肝细胞癌抗原587基因甲基化调节HCA587-TAF9互作介导肝细胞癌的侵袭和迁移

目的：研究肝细胞癌抗原587（HCA587）在肝细胞癌（HCC）组织中的表达和启动子区甲基化状态,探 讨HCA587对肝细胞癌细胞迁移和侵袭的调节机制。方法：纳入肝细胞癌肿瘤组织114 例,分为HCC组和癌旁 非癌组织（NT）组。荧光定量PCR 检测HCA587的mRNA表达量;免疫组织化学和免疫印迹检测HCC组和NT 组组织中HCA587的蛋白表达。基于甲基化敏感酶和甲基化依赖酶酶切,并结合荧光定量PCR 方法分析肝细胞 癌组织中HCA587基因启动子区甲基化状态。构建重组HCA587过表达质粒（pcDNA3.1-HCA587）,培养人肝 细胞癌细胞系BEL-7404,转染pcDNA3.1-HCA587 或者使用甲基化抑制剂5-Azacytidin 处理细胞。细胞分为对照 组、5-Azacytidin 组、pcDNA3.1-HCA587 组和pcDNA3.1-HCA587 空载体（EV） 组。免疫沉淀法分析HCA587 与TATA 盒结合蛋白相关因子9（TAF9）的结合,Transwell 小室检测细胞的迁移和侵袭能力。结果： 与癌旁非 癌组织组比,HCC组的HCA587在mRNA和蛋白水平均上调。免疫组织化学证实HCC组组织中HCA587阳性表 达。HCC组中HCA587的启动子区CpG 岛甲基化水平降低。体外实验结果显示,5-Azacytidin 促进BEL-7404 中 HCA587的表达、HCA587与TAF9的结合、BEL-7404 细胞的迁移和侵袭能力,但抑制HCA587甲基化水平;另外, HCA587过表达增强BEL-7404 细胞的迁移和侵袭能力。结论：HCA587高表达或抑制其启动子区甲基化可以促进 HCA587与TAF9的结合及导致肝细胞癌细胞的迁移和侵袭。     

肝细胞癌肿瘤抑制基因的杂合性缺失和微卫星不稳定性研究

目的　了解肿瘤抑制基因(TSG)杂合性缺失(LOH)与微卫星不稳定性(MSI)在肝细胞癌发生机制中的作用,并探讨其临床病理学意义。方法　采用显微组织切割基础上的DNA直接测序法,从92例手术切除肝细胞癌中筛选出36例信息性肝细胞癌进行6种TSG(APC、DCC、MCC、OGG1、p53和RB1)的LOH检测,对其中15例肝细胞癌进行13个多态性微卫星位点的LOH和MSI检测,并与临床病理学参数的相关性进行统计学分析。结果　TSG的LOH总发生率为41 .7% (15 /36),仅MCC基因未出现LOH。15例肝细胞癌中有9例(60% )发生微卫星LOH,占检测微卫星的46 .2% (6 /13),但无1例肝细胞癌出现MSI。若将APC、OGG1和DCC基因LOH作为Ⅰ型(n=7 ),将p53和RB1基因LOH作为Ⅱ型(n=8)进行统计学处理,则两组肝细胞癌的平均瘤体直径分别为( 2. 9 ±1 .7)cm和(7 .2 ±3 .4)cm (P<0 .01),两组患者术后平均生存期分别为( 72. 0 ±38 6 )个月和(51 .0±30. 4)个月(P<0 .05 )。肝细胞癌基因变异型与患者的年龄、性别、血清甲胎蛋白水平、HBsAg阳性率、合并肝炎/肝硬化、肝细胞癌分化程度和组织学类型之间无明显相关性。结论　在肝细胞癌发生的多阶段演进与多基因变异过程中,LOH路径所起的作用要比MSI路径更大。Ⅰ型基因变异(APC、OGG1和DCC)主要在肝细胞癌早期阶段起作     

Current approaches to the diagnosis and management of hepatocellular carcinoma

Abstract Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide, and incidence rates in Western countries are on the rise. Despite many options, no ideal treatment yet exists for this highly malignant tumour, and management strategies have varied accordingly. This review summarises current strategies for the diagnosis and management of HCC.     

Hepatitis B surface antigen and hepatocellular carcinoma in Southern Africa

Summary Most series in Africa show a high percentage of hepatitis B surface Hepatitis antigen in hepatocellular carcinoma. Two groups of cases were investigated in this study. The one was derived from the autopsy material at Baragwanath hospital from subjects who had lived in Soweto, a large Black urban town. The second group consisted of male Black mineworkers generally originating from rural areas. A combination of the aldehydefuchsin stain and immunoperoxidase technique was used. The two groups showed totally different results. The Baragwanath series consisted of 24 hepatocellular carcinomas of which only 4 (17%) were HBsAg positive. Of the 24 cases, 14 had cirrhosis of which 9 were macronodular and 5 micronodular. Ten of these cases showed heavy iron overload. The series of male Black mineworkers comprised 22 cases of which 16 (72%) were HBsAg positive. Twelve of the 22 cases showed a macronodular cirrhosis and there were no micronodular cirrhoses. Only one case showed severe iron overload. These findings delineate two different populations of hepatocellular carcinoma in Southern Africa.     

Changes of guidelines diagnosing hepatocellular carcinoma during the last ten-year period

Hepatocellular carcinoma (HCC) is the third most common cause of cancer deaths in the world. There have been many advances in the diagnosis of HCC during the last ten years, especially in the imaging techniques. The Korean Liver cancer study group (KLCSG), European Association for the Study of the Liver (EASL), American Association for the Study of Liver disease (AASLD), and Asian-Pacific Association for the Study of Liver (APASL) have made and changed the HCC guidelines with the advances in the imaging techniques and according to the results of the researches on HCC. We reviewed the changes of the imaging guidelines in HCC diagnosis according to the advances in the imaging techniques. Further studies will be necessary to resolve the controversies in the diagnosis of HCC smaller than 1 cm in size.     

Carcinoembryonic antigen and lectin binding in the bile canalicular structures of hepatocellular carcinoma

Summary Bile canalicular structures of 32 hepatocellular carcinomas and 36 cirrhotic livers were investigated by light microscopy using immunohistochemistry for carcinoembryonic antigen (CEA) and lectin histochemistry. CEA positive bile canalicular structures were found in 17 out of 32(53%) hepatocellular carcinomas and in 33 of 36(92%) cirrhotic livers. Among the 10 lectins examined, about 40% of the CEA positive bile canalicular structures of hepatocellular carcinomas showed positive binding of MPA, DBA, WGA, RCA-I or UEA-I, whereas only MPA or RCA-I bound to the CEA positive bile canalicular structures of cirrhotic liver, in about 20% of cases. It has been shown that the CEA positive bile canalicular structures of hepatocellular carcinomas are heterogeneous and differ from those of cirrhotic liver in lectin histochemistry.Presented at the XVI International Congreess of International Academy of Pathology (Rikuo Machinami 1986)     

Histone-modifying genes as biomarkers in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the world’s fifth most common cancer and second leading cause of cancer-related death in Taiwan. Over 600,000 HCC patients die each year worldwide despite recent advances in surgical techniques and medical treatments. Epigenetic regulations including DNA methylation and histone modification control gene expressions and play important roles during tumorigenesis. This study evaluates association between histone-modifying genes and prognosis of HCC to ferret out new diagnostic markers. We collected 50 paired HCC and adjacent non-cancerous tissues from Taiwanese patients for survey by RT-qPCR and tissue microarray-based immunohistochemistry (TMA-based IHC) staining. RT-qPCR data showed four of twenty-four genes over eightfold up-regulated in tumor tissues: e.g., histone phosphorylation gene-ARK2, methylation genes-G9a, SUV39H2, and EZH2 (n = 50, all p < 0.0001). Results of TMA-based IHC staining showed proteins of ARK2, EZH2, G9a, and SUV39H2 also overexpressed in tumor tissues. Staining intensity of SUV39H2 correlated with HCV infection (p = 0.025). We further restricted the analysis only in tumor tissues, we found EZH2 staining intensity associated with tumor stage (p = 0.016) and survival (p = 0.007); SUV39H2 intensity associated with tumor stage (p = 0.044). Our findings indicate overexpression of histone-modifying genes EZH2 and SUV39H2 associated with prognosis of HCC cases. EZH2 expression can serve as a novel prognostic biomarker during HCC progression among Taiwanese.     

Clinical and epidemiological aspects of hepatocellular carcinoma in Brazil

OBJECTIVES:

We performed a national survey to update hepatocellular carcinoma (HCC) epidemiology in Brazil and determined the clinical and epidemiological profiles of patients with HCC in different Brazilian regions.

METHODS:

Data from 29 centers included 1,405 patients diagnosed with HCC from 2004 to 2009.

RESULTS:

The median age was 59 (1–92 years old; 78% male). At diagnosis, females were older than males (median age: 62 vs. 59 years old respectively; p<0.0001). Ninety‐eight percent of the patients had cirrhosis (1279/1308). Hepatitis C virus was the main etiology (54%), followed by hepatitis B virus (16%) and alcohol (14%). In Southeastern and Southern Brazil, hepatitis C virus accounted for over 55% of cases. In the Northeast and North, hepatitis C virus accounted for less than 50%, and hepatitis B virus accounted for 22–25% of cases; hepatitis B was more prevalent in the Northern than in the Southern regions. Some 43%, 35%, and 22% of patients were in early, intermediate, and advanced stages respectively. Initial therapies for HCC included chemoembolization or embolization (36%), percutaneous ablation (13%), liver resection (7%), and sorafenib (1%). Liver transplantation was performed in 242 patients (19%), but it was the initial therapy for only 56 patients (4%).

CONCLUSION:

The epidemiology, classification, and therapy selection for HCC varied among Brazilian regions. Hepatitis C infection was the most common etiology of liver cirrhosis; chemoembolization was the most common therapy employed. Liver cirrhosis was the main risk factor for HCC development in Brazil.     

基于癌症基因图集数据库与免疫组织化学方法分析SMARCB1对肝细胞癌早期诊断及预后的作用

目的:通过研究SMARCB1在肝细胞癌(hepatocellular carcinoma,HCC)组织的表达,阐明其对HCC的早期诊断及预后的作用。方法:在癌症基因组图集(The Cancer Genome Atlas,TCGA)数据库中筛选出SMARCB1基因,运用免疫组织化学(immunohistochemistry,IHC)技术和TCGA分析SMARCB1在HCC组织和正常组织的表达情况,阐述其在HCC发生、发展进程中的作用。结果:IHC结果证实,与正常肝组织相比,HCC中SMARCB1的蛋白表达量显著上升(P0.01)。IHC的结果显示SMARCB1的蛋白表达量与原发肿瘤分期呈正相关(P0.05),即SMARCB1表达量越高,原发肿瘤分期越趋向晚期。TCGA的结果显示SMARCB1的高表达是HCC的独立预后因素(P0.05)。结论:SMARCB1可能起着促癌基因的作用,临床上根据其在组织中的表达差异,可鉴别早期的HCC及良性组织,并可能有效地进行预后判断。     

HLA-DR抗原在慢性乙型肝炎和肝细胞癌中的表达及其意义

目的　探讨HLA DR抗原在慢性乙型肝炎和肝细胞癌 (HCC)中的表达及其意义。方法采用免疫组化技术对 2 0例正常肝组织、36例慢性乙型肝炎和 44例HCC中HLA DR抗原的表达进行检测。结果　正常肝组织中肝细胞未见HLA DR抗原表达。慢性乙型肝炎肝细胞HLA DR抗原表达阳性率为 2 7.8% ,其中 ,中度和重度肝炎HLA DR抗原阳性率明显高于轻度肝炎 (阳性率分别为 37.5 %和 2 0 % ,χ2 =13.6 ,P <0 .0 1)。HCC中肿瘤细胞HLA DR抗原表达阳性率为 43.2 %。HLA DR抗原表达与癌周淋巴细胞浸润 (χ2 =0 .5 1,P >0 .0 5 )和转移 (χ2 =2 .9,P >0 .0 5 )无关 ,但与癌组织分化程度有关 (χ2 =4.9,P <0 .0 5 )。结论　HLA DR抗原的异常表达在慢性乙型肝炎免疫损伤、免疫保护和HCC发生、发展中起重要作用