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)

It was found that a human hepatoma-associated ALP (orthophosphoric monoester phosphohydrolase, E.C. 3.1.3.1) shared electrophoretic mobility, inactivation by urea, inhibition by inorganic phosphate, ethylenediaminetetraacetate, and amino acids (L-phenylalanine, L-leucine and L-homoarginine), heat stability, sensitivity to neuraminidase, pH optimum, Km value, and antigen site with fast moving ALP isozymes of FL cell strain derived from human amniotic membrane. However, 40-week-old fresh amniotic membrane lacked this isozyme. Instead, it had a placental type ALP consisting of minor components. The other ALP isozyme of FL cells had properties common to hepatoma ALP with regard to L-phenylalanine sensitivity, inhibition by ethylenediaminetetraacetate, inactivation by urea, and antigen site, but differed from it in electrophoretic mobility, sensitivity to L-leucine and L-homoarginine, and the presence of another antigen site. It was more heat stable and more sensitive to inhibition by inorganic phosphate than Hepatoma AP. The possible regulatory mechanism between the hepatoma-type ALP and the placental type ALP in the amnion cells is considered.
 ...
PMID:A hepatoma-associated alkaline phosphatase, the Kasahara isozyme, compared with one of the isozymes of FL amnion cells. 0 Sep 48

Amino acid starvation causes an adaptive increase in the initial rate of transport of selected neutral amino acids in an established line of rat hepatoma cells in tissue culture. After a lag of 30 min, the initial rate of transport of alpha-aminoisobutyric acid (AIB) increases to a maximum after 4 to 6 h starvation of 2 to 3 times that seen in control cells. The increased rate of transport is accompanied by an increase in the Vmax and a modest decrease in the Km for this transport system, and is reversed by readdition of amino acids. The enhancement is specific for amino acids transported by the A or alanine-preferring system (AIB, glycine, proline); uptake of amino acids transported by the L or leucine-preferring system (threonine, phenylalanine, tyrosine, leucine) or the Ly+ system for dibasci amino acids (lysine) is decreased under these conditions. Amino acids which compete with AIB for transport also prevent the starvation-induced increase in AIB transport; amino acids which do not compete fail to prevent the enhancement. Paradoxically threonine, phenylalanine, tryptophan, and tyrosine, which do not compete with AIB for transport, block the enhancement of transport upon amino acid starvation. The starvation-induced enhancement of amino acid transport does not appear to be the result of a release from transinhibition. After 30 min of amino acid starvation, AIB transport is either unchanged or slightly decreased even though amino acid pools are already depleted. Furthermore, loading cells with high concentrations of a single amino acid following a period of amino acid starvation fails to prevent the enhancement of AIB transport, whereas incubation of the cells with the single amino acid for the entire duration of amino acid starvation prevents the enhancement; intracellular amino acid pools are similar under both conditions. The enhancement of amino acid transport requires concomitant RNA and protein synthesis, consistent with the view that the adaptive increase reflects an increased amount of a rate-limiting protein involved in the transport process. Dexamethasone, which dramatically inhibits AIB transport in cells incubated in amino acid-containing medium, both blocks the starvation-induced increase in AIB transport, and causes a time-dependent decrease in transport velocity in cells whose transport has previously been enhanced by starvation.
 ...
PMID:Derepression of amino acid transport by amino acid starvation in rat hepatoma cells. 1 7

1. A serine protease of hepatoma 8999, isolated in the mitochondrial fraction, was purified and crystallized. The purified enzyme was apparently homogeneous on ultracentrifugal analysis and polyacrylamide disc gel electrophoresis. The ratio of absorbance at 280 nm and 260 nm, A280/A260, was 1.90 and its absorption coefficient, A280 1% was 10.5 cm-1 estimated from dry weight measurements. Its S20, w value was 2.23 S and its molecular weight was estimated to be 24000 +/- 1000. The enzyme contained twice as much lysine, arginine and histidine as chymotrypsinogen did, but had a very similar amino acid composition to serine protease from skeletal muscle. Its isoelectric point was pH 10.6. 2. The substrate specificity of the enzyme was the same as that of chymotrypsin A. Its Km and kcat values for N-acetyl-L-tyrosine ethyl ester, N-acetyl-L-phenylalanine ethyl ester and N-acetyl-L-tryptophan ethyl ester were 0.35 mM and 10.69 s-1, 0.38 mM and 10.7 s-1, and 0.11 mM and 11.8 s-1, respectively. Its activity was completely inhibited by phenylmethylsulfonyl fluoride and partially inhibited with tosylphenylalanine chloromethyl ketone. 3. The enzyme was shown to be located in different granules from the intracellular particules (light and heavy mitochondrial fraction) by sucrose density gradient centrifugation, and it was stained in mast cells of the hepatoma 8999 by the immunofluorescent technique. 4. Serine protease is present in different amounts in various organs of rat and the enzyme from hepatoma 8999 gave a single band that fused completely with those of the enzymes from skeletal muscle, heart, liver and kidney, respectively, on Ouchterlony double-diffusion analysis using antiserum to the crystalline enzyme of hepatoma 8999, but the enzyme from small intestine did not react with the antiserum.
 ...
PMID:Purification, characterization and localization of serine protease of Morris hepatoma 8999. 11 11

The M4 isozyme of lactate dehydrogenase was purified to homogeneity from normal rat liver and from two Morris hepatomas (7777 and 7793). Amino-terminal analyses with fluorodinitrobenzene failed to detect the presence of free amino-terminal residues in each enzyme studied. Each enzyme contained between 3.7 and 4.1 moles of protein-bound acetyl groups per mole of enzyme. The amino-terminal peptide, characterized as N-acetylalanylalanine, was isolated from Pronase digests of each isozyme preparation, and quantitative recovery experiments indicated that all acetyl residues were bound at the amino termini. Carboxylterminal analyses demonstrated phenylalanine to be the carboxyl-terminal residue in each enzyme studied. These data indicate no differences in either amino- or carboxyl-terminal regions of the hepatoma M4 isozymes compared to normal liver M4 isozyme.
 ...
PMID:Amino- and carboxyl-terminal analyses of hepatoma lactate dehydrogenase isozymes. 16 83

We have previously reported that from 350 amino acid (A-A) derivatives five were selected after the primary in vivo and in vitro screening tests. The five compounds which were found to possess potential antitumor activity against Ehrlich ascites carcinoma are as follows: beta-naphthalene-sulfonyl-DL-tryptophan (A-91), beta-naphthyl-aminomethyl-gamma-aminobutyric acid (A-144), N-ethylcarbaminomethyl-L-isoleucine (A-145), n-9-fluorenylactyl-L-phenylalanine (A-192), and N-propoinyl-L-valine (A-195). The effect on life prolongation and tumor growth of these selected A-A derivatives against various types of tumors, including ascites and solid tumors in mice and ascites hepatomas in rats, was examined. A-A derivatives were administered once daily 3 consecutive days starting 24 hours after tumor implantation. Experimental results showed that among the five A-A derivatives possessing considerable activity against Ehlich carcinoma, A-144 and A-145 were found to be more effective than chromomycin A and showed activity similar to that of cyclophosphamide against ascites Sarcoma 180. A-A derivatives showed slight antitumor activity against SR61 and L1210 leukemias. In rat ascites hepatoma, such as AH13, AH7974, AH60C, and Yoshida sarcoma, only A-145 showed a significant prolongation of the lifespan in the control groups. The five selected A-A derivatives significantly inhibited the growth of Nakahara-Fukuoka sarcoma and solid Sarcoma 180. These findings indicate that among the five A-A derivatives, A-15 appeared to be the most active against ascites and solid tumors.
 ...
PMID:Antitumor activity of selected amino acid derivatives against various tumor systems. 16 35

Approximately 350 amino acid derivatives were synthesized and tested for antitumor activity in four tumor systems. The effect on life prolongation and tumor growth was examined using mouse leukemia SR-61, Ehrlich ascites carcinoma, ascites sarcoma-180, and rat ascites hepatoma (AH-60C). Among these 350 derivatives, 29 compounds were found to be significantly effective in prolongation of the median life-span and inhibitory effect on tumor growth in the primary screening. Among these 29 compounds, the following five compounds were found to possess potential antitumor activity: N-(2-Naphthalene)sulfonyl-DL-tryptophan (A-91), 2-naphthylaminomethyl-gamma-aminobutyric acid (A-144), N-ethylcarbaminomethyl-L-isoleucine (A-145), N-9-fluorenylacetyl-L-phenylalanine (A-192), and N-propionyl-L-valine (A-195). These five compounds were active in prolongation of the life-span of mice bearing Ehrlich ascites carcinoma and in the inhibition of the cell growth. Some of these amino acid derivatives inhibited biosynthesis of macromolecules, DNA, RNA, and protein, in tumor cells. These results suggest that the site of action of the five amino acid derivatives appears to result from the inhibition of macromolecules and another unknown mechanism.
 ...
PMID:Antitumor activity of amino acid derivatives in the primary screening. 16 14

Continued high levels of phenylalanine hydroxylase in cultured H4-II-E-C3 rat hepatoma cells require either serum or glucocorticoids in the culture medium. Upon withdrawal of serum, cellular phenylalanine hydroxylase levels decay exponentially with a half-life of 22 hours for about 60 hours, after which time a low, constant enzyme content persists for at least 96 hours. This decline of phenylalanine hydroxylase is fully reversible; normal enzyme levels are restored in a time- and dosage-dependent fashion upon addition of serum to basal cultures. The serum factor is nondialyzable and moderately heat-stable. The stimulation by serum of the phenylalanine hydroxylas content of basal cultures is blocked by 3-[2-(3,5-dimethyl-2-oxocyclohexyl)-2-hydroxyethyl]glutarimide and requires ongoing cellular protein synthesis. When added to the enzyme-assay mixture in vitro, serum does not alter the phenylalanine hydroxylase activity of extracts from basal cultures. Three lines of evidence suggest that serum contains a nonsteroidal phenylalanine hydroxylase stimulatory components(s): (a) glucocorticoid antagonists inhibit less than one-half of the biological activity of serum; (b) exhaustive extraction of endogenous serum glucocorticoids with charcoal reduces the activity of serum to about one-half of control values; and (c) the stimulatory effects of charcoal reduces the values; and (c) the stimulatory effects of charcoal-extracted serum and hydrocortisone are additive. The phenylalanine hydroxylase stimulatory activities of the charcoal-extracted sera from four mammalian species and from three stages in development in one mammalian species are comparable. A survey of partially purified preparations of a number of known hormones failed to reveal any one capable of elevating the phenylalanine hydroxylas levels of basal cultures in a manner comparable to that of charcoal-extracted serum.
 ...
PMID:Effect of serum on phenylalanine hydroxylase levels in cultured hepatoma cells. 17

The kinetic and immunologic properties of phenylalanine hydroxylase of adult rat liver were compared to the properties of the similar enzyme present in cultured H4-II-E-C3 hepatoma cells. The enzymes from the two sources could not be distinguished by the Km values for either phenylalanine or 6,7-dimethyltetrahydropterin. Analysis by double immunodiffusion showed that phenylalanine hydroxylase from the two sources had identical immunologic determinants, but immunotitrations revealed a small but significant difference between the enzyme of the normal adult rat liver and the enzyme of cultured hepatoma cells. The results of double immunodiffusion and immunotitration experiments indicated also that the increased levels of phenylalanine hydroxylase seen in the hepatoma cells grown in the presence of hydrocortisone resulted from the accumulation of enzyme protein, but it could not be decided whether this accumulation resulted from an increased rate of synthesis or decreased rate of degradation.
 ...
PMID:Properties of phenylalanine hydroxylase of cultured hepatoma cells. 18 50

The effects of essential amino acids on albumin synthesis by a mouse hepatoma cell line have been investigated. The amino acids tested were tryptophan, phenylalanine, histidine, isoleucine and leucine. Cellular rates of synthesis (molecules albumin/cell per min) were determined from rates of [3H]leucine incorporation into immunoprecipitable albumin in the culture medium. The effects of amino acids on albumin synthesis fall into three distinct groups. The concentration of tryptophan producing half-maximal synthesis is 4 micronM. The corresponding concentration for leucine is 100 micronM. Histidine, phenylalanine and isoleucine were very similar, the half-maximal concentrations being approximately 15 micronM. The concentrations of amino acids producing half-maximal synthesis correlate directly with the amino acid composition of albumin. The levels of these essential amino acids necessary to saturate albumin synthesis have been compared with amino acid levels in normal plasma.
 ...
PMID:Albumin synthesis in cultured hempatoma cells. Regulation by essential amino acids. 19 Oct 77

Cultured rat hepatoma cells, H4-II-E-C3, are known to possess a phenylananine hydroxylating system which is sufficient to enable them to grow in tyrosine-depleted medium. Using standard procedures of auxotroph enrichment with this cell line, we have isolated tyrosine auxotrophs for the first time. We report in this paper the class of auxotrophs with (a) reduced (15-64% of wild type) or (b) absent activity of phenylalanine hydroxylase, an enzymic component of the phenylalanine hydroxylating system. This class of auxotroph presumably contains either lower (a) [or zero (b)] levels of normal phenylalanine hydroxylase protein than wild type, or mutant phenylalanine hydroxylase protein with lowered (or zero) activity. The two subgroups of auxotrophs (a) and (b) differ from each other in their revertibility and their growth behavior in the tyrosine-free medium. Over a 12-month period of testing, the auxotrophs have been highly stable with respect to their phenylalanine hydroxylase activity and growth phenotype in tyrosine-free medium. Such auxotrophs should facilitate genetic and biochemical study of the genes controlling the phenylalanine hydroxylation system and the study of phenylketonuria.
 ...
PMID:Genetics of the mammalian phenylalanine hydroxylase system: I. Isolation of phenylalanine hydroxylase-deficient tyrosine auxotrophs from rat hepatoma cells. 19 52


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