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 L-1-tosylamido-2-phenylethyl chloromethyl ketone (TPCK) at a level of 10 mg/100 g body weight inhibited the incorporation of 3H-labeled amino acids into protein in Morris hepatomas 7777and 9618A2. The degree of inhibition was similar in cytoplasmic proteins and in histone and nonhistone nuclear protein fractions. There was no inhibitory effect on 3H-labeled amino acid incorporation in the livers of the tumor-bearing rats. The inhibitory effect of N-tosyl-L-lysine chloromethyl ketone (TLCK) on incorporation of 3H-labeled amino acids was observed in both the slowly growing hepatoma 7787 and the rapidly growing hepatoma 7777. In hepatoma 7777, TLCK (2.5 mg/100 g body wt) exerted a greater inhibitory effect on incorporation when administered 60 minutes before [3H]leucine injection than when injected simultaneously. Studies on tissue uptake of amino acids, thymidine, and phosphate indicated that inhibitory effects of TPCK and TLCK on active transport may be a major factor in the action of these drugs on macromolecular synthesis. The inhibitory effects of TPCK and TLCK seen in transplanted hepatomas and a colon tumor were not generally seen in normal tissues of the tumor-bearing rats.
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PMID:Selective effects of two chloromethyl ketones on amino acid and phosphate uptake in rat liver and tumors. 28 72

GABA added to rat hepatoma (HTC) cells in spinner culture at the time of induction of cell proliferation increased levels of ornithine decarboxylase (ODC) up to two- to threefold above that of control cells. The increases in ODC were also reflected by concomitant increases of intracellular putrescine levels, while spermidine and spermine were unchanged. GABA seems to have a direct stabilizing effect on ODC, since the turnover of the enzyme was slowed almost twofold when measured in cells treated with 10(-2) M GABA. The stabilizing effect is most pronounced for GABA, although some amino acids such as asparagine, glutamine, and lysine as well as some GABA analogues and homologues also tend to increase ODC but to a significantly lesser extent than GABA itself. GABA metabolites had no effect on ODC. S-Adenosylmethionine decarboxylase and tyrosine aminotransferase were not affected by the presence of GABA. The GABA effect on ODC may be important in certain types of cells for the regulation of polyamine biosynthesis.
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PMID:Regulatory interrelations between GABA and polyamines. II. Effect of GABA on ornithine decarboxylase and putrescine levels in cell culture. 48 79

Buoyant-density centrifugation of unfixed chromatin has been performed in a newly devised medium containing 3-iodo-1,2-propanediol and metrizamide. Chromatins were obtained from isotopically labeled mouse hepatoma cells in suspension culture, either grown normally or density labeled in a medium containing bromodeoxyuridine, by mild digestion of isolated nuclei with micrococcal nuclease. When a mixture of normal and density labeled chromatin, marked with [14C]thymidine and [3H]bromodeoxyuridine, respectively, was centrifuged in the medium, chromatin peaks represented by labeled DNA were resolved to the extent expected from their separate banding profiles. Centrifugation of an equivalent chromatin mixture labeled with [14C] and [3H]lysine, respectively, also yielded resolution of chromatin peaks represented by labeled proteins. Only small amounts of labeled proteins were dissociated from chromatin in the gradient medium. Labeled proteins recovered from the gradient fractions were analyzed by electrophoresis on sodium dodecyl sulfate-polyacrylamide gels. The results suggested that most of the histones remained associated with the original stretches of DNA during the centrifual fractionation period. Essentially all of the dissociated proteins were found to be non-histone proteins.
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PMID:Fractionation of unfixed chromatin by buoyant-density centrifugation in gradients containing 3-iodo-1,2-propanediol and metrizamide. 64 Oct 28

Ricinoleic-like haemolytic substances were isolated from tumour cells and peritoneal liquid fractions in rats with Yoshida's ascities hepatoma. Their activity was measured by means of photometric techniques. Crossed haemolytic tests showed differences in the choice expressed by these substances for the red cells of animals of various species. Whole body irradiation led to changes in the quantity of these substances. Their metabolism was examined by administering 3H2- and 14C6-labelled oleic acid. A variety of results was observed. Microscopic examination of target red cells in a study of the oleic acid-lysine-membrane bond confirmed the results given by the densitometer.
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PMID:[Effect of x-rays on the hemolytic substances of the Yoshida ascites tumor]. 122 84

A soluble construct consisting of a plasmid carrying the gene of the SV40 large T-antigen and an insulin-poly-L-lysine conjugate is able to selectively transfect PLC/PRF/5 human hepatoma cells which possess insulin receptors. Transfection can be efficiently competed by excess free insulin. To examine intracellular transport of the construct, it was fluorescently labeled and its accumulation on and in cells visualized by video-enhanced microscopy and quantitative confocal laser scanning microscopy. After 2 h at 37 degrees C, the labeled construct was found predominantly in intracellular acidic compartments, with a substantial portion of fluorescence localized both near and in the cell nucleus. Binding, endocytosis, and nuclear localization of the labeled conjugate could all be competed by excess free insulin, thus indicating that entry of the conjugate into cells was specifically mediated by the insulin receptor.
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PMID:Receptor-mediated endocytosis and nuclear transport of a transfecting DNA construct. 131 9

The binding, internalization, and degradation of tissue-type plasminogen activator (t-PA) were studied in a rat hepatoma (Novikoff) cell line. Binding of t-PA to specific saturable high affinity binding sites (Kd = 12 nM, 54,000 sites/cell) was followed by internalization and degradation and did not require a functional active site. The catabolism of t-PA was not inhibited by an excess of urokinase-type plasminogen activator (u-PA), and t-PA bound to Novikoff membranes was not complexed to PAI-1, suggesting a mechanism independent of PAI-1. Additionally, a mannose receptor is not involved since t-PA binding was not influenced by an excess of mannose, galactose, ovalbumin, or EDTA. Furthermore, the degradation of t-PA was not influenced by 10 mM 6-aminohexanoic acid, a lysine analogue. The t-PA receptor binds to and can be eluted from wheat germ agglutinin-Sepharose. Cross-linking of t-PA with partially purified receptor and ligand blot analysis, suggest that t-PA binds to two proteins, a principal one of 55 kDa and a minor one of 43 kDa. Novikoff cells are able also to bind (Kd = 1.4 nM, 25,000 sites/cell) and degrade u-PA. The binding was inhibited by pro-u-PA and the amino-terminal fragment of u-PA, but not by an excess of t-PA. The u-PA receptor, but not the t-PA receptor, was removed by treatment with phosphatidylinositol-specific phospholipase C. Our results show that the clearance receptor for t-PA on Novikoff cells is different from the mannose receptor and the PAI-1-dependent receptor described in other cells. The rat hepatoma cells are thus a good model to study the PAI-1 independent hepatocyte-specific clearance of t-PA.
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PMID:Demonstration of a specific clearance receptor for tissue-type plasminogen activator on rat Novikoff hepatoma cells. 131 32

The authors investigated whether immunocytochemical staining with a monoclonal antibody to proliferating cell nuclear antigen (PCNA/cyclin) could be used to identify proliferative hepatocytes in frozen sections fixed in a mixture of periodate, lysine, and 2% paraformaldehyde. Paraffin sections also were used, which were fixed in 10% formaldehyde. Specimens of liver tissue were obtained from 27 patients with various hepatic diseases. Hepatocytes that were positive for PCNA/cyclin were observed in both types of substrate specimens. In acute hepatitis and chronic active hepatitis, most hepatocytes that were labeled for PCNA/cyclin were located near necrotic foci. However, in cirrhosis, they were detected most often near fibrotic septa; the number of immunoreactive cells varied greatly in different areas of tissue sections in such cases. In hepatocellular carcinoma, many PCNA/cyclin-positive tumor cells were seen throughout the neoplasms. Hepatocytes that were positive for DNA polymerase-alpha showed a similar distribution pattern in serial sections of study cases.
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PMID:Immunocytochemical identification of proliferative hepatocytes using monoclonal antibody to proliferating cell nuclear antigen (PCNA/cyclin). Comparison with immunocytochemical staining for DNA polymerase-alpha. 137 17

Alpha-fetoprotein in sera from patients with hepatocellular carcinoma was fractionated into three peaks by affinity chromatography on a column of Lens culinaris agglutinin-Sepharose 4B. One peak (the first peak), which passed through the column without adsorption, was found in both healthy subjects and patients with liver cirrhosis and hepatocellular carcinoma. The second and third peaks were reactive with L. culinaris agglutinin and found only in patients with hepatocellular carcinoma. For alpha-fetoprotein in the second and third peaks, a novel and sensitive enzyme immunoassay (immune-complex-transfer enzyme immunoassay) was developed. Alpha-fetoprotein in test serum was reacted with dinitrophenyl affinity-purified anti-alpha-fetoprotein IgG, and the complex formed was trapped onto affinity-purified (antidinitrophenyl bovine serum albumin) IgG-coated polystyrene balls. The polystyrene balls were washed to eliminate substance(s) other than alpha-fetoprotein in the test serum, and the complex was eluted from the polystyrene balls with dinitrophenyl-L-lysine. The eluted complex containing alpha-fetoprotein in the second and third peaks was trapped onto L. culinaris agglutinin-coated polystyrene balls and reacted with affinity-purified anti-alpha-fetoprotein Fab'-beta-D-galactosidase conjugate. Beta-D-galactosidase activity bound to the polystyrene balls was assayed by fluorimetry. The maximal volume of serum that could be used without interference was 20 microliters, which was 100-fold larger than that in the previous enzyme immunoassay.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Novel and sensitive enzyme immunoassay (immune-complex-transfer enzyme immunoassay) for alpha-fetoprotein from hepatocellular carcinoma. 169 71

In vivo antitumor activity of a deoxyribonucleic acid fraction obtained from Mycobacterium bovis BCG (named MY-1) increased when it was complexed with poly-L-lysine (poly LL) solubilized by addition of carboxymethylcellulose (CMC). The complex of MY-1 and poly LL/CMC induced interferon in vivo at a low dose of MY-1 which alone exerted no IFN induction. With Line 10 hepatoma (L10) which is syngeneic with strain 2 guinea pigs, it was demonstrated that repeated intralesional injections of the complex resulted in delay of tumor growth and complete cure of animals from L10 tumor inoculated. Similar treatment of the animals with the same amount of MY-1 or poly LL/CMC alone had little therapeutic effect on the tumor growth.
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PMID:Immunotherapeutic potential in guinea-pig tumor model of deoxyribonucleic acid from Mycobacterium bovis BCG complexed with poly-L-lysine and carboxymethylcellulose. 170 24

Poly(amidoamine)s were synthesized by polyaddition reaction: to bis-acryloylpiperazine of piperazine (1), or N,N'-bis(2-hydroxyethyl)ethylenediamine (2), and to 2,2-bis(acrylamido)acetic acid of piperazine (3). Compound 2 was also end-capped with 4-hydroxythiophenol, thus introducing a terminal moiety suitable for radio-iodination using the chloramine T method (4). Such polymers behave as bases in aqueous solution, and their net average charge alters considerably as the pH changes from 7.4 to 5.5. This results in a change in polymer conformation which may prove useful in the design of polymeric drug delivery systems. However, their suitability for use in the organism will depend on polymer toxicity and also on their rate of biodegradation. Here we studied the biological properties of the above poly(amidoamine)s with a view to optimizing the synthesis of novel drug carriers. The general cytotoxicity of compounds 1, 2, 3, and 4 was examined in vitro using two human cell lines, hepatoma (HepG2) and a lymphoblastoid leukaemia (CCRF). Several different methods [the tetrazolium (MTT) test, [3H]leucine or [3H]thymidine incorporation, or counting cell numbers] were used to measure cell viability. Compounds 1, 2, and 4 were much less toxic to both cell lines than equivalent concentrations of the polycationic poly-L-lysine, and in no case did viability fall below 50% (concentrations up to 2 mg/ml). Although compound 2 was not markedly toxic to HepG2 cells, concentration-dependent toxicity was observed against CCRF cells. In this case, the polymer concentration decreasing viability by 59% (ID50) was approximately 50 micrograms/ml for compound 2 compared with an ID50 of approximately 10 micrograms/ml for poly-L-lysine. The rate of hydrolytic degradation of compound 2 was examined using viscometric measurements and gel permeation chromatography (GPC). After incubation at pH 7.5 and 8.0 for 24 h, polymer intrinsic viscosity was decreased by approximately 50% and GPC elution profiles showed a simultaneous increase in polymer retention time, indicating a fall in molecular weight. Hydrolytic degradation progressed much more slowly at pH 5.5. Compound 4 was also incubated with a mixture of isolated rat liver lysosomal enzymes (tritosomes) at pH 5.5, but no increase in the rate of degradation was observed.
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PMID:Poly(amidoamine)s with potential as drug carriers: degradation and cellular toxicity. 177 34


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