hydroxyurea

Summary

Summary: An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase.

Top Publications

  1. ncbi Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia: risks and benefits up to 9 years of treatment
    Martin H Steinberg
    Boston University School of Medicine, Center of Excellence in Sickle Cell Disease, Boston Medical Center, Boston, Mass 02118, USA
    JAMA 289:1645-51. 2003
  2. pmc Hydroxyurea-stalled replication forks become progressively inactivated and require two different RAD51-mediated pathways for restart and repair
    Eva Petermann
    Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford OX3 7DQ, UK
    Mol Cell 37:492-502. 2010
  3. ncbi Fork reversal and ssDNA accumulation at stalled replication forks owing to checkpoint defects
    Jose M Sogo
    Institute of Cell Biology, ETH Honggerberg, CH 8093 Zurich, Switzerland
    Science 297:599-602. 2002
  4. ncbi The structure-specific endonuclease Mus81 contributes to replication restart by generating double-strand DNA breaks
    Katsuhiro Hanada
    Department of Cell Biology and Genetics, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands
    Nat Struct Mol Biol 14:1096-104. 2007
  5. pmc Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG)
    Winfred C Wang
    St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Lancet 377:1663-72. 2011
  6. ncbi ATR homolog Mec1 promotes fork progression, thus averting breaks in replication slow zones
    Rita S Cha
    Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
    Science 297:602-6. 2002
  7. pmc DNA polymerase stabilization at stalled replication forks requires Mec1 and the RecQ helicase Sgs1
    Jennifer A Cobb
    University of Geneva, Department of Molecular Biology, Quai Ernest Ansermet 30, CH 1211 Geneva, Switzerland
    EMBO J 22:4325-36. 2003
  8. pmc Characterization of homologous recombination induced by replication inhibition in mammalian cells
    Y Saintigny
    UMR217 CNRS-CEA and CEA, Direction des Sciences du Vivant, , , 92 265 Fontenay aux Roses Cedex, France
    EMBO J 20:3861-70. 2001
  9. pmc ERAD inhibitors integrate ER stress with an epigenetic mechanism to activate BH3-only protein NOXA in cancer cells
    Qiuyan Wang
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 106:2200-5. 2009
  10. ncbi Human Asf1 regulates the flow of S phase histones during replicational stress
    Anja Groth
    Institute of Cancer Biology, The Danish Cancer Society, Strandboulevarden 49, DK 2100 Copenhagen, Denmark
    Mol Cell 17:301-11. 2005

Research Grants

Detail Information

Publications336 found, 100 shown here

  1. ncbi Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia: risks and benefits up to 9 years of treatment
    Martin H Steinberg
    Boston University School of Medicine, Center of Excellence in Sickle Cell Disease, Boston Medical Center, Boston, Mass 02118, USA
    JAMA 289:1645-51. 2003
    b>Hydroxyurea increases levels of fetal hemoglobin (HbF) and decreases morbidity from vaso-occlusive complications in patients with sickle cell anemia (SCA). High HbF levels reduce morbidity and mortality.
  2. pmc Hydroxyurea-stalled replication forks become progressively inactivated and require two different RAD51-mediated pathways for restart and repair
    Eva Petermann
    Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford OX3 7DQ, UK
    Mol Cell 37:492-502. 2010
    Faithful DNA replication is essential to all life. Hydroxyurea (HU) depletes the cells of dNTPs, which initially results in stalled replication forks that, after prolonged treatment, collapse into DSBs...
  3. ncbi Fork reversal and ssDNA accumulation at stalled replication forks owing to checkpoint defects
    Jose M Sogo
    Institute of Cell Biology, ETH Honggerberg, CH 8093 Zurich, Switzerland
    Science 297:599-602. 2002
    ..We speculate that, in checkpoint mutants, abnormal replication intermediates begin to form because of uncoordinated replication and are further processed by unscheduled recombination pathways, causing genome instability...
  4. ncbi The structure-specific endonuclease Mus81 contributes to replication restart by generating double-strand DNA breaks
    Katsuhiro Hanada
    Department of Cell Biology and Genetics, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands
    Nat Struct Mol Biol 14:1096-104. 2007
    ..We suggest that Mus81 suppresses chromosomal instability by converting potentially detrimental replication-associated DNA structures into intermediates that are more amenable to DNA repair...
  5. pmc Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG)
    Winfred C Wang
    St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Lancet 377:1663-72. 2011
    ..We assessed the effect of hydroxycarbamide therapy on organ dysfunction and clinical complications, and examined laboratory findings and toxic effects...
  6. ncbi ATR homolog Mec1 promotes fork progression, thus averting breaks in replication slow zones
    Rita S Cha
    Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
    Science 297:602-6. 2002
    ..Thus, Mec1 has important functions in normal S phase and the genome instability of mec1 (and, analogously, ATR-/-) mutants stems from defects in these basic roles...
  7. pmc DNA polymerase stabilization at stalled replication forks requires Mec1 and the RecQ helicase Sgs1
    Jennifer A Cobb
    University of Geneva, Department of Molecular Biology, Quai Ernest Ansermet 30, CH 1211 Geneva, Switzerland
    EMBO J 22:4325-36. 2003
    ..Here we demonstrate by chromatin immunoprecipitation that when yeast replication forks stall due to hydroxyurea (HU) treatment, DNA polymerases alpha and epsilon are stabilized for 40-60 min...
  8. pmc Characterization of homologous recombination induced by replication inhibition in mammalian cells
    Y Saintigny
    UMR217 CNRS-CEA and CEA, Direction des Sciences du Vivant, , , 92 265 Fontenay aux Roses Cedex, France
    EMBO J 20:3861-70. 2001
    ..We propose that replication inhibition produces DSBs, which are first processed by the NHEJ; then, following DSB accumulation, RAD51 recombination can act...
  9. pmc ERAD inhibitors integrate ER stress with an epigenetic mechanism to activate BH3-only protein NOXA in cancer cells
    Qiuyan Wang
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 106:2200-5. 2009
    ..Our results identify a class of anticancer agents that integrate ER stress response with an epigenetic mechanism to induce cell death...
  10. ncbi Human Asf1 regulates the flow of S phase histones during replicational stress
    Anja Groth
    Institute of Cancer Biology, The Danish Cancer Society, Strandboulevarden 49, DK 2100 Copenhagen, Denmark
    Mol Cell 17:301-11. 2005
    ....
  11. pmc Cdc7p-Dbf4p kinase binds to chromatin during S phase and is regulated by both the APC and the RAD53 checkpoint pathway
    M Weinreich
    Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
    EMBO J 18:5334-46. 1999
    ..Arresting cells with hydroxyurea (HU) or with mutations in genes encoding DNA replication proteins results in a more stable, hyper-..
  12. pmc Damage-induced phosphorylation of Sld3 is important to block late origin firing
    Jaime Lopez-Mosqueda
    Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94158 9001, USA
    Nature 467:479-83. 2010
    ..SLD3-m25 dbf4-m25 cells grow poorly in the presence of the replication inhibitor hydroxyurea and accumulate multiple Rad52 foci...
  13. ncbi Predicting clinical severity in sickle cell anaemia
    M H Steinberg
    Department of Medicine, Boston University School of Medicine and the Center of Excellence in Sickle Cell Disease, Boston Medical Center, 88 E Newton Street, Boston, MA 02118, USA
    Br J Haematol 129:465-81. 2005
    ....
  14. pmc Differential regulation of homologous recombination at DNA breaks and replication forks by the Mrc1 branch of the S-phase checkpoint
    Constance Alabert
    Department of Genome Dynamics, Institute of Human Genetics, CNRS UPR 1142, Montpellier, France
    EMBO J 28:1131-41. 2009
    ..Taken together, these data indicate that the DNA replication checkpoint suppresses genomic instability in S phase by blocking recombination at chromosome breaks and permitting helpful recombination at stalled forks...
  15. ncbi Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress
    I M Ward
    Division of Oncology Research, Mayo Clinic, Rochester, Minnesota 55905, USA
    J Biol Chem 276:47759-62. 2001
    ..Here we report that inhibition of DNA replication by hydroxyurea or ultraviolet irradiation also induces phosphorylation and foci formation of H2AX...
  16. pmc Stroke With Transfusions Changing to Hydroxyurea (SWiTCH)
    Russell E Ware
    Center for Global Health, Baylor College of Medicine and Texas Children s Hospital, 1102 Bates Street, Houston, TX 77030, USA
    Blood 119:3925-32. 2012
    ..Stroke With Transfusions Changing to Hydroxyurea (SWiTCH) was a multicenter phase 3 randomized trial comparing standard treatment (transfusions/chelation) to ..
  17. ncbi Sustained long-term hematologic efficacy of hydroxyurea at maximum tolerated dose in children with sickle cell disease
    Sherri A Zimmerman
    Duke Pediatric Sickle Cell Program and Division of Pediatric Hematology Oncology, Duke University Medical Center, PO Box 2916, Durham, NC 27710, USA
    Blood 103:2039-45. 2004
    b>Hydroxyurea improves hematologic parameters for children with sickle cell disease (SCD), but its long-term efficacy at maximum tolerated dose (MTD) has not been determined...
  18. pmc Hydroxyurea nitrosylates and activates soluble guanylyl cyclase in human erythroid cells
    Vladan P Cokic
    Laboratory of Experimental Hematology, Institute for Medical Research, Belgrade, Serbia
    Blood 111:1117-23. 2008
    b>Hydroxyurea, a drug widely used for treating myeloproliferative diseases, has also been approved for the treatment of sickle cell disease by raising fetal hemoglobin (HbF)...
  19. pmc Distinct functions of human RECQ helicases WRN and BLM in replication fork recovery and progression after hydroxyurea-induced stalling
    Julia M Sidorova
    Department of Pathology, University of Washington, Seattle, WA 98195 7705, United States
    DNA Repair (Amst) 12:128-39. 2013
    ..progression, and non-additively, in a RAD51-dependent pathway, to resumption of replication after arrest by hydroxyurea (HU), a replication-stalling drug. WRN but not BLM is required to support fork progression after HU...
  20. ncbi Predictors of fetal hemoglobin response in children with sickle cell anemia receiving hydroxyurea therapy
    Russell E Ware
    Duke University Medical Center, Durham, NC 27710, USA
    Blood 99:10-4. 2002
    In the phase I/II pediatric hydroxyurea safety trial (HUG-KIDS), school-aged children with sickle cell anemia receiving hydroxyurea at the maximally tolerated dose (MTD) had variable increases in the percentage of fetal hemoglobin (%HbF)...
  21. ncbi Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia
    Claire N Harrison
    Department of Haematology, University of Cambridge, and Addenbrooke s National Health Service Trust, Cambridge, United Kingdom
    N Engl J Med 353:33-45. 2005
    We conducted a randomized comparison of hydroxyurea with anagrelide in the treatment of essential thrombocythemia.
  22. pmc The ERAD inhibitor Eeyarestatin I is a bifunctional compound with a membrane-binding domain and a p97/VCP inhibitory group
    Qiuyan Wang
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
    PLoS ONE 5:e15479. 2010
    ..We recently reported that the ERAD inhibitor Eeyarestatin I (EerI) also disturbs ER homeostasis and has anti-cancer activities resembling that of Bortezomib...
  23. pmc Phosphorylation of the Bloom's syndrome helicase and its role in recovery from S-phase arrest
    Sally L Davies
    Cancer Research UK Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom
    Mol Cell Biol 24:1279-91. 2004
    ..fission yeasts, loss of RecQ helicase function confers sensitivity to inhibitors of DNA replication, such as hydroxyurea (HU), by failure to execute normal cell cycle progression following recovery from such an S-phase arrest...
  24. ncbi The DNA replication checkpoint response stabilizes stalled replication forks
    M Lopes
    Istituto F.I.R.C. di Oncologia Molecolare, Via Serio 21, 20141, Milano, Italy
    Nature 412:557-61. 2001
    ..We used the two-dimensional gel technique to examine replication intermediates in response to hydroxyurea-induced replication blocks...
  25. ncbi Phase I study of bevacizumab added to fluorouracil- and hydroxyurea-based concomitant chemoradiotherapy for poor-prognosis head and neck cancer
    Tanguy Y Seiwert
    Section of Hematology Oncology, Department of Medicine, University of Chicago, 5841 S Maryland Ave, MC2115, Chicago, IL 60637, USA
    J Clin Oncol 26:1732-41. 2008
    ..dose (MTD) and dose-limiting toxicity (DLT) of bevacizumab, when added to the standard FHX (fluorouracil [FU], hydroxyurea [HU], radiation) chemoradiotherapy platform in poor-prognosis head and neck cancer (HNC) patients.
  26. pmc Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint
    Q Liu
    Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030, USA
    Genes Dev 14:1448-59. 2000
    ..We show that in human cells, Chk1 is phosphorylated on serine 345 (S345) in response to UV, IR, and hydroxyurea (HU)...
  27. ncbi Mitotic checkpoint genes in budding yeast and the dependence of mitosis on DNA replication and repair
    T A Weinert
    Department of Molecular and Cellular Biology, University of Arizona, Tucson 85721
    Genes Dev 8:652-65. 1994
    ..at the restrictive temperature and by the response of rad and mec mutant alleles to DNA damaging agents and to hydroxyurea, a drug that inhibits DNA replication...
  28. ncbi Hydroxyurea arrests DNA replication by a mechanism that preserves basal dNTP pools
    Ahmet Koc
    Department of Biochemistry and Biophysics, Oregon State University, Corvallis 97331, USA
    J Biol Chem 279:223-30. 2004
    ..was investigated using alpha factor-synchronized yeast treated with the ribonucleotide reductase inhibitor hydroxyurea (HU)...
  29. ncbi Components and dynamics of DNA replication complexes in S. cerevisiae: redistribution of MCM proteins and Cdc45p during S phase
    O M Aparicio
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA
    Cell 91:59-69. 1997
    ..Our results identify protein components of the pre-RC and a novel replication complex appearing at the G1/S transition (the RC), and suggest that after initiation MCM proteins and Cdc45p move with eukaryotic replication forks...
  30. pmc Hydroxyurea induces hydroxyl radical-mediated cell death in Escherichia coli
    Bryan W Davies
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Mol Cell 36:845-60. 2009
    b>Hydroxyurea (HU) specifically inhibits class I ribonucleotide reductase (RNR), depleting dNTP pools and leading to replication fork arrest...
  31. pmc Stabilization of stalled DNA replication forks by the BRCA2 breast cancer susceptibility protein
    Mikhail Lomonosov
    University of Cambridge, CR UK Department of Oncology, Hutchison MRC Research Centre, Cambridge CB2 2XZ, UK
    Genes Dev 17:3017-22. 2003
    ....
  32. pmc Replication checkpoint kinase Cds1 regulates Mus81 to preserve genome integrity during replication stress
    Mihoko Kai
    Department of Pathology, Stanford University School of Medicine, Stanford, California 94305 5324, USA
    Genes Dev 19:919-32. 2005
    ..the deletion mutator phenotype of a replication mutant, and induces a hyper-recombination phenotype in hydroxyurea-treated cells. In unperturbed cells, Mus81 associates with chromatin throughout S phase...
  33. pmc Inhibition of p97-dependent protein degradation by Eeyarestatin I
    Qiuyan Wang
    Laboratory of Molecular Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 283:7445-54. 2008
    ..Interestingly, p97-associated deubiquitination is also involved in degradation of a soluble substrate. Our analyses establish a role for a novel deubiquitinating process in proteasome-dependent protein turnover...
  34. pmc Cleavage of stalled forks by fission yeast Mus81/Eme1 in absence of DNA replication checkpoint
    Benoît Froget
    Institut Curie Centre National de la Recherche Scientifique, Régulation de la réplication des eucaryotes, Universite Paris Sud XI, Bat 110, 91405 Orsay, France
    Mol Biol Cell 19:445-56. 2008
    ..Here, we report that, in response to hydroxyurea (HU) treatment, the replication checkpoint prevents S-phase-specific DNA breakage resulting from Mus81 nuclease ..
  35. ncbi Knock-down of human MutY homolog (hMYH) decreases phosphorylation of checkpoint kinase 1 (Chk1) induced by hydroxyurea and UV treatment
    Soo Hyun Hahm
    Department of Advanced Technology Fusion, Konkuk University, Seoul, Korea
    BMB Rep 44:352-7. 2011
    The effect of human MutY homolog (hMYH) on the activation of checkpoint proteins in response to hydroxyurea (HU) and ultraviolet (UV) treatment was investigated in hMYH-disrupted HEK293 cells...
  36. pmc BLM helicase-dependent transport of p53 to sites of stalled DNA replication forks modulates homologous recombination
    Sagar Sengupta
    Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    EMBO J 22:1210-22. 2003
    ..We show that p53 and BLM accumulated after hydroxyurea (HU) treatment, and physically associated and co-localized with each other and with RAD51 at sites of stalled ..
  37. ncbi Hydroxyurea in sickle cell disease--a study of clinico-pharmacological efficacy in the Indian haplotype
    Khushnooma Italia
    National Institute of Immunohaematology, KEM Hospital Campus, Parel, Mumbai, India
    Blood Cells Mol Dis 42:25-31. 2009
    ..Vaso-occlusive crisis is common among non-tribal patients. Hydroxyurea, induces fetal hemoglobin (HbF) synthesis and reduces the clinical severity of sickle cell disease but ..
  38. ncbi Hydroxyurea and arginine therapy: impact on nitric oxide production in sickle cell disease
    Claudia R Morris
    Department of Emergency Medicine, Children s Hospital and Research Center at Oakland, Oakland, California 94609, USA
    J Pediatr Hematol Oncol 25:629-34. 2003
    Recent data suggest that hydroxyurea (HU) increases the production of nitric oxide (NO), a potent vasodilator. NO is normally metabolized from l-Arginine (Arg)...
  39. ncbi Fission yeast chk1 protein kinase links the rad checkpoint pathway to cdc2
    N Walworth
    Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York 11724
    Nature 363:368-71. 1993
    ..for their sensitivity to DNA damage caused by radiation (rad mutants) or to the DNA synthesis inhibitor hydroxyurea (hus mutants) have been classified as checkpoint mutants because they fail to arrest the cell cycle in response ..
  40. pmc Epigenetic and molecular profiles of erythroid cells after hydroxyurea treatment in sickle cell anemia
    Aisha L Walker
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA
    Blood 118:5664-70. 2011
    b>Hydroxyurea has been shown to be efficacious for the treatment of sickle cell anemia (SCA), primarily through the induction of fetal hemoglobin (HbF)...
  41. pmc Werner's syndrome protein is required for correct recovery after replication arrest and DNA damage induced in S-phase of cell cycle
    P Pichierri
    Laboratorio di Citogenetica Molecolare e Mutagenesi, DABAC, , 01100 Viterbo, Italy
    Mol Biol Cell 12:2412-21. 2001
    ..With the use of two drugs, camptothecin and hydroxyurea, which produce replication-associated DNA damage and/or inhibit replication fork progression, we find that WS ..
  42. ncbi Concordant fetal hemoglobin response to hydroxyurea in siblings with sickle cell disease
    Martin H Steinberg
    Boston University School of Medicine, Room 211, 88 E Newton Street, Boston, MA 02118, USA
    Am J Hematol 72:121-6. 2003
    Fetal hemoglobin (HbF) level and the HbF responses to hydroxyurea (HU) vary among patients with sickle cell disease and are, at least in part, genetically regulated...
  43. ncbi Genotoxic stress leads to centrosome amplification in breast cancer cell lines that have an inactive G1/S cell cycle checkpoint
    Antonino B D'Assoro
    Tumor Biology Program, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA
    Oncogene 23:4068-75. 2004
    ..Introduction of DNA damage in the MCF-7 cell line by treatment with hydroxyurea (HU) or daunorubicin (DR) resulted in the arrest of both G(1)/S cell cycle progression and centriole ..
  44. pmc Hyperactivation of the yeast DNA damage checkpoint by TEL1 and DDC2 overexpression
    M Clerici
    Dipartimento di Biotecnologie e Bioscienze, Universita degli Studi di Milano Bicocca, 20126 Milan, Italy
    EMBO J 20:6485-98. 2001
    ..In addition, Tel1 overproduction results in transient nuclear division arrest and concomitant Rad53 phosphorylation in the absence of exogenous DNA damage independently of Mec1 and Ddc1...
  45. ncbi National Institutes of Health Consensus Development Conference statement: hydroxyurea treatment for sickle cell disease
    Otis W Brawley
    American Cancer Society, 250 Williams Street, Atlanta, GA 30303, USA
    Ann Intern Med 148:932-8. 2008
  46. pmc Pharmacokinetics, pharmacodynamics, and pharmacogenetics of hydroxyurea treatment for children with sickle cell anemia
    Russell E Ware
    International Hematology Center of Excellence, Department of Pediatrics, Baylor College of Medicine, Houston TX, USA
    Blood 118:4985-91. 2011
    b>Hydroxyurea therapy has proven laboratory and clinical efficacies for children with sickle cell anemia (SCA)...
  47. pmc The MRX complex stabilizes the replisome independently of the S phase checkpoint during replication stress
    Mireille Tittel-Elmer
    Department of Biochemistry and Molecular Biology, Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada
    EMBO J 28:1142-56. 2009
    ....
  48. ncbi Mrc1 and Tof1 promote replication fork progression and recovery independently of Rad53
    Hélène Tourrière
    Institute of Human Genetics, Centre National de la Recherche Scientifique, UPR 1142, 34396 Montpellier Cedex 5, France
    Mol Cell 19:699-706. 2005
    ..Interestingly, stalled forks did not collapse in mrc1Delta cells exposed to hydroxyurea (HU) as they do in rad53 mutants...
  49. pmc Hydroxyurea induces de novo copy number variants in human cells
    Martin F Arlt
    Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA
    Proc Natl Acad Sci U S A 108:17360-5. 2011
    ..Here we report that low doses of hydroxyurea, an inhibitor of ribonucleotide reductase and an important drug in the treatment of sickle cell disease and ..
  50. pmc Eeyarestatin 1 interferes with both retrograde and anterograde intracellular trafficking pathways
    Mina Olga Aletrari
    School of Life Sciences, University of Warwick, Coventry, United Kingdom
    PLoS ONE 6:e22713. 2011
    ..We therefore investigated ESI as a potential inhibitor of toxin dislocation...
  51. ncbi Pulmonary hypertension as a risk factor for death in patients with sickle cell disease
    Mark T Gladwin
    Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892 1662, USA
    N Engl J Med 350:886-95. 2004
    ..The prevalence of pulmonary hypertension in adults with sickle cell disease, the mechanism of its development, and its prospective prognostic significance are unknown...
  52. pmc Protein phosphatase 2A-dependent dephosphorylation of replication protein A is required for the repair of DNA breaks induced by replication stress
    Junjie Feng
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, La Salle Street Extension, Durham, NC 27710, USA
    Mol Cell Biol 29:5696-709. 2009
    ..We report here that in cells recovering from hydroxyurea (HU)-induced genotoxic stress, RPA32 is dephosphorylated by the serine/threonine protein phosphatase 2A (PP2A)...
  53. ncbi Phase 2 trial of concurrent 5-fluorouracil, hydroxyurea, cetuximab, and hyperfractionated intensity-modulated radiation therapy for locally advanced head and neck cancer
    Johnny Kao
    Department of Radiation Oncology, Mount Sinai School of Medicine, New York, New York, USA
    Cancer 117:318-26. 2011
    ..the tolerability and efficacy of incorporating cetuximab and simultaneous integrated-boost (SIB), intensity-modulated radiation therapy (IMRT) into a well described 5-fluorouracil (5-FU) and hydroxyurea (HU)-based chemoradiation regimen.
  54. ncbi Combination of the histone deacetylase inhibitor valproic acid with oral hydroxyurea or 6-mercaptopurin can be safe and effective in patients with advanced acute myeloid leukaemia--a report of five cases
    Hanne Fredly
    Section for Hematology, Institute of Medicine and Dentistry, University of Bergen, Bergen, Norway
    Hematology 15:338-43. 2010
    ..We describe five patients receiving oral treatment with low-dose oral 6-mercaptopurin and/or hydroxyurea together with ATRA+valproric acid+theophylline...
  55. ncbi Hydroxyurea (therapeutics and mechanism): metabolism, carbamoyl nitroso, nitroxyl, radicals, cell signaling and clinical applications
    Peter Kovacic
    Department of Chemistry and Biochemistry, San Diego State University, San Diego, CA 92182, USA
    Med Hypotheses 76:24-31. 2011
    During a century, hydroxyurea has received much attention in relation to its physiological properties. This review mainly deals with the metabolism, mechanism, cell signaling, therapeutic properties, bioactivity, receptors, and toxicity...
  56. pmc Endogenous DNA replication stress results in expansion of dNTP pools and a mutator phenotype
    Marta B Davidson
    Department of Biochemistry and Donnelly Centre, University of Toronto, Toronto, Ontario, Canada
    EMBO J 31:895-907. 2012
    ..dNTP) pools in G1 that allows cells to synthesize significant fractions of the genome in the presence of hydroxyurea in the subsequent S phase...
  57. pmc Inhibition of protein translocation at the endoplasmic reticulum promotes activation of the unfolded protein response
    Craig McKibbin
    Faculty of Life Sciences, University of Manchester, UK
    Biochem J 442:639-48. 2012
    ..These results suggest that the accumulation of non-translocated proteins in the cytosol may represent a novel mechanism that contributes to UPR activation...
  58. ncbi Intensive concurrent chemoradiotherapy for head and neck cancer with 5-Fluorouracil- and hydroxyurea-based regimens: reversing a pattern of failure
    Athanassios Argiris
    Division of Hematology Oncology, Northwestern University, The Feinberg School of Medicine and the Robert H Lurie Comprehensive Cancer Center, Chicago, Illinois 60611, USA
    Oncologist 8:350-60. 2003
    ..developed multiagent chemoradiotherapy regimens based on initial observations with the 5-fluorouracil (5-FU), hydroxyurea, and concomitant radiotherapy combination...
  59. pmc Nse2, a component of the Smc5-6 complex, is a SUMO ligase required for the response to DNA damage
    Emily A Andrews
    Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9RQ, United Kingdom
    Mol Cell Biol 25:185-96. 2005
    ..SA strain. Since nse2.SA cells are sensitive to DNA-damaging agents and to exposure to hydroxyurea, this implicates the Nse2-dependent sumoylation activity in DNA damage responses but not in the essential ..
  60. doi Hydroxyurea for the treatment of sickle cell anemia
    Orah S Platt
    Department of Laboratory Medicine, Children s Hospital Boston, MA 02115, USA
    N Engl J Med 358:1362-9. 2008
  61. ncbi A comparison of low-dose cytarabine and hydroxyurea with or without all-trans retinoic acid for acute myeloid leukemia and high-risk myelodysplastic syndrome in patients not considered fit for intensive treatment
    Alan K Burnett
    Department of Haematology, Wales School of Medicine, Cardiff University, Cardiff, United Kingdom
    Cancer 109:1114-24. 2007
    ..The survival of older patients with acute myeloid leukemia has not improved. Few clinical trials have been available for older patients who are not considered fit for an intensive chemotherapy approach...
  62. ncbi Thrombocytosis
    Andrew I Schafer
    Department of Medicine, University of Pennsylvania School of Medicine and University of Pennsylvania Health System, Philadelphia 19104, USA
    N Engl J Med 350:1211-9. 2004
  63. pmc Involvement of a chromatin remodeling complex in damage tolerance during DNA replication
    Karina B Falbo
    Department of Carcinogenesis, Science Park Research Division, MD Anderson Cancer Center, Smithville, Texas, USA
    Nat Struct Mol Biol 16:1167-72. 2009
    ..by methyl methane sulfonate (MMS), it is not required for replication fork collapse after treatment with hydroxyurea (HU)...
  64. ncbi The cell-cycle checkpoint kinase Chk1 is required for mammalian homologous recombination repair
    Claus Storgaard Sørensen
    Danish Cancer Society, Institute of Cancer Biology, DK 2100 Copenhagen, Denmark
    Nat Cell Biol 7:195-201. 2005
    ..to persistent unrepaired DNA double-strand breaks (DSBs) and cell death after replication inhibition with hydroxyurea or DNA-damage caused by camptothecin...
  65. pmc Critical role of DNA checkpoints in mediating genotoxic-stress-induced filamentous growth in Candida albicans
    Qing Mei Shi
    Institute of Molecular and Cell Biology, Agency for Science, Technology and Research Biological Sciences Institutes, Singapore 138673
    Mol Biol Cell 18:815-26. 2007
    ..to filamentous growth in response to a range of genotoxic insults, including inhibition of DNA synthesis by hydroxyurea (HU) or aphidicolin (AC), depletion of the ribonucleotide-reductase subunit Rnr2p, and DNA damage induced by ..
  66. ncbi Efficacy and tolerability of hydroxyurea in the treatment of the hyperproliferative manifestations of myelofibrosis: results in 40 patients
    Alejandra Martínez-Trillos
    Hematology Department, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain
    Ann Hematol 89:1233-7. 2010
    b>Hydroxyurea (HU) is frequently given as treatment for myelofibrosis (MF), but data on its efficacy and tolerability are scarce...
  67. pmc Yeast ASF1 protein is required for cell cycle regulation of histone gene transcription
    A Sutton
    Department of Biochemistry and Cell Biology, State University of New York, Stony Brook, NY 11794, USA
    Genetics 158:587-96. 2001
    ..of histone gene transcription during the cell cycle and in cells arrested in early S phase in response to hydroxyurea. asf1 and hir1 mutations also show very similar synergistic interactions with mutations in cac2, a subunit of ..
  68. pmc Human Timeless and Tipin stabilize replication forks and facilitate sister-chromatid cohesion
    Adam R Leman
    Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19102, USA
    J Cell Sci 123:660-70. 2010
    ..These results suggest that Timeless-Tipin functions as a replication fork stabilizer that couples DNA replication with sister chromatid cohesion established at replication forks...
  69. pmc Dormant origins licensed by excess Mcm2-7 are required for human cells to survive replicative stress
    Xin Quan Ge
    Wellcome Trust Biocentre, University of Dundee, Dundee DD1 5EH, United Kingdom
    Genes Dev 21:3331-41. 2007
    ..We propose that checkpoint kinase activity can preferentially suppress initiation within inactive replicon clusters, thereby directing new initiation events toward active clusters that are experiencing replication problems...
  70. pmc Rad52 recruitment is DNA replication independent and regulated by Cdc28 and the Mec1 kinase
    Jacqueline H Barlow
    Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032 2704, USA
    EMBO J 28:1121-30. 2009
    ..Induction of the intra-S-phase checkpoint by hydroxyurea (HU) inhibits Rad52 focus formation in response to ionizing radiation...
  71. pmc The risks and benefits of long-term use of hydroxyurea in sickle cell anemia: A 17.5 year follow-up
    Martin H Steinberg
    Department of Medicine, Boston University School of Medicine, Boston Medical Center, Massachusetts, USA
    Am J Hematol 85:403-8. 2010
    A randomized, controlled clinical trial established the efficacy and safety of short-term use of hydroxyurea in adult sickle cell anemia...
  72. ncbi S-phase checkpoint proteins Tof1 and Mrc1 form a stable replication-pausing complex
    Yuki Katou
    Genome Structure and Function Team, Human Genome Research Group, RIKEN Genomic Science Center, 1 7 22 Suehiro cho, Japan
    Nature 424:1078-83. 2003
    ..When hydroxyurea blocks chromosomal replication, this assembly forms a stable pausing structure that serves to anchor subsequent ..
  73. ncbi Histone deacetylase inhibitors and hydroxyurea modulate the cell cycle and cooperatively induce apoptosis
    O H Krämer
    Institute of Biochemistry and Biophysics, Friedrich Schiller University Jena, Jena, Germany
    Oncogene 27:732-40. 2008
    ..Our study shows that the HDACi valproic acid (VPA) and the ribonucleotide reductase inhibitor hydroxyurea (HU) potentiate the pro-apoptotic effects of each other towards several cancer cell lines...
  74. pmc Fetal haemoglobin response to hydroxycarbamide treatment and sar1a promoter polymorphisms in sickle cell anaemia
    Chutima Kumkhaek
    Molecular and Clinical Hematology Branch, NIDDK, NIH, Bethesda, MD, USA
    Br J Haematol 141:254-9. 2008
    ..These data suggest that variation within SAR1A regulatory elements might contribute to inter-individual differences in regulation of HbF expression and patient responses to HC in SCD...
  75. ncbi Degradation of human exonuclease 1b upon DNA synthesis inhibition
    Mahmoud El-Shemerly
    Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland
    Cancer Res 65:3604-9. 2005
    ..Our data support the evidence that control of exonuclease 1 activity may be critical for the maintenance of stalled replication forks...
  76. pmc S-phase-specific activation of Cds1 kinase defines a subpathway of the checkpoint response in Schizosaccharomyces pombe
    H D Lindsay
    Medical Research Council MRC Cell Mutation Unit, Sussex University, Falmer, Sussex BN1 9RR, UK
    Genes Dev 12:382-95. 1998
    ..This model suggests that an intrinsic mechanism linking S phase and mitosis may function independently of the known checkpoint proteins...
  77. pmc Replication stress induces micronuclei comprising of aggregated DNA double-strand breaks
    Bing Xu
    Key Laboratory of Experimental Teratology, Ministry of Education, and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong, China
    PLoS ONE 6:e18618. 2011
    ..DNA double-strand breaks are marked by phosphorylation of H2AX at serine 139 (γ-H2AX). One subclass of MN contains massive and uniform γ-H2AX signals. This study tested whether this subclass of MN can be induced by replication stress...
  78. ncbi Hydroxyurea adherence and associated outcomes among Medicaid enrollees with sickle cell disease
    Sean D Candrilli
    RTI Health Solutions, Research Triangle Park, North Carolina, USA
    Am J Hematol 86:273-7. 2011
    While laboratory and clinical benefits of hydroxyurea for patients with sickle cell disease (SCD) are well-established, few data describe the extent and implications of non-adherence...
  79. ncbi Replication checkpoint enforced by kinases Cds1 and Chk1
    M N Boddy
    Departments of Molecular Biology and Cell Biology, Scripps Research Institute, La Jolla, CA 92037, USA
    Science 280:909-12. 1998
    ..Effectors of the replication checkpoint evoked by hydroxyurea (HU) are unknown...
  80. ncbi Identification of fetal hemoglobin-inducing agents using the human leukemia KU812 cell line
    Sima Zein
    Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Exp Biol Med (Maywood) 235:1385-94. 2010
    ..We also tested several drugs including butyrate, trichostatin A, scriptaid, suberoylanilide hydroxamic acid and hydroxyurea, which induced γ-globin in KU812 cells; however, some agents also induced β-globin...
  81. pmc Genome-wide screening with hydroxyurea reveals a link between nonessential ribosomal proteins and reactive oxygen species production
    Toru Nakayashiki
    Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara, Japan
    J Bacteriol 195:1226-35. 2013
    We performed a screening of hydroxyurea (HU)-sensitive mutants using a single-gene-deletion mutant collection in Escherichia coli. HU inhibits ribonucleotide reductase (RNR), which leads to arrest of the replication fork...
  82. ncbi Caffeine can override the S-M checkpoint in fission yeast
    S W Wang
    Imperial Cancer Research Fund, Cell Regulation Laboratory, PO Box 123, Lincoln s Inn Fields, London WC2 A3P, UK
    J Cell Sci 112:927-37. 1999
    ..The lethality of a combination of caffeine with the DNA replication inhibitor hydroxyurea was suppressed by overexpression of Cds1 or Chk1, protein kinases previously implicated in S-M checkpoint ..
  83. pmc Hydroxyurea therapy of a murine model of sickle cell anemia inhibits the progression of pneumococcal disease by down-modulating E-selectin
    Jeffrey D Lebensburger
    Department of Hematology, St Jude Children s Research Hospital, Memphis, TN, USA
    Blood 119:1915-21. 2012
    ..Current treatments to reduce vaso-occlusive complications include chronic hydroxyurea therapy to induce fetal hemoglobin...
  84. pmc Plasma thrombospondin-1 is increased during acute sickle cell vaso-occlusive events and associated with acute chest syndrome, hydroxyurea therapy, and lower hemolytic rates
    Enrico M Novelli
    Division of Hematology Oncology, University of Pittsburgh Medical Center UPMC, Vascular Medicine Institute VMI, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
    Am J Hematol 87:326-30. 2012
    ..50, P = 0.009). Analysis of the walk-PHaSST cohort also showed a positive association between TSP1 levels and hydroxyurea use (r = 0.14, P = 0.003), and confirmed the negative associations with the severity of hemolysis...
  85. pmc Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma
    D A Reardon
    The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Box 3624, Durham, NC 27710, USA
    Br J Cancer 101:1995-2004. 2009
    We evaluated the efficacy of imatinib mesylate in addition to hydroxyurea in patients with recurrent glioblastoma (GBM) who were either on or not on enzyme-inducing anti-epileptic drugs (EIAEDs).
  86. ncbi Hydroxyurea for sickle cell disease: a systematic review for efficacy and toxicity in children
    John J Strouse
    Department of Pediatrics, Johns Hopkins University School of Medicine, Division of Pediatric Hematology, 720 Rutland Ave, Ross 1125, Baltimore, MD 21205, USA
    Pediatrics 122:1332-42. 2008
    b>Hydroxyurea is the only approved medication for the treatment of sickle cell disease in adults; there are no approved drugs for children.
  87. ncbi Nonselective DNA damage induced by a replication inhibitor results in the selective elimination of extrachromosomal double minutes from human cancer cells
    Noriaki Shimizu
    Graduate School of Biosphere Science, Hiroshima University, 1 7 1 Kagamiyama, Higashi Hiroshima, Japan
    Genes Chromosomes Cancer 46:865-74. 2007
    ..We and others had shown that treatment with low-dose hydroxyurea (HU) results in the elimination of dmin and reversion of the cancer cell phenotype...
  88. pmc Depletion of a polo-like kinase in Candida albicans activates cyclase-dependent hyphal-like growth
    Catherine Bachewich
    Health Sector, Biotechnology Research Institute, National Research Council of Canada, Montreal, Quebec, H4P 2R2, Canada
    Mol Biol Cell 14:2163-80. 2003
    ..in spindle elongation and a corresponding induction of filaments occurred when yeast cells were exposed to hydroxyurea. Because CaCdc5p does not appear to act as a direct repressor of hyphal growth, the data suggest that a target ..
  89. ncbi A randomized phase II study of 5-fluorouracil, hydroxyurea, and twice-daily radiotherapy compared with bevacizumab plus 5-fluorouracil, hydroxyurea, and twice-daily radiotherapy for intermediate-stage and T4N0-1 head and neck cancers
    J K Salama
    Department of Radiation Oncology, Duke University, Durham 27710, USA
    Ann Oncol 22:2304-9. 2011
    We conducted a randomized phase II study to evaluate the impact of adding bevacizumab (B) to 5-fluorouracil (5-FU), hydroxyurea (HU), and radiotherapy (FHX) for intermediate-stage and select T4 head and neck squamous cell cancers (HNSCC).
  90. pmc Regulation of fragile sites expression in budding yeast by MEC1, RRM3 and hydroxyurea
    Nadia Hashash
    Stem Cell Biology and Developmental Genetics, National Institute for Medical Research, MRC, The Ridgeway, London NW7 1AA, UK
    J Cell Sci 124:181-5. 2011
    ..Here, we investigated this by examining the combined effects of rrm3Δ, mec1 and hydroxyurea (HU), three conditions that induce fragile sites, on expression of the replication slow zone (RSZ), a type of ..
  91. pmc Expression patterns of fetal hemoglobin in sickle cell erythrocytes are both patient- and treatment-specific during childhood
    Emily Riehm Meier
    Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
    Pediatr Blood Cancer 56:103-9. 2011
    ..The objective of this study was to compare HbF expression profiles (HbF and F-cells) in the peripheral blood of pediatric SCD patients receiving hydroxyurea (HU), chronic transfusions (Tx) or no chronic therapy (Ctrl).
  92. ncbi Stabilization of disease progression by hydroxyurea in patients with recurrent or unresectable meningioma
    Warren P Mason
    Department of Medicine, Princess Margaret Hospital, and University of Toronto, Ontario, Canada
    J Neurosurg 97:341-6. 2002
    ..In recent reports it has been suggested that hydroxyurea chemotherapy can cause regression of unresectable and recurrent meningiomas...
  93. pmc Hydroxyurea for sickle cell anemia: what have we learned and what questions still remain?
    Patrick T McGann
    Department of Hematology, St Jude Children s Research Hospital, Memphis, Tennessee, USA
    Curr Opin Hematol 18:158-65. 2011
    ..b>Hydroxyurea is a potent inducer of fetal hemoglobin, and evidence over the past 25 years has documented its laboratory and ..
  94. ncbi Hydroxyurea chemotherapy in the treatment of meningiomas
    Herbert B Newton
    Dardinger Neuro Oncology Center and Division of Neuro Oncology, Department of Neurology, The Ohio State University Medical Center, Columbus, Ohio 43210, USA
    Neurosurg Focus 23:E11. 2007
    ..b>Hydroxyurea, an inhibitor of ribonucleotide reductase, is one of the most active agents and is known to induce apoptosis in ..
  95. ncbi Hydroxyurea-induced global transcriptional suppression in mouse ES cells
    Peng Cui
    CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, No 7 Beitucheng West Road, Chaoyang, 100029 Beijing, China
    Carcinogenesis 31:1661-8. 2010
    b>Hydroxyurea (HU), as a therapeutic medicine, has been extensively used clinically...
  96. ncbi Gastrointestinal and hepatic complications of sickle cell disease
    Ellen C Ebert
    Department of Medicine, UMDNJ Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901, USA
    Clin Gastroenterol Hepatol 8:483-9; quiz e70. 2010
    ..The safety of liver biopsies has been questioned, particularly during acute sickling crisis. Treatments include blood transfusions, exchange transfusions, iron-chelating agents, hydroxyurea, and allogeneic stem-cell transplantation.
  97. pmc Hydroxyurea sensitivity reveals a role for ISC1 in the regulation of G2/M
    Nabil Matmati
    Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29403, USA
    J Biol Chem 284:8241-6. 2009
    ..inositol phosphosphingolipase C) exhibit sensitivity to genotoxic agents such as methyl methanesulfonate and hydroxyurea (HU)...
  98. ncbi Study of correlation of nitrite levels with malonaldehyde and the prognosis of patients with sickle cell disease on hydroxyurea, Ceará-Brazil
    Romélia Pinheiro Gonçalves
    Department of Clinical Analysis and Toxicology, Pharmacy Program, Universidade Federal do Ceara, Ceara, Brazil
    J Clin Lab Anal 25:369-73. 2011
    b>Hydroxyurea (HU) is the only drug approved for the induction of fetal hemoglobin. Besides this benefit, there are others such as the reduction of leukocyte and generation of nitric oxide (NO)...
  99. pmc Arabidopsis T-DNA insertional lines for CDC25 are hypersensitive to hydroxyurea but not to zeocin or salt stress
    Natasha D Spadafora
    School of Biosciences, Cardiff University, Main College, Cardiff, UK
    Ann Bot 107:1183-92. 2011
    ..Methods arath;cdc25 T-DNA insertion lines, Arath;CDC25 over-expressing lines and wild type were challenged with hydroxyurea (HU) and zeocin, substances that stall DNA replication and damage DNA, respectively, together with an abiotic ..
  100. pmc Genetic modifiers of HbF and response to hydroxyurea in sickle cell disease
    Nancy S Green
    Department of Pediatrics, Columbia University Medical Center, New York, New York 10032, USA
    Pediatr Blood Cancer 56:177-81. 2011
    ..We review these methods and findings, and speculate on applying pharmaco-genetics to optimize hydroxyurea therapy aimed at increasing HbF.
  101. ncbi Non-resectable slow-growing meningiomas treated by hydroxyurea
    David Loven
    Institute of Oncology, Ha Emek Medical Center, Afula, Israel
    J Neurooncol 67:221-6. 2004
    To test the benefit of hydroxyurea in the treatment of recurrent and non-resectable slow-growing meningiomas.

Research Grants73

  1. Prevention of Complications in Thalassemia
    Elliott P Vichinsky; Fiscal Year: 2011
    ..New therapy Our approach to therapy has focused on fetal hemoglobin F modulator trials, including hydroxyurea, darbepoietin, and recently Decitabine25, 26, 59-63...
  2. Mechanisms of Endothelin 1-Induced Sickle Cell Pathology
    Alicia Rivera; Fiscal Year: 2011
    ..Thus far, hydroxyurea has been the only drug approved for SCD therapy;it induces the production of fetal hemoglobin, which inhibits ..
  3. Environmental Risk Factors for Copy Number Variation in Human Chromosomes
    THOMAS EDWARD WILSON; Fiscal Year: 2010
    ..Specifically, we will examine hydroxyurea and folate stress, which inhibit replication through different mechanisms than aphidicolin, and on ionizing ..
  4. Non-viral gene therapy for sickle cell anemia
    CLIFFORD JOHN STEER; Fiscal Year: 2012
    ..Therapies including hydroxyurea, exchange transfusion, prophylactic antibiotics, and stem cell transplants have improved the outlook for these ..
  5. Reactivation of Fetal Gamma-globin Genes for the Treatment of Beta-globin Disorde
    Osamu Tanabe; Fiscal Year: 2010
    ..Because the effects of gamma-globin inducers such as hydroxyurea, 5- azacytidine, and butyrates are mediated either through non-specific cytotoxicity or global changes in ..
  6. Beta-Globin Gene Correction Using Peptide Nucleic Acids for the Treatment of Sick
    GERALD FRANCIS VOVIS; Fiscal Year: 2010
    ..b>Hydroxyurea is currently the only FDA-approved treatment for SCD...
  7. Enhancing Suicide Gene Therapy Through Mechanism-Based Approaches
    Donna S Shewach; Fiscal Year: 2012
    ..The results demonstrated that pharmacologic modulation (with ribonucleotide reductase inhibitors dFdCyd or hydroxyurea) was more efficacious than enhancing GJIC...
  8. Transactivation of Fetal Hemoglobin
    Kenneth R Peterson; Fiscal Year: 2011
    ..Treatments, such as hydroxyurea (HU), that induce fetal hemoglobin (HbF), have enormous benefit to patients suffering from this ..
  9. The MRAD9 Radioresistance Gene
    Howard B Lieberman; Fiscal Year: 2013
    ..rad9, a gene that promotes gamma-ray resistance, UV-resistance, resistance to the DNA replication inhibitor hydroxyurea, and regulates the associated cell cycle checkpoints...
  10. Ribonucleotide Reductase: Structure and Function
    JoAnne Stubbe; Fiscal Year: 2013
    ..has made them the successful target of at least three drugs used clinically in the treatment of cancers, hydroxyurea, gemcitabine, and clofarabine, as well as the clinical drug candidate, triapine...
  11. Effect of anti-S phase agents on human chromosomes
    Anindya Dutta; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Anti-S phase agents like doxorubicin, gemcitabine, cytarabine and hydroxyurea are in extensive use for the treatment of cancers and of hematological diseases such as essential thrombocytopenia, ..
  12. De novo CNV formation in vivo with sickle cell anemia therapy
    Thomas W Glover; Fiscal Year: 2013
    ..b>Hydroxyurea (HU) is currently the only approved disease- modifying therapy for adult SCD and is in late-stage clinical ..
  13. Elucidation of Antisickling Molecules in a Botanical with Antisickling Activity
    Robert Swift; Fiscal Year: 2013
    ..The only FDA approved disease-modifying drug for use in SCD is the anti-cancer drug hydroxyurea, which has serious side effects and is only approved for use in adults...
  14. First Clinical Trial of an Anti-Sickling Botanical Drug for Sickle Cell Dise
    Robert Swift; Fiscal Year: 2013
    ..The only FDA approved disease-modifying drug for use in SCD is the anti-cancer drug hydroxyurea, which has serious side effects and is only approved for use in adults...
  15. Formulation and Standardization of a Sickle Cell Disease Drug for Clinical Trial
    Robert Swift; Fiscal Year: 2010
    ..decades, there has been little progress in the development of additional disease modifying agents beyond hydroxyurea. Therefore, new safer and more effective therapeutic antisickling agents are needed to treat patients with SCD, ..
  16. Stroke with Transfusions Changing to Hydroxyurea
    Russell E Ware; Fiscal Year: 2010
    ..b>Hydroxyurea can prevent acute vaso-occlusive events in SCA, but its utility for cerebrovascular disease and specifically ..
  17. Genetic Modifiers of Beta-like Globin Gene Switching
    Luanne L Peters; Fiscal Year: 2013
    ..in SCD and [unreadable]-thalassemia via co-inheritance of positive genetic modifiers of HbF production or hydroxyurea (HU) treatment can significantly alleviate disease severity...
  18. Globin Gene Expression in Sickle Cell Genotype-Specific iPS cells
    Martin H Steinberg; Fiscal Year: 2013
    ..Only one FDA approved drug is available for its pathophysiologically-based treatment. This agent, hydroxyurea, works through its ability to induce fetal hemoglobin (HbF) expression, which thwarts sickle hemoglobin ..
  19. Sparing Conversion to Abnormal TCD Elevation
    Russell E Ware; Fiscal Year: 2012
    ..Our preliminary data suggest that hydroxyurea can reduce TCD velocities in children with sickle cell anemia, but further investigation is necessary to define ..
  20. TUT ase mediated degradation of histone mRNA
    MICHAEL KEITH SLEVIN; Fiscal Year: 2010
    ..Inhibition of DNA replication by hydroxyurea or UV induced checkpoint pathways result in a reduction in histone transcription and rapid degradation of ..
  21. Enhancing Use of Hydroxyurea In Sickle Cell Disease Using Patient Navigators
    Wally R Smith; Fiscal Year: 2013
    ..For adults, not having specialty care may be fatal, because specialists may prescribe Hydroxyurea (HU), the first and only FDA approved remittive drug for SCD...
  22. in vivo Studies of Clinical Stage Globin Modulators
    SUSAN PARK PERRINE; Fiscal Year: 2011
    ..to induce HbF in sickle cell disease and beta-thalassemia include: cytotoxic chemotherapeutic agents (such as hydroxyurea (HU), 5-azacytidine, and decitabine), short chain fatty acids (SCFAs) and derivatives (SCFADs), and some HDAC ..
  23. MElll2_Y_Me_Fe_Mn_Cluster Assembly and Maintenance in Ribonucleotide Reductase
    JoAnne Stubbe; Fiscal Year: 2013
    ..e., if the Y[unreadable]is reduced inside the cell by endogenous reductants or the chemotherapeutic hydroxyurea, how the MeIII2-cluster is re-converted to active cofactor...
  24. TCD With Transfusions Changing to Hydroxyurea
    Russell E Ware; Fiscal Year: 2013
    ..anemia (SCA) and abnormal Transcranial Doppler (TCD) velocities, termed the "TCD With Transfusions Changing to Hydroxyurea" (TWiTCH) trial...
  25. TCD with Transfusions Changing to Hydroxyurea - SDMC
    Barry R Davis; Fiscal Year: 2013
    ..anemia (SCA) and abnormal Transcranial Doppler (TCD) velocities, termed the "TCD With Transfusions Changing to Hydroxyurea" (TWiTCH) trial...
  26. Identification and Characterization of Novel Replication Stress Response Proteins
    Gina M Kavanaugh; Fiscal Year: 2013
    ..An immunofluorescence assay utilizing thymidine analog incorporation and the replication stress inducer hydroxyurea has been designed to uncover proteins that are necessary for replication stress repair and replication restart...
  27. Inactivation of LSD1 as a possible treatment for sickle cell disease
    James Douglas Engel; Fiscal Year: 2013
    ..The only current therapy for SCD is treatment with hydroxyurea (HU)...
  28. Checkpoint Regulation of Stalled and Collapsed Replication Forks
    FRANK BENJAMIN COUCH; Fiscal Year: 2013
    ..This proposal will use hydroxyurea (HU), which effects rapid replication fork stalling, to study th function of ATR using newly developed ..
  29. Sickle Cell Disease: First steps toward understanding barriers to care for adults
    SOPHIE M LANZKRON; Fiscal Year: 2012
    ..This research will examine Hydroxyurea (HU) utilization in adults with sickle cell disease (SCD)as well as try to identify some of the barriers to the ..
  30. Understanding the Mechanistic Roles of Mec1-dependent Phosphorylation in Replicat
    Patrice Y Ohouo; Fiscal Year: 2012
    ..how cells can survive in the presence of fork damaging agents such as camptothecin analogues, cisplatin and hydroxyurea, which are commonly used in cancer treatment...
  31. Multiscale Modeling of Sickle Cell Anemia: Methods and Validation
    Peter G Vekilov; Fiscal Year: 2013
    ..therapeutic interventions for SCD, including simple transfusion, fetal hemoglobin (HbF) induction by hydroxyurea, and RBC hydration...
  32. Stroke with Transfusions Changing to Hydroxyurea (SWITCH) Trial Data Coordinating
    Ronald W Helms; Fiscal Year: 2010
    ..Deferoxamine chelation therapy is difficult to tolerate. Our pilot data indicate that hydroxyurea (HU) is an effective alternative to transfusions for secondary stroke prevention that also addresses the issue ..
  33. Drug Development of Ribonucleotide Reductase Inhibitor
    Yun Yen; Fiscal Year: 2012
    ..that are more effective than any of the existing small molecule therapies, and can overcome resistance to Hydroxyurea (HU), the only FDA approved drug for targeting RR- based cancers...
  34. Next Generation Therapeutics for Hemoglobinopathies
    SUSAN PARK PERRINE; Fiscal Year: 2012
    ..b>Hydroxyurea (HU) is the sole FDA-approved drug for treatment of sickle cell disease, its beneficial effects are due ..
  35. CTRIP: Treatment of Sickle Cell Crisis with inhibitors of NKT cell activation
    DAVID G contact NATHAN; Fiscal Year: 2010
    ..These include the Co-PI, David Nathan, M.D., a thought leader in SCD treatment who originated hydroxyurea therapy;and four other clinician scientists who direct adult and juvenile SCD clinics that will provide ..
  36. Mechanisms of Cytotoxicity and Radiosensitization for Antimetabolites
    Donna S Shewach; Fiscal Year: 2013
    ..antimetabolites that produce alterations in deoxynucleotide pools and function as radiosensitizers, such as hydroxyurea (ribonucleotide reductase inhibitor), and fluorodeoxyuridine, methotrexate and pemetrexed (thymidylate synthase ..
  37. Long-range function of the ERV-9 LTR in regulating globin gene switching
    DOROTHY Y TUAN; Fiscal Year: 2012
    ..Such [unreadable]-globin gene-specific drugs may avoid producing the undesirable side effects of currently prescribed cytotoxic drugs such as hydroxyurea.
  38. Hydroxyurea Pharmacokinetics and Pharmacogenomics
    Russell E Ware; Fiscal Year: 2011
    The use of hydroxyurea for children and adults with sickle cell anemia (SCA) is increasing, but substantial inter-individual differences exist that limit its utility as a routine and effective therapeutic agent...
  39. NCMHD Southeastern Exploratory Sickle Cell Center of Excellence
    Abdullah Kutlar; Fiscal Year: 2013
    ..i) investigating the basic mechanism of action of a highly successful and effective hemoglobin F inducing drug, hydroxyurea, ii) identifying genetic variations underlying the frequency of pain, response to narcotics, and thus ..
  40. The Pathogenesis of Sickle Cell Nephropathy
    Antonio Guasch; Fiscal Year: 2010
    ..Then we will study the effects of hydroxyurea treatment in pediatric and adult sickle cell patients with early kidney disease to assess the ability of this ..
  41. Hydroxyurea to Prevent CNS Complications of Sickle Cell Disease in Children
    MICHAEL RUTLEDGE DEBAUN; Fiscal Year: 2012
    ..b>Hydroxyurea (HU) reduces the frequency of painful crisis, acute chest syndrome and transfusion and may have beneficial ..
  42. COMPREHENSIVE SICKLE CELL CENTER
    Kwaku Ohene Frempong; Fiscal Year: 2010
    ..For the first time in the history of research in this genetic disease, a drug, hydroxyurea, has been licensed specifically for preventive management...
  43. Targeting of EBV Latency in Burkitt's Lymphoma
    Juan Carlos Ramos; Fiscal Year: 2010
    ..These studies should lead to new, non-carcinogenic, abbreviated therapy that is applicable in developing nations for this common tumor. ..
  44. Single Stranded DNA: The Genome's Achilles Heel
    Wenyi Feng; Fiscal Year: 2009
    ..contain stalled replication forks and accumulate large regions of ssDNA upon treatment with the genotoxic agent hydroxyurea (HU);(2) the ability of rad53 cells to recover from transient exposure to HU decreases as the duration of ..
  45. Primary Prevention of Strokes in Nigerian Children with Sickle Cell Disease
    LORI CHAFFIN JORDAN; Fiscal Year: 2013
    ..In the United States, hydroxyurea (HU) is standard therapy for adults with SCD and may be a reasonable prevention alternative to regular blood ..
  46. Pharmacogenetics of Pediatric Sickle Cell Disease
    Kathleen A Neville; Fiscal Year: 2010
    ..in the pathogenesis of vaso-occlusive crisis as well as the pharmacologic barriers to successful treatment with hydroxyurea, a drug that targets disease pathogenesis...
  47. Phase 2 Study of Montelukast for the Treatment of Sickle Cell Anemia
    JOSHUA JEFFREY FIELD; Fiscal Year: 2013
    Abstract Hydroxyurea (HU) is the only drug approved by the Food and Drug Administration (FDA) for the prevention of vaso-occlusive pain episodes in sickle cell disease (SCD)...
  48. MUTAGENESIS AND REPAIR OF DNA
    Graham C Walker; Fiscal Year: 2013
    ..They will also provide in vivo and in vitro tests of our models of NusA-dependent TCR and TC-TLS. Hydroxyurea (HU), an inhibitor of class I ribonucleotide reductases, is widely used to block DNA replication...
  49. Mechanisms of Sensitivity to Cell Cycle Checkpoint Kinase Inhibitors
    ALAN R EASTMAN; Fiscal Year: 2013
    ..Accordingly, Chk1 inhibitors can dramatically sensitize cells to antimetabolites such as hydroxyurea and gemcitabine...
  50. Hydroxyurea Adherence for Personal Best in Sickle Cell Treatment: HABIT
    Arlene M Smaldone; Fiscal Year: 2013
    DESCRIPTION: Hydroxyurea Adherence for "Personal Best" in Sickle Cell Treatment: "HABIT" The overall goal is to test an intervention to improve the health of children with sickle cell disease (SCD) by enhancing long-term self-managed ..
  51. Improving Access to Hydroxyurea for Adults with Sickle Cell Disease
    SOPHIE M LANZKRON; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Our overall goal is to improve utilization of hydroxyurea for adults with sickle cell disease...
  52. PEDIATRIC HYDROXYUREA PHASE III CLINICAL TRIAL
    James F Casella; Fiscal Year: 2009
    Purpose: The objective of this contract is for the Contractor to serve as a clinical center for the Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG)...
  53. PEDIATRIC HYDROXYUREA PHASE III CLINICAL TRIAL
    Zora R Rogers; Fiscal Year: 2010
    Purpose: The objective of this contract is for the Contractor to serve as a clinical center for the Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG)...
  54. PEDIATRIC HYDROXYUREA PHASE III CLINICAL TRIAL
    Scott T Miller; Fiscal Year: 2010
    Purpose: The objective of this contract is for the Contractor to serve as a clinical center for the Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG)...
  55. PEDIATRIC HYDROXYUREA PHASE III CLINICAL TRIAL
    Zora R Rogers; Fiscal Year: 2011
    Purpose: The objective of this contract is for the Contractor to serve as a clinical center for the Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG)...
  56. PEDIATRIC HYDROXYUREA PHASE III CLINICAL TRIAL
    LINDA MONUM; Fiscal Year: 2011
    ..objective of this contract is for the Contractor to serve as the Medical Coordinating Center for the Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG)...
  57. Intracelllar Pathways That Silence the Fetal Globin Gene
    Tohru Ikuta; Fiscal Year: 2006
    Considerable concerns and efforts have been directed to the development of new fetal hemoglobin (Hb F) inducers. Hydroxyurea (HU) is being used for treating sickle cell anemia (SCA), but the magnitude of response to HU significantly ..
  58. A QTL for fetal hemoglobin and F cells on chromosome 8q
    Swee Thein; Fiscal Year: 2003
    ..hemoglobin production in patients with SCD and beta thalassemia, one of which involves the use of drugs such as hydroxyurea and butyrate analogues...
  59. N3 FATTY ACIDS EFFECT ON SICKLE CELL PAIN EPISODES
    James Eckman; Fiscal Year: 2001
    ..In addition, the Multicenter Study of Hydroxyurea in Sickle Cell Anemia reports that reduction in pain frequency with hydroxyurea was directly correlated to ..
  60. ORAL L GLUTAMINE THERAPY FOR SICKLE CELL ANEMIA
    Yutaka Niihara; Fiscal Year: 2001
    ..No safe, effective therapy is yet available. Within the last few years, hydroxyurea has been used in an increasing number of sickle cell anemia patients...
  61. Induction of HbF by Prolyl Hydroxylase Inhibitors
    Stephen Klaus; Fiscal Year: 2004
    ..expression during adulthood has recently been achieved by pharmacological means, and led to the approval of hydroxyurea (HU) to treat patients with SCD...
  62. NOVEL TREATMENT OF REFRACTORY GI MALIGNANCIES
    Scott Wadler; Fiscal Year: 1999
    ..Applicant's Abstract) The overall goals of this project are to test a high-dose parenteral infusion of hydroxyurea (HU) incorporated into a weekly regimen with high-dose fluorouracil (5FU), interferon-alpha (IFN) and ..
  63. Enhancing Suicide Gene Therapy Through Mechanism-Based Approaches
    Donna Shewach; Fiscal Year: 2007
    ..The results demonstrated that pharmacologic modulation (with ribonucleotide reductase inhibitors dFdCyd or hydroxyurea) was more efficacious than enhancing GJIC...
  64. Biomakers in Sickle Cell Anemia: Response to Hydroxyurea
    Marie Stuart; Fiscal Year: 2004
    In a landmark clinical trial, oral hydroxyurea (HU) decreased the frequency of vaso-occlusive crises and acute chest syndrome, and reduced the need for transfusions and hospitalizations in adult patients with homozygous SS disease (HbSS)..
  65. Ribonucleotide Reductase Inhibitors for Restenosis
    Howard Elford; Fiscal Year: 2009
    ..of balloon-mediated carotid injury evaluated two MFH drugs, Didox and Imidate, and the classic RR inhibitor hydroxyurea. RR inhibition resulted in a 65% or greater decrease in the intima/media ratio at two weeks post injury with ..
  66. NHLBI MINORITY INSTITUTION RESEARCH SCIENTIST DEVELOPMEN
    MARIA DEL PILAR AGUINAGA; Fiscal Year: 2004
    ..Relatively new chemotherapies like hydroxyurea has decreased the frequency of the painful episodes, and alleviated some of the disease symptoms, but does not ..
  67. The Role of RR in Chemotherapeutic Drug Resistance
    Yun Yen; Fiscal Year: 2005
    ..We have shown that gemcitabine resistant as well as hydroxyurea resistant clones both overexpress the RR small subunit, hRRM2, mRNA and RR protein...
  68. HYDROXYUREA SYNERGY WITH OTHER ANTICANCER DRUGS IN VIVO
    William Vaughan; Fiscal Year: 1990
    ..b>Hydroxyurea (HU) is a drug which inhibits ribonucleotide reductase resulting in decreased intracellular deoxyribonucleotide ..