Serial pathologic changes in livers of Tree shrews and Macaca assamensises infected with human Hepatitis B virus / 中华实验和临床病毒学杂志

<p><b>BACKGROUND</b>To serially observe the pathologic changes in livers of tree shrews and macaca assamensises infected with HHBV.</p><p><b>METHODS</b>10 adult tree shrews and 28 macaca assamensises were inoculated with HBV rich human sera. The liver of the animals were regularly biopsied. The liver samples were examined histopathologically by HE staining. Some samples were stained for HBsAg by immunohistochemistry (IH), and HBV DNA by in situ hybridization (ISH).</p><p><b>RESULTS</b>HBsAg in 80% of tree shrews infected with HHBV can be detected by IH, HBV DNA in 50% of those can be found by ISH.The positive rates of HBsAg in macaca assamensises' livers were 25% by IH, none HBV DNA was detected.</p><p><b>CONCLUSION</b>The tree shrew model seems to be applicable for the research of human hepatitis B.</p>

Human hepatitis B virus infection of tree shrews and Macaca assamensis in vivo / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To examine sensitivity of the tree shrews and Macaca assamensis to human hepatitis B virus (HHBV) by serologic methods.</p><p><b>METHODS</b>Totally 233 tree shrews and 28 Macaca assamensis were inoculated with human sera containing HBV. After inoculation, the sera were collected weekly from them and HBV markers were detected with HBV ditecting ELISA kits.</p><p><b>RESULTS</b>Ninety percent of the tree shrews developed acute infection, among them, 44.4 % persisted for over one year, 33.3% of them developed chronic infection persisted for 2 years and one month; the persistence of HBV in Macaca assamensis was much shorter.</p><p><b>CONCLUSION</b>These data clearly indicated that tree shrew may be used as an animal model for study of chronic HBV infection, whereas, Macaca assamensis, showed only a transient sensitivity to HHBV.</p>

Different gene expression during hepatocarcinogenesis in tree shrew induced by aflatoxin B1 / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To understand the molecular mechanism and find out the responsible genes for liver cancer by exploring the regulation of gene expression during hepatocarcinogenesis in tree shrew induced by aflatoxin B1 (AFB1).</p><p><b>METHODS</b>The tissues from tree shrew of different stages during the pathogenesis and development of hepatocellular carcinoma (HCC), liver cancer tissue, para-cancerous tissues, pre-cancerous liver tissues, liver tissues of the same stage from normal controls and the liver tissues taken before AFB1-treatment were analyzed for gene expression by cDNA array.</p><p><b>RESULTS</b>Four patterns of gene expression were observed during AFB1-induced hepatocarcinogenesis. They were: genes up-regulated in HCC tissue and para-cancerous tissue, especially in HCC tissues; genes with similar expressing level in both HCC tissue and para-cancerous tissue, but higher than that in pre-cancerous tissue; genes down-regulated in HCC tissue; genes up-regulated before HCC appeared but down-regulated after HCC appeared.</p><p><b>CONCLUSION</b>Dynamic observation of gene expression will be beneficial to elucidate the mechanisms of AFB1- induced hepatocarcinogenesis and locate the responsible genes.</p>

Expression of tumor-specific cancer/testis antigens in hepatocellular carcinoma / 中华肝脏病杂志

<p><b>OBJECTIVE</b>(1) To investigate the expression and gene diversity of the 7 major cancer/testis (CT) antigens, MAGE-1, MAGE-3, MAGE-4, MAGE-10, NY-ESO-1, SSX-2 and SCP-1, in hepatocellular carcinoma (HCC). (2) To analyze the correlations between the clinical characters and CT antigens' expression.</p><p><b>METHODS</b>The cancer and para-cancer tissues were collected from 30 HCC patients. The mRNAs of seven CT antigens were detected by reverse transcription-polymerase chain reaction (RT-PCR) with the specific primers. The PCR products were sequenced to analyze the CT genes.</p><p><b>RESULTS</b>The MAGE-1, MAGE-3, MAGE-4, MAGE-10, NY-ESO-1, SSX-2 and SCP-1 were expressed in 66.7%, 70.0%, 20.0%, 36.7%, 40.0%, 33.3% and 33.3% of the tumor tissues from HCC patients respectively, however, they were not expressed in the para-cancer tissues. Among the 30 patients investigated, 90.0% expressed one CT gene at least, 70.0% expressed two CT genes, and 53.3% expressed three CT genes of the seven CT genes. The coding genes of these CT antigens were highly conserved between in Chinese patients and patients abroad. There were discernible correlations between alpha-fetoprotein level and MAGE-10 or SCP-1 expression level, as well as between average age and MAGE-3 or SSX-2 expression levels (P<0.05).</p><p><b>CONCLUSIONS</b>With a highly conserved coding gene, seven CT antigens were expressed in 20.0% - 70.0% of Chinese HCC patients. CT antigens' expression had correlations with some clinical characters.</p>

Alteration of p53 gene during tree shrews' hepatocarcinogenesis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To detect the expression and variation of p53 gene during tree shrews' hepatocarcinogenesis induced by hepatitis B virus (HBV) and aflatoxin B1 (AFB1).</p><p><b>METHODS</b>Tree shrews were divided into four groups: the tree shrews were infected with HBV and fed with AFB1 in group A, only infected with HBV in group B, fed with AFB1 alone in group C, and normal control in group D. All the tree shrews were performed liver biopsy every 15 weeks. The tissues of liver and tumor were detected by immunohistochemistry and molecular biotechnologies.</p><p><b>RESULTS</b>(1) The incidence of hepatocellular carcinoma (HCC) in group A (66.7%) was higher than that in Group B and C (30%). HCC appearance in group A was earlier than that in group C (120.0 weeks +/-16.6 weeks vs 153.3 weeks +/-5.8 weeks, t = 3.336, P<0.01). (2) Mutated p53 protein was not found before the 75th week of the experiment in each group. (3) At the 105th week, the expression rates of mutated p53 protein were 78.6%, 60% and 71.4% in group A, B and C respectively, which were much higher than that (10%) in group D (x2 > or = 5.03, P<0.05). An abnormal band of p53 gene was detected in both group A and C. (4) The mutation points of p53 gene in liver cancer of tree shrew were at codon 275, 78 and 13. The nucleotide sequence and amino acids sequence of tree shrew's wild-type p53 showed 91.7% and 93.4% homology with those of human p53 respectively.</p><p><b>CONCLUSIONS</b>There is a remarkable synergistic effect between HBV and AFB1 on HCC. Mutated p53 protein is expressed before HCC occurrence, which promotes the development and progress of HCC. HBV and AFB1 may synergistically induce p53 gene mutation.</p>