Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A semi-purified corn-based diet containing 50 mg/kg of pure (not less than 90%) fumonisin B1 (FB1), isolated from culture material of Fusarium moniliforme strain MRC 826, was fed to a group of 25 rats over a period of 26 months. A control group of 25 rats received the same diet without FB1. Five rats from each group were killed at 6, 12, 20 and 26 months. The liver was the main target organ in the FB1-treated rats and the hepatic pathological changes were identical to those previously reported in rats fed culture material of F.moniliforme MRC 826. All FB1-treated rats that died or were killed from 18 months onwards suffered from a micro- and macronodular cirrhosis and had large expansile nodules of cholangiofibrosis at the hilus of the liver. Ten out of 15 FB1-treated rats (66%) that were killed and/or died between 18 and 26 months developed primary hepatocellular carcinoma. Metastases to the heart, lungs or kidneys were present in four of the rats with hepatocellular carcinoma. No neoplastic changes were observed in any of the control rats. Chronic interstitial nephritis was present in the kidneys of FB1-treated rats killed after 26 months. No lesions were observed in the esophagus, heart or forestomach of FB1-treated rats and this is contrary to previous findings when culture material of the fungus was fed to rats. It is concluded that FB1 is responsible for the hepatocarcinogenic and the hepatotoxic but not all the other toxic effects of culture material of F.moniliforme MRC 826 in rats.
Carcinogenesis 1991 Jul
PMID:Toxicity and carcinogenicity of the Fusarium moniliforme metabolite, fumonisin B1, in rats. 164 15

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

The importance of chronic hepatitis B virus (HBV) infection in the development of primary liver cancer has been established by epidemiological studies. However, the evidence for a direct role of the virus in liver carcinogenesis is still tentative. In addition, the findings of HBV DNA sequences in HBsAg-negative subjects with liver cancer has been reported, although it is controversial. Here we report the use of the polymerase chain reaction to detect HBV DNA in the serum and liver of HBsAg-negative patients. This technique allows both for the detection and cloning of HBV variants. In addition, the demonstration of HBV DNA and RNA molecules in HCC of HBsAg-negative individuals as determined by standard techniques reinforces the role of HBV in the pathogenesis of this tumor.
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PMID:The detection of hepatitis B virus (HBV) in HBsAG negative individuals with primary liver cancer. 165 Jun 88

Despite the epidemiological evidence of a correlation between ethanol abuse and hepatocellular carcinoma, some of the results of experimental and clinical studies remain controversial. Apart from inducing cirrhosis, which may be viewed as a precancerous liver lesion, ethanol may act as a cocarcinogen. Most investigations on this topic have focused on two aspects: ethanol's capacity to induce the cytochrome P-450-dependent microsomal biotransformation system and its interference with at least one DNA repair mechanism. Ethanol exposure enhances the capacity of mixed function oxidases to activate many chemical carcinogens, such as dimethylnitrosamine (DMN). On the other hand, ethanol exposure fails to influence DMN-induced liver carcinogenesis. The capacity of alcohol to inhibit DMN-demethylase activity has not been clearly demonstrated in experiments carried out with human tissue. In conclusion, both the effects of ethanol and their underlying mechanisms as regards liver carcinogenesis are open to debate. The link between ethanol abuse and hepatocellular carcinoma appears to be mediated mainly by its capacity to induce cirrhosis.
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PMID:Hepatocellular carcinoma, alcohol, and cirrhosis: facts and hypotheses. 165 Jun 91

A comparative study on HBV status and ets-2, IGF-II, C-myc and N-ras expression in 12 pairs of human primary hepatocellular carcinoma (PHC) and adjacent non-tumorous tissues (NT) showed that integrated forms of HBV DNA were present in 91.5% PHC and 75% NT. No specific integration sites were detected. Three PHC and 4 NT were found to have free forms of HBV DNA, which were defective in 2 PHC and 3 NT, i. e., being able to replicate but not to be secreted into the blood. At least one of four oncogenes studied was overexpressed in the 12 pairs of samples. IGF-II was expressed as 5.0 and 2.0 Kb fetal transcripts in 3 pairs of samples and 1 NT. Six NT had more than one of the four oncogenes that was expressed higher than PHC. This was commonly encountered in tissues with free forms of HBV DNA. The relation between HBV status, expression of ets-2, IGF-II, C-myc and N-ras and carcinogenesis of PHC is discussed.
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PMID:[HBV status and expression of ets-2, IGF-II, C-myc and N-ras in human hepatocellular carcinoma and adjacent nontumorous tissues--a comparative study]. 165 92

A recently introduced enzyme immunoassay procedure for antibodies against the hepatitis-C virus (HCV) was used to test samples from 185 cases with hepatocellular carcinoma (HCC) and 432 hospital controls. The anti-HCV results were examined in conjunction with previously reported data from this study concerning hepatitis-B virus (HBV) serology, hepatitis-D virus (HDV) antibodies, presence of cirrhosis and tobacco smoking. There was evidence for interaction between HBV and HCV in the causation of HCC: as previously reported, the rate ratio (RR) linking the presence of anti-HCV to HCC among subjects positive for hepatitis-B surface antigen (HBsAg) was substantially higher than the corresponding RR among those negative for this marker; furthermore, among HCC patients positive for HBsAg, a high proportion (33/61) of those who were positive for hepatitis-Be antigen (HBeAg) or its antibody were positive for anti-HCV, whereas among HBsAg-positive controls who were also positive for HBeAg or its antibody, none was positive for anti-HCV (0/18; p less than 10(-4)). The anti-HCV-related RR for HCC was also higher among HCC patients with cirrhosis than among those without evidence of co-existing cirrhosis (RR 11.4 vs. 4.4; p = 0.06). In addition, there was some evidence of interaction between tobacco smoking and HCV in the origin of HCC; after controlling for age, sex and HBsAg status, the RR for subjects positive for anti-HCV was 6.8 among smokers but only 3.2 among non-smokers (p = 0.26). By contrast, there was no suggestion of an interaction between anti-HCV and anti-HDV, in agreement with the presumed minimal role, if any, of HDV in HCC etiology. These results support the notion that HCV is involved in the etiology of HCC by advancing, through a chronic liver disease process, carcinogenesis initiated by other factors.
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PMID:Epidemiologic assessment of interactions of hepatitis-C virus with seromarkers of hepatitis-B and -D viruses, cirrhosis and tobacco smoking in hepatocellular carcinoma. 165 59

Hepatocarcinogenesis in woodchucks that are persistently infected with woodchuck hepatitis virus (WHV) follows a progressive course characterized by foci of altered hepatocytes, benign neoplastic nodules and finally hepatocellular carcinoma (HCC). In situ hybridization studies have demonstrated that insulin-like growth factor II (IGF-II) is expressed in most HCCs in woodchucks but that the patterns of expression are variable from tumor to tumor. In some cases, expression of IGF-II is high throughout the tumor, and in others expression is limited to the growing edge of the tumor. IGF-II expression is also activated in focal groups of cells in neoplastic nodules. The major IGF-II mRNA in nodules and HCCs is a 3.4 kb transcript corresponding to one of two IGF-II RNAs in fetal woodchuck liver. A single 15 kDa IGF-II polypeptide accumulates in the perinuclear cytoplasm of hepatocytes in fetal woodchuck liver, neoplastic nodules and HCCs. Thus IGF-II expression in woodchuck liver is reactivated in lesions which are believed to be the precursors of HCC and continues to be expressed as HCCs develop.
Carcinogenesis 1991 Oct
PMID:Analysis of insulin-like growth factor II (IGF-II) expression in neoplastic nodules and hepatocellular carcinomas of woodchucks utilizing in situ hybridization and immunocytochemistry. 165 28

The male hybrid B6C3F1 mouse exhibits a 30% spontaneous hepatoma incidence, and both males and females of this strain are sensitive to chemical induction of liver tumors. The Ha-ras, Ki-ras, and myc oncogenes have been implicated in a variety of solid tumors. Specifically, Ha- and, less frequently Ki-ras have been reported to be activated in B6C3F1 mouse liver tumors, and such activated oncogenes frequently contain a particular point mutation. In light of indications that the transforming capacity of some oncogenes is directly related to the level of the gene product, we hypothesized that transcriptional control of Ha-ras, Ki-ras, and myc is compromised in B6C3F1 mouse liver tumors. A positive correlation has been established between gene expression and hypomethylation. Therefore, the methylation states of these genes were examined in spontaneous liver tumors and in tumors induced by two diverse hepatocarcinogens: phenobarbital and chloroform. Ha-ras was found to be hypomethylated in all tumors examined, whereas Ki-ras was sometimes hypomethylated; such hypomethylation might play a role in the promotion stage of carcinogenesis. The methylation state of myc was unaltered, although this gene appeared to be amplified in tumors. These results suggest that a component of the mechanism by which these oncogenes are activated in B6C3F1 mouse liver tumors involves loss of stringent control of expression, via hypomethylation of the ras oncogenes and, possibly, amplification of myc. These results support the assertion that tumors induced by different classes of carcinogens or arising spontaneously share common biochemical pathways of oncogene activation during tumorigenesis.
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PMID:Hypomethylation of ras oncogenes in chemically induced and spontaneous B6C3F1 mouse liver tumors. 165 50

Indole-3-carbinol (I3C) is a secondary plant metabolite produced in vegetables of the Brassica genus, including cabbage, cauliflower, and brussels sprouts. I3C is both an anti-initiator and a promoter of carcinogenesis. Consumption of I3C by humans and rodents can lead to marked increases in activities of cytochrome P-450-dependent monooxygenases and in a variety of phase II drug-metabolizing enzymes. We have reported previously that the enzyme-inducing activity of I3C is mediated through a mechanism requiring exposure of the compound to the low-pH environment of the stomach. We report here the aromatic hydrocarbon responsiveness-receptor Kd values (22 nM-90 nM), determined with C57BL/6J mouse liver cytosol and the in vitro- and in vivo-molar yields (0.1-6%) of the major acid condensation products of I3C. We also show that indolo[3,2-b]carbazole (ICZ) is produced from I3C in yields on the order of 0.01% in vitro and, after oral intubation, in vivo. ICZ has a Kd of 190 pM for aromatic hydrocarbon responsiveness-receptor binding and an EC50 of 269 nM for induction of cytochrome P4501A1, as measured by ethoxyresorufin O-deethylase activity in murine hepatoma Hepa 1c1c7 cells. The binding affinity of ICZ is only a factor of 3.7 x 10(-2) lower than that of the highly toxic environmental contaminant and cancer promoter 2,3,7,8-tetrachlorodibenzo-p-dioxin. ICZ and related condensation products appear responsible for the enzyme-inducing effects of dietary I3C.
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PMID:Aromatic hydrocarbon responsiveness-receptor agonists generated from indole-3-carbinol in vitro and in vivo: comparisons with 2,3,7,8-tetrachlorodibenzo-p-dioxin. 165 85

A precise targeting of the SV40 T early region expression in the liver of transgenic mice was obtained using 700 bp of the antithrombin III regulatory sequences to control oncogene expression. In the strain expressing the highest level of large T antigen (Tag), the incidence of hepatocarcinoma was 100%. The evolution was reproducible and characterized by a marked cytolysis occurring as early as 4 weeks, when no morphological and histological modifications were visible, a preneoplastic state marked by a progression from hyperplasia to proliferative nodules composed of highly differentiated cells exhibiting a high Tag expression, which elicited tumor formation in nude mice and could proliferate in vitro, and hepatocellular carcinoma associated, in 10% of the cases, with lung metastasis. These transgenic mice constituted a useful model for therapeutic assays and fundamental studies on carcinogenesis.
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PMID:Time-course development of differentiated hepatocarcinoma and lung metastasis in transgenic mice. 166 May 4


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