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)

Three liver-specific growth media, respectively free of arginine (Arg-), tyrosine (Tyr-) and glucose (G-), have been used to characterize cells of the rat H4IIEC3, human HepG2 and mouse BW hepatoma lines. Cells of clone FaO, a derivative of line H4IIEC3, freely grew in Tyr- and G- media, and gave rise to stable variants in Arg- conditions. Cells of line HepG2 and clone BWTG3, a derivative of line BW, degenerated in all three media. Arg and tyr variants were however derived from HepG2 cells; their genesis appeared to be pathway specific, illustrating the complexity of the regulatory loops that are implicated in the control of the differentiated state. No variant was ever obtained with BWTG3 cells, demonstrating the stability of their deficiency in the post-natal hepatic functions that are involved in Arg-, Tyr- and G- selections. Variant clones of HepG2 and FaO cells that have been isolated in Arg- medium were characterized in details for liver-specific urea-cycle enzyme activities and mRNA. These variants were shown to be controlled at the mRNA level, most likely at transcription. Isolation of stable FaO and HepG2 variant clones as well as the converse demonstration of the stable deficiency of BWTG3 cells in post-natal hepatic functions were aimed at expression cloning. Our results are thus discussed in terms of transfection with full-length cDNA expression libraries and cloning of regulatory genes that could activate or extinguish liver specific genes.
 ...
PMID:Selection of variant hepatoma cells in liver-specific growth media: regulation at the mRNA level. 132 34

A number of plasticizers and lipid-lowering drugs induce peroxisomes and cause hepatocellular carcinoma in rodents by mechanisms which remain unknown. In this study, seven structurally dissimilar peroxisome proliferating agents were shown to uncouple oxidative phosphorylation in isolated rat liver mitochondria. For example, perfluorooctanoate (0.5 mM) increased succinate-induced (state 4) mitochondrial respiration by over 50% while stimulation of state 3 respiration with ADP was minimal (i.e., uncoupling occurred). Interestingly, compounds which are potent carcinogens in vivo (e.g., Wy-14,643 and perfluorooctanoate) were more powerful uncouplers of oxidative phosphorylation in vitro than weak tumor-causing agents (e.g., valproate). Uncoupling also occurred in vivo. Basal rates of oxygen uptake in perfused livers from chronically treated rats were increased from 137 +/- 7 mumol g-1/h in pair-fed controls to 153 +/- 5 mumol g-1/h after 2.5 months of feeding Wy-14,643 (0.1% w/v in diet). Concomitantly, rates of urea synthesis from ammonia, a process highly dependent on ATP supply, were reduced almost completely from 104 +/- 10 mumol g-1/h to 13 +/- 6 mumol g-1/h. Bile flow, another energy-dependent process, was also reduced significantly by treatment with Wy-14,643 in vivo for 24 h. Taken together, these data indicate that energy supply for cellular processes such as urea synthesis and bile flow was disrupted in vivo due to uncoupling of oxidative phosphorylation by Wy-14,643. It is proposed that peroxisomal proliferators accumulate in the liver where they uncouple mitochondrial oxidative phosphorylation and interfere with cellular energetics.
 ...
PMID:Several nongenotoxic carcinogens uncouple mitochondrial oxidative phosphorylation. 139 Aug 25

The contribution of extracellular components to the measurement of pHMRS of a variety of rat tumours (nitrosomethyl urea induced mammary tumours, GH3 prolactinomas, Hepatoma 9618a, UA hepatomas and Walker sarcomas) has been assessed. Acid extractable P(i) was between 2.6 and 12.5 mumol/G wet wt depending on tumour type, and of this 53 +/- 4.8% (mean +/- SEM) was MRS-visible. The P(i) content of tumour exudate was 2-3 mM, of interstitial fluid (sampled from a micropore chamber incorporated within a tumour) 1.7 mM, and of blood plasma 1.95 mM. The mean extracellular volumes of the tumours, measured by distribution of 3H2O and [14C]inulin, were 49-55% depending on tumour type and were at least twice that found in normal liver. Calculations suggested that for most tumours with an extracellular volume not exceeding 55%, at least 65% of the P(i)(MRS) signal was derived from intracellular P(i), and thus that pH(MRS) is a measure of pHi. For each tumour type, pHMRS was measured both in 'pulse-acquire' mode at 1.9 T which may include signals from surrounding tissue, and in localized mode at 4.7 T where the signal came uniquely from tumour tissue. The steady state pHMRS was either neutral or on the alkaline side of neutrality (pH range 7.04-7.37). Raised lactate content and decreased buffering capacity (compared to normal tissues) accompanied these neutral to alkaline pH values.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:An assessment of 31P MRS as a method of measuring pH in rat tumours. 148 71

Co-secretion of plasminogen activator inhibitor type 1 (PAI-1) and urokinase-type plasminogen activator was identified in short-term cultures of primary type II pneumocytes isolated from adult rats. After separation by sodium dodecyl sulfate (SDS)-PAGE and reverse fibrin autography (reverse FA) of serum-free conditioned medium (SFCM), cellular lysate, and extracellular matrix (ECM), the inhibitor was seen as a zone of spared lysis at an apparent molecular mass of 46 to 48 kD. The plasminogen activator (PA) activity could only be visualized when human instead of bovine fibrin was used in the indicator gel. It presented as a single band of lysis at an apparent molecular mass of 45 kD when tested by regular FA and was found adjacent to PAI-1 when examined by reverse FA. Immunoblot analysis of type II pneumocyte SFCM, cellular lysate, and ECM revealed two bands at 46 and 48 kD, consistent with the apparent molecular masses (Mr) reported for rat PAI-1 from HTC hepatoma cells. Type II pneumocyte PAI-1 formed SDS-resistant complexes with tissue-type and urokinase-type plasminogen activator and was found to be stable to acid, to short-term exposure to heat, and to the denaturants guanidine HCl and SDS, while being sensitive to treatment with alkali and urea. When levels of type II pneumocyte PAI-1 activity were monitored over time during short-term culture conditions, the level of PAI-1 in SFCM remained stable, whereas activity in the lysate accumulated and activity in the ECM declined.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Plasminogen activator inhibitor type 1 production by rat type II pneumocytes in culture. 154 Mar 77

To delineate the natural clinical course of spontaneous bacterial peritonitis in hepatitis B-related cirrhosis and to determine if it occurs in hepatocellular carcinoma, a prospective survey was conducted in 262 patients over 2 1/2 years. The in-hospital incidence and mortality rates of spontaneous bacterial peritonitis were 21.6% and 36.4%, respectively, in cirrhosis and 7.3% and 50% in hepatocellular carcinoma. In cirrhosis, the cumulative probability of annual recurrence of spontaneous bacterial peritonitis was 47.3%, which was significantly higher than the annual probability of occurrence of 11.3% in those with no previous attack (P less than 0.0001). The cumulative probability of annual survival was 27.6% in the spontaneous bacterial peritonitis patients, significantly lower than the probability of 64.0% in the control group (P = 0.0001). A univariate analysis, with Kaplan-Meier curves compared by the Mantel-Cox test, and subsequent multivariate analysis by stepwise Cox regression procedure were used to evaluate 37 variables recorded immediately after admission. Blood urea nitrogen concentration greater than 10.5 mmol/L urea (greater than 30 mg/dL) and ascitic fluid protein concentration less than 7.35 g/L (less than 735 mg/dL) were found to be the only significant predictors of lower annual survival; ascitic fluid protein concentration less than 7.50 g/L (less than 750 mg/dL) was the only significant predictor of higher annual recurrence. The authors conclude that spontaneous bacterial peritonitis has a high risk of recurrence in hepatitis B-related cirrhosis and that the same disease occurring in patients with hepatocellular carcinoma is related to the underlying cirrhosis rather than the hepatocellular carcinoma.
 ...
PMID:Spontaneous bacterial peritonitis in patients with hepatitis B-related cirrhosis and hepatocellular carcinoma. 165 49

Lysyl oxidase was partially purified from serum by a diethylaminoethyl batch procedure in the presence of 6 mol/L urea and dialyzed against 3 mol/L KSCN. Using this method, we determined serum lysyl oxidase activity in 52 patients with liver disease and in 14 healthy controls, and we examined usefulness of serum lysyl oxidase in assessing liver fibrogenesis. For this purpose, serum lysyl oxidase activity in chronic liver disease was compared with serum levels of prolyl hydroxylase and laminin P1. As compared with controls, serum lysyl oxidase activity increased 1.6-fold in chronic persistent hepatitis, 4.4-fold in chronic active hepatitis and 11.8-fold in cirrhosis, indicating an increase in concert with the development of liver fibrosis. In hepatocellular carcinoma, the serum activity, although significantly increased, was lower than that in cirrhosis. Serum prolyl hydroxylase was significantly increased in chronic active hepatitis, in liver cirrhosis and in hepatocellular carcinoma. Serum laminin P1 was significantly increased in chronic active hepatitis, in cirrhosis and in hepatocellular carcinoma. Serum lysyl oxidase activity did not correlate significantly with serum levels of prolyl hydroxylase and laminin P1 in any subject or in any subgroup. The magnitude of the increase and the abnormal percentage of serum lysyl oxidase activity were larger than those for serum prolyl hydroxylase and laminin P1. These results suggest that serum lysyl oxidase activity is a more sensitive indicator of liver fibrosis than serum prolyl hydroxylase and laminin P1.
 ...
PMID:Serum lysyl oxidase activity in chronic liver disease in comparison with serum levels of prolyl hydroxylase and laminin. 168 40

The regulation of ornithine delta-aminotransferase (OAT) expression is poorly characterized in humans, but in rat there are tissue-specific responses to nutritional and hormonal stimuli. We analyzed 1.3 kilobases of 5'-flanking sequence and part of intron 1 of the human OAT gene and found several candidate regulatory sequences including four copies of a motif also present in the promoters of three other urea cycle-related enzymes (urea cycle element). We transfected a series of promoter deletion constructs into HepG2 (human hepatoma), H4 (rat hepatoma), and HEK (human embryonic kidney) cells and obtained maximal expression with 134 base pairs (bp) of 5'-flanking DNA. One of the urea cycle elements and the 3' end of exon 1 had positive effects on expression in all cell lines. However, mutations in a 22-bp element which overlaps the transcriptional start site decreased activity 4-fold in H4 cells only. cAMP increased endogenous OAT mRNA 4-fold in HepG2 cells and the expression of constructs containing as little as -85 bp of 5'-flanking DNA 2- 5-fold in HepG2 and H4 cells. DNase I protection analysis of the first 134 bp of 5'-flanking sequence with nuclear extracts from rat liver, rat kidney, HEK, and HepG2 cells showed two patterns of protection over one of the urea cycle elements. These studies provide the foundation for the understanding of tissue-specific regulation of OAT.
 ...
PMID:Transcriptional analysis of the human ornithine aminotransferase promoter. 184 93

To investigate the prognostic factors in Western patients with hepatocellular carcinoma, 206 patients with confirmed diagnoses of hepatocellular carcinoma were studied in terms of survival. All patients were diagnosed between 1983 and 1987. A multivariate survival analysis (Cox regression model) using clinical, biochemical, ultrasonographical and pathological data obtained at diagnosis disclosed that bilirubin (p = 0.0001), ascites (p = 0.0001), toxic syndrome (defined by the presence of weight loss greater than 10% premorbid weight, malaise and anorexia) (p = 0.009), blood urea nitrogen (p = 0.025), tumor size (p = 0.001), gamma-glutamyltranspeptidase (p = 0.0006), age (p = 0.0005), serum sodium (p = 0.003) and presence of metastases (p = 0.002) were independent predictors of survival. According to the contribution of each of these factors to the final model, a prognostic index was constructed allowing division of patients in different groups according to their relative risk of death: RRD = EXP (Age x 0.03 + Ascites x 0.8281 + BUN x 0.0137 + Serum sodium x (-0.0538) + gamma-Glutamyltranspeptidase x 0.0019 + Bilirubin x 0.0734 + Tumor size x 0.33 + Toxic syndrome x 0.4965 + Metastases x 0.55). These results facilitate the stratification of hepatocellular carcinoma patients to design and evaluate future controlled trials.
 ...
PMID:Prognostic factors of hepatocellular carcinoma in the west: a multivariate analysis in 206 patients. 217 Feb 67

Experience with high-dose cytosine arabinoside (HDAC) in pediatric solid tumors is limited. Sixteen children with solid tumors resistant to conventional therapies were registered in a pilot Pediatric Oncology Group (POG) study that required the administration of HDAC at 3 g/m2 every 12 hours for four doses. There were four cases of rhabdomyosarcoma, two cases of fibrosarcoma, four cases of neuroblastoma, and one case each of germ cell tumor, Wilm's tumor, retinoblastoma, hepatocellular carcinoma, Ewing's sarcoma, and Burkitt's lymphoma. All eligible patients had advanced diseases and had previously received extensive chemotherapy. Thirteen patients received one course of HDAC and three patients received two courses of HDAC. Due to prior treatments, patients had less than normal marrow reserves. Short-term toxicity included nausea, vomiting, suppression of hemopoiesis, drug fever, and increased blood urea nitrogen (BUN), creatinine, and liver enzymes. All evaluable patients recovered from their toxicities. There were no drug-related deaths. None of the patients had neurologic problems, including the only patient with prior irradiation to the skull. With the above schedule, HDAC appears to have manageable toxicity.
 ...
PMID:Toxicity of high-dose cytosine arabinoside in the treatment of advanced childhood tumors resistant to conventional therapy. A Pediatric Oncology Group study. 222 60

The gene for ornithine transcarbamylase (OTC; EC 2.1.3.3), a urea cycle enzyme, is expressed almost exclusively in the liver and small intestine. To identify DNA elements regulating transcription of the OTC gene in the liver, transient expression analysis was carried out by using hepatoma (HepG2) and nonhepatic (CHO) cell lines. The 1.3-kilobase 5'-flanking region of the rat OTC gene directed expression of the fused chloramphenicol acetyltransferase gene in HepG2 cells much more efficiently than in CHO cells. Analysis of deletion mutants of the 5'-flanking region in HepG2 cells revealed that there are at least one negative and two positive regulatory elements within the about 220-base-pair immediate 5'-flanking region. DNase I footprint analysis showed the presence of factors binding to these regulatory elements in nuclear extracts of rat liver and brain, and footprint profiles at the two positive elements exhibited liver-specific features. Transient expression analysis also revealed the existence of an enhancer region located 11 kilobases upstream of the transcription start site. The OTC enhancer was able to activate both its own and heterologous promoters in HepG2 but not in CHO cells. The enhancer was delimited to an about 230-base-pair region, and footprint analysis of this region revealed four protected areas. Footprint profiles at two of the four areas exhibited liver-specific features, and gel shift competition analysis showed that a factor(s) binding to the two liver-specific sites is related to C/EBP. These results suggest that both liver-specific promoter and enhancer elements regulate expression of the OTC gene through interaction with liver-specific factors binding to these elements.
 ...
PMID:Promoter and 11-kilobase upstream enhancer elements responsible for hepatoma cell-specific expression of the rat ornithine transcarbamylase gene. 230 62


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