Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Changes of nucleotide sequences and expressions of cellular oncogenes in human hepatoma cell lines, PLC/PRF/5, HCC-M and HCC-T cells, were examined by Southern and Northern blot analyses. The probes used are DNA fragment of myc, N-, H-, K-ras, fos, fms, raf, erb-A, erb-B, and erb-B2 genes and synthetic oligonucleotides corresponding to the part of N-, H-, K-ras genes. The results are as follows. DNA amplification and rearrangement were not detected in these three human hepatoma cell lines. Point mutations at codons 12, 13, and 61 in N- and K-ras genes were not demonstrated in these cell lines. N-, H-, K-ras and myc transcripts were detected in these three cell lines. However, fos gene transcript was detected only in PLC/PRF/5 and HCC-M cells which were derived from hepatitis B related hepatocellular carcinoma and having integrated hepatitis B virus (HBV) DNA. These data showed that there are no specific proto-oncogene expression into RNA except for myc and ras genes, nor DNA rearrangement in these 3 human hepatoma cell lines with regards to at least 10 different oncogenes examined and suggest the relationship between fos gene expression and integration of HBV DNA in host cell DNA.
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PMID:Proto-oncogene expression in three human hepatoma cell lines, HCC-M, HCC-T and PLC/PRF/5. 166 47

The in vitro effect of sodium butyrate (SB) on human hepatoma cell lines PLC/PRF/5, HCC-M and HCC-T was investigated. SB was added at the non-toxic but cytostatic concentration of 1 mM. In all these cell lines, SB reduced cell proliferation and changed the morphology of the cells into a fibroblast-like shape. In PLC/PRF/5, alpha-fetoprotein production and c-myc expression were inhibited. In contrast, gene expression of albumin, one of the normal liver-cell products, and that of integrated hepatitis B virus genome, was increased. In HCC-M and HCC-T, c-myc expression, which was enhanced in the naive state, was reduced. In HCC-M, fos expression was inhibited but the expression of N- and K-ras genes did not change. SB seemed to induce normal or mature properties of hepatocytes in human hepatoma cell lines.
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PMID:Differentiating effect of sodium butyrate on human hepatoma cell lines PLC/PRF/5, HCC-M and HCC-T. 170 67

We have established two cell lines of hepatocellular carcinoma [Hep-KANO, clone 1 (CL-1) and clone 2 (CL-2)] from tissue obtained at autopsy of a hepatitis B virus (HBV) carrier without histological signs of hepatitis or liver cirrhosis. These cell lines differed considerably from each other in morphology, proliferation pattern, alpha-fetoprotein secretion, albumin synthesis, cytokine secretion, modal chromosome number and transplantability to nude mice. Histologic examinations also revealed differences between them. Amplification of N-myc, L-myc, H-ras, K-ras, N-ras, c-erb-B and c-erb-B-2 and rearrangement of p53 were not found in either of the cell lines. However, CL-1 and CL-2 showed an identical HBV-DNA integration pattern. A 4-fold amplification of c-myc was observed in CL-1, but not in CL-2. Hep-KANO cell lines, CL-1 and CL-2 may be useful in clarifying the question of whether hepatocarcinogenesis is directly caused by HBV infection.
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PMID:Characteristics of human hepatocellular carcinoma cell lines (Hep-KANO) derived from a non-hepatitic, non-cirrhotic hepatitis B virus carrier. 782 95

Hepatobiliary neoplasms comprise a significant portion of the worldwide cancer burden. Advances in basic science research have led to rapid progress in our understanding of the molecular events responsible for these dreaded diseases. The genetic changes associated with hepatocellular carcinoma (HCC) have received the most attention. Aflatoxin B1 exposure leads to mutations in the p53 tumor suppressor gene, most commonly a transversion in codon 249 that leads to a substitution of serine for arginine in the p53 protein. Numerous other tumor suppressor genes, oncogenes, and tumor gene pathways are altered in HCC. Hepatitis B virus (HBV) infection is strongly associated with HCC. HBV may cause HCC either directly via the HBV X protein, or indirectly by causing liver inflammation and cirrhosis. Hepatitis C virus (HCV) infection is also associated with HCC. Recent evidence suggests that the HCV core protein may play a role in hepatocarcinogenesis. Several inherited metabolic diseases are associated with HCC. It is likely that these diseases cause HCC indirectly by causing cirrhosis. The molecular pathogenesis of cholangiocarcinoma and gallbladder cancer has not been well defined. However, multiple tumor suppressor genes and oncogenes, including p53 and K-ras, are altered in these tumors. Further molecular characterization of hepatobiliary tumors may lead to earlier diagnosis, better staging, improved treatment planning, and the development of more effective therapies.
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PMID:Genes and viruses in hepatobiliary neoplasia. 1112 84

Loss of the RASSF2A expression induced by methylation-mediated silencing has been reported in several human cancers, but the methylation status of RASSF2A in hepatocellular carcinoma (HCC) is rarely studied so far. In this study, we investigated the RASSF2A expression and its methylation status in a cohort of 45 hepatitis B virus-associated HCC tissues and their adjacent non-carcinoma tissues by using RT-PCR and MS-PCR. Promoter methylation of RASSF2A was found in 31 (68.9%) out of 45 HCC tissues and 12 (40%) out of 30 adjacent normal tissues, respectively (P<0.05). The methylation status of PASSF2A was closely associated with the loss of RASSF2A expression and elevated serum alpha-fetoprotein level, but not significantly with clinical stage, hepatic fibrosis and K-ras mutation. It was concluded that aberrant methylation of the RASSF2A gene with the subsequent loss of RASSF2A expression plays an important role in the pathogenesis of HCC.
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PMID:RASSF2A promoter methylation in hepatitis B virus-related hepatocellular carcinogenesis and its correlation with elevated serum alpha-fetoprotein level. 1951 12

In the etiology of hepatocellular carcinoma (HCC), in addition to hepatitis B virus and hepatitis C virus infections, chemical carcinogens also play important roles. For example, aflatoxin B(1) (AFB(1)) epoxide reacts with guanine in DNA and can lead to genetic changes. In HCC, the tumor suppressor gene p53 codon 249 mutation is associated with AFB(1) exposure and mutations in the K-ras oncogene are related to vinyl chloride exposure. Numerous genetic alterations accumulate during the process of hepatocarcinogenesis. Chemical carcinogen DNA-adduct formation is the basis for these genetic changes and also a molecular marker which reflects exposure level and biological effects. Metabolism of chemical carcinogens, including their activation and detoxification, also plays a key role in chemical hepatocarcinogenesis. Cytochrome p450 enzymes, N-acetyltransferases and glutathione S-transferases are involved in activating and detoxifying chemical carcinogens. These enzymes are polymorphic and genetic variation influences biological response to chemical carcinogens. This genetic variation has been postulated to influence the variability in risk for HCC observed both within and across populations. Ongoing studies seek to fully understand the mechanisms by which genetic variation in response to chemical carcinogens impacts on HCC risk.
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PMID:Interactions of chemical carcinogens and genetic variation in hepatocellular carcinoma. 2116 Sep 80

Hepatitis B virus (HBV) infection is considered as one of the major risk factors in the development of human hepatocellular carcinoma (HCC). Recent studies have also suggested the implication of oncogene and onco-suppressor genes in liver carcinogenesis. We studied 41 cases of HCC for the presence of HBV DNA and point mutations in codon 12 of K-ras and codon 249 of p53. We used 'nested' PCR for the amplification of HBV because of the expected low incidence of the virus DNA in the samples. PCR was also used for the amplification of K-ras and p53 regions that contain the codons of interest, followed by RFLP analysis for the detection of point mutations. HBV DNA was amplified in 22 cases (53.7%), while 5 cases (12.2%) appeared to carry mutations in codon 12 of K-ras and 7 cases (17.1%) had mutations in codon 249 of the p53 gene. These results further support the correlation between HBV infection and HCC and also indicate an implication of K-ras and p53 genes in hepatocarcinogenesis.
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PMID:Detection of hepatitis-B virus-DNA and mutations in k-ras and p53 genes in human hepatocellular carcinomas. 2157 4

An abnormality in the Lin28/let-7a axis is relevant to the progression of hepatitis B virus (HBV)-positive hepatocellular carcinoma (HCC), which could be a novel therapeutic target for this malignant tumor. The present study aimed to investigate the antiproliferative and anti-invasive effects of urolithin A in a stable full-length HBV gene integrated cell line HepG2.2.15 using CCK-8 and transwell assays. The RNA and protein expressions of targets were assessed by quantitative PCR and western blot, respectively. Results revealed that urolithin A induced cytotoxicity in HepG2.2.15 cells, which was accompanied by the cleavage of caspase-3 protein and down-regulation of Bcl-2/Bax ratio. Moreover, urolithin A suppressed the protein expressions of Sp-1, Lin28a, and Zcchc11, and elevated the expression of microRNA let-7a. Importantly, urolithin A also regulated the Lin28a/let-7a axis in transient HBx-transfected HCC HepG2 cells. Furthermore, urolithin A decelerated the HepG2.2.15 cell invasion, which was involved in suppressing the let-7a downstream factors HMGA2 and K-ras. These findings indicated that urolithin A exerted the antiproliferative effect by regulating the Lin28a/let-7a axis and may be a potential supplement for HBV-infected HCC therapy.
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PMID:Antiproliferative effect of urolithin A, the ellagic acid-derived colonic metabolite, on hepatocellular carcinoma HepG2.2.15 cells by targeting Lin28a/let-7a axis. 2974 65