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)

Acute administration of iron to rats has been previously shown to induce liver ferritin synthesis by increasing the translation of inactive cytoplasmic ferritin mRNAs for both heavy (H) and light (L) subunits by mobilizing them onto polyribosomes. In this report rat hepatoma cells in culture are used to explore the relationship of this response to intracellular iron levels. After adding iron as ferric ammonium citrate to the medium, latent ferritin H- and L-mRNAs were extensively transferred to polyribosomes, accompanied by increased uptake of [35S]methionine into ferritin protein. Because total cellular levels of L- and H-mRNA were not significantly changed by exposure to iron, the increased ferritin mRNAs on polyribosomes most probably come from an inactive cytoplasmic pool, consistent with the inability of actinomycin-D and of cordycepin to inhibit iron-induced ferritin synthesis. When deferoxamine mesylate, an intracellular iron chelator, was added after the addition of iron to the medium, ferritin mRNA on the polyribosomes was reduced, while the free messenger pool increased, and ferritin synthesis diminished. In contrast, the extracellular iron chelator diethylenetriaminepentaacetic acid failed to inhibit the induction of ferritin protein synthesis. Addition of iron in the form of hemin also caused translocation of mRNA to polyribosomes, a response that could be similarly quenched by deferoxamine. Because hemin does not release chelatable iron extracellularly, we conclude that the level of chelatable iron within the cell has a regulatory role in ferritin synthesis through redistribution of the messenger RNAs between the free mRNA pool and the polyribosomes.
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PMID:Translation of ferritin light and heavy subunit mRNAs is regulated by intracellular chelatable iron levels in rat hepatoma cells. 347 Jul 92

In previous studies, we showed that acute administration of iron to intact rats or to rat hepatoma cells in culture induces synthesis of the iron-storage protein ferritin by activating translation of inactive cytoplasmic ferritin mRNAs for both the heavy (H) and the light (L) subunits. In the course of activation, these ferritin mRNAs are recruited onto polysomes. To elucidate the structural features of these mRNAs involved in the translational response to iron, a chimera was constructed from the 5' and 3' untranslated regions (UTRs) of ferritin L subunit mRNA fused to the reading frame of the mRNA of bacterial chloramphenicol acetyltransferase (CAT). This chimera and deletion constructs derived from it were introduced into a rat hepatoma cell line by retrovirus-mediated gene transfer. The complete chimera showed increased CAT activity in response to iron enrichment of the medium, whereas deletion of the first 67 nucleotides of the 5' UTR, which contain a highly conserved sequence, caused loss of regulation by iron. Whereas cis-acting sequences located in the 5' flanking regions of many genes have been repeatedly implicated in modulating their transcriptional expression, we report here a specific regulatory translational sequence found within the 5' UTR of a eukaryotic mRNA.
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PMID:Iron regulates ferritin mRNA translation through a segment of its 5' untranslated region. 347 2

The human hepatoma cell line Hep 3B, which has the hepatitis B virus genome, shows over 80% decrease of copper/zinc superoxide dismutase activity, over 90% decrease of manganese superoxide dismutase activity, over 70% decrease of catalase activity, absence of glutathione peroxidase and glutathione S-transferase activities, over 270-fold increase of ferritin content and 25-fold increase of total iron compared to normal autopsy liver. These conditions of low antioxidant enzyme activities and iron overload are those which support the accumulation of oxygen free-radicals and DNA damage commonly considered to be carcinogenic mechanisms.
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PMID:Antioxidant systems in tumour cells: the levels of antioxidant enzymes, ferritin, and total iron in a human hepatoma cell line. 350 92

Biochemical and ultrastructural studies of insulin binding and cellular processing by cultured H4IIEC3 hepatoma cells were performed. Insulin binding and intracellular accumulation were rapid and after 30 min at 37 degrees C, 65% of the total cell-associated 125I-insulin was in an acid-stable compartment. Chloroquine had no significant effect on the amount of total cell-associated insulin or the percentage of insulin in the acid-stable compartment or cell-associated insulin degradation under those conditions, but after 60-min incubations, it slightly decreased the rate of dissociation of internalized hormone. Ultrastructural analysis revealed that monomeric ferritin-insulin (Fm-I) initially bound to single or paired receptors on microvilli. Within 5 min occupied insulin receptors microaggregated and migrated to the intervillous cell surface. During the next 5-10 min occupied receptors aggregated into large clusters on the plasma membrane. Large amounts of insulin were internalized by macropinocytosis and the majority of internalized Fm-I was found in phagosomes. Less than 10% of the membrane-bound insulin was associated with pinocytotic invaginations or coated pits and less than 5% of the total cell-associated insulin was found in lysosomes. Chloroquine had no detectable effect on the amount of Fm-I or its distribution among the intracellular organelles. These studies demonstrated that, compared to previous studies with rat adipocytes or 3T3-L1 adipocytes, insulin interalization and intracellular processing in this hepatoma cell were unique. These differences provide further evidence that insulin binding and processing may be controlled by cell-specific mechanisms and that substantial heterogeneity exists in pathways previously presumed to be similar for all cell types.
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PMID:Insulin binding and processing by H4IIEC3 hepatoma cells: ultrastructural and biochemical evidence for a unique route of internalization and processing. 354 44

We have measured serum ferritin level using double antibody radioimmunoassay kit (Eiken ICL) and evaluated the characteristics of the kit and clinical usefulness. Satisfactory results were observed in standard curve, reproducibility, dilution and recovery test. In clinical evaluation, we have measured in normal subjects and patients with various diseases. The range in normal males and females were 13.0-158.7 ng/ml and 7.3-73.0 ng/ml, respectively. Serum ferritin level was elevated in patients with hepatoma, biliary cancer, lung cancer and other malignant diseases. Measurement of serum ferritin value would be useful in the monitoring of cancer patients.
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PMID:[A fundamental and clinical study of ferritin 'Eiken' radioimmunoassay kit]. 356 8

Monoclonal antibody (mAb.) against liver ferritin was produced by immunization of human liver ferritin. Using this mAb., an RPHA system for measurement of the serum ferritin level was established. This system had a good correlation coefficient (0.8625) with the RIA method and could measure levels of more than 2 ng/ml. The reactivity to heart ferritin in this RPHA system was not distinguished from that to liver ferritin. The positive rate in various conditions was as follows: 68.6% in pancreatic cancer, 59.1% in hepatoma, and 18% in healthy individuals. In pancreatic cancer and hepatoma, the serum ferritin levels were statistically higher than in healthy subjects or those with chronic pancreatitis.
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PMID:[Production and clinical study of monoclonal antibodies against liver ferritin]. 374 63

Polyclonal 131I rabbit antirat ferritin localizes in certain hepatoma models. The effect of intraperitoneal iron dextran on tumor and sera ferritin content and tumor and normal tissue localization with 131I antiferritin was studied. Separate groups of 10-12 animals were injected with escalating doses of 131I-antiferritin IgG, or nonspecific IgG, one week after injection with iron dextran or normal saline. The results demonstrate that tumor, serum, and normal tissue ferritin content was increased after iron dextran administration but tumor localization increased after administration of 131I-antiferritin in the H4II-E and 7800 models. The 3924A and 7777 models showed no tumor localization with or without iron dextran but did show an increase in normal tissue localization after iron dextran. Immunoperoxidase staining of tissues with antiferritin revealed increased staining in the liver and spleen and only a slight increase in the tumors after iron dextran was administered. The results demonstrate that tumor localization is a complex phenomenon that depends on normal tissue, sera, and tumor-antigen distribution.
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PMID:The effect of iron dextran on ferritin content and 131I-antiferritin localization in experimental hepatomas. 390 93

The effect of tumor size, vascularity, ferritin content and the amount of injected 131I-antiferritin on tumor localization was studied in four hepatoma models with varying growth rates, histology, vascularity, and ferritin content. Separate groups of 12 animals with the H-4-II-E, 7800, 7777, and 3924A rat hepatomas with less than 2 g or greater than 2 g tumors were injected with escalating doses of 131I-antiferritin or 131I nonspecific IgG (control). Tumor vascularity was measured by 51Cr-labeled erythrocyte injection, ferritin content of tumors by radioimmunoassay and immunoperoxidase staining, and the histological location of 131I-antiferritin by autoradiography. 131I-antiferritin specifically localized in the H-4-II-E and 7800 models and correlated with the tumor size, vascular content, and amount of injected antiferritin. No localization took place in the 7777 or 3924A tumors despite the presence of ferritin in these models. The only factor that correlated with localization in the models was vascularity. The vascularity of 3924A and 7777 tumors was significantly reduced in comparison to the H-4-II-E and 7800 tumors. The dependence of targeting on vascularity was demonstrated with autoradiography as well. These findings indicate the correlation of vascularity and tumor localization with 131I-antiferritin.
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PMID:Factors that affect antiferritin localization in four rat hepatoma models. 390 94

Polyclonal 131I-labeled rabbit anti-rat ferritin was shown to specifically localize in the H4IIe rat hepatoma model. Tumor targeting was shown to be maximal in primary tumors or metastatic lesions less than 1 gram. Radiolabeled antiferritin tumor targeting decreased with increasing tumor size. In this study, ferritin levels were measured in H4IIe tumors grown both in vitro and in vivo. In vitro tumor cells synthesized and secreted ferritin into the medium as measured by radioimmunoassay, and confirmed by the incorporation of 14C-leucine into ferritin synthesis. The concentration of ferritin in the tumor cells as measured by radioimmunoassay remained relatively constant over this same time period. In vivo tumor ferritin levels in whole tumor extracts were highest in small tumors (less than 1 gram) and decreased as the tumors became larger. Serum ferritin levels of tumor-bearing animals paralleled the level in the tumors themselves. The elevated serum ferritin levels in animals with small tumors did not inhibit tumor targeting with radiolabeled antiferritin antibody. These findings are a foundation for understanding the selective tumor targeting of tumor associated proteins by radiolabeled antibodies, which includes factors such as tumor size, vascularity, antigen content, and circulating antigen.
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PMID:Ferritin concentration and 131I-antiferritin tumor localization in an experimental hepatoma. 394 85

1. The ribosomal components in the postmitochondrial supernatant of a rat hepatoma (hepatoma 7800) and the corresponding host liver were examined for diversity and functional competence. 2. The ;free' and ;membrane-bound' polyribosomes of both tissues were equally active in vivo and had equilibrated with newly synthesized ribosomes 4hr. after administration of [6-(14)C]orotic acid. 3. The inactive monomer-dimer pool in hepatoma 7800 was unattached to membranes and a larger fraction of the polyribosomes was free in hepatoma than in liver. 4. By using sensitivity to puromycin as a criterion, evidence was obtained that most of the polyribosomes in hepatoma 7800 were active in vivo. 5. Actinomycin, azaguanine and carbon tetrachloride caused marked conversion of polyribosomes into inactive monomers and dimers in the host liver and moderate conversion in the hepatoma. 6. Significant accumulation of ferritin and shifts in the mean polyribosome size to the lighter species occurred in the host liver of rats bearing large hepatomas.
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PMID:Diversity and nature of ribosomal pools in hepatoma 7800 and host liver. 430 Aug 30


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