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)

Injection of 3,4-benz(a)pyrene, methyl nitrosourea and phenobarbital into healthy mice of the C3HA line results in a rapid, sharp increase of [14C]-thymidine incorporated into liver microsomal DNA, accompanied by a suppression of nuclear DNA synthesis. In the liver of neoplastic mice and in the ascite cells of hepatoma 22A the system of microsomal DNA synthesis was insensitive to the injection of methyl nitrosourea. Cycloheximide and puromycin, which strongly inhibited nuclear DNA synthesis, had no effect on the synthesis of microsomal DNA. Stimulation of [14C]-thymidine incorporation into microsomal DNA after injection of methyl nitrosourea and 3,4-benz(a)pyrene may be accounted for not only by an increase of the DNA reparation processes, since caffeine, the inhibitor of post-replicatory reparation of DNA, did not eliminate the induction of microsomal DNA synthesis in the liver. Hydroxyurea in combination with methyl nitrosourea and phenobarbital significantly suppressed the synthesis of nuclear DNA in the liver and did not affect the synthesis of mtDNA; the stimulating effects of these inducers on the synthesis of microsomal DNA was thereby removed. This is indicative of independence of synthesis of microsomal DNA on that of nuclear DNA and mtDNA. Different specific radioactivities of microsomal, nuclear and mtDNAs in the regenerating mouse liver on the 5th, 10th and 15th post-hepatectomy days may be due to different metabolic stability of these DNAs. A possible role of microsomal DNA as a xenobiotic system component is discussed.
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PMID:[Accelerated microsomal DNA synthesis under the influence of xenobiotics and chemical carcinogens]. 43 79

Metallothionein (MT) protein is readily induced in vivo in rat liver by adenosine and adenosine agonists (2-chloroadenosine, 5-(N-ethyl) carboxamido adenosine, and 5-chloro-5-deoxyadenosine). These presumably operate via AMP/adenosine receptors of the P1 (A2) type, which use the cAMP pathway. ATP was ineffective as an inducer for MT. 2-Chloroadenosine was the most effective inducer (7.27-fold at 11 hr). This induction was blockable by the adenosine antagonists, caffeine and theophylline. MT protein induction by 2-chloroadenosine in primary cultured rat hepatocytes was modest (1.55-fold), but this was also blocked by theophylline. MT mRNA induction was assessed using dot blot and Northern gel assays. Large inductions by 2-chloroadenosine (5.1- to 41-fold) were seen, and these were detectable as early as 2 hr in vivo. Two rat hepatoma cell lines (EC3 and 2M) were studied in vitro. Modest inductions of MT mRNA were seen: 2.10-fold for EC3 and 4.12-fold for 2M. Our studies implicate the potential role of the purinergic system in the modulation of transcription of MT genes in rat liver. The sources of adenosine in vivo that might cause induction of MT mRNA and protein are not well defined, but adenosine may be important as a signal in stress response situations involving tissue damage, such as ischemia, hypoxia, and hemorrhagic shock.
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PMID:Purinergic agonist induction of metallothionein. 152 9

Induction of C-reactive protein (CRP) by conditioned medium from lipopolysaccharide-stimulated human monocytes in two human hepatoma-cell lines, Hep 3B and NPLC/PRF/5, was potentiated 3-6-fold by the methylxanthine caffeine. The induction observed in the presence of conditioned medium plus caffeine was as much as 180-fold, comparable with that seen after many stimuli in vivo. This potentiation was accompanied by an increase in the levels of CRP mRNA. By contrast, no potentiating effect on CRP induction by conditioned medium was found when we tested theophylline, forskolin, 8-bromo cyclic AMP or two Ca2+ ionophores, namely ionomycin and A23187. None of the above compounds, including caffeine, when tested alone, had any detectable effect on the synthesis and secretion of CRP. Our previous study [Ganapathi, May, Schultz, Brabenec, Weinstein, Sehgal & Kushner (1988) Biochem. Biophys. Res. Commun. 157, 271-277], employing defined cytokines, had shown that induction of CRP in Hep 3B cells requires IL(interleukin)-6 plus IL-1, whereas, in the NPLC/PRF/5 cell line, IL-6 alone is effective. Caffeine similarly potentiated induction of CRP by these defined cytokine signals in these two cell lines. Changes in synthesis of other acute-phase proteins, including serum amyloid A (SAA), alpha 1-proteinase inhibitor, alpha 1-antichymotrypsin and albumin, induced by conditioned medium or, in some cases, by IL-6 and/or IL-1 alpha, were only minimally affected by caffeine. Thus these results indicate that the mechanism by which caffeine potentiates CRP induction by cytokines appears to be independent of increases in intracellular concentrations of the two second messengers, cyclic AMP and Ca2+; the precise nature of this mechanism is unclear at the present time. Our results also indicate that the intracellular mechanisms by which cytokines regulate synthesis of CRP may differ from those regulating synthesis of some other acute-phase proteins. The differential response of CRP and SAA to caffeine is of particular interest, since induction of both of these two major acute-phase proteins can be accomplished by identical extracellular signals.
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PMID:Induction of C-reactive protein by cytokines in human hepatoma cell lines is potentiated by caffeine. 216 98

The effects of two methylxanthines, caffeine and isobutylmethylxanthine (IBMX), on the response to radiation given at two low dose rates were studied in a human hepatoma cell line, HepG2. These dose rates are in the range to which tumor cells are exposed in radiolabeled immunoglobulin therapy of primary hepatoma. At the higher dose rate (0.3 Gy/hr for 24 hr), the radiation completely inhibited growth, and cells accumulated in the G2 phase of the cell cycle. Caffeine (1 mM), given either continuously or during the last 4 hours of the radiation exposure, counteracted the growth inhibition and G2 accumulation and enhanced cell killing. The 0.5-mM dose of IBMX had little effect on cells. For a lower dose rate and longer exposure period (0.06 Gy/hr for 3 days), the radiation partially inhibited growth and the accumulation of cells in G2 was small. Continuous, but not short, exposure to caffeine enhanced killing at this dose rate and counteracted the G2 accumulation. At the lower dose rate, IBMX enhanced the growth inhibition, G2 accumulation, and killing above that with radiation alone.
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PMID:Effects of methylxanthines on cell-cycle redistribution and sensitization to killing by low-dose-rate radiation. 245 Nov 34

Theophylline, caffeine, isobutylmethylxanthine, papaverine, N6-cyclohexyladenosine, N6-allyl-N6-cyclohexyladenosine ( ACHA ) and N6-L-phenylisopropyladenosine (L-PIA) inhibited the transport of adenosine, uridine and hypoxanthine in Novikoff rat hepatoma cells. The IC50 values for the inhibition of uridine transport ranged from 5 microM for ACHA to 3200 microM for caffeine and were inversely proportional to the lipid solubility of the inhibitors. L-PIA and papaverine inhibited uridine influx in a non-competitive manner, having a greater influence on the Michaelis-Menten constant than on maximum velocity, just as observed previously for the inhibition of nucleoside transport by dipyridamole and hypoxanthine. [3H]L-PIA rapidly accumulated in Novikoff cells at 25 degrees to about five times higher levels than present extracellularly. The initial rates of L-PIA uptake were directly proportional to its extracellular concentration between 0.01 and 240 microM and not affected by structurally related analogs, methylxanthines, papaverine, dipyridamole, or 2 mM uridine, but were dependent on temperature. We conclude that L-PIA inhibits nucleoside transport in these cells without being significantly transported by the carrier, that it equilibrates rapidly across the plasma membrane without carrier mediation consistent with its lipophilicity, and that it accumulates concentratively in cells due to partitioning into membrane lipids and binding to intracellular components.
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PMID:Inhibition of the transport of adenosine, other nucleosides and hypoxanthine in novikoff rat hepatoma cells by methylxanthines, papaverine, N6-cyclohexyladenosine and N6-phenylisopropyladenosine. 620 40

An artificial capillary system was devised for growth of hepatoma cells that yields very high titers of hepatitis B surface antigen (HBsAg). High yield of antigen was facilitated by slowing cellular metabolism through reduction of incubation temperature and addition of 0.1 mM caffeine. Deletion of serum from the medium did not reduce the yield of antigen. HBsAg prepared from the culture fluid by affinity chromatography and additional chemical and enzymatic steps was essentially pure and was indistinguishable from HBsAg prepared from infected human plasma. Preparation of HBsAg from the cell culture source presents advantages over that of human plasma and might be a source of HBsAg for vaccine preparation.
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PMID:Production of purified hepatitis B surface antigen from Alexander hepatoma cells grown in artificial capillary units. 633 Jan 45

The effect of caffeine, the methylated xanthine, in sensitizing the lethal action of ionizing radiation in vitro was investigated in human cancer cells which were clinically known to be radioincurable. The tumor lines were hepatocellular carcinoma and colon adenocarcinoma. Plateau phase cultures, after absorbing doses of 2 Gy, survived at a rate of 56.30 per cent for colon cancer and at 66.05 per cent for liver cancer. Both lines were radiosensitized by caffeine but at different potencies. Noteworthily, hepatocellular carcinoma whilst less radiosensitive than colon adenocarcinoma was 4 times more susceptible to caffeine. The lowest effective caffeine concentration for liver cancer was 2 mM which slightly exceeded the anticipated lethal concentration in humans. Research on radiosensitizing effect of methylated xanthines on hepatoma system still remains intriguing. Future work should be pursued with the use of less toxic compounds, such as theobromine.
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PMID:Differential radiosensitization of radioresistant human cancer cells by caffeine. 800 58

The effects of dietary bioantimutagens (compounds which have been shown to inhibit mutagenesis via interaction with DNA repair processes) on spontaneous and heterocyclic amine (HCA)-induced micronucleus (MN) frequencies were studied in metabolically competent human hepatoma (Hep-G2) cells. All the compounds tested (coumarin, vanillin, caffeine, tannic acid and cinnamaldehyde) caused a moderate increase of MN numbers in Hep-G2 cells at high concentrations (500 microg/ml); only tannic acid was also active at lower dose levels. In combination experiments with the HCA 2-amino-3-methylimidazo-[3,4-f]quinoline (IQ), post-treatment of the cells with bioantimutagens resulted in a pronounced (75-90%) decrease in MN. The most drastic effects were seen with vanillin, coumarin and caffeine which were active at concentrations < or = 5 microg/ml. Further experiments indicated that these compounds also attenuate the mutagenic effects of other HCAs (PhIP, MeIQ, MeIQx, Trp-P-1).
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PMID:Inhibition of the genotoxic effects of heterocyclic amines in human derived hepatoma cells by dietary bioantimutagens. 923 77

Some patients with early-stage cirrhosis preserve hepatic function, whereas others have little hepatic reserve and rapidly deteriorate. The aim of this study was to use quantitative tests of liver function (QLFTs) to define the degree of functional hepatic impairment in patients with early-stage cirrhosis (Child-Pugh score 5-7) and to determine whether the tests predicted subsequent hepatic decompensation. We recruited 10 cirrhotic (Cr) patients and 10 healthy controls (NI), who were well matched for race, age, weight, and gender. Clearances of caffeine (CF) and antipyrine (AP) after oral administration were measured from timed samples of saliva. The clearance of cholate (CA) was measured from serum samples obtained after simultaneous oral ([2,2,4,4-2H]CA) and intravenous ([24-13C]CA) administration. CA shunt was calculated as (Cl i.v./Clo x 100%). CF elimination rate (Cr v NI, mean +/- SD: 0.03 +/- 0.02 v 0.075 +/- 0.018 h-1, P < .0005) and AP clearance (24 +/- 16 v 40 +/- 7 mL/minute, P < .02) were reduced in Cr patients. CA shunt was increased in Cr patients (43 +/- 18 v 18 +/- 7%, P < .002). Five Cr patients decompensated during follow-up and had the worst CA shunts (76%, 66%, 51%, 48%, and 45%). Three subsequently received successful orthotopic liver transplantation, 1 died of hepatoma, and 1 is on the waiting list for transplantation. In conclusion, QLFTs define the degree of functional impairment in early cirrhosis and may identify Cr patients at greatest risk of decompensation who may require transplantation for survival.
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PMID:Quantitative liver function tests define the functional severity of liver disease in early-stage cirrhosis. 934 31

The purpose of this study was to evaluate hepatic metabolic capacity in cirrhotic patients with hepatocellular carcinoma (HCC). We compared plasma caffeine clearance, calculated by two point analysis, between patients with cirrhosis alone and cirrhosis complicated with HCC. These two groups were comparable with regards to age, sex, and the severity of liver disease, graded by Child-Pugh score as compensated and decompensated cases. From our result, caffeine clearance in compensated cases was clearly higher than that of decompensated cases in both groups studied, particularly in the HCC group (p = 0.001). The mean value of caffeine clearance in HCC patients correlated well with the tumor staging as classified by Okuda's criteria. There was also a reversal correlation between tumor size and the clearance tested in compensated cases of HCC (p = 0.046), but this finding was not detected in decompensated cases (p > 0.05). We conclude that the determination of caffeine clearance can serve as a useful parameter for the assessment of hepatic functional reserve in cirrhotic patients complicated with HCC, and may be a useful predictor for survival outcome.
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PMID:Caffeine clearance study in hepatocellular carcinoma. 1041 Apr 86


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