morpholines

Summary

Top Publications

  1. ncbi AZD8055 is a potent, selective, and orally bioavailable ATP-competitive mammalian target of rapamycin kinase inhibitor with in vitro and in vivo antitumor activity
    Christine M Chresta
    AstraZeneca, Cheshire, United Kingdom
    Cancer Res 70:288-98. 2010
  2. ncbi Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt
    L del Peso
    Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Science 278:687-9. 1997
  3. ncbi Akt/protein kinase B is constitutively active in non-small cell lung cancer cells and promotes cellular survival and resistance to chemotherapy and radiation
    J Brognard
    Developmental Therapeutics Department, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20889, USA
    Cancer Res 61:3986-97. 2001
  4. pmc Ku-0063794 is a specific inhibitor of the mammalian target of rapamycin (mTOR)
    Juan M García-Martínez
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee DD15EH, Scotland, UK
    Biochem J 421:29-42. 2009
  5. ncbi Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty
    Bengt I Eriksson
    Sahlgrenska University Hospital Ostra, Gothenburg, Sweden
    N Engl J Med 358:2765-75. 2008
  6. ncbi Effective targeted gene 'knockdown' in zebrafish
    A Nasevicius
    Arnold and Mabel Beckman Center for Transposon Research at the University of Minnesota, Department of Genetics, Cell Biology and Development, Minneapolis, Minnesota, USA
    Nat Genet 26:216-20. 2000
  7. ncbi Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty
    Michael R Lassen
    Nordsjaellands Hospital, Hørsholm, Denmark
    N Engl J Med 358:2776-86. 2008
  8. ncbi Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial
    Alexander G G Turpie
    McMaster University, Hamilton, Ontario L8L 2X2, Canada
    Lancet 373:1673-80. 2009
  9. ncbi Characterization of a novel, water-soluble hydrogen sulfide-releasing molecule (GYY4137): new insights into the biology of hydrogen sulfide
    Ling Li
    Department of Pharmacology, National University of Singapore, Singapore
    Circulation 117:2351-60. 2008
  10. ncbi Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial
    Ajay K Kakkar
    Barts and the London School of Medicine and Dentistry, London, UK
    Lancet 372:31-9. 2008

Detail Information

Publications291 found, 100 shown here

  1. ncbi AZD8055 is a potent, selective, and orally bioavailable ATP-competitive mammalian target of rapamycin kinase inhibitor with in vitro and in vivo antitumor activity
    Christine M Chresta
    AstraZeneca, Cheshire, United Kingdom
    Cancer Res 70:288-98. 2010
    ..Notably, AZD8055 results in significant growth inhibition and/or regression in xenografts, representing a broad range of human tumor types. AZD8055 is currently in phase I clinical trials...
  2. ncbi Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt
    L del Peso
    Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Science 278:687-9. 1997
    ..Thus, the proapoptotic function of BAD is regulated by the PI 3-kinase-Akt pathway...
  3. ncbi Akt/protein kinase B is constitutively active in non-small cell lung cancer cells and promotes cellular survival and resistance to chemotherapy and radiation
    J Brognard
    Developmental Therapeutics Department, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20889, USA
    Cancer Res 61:3986-97. 2001
    ....
  4. pmc Ku-0063794 is a specific inhibitor of the mammalian target of rapamycin (mTOR)
    Juan M García-Martínez
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee DD15EH, Scotland, UK
    Biochem J 421:29-42. 2009
    ..Our results indicate that Ku-0063794 will be useful in delineating the physiological roles of mTOR and may have utility in treatment of cancers in which this pathway is inappropriately activated...
  5. ncbi Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty
    Bengt I Eriksson
    Sahlgrenska University Hospital Ostra, Gothenburg, Sweden
    N Engl J Med 358:2765-75. 2008
    ..This phase 3 trial compared the efficacy and safety of rivaroxaban, an oral direct inhibitor of factor Xa, with those of enoxaparin for extended thromboprophylaxis in patients undergoing total hip arthroplasty...
  6. ncbi Effective targeted gene 'knockdown' in zebrafish
    A Nasevicius
    Arnold and Mabel Beckman Center for Transposon Research at the University of Minnesota, Department of Genetics, Cell Biology and Development, Minneapolis, Minnesota, USA
    Nat Genet 26:216-20. 2000
    ..Conserved vertebrate processes and diseases are now amenable to a systematic, in vivo, reverse-genetic paradigm using zebrafish embryos...
  7. ncbi Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty
    Michael R Lassen
    Nordsjaellands Hospital, Hørsholm, Denmark
    N Engl J Med 358:2776-86. 2008
    ..We investigated the efficacy of rivaroxaban, an orally active direct factor Xa inhibitor, in preventing venous thrombosis after total knee arthroplasty...
  8. ncbi Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial
    Alexander G G Turpie
    McMaster University, Hamilton, Ontario L8L 2X2, Canada
    Lancet 373:1673-80. 2009
    ..We aimed to test the efficacy and safety of oral rivaroxaban for the prevention of venous thromboembolism after total knee arthroplasty...
  9. ncbi Characterization of a novel, water-soluble hydrogen sulfide-releasing molecule (GYY4137): new insights into the biology of hydrogen sulfide
    Ling Li
    Department of Pharmacology, National University of Singapore, Singapore
    Circulation 117:2351-60. 2008
    ....
  10. ncbi Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial
    Ajay K Kakkar
    Barts and the London School of Medicine and Dentistry, London, UK
    Lancet 372:31-9. 2008
    ..Our aim was to compare the use of rivaroxaban for extended thromboprophylaxis with short-term thromboprophylaxis with enoxaparin...
  11. pmc Exploring the specificity of the PI3K family inhibitor LY294002
    Severine I Gharbi
    Ludwig Institute for Cancer Research, Proteomics Unit, Cruciform Building, Gower Street, London WCE1 6BT, UK
    Biochem J 404:15-21. 2007
    ..The present study reveals that LY294002 not only binds to class I PI3Ks and other PI3K-related kinases, but also to novel targets seemingly unrelated to the PI3K family...
  12. ncbi Identification and characterization of a novel and specific inhibitor of the ataxia-telangiectasia mutated kinase ATM
    Ian Hickson
    KuDOS Pharmaceuticals Ltd, Cambridge Science Park, Milton Road, Cambridge, UK
    Cancer Res 64:9152-9. 2004
    ..We conclude that KU-55933 is a novel, specific, and potent inhibitor of the ATM kinase...
  13. ncbi Safety, pharmacodynamics, and pharmacokinetics of single doses of BAY 59-7939, an oral, direct factor Xa inhibitor
    Dagmar Kubitza
    Bayer HealthCare AG, Institute of Clinical Pharmocology, D 42096 Wuppertal, Germany
    Clin Pharmacol Ther 78:412-21. 2005
    ..The aim of this study was to investigate the safety, pharmacodynamics, and pharmacokinetics of BAY 59--7939, an oral, direct factor Xa inhibitor...
  14. ncbi Inhibition of nitric oxide production in RAW264.7 macrophages by cannabinoids and palmitoylethanolamide
    R A Ross
    Department of Biomedical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, AB25 2ZD, Scotland, Aberdeen, UK
    Eur J Pharmacol 401:121-30. 2000
    ..In contrast, the inhibition by palmitoylethanolamide does not appear to be mediated by cannabinoid receptors...
  15. ncbi Safety, pharmacodynamics, and pharmacokinetics of BAY 59-7939--an oral, direct Factor Xa inhibitor--after multiple dosing in healthy male subjects
    Dagmar Kubitza
    Institute of Clinical Pharmacology, Bayer HealthCare AG, 42096 Wuppertal, Germany
    Eur J Clin Pharmacol 61:873-80. 2005
    ....
  16. ncbi Phosphatidylinositol-3-kinase as a therapeutic target in melanoma
    Saadia A Aziz
    Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA
    Clin Cancer Res 15:3029-36. 2009
    ..We assessed expression of PI3K in melanomas and nevi, and studied associations between PI3K pathway members and in vitro response to a PI3K inhibitor, LY294002...
  17. ncbi Inhibition of phosphatidylinositol 3'-kinase increases efficacy of paclitaxel in in vitro and in vivo ovarian cancer models
    Limin Hu
    Center for Reproductive Sciences, University of California, San Francisco, San Francisco, California 94143 0556, USA
    Cancer Res 62:1087-92. 2002
    ..Our data suggest that a combination of a PI3k inhibitor and conventional chemotherapy may provide an effective approach to inhibiting tumor growth and ascites production in ovarian cancer with acceptable side effects...
  18. ncbi Dose-escalation study of the pharmacokinetics and pharmacodynamics of rivaroxaban in healthy elderly subjects
    Dagmar Kubitza
    Clinical Pharmacology, Bayer HealthCare AG, D 42096 Wuppertal, Germany
    Curr Med Res Opin 24:2757-65. 2008
    ..The aim of this study was to investigate the pharmacokinetics and pharmacodynamics of rivaroxaban--a novel, oral, direct Factor Xa (FXa) inhibitor--in healthy elderly subjects...
  19. pmc Hydrogen sulfide inhibits proliferation and release of IL-8 from human airway smooth muscle cells
    Mark M Perry
    Experimental Studies, National Heart and Lung Institute, Imperial College London, London, United Kingdom
    Am J Respir Cell Mol Biol 45:746-52. 2011
    ..Therefore, regulation of H(2)S may represent a novel approach to controlling ASM proliferation and cytokine release that is found in patients with asthma...
  20. pmc Phosphatidylinositol 3-kinase inhibitor(LY294002) induces apoptosis of human nasopharyngeal carcinoma in vitro and in vivo
    Hanguo Jiang
    Department of Pathology, School of Medicine, Shandong University, 250012 Jinan, China
    J Exp Clin Cancer Res 29:34. 2010
    ..To evaluate whether PI3K/Akt pathway could effect on apoptosis and its mechanism in nasopharyngeal carcinoma cells...
  21. ncbi G1 cell cycle progression and the expression of G1 cyclins are regulated by PI3K/AKT/mTOR/p70S6K1 signaling in human ovarian cancer cells
    Ning Gao
    1820 MBR Cancer Center and Dept of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 9300, USA
    Am J Physiol Cell Physiol 287:C281-91. 2004
    ..These results indicate that PI3K mediates G(1) progression and cyclin expression through activation of an AKT/mTOR/p70S6K1 signaling pathway in the ovarian cancer cells...
  22. pmc Improved ATM kinase inhibitor KU-60019 radiosensitizes glioma cells, compromises insulin, AKT and ERK prosurvival signaling, and inhibits migration and invasion
    Sarah E Golding
    Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA 23298 0058, USA
    Mol Cancer Ther 8:2894-902. 2009
    ..Altogether, KU-60019 inhibits the DNA damage response, reduces AKT phosphorylation and prosurvival signaling, inhibits migration and invasion, and effectively radiosensitizes human glioma cells...
  23. ncbi Inhibition of interneuron firing extends the spread of endocannabinoid signaling in the cerebellum
    Anatol C Kreitzer
    Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, Massachusetts 02115, USA
    Neuron 34:787-96. 2002
    ..Because interneurons can project over several hundred micrometers, this inhibition of firing allows cells to regulate synaptic inputs at distances well beyond the limits of endocannabinoid diffusion...
  24. ncbi Assessment of laboratory assays to measure rivaroxaban--an oral, direct factor Xa inhibitor
    Meyer Michel Samama
    Hotel Dieu University Hospital, Paris, France 2Biomnis Laboratory, Ivry sur Seine, France
    Thromb Haemost 103:815-25. 2010
    ..Finally, all clotting and chromogenic assays showed a concentration-dependent effect induced by rivaroxaban...
  25. pmc The effect of hydrogen sulfide donors on lipopolysaccharide-induced formation of inflammatory mediators in macrophages
    Matthew Whiteman
    Peninsula Medical School, University of Exeter, St Luke s Campus, Exeter, Devon, England
    Antioxid Redox Signal 12:1147-54. 2010
    ..This study may also explain some of the apparent discrepancies in the literature regarding the pro- versus antiinflammatory role of H(2)S...
  26. ncbi Population pharmacokinetics and pharmacodynamics of rivaroxaban--an oral, direct factor Xa inhibitor--in patients undergoing major orthopaedic surgery
    Wolfgang Mueck
    Clinical Pharmacology, Bayer HealthCare AG, Aprather Weg 18a, Wuppertal, Germany
    Clin Pharmacokinet 47:203-16. 2008
    ....
  27. ncbi The novel proangiogenic effect of hydrogen sulfide is dependent on Akt phosphorylation
    Wen Jie Cai
    Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, Shanghai, China
    Cardiovasc Res 76:29-40. 2007
    ..Hydrogen sulfide (H(2)S) has been reported to be a gasotransmitter which regulates cardiovascular homeostasis. The present study aims to examine the hypothesis that hydrogen sulfide is able to promote angiogenesis...
  28. ncbi Akt inhibitor A-443654 induces rapid Akt Ser-473 phosphorylation independent of mTORC1 inhibition
    E K H Han
    Abbott Laboratories, Global Pharmaceutical Research Division, Cancer Research, IL 60064, USA
    Oncogene 26:5655-61. 2007
    ....
  29. pmc ER-alpha36, a variant of ER-alpha, promotes tamoxifen agonist action in endometrial cancer cells via the MAPK/ERK and PI3K/Akt pathways
    Sheng Li Lin
    State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences and Graduate School, Chinese Academy of Sciences, Beijing, China
    PLoS ONE 5:e9013. 2010
    ..ER-alpha36 lacks intrinsic transcription activity and mainly mediates nongenomic estrogen signaling. Here, we studied the role of nongenomic estrogen signaling pathways mediated by ER-alpha36 in tamoxifen resistance and agonist action...
  30. ncbi Activation of Akt/GSK-3beta signaling pathway is involved in intermedin(1-53) protection against myocardial apoptosis induced by ischemia/reperfusion
    Jun Qiu Song
    Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China
    Apoptosis 14:1299-307. 2009
    ..In conclusion, IMD(1-53) exerts cardioprotective effect against myocardial I/R injury through the activation of the Akt/GSK-3beta signaling pathway to inhibit mitochondria-mediated myocardial apoptosis...
  31. ncbi Bidirectional regulation of mu-opioid and CB1-cannabinoid receptor in rats self-administering heroin or WIN 55,212-2
    Liana Fattore
    Institute of Neuroscience, National Research Council CNR, Section of Cagliari, Italy
    Eur J Neurosci 25:2191-200. 2007
    ....
  32. ncbi Simultaneous inhibition of mTORC1 and mTORC2 by mTOR kinase inhibitor AZD8055 induces autophagy and cell death in cancer cells
    Patrizia Sini
    AstraZeneca Cancer and Infection Research Area, Alderley Park, UK
    Autophagy 6:553-4. 2010
    ..pAKT also phosphorylates PRAS40, releasing it from the mTORC1 complex, increasing its kinase activity. Finally, AKT regulates FOXO3 phosphorylation, sequestering it in the cytosol in an inactive state...
  33. ncbi Glioblastoma: synergy of growth promotion between CCL5 and NK-1R can be thwarted by blocking CCL5 with miraviroc, an FDA approved anti-HIV drug and blocking NK-1R with aprepitant, an FDA approved anti-nausea drug
    R E Kast
    Department of Psychiatry, University of Vermont, Burlington, VT 05401, USA
    J Clin Pharm Ther 35:657-63. 2010
    ..The anti-HIV drug, maraviroc, inhibits human CCR5's ligand from binding, and hence blocks CCR5 stimulation. The anti-nausea drug aprepitant blocks substance P signaling at NK-1R...
  34. ncbi Morpholino antisense oligomers: the case for an RNase H-independent structural type
    J Summerton
    Gene Tools, Corvallis, OR 97339, USA
    Biochim Biophys Acta 1489:141-58. 1999
    ....
  35. ncbi Chlorambucil cytotoxicity in malignant B lymphocytes is synergistically increased by 2-(morpholin-4-yl)-benzo[h]chomen-4-one (NU7026)-mediated inhibition of DNA double-strand break repair via inhibition of DNA-dependent protein kinase
    Lilian Amrein
    Montreal Centre for Experimental Therapeutics in Cancer Lady Davis Institute for Medical Research, Sir Mortimer B Davis Jewish General Hospital, McGill University, Montreal, Quebec, Canada
    J Pharmacol Exp Ther 321:848-55. 2007
    ....
  36. ncbi A novel DNA-dependent protein kinase inhibitor, NU7026, potentiates the cytotoxicity of topoisomerase II poisons used in the treatment of leukemia
    Elaine Willmore
    School of Cell and Molecular Biosciences, University of Newcastle upon Tyne Medical School, Newcastle upon Tyne NE2 4HH, United Kingdom
    Blood 103:4659-65. 2004
    ..A concentration-dependent increase in etoposide-induced DSB levels was increased by NU7026. The mechanism of NU7026 potentiation of topo II poisons involves inhibition of NHEJ and a G2/M checkpoint arrest...
  37. ncbi Targeting glucosylceramide synthase sensitizes imatinib-resistant chronic myeloid leukemia cells via endogenous ceramide accumulation
    Yusuf Baran
    Department of Molecular Biology and Genetics, Izmir Institute of Technology, Faculty of Science, Gulbahce Campus, 35430, Urla, Izmir, Turkey
    J Cancer Res Clin Oncol 137:1535-44. 2011
    ..2 and K562/IMA-1 human CML cells, which exhibit about 2.3- and 19-fold imatinib resistance, respectively...
  38. ncbi Two distinct classes of muscarinic action on hippocampal inhibitory synapses: M2-mediated direct suppression and M1/M3-mediated indirect suppression through endocannabinoid signalling
    Yuko Fukudome
    Department of Cellular Neurophysiology, Graduate School of Medical Science, Kanazawa University, 13 1 Takara machi, Kanazawa 920 8640, Japan
    Eur J Neurosci 19:2682-92. 2004
    ..Thus, the muscarinic system can influence hippocampal functions by controlling different subsets of inhibitory synapses through the two distinct mechanisms...
  39. ncbi Further characterisation of the cellular activity of the DNA-PK inhibitor, NU7441, reveals potential cross-talk with homologous recombination
    Michele Tavecchio
    Northern Institute for Cancer Research, School of Medical Sciences, Newcastle University, Paul O Gorman Building, Framlington Place, NE2 4HH Newcastle upon Tyne, UK
    Cancer Chemother Pharmacol 69:155-64. 2012
    ..One promising target is DNA-PK, a pivotal kinase in double-strand break repair. The purpose of this study was to further characterise the activity of the DNA-PK inhibitor NU7441, giving some new insights into the biology of DNA-PK...
  40. ncbi Dynamic and reversible restructuring of the ER induced by PDMP in cultured cells
    Teresa Sprocati
    Consiglio Nazionale delle Ricerche Institute of Neuroscience and Department of Medical Pharmacology, Via Vanvitelli 32, University of Milano, 20129 Milano, Italy
    J Cell Sci 119:3249-60. 2006
    ..Our results demonstrate a dynamic relationship between smooth and rough ER and have implications for the mechanisms regulating ER architecture...
  41. ncbi Molecular characterization of a peripheral receptor for cannabinoids
    S Munro
    MRC Laboratory of Molecular Biology, Cambridge, UK
    Nature 365:61-5. 1993
    ..Here we report the cloning of a receptor for cannabinoids that is not expressed in the brain but rather in macrophages in the marginal zone of spleen...
  42. ncbi Neurokinin-1 receptor antagonists for chemotherapy-induced nausea and vomiting: a systematic review
    Lucas Vieira dos Santos
    Medical Oncology Department, Gastrointestinal Oncology Division, Barretos Cancer Hospital, 520 Brasil St, Barretos, Sao Paulo 14784 011, Brazil
    J Natl Cancer Inst 104:1280-92. 2012
    ..We sought to systematically review the overall impact of NK1R antagonists on CINV prevention...
  43. ncbi Effects of the oral, direct factor xa inhibitor rivaroxaban on platelet-induced thrombin generation and prothrombinase activity
    Jochen Graff
    Pharmazentrum frankfurt ZAFES, Institute of Clinical Pharmacology, University Hospital, Frankfurt Main, Theodor Stern Kai 7, D 60590 Frankfurt am Main, Germany
    J Clin Pharmacol 47:1398-407. 2007
    ..Rivaroxaban strongly inhibits platelet-induced thrombin generation, after activation of either platelets or the coagulation pathway, even in the presence of minimal factor Xa inhibition in plasma...
  44. ncbi Safety and efficacy of a bolus injection of landiolol hydrochloride as a premedication for multidetector-row computed tomography coronary angiography
    Kazuhiro Osawa
    Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
    Circ J 77:146-52. 2013
    ....
  45. ncbi Salmonella transforms follicle-associated epithelial cells into M cells to promote intestinal invasion
    Amin Tahoun
    The Roslin Institute and Royal School of Veterinary Studies, University of Edinburgh, Edinburgh EH25 9RG, UK
    Cell Host Microbe 12:645-56. 2012
    ..Thus, via the activity of a single secreted effector, S. Typhimurium transforms primed epithelial cells into M cells to promote host colonization and invasion...
  46. ncbi Cannabinoids prevent lipopolysaccharide-induced neurodegeneration in the rat substantia nigra in vivo through inhibition of microglial activation and NADPH oxidase
    Eun Sook Chung
    Department of Biochemistry and Molecular Biology, School of Medicine Kyung Hee University, Seoul 130 701, Korea
    Brain Res 1451:110-6. 2012
    ..The present data suggest that cannabinoids may be beneficial for the treatment of neurodegenerative diseases, such as PD, that are associated with microglial activation...
  47. ncbi Posttraining activation of CB1 cannabinoid receptors in the CA1 region of the dorsal hippocampus impairs object recognition long-term memory
    Julia R Clarke
    Centro de Memoria, Instituto de Pesquisas Biomédicas, Pontificia Universidade Catolica do Rio Grande do Sul, Av Ipiranga 6690, RS 90610 000 Porto Alegre, Brazil
    Neurobiol Learn Mem 90:374-81. 2008
    ..Our data indicate that activation of hippocampal CB1 receptors early after training hampers consolidation of object recognition memory...
  48. ncbi In smooth muscle, FK506-binding protein modulates IP3 receptor-evoked Ca2+ release by mTOR and calcineurin
    Debbi MacMillan
    Institute of Biomedical and Life Sciences, Neuroscience and Biomedical Systems, West Medical Building, University of Glasgow, Glasgow, G12 8QQ, UK
    J Cell Sci 118:5443-51. 2005
    ..However, FKBP12 might indirectly modulate Ca2+ release through two effector proteins: (1) mTOR, which potentiates and (2) calcineurin, which inhibits Ca2+ release from IP3R in smooth muscle...
  49. ncbi Cannabinoids attenuate the effects of aging upon neuroinflammation and neurogenesis
    Yannick Marchalant
    Department of Psychology, The Ohio State University, Columbus, 43210, USA
    Neurobiol Dis 34:300-7. 2009
    ..Our results provide insight into the role of the endocannabinoid and vanilloid systems upon two different and detrimental aspects of normal and pathological aging, chronic neuroinflammation and decline in neurogenesis...
  50. ncbi Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF
    Graeme J Hankey
    Stroke Unit, Department of Neurology, Royal Perth Hospital, Perth, Australia
    Lancet Neurol 11:315-22. 2012
    ..We aimed to investigate whether the efficacy and safety of rivaroxaban compared with warfarin is consistent among the subgroups of patients with and without previous stroke or transient ischaemic attack (TIA)...
  51. ncbi Cost-effectiveness of rivaroxaban compared to warfarin for stroke prevention in atrial fibrillation
    Soyon Lee
    University of Connecticut School of Pharmacy, Storrs, CT, USA
    Am J Cardiol 110:845-51. 2012
    ..In conclusion, this Markov model suggests that rivaroxaban therapy may be a cost-effective alternative to adjusted-dose warfarin for stroke prevention in AF...
  52. ncbi Constitutive and inducible Akt activity promotes resistance to chemotherapy, trastuzumab, or tamoxifen in breast cancer cells
    Amy S Clark
    Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20889, USA
    Mol Cancer Ther 1:707-17. 2002
    ....
  53. ncbi Dabigatran and rivaroxaban for prevention of venous thromboembolism--systematic review and adjusted indirect comparison
    Y K Loke
    School of Medicine, Health Policy and Practice, University of East Anglia, Norwich, UK
    J Clin Pharm Ther 36:111-24. 2011
    ..Dabigatran and rivaroxaban are new oral anticoagulants for thromboprophylaxis after elective orthopaedic surgery. We aimed to systematically compare their relative benefits and harms through meta-analysis, and adjusted indirect comparison...
  54. ncbi Involvement of PI3K/Akt signaling in PTTH-stimulated ecdysteroidogenesis by prothoracic glands of the silkworm, Bombyx mori
    Shi Hong Gu
    Department of Zoology, National Museum of Natural Science, 1 Kuan Chien Road, Taichung 404, Taiwan, ROC
    Insect Biochem Mol Biol 41:197-202. 2011
    ..mori prothoracic glands between insulin and PTTH signaling, which may play a critical role in precisely regulated ecdysteroidogenesis during development...
  55. pmc Opposing actions of chronic Delta9-tetrahydrocannabinol and cannabinoid antagonists on hippocampal long-term potentiation
    Alexander F Hoffman
    United States Department of Health and Human Services, National Institutes of Health, National Institute on Drug Abuse, Intramural Research Program, Cellular Neurobiology Branch, Electrophysiology Research Unit, Baltimore, Maryland 21224, USA
    Learn Mem 14:63-74. 2007
    ..These data define consequences of repeated Delta(9)-THC exposure for synaptic plasticity in the hippocampus that may help explain memory impairments in humans following chronic marijuana use...
  56. ncbi Preclinical evaluation of a potent novel DNA-dependent protein kinase inhibitor NU7441
    Yan Zhao
    Northern Institute for Cancer Research, Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom
    Cancer Res 66:5354-62. 2006
    ..In conclusion, NU7441 shows sufficient proof of principle through in vitro and in vivo chemosensitization and radiosensitization to justify further development of DNA-PK inhibitors for clinical use...
  57. pmc t-DARPP regulates phosphatidylinositol-3-kinase-dependent cell growth in breast cancer
    Bhavatarini Vangamudi
    Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA
    Mol Cancer 9:240. 2010
    ..In this study, we evaluated expression of t-DARPP in human primary breast tumors, and investigated the role of t-DARPP in regulating growth and proliferation in breast cancer cells...
  58. pmc Reboxetine for acute treatment of major depression: systematic review and meta-analysis of published and unpublished placebo and selective serotonin reuptake inhibitor controlled trials
    Dirk Eyding
    German Cancer Society, Berlin, Germany
    BMJ 341:c4737. 2010
    ..To assess the benefits and harms of reboxetine versus placebo or selective serotonin reuptake inhibitors (SSRIs) in the acute treatment of depression, and to measure the impact of potential publication bias in trials of reboxetine...
  59. pmc Synthetic cannabinoid receptor agonists inhibit tumor growth and metastasis of breast cancer
    Zahida Qamri
    Department of Pathology, Ohio State University Medical Center, Columbus, OH 43210, USA
    Mol Cancer Ther 8:3117-29. 2009
    ..These results indicate that CB1 and CB2 receptors could be used to develop novel therapeutic strategies against breast cancer growth and metastasis...
  60. ncbi Radiation sensitization of human cancer cells in vivo by inhibiting the activity of PI3K using LY294002
    Anjali K Gupta
    Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA 19104, USA
    Int J Radiat Oncol Biol Phys 56:846-53. 2003
    ..Inhibition of PI3K by LY294002 can synergistically enhance radiation efficacy. This acts as a proof of principle that inhibition of the Ras to PI3K pathway could be useful clinically...
  61. pmc The slow-releasing hydrogen sulfide donor, GYY4137, exhibits novel anti-cancer effects in vitro and in vivo
    Zheng Wei Lee
    Department of Biochemistry, National University of Singapore, Singapore, Singapore
    PLoS ONE 6:e21077. 2011
    ..We also propose that a combination of apoptosis and cell cycle arrest contributes to this effect and that H₂S donors should be investigated further as potential anti-cancer agents...
  62. ncbi Mutant PIK3CA promotes cell growth and invasion of human cancer cells
    Yardena Samuels
    The Sidney Kimmel Comprehensive Cancer Center and The Howard Hughes Medical Institute, The Johns Hopkins University Medical Institutions, Baltimore, MD 21231, USA
    Cancer Cell 7:561-73. 2005
    ..Treatment with the PI3K inhibitor LY294002 abrogated PIK3CA signaling and preferentially inhibited growth of PIK3CA mutant cells. These data have important implications for therapy of cancers harboring PIK3CA alterations...
  63. ncbi Adiponectin stimulates angiogenesis by promoting cross-talk between AMP-activated protein kinase and Akt signaling in endothelial cells
    Noriyuki Ouchi
    Molecular Cardiology Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02118, USA
    J Biol Chem 279:1304-9. 2004
    ..These data indicate that adiponectin can function to stimulate the new blood vessel growth by promoting cross-talk between AMP-activated protein kinase and Akt signaling within endothelial cells...
  64. ncbi Suppression of HIV-1 infection by a small molecule inhibitor of the ATM kinase
    Alan Lau
    KuDOS Pharmaceuticals Limited, 327 Cambridge Science Park, Milton Road, Cambridge CB4 0WG, UK
    Nat Cell Biol 7:493-500. 2005
    ..Consistent with these observations, we demonstrate that a novel and specific small molecule inhibitor of ATM kinase activity, KU-55933, is capable of suppressing the replication of both wild-type and drug-resistant HIV-1...
  65. ncbi Electrophysiologic, cardiohemodynamic and beta-blocking actions of a new ultra-short-acting beta-blocker, ONO-1101, assessed by the in vivo canine model in comparison with esmolol
    A Sugiyama
    Department of Pharmacology, Yamanashi Medical University, Japan
    J Cardiovasc Pharmacol 34:70-7. 1999
    ..These results suggest that the suppressive effects of ONO-1101 on cardiovascular performance are significantly less potent than those of esmolol at equipotent beta-blocking doses...
  66. ncbi GYY4137, a novel hydrogen sulfide-releasing molecule, protects against endotoxic shock in the rat
    Ling Li
    Pharmaceutical Science Research Division, King s College, University of London, London, UK
    Free Radic Biol Med 47:103-13. 2009
    ..These results suggest an anti-inflammatory effect of GYY4137. The possibility that GYY4137 and other slow-releasing H(2)S donors exert anti-inflammatory activity in other models of inflammation and in humans warrants further study...
  67. ncbi Loss in oxidative stress tolerance with aging linked to reduced extracellular signal-regulated kinase and Akt kinase activities
    Shizuo Ikeyama
    Laboratory of Cellular and Molecular Biology, National Institute on Aging IRP, Baltimore, Maryland 21224, USA
    FASEB J 16:114-6. 2002
    ..Strategies aimed at boosting these host responses to acute oxidant injury could have significant anti-aging benefits...
  68. pmc Diminished neural processing of aversive and rewarding stimuli during selective serotonin reuptake inhibitor treatment
    Ciara McCabe
    Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford OX3 7JX, United Kingdom
    Biol Psychiatry 67:439-45. 2010
    ..There are few studies of the effect of SSRIs on neural reward mechanisms in humans...
  69. ncbi Cytoprotective effect of glucosylceramide synthase inhibition against daunorubicin-induced apoptosis in human leukemic cell lines
    Solène Grazide
    INSERM U563 Centre de Physiopathologie Toulouse Purpan, Institut Claudius Regaud, Toulouse 31052, France
    J Biol Chem 279:18256-61. 2004
    ..In conclusion, this study suggests that sphingomyelin-derived CER in itself is not a second messenger but rather a precursor of both an apoptosis second messenger (GD3) and an apoptosis "protector" (GalCER)...
  70. ncbi LY294002 and LY303511 sensitize tumor cells to drug-induced apoptosis via intracellular hydrogen peroxide production independent of the phosphoinositide 3-kinase-Akt pathway
    Tze Wei Poh
    Department of Physiology, National University Medical Institute, Faculty of Medicine, National University of Singapore, Singapore, Singapore
    Cancer Res 65:6264-74. 2005
    ....
  71. pmc Chronic systemic therapy with low-dose morpholino oligomers ameliorates the pathology and normalizes locomotor behavior in mdx mice
    Alberto Malerba
    School of Biological Sciences, Royal Holloway, University of London, Surrey, UK
    Mol Ther 19:345-54. 2011
    ....
  72. ncbi Interactive competition between homologous recombination and non-homologous end joining
    Chris Allen
    Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA
    Mol Cancer Res 1:913-20. 2003
    ..By blocking the two major DSB repair pathways, DNA-PKcs inhibitors should radiosensitize at all cell-cycle stages and are therefore excellent candidates for augmenting cancer radiotherapy...
  73. ncbi Clinical laboratory measurement of direct factor Xa inhibitors: anti-Xa assay is preferable to prothrombin time assay
    Yu Chen Barrett
    Bristol Myers Squibb, Princeton, New Jersey, USA
    Thromb Haemost 104:1263-71. 2010
    ..88-0.89) compared with PT/INR (r2 = 0.36) in patients undergoing VTE treatment suggested that anti-Xa activity was the better indicator of apixaban plasma concentrations...
  74. ncbi The cannabinoid CB1 receptor mediates retrograde signals for depolarization-induced suppression of inhibition in cerebellar Purkinje cells
    Takayuki Yoshida
    Department of Cellular Neurophysiology, Graduate School of Medical Science, Kanazawa University, Kanazawa 920 8640, Japan
    J Neurosci 22:1690-7. 2002
    ..These results clearly indicate that the CB1 receptor mediates retrograde signal for DSI in cerebellar Purkinje cells...
  75. ncbi Reversine, a novel Aurora kinases inhibitor, inhibits colony formation of human acute myeloid leukemia cells
    Anna Morena D'Alise
    CEINGE, Biotecnologie Avanzate, Via Comunale Margherita 482, 80131 Naples, Italy
    Mol Cancer Ther 7:1140-9. 2008
    ..Thus, although our studies raise serious doubts on the application of reversine in regenerative medicine, they support the paradigm that reversine might be a useful agent in cancer chemotherapy...
  76. ncbi Synchronous activation of ERK and phosphatidylinositol 3-kinase pathways is required for collagen and extracellular matrix production in keloids
    Ivor J Lim
    Departments of Surgery and Orthopaedic Surgery, National University of Singapore, 5, Lower Kent Ridge Road, Singapore 119074
    J Biol Chem 278:40851-8. 2003
    ..These pathways additionally appear to affect the side chain attachments of fibronectin. Modulation of these pathways may suggest a direction for keloid therapy...
  77. ncbi In vitro and in vivo studies of the novel antithrombotic agent BAY 59-7939--an oral, direct Factor Xa inhibitor
    E Perzborn
    Cardiovascular Research, Bayer HealthCare AG, Wuppertal, Germany
    J Thromb Haemost 3:514-21. 2005
    ..Bleeding times in rats and rabbits were not significantly affected at antithrombotic doses (3 mg kg(-1) p.o., AV shunt). Based on these results, BAY 59-7939 was selected for clinical development...
  78. pmc Effective rescue of dystrophin improves cardiac function in dystrophin-deficient mice by a modified morpholino oligomer
    Bo Wu
    McColl Lockwood Laboratory for Muscular Dystrophy, Neuromuscular ALS Center, Carolinas Medical Center, Charlotte, NC 28231, USA
    Proc Natl Acad Sci U S A 105:14814-9. 2008
    ..The high degree of potency of the oligomer in targeting all muscles and the lack of detectable toxicity and immune response support the feasibility of testing the novel oligomer in treating Duchenne muscular dystrophy patients...
  79. ncbi Effect of food, an antacid, and the H2 antagonist ranitidine on the absorption of BAY 59-7939 (rivaroxaban), an oral, direct factor Xa inhibitor, in healthy subjects
    Dagmar Kubitza
    Institute of Clinical Pharmacology, Bayer HealthCare AG, Wuppertal, Germany
    J Clin Pharmacol 46:549-58. 2006
    ..Time to maximum PT prolongation was delayed by 0.5 to 1.5 hours after food, with no relevant influence of food type. No significant difference in C(max) and AUC was observed with coadministration of BAY 59-7939 and ranitidine or antacid...
  80. ncbi Body weight has limited influence on the safety, tolerability, pharmacokinetics, or pharmacodynamics of rivaroxaban (BAY 59-7939) in healthy subjects
    Dagmar Kubitza
    Clinical Pharmacology, Bayer HealthCare AG, Building 429, Aprather Weg 18a, Wuppertal, D 42096, Germany
    J Clin Pharmacol 47:218-26. 2007
    ..The area under the curve was unaffected by body weight or gender. No other clinically relevant differences were observed, suggesting that rivaroxaban is unlikely to require dose adjustment for body weight or gender...
  81. ncbi Neuroprotection by brain-derived neurotrophic factor is mediated by extracellular signal-regulated kinase and phosphatidylinositol 3-kinase
    M Hetman
    Toxicology Program, Department of Environmental Health, the Graduate Program in Neurobiology and Behavior, The Graduate Program in Molecular and Cell Biology, University of Washington, Seattle, Washington 98195 7234, USA
    J Biol Chem 274:22569-80. 1999
    ..Furthermore, the relative contribution of the ERK and PI 3-kinase pathways to neuronal survival may depend on the type of cellular injury...
  82. ncbi FOXO3a is activated in response to hypoxic stress and inhibits HIF1-induced apoptosis via regulation of CITED2
    Walbert J Bakker
    Campbell Family Institute for Breast Cancer Research, University Health Network, Ontario Cancer Institute and Princess Margaret Hospital, Toronto, ON M5G 2C1, Canada
    Mol Cell 28:941-53. 2007
    ..Thus, by fine-tuning HIF1 activity, FOXO3a plays an important role in the survival response of normal and cancer cells in response to hypoxic stress...
  83. ncbi Population model of the pharmacokinetics and pharmacodynamics of rivaroxaban--an oral, direct factor xa inhibitor--in healthy subjects
    W Mueck
    Clinical Pharmacology, Pharmacometry, Bayer HealthCare AG, Wuppertal, Germany
    Int J Clin Pharmacol Ther 45:335-44. 2007
    ..This analysis aimed to define population models for the pharmacokinetics (PK) and pharmacodynamics (PD) ofrivaroxaban in healthy males...
  84. ncbi Cardioprotection induced by hydrogen sulfide preconditioning involves activation of ERK and PI3K/Akt pathways
    Yeshi Hu
    Cardiovascular Biology Research Group, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
    Pflugers Arch 455:607-16. 2008
    ..In conclusion, K(ATP)/PKC/ERK1/2 and PI3K/Akt pathways contributed to SP-induced cardioprotection...
  85. ncbi Population pharmacokinetics and pharmacodynamics of once- and twice-daily rivaroxaban for the prevention of venous thromboembolism in patients undergoing total hip replacement
    Wolfgang Mueck
    Bayer HealthCare AG, Aprather Weg 18a, Wuppertal, Germany
    Thromb Haemost 100:453-61. 2008
    ....
  86. ncbi Effect of ZSTK474, a novel phosphatidylinositol 3-kinase inhibitor, on DNA-dependent protein kinase
    Dexin Kong
    Division of Molecular Pharmacology, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan
    Biol Pharm Bull 32:297-300. 2009
    ..These results indicated that ZSTK474 was the most specific agent among these PI3K inhibitors...
  87. ncbi Inhibition of the phosphatidylinositol 3-kinase/p70(S6)-kinase pathway induces B16 melanoma cell differentiation
    R Busca
    INSERM U385, Faculte de Medecine, 06107 Nice, Cedex 02, France
    J Biol Chem 271:31824-30. 1996
    ..Furthermore, we provide evidence which suggests that cAMP-induced melanogenesis and dendricity are, at least partially, mediated by the cAMP inhibition of the phosphatidylinositol 3-kinase/p70(S6)-kinase signaling pathway...
  88. ncbi Oral, direct Factor Xa inhibition with BAY 59-7939 for the prevention of venous thromboembolism after total hip replacement
    B I Eriksson
    Sahlgrenska University HospitalOstra, Gothenburg, Sweden
    J Thromb Haemost 4:121-8. 2006
    ..Joint replacement surgery is an appropriate model for dose-ranging studies investigating new anticoagulants...
  89. ncbi Critical role for PI 3-kinase in the control of erythropoietin-induced erythroid progenitor proliferation
    Didier Bouscary
    Departement d Hematologie, Institut Cochin, Institut National de la Sante et de la Recherche Medicale U567, Centre National de la Recherche Scientifique, UMR 8104, Universite Rene Descartes, Paris, France
    Blood 101:3436-43. 2003
    ....
  90. pmc Potent dual inhibitors of TORC1 and TORC2 complexes (KU-0063794 and KU-0068650) demonstrate in vitro and ex vivo anti-keloid scar activity
    Farhatullah Syed
    Plastic and Reconstructive Surgery Research, Manchester Institute of Biotechnology, University of Manchester, Manchester, UK
    J Invest Dermatol 133:1340-50. 2013
    ..In contrast, Rapamycin induced minimal antitumor activity. In conclusion, potent dual mTORC1 and mTORC2 inhibitors display therapeutic potential for the treatment of KD...
  91. pmc Role of phosphoinositide 3-kinase in activation of ras and mitogen-activated protein kinase by epidermal growth factor
    S Wennström
    Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom
    Mol Cell Biol 19:4279-88. 1999
    ....
  92. pmc Regulation of 4E-BP1 phosphorylation: a novel two-step mechanism
    A C Gingras
    Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec, H3G 1Y6, Canada
    Genes Dev 13:1422-37. 1999
    ..Taken together, our results suggest that 4E-BP1 phosphorylation by FRAP/mTOR on Thr-37 and Thr-46 is a priming event for subsequent phosphorylation of the carboxy-terminal serum-sensitive sites...
  93. ncbi Roles of ceramide synthase and ceramide clearence genes in nilotinib-induced cell death in chronic myeloid leukemia cells
    Aylin Camgoz
    Department of Molecular Biology and Genetics, Faculty of Science, Izmir Institute of Technology, Urla, Izmir, Turkey
    Leuk Lymphoma 52:1574-84. 2011
    ..On the other hand, manipulating bioactive sphingolipids toward generation/accumulation of ceramides increased the apoptotic effects of nilotinib in CML cells...
  94. ncbi Safety evaluation of aprepitant for the prevention of chemotherapy-induced nausea and vomiting
    Christina H Ruhlmann
    Odense University Hospital, Department of Oncology, Sdr Boulevard 29, DK 5000 Odense C, Denmark
    Expert Opin Drug Saf 10:449-62. 2011
    ..Aprepitant is co-administered with a 5-HT(3) RA and a corticosteroid. Although aprepitant is safe, in most clinical settings potential drug-drug interactions need to be considered before prescription...
  95. ncbi Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with cisplatin therapy: randomized, double-blind study protocol--EASE
    Steven Grunberg
    University of Vermont, Dept of Medicine, Fletcher Allen Health Care, 89 Beaumont Ave, Given Bldg E 214, Burlington, VT 05405, USA
    J Clin Oncol 29:1495-501. 2011
    ..This study compared a 3-day oral aprepitant schedule to a regimen containing a single dose of the intravenous NK1RA fosaprepitant...
  96. ncbi Sigma receptor agonist 2-(4-morpholinethyl)1 phenylcyclohexanecarboxylate (Pre084) increases GDNF and BiP expression and promotes neuroprotection after root avulsion injury
    Clara Penas
    Group of Neuroplasticity and Regeneration, Institute of Neurosciences, Department of Cell Biology, Physiology and Immunology, Universitat Autonoma de Barcelona, Bellaterra, Spain
    J Neurotrauma 28:831-40. 2011
    ..Therefore, early application of Sig-1R agonist appears to be a promising therapy to improve MN survival after root avulsion...
  97. ncbi Benefits of mTOR kinase targeting in oncology: pre-clinical evidence with AZD8055
    Gayle Marshall
    Oncology iMED, AstraZeneca, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK
    Biochem Soc Trans 39:456-9. 2011
    ..Potential ways to develop rational combinations with mTOR kinase inhibitors are also discussed. Overall, AZD8055 may provide a better therapeutic strategy than rapamycin and analogues...
  98. ncbi Aprepitant (EMEND): the role of substance P in nausea and vomiting
    Eric Prommer
    UCLA School of Medicine, Division of Hematology Oncology, Los Angeles, CA 90073, USA
    J Pain Palliat Care Pharmacother 19:31-9. 2005
    ..Its broad range of activity against a wide variety of central and peripheral emetogenic stimuli make it potentially useful in non-chemotherapy related nausea and vomiting...
  99. ncbi Synergistic interaction between 17-AAG and phosphatidylinositol 3-kinase inhibition in human malignant glioma cells
    Daniel R Premkumar
    Department of Neurosurgery, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute Brain Tumor Center, Pittsburgh, Pennsylvania, USA
    Mol Carcinog 45:47-59. 2006
    ....
  100. ncbi Modulation of amyloid precursor protein processing by synthetic ceramide analogues
    Hongyun Li
    Prince of Wales Medical Research Institute, Randwick, NSW 2031, Australia
    Biochim Biophys Acta 1801:887-95. 2010
    ..In conclusion, this study provides novel information regarding the regulation of APP processing by synthetic ceramide analogues and reveals that the most potent of these compounds is EtDO-P4...
  101. ncbi The NK-1 receptor antagonist aprepitant as a broad spectrum antitumor drug
    Miguel Munoz
    Research Laboratory on Neuropeptides, Virgen del Rocío University Children s Hospital, Sevilla, Spain
    Invest New Drugs 28:187-93. 2010
    ..These findings reported here for the first time indicate that aprepitant is a new and promising broad spectrum antitumor drug in the treatment of cancer...

Research Grants68

  1. Synthesis and Evaluation of Novel PET NET Tracers
    Jun Zhao; Fiscal Year: 2007
    ..R)-N-methyl 3-(substituted)-pyridinoxyl-3-phenylpropanamines (MPPA) and (S,S)-2-substituted- phenoxypyridinyl morpholines (PPYM), designed starting from the NET binding medications nisoxetine and reboxetine, will be synthesized...
  2. Pretargeting mouse tumor with anti-PSMA antibody-MORF
    Guozheng Liu; Fiscal Year: 2005
    ..Based on our experiences in this pretargeting strategy, we are confident that these investigations on the pretargeting imaging of prostate cancer models with MORFs will be successful. ..
  3. Cannabinoid Regulation of Basal Ganglia Glutamate and GABA
    SCOTT RAWLS; Fiscal Year: 2007
    ..Our outcomes will be a first step in determining whether blocking endocannabinoid inactivation offers any therapeutic advantage over direct activation of cannabinoid receptors with marijuana. [unreadable] [unreadable] [unreadable]..
  4. Can beta-lactam antibiotics decrease morphine physical dependence?
    SCOTT RAWLS; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  5. Drug discrimination and THC withdrawal in monkeys
    LANCE MCMAHON; Fiscal Year: 2005
    ..abstract_text> ..
  6. Pharmacotherapy of Cannabinoid Withdrawal: Pre-Clinical Studies
    Lance R McMahon; Fiscal Year: 2010
    ..Collectively, these specific aims provide a framework for developing novel pharmacotherapies of marijuana withdrawal that could markedly decrease marijuana use and dependence. ..
  7. HISTAMINERGIC MECHANISMS OF ANTINOCICEPTION
    LINDSAY HOUGH; Fiscal Year: 2009
    ..abstract_text> ..
  8. NON-OPIOID ANALGESICS DERIVED FROM IMPROGAN
    LINDSAY HOUGH; Fiscal Year: 2006
    ..These experiments will help to discover the mechanism of action of this novel class of agents, and lead to the development of new pharmacotherapies for pain. ..
  9. Leptin Action and Resistance in POMC-Neurons
    SHANE HENTGES; Fiscal Year: 2005
    ..abstract_text> ..
  10. NICOTINIC RECEPTORS IN MAMMALIAN INTRACARDIAC NEURONS
    Javier Cuevas; Fiscal Year: 2001
    ..An understanding of the properties and physiological role of the receptors is necessary to comprehend neural control of the heart. ..
  11. Joint Action Analysis of Poly-drug Withdrawal
    Robert Raffa; Fiscal Year: 2006
    ..g., electrophysiologic or molecular biology techniques. An improved understanding of how withdrawal is influenced by poly-drug abuse could lead to development of enhanced clinical treatment. ..
  12. ANGIOGENESIS FACTORS AND CEREBRAL ISCHEMIA
    David Greenberg; Fiscal Year: 2001
    ..4. Evaluate whether angiogenesis induced by prior focal ischemia or by administration of VEGF can decrease the size of cerebral infarcts in the same model. ..
  13. Dedifferentiation Following Renal Cell Injury
    Shougang Zhuang; Fiscal Year: 2009
    ..These studies will increase our knowledge of the mechanisms of RPTC dedifferentiation after injury and may contribute to the development of novel treatment for patients with ARF. ..
  14. CELLULAR INTERACTIONS IN PULMONARY OXYGEN TOXICITY
    ANBUKILI CHETTY; Fiscal Year: 2006
    ..This mentored work will provide extensive education and technical experience in Molecular Biology and the development of a model of hyperoxic lung injury. ..
  15. New Neural Targets for Opioid Use Disorders: Human Studies
    Sharon L Walsh; Fiscal Year: 2010
    ..Thus, these studies, conducted in healthy humans, will provide fundamental information regarding the potential for this system as a target for development of new treatment agents for opioid use disorders. ..
  16. GENERAL CLINICAL RESEARCH CENTERS ANNUAL MEETING
    Paul Watkins; Fiscal Year: 2006
    ..abstract_text> ..
  17. Mechanisms of Growth Factor-Estrogen Receptor Crosstalk
    Stephen Safe; Fiscal Year: 2006
    ..abstract_text> ..
  18. Renal Epithelial Sodium Channels and Syntaxins
    Sunil Saxena; Fiscal Year: 2006
    ..Epitope mapping will be used to optimize the specificity of polyclonal antibodies, and anti-sense oligonucleotides will be used to modulate the level of endogenous proteins in the mpkCCDC14 line. ..
  19. MECHANISMS OF CANNABINOID'S ANTIEMETIC ACTIONS
    NISSAR DARMANI; Fiscal Year: 2007
    ..The results will have important implications for the therapeutic utility of these "agonist antiemetics". [unreadable] [unreadable]..
  20. SYNTHESIS OF ANTICANCER AGENTS
    K C Nicolaou; Fiscal Year: 2010
    ..abstract_text> ..
  21. Choroid plexus macrophages in FIV neuropathogenesis
    RICK MEEKER; Fiscal Year: 2009
    ..Together, these studies will provide a a much needed model of HIV infection that will foster the development of therapies that restrict entry of the virus into the brain and minimize the brain damage associated with HIV infection. ..
  22. Gender differences in the interactions between endocannabinoids and stress
    Cecilia Hillard; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  23. Detection of Amyloid Plaques
    Gilles Tamagnan; Fiscal Year: 2008
    ..In this application we proposed to develop a selective compound to quantify these plaques in human. [unreadable] [unreadable] [unreadable] [unreadable]..
  24. AIDS CLINICAL TRIALS UNIT
    Pablo Tebas; Fiscal Year: 2007
    ..The investigators have credentials in basic and patient-oriented clinical research. ..
  25. Opioids: Relative Reinforcing Strength and Dependence
    Carol Paronis; Fiscal Year: 2008
    ..Results of these studies will improve our ability to assess the effectiveness with which agonist-based medications may combat its addictive power. ..
  26. Nicotine and Cognition in Parkinsonism
    Jay Schneider; Fiscal Year: 2008
    ..Information obtained from these studies will hopefully lead to more efficient design of nicotinic therapeutics for patients with a variety of cognitive disorders. ..
  27. Design and Development of Pharmacotherapies for Treating Stimulant Abuse
    Frank Ivy Carroll; Fiscal Year: 2010
    ..3) To continue on a limited basis our development of selected 3-phenyltropane analogs as second-generation pharmacotherapies to treat cocaine addiction. ..
  28. FURANOCOUMARINS AND DRUGS EFFECT ON CYP3A4
    Paul Watkins; Fiscal Year: 2007
    ..abstract_text> ..
  29. 2,3,7,8,--TCDD Effects on the Estrogenic Responses
    Stephen Safe; Fiscal Year: 2006
    ..The proposed Aims will address important mechanistic considerations on IDRE-independent inhibitory AhR-ERa crosstalk and pathways critical for inhibition of mammary tumor growth by SAhRMs. ..
  30. AZABICYCLONONANE SEROTONIN TRANSPORTER RADIOTRACERS
    Gilles Tamagnan; Fiscal Year: 2005
    ..The most promising candidates will be radiolabeled with radionuclides, F-18, or 1-123 as appropriate to the molecule, and evaluated by imaging in vivo in non-human primates in a dedicated PET or SPECT imaging device. ..
  31. A Novel VMAT 2 Radioligand for Imaging Parkinson's
    Gilles Tamagnan; Fiscal Year: 2004
    ..abstract_text> ..
  32. NEUROLOGICAL BASIS OF PAIN: ROLE OF CANNABINOIDS
    J Walker; Fiscal Year: 2003
    ..The results of these studies will reveal mechanisms by which cannabinoids modulate the pathological pain, and suggests future studies directed at determining the role of endocannabinoids in pain processing. ..
  33. ESTROGEN INDUCED RESPONSES VIA ER/SPL COMPLEXES
    Stephen Safe; Fiscal Year: 2002
    ..These results will ultimately facilitate design of chemotherapeutic approaches which target specific genes. ..
  34. BRAIN CELL APOPTOSIS AFTER INTRACEREBRAL HEMORRHAGE
    ENG LO; Fiscal Year: 2003
    ..Results may be used to improve the clinical management and treatment of intracerebral hemorrhage. ..
  35. Research Conference:Mutagenesis and Carcinogenesis
    LAWRENCE MARNETT; Fiscal Year: 2004
    ..Leading scientists in the field will present and evaluate the latest research at the frontiers of mutagenesis and carcinogenesis. ..
  36. CARDINAL BERNARDIN CANCER CENTER, LOYOLA UNIVERSITY
    Patrick Stiff; Fiscal Year: 2002
    ..At the completion of this grant, the Cardinal Bernardin Cancer Center plans to be positioned to successfully apply for a P-30 Cancer Center Support Grant. ..
  37. PERFUSION AND METABOLISM IN COLLATERALIZED MYOCARDIUM
    ROBERT BACHE; Fiscal Year: 2001
    ..A final study will determine whether endogenous NO production is decreased in collateral-dependent myocardium, and whether supplying NO improves the energy demand/supply relationship as indicated by an increase in the PCr/ATP ratio. ..
  38. Convergent central pathways for sympatho-inhibition
    CARON DEAN BERNHOFT; Fiscal Year: 2005
    ..These novel data will be of potential significance to an array of pathologies and behaviors including emotional behaviors, analgesia, shock, sexual function and fainting. ..
  39. EPIDEMIOLOGY OF ANTICOAGULATION IN ATRIAL FIBRILLATION
    Daniel Singer; Fiscal Year: 2005
    ..In all, continued study of our cohort will efficiently provide powerful insights into optimizing stroke prevention strategies for the many older Americans with AF. ..
  40. Factors in Drug Dependence
    Sharon Walsh; Fiscal Year: 2005
    ..abstract_text> ..
  41. Chronic Cannabinoids, Tumor Growth and Hyperalgesia
    DARRYL HAMAMOTO; Fiscal Year: 2005
    ..Positive results from these studies would suggest that cannabinoids could be useful for the treatment of cancer pain. ..
  42. Fatty Acid Synthase in Prostate Tumorigenesis
    BETH PFLUG; Fiscal Year: 2007
    ....
  43. PI3K Signaling in Single Lymphocytes Analyzed by LMS
    David Fruman; Fiscal Year: 2005
    ..Our second aim is to apply this technology to address the role of the PI3K regulatory isoform p85alpha in activation of different downstream signaling molecules. ..
  44. MTOR as a Therapeutic Target in Childhood Cancer
    Peter Houghton; Fiscal Year: 2005
    ..abstract_text> ..
  45. THERAPEUTIC POTENTIAL OF KAPPA-OPIOIDS AGAINST COCAINE
    Sharon Walsh; Fiscal Year: 2002
    ..These studies are relevant to the treatment of cocaine abuse and may lead to the development of an effective pharmacotherapy, thereby, reducing the HIV and other health risks associated with cocaine abuse and intravenous drug abuse. ..
  46. tPA plus MMP inhibition for combination stroke therapy
    Eng H Lo; Fiscal Year: 2010
    ..abstract_text> ..
  47. Molecular Analysis-Directed Individualised Therapy in Ad
    George Simon; Fiscal Year: 2005
    ..Patients will be followed till death and survival curves will be generated. ..
  48. Pathogenic Mechanism of Polycystic Kidney Disease
    Yumay Chen; Fiscal Year: 2010
    ..Our studies will provide novel insight into the molecular pathogenesis of PKD. They will help explain why cysts progress at different rates and how therapies to slow the progression of PKD can be designed rationally. ..
  49. MYOCARDIAL PERFUSION IN THE HYPERTROPHIED HEART
    ROBERT JAMES BACHE; Fiscal Year: 2010
    ..These studies will characterize responses of myocardial KATP channels that may contribute to the development of CHF in the chronically overloaded heart. ..
  50. MARIJUANA WITHDRAWAL
    J Walker; Fiscal Year: 2002
    ..In addition, the investigations in the hippocampus may have relevance to learning and memory and thus have implications for certain mental illnesses such as Alzheimer's disease or other diseases that affect mental health. ..
  51. Cannabinoid Receptors and Cerebrovascular Function
    Cecilia Hillard; Fiscal Year: 2006
    ..Increased understanding of the mediators that are released by activated microglia and their targets may provide new therapeutic approaches to CNS diseases with an inflammatory component. ..
  52. EFFECTS OF NITRIC OXIDE ON FETOPLACENTAL ANGIOGENESIS
    Jing Zheng; Fiscal Year: 2008
    ..An additional Specific Aim IV will use the HPME cell line to confirm the key observations made from OFPAE cells. These studies will glean important information on the mechanisms regulating placental angiogenesis. ..
  53. Harvard Planning Grant for Institutional Clinical and Translational Science Award
    Daniel Singer; Fiscal Year: 2006
    ..We believe our planning process is specific, innovative yet disciplined, and should be robust. A full and competitive CTSA application will be produced in a timely manner. [unreadable] [unreadable] [unreadable]..
  54. CHEMISTRY AND BIOLOGY OF MALONDIALDEHYDE DNA ADDUCTS
    LAWRENCE MARNETT; Fiscal Year: 2004
    ..The results of these experiments will define the chemistry and biology of a family of structurally dynamic lesions in the genome derived from an endogenous metabolic product of lipid oxidation. ..
  55. Engineered Outer Membrane Vesicles as DNA Vaccine Delivery Vehicles
    David Putnam; Fiscal Year: 2007
    ..Validation of the hypothesis will support the future engineering of OMVs with more intricate characteristics, such as cell specific ligands, fusogenic proteins and conformational protein adjuvants. [unreadable] [unreadable] [unreadable]..
  56. CCM proteins and vascular MAPK signal transduction
    Michael Malone; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  57. MATRIX METALLOPROTEINASE AND APOPTOSIS IN BRAIN TRAUMA
    ENG LO; Fiscal Year: 2004
    ..To date, there are not effective treatments for traumatic brain injury. Results from these proposed experiments will help identify MMP and upstream MAP kinase pathways as viable therapeutic targets for this devastating condition. ..
  58. IMMUNOMODULATION IN INFLAMMATORY BOWEL DISEASE
    BRUCE SANDS; Fiscal Year: 2004
    ..The principal investigator seeks to become an independent clinical investigator by completing the didactic and scientific portions of this proposal. ..
  59. Enabling Technologies for Combinatorial Chemistry
    K Nicolaou; Fiscal Year: 2005
    ..abstract_text> ..
  60. IMURAN Dose Ranging Study in Crohn's Disease
    BRUCE SANDS; Fiscal Year: 2005
    ..Abstract Not Provided ..
  61. The role of Gq in insulin resistant cardiac hypertrophy
    Patrick Yue; Fiscal Year: 2006
    ..Specific Aim 3: To study the effect of Gq ablation on the MAPK signaling cascade, a major pathway leading to hypertrophy. ..
  62. Role of inositol trisphosphate in preconditioning
    Karin Przyklenk; Fiscal Year: 2004
    ....
  63. TOTAL SYNTHESIS OF AZADIRACHTIN
    K Nicolaou; Fiscal Year: 2008
    ..The proposed work is expected to impact the general areas of pharmaceutical and agricultural research, and infectious diseases in particular, through discoveries in synthetic organic chemistry and chemical biology. ..
  64. Aging, Adenosine and Platelet-Mediated Thrombosis
    Karin Przyklenk; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  65. TOTAL SYNTHESIS OF APOPTOLIDIN
    K Nicolaou; Fiscal Year: 2004
    ..The proposed work is expected to have significant impact in the area of cancer chemotherapy and should provide enabling technologies and tools for biology and medicine. ..
  66. OSCCAR: A Novel, Population-based Prospective Inception Cohort of Inflammatory Bo
    BRUCE SANDS; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  67. Preconditioning Improves Coronary Patency
    Karin Przyklenk; Fiscal Year: 2007
    ..The resulting mechanistic insights may, ultimately, be exploited in the future design of novel therapies for the clinical treatment of recurrent thrombosis. ..