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)

Studies were conducted to explore the effects of glucocorticoid hormones on the regulation of the metabolism of retinol-binding protein (RBP) by H4II EC4 rat hepatoma cells in culture. Cortisol, corticosterone, and the synthetic glucocorticoid analog dexamethasone all induced a 2- to 3-fold increase in accumulation of RBP. Half-maximal stimulation occurred at concentrations of dexamethasone in the range of 1-5 nM. Progesterone in the concentration range of 1-10 microM, inhibited the stimulatory effect of dexamethasone. Progesterone alone in this concentration range had no effect on RBP metabolism. By analogy with the studies of others, these observations with progesterone suggest that glucocorticoid receptors are involved in the effect of dexamethasone on RBP. As previously reported, RBP accumulated in the hepatoma cells when they were incubated in a medium free of serum and of vitamin A. The addition of retinol over a range from 3.5 nM to 3.5 microM stimulated a dose-dependent secretion of RBP from the cells into the medium. In longer experiments, retinol also stimulated the accumulation of RBP. Neither dexamethasone nor retinol had an effect on the accumulation or the cell to medium distribution of rat serum albumin or prealbumin at concentrations which were maximally stimulatory for RBP. When studied over a wide range of concentrations, retinol and dexamethasone incubated together produced approximately additive increases in the accumulation of RBP. Dexamethasone, moreover, did not affect the retinol-induced secretion of RBP. Thus, retinol and dexamethasone appear to function via different and independent mechanisms to regulate the metabolism of RBP by the liver cell.
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PMID:Regulation of retinol-binding protein metabolism by glucocorticoid hormones in cultured H4II EC3 liver cells. 719 3

The effect of progesterone on the movement of sterols from the cell surface to the rough endoplasmic reticulum (ER) was examined in rat hepatoma cells. Plasma membranes were labeled exogenously with [3H]cholesterol or [3H]zymosterol. Translocation of the labeled sterols to the rough ER was inferred from their conversion to [3H]cholesteryl esters and [3H]cholesterol, respectively. Progesterone inhibited both of these reactions by more than 90%. The concentration for half-maximal inhibition was 0.7 microgram/ml. Progesterone did not inhibit acyl-CoA:cholesterol acyltransferase activity itself, since the steroid had no effect on the esterification of [3H]cholesterol synthesized in vitro in the rough ER from [3H]zymosterol. Moreover, the small amount of [3H]cholesterol synthesized from plasma membrane [3H]zymosterol in progesterone-treated intact cells was esterified at the same fractional rate as cholesterol in control cells. Subcellular fractionation of cells pulse-labeled with [3H]cholesterol and treated with progesterone suggested that the block in plasma membrane cholesterol transfer to the rough ER occurred at the level of the plasma membrane.
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PMID:Cholesterol movement from plasma membrane to rough endoplasmic reticulum. Inhibition by progesterone. 810 80

Marked loss of body weight and profound waste of both skeletal muscle and white adipose tissue occur in rats into which the ascites hepatoma Yoshida AH-130 has been transplanted, associated with marked perturbations in the hormonal homoeostasis and the presence of circulating tumour necrosis factor and high plasma levels of prostaglandin E2 [Tessitore, Costelli and Baccino (1993) Br. J. Cancer 67, 15-23]. On the basis of previous findings, the present study examined whether the development of cachexia in this model system could be significantly affected by adrenalectomy or by pharmacological treatments that may interfere with proximal or distal mediators of tissue hypercatabolism. In no instance was tumour growth modified. Medroxyprogesterone acetate, an anabolic-hormone-like drug, was completely ineffective. In adrenalectomized animals, although changes such as the elevation of plasma triacylglycerols and corticosterone were corrected, the general course of cachexia was not modified. A partial prevention of muscle waste was observed with acetylsalicylic acid, a non-steroidal anti-inflammatory drug, or with leupeptin, a proteinase inhibitor. Insulin afforded the most significant preservation of muscle protein and adipose-tissue mass, which were maintained close to control values even 10 days after transplantation. The effects of insulin on gastrocnemius muscle and liver protein content were exerted by slowing down protein turnover, mainly enhancing synthesis. Consistently, the total free amino acid concentration in the gastrocnemius of insulin-treated rats 10 days after tumour transplantation was close to that of controls. Although treatment with insulin decreased plasma corticosterone to normal values, it did not modify the circulating level of tumour necrosis factor. On the whole these data show that it seems possible to prevent, at least in part, the tissue waste that characterizes cancer cachexia by purely pharmacological means.
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PMID:Pharmacological interference with tissue hypercatabolism in tumour-bearing rats. 816 61

Several biochemical events accompany and mediate the development of chronic liver disease and its evolution into cancer. Low plasma zinc and high copper levels have been observed in various liver diseases, such as liver cirrhosis and viral hepatitis, while increased oestradiol levels have been documented in chronic liver damage and hepatocellular carcinoma. We administered CCL4 intragastrically to 10 female Sprague Dawley rats for 30 weeks. All animals developed cirrhosis and four also developed hepatocellular carcinoma. Plasma levels of zinc, copper and oestradiol were significantly higher in the latter group than in animals with simple cirrhosis. Progesterone, AST and bilirubin showed a trend toward significant differences whereas testosterone and ALP levels were unchanged. These findings add to the evidence that sex hormones and trace elements are involved in the process of the development of chronic liver damage and carcinogenesis.
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PMID:Sex hormones and trace elements in rat CCL4-induced cirrhosis and hepatocellular carcinoma. 835 89

The expression of hsp70-the inducible member of the corresponding heat shock gene family-of the oxidative stress marker gene heme oxygenase (HOx), and of the immediate early response genes c-fos and c-jun has been studied in FAO hepatocarcinoma cells depleted of polyamines and exposed to heat shock. Depletion of polyamines was obtained in short-term experiments (24-48 hours) by the use of alpha difluoromethylornithine (DFMO), a classical inhibitor of ornithine decarboxylase (ODC), or of the combination of the newly available inhibitors of ODC and S-adenosylmethionine decarboxylase, i.e., (2R,5R)-hept-6-yne-2,5-diamine (MAP) and 5'{[(Z)-4-aminobut-2-enyl]methylanino}-5-deoxyadeno-si ne (AbeAdo). Under our experimental conditions polyamine imbalance was realized without appreciable growth-related genes. Decreases of putrescine and spermidine 48 hours after DFMO prevented the induction of hsp70 messenger RNA (mRNA), whereas depletion spermidine and spermine obtained with MAP/AbeAdo decreased intensity and duration of post-heat shock accumulation of hsp70 mRNA. Inductions of HOx, c-jun and c-fos were also inhibited. Because MAP/AbeAdo caused also an intracelluar accumulation of putrescine, we tested the effect of exogenous putrescine, which was found to stabilize the mRNAs for hsp70 and c-jun. Hsp70 and HOx are thought to play a protective role, and the proteins of c-jun and c-fos constitute the transcription factor activator protein-1, which is involved in the transcription of many defensive products. Therefore, the integrity of polyamine pool seems to be a necessary permissive condition for an effective response of the cells to adverse environmental changes.
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PMID:Effects of polyamine imbalance on the induction of stress genes in hepatocarcinoma cells exposed to heat shock. 870 55

An estrogen receptor (ER) positive cell line was newly established from a Wistar King Aptekman (WKA) rat, 3'-methyl-4-dimethylaminoazobenzene (DAB) induced hepatoma cell lines. The impact of hormonal therapy on cell growth was investigated. This cell line produced alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and ferritin in the conditioned medium. Progesterone receptors (PgR) were positive but androgen receptors (AR) were not detected. This cell line's doubling time was about 10.5 hours in a routine medium and 12.2 hours in the endogenous estrogen removed medium (exponential phase). The morphological features of the cell were of a hepatocellular type as observed by light microscopy. The modal chromosome number was 56 and the DNA ploidy pattern was aneuploid as observed by flow cytometry. The addition of 17 beta-estradiol (E2) did not increase cell growth but tamoxifen (TAM) in vitro inhibited cell growth in the lag phase. Surgical castration or oral administration of E2 or TAM in vivo inhibited tumor growth in the early phase. There were no additional effects between surgical castration and the administration of E2. Surgical castration plus the administration of TAM were not effective when combined. The administration of TAM caused the physiological effect of castration eg., diminished blood testosterone level same as E2 administration. TAM also decreased the maximal binding capacity (Bmax) of ER. A morphological change to the cholangiocell carcinoma type was noticed. These results that this cell line was ER dependent in the early phase of tumor growth.
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PMID:[Establishment of an estrogen receptor positive 3'-methyl-4-dimethylaminoazobenzene induced hepatoma cell line of rat and investigation of hormonal therapy]. 899 40

The influence of aniso-osmolarity on the activity of the MAP kinases Erk-1 and Erk-2 was studied in C6 glioma cells. Hypo-osmotic treatment (205 mosmol/l) led to an increased activity of Erk-1 and Erk-2 within 3 min, which became maximal at 10 min and returned to basal level within 120 min. In contrast, Erk activity was reduced under hyper-osmotic conditions (405 mosmol/l), compared to the normo-osmotic control (305 mosmol/l). Erk activation was accompanied by a mobility shift of Raf-1. Hypo-osmotic exposure increased the cytosolic Ca2+ concentration ([Ca2+]i). Absence of extracellular Ca2+ largely abolished the [Ca2+]i response to hypo-osmolarity, whereas Erk activation following hypo-osmotic stimulation remained unaffected, suggesting a Ca2+ independence of the osmosignalling pathway to the MAP kinases. Both the Ca2+ response as well as the Erk activation following hypo-osmotic exposure were maintained in the presence of the phospholipase C inhibitor U73122. Application of 8-CPT cAMP, forskolin/isobutylmethylxanthine or isoproterenol blocked Erk activation following hypo-osmotic treatment of the cells, suggesting a role of the Ras/Raf pathway upstream from Erk-1 and Erk-2. Protein kinase C (PKC) is unlikely to play a role in the hypo-osmolarity- induced signalling towards MAP kinases, as revealed by inhibition of PKC with Go6850. Inhibition of pertussis- or cholera toxin-sensitive G-proteins as well as inhibition of tyrosine kinases with genistein and of PI3 kinase by wortmannin had no effect on the Erk response to hypo-osmolarity. It is concluded that osmosignalling in C6 glioma cells differs upstream of the MAP kinases from that observed in primary rat astrocytes, H4IIE rat hepatoma cells and isolated rat hepatocytes.
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PMID:Osmosignalling in C6 glioma cells. 900 90

The action of hyperosmotic stress on the MAP kinase phosphatase MKP-1 mRNA expression was studied in H4IIE rat hepatoma cells. Hyperosmotic (405 mosmol/L) challenge of the cells led to a transient expression of MKP-1 mRNA, which was maximal after 6-8 h and disappeared completely after 24 h. Hyperosmotic MKP-1 mRNA induction was preceded by a transient activation of the MAP kinases Erk-1, Erk-2, and JNK-2, which were not prerequisite for MKP-1 mRNA accumulation. However, the hyperosmolarity-induced MKP-1 mRNA expression was sensitive to antioxidants and to inhibition of p38 by SB203580. A reduced sensitivity of Erk-1/Erk-2 to other stimuli was found after prolonged hyperosmotic exposure. The data are consistent with a hyperosmolarity-induced MKP-1 expression via reactive oxygen intermediates and p38, which may participate in the termination of MAP kinase activation and contribute to desensitization of the MAP kinases after prolonged hyperosmotic exposure of the cells.
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PMID:Hyperosmotic induction of the mitogen-activated protein kinase phosphatase MKP-1 in H4IIE rat hepatoma cells. 950 Aug 41

The authors previously reported that transforming growth factor beta1 (TGF-beta1) induces apoptosis in McA-RH7777 (7777) and McA-RH8994 (8994) rat hepatoma cell lines. Although these cell lines exhibit different responses to glucocorticoid treatment in various cellular functions and gene expression, dexamethasone (DEX) inhibited spontaneous and TGF-beta1-induced apoptosis in both. Analysis of analogous hormones in TGF-beta1-induced apoptosis in 8994 cells suggested the inhibitory effect to be glucocorticoid-specific. By cell-cycle analysis and DNA fragmentation assay using sodium butyrate, a G1-arrest-inducing reagent, regulation of apoptosis by TGF-beta1 and DEX was shown independent of the cell cycle. For elucidation of the mechanisms of anti-apoptotic action of DEX, the effects of various chemical probes on this apoptosis model were examined, and various reagents known to exhibit anti-apoptotic activity in other experimental systems were found to be ineffective. The effect of TGF-beta1 and DEX on cellular amounts of several apoptosis-related proteins, members of the Bcl-2 family, Bcl-2, Bcl-xL, Bcl-xS, Bad, and Bax was also examined. DEX drastically increased Bcl-xL in both cell lines irrespective of the presence of TGF-beta1. Bcl-2 and Bcl-xS proteins were not detected, and Bax and Bad content did not change by treatment with TGF-beta1 or DEX. Progesterone (Prog), a partial antagonist for glucocorticoid receptor, inhibited the effects of DEX on apoptosis and Bcl-xL expression in 8994 cells. Thus, Bcl-xL induction by DEX would appear closely associated with its inhibitory effect on spontaneous and TGF-beta1-induced apoptosis in the hepatoma cell lines.
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PMID:Inhibition by dexamethasone of transforming growth factor beta1-induced apoptosis in rat hepatoma cells: a possible association with Bcl-xL induction. 953 34

The effects of hypo- and hyper-osmotic shock on endogenous MAP-kinase activities and MKP-1 and c-jun mRNA levels were studied in H4IIE rat hepatoma cells. In presence of vanadate hypo-osmolarity stimulated a rapid and sustained activation of MAP-kinases (Erk-2, JNK-2 and p38). In the absence of vanadate a hypo-osmotic MAP-kinase response was not detectable. Hyper-osmolarity stimulated a delayed and transient MAP-kinase activation and vanadate was not required for its detection. Vanadate, however, amplified the hyper-osmotic MAP-kinase stimulation. c-jun and MKP-1 mRNA levels were maximal after 0.5-1 h of hypo-osmotic exposure and returned towards basal levels within 2 h, whereas the hyper-osmotic induction of c-jun and MKP-1 mRNA was delayed. Vanadate was not required for the aniso-osmotic effects on MKP-1 and c-jun mRNA levels. Whereas the hyper-osmolarity-induced c-jun mRNA accumulation returned towards basal levels within 8 h, MKP-1 mRNA was still highly expressed at this time point. The role of MAP-kinases for the induction of aniso-osmolarity-induced gene expression and the potential importance of MKP-1 for termination of aniso-osmotic MAP-kinase activation are discussed.
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PMID:Osmotic regulation of MAP-kinase activities and gene expression in H4IIE rat hepatoma cells. 968 15


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