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)

The copper(II)-binding ability of human alpha-fetoproteins, which were purified from umbilical cord serum and from ascites fluid of a hepatoma-bearing patient, was examined by equilibrium dialysis and gel filtration methods. The pH dependence of the copper(II)-binding ability of alpha-fetoprotein was quite similar to that of albumin. Alpha-fetoprotein bound 1 mol of copper(II) ion per mol of protein above pH 6.0 and 0.5 mol of copper(II) ion at pH 5.4, which is close to the pK value of the imidazole group of histidine. Photooxidation of alpha-fetoprotein in the presence of methylene blue resulted in the loss of the copper(II)-binding ability of the protein in parallel with the destruction of the histidyl residues. A synthetic amino-terminal undecapeptide of alpha-fetoprotein also bound copper(II) ion. These results indicate that the histidyl residue at the amino-terminal region of alpha-fetoprotein plays an important role in the copper(II)-binding ability of the protein.
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PMID:Copper(II)-binding ability of human alpha-fetoprotein. 8 Feb 65

Nucleoli isolated from Novikoff hepatoma cells of the rat were previously shown to carry out synthesis of predominantly ribosomal precursor RNA and methylation of this RNA in vitro. In order to develop in vitro systems for further detailed study of these processes and their interrelationships, isolated nucleoli were incubated in a complete RNA-synthesizing medium using (5-3H)cytidine 5'-triphosphate or S-adenoxyl(methyl-3H)methionine to measure the activities of RNA synthesis and methylation, respectively, under the same reaction conditions. Methylation of the ribose of the nascent ribosomal precursor RNA predominated. It occurred in close coordination with the transcriptional step by RNA polymerase as shown by the kinetic data, the analysis of labeled RNA in sucrose gradients, the inhibition by increased ionic strength or actinomycin D, and the release of labeled nucleotides by a 3'-exonuclease, venom phosphodiesterase. Methylation of the RNA bases occurred more slowly, continued longer after transcription ceased, and appeared to follow later in the processing of the RNA. Certain divalent cations (Mg2+, Mn2+, and Ca2+ at higher concentrations, and Zn2+ and Cu2+) inhibited both RNA synthesis and methylation to similar extents. RNase inhibitors (bentonite and dextran sulfate) at low concentration inhibited methylation while stimulating RNA synthesis, and pyrophosphate greatly decreased RNA synthesis with relatively little effect on methylation. These results indicated that RNA polymerase and ribosomal RNA methylases can function independently despite their close relationship. An exogenous substrate for the nucleolar rRNA methylases was found: nuclear RNA prepared from Novikoff hepatoma cells, cultured in the absence of methionine, served as a good substrate for methylation of both ribose and bases. Other exogenous RNAs, including cytoplasmic ribosomal RNA from these methionine-starved cells, nucleolar RNA from normal cells, and wheat germ ribosomal RNA were almost devoid of methyl-acceptor activity. A description of these parameters helps establish isolated nucleoli as a suitable system for further study of interaction of RNA polymerase, methylases, and nucleases in control of synthesis of ribosomal RNA.
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PMID:Interrelationships between synthesis and methylation of ribosomal RNA in isolated Novikoff Tumor nucleoli. 16 25

Histological study of 69 cases of cirrhosis, 9 of severe generalised hepatic fibrosis, and 19 of hepatocellular carcinoma showed an association with alcohol, hepatitis B surface antigen (HBsAg) or a1-antitrypsin bodies in, respectively, 41 (cirrhosis), 5 (fibrosis), and 9 (carcinoma). Eight of the cirrhotic cases and two of the carcinoma cases had double associations, HBsAg being present in all. Torcein and aldehyde fuchsin staining gave both false positive and false negative results when compared with immunofluorescence and immunoperoxidase methods for HBsAg. Large amounts of copper were found in four cirrhotic livers, and moderate amounts in 13: the diagnostic value of copper staining is questioned.
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PMID:Aetiology of cirrhosis, hepatic fibrosis, and hepatocellular carcinoma. 19 27

Copper (Cu), iron (Fe), zinc (Zn) and manganese (Mn) levels in organs of LEC rats (Long-Evans rats with a cinnamon-like coat color), which develop spontaneous jaundice with hereditary hepatitis, were determined by instrumental neutron activation analysis method. Unusual accumulations of Cu in the liver of LEC rats were found, depending on the age of the animals, the metal concentration being more than approximately 20-40 times those of normal LEA rats (Long-Evans rats with an agouti coat color). Fe and Zn were also accumulated, in addition to Cu, significantly in the LEC rats. The unusual Cu accumulations in the liver of LEC rats were associated with the induction of metallothionein, estimated by radioimmunoassay method, in the liver of LEC rats, rather than that of superoxide dismutase, estimated by electron spin resonance -spin trapping method. These findings suggest that the unusual Cu accumulation in LEC rats is involved in the development of jaundice, hepatic injury and hepatocellular carcinoma.
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PMID:Unusual accumulation of copper related to induction of metallothionein in the liver of LEC rats. 131 72

Experiments were carried out to investigate the uptake and accumulation of Zn in rat hepatoma HTC cells, as affected by interfering metals (Cd, Cu), metallothionein synthesis inhibiting compounds (Actinomycin D, cycloheximide) and metallothionein synthesis stimulating compounds (dexamethasone, dibu-cAMP). Cell viability was tested under all experimental conditions by the measurement of LDH leakage, K+ uptake and total cell protein. Determinations of Zn were performed by AAS (total Zn) or by gamma-ray spectrometry (65Zn). Metallothionein analysis was carried out by Cd-saturation tests. The results indicate that cellular responses in rat hepatoma HTC cells with respect to the uptake and accumulation of 65Zn are fully comparable with literature data existing for 65Zn accumulation in rat hepatocytes, under all experimental conditions applied. Cu2+ and dibutyryl-cAMP did not significantly affect rates of 65Zn accumulation. Cd2+, Actinomycin D and cycloheximide reduced 65Zn uptake, but dexamethasone additions resulted in increased 65Zn accumulation in the cells. Effects on 65Zn were shown both in cytosolic and in the membranes/organelles cell fractions. HPLC chromatography in control cells suggested that newly accumulated cytosolic 65Zn was predominantly MT-associated. Dexamethasone-induced 65Zn accumulation could not be related to elevated cellular MT levels, nor were the total cytosolic Zn levels significantly affected. Non-specific attenuations in MT levels (Actinomycin D, cycloheximide and dibu-cAMP) yielded linear relations between cytosolic 65Zn and MT levels, without any change in cytosolic Zn (AAS). Combined addition of Cd and dexamethasone yielded elevated MT levels, but severely reduced total cytosolic Zn and 65Zn concentrations. The results further indicate the non-Zn-specific nature of dexamethasone-action and suggest the relatively easy Zn-complexing and Zn-release of MT. The simultaneous determinations of total cytosolic zinc and cytosolic 65Zn levels showed that the application and sole measurement of radiotracers may yield only one-sided views of what is actually present or occurring in the cells.
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PMID:Effects of cadmium, copper and metallothionein synthesis inhibiting and stimulating compounds on zinc uptake and accumulation in rat hepatoma HTC cells. 133 Mar 37

The Long-Evans Cinnamon rat is a mutant strain that contracts hereditary hepatitis and, eventually, spontaneous hepatocellular carcinoma. Because we found a corresponding gross copper accumulation in the liver of the rats, we examined whether the development of hepatitis in our rat system could be prevented by administration of D-penicillamine. D-Penicillamine is a copper-chelating agent and one of the drugs effective for human Wilson's disease, in which abnormal copper metabolism is also observed. The results show that D-penicillamine treatment inhibited the elevation of serum transaminases, suppressed abnormal histological changes in the liver and completely prevented the onset of hepatitis in the Long-Evans Cinnamon rats. We further found that the copper concentration in the liver and serum copper and ceruloplasmin levels were decreased, whereas the urinary copper level was increased in the D-penicillamine-treated Long-Evans Cinnamon rats. These findings demonstrate that the pathogenesis of hereditary hepatitis in Long-Evans Cinnamon rats is due to abnormal copper accumulation in the liver.
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PMID:D-penicillamine prevents the development of hepatitis in Long-Evans Cinnamon rats with abnormal copper metabolism. 137 Jan 62

The presumed involvement of the transition metals manganese and copper in the regulation of the expression of the Mn- and CuZn-containing superoxide dismutase genes has been investigated in normal and neoplastic tissues of the rat. Two hepatomas of the Morris line have been employed, the slow growing, highly differentiated 9618A and the fast growing, poorly differentiated 3924A. The data obtained indicate a control at the pretranslational level of the Mn-containing enzyme, presumably exerted by the manganese ion. The CuZn-containing superoxide dismutase is also regulated pretranslationally in the normal tissues examined and in the hepatoma 3924A. However, there is no indication for the involvement of the copper ion, which in the liver is mostly located in the cytosol bound to CuZnSOD, in such regulation. The possible role of a reduced redox state, concomitant to the manganese deficiency in hepatoma tissues, in the down regulation of Mn-containing superoxide dismutase is discussed.
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PMID:Manganese deficiency and transcriptional regulation of mitochondrial superoxide dismutase in hepatomas. 139 81

Small (less than 5 cm) hepatocellular carcinomas (HCCs) in 45 of 112 patients (40.2%) had a high-signal-intensity pattern (relative to that of liver) on T1-weighted magnetic resonance (MR) images. To identify the cause of this pattern, specimens of histologically defined HCC with high- (n = 21), iso- (n = 6), and low- (n = 22) intensity patterns were histologically evaluated for paramagnetic ionic forms of metals. The incidence of steatosis, clear cell formation, and copper accumulation was statistically (P less than .01) higher in tumors with the high-intensity pattern than in those with other patterns. Of 17 HCCs that stained positive for copper, 16 (94%) had a high-intensity pattern; the pattern of one tumor (6%) was isointense. All 21 tumors with the high-intensity pattern had at least one of the findings of steatosis, clear cell formation, or copper accumulation. These features were evident in only four of 28 tumors (14%) with an iso- or low-intensity pattern. Thus, copper accumulation might be a cause of the high-intensity pattern on T1-weighted images of small HCCs.
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PMID:MR imaging of small hepatocellular carcinoma: effect of intratumoral copper content on signal intensity. 165 23

Superoxide dismutase (SOD) activity and content of lipid peroxides (LPO) in human hepatocellular carcinoma (HCC) tissue were studied. It was observed that SOD activity and LPO content in HCC tissue were lower than those in normal liver tissue (P less than 0.001 respectively). The contents of copper, zinc and manganese in HCC tissue were also lower than those in normal liver tissue (P less than 0.001, P less than 0.05). Furthermore, LPO content in necrotic HCC tissue was higher than that in non-necrotic HCC tissue (P less than 0.05). The results suggest that deficiency of copper, zinc and manganese in HCC tissue may be a contributing factor that leads to impairment of SOD activity. Decreased SOD activity in liver cancer cells was a negative feedback of the multiplication of cancer cells loss of lipid peroxidation explains the malignancy of HCC, and enhanced lipid peroxidation in liver cancer cells may cause the necrosis of cancer cells.
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PMID:[Impaired superoxide dismutase activity and decreased content of lipid peroxides in hepatocellular carcinoma tissue]. 165 38

A 36-year-old woman was admitted to our hospital because of general fatigue. The physical and laboratory findings on admission revealed splenomegaly, pancytopenia, hypocoagulopathy, liver hypofunction with a hepaplastin test of 55% and ICG Rmax of 0.6 mg/kg/min. Diagnostic imaging showed a hypoechoic mass 1.5 in diameter a low density area on the CT scan and a faint tumor stain on the AAG in the posterior inferior area of the liver. On a diagnosis of hepatocellular carcinoma with liver cirrhosis and hypersplenism, partial hepatectomy and splenectomy were performed. The resected hepatic specimen revealed a small liver cancer of 1.9 x 1.5 x 1.3 cm with liver cirrhosis. The specimen consisted of a firm rubbery mass. Macroscopically, the tumor appeared oval and was lobulated with a thin capsule. A fibrous scar was observed in the central area. Microscopically, malignant hepatocytes showed various shapes, ranging from polygonal to spindle form, with eosinophilic granular cytoplasm and were surrounded by abundant fibrous stroma. Orcein stain, revealed that these malignant hepatocytes contained many black granules of copper-binding protein. Immunoperoxidase staining for alpha 1-antitrypsin was also positive in the malignant hepatocytes. However, within this lamellar fibrous regions, there were many cords of tumor cells in which nucleoli were absent and abortive biliary differentiation was suggested. Consequently this tumor was diagnosed as an atypical fibrolamellar hepatocellular carcinoma. We think that this case is the 3rd case reported in Japan and the 2nd case in a Japanese person.
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PMID:Fibrolamellar carcinoma of the liver--a case report. 165 47


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