CHANGES OF SERUM ALPHA FETOPROTEIN BEFORE AND AFTER RADIOIMMUNOTHERAPY IN PATIENTS WITH HEPATOCELLULAR CARCINOMA

ＣＨＡＮＧＥＳＯＦＳＥＲＵＭＡＬＰＨＡＦＥＴＯＰＲＯＴＥＩＮＢＥＦＯＲＥＡＮＤＡＦＴＥＲＲＡＤＩＯＩＭＭＵＮＯＴＨＥＲＡＰＹＩＮＰＡＴＩＥＮＴＳＷＩＴＨＨＥＰＡＴＯＣＥＬＬＵＬＡＲＣＡＲＣＩＮＯＭＡＺｅｎｇＺｈａｏｃｈｏｎｇ;曾昭冲;ＴａｎｇＺｈａｏ...     

HEPATITIS B AND C VIRUSES AND THEIR INTERACTION IN THE PTHOGENESIS OF HEPATOCELLULAR CARCINOMA

王树林，张耀铮ＨＥＰＡＴＩＴＩＳＢＡＮＤＣＶＩＲＵＳＥＳＡＮＤＴＨＥＩＲＩＮＴＥＲＡＣＴＩＯＮＩＮＴＨＥＰＴＨＯＧＥＮＥＳＩＳＯＦＨＥＰＡＴＯＣＥＬＬＵＬＡＲＣＡＲＣＩＮＯＭＡ￥ＷａｎｇＳｈｕｌｉｎ；ＺｈａｎｇＹａｏｚｈｅｎｇ；（Ｄｅｐａｒｔｍｅｎｔ...     

RISK FACTORS FOR RECURRENCE IN PATIENTS WITH HEPATOCELLULAR CARCINOMA AFTER RADICAL RESECTION

ＲＩＳＫＦＡＣＴＯＲＳＦＯＲＲＥＣＵＲＲＥＮＣＥＩＮＰＡＴＩＥＮＴＳＷＩＴＨＨＥＰＡＴＯＣＥＬＬＵＬＡＲＣＡＲＣＩＮＯＭＡＡＦＴＥＲＲＡＤＩＣＡＬＲＥＳＥＣＴＩＯＮＺｈａｎｇＢｏｈｅｎｇ张博恒ＺｈｏｕＸｉｎｄａ周信达ＹｕＹｅｑｉｎ余业勤ＴａｎｇＺｈａ...     

PROMOTER HYPERMETHYLATION OF p16 GENE AND DAPK GENE IN SERA FROM HEPATOCELLULAR CARCINOMA （HCC） PATIENTS

Objective： To analyze the aberrant methylation of p16 gene and DAPK gene in sera from primary liver cancer patients ad to evaluate the clinical significance. Methods： A methylation-specific PCR was performed for the detection of promoter hypermethylation of p16 gene and DAPK gene in blood DNA from 64 cases of HCC patients, and to analyze the relation of the aberrant methylation of p16 gene and KAPK gene and the clinical pathological data. Results： 76.6%（49/64） of the sera from 64 cases of HCC patients showed hypermethylation for p16 promoter and 40.6% （26/64） for KAPK promoter, whereas no methylated p16 gene promoter and DAPK gene promoter were found in sera from benign liver diseases patients and normal control. Methylated p16 gene and KAPK gene promoters in sera did not strongly correlated with HBsAg, stage, metastasis and differentiation in HCC; but strongly correlated with AFP. Conclusion： Detection of the aberrant methylation of p16 gene and KAPK gene in blood DNA from HCC patients might offer an effective means for the earlier auxiliary diagnosis of the malignancy.     

THE EFFECT OF PHENYLACETATE ON THE EXPANSION AND CYTOTOXIC ACTIVITY OF ADHERENT LAK CELLS FROM PATIENTS WITH HEPATOCELLULAR CARCINOMA

Biotherapy of cancer, as the fourth modality of tumor treatment, has been accepted[1-3]. Adoptive transfer of LAK cells together with IL-2 have been found to be an effective immunotherapeutic modality for eradication of several tumors[4-6]. However, some reports indicated that clinical responses were infrequent and transient, and that severe toxicity was associated with the administration of high doses of rIL-2[6, 7]. Adherent-lymphokine activated killer (A-LAK) cells have significantly hi…     

EXPRESSION OF INSULIN-LIKE GROWTH FACTOR Ⅱ(IGF-Ⅱ)IN HUMAN HEPATOCELLULAR CARCINOMA AND LIVER CIRRHOSIS:ITS RELATIONSHIP WITH HEPATITIS B VIRUS X PROTEIN EXPRESSION

Sixty cases of hepatocellular carcinoma (HCC) and47 cases of liver cirrhosis (LC) were examined withimmunocytochemistry method using antibodies againstIGF-II and HBxAg on formalin-fixed, paraffin-embeddedtissue sections. 32 HCC and 37 LC were found to bepositive to HBxAg, in which the positive rates of IGF-IIwere 100% (32/32) and 94.6% (35/37) respectively. 28HCC and 10 LC were found to be HBxAg negative, IGF-IIwas positive in 23 HCC (83.1%) and 6 LC:(60%) Thepositive expression rates of IGF-II in HBxAg positivetissues were significanfly higher than those in HBxAgnegative tissues (P<0.05). There were three types ofdistribution of IGF-II expression in HCC and LC (1)perinucleus: (2) diffuse in cytoplasm; (3) inside nucleus.IGF-II was highly expressed in most of hyperplastic andneoplastic nodules hepatocytes and some of regenerationnodules. Small polygonal liver cells (SPLCs) were foundin the liver tissues surrounding the tumor and cirrhosisand they were positive to both IGF-II and HBxAg. Thepositive rates     

EXPRESSION OF FcγR AND REGULATION OF rIFNγ ON FcγR EXPRESSION ON PATIENTS WITH PRIMARY HEPATOCELLULAR CARCINOMA

The level of FcγR on peripheral blood mononuclear cells (PBMC) was determined by ABC-ELIsA in 43 patients with primary hepatocellular carcinoma (PHC) and in 8 patients with space-occupying benign lesion (BL) in liver, twelve patients who received carcinomaectomy were followed up to detect their FcγR.Nine PBMC samples from PHC were treated with rIFNγ-The results showed that: 1. the level of FcγR in PHC patients was significantly lower than that in BL and In normal control; 2. the expression of FcγR was enhanced in postoperated PHC patients; and 3. the production of IFNγ in PHC patients was defective. The level of FcγR on PBMC was increased obviously in PHC after PBMC being treated with rIFNγ but was still lower than that in control. These results suggested; (1) FcyR detection is helpful tor distinguishing malignant liver lesion from benign; (2) the inhibited expression of FcγR in PHC could be related to some factors secreted by cancer tissues and also to low level of IFNγ; and (3) IFNγstimulat     

THE EXPRESSIONS OF HBV X GENE AND ets-2, IGF-Ⅰ, c-myc AND N-ras ONCOGENES IN HUMAN HEPATOCELLULAR CARCINOMA AND TUMOR-ADJACENT TISSUES

The expressions of HBV X gene and ets-2, IGF-I, c-myc and N-ras were studied in 7 pairs of human primary hepatocellular carcinoma (PHC) and tumor-adjacent tissues, using RNA hybridization and im-munoblot methods. The results showed that specific 17 and 28 kD HBV X gene products (HBxAg) were existed in a portion of PHC and tumor-adjacent tissues. The 17 kD HBxAg was detected in the sera of 3 patients who also had 17 kD HBxAg in their liver tissues. Multiple expressions of oncogenes such as ets-2, c-myc and N-ras were observed in PHC and tumor-adjacent tissues that had HBxAg expressed, indicating HBxAg might function as a transactivator in the course of intracellular proto-oncogene activation. It is also observed that in some tumor-adjacnet tissues the expressions of ets-2, c-myc and N-ras were higher than those in corresponding PHC. The relationship of HBxAg to the expression of est-2, IGF-Ⅱ, c-myc and their possible roles in the carcinogenesis of PHC are discussed.     

DETECTION OF OCCULT TUMOR CELLS IN RESECTED LYMPH NODES OF PATIENTS WITH STAGE I CARCINOMA AND ITS CLINICOPATHOLOGICAL SIGNIFICANCE

ＤＥＴＥＣＴＩＯＮＯＦＯＣＣＵＬＴＴＵＭＯＲＣＥＬＬＳＩＮＲＥＳＥＣＴＥＤＬＹＭＰＨＮＯＤＥＳＯＦＰＡＴＩＥＮＴＳＷＩＴＨＳＴＡＧＥＩＣＡＲＣＩＮＯＭＡＡＮＤＩＴＳＣＬＩＮＩＣＯＰＡＴＨＯＬＯＧＩＣＡＬＳＩＧＮＩＦＩＣＡＮＣＥＣｈｅｎＺｈａｏｌｕｎ...     

X-RAY REPAIR CROSS-COMPLEMENTING GROUP 1 （XRCC1） Arg 399 Gin POLYMORPHISM AND AFLATOXIN B1 （AFB1）-RELATED HEPATOCELLULAR CARCINOMA （HCC） IN GUANGXI POPULATION

In Guangxi Zhuang Autonomous Region,Hepatocellular carcinoma(HCC)is one of the maincancer killers,the incidence rate of which is5～40/1,000,000per year.Clinic-epidemiological evidencesuggests AFB1exposure is the most cause[1].However,the exact mechanisms of AFB1hepatocarcinogenesishave not been fully elucidated.Recently,there is agrowing realization that genetic constitution is ofimportance in determining individual’s susceptibility toHCC.This genetic susceptibility may result frominhe…     

广西抗－HCV阴性肝癌病人血清及肝癌组织丙型肝炎病毒核酸检测

１９９２年曾用Ａｂｂｏｔｔ公司第二代酶免疫试剂盒检测１８６例广西肝癌病人抗－ＨＣＶ抗体，结果阳性率仅５．４％，但抗－ＨＣＶ阴性并不能排除丙型肝炎病毒感染，为了更确切地了解广西肝癌病人中的丙肝病毒感染状况，本研究用聚合酶链反应技术（ＰＣＲ）对５９例抗－ＨＣＶ阴性肝癌病人血清及１７例石蜡包埋肝癌组织进行了丙肝病毒核酸（ＨＣＶＲＮＡ）检测，结果５９例血清中检出ＨＣＶＲＮＡ阳性６例（１０．２％）．但１７例肝癌组织中无１例检出ＨＣＶＲＮＡ。又用ＰＣＲ方法检测这１７例肝癌组织之ＨＢＶＤＮＡ，结果７例显示阳性。以上结果表明，抗－ＨＶＶ加检ＨＶＶＲＮＡ可以提高丙肝病毒感染的检出率。尽管如此，与其他国家和地区相比，广西肝癌中总的丙肝病毒感染率（估计为１５．０％）仍然是较低的。     

Viral hepatitis (HBV and HCV) background in Chinese patients with hepatocellular carcinoma

Antibody to hepatitis C virus (Anti-HCV) was detected using anti-HCV EIA (Abbott Kit) in the sera of Chinese patients with hepatocellular carcinoma (HCC), acute hepatitis, chronic hepatitis and blood donors, the positive rates being 10.4% (61/586), 11.8% (10/85), 19.2% (44/229), and 1.9% (3/160) respectively. HBV DNA was detected by polymerase chain reaction (PCR) in sera from 61 HCC patients with positive anti-HCV, the positive rate for HBV DNA being 55.7% (34/61), which was lower than those with negative anti-HCV (78.7%, 413/525). These results indicate that in China the role of HBV infection in the causation of HCC seems to be more important than that of HCV infection. This paper is one of the symposium papers on primary liver cancer research (Chin J Cancer Res 6(1), 1994)     

存档肝癌、肝硬化蜡块组织中HCV－RNA的检出

以逆转录——巢式聚合酶链反应检测５６例肝细胞癌（ＨＣＣ）和１４例肝硬变（ＬＣ）福尔马林固定、石蜡包埋肝组织中的丙型肝炎病毒（ＨＣＶ）ＲＮＡ，并与其中２７例ＨＣＣ病人的血清ＨＣＡＲＮＡ进行比较。发现在组织与血清配对的２７例ＨＣＣ中，有２２例组织与血清检出结果完全一致ＨＣＶＲＮＡ在５６例ＨＣＣ中共检出２１例（３７．５％），在１４例ＬＣ中检出４例（２８．６％）。表明这种存档组织用于ＨＣＶ感染的回顾性研究是可行的，提示ＨＣＶ感染在ＨＣＣ发生中可能起着重要作用。     

广州地区肝细胞癌与HCV,HBV感染关系的病例对照研究

在肝细胞癌（ＨＣＣ）中度流行区广州地区，对６４例ＨＣＣ患者抗－ＨＣＶ和ＨＢｓＡｇ状况按性别、年龄配对和１：２数量比设对照组进行了病例对照研究。结果表明：ＨＣＣ组抗－ＨＣＶ和ＨＢｓＡｇ阳性率分别为１８．７５％（１２／６４）和８４．３８％（５４／６４），分别显著高于对照组的２．３４％（３／１２８，Ｐ＜０．００１）和１４．０６％（１８／１２８，Ｐ＜０．００１）。与抗－ＨＣＶ、ＨＢｓＡｇ双阴性组比较，仅抗－ＨＣＶ阳性，仅ＨＢｓＡｇ阳性时发生ＨＣＣ的相对危险度分别为４６．７１和４３．７９，二者双阳性时上升至７０．０７。显示ＨＣＶ、ＨＢＶ均与ＨＣＣ显著相关，两者重叠感染具有协同致癌作用。作者提出预防和控制ＨＢＶ、ＨＣＶ感染对降低ＨＣＣ发病率意义重大。     

肝硬变和肝癌组织内HCV RNA及HBV X基因的存在及意义

采用原位分子杂交对７９例肝硬变及６４例肝细胞癌组织进行ＨＣＶ ＲＮＡ和ＨＢＶ Ｘ基因定位检测，ＨＣＶ ＲＮＡ，ＨＶＢ Ｘ基因在两种组织的阳性率分别是４８％及７２％；３９％，及８１％；二者同时阳性在两种组织分别为３８％及３３％。ＨＣＶ ＲＮＡ主要定位于肝细胞和癌细胞胞浆内，阳性细胞呈散在、灶状及弥漫分布三种形式。ＨＢＶ Ｘ基因在肝细胞及肝癌细胞中的分布呈胞浆型、核型及核浆型，阳性细胞也呈上述三种分布     

HCV感染对肝癌一些癌相关基因产物表达的影响

目的 研究丙型肝炎病毒（ＨＣＶ）的致癌机理。方法 以免疫组化ＡＢＣ法对４６例肝细胞癌（ＨＣＣ）及其癌旁肝组织的ＨＣＶＣＰ１０、ＮＳ３及ＮＳ５抗原和rasp２１、c-myc、c-erbB-2、突变型p５３及p１６蛋白进行染色,并将ＨＣＣ分为ＨＣＶ抗原阳性组和ＨＣＶ抗原阴性组,对比分析ＨＣＶ感染对上述癌相关基因蛋白产物表达的影响。结果 ４６例ＨＣＣ患者中,１～３种ＨＣＶ抗原性２０例（４３．５％）,２～３种ＨＣＶ抗原阳性     

肝癌高发区抗-HBc阳性慢性乙肝患者HBVDNA血清学分析

目的：了解启东肝癌高发区抗－HBc阳性慢性乙肝患者HDVDNA分布 情况。方法：采用ELISA法筛选慢性乙肝患者中抗－HBc阳性者，再用聚合酶链反应（PCR）检测这些血清中的HBVDNA。结果：HBVDNA总检出率为75．24％（158／210）。抗－HBc与HBsAg、HBeAg同在时HBVDNA阳性率最高，达97．26％（71／73），显著高于其它模式（P＜0．005）。抗－HBc/HBsAg阳性血清中HBVDNA检出率为81．08％（150／185），单纯抗HBc/HBsAg阳性血清中HBVDNA检出率为80．77％（42／52），单纯抗－HBc阳性血清中检出率为20％（1／5）。结论：抗－HBc是乙肝病毒感染的一个直接标志。判断患者的传染性应通过免疫学和基因学两种方法来检测。启东慢性乙肝患者中HBVDNA整合现象可能要高于其它地区，这或许是启东肝癌高发的机制之一，值得进一步研究。基因学和免疫学方法检测乙肝病毒感染情况各有利弊，应互补共存。     

启东地区鸭肝癌中人HBV变异体蛋白产物的表达

本文分析了启东鸭肝癌组织中人ＨＢＶ变异体的蛋白产物，用ＷｅｓｔｅｒｎＢｌｏｔ方法检测１２例启东鸭肝癌组织中人ＨＢｓＡｇ，ＨＢｃＡｇ的表达。９例标本检测到３５ｋｄ和（或）大于３５ｋｄ的ＨＢｓＡｇ。７例标本出现２４ｋｄ的ＨＢｃＡｇ。９例标本有ＨＢｘＡｇ的表达。其其分子量为１２ｋｄ和（或）２５ｋｄ。本文同时也分析了ＤＨＢＶ基因产物ＤＨＢｓＡｇ．７例鸭肝癌标本检测ＤＨＢｓＡｇ，４例阳性，分子量为４０ｋｄ。     

应用原位PCR法检测肝癌组织中的HBV DNA

目的 探讨乙型肝为病毒（ＨＢＶ）与肝细胞癌（ＨＣＣ）的关系。方法 采用直接原位聚合酶链反应（ｉｎｓｉｔｕＰＣＲ，ＩＳＰＣＲ）对６４例福尔马林固定石蜡包埋的ＨＣＣ组织（其中６１例附癌周组织）切片中的ＨＢＶＤＮＡ进行检测，与并传统的免疫组织化学原位杂交和组织抽提酸ＰＣＲ法进行了比较。结果 ＩＳＰＣＲ对石蜡包埋的ＨＣＣ组织中ＨＢＶＤＮＡ检测高度敏感，检出率为７１．９％（４６／６４），而相应组织应用免疫组     

The Therapeutic Effect of Myrrh (Commiphora molmol) and Doxorubicin on Diethylnitrosamine Induced Hepatocarcinogenesis in Male Albino Rats

Background: This study was conducted to assess the therapeutic effect of Myrrh on Diethylnitrosamine (DEN)-induced hepatocarcinogenesis (HCC) in male albino rats. Methods: Fifty male albino rats were divided into five groups (10 rats each).  Group 1 (control group) received distilled water. Group 2 (positive control) was injected intraperitoneally with DEN (55 mg/kg b.w) twice a week for two weeks, while group 3 (DOX) received doxorubicin i.p (10 mg/ kg b.w) after concomitant with DEN twice a week for four weeks.  Groups 4 and 5 received a low dose of Myrrh (250 mg/kg b.w) and a high dose of Myrrh (500 mg/kg b.w) respectively daily for four weeks after the induction with DEN. The sera were used to estimate the liver enzymes (ALT, AST, and ALP), Alpha-fetoprotein (AFP), Total antioxidant capacity (TAC), and Tumor necrosis factor-ἁ (TNF-ἁ). Also, the liver tissues were collected to determine the oxidative stress markers in addition to the histopathological and immunohistochemical investigations. Results: The results showed that the induction of DEN causes a significant increase in the level of liver enzymes (ALT, AST, and ALP), AFP and TNF-ἁ as well as produce oxidative stress indicated by increasing of malondialdehyde (MDA) with the reduction in TAC and glutathione (GSH). Meanwhile, there are noticeable histopathological lesions with loss of hepatic architecture. This was accompanied by a significant increase of immunohistochemical markers; Caspase-3, vascular endothelial growth factor (VEGF), transforming growth factor β1(TGF- β1), and carcinoembryonic antigen (CEA) percentage area. The treatment of DEN rats with DOX reduced the alterations in most parameters. A marked amelioration of all parameters in a dose-dependent manner of Myrrh to the values almost near to those of the control group. Conclusion: Our data revealed that Water extract of Myrrh (C. molmol) has a potential therapeutic effect in attenuation of HCC induced DEN.