Arabinofuranosylcytosine Triphosphate: A triphosphate nucleotide analog which is the biologically active form of CYTARABINE. It inhibits nuclear DNA synthesis.Cytarabine: A pyrimidine nucleoside analog that is used mainly in the treatment of leukemia, especially acute non-lymphoblastic leukemia. Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Its actions are specific for the S phase of the cell cycle. It also has antiviral and immunosuppressant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p472)Adenosine Triphosphate: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.Guanosine Triphosphate: Guanosine 5'-(tetrahydrogen triphosphate). A guanine nucleotide containing three phosphate groups esterified to the sugar moiety.Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).ThymidineDNA Replication: The process by which a DNA molecule is duplicated.Arabinonucleotides: Nucleotides containing arabinose as their sugar moiety.Vidarabine: A nucleoside antibiotic isolated from Streptomyces antibioticus. It has some antineoplastic properties and has broad spectrum activity against DNA viruses in cell cultures and significant antiviral activity against infections caused by a variety of viruses such as the herpes viruses, the VACCINIA VIRUS and varicella zoster virus.Vidarabine Phosphate: An adenosine monophosphate analog in which ribose is replaced by an arabinose moiety. It is the monophosphate ester of VIDARABINE with antiviral and possibly antineoplastic properties.Leukemia, Myeloid, Acute: Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Prince Edward Island: An island in the Gulf of St. Lawrence constituting a province of Canada in the eastern part of the country. It is very irregular in shape with many deep inlets. Its capital is Charlottetown. Discovered by the French in 1534 and originally named Ile Saint-Jean, it was renamed in 1799 in honor of Prince Edward, fourth son of George III and future father of Queen Victoria. (From Webster's New Geographical Dictionary, 1988, p981 & Room, Brewer's Dictionary of Names, 1992, p433)District of Columbia: A federal area located between Maryland and Virginia on the Potomac river; it is coextensive with Washington, D.C., which is the capital of the United States.Architectural Accessibility: Designs for approaching areas inside or outside facilities.Research: Critical and exhaustive investigation or experimentation, having for its aim the discovery of new facts and their correct interpretation, the revision of accepted conclusions, theories, or laws in the light of newly discovered facts, or the practical application of such new or revised conclusions, theories, or laws. (Webster, 3d ed)TexasSoybeans: An annual legume. The SEEDS of this plant are edible and used to produce a variety of SOY FOODS.Typhus, Endemic Flea-Borne: An infectious disease clinically similar to epidemic louse-borne typhus (TYPHUS, EPIDEMIC LOUSE-BORNE), but caused by RICKETTSIA TYPHI, which is transmitted from rat to man by the rat flea, XENOPSYLLA CHEOPIS.Water SofteningEczema: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed).Preservatives, Pharmaceutical: Substances added to pharmaceutical preparations to protect them from chemical change or microbial action. They include ANTI-BACTERIAL AGENTS and antioxidants.Emulsifying Agents: SURFACE-ACTIVE AGENTS that induce a dispersion of undissolved material throughout a liquid.Ion Exchange: Reversible chemical reaction between a solid, often one of the ION EXCHANGE RESINS, and a fluid whereby ions may be exchanged from one substance to another. This technique is used in water purification, in research, and in industry.Food Preservatives: Substances capable of inhibiting, retarding or arresting the process of fermentation, acidification or other deterioration of foods.Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.PubMed: A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.DNA Polymerase II: A DNA-dependent DNA polymerase characterized in E. coli and other lower organisms. It may be present in higher organisms and has an intrinsic molecular activity only 5% of that of DNA Polymerase I. This polymerase has 3'-5' exonuclease activity, is effective only on duplex DNA with gaps or single-strand ends of less than 100 nucleotides as template, and is inhibited by sulfhydryl reagents. EC 2.7.7.7.Periodicals as Topic: A publication issued at stated, more or less regular, intervals.DNA-Directed DNA Polymerase: DNA-dependent DNA polymerases found in bacteria, animal and plant cells. During the replication process, these enzymes catalyze the addition of deoxyribonucleotide residues to the end of a DNA strand in the presence of DNA as template-primer. They also possess exonuclease activity and therefore function in DNA repair.DNA Polymerase I: A DNA-dependent DNA polymerase characterized in prokaryotes and may be present in higher organisms. It has both 3'-5' and 5'-3' exonuclease activity, but cannot use native double-stranded DNA as template-primer. It is not inhibited by sulfhydryl reagents and is active in both DNA synthesis and repair. EC 2.7.7.7.Encyclopedias as Topic: Works containing information articles on subjects in every field of knowledge, usually arranged in alphabetical order, or a similar work limited to a special field or subject. (From The ALA Glossary of Library and Information Science, 1983)Copyright: It is a form of protection provided by law. In the United States this protection is granted to authors of original works of authorship, including literary, dramatic, musical, artistic, and certain other intellectual works. This protection is available to both published and unpublished works. (from Circular of the United States Copyright Office, 6/30/2008)Organizations, Nonprofit: Organizations which are not operated for a profit and may be supported by endowments or private contributions.Patents as Topic: Exclusive legal rights or privileges applied to inventions, plants, etc.MedlinePlus: NATIONAL LIBRARY OF MEDICINE service for health professionals and consumers. It links extensive information from the National Institutes of Health and other reviewed sources of information on specific diseases and conditions.Computer Security: Protective measures against unauthorized access to or interference with computer operating systems, telecommunications, or data structures, especially the modification, deletion, destruction, or release of data in computers. It includes methods of forestalling interference by computer viruses or so-called computer hackers aiming to compromise stored data.Confidentiality: The privacy of information and its protection against unauthorized disclosure.Viola: A plant genus of the family VIOLACEAE. Some species in this genus are called bouncing bet which is a common name more often used with SAPONARIA OFFICINALIS. Members contain macrocyclic peptides.Pharmacy Service, Hospital: Hospital department responsible for the receiving, storing, and distribution of pharmaceutical supplies.Hydroxyeicosatetraenoic Acids: Eicosatetraenoic acids substituted in any position by one or more hydroxy groups. They are important intermediates in a series of biosynthetic processes leading from arachidonic acid to a number of biologically active compounds such as prostaglandins, thromboxanes, and leukotrienes.Isoxsuprine: A beta-adrenergic agonist that causes direct relaxation of uterine and vascular smooth muscle. Its vasodilating actions are greater on the arteries supplying skeletal muscle than on those supplying skin. It is used in the treatment of peripheral vascular disease and in premature labor.Acetohexamide: A sulfonylurea hypoglycemic agent that is metabolized in the liver to 1-hydrohexamide.Pharmacists: Those persons legally qualified by education and training to engage in the practice of pharmacy.Child Advocacy: Promotion and protection of the rights of children; frequently through a legal process.Myelodysplastic Syndromes: Clonal hematopoietic stem cell disorders characterized by dysplasia in one or more hematopoietic cell lineages. They predominantly affect patients over 60, are considered preleukemic conditions, and have high probability of transformation into ACUTE MYELOID LEUKEMIA.Anemia, Refractory: A severe sometimes chronic anemia, usually macrocytic in type, that does not respond to ordinary antianemic therapy.Myelodysplastic-Myeloproliferative Diseases: Clonal myeloid disorders that possess both dysplastic and proliferative features but are not properly classified as either MYELODYSPLASTIC SYNDROMES or MYELOPROLIFERATIVE DISORDERS.Leukemia, Myeloid: Form of leukemia characterized by an uncontrolled proliferation of the myeloid lineage and their precursors (MYELOID PROGENITOR CELLS) in the bone marrow and other sites.Prognosis: A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.Myeloproliferative Disorders: Conditions which cause proliferation of hemopoietically active tissue or of tissue which has embryonic hemopoietic potential. They all involve dysregulation of multipotent MYELOID PROGENITOR CELLS, most often caused by a mutation in the JAK2 PROTEIN TYROSINE KINASE.

All-trans-retinoic acid increases cytosine arabinoside cytotoxicity in HL-60 human leukemia cells in spite of decreased cellular ara-CTP accumulation. (1/66)

BACKGROUND: Accumulation of the cytosine arabinoside (ara-C) metabolite ara-C-triphosphate (ara-CTP) in leukemic blast cells is considered to be the main determinant of ara-C cytotoxicity in vitro and in vivo. Retinoids such as all-trans-retinoic acid (ATRA) have been shown to increase the sensitivity of acute myelogenous leukemic (AML) blast cells to ara-C. To investigate the mechanism of this sensitisation, the hypothesis was tested that ATRA augments cellular ara-CTP levels in human-derived myelogenous leukemia HL-60 cells. MATERIALS AND METHODS: The effect of ATRA and 13-cis-retinoic acid on ara-CTP accumulation and ara-C-induced apoptosis was studied. Ara-CTP levels were measured by high-performance liquid chromatography (HPLC), cytotoxicity by the tetrazolium (MTT) assay, and apoptosis by occurrence of DNA fragmentation (gel electrophoresis), cell shrinkage and DNA loss (flow cytometry). RESULTS: Pretreatment of HL-60 cells with ATRA (0.01-1 microM) caused a significant decrease in intracellular ara-CTP levels; e.g., incubation for 72 hours with ATRA 1 microM prior to one hour ara-C 10 microM reduced ara-CTP levels to 41% +/- 4% of control. Similar results were obtained after preincubation with 13-cis-retinoic acid. In spite of decreased ara-CTP levels, the cytotoxicity of the combination was supraadditive and ATRA augmented ara-C-induced apoptosis. CONCLUSION: At therapeutically relevant concentrations ATRA increased ara-C cytotoxicity and ara-C induced apoptosis but this augmentation is not the corollary of elevated ara-CTP levels. The feasibility of ara-C treatment optimisation via strategies other than those involving elevation of ara-CTP levels should be investigated further.  (+info)

Interim comparison of a continuous infusion versus a short daily infusion of cytarabine given in combination with cladribine for pediatric acute myeloid leukemia. (2/66)

PURPOSE: To identify the optimal schedule for infusion of cytarabine (ara-C) given with cladribine (2-CdA) to pediatric patients with acute myeloid leukemia (AML), and to compare the effects of the two schedules on the pharmacokinetics of ara-C triphosphate (ara-CTP) in leukemic cells. PATIENTS AND METHODS: Forty-nine pediatric patients with newly diagnosed primary AML received a 5-day course of ara-C 500 mg/m(2)/d and 2-CdA 9 mg/m(2)/d. They were randomly assigned to receive ara-C as either a 2-hour daily infusion (arm A) or a continuous infusion (arm B). Cellular pharmacokinetics were studied on days 1 and 2. All patients then received two courses of remission induction chemotherapy with daunorubicin, ara-C, and etoposide (DAV). RESULTS: Thirty-two percent of patients (seven of 22) in arm A and 63% (17 of 27) in arm B entered complete remission (P =.045) after ara-C and 2-CdA therapy. Coadministration of 2-CdA increased the intracellular concentration of ara-CTP in 20 of 36 patients, although we found no statistically significant difference between the treatment arms in this effect (P =.63). The incidence of toxicity did not differ significantly between the two treatment arms (P =.53). After two courses of DAV, the rate of complete remission was 91% in arm A and 96% in arm B (P =.58). CONCLUSION: Intracellular accumulation of ara-CTP is increased when 2-CdA is given with ara-C, but no schedule-dependent differences in this effect were seen. The combination of 2-CdA and ara-C seems to be effective therapy for pediatric AML.  (+info)

Differential mRNA expression of Ara-C-metabolizing enzymes explains Ara-C sensitivity in MLL gene-rearranged infant acute lymphoblastic leukemia. (3/66)

Infant acute lymphoblastic leukemia (ALL) is characterized by a high incidence of mixed lineage leukemia (MLL) gene rearrangements, a poor outcome, and resistance to chemotherapeutic drugs. One exception is cytosine arabinoside (Ara-C), to which infant ALL cells are highly sensitive. To investigate the mechanism underlying Ara-C sensitivity in infants with ALL, mRNA levels of Ara-C-metabolizing enzymes were measured in infants (n = 18) and older children (noninfants) with ALL (n = 24). In the present study, infant ALL cells were 3.3-fold more sensitive to Ara-C (P =.007) and accumulated 2.3-fold more Ara-CTP (P =.011) upon exposure to Ara-C, compared with older children with ALL. Real-time quantitative reverse trancriptase-polymerase chain reaction (RT-PCR) (TaqMan) revealed that infants express 2-fold less of the Ara-C phosphorylating enzyme deoxycytidine kinase (dCK) mRNA (P =.026) but 2.5-fold more mRNA of the equilibrative nucleoside transporter 1 (hENT1), responsible for Ara-C membrane transport (P =.001). The mRNA expression of pyrimidine nucleotidase I (PN-I), cytidine deaminase (CDA), and deoxycytidylate deaminase (dCMPD) did not differ significantly between both groups. hENT1 mRNA expression inversely correlated with in vitro resistance to Ara-C (r(s) = -0.58, P =.006). The same differences concerning dCK and hENT1 mRNA expression were observed between MLL gene-rearranged (n = 14) and germ line MLL cases (n = 25). An oligonucleotide microarray screen (Affymetrix) comparing patients with MLL gene-rearranged ALL with those with nonrearranged ALL also showed a 1.9-fold lower dCK (P =.001) and a 2.7-fold higher hENT1 (P =.046) mRNA expression in patients with MLL gene-rearranged ALL. We conclude that an elevated expression of hENT1, which transports Ara-C across the cell membrane, contributes to Ara-C sensitivity in MLL gene-rearranged infant ALL.  (+info)

The antimetabolite ara-CTP blocks long-term memory of conditioned taste aversion. (4/66)

We examined the hypothesis that processes related to DNA recombination and repair are involved in learning and memory. Rats received intracerebroventricular (i.c.v.) infusions of the antimetabolite 1-beta-D-arabinofuranosylcytosine triphosphate (ara-CTP) or its precursor cytosine arabinoside (ara-C) 30 min prior to conditioned taste aversion (CTA) training. Both ara-CTP and ara-C caused significant impairments in long-term memory (LTM) of CTA. Control experiments indicate that the effect of ara-CTP on CTA memory is related to interference with learning. Furthermore, as it was previously demonstrated for the protein synthesis inhibitor anisomycin, ara-CTP had no effect on CTA memory when it was injected 1 h after training. Importantly, although both ara-CTP and anisomycin significantly blocked LTM in the task, short-term memory (STM) measured 1 h after training was not affected by either of the drugs. Finally, ara-CTP had no effect on in vitro transcription, but it did effectively block nonhomologous DNA end joining (NHEJ) activity of brain protein extracts. We suggest that DNA ligase-mediated DNA recombination and repair processes are necessary for the expression of LTM in the brain.  (+info)

The value of fludarabine in addition to ARA-C and G-CSF in the treatment of patients with high-risk myelodysplastic syndromes and AML in elderly patients. (5/66)

Fludarabine in addition to cytosine-arabinoside (ARA-C) increases the accumulation of ARA-C-5'-triphosphate (ARA-CTP), which is responsible for the cytotoxic effect in leukemic blasts. In a randomized phase 3 trial, patients with high-risk myelodysplastic syndrome (MDS) (n = 91) or elderly patients with acute myeloid leukemia (AML) (n = 43) were randomized to receive 2 induction courses consisting of ARA-C (2 g/m2 days 1 through 5) and granulocyte colony-stimulating factor (G-CSF) (filgrastim, 5 microg/kg) during and after chemotherapy with or without fludarabine (25 mg/m2, days 1 through 5) (FLAG versus AG). Consolidation consisted of daunorubicin (45 mg/m2, days 1 through 3) and ARA-C (200 mg/m2, days 1 through 7). Complete remission (CR) rate following AG was 65% versus 71% with FLAG (P =.49). Overall survival (OS) at 24 months was 24% for AG treatment and 39% for FLAG (P =.32). Event-free survival (EFS) at 2 years was 10% and 19% (P =.31) for the AG and FLAG treatments, respectively. Platelet and granulocyte recovery times after the second cycle were prolonged in the FLAG treatment group. Grades 3 to 4 neurotoxicities were more often reported in the FLAG arm (14% versus 3%, P =.03), whereas no significant differences in other toxicities were observed. In a cohort of patients, the in vivo accumulation of ARA-CTP in leukemic cells was determined. Although ARA-CTP accumulation in leukemic cells after FLAG was enhanced, clinical outcome in terms of CR rate, OS, EFS, and disease-free survival (DFS) was not significantly improved by combining fludarabine with ARA-C.  (+info)

Human immunodeficiency virus type 1 induces 1-beta-D-arabinofuranosylcytosine resistance in human H9 cell line. (6/66)

We have found that chronically HIV-1(IIIB)-infected H9 cells showed 21-fold resistance to 1-beta-D-arabinofuranosylcytosine (ARA-C) compared with uninfected H9 cells. In the infected H9 cells, a 37% increase of dCTP pool and a 34% increase of dATP were observed, and no alteration of dTTP and dGTP was observed, compared with the uninfected H9 cells. A marked decrease of ARA-CTP generation was observed in the infected H9 cells after 3-h incubation with 0.1-10 microM ARA-C. The level of deoxycytidine kinase activity with ARA-C as substrate was similar in both the infected and the uninfected cells; however, a 37-fold increase of cytidine deaminase activity was observed in the infected H9 cells. These results indicate that the induction of cytidine deaminase activity by HIV-1(IIIB) infection conferred ARA-C resistance to H9 cells. This conclusion was supported by the observation that a marked reversal of ARA-C resistance in the infected H9 cells occurred after treatment with the inhibitor of cytidine deaminase, 3,4,5,6-tetrahydrouridine. The understanding of these cellular alterations in drug sensitivity may facilitate the development of effective therapeutic strategies against HIV-1-infected cells.  (+info)

GATA1, cytidine deaminase, and the high cure rate of Down syndrome children with acute megakaryocytic leukemia. (7/66)

Down syndrome children with acute megakaryocytic leukemia (AMkL) have higher cure rates than non-Down syndrome acute myeloid leukemia (AML) patients treated with cytosine arabinoside (ara-C). Megakaryoblasts from Down syndrome AML patients are more sensitive in vitro to ara-C than cells from non-Down syndrome AML patients. Somatic mutations in the GATA1 transcription factor have been detected exclusively and almost uniformly in Down syndrome AMkL patients, suggesting a potential linkage to the chemotherapy sensitivity of Down syndrome megakaryoblasts. Stable transfection of wild-type GATA1 cDNA into the Down syndrome AMkL cell line CMK resulted in decreased (8- to 17-fold) ara-C sensitivity and a threefold-lower generation of the active ara-C metabolite ara-CTP compared with that for mock-transfected CMK cells. High intracellular levels of uridine arabinoside (ara-U) (an inactive ara-C catabolite generated by cytidine deaminase) and cytidine deaminase transcripts were detected in GATA1-transfected CMK sublines, whereas no ara-U was detected in mock-transfected cells. Cytidine deaminase transcripts were a median 5.1-fold (P = .002) lower in Down syndrome megakaryoblasts (n = 16) than in blast cells from non-Down syndrome patients (n = 56). These results suggest that GATA1 transcriptionally upregulates cytidine deaminase and that the presence or absence of GATA1 mutations in AML blasts likely confers differences in ara-C sensitivities due to effects on cytidine deaminase gene expression, which, in turn, contributes to the high cure rate of Down syndrome AMkL patients.  (+info)

An inhibitor of DNA recombination blocks memory consolidation, but not reconsolidation, in context fear conditioning. (8/66)

Genomic recombination requires cutting, processing, and rejoining of DNA by endonucleases, polymerases, and ligases, among other factors. We have proposed that DNA recombination mechanisms may contribute to long-term memory (LTM) formation in the brain. Our previous studies with the nucleoside analog 1-beta-D-arabinofuranosylcytosine triphosphate (ara-CTP), a known inhibitor of DNA ligases and polymerases, showed that this agent blocked consolidation of conditioned taste aversion without interfering with short-term memory (STM). However, because polymerases and ligases are also essential for DNA replication, it remained unclear whether the effects of this drug on consolidation were attributable to interference with DNA recombination or neurogenesis. Here we show, using C57BL/6 mice, that ara-CTP specifically blocks consolidation but not STM of context fear conditioning, a task previously shown not to require neurogenesis. The effects of a single systemic dose of cytosine arabinoside (ara-C) on LTM were evident as early as 6 h after training. In addition, although ara-C impaired LTM, it did not impair general locomotor activity nor induce brain neurotoxicity. Importantly, hippocampal, but not insular cortex, infusions of ara-C also blocked consolidation of context fear conditioning. Separate studies revealed that context fear conditioning training significantly induced nonhomologous DNA end joining activity indicative of DNA ligase-dependent recombination in hippocampal, but not cortex, protein extracts. Finally, unlike inhibition of protein synthesis, systemic ara-C did not block reconsolidation of context fear conditioning. Our results support the idea that DNA recombination is a process specific to consolidation that is not involved in the postreactivation editing of memories.  (+info)

Arabinofuranosylcytosine Triphosphate: A triphosphate nucleotide analog which is the biologically active form of CYTARABINE. It inhibits nuclear DNA synthesis.
Le page, G and White, S, "Scheduling of arabinosylcytosine (ara-c) and 6-thioguanine (6-tg) therapy. Abstr." (1972). Subject Strain Bibliography 1972. 390 ...
1-beta-d-Arabinofuranosylcytosine (ara-C), an effective drug for acute leukemias, must be phosphorylated to its 5-triphosphate, ara-CTP, for activity. Our previous studies during therapy of acute myelogenous leukemia (AML) patients demonstrated that the accumulation of ara-CTP in circulating leukemia blasts was increased by a median of 2-fold when fludarabine (30 mg/m2/day over 30 min) was infused 4 h prior to intermediate dose ara-C. The augmentation was dependent on the cellular concentration of fludarabine triphosphate (F-ara-ATP). To determine the lowest dose of fludarabine needed for modulation of ara-C metabolism, the present study administered fludarabine at a test dose (15 mg/m2 over 30 min) followed by 2 g/m2 ara-C infused over 4 h. The next day, the fludarabine/ara-C couplet was repeated but with a standard dose (30 mg/m2) of fludarabine. There was a dose-dependent accumulation of F-ara-ATP in circulating leukemia blasts; the median peak concentrations were 33 and 41 microM with 15 ...
Okabayashi, T; Mihara, S; Repke, D B.; and Moffatt, J G., "A radioimmunoassay for 1-beta-d-arabinofuranosylcytosine." (1977). Subject Strain Bibliography 1977. 1646 ...
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TY - JOUR. T1 - Time controlled release of arabinofuranosylcytosine (Ara-C) from agarose hydrogels using layer-by-layer assembly. T2 - Journal of Biomaterials Science, Polymer Edition. AU - Mehrotra,Sumit. AU - Lynam,Daniel. AU - Liu,Chun. AU - Shahriari,Dena. AU - Lee,Ilsoon. AU - Tuszynski,Mark. AU - Sakamoto,Jeffrey. AU - Chan,Christina. PY - 2012. Y1 - 2012. N2 - Experimentally induced axonal regeneration is compromised by glial scar formation arising from leptomeningeal fibroblasts cells in and around the hydrogel scaffold implanted for nerve repair. Strategies are needed to prevent such fibroblastic reactive cell layer formation for enhanced axonal regeneration. Here, we implement the technique of layer-by-layer assembled degradable, hydrogen bonded multilayers on agarose hydrogels to incorporate an anti-mitotic drug (1-β-D-arabinofuranosylcytosine (Ara-C)) within the agarose hydrogels. We show controlled release of Ara-C under physiological conditions over a period of days. The ...
The cytocidal activity of arabinosyl-5-azacytosine (araAC) and its effect on the synthesis and methylation of DNA in the human colon carcinoma cell line HT-29 was examined and compared with three other cytidine analogues. Treatment for 2 hr with 10(-6)M arabinosylcytosine (araC), araAC, 5-azacytidine (AZC), or 2-deoxy-5-azacytidine (dAZC) produced a 7-30% reduction in cell viability. Prolongation of drug exposure to 24 hr significantly enhanced the cytotoxicity of all analogues, and particularly dAZC. AZC and dAZC were potent inhibitors of DNA methylation in the absence of inhibition of DNA synthesis, whereas araC and araAC primarily affected DNA synthesis. RNA synthesis was not affected by any of the analogues. dAZC and AZC were incorporated into DNA to a greater extent than were araC or araAC upon short- and long-term drug exposure, whereas only AZC was incorporated into RNA. These data indicate that araAC appears to behave more as an analogue of araC rather than of dAZC or AZC, wherein it ...
Anderson, E., Conway, M. E., Alloush, H., OMalley, K., Smith, A., Ashley, M., Ruddock, M., Reid, C., Lamont, J., Fitzgerald, P., Smith, G., Mehta, P. and Salisbury, V. (2014) Investigation and verification of a bioluminescent biosensor for the quantitation of ara-CTP generation: A biomarker for cytosine arabinoside sensitivity in acute myeloid leukaemia. Biosensors and Bioelectronics, 52. pp. 345-353. ISSN 0956-5663 Available from: http://eprints.uwe.ac.uk/21585 Anderson, E., Smith, M. A., Martin, A., Ruddock, M., Lamont, J., Alloush, H., Conway, M. E., Mehta, P., Smith, J. G. and Salisbury, V. (2013) A novel bioluminescent bacterial biosensor for measurement of Ara-CTP and cytarabine potentiation by fludarabine in seven leukaemic cell lines. Leukemia Research, 37 (6). pp. 690-696. ISSN 0145-2126 Available from: http://eprints.uwe.ac.uk/21670 Turner, D., Hezwani, M., Nelson, S., Salisbury, V. and Reynolds, D. M. (2012) Characterization of the Salmonella bacteriophage vB_SenS-Ent1. Journal of ...
The nucleoside analog cytarabine (ara-C) has been the mainstay of acute myeloid leukemia (AML) chemotherapy for more than 40 years and is one of the most import...
Fifty-three patients with disseminated herpes zoster were studied; 20 of them received intravenous cytosine arabinoside. Experience with an early treatment (first 2 days of dissemination) program suggested cytosine arabinoside shortened dissemination compared with untreated patients seen previously. With increased referral of early disseminated cases, the study population changed to include a greater proportion with milder disease. A double blind study was initiated and is currently in progress. To date, the results (11 patients) in the placebo and cytosine arabinoside groups arent significantly different. Treatment with cytosine arabinoside shortens dissemination in some patients destined to have prolonged dissemination and visceral complications: ...
The nucleotide fraction of cultured 3T6 and 3T3 mouse fibroblasts contains deoxy-CDP choline and deoxy-CDP ethanolamine as well as the corresponding riboliponucleotides. In permeabilized cells both deoxyliponucleotides were formed from dCTP. In intact cells they could be labeled from [5-3H] deoxycytidine or cytidine via transformation of the nucleosides to dCTP. Their turnover was slow compared to that of dCTP. When rapidly growing 3T3 cells were labeled during 90 min from deoxycytidine the specific activity of dCDP choline was 2.4 times higher than that of dCTP while after labeling from cytidine both nucleotides (and CTP) reached the same specific activity under steady state conditions. Also dCDP ethanolamine was labeled more rapidly from deoxycytidine than from cytidine. Our results suggest that the deoxyliponucleotides were synthesized from a dCTP pool that was labeled preferentially from deoxycytidine. Earlier work (Nicander, B., and Reichard, P. (1983) Proc. Natl. Acad. Sci. U. S. A. 80, ...
Fludarabine (NSC 118218) is a DNA synthesis inhibitor, which also inhibits phosphorylation of STAT1. Fludarabine, a pro-drug, is converted metabolically by dephosphorylation to the antimetabolite, F-ara-A. - Mechanism of Action & Protocol.
TY - JOUR. T1 - Ara-C scheduling. T2 - Theoretical and experimental considerations. AU - Gray, Joe. AU - Pallavicini, M. G.. PY - 1982. Y1 - 1982. N2 - In this paper, we discuss the cytokinetic basis for optimization of cancer therapy in humans. Specifically, we define a quantitative procedure for determination of the therapeutic acceptability of therapy schedule, discuss studies of the therapeutic gain that might result from treatment of acute lymphoid leukemia (ALL) with cytosine arabinoside (Ara-C), and indicate the kinds of cytokinetic information necessary for therapy scheduling. These studies suggest 1) that substantial therapeutic improvements may result from optimal therapy scheduling, 2) that therapy schedules selected at random are not likely to be beneficial, and 3) that consideration of the cytokinetic properties of the dose limiting normal tissues is critical during therapy design. We also discuss experimental studies of the response to Ara-C of the murine KHT sarcoma. These studies ...
TY - JOUR. T1 - Activation of deoxycytidine kinase by inhibition of DNA synthesis in human lymphocytes. AU - Csapó, Z.. AU - Sasvári, M.. AU - Spasokoukotskaja, T.. AU - Talianidis, Iannis. AU - Eriksson, Staffan. AU - Staub, M.. PY - 2001/1/15. Y1 - 2001/1/15. N2 - Deoxycytidine kinase (dCK, EC.2.7.1.74) is a key enzyme in the intracellular metabolism of 2-chlorodeoxyadenosine, 1β-D-arabinofuranosylcytosine, difluorodeoxycytidine, and other drugs used in chemotherapy of different leukaemias and solid tumours. Recently, stimulation of dCK activity was shown by these analogues and by other genotoxic agents such as etoposide and NaF, all of which cause severe inhibition of DNA synthesis in cell cultures. Here we describe that direct inhibition of DNA polymerases by aphidicolin stimulated dCK activity in normal lymphocytes and acute myeloid leukaemic cells, as well as in HL 60 promyelocytic cell cultures. Increased dCK activity was not due to new protein synthesis under our conditions, as ...
This trial will compare the efficacy and tolerability of cytarabine [cytosine arabinoside] with or without laromustine [Cloretazine, VNP40101M] in patients with
TY - JOUR. T1 - Cytosine arabinoside induces programmed endothelial cell death through the caspase-3 pathway. AU - Moore, Ida M. AU - Merkle, Carrie J. AU - Miketova, Petra. AU - Salyer, Renee K.. AU - Torres, Bonny J.. AU - Schaeffer, Richard C.. AU - Montgomery, David W. PY - 2006/4. Y1 - 2006/4. N2 - The anti-cancer effects of cytosine arabinoside (ARA-C) are well known. However, effects on nonmalignant cells have not been elucidated and may be important to understanding treatment-related toxicity. The purpose of this study was to examine the effect of ARA-C on nondividing vascular endothelial cells. The objectives were to determine the effects of ARA-C on cell viability and to ascertain whether ARA-C caused apoptosis in cultured vascular endothelial cells and hydrocortisone blunted caspase-3-induced apoptosis. Endothelial cells were cultured until confluent and mitotically quiescent then exposed to ARA-C (10 -7 to 10 -3 M) for 1 to 4 days. Some experiments involved cotreatment with ...
... arabinofuranosylcytosine triphosphate MeSH D13.695.740.246.115 --- cyclic cmp MeSH D13.695.740.246.150 --- cytidine diphosphate ... arabinofuranosylcytosine triphosphate MeSH D13.695.065.900 --- vidarabine phosphate MeSH D13.695.201.100 --- deoxyadenine ... ethenoadenosine triphosphate MeSH D13.695.667.138.382 --- coenzyme a MeSH D13.695.667.138.382.300 --- acyl coenzyme a MeSH ... ethenoadenosine triphosphate MeSH D13.695.827.068.382 --- coenzyme a MeSH D13.695.827.068.382.300 --- acyl coenzyme a MeSH ...
... is a nucleotide that inhibits the synthesis of DNA by acting as an antimetabolic agent ...
Arabinofuranosylcytosine triphosphate. *Arabitol. *Arachidic acid. *Araloside A. *Arcapillin. *Archaeol. *Arisugacin A. * ...
... -5´-triphosphate is a substrate for SAMDH1. Furthermore, SAMHD1 has been shown to limit the efficacy of cytarabine ... It is an antimetabolic agent with the chemical name of 1β-arabinofuranosylcytosine. Certain sponges, where it was originally ... Its mode of action is due to its rapid conversion into cytosine arabinoside triphosphate, which damages DNA when the cell cycle ... When used as an antiviral, cytarabine-5´-triphosphate functions by inhibiting viral DNA synthesis. Cytarabine is able to ...
Arabinofuranosylcytosine triphosphate is a nucleotide that inhibits the synthesis of DNA by acting as an antimetabolic agent ...
A triphosphate nucleotide analog which is the biologically active form of CYTARABINE. It inhibits nuclear DNA synthesis. ... Arabinofuranosylcytosine Triphosphate. Subscribe to New Research on Arabinofuranosylcytosine Triphosphate A triphosphate ... Ara CTP; Triphosphate, Arabinofuranosylcytosine; Triphosphate, Arabinosylcytosine; Triphosphate, Cytarabine; Triphosphate, ... Arabinofuranosylcytosine Triphosphate: 72*1-(2-deoxy-2-fluoro-beta-arabinofuranosyl)-5-methylcytosine triphosphate ...
1-beta-d-Arabinofuranosylcytosine (ara-C), an effective drug for acute leukemias, must be phosphorylated to its 5-triphosphate ... Minimum dose of fludarabine for the maximal modulation of 1-beta-D-arabinofuranosylcytosine triphosphate in human leukemia ... Minimum dose of fludarabine for the maximal modulation of 1-beta-D-arabinofuranosylcytosine triphosphate in human leukemia ... Minimum dose of fludarabine for the maximal modulation of 1-beta-D-arabinofuranosylcytosine triphosphate in human leukemia ...
Role of Uridine Triphosphate in the Phosphorylation of 1-β-d-Arabinofuranosylcytosine by Ehrlich Ascites Tumor Cells ... Role of Uridine Triphosphate in the Phosphorylation of 1-β-d-Arabinofuranosylcytosine by Ehrlich Ascites Tumor Cells ...
... triphosphate of 1-β-d-arabinofuranosylcytosine and the 5′-triphosphate of 9-β-d-arabinofuranosyladenine. Cancer Res. 28, 2061- ... Since homophymine A lacks structural features to act as mimics of natural nucleotide triphosphates, it is likely to impede the ... deoxyribose). The natural nucleoside mimics Ara-A and Ara-C are easily phosphorylated as their triphosphate derivatives by ... one that directly competes with natural nucleotide triphosphates and the other that either directly blocks the catalytic ...
Inhibitory Effect of 1-β-d-Arabinofuranosylthymine 5′-Triphosphate and 1-β-d-Arabinofuranosylcytosine 5′-Triphosphate on DNA ...
Quantitation of 1-beta-D-arabinofuranosylcytosine 5′-triphosphate in the leukemic cells from bone marrow and peripheral blood ... deoxyadenosine triphosphate, deoxycytidine triphosphate, and thymidine triphosphate TTP (n = 5; data not shown). ... 3H]deoxyadenosine triphosphate and [3H]deoxythymidine triphosphate were purchased from PerkinElmer Life Sciences and MP ... Intracellular deoxyguanosine triphosphate (dGTP) increase was very modest, from median of 6μM to 10μM. Compared with in vivo, ...
06/15/1987 - "The intracellular half-life for retention of the active triphosphate metabolite 1-beta-D-arabinofuranosylcytosine ... triphosphate; sodium tripolyphosphate; potassium triphosphate; sodium triphosphate; tetrasodium tripolyphosphate; triphosphoric ... 12/01/1990 - "Metabolism and toxicity of electroporated 1-beta-D-arabinofuranosylcytosine triphosphate in a human leukemia cell ... triphosphoric acid (triphosphate). Subscribe to New Research on triphosphoric acid used as water softener, peptizing agent, ...
1-beta-D-arabino-furanosylcytosine triphosphate, and aphidicolin. Marked difference between the two forms was preference of ...
... arabinofuranosylcytosine triphosphate MeSH D13.695.740.246.115 --- cyclic cmp MeSH D13.695.740.246.150 --- cytidine diphosphate ... arabinofuranosylcytosine triphosphate MeSH D13.695.065.900 --- vidarabine phosphate MeSH D13.695.201.100 --- deoxyadenine ... ethenoadenosine triphosphate MeSH D13.695.667.138.382 --- coenzyme a MeSH D13.695.667.138.382.300 --- acyl coenzyme a MeSH ... ethenoadenosine triphosphate MeSH D13.695.827.068.382 --- coenzyme a MeSH D13.695.827.068.382.300 --- acyl coenzyme a MeSH ...
... triphosphate accumulation was approximately 30% of control values. Thus, ara-G differs from 1-beta-D-arabinofuranosylcytosine ... All patients who suffered major organ toxicity had red blood cell deoxyadenosine triphosphate/adenosine triphosphate ratios ... These data suggest that the degree of replacement of adenosine triphosphate by deoxyadenosine triphosphate in erythrocytes ... nor did the accumulation of 1-beta-D-arabinofuranosylcytosine 5-triphosphate in the freshly isolated leukemic cells differ ...
... arabinofuranosylcytosine triphosphate ara u = arabinofuranosyluracil aras = atherosclerotic renal artery stenosis arbkt = aids ... cytidine triphosphate ctr = carpal tunnel release ctr = center ctr = central ctrl = control key cts = carpal tunnel syndrome ... copper adenosine triphosphate cuc = chronic ulcerative colitis cult = culture culys = copper lysine cuo = calovo fever cup = ... adenosine triphosphate atp = advanced technology program atp = azathioprine atra = all trans-retinoic acid ats = alport ...
Arabinofuranosylcytosine triphosphate. *Arabitol. *Arachidic acid. *Araloside A. *Arcapillin. *Archaeol. *Arisugacin A. * ...
P. Chiba, T. Szekeres, W. Jäger: Determination of Pyrimidine Deoxynucleoside 1-ß-D-Arabinofuranosylcytosine Triphosphate. Eur. ... Effects in human HL-60 promyelocytic leukemia cells and synergism with arabinofuranosylcytosine (Ara-C). Biochem. Pharmacol. 81 ... Heterodinucleoside phosphates of 5-fluorodeoxyuridine and arabinofuranosylcytosine-new drugs in cancer chemotherapy? In Vivo 19 ... Cytotoxic effects of novel amphiphilic dimers consisting of 5-fluorodeoxyuridine and arabinofuranosylcytosine in cross- ...
Saturation of 1-beta-D-arabinofuranosylcytosine 5-triphosphate accumulation in leukemia cells during high-dose 1-beta-D- ... arabinofuranosylcytosine therapy. Cancer Res. 1987;47(11):3005-11.. *Mayer RJ, Davis RB, Schiffer CA, Berg DT, Powell BL, ...
For example, these unique gene products include ribonucleoside-triphosphate reductase, dTDP-d-glucose 4,6 dehydratase, ... Arabinofuranosylcytosine Triphosphate. *Genus. Citations. Publications citing this paper.. Showing 1-10 of 31 extracted ...
Arabinofuranosylcytosine Triphosphate. *Cyclic CMP. *Cytidine Diphosphate. *Cytidine Monophosphate. *Cytidine Triphosphate. * ...
The structure reveals a binding site that accommodates triphosphate nucleotides such as ATP, and biochemical studies ... The structure reveals a binding site that accommodates triphosphate nucleotides such as ATP, and biochemical studies ... Arabinofuranosylcytosine Triphosphate. *Nucleotides. *Nociception. *Pain, Burning. *Pain Perception. *hypersensitivity ...
... is modified with the cardenolide-hapten digoxigenin by enzymatic incorporation of digoxigenin-labeled deoxyuridine-triphosphate ... is modified with the cardenolide-hapten digoxigenin by enzymatic incorporation of digoxigenin-labeled deoxyuridine-triphosphate ...
... that further escalation of the cytarabine dose beyond levels that saturate intracellular arabinofuranosylcytosine triphosphate ...
... triphosphate of 1-beta-d-arabinofuranosylcytosine and the 5-triphosphate of 9-beta-d-arabinofuranoxyladenine. Cancer Res. 1968 ... Jamieson GP, Finch LR, Snook M, Wiley JS: Degradation of 1-beta-D-arabinofuranosylcytosine 5-triphosphate in human leukemic ... Colly LP, Willemze R, Honders W, vd Hoorn F, Edelbroek PM: In vivo studies on high-dose 1-beta-D-arabinofuranosylcytosine ( ... Graham FL, Whitmore GF: Studies in mouse L-cells on the incorporation of 1-beta-D-arabinofuranosylcytosine into DNA and on ...
... to a compound comprising a cytosine base and an arabinose sugar that is converted into Arabinofuranosylcytosine triphosphate in ...
This MNNG-induced in vitro DNA synthesis was inhibited by aphidicolin, but not by 2,3-dideoxythymidine-5-triphosphate. It ... The presence of hydroxyurea and arabinofuranosyl cytosine during in vivo incubation with MNNG was necessary for enhancement of ...
Inhibitory effect of 1-beta-D-arabinofuranosylthymine 5-triphosphate and 1-beta-D-arabinofuranosylcytosine 5-triphosphate on ...
Since troxacitabine triphosphate is a poor feedback inhibitor of dCK [18], it is not likely to limit accumulation of ... Yamauchi T, Ueda T, Nakamura T: A new sensitive method for determination of intracellular 1-beta-D-arabinofuranosylcytosine 5- ... Kukhanova M, Liu SH, Mozzherin D, Lin TS, Chu CK, Cheng YC: L- and D-enantiomers of 2,3-dideoxycytidine 5-triphosphate ... HPLC analysis of 15 nmol each of troxacitabine, troxacitabine mono-, di- and triphosphates standards yielded retention times of ...
  • Minimum dose of fludarabine for the maximal modulation of 1-beta-D-arabinofuranosylcytosine triphosphate in human leukemia blasts during therapy. (aacrjournals.org)
  • Our previous studies during therapy of acute myelogenous leukemia (AML) patients demonstrated that the accumulation of ara-CTP in circulating leukemia blasts was increased by a median of 2-fold when fludarabine (30 mg/m2/day over 30 min) was infused 4 h prior to intermediate dose ara-C. The augmentation was dependent on the cellular concentration of fludarabine triphosphate (F-ara-ATP). (aacrjournals.org)
  • The purified two active forms differed in chromatographic and electrophoretic behaviors, in their salt requirement for optimal activity, and in preference of template-primers, although both forms exhibited properties characteristic of DNA polymerase alpha such as sensitivity of N-ethylmaleimide, 1-beta-D-arabino-furanosylcytosine triphosphate, and aphidicolin. (nih.gov)
  • Greco, W. R., Park, H. S., and Rustum, Y. M. Application of a new approach for the quantitation of drug synergism to the combination of cis -diamminedichloro-platinum and 1-D-arabinofuranosylcytosine. (springer.com)