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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatocellular carcinomas in woodchuck were characterized for woodchuck hepatitis virus integration near c-myc oncogene. In one tumor, viral integration resulted in overexpression of a c-myc viral cotranscript. In a second tumor, viral insertion, 600 bp upstream of c-myc exon 1, was associated with increased levels of normal c-myc mRNA. These results demonstrate that integration of woodchuck hepatitis virus near a proto-oncogene can contribute to the genesis of liver tumors. From a comparison of a single hepatitis B virus (HBV) integration site in a human hepatoma with the corresponding unoccupied site have shown HBV DNA insertion in a putative cellular exon. This exon presented striking similarity to the DNA-binding domain of the thyroid/steroid hormones receptors. The corresponding cDNA has been isolated (hap gene) a shown to encode the retinoic acid receptor. It is most probable that consequent to HBV insertion, has became inappropriately expressed as an altered chimaeric gene retinoic acid receptor, thus contributing to the cell transformation. As for woodchuck these results strongly support the possibility that HBV may play a direct role in liver carcinogenesis by insertional mutagenesis.
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PMID:[Hepatitis B virus and hepatocellular carcinoma]. 165 Jun 25

Several epidemiological studies have demonstrated a link between chronic B virus infection and primary hepatocellular carcinoma (PHC). HBV DNA sequence integrations into the host cell genome have often been observed in hepatocarcinoma tissues. However, since only in a few cases of PHC the target of HBV-DNA insertion has been identified, alternative mechanisms for HBV-induced hepatocyte transformation have been investigated. Like many other DNA viruses, the hepatitis B virus bears a transactivational potential. Both full length and truncated versions of HBV X protein are able to influence the expression of cellular nuclear protooncogenes c-fos and c-myc. A second transcriptional activator is encoded by the PreS/S region of HBV, but its activity on viral and cellular genes become evident only after dislocations from its downstream sequences. Thus, HBV is able to influence infected cell growth and differentiation using both native proteins, newly generated truncated proteins and virus-cell fusion polypeptides.
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PMID:Hepatitis B virus and hepatocellular carcinoma: a possible role for the viral transactivators. 166 93

Hep G2 and Hep 3B cells, two human hepatoma cell lines, showed decreased thymidine (Thd) incorporation into intracellular acid-insoluble pools when exposed to Wellferon, human lymphoblastoid interferon (IFN). Inhibition was maximal after 48 h treatment with Wellferon and was reversible. Significant inhibition in Wellferon-treated Hep 3B cells was noted at concentrations of 1 IFN unit/ml, which was over 1000-fold less than that required to produce equivalent effects in Hep G2 cells. The decrease in Thd incorporation into acid-insoluble pools was due to both alterations in Thd anabolism and a small but significant decrease in incorporation into DNA with no apparent effect on nucleoside transport. The small but significant Wellferon-induced decrease in Thd incorporation into DNA was reflected in a small but significant decrease in cell proliferation in both cell lines. In addition, Wellferon induced a decrease in the steady-state level of c-myc- and P450-specific RNA transcripts but did not affect the steady-state levels of transforming growth factor-B, fos, N-Ras, or erb-B RNA transcripts. These Wellferon effects, however, did not result in any significant antitumour effects when Hep 3B or Hep G2 cells were grown in athymic nude mice treated intraperitoneally with 8 mu/kg/day Wellferon. Wellferon can induce an antiviral state in both cell lines using Semliki Forest virus and Herpes simplex virus as viral challenges. Taken collectively, these data indicate that Wellferon produces both antiviral and slight but significant antiproliferative effects in Hep G2 and Hep 3B cells, but does not produce significant antitumor effects in vivo using these cell lines in nude mice xenografts.
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PMID:Effects of human lymphoblastoid interferon on proliferation, gene expression and tumourigenicity of human hepatoma cell lines. 166 28

The relationship between levels of gene transcripts and tumor growth was studied in rat hepatomas showing a wide spectrum of growth rates. The level of c-myc and actin gene transcripts were generally increased in the hepatomas but were independent of the growth rate of the tumors. Oncogene expression was studied in the livers of rats on diets which cause a nucleotide imbalance in the liver and which have been reported to be promotional for hepatocarcinogenesis. The levels of c-myc transcripts were elevated three-fold with an arginine-deficient diet but were little changed with a high-orotate diet. The data suggested that levels of c-myc transcripts in rat liver cannot be related in a uniform manner to nucleotide imbalance, tumor promotion or hepatoma growth.
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PMID:Levels of oncogene transcripts in hepatomas of different growth rates and in liver in response to diets which cause a nucleotide imbalance. 169 22

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

Hepato-specific regulatory (promoter/enhancer) DNA sequences were used for targeting the expression of onc genes, such as murine c-myc and Simian Virus 40 T Antigen, to hepatocytes of transgenic mice which subsequently developed hepatocellular carcinomas after a variable period of time (depending on the type of onc gene employed). Several trans-immortalized cell lines were established and compared with respect to the expression of adult hepatic markers and response to growth factors. Despite the morphological differences observed between trans-hepatomas, owing to the expression of the two different onc genes, all tumor-derived cell lines behaved in a comparable fashion during long-term culture displaying an adult hepatic phenotype for at least 40 passages. They differed, however, in response to epidermal growth factor. When the gene coding for human alpha 1-antitrypsin was placed under the control of the same hepato-specific promoter/enhancer, high levels of the human recombinant protein could be harvested from the supernatants of trans-hepatoma-derived cell lines.
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PMID:Characterization of trans-immortalized hepatic cell lines established from transgenic mice. 171 73

LEC (Long-Evans with a cinnamon-like coat color) rats develop hepatocellular carcinomas (HCCs) spontaneously. We examined mutations of codons 12, 13, and 61 of the Ha-ras, Ki-ras, and N-ras genes in four HCCs by the polymerase chain reaction (PCR)-single-stranded DNA direct sequencing method. No ras gene mutations were observed, suggesting that ras activation is not involved in spontaneous hepatocarcinogenesis in LEC rats. The expression of mRNAs for c-myc, Ha-ras, c-raf, and the protein phosphatase 2A alpha gene (PP-2A alpha) was also examined in the four HCCs by northern blot analysis. Three of the four HCCs had c-myc expression levels approximately 30-fold higher than that in the liver of control Long-Evans rats with an agouti coat color (LEA), a sibling line of LEC rats, while the remaining HCC had an expression level sevenfold higher than that of control. In contrast, the expression levels of the Ha-ras, c-raf, and PP-2A alpha genes were the same as those in the livers of control rats. Studies of c-myc expression and mitotic index in five other HCCs, two hyperplastic nodules, and two nontumorous portions of livers of HCC-bearing LEC rats that had chronic-phase hepatitis suggested that the high level of c-myc gene expression was not due only to increased cell proliferation but might possibly be more integrally involved in hepatocarcinogenesis.
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PMID:Possible involvement of c-myc but not ras genes in hepatocellular carcinomas developing after spontaneous hepatitis in LEC rats. 171 40

Hepatocellular carcinoma in woodchuck were characterized for woodchuck hepatitis virus integration nea c-myc oncogene. In one tumor, viral integration resulted in overexpression of a c-myc viral cotranscript. In a second tumor, viral insertion, 600 bp upstream of c-myc exon 1, was associated with increased levels of normal c-myc mRNA. These results demonstrate that integration of woodchuck hepatitis virus near a proto-oncogene can contribute to the genesis of liver tumors. From a comparison of a single hepatitis B virus (HBV) integration site in a human hepatoma with the corresponding unoccupied site have shown HBV DNA insertion in a putative cellular exon. This exon presented striking similarity to the DNA-binding domain of the thyroid/steriod hormones receptors. The corresponding cDNA has been isolated (hap gene) as shown to encode the retinoic acid receptor. It is most probable that consequent to HBV insertion, hap gene became inappropriately expressed as an altered chimaeric gene retinoic acid receptor, thus contributing to the cell transformation. As for woodchuck these results strongly support the possibility that HBV, may play a direct role in liver carcinogenesis by insertional mutagenesis.
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PMID:[Hepatitis B virus and hepatocellular carcinoma]. 177 42

One of insulin's least studied actions is its ability to induce DNA synthesis and cell division. In rat H4IIE hepatoma cells insulin, acting through its own receptor, stimulates cell division. However, little is known about the molecular mechanisms involved in this effect. The proto-oncogene c-myc is a cellular gene which when expressed at abnormal levels is often associated with the process of tumorigenesis. Expression of the normal cellular myc gene may be necessary for growth factor-induced cell cycling. In the present work, insulin was shown to regulate cellular accumulation and transcription of the c-myc gene in rat hepatoma cells. The control of c-myc by insulin was complex, with an initial-induced decrease in c-myc transcription to 50% of control values at 15 and 30 min. This was followed by an increase in transcription of about 3-fold by 60-120 min. Similar to the initial inhibitory effect of insulin, the protein synthesis inhibitors cycloheximide or anisomycin decreased c-myc transcription. However, there was no secondary induction of c-myc transcription by protein synthesis inhibitors. The effects of both insulin and protein synthesis inhibitors were shown to be through alterations in intragenic pausing of transcription of the sense mRNA, not through changes initiation of transcription.
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PMID:Inhibition and stimulation of c-myc gene transcription by insulin in rat hepatoma cells. Insulin alters the intragenic pausing of c-myc transcription. 191 37

With dot blot and cytoplasmic hybridization techniques we found that the c-Ha-ras, c-Ki-ras, c-N-ras, c-myc and c-fos oncogenes were over-expressed in human hepatocellular carcinoma cell line BEL 7402 cells. The mRNA expression of c-Ha-ras, c-Ki-ras, c-N-ras and c-myc oncogenes could be inhibited by 2 mmol/L sodium butyrate treatment, but this had no effect on the expression of c-fos. However, the mRNA expression of c-Ha-ras, c-N-Ras and c-myc oncogenes was enhanced by 4 mmol/L sodium butyrate treatment, while the expression of c-Ki-ras and c-fos remained unchanged. No significant effect on the expression of carbamyl phosphate synthetase I, a tissue-specific enzyme associated with the differentiation of liver cells, was observed by 2 mmol/L or 4 mmol/L sodium butyrate treatment of the hepatoma cells.
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PMID:[Expression of cellular oncogenes in human hepatocellular carcinoma cell line BEL 7402 and the effect of sodium butyrate on the expression of cellular oncogenes]. 196 12


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