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)

Concentration-effectivity curves of Triton X-100 activity on ascitic cells of mouse leukemia 1210 and Zajdela-Hepatoma in rats have been plotted by electronic determination of cell numbers, indicating only one part of cytolysis which follows a sudden decrease of cell volumes. A better characterization of the whole cytolysis can be realised by volumetricall particle counter analysis. It first displays an increase in cell volumes for several concentrations in connection with microscopically observed increase in cells staining relatively weak by eosin. Staining and swelling nearly simultaneosly reach their maximum. Furthermore a sudden diminution of the cells follows with a shift of cell volumes distribution curves to the left, determined by particle counter depending on temperature, e. g. a strong delay at 0 degrees C.
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PMID:[Volumetric and cytologic investigations of cytolysis of ascites tumor cells provoked by triton X-100 (author's transl)]. 6 63

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.
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PMID:Antitumor activity of amino acid derivatives in the primary screening. 16 14

The activity of the malate-aspartate shuttle for the reoxidation of cytoplasmic reduced nicotinamide adenine dinucleotide (NADH) by mitochondria was assessed in six lines of rodent ascites tumor cells (two strains of Ehrlich ascites carcinoma, Krebs II carcinoma, Novikoff hepatoma, AS-30D hepatoma, and L1210 mouse leukemia). All the tumor cells examined showed mitochondrial reoxidation of cytoplasmic NADH, as evidenced by the accumulation of pyruvate when the cells were incubated aerobically with L-lactate. Reoxidation of cytoplasmic NADH thus generated was completely inhibited by the transaminase inhibitor aminooxyacetate. The involvement of the respiratory chain in the reoxidation of cytoplasmic NADH was demonstrated by the action of cyanide, rotenone, and antimycin A, which strongly inhibited the formation of pyruvate from added L-lactate. Compounds that inhibit the carrier-mediated entry of malate into mitochondria, such as butylmalonate, benzenetricarboxylate, and iodobenzylmalonate, also inhibited the accumulation of pyruvate from added L-lactate by the tumor cells. The maximal rate of the malate-aspartate shuttle was established by addtion of arsenite to inhibit the mitochondrial oxidation of the pyruvate formed from added lactate. The capacity of the various tumor lines for the reoxidation of cytoplasmic NADH via the malate-aspartate shuttle approaches 20% of the total respiratory rate of the cells and thus appears to be sufficient to account for the mitochondrial reoxidation of that fraction of glycolytic NADH not reoxidized by pyruvate and lactate dehydrognenase in the cytoplasm.
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PMID:Occurrence of the malate-aspartate shuttle in various tumor types. 17 6

The effects of 5-trifluoromethyluracil (F3Thy), 5-trifluoromethyl-2'-deoxyuridine (F3dThd), F3dThd-5'-P, and F3dThd-5'-methylphosphonate on the growth of HeLa cells, Novikoff hepatoma cells, L5178Y mouse leukemia cells, and on the replication of vaccinia virus in HeLa cells have been determined. F3Thy and F3dThd-5'-methylophosphonate were approximately 500-fold and 100-fold less effective, respectively, than F3dThd or F3dThd-5'-P in their inhibition of these cells. F3dThd and F3dThd-5'-P are potent inhibitors of vaccinia viral replication of HeLa cells. The nucleoside and nucleotide were 1,000-fold more inhibitory than the free base. F3dThd was nost inhibitory when added between 1 and 2 h post-infection; however, it was also somewhat inhibitory when added at later times.
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PMID:Growth inhibition of cells in cultures and of vaccinia virus infected HeLa cells by derivatives of trifluorothymidine. 17 85

Reaction of the trimethylsilyl derivative of 2,3-dihydro-6H-1,3-oxazine-2,6-dione (2, "uracil anhydride") with protected 1-O-acetylribofuranoses in the presence of stannic chloride gave the corresponding block nucleosides. 3-(2,3-5-Tri-O-2',2',2'-trichloroethoxycarbonyl-beta-d-ribofuranosyl)-2,3-dihydro-6H-1,3-oxazine-2,6-dione (4c) thus prepared from the protected sugar 3c, 1-O-acetyl-2,3,5-tri-O-(2,2,2-trichloroethoxycarbonyl)ribofuranose, gave, on removal of the protecting groups with zinc dust,3-(beta-d-ribofuranosyl)-2,3-dihydro-6H-1,3-oxazine-2,6-dione (1). The structure of 1 was confirmed by uv, ir, NMR, and CD spectral data and was shown to be an N nucleoside. Uracil anhydride, 2, and, to a lesser extent, its ribonucleoside 1 exert a moderate growth inhibition of mouse leukemia L5178Y, HeLa, and Novikoff hepatoma cells i- culture. Both compounds produce weak inhibition of vaccinia viral replication in HeLa cells.
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PMID:Synthesis and biological studies of 3-(beta-D-ribofuranosyl)-2,3,-dihydro-6H-1,3-oxazine-2,6-dione, a new pyrimidine nucleoside analog related to uridine. 17 70

Inosine dialdehyde (INOX), the periodate oxidation product of inosine, inhibited the proliferation of various tumor cell lines in suspension culture in a concentration-dependent manner. A concentration of about 1 mM was required to completely inhibit the proliferation of Novikoff rat hepatoma and mouse L-cells, whereas about 0.1 mM completely inhibited the proliferation of L1210 and P388 mouse leukemia and Chinese hamster ovary cells. INOX inhibited in a similar time- and concentration-dependent manner the synthesis of protein, RNA, and DNA, as measured by the incorporation of labeled amino acid, uridine, and thymidine, into acid-insoluble material, without significantly affecting the incorporation of these precursors into the acid-soluble pool. Flow microfluorometric analyses showed that many of the INOX-treated cells became arrested in G2 + M. The results are consistent with the view that INOX affects multiple metabolic steps. The effects of INOX were quite different from those caused by typical inhibitors of ribonucleotide reductase, hydroxyurea, and 2,3-dihydro-1H-pyrazolo(2,3-a)imidazole, which very rapidly inhibited DNA synthesis and caused arrest of the cells in G1, with minimal effects on RNA and protein synthesis.
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PMID:Mechanism of action of inosine dialdehyde (NSC 118994) in the inhibition of proliferation of tumor cells in culture. 19 37

Polymethylene-bis(1-nitrosourea), polymethylene-bis(1-nitroso-3-nitroguanidine), and polymethylene-bis(1-nitroso-p-toluenesulfonamide) derivatives were tested for antitumor effect against rat ascites hepatoma AH-13 and mouse leukemia L-1210. Bisnitrosoureas were effective against AH-13 and L-1210, bisnitrosoguanidines were effective against AH-13 alone, and bisnitrosotoluene-sulfonamides were ineffective against both tumor lines. Of all these compounds, 1,1'-ethylene-bis(1-nitrosourea) (EBNU) was the most effective. The antitumor effect of EBNU was compared with that of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). Intraperitoneal administration of EBNU according to the schedule, day 1, days 1 and 5, and days 1, 5, and 9 after intraperitoneal inoculation of L-1210 showed marked prolongation of host survival, although the effective doses used were a few times higher than those used in BCNU to obtain a similar effect. The minimum effective dose (MED) of EBNU on AH-13 cells was estimated as 1 mg/kg, which was 10 times less than that of BCNU, suggesting that EBNU was more effective than BCNU against AH-13.
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PMID:Antitumor effect of 1,1'-polymethylene-bis (1-nitrosourea) and related compounds. 20 35

The zero-trans uptake of purines and pyrimidines was measured in suspensions of Novikoff rat hepatoma, mouse L, P388 mouse leukemia, and Chinese hamster ovary cells by a rapid kinetic technique which allows the determination of uptake time points in intervals as short as 1.5 s. Kinetic parameters for purine/pyrimidine transport were determined by measuring substrate influx into cells in which substrate conversion to nucleotides was negligible either due to lack of the appropriate enzymes or to depletion of the cells of ATP (5'-phosphoribosylpyrophosphate), and by computer fitting exact, integrated rate equations derived for various carrier-mediated transport models directly to zero-trans influx data. The results indicate that different carriers function in the transport of hypoxanthine/guanine, adenine, and uracil with substrate:carrier association constants (K) at 24 degrees C of 300 to 400 muM, 2 to 3 mM, and about 14 mM, respectively, for Novikoff cells. K and Vmax for hypoxanthine transport by L and P388 cells are similar to those for Novikoff cells, but the transport capacity of Chinese hamster ovary cells is much lower and K = 1500 muM. All transport systems are completely symmetrical. Hypoxanthine transport is so rapid that an intracellular concentration of free hypoxanthine (90%) close to that in the medium is attained within 20 to 50 s of incubation at 24 degrees C, at least at extracellular concentrations below K. In cells in which conversion to nucleotides is not blocked free hypoxanthine accumulates intracellularly to steady state levels with equal rapidity and thereafter the rate of hypoxanthine uptake into total cell material is strictly a function of the rate of phosphoribosylation. The low Km systems for hypoxanthine (1 to 9 muM) and adenine (0.2 to 40 muM) uptake detected previously in many types of cells reflect the substrate saturation of the respective phosphoribosyltransferases rather than of the transport system.
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PMID:Purine and pyrimidine transport and phosphoribosylation and their interaction in overall uptake by cultured mammalian cells. A re-evaluation. 42 88

A clone of about 1 kb has been isolated from a human brain cDNA library. The clone possesses a 151 amino acid open reading frame that exhibits 72% amino acid identity with the E2 ubiquitin-conjugating enzyme encoded by the RAD6 gene of Saccharomyces cerevisiae. A 90% amino acid identity was observed in a central sequence surrounding a cysteine, which most likely contributes the sulfhydryl group involved in the formation of the ubiquitin-E2 thiolester linkage. Northern hybridization analyses have identified a poly(A)-containing mRNA of about 1 kb encoding the E2-like sequence in human CEM lymphoblastoid and HeLa cells, Novikoff rat hepatoma cells and S49 mouse leukemia cells. Southern hybridization analyses indicate the presence of a single gene encoding this sequence in both human cell lines, but of two or more related genes in the rodent cell lines.
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PMID:Mammalian mRNAs encoding protein closely related to ubiquitin-conjugating enzyme encoded by yeast DNA repair gene RAD6. 188 45

Resorthiomycin, a novel antitumor antibiotic, was isolated from the fermentation broth of a strain of Streptomyces collinus by ethyl acetate extraction, silica gel chromatography and HPLC. Resorthiomycin exhibited an in vitro cytotoxic activity against mouse leukemia L5178Y cells (IC50, 15.5 micrograms/ml) and also inhibited the clonogenic activity of a multidrug-resistant mutant of human hepatoma PLC/PRF/5 cells to a greater extent than that of the parental cells. On the other hand, this antibiotic does not possess any antibacterial or antifungal activity.
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PMID:Resorthiomycin, a novel antitumor antibiotic. I. Taxonomy, isolation and biological activity. 215 95


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