Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Groups of 15 mice of three different laboratory strains (BALB/c, C3H/He, DBA/2) were fed on a low iron diet (5 mg iron/kg diet), and three similar groups of 15 mice were maintained on a normal iron diet (312 mg iron/kg diet). When the low iron diet group became iron deficient, tumor cells (5 x 10(5) cells/mouse) of CA07-A (colon adenocarcinoma), HE129 (hepatoma), and M119 (mammary adenocarcinoma) were inoculated s.c. in BALB/c, C3H/He, and DBA/2 mice, respectively. All mice developed tumors, tumors grew more slowly, and the mean tumor sizes were smaller in the low iron diet group at nearly all weekly observations in all three strains of mice. No apparent differences in the behavior, activity (e.g., movement, climbing, running, grooming, etc.), and appearance were observed between low iron diet and normal iron diet mice. The mean body weight of mice at transplantation was less in the low iron than in the normal iron groups for the BALB/c strain but higher in the low iron groups of C3H/He and DBA/2 mice, indicating that food intake of mice on a low iron diet was not impaired. These results suggest that iron nutrition of the host affects tumor growth; tumor cells grow better in an iron-rich environment. This knowledge should be considered when designing treatment for patients with cancer. Iron oversupply in cancer patients might enhance tumor growth and adversely affect cancer therapy.
 ...
PMID:Iron nutrition and tumor growth: decreased tumor growth in iron-deficient mice. 339 Aug 10

A flow-through cuvette in which cells attach as a monolayer to a quartz plate was developed for measurement of the light absorbance of anthracyclines in cells. Despite the drawback of a short path-length (of the order of the cell diameter), a dynamic flow-through set-up and baseline storage made it possible to measure intracellular absorbance and obtain spectral data for daunomycin and carminomycin. Stopping the flow and allowing the drug to equilibrate between medium and cells led to a 20% decrease of molar light absorption of cellular anthracycline, which permitted measurement of the total cellular concentration. Furthermore, accumulation and efflux kinetics were determined for H35 rat hepatoma cells. On the basis of the reported formation constant of the iron-complex of carminomycin, which is of the order of 10(34), we expected to find this complex within the cells. However, the spectrum of cellular drug did not show absorbance bands characteristic of the complex. A red shift and hypochromism were found in the daunomycin spectrum after intracellular binding, which corresponds with the spectral change observed after intercalation of daunomycin into DNA.
 ...
PMID:In-beam light absorption measurement of anthracyclines in cells with a flow-through system. 342 71

Purified recombinant human ferritin composed solely of H subunit was radiolabeled and incubated with proerythroleukemic K562 human cells. A specific binding was detected, and it could be displaced only by ferritins, natural or recombinant, containing large proportion of the H subunit. The specific ferritin H-chain binding was saturable, and cells showed 17,000 to 23,000 binding sites per cell. The affinity constant measured at 37 degrees C was of 3 x 10(8) M-1. Treatment with pronase eliminated the specific binding. The binding sites were expressed in a high number during the cellular exponential phase of growth and progressively decreased to disappear when cells reached the plateau phase. Treatment of the cells with desferrioxamine increased recombinant H-ferritin binding, while iron had little effect. K562 cells induced to differentiate by hemin failed to bind ferritin H. Ferritin H-chain binding capacity is present on various cell lines such as HL60, lung cancer, and hepatoma cells. Analysis of the binding sites by western blotting showed a peptide with apparent mol wt of about 100 kd.
 ...
PMID:Characteristics and expression of binding sites specific for ferritin H-chain on human cell lines. 342 30

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.
 ...
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.
 ...
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.
 ...
PMID:Antioxidant systems in tumour cells: the levels of antioxidant enzymes, ferritin, and total iron in a human hepatoma cell line. 350 92

Lipid peroxidation has been found decreased in several hepatomas. The decline has been shown already at the level of preneoplastic nodules obtained after DEN treatment of rats. A substantial exception is represented by the hepatoma cell line MH1C1, deriving from a slightly deviated Morris tumor. Most of the described experiments estimated lipid peroxidation levels in terms of malonaldehyde production by the thiobarbituric acid test. It is now clear that this test does not account for several other aldehydes produced during lipid peroxidation. We now investigated by high performance liquid chromatography (HPLC) the whole range of non-polar aldehydes produced by tumor homogenates and by preneoplastic nodules both in basal conditions and after stimulation with ADP-iron or ascorbate. It was reduced in the preneoplastic nodules as well as in the DEN-induced hepatoma. The susceptibility to the prooxidant effect of ADP-iron or ascorbate was strongly decreased in all hepatomas as well as in preneoplastic nodules. It has been recently published that hepatoma cells are more susceptible than normal liver to the toxic action of aldehydes. This was attributed at least in part to the decreased activity of aldehyde dehydrogenases, as well as to their different distribution in tumor cells. A deeper study on aldehyde metabolism in hepatomas has shown that alcohol dehydrogenase and NADPH-aldehyde reductase also are markedly decreased in Yoshida hepatoma cells and the MH1C1 cell line. However, glutathione transferase, that can use hydroxynonenal as a substrate, is strongly decreased in Yoshida hepatoma cells but not in MH1C1 cells.
 ...
PMID:New data on kinetics of lipid peroxidation in experimental hepatomas and preneoplastic nodules. 380 93

In this investigation, the effect of transferrin on 67Ga uptake by rat hepatoma was studied at three levels: at the level of individual tumor cells in culture; at the level of isolated, perfused livers with implanted intrahepatic tumors; and in intact animals bearing intrahepatic tumors. This approach was possible using H-4-II-E hepatoma cells which grew into discrete tumors when implanted intrahepatically. Transferrin at low concentrations (0.05-0.5 mg/ml) stimulated, while at a higher concentration (1.0 mg/ml) it inhibited 67Ga uptake by tumor cells in culture. In contrast, in isolated, perfused livers with intrahepatic tumors, transferrin at concentration levels of 0.05 and 0.1 mg/ml had no effect, while at 0.25-1.0 mg/ml transferrin inhibited 67Ga uptake by intact tumors. Administration of transferrin which markedly enhanced the serum unsaturated iron binding capacity, had no effect on 67Ga accumulation in the intrahepatic tumors in vivo. These results indicate that, although transferrin at low concentration promotes the uptake of 67Ga by individual tumor cells in culture, it does not do so in intact tumors in isolated rat liver preparations or in tumor bearing rats. We conclude that the mechanism of 67Ga uptake by intact tumors is different from that of tumor cells growing in culture.
 ...
PMID:Gallium-67 uptake by hepatoma: studies in cell cultures, perfused livers, and intact rats. 386 44

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.
 ...
PMID:The effect of iron dextran on ferritin content and 131I-antiferritin localization in experimental hepatomas. 390 93

The localization of 111In activity in the tumor and draining lymph nodes of the H-4-II-E ACI rat hepatoma was investigated following the injection of 111In-chloride. In this tumor model, the tumors metastasize to the regional lymph nodes in male rats only. The following experiments were performed: (a) biodistribution of 111In; (b) correlation of 111In uptake with [3H]thymidine; (c) gamma camera imaging; (d) autoradiography; (e) iron competition and (f) binding of 131I-transferrin to H-4-II-E cells. Tumor-to-muscle ratios of 111In in males were 4.9:1 in the primary tumor and 9.1:1 in the metastatic lymph nodes 24 h post injection. In the lymph node metastases in the males, a significant correlation between 111In uptake and [3H]thymidine was observed (r = 0.737) suggesting that 111In uptake in the metastases is related to cellular proliferation. No such correlation was observed in either primary tumors (both male and female) or in the draining lymph nodes of the females. Metastatic lymph nodes in males could be detected in gamma camera images while draining nodes in females could not be delineated. Injection of ferric citrate prior to 111In administration resulted in a significant reduction of 111In uptake in the liver, spleen and tumor and increased the amount of activity recovered from the kidney. Measurements of the binding of 131I-labeled rat transferrin to H-4-II-E cells in vitro suggest that these cells display transferrin receptors.
 ...
PMID:Distribution and mechanism of uptake of 111InCl3 in a tumor model for lymph node metastases. 404 44


<< Previous 1 2 3 4 5 6 7 8 9 10