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

In both cirrhotic and non cirrhotic livers, hepatic carcinogenesis appears as a multistep process commonly starting from hyperplastic nodules and reaching HCC via a continuous spectrum of lesions. Minute HCC without a background of hyperplastic lesions have also been identified in cirrhotic livers. These observations suggest that the morphological progression of carcinogenesis in the human liver can develop through two different main pathways.
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PMID:The morphogenesis of human hepatocellular carcinoma. 166 96

Levels of unscheduled DNA synthesis (UDS) of peripheral blood lymphocytes were measured by liquid scintigraphy in 23 patients with hepatocellular carcinoma (HCC), 42 first-degree relatives of HCC, 17 carriers of HBsAg, and 47 controls in order to evaluate the effects of HN2.HCl on the damage and repair of cell DNA, the effects of genetic susceptibility on the development of HCC, and the relationship between genetic susceptibility and hepatitis B virus (HBV) infection. The results were: 1. UDSs were significantly increased in the peripheral blood lymphocytes from patients with HCC and their first-degree relatives, and higher than those of the controls (P less than 0.005). 2. UDS in HBsAg carriers was significantly higher than that of the controls (P less than 0.05), 3. The difference of UDS was also remarkable between the HBsAg-negative patients with HCC and their first-degree relatives and the controls (P less than 0.01). These results suggest that the development of HCC might be due to the combined effects of environmental factors and genetic susceptibility. As an environmental factor, HBV infection might play role in hepato-carcinogenesis in individuals with or without a genetic background.
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PMID:[Unscheduled DNA synthesis of peripheral blood lymphocytes in pedigrees of hepatocellular carcinoma patients]. 166 15

The etiologic relationship of hepatocellular carcinoma (HCC) and chronic hepatitis B viral infection was proved clinically, epidemiologically, virologically, serologically and by other methods. Together with viruses, carcinogenesis is promoted by faster recovery of hepatocytes (liver cirrhosis, chronic hepatitis, etc.). We have discovered 103 HCC in the period of 21 years. There were 81 men and 22 women; they were in the sixth and seventh decade of life in 90% of cases. Liver cirrhosis was also confirmed in 55% of cases and chronic hepatitis in 19%, namely, in 74% of patients HCC has developed on the changed liver. Fifty three patients were HBsAg positive (51.45%). The ultrasound and determination of alpha-feto proteins proved to be most valuable. It is a slow growing tumour and by its early detection surgical treatment is possible.
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PMID:[Hepatocellular carcinoma--retrospective analysis]. 166 95

Expression plasmids (pKCPS-CAT) containing carbamyl phosphate synthetase (CPS I) upstream sequences of different lengths were constructed, and the function and characteristics of the sequences were studied with the CAT assay. Results showed that the CPS I upstream sequences exerted highly tissue-specific control on CPS I gene expression, and the -113 approximately -38 bp region relative to the cap site was found to be indispensable for CPS I gene transcription. The -1700 approximately -161 bp region contains sequences which confer an enhancing effect on CPS I gene transcription. Dexamethasone and thioproline (a differentiation inducer) showed enhancing effects on CPS I gene transcription in hepatoma cells. These results would have significance in studies on the gene regulation of CPS I associated with the mechanism of hepatocyte differentiation and carcinogenesis.
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PMID:Functional analysis of the CPS I upstream sequences with a cat assay. 166 83

The involvement of the hepatitis B virus in the pathogenesis of hepatocellular carcinoma was initially suggested on the basis of epidemiological studies. In recent years several kinds of experimental evidence have supported this hypothesis; however, the role played by hepatitis B virus in hepatocarcinogenesis still needs to be elucidated. Several groups of researchers are presently involved in establishing whether hepatitis B virus makes a specific genetic contribution to carcinogenesis or predisposes to neoplastic transformation by causing chronic inflammation and cell regeneration. A comprehensive examination of the data available in the literature suggests that the two hypotheses may not be mutually exclusive.
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PMID:Molecular biology of hepatocellular carcinoma and hepatitis B virus association. 166 38

Hepatocellular carcinoma (HCC) is a prevalent cancer in sub-Saharan Africa and eastern Asia. Hepatitis B virus and aflatoxins are risk factors for HCC, but the molecular mechanism of human hepatocellular carcinogenesis is largely unknown. Abnormalities in the structure and expression of the tumour-suppressor gene p53 are frequent in HCC cell lines, and allelic losses from chromosome 17p have been found in HCCs from China and Japan. Here we report on allelic deletions from chromosome 17p and mutations of the p53 gene found in 50% of primary HCCs from southern Africa. Four of five mutations detected were G----T substitutions, with clustering at codon 249. This mutation specificity could reflect exposure to a specific carcinogen, one candidate being aflatoxin B1 (ref. 7), a food contaminant in Africa, which is both a mutagen that induces G to T substitution and a liver-specific carcinogen.
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PMID:Selective G to T mutations of p53 gene in hepatocellular carcinoma from southern Africa. 201 Nov 86

The methylation status of the rat gamma-glutamyl transpeptidase (GGT) gene was investigated during liver development and hepatocarcinogenesis. The analysis with the restriction enzymes MspI/HpaII revealed that, during ontogeny, there is a progressive methylation of the GGT gene that coincides with a progressive decrease in GGT activity. Thus, there is an inverse correlation between methylation and expression of the GGT gene, suggesting a role for DNA methylation in the regulation of the gene during normal differentiation. The methylation patterns of the GGT gene in liver tumours induced by aflatoxin B1 exhibit heterogeneity. Nevertheless, a band of 5.7 kb was observed in all the DNA samples from aflatoxin B1-induced tumours which was not present in control liver DNA. The specificity of the DNA methylation changes was assessed using nafenopin, which induces hepatic tumours without elevation of GGT activity. We conclude that, during hepatocarcinogenesis, there is a modification of the DNA methylation pattern of the GGT gene, but there is no simple correlation with GGT activity. In no case was the GGT gene methylation in hepatocarcinogenesis found to be equivalent to the pattern observed in fetal liver. Thus if methylation is involved in the regulation of GGT gene transcription, the mechanisms must be different in fetal liver and hepatocarcinoma.
Carcinogenesis 1991 Jun
PMID:DNA methylation patterns of the rat gamma-glutamyl transpeptidase gene in embryonic, adult and neoplastic liver. 167 60

Previous studies have demonstrated that dietary administration of the schistosomicidal drug 5-(2-pyrazinyl)-4-methyl-1,2-dithiole-3-thione (oltipraz) ameliorates the hepatotoxicity of aflatoxin B1 (AFB1). Notably, mortality, altered hepatic function, hepatic AFB1-DNA adduct levels, and expression of hepatic enzyme-altered foci were markedly reduced in the rat by concurrent feeding of oltipraz during exposures to AFB1. Collectively, these studies prompted us to evaluate the chemoprotective properties of oltipraz against AFB1-induced liver cancer. In addition, preliminary molecular dosimetry studies were undertaken to determine the utility of measurements of urinary aflatoxin-N7-guanine excretion as a marker of relative risk for hepatocarcinogenesis in AFB1-exposed rats. For the carcinogenesis studies, 5-wk-old male F344 rats were randomly divided into two groups. One group (55 rats) received the AIN-76A diet, and the other group (56 rats) received the AIN-76A diet supplemented with 0.075% oltipraz. The oltipraz-supplemented diet was fed for 4 wk. Beginning 1 wk after starting the experimental diets, all rats in both groups received 25 micrograms of AFB1/rat/day by gavage for 5 days per wk over the next 2 wk. One wk following cessation of dosing with AFB1, oltipraz was removed from the diet, and all rats were fed the AIN-76A diet for the remainder of the experiment. At 3 mo after dosing, livers of ten sentinel rats from each group were analyzed for the burden of gamma-glutamyltranspeptidase-positive foci. In accord with previous findings, rats fed the oltipraz-supplemented diet exhibited substantial reductions in the focal burden (97% reduction; P less than 0.05) of these AFB1-induced lesions. The remaining rats were maintained for the cancer study until they became moribund or the termination of the experiment at 23 mo. Gross liver lesions were identified at autopsy and confirmed by microscopic evaluation. An 11% incidence of hepatocellular carcinoma was observed in the AFB1-treated, control diet-fed rats. An additional 9% of this group had hepatocellular adenomas. Oltipraz afforded complete protection against both AFB1-induced hepatocellular neoplasms. Using Kaplan-Meier survival analyses, rats in the oltipraz group had a significantly (P less than 0.02) longer life span and an increased survival free of liver tumors (P less than 0.0002). Molecular dosimetry studies used rats fed either the oltipraz-supplemented or control diet for 1 wk and then challenged with a single dose of AFB1 to examine the initial rates of 8,9-dihydro-8-(N7-guanyl)-9-hydroxyaflatoxin B1 excreted in the urine.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Protection against aflatoxin B1-induced hepatocarcinogenesis in F344 rats by 5-(2-pyrazinyl)-4-methyl-1,2-dithiole-3-thione (oltipraz): predictive role for short-term molecular dosimetry. 168 May 53

Perfluorooctanoic acid (PFOA) is a peroxisome proliferator. The aim of this study was to test for its ability to act as a positive modulator of hepatocarcinogenesis, in the so-called biphasic (initiation by diethylnitrosamine 200 mg/kg ip followed by treatment with the suspected modulators) and triphasic (initiation by the same dose of diethylnitrosamine followed by a selection procedure for 2 weeks consisting of giving 2-acetylaminofluorene and in the middle of this treatment a single dose of CCl4 followed by treatment with the suspected modulators) protocols of liver carcinogenesis. In both protocols treatment with PFOA increased the incidence of malignant hepatocellular carcinoma (HCC). As compared to phenobarbital, the modulating effect of PFOA is more pronounced in a biphasic than in the triphasic protocol. In parallel with positive modulation of HCC, PFOA also selectively induced the peroxisomal acyl-CoA oxidase activity and, to a lesser extent, catalase activity.
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PMID:The modulation of rat liver carcinogenesis by perfluorooctanoic acid, a peroxisome proliferator. 168 73

It is known that a high incidence of hepatocellular carcinoma in rat liver can be induced by such azo dye carcinogens as 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB). Thymidine kinase (TK) catalyzes the formation of deoxythymidine monophosphate (dTMP) by the phosphorylation of thymidine via the salvage pathway. In the present study, we investigated serum alpha-fetoprotein (AFP) and TK levels, and tissue TK and its isozyme activities in the liver of rats treated with 3'-MeDAB. Serum TK activities rose abruptly directly after the onset of 3'-MeDAB treatment, peaking after 1 week and then gradually decreasing. At 3 weeks, though serum TK was decreasing, serum AFP and tissue TK began to increase, and oval cells appeared in the liver. At 5 weeks, though serum TK reached a nadir, serum AFP and tissue TK formed transient peaks, and oval cells occupied a major part of the hepatic lobules with hyperplastic nodules. Thereafter, serum TK continued to increase, and serum AFP and tissue TK, after transiently decreasing, re-increased; at 20 weeks, each value was at high level, and mixed type hepatocarcinoma was observed. The liver TK isozymes were separated into three types by DEAE-cellulose column chromatography. A 3'-MeDAB diet induced a remarkable increase in activity of cytosolic and fetal type isozyme in non-tumorous regions of livers at 5 weeks and tumorous regions at 20 weeks. These results indicate that early biochemical changes in 3'-MeDAB-induced hepatocarcinoma in rats may serve as a useful model and provide a valuable insight in hepatocarcinogensis.
Carcinogenesis 1990 Jan
PMID:Thymidine kinase and alpha-fetoprotein as biochemical markers of hepatocarcinogenesis induced by 3'-methyl-4-dimethylaminoazobenzene treatment in rats. 168 18


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