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)

Immunocytochemical staining of tryptophan 2, 3-dioxygenase (TO, EC 1.13.11.11), which is a typical marker of terminal differentiation of rat hepatocytes, showed that TO was expressed as early as the first day after birth by a few hepatocytes, and that the number of hepatocytes expressing TO gradually increased during early neonatal development. In contrast, immature hepatocytes grew actively in culture even without growth factors and serum, showing a labelling index with [3H]thymidine of over 80% just after birth, but their ability to show autonomous growth decreased rapidly during postnatal development. Double staining of hepatocytes from neonatal rats indicated that hepatocytes showing DNA synthesis were distinct from those expressing TO, suggesting that immature cells proliferate, but do not express TO, and then become fully differentiated expressing TO, but not proliferating any more. On the contrary, albumin was fully expressed in most hepatocytes of 0-day-old rats, in which the hepatocytes were still growing. When immature hepatocytes without TO from 0-day-old rats were cultured on a feeder layer of adult rat hepatocytes for 3.5 days, their expression of TO increased rapidly to almost the adult level (over 70% of the cells became TO-positive). Conversely, this feeder layer strongly inhibited autonomous growth of the neonatal rat hepatocytes. Other feeder layers, such as non-parenchymal liver cells of adult rats, Reuber hepatoma, and Swiss 3T3 fibroblasts, had no effect on the reciprocal changes of terminal differentiation and autonomous growth of immature rat hepatocytes. A feeder layer of dead adult rat hepatocytes, obtained by treating the cells with cytosine arabinoside for 24 h or drying them at 37 degrees C, had the same ability as a feeder layer of living cells to induce cytodifferentiation of immature cells. When the dead feeder layer was treated with 1 N HCl or digested with 0.1% trypsin, its ability to induce differentiation was almost completely lost. These results suggest that a cell surface component of adult rat hepatocytes, probably an acid-labile protein, controls terminal differentiation and growth of immature hepatocytes.
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PMID:In vitro induction of terminal differentiation of neonatal rat hepatocytes by direct contact with adult rat hepatocytes [corrected]. 348 31

The non-specific lipid transfer protein (nsL-TP) purified from rat and bovine liver accelerates the transfer of all common diacylglycerophospholipids, cholesterol as well as glycosphingolipids and gangliosides between membranes. These proteins have molecular weights in the order of 14 500 and are highly basic (isoelectric points between 8.5 and 9.5). The primary structure of nsL-TP from bovine liver has been elucidated yielding a single polypeptide chain of 121 aminoacid residues. The protein contains one cysteine residue, essential for transfer activity, a single tryptophan residue and lacks histidine, arginine and tyrosine residues. Rat liver nsL-TP was found to be identical to sterol carrier protein 2, stimulating the microsomal conversion of intermediates between lanosterol and cholesterol. Evidence was presented that nsL-TP binds cholesterol, suggesting that it acts as a carrier. On the other hand, failure to bind phospholipids disagrees with this proposed mode of action. A sensitive enzyme immunoassay was developed to determine levels of nsL-TP in rat tissues. By use of this assay, nsL-TP was found to be most prominently present in liver and intestinal mucosa (0.78 and 0.46 microgram nsL-TP per mg protein in 105 000 X g supernatant, respectively). Subfractionation studies showed that approx. 70% of nsL-TP was present in the membrane-free cytosol. However, application of an immunosorbent-purified antibody and protein A-linked gold particles to rat liver slices demonstrated a concentration of label over the peroxisomes. By way of immunoblotting it was shown that nsL-TP was absent from peroxisomes and that the immunoreactive material was a protein of mol. wt. 58 000. nsL-TP is capable of mediating net transfer of cholesterol to membranes, deficient in this lipid. Under such conditions of net transfer, nsL-TP stimulated the microsomal esterification of cholesterol and its conversion to pregnenolone by adrenal mitochondria. Levels of nsL-TP in Reuber H35 hepatoma cells was six per cent of that found in rat hepatocytes. This very low level of nsL-TP had no effect on de novo cholesterol biosynthesis and intracellular cholesterol esterification. These results raise doubts as to whether nsL-TP has a function in in situ cholesterol metabolism.
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PMID:The non-specific lipid transfer protein (sterol carrier protein 2) from rat and bovine liver. 406 21

-A comparison of the elution profiles of 18 aminoacyl-tRNA's from Novikoff hepatoma with those from normal liver on a methylated albuminkieselguhr column revealed the occurrence of new species of tRNA for histidine, tyrosine, and asparagine in the hepatoma. In addition, the hepatoma tRNA's for arginine, isoleucine, lysine, methionine, serine, alanine, and tryptophan eluted at a higher salt concentration than the corresponding tRNA's of normal liver. The remaining eight amino acids did not show any significant differences in the elution profiles.
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PMID:Differences in the transfer RNA's of normal liver and Novikoff hepatoma. 430 99

Cytoplasmic changes were investigated in livers of rats at various intervals up to 50 weeks during primary induction of hepatoma by thioacetamide feeding.Microsomal Glucose-6-phosphatase and ATPase activities were shown to decrease progressively with increased period of thioacetamide feeding the fall in activities being more pronounced during the first 15 weeks.Hormonal induction of tryptophan pyrrolase and tyrosine transaminase activities was shown to undergo a significant decrease of 65% and 55% respectively at the end of 50 weeks feeding.The substrate induced tryptophan pyrrolase activity was decreased to 50% during the 50 weeks period whereas the substrate induced tyrosine transaminase activity gradually increased to 200%. The latter is attributable to differences in the optimal induction dose of tyrosine in normal and carcinogen fed rats.The m-RNA template lifetime for tryptophan pyrrolase was shown to be exceeding 24 hours in normal rats as against that of 13 hours in rats fed with carcinogen for 30 weeks. On the other hand the m-RNA template lifetime for tyrosine transaminase was 3 hours in control rats while it was 7 hours in the carcinogen fed rats.The observed changes were shown to occur long before the onset of malignant transformation.The alterations in terms of decreased Glucose-6-phosphatase and substrate induced tryptophan pyrrolase activities were shown to be reversible when the carcinogen was withdrawn from the diet after 30 weeks of feeding.The significance of these observations is discussed in relation to damage to endoplasmic reticulum during hepatocarcinogenesis.
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PMID:Cytoplasmic changes during thioacetamide induced hepatocarcinogenesis in rats. 439 24

Fasting serum levels of total and free tryptophan, and free fatty acids and albumin, were measured and compared by blood biochemical analysis in patients with hepatobiliary disease and neuropsychiatric symptoms. The serum total tryptophan level tended to be elevated in patients with chronic active hepatitis, hepatic coma and obstructive jaundice, but not significantly. The serum free tryptophan level was significantly elevated in patients with chronic active hepatitis, liver cirrhosis, primary hepatocellular carcinoma and obstructive jaundice. The free tryptophan level was related to the decreased serum albumin level and elevated serum free fatty acid levels, which seems to indicate a connection with liver parenchymal function. The level, however, seemed not to correlate with neuropsychiatric symptoms.
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PMID:Clinical evaluation of serum levels of tryptophan in hepatobiliary disease. 624 22

Two enzyme forms of alkaline phosphatase have been partially purified from the medium spent for the culture of HUH-6 clone 5 cells, which were originally derived from hepatoblastoma tissue. The purification methods used are ammonium sulfate precipitation, ethanol precipitation, diethylaminoethyl cellulose chromatography, Affi-Gel Blue chromatography, and Sephadex G-200 gel filtration. These alkaline phosphatases have been characterized by thermostability, inhibition, and immunological and electrophoretic studies. Both are L-phenylalanine and L-tryptophan sensitive and L-homoarginine and L-leucylglycylglycine insensitive, and both react with an antiserum against intestinal alkaline phosphatase. The major enzyme form is a neuraminidase-cleavable, moderately thermostable isoenzyme which on polyacrylamide gel shows an electrophoretic mobility similar to that of liver alkaline phosphatase. The minor enzyme form is a neuraminidase-uncleavable, thermolabile isoenzyme which shows an intermediate electrophoretic mobility between liver and hepatoma alkaline phosphatases. The molecular weights of the major and minor enzymes have been estimated by gel filtration to be 170,000 and 110,000, respectively. These results support the conclusion that the two enzyme forms of HUH-6 alkaline phosphatase are intestinal in type, with the major enzyme form closely resembling hepatoma and oncoamnionic alkaline phosphatases, and the minor enzyme form resembling "intestine-like liver alkaline phosphatase." HUH-6 clone 5 cell line may be a useful in vitro model to study the regulatory mechanism for phenotypic expression of intestinal-type alkaline phosphatase isoenzymes in liver cancer cells.
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PMID:Intestinal-type alkaline phosphatase produced by human hepatoblastoma cell line HUH-6 clone 5. 631 71

Free tryptophan in plasma was separated by centrifugation through an Amicon ultrafiltration membrane cone. The value obtained without control of pH was found to be lower than that obtained with control of pH by an improved method ( Hijikata et al. (1981) Anal. Biochem. 118, 10-16). For determination of the total tryptophan concentration in the plasma, high performance liquid chromatography (HPLC) was better than the method of Denckla Dewey as modified by Bloxam & Warren ( (1974) Anal. Biochem. 60, 621-625), as judged on the basis of sensitivity, recovery rate and coefficient of variance. The total tryptophan concentration in the plasma determined by HPLC was lower than that determined by the Bloxam & Warren method. The total tryptophan concentration (t-Trp), free tryptophan concentration (f-Trp) and f-Trp/t-Trp ratio were 55.8 +/- 10.2 mumol/l, 11.6 +/- 1.5 mumol/l and 0.211 +/- 0.03 (mean +/- 1 SD) respectively, in healthy subjects (controls). No significant difference was observed between the values of controls and those of patients with liver cirrhosis, hepatocellular carcinoma, liver cirrhosis with hepatocellular carcinoma and hepatic encephalopathy of liver cirrhosis without bleeding. But in liver cirrhosis with bleeding, free tryptophan concentration (f-Trp, 48.0 +/- 23.3 mumol/l, p less than 0.001) and f-Trp/t-Trp ratio (0.645 +/- 0.289, p less than 0.001) were significantly higher than those of controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Determination of free tryptophan in plasma and its clinical applications. 633 Feb 73

This study was undertaken to evaluate the carcinogenic effect of benzidine on the urinary bladder of mice, and the effect of DL-tryptophan on the induction of bladder cancer. Benzidine plus DL-tryptophan or benzidine alone mixed with a commercial basal diet was fed to groups of ICR strain female mice for 20 weeks, after a glass bead had been inserted into the bladder. Control mice were fed the basal diet throughout the experimental period. All the surviving mice were killed 63 weeks after start of the study. Benzidine administered with or without DL-tryptophan did not induce tumors of the urinary bladder in these mice. Hepatomas developed in 34 of 41 mice (82.9%) fed benzidine and in 24 of 51 mice (47.1%) fed benzidine with tryptophan. DL-Tryptophan counteracted the effect of benzidine and significantly reduced the development of hepatomas.
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PMID:Protective effects of DL-tryptophan on benzidine-induced hepatic tumor in mice. 705 8

Adult rat hepatocytes placed in primary culture contain at least two distinct Na+-independent transport systems for neutral amino acids. The characteristics of the two systems do not allow assignment to previously described Na+ independent agencies, so we have tentatively termed the two processes Systems L1 and L2. Uptake by System L1 is substantially inhibited by cysteine, valine, isoleucine, leucine, methionine, histidine, tryptophan, tyrosine, phenylalanine, and 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid. In contrast, System L2-mediated transport is completely inhibited by isoleucine, leucine, phenylalanine, and 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid. Amino acids transported by both systems show biphasic kinetics yielding Km values for the System L1 component in the micromolar range, whereas the corresponding values for System L2 are an order of magnitude higher. In freshly isolated hepatocytes, the activity of System L2 is relatively high and declines over the initial 24 to 48 h of culture. The Na+-dependent Systems N and ASC also show a significant decay in activity during this time period. In contrast to the decrease in uptake by System L2, transport by System L1 increases during culture following an initial lag period of 12 to 24 h. The increase in System L1 activity can be blocked by the addition of either cycloheximide or actinomycin D. System L1 appears to be present also in fetal hepatocytes, although, in the hepatoma cell line, HTC, the Na+-independent component appears to be homogeneous as though one of the two systems present in the normal adult hepatocyte is not expressed in these transformed cells.
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PMID:Evidence for two Na+-independent neutral amino acid transport systems in primary cultures of rat hepatocytes. Time-dependent changes in activity. 711 28

The basic fraction of a tryptophan pyrolysate (Trp-P-BF) was given orally to Wistar rats for about 2 years. In Experiment I, 5 male rats each were given 0.2, 0.4, 0.6 and 0.8% Trp-P-BF. Dose-dependent growth retardation was observed in these groups and neoplastic nodules were found in the liver of 1 rat given 0.2% Trp-P-BF and a hepatocellular carcinoma was found in 1 rat given 0.4% Trp-P-BF diet. In Experiment II, 25 rats of both sexes were fed 0.5% or 0.2% Trp-P-BF diet. Neoplastic nodules were induced in 2 of 22 males and 5 of 18 females given 0.2% Trp-P-BF diet. Mammary adenomas developed, but no neoplastic nodules were found in the liver of rats fed on 0.05% Trp-P-BF or control diet. Females were more sensitive to Trp-P-BF than males.
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PMID:Liver cancer and precancerous changes in rats induced by the basic fraction of tryptophan pyrolysate. 729 29


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