DISTRIBUTION PATTERNS OF EXTRACELLULAR MATRICES IN HEPATOCELLULAR CARCINOMA AND THEIR CLINICAL SIGNIFICANCE

Extracellular matrix (ECM) including collagen, matrix glycoprotein and proteoglycans is now believed to be not only supportive structure, but also metabolic components of tisues. Moreover, it has also been proved that ECM is closely related to tumor growth, invasion and metastasis.[1-5] There have been some studies linking ECM and hepatocellular caricnoma (HCC) in the literature,[6,7] but in China still few.[8] In order to study the distribution patterns of ECM in HCC, 40 cases of HCC…     

EXPRESSION OF PRE-S_1 AND PRE-S_2 ANTIGENS OF HEPATITIS B VIRUS AND THEIR SIGNIFICANCE IN HUMAN PRIMARY HEPATIC CARCINOMA

The specimens of 135 cases of primary hepatic carcinoma were obtained from the Pathological Laboratory of the First Affiliated Hospital of the Fourth Military Medical University, Xi' an, PRC. Ten percent formalin-fixed and paraffin- embedded sections were stained by HE and by ABC and PAP immunohistochemical methods. Positive rates of pre- S1 and pre- S2 antigens in cancerous tissue were 22. 2% and 20. 0%, respectively, while those in surrounding hepatic tissue were 60.6% and 59.6%, separately. The pre- S1 and pre- S2 antigens were found to coexist In 16. 3% of cancerous tissue and in 55. 6% of surrounding hepatic tissue. In all the 135 cases of hepatic carcinoma, the cancerous tissue showed positive HBsAg in 16. 3%, HBxAg in 55. 6% and HBcAg in 8. 9%; in the surrounding hepatic tissue, positive HBsAg was 59.6%, HBxAg 78.8% and HBcAg 24.2%. The results of this study suggestes that positive rates of pre- S1 and pre-S2 antigens in cancerous tissue were slightly higher than that of HBsAg, but markedly lower     

THE ROLE OF TARGETING THERAPY IN CYTOREDUCTION AND SEQUENTIAL RESECTION OF UNRESECTABLE HEPATOCELLULAR CARCINOMA

ＴＨＥＲＯＬＥＯＦＴＡＲＧＥＴＩＮＧＴＨＥＲＡＰＹＩＮＣＹＴＯＲＥＤＵＣＴＩＯＮＡＮＤＳＥＱＵＥＮＴＩＡＬＲＥＳＥＣＴＩＯＮＯＦＵＮＲＥＳＥＣＴＡＢＬＥＨＥＰＡＴＯＣＥＬＬＵＬＡＲＣＡＲＣＩＮＯＭＡＴａｎｇＺｈａｏｙｏｕ汤钊猷ＹｕＹｅｑｉｎ余业勤Ｚｈ...     

THE EXPRESSION OF CYTOKERATINS IN HUMAN HEPATOCELLULAR AND CHOLANGIOCELLULAR CARCINOMAS

ＴＨＥＥＸＰＲＥＳＳＩＯＮＯＦＣＹＴＯＫＥＲＡＴＩＮＳＩＮＨＵＭＡＮＨＥＰＡＴＯＣＥＬＬＵＬＡＲＡＮＤＣＨＯＬＡＮＧＩＯＣＥＬＬＵＬＡＲＣＡＲＣＩＮＯＭＡＳ￥ＳｕＱｉｎ；苏勤；Ｌｉｕｙａｎｆａｎｇ；刘彦仿（ＤｅｐａｒｔｍｅｎｔｏｆＰａｔｈｏｌｏｇｙ，...     

INVESTIGATION OF THE THERAPEUTIC EFFECT OF EXPRESSION OF TRAIL IN VIVO ON MOUSE HEPATOCELLULAR CARCINOMA

Objective: To construct an eukaryotic expressing plasmid of mouse TRAIL (mTRAIL), and investigate its ability to induce the apoptosis of hepatocellular carcinoma cells in vitro and in vivo, its inhibitory effect on the growth of hepatocellular carcinoma, and its synergism with pCH510, an eukaryotic expressing plasmid of recombinant human FN polypeptide.Methods: The eukaryotic expressing plasmid of mTRAIL was constructed by RT-PCR and DNA recombination techniques. Gene transfection was performed in vitro and in vivo. The apoptosis rate of hepatocellular carcinoma cells was measured by Flow Cytometry. The apoptosis of hepatocellular carcinoma cells was measured by Flow Cytometry.The apoptosis of hepatocellular carcinoma cells was detected by TdT-mediated dUTP nick end labeling (TUNEL) and histochemistry techniques. The inhibitory effect of gene transfection on solid tumor was observed in mice. Results: The cDNA of mTRAIL was amplified by RT-PCR from the RNA of mouse spleen cells, and cloned into the eukaryotic expressing vector pcDNA3.1. The recombinant plasmid was designated as pX1. The BHK cells transfected with plasmid pX1 could attack H22 hepatocellular carcinoma cells and induce the apoptosis of them. The transfection of plasmid pX1 through injection into mouse muscles could inhibit the growth of hepatocellular carcinoma by inducing the apoptosis of tumor cells. Plasmid pX1 and pCH510 had a synergistic inhibitory effect on the hepatocellular carcinoma growth. Conclusion: Plamid pX1 could be expressed in cells and in vivo in mouse. The expression of pX1 in vivo and in vitro could induce the apoptosis of hepatocellular carcinoma ceils and inhibit the growth of hepatocellular carcinoma. Plasmid pX1 and pCH510 had a synergistic inhibitory effect on the hepatocellular carcinoma growth.     

STUDY ON THE EXPRESSION OF CYCLOOXYGENASE-2 IN HEPATOCELLULAR CARCINOMA CELL LINES AND ON THE GROWTH INHIBITION EFFECT OF NS-398

Objective： To investigate the expression of cyclooxygenase -2 （COX-2） in hepatocellular carcinoma cell lines and to explore the effect of NS-398, a selective inhibitor for COX-2, on HepG-2 cell line. Methods： lmmunohistochemistry and RT-PCR were used to investigate COX-2 expression in 6 HCC cell lines. MTT and Flowcytometry were used to evaluate the effect of the selective inhibitor of COX-2, NS-398, on HepG-2 cell lines. Results： All six HCC cell lines showed COX-2 expression at protein level. Five out of 6 cell lines showed COX-2 expression at mRNA level. NS-398 could suppress the growth of HepG-2 cell line, in a time and dose dependant manner. Conclusion： NS-398, a selective inhibitor of COX-2, showed inhibition effect on HepG-2 HCC cell line. The efficacy of inhibition was time and dose dependent, providing a new evidence for chemoprovention of hepatocellular carcinorma with COX-2 selective inhibitors.     

OVEREXPRESSION OF Akt-1 GENE IN HUMAN HEPATOCELLULAR CARCINOMA

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, which ranks the eighth in frequency among human cancer especially in Asia, Africa and South Europe, accounting for anestimated 1 million deaths annually. Men are afflicted at least twice as often as women. Although HCC ranks eighth in frequency among cancers worldwide, it is sixth among men and eleventh among women[1]. It is one of the few human cancers for which an underlying etiology can be identified in…     

A MOLECULAR EPIDEMIOLOGIC MARKER OF HEPATOCELLULAR CARCINOMA FROM AFLATOXIN B1 CONTAMINATED AREA IN THE SOUTHWEST OF GUANGXI

ＡＭＯＬＥＣＵＬＡＲＥＰＩＤＥＭＩＯＬＯＧＩＣＭＡＲＫＥＲＯＦＨＥＰＡＴＯＣＥＬＬＵＬＡＲＣＡＲＣＩＮＯＭＡＦＲＯＭＡＦＬＡＴＯＸＩＮＢ１ＣＯＮＴＡＭＩＮＡＴＥＤＡＲＥＡＩＮＴＨＥＳＯＵＴＨＷＥＳＴＯＦＧＵＡＮＧＸＩＤｅｎｇＺｈｕｏｌｉｎ邓卓霖ＭａＹ...     

EXPRESSION OF CELLULAR ONCOGENES IN HUMAN PRIMARY HEPATOCELLULAR CARCINOMA

With DNA-mRNA hybridization in situ technique, the expression of five oncogenes, c-N-ras, c-Ki-ras. c-Ha-ras, c-myc and c-fos, was observed in two cases of human hepatocellular carcinoma. The expression of c-N-ras &; c-fos was greatly enhanced in tumor tissues of the two cases, and about 25%–50% of the tumor cells showed positive expression. The other three oncogenes namely c-Ki-ras, c-Ha-ras &; c-myc, were not detected in these two carcinomas or in the non-cancerous liver tissues adjacent to the carcinomas. It is surmised that c-N-ras and c-fos may play coordinative role in maintaining the malignant phenotype of human primary hepatocellular carcinoma.     

THE STUDY OF ESTROGEN AND PROGESTERONE RECEPTOR IN NASOPHARYNGEAL CARCINOMA

ＴＨＥＳＴＵＤＹＯＦＥＳＴＲＯＧＥＮＡＮＤＰＲＯＧＥＳＴＥＲＯＮＥＲＥＣＥＰＴＯＲＩＮＮＡＳＯＰＨＡＲＹＮＧＥＡＬＣＡＲＣＩＮＯＭＡＺｈｅｎｇＴｉａｎｒｏｎｇ郑天荣；ＬｉＪｉａｎｃｈｅｎｇ李建成；ＬｉｕＸｉｕｙｉｎｇ刘秀英；（Ｄｅｐａｒｔｍｅｎｔｏｆ...     

Hepatitis B virus-induced hepatocellular carcinoma

Many factors are considered to contribute to hepatitis B virus (HBV) associated hepatocellular carcinoma (HCC), including products of HBV, HBV integration and mutation, and host susceptibility. HBV X protein (HBx) can interfere with several signal pathways that associated with cell proliferation and apoptosis, and the impact of HBx C-terminal truncation in the development of HCC has been implicated. Recent studies by advanced sequencing technologies have revealed recurrent HBV DNA integration sites in hepatoma cells and susceptible genes/SNPs play an important role in the pathogenesis of liver cancer. Epigenetic changes, immune and inflammatory factors are also important contributing factors for liver cancer. This mini-review provides an overview on the recent development of HBV induced HCC.     

原发性肝细胞癌患者的乙型肝炎病毒基因分型研究

目的：研究原发性肝细胞癌（HCC）患者乙型肝炎病毒（HBV）基因型分布及其特点。方法：采用聚合酶链式反应结合TaqmanMGB探针技术对70例HCC患者和57例慢性乙型肝炎（CHB）患者进行HBV基因分型。结果：HCC患者中C基因型占74.29%,B型占24.29%%,BC型占5.71%,未发现A、D、E、F、G基因型。HCC患者中C型所占比例明显高于CHB患者（P〈0.05）,B型所占比例明显低于CHB患者（P〈0.05）。B基因型HCC患者的年龄、性别、血清e抗原阳性率、e抗体阳性率、e系统阴性（HBeAg-、HBeAb-）率及HBVDNA水平与C基因型比较差异均无显著性（P均〉0.05）。结论：C型为南京地区HCC的主要基因型。HCC患者的年龄、性别、e抗原表达状态以及HBVDNA复制水平与基因型之间均无明显相关性。     

The effect of interaction between hepatitis C virus and cigarette smoking on the risk of hepatocellular carcinoma

We evaluated the interaction between hepatitis C virus (HCV) and cigarette smoking on death from hepatocellular cancer in The Japan Collaborative Cohort Study. The odds ratio of death from HCC for smoking was 9.60 (1.50-61.35) and 1.71(0.58-5.08) among anti-HCV positive and negative individuals, respectively.     

肝细胞癌组织中乙型肝炎病毒和丙型肝炎病毒的检测

目的检测肝细胞癌（hepatocellular carcinoma，HCC）组织中乙型病毒性肝炎（virus hepatitis type B）表面抗原（HB—sAg）和丙型病毒性肝炎（virus hepatitis type C）核心抗原（HCVAg）的表达。方法应用免疫组织化学法检测78例HCC及癌旁肝组织HBsAg和HCVAg的表达。同时比较患者的HBsAg和HCVAg血清学检测结果。结果HCC及癌旁肝组织中HBsAg和HCVAg阳性及HBsAg和HCVAg双重阳性表达率分别为9.1％、6．4％、2．6％和80．8％、44．9％、29．5％。HCC与癌旁肝组织HBsAg和HCVAg阳性及HBsAg和HCVAg双阳性表达率相互比较有非常显著性差异（P〈0．01）。合并肝硬化组和无肝硬HCC组中HCC与癌旁肝组织HBsAg和HCVAg阳性、HBsAg及HCVAg双阳性表达率相互比较也有非常显著性差异（P〈0．01）。HCC的HBsAg和HCVAg血清学检测的结果与手术标本HBsAg和HCVAg免疫组织化学检测的结果相吻合。结论HCC的发生与HBV和HCV的感染密切相关。     

Upregulated in Hepatitis B virus-associated hepatocellular carcinoma cells,miR-331-3p promotes proliferation of hepatocellular carcinoma cells by targeting ING5

Hepatitis B virus (HBV) is a major risk factor for development and progression of hepatocellular carcinoma (HCC). It has been reported that viral infection can interfere with cellular microRNA (miRNA) expression and participate in the pathogenesis of oncogenicity. Our miRNAs array data indicated that miR-331-3p expression in HCC cell lines increased, but the relationship between miR-331-3p expression and HBV activity is unclear. Here, we observed elevated expression of miR-331-3p in different HCC cell lines expressing HBV. HBV, especially HBx, promotes miR-331-3p expression by enhancing its promoter activity. Using a miRNA target prediction database miRBase, we identified ING5 to be a novel target gene of miR-331-3p. miR-331-3p could inhibit ING5 expression by directly targeting its 3′-untranslated region (3′-UTR). As predicted, HBV was confirmed to repress ING5 at both mRNA and protein levels by promoting miR-331-3p expression. Our result indicated that miR-331-3p expression promotes proliferation of SMMC7721 cells by inhibiting ING5. ING5 overexpression promoted cell apoptosis in HCC cell lines. We also found ING5 expression was decreased in tumor tissue of HCC patient with HBV infection compared to its expression in para-carcinoma tissues. Conclusion: These results showed that miR-331-3p is upregulated by HBV and promotes proliferation of HCC cells though repression of ING5 expression. These data provide new insights for understanding the mechanisms of HBV-related HCC pathogenesis.     

Feasibility of Autologous Stem Cell Transplantation in Chronic Carriers of Hepatitis B and Hepatitis C Virus

There are several reports describing acute liver decompensation in chronic carriers of HBsAg after withdrawal of chemotherapy or immunosuppressive therapy; recently the same was also reported for chronic HCV-RNA carriers. We retrospectively evaluated hepatic toxicity in eleven patients (6 carriers of HCV-RNA and 5 of HBsAg) autotransplanted at our Institution between March '92 and June '98. Male/female ratio was 7/4, median age 41 years (26-56). Nine patients (4 HBsAg) were affected by non-Hodgkin's lymphoma, 1 (HCV-RNA) by chronic myelogenous leukaemia and 1 (HBsAg) by breast cancer. In the immediate post-transplant period in only 1 patient (HBsAg carrier and affected by breast cancer) was hepatitis documented (at about 1 month from transplant) with an elevation of transaminase levels (x20-40 n.v.). Neither other complications, nor toxic deaths were observed. During the post-transplant follow-up (median 31 months, range 9-83) no hepatic abnormalities were observed. All patients are alive at 56 months (20 - 122) from diagnosis. Currently 10/11 patients are in complete remission, while 1 patient, affected by follicular centre lymphoma, is alive with disease 52 months from autologous stem cell transplantation. Our study shows that both conventional therapy and high-dose chemotherapy can be performed safely in chronic hepatitis B and C virus carriers.     

Targeting blockage of STAT3 inhibits hepatitis B virus-related hepatocellular carcinoma

Hepatitis B virus (HBV) infection is a significant cause of liver disease pathogenesis, which results in the development of hepatic dysfunction, cirrhosis and hepatocellular carcinoma (HCC). Our previous studies showed that oncogene STAT3 might be an ideal target for HCC therapy. Here, we investigated whether targeting blockage of STAT3 signaling is efficient for HBV-related HCC. Based on the refractory of HCC and the persistence of HBV, in this study, we designed shRNAs targeting STAT3. The results showed that blocking STAT3 signaling by shRNAs could promote HBV positive HCC cell apoptosis and induce cell cycle arrest, resulting in HCC cell growth inhibition in vitro. Importantly, STAT3-shRNAs efficiently suppressed HBV replication, which would reduce HBV-derived stimulation to STAT3 signaling and augment STAT3-shRNAs-mediated anti-HCC effect. Finally, STAT3-shRNAs-mediated anti-HBV positive HCC effect was confirmed in xenograft nude mice. This study suggested that targeting STAT3 therapies such as STAT3-shRNAs may be an efficacious strategy for HBV-related HCC.     

Hepatitis B virus and intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (ICC) is a rare type of primary liver cancer that arises from intrahepatic bile ducts. Its etiopathogenesis has been considered to be independent of the presence of chronic viral hepatitis infections or cirrhosis. These factors, particularly the hepatitis C virus, have been reported to play a role in the development of cholangiocarcinoma in a few studies, with inconclusive results. We report 2 cases of ICC that presented with a background of hepatitis B virus (HBV) infection and discuss the possible pathophysiological relationships between ICC and HBV infection, with an emphasis on the x gene of HBV.