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)

Selenium-75 selenite and technetium-99m sulphur colloid scans were performed on 38 South African Blacks with intrahepatic space-occupying lesions. Uptake of selenite was demonstrated in the 'cold area' on the sulphur colloid scan in 17 out of 19 patients with hepatocellular carcinoma, but in 16 patients with amoebic liver abscess there was no uptake of selenite in the 'cold area'. In 3 patients with secondary involvement in the liver, 2 had positive uptake of selenite in the affected region. 75Se selenite was found to be useful in the differential diagnosis of intrahepatic lesions.
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PMID:Radioactive sodium selenite in the differentiation of hepatic lesions. 19 48

The effect of methyl mercury and two selenium compounds have been studied in cell cultures. Methyl mercury in concentrations above 1 microM had a pronounced inhibiting effect on the growth of rat Morris hepatoma cells. Glucose and lactate uptake in relation to cell protein was appreciably stimulated by the organic mercury compound. Selenite in low concentration (0.5 microM) and seleno-di-N-acetyl glycine in thousandfold higher concentrations offered considerable protection against these effects of methyl mercury. The same selenite concentration (0.5 microM), which did not affect cell growth, caused an appreciable protection against methyl mercury (6 microM), even if it was added 3 days after methyl mercury. The methyl mercury inhibited the growth of human embryonic fibroblasts and the DNA-synthesis in the human lymphocytes. However, no protective effect of selenite were observed in these cell types. These results suggest that selenium compounds exert their protective effect through cell specific processes rather than by a direct chemical reaction between selenite and methyl mercury.
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PMID:The influence of selinium on methyl mercury toxicity in rat hepatoma cells, human embryonic fibroblasts and human lymphocytes in culture. 53 35

The distribution of selenate and selenite selenium in C57L/J mice during the progression of BW7756 murine hepatoma was investigated using intra-ocular injection with the oxyanions labeled with 75Se radioisotope. Comparison is made with the normal distribution of selenium studied by the RIXRF method. The trace elemental profiles, TEP, for the two oxidation states are compared in healthy and disease states. It has been found that the presence of tumor significantly changes the level of tracer in various uninvolved organs. These changes are prominent in the early growth phase of the tumor. The two oxidation states show differences in the TEP for kidney, spleen, stomach and testes.
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PMID:[75Se]selenite and [75Se]selenate fluctuations during the development of murine hepatoma. 139 86

We have compared some mechanisms involved in the defense against doxorubicin-induced free radical damage in rat hepatoma and glioblastoma cell lines and their doxorubicin-resistant variants presenting an overexpression of the multidrug resistance gene. Immediate in vivo production of malondialdehyde was minor and was not different in sensitive and resistant cells. Alpha-tocopherol was undetectable in all cell lines. Glutathione levels were not different in sensitive and resistant cells and these levels did not vary upon doxorubicin treatment. Resistant cells exhibited either a 50% decrease (hepatoma) or a 25% increase (glioblastoma) of glutathione-S-transferase activity. Glutathione reductase presented no important change upon acquisition of resistance. In contrast, selenium-dependent glutathione peroxidase activity was consistently 2-6-fold increased in the resistant cells, which suggests a magnification of protection mechanisms against hydroxyle radical formation from H2O2 in resistant cells. Depletion of glutathione levels by buthionine sulfoximine sensitized hepatoma resistant cells to doxorubicin, but had no effect on doxorubicin cytotoxicity to glioblastoma cells.
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PMID:Development of mechanisms of protection against oxidative stress in doxorubicin-resistant rat tumoral cells in culture. 196 16

The effects of selenium (Na2SeO3) on aflatoxin B1 (AFB1)-induced hepatic neoplasia were studied in the rat. Putative preneoplastic foci and nodules composed of basophilic, eosinophilic, and clear cells developed early. Basophilic foci were seen first; in the later stages basophilic and eosinophilic nodules predominated. At each stage the AFB1 + Se groups showed fewer and smaller foci and nodules than the AFB1 - Se group. The number of foci in the AFB1 + 3 ppm Se group and their mean area were smaller than those in the 6 ppm Se + AFB1 group. At the end of the experiment hepatocellular carcinoma (HCC) was found in 11/18 rats (61%) of the AFB1 - Se group. HCC was not found in either of the groups given AFB1 + Se. We conclude that Se had an inhibitory effect on the initiation and promotion stages of AFB1-induced preneoplastic foci and nodules. Se also prevented progression of these nodules to HCC even after cessation of AFB1 administration. The inhibitory effect of Se at 3 ppm was greater than at 6 ppm. The 6 ppm Se group also showed evidence of toxicity.
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PMID:Effect of selenium on aflatoxin hepatocarcinogenesis in the rat. 210 86

DBA/2 mice were fed for 16 weeks with Torula yeast-based synthetic diet containing various concentrations of selenium (Se). At 13th week, the mice were immunized with syngenetic L5178 Y lymphoma cells and their specific and non-specific tumor immune responses were examined 3 weeks after immunization. The results indicated that in mice fed with a diet containing 0.007 ppm Se, the serum Se level was extremely low (0.02 micrograms/ml). These Se-deficient mice were unable to elicit normal tumor-specific immune responses. Both the specific proliferation of T cells in MLTC and tumoricidal activity of CTL were very much depressed. In addition, these mice also showed impaired NK and LAK cell activity. The effects of Se supplementation varied depending on the amount of Se given. When 0.170 ppm Se was added to the low Se diet, all the immune parameters examined were restored to the normal level. When 0.567 ppm Se was added, however, the tumor immune responses remained as low as those in Se-deficient mice. This study implies that the prevalence of primary hepatocellular carcinoma in areas where Se is deficient has a profound immunological basis. Se supplementation is obviously indicated for cancer prevention in these areas but the amount of Se supplied is crucial.
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PMID:[Effects of selenium deficiency and supplementation on tumor immune response in mice]. 227 20

Glutathione S-transferases play a central role in drug detoxification and have been implicated in the sensitivity of tumour cells to anticancer drugs. In this study, glutathione S-transferase (GST) isozyme expression in normal and tumour tissue from human lung, colon, stomach, breast, kidney and liver tissue has been quantified using sensitive and subunit specific radioimmunoassays (RIA), together with Western blot analysis and measurement of substrate metabolism. Glutathione S-transferase pi was the predominant GST in the majority of the tumours examined. The concentration of this enzyme was increased significantly in tumour tissue relative to normal lung, colon, and stomach tissue. A strong correlation was observed (r = 0.77, P less than 0.01) between GST activity and GST pi levels in those tumour samples. The concentrations of the alpha class GST, the predominant isoenzymes in normal stomach, kidney and liver, decreased dramatically in tumour tissue from these organs. Western blot analysis revealed the presence of novel polypeptides that cross-reacted with antisera raised against alpha and mu class GST. Our data demonstrates that although GST pi is the predominant GST isoenzyme in many tumours, significant levels of the other GST subunits are also present and collectively can represent a significant proportion of the GST content. Therefore the properties of all the GST isoenzymes need consideration when assessing the role of these proteins in drug resistance. Selenium-dependent glutathione peroxidase, an enzyme activity also implicated in the mode of action of certain antitumour agents, was also studied and shown to be the predominant glutathione-dependent peroxidase in all tumours except the hepatoma.
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PMID:Glutathione S-transferase and glutathione peroxidase expression in normal and tumour human tissues. 231 Nov 89

The effects of selenomethionine (SeMet) on the growth of 17 cultured cell lines were studied. SeMet in the culture medium of three hepatoma cell lines promoted cell growth at subcytotoxic levels (1-20 microM), but the growth of malignant lymphoid and myeloid cells was not stimulated. L-SeMet was cytotoxic to all 17 cell lines when assayed after culture for 3-10 days. A 50% growth inhibition was observed by 30-160 microM-SeMet in a culture medium containing 100 microM-methionine. SeMet cytotoxicity to normal (fibroblasts) and malignant cells was rather similar, excluding specific antineoplastic cytotoxicity. Cytotoxicity was increased by decreasing concentrations of methionine. The DL form of SeMet was less cytotoxic than the L form. L-SeMet was metabolized to a selenium analogue of S-adenosylmethionine approximately as effectively as the natural sulphur analogue methionine in malignant R1.1 lymphoblasts. Concomitantly, S-adenosylmethionine pools were decreased. This occurred early and at cytotoxic SeMet levels. Methionine adenosyltransferase activity was not altered by SeMet treatment. ATP pools were not affected early, and decreases in the synthesis of DNA and protein took place late and were apparently related to cell death. RNA synthesis was slightly stimulated at low cytotoxic SeMet levels by 24 h, but was markedly inhibited after 48 h. The SeMet analogue of S-adenosylmethionine could be effectively utilized in a specific enzymic transmethylation. Neither S-adenosylhomocysteine nor its selenium analogue accumulated in the treated cells. These findings together suggest a direct or indirect involvement of S-adenosylmethionine metabolism in SeMet cytotoxicity, but exclude a gross blockage of transmethylations.
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PMID:Effects of selenomethionine on cell growth and on S-adenosylmethionine metabolism in cultured malignant cells. 233 86

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

Three protocols were used to determine the effects of dietary selenium concentration on the development of gamma-glutamyl-transpeptidase (GGT)-positive foci and hepatocellular carcinoma induced by either diethylnitrosamine (DEN) or N-acetylaminofluorene in rats. In the first experiment, foci were induced by a carcinogenic dose of DEN (100 mg/kg body weight, p.o.) at 20-22 h after two-thirds partial hepatectomy. One wk after DEN administration, during which time 0.1 ppm (representing a control level), 3.0, or 6.0 ppm selenium as Na2SeO3 was fed for 8 or 16 wk, at which time focal analysis was conducted using quantitative stereology. The results demonstrated that 3.0 and 6.0 ppm dietary selenium, initiated 1 wk following carcinogen administration, decreased focal growth rate without affecting the number of GGT foci compared to 0.1 ppm selenium. Decreased focal growth was temporary and reversible with 6.0 ppm selenium which may be related to chronic selenosis observed after 16 wk of 6.0 ppm selenium feeding. A second experiment involved a noncarcinogenic dose of DEN (25 mg/kg body weight, p.o.), then 0.1 or 6.0 ppm selenium feeding for 8 wk, followed by 0.05% phenobarbital (PB), a liver tumor promoter in a diet containing 0.1 ppm selenium. Analysis of GGT foci at 5 or 8 wk of PB feeding indicated that 6.0 ppm selenium caused a trend towards an increase in the number of foci/cm3 of liver and mean focal volume and a significant increase in GGT focal volume as a percentage of liver volume by 8 wk of PB feeding. Thus, high dietary selenium concentrations prior to PB enhance the tumor-promoting ability of PB. In a third experiment, using male Fischer 344 rats (150 g), 0.1 or 6.0 ppm selenium was fed concurrently with 0.02% AAF which was fed in a cyclic regimen. After 4 cycles, where 1 cycle equalled 4 wk of AAF, followed by 1 wk of control diet (0.1 ppm selenium), 6.0 ppm selenium significantly decreased the mean focal volume and focal volume as a percentage of liver volume, while not affecting the number of foci/cm3 of liver, again indicating a selenium effect on focal growth while not affecting the number of "preneoplastic" lesions in the liver. Six ppm selenium feeding after AAF treatment had no effect on the percentage of incidence of hepatocellular carcinoma (100%) but did cause a significant decrease in the percentage of liver volume occupied by macroscopic subcapsular liver lesions compared to 0.1 ppm selenium.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of dietary selenium concentration on the development of enzyme-altered liver foci and hepatocellular carcinoma induced by diethylnitrosamine or N-acetylaminofluorene in rats. 286 4


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