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)

This study was conducted to determine and compare serum trace metal levels in viral hepatitis-associated chronic liver disease. Of 98 patients aged 43 (+/- 13) [mean (+/- SD)] years, 83 (85%) were seropositive for hepatitis B surface antigen (HBsAg) and 15 (15%) were seropositive for anti-hepatitis C virus (HCV). Twenty-five patients had chronic persistent hepatitis, 32 chronic active hepatitis, 21 post-necrotic cirrhosis, and 20 hepatocellular carcinoma. Determination of fasting serum trace metal levels (zinc, copper, calcium, magnesium, and phosphorus) was performed after the patients had been on a 2-day diet containing 10-12 mg zinc/day. Compared to healthy volunteers (n = 30), serum zinc levels were significantly decreased in patients with chronic active hepatitis, cirrhosis, and hepatocellular carcinoma (P < or = 0.0001), and copper levels were significantly elevated only in patients with hepatocellular carcinoma (P < 0.0001). The overall serum levels of calcium, magnesium, and phosphorus were within normal ranges, and levels of calcium and magnesium correlated with serum zinc (P = 0.01-0.03). Serum zinc levels correlated with bilirubin, albumin, and cholesterol (P = 0.0004 < or = 0.0001), but not with daily urinary zinc excretion. Serum copper levels correlated with alkaline phosphatase and gamma-glutamyltransferase (P = 0.008-0.0001). These results suggested that changes in liver cell pathology compounded by functional impairment may alter the metabolism of trace metals, in particular, zinc and copper. The possible relationship of these changes to the pathogenesis of chronic liver disease is discussed.
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PMID:Serum trace metals in chronic viral hepatitis and hepatocellular carcinoma in Thailand. 800 May 10

Copper contents (Cu) in bodies and serum ceruloplasmin (Cp) were assayed in patients with liver cirrhosis (LC) and hepatocarcinoma (HCC) with atomic absorption and other methods. The results were shown as follows: 1. The mean levels of serum Cp and urine Cu in LC were higher than those of normal (P < 0.05 and 0.01). 2. Serum Cu and Cp levels were consistently high in HCC. Urine Cu level was also elevated and had positive correlation with that of serum Cu (r = 0.567, P < 0.01). 3. Cirrhotic liver Cu content was almost the same as that of pericarcinomatous liver Cu, being higher than that of normal and carcinomatous liver. 4. Hair Cu level in both LC and HCC was apparently lower than that of normal subjects. 5. Serum Cu level in patients with tumor more than 5 cm in size was higher than that in patients with tumor less than 5 cm (P < 0.05). 6. Serum Cu level decreased along with the reduction of tumor size after treatment. 7. Serum Cu and Cp levels may be used as markers for detection of HCC, especially for AFP-negative HCC. Serum Cu estimation is valuable in assessment of the therapeutic effect and prognosis in patients with HCC.
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PMID:[The changes in copper contents and its clinical significance in patients with liver cirrhosis and hepatocarcinoma]. 807 Feb 91

1. The differentiation status of cells is considered to represent an important factor in determining the effects of toxic components. 2. Two rat hepatoma cell lines, MH1C1 and HTC, were used to study differences in the sensitivity to two toxic metals: copper and zinc. 3. The differentiation of the cell lines was characterized using light microscopy, growth pattern, gamma glutamyltransferase (GGT) activity and albumin production as parameters. 4. The MH1C1 cell line was described to be more differentiated. 5. Albumin production in the MH1C1 cells was significantly higher than in the HTC cells whereas the GGT activity was only slightly different. 6. Toxicity of Cu and Zn was compared. Zn appeared to be more toxic to the cells than Cu, when leakage of lactate dehydrogenase and potassium were measured, whereas both metals were equally toxic when expressed as DNA remaining after 24 hr. 7. The MH1C1 cell line appeared to be more sensitive to Cu and Zn than the HTC. 8. The two metals appeared to have different targets in the cell; Cu may affect the nucleus and Zn the cell membrane.
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PMID:Copper and zinc toxicity in two rat hepatoma cell lines varying in differentiation. 809 79

Long-Evans Cinnamon (LEC) rats which have an abnormal copper accumulation in the liver develop hereditary hepatitis and subsequent hepatocellular carcinoma (HCC). We studied the correlation of MR images of the HCCs developed in LEC rats and histopathological features. The HCCs of LEC rats had high intensity on T 1-weighted images and iso-low intensity on T 2*-weighted images. Histopathological examination showed that the HCCs were highly differentiated. Copper concentration in the HCCs was lower than that in the surrounding non-cancerous liver tissues. From these results, we suggest that copper accumulation may not be responsible for the high intensity of HCCs on T 1-weighted images.
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PMID:[MR images of the hepatocellular carcinoma in Long-Evans cinnamon (LEC) rats]. 810 51

The Long-Evans Cinnamon rat is a mutant strain that contracts hereditary hepatitis and, eventually, spontaneous hepatoma. Recently, abnormal copper accumulations in Long-Evans Cinnamon rat livers were shown to be genetically linked to the development of hepatitis. Because reduced glutathione and glutathione-related enzymes are known to play important roles in cellular resistance to transition metal toxicity, we determined the levels of reduced glutathione and glutathione-related enzymes in seven different tissues of Long-Evans Cinnamon and control Long-Evans Agouti rats. Of the enzymes examined, only hepatic glutathione peroxidase was markedly decreased in Long-Evans Cinnamon rats. Glutathione peroxidase content in the liver of Long-Evans Cinnamon rats was 39%, 53% and 58% of the control values at 9 (normal stage), 19 (acute hepatitis stage) and 27 (chronic hepatitis stage) wk of age, respectively. Northern-blot analysis revealed that messenger RNA levels of glutathione peroxidase in the livers of Long-Evans Cinnamon rats were about 40% of the control levels. The activity of glutathione S-transferase was slightly decreased in the livers of Long-Evans Cinnamon rats. These data suggest that the liver of the Long-Evans Cinnamon rat is poorly protected against active oxygen species, the production of which is enhanced in the presence of excess copper. Glutathione-reductase activity in the livers of Long-Evans Cinnamon rats increased to 166% and 148% of the control levels at 19 and 27 wk of age, respectively. No significant changes were observed in the activity of gamma-glutamylcysteine synthetase or in the content of total reduced glutathione in the liver of the Long-Evans Cinnamon rat.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Decreased expression of liver glutathione peroxidase in Long-Evans cinnamon mutant rats predisposed to hepatitis and hepatoma. 811 95

Cellular responses to copper, applied in concentrations varying from 0.5 to 200 microM Cu2+, were investigated in two different cell types: rat hepatoma cells (HTC) and primary cultured rat hepatocytes. Accumulation of 64Cu, copper (AAS) levels, cellular viability parameters (cell growth and proliferation, LDH leakage, total cell protein, K+ uptake, and ATP levels), and cell toxicity parameters (metallothionein (MT), glutathione (GSH) and superoxide dismutase (SOD)) were examined over 24 hr incubation periods. Accumulation of radiolabeled copper (applied copper concentrations: 15-200 microM Cu2+) showed a four-fold increase in HTC cells (0.88-3.45 nmol Cu/mg cell protein) and a three-fold increase in hepatocytes (4.94-14.66 nmol Cu/mg cell protein), although quantitative uptake in HTC cells was five times lower. Most of the copper accumulated in the hepatoma cells and hepatocytes was found predominantly in the particulate fraction (i.e., cell membranes and organelles), while only a small quantity was present in the soluble fraction (cell cytosol). Metallothionein concentrations in HTC cells were increased from 43 pmol/mg cell protein (0.5 microM Cu2+ application) up to 223 pmol/mg cell protein (200 microM Cu2+ application), whereas MT in rat hepatocytes were elevated from 139 pmol/mg cell protein to 546 pmol/mg cell protein over the same range of administered Cu2+. Metallothionein synthesis rendered both cell types well equipped to deal with increasing intracellular copper levels. In hepatocytes however, MT synthesis resulted in decreasing non-MT-associated copper levels in the cytosol for Cu administrations up to 100 microM. Above that point however, MT failed to stay in line with increasing cytosolic Cu levels, resulting in cytotoxic effects shown by changes in cell viability and GSH/SOD levels. In HTC cells MT synthesis suppressed the free Cu levels in the cytosol to below 0.1 nmol Cu/mg cell protein over the total range of copper concentrations applied. The results presented indicate that hepatoma HTC cells are more capable of dealing with high accumulated Cu levels than the better established rat hepatocytes. Furthermore, it is clear that comparison of these two cell types regarding their ability to respond on (sub)toxic Cu should be discussed with full consideration for the copper applications involved.
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PMID:Effects of copper on rat hepatoma HTC cells and primary cultured rat hepatocytes. 813 49

Molecular size exclusion (MSE), reversed-phase (RP), and anion-exchange (AE) high-performance liquid chromatography (HPLC) techniques were employed in combination with on-line radioactivity detection, in a study on the kinetic behaviour of 65Zn-, 64Cu- and [35S]cysteine-labelled metallothionein (MT) in rat hepatoma tissue culture (HTC) cells. MSE-HPLC of [35S]cysteine-labelled HTC cell cytosol resulted in co-eluting MT-I and MT-II isoforms (tR 19.80 min; Ve/Vo: 1.85). AE-HPLC of 65Zn-treated HTC cell cytosol yielded separated 65Zn MT-I (tR 11.5 min; I = 64 mM) and 65Zn MT-II (tR 14.5 min; I = 104 mM). RP-HPLC of 64Cu-treated HTC cytosol resulted in separated 64Cu MT-I (tR 26.4 min) and 64Cu MT-II (tR 23.4 min). Determination of the amino acid composition, apparent molecular mass and cysteine content of HTC MT-I and MT-II isoforms showed the characteristics of class I metallothioneins. The rate of dissociation of Zn2+ from Zn-MT could be determined from the losses of 65Zn from MT during a single AE-HPLC run, showing a Zn-MT dissociation half-life of 0.66 h. RP-HPLC showed a delay in incorporation of newly accumulated 64Cu into MT, possibly owing to the appearance of reduced glutathione as an intracellular copper-transfer compound. Application of compartmental analysis in [35S]-cysteine accumulation experiments permitted the determination of the actual rate of MT degradation; when 200 microM of Zn were applied, the MT degradation half-life was 2.0 +/- 0.8 h. These results indicate the potential of combined HPLC techniques and application of radionuclides in studies on the synthesis and degradation of MT and metal-MT complexes.
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PMID:Determination of zinc-65, copper-64 and sulphur-35 labelled rat hepatoma tissue culture metallothioneins by high-performance liquid chromatography with on-line radioactivity detection. 826 92

Livers of LEC rats were histochemically stained for copper according to the modified Timm's method, which includes trichloroacetic acid (TCA) treatment. TCA pretreatment was effective in removing zinc and iron, leaving as the major metal in the liver. Hepatocytes in 3-month-old rats were stained intensely by the modified Timm's method, both in frozen sections and in paraffin-embedded specimens. The centrilobular hepatocytes were usually stained, but positive cells were also randomly distributed in the hepatic lobes, showing a mosaic pattern. The staining was intensified in 8- compared to 3-month-old LEC rats. In contrast hepatocytes from LEA rats, the normal counterpart of LEC rats, were faintly stained for copper. Proliferating cholangioles found in older LEC rats were shown to lack copper deposition, and hepatocellular carcinoma showed less copper deposits than the hepatocytes surrounding the tumor. The copper staining was augmented in livers of LEC rats subjected to copper-loading, but was less intense in the livers treated with D-penicillamine. The staining intensity under the various experimental conditions showed good correlation with the copper concentration. Lysosomal deposition of copper in hepatocytes was demonstrated by electron microscopic analysis for copper. Thus the modified Timm's method was shown to produce valuable results in demonstrating copper in LEC rat livers, providing important information for an understanding of the mechanism of copper deposition and hepatic disease of the animal.
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PMID:Histochemical demonstration of copper in LEC rat liver. 827 38

Long-Evans Cinnamon (LEC) rats, a mutant strain originating from Long-Evans rats, spontaneously develop hereditary hepatitis followed by hepatocellular carcinoma. The hepatic disorder in LEC rats is associated with their abnormal copper metabolism; metal-catalyzed reactions often give rise to oxygen radicals, which may be related to the carcinogenesis. By means of high-pressure liquid chromatography with electrochemical detection, cellular DNA damage caused by oxygen radicals can be assessed in terms of the amount of 8-hydroxydeoxyguanosine (oh8dG). We assayed the amount of oh8dG in DNA of liver, kidneys, and brain of LEC and Long-Evans Agouti (LEA) control rats in seven groups (n = 3 to 6) aged from 5 weeks to 24 months. Control rats, a healthy sibling line, were age-matched. The amount of oh8dG was correlated with the severity of the age-related clinical symptoms in LEC rats. The amount was higher in LEC rats than in the controls, especially in the liver at the acute stage of hepatitis. These findings suggest that oxygen radicals may be important in the carcinogenesis that occurs in LEC rats.
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PMID:Elevated level of 8-hydroxydeoxyguanosine in DNA of liver, kidneys, and brain of Long-Evans Cinnamon rats. 832 Jan 67

Several biochemical events accompany and mediate the development of chronic liver disease and its evolution into cancer. Low plasma zinc and high copper levels have been observed in various liver diseases, such as liver cirrhosis and viral hepatitis, while increased oestradiol levels have been documented in chronic liver damage and hepatocellular carcinoma. We administered CCL4 intragastrically to 10 female Sprague Dawley rats for 30 weeks. All animals developed cirrhosis and four also developed hepatocellular carcinoma. Plasma levels of zinc, copper and oestradiol were significantly higher in the latter group than in animals with simple cirrhosis. Progesterone, AST and bilirubin showed a trend toward significant differences whereas testosterone and ALP levels were unchanged. These findings add to the evidence that sex hormones and trace elements are involved in the process of the development of chronic liver damage and carcinogenesis.
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PMID:Sex hormones and trace elements in rat CCL4-induced cirrhosis and hepatocellular carcinoma. 835 89


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