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Showing papers in "Advances in Enzyme Regulation in 1985"


Journal ArticleDOI
TL;DR: The observation of low-level chemiluminescence under conditions which favor the one-electron reduction process or which diminished the two-electrons reduction process indicates the practicability ofLow- level chemilUMinescence measurements in monitoring changes in quinone metabolism and related cytotoxic effects.

111 citations


Journal ArticleDOI
TL;DR: Using X-rays to eliminate well oxygenated cells of a solid tumor implant of the EMT6 carcinoma, the combination of dicoumarol plus mitomycin C is more toxic to hypoxic tumor cells in vivo than mitomyin C alone.

61 citations


Journal ArticleDOI
Robert H. Earhart1, G. L. Neil1
TL;DR: This review, as its title indicates, views acivicin at a particular point in the ongoing process of its development, with a large body of biochemical information which permits the formulation of a number of hypotheses regarding the drug's optimal regimen, mechanism of CNS toxicity, and potential role in combination chemotherapy.

52 citations


Journal ArticleDOI
TL;DR: Phosphorylation of myosin P-light chain in vertebrate fast-twitch skeletal muscle may play a modulatory role in calcium regulation of muscle contractility, and the extent of P- light chain phosphorylation correlates with enhancement of isometric twitch tension in fast- twitch muscle under a variety of experimental conditions.

51 citations


Journal ArticleDOI
TL;DR: These and related studies show that each of these nucleosides form nucleotide metabolites which act as enzyme inhibitors at additional sites other than IMP dehydrogenase, which may result in an increased "self potentiation" by the lowering of guanylate pools in those instances where Guanylate analogs are involved as inhibitors of viral specific or viral induced enzymes.

49 citations


Journal ArticleDOI
TL;DR: CI-920 is a structurally novel, phosphate-containing polyene lactone antitumor agent isolated from a previously undescribed subspecies of Streptomyces pulveraceus cultured from a Brazilian soil sample and appears to enter cells by this receptor.

40 citations


Journal ArticleDOI
TL;DR: Although ornithine decarboxylase under most conditions is the rate-controlling enzyme of polyamine biosynthesis and thus the most logical target for chemical intervention, the inhibition of the enzyme triggers a series of compensatory reactions all aimed to circumvent the inhibition.

36 citations


Journal ArticleDOI
Olle Heby1
TL;DR: This chapter reviews recent reports on the purification and properties of the pure enzyme, and on the localization, synthesis and regulation of the enzyme in the cell, and a selection of the most potent inhibitors of ornithine decarboxylase are presented.

29 citations


Journal ArticleDOI
TL;DR: 6-Azauridine and 5-azacytidine were used with certain success in human chemotherapy, the first one as a drug affecting recalcitrant psoriasis, the second one for the treatment of different forms of leukemia.

28 citations


Journal ArticleDOI
TL;DR: A comparison of the biochemical expression of resistance to tiazofurin in drug-induced resistant lines of hepatoma 3924A, leukemias L1210 and P388 revealed that the 3 lines expressed similar genetic alterations related to reduced TAD content, decreased NAD pyrophosphorylase activity and increased synthesis of guanylates from salvaging preformed guanine indicating that these 3 factors play an important role in the resistance to TAD.

28 citations


Journal ArticleDOI
TL;DR: In this chapter, synthesis of alkylating oligonucleotide derivatives is described in detail and the results of their application for modification of nucleic acids in vitro are summarized.

Journal ArticleDOI
TL;DR: On the basis of the biochemical action of acivicin, actinomycin and dipyridamole were selected for testing in combination chemotherapy and both drugs acted synergistically with ac civicin.

Journal ArticleDOI
TL;DR: Detailed evidence was brought showing that in the rat insulin exerted a profound effect on liver purine and pyrimidine metabolism by regulating the concentrations of nucleotides through controlling the activities of strategic enzymes involved in their biosynthesis.

Journal ArticleDOI
TL;DR: The structural requirements for a compound to serve as a specific inhibitor of ribonucleotide reductase, either as the non-heme iron or effector-binding subunit, are stringent and strong synergistic inhibition of L1210 cell growth and synergistic cytotoxicity result.

Journal ArticleDOI
TL;DR: It is concluded that DNA cross-links alone are not sufficient to explain the inhibition of cell multiplication by alkylating agents and that additional mechanisms have to be considered.

Journal ArticleDOI
TL;DR: It is proposed that lack of GMP for functions, other than its role in pterin de novo synthesis, accounts for the features of the Lesch-Nyhan syndrome which do not occur when only tetrahydrobiopterin production is deficient as in the inborn errors of tetrahytobiopterin synthesis.

Journal ArticleDOI
TL;DR: Differences in the interaction of aphidicolin with virus enzyme differs from that with host enzyme, and these differences suggest new strategies for antiviral chemotherapy using aphidIColin derivatives.

Journal ArticleDOI
TL;DR: The results suggest that antizyme plays an essential role in the degradation of ODC by a catalytic effect both in the presence and absence of exogenous putrescine and that antIZyme inhibitor stabilizes O DC by removing antizYme.

Journal ArticleDOI
TL;DR: The molecular correlation concept proposed that IMP dehydrogenase activity should be a sensitive target of chemotherapy and received support from an array of evidence.

Journal ArticleDOI
TL;DR: Strategies that are selective for eradicating methotrexate resistant cells are described, based on knowledge of the mechanism of drug resistance encountered in experimental systems and in the clinic.

Journal ArticleDOI
TL;DR: Specific, irreversible, inhibition of ODC activity with DFMO and resultant low levels of intracellular polyamines markedly suppress the induction of experimental colonic and mammary cancers and hold promise for augmenting the multidrug chemotherapy of established colonic, pancreatic, renal and Mammary cancers without increasing systemic toxicity.

Journal ArticleDOI
TL;DR: Determination of the rates of de novo pyrimidine synthesis, of the formation of RNA pyrimidines, and of pyridine nucleoside excretion indicates that de noVO synthesis provides only about 67% of the pyrimids required for the consuming processes.

Journal ArticleDOI
TL;DR: The rationale for the clinical use of a new lipid-soluble folate antagonist, BW 301U, in terms of its potential for killing several classes of methotrexate-resistant cells is provided and some possible mechanisms for this unusual collateral resistance are discussed.

Journal ArticleDOI
TL;DR: The dynamic and functional organization of the fructose-6-phosphate/fructose-1,6-bisphosphatase cycle has been investigated in an open and homogeneous reconstituted enzyme system and it could be shown that in a broad parameter region sustained oscillations arise.

Journal ArticleDOI
TL;DR: During the time that cathepsin B plus L activities in autophagic vacuoles are inhibited by the injection of leupeptin, cytosolic enzymes are being accumulated in autolysis suggesting that leupe leptin blocks intralysosomal proteolysis, and that cytosol enzymes are sequestered continuously into autophagosomes.

Journal ArticleDOI
TL;DR: Cell cycle dependent fluctuations of O6-methylguanine DNA transferase with an increasing enzyme activity in late G1 and a maximum in early S phase indicate that cells possess an increased potential for eliminating promutagenic O 6-methyl Guanine during the most transformation sensitive parts of the cell cycle to prevent base-mispairing during DNA replication or transcription.

Journal ArticleDOI
TL;DR: A wide variety of nucleoside analogues have been synthesized which interfere with the functions of natural nucleosides at many different loci and have found important uses as antitumor, antiviral, antiparasitic and immunomodulating agents.

Journal ArticleDOI
TL;DR: The antitumor antibiotic adriamycin was found to be a potent modulator of the human erythrocyte discocyte echinocyte transition and may maintain levels of the inositide polyphosphates, congruent with the maintenance of the discocyte morphology.

Journal ArticleDOI
TL;DR: The chemotherapeutic action of 5-fluorouridine in rats and mice, carrying the AS-30D and the TA3 ascites tumor, respectively, is significantly improved by pretreatment with an amino sugar together with 6-azauridine.

Journal ArticleDOI
TL;DR: From these results, it is clear that combination chemotherapy directed at independent sites of the same key target enzyme can result in strong synergistic inhibition of cell growth and cytotoxicity offering a clear therapeutic advantage.