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)

Tocopherol, a well known tissue anti-oxidant, given before local X-ray irradiation of 2 transplantable rat tumours was previously found to increase significantly the effect of irradiation. In the present study tocopherol did not influence the development of tumour necroses during growth of a transplantable rat hepatoma. The tumour tissue oxygenation of a transplantable rat sarcoma was neither found to be influenced by tocopherol. This suggests that an enhanced tumour radio-sensitivity by tocopherol is probably not explained by an influence on tumour cell oxygenation.
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PMID:Influence of tocopherol on tumour cell oxygenation. 68

Albumin carries fatty acids and has also been suggested to act as an antioxidant. In the present work, polyunsaturated fatty acids (linoleic, arachidonic, eicosapentaenoic and docosahexaenoic acids)--but not palmitic and oleic acid--inhibited growth of human hepatoma cells in low albumin concentration (0.5%). Growth inhibition by polyunsaturated fatty acids was prevented by albumin in a dose-related manner in the range 0.7-5.0%. Albumin also protected against growth inhibition following catabolism (by lipoprotein lipase) of very low density lipoproteins. Vitamin E strongly counteracted the inhibitory effect of polyunsaturated fatty acids. Vitamin E and albumin appeared to have additive effects in protecting against growth inhibition by polyunsaturated fatty acids. Indomethacin did not greatly modify the polyunsaturated fatty acids effect. Growth inhibition by polyunsaturated fatty acids, as well as the level of thiobarbituric acid reacting substances (a measure of lipid peroxidation) in growth media, increased with increasing number of fatty acids double bonds. Vitamin E and albumin prevented both thiobarbituric acid reacting substances formation and growth inhibition by polyunsaturated fatty acids. The results suggest that the concentrations of albumin and vitamin E in the incubation medium are essential when studying polyunsaturated fatty acids effects on cell growth.
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PMID:Growth inhibition of human hepatoma cells (HepG2) by polyunsaturated fatty acids. Protection by albumin and vitamin E. 131 55

The levels of vitamin A (retinol) and vitamin E were measured in the blood, in tissues of human hepatocellular carcinoma (HCC), and in adjacent liver parenchyma. The median values of vitamin A were 11.5 micrograms/g (ranging 0-82.5 micrograms/g) in HCC and 52.1 micrograms/g (ranging 0.4-895.2 micrograms/g) in normal liver tissues; the difference was statistically significant (p less than 0.05). By contrast, there was no significant difference in vitamin E levels between the two tissues. Although the levels of vitamin A were significantly lower in HCC in 10 patients, no significant difference was noted in the cellular retinol binding protein levels in the normal and malignant tissues. These results suggest that the decreased levels of vitamin A in HCC are not due to altered cellular retinol binding protein levels in tumors and the different vitamin A blood supply system. We conclude that either the decreased uptake of vitamin A, but not vitamin E, by HCC cells or the lack of vitamin A-storing cells in tumors might be responsible for the low levels of vitamin A in HCC.
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PMID:Levels of vitamin A and cellular retinol binding protein in human hepatocellular carcinoma and adjacent normal tissue. 255 57

A new parameter, the ratio of lipid peroxide and vitamins E and C [LPO/(VE + VC)], has been proposed and used to reflect the balance between lipid peroxidation and antioxidation capability of cancer patients and of healthy human controls. The effects of vitamins E, C, and selenium on the serum LPO level in mice bearing Ascites Hepatomas (H22) have also been examined. The results showed that the average of LPO/(VE + VC) ratios in cancer patients (135 cases) was significantly higher than that of the normal controls (222 cases). The authors suggest that this ratio might be used as one of the parameters for early diagnosis and prognosis of diseases (including cancers) caused by free radicals and lipid peroxides. The results also showed that antioxidants - Se(Na2SeO3, 1mg/kg) or vitamin E (5mg/kg) could markedly decrease the level of serum LPO in the tumor-bearing animals. A smaller dose of VE (1mg/kg) and doses of Vc up to 300mg/kg showed no effect on the serum LPO levels when given separately. However, synergistic effects were observed when any 2 out of 3 or three nutrients were given together. Those with three nutrients significantly lowered the serum LPO level. These antioxidants also inhibited the proliferation of tumour cells.
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PMID:The relationship between nutritional antioxidants and serum lipid peroxides in cancer patients. 256 28

Ascitic hepatoma cells of mice were incubated with three HPD. After the cell-bound HPD was treated by visible light, the product of membrane lipid peroxidation--malondialdehyde (MDA) was determined. The results showed that the MDA level increased with HPD concentration and exposure time, but it was unchanged in the control. Beta-carotene, a quencher of singlet oxygen, could inhibit the lipid photooxidation of the membrane of cell-bound HPD resulting in a decrease of MDA level which decreased with increase of beta-carotene concentration. Adding vitamin E in vitro and vivo, formation of the product of membrane lipid peroxidation of cell-bound HPD by light was inhibited and the MDA level decreased with the increase of vitamin E concentration. These results show that the singlet oxygen, produced by HPD bound cells following light activation, reacts directly with the polyunsaturated fatty acids on cell membrane to produce lipid peroxides leading to cellular damage.
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PMID:[Mechanism of cell damage by hematoporphyrin derivatives (HPD) plus light--I. Photooxidation of hepatoma cell membrane by HPD plus light]. 295 83

Lipid peroxidation of microsomal membranes isolated from rat liver, and Morris hepatomas 9618A (slow-growing) and 3924A (fast-growing) was induced by superoxide radicals generated by the action of xanthine oxidase on xanthine. The peroxidation, measured as malondialdehyde and lipid hydroperoxide formation, was optimized with regard to iron concentration and chelation of iron by ADP. In such conditions hepatoma microsomes catalyze lower rates of lipid peroxidation than the normal counterpart. However, while microsomes from hepatoma 3924A show a marked decrease in both the malondialdehyde and hydroperoxide production rates, microsomes from hepatoma 9618A differ moderately from the control, mainly in the long-term production of hydroperoxides. It is also reported here that the 9618A microsomes partially lack cytochrome P-450 (about 40% deficiency), but they have a fatty acid composition similar to that of control. No differences were found in the content of vitamin E between normal and hepatoma 3924A microsomes. Moreover, induction of vitamin E deficiency in hepatoma 3924A microsomes does not influence the rate of either malondialdehyde or lipid hydroperoxide production. On the basis of these results and previous data on the lipid composition of hepatoma 3924A microsomes it is proposed that the high resistance to superoxide-dependent lipid peroxidation of hepatoma 3924A microsomes is related to the low substrate availability rather than the content of membrane antioxidants; and a limitation only in the propagation phase characterizes the hepatoma 9618A microsomal lipid peroxidation and would be due to the partial deficiency of the endogenous propagating agent, cytochrome P-450.
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PMID:Superoxide-dependent lipid peroxidation and vitamin E content of microsomes from hepatomas with different growth rates. 298 56

Cell growth using homocysteine as a source of cysteine-sulphur requires two enzymes, cystathionine synthase (CS) and gamma-cystathionase (CT). The second of these enzymes, CT, is apparently present in most cell lines regardless of their tissues of origin, since most cells can grow in vitro in the absence of cystine if they are provided with cystathionine, the intermediate in the pathway. Likewise, homocysteine will support the growth of many human cells. However, of a wide range of rodent cells, only well-differentiated rat hepatoma cells were found to grow using homocysteine in place of cystine. It is shown that cell growth in homocysteine-medium correlates well with the presence in the cells of detectable levels of CS. Furthermore, in cells able to grow in homocysteine-medium, it is possible to demonstrate the homocysteine-dependent trans-sulphuration of serine to cysteine. Growth in homocysteine-medium is not dependent on the release of preformed cysteine from disulphide complexes with serum proteins. In cell hybrids, and in 'dedifferentiated' variants of rat hepatomas, CS, but not CT, is subject to extinction coordinately with well-characterized liver-specific traits. For rodent cells, homocysteine-medium thus acts as a selective medium requiring the expression of a single liver-specific trait, CS. In addition it is shown that, in certain hepatoma variants, CS is regulated co-ordinately with a urea-cycle enzyme (carbamoyl phosphate synthetase I) by glucocorticoids and cyclic-AMP. Cell death through cysteine starvation is briefly considered. The immediate cause of death is apparently an insufficient supply of reduced glutathione. Selenium and vitamin E assist cell growth when the supply of cysteine is limiting.
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PMID:Characterization of cystathionine synthase as a selectable, liver-specific trait in rat hepatomas. 379 84

Measurements of the absolute rate constants for the reaction with peroxyl radicals of alpha, beta, gamma and delta-tocopherol and several model compounds are described. The peroxyl radicals were obtained either by the autoxidation of styrene or by the flash photolysis of di-t-butyl ketone in an oxygen-saturated environment. The kinetic data are discussed in stereoelectronic terms. Vitamin E and total lipid-soluble, chain-breaking antioxidant concentrations in some normal and cancerous tissues have been measured. In human blood plasma and erythrocyte ghost membranes vitamin E is the major, and possibly the only, chain-breaking antioxidant. Lipid extracts of Novikoff ascites hepatoma cells contain considerably more vitamin E relative to lipid than do extracts of normal rat liver. These tumour lipids contain relatively fewer highly unsaturated fatty acids and are present at lower lipid/wet tissue ratios than the normal liver lipids. A number of unresolved problems relating to the action of vitamin E in vivo are discussed.
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PMID:Vitamin E as an antioxidant in vitro and in vivo. 655 6

We have established an experimental model of oral contraceptive-induced hepatocellular carcinomas (HCCs) in female Wistar rats, revealing that ethynylestradiol (EE) and norethindrone acetate have actions as both initiators and promoters. The present time-sequence study was undertaken to clarify the role of free radicals in estrogen induction of HCC by measuring detoxifying enzyme activities and levels of 8-hydroxydeoxyguanosine (8-OH-dG) and by assessing the effects of concomitant vitamin C, vitamin E or beta-carotene administration on hepatocarcinogenesis. During 12 months oral administration of EE (0.075 or 0.75 mg/day), the 8-OH-dG levels reached peak values after 1 month, when they were significantly elevated as compared with the controls. Glutathione peroxidase demonstrated a tendency to decrease. Histologically, pre-neoplastic lesions assessed by immunohistochemical staining for placental glutathione S-transferase (GST-P) were first observed at 2 months in the groups given 0.075 and 0.75 mg/day of EE alone, with incidences of HCC at 12 months being 8.7% and 38.5% respectively. Combined administration of vitamins with 0.075 mg EE/day reduced the elevation of the 8-OH-dG levels. GST-P-positive lesions were first observed at 4 months in the vitamin E group and at 6 months in the vitamin C and beta-carotene groups. As compared with the value in the 0.075 mg EE alone group, vitamin administration significantly reduced the numbers of GST-P-positive foci after 12 months of treatment. The incidences of HCC at 12 months were 0% in the vitamin C group, 4.5% in the vitamin E group and 4.8% in the beta-carotene group, i.e. administration of the vitamins inhibited the development of GST-P-positive foci, with suppression of HCC. The results thus suggest that free radicals play an important role in the induction of HCC by estrogen.
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PMID:Role of reactive oxygen in synthetic estrogen induction of hepatocellular carcinomas in rats and preventive effect of vitamins. 772 63

Excretion of methylmalonic acid by vitamin E-deficient patients and decreased labeling of adenosylcobalamin (AdoCbl) from cyanocobalamin in vitamin E-deficient rats suggest an interaction of vitamins E and B-12. We studied this interaction in two human cell culture systems: foreskin fibroblasts and a hepatoma cell line (HepG2). We measured radiolabeling of AdoCbl and methylcobalamin from [57Co]hydroxycobalamin for 6 d in the presence and absence of linoleate (an oxidative stressor) and alpha-tocopherol. In both cell types, labeling of AdoCbl was lower in the presence of linoleate unless alpha-tocopherol was present. The decrease was accentuated by peroxidized linoleic acid; AdoCbl synthetic rate was inversely associated with thiobarbituric acid-reactive compound concentration. Subcellular partitioning of labeled cobalamin revealed less in mitochondria in the linoleate-stressed cells that were not treated with alpha-tocopherol. We conclude that lipoperoxidation reduces mitochondrial AdoCbl formation and that alpha-tocopherol exerts a protective effect in oxidatively stressed cells. We suggest that this subcellular deficiency in AdoCbl may be one mechanism by which vitamin E deficiency leads to neurologic injury. The mechanism seems primarily to involve an alteration in intracellular cobalamin distribution with perhaps a minor effect upon enzymes of AdoCbl synthesis.
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PMID:Alpha-tocopherol protects against a reduction in adenosylcobalamin in oxidatively stressed human cells. 839 65


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