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)

1. Rates of degradation of normal and abnormal protein were measured in hepatoma cells after labelling first for 16h with [14C]leucine plus L-arginine and then for 3h with [3H]-leucine plus the arginine analogue, L-canavanine. 2. Over the first 2h of the degradation period, canavanine-containing proteins were degraded at approximately 5 times the average degradation rate of normal proteins. 3. Degradation of normal proteins was inhibited by about 30% by insulin, cycloheximide, puromycin, leupeptin, antipain and foetal calf serum, whereas these agents had a negligible effect on the breakdown of canavanine-containing proteins. 4. Other compounds inhibited degradation of both classes of protein to equal extents. 5. Combination experiments showed no additional inhibitory effects on the degradation of normal proteins over degradation measured in the presence of a single selective inhibitor. 6. In contrast with the results with a 16 h labelling period, the degradation of normal proteins labelled for only 3 h was not inhibited by insulin. 7. These results are explained by a model with two distinct pathways of protein turnover. The first of these pathways involves the formation of autophagic vacuoles and would be completely inhibited by each of the selective inhibitors. Normal and canavanine-containing proteins would be catabolized by this pathway at equal rates. We propose that degradation by a second pathway is not regulated by the agents tested, but by the inherent stability of each protein.
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PMID:Selective control of the degradation of normal and aberrant proteins in Reuber H35 hepatoma cells. 18 57

Various aspects of hormone treatment of tumor cells are reported; it is shown that following treatment with certain hormones, the cells are less susceptible to killing by antibody and complement. The diethylnitrosamine-induced guinea pig hepatoma, designated Line 1, is susceptible to killing by anti-Forssman immunoglobulin M (IgM) antibody and guinea pig complement (GPC) but not by specific antitumor antibody and GPC. The antigenetically distinct Line 10 hepatoma, when sensitized with either antibody, is susceptible to killing by human complement (HUC) but not by GPC. Strain 2 of Servall-Wright male guinea pigs were used. 2 antigenetically distinct diethylnitrosamine-induced hepatic tumors (ascites form), Lines 1 and 10, passed in Strain 2 guinea pigs, were collected and suspended in RPMI 1640-20% FCS. Toxicity assays were performed in VBS-gel. The hormones used were hydrocortisone sodium succinate, prednisolone sodium succinate, NSC9151, bovine insulin, L-epinephrine methyl ether HC1, DL-epinephrine, beta-estradiol, testosterone, pork insulin, chicken insulin, pork proinsulin, pork DAA insulin, and the A and B chains of pork insulin. Tumor cells were cultured in 10-ml volumes of RPMI 1640-20% FCS in plastic Petri dishes. After incubation, cell cultures were washed 5 times in VBS-gel and tested for their susceptibility to killing by antibody and complement. Rabbit antiserum to sheep Forssman antigen was prepared and stored at -20 degrees until used. Tumor specific rabbit Antilines 1 and 10 antisera were prepared and similarly stored. Results of tests show that Line 1 tumor cells incubated in a medium containing the polypeptide hormone, insulin, the catecholamine, L-epinephrine HCl, or the glucocorticoid steroids, hydrocortisone sodium succinate, or prednisolone sodium succinate were rendered resistant to killing byanti-Forssman IgM antibody and GPC. This effect was dependent on hormone concentration, temperature, and time. Effects were reversible. Similar results were obtianed with Line 10 cells under attack by specific antitumor and HUC or anti-Forssman antibodies. Less physiologically active analogs of the hormones did not have this effect. Tumor cells showed maximum resistance within 30-60 minutes of exposure to the hormones and reverted to the sensitive state within 4 hours. Resistance of the cells to killing was observed at 37 degrees but not at 0 degrees. It is concluded that the effect of hormone treatment was not due to a direct inactivation of bound or fluid-phase complement components by the hormones or to a decrease in the ability of the cells to bind complement-fixing antibody.
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PMID:Inhibition of antibody-complement-mediated killing of tumor cells by hormones. 18 62

We examined whether hormones would modify the carcinogenic action of aflatoxin B1 (AFB1). Four groups of inbred Fischer rats received AFB1, 125 mug per animal, weekly per os. In three of the groups, certain hormones were administered simultaneously: One group received 1 U growth hormone (GH) sc weekly, another was given 4 U adrenocorticotropin (ACTH) weekly, and a third received 0.5 U insulin weekly sc. AFB1, ACTH, and insulin were given for 20 weeks; GH was given for only 10 weeks. The control group did not receive hormone adjuvant. In each group, 4 animals were killed at 7, 14, 21, 28, and 35 weeks; the remaining rats were killed at 77 weeks. Their livers were carefully examined and samples prepared for light and electron microscopy. Animals receiving AFB1 and ACTH failed to exhibit hepatocellular carcinoma. On the other hand, malignant lymphoma appeared at 56 weeks in 3 of the 6 surviving males on this regime. AFB1, alone or when given with insulin or GH, caused hepatocellular carcinoma in all animals; in these, lymphoma was not observed. Lymphoma comprised two cell types, each with similar neclear characteristics but differing in their nucleocytoplasmic ratios and in the amount and distribution of cytoplasmic organelles. Alterations leading to hepatocellular carcinoma were examined at various stages of development. "Basophilic hyperplasia" reflected an increase in free ribosomes. "Hyperplastic nodules" were composed of hepatocyte aggregates with characteristics similar to those encountered in the earlier stage. Both the "neoplastic nodules" and hepatocellular carcinomas were formed by cells containing large, "smooth fingerprints" and free ribosomal aggregates. These features supported the concept that AFB1 impairs ribosomal binding to endoplasmic reticulum membranes. The failure of ACTH-treated animals to develop hepatocellular carcinoma was ascribed to the effect of adrenal cortical stimulation upon membrane-polysome binding.
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PMID:Inhibition of hepatocarcinogenesis by adrenocorticotropin in aflatoxin B1-treated rats. 18 49

Line 1, a chemically induced guinea pig hepatoma, is susceptible to killing by anti-Forssman immunoglobulin M antibody and guinea pig complement. When these tumor cells are pretreated with insulin, L-epinephrine, hydrocortisone, or prednisolone, the cells show a marked reduction in their susceptibility to antibody-complement-mediated killing within 15 to 60 min; this effect reverses within 4 hr in the continued presence of hormone. Maximal binding of the hormones to the line 1 cells was observed within 60 min. However, the hormones remained bound to the cells after 4 hr of incubation, suggesting that line 1 cells incubated in the continued presence of hormone revert to the susceptible state despite the persistence of cell-bound hormone. Hormone-treated tumor cells, washed free of hormone and reincubated in hormone-free medium, lost nearly all their bound hormone within 15 to 30 min of washing. These cells, however, remained resistant to antibody-complement-mediated killing for up to 2 hr after washing. Line 1 cells, reverted in the continued presence of hormone, remained susceptible to killing by antibody and guinea pig complement after reexposure to the same, but not to a different, hormone. Hormone-treated cells reverted after prolonged incubation in hormone-free media; however, they were rendered resistant to killing after reexposure to the same hormone. The temporary refractoriness of reverted cells to further hormone stimulation was not due to an inability of the cells to bind hormone.
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PMID:Kinetics of hormone-induced tumor cell resistance to killing by antibody and complement. 18 14

Plasma membranes (PM) of helathy rats as well as those hepatomas and PM of tumor-bearing rats were found (radioreceptor assay) to have apparently two groups of receptors for insulin with a high and low affinity for the hormone respectively and different insulin-binding capacities. Kass values of the receptors with a high affinity for insulin are drastically decreased in the PM of ascites Zajdela hepatoma (AZH) and of solid hepatoma 27 (SH-27) as well as in the liver of SH-27-bearing animals, but not in the liver of the AZH-bearing rats. Kass values of the receptors with a low affinity for insulin in the PM of AZH and in those of the liver of AZH-bearing rats appear nearly normal. In contrary, above Kass the receptors in the PM of SH-27 and SH-27-bearing animals are significantly decreased. The insulin-binding capacity of the receptors with a high affinity for the hormone in the PM of SH-27, AZH and the liver of both tumor-bearing rats is shown to be significantly higher than that in the PM of normal animals. The same property of the receptors with a low is affinity in the PM of the hepatomas and theliver of their hosts is also increased, especially in the PM of SH-27 and of the liver of SH-27-carring rats.
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PMID:[Study of insulin receptors on liver and hepatoma cell plasma membranes]. 20 60

Properties of insulin receptor on plasma membranes isolated from AH-66 ascites hepatoma cells and liver of tumor-bearing rats were studied. Specific binding (total binding minus nonspecific binding) of 125-I-labeled insulin to plasma membranes from AH-66 tumor cells and liver of normal and tumor-bearing rats were 33, 31, and 16% of a fixed amount of labeled insulin (1 x 10(5) cpm) added to each membrane preparation, respectively. Using Nisonoff plot, these membranes were found to possess at least two types of insulin receptors with a high affinity-low capacity and a low affinity-high capacity, as has been shown in normal liver. Total number of binding sites (high affinity plus low affinity sites, 8.4 x 10(-12) mol/mg protein) in hepatoma cells was more than that (7.0 x 10(-12) mol/mg protein) in normal rat liver. However, kinetic constants of binding in receptors of two types on tumor cells and tumor-bearing rat liver were similar to those of membrane receptors from normal rat liver. Insulin receptors of the hepatoma cells were considered to be highly specific for insulin from the results of competition with other peptide hormones. Inhibition of insulin binding with the tumor cell membranes by concanavalin-A, a competitive inhibitor for insulin receptor sites, did not differ very greatly from that of normal liver.
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PMID:Insulin receptors in AH-66 ascites hepatoma cells and liver of tumor-bearing rats. 22 Jan 27

The specific rate of synthesis of tyrosine aminotransferase (EC 2.6.1.5; L-tyrosine:2-oxoglutarate aminotransferase) is used as a measure of the level of functional, cytoplasmic, tyrosine aminotransferase-specific mRNA in cultured rat hepatoma cells. An analysis of the kinetics of change in this rate after the addition or withdrawal of glucocorticosteroids sets an upper limit on the half-life of the enzyme-specific mRNA of 1-1.5 hr, whether or not steroid is present. The inactivation rate of the enzyme mRNA is independent of the growth condition of the cells, occuring equally rapidly in the presence or absence of serum or insulin, both of which induce tyrosine aminotransferase in these cells. The implications of these results for the mechanism of steroid induction are discussed.
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PMID:Kinetics of steroid induction and deinduction of tyrosine aminotransferase synthesis in cultured hepatoma cells. 23 68

Glucocorticoids affect the composition and function of the plasma membrane in a variety of cell types. Cultured rat hepatoma (HTC) cells in tissue culture provide an excellent model system for analysis of such effects. In these cells, dexamethasone rapidly and dramatically inhibits the influx of amino acids sharing the A or alanine-preferring transport system. Inhibition is half-maximal within 2 h, and maximal after 6 h incubation with the hormone. The inhibition is rapidly reversed by insulin, and more slowly by removing the steroid. Microtubules and microfilaments are not apparently involved in this hormonal effect, but continuous protein synthesis is required for the glucocorticoid inhibition of transport. Dexamethasone also decreases the number of microvilli on the surface of HTC cells, increases their adhesiveness to a substratum, and dramatically decreases the production of plasminogen activator, but it does not affect the growth rate or plating efficiency of the cells. Variant cell lines stably resistant to dexamethasone inhibition of plasminogen activator production have been isolated using an agar-fibrin overlay technique to detect protease production by individual colonies of HTC cells. The hormonal resistance to inhibition of protease production is associated witha maintenance of inducibility of other glucocorticoid-regulated functions and therefore is not apparently secondary to abnormal or absent glucocorticoid receptor, but due to a lesion in a later step in hormone action specific for plasminogen activator. Combined genetic and biochemical analysis of such dexamethasone-resistant variants should facilitate study of the hormonal regulation of specific membrane phenotypes and of the role of proteases in this regulation.
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PMID:Glucocorticoids and the plasma membrane. 38 92

Line 10 guinea pig hepatoma cells are resistant to killing by antibody plus guinea pig complement but not by antibody plus human complement. Agents that increase (metabolic inhibitors) or decrease (hormones) the sensitivity of the cells to killing by antibody plus complement were examined for their effects on the chemical, physical, and enzymic composition of the cells. The effects of these agents on the chemical and enzymic characteristics of isolated plasma membrane and intracellular fractions of these cells were also measured. Adriamycin treatment resulted in a decrease in the amount of ribonucleoprotein and smooth endoplasmic reticulum isolated from the cells as compared to untreated cells. Hormone (insulin or hydrocortisone)-treated cells were enhanced in their yield of this fraction but were decreased in their yield of mitochondria as compared to controls. Generally, the drug-treated cells were decreased, whereas hormone-treated cells were enhanced, in protein, lipid phosphate, and total phosphate content, as compared to untreated controls. This pattern was also noted in the plasma membrane fraction of the cells and, in several cases, in intracellular membrane fractions. These data suggest that the protein, lipid phosphate, and total phosphate content of the plasma membrane and intracellular membranes of these cells may correlate with their ability to resist humoral immune attack.
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PMID:Physical and chemical composition of subcellular fractions from tumor cells treated with metabolic inhibitors or hormones. 42 Dec 20

Endotoxin-stimulated glucocorticoid-antagonizing factor (GAF) was assayed by its specific inhibition of hydrocortisone-induced synthesis of phosphoenolpyruvate carboxykinase. Defined induction of phosphoenolpyruvate carboxykinase synthesis in hydrocortisone-treated rat hepatoma cells permitted reliable quantitation of GAF and analysis of the mechanism of cortisol antagonism. GAF was present maximally in serum 2 hours after endotoxin challenge in mice; however, GAF production could be suppressed by pretreating mice with indomethacin or cortisol. Endotoxin-tolerant mice were also nonresponsive to endotoxin-stimulated GAF production. Gel filtration on Sephadex G-200 resolved four regions of glucocorticoid-antagonizing activity in serum from endotoxin-poisoned mice, two of which were not present in normal serum. Cortisol antagonism by GAF resembled that of insulin; however, insulin differed from GAF in its ability to antagonize dibutyryl cyclic AMP. Unlike insulin, endotoxin-induced serum glucocorticoid-antagonizing activity was heat-labile at 70 degrees C. GAF antagonism of hydrocortisone was partially reversible but did not act in a competitive manner. Production of hepatoma growth inhibitory activity and glucocorticoid-antagonizing activity in serum were closely associated, indicating a common methanism for their generation.
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PMID:The use of Reuber hepatoma cells for the study of a lipopolysaccharide-induced macrophage factor: glucocorticoid-antagonizing factor. 45 33


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