Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antitumor activity of the cell-wall skeleton (CWS) of Propionibacterium acnes C7 was examined by using transplantable tumors in syngeneic mice and in guinea pigs, and autochthonous tumors in mice. P. acnes-CWS was shown to suppress the growth of fibrosarcomas, EL4 leukemia, and MH134 hepatoma in syngeneic mice, and to regress the established tumors of a fibrosarcoma (MC104) in C57BL/6J mice, and a hepatoma (line-10) in strain-2 guinea pigs. The oil-attached P. acnes-CWS mixed with fructose mycolate was effective for suppression of the autograft of fibrosarcoma in mice. The repeated intralesional injections of suspension of P. acnes-CWS in phosphate-buffered saline was effective for prolongation of survival period of mice bearing 3-methylcholanthrene-induced fibrosarcoma. The test results on the cell fractions of P. acnes indicated that the CWS, but not the cytoplasmic or glucan fraction, of P. acnes had anti-tumor activity. The activation of peritoneal macrophages of mice was observed when P. acnes-CWS, but not the cytoplasmic fraction, was injected intraperitoneally 4 days before. The relationship between the cytolytic activity of peritoneal macrophages and antitumor activities of P. acnes-CWS was also discussed.
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PMID:Antitumor activity of cell-wall skeleton of Propionibacterium acnes C7 in mice and guinea pigs. 39 8

The activity of 5'-nucleotidase in L 1210 leukaemia cells fixed in situ by glutaraldehyde was established by electron microscopic cytochemistry and biochemical assays. The enzyme activity is localized uniquely on the cell surface. In biochemical assays the time course of phosphate liberation by the suspension of glutaraldehyde fixed cells was linear up to 15 min incubation. The activity was proportional to the number of cells in the suspension, amounting of 0.019 units activity per 10(8) cells.
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PMID:5'-Nucleotidase of L 1210 cells. Cytochemical and kinetic studies. 43 76

1-beta-D-Arabinofuranosyl-2-amino-1,4(2H)-imino-5-fluoropyrimidine (10), 1-beta-D-arabinofuranosyl-2-amino-1,4(2H)-imino-5-fluoropyrimidine 3'-phosphate (9), and 1-beta-D-arabinofuranosyl-2-amino-1,4(2H)-imino-5-chloropyrimidine (11) have been synthesized from 2,2'-anhydro-1-beta-D-arabinofuranosyl-5-fluorocytosine (5), 2,2'-anhydro-1-beta-D-arabinofuranosyl-5-fluorocytosine 3'-phosphate (4), and 2,2'-anhydro-1-beta-D-arabinofuranosyl-5-chlorocytosine (6), respectively. 2,2'-Anhydro-1-beta-D-arabinofuranosylcytosine 3'-phosphate (7), 1-beta-D-arabinofuranosyl-2-amino-1,4-(2H)-iminopyrimidine (13), 1-beta-D-arabinofuranosyl-2-amino-1,3(2H)-iminopyrimidine 3'-phosphate (12), and compounds 4, 5, and 9 showed significant in vitro activity against a number of DNA viruses. Compounds 7 and 12 were also effective in vivo against type 1 herpes simplex virus. Compounds 7, 12, and 13 were extremely effective in the treatment of mice bearing leukemia L1210.
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PMID:Synthesis and antitumor and antiviral activities of 1-beta-D-arabinofuranosyl-2-amino-1,4(2H)-iminopyrimidine and its derivatives. 45 2

A series of 3',5'-diesters of a 2,2'-anhydro-1-(beta-D-arabinofuranosyl)cytosine salt bearing functional substituents on the ester side chains (4--16) have been synthesized. The synthesis of these diesters involved the reaction between cytidine and the corresponding acid anhydride or acid chloride in the presence of boron trifluoride etherate. Similar reaction of bis(cytidine 5'-)suberate (21) with pivaloyl chloride gave bis[2,2'-anhydro-1-(3'-O-pivaloyl-beta-D-arabinofuranosyl)cytosine 5'-]suberate dihydrochloride (22). The reaction could also be extended to a one-step synthesis of 3'-esters of 2,2'-anhydro-1-(beta-D-arabinofuranosyl)cytosine 5'-phosphate (24) from 5'-cytidylic acid. These compounds have been examined for antitumor activity against L1210 leukemia in BDF1 mice. The diesters with a long-chain carboxylic acid (4c, 7c, 12, and 24d) showed high activity when administered intraperitoneally. The compound 24d exhibited moderate activity when administered orally.
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PMID:Studies on biologically active nucleosides and nucleotides. 5. Synthesis and antitumor activity of some 2,2'-anhydro-1-(3',5'-di-O-acyl-beta-D-arabinofuranosyl)cytosine salts and 2,2'-anhydro-1-(3'-O-acyl-beta-D-arabinofuranoxyl)cytosine 5'-phosphates. 45 20

Continuous exposure to inhibitory concentrations of methotrexate produces distinct rates of steady-state growth of murine leukemia L1210 and human leukemia CCRF-CEM cells in culture. Addition of thymidine to the medium produces reversal (6 to 40%) of this steady-state growth rate inhibition. This study utilized combinations of methotrexate and thymidine for an evaluation of the accompanying relationship between steady-state growth rate and changes in the ribo- and deoxyribonucleoside triphosphate pools. In L1210 cells exposed to methotrexate alone, the deoxythymidine 5'-phosphate (dTTP) pools decreased, whereas deoxyadenosine 5'-triphosphate, deoxyguanosine 5'-triphosphate, and deoxycytidine 5'-triphosphate (dCTP) remained relatively constant up to 70% inhibition of growth rate, with dCTP at a constant 112% of controls. The corresponding ribonucleoside triphosphates decreased only slightly. With the combination of methotrexate and thymidine resulting in up to 40% inhibition of growth rate, there was also a decrease in the dTTP pool while the other deoxyribonucleoside triphosphates remained relatively constant, and the corresponding ribonucleoside triphosphates again decreased only slightly. The dCTP pool was reduced to a constant 42% of control comparable to that produced by thymidine alone. With greater than 40% (with thymidine) or 70% (without thymidine) inhibition of growth rate, all pools decreased, but only dTTP was substantially reduced in proportion to the growth rate inhibition caused by methotrexate. The dTTP pool became depleted in spite of the presence of exogenous thymidine. Evaluation of CCRF-CEM cells indicated that inhibition of growth rate and nucleotide pool perturbations by methotrexate were similar to those observed in L1210 cells. However, in the presence of thymidine, inhibition of growth rate appeared related to decreased pools of dCTP, deoxyadenosine 5'-triphosphate, and deoxyguanosine 5'-triphosphate, rather than dTTP as was observed for L1210 cells. Hence, mammalian cells were capable of responding in a differential fashion to pharmacological perturbations, and this capacity may play a role in determining therapeutic selectivity. Since the ribonucleoside triphosphate decreases were slight and relatively uniform during methotrexate-induced perturbations, the deoxyribonucleoside triphosphate pools appear to be more directly related to inhibition of growth rate. The results are consistent with the concept that slight imbalances in the deoxyribonucleoside triphosphate pools dramatically inhibit DNA synthesis, as mediated through their interaction with DNA polymerase.
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PMID:Evaluation of ribonucleoside and deoxyribonucleoside triphosphate pools in cultured leukemia cells during exposure to methotrexate or methotrexate plus thymidine. 47 79

Post-translational modifications of retrovirus gag gene-encoded polyproteins include proteolytic cleavage, phosphorylation, and glycosylation. To study the sequence of these events, we labeled JLS-V9 cells chronically infected with Rauscher murine leukemia virus in pulse-chase experiments with the radioactive precursors [35S]methionine, [14C]mannose, [3H]glucosamine, and [32P]phosphate. Newly synthesized gag polyproteins which incorporated label, and the modified products derived from them, were identified by immunoprecipitation of cell lysates with anti-p30 rabbit serum, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Pulse-chase experiments were carried out in the presence as well as in the absence of tunicamycin, an inhibitor of glycosylation. Among the three major polyproteins synthesized in the absence of tunicamycin, two were found to be glycosylated but not phosphorylated. These were designated gPr80gag and gP94gag. Both shared identical [35S]methionine peptides with Pr65gag and p30. Of the two nonglycosylated precursors, Pr65gag and Pr75gag, only Pr65gag was found to be detectably phosphorylated, and Pr75gag could be readily identified only when glycosylation was inhibited. On the basis of these results, a scheme for the post-translational modification of gag polyproteins is proposed. According to this scheme the gag gene-encoded polyproteins are processed from a common precursor, Pr75gag, by two divergent pathways: one leading through the intermediate Pr65gag to internal virion components via cleavage and phosphorylation and the other via tunicamycin-sensitive mannosylation to the intermediate gPr80gag, which is further glycosylated to yield cell surface polyprotein gP94gag.
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PMID:Post-translational modification of Rauscher leukemia virus precursor polyproteins encoded by the gag gene. 48 Apr 54

Clinical interest in the pharmacology of medicinals from marine organisms has heightened due to anticancer effects indicated for Mercenaria marine clam components. This report further characterizes the anticancer principle. Hydrophilic products were extracted by aqueous and/or salting-out methods followed by dialysis. Organic solvent extraction produced a new family of active agents related to the hydrophilic component. Thin layer and liquid column chromatography as well as enzymatic degradation were used to secure a more pure product for analysis. Assay included P388 leukemia and B16 melanoma. Oligonucleotide fractions and smaller components were observed to increase survival rate; treated mice remained at 67% survival when control animals had reached zero. A many-fold purified product was effectively reduced from 300 mg/kg body weight to 5 mg/kg to achieve anticancer activity. Chemical analysis suggested a product composed of carbohydrate, phosphate, peptide, and an unidentified material. Acid hydrolysis revealed the presence of hexoses, pentoses, and a full spectrum of amino acids. Several distinct components found to comprise the active samples may act as the effective product or as a carrier.
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PMID:Chemical characterization and biological activity of an anticancer agent of marine origin. 54 3

A direct ligand-banding radioassay for methotrexate (MTX) has been developed using dihydrofolate reductase, contained in the lysate of L1210 leukemia cells, as the binding determinant. The procedure is a two-phase reaction system where standard MTX concentrations or the sample being assayed in incubated with the reagent lysate in the first phase, and [3H]MTX is then added in the second phase to titrate the remaining unoccupied binding sites on the enzyme. This method eliminates the need for measuring the residual catalytic activity of the enzyme. The sensitivity of the radioassay is limited only by the specific activity of the [3H]MTX and how approximates 10 pg of the drug. Folic acid, methyltetrahydrofolate, formyltetrahydrofolate, and dehydrofolate in concentrations that are physiological do not interfere in the radioassay. Both mercaptoethanol and reduced nicotinamide andnine dinucleotide phosphate increase the binding capacity of the lysate for MTX; but the reduced nucleotide also increases the affinity of the enzyme for the inhibitor. MTX added to serum can be assayed without extraction if the concentration is greater than 500 pg/ml and recovery of the drug added to serum is about 92%. MTX has been assayed in serum, spinal fluid, and urine of patients who were treated with this drug. It has also been assayed in the lysates of L1210 cells from C57BL X DBA/2 F1 mice treated with MTX. The procedure is simple, rapid, and accurate and should permit better correlation of the therapeutic and toxic effects of MTX with blood concentrations over long-term treatment periods.
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PMID:A direct ligand-binding radioassay for the measurement of methotrexate in tissues and biological fluids. 80 20

The purified p12 phosphoprotein of Rauscher murine leukemia virus was fractionated by ion exchange chromatography into subpopulations of molecules containing different amounts of covalently linked phosphate. Of the various phosphorylated forms of p12 protein purified from virions, only a species containing relatively little phosphate can bind in vitro to purified homologous 70S viral RNA. Using ultraviolet irradiation to stabilize ribonucleoprotein complexes in intact virions, the same molecular species of p12 phosphoprotein can be isolated in close association with the 70S viral genome. The results show that phosphorylation of type C viral p12 proteins influences the extent, but not the specificity, of their interaction with homologous viral RNA.
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PMID:Phosphorylation of murine type C viral p12 proteins regulates their extent of binding to the homologous viral RNA. 84 4

DNA polymerase gamma has been purified over 60 000-fold from HeLa cells which contain no detectable type C viral particles. This purified enzyme shows a specific activity of 25 000 units/mg of protein which is comparable to the known specific activity of homogeneous preparations of human alpha and beta polymerases. The isolated enzyme shows apparent molecular weights ranging from 160 000 to 330 000 according to the method of analysis. The enzyme exhibits optimal activity for copying poly(A) in the presence of 50 mM KPO4 and 130 mM KCl and, under these conditions, copies poly(A) 20 times more rapidly than activated DNA. These assay conditions permit a clear distinction between the gamma-polymerase and DNA polymerase beta which is markedly inhibited by phosphate at this concentration. A comparison of the copying of activated DNA, poly(dA) and poly(A) by DNA polymerases alpha, beta, and gamma under optimal assay conditions for each enzyme is presented. Studies with synthetic and natural nucleic acid templates also show the gamma-polymerase to behave differently that the reverse transcriptases of avian myeloblastosis virus or Rauscher leukemia virus.
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PMID:HeLa cell DNA polymerase gamma: further purification and properties of the enzyme. 97 75


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