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)

Paradoxical growth hormone (GH) responses in 50 g or 75 g oral glucose tolerance tests (OGTT) have been demonstrated in 24 patients with hepatocellular carcinoma, whereas no significant changes in serum GH levels after OGTT were shown in 10 normal controls, 6 patients with cirrhosis of liver, and with chronic active hepatitis. There were no significant difference in the GH responses in OGTT as well as in the incidence of paradoxical GH responses between diabetic and non-diabetic patients with HCC. Informatively, the basal somatomedin C level was very low in all cases examined.
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PMID:[Clinical studies on the relation of abnormal growth hormone secretions to hepatic diabetes mellitus in patients with hepatocellular carcinoma]. 254 47

The 5' flanking regions of the rat phosphoenolpyruvate carboxykinase gene were used to form chimeric gene constructs with the human growth hormone gene. These constructs were transfected into several renal and one liver cell line and the production of growth hormone (HGH) measured by immunoassay. Cyclic-AMP and glucocorticoid responsiveness of HGH production was observed in all cell lines. In two lines, the rat NRK52E renal epithelial line and the rat H4IIE hepatoma cell line, both capable of expressing PEPCK, lowering extracellular pH increased HGH production several fold. Comparison of hormone and pH effect on cells transfected with a thymidine kinase promoter-HGH chimera indicated that the PEPCK 5' flanking region effects were specific. Thus, part of the pH responsiveness of the PEPCK gene in vivo may be attributed to properties of the 5' flanking regions.
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PMID:The 5'region of the rat phosphoenolpyruvate carboxykinase gene confers pH sensitivity to chimeric genes expressed in renal and liver cell lines capable of expressing PEPCK. 255 24

Dihydrodiol dehydrogenase (EC 1.3.1.20) catalyzes the NADP+-dependent oxidation of a variety of trans-dihydrodiol proximate carcinogens, a reaction that may suppress their carcinogenicity. Using benzenedihydrodiol [(+)-trans-1,2-dihydroxy-3,5-cyclohexadiene] as a substrate, this enzyme can be detected spectrophotometrically in rat H-4IIe hepatoma cells with a specific activity similar to that observed in rat liver cytosol. The hepatoma cell enzyme is potently inhibited by 6-medroxy-progesterone acetate (IC50 = 38 nM) and indomethacin (IC50 = 3.5 microM). These cells contain 3 alpha-hydroxysteroid dehydrogenase which is also sensitive to inhibition by the same two drugs. Chromatofocusing of hepatoma cell lysates indicates that both dihydrodiol dehydrogenase and 3 alpha-hydroxysteroid dehydrogenase activities coelute with a pI = 5.8. Western blot analysis of hepatoma cell lysates, using rabbit anti-rat 3 alpha-hydroxy-steroid/dihydrodiol dehydrogenase serum detects a single immunoreactive species with a Mr 34,000. Using this antiserum it was possible to immunotitrate both these enzyme activities in H-4IIe lysates. Exposure of confluent cells to either 10 microM benz[a]anthracene or 10 microM dexamethasone, which are known inducers in H-4IIe cells of aryl-hydrocarbon hydroxylase and tyrosine aminotransferase respectively, failed to elevate dihydrodiol dehydrogenase activity. The following agents also failed to induce dihydrodiol dehydrogenase activity: phenobarbital, ethoxyquin, phenolic anti-oxidants, testosterone, estradiol-17 beta, and growth hormone. Since the hepatoma cell enzyme has properties in common with the purified rat liver enzyme (which is identical to 3 alpha-hydroxysteroid dehydrogenase) including, Mr, pI, immunoreactivity, and sensitivity to drug inhibition, this cell line represents a useful system for studying the role of dihydrodiol dehydrogenase in the further metabolism of trans-dihydrodiols. Interestingly, the enzyme does not appear to be under the control of known inducers of phase I and phase II drug metabolizing enzymes.
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PMID:Characterization of dihydrodiol dehydrogenase in rat H-4IIe hepatoma cells. 268 4

Hepatoma cells were infected with replication-incompetent murine retroviruses containing the selectable gene for amino-3'-glycosyl phosphotransferase (neo) and/or the nonselectable gene for bovine growth hormone (bGH). Expression of these genes was controlled by the promoter regulatory region of the gene for the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) (PEPCK) from the rat, which contains hormone and tissue-specific regulatory elements. Expression of the transduced PEPCK-neo gene was stimulated by Bt2cAMP and glucocorticoids and inhibited by insulin. The amount of RNA which initiated within the retroviral 5' long terminal repeat (5' LTR) was inhibited when internal promoters were present in the retroviral vector. When no internal promoter was present, expression from the 5' LTR was higher and stimulated by glucocorticoids, due to the presence of a glucocorticoid regulatory element in the 5' LTR. Infection of cells with retroviruses altered the basal expression and hormonal regulation of the endogenous PEPCK gene, but had no effect on the expression of the tyrosine aminotransferase gene, which is regulated in a similar manner by cAMP and glucocorticoids. A segment of the PEPCK promoter acted as a hormonally regulated enhancer, bringing the SV40 early promoter under the control of Bt2cAMP. A second, nonselectable gene (PEPCK-bGH), contained in the retroviral vector together with PEPCK-neo, was expressed and regulated appropriately when introduced into hepatoma cells. The proviruses were initially integrated randomly into the host cell genome, but after prolonged selection for expression of the transduced PEPCK-neo gene, cells were selected which contain a predominant site(s) of integration. Among populations of cells, however, the predominant site(s) of proviral integration was different. The selection of cells with a specific site of integration from a population was accelerated by the presence of PEPCK promoter sequences in the provirus. Despite the need to better characterize their effects on the host cell, retroviruses appear to be versatile tools for the specific introduction of regulated genes into cells.
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PMID:Hormonal regulation of chimeric genes containing the phosphoenolpyruvate carboxykinase promoter regulatory region in hepatoma cells infected by murine retroviruses. 284 79

A growth hormone-dependent binding protein for insulin-like growth factors (IGF-I and IGF-II) has been isolated from human plasma. Analyzed on SDS gels, the preparation contained a major protein band of 53 kDa, and a minor band of 47 kDa. After transfer to nitrocellulose, both species bound iodinated IGF-I, and could be detected using an antibody raised against the purified preparation. In contrast, an IGF binding protein purified from human amniotic fluid bound IGF-I but was not detectable immunologically. The amino acid comparison of the plasma binding protein preparation was different from that reported for amniotic fluid and HEP G2 hepatoma proteins, and the unique amino-terminal sequence, Gly-Ala-Ser-Ser-Ala-Gly-Leu-Gly-Pro-Val-, was different from that of the amniotic fluid and hepatoma proteins. This study indicates that the growth hormone-dependent IGF binding protein of human plasma is structurally and immunologically distinct from other IGF binding proteins.
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PMID:Growth hormone-dependent insulin-like growth factor (IGF) binding protein from human plasma differs from other human IGF binding proteins. 294 61

Basal T4, T3, TSH, prolactin and growth hormone levels were determined in several groups: patients with postnecrotic cirrhosis with hepatocellular carcinoma (n = 14); patients with postnecrotic cirrhosis but without hepatocellular carcinoma (n = 26); cholangiolar carcinoma (n = 9); and normal controls age-matched to within 5 yr of the liver disease subjects studied. In addition, TRH stimulation (400 micrograms TRH) was performed; TSH, prolactin and growth hormone responses over a 180-min time interval were evaluated for each subject. The responses observed varied between liver disease groups. The presence or absence of hepatocellular carcinoma was found to determine, at least in part, the type of response observed. Similarly, the presence or absence of hepatic encephalopathy determined, and/or reflected, at least in part, the type of response observed. Finally, for purposes of continuity, basal and TRH-stimulated levels of TSH, prolactin, growth hormone, T4 and T3 are compared in 3 settings of cirrhosis: alcoholic, nonalcoholic postnecrotic cirrhosis, and postnecrotic cirrhosis with hepatocellular carcinoma.
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PMID:Thyroid and pituitary hormone responses to TRH in advanced nonalcoholic liver disease. 303 51

Liver alcohol dehydrogenase activity was present in rat H4IIE hepatoma cells. Dexamethasone increased the enzyme activity two- to fourfold in these cells, but not in HepG2 cells. Enzyme induction was observed at dexamethasone concentrations as low as 10(-9) M, and the induction was maximal at 3 days. The increase in enzyme activity was accompanied by an increase in alcohol dehydrogenase mRNA on Northern blots and a two- to fourfold increase in alcohol dehydrogenase mRNA levels as estimated from cytoplasmic dot blots. There was no effect of dexamethasone on alpha-tubulin mRNA levels. Insulin, triiodothyronine, and growth hormone had no effect on alcohol dehydrogenase activity or mRNA levels. The induction of alcohol dehydrogenase mRNA by dexamethasone could be blocked by actinomycin D, but not by protein synthesis inhibitors. Superinduction of the mRNA (approximately twofold) was observed with dexamethasone in the presence of cycloheximide. Southern blots of genomic DNA from rat liver and H4IIE cells revealed no differences in alcohol dehydrogenase gene structure. The induction of alcohol dehydrogenase activity and mRNA levels by dexamethasone may be due to an increase in the rate of transcription of the alcohol dehydrogenase gene.
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PMID:Induction of alcohol dehydrogenase activity and mRNA in hepatoma cells by dexamethasone. 336 66

The levels of growth hormone (GH) in the blood of rats with ascite Zajdela hepatoma and hepatoma 27 (H-27) are shown to increase during the tumour growth. Stimulation of the GH secretion is a result of the hypoglycaemic stress. An increase in the blood GH secretion is also observed in the fasting rats. To reveal the predominance of catabolic GH effects over the anabolic ones in the tumour host determination of the molar insulin/GH ratio in the blood is suggested. A direct correlation is found between reduction of this index, glycaemia and the content of liver glycogen. A short-term induced hyperglycaemia evokes a paradoxical reaction in terms of GH secretion. In contrast to control fasting rats, in tumour-bearing animals no correlation between thyrotropin and thyroxine blood concentration could be observed. Anaemia increasing progressively in the course of the tumour growth may be the cause of the above phenomenon.
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PMID:[Relation between disorders of glucose metabolism, secretion of somatotropic hormone, thyroxine, thyrotropin and hematocrit indices in rats with transplanted hepatomas]. 343 92

A well characterized human hepatocellular carcinoma cell line (PLC/PRF/5) containing complete sequences of HBV-DNA in integrated form into host DNA and growing under serum-free conditions was used to test the effect of human growth hormone (hGH) on the expression of the integrated viral DNA. Data in our hands point to an early, specific effect of hGH on HBV-DNA integrated sequences which appears to be unrelated to the late effect on total protein synthesis. Moreover this approach enabled us to detect specific hGH receptors on the cell membrane of PLC/PRF/5 cell line.
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PMID:Human growth hormone induced modulation of hepatitis B virus (HBV) gene expression. 358 66

Rat pituitary adenoma cells (GH3) that spontaneously synthesize and secrete both prolactin (Prl) and growth hormone (GH) were used in this study. Bromocriptine (5 X 10(-5) mol/l), a dopamine (DA) agonist, induced a rapid reduction in Prl and GH secretion with maximum effect (approximately 60%) after 15 min of treatment. Bromocriptine also inhibited Prl and GH production in a time- and dose-dependent manner with ED50 at 4 X 10(-6) mol/l and 7 X 10(-6) mol/l, respectively. Maximum effect was obtained at 5 X 10(-5) mol/l of bromocriptine which after 24 h of treatment reduced the production of Prl and GH by approximately 70 and approximately 50%, respectively. After 9 days of treatment both Prl and GH production was reduced by more than 95%. Bromocriptine also reduced cellular growth rate. The ED50 was approximately 1 X 10(-5) mol/l and the maximum effect (greater than 50%) was observed at 5 X 10(-5) mol/l. All effects of bromocriptine were reversible upon cessation of treatment. The antiproliferative effect of bromocriptine was also observed using a rat hepatoma cell line (MH1C1) and a human epithelial cell line (HE), suggesting a non-receptor mediated growth inhibition at high concentrations of the drug. In conclusion, the inhibitory effect of bromocriptine on secretion and production of both Prl and GH in GH3 cells occurs at a lower concentration than its effect on cell proliferation. The pharmacological effects of bromocriptine in vivo on Prl and GH producing adenomas may be explained by an action directly at the pituitary level.
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PMID:Effects of bromocriptine on hormone production and cell growth in cultured rat pituitary cells. 406 Sep 70


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