immunosuppressive agents

Summary

Summary: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging.

Top Publications

  1. ncbi Sirolimus: its discovery, biological properties, and mechanism of action
    S N Sehgal
    Wyeth Ayerst Research, Collegeville, Pennsylvania, USA
    Transplant Proc 35:7S-14S. 2003
  2. ncbi A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis
    Ludwig Kappos
    Department of Neurology, University Hospital, University of Basel, Switzerland
    N Engl J Med 362:387-401. 2010
  3. ncbi Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen
    A M Shapiro
    Surgical Medical Research Institute and the Department of Surgery, University of Alberta, Edmonton, Canada
    N Engl J Med 343:230-8. 2000
  4. ncbi Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis
    Jeffrey A Cohen
    Mellen Center, Cleveland Clinic, Cleveland, OH 44195, USA
    N Engl J Med 362:402-15. 2010
  5. ncbi Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent
    J Keane
    Pulmonary Center, Department of Medicine, Boston University School of Medicine, MA 02118, USA
    N Engl J Med 345:1098-104. 2001
  6. ncbi Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery
    Jeffrey W Moses
    Cardiovascular Research Foundation and Lenox Hill Heart and Vascular Institute of New York, New York 10021, USA
    N Engl J Med 349:1315-23. 2003
  7. ncbi International trial of the Edmonton protocol for islet transplantation
    A M James Shapiro
    Clinical Islet Transplant Program, University of Alberta, Edmonton, AB, Canada
    N Engl J Med 355:1318-30. 2006
  8. ncbi Reduced exposure to calcineurin inhibitors in renal transplantation
    Henrik Ekberg
    Lund University, Malmo, Sweden
    N Engl J Med 357:2562-75. 2007
  9. ncbi The pharmacology of mTOR inhibition
    David A Guertin
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02141, USA
    Sci Signal 2:pe24. 2009
  10. ncbi Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial
    Robert J Motzer
    Memorial Sloan Kettering Cancer Center, New York, NY, USA
    Lancet 372:449-56. 2008

Detail Information

Publications315 found, 100 shown here

  1. ncbi Sirolimus: its discovery, biological properties, and mechanism of action
    S N Sehgal
    Wyeth Ayerst Research, Collegeville, Pennsylvania, USA
    Transplant Proc 35:7S-14S. 2003
    ..its unique mechanism of action, its unique side-effect profile, and its ability to synergize with other immunosuppressive agents. The molecular mechanism underlying the antifungal, antiproliferative, and immunosuppressive activities ..
  2. ncbi A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis
    Ludwig Kappos
    Department of Neurology, University Hospital, University of Basel, Switzerland
    N Engl J Med 362:387-401. 2010
    ....
  3. ncbi Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen
    A M Shapiro
    Surgical Medical Research Institute and the Department of Surgery, University of Alberta, Edmonton, Canada
    N Engl J Med 343:230-8. 2000
    ..Registry data on patients with type 1 diabetes mellitus who undergo pancreatic islet transplantation indicate that only 8 percent are free of the need for insulin therapy at one year...
  4. ncbi Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis
    Jeffrey A Cohen
    Mellen Center, Cleveland Clinic, Cleveland, OH 44195, USA
    N Engl J Med 362:402-15. 2010
    ..Fingolimod (FTY720), a sphingosine-1-phosphate-receptor modulator that prevents lymphocyte egress from lymph nodes, showed clinical efficacy and improvement on imaging in a phase 2 study involving patients with multiple sclerosis...
  5. ncbi Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent
    J Keane
    Pulmonary Center, Department of Medicine, Boston University School of Medicine, MA 02118, USA
    N Engl J Med 345:1098-104. 2001
    ..There is no direct evidence of a protective role of TNF-alpha in patients with tuberculosis...
  6. ncbi Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery
    Jeffrey W Moses
    Cardiovascular Research Foundation and Lenox Hill Heart and Vascular Institute of New York, New York 10021, USA
    N Engl J Med 349:1315-23. 2003
    ..Preliminary reports of studies involving simple coronary lesions indicate that a sirolimus-eluting stent significantly reduces the risk of restenosis after percutaneous coronary revascularization...
  7. ncbi International trial of the Edmonton protocol for islet transplantation
    A M James Shapiro
    Clinical Islet Transplant Program, University of Alberta, Edmonton, AB, Canada
    N Engl J Med 355:1318-30. 2006
    ..We conducted an international, multicenter trial to explore the feasibility and reproducibility of islet transplantation with the use of a single common protocol (the Edmonton protocol)...
  8. ncbi Reduced exposure to calcineurin inhibitors in renal transplantation
    Henrik Ekberg
    Lund University, Malmo, Sweden
    N Engl J Med 357:2562-75. 2007
    ..Immunosuppressive regimens with the fewest possible toxic effects are desirable for transplant recipients. This study evaluated the efficacy and relative toxic effects of four immunosuppressive regimens...
  9. ncbi The pharmacology of mTOR inhibition
    David A Guertin
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02141, USA
    Sci Signal 2:pe24. 2009
    ..Here, we summarize exciting findings regarding mTOR signaling and the outlook for mTOR inhibitors as tools to study the mTOR pathway and as drugs in the clinic...
  10. ncbi Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial
    Robert J Motzer
    Memorial Sloan Kettering Cancer Center, New York, NY, USA
    Lancet 372:449-56. 2008
    ..We did a phase III, randomised, double-blind, placebo-controlled trial of everolimus in patients with metastatic renal cell carcinoma whose disease had progressed on vascular endothelial growth factor-targeted therapy...
  11. pmc Immunoregulatory functions of mTOR inhibition
    Angus W Thomson
    Starzl Transplantation Institute and Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    Nat Rev Immunol 9:324-37. 2009
    ..In this Review, we discuss our current understanding of the mTOR pathway and the consequences of mTOR inhibition, both in DCs and T cells, including new data on the regulation of forkhead box P3 expression...
  12. pmc Rituximab versus cyclophosphamide for ANCA-associated vasculitis
    John H Stone
    Massachusetts General Hospital, Boston, USA
    N Engl J Med 363:221-32. 2010
    ..Uncontrolled studies suggest that rituximab is effective and may be safer than a cyclophosphamide-based regimen...
  13. ncbi Banff 07 classification of renal allograft pathology: updates and future directions
    K Solez
    Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Canada
    Am J Transplant 8:753-60. 2008
    ....
  14. ncbi Oral fingolimod (FTY720) for relapsing multiple sclerosis
    Ludwig Kappos
    Department of Neurology, University Hospital, Basel, Switzerland
    N Engl J Med 355:1124-40. 2006
    ..Fingolimod (FTY720) is a new oral immunomodulating agent under evaluation for the treatment of relapsing multiple sclerosis...
  15. ncbi Cyclosporin A suppresses replication of hepatitis C virus genome in cultured hepatocytes
    Koichi Watashi
    Laboratory of Human Tumor Viruses, Department of Viral Oncology, Institute for Virus Research, Kyoto University, Kyoto, Japan
    Hepatology 38:1282-8. 2003
    ..This anti-HCV activity of CsA appeared to be independent of its immunosuppressive function. In conclusion, our results suggest that CsA may represent a new approach for the development of anti-HCV therapy...
  16. pmc Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis
    Gerald B Appel
    Department of Nephrology, Columbia University, New York, New York, USA
    J Am Soc Nephrol 20:1103-12. 2009
    ..Although most patients in both treatment groups experienced clinical improvement, the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis...
  17. ncbi A phase III study of belatacept-based immunosuppression regimens versus cyclosporine in renal transplant recipients (BENEFIT study)
    F Vincenti
    Kidney Transplant Service, University of California San Francisco, San Francisco, CA, USA
    Am J Transplant 10:535-46. 2010
    ..Belatacept was associated with superior renal function and similar patient/graft survival versus cyclosporine at 1 year posttransplant, despite a higher rate of early acute rejection...
  18. ncbi Sphingosine 1-phosphate receptors in health and disease: mechanistic insights from gene deletion studies and reverse pharmacology
    Volker Brinkmann
    Autoimmunity and Transplantation, Novartis Institutes for BioMedical Research, Lichtstrasse 35, CH 4002 Basel, Switzerland
    Pharmacol Ther 115:84-105. 2007
    ..This review provides an overview on S1P activities and S1P receptor function in health and disease, and summarizes the clinical experience with FTY720 in transplantation and multiple sclerosis...
  19. pmc Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors
    R Westhovens
    UZ Gasthuisberg, Department of Rheumatology, B 3000 Leuven, Belgium
    Ann Rheum Dis 68:1870-7. 2009
    ..To assess the efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis (RA) and poor prognostic factors...
  20. ncbi Everolimus-based, calcineurin-inhibitor-free regimen in recipients of de-novo kidney transplants: an open-label, randomised, controlled trial
    Klemens Budde
    Department of Nephrology, Charite University, Berlin, Germany
    Lancet 377:837-47. 2011
    ..Immunosuppression based on the mammalian-target-of-rapamycin inhibitor everolimus was assessed as a strategy for elimination of calcineurin-inhibitor exposure and optimisation of renal-graft function while maintaining efficacy...
  21. pmc Mechanism of action of oral fingolimod (FTY720) in multiple sclerosis
    Jerold Chun
    Department of Molecular Biology, Helen L Dorris Child and Adolescent Neuropsychiatric Disorder Institute, The Scripps Research Institute, La Jolla, CA, USA
    Clin Neuropharmacol 33:91-101. 2010
    ..Therapeutic efficacy observed in animal studies has been substantiated in phase 2 and 3 trials involving patients with relapsing or relapsing-remitting MS...
  22. ncbi Infusion of mesenchymal stem cells and rapamycin synergize to attenuate alloimmune responses and promote cardiac allograft tolerance
    W Ge
    Department of Surgery, The University of Western Ontario, London, Ontario, Canada
    Am J Transplant 9:1760-72. 2009
    ..This study supports the clinical applicability of MSCs in transplantation...
  23. pmc A major determinant of cyclophilin dependence and cyclosporine susceptibility of hepatitis C virus identified by a genetic approach
    Feng Yang
    Department of Biological Science, Florida State University, Tallahassee, Florida, United States of America
    PLoS Pathog 6:e1001118. 2010
    ..This study describes a new genetic approach to identifying viral targets of cellular cofactors and identifies a major regulator of HCV's susceptibility to CsA and its derivatives that are currently in clinical trials...
  24. pmc Rapamycin ameliorates PKD resulting from conditional inactivation of Pkd1
    Jonathan M Shillingford
    Department of Molecular, Cellular, and Developmental Biology, University of California Santa Barbara, Santa Barbara, CA 93106 9610, USA
    J Am Soc Nephrol 21:489-97. 2010
    ..These data provide in vivo evidence that rapamycin is effective in a human-orthologous mouse model of PKD...
  25. pmc Rapamycin derivatives reduce mTORC2 signaling and inhibit AKT activation in AML
    Zhihong Zeng
    Section of Molecular Hematology and Therapy, Department of Stem Cell Transplantation, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Blood 109:3509-12. 2007
    ..Our study provides the first evidence that rapamycin derivatives inhibit AKT signaling in primary AML cells both in vitro and in vivo, and supports the therapeutic potential of mTOR inhibition strategies in leukemias...
  26. ncbi Infection in solid-organ transplant recipients
    Jay A Fishman
    Transplant Infectious Disease and Compromised Host Program, Massachusetts General Hospital, and Harvard Medical School, Boston, MA 02114, USA
    N Engl J Med 357:2601-14. 2007
  27. ncbi Immunosuppressive drugs for kidney transplantation
    Philip F Halloran
    Division of Nephrology and Transplantation Immunology, University of Alberta, Edmonton, Canada
    N Engl J Med 351:2715-29. 2004
  28. ncbi Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel
    D A Jabs
    Wilmer Eye Institute and the Departments of Ophthalmology and Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Am J Ophthalmol 130:492-513. 2000
    ..To provide recommendations for the use of immunosuppressive drugs in the treatment of patients with ocular inflammatory disorders...
  29. ncbi Efficacy and safety of the selective co-stimulation modulator abatacept following 2 years of treatment in patients with rheumatoid arthritis and an inadequate response to anti-tumour necrosis factor therapy
    M C Genovese
    Stanford University, Division of Immunology and Rheumatology, 1000 Welch Road 203, Palo Alto, CA 94304, USA
    Ann Rheum Dis 67:547-54. 2008
    ..To evaluate the safety and efficacy of abatacept during 2 years of the ATTAIN (Abatacept Trial in Treatment of Anti-TNF INadequate responders) trial in patients with rheumatoid arthritis...
  30. ncbi Calcineurin inhibitor nephrotoxicity
    Maarten Naesens
    Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Herestraat 49, B 3000 Leuven, Belgium
    Clin J Am Soc Nephrol 4:481-508. 2009
    ..Better insight into the mechanisms underlying calcineurin inhibitor nephrotoxicity might pave the way toward more targeted therapy or prevention of calcineurin inhibitor nephrotoxicity...
  31. ncbi Effect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): a randomised, double-blind, placebo-controlled trial
    G Comi
    Institute of Experimental Neurology, Department of Neurology, University Vita Salute, Scientific Institute San Raffaele, Milan, Italy
    Lancet 374:1503-11. 2009
    ..We assessed the efficacy of early treatment with glatiramer acetate in delaying onset of clinically definite multiple sclerosis...
  32. pmc Regulatory CD56(bright) natural killer cells mediate immunomodulatory effects of IL-2Ralpha-targeted therapy (daclizumab) in multiple sclerosis
    Bibiana Bielekova
    Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 103:5941-6. 2006
    ..This immunoregulation has potential importance for the treatment of autoimmune diseases and transplant rejection and toward modification of tumor immunity...
  33. ncbi Conversion from calcineurin inhibitors to sirolimus maintenance therapy in renal allograft recipients: 24-month efficacy and safety results from the CONVERT trial
    Francesco P Schena
    Renal, Dialysis and Transplant Unit, Department of Emergency and Organ Transplant, University of Bari, Bari, Italy
    Transplantation 87:233-42. 2009
    ..The efficacy and safety of converting maintenance renal transplant recipients from calcineurin inhibitors (CNIs) to sirolimus (SRL) was evaluated...
  34. ncbi Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis
    Rachel B Jones
    Vasculitis and Lupus Clinic, Renal Unit, Addenbrooke s Hospital, Cambridge, United Kingdom
    N Engl J Med 363:211-20. 2010
    ..Treatment with rituximab has led to remission rates of 80 to 90% among patients with refractory ANCA-associated vasculitis and may be safer than cyclophosphamide regimens...
  35. ncbi The 10-year follow-up data of the Euro-Lupus Nephritis Trial comparing low-dose and high-dose intravenous cyclophosphamide
    F A Houssiau
    Rheumatology Department, Cliniques Universitaires Saint Luc, Universite Catholique de Louvain, Avenue Hippocrate, 10, B 1200 Bruxelles, Belgium
    Ann Rheum Dis 69:61-4. 2010
    ....
  36. ncbi A phase III study of belatacept versus cyclosporine in kidney transplants from extended criteria donors (BENEFIT-EXT study)
    A Durrbach
    Bicetre Hospital, Kremlin Bicetre, IFRNT, Universite Paris Sud, France
    Am J Transplant 10:547-57. 2010
    ....
  37. pmc Sirolimus is associated with new-onset diabetes in kidney transplant recipients
    Olwyn Johnston
    Division of Nephrology, St Paul s Hospital, University of British Columbia, 1081 Burrard Street, Vancouver, BC, Canada
    J Am Soc Nephrol 19:1411-8. 2008
    ..Given the negative impact of NOD on posttransplantation outcomes, these findings should be confirmed in prospective studies or in meta-analyses of existing trials that involved sirolimus...
  38. pmc Efficacy and safety of certolizumab pegol plus methotrexate in active rheumatoid arthritis: the RAPID 2 study. A randomised controlled trial
    J Smolen
    Department of Internal Medicine III, Medical University of Vienna and 2nd Department of Medicine, Hietzing Hospital, Austria
    Ann Rheum Dis 68:797-804. 2009
    ..Certolizumab pegol is a PEGylated tumour necrosis factor inhibitor...
  39. ncbi Induction and long-term treatment with cyclosporine in membranous nephropathy with the nephrotic syndrome
    Efstathios Alexopoulos
    Department of Nephrology, Hippokration General Hospital, 49, Konstantinoupoleos str, 54642 Thessaloniki, Greece
    Nephrol Dial Transplant 21:3127-32. 2006
    ..However, the optimal dose and the duration of treatment remain controversial issues. We evaluated the efficacy of low-dose CyA alone or combined with corticosteroids as induction and long-term treatment for nephrotic patients with MN...
  40. pmc A CD8+ T cell transcription signature predicts prognosis in autoimmune disease
    Eoin F McKinney
    Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Institute for Medical Research, Addenbrooke s Hospital, Cambridge, UK
    Nat Med 16:586-91, 1p following 591. 2010
    ..These subgroups, which are also found in the normal population and can be identified by measuring expression of only three genes, raise the prospect of individualized therapy and suggest new potential therapeutic targets in autoimmunity...
  41. pmc NFATc1 balances quiescence and proliferation of skin stem cells
    Valerie Horsley
    Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10065, USA
    Cell 132:299-310. 2008
    ..Our findings may explain why patients receiving cyclosporine A for immunosuppressive therapy display excessive hair growth, and unveil a functional role for calcium-NFATc1-CDK4 circuitry in governing stem cell quiescence...
  42. ncbi The ORION study: comparison of two sirolimus-based regimens versus tacrolimus and mycophenolate mofetil in renal allograft recipients
    S M Flechner
    Cleveland Clinic Foundation, OH, USA
    Am J Transplant 11:1633-44. 2011
    ..2, 17% vs. 6%; p = 0.004). Between-group malignancy rates were similar. The SRL-based regimens were not associated with improved outcomes for kidney transplantation patients...
  43. pmc A novel clinically relevant strategy to abrogate autoimmunity and regulate alloimmunity in NOD mice
    Andrea Vergani
    Transplantation Research Center, Children s Hospital and Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    Diabetes 59:2253-64. 2010
    ....
  44. ncbi Tacrolimus once daily (ADVAGRAF) versus twice daily (PROGRAF) in de novo renal transplantation: a randomized phase III study
    B K Krämer
    V Medizinische Klinik, Universitatsklinikum Mannheim, University of Heidelberg, Mannheim, Germany
    Am J Transplant 10:2632-43. 2010
    ..Overall results obtained with either Tacrolimus QD or BID, without antibody induction, were good, supporting use of the once-daily formulation as an effective alternative to the established twice-daily formulation...
  45. ncbi Transplant outcomes and economic costs associated with patient noncompliance to immunosuppression
    B W Pinsky
    Center for Outcomes Research, Saint Louis University School of Medicine, St Louis, MO, USA
    Am J Transplant 9:2597-606. 2009
    ..These findings suggest that interventions to improve medication compliance among kidney transplant recipients should emphasize the benefits of maximal compliance, rather than discourage low compliance...
  46. ncbi Immunosuppressive and anti-angiogenic sphingosine 1-phosphate receptor-1 agonists induce ubiquitinylation and proteasomal degradation of the receptor
    Myat Lin Oo
    Center for Vascular Biology, University of Connecticut Health Center, Farmington, Connecticut 06030 3501, USA
    J Biol Chem 282:9082-9. 2007
    ..We propose that the ability of FTY720-P to target the S1P1 receptor to the ubiquitinylation and proteasomal degradation pathway may at least in part underlie its immunosuppressive and anti-angiogenic properties...
  47. pmc Development of a cross-platform biomarker signature to detect renal transplant tolerance in humans
    Pervinder Sagoo
    MRC Centre for Transplantation, King s College London, London, United Kingdom
    J Clin Invest 120:1848-61. 2010
    ..This study provides an immunological profile of the tolerant state that, with further validation, should inform and shape drug-weaning protocols in renal transplant recipients...
  48. ncbi A retrospective seven-year analysis of the use of B cell depletion therapy in systemic lupus erythematosus at University College London Hospital: the first fifty patients
    Tim Y T Lu
    University College of London, London, UK
    Arthritis Rheum 61:482-7. 2009
    ....
  49. ncbi Inflammatory bowel disease
    Daniel K Podolsky
    Gastrointestinal Unit and the Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, USA
    N Engl J Med 347:417-29. 2002
  50. ncbi EULAR recommendations for the management of primary small and medium vessel vasculitis
    C Mukhtyar
    University of Oxford, Oxford, UK
    Ann Rheum Dis 68:310-7. 2009
    ..To develop European League Against Rheumatism (EULAR) recommendations for the management of small and medium vessel vasculitis...
  51. ncbi Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis
    Ellen M Ginzler
    Division of Rheumatology, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA
    N Engl J Med 353:2219-28. 2005
    ..Since anecdotal series and small, prospective, controlled trials suggest that mycophenolate mofetil may be effective for treating lupus nephritis, larger trials are desirable...
  52. pmc "Inside-out" signaling of sphingosine-1-phosphate: therapeutic targets
    Kazuaki Takabe
    Department of Surgery, Division of Surgical Oncology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA
    Pharmacol Rev 60:181-95. 2008
    ....
  53. ncbi Th17 central memory T cells are reduced by FTY720 in patients with multiple sclerosis
    M Mehling
    Department of Neurology, University Hospitals Basel, Petersgraben 4, CH 4031 Basel, Switzerland
    Neurology 75:403-10. 2010
    ..In this study, we determined the phenotype and frequency of Th17 cells in blood of untreated, FTY720-treated, and interferon-beta (IFNbeta)-treated patients with MS and healthy donors...
  54. ncbi Brain penetration of the oral immunomodulatory drug FTY720 and its phosphorylation in the central nervous system during experimental autoimmune encephalomyelitis: consequences for mode of action in multiple sclerosis
    Carolyn A Foster
    Novartis Institutes for BioMedical Research, Vienna, Austria
    J Pharmacol Exp Ther 323:469-75. 2007
    ..FTY720 effectiveness is likely due to a culmination of mechanisms involving reduction of autoreactive T cells, neuroprotective influence of FTY720-P in the CNS, and inhibition of inflammatory mediators in the brain...
  55. pmc Azathioprine versus mycophenolate mofetil for long-term immunosuppression in lupus nephritis: results from the MAINTAIN Nephritis Trial
    Frédéric A Houssiau
    Rheumatology Department, Cliniques Universitaires Saint Luc, Universite Catholique de Louvain, Saint Luc University Hospital, Brussels 1200, Belgium
    Ann Rheum Dis 69:2083-9. 2010
    ..This investigator-initiated randomised trial tested whether mycophenolate mofetil (MMF) was superior to azathioprine (AZA) as maintenance treatment...
  56. pmc Randomized comparison of systemic anti-inflammatory therapy versus fluocinolone acetonide implant for intermediate, posterior, and panuveitis: the multicenter uveitis steroid treatment trial
    John H Kempen
    Ocular Inflammation Service, The University of Pennsylvania, Philadelphia, Philadelphia, PA 19104, USA
    Ophthalmology 118:1916-26. 2011
    ....
  57. ncbi Different effects of FK506, rapamycin, and mycophenolate mofetil on glucose-stimulated insulin release and apoptosis in human islets
    James D Johnson
    Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada
    Cell Transplant 18:833-45. 2009
    ..Together, our results demonstrate that immunosuppressants impair human beta-cell function and survival, and that these defects can be circumvented to a certain extent with exenatide treatment...
  58. ncbi Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide
    Frédéric A Houssiau
    Cliniques Universitaires St Luc, Universite Catholique de Louvain, Brussels, Belgium
    Arthritis Rheum 46:2121-31. 2002
    ..Given the side effects of this regimen, we evaluated the efficacy and the toxicity of a course of low-dose IV CYC prescribed as a remission-inducing treatment, followed by azathioprine (AZA) as a remission-maintaining treatment...
  59. ncbi Nonadherence consensus conference summary report
    R N Fine
    Stony Brook University Medical Center, Stony Brook, NY, USA
    Am J Transplant 9:35-41. 2009
    ..This consensus report provided some roadmaps for future studies on this complicated, multifaceted problem...
  60. ncbi Reduced necrosis of dystrophic muscle by depletion of host neutrophils, or blocking TNFalpha function with Etanercept in mdx mice
    Stuart Hodgetts
    School of Anatomy and Human Biology, The University of Western Australia, 35 Stirling Highway, Crawley, Western Australia 6009, Australia
    Neuromuscul Disord 16:591-602. 2006
    ..Etanercept is a highly specific anti-inflammatory drug, widely used clinically, and potential application to muscular dystrophies is suggested by this reduced breakdown of mdx skeletal muscle...
  61. ncbi Noninfectious pneumonitis after everolimus therapy for advanced renal cell carcinoma
    Dorothy A White
    Memorial Sloan Kettering Cancer Center, Pulmonary Medicine, New York, NY 10021, USA
    Am J Respir Crit Care Med 182:396-403. 2010
    ..Noninfectious pneumonitis is a known class effect of mammalian target of rapamycin (mTOR) inhibitors...
  62. ncbi Prospective study of polyomavirus type BK replication and nephropathy in renal-transplant recipients
    Hans H Hirsch
    Division of Infectious Diseases, University of Basel, Basel, Switzerland
    N Engl J Med 347:488-96. 2002
    ....
  63. pmc Selective suppression of dendritic cell functions by Mycobacterium ulcerans toxin mycolactone
    Emmanuelle Coutanceau
    Unite de Genetique Moleculaire Bacterienne, Genomes and Genetics Department, Institut Pasteur, 75724 Paris, Cedex 15, France
    J Exp Med 204:1395-403. 2007
    ..Structural similarities between mycolactone and immunosuppressive agents led us to investigate the immunomodulatory properties of mycolactone on dendritic cells (DCs), the key ..
  64. ncbi A novel mechanism of action for anti-thymocyte globulin: induction of CD4+CD25+Foxp3+ regulatory T cells
    Marta Lopez
    Brigham and Women s Hospital, Transplantation Research Center, EBRC, 221 Longwood Avenue, 3rd Floor, Boston, MA 02115, USA
    J Am Soc Nephrol 17:2844-53. 2006
    ..These novel data suggest that ATG not only may promote expansion/generation of regulatory T cells but also may be useful in future ex vivo expansion of these cells for cellular therapy in autoimmunity and clinical transplantation...
  65. ncbi Cyclophosphamide versus placebo in scleroderma lung disease
    Donald P Tashkin
    University of California at Los Angeles, Los Angeles, USA
    N Engl J Med 354:2655-66. 2006
    ....
  66. ncbi Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells
    Manuela Battaglia
    San Raffaele Telethon Institute for Gene Therapy HSR TIGET, Milan, Italy
    Blood 105:4743-8. 2005
    ..Based on this new mode of action, rapamycin can be used to expand CD4(+)CD25(+)FoxP3(+) Tr cells for ex vivo cellular therapy in T-cell-mediated diseases...
  67. ncbi Clinical relevance of pretransplant donor-specific HLA antibodies detected by single-antigen flow-beads
    Patrizia Amico
    Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland
    Transplantation 87:1681-8. 2009
    ..The aims of this study were to investigate to which extent HLA-DSA detected by SAFB represent a risk for antibody-mediated rejection (AMR) and diminished allograft survival, and to define HLA-DSA characteristics predictive for AMR...
  68. ncbi Lower variability of tacrolimus trough concentration after conversion from prograf to advagraf in stable kidney transplant recipients
    Ming Ju Wu
    Division of Nephrology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
    Transplantation 92:648-52. 2011
    ..Variability of blood trough concentration (C0) in immunosuppressant leads to rejection and graft loss after kidney transplantation...
  69. ncbi Efficacy and safety of early cyclosporine conversion to sirolimus with continued MMF-four-year results of the Postconcept study
    Y Lebranchu
    Department of Nephrology, Clinical Immunology, University Hospital, Francois Rabelais University, Tours, France
    Am J Transplant 11:1665-75. 2011
    ..42 ± 0.44 vs. 0.26 ± 0.37; p = 0.018). In summary, the renal benefits associated with conversion of CsA to SRL, at 3 months posttransplantation, in combination with MMF were maintained for 4 years posttransplantation...
  70. ncbi Stem cell factor/c-kit up-regulates cyclin D3 and promotes cell cycle progression via the phosphoinositide 3-kinase/p70 S6 kinase pathway in spermatogonia
    L X Feng
    Department of Cell Biology, Georgetown University Medical Center, Washington, DC. 20007, USA
    J Biol Chem 275:25572-6. 2000
    ..Constitutively active v-AKT highly phosphorylated p70S6K, which was totally inhibited by rapamycin. Thus, SCF/c-kit uses a rapamycin-sensitive PI3-K/AKT/p70S6K/cyclin D3 pathway to promote spermatogonial cell proliferation...
  71. ncbi Clinical pharmacokinetics and pharmacodynamics of tacrolimus in solid organ transplantation
    Christine E Staatz
    School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia
    Clin Pharmacokinet 43:623-53. 2004
    ..Little is known about the magnitude of the pharmacodynamic variability of tacrolimus...
  72. pmc Novel polymorphisms associated with tacrolimus trough concentrations: results from a multicenter kidney transplant consortium
    Pamala A Jacobson
    Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA
    Transplantation 91:300-8. 2011
    ..Although its effect is important, it incompletely explains the variability in tacrolimus concentrations and has a relatively low minor allele frequency in whites relative to African Americans (AA)...
  73. ncbi Brain sphingosine-1-phosphate receptors: implication for FTY720 in the treatment of multiple sclerosis
    Kumlesh K Dev
    Department of Anatomy and Neuroscience, University College Cork, Windle Building, Cork, Ireland
    Pharmacol Ther 117:77-93. 2008
    ..Here, we outline the direct roles that S1P receptors play in the central nervous system (CNS) and discuss additional modalities by which FTY720 may provide direct neuroprotection in MS...
  74. pmc Treatment of intestinal Behçet's syndrome with chimeric tumour necrosis factor alpha antibody
    S P Travis
    Gastroenterology Unit, Derriford Hospital, Plymouth PL6 8DH, UK
    Gut 49:725-8. 2001
    ..Infliximab could have a role for inducing remission in Behçet's syndrome...
  75. ncbi Intraocular methotrexate in the treatment of uveitis and uveitic cystoid macular edema
    Simon R J Taylor
    Department of Clinical Ophthalmology, UCL Institute of Ophthalmology, Moorfields Eye Hospital, London, UK
    Ophthalmology 116:797-801. 2009
    ..A pilot study to evaluate the use of intravitreal methotrexate (MTX) for the treatment of uveitis and uveitic cystoid macular edema (CME)...
  76. ncbi mTOR inhibition with rapamycin causes impaired insulin signalling and glucose uptake in human subcutaneous and omental adipocytes
    Maria J Pereira
    The Lundberg Laboratory for Diabetes Research, Department of Molecular and Clinical Medicine, the Sahlgrenska Academy at University of Gothenburg, 413 45 Gothenburg, Sweden
    Mol Cell Endocrinol 355:96-105. 2012
    ..This is the first study to show that rapamycin reduces glucose uptake in human adipocytes through impaired insulin signalling and this may contribute to the development of insulin resistance associated with rapamycin therapy...
  77. ncbi Noninfectious gastrointestinal (GI) complications of mycophenolic acid therapy: a consequence of local GI toxicity?
    W Arns
    Cologne General Hospital, Merheim Medical Center, Cologne, Germany
    Transplant Proc 39:88-93. 2007
    ..Research which more closely focuses on the local gut pathobiology of MPA-containing drugs may provide a much clearer understanding of the dose-limiting toxicity of this drug class...
  78. ncbi Results of an international, randomized trial comparing glucose metabolism disorders and outcome with cyclosporine versus tacrolimus
    F Vincenti
    University of California San Francisco Kidney Transplant Service, San Francisco, CA, USA
    Am J Transplant 7:1506-14. 2007
    ..The incidence of NODAT or IFG at 6 months post-transplant is significantly lower with CsA-ME than with tacrolimus without a significant difference in short-term outcome...
  79. ncbi Cyclosporine A and adverse effects on organs: histochemical studies
    Rita Rezzani
    Anatomy Section, Department of Biomedical Sciences and Biotechnology, Viale Europa, 11, Brescia 25123, Italy
    Prog Histochem Cytochem 39:85-128. 2004
    ..Moreover, the histochemical and immunohistochemical variations in cellular metabolism and antigenic properties of cells present in the parenchyma of these organs are discussed...
  80. ncbi Sirolimus-eluting and paclitaxel-eluting stents for coronary revascularization
    Stephan Windecker
    Department of Cardiology, University Hospital Bern, Bern, Switzerland
    N Engl J Med 353:653-62. 2005
    ..Sirolimus-eluting stents and paclitaxel-eluting stents, as compared with bare-metal stents, reduce the risk of restenosis. It is unclear whether there are differences in safety and efficacy between the two types of drug-eluting stents...
  81. pmc Cyclosporine for ocular inflammatory diseases
    R Oktay Kaçmaz
    Department of Ophthalmology, The Mount Sinai School of Medicine, New York, New York, USA
    Ophthalmology 117:576-84. 2010
    ..To evaluate the clinical outcomes of cyclosporine treatment for noninfectious ocular inflammation...
  82. ncbi Rapamycin is an effective inhibitor of human renal cancer metastasis
    Fu L Luan
    Department of Medicine, Weill Medical College of Cornell University, New York Presbyterian Hospital New York, New York, USA
    Kidney Int 63:917-26. 2003
    ..Rapamycin is an effective inhibitor of human renal cancer metastasis...
  83. ncbi The immunomodulatory sphingosine 1-phosphate analog FTY720 reduces lesion size and improves neurological outcome in a mouse model of cerebral ischemia
    Bozena Czech
    Pharmazentrum Frankfurt, Klinikum der Johann Wolfgang Goethe Universitat, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany
    Biochem Biophys Res Commun 389:251-6. 2009
    ....
  84. ncbi Incidence of BK with tacrolimus versus cyclosporine and impact of preemptive immunosuppression reduction
    Daniel C Brennan
    Washington University School of Medicine, Department of Internal Medicine, St Louis, Missouri, USA
    Am J Transplant 5:582-94. 2005
    ..Viruria was highest with FK506-MMF and lowest with CyA-MMF. Monitoring and preemptive withdrawal of immunosuppression were associated with resolution of viremia and absence of BK nephropathy without acute rejection or graft loss...
  85. ncbi Opportunities to optimize tacrolimus therapy in solid organ transplantation: report of the European consensus conference
    Pierre Wallemacq
    Department of Clinical Chemistry, Laboratory of Toxicology and Therapeutic Drug Monitoring, Universite Catholique de Louvain, University Hospital St Luc, 10 Hippocrate Avenue, Brussels, Belgium
    Ther Drug Monit 31:139-52. 2009
    ....
  86. ncbi The immunosuppressant FTY720 is phosphorylated by sphingosine kinase type 2
    Steven W Paugh
    Department of Biochemistry, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA
    FEBS Lett 554:189-93. 2003
    ..FTY720 inhibited phosphorylation of sphingosine catalyzed by SphK2 to a greater extent than it inhibits SphK1. Thus, SphK2 may be the relevant enzyme that is responsible for in vivo phosphorylation of FTY720...
  87. ncbi Cyclosporine in patients with steroid-resistant membranous nephropathy: a randomized trial
    D C Cattran
    Department of Medicine, University of Toronto, Toronto, Ontario, Canada
    Kidney Int 59:1484-90. 2001
    ..Cyclosporine has been shown to be effective in cases of progressive MGN, but it has not been used in controlled studies at an early stage of the disease...
  88. ncbi Affinity-driven peptide selection of an NFAT inhibitor more selective than cyclosporin A
    J Aramburu
    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Science 285:2129-33. 1999
    ..Compounds that interfere selectively with the calcineurin-NFAT interaction without affecting calcineurin phosphatase activity may be useful as therapeutic agents that are less toxic than current drugs...
  89. ncbi Effect of tumor microenvironment modulation on the efficacy of oncolytic virus therapy
    Kazuhiko Kurozumi
    Dardinger Laboratory for Neuro oncology and Neurosciences, Department of Neurological Surgery, The Ohio State University, Columbus, OH 43210, USA
    J Natl Cancer Inst 99:1768-81. 2007
    ..We investigated oncolytic virus (OV) therapy-induced changes in tumor blood vessels and the impact of modulating tumor vasculature on the efficacy of oncolytic virus therapy...
  90. ncbi EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases
    S van Assen
    Department of Internal Medicine, Division of Infectious Diseases, University Medical Centre Groningen, AA41 P O Box 30 001, 9700 RB Groningen, The Netherlands
    Ann Rheum Dis 70:414-22. 2011
    ..To develop evidence-based European League Against Rheumatism (EULAR) recommendations for vaccination in patients with autoimmune inflammatory rheumatic diseases (AIIRD)...
  91. pmc Calcineurin regulates innate antifungal immunity in neutrophils
    Matthew B Greenblatt
    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA
    J Exp Med 207:923-31. 2010
    ....
  92. ncbi Immunosuppression: evolution in practice and trends, 1994-2004
    H U Meier-Kriesche
    University of Florida, Gainesville, FL, USA
    Am J Transplant 6:1111-31. 2006
    ..management and strategies for solid-organ transplantation, characterized by the use of new immunosuppressive agents and regimens...
  93. ncbi Sirolimus therapy after early cyclosporine withdrawal reduces the risk for cancer in adult renal transplantation
    Josep M Campistol
    Hospital Clinic i Provincial, Barcelona, Spain
    J Am Soc Nephrol 17:581-9. 2006
    ..Longer follow-up and additional trials are needed to confirm these promising results...
  94. ncbi Everolimus for the prevention of allograft rejection and vasculopathy in cardiac-transplant recipients
    Howard J Eisen
    Section of Cardiology, Temple University, Philadelphia, PA 19140, USA
    N Engl J Med 349:847-58. 2003
    ..We conducted a randomized, double-blind, clinical trial comparing everolimus with azathioprine in recipients of a first heart transplant...
  95. pmc Regulation of presynaptic neurotransmission by macroautophagy
    Daniela Hernandez
    Department of Neuroscience, Columbia University Medical Campus, New York, NY 10013, USA
    Neuron 74:277-84. 2012
    ..Macroautophagy that follows mTOR inhibition in presynaptic terminals, therefore, rapidly alters presynaptic structure and neurotransmission...
  96. ncbi Consensus report on therapeutic drug monitoring of mycophenolic acid in solid organ transplantation
    Dirk R J Kuypers
    Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium
    Clin J Am Soc Nephrol 5:341-58. 2010
    ..Although this consensus report does not evaluate the final role of MPA TDM in transplantation, it seeks to examine the current scientific evidence for concentration-controlled dosing of MPA...
  97. ncbi Everolimus in metastatic renal cell carcinoma: Subgroup analysis of patients with 1 or 2 previous vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapies enrolled in the phase III RECORD-1 study
    E Calvo
    START Madrid, Centro Integral Oncologico Clara Campal, Hospital Madrid Norte Sanchinarro, Madrid, Spain
    Eur J Cancer 48:333-9. 2012
    ..9months with placebo (hazard ratio [HR], 0.33; P<.001). This preplanned, prospective sub-analysis evaluated PFS benefit of everolimus versus placebo in patients who had previously received 1 or 2 VEGFr-TKIs...
  98. pmc Local and regional re-establishment of cellular immunity during curative antibiotherapy of murine Mycobacterium ulcerans infection
    Teresa G Martins
    Life and Health Sciences Research Institute ICVS, School of Health Sciences, University of Minho, Braga, Portugal
    PLoS ONE 7:e32740. 2012
    ..Histological analysis of human tissue samples suggests that such antibiotic treatment reverses the mycolactone-induced local immunosuppression, leading to increased inflammatory infiltrations and phagocytosis of bacilli...
  99. ncbi FTY720 improves functional recovery after spinal cord injury by primarily nonimmunomodulatory mechanisms
    Yusuke Norimatsu
    Department of Orthopedics, Jichi Medical University School of Medicine, Tochigi, Japan
    Am J Pathol 180:1625-35. 2012
    ..Our data highlight the importance of immune-independent functions of FTY720 in decreasing vascular permeability and astrogliosis in the injured spinal cord and promoting locomotor function recovery after SCI...
  100. ncbi Comparison of zotarolimus-eluting and sirolimus-eluting stents in patients with native coronary artery disease: a randomized controlled trial
    David E Kandzari
    Duke Clinical Research Institute, Durham, North Carolina 27705, USA
    J Am Coll Cardiol 48:2440-7. 2006
    ..This trial examined the relative clinical efficacy, angiographic outcomes, and safety of zotarolimus-eluting coronary stents (ZES) with a phosphorylcholine polymer versus sirolimus-eluting stents (SES)...
  101. pmc Phase I clinical and pharmacokinetic study of RAD001 (everolimus) administered daily to Japanese patients with advanced solid tumors
    Isamu Okamoto
    Department of Medical Oncology, Kinki University School of Medicine, 377 2 Ohno Higashi, Osaka Sayama, Osaka 589 8511, Japan
    Jpn J Clin Oncol 40:17-23. 2010
    ..To determine the pharmacokinetics and safety of RAD001 (everolimus) in Japanese patients with advanced solid tumors...

Research Grants68

  1. STATISITICAL DESIGN, MONITORING &COORD. OF VISION CLINICAL TRIALS &EPIDEMIOLOGY
    Keri Hammel; Fiscal Year: 2013
    ..Patients with AIR are generally treated with immunosuppressive agents to treat the eye inflammation;however, the standard treatment for this disease is still being developed...
  2. STATISITICAL DESIGN, MONITORING &COORD. OF VISION CLINICAL TRIALS &EPIDEMIOLOGY
    Keri Hammel; Fiscal Year: 2012
    ..Patients with AIR are generally treated with immunosuppressive agents to treat the eye inflammation;however, the standard treatment for this disease is still being developed...
  3. Targeting Galectin-3 with novel drugs for treatment of eczema
    Fu Tong Liu; Fiscal Year: 2010
    ..We hope the proposed studies will definitively validate galectin-3 as a target for treating atopic dermatitis and lead to the development of a novel therapy for this disease. ..
  4. Non-viral Genetic Modification of Antigen-presenting Cells in Allografts
    Wilson S Meng; Fiscal Year: 2011
    ..Successful completion of the study will lead to improved health outcome of a significant number of patients by decreasing the need for indefinite use of non-specific immunosuppressants in transplant recipients. ..
  5. OLIGOCLONAL T CELL EXPANSION AND RHEUMATOID ARTHRITIS
    Cornelia M Weyand; Fiscal Year: 2012
    ..PUBLIC HEALTH REVELANCE. Despite the development of powerful immunosuppressive agents, we have not succeeded yet in curing patients with RA...
  6. Anti-Fibrotic Therapy for Scleroderma/SSc
    Latha Paka; Fiscal Year: 2010
    ..Common treatments for scleroderma/SSc include immunosuppressive agents, anti-inflammatory agents, vasodilators and anti-fibrotic agents...
  7. Effect Ultraviolet Radiation on Latent M. tuberculosis Infection in Guinea Pigs
    Amminikutty Jeevan; Fiscal Year: 2010
    ..in some individuals as their immune system is compromised by HIV infection, malnutrition or the use of immunosuppressive agents. It is clear from epidemiological studies that reactivation of latent infection is one of the ..
  8. Endothelial-reactive antibodies: a diagnostic test for Susac's syndrome
    WILLIAM JAMES WALDMAN; Fiscal Year: 2011
    ..However, the apparent (but variably) successful treatment of SS with immunosuppressive agents implies an immunologic basis for this disorder...
  9. RNA polymerase II Elongation Complex: Structure and Function
    Daniel Reines; Fiscal Year: 2013
    ..The parts of the transcription machinery studied here are involved in neurological, visual, and immunological diseases. ..
  10. A Novel Model of, and Pre-clinical Therapy for, Scleroderma Lung Disease
    Sergei P Atamas; Fiscal Year: 2012
    ..and expression of cell surface molecules, and resistance to treatment with corticosteroids and other immunosuppressive agents. These experiments will also identify key secondary mediators induced by mIL-442, and determine whether ..
  11. Eotaxin in Colitis and Colitis-Associated Carcinogenesis
    Lori A Coburn; Fiscal Year: 2013
    ..Current treatment regimens for IBD are selected from an assortment of immunosuppressive agents, which can be complicated by multiple side effects and expense...
  12. GAMMA DELTA T CELLS IN LYME ARTHRITIS
    Ralph C Budd; Fiscal Year: 2011
    ..closely resemble autoimmune rheumatoid arthritis in the composition of the synovial tissue, response to immunosuppressive agents, and even the same HLA-DR4 association...
  13. The role of neutrophil extracellular traps and NADPH oxidase in SLE pathogenesis
    ALLISON MARIE CAMPBELL; Fiscal Year: 2012
    ..organ systems, but renal manifestations are the primary contributor to the morbidity of this disease, and immunosuppressive agents are required to slow progression to end stage renal disease...
  14. Anti-Fibrotic Therapy for Scleroderma/SSc
    Latha Paka; Fiscal Year: 2013
    ..Common treatments for scleroderma/SSc include immunosuppressive agents, anti-inflammatory agents, vasodilators and anti-fibrotic agents...
  15. Function and regulation of OATP1B1 and OATP1B3
    Wei Yue; Fiscal Year: 2013
    ..The outcomes of these experiments will greatly broaden our ability to predict and prevent transport-mediated drug-drug interactions. ..
  16. Novel Antifungal Therapeutic Approaches
    Joseph Heitman; Fiscal Year: 2012
    ..The goal is to harness signaling cascades to develop novel antifungal therapies. ..
  17. Role of epithelial HLA-G in lung transplantation
    Steven R White; Fiscal Year: 2010
    ..to long-term survival, yet its pathogenesis is poorly understood and current therapies, including potent immunosuppressive agents, are largely ineffective...
  18. Identification of Immune modulators associated with JC virus replication
    Jennifer Gordon; Fiscal Year: 2013
    ..It is believed that immunosuppression with potent new classes of immunosuppressive agents, including the anti-CD20 molecule, rituximab, allows JC virus to replicate in patients which leads to the ..
  19. Delayed Tolerance Induction in Living Related Donor Renal Transplant Recipients
    Suzanne T Ildstad; Fiscal Year: 2012
    ..solid organ, vascularized composite tissue, and islet transplantation currently require nonspecific immunosuppressive agents indefinitely for graft maintenance...
  20. MicroRNA expression in the NZB/W lupus mouse
    CHRISTOPHER MICHAEL REILLY; Fiscal Year: 2013
    ..mice will show an altered miRNA profile in the initiation and progression of glomerulonephritis and that immunosuppressive agents used in the therapeutic management of SLE act to correct disease, in part, by altering miRNA profiles...
  21. B7-based, CD28 or CTLA-4-specific agonists and antagonists for tolerance inductio
    Roland K Strong; Fiscal Year: 2013
    ..of graft rejection and GVHD, allogeneic HCT recipients are generally treated with combinations of immunosuppressive agents for extended periods of time...
  22. BK Virus Receptor and polyomavirus nephropathy
    Andrey Sorokin; Fiscal Year: 2012
    ..Currently, the only efficient therapy against BKV nephritis appears to be a reduction/change of immunosuppressive agents, and this may increase the inherent risk of rejection...
  23. The role of tolerogenic dendritic cells in islet-cell allograft transplantation
    SHERRIE JILL DIVITO; Fiscal Year: 2010
    ..cellular therapies, and for design of protocols using DC therapy in conjunction with sub-therapeutic immunosuppressive agents to indefinitely prolong islet-cell allograft survival...
  24. NK and T Cell Regulation of ES-Derived Hematopoietic Progenitor Cell Engraftment
    WILLIAM TABAYOYONG; Fiscal Year: 2010
    ..under which ES-derived cells can be transplanted in allogeneic recipients without the use of severe immunosuppressive agents. The objectives of this proposal are to study both the innate and adaptive immune responses directed ..
  25. A High-throughput Screen of Lytic Granule Exocytosis
    Adam Zweifach; Fiscal Year: 2012
    ..via high-throughput screening could lead to new clinically-important drugs that could be used as immunosuppressive agents, and could also provide important insights into the signaling pathways that control the process...
  26. Translational control and latent Toxoplasma infection
    RONALD C contact WEK; Fiscal Year: 2010
    ..The regulation of gene expression plays a key role in this pathogenic process;therefore, our results will be important for new therapies to combat opportunistic infectious diseases, such as Toxoplasma. ..
  27. Mechanisms and Treatment of Chronic, Latent Human Strongyloidiasis
    James B Lok; Fiscal Year: 2013
    ..Milestones indicating success in the R33 phase will be three lead compounds that clear hyperchronic S. stercoralis infection. ..
  28. Translation Regulation of Collagen-1 in Liver Fibrosis: Target of Drug Discovery
    Zarko Manojlovic; Fiscal Year: 2013
    ....
  29. Preserving Renal Function &Protective Immunity Via Anti-LFA1-Based CNI Avoidance
    Kenneth A Newell; Fiscal Year: 2013
    ..In the face of this the pressing unmet need, there have been no fundamentally new immunosuppressive agents that have been approved in the new millennium...
  30. A Total Synthesis of Gambierol Using an Epoxide-Opening Cascade Approach
    DENISE ANN COLBY; Fiscal Year: 2010
    ..An increased understanding of ion channel structure and function could lead to treatments for arrhythmia and disorders of the central nervous system. ..
  31. Redefining membranous nephropathy by autoantibody-specific subclassification
    Laurence H Beck; Fiscal Year: 2013
    ..Treatment for IMN often requires toxic immunosuppressive agents, which themselves cause health problems and risk of serious infection...
  32. PANCREAS AND ISLET TRANSPLANTATION IN HUMANS
    RODERICK PAUL ROBERTSON; Fiscal Year: 2013
    ..carries the huge advantage of examining islet function in a setting without the confounding problems of immunosuppressive agents that are beta-cell toxic and the autoimmune state of type 1 diabetes...
  33. NMR studies of heterocyclization and epimerization in yersiniabactin synthesis
    DOMINIQUE PASCAL FRUEH; Fiscal Year: 2013
    ....
  34. THE IMMUNOBIOLOGY OF CORNEAL ALLOGRAFTS
    Jerry Niederkorn; Fiscal Year: 2013
    ..Even though HLA typing is not performed and topical corticosteroids are the only immunosuppressive agents used, 90% of the corneal transplants will survive the first year...
  35. Imaging of Cardiac Transplant Rejection
    Matthias Nahrendorf; Fiscal Year: 2013
    ..These longitudinal studies will be used to validate functional macrophage-targeted agents for noninvasive heart transplant imaging. ..
  36. Novel Costimulation Blockers in Islet Transplantation
    Scott M Krummey; Fiscal Year: 2013
    ..Current immunosuppressive agents, in particular calcineurin inhibitors (CNIs), induce significant renal toxicity, adverse cardiovascular ..
  37. Pathogenesis of Murine Polyomavirus Allograft Nephropathy
    Kenneth A Newell; Fiscal Year: 2012
    ..aim we will evaluate the source and timing of PyV infection as well as the effects of clinically relevant immunosuppressive agents and anti-viral therapies on the development of PVAN...
  38. Rituximab for Treatment of Type 1 Diabetes: Impact on JC Viral Proliferation
    MARK DAVID PESCOVITZ; Fiscal Year: 2010
    ..with lymphoma, lupus and rheumatoid arthritis treated with rituximab in combination with other potent immunosuppressive agents. With the complex drug history, it is difficult to ascertain the specific role, if any, of rituximab in ..
  39. Calcineurin Phosphatase in Cell Signaling Pathways
    Chi Wing Chow; Fiscal Year: 2010
    ..Defining the role of calcineurin in the 2- adrenergic receptor signaling pathways, therefore, will advance our knowledge of post- transplantation care. ..
  40. DC-ASGPR AS A NOVEL TARGET FOR CONTROLLING GVHD AND ALLOGRAFT REJECTION
    SangKon Oh; Fiscal Year: 2013
    ..Over the past several decades, a large array of immunosuppressive agents has been developed and used for patients...
  41. Consequences of Aging on Immune Response and Transplant Outcome
    STEFAN GUNTHER TULLIUS; Fiscal Year: 2013
    ..Therefore, this study is important because it is novel and it will permit us to develop effective and new therapies to prevent allograft rejection in elderly patients. ..
  42. NK Cell Interactions in Transplantation
    SHERI KRAMS; Fiscal Year: 2009
    ..3) analyze the establishment of mixed chimerism in the absence of NK cells and 4) determine the effect of Immunosuppressive agents on NK cell effector function...
  43. Angiotensin II Blockade for Chronic Allograft Nephropathy
    Hassan N Ibrahim; Fiscal Year: 2011
    ..The drug being studied, Losartan, has proven efficacious in a number of kidney diseases. ..
  44. Quantification and monitoring inflammation in IBD with Molecular Ultrasound
    JUERGEN KARL WILLMANN; Fiscal Year: 2013
    ....
  45. Interdisciplinary Training in Transplantation Biology
    Angus W Thomson; Fiscal Year: 2013
    ..tissue transplantation, evolution of allo- and xenorecognition, xenotransplantation and novel therapeutic immunosuppressive agents/regimens...
  46. Effector function of natural killer T (NKT) cells in sarcoidosis
    Laura L Koth; Fiscal Year: 2010
    ..In addition, by achieving a better understanding of the immunology of sarcoidosis, we may be able to prevent this lung disease. ..
  47. Clinical Refinement of islet transplantation
    NICOLE ANN TURGEON; Fiscal Year: 2011
    ..including LEA29Y (BMS224818) and low dose sirolimus thus avoiding the use of two potent but diabetogenic immunosuppressive agents- steroids and calcineurin inhibitors...
  48. Induction of Donor Tolerance in Renal Transplants
    Suzanne T Ildstad; Fiscal Year: 2012
    ..However, the chronic use of immunosuppressive agents is critical to prevent rejection...
  49. Keratinocyte TLR in Cutaneous Immunity
    Cheryl A Armstrong; Fiscal Year: 2010
    ..bacteria, structural components derived from these bacteria, as well as selected proinflammatory and immunosuppressive agents. Specific Aim #2: To assess selected TLR2 and TLR4 mediated innate immune responses in cultured murine ..
  50. Novel Therapeutic Targets For Calcineurin Inhibitor-Induced And mTOR-Mediated Can
    Soumitro Pal; Fiscal Year: 2013
    ..Renal cancer is one of the major types of cancers in transplant patients. Interestingly, the immunosuppressive agents used in transplant recipients to prevent organ rejection can play a vital role in tumor progression...
  51. The Development Epithelial Sodium Channel Blockers for Chronic Dry Eye
    Benjamin Yerxa; Fiscal Year: 2011
    ..The few current therapies available, which include immunosuppressive agents and over-the-counter tear replacements, are not sufficiently efficacious for many users or only provide ..
  52. The Development Epithelial Sodium Channel Blockers for Chronic Dry Eye
    KARL H DONN; Fiscal Year: 2010
    ..The few current therapies available, which include immunosuppressive agents and over-the-counter tear replacements, are not sufficiently efficacious for many users or only provide ..
  53. Characterization of Autoreactivity to Muscle Proteins in Inclusion Body Myositis
    Mohammad Salajegheh; Fiscal Year: 2013
    ..other inflammatory myopathies, leading to months of unnecessary treatment with glucocorticoid drugs or immunosuppressive agents with significant side effects...
  54. A central role for mTOR in Determining T Cell Activation versus Tolerance
    Jonathan D Powell; Fiscal Year: 2013
    ..Our approach will have important implications with regard to the rationale design of immunosuppressive agents for the treatment of autoimmune disorders and organ transplantation as well as devising strategies to ..
  55. A membrane-based immunotherapy for triple negative breast cancer
    Christopher D Pack; Fiscal Year: 2013
    ..B) Investigate whether co-administration of anti-immunosuppressive agents augments efficacy of the membrane- based TNBC immunotherapy...
  56. Approaches to Tolerance of Allogeneic Kidney and Islet Transplants
    David H Sachs; Fiscal Year: 2013
    ..transplanted organs and tissues as well as the morbidities associated with the administration of lifelong immunosuppressive agents. We have previously shown that allograft tolerance can be induced in NHP via several approaches, one of ..
  57. Amphiregulin in Psoriatic Epidermal Hyperplasia
    JAMES TILFORD ELDER; Fiscal Year: 2010
    ..If successful, this research will have important public health consequences not only in psoriasis but also in a wide variety of dermatoses characterized by epidermal hyperplasia. ..
  58. Does UV-induced Unconventional Mast Cell Migration Activate Immune Suppression?
    Stephen E Ullrich; Fiscal Year: 2012
    ....
  59. Generation of Regulatory T cells ex-vivo for the treatment of systemic lupus eryt
    DAVID O'NEIL; Fiscal Year: 2011
    ..prevention of allograft rejection in a manner that will minimize the use of toxic anti-inflammatory or immunosuppressive agents. PUBLIC HEALTH RELEVANCE: Present pharmaceutical agents used to treat life-threatening autoimmune ..
  60. PROLIFERATIVE CONDITIONING OF TUMOR-COMPETENT DENDRITIC CELL PRECURSORS
    Peter A Cohen; Fiscal Year: 2010
    ..This project aims to provide the information needed to bring this research to a clinical trial for treating cancer patients. ..
  61. Complications of Immunosuppression for Eye Diseases
    John H Kempen; Fiscal Year: 2013
    ..TNF inhibitor therapy;2) evaluate cancer incidence (fatal and non-fatal) for all four major classes of immunosuppressive agents;3) generalize statistical methodology accounting for time- dependent confounding to the paired organ ..
  62. Characterization and Targeting of Immune-evasive Adaptations in Early Neoplasms
    BRADLEY KUBICK; Fiscal Year: 2013
    ..Knowledge of these mechanisms will be used to develop preventative strategies that either target the transformed cells directly or sensitize them to the immune system. ..
  63. THE YEAST ERGOSTEROL PATHWAY
    Martin Bard; Fiscal Year: 2007
    ..DESCRIPTION (provided by applicant): Serious fungal infections are rising due to the increased use of immunosuppressive agents (either employed to sustain organ transplants or as the result of cancer therapy)...
  64. NOVEL COFACTOR ANALOGUES AS IMMUNOSUPPRESSANTS
    Krzysztof Pankiewicz; Fiscal Year: 2000
    ..However, its clinical use is limited due to undesirable metabolism. Certainly, new and specific inhibitors of IMPDH are expected to be of great therapeutic interest and commercial potential. ..
  65. Nitric oxide as a target for dietary intervention in colitis
    Michael Wargovich; Fiscal Year: 2007
    ..applicant): Current medical interventions for colitis consist of application of anti-inflammatory and/or immunosuppressive agents, each complicated by the development of undesirable side effects...
  66. Inosine Monophosphate Dehydrogenase: Regulation and Function
    Beverly Mitchell; Fiscal Year: 2007
    ..IMPDH inhibitors are in current use and under development as immunosuppressive agents and have potential for the treatment of hematologic malignancies...
  67. ENGINEERING PRECURSOR SUPPLY FOR POLYKETIDE BIOSYNTHESIS
    Kevin Reynolds; Fiscal Year: 2003
    ..The use of KSIII and KSIII homologs to generate novel acyl ACP starter units for polyketide biosynthesis and the ability of the PKSs to process these starter units will also be investigated. ..
  68. A Pilot Study of Etanercept in Dermatomyositis
    Anthony Amato; Fiscal Year: 2007
    ..the long-term side effects of prednisone, and the many side effects associated with other second-line immunosuppressive agents (e.g., methotrexate, azathioprine), better treatment options are needed...