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)

Long-Evans Cinnamon (LEC) rats are autosomal recessive mutants that develop hepatitis and hepatocellular carcinoma. Because copper accumulates in the livers of these rats, and some of their clinical and pathological features are similar to those of patients with Wilson's disease, LEC rats are proposed as an animal model of Wilson's disease. It has been thought that unbound copper generates free radicals, which act as hemolytic and hepatocytotoxic agents. To examine the effects of vitamin E as an antioxidant on hereditary hepatitis in LEC rats, we fed 3-week-old rats for 25 weeks either vitamin E-deficient, control, or vitamin E-supplemented diets which contained < 0.01 mg of total tocopherols, 2 mg of d,l-alpha-tocopheryl acetate (2 I.U.), and 58.5 mg of d,l-alpha-tocopheryl nicotinate (50 I.U.), respectively, per 100 mg of feed. In males, body weight loss was first observed in the vitamin E-deficient group, and mean ages at which jaundice occurred were in the order: deficient younger than control younger than supplemented groups. The ages when plasma glutamic oxaloacetic transaminase and glutamic pyruvic transaminase activities began to increase sharply and peaked followed the same order. Thus, it is likely that free radicals are involved in jaundice and hepatitis in LEC male rats, and they are a model for studying the relationship of copper, free radicals, and hepatitis. Conversely, in females, no apparent differences in clinical and biochemical changes were observed among the three groups. Causes for the discrepancy between the sexes remain to be clarified.
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PMID:Effects of dietary vitamin E on clinical course and plasma glutamic oxaloacetic transaminase and glutamic pyruvic transaminase activities in hereditary hepatitis of LEC rats. 845 79

Dietary intake of fish oils, rich in the polyunsaturated fatty acids (PUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), has given inconsistent results as to their influence on the plasma fibrinogen level (1, 2, 3, 4, 5, 6). In the present study we have examined the effects of various fatty acids, the PUFAs and the saturated fatty acid palmitic acid (PA), alone or combined with the antioxidant vitamin E (Vit.E), on the fibrinogen concentration in the growth medium of human hepatoma (HepG2) cells. Vit.E alone decreased the amount of fibrinogen in the medium in a dose dependent fashion, where fibrinogen was measured as Fibrinopeptide A (FPA) releasable by thrombin. EPA and Vit.E decreased the amount of fibrinogen additively. PUFAs alone increased the fibrinogen concentration in a dose dependent manner. PUFAs combined with a fixed dose of Vit.E decreased the fibrinogen concentration, also dose dependently. OA and PA had an inhibitory effect, both alone and combined with Vit.E. These results indicate that Vit.E may be necessary for PUFAs to have a fibrinogen lowering effect, whereas both OA and PA apparently may decrease the fibrinogen concentration in the cell medium of HepG2 cells, both alone and combined with Vit.E. Possibly, peroxidation of the PUFAs may increase the fibrinogen production, that may be counteracted and reversed by the simultaneous presence of Vit.E.
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PMID:Effects of various fatty acids alone or combined with vitamin E on cell growth and fibrinogen concentration in the medium of HepG2 cells. 857 40

An important role in O2 sensing has been assigned to microsomal and membrane-bound b-type cytochromes which generate regulatory reactive O2 species (ROS). Recently, ROS have been shown to suppress the in vitro synthesis of erythropoietin (Epo). We investigated the potential of the antioxidant vitamins A, E and C to enhance renal and hepatic Epo production. Renal effects were studied in isolated serum-free perfused rat kidneys. In control experiments without antioxidant vitamins, Epo secretion amounted to 441 +/- 23 mU/g kidney (mean +/- SEM, N = 5) during the three hour period of hypoxic perfusion (arterial pO2 35 mm Hg). Epo secretion significantly increased to 674 +/- 92 mU/g kidney (N = 7) when vitamins A (0.5 microgram/ml), E (0.5 microgram/ml) and C (10 micrograms/ml) in combination were added to the perfusion medium. The effects of the single vitamins were studied in Epo-producing hepatoma cell cultures (lines HepG2 and Hep3B). Vitamin A induced a dose-dependent increase (half-maximal stimulation at 0.2 microgram/ml) in the production of immunoreactive Epo during 24 hours of incubation (such as 680 +/- 51 U Epo/g cell protein in HepG2 cultures with 3 micrograms/ml retinol acetate compared to 261 +/- 15 U/g in untreated controls; N = 4). In contrast, vitamin E (tested from 0.05 to 500 micrograms/ml) and vitamin C (tested from 2 to 200 micrograms/ml) did not increase Epo production in hepatoma cell cultures. Thus, while vitamins E and C may have the potential to protect cells from oxidative damage, vitamin A exerts a specific stimulation of Epo production. Preliminary evidence suggests that this effect of vitamin A involves increased mRNA levels of hypoxia-inducible factor 1 alpha (HIF-1 alpha).
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PMID:Effects of antioxidant vitamins on renal and hepatic erythropoietin production. 902 29

The high incidence of hepatocellular carcinoma (HCC) in cirrhosis, where previous studies have indicated a severe reduction in several antioxidant vitamin factors, prompted us to compare plasma liposoluble vitamins with tocopherol content in healthy and neoplastic liver tissue in humans. This, with a view to a more positive preventive dietary approach, given the conflicting results obtained by liposoluble vitamin dietary supplementation in different malignancies. Eleven patients with cirrhosis, 18 patients affected by cirrhosis with HCC, and 10 patients with liver metastases (LM) from digestive tract adenocarcinomas were compared with controls who had undergone perlaparoscopic cholecistectomy. Plasma alpha- and beta-carotene, retinol and tocopherol, together with liver tocopherol, from both nonmalignant portions and malignant nodules of the same organ, were determined by high-performance liquid chromatography following a well-assessed technique. The results confirm a trend towards a reduction in circulating carotenoids and tocopherol in cirrhosis and in patients affected by cirrhosis with HCC. Tocopherol content in liver tissue is significantly decreased in cirrhosis (0.26 + 0.03 micromol/g prot., mean + SEM, P < .001) and in cirrhotic areas of the HCC group (0.31 + 0.02, P < .002), with respect to its content in liver specimens of healthy controls (0.46 + 0.03) and in healthy areas of the same organ in patients with LM (0.41 + 0.03). Tocopherol concentration is further reduced by 50% in malignant liver nodules of HCC, with respect to surrounding cirrhotic tissue, whereas in metastatic liver nodules from digestive neoplasms the tocopherol content is almost twice that of healthy surrounding areas. This unpredictable tocopherol behavior in liver specimens, of secondary as opposed to primary malignancies of the liver, affords further insight into the conflicting effects of liposoluble vitamins employed in the chemopreventive treatment of different malignant diseases, where hepatic tocopherol concentration show opposite trends: halved in primary HCC and doubled in LM of digestive adenocarcinomas, with respect to healthy controls.
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PMID:Hepatic tocopherol content in primary hepatocellular carcinoma and liver metastases. 921 53

Vitamin E (alpha-tocopherol) is a fat-soluble antioxidant that is transported by plasma lipoproteins in the body. alpha-Tocopherol taken up by the liver with lipoprotein is thought to be resecreted into the plasma in very low density lipoprotein (VLDL). alpha-Tocopherol transfer protein (alphaTTP), which was recently identified as a product of the causative gene for familial isolated vitamin E deficiency, is a cytosolic liver protein and plays an important role in the efficient recycling of plasma vitamin E. To throw light on the mechanism of alphaTTP-mediated alpha-tocopherol transfer in the liver cell, we devised an assay system using the hepatoma cell line McARH7777. Using this system, we found that the secretion of alpha-tocopherol was more efficient in cells expressing alphaTTP than in matched cells lacking alphaTTP. Brefeldin A, which effectively inhibits VLDL secretion by disrupting the Golgi apparatus, had no effect on alpha-tocopherol secretion, indicating that alphaTTP-mediated alpha-tocopherol secretion is not coupled to VLDL secretion. Among other agents tested, only 25-hydroxycholesterol, a modulator of cholesterol metabolism, inhibited alpha-tocopherol secretion. This inhibition is most likely mediated by oxysterol-binding protein. These results suggest that alphaTTP present in the liver cytosol functions to stimulate secretion of cellular alpha-tocopherol into the extracellular medium and that the reaction utilizes a novel non-Golgi-mediated pathway that may be linked to cellular cholesterol metabolism and/or transport.
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PMID:alpha-tocopherol transfer protein stimulates the secretion of alpha-tocopherol from a cultured liver cell line through a brefeldin A-insensitive pathway. 935 67

Chlorinated fatty acids represent a major fraction of extractable, organically bound chlorine in fish. After dietary intake such fatty acids may be transferred from the mother to the foetus through the placenta, and via breast milk to the child. In the present work we have studied the effect of chlorinated oleic acid on the growth of three widely differing types of cells in culture. Chlorinated oleic acid inhibited growth of Human Microvascular Endothelial Cells (HMVEC), Immortilized Human Kidney Epithelial (IHKE) cells, and human Hepatoma cells (HepG2). The order of potency was: HMVEC > IHKE > HepG2. Vitamin E counteracted the inhibitory effect of chlorinated oleic acid on HepG2 cells, but did not significantly affect the fatty acid effect on HMVEC or IHKE. Defatted serum albumin stimulated the growth of HMVEC and IHKE. With HMVEC there was no major interaction between the effect of albumin and chlorinated oleic acid on cell growth. In contrast, with IHKE albumin at low concentration abolished the growth inhibiting effect of chlorinated oleic acid and appreciably counteracted growth inhibition by the fatty acid of HepG2. We conclude that the growth modulation by chlorinated oleic acid and its interaction with vitamin E and albumin are cell specific.
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PMID:Growth modulating effects of chlorinated oleic acid in cell cultures. 976 23

The antioxidant defence system which plays a critical role in carcinogenesis is severely altered in aflatoxin B1 induced hepatocellular carcinoma conditions. In order to assess the antitumour activity of Semecarpus anacardium nut extract, a flavonoid containing drug, non-enzymic antioxidant levels were analysed in control and experimental animals. Plasma was analysed for uric acid, vitamin E and vitamin C. Glutathione, total thiols, non-protein thiols, vitamin E, vitamin C and cytochrome P450 were estimated in liver and kidney homogenates. Depletion of all these antioxidants were recorded in cancer conditions. These deleterious effects are controlled by the administration of Semecarpus anacardium nut extract. Following drug administration, there was a marked increase in antioxidant levels and a dramatic elevation in cytochrome P450 content. It can be concluded that the observed anticancer property of Semecarpus anacardium nut extract may also be explained by its strong antioxidant capacity and capability to induce the in vivo antioxidant system.
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PMID:Semecarpus anacardium L. nut extract administration induces the in vivo antioxidant defence system in aflatoxin B1 mediated hepatocellular carcinoma. 1043 69

Hepatitis C is emerging as a serious worldwide problem. In the United States the current mortality figures may triple in the next ten years, rivaling HIV. The disease has a latency of 10-30 years and symptoms or signs may not appear until cirrhosis is evident. Adequate diagnosis, including liver biopsy, is essential in assessing the current stage of the viral infection and the need for treatment. Hepatitis C may manifest as hepatic fibrosis, cirrhosis, hepatocellular carcinoma, lichen planus, glomerulonephritis, mixed cryoglobulinemia, or porphyria. The hepatic damage is due both to the cytopathic effect of the virus and the inflammatory changes secondary to immune activation. The use of the botanical components glycyrrhizin, catechin, silymarin and phytosterols, and the antioxidants N-acetylcysteine and vitamin E are reviewed for their efficacy in treating chronic hepatitis and affecting liver damage.
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PMID:Hepatitis C: epidemiology and review of complementary/alternative medicine treatments. 1046 47

Peroxisome proliferators are a class of hepatic carcinogens in rodents and are proposed to act in part by increasing reactive oxygen species such as hydrogen peroxide. We previously showed that treatment of rats with ciprofibrate, a peroxisome proliferator, results in increased hepatic nuclear factor-kappaB (NF-kappaB) DNA binding activity. In this study, we have examined the link between peroxisome proliferators and NF-kappaB activation in hepatoma cell lines to test whether increased nuclear NF-kappaB levels activate NF-kappaB-regulated genes and to determine the mechanism of NF-kappaB activation. Electrophoretic mobility shift assays demonstrated NF-kappaB induction by ciprofibrate in peroxisome proliferator-responsive H4IIEC3 rat hepatoma cells but not in peroxisome proliferator-insensitive HepG2 human hepatoma cell lines. In addition, we found that stably transfected NF-kappaB-regulated reporter genes were activated by ciprofibrate in H4IIEC3 cells. This reporter gene activation was blocked by the antioxidants N-acetylcysteine and vitamin E. These studies suggest that hepatocytes are at least partially responsible for peroxisome proliferator-mediated hepatic NF-kappaB activation, and support the possibility that this activation is dependent upon reactive oxygen species.
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PMID:Activation of nuclear factor-kappaB by the peroxisome proliferator ciprofibrate in H4IIEC3 rat hepatoma cells and its inhibition by the antioxidants N-acetylcysteine and vitamin E. 1064 51

T-2 toxin is a secondary fungal metabolite produced by various species of Fusarium. It is capable of killing cells by causing extensive damage to the cellular membrane. In this study, cytotoxicity of T-2 toxin in combination with different antioxidant materials, including vitamin C (vit. C), vitamin E (vit. E) and selenium (sel) was investigated in vitro using the neutral red cytotoxicity assay. Eleven primary and transformed cell lines established from different tissues were used in pre-test experiments to identify the most sensitive and resistant lines by measuring the half lethal concentration (LC(50)) of the toxin. Three cell lines including human gingival fibroblast (HGF), the most sensitive (LC(50)=0.25 ng/ml), human colorectal adenocarcinoma (SW742), the most resistant (LC(50)=5.5 ng/ml) and human hepatoma (HepG2), with median susceptibility (LC(50)=2 ng/ml) were selected to investigate the inhibitory effects of the antioxidant agents, on cytotoxicity of T-2 toxin. Our results demonstrated that co-incubation of cell lines with different concentrations of T-2 toxin and antioxidants decreased significantly, but did not totally inhibit, the cytotoxicity of T-2 toxin (P<0.001). These findings suggest that in addition to lipid peroxidation, which is inhibited by antioxidants, other unidentified mechanism(s) seem to be involved in cytotoxicity of T-2 toxin.
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PMID:In vitro inhibitory effects of antioxidants on cytotoxicity of T-2 toxin. 1081 49


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