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)

Enzyme deviations in injured livers were studied by analyzing isozyme patterns of phosphorylase using a newly developed electrophoretic method, which separates six molecular species of this enzyme, i.e. M,FM,F,L,L', and FL'. In hepatic injuries caused by CCl4 and galactosamine intoxications of rats, F appeared in early stages and L' (and FL') in later stages of the injuries with a concurrent decrease or loss of L, which is a sole isozyme component of adult liver. In injured livers of patients with hepatitis and cirrhosis of the liver, increases in FL' activity were also found. Appearance of F was found only in hepatocellular carcinoma. The results obtained with phosphorylase isozyme analysis support the idea that an undifferentiated gene expression takes place in the injured livers of non-malignant hepatic disorders.
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PMID:Studies of liver phosphorylase in hepatic injuries II. Alteration in isozyme pattern. 15 93

Liver carcinogenesis with a single dose of aflatoxin B1 (7 mg/kg body weight) has been investigated in a group of female Wistar strain rats by repeated biopsies and necropsies. Another group received a subsequent intoxication with carbon tetrachloride by inhalation (approximately 200 doses) and another one was overloaded with riboflavin (25 parts/10(6) in drinking water). The frequency of hepatomata was almost equal in the aflatoxin and aflatoxin-carbon tetrachloride group. It was lowere in the riboflavin-aflatoxin group. In these 3 groups cirrhosis was never present in neoplastic livers. Megalocytosis was the first lesion observed. All tumoral livers had previous or concomitant megalocytosis. This modification was about as frequent, intense and widespread in aflatoxin-CCl4 and aflatoxin groups but appeared much earlier, as did the first hepatoma, in the aflatoxin-CCl4 group. It was less frequent, less intense and less widespread in the riboflavin-aflatoxin group than in the aflatoxin group. There was also a lower frequency of hepatomata in the riboflavin-aflatoxin group, but the difference was not significant due to the too small number of animals involved. The facts are not a proof of the existence of an obligatory link between megalocytosis and carcinogenesis since a slight megalocytosis was observed in the riboflavin group not affected by the neoplastic process. However, the simplest explanation of our results would be to consider that the potential tumour cells are located among the megalocytic cells, without admitting that every megalocyte is obligatorily a precancerous cell. CCl4 seems to act in shortening the time of appearance of megalocytosis. The protective effect of riboflavine should be regarded with more caution.
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PMID:Influence of carbon tetrachloride or riboflavin on liver carcinogenesis with a single dose of aflatoxin b1. 17 84

A dose of 10 or 20 mg of N-butylnitrosourea (BNU) dissolved in 50% ethanol was administered by a gastric tube to 6-week-old male ICR/JCL strain mice and they were sacrificed 15 months later. One of 18 animals developed a hepatoma, but none of the mice given CCl4 in 0.1 ml of 50% oliver oil subcutaneously at the right thigh developed hepatoma. However, a marked enhancement of hepatoma induction was observed in mice injected with CCl4 one day before the single intragastric administration of BNU, with 12 out of 28 mice developing one or more hepatomas (average 3.2/mouse) ranging in diameter from 0.5 to 1.5 cm. By extending the administration interval between CCl4 and BNU to 1 week or 1 month, or by reversing the order of administration, the hepatotumorigenic action was virtually lost. There was no occurrence of hepatoma but a predominant development of leukemia, of either thymic or nonthymic origin, was observed in mice of younger age treated with CCl4 one day before continuous oral administration of BNU (1 mg/day/mouse). It is thus concluded that the preparative (cocarcinogenic) action of CCl4 is indispensable for hepatotumorigenesis with a single large dose of BNU.
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PMID:Preparative action of carbon tetrachloride in liver tumorigenesis by a single application of N-butylnitrosourea in male ICR/JCL strain mice. 17 59

Female inbred BUF rats bearing intrahepatically transplanted hepatomas (5123 or 19) were subjected to acute exposure to a variety of hepatotoxic agents (actinomycin D, aflatoxin B1, CCl4, dimethylnitrosamine, ethionine, puromycin, or sparsomycin) or of stimulatory agents (hydrocortisone, phenobarbital, or whole-body X-ray). The responses in terms of changes in polyribosomes and protein synthesis (in vitro and in vivo) of host liver and hepatoma were evaluated. The responses of the host livers and hepatomas to the different agents varied. In general, the host livers responded much more than did the hepatomas. Of the two hepatomas, hepatoma 19 responded less (particularly in terms of polyribosome changes) than did hepatoma 5123. In a few experiments, different doses of actinomycin D, ethionine, or sparsomycin were used and in all instances the host livers responded more than did the hepatomas.
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PMID:Effect of inhibitory and stimulatory agents on protein synthesis in hepatomas and host livers of rats. 28 39

In order to know the clinical significance of serum ribose-5-phosphate isomerase (RPI), the activity of this enzyme was determined in sera of normal subjects and patients with hepatic disorders or malignant tumors. Experimentally, the enzyme activity in sera and liver tissue was followed in rats with acute hepatic damage induced by carbon tetrachloride (CCl4) or rats with hepatoma induced by 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB). The following results were obtained: 1) Serum RPI activity increased markedly in rats with CCl4-induced liver damage, whereas the activity in liver tissue decreased, both being related with reciprocally. 2) In the early phase of acute hepatitis, serum RPI activity increased and gradually decreased thereafter. No significant increase was observed in other hepatic disorders. 3) Both serum and liver RPI activity increased in rats with hepatoma induced by 3'-Me-DAB. 4) An increase in serum RPI activity was seen in higher percentage in cancer patients. Higher enzyme activity and its higher incidence were observed in patients with hepatic metastasis or primary hepatoma than in patients without metastasis. From these results it is concluded that serum RPI activity as a diagnostic aid is useful in estimating clinical course of hepatic disorders and also in diagnosing malignant tumors, especially in substantiating a diagnosis of metastasis to the liver.
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PMID:[Experimental and clinical studies on ribosephosphate isomerase (author's transl)]. 52 26

3H-Demethylphalloin (3H-DMP) a cyclopeptide very similar to phalloidin is taken up by isolated hepatocytes in vitro. Hepatocytes prepared from newborn animals are less sensitive to phalloidin. Their uptake of 3H-DMP is about one tenth of that of cells from adult animals. Ascites hepatoma cells, known to be insensitive to phalloidin took up negligible amounts of 3H-DMP. Cells prepared from regenerating livers took up insignificantly lower amounts of the toxin than in hepatocytes from adult animals. Treatment of hepatocytes with low concentrations of trypsin was found to switch off the phalloidin sensitivity in a reversible manner. This inhibition is due to a reduced uptake of 3H-DMP. Pretreatment of animals with CCl4, known to reduce the sensitivity to phalloidin, also decreases the uptake of 3H-DMP in isolated hepatocytes. Various agents, drugs and reagents were found to inhibit the response of isolated hepatocytes to phalloidin. All these compounds (bile acids, rifampicin, silybin, DIDS, glutardialdehyde, bromosulphophthalein, fusidic acid, antamanide, novobiocin) inhibit also the uptake of 3H-DMP in isolated hepatocytes. The results confirm our working hypothesis, presented in several previous papers, that decreased sensitivity to phalloidin is probably due to a reduced or blocked uptake of the toxin.
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PMID:Inhibition of 3H-demethylphalloin uptake in isolated rat hepatocytes under various experimental conditions. 55 48

The phenolic method was employed to isolate 2--3 microgram/ml of nucleic acid from rat blood serum. Electrophoresis in an 8% polyacrylamide gel revealed 3 fractions corresponding to 7--9S RNA, and a highly polymer material retained at the beginning of the gel. The blood of the rats with transplanted Zajdela's hepatoma, pre-treated with CCl4, contained an immunodepressive nucleic factor (5S DNA) undetected in healthy animals. This factor may contribute to the suppression of antitumor immunity. The nucleic factor was not detected following treatment with CCl4 alone. It is suggested that the liver hinders nucleic factor transfer from the tumor environs into the blood.
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PMID:Low-molecular weight nucleic acids in the blood of rats with Zajdela's hepatoma. 72 91

Reports of an increase in a serum epoxide hydrolase (sEH), immunochemically related to microsomal EH in humans and rats with hepatocellular carcinoma (HCC), suggested its use as a serum marker for this disease. We have now measured sEH levels (as either immunochemically determined content or enzyme activity) in a number of human and experimental models of liver disease. sEH was elevated above the normal range in at least 50% of individuals with HCC, including: 3 of 6 northern Californians; 4 of 7 Koreans with hepatitis B-associated HCC; hepatitis B-associated HCC in woodchucks; and male rats receiving chronic treatment with aflatoxin B1 or ciprofibrate. sEH was rarely elevated in other forms of chronic liver disease. Only 2 of 9 Koreans with hepatitis B-associated cirrhosis, 1 of 8 carriers, but none with chronic active hepatitis or infection with no apparent liver disease had elevated sEH. In addition, no elevations were found in woodchucks with noncancerous viral hepatitis. In aflatoxin B1- and M1-treated rats sEH was not elevated in those with only hyperplastic foci or hepatocellular adenomas, and in two rat initiation-promotion protocols sEH was elevated only in those rats which received the entire set of treatments. sEH was also increased during acute hepatotoxicity in rats treated with CCl4 or 1,2-dibromo-3-chloropropane. The mechanism of increase in sEH during hepatocarcinogenesis appears to be different from that of other markers of HCC, for in the Korean patients, there was no correlation between sEH concentrations and those of alpha-fetoprotein or ferritin, nor was there a correlation with alpha-fetoprotein concentrations in the aflatoxin-treated rats. Furthermore, the increase in sEH does not correlate with induction of microsomal EH in the liver of experimental animals. Studies to date indicate that sEH is selective for HCC and severe hepatonecrotic injury, and may be of some use in the diagnosis of HCC, particularly as a complement to other serum markers.
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PMID:Serum epoxide hydrolase (preneoplastic antigen) in human and experimental liver injury. 133 49

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

To investigate molecular responses to lipid peroxidative stimuli in neoplastic cells, lipid peroxidation was induced in liver of rats bearing 3'-methyl-4-dimethylaminoazobenzene-induced hepatocellular carcinoma by injecting a high dose of carbon tetrachloride (CCl4), a strong lipoperoxidative reagent. Normal rat livers with or without CCl4 treatment served as controls. CCl4 administration markedly provoked fatty metamorphosis, visualized by oil red O staining, in normal livers while minimal fatty changes were seen in hepatocellular carcinomas, where necrosis was often observed instead. After CCl4 treatment, the thiobarbituric acid values (representing levels of lipid peroxides in the tissue) were increased two-fold in the untreated normal liver, but were unchanged in the cancer tissue. Levels of vitamin C, an acutely reactive antioxidant, measured by high-performance liquid chromatography were not influenced by the CCl4 injection in the cancer tissue whereas a significant decrease was evident in normal livers. The total fatty acid content, measured by gas chromatography, was significantly lower in the cancer tissue than in the normal liver while the ratio of polyunsaturated fatty acids (PUFAs) in total fatty acids was little changed. Resistance of hepatocellular cancer cells to fatty metamorphosis and their susceptibility to necrosis induced by free radicals may be due to the paucity of the target PUFAs in their cell membrane fraction, resulting in low levels of lipid peroxides. Peroxidation of PUFAs might act as a "shock absorber" against free radical-induced toxic cell death in normal cells.
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PMID:Different effects of carbon tetrachloride on carcinogen-induced hepatocellular carcinoma and normal liver of the rat: lowered lipid peroxidation and accelerated necrosis in cancer. 190 97


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