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)

Inhibition of human hepatocellular carcinoma (PLC/PRF/5 and Hep3B) or hepatoblastoma (Hep G2) cell lines by inclusion of deferoxamine mesylate (desferrioxamine) (DFX) in the culture medium was evaluated. When PLC/PRF/5 cells were maintained for 7 days in 30 or 60 microM DFX, the cell number was decreased by 30-60%, little or no alpha-fetoprotein (AFP) was produced, and supernatant endpoint dilution titers of hepatitis B surface antigen (HBsAg) were reduced 1-2 logs. PLC/PRF/5 cells maintained for 7 days without DFX (simultaneous controls) grew to confluence, produced AFP that reached 10-60 ng/ml in the supernate, and the HBsAg titer remained constant or increased 1 log. Similar effects were observed in Hep3B and Hep G2 cells maintained in DFX (except that Hep G2 cells do not produce HBsAg), compared to simultaneous control cells grown in the absence of DFX. The growth of a human embryonic lung fibroblast cell line (Wl 38) was not significantly inhibited by DFX, although it grew at a slower rate than simultaneous control cells grown without DFX. Subsequent growth in FeSO4 of PLC/PRF/5, Hep3B, and Hep G2 cells that previously had been maintained in DFX did not reverse the effects of DFX. PLC/PRF/5 cells were also inhibited when maintained in medium containing equimolar concentrations of DFX and FeCl3 and in medium containing equimolar concentrations of DFX and FeSO4. PLC/PRF/5 cells were not inhibited by maintenance in up to 60 microM of another chelating agent that has a similar affinity for iron, calcium disodium versenate (EDTA). These studies show that DFX inhibits the growth of human hepatocellular carcinoma and hepatoblastoma cell lines regardless of the presence (PLC/PRF/5, Hep3B) or absence (Hep G2) of integrated hepatitis B virus DNA. The findings also suggest that the inhibition may have been due to mechanisms other than iron chelation.
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PMID:Inhibition of human hepatocellular carcinoma and hepatoblastoma cell lines by deferoxamine. 171 97

In this study, the target-specific behavior of magnetic resonance (MR) imaging contrast agents directed at human hepatic asialoglycoprotein (ASG) receptors was evaluated in vitro with use of two novel assays: relaxation time measurements of incubated human cell membrane solutions and iron staining of biopsy samples. Specific uptake of ASG receptor-directed agents was demonstrated in human samples of normal liver tissue, areas of hepatitis, regenerating nodules, areas of focal nodular hyperplasia, and hepatic adenomas. A conventional iron oxide preparation not directed at ASG receptors failed to demonstrate specific uptake in these tissues. Attachment of the ASG receptor-directed agents was competitively blocked with a receptor agonist (D(+)-galactose) in these tissues. No attachment of conventional or receptor agents was seen in areas of hepatocellular carcinoma, cholangiocarcinoma, or liver metastases. The studies indicate that in vitro receptor assays are useful in predicting the affinity of new receptor-directed MR imaging contrast agents in human tissue prior to clinical trials.
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PMID:Receptor-directed contrast agents for MR imaging: preclinical evaluation with affinity assays. 173 82

Hereditary haemochromatosis is a recessive disease in which primary hepatocellular carcinoma, complicating cirrhosis, is responsible for about one-third of deaths in affected homozygotes. We describe a unique HLA haplo-identical pedigree showing parent-to-offspring transmission of hereditary haemochromatosis in whom HLA typing studies, including class I and class II allogenotype analysis, were of no benefit in identifying affected homozygotes. However, affected siblings in the pre-cirrhotic stage of haemochromatosis, with apparent discordance between the haemochromatosis allele and class I loci on chromosome 6, were detected by undertaking a family study, using analysis of serum parameters of iron status in combination with magnetic resonance imaging (MRI). This pedigree emphasises the critical importance of genetic and non-invasive methods for the identification of asymptomatic homozygotes before cirrhosis develops.
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PMID:Detection of hereditary haemochromatosis in an HLA-identical pedigree showing discordance between HLA class I genes and the disease locus. 175 96

Transferrin receptors take up transferrin-iron complexes into hepatic cells. Although the receptor is not highly expressed in normal liver cells, malignant transformation of the cells increases its expression. As part of the expressed receptors are released into blood, a significant increase of serum receptors are observed in cases of hepatoma. Therefore, measurement of transferrin receptors in blood from patients with hepatoma may be useful for estimating the tumor burden and determinating therapeutic effects. Asialoglycoprotein receptors are expressed strongly in normal liver cells, whereas the expression is decreased in various chronic liver diseases and hepatoma. Although the active shedding of the receptors clearly occurs in vitro, as does that of the transferrin receptor, determination of the significance of these shed receptors in blood will require further studies.
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PMID:Mechanism and clinical significance of soluble hepatic cell-surface receptors. 179 62

Large regenerative nodules in cirrhotic livers may accumulate iron and develop internal iron-poor foci of hyperplasia or malignancy. Magnetic resonance examinations were performed on 23 patients with biopsy-proved cirrhosis. A "nodule-within-nodule" appearance was noted in two patients. This appearance consisted of markedly low intensity of a large nodule on gradient-echo images, with one or two internal foci that were isointense to the liver. Each of the large nodules was 2 cm in diameter, and each of the internal foci was less than 1 cm. Serum alpha-fetoprotein levels were normal in both patients. Aspiration biopsy performed in one patient failed to show malignancy, but histologic confirmation of hepatocellular carcinoma was obtained eventually in both cases. The nodule-within-nodule sign, which reflects the unique histopathology of hepatocellular carcinoma in large siderotic regenerative nodules, is strongly suggestive of early hepatocellular carcinoma, even if serologic markers and biopsy results do not support this diagnosis.
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PMID:Hepatocellular carcinoma within siderotic regenerative nodules: appearance as a nodule within a nodule on MR images. 184 84

Iron is essential for life, but iron overload is toxic and potentially fatal. The liver is a major site of iron storage and is particularly susceptible to injury from iron overload, especially when (as in primary hemochromatosis) the iron accumulates in hepatocytes. Iron can be taken up by the liver in several forms and by several pathways including: (1) receptor-mediated endocytosis of diferric or monoferric transferrin or ferritin, (2) reduction and carrier-facilitated internalization of iron from transferrin without internalization of the protein moiety of transferrin, (3) electrogenic uptake of low molecular weight, non-protein bound forms of iron, and (4) uptake of heme from heme-albumin, heme-hemopexin, or hemoglobin-haptoglobin complexes. Normally, pathway 2 is probably the major one for uptake of iron by hepatocytes. Iron is stored in the liver in the cores of ferritin shells and as hemosiderin, an insoluble product derived from iron-rich ferritin. Iron in hepatocytes stimulates translation of ferritin mRNA and represses transcription of DNA for transferrin and transferrin receptors. The major pathologic effects of chronic hepatic iron overload are: (1) fibrosis and cirrhosis, (2) porphyria cutanea tarda, and (3) hepatocellular carcinoma. Although precise pathogenetic mechanisms remain unknown, iron probably produces these and other toxic effects by increasing oxidative stress and lysosomal lability. Vigorous efforts at diagnosis and treatment of iron overload are essential since the pathologic effects of iron are totally preventable by early vigorous iron removal and prevention of iron re-accumulation.
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PMID:Iron and the liver. 184 76

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

Six alkyl ethers of 7-hydroxycoumarin, ranging from methoxy- to hexoxycoumarin, were studied for their NADPH-dependent metabolism by liver microsomes of male rats treated with phenobarbital (PB) or 3-methyl-cholanthrene (MC). The six alkyl ethers were metabolized by both types of microsomes, forming 7-hydroxycoumarin as the major product. Among the test compounds, 7-methoxycoumarin was unusual in that its dealkylation was inducible only by PB and not by MC. PB increased 7-methoxycoumarin-O-demethylase (MOCD) activity about four- to eightfold. Metyrapone strongly inhibited MOCD in PB-treated microsomes but not in MC-treated microsomes. Similarly, monoclonal antibodies directed toward PB-induced cytochrome P450s selectively suppressed MOCD in PB-treated microsomes. MOCD activity was observed in preparations of SD1 cells containing only cytochrome P450IIB1, while it was not found in preparations of XEM1 cells containing only cytochrome P450IA1. Demethylation of 7-methoxycoumarin was also mediated by the constitutive cytochrome P450 form(s) of liver, lung, small intestine, and kidney (in decreasing order). PB increased MOCD activity of small intestine by 40% but was without effect on the dealkylation activity of lung and kidney. MOCD activity was also detectable in differentiated rat hepatoma lines H4IIEC3 and 2sFou. The studies indicate that dealkylation of 7-methoxycoumarin is a highly sensitive, simple, and practical assay for estimating constitutive and PB-inducible cytochrome P450-dependent monooxygenase activities.
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PMID:Dealkylation of 7-methoxycoumarin as assay for measuring constitutive and phenobarbital-inducible cytochrome P450s. 186 30

Relaxation time measurements and magnetic resonance (MR) imaging were performed in three different animal models of hepatocellular carcinoma (HCC). After intravenous administration of asialoglycoprotein-directed arabinogalactan-stabilized ultrasmall superparamagnetic iron oxide (10 mumol Fe/kg receptor agent), T2 of normal liver decreased from 41.6 msec +/- 1.0 to 19.4 msec +/- 1.7 (P less than .05) in rats. T2 of HCC implanted in normal liver or liver with chronic hepatitis was essentially unchanged. These results were similar to those obtained by administration of a reticuloendothelial cell-directed conventional iron oxide; however, the required dose of receptor agent was lower. MR imaging in a woodchuck model of virally induced HCC confirmed the distribution of the hepatocyte-directed agent to regions of functioning and differentiated hepatocytes but not to malignant tumor tissue. The results suggest that MR receptor imaging may play a role in the differentiation between primary liver tumor and functional liver tissue such as that in normal liver hepatitis or regenerating nodules.
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PMID:Experimental hepatocellular carcinoma: MR receptor imaging. 187 Dec 73

Synthesis of the iron-storage protein ferritin is thought to be regulated at the translational level by the cytosolic content of chelatable iron. This response to iron is regulated by the iron-modulated binding to ferritin mRNAs of a repressor protein, the iron regulatory element-binding protein. From measurements made in a cell-free system, regulation of the iron regulatory element-binding protein has been recently suggested to involve direct interaction with hemin. The following observations on the synthesis of ferritin and of heme oxygenase (HO), the heme-degrading enzyme, in rat fibroblasts or hepatoma cells lead us to conclude that chelatable iron is a direct physiological regulator of ferritin synthesis in intact cells: (i) the inhibitor of heme degradation, tin mesoporphyrin IX, reduces the ability of exogenous hemin to induce ferritin synthesis but enhances HO synthesis; (ii) the iron chelator desferal suppresses the ability of hemin to induce synthesis of ferritin but not of HO; (iii) the heme synthesis inhibitor succinylacetone does not block iron induction of ferritin synthesis; (iv) there is no apparent relationship between the ability of various metalloporphyrins to inactivate the iron regulatory element-binding protein in cell-free extracts and their capacity to induce ferritin synthesis in intact cells; (v) administered inorganic iron significantly induces the synthesis of ferritin but not of HO; (vi) addition of delta-aminolevulinic acid to stimulate heme synthesis represses the ability of inorganic iron to induce ferritin synthesis while activating HO synthesis. Taken together, our results demonstrate that (i) release of iron by HO plays an essential role in the induction of ferritin synthesis by heme and (ii) chelatable iron can regulate ferritin synthesis independently of heme formation.
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PMID:Regulation of ferritin and heme oxygenase synthesis in rat fibroblasts by different forms of iron. 199 60


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