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)

Hypercitrullinemia (adult type), believed to be one of the hereditary urea cycle disorders, is known to be complicated by hepatocellular carcinoma at a high incidence (approximately 14%). We investigated the relationship between this hypercitrullinemia and hepatocarcinogenesis. After the addition of citrulline, incorporation of tritiated thymidine into primary cultured hepatocytes of adult rat increased in a dose-dependent fashion in the range of 0.1 to 5 mmol/L. The citrulline-added group also showed significant increase in ornithine and polyamine contents in hepatocytes. The incidence of epithelial cell foci in the in vivo-in vitro tumor promotion analyzing system significantly rose in the group maintained with 5 mmol/L citrulline and in the group maintained with 1.5 mmol/L phenobarbital. These findings suggest the possibility that citrulline has a promotion effect on hepatocyte proliferation and that at high concentrations it plays the role of a hepatocarcinogenesis promoter.
 ...
PMID:Promoting effect of citrulline in hepatocarcinogenesis: possible mechanism in hypercitrullinemia. 234 56

The in vitro effects of alpha-difluoromethyl ornithine (DFMO) on the growth and the secretion of alpha-fetoprotein (AFP) and albumin in human hepatoma cell line PLC/PRF/5 were studied. DFMO caused a marked reduction in the growth rate and de novo synthesis of DNA, whereas secretion of AFP and albumin was not altered. These data indicate that AFP and albumin secretion are neither linked to polyamine synthesis nor to cellular proliferation in human hepatoma cells.
 ...
PMID:Effects of alpha-difluoromethyl ornithine on alpha-fetoprotein and albumin secretion in human hepatoma cell line, PLC/PRF/5. 241 87

Hepatocytes were isolated from human fetal liver in order to analyze the direct effects of growth factors and hormones on human hepatocyte proliferation and function. Mechanical fragmentation and then dissociation of fetal liver tissue with a collagenase/dispase mixture resulted in high yield and viability of hepatocytes. Hepatocytes were selected in arginine-free, ornithine-supplemented medium and defined by morphology, albumin production and ornithine uptake into cellular protein. A screen of over twenty growth factors, hormones, mitogenic agents and crude organ and cell extracts for effect on the stimulation of hepatocyte growth revealed that EGF, insulin, dexamethasone, and factors concentrated in bovine neural extract and hepatoma cell-conditioned medium supported attachment, maintenance and growth of hepatocytes on a collagen-coated substratum. The population of cells selected and defined as differentiated hepatocytes had a proliferative potential of about 4 cumulative population doublings. EGF and insulin synergistically stimulated DNA synthesis in the absence of other hormones and growth factors. Although neural extracts enhanced hepatocyte number, no effect on DNA synthesis of neural extracts or purified heparin-binding growth factors from neural extracts could be demonstrated in the absence or presence of defined hormones, hepatoma-conditioned medium or serum. Hepatoma cell-conditioned medium had the largest impact on both hepatocyte cell number and DNA synthesis under all conditions. Dialyzed serum protein (1 mg/ml) at 10 times higher protein concentration had a similar effect to hepatoma cell-conditioned medium (100 micrograms/ml). The results suggest that hepatoma cell conditioned medium may be a concentrated and less complicated source than serum for purification and characterization of additional normal hepatocyte growth factors.
 ...
PMID:Direct analysis of growth factor requirements for isolated human fetal hepatocytes. 244 74

Cocultured adult rat hepatocytes and a human hepatoma cell line (HepG2) were maintained in an arginine-free medium with or without ornithine alpha-ketoglutarate. This drug increased greatly hepatocyte albumin secretion in both culture models. L-Ornithine was the component accounting for these effects since similar data were obtained by using this sole amino acid. Moreover, we observed that L-ornithine stimulation of albumin production was via polyamine synthesis. Since a correlated increase in albumin mRNA was observed, it may be postulated that ornithine alpha-ketoglutarate acts at a pretranslational level.
 ...
PMID:Modulation of albumin secretion by ornithine alpha-ketoglutarate in adult rat hepatocyte cultures and a human hepatoma cell line (HepG2). 262 35

Fetal rat or neonatal human hepatocytes and a human hepatoma cell line were cultured in an arginine-free medium, supplemented or not with L-ornithine. This amino-acid improved survival of hepatocytes and strongly enhanced their transferrin secretion. Moreover, this increase observed in transferrin production was well correlated with a higher corresponding mRNA level. Thus, it may be postulated that the mechanism involved in the increased transferrin secretion by L-ornithine is of pretranslational origin.
 ...
PMID:Effect of ornithine on transferrin secretion of rat and human hepatocyte cultures. 321 74

Reuber hepatoma H-35 cells actively synthesize the urea cycle enzyme, carbamoyl-phosphate synthetase I. Treatment of H-35 cells with dexamethasone (0.14 microM), however, enhanced synthesis of the enzyme (as measured by incorporation of [35S]methionine) by 4-5-fold. Insulin (0.18 microM) completely inhibited dexamethasone-dependent stimulation of enzyme synthesis. In vitro translation and cDNA hybridization assays were employed to measure effects of dexamethasone plus or minus insulin on levels of mRNA encoding the biosynthetic precursor of carbamoyl-phosphate synthetase I (pCPS) in Reuber H-35 cells. Both measurements yielded similar results: dexamethasone increased pCPS mRNA levels by 4-5-fold and insulin suppressed this response, but only by 50%. Specific cDNA hybridization assays also demonstrated that Reuber H-35 cells, even after hormone treatments, contain only very low levels of albumin mRNA, and no detectable ornithine carbamoyl-transferase mRNA.
 ...
PMID:Expression of carbamoyl-phosphate synthetase I mRNA in Reuber hepatoma H-35 cells. Regulation by glucocorticoid and insulin. 389 Sep 50

Two X-linked genes, specifying ornithine transcarbamoylase (OTC) and glucose-6-phosphate dehydrogenase (Glc-6-PD), are reversibly suppressed in certain derivatives of the rat H4-II-E hepatoma. Either gene can become reactivated spontaneously, and it is shown that both can be reactivated by azacytidine treatment. This gene reactivation has been investigated by enzyme assay and by the use of selective growth media ('ornithine-medium' to select for OTC, and medium containing diamide to select for Glc-6-PD). There is a clear tendency for both genes to be reactivated together, though either can become active alone. Since OTC is an enzyme of the urea-cycle, and Glc-6-PD is an enzyme of the hexose monophosphate shunt, and since these two pathways are normally under quite separate control, it would seem that the coupled regulation of the two genes in these hepatomas is abnormal. It is suggested that the suppression of the two genes resembles X-inactivation: in both cases, azacytidine treatment induces gene reactivation with a high frequency and results in different clones of cells expressing widely varying amounts of enzyme activity. The association between the re-expression of OTC and Glc-6-PD might indicate that some phenomenon like the position-effect is occurring.
 ...
PMID:The associated reactivation of two X-linked genes. The spontaneous and azacytidine-induced reexpression of ornithine transcarbamoylase and glucose-6-phosphate dehydrogenase in a rat hepatoma. 608 29

'77orn', a derivative of the Morris rat hepatoma 7777, stably expresses high levels of ornithine transcarbamoylase (OTC) and carbamoylphosphate synthetase I (CPS-I), and is able to grow indefinitely in ornithine-medium (medium with ornithine in place of arginine). Variants that have lost this ability are isolated from 77orn by a 'suicide' selective technique dependent on the cellular incorporation of [3H]ornithine. These variants, which have reduced levels of CPS-I, or of both CPS-I and OTC, are shown to have developed multiple hormonal requirements; their enzyme deficiencies can be reversed by use of an appropriately supplemented medium. In particular, CPS-I is inducible by dexamethasone and dibutyryl-cyclic-AMP in combination. Cholera toxin can be used instead of cyclic-AMP, but then butyrate is additionally required if the induction is to be maintained in the long term. The use of these agents in excess can depress OTC. Several other hepatomas, and alos explanted foetal rat liver cells, have similar requirements for CPS-I expression. It is argued that multiple hormonal requirements for CPS-I production are normal in liver cells in vitro, and that hormone-independent hepatomas should be regarded as abnormal. The implications of this for the somatic cell genetic investigation of differentiation are briefly discussed.
 ...
PMID:Arginine synthesis by hepatomas in vitro. II. Isolation and characterization of Morris hepatoma variants unable to convert ornithine to arginine, and modulation of urea-cycle enzymes by dexamethasone and cyclic-AMP. 609 98

The rat hepatoma cell line, H4-II-E, was grown serially over a 1-year period and about 30 passages in arginine-, glutamine-, and tyrosine-deprived and ornithine-supplemented Eagle's minimum essential medium with no supplements other than biotin. The adapted cell line, R-Y121B, proliferates in the above mentioned medium with a doubling time of about 4 days and maintains hepatic "marker" enzymes such as tyrosine aminotransferase, phenylalanine hydroxylase, and all the enzymes of the urea cycle.
 ...
PMID:Continuous culture of Reuber hepatoma cells in serum-free arginine-, glutamine- and tyrosine-deprived chemically defined medium. 610 14

Rat hepatoma cells that do not synthesize the hepatic enzyme ornithine carbamoyl transferase spontaneously give rise to producing cells at a low frequency. Reexpression of this differentiation trait is strongly increased by 5-azacytidine treatment, suggesting that hypermethylation plays a critical role in the impaired expression of the ornithine carbamoyl transferase gene in hepatoma cells.
 ...
PMID:Spontaneous and 5-azacytidine-induced reexpression of ornithine carbamoyl transferase in hepatoma cells. 620 23


<< Previous 1 2 3 4 5 6 7 Next >>