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)

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

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

Twenty patients with focal liver lesions (18 metastases, 1 hepatocellular carcinoma, 1 cholangiocarcinoma) were given manganese DPDP as part of a multicentric phase II study of paramagnetic hepatobiliary MR contrast media. 5 mumol/kg manganese DPDP were injected into 10 patients in a concentration of 50 mumol/ml or 10 mumol/ml (3 ml/min). Blood pressure, pulse rate, ECG, respiratory rate, body temperature, blood and serum parameters and the patients' subjective feelings were recorded. MRI was performed with 1.5 T using T1- and T2-weighted sequences. 6 patients reported 8 side effects (flushing, feeling of warmth, metallic taste); 7 of these were produced by the 50 mumol concentration. Two hours after injection there was a significant reduction in alkaline phosphatase which was no longer present after 24 hours. On T1-weighted images manganese DPDP resulted in marked improvement in the contrast difference between the lesions and the liver parenchyma which resulted in a marked increase in the signal to noise ratio. Comparing the two concentrations, better results were obtained by the lower concentration. Extrahepatic uptake was found in the gallbladder, duodenum, pancreas, kidneys, gastric mucosa and myocardium. Manganese DPDP in a concentration of 10 mumol/ml and a dose of 5 mumol/kg is a well tolerated contrast medium which improves the demonstration of focal liver lesions in view of its distribution and uptake. The mechanisms for the transitory side effects require further studies.
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PMID:[Manganese DPDP as a contrast medium for MR tomography of focal liver lesions. Tolerance and image quality in 20 patients]. 145 88

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

DNase activity in the presence of Ca2+ + Mg2+, Mg2+ alone, Mn2+ alone, or EDTA, and topoisomerase I activity were measured in nuclear extracts of diethylnitrosamine (DEN)-induced hepatomas, regenerating, fetal, and normal rat livers. In hepatoma tissue, the Ca/Mg-dependent DNase activity was lower than in normal tissue and nearly the same as in fetal liver. In the poorly differentiated hepatomas, Mn-dependent DNase activity was higher than in both moderately and well differentiated ones and than in normal liver tissue. The activity of topoisomerase I in hepatomas and in regenerating liver was lower than in normal liver tissue.
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PMID:Nuclear topoisomerase I and DNase activities in rat diethylnitrosamine-induced hepatoma, in regenerating and fetal liver. 166 44

With a recently described rat model technique for direct hepatic injection of tumor cells for imaging research, there were concerns that the injection itself might produce lesions detectable with magnetic resonance (MR) imaging, thereby producing false-positive results. To examine this possibility, the authors prospectively studied 14 Sprague-Dawley rats after direct hepatic injection of cells from a rat hepatoma cell line. The rats were imaged with a variety of pulse sequences before and after intravenous injection of the contrast agent manganese dipyridoxal diphosphate at a dose of 8 mumol/kg. No intrahepatic lesions could be detected with MR imaging during the first 6 days after direct hepatic injection of the tumor cells. Therefore, the direct injection technique should be accurate for evaluating various MR imaging sequences and contrast agents for early hepatic tumor detection.
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PMID:Direct hepatic tumor injection in rats: can it be used for analysis of MR imaging contrast agent? 183 62

To determine whether abnormal metabolism of L-fucose in hepatocellular carcinoma is accompanied by alterations in the activities of fucosyltransferases, the latter were determined in plasma and liver tissue of patients with this disease and in cirrhotic and normal subjects. Activities of alpha-2/alpha-3 and alpha-6-L-fucosyltransferases were all significantly greater in plasma from patients with hepatocellular carcinoma than in plasma from cirrhotic patients or normal subjects (p less than 0.025). The activity of each enzyme was dependent, to a similar extent, on Mn2+, Mg2+ and triton X-10, irrespective of the source, and all displayed pH optimums in the range of 7.5 to 8.0. In contrast, activities of alpha-2/alpha-3 fucosyltransferases were significantly lower (p less than 0.025) in homogenates prepared from tumorous liver tissue than in that prepared from nontumorous tissue from hepatocellular carcinoma and cirrhotic patients, whereas for the alpha-6 enzyme the situation was reversed (typically, tumor tissue levels were 5 pmol/hr/mg; in nontumor tissue they were 2 pmol/hr/mg). Activities of galactosyl and mannosyltransferase in tumor tissue were greater in all cases than in nontumor cirrhotic tissue. Plasma fucosyltransferases are specifically elevated in hepatocellular carcinoma but different mechanisms appear to underlie the changes seen for alpha-2/alpha-3 and alpha-6-L-fucosyltransferases.
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PMID:Fucosyltransferases: differential plasma and tissue alterations in hepatocellular carcinoma and cirrhosis. 184 14

Various contrast agents are applied in both CT and MR imaging to improve the detection as well as the differentiation of focal liver lesions. In detecting hepatocellular carcinoma, the accuracy of Lipiodol-enhanced CT is comparable to that of CT during arterial portography. Tissue-specific contrast agents for the liver are superparamagnetic iron oxide particles, which are characterized by uptake in the reticuloendothelial system, and the paramagnetic hepatobiliary contrast agent manganese (II)-N,N'-dipyridoxylethylenediamine-N,N'-diacetate-5,5'-bis(phosphate). Both substances have the potential for markedly improving the detection of malignant liver tumors. The already good differentiation of focal hepatic lesions on plain MR images can be further improved by dynamic gadolinium diethylenetriamine penta-acetic acid-enhanced MR imaging. In the diagnosis of bile duct disorders, contrast-enhanced CT continues to be the method of choice. Water applied as a gastrointestinal contrast agent improves the staging of rectal carcinoma by CT. The development of suitable orally applied gastrointestinal contrast agents has now also improved the differentiation of the intestine from other abdominal structures on MR images, and this will lead to a general improvement of abdominal MR imaging.
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PMID:Contrast material for computed tomography and magnetic resonance imaging of the gastrointestinal tract. 185 83

We investigated spatiotemporal changes in cytoplasmic free Ca2+ concentration ([Ca2+]i) in norepinephrine (NE)-stimulated and fura-2-loaded individual H-35 rat hepatoma cells, using digital imaging microscopy and high time-resolution microspectrofluorometry. Application of NE (5 x 10(-6) M) resulted in an initial transient increase in [Ca2+]i, followed by a small sustained [Ca2+]i plateau above the pre-stimulation level. The initial peak and the small sustained plateau originated from intracellular stores and the extracellular space, respectively. The initial transient evoked by NE was totally blocked by phentolamine, an alpha-adrenergic antagonist, but was not blocked by either pre-incubation with nominally Ca(2+)-free medium or by pre-treatment of cells with La3+. On the other hand, the sustained plateau was eliminated by Ca(2+)-free medium or La3+. Therefore, H-35 cells have a Ca(2+)-signaling pathway which is activated via alpha-adrenergic receptors. Mn2+ entered the cytosol after NE stimulation, as shown by quenching of fura-2. This indicates that H-35 hepatoma cells possess Mn(2+)-permeable Ca2+ channels at the plasma membrane. In addition, the Ca2+ efflux pattern from H-35 cells to the extracellular space during NE stimulation was visualized by digital imaging microscopy when free fura-2 was equilibrated between the cells and the extracellular space. The efflux of Ca2+ from H-35 begins between the initial [Ca2+]i transient and the sustained [Ca2+]i plateau.
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PMID:Dynamics of Ca2+ transients in norepinephrine-stimulated individual H-35 hepatoma cells: fura-2 digital imaging microscopy and high time-resolution microspectrofluorometry. 194 Mar 4

In previous publications, one of us demonstrated that variation in paramagnetic-ion contents is a major contributing factor to the different NMR relaxation times, T1 and T2, of water protons among normal mouse tissues; and between normal tissues and cancer cells. The nature of the paramagnetic ions involved was not determined. In the present communication, we report results of analysis of the contents of three biologically prominent paramagnetic ions (manganese, iron and copper) in 9 normal mouse tissues (brain, heart, small intestine, kidney, liver, lung, voluntary muscle, spleen and stomach); one strain of rat cancer cells (As-30, rat hepatoma); and 6 strains of mouse cancer cells (Ehrlich mammary adenocarcinoma, LSA lymphoma, Krebs carcinoma of the inguinal region; sarcoma 180; Klein TA3 mammary adenocarcinoma; P815 mast cell leukemia). Our data indicate that manganese and iron are by far the two most important paramagnetic ions contributing to the diversity of NMR relaxation times. The average manganese content of all the normal mouse tissues studied (29.6 +/- 4.99 mu mole/kg) is 24 times higher than the average manganese contents of all the cancer cells studied (1.22 +/- 0.27 mu moles/kg) and there is essentially no overlap between the two groups of data. The average iron content of the normal mouse tissues (281.6 +/- 51.2 mumoles/kg) is 4 times the average in cancer cells (66.7 +/- 7.74 mumoles/kg) but there is some overlap here. The observed differences in both the manganese and iron contents are statistically highly significant, with P's below 0.0001. The copper contents of the cancer cells is lower than the average of normal mouse tissues but only by some 20%. The difference is statistically insignificant at the 0.05 level but significant at the 0.2 level.
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PMID:Low paramagnetic-ion content in cancer cells: its significance in cancer detection by magnetic resonance imaging. 159 62


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