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)

The effects of phorbol ester on cell growth inhibition by transforming growth factor beta 1 (TGF-beta 1) in human hepatoma cell lines, Mahlavu and PLC/PRF/5, were investigated. TGF-beta 1 (2.5 to 10 pM) alone could not inhibit the growth of Mahlavu cells, whereas in the presence of 12-O-tetradecanoyl phorbol 13-acetate (TPA) at 1 ng/ml, TGF-beta 1 could suppress their growth in a dose-dependent manner. The growth of PLC/PRF/5 cells could be inhibited by addition of TGF-beta 1 (2.5 to 10 pM) alone in a dose-dependent manner, and this action was not affected by TPA (1 ng/ml). The TGF-beta 1 inhibition induced by TPA in Mahlavu cells could not be cancelled by addition of protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7) (10 microM) or staurosporin (1 nM). Thus, TPA could induce TGF-beta 1 inhibition of cell growth in Mahlavu cells which did not respond to TGF-beta 1 alone, and activation of protein kinase C does not seem to be behind this TPA action.
 ...
PMID:Effects of phorbol ester on cell growth inhibition by transforming growth factor beta 1 in human hepatoma cell lines. 216 81

Several human cell lines were studied for the production of gelatinases. Diploid fibroblasts, the melanoma cell line Bowes, the MG-63 osteosarcoma cell line and the human hepatoma cell line Malavu all constitutively produced a 67 kDa gelatinase. Gelatinolytic enzymes were quantified by a sensitive zymographic substrate conversion assay. Upon induction with phorbol 12-myristate 13-acetate (PMA), the human hepatoma cell line secreted considerable amounts of an 85 kDa gelatinase activity. The induction process was time- and dose-dependent. It represented a true increase in production per individual cell and was associated by a marked change of the cell morphology. The effect of various proteinase inhibitors and the maximal activity of the enzyme near neutral pH demonstrate that it is a neutral metalloproteinase. Characterization studies showed the 85 kDa gelatinase to be transformed to lower molecular weight, active forms by treatment with p-aminophenylmercuric acetate (APMA) or trypsin.
 ...
PMID:Human hepatoma cells produce an 85 kDa gelatinase regulated by phorbol 12-myristate 13-acetate. 216 96

Glucagon at a low concentration has a stimulatory effect on Ki-ras expression, whereas, at high concentrations the hormone suppresses the level of the Ki-ras transcripts. Incubation of the hepatoma cells with 10 microM dibutyryl cyclic AMP results in suppression of Ki-ras expression but the phorbol ester, 21-O-tetradecanoylphorbol 13-acetate (TPA) causes an increase. Down regulation of protein kinase C by prolonged exposure of hepatoma cells to TPA causes a dramatic decrease in the glucagon-stimulated effect on Ki-ras expression. The presence of diacylglycerol for 2 h in the culture medium results in a significant increase in Ki-ras expression, while treatment of the cells with 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine, a potent inhibitor of protein kinase C, leads to a dramatic reduction. The calcium ionophore, A23187 is able to stimulate Ki-ras expression, whereas, addition of verapamil or EGTA results in its suppression. The present findings suggest that the inductive effect of glucagon on Ki-ras expression at low concentrations is via the activation of protein kinase C which causes phosphorylation of some regulatory proteins that may eventually affect the level of Ki-ras mRNA. The suppressive effect of glucagon at higher concentrations is via an increase in cAMP through activation of adenylate cyclase.
 ...
PMID:Regulation of Ki-ras expression in Reuber H35 cells. 217 64

The metabolism of low density lipoprotein (LDL) subfractions was investigated in the human hepatoma cell line Hep G2. By means of a density gradient ultracentrifugation method three LDL subfractions were isolated from pooled serum of normolipidemic subjects: very light LDL-1A, light LDL-1B and heavy LDL-2, differing in size, relative lipid and protein content. Cell specific association, stimulation of cholesterol esterification and inhibition of sterol synthesis were determined in parallel after incubation of Hep G2 cells with increasing amounts of LDL-protein of the three LDL subfractions. These parallel experiments were repeated four times with freshly prepared LDL subfractions. Response curves were parametrized with the function y = a square root of x, depicting the relation between the cellular metabolic event (y) and the LDL-protein (x) or LDL-cholesterol (x) levels. An analysis of covariance model was used to test differences between parameters of the three LDL subfractions. When the results of all four experiments were taken into account, the cell specific association increased more with increasing LDL-protein concentration for LDL-1A than for LDL-2 (P less than 0.05). At the LDL-protein level of 80 micrograms/ml the cell specific association for LDL-2 amounted to 85.5% of that for LDL-1A. Results for LDL-1B were intermediate between those for LDL-1A and LDL-2. The corresponding cholesteryl ester formation increased more with increasing LDL-protein concentration for LDL-1A than for LDL-1B (P less than 0.001), and for LDL-1B more than for LDL-2 (P less than 0.001). At the LDL-protein level of 70 micrograms/ml the cholesterol ester accumulation for LDL-2 and LDL-1B was 48.4% and 70.3%, respectively, of that for LDL-1A. These differences between LDL subfractions in cholesteryl esterification were independent of the cholesterol content of the subfractions. Consistent with these findings, the [14C]acetate incorporation to sterols decreased more with increasing LDL-protein concentration for LDL-1A and LDL-1B than for LDL-2 (P less than 0.05). At the LDL-protein concentration of 70 micrograms/ml the decrease in sterol synthesis after incubation with LDL-2 and LDL-1B was 79.2% and 98.0%, respectively, relative to that for LDL-1A. When adjusted for differences in cholesterol content of the LDL subfractions these differences with regard to the 14C-acetate incorporation were not significant. The metabolic differences between LDL subfractions in vitro may have implications for the metabolism and atherogenic potential of the distinct LDL subfractions in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Differences in metabolism of three low density lipoprotein subfractions in Hep G2 cells. 217 3

Several clinical observations suggest that hepatocellular carcinoma (HCC or "hepatoma") may be a hormone-dependent tumour; the apparent relation to anabolic steroids and oral contraceptive preparations, and the striking male predominance particularly among patients with cirrhosis. In many animal models thyroid hormones, prolactin and testosterone stimulate tumour growth, and the latter may enhance the progression of chemically-induced hyperplastic nodules to frank malignancy. In animals and humans, both oestrogen and androgen receptors have been reported in normal and malignant liver tissue though some of the evidence is conflicting and the amounts detected vary widely. From a therapeutic standpoint, we failed to show any advantage from the addition of tamoxifen to adriamycin, in a controlled trial although other workers have, more recently, reported prolonged survival using tamoxifen alone. About 20% of HCC patients receiving the antiandrogen cyproterone acetate showed a clinical response.
 ...
PMID:Growth factors, endocrine aspects and hormonal treatment in hepatocellular carcinoma--an overview. 217 61

Modulation of c-myc gene expression by extracellular stimuli in H4IIE rat hepatoma cells was investigated by Northern blot analysis. Treatment of these cells with phorbol 12-O-tetradecanoate 13-acetate (TPA), insulin and concanavalin A (Con A) resulted in transient accumulation of c-myc transcripts within 2 hours. The induction of c-myc mRNA was dose dependent with similar responses for all three agents. The maximally induced c-myc mRNA levels varied from 5- to 15-fold of the control. Treatment with cycloheximide (10 micrograms/ml) and H7, a protein kinase C inhibitor (20 microM), inhibited this induction, suggesting that c-myc induction by these agents requires protein synthesis and protein kinase C activation.
 ...
PMID:Modulation of c-myc gene expression by extracellular stimuli in rat hepatoma cells. 220 Sep 3

We have studied the effects of the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) on cytochrome P-450-dependent monooxygenase activities in several differentiated and dedifferentiated Reuber rat hepatoma cell lines using aryl hydrocarbon (benzo[a]pyrene) hydroxylase (AHH), ethoxyresorufin O-deethylase (EROD), and aldrin epoxidase (AE) as test systems. The following results were obtained: (1) Exposure of cultures to 400 nM TPA for 18-24 h increased AHH activities in the differentiated lines 2sFou, H41IEC3/G- and Fao as well as in the dedifferentiated line 5L, 1.5-2.5-fold. The phorbol ester did not affect AHH activity in the dedifferentiated line H5. (2) EROD, a marker for P-450I, was induced by the phorbol ester to a similar degree as AHH. (3) A monoclonal antibody directed against P-450I strongly inhibited the AHH activity induced by TPA. (4) The onset of AHH or EROD induction by TPA was much later than that elicited by benz[a]anthracene. (6) In contrast to the induction of AHH and EROD, TPA decreased AE activity, a marker for P-450II, by about 50% in all the cell lines containing this monooxygenase activity. (7) The half-maximum-effect concentration of TPA for inducing or suppressing AHH and AE, respectively, was approximately 20 nM. (8) TPA did not interfere with AHH induction by benz[a]anthracene. However, the phorbol ester moderately decreased AHH induction and markedly suppressed AE induction by dexamethasone. The results indicate that TPA simultaneously induces P-450I and suppresses P-450II forms in rat hepatoma cells. P-450I induction by TPA in these cells did not appear to depend on their status of differentiation. Furthermore, the results suggest that the mechanism of P-450I induction by TPA differs from that elicited by polycyclic aromatic hydrocarbons or glucocorticoids.
 ...
PMID:Differential effects of 12-O-tetradecanoylphorbol 13-acetate on cytochrome P-450-dependent monooxygenase activities in rat hepatoma cells: induction of P-450I and suppression of P-450II. 232 Dec 43

The cellular metabolism of apoE-free HDL (HDL) was studied in rat hepatoma cells (FU5AH). Cells incubated with HDL showed a dose-dependent decreased incorporation of [14C]acetate into cell sterol, indicating a net cholesterol delivery to the cells. HDL was localized both at the cell surface and inside the cell. This conclusion was drawn from both the association of 125I-labeled HDL with the cells under different experimental conditions and morphological evidence based on the association of colloidal gold-labeled HDL with the cells. Up to 63% of the 125I-labeled HDL protein initially inside the cell was subsequently recovered in the media as trichloroacetic acid precipitable (TCA-ppt) protein after a 30-min, 37 degrees C chase with a 100-fold concentration of unlabeled HDL. About 27% of the TCA-ppt apoprotein originally inside the cell was recovered as TCA-soluble material. Thus, we conclude that of the HDL apoprotein taken up by the cells, the majority is resecreted by a retroendocytosis pathway. The quantity of HDL apoprotein reappearing in the media was stimulated by the presence of unlabeled HDL in the media, while the amount of TCA-soluble material produced was not. Retroendocytosis of HDL was inhibited at 0 degree C and by the presence of 10 mM NaCN, 20 mM 2-deoxy-D-glucose in the media. Thus, the pathway appears to be both temperature- and energy-sensitive. HDL resecreted by the cell were depleted of cholesteryl ester and showed an altered size distribution, indicative of lipoprotein catabolism and remodeling. This study provides evidence for the existence of an endocytosis-retroendocytosis pathway for HDL apoproteins in a rat hepatoma cell and for the possibility that the endocytosis-retroendocytosis pathway may be involved in lipid delivery to the cell.
 ...
PMID:Metabolism of apoE-free high density lipoproteins in rat hepatoma cells: evidence for a retroendocytic pathway. 232 43

The addition of calf serum to culture medium alters the biological response of Morris hepatoma 7777 (MH) cells to autocrine growth factors isolated from conditioned medium of the investigated cells. Acetic acid (AA) extract obtained from conditioned medium of MH cells showed a change in anchorage-independent growth-regulatory activity from stimulation (serum-free) to inhibition (10% calf serum). Two protein fractions of apparent molecular weight 15 and 7.5 kDa isolated from AA-extract by Bio-Gel P-60 filtration also changed their growth-regulatory activity after supplementation of culture medium with calf serum. The contradictory effect of autocrine regulators estimated in soft agar using the 3H-thymidine (3H-TdR) incorporation test and colony formation assay gave generally comparable results, except in the case of the 15-kDa fraction. The most active 7.5-kDa fraction stimulated 3H-TdR incorporation and colony formation in serum-free medium up to about 300 and 500% respectively, while in the presence of 10% calf serum inhibition of about 20 and 50% has been observed. Our results suggest that the fraction contains an autocrine growth factor(s), whose activity is inverted in the presence of serum.
 ...
PMID:Serum changes the response of cultured Morris hepatoma 7777 cells to autocrine growth factors. 236 97

A newly developed human hepatoma cell line, designated Hep G-2, expresses high-affinity insulin receptors meeting all the expected criteria for classic insulin receptors. 125I-insulin binding is time-dependent and temperature-dependent and unlabeled insulin competes for the labeled hormone with a half-maximal displacement of 1-3 ng/ml. This indicates a Kd of about 10(-10) M. Since Scatchard analysis of the binding data results in a curvilinear plot and unlabeled insulin accelerates the dissociation of bound hormone, these receptors exhibit the negative cooperative interactions characteristic of insulin receptors in many other cell and tissue types. Proinsulin and des(Ala, Asp)-insulin compete for 125I-insulin binding with 4% and 2%, respectively, of the potency of insulin. Anti-(insulin receptor) antibody competes fully for insulin binding. The two insulin-like growth factors, multiplication-stimulating activity and IGF-I are 2% as potent as insulin against the Hep G-2 insulin receptor. Furthermore, Hep G-2 cells respond to insulin in several bioassays. Glucose uptake, glycogen synthase, uridine incorporation into RNA and acetate incorporation into lipid are all stimulated to varying degrees by physiological concentrations of insulin. In addition, these cells 'down-regulate' their insulin receptor, internalize 125I-insulin and degrade insulin in a manner similar to freshly isolated rodent hepatocytes. This is the first available human liver cell line in permanent culture in which both insulin receptors and biological responses have been carefully examined.
 ...
PMID:Insulin receptors and bioresponses in a human liver cell line (Hep G-2). 241 Feb 71


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