sirolimus

Summary

Summary: A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.

Top Publications

  1. ncbi Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer
    Jose Baselga
    Division of Hematology Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA
    N Engl J Med 366:520-9. 2012
  2. pmc Rapamycin fed late in life extends lifespan in genetically heterogeneous mice
    David E Harrison
    The Jackson Laboratory, Bar Harbor, Maine 04609, USA
    Nature 460:392-5. 2009
  3. ncbi Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB
    Dos D Sarbassov
    Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA
    Mol Cell 22:159-68. 2006
  4. ncbi mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery
    Do Hyung Kim
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
    Cell 110:163-75. 2002
  5. 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
  6. pmc mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt
    Kathryn E O'Reilly
    Program in Molecular Pharmacy and Chemistry, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Cancer Res 66:1500-8. 2006
  7. ncbi Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease
    Brinda Ravikumar
    Department of Medical Genetics, Cambridge Institute for Medical Research, Wellcome MRC Building, Addenbrooke s Hospital, Hills Road, Cambridge CB2 2XY, UK
    Nat Genet 36:585-95. 2004
  8. pmc Everolimus for advanced pancreatic neuroendocrine tumors
    James C Yao
    University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    N Engl J Med 364:514-23. 2011
  9. ncbi Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton
    D D Sarbassov
    Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, MA 02142, USA
    Curr Biol 14:1296-302. 2004
  10. pmc An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1
    Carson C Thoreen
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
    J Biol Chem 284:8023-32. 2009

Detail Information

Publications311 found, 100 shown here

  1. ncbi Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer
    Jose Baselga
    Division of Hematology Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA
    N Engl J Med 366:520-9. 2012
    ..In early studies, the mTOR inhibitor everolimus added to endocrine therapy showed antitumor activity...
  2. pmc Rapamycin fed late in life extends lifespan in genetically heterogeneous mice
    David E Harrison
    The Jackson Laboratory, Bar Harbor, Maine 04609, USA
    Nature 460:392-5. 2009
    ..These findings have implications for further development of interventions targeting mTOR for the treatment and prevention of age-related diseases...
  3. ncbi Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB
    Dos D Sarbassov
    Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Department of Biology, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA
    Mol Cell 22:159-68. 2006
    ..Our work describes an unforeseen mechanism of action for rapamycin that suggests it can be used to inhibit Akt/PKB in certain cell types...
  4. ncbi mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery
    Do Hyung Kim
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
    Cell 110:163-75. 2002
    ..We propose that raptor is a missing component of the mTOR pathway that through its association with mTOR regulates cell size in response to nutrient levels...
  5. 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...
  6. pmc mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt
    Kathryn E O'Reilly
    Program in Molecular Pharmacy and Chemistry, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Cancer Res 66:1500-8. 2006
    ..Reversal of this feedback loop by rapamycin may attenuate its therapeutic effects, whereas combination therapy that ablates mTOR function and prevents Akt activation may have improved antitumor activity...
  7. ncbi Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease
    Brinda Ravikumar
    Department of Medical Genetics, Cambridge Institute for Medical Research, Wellcome MRC Building, Addenbrooke s Hospital, Hills Road, Cambridge CB2 2XY, UK
    Nat Genet 36:585-95. 2004
    ..Our data provide proof-of-principle for the potential of inducing autophagy to treat Huntington disease...
  8. pmc Everolimus for advanced pancreatic neuroendocrine tumors
    James C Yao
    University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    N Engl J Med 364:514-23. 2011
    ..We evaluated the agent in a prospective, randomized, phase 3 study...
  9. ncbi Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton
    D D Sarbassov
    Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, MA 02142, USA
    Curr Biol 14:1296-302. 2004
    ..We find that the rictor-mTOR complex modulates the phosphorylation of Protein Kinase C alpha (PKCalpha) and the actin cytoskeleton, suggesting that this aspect of TOR signaling is conserved between yeast and mammals...
  10. pmc An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1
    Carson C Thoreen
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
    J Biol Chem 284:8023-32. 2009
    ..Our findings challenge the assumption that rapamycin completely inhibits mTORC1 and indicate that direct inhibitors of mTORC1 kinase activity may be more successful than rapamycin at inhibiting tumors that depend on mTORC1...
  11. pmc Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity
    Dudley W Lamming
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Science 335:1638-43. 2012
    ..Thus, mTORC2 disruption is an important mediator of the effects of rapamycin in vivo...
  12. pmc DNA damaging agents and p53 do not cause senescence in quiescent cells, while consecutive re-activation of mTOR is associated with conversion to senescence
    Olga V Leontieva
    Department of Cell Stress Biology, Roswell Park Cancer Institute, BLSC, L3 312, Elm and Carlton Streets, Buffalo, NY 14263, USA
    Aging (Albany NY) 2:924-35. 2010
    ..We conclude that induction of p53 does not activate the senescence program in quiescent cells. In cells with induced p53, re-activation of mTOR by serum stimulation causes senescence, as an equivalent of cellular growth...
  13. pmc Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer
    Arkaitz Carracedo
    Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Harvard Medical School, Boston, Massachusetts, USA
    J Clin Invest 118:3065-74. 2008
    ....
  14. ncbi Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control
    Robbie Loewith
    Division of Biochemistry, Biozentrum, University of Basel, Klingelbergstrasse 70, CH 4056 Basel, Switzerland
    Mol Cell 10:457-68. 2002
    ..Thus, the distinct TOR complexes account for the diversity, specificity, and selective rapamycin inhibition of TOR signaling. TORC1 and possibly TORC2 are conserved from yeast to man...
  15. ncbi Rapamycin increases lifespan and inhibits spontaneous tumorigenesis in inbred female mice
    Vladimir N Anisimov
    Department of Carcinogenesis and Oncogerontology, N N Petrov Research Institute of Oncology, St Petersburg, Russia
    Cell Cycle 10:4230-6. 2011
    ..Thus we demonstrated for the first time in normal inbred mice that lifespan can be extended by rapamycin. This opens an avenue to develop optimal doses and schedules of rapamycin as an anti-aging modality...
  16. pmc mTOR regulates memory CD8 T-cell differentiation
    Koichi Araki
    Emory Vaccine Center and Department of Microbiology and Immunology, Atlanta, Georgia, USA
    Nature 460:108-12. 2009
    ..Thus these studies identify a molecular pathway regulating memory formation and provide an effective strategy for improving the functional qualities of vaccine- or infection-induced memory T cells...
  17. pmc Cell cycle arrest is not yet senescence, which is not just cell cycle arrest: terminology for TOR-driven aging
    Mikhail V Blagosklonny
    Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
    Aging (Albany NY) 4:159-65. 2012
    ....
  18. pmc Rapamycin slows aging in mice
    John E Wilkinson
    Unit for Laboratory Animal Medicine and Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA
    Aging Cell 11:675-82. 2012
    ....
  19. ncbi Rapamycin decelerates cellular senescence
    Zoya N Demidenko
    Oncotarget, Albany, NY, USA
    Cell Cycle 8:1888-95. 2009
    ..During cell cycle arrest, rapamycin transformed the irreversible arrest into a reversible condition. Our data demonstrate that senescence can be pharmacologically suppressed...
  20. pmc Mechanisms of life span extension by rapamycin in the fruit fly Drosophila melanogaster
    Ivana Bjedov
    Institute of Healthy Ageing, Department of Genetics, Evolution and Environment, University College London, UK
    Cell Metab 11:35-46. 2010
    ..Rapamycin could increase life span of weak insulin/Igf signaling (IIS) pathway mutants and of flies with life span maximized by dietary restriction, indicating additional mechanisms...
  21. ncbi Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive
    Estela Jacinto
    Biozentrum, University of Basel, Klingelbergstrasse 70, CH 4056 Basel, Switzerland
    Nat Cell Biol 6:1122-8. 2004
    ..mTORC2 is not upstream of the mTORC1 effector S6K. Thus, two distinct TOR complexes constitute a primordial signalling network conserved in eukaryotic evolution to control the fundamental process of cell growth...
  22. pmc Rapamycin extends lifespan and delays tumorigenesis in heterozygous p53+/- mice
    Elena A Komarova
    Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
    Aging (Albany NY) 4:709-14. 2012
    ..In addition, rapamycin decreased the incidence of spontaneous tumors. This observation may have applications in management of Li-Fraumeni syndrome patients characterized by heterozygous mutations in the p53 gene...
  23. ncbi TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth
    Ken Inoki
    Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA
    Cell 126:955-68. 2006
    ..Furthermore, the sequential phosphorylation of TSC2 by AMPK and GSK3 reveals a molecular mechanism of signal integration in cell growth regulation...
  24. pmc Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling
    Yonghao Yu
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Science 332:1322-6. 2011
    ....
  25. ncbi Phase 3 trial of everolimus for metastatic renal cell carcinoma : final results and analysis of prognostic factors
    Robert J Motzer
    Department of Medicine, Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Cancer 116:4256-65. 2010
    ..Final results and analysis of prognostic factors are reported...
  26. ncbi mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha transcriptional complex
    John T Cunningham
    Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 450:736-40. 2007
    ..These results have important implications for our understanding of how these pathways might be altered in metabolic diseases and cancer...
  27. ncbi The TOR pathway: a target for cancer therapy
    Mary Ann Bjornsti
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Nat Rev Cancer 4:335-48. 2004
  28. ncbi Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells
    Omer H Yilmaz
    Howard Hughes Medical Institute, Life Sciences Institute, Department of Internal Medicine, and Center for Stem Cell Biology, University of Michigan, Ann Arbor, Michigan 48109 2216, USA
    Nature 441:475-82. 2006
    ..Mechanistic differences between normal stem cells and cancer stem cells can thus be targeted to deplete cancer stem cells without damaging normal stem cells...
  29. pmc Rapamycin extends maximal lifespan in cancer-prone mice
    Vladimir N Anisimov
    Department of Carcinogenesis and Oncogerontology, N N Petrov Research Institute of Oncology, St Petersburg, Russia
    Am J Pathol 176:2092-7. 2010
    ..Rapamycin dramatically delayed tumor onset as well as decreased the number of tumors per animal and tumor size. We suggest that, by slowing down organismal aging, rapamycin delays cancer...
  30. ncbi Rapamycin and quasi-programmed aging: four years later
    Mikhail V Blagosklonny
    Roswell Park Cancer Institute, Buffalo, NY, USA
    Cell Cycle 9:1859-62. 2010
    ..Taken together with the analysis of clinical data, this pointed to Sirolimus (rapamycin) as a genuine anti-aging drug which will prolong life in humans and prevent age-related diseases by ..
  31. pmc Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2
    Morris E Feldman
    Howard Hughes Medical Institute and Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, USA
    PLoS Biol 7:e38. 2009
    ..These potent new pharmacological agents complement rapamycin in the study of mTOR and its role in normal physiology and human disease...
  32. ncbi Synergistic augmentation of rapamycin-induced autophagy in malignant glioma cells by phosphatidylinositol 3-kinase/protein kinase B inhibitors
    Hayato Takeuchi
    Department of Neurosurgery, University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Cancer Res 65:3336-46. 2005
    ....
  33. pmc Caveolin-1 and accelerated host aging in the breast tumor microenvironment: chemoprevention with rapamycin, an mTOR inhibitor and anti-aging drug
    Isabelle Mercier
    Department of Stem Cell Biology and Regenerative Medicine, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA
    Am J Pathol 181:278-93. 2012
    ..Since stromal loss of Cav-1 is a marker of a lethal tumor microenvironment in breast tumors, these high-risk patients might benefit from treatment with mTOR inhibitors, such as rapamycin or other rapamycin-related compounds (rapalogues)...
  34. pmc Deregulation of the PI3K and KRAS signaling pathways in human cancer cells determines their response to everolimus
    Federica Di Nicolantonio
    Laboratory of Molecular Genetics, Institute for Cancer Research and Treatment, IRCC, University of Turin Medical School, Turin, Italy
    J Clin Invest 120:2858-66. 2010
    ..Thus, our results demonstrate that alterations in the KRAS and PIK3CA genes may represent biomarkers to optimize treatment of patients with mTOR inhibitors...
  35. 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.
  36. pmc Targeting the mTOR signaling network for cancer therapy
    Funda Meric-Bernstam
    Department of Surgical Oncology, Unit 444, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
    J Clin Oncol 27:2278-87. 2009
    ..A better understanding of mTOR signaling, the mechanism of action of rapamycin, and the identification of biomarkers of response will lead to more optimal targeting of this pathway for cancer therapy...
  37. pmc New nanoformulation of rapamycin Rapatar extends lifespan in homozygous p53-/- mice by delaying carcinogenesis
    Maria Comas
    Departments of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
    Aging (Albany NY) 4:715-22. 2012
    ..Our data demonstrate that water soluble Rapatar micelles represent safe, convenient and efficient form of rapamycin suitable for a long-term treatment and that Rapatar may be considered for tumor prevention...
  38. pmc Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice
    Richard A Miller
    Department of Pathology, University of Michigan, Ann Arbor, MI 48109 2200, USA
    J Gerontol A Biol Sci Med Sci 66:191-201. 2011
    ....
  39. ncbi Sch9 is a major target of TORC1 in Saccharomyces cerevisiae
    Jörg Urban
    Department of Molecular Biology, University of Geneva, Geneva, CH 1211, Switzerland
    Mol Cell 26:663-74. 2007
    ..Our results suggest that Sch9 functions analogously to the mammalian TORC1 substrate S6K1 rather than the mTORC2 substrate PKB/Akt...
  40. ncbi Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma
    Gary Hudes
    Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
    N Engl J Med 356:2271-81. 2007
    ..Interferon alfa is widely used for metastatic renal-cell carcinoma but has limited efficacy and tolerability. Temsirolimus, a specific inhibitor of the mammalian target of rapamycin kinase, may benefit patients with this disease...
  41. ncbi Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis
    Darcy A Krueger
    Department of Pediatrics, Tuberous Sclerosis Clinic, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229, USA
    N Engl J Med 363:1801-11. 2010
    ..An alternative may be the use of everolimus, which inhibits the mammalian target of rapamycin, a protein regulated by gene products involved in the tuberous sclerosis complex...
  42. ncbi Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast
    T Noda
    National Institute for Basic Biology, Department of Cell Biology, Nishigonaka 38, Myodaijicho, Okazaki 444, Japan
    J Biol Chem 273:3963-6. 1998
    ..In nutrient-rich medium, Apg proteins are involved also in the transport of aminopeptidase I from the cytosol to the vacuole. Tor may act to switch Apg function between autophagy and transport of aminopeptidase I...
  43. ncbi Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk
    Michael Joner
    CVPath, International Registry of Pathology, Gaithersburg, Maryland 20878, USA
    J Am Coll Cardiol 48:193-202. 2006
    ..This study examined human drug-eluting stents (DES) to determine the long-term effects of these stents on coronary arterial healing and identified mechanisms underlying late stent thrombosis (LST)...
  44. ncbi mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1)
    Juan M García-Martínez
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 416:375-85. 2008
    ..The results of the present study indicate that NDRG1 phosphorylation represents an excellent biomarker for mTORC2 activity...
  45. pmc Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-beta levels in a mouse model of Alzheimer's disease
    Patricia Spilman
    Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America
    PLoS ONE 5:e9979. 2010
    ..Whether inhibition of the mTOR pathway would delay or prevent age-associated disease such as AD remained to be determined...
  46. pmc Regulation of insulin-like growth factor-mammalian target of rapamycin signaling by microRNA in childhood adrenocortical tumors
    Mabrouka Doghman
    Institut de Pharmacologie Moleculaire et Cellulaire, 660 route des Lucioles, 06560 Valbonne, France
    Cancer Res 70:4666-75. 2010
    ..Our results reveal a novel mechanism of regulation of mTOR signaling by miRNAs, and they lay the groundwork for clinical evaluation of drugs inhibiting the mTOR pathway for treatment of adrenocortical cancer...
  47. pmc mTORC1 activation in podocytes is a critical step in the development of diabetic nephropathy in mice
    Ken Inoki
    Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA
    J Clin Invest 121:2181-96. 2011
    ..These results indicate that mTORC1 activation in podocytes is a critical event in inducing DN and suggest that reduction of podocyte mTORC1 activity is a potential therapeutic strategy to prevent DN...
  48. pmc Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling
    Ken Inoki
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    Genes Dev 17:1829-34. 2003
    ..Our data demonstrate that Rheb acts downstream of TSC1/TSC2 and upstream of mTOR to regulate cell growth...
  49. 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...
  50. pmc Regulation of hypoxia-inducible factor 1alpha expression and function by the mammalian target of rapamycin
    Christine C Hudson
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Mol Cell Biol 22:7004-14. 2002
    ..These studies position mTOR as an upstream activator of HIF-1 function in cancer cells and suggest that the antitumor activity of rapamycin is mediated, in part, through the inhibition of cellular responses to hypoxic stress...
  51. ncbi A mammalian protein targeted by G1-arresting rapamycin-receptor complex
    E J Brown
    Department of Chemistry, Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts 02138
    Nature 369:756-8. 1994
    ....
  52. pmc Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis
    John J Bissler
    Division of Nephrology and Hypertension, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229 3039, USA
    N Engl J Med 358:140-51. 2008
    ..The drug sirolimus suppresses mTOR signaling.
  53. ncbi Pseudo-DNA damage response in senescent cells
    Tatyana V Pospelova
    Institute of Cytology, Russian Academy of Sciences, St Petersburg, Russia
    Cell Cycle 8:4112-8. 2009
    ..Thus, cellular senescence leads to activation of atypical DDR without detectable DNA damage. Pseudo-DDR may be a marker of general over-activation of senescent cells...
  54. 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...
  55. ncbi Outcomes associated with drug-eluting and bare-metal stents: a collaborative network meta-analysis
    Christoph Stettler
    Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
    Lancet 370:937-48. 2007
    Whether the two drug-eluting stents approved by the US Food and Drug Administration-a sirolimus-eluting stent and a paclitaxel-eluting stent-are associated with increased risks of death, myocardial infarction, or stent thrombosis ..
  56. pmc TSC-mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species
    Chong Chen
    Program of Cell and Developmental Biology, Division of Immunotherapy, Department of Surgery, University of Michigan Medical School and Comprehensive Cancer Center, Ann Arbor, MI 48109, USA
    J Exp Med 205:2397-408. 2008
    ..The detrimental effect of up-regulated ROS in metabolically active HSCs may explain the well-documented association between quiescence and the "stemness" of HSCs...
  57. ncbi Fighting neurodegeneration with rapamycin: mechanistic insights
    Jordi Bove
    Neurodegenerative Diseases Research Group, Vall d Hebron Research Institute CIBERNED, 08035 Barcelona, Spain
    Nat Rev Neurosci 12:437-52. 2011
    ..Here, we review the molecular mechanisms underlying the neuroprotective effects of rapamycin and discuss the therapeutic potential of this compound for neurodegenerative diseases...
  58. ncbi Prevention of age-related macular degeneration-like retinopathy by rapamycin in rats
    Nataliya G Kolosova
    Institute of Cytology and Genetics, The Siberian Division of the Russian Academy of Sciences, Novosibirsk, Russia
    Am J Pathol 181:472-7. 2012
    ..Rapamycin did not exert any adverse effects on the retina in control disease-free Wistar rats. Taken together, our data suggest the therapeutic potential of rapamycin for treatment and prevention of retinopathy...
  59. ncbi RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs
    D M Sabatini
    Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
    Cell 78:35-43. 1994
    ..We propose that RAFT1 is the direct target of FKBP12-rapamycin and a mammalian homolog of the TOR proteins...
  60. pmc Efficacy and safety of sirolimus in lymphangioleiomyomatosis
    Francis X McCormack
    University of Cincinnati, Cincinnati, OH, USA
    N Engl J Med 364:1595-606. 2011
    ..b>Sirolimus (also called rapamycin) inhibits mTOR and has shown promise in phase 1-2 trials involving patients with LAM.
  61. ncbi Daily oral everolimus activity in patients with metastatic pancreatic neuroendocrine tumors after failure of cytotoxic chemotherapy: a phase II trial
    James C Yao
    Department of Gastrointestinal Medical Oncology, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, Unit 426, Houston, TX 77030, USA
    J Clin Oncol 28:69-76. 2010
    ....
  62. pmc The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling
    Peggy P Hsu
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA
    Science 332:1317-22. 2011
    ..Our work clarifies how mTORC1 inhibits growth factor signaling and opens new areas of investigation in mTOR biology...
  63. ncbi Phase II randomized study of neoadjuvant everolimus plus letrozole compared with placebo plus letrozole in patients with estrogen receptor-positive breast cancer
    Jose Baselga
    Medical Oncology Department, Vall d Hebron University Hospital, P Vall d Hebron, Barcelona, Spain
    J Clin Oncol 27:2630-7. 2009
    ..This study explored whether sensitivity to letrozole was enhanced with the oral mTOR inhibitor, everolimus (RAD001)...
  64. pmc Characterization of the rapamycin-sensitive phosphoproteome reveals that Sch9 is a central coordinator of protein synthesis
    Alexandre Huber
    Department of Molecular Biology, University of Geneva, Geneva, Switzerland
    Genes Dev 23:1929-43. 2009
    ..This demonstrates that Sch9 is a master regulator of protein synthesis...
  65. ncbi Regulation of translation initiation by FRAP/mTOR
    A C Gingras
    Department of Biochemistry, McGill University, Montreal, Quebec H3G 1Y6, Canada
    Genes Dev 15:807-26. 2001
  66. pmc mTORC1-mediated cell proliferation, but not cell growth, controlled by the 4E-BPs
    Ryan J O Dowling
    Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec H3A 1A3, Canada
    Science 328:1172-6. 2010
    ..Thus, control of cell size and cell cycle progression appear to be independent in mammalian cells, whereas in lower eukaryotes, 4E-BPs influence both cell growth and proliferation...
  67. ncbi Adipose-specific knockout of raptor results in lean mice with enhanced mitochondrial respiration
    Pazit Polak
    Biozentrum, University of Basel, Basel, CH 4056, Switzerland
    Cell Metab 8:399-410. 2008
    ..These results suggest that adipose mTORC1 is a regulator of adipose metabolism and, thereby, controls whole-body energy homeostasis...
  68. ncbi Rapamycin induces feedback activation of Akt signaling through an IGF-1R-dependent mechanism
    X Wan
    Molecular Oncology Section, Pediatric Oncology Branch, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, MD 20892 1928, USA
    Oncogene 26:1932-40. 2007
    ..Thus, combining an mTOR inhibitor and an IGF-1R antibody/inhibitor may be an appropriate strategy to enhance mTOR-targeted anticancer therapy...
  69. pmc mTOR is essential for growth and proliferation in early mouse embryos and embryonic stem cells
    Mirei Murakami
    Research and Education Center for Genetic Information, Nara Institute of Science and Technology, Nara 630 0192, Japan
    Mol Cell Biol 24:6710-8. 2004
    ..These data show that mTOR controls both cell size and proliferation in early mouse embryos and embryonic stem cells...
  70. ncbi Pharmacologic inhibition of MEK and PI-3K converges on the mTOR/S6 pathway to decelerate cellular senescence
    Zoya N Demidenko
    Oncotarget, Albany, NY, USA
    Cell Cycle 8:1896-900. 2009
    ..Taken together this suggests that (a) simultaneous activation of PI-3K and MEK is required to ensure cellular senescence and (b) U0126 and LY294002 suppress senescence via the rapamycin-sensitive pathway...
  71. pmc Attenuation of TORC1 signaling delays replicative and oncogenic RAS-induced senescence
    Marina Kolesnichenko
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA
    Cell Cycle 11:2391-401. 2012
    ..These results indicate that TORC1 is an integral component of the signaling pathway that mediates cellular senescence...
  72. pmc The mammalian target of rapamycin signaling pathway mediates epileptogenesis in a model of temporal lobe epilepsy
    Ling Hui Zeng
    Department of Neurology and the Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Neurosci 29:6964-72. 2009
    ..These findings indicate that mTOR signaling mediates mechanisms of epileptogenesis in the kainate rat model and that mTOR inhibitors have potential antiepileptogenic effects in this model...
  73. pmc SREBP activity is regulated by mTORC1 and contributes to Akt-dependent cell growth
    Thomas Porstmann
    Gene Expression Analysis Laboratory, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Cell Metab 8:224-36. 2008
    ..Our results suggest that the PI3K/Akt/TOR pathway regulates protein and lipid biosynthesis in an orchestrated manner and that both processes are required for cell growth...
  74. pmc Role of mTOR in podocyte function and diabetic nephropathy in humans and mice
    Markus Gödel
    Renal Division, University Hospital Freiburg, Freiburg, Germany
    J Clin Invest 121:2197-209. 2011
    ..These results demonstrate the requirement for tightly balanced mTOR activity in podocyte homeostasis and suggest that mTOR inhibition can protect podocytes and prevent progressive diabetic nephropathy...
  75. pmc S6K1(-/-)/S6K2(-/-) mice exhibit perinatal lethality and rapamycin-sensitive 5'-terminal oligopyrimidine mRNA translation and reveal a mitogen-activated protein kinase-dependent S6 kinase pathway
    Mario Pende
    Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland
    Mol Cell Biol 24:3112-24. 2004
    ..These data reveal a redundancy between the S6K and the MAPK pathways in mediating early S6 phosphorylation in response to mitogens...
  76. pmc Reversal of learning deficits in a Tsc2+/- mouse model of tuberous sclerosis
    Dan Ehninger
    Department of Neurobiology, Brain Research Institute, University of California, Los Angeles, 695 Charles E Young Drive South, Los Angeles, California 90095, USA
    Nat Med 14:843-8. 2008
    ....
  77. ncbi Comparison of zotarolimus-eluting and everolimus-eluting coronary stents
    Patrick W Serruys
    Department of Cardiology, Erasmus Medical Center, Molewaterplein 40, Ba 583, 3015 GD Rotterdam, The Netherlands
    N Engl J Med 363:136-46. 2010
    ..However, it is unclear whether there are differences in efficacy and safety between the two types of stents on the basis of prospectively adjudicated end points endorsed by the Food and Drug Administration...
  78. pmc Extension of chronological life span by reduced TOR signaling requires down-regulation of Sch9p and involves increased mitochondrial OXPHOS complex density
    Yong Pan
    Department of Pathology, Yale University School of Medicine, New Haven CT 06520, USA
    Aging (Albany NY) 1:131-45. 2009
    ....
  79. pmc Inhibition of mammalian S6 kinase by resveratrol suppresses autophagy
    Sean M Armour
    Department of Pathology and Paul F Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, Boston, MA 02115, USA
    Aging (Albany NY) 1:515-28. 2009
    ..These data indicate that S6K1 is important for the full induction of autophagy in mammals and raise the possibility that some of the beneficial effects of resveratrol are due to modulation of S6K1 activity...
  80. pmc Effective and selective targeting of leukemia cells using a TORC1/2 kinase inhibitor
    Matthew R Janes
    Department of Molecular Biology and Biochemistry, Institute for Immunology, University of California Irvine, Irvine, California, USA
    Nat Med 16:205-13. 2010
    ..These findings establish that Ph(+) transformed cells are more sensitive than normal lymphocytes to selective TORC1/2 inhibitors and support the development of such inhibitors for leukemia therapy...
  81. pmc Rapamycin differentially inhibits S6Ks and 4E-BP1 to mediate cell-type-specific repression of mRNA translation
    Andrew Y Choo
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 105:17414-9. 2008
    ..Finally, we show that mTOR catalytic inhibitors are effective inhibitors of the rapamycin-resistant phenotype...
  82. ncbi Pathological correlates of late drug-eluting stent thrombosis: strut coverage as a marker of endothelialization
    Aloke V Finn
    Cardiac Unit, Department of Internal Medicine, Massachusetts General Hospital, Boston, USA
    Circulation 115:2435-41. 2007
    ..Although the clinical predictors of LST have been reported, specific morphological and histological correlates of LST remain unknown...
  83. ncbi mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways
    Pradip K Majumder
    Department of Medical Oncology, Dana Farber Cancer Institute, and Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Med 10:594-601. 2004
    ....
  84. ncbi mSin1 is necessary for Akt/PKB phosphorylation, and its isoforms define three distinct mTORC2s
    Maria A Frias
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA
    Curr Biol 16:1865-70. 2006
    ..Even though all mTORC2s can phosphorylate Akt/PKB in vitro, insulin regulates the activity of only two of them. Thus, we propose that cells contain several mTORC2 flavors that may phosphorylate Akt/PKB in response to different signals...
  85. pmc mTOR controls cell cycle progression through its cell growth effectors S6K1 and 4E-BP1/eukaryotic translation initiation factor 4E
    Diane C Fingar
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell Biol 24:200-16. 2004
    ..These data demonstrate that, as for the regulation of cell growth and cell size, the S6K1 and 4E-BP1/eIF4E pathways each represent critical mediators of mTOR-dependent cell cycle control...
  86. ncbi Aging and immortality: quasi-programmed senescence and its pharmacologic inhibition
    Mikhail V Blagosklonny
    Cell Cycle 5:2087-102. 2006
    ..Finally, I discuss that extended life span will reveal new causes for aging (e.g., ROS, 'wear and tear', Hayflick limit, stem cell exhaustion) that play a limited role now, when quasi-programmed senescence kills us first...
  87. pmc Efficacy of RAD001 (everolimus) and octreotide LAR in advanced low- to intermediate-grade neuroendocrine tumors: results of a phase II study
    James C Yao
    Department of Gastrointestinal Medical Oncology, Unit 426, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
    J Clin Oncol 26:4311-8. 2008
    ..Evaluate the activity of everolimus (RAD001) in combination with octreotide long-acting repeatable (LAR) in patients with advanced low- to intermediate-grade neuroendocrine tumors...
  88. ncbi Autophagy enhances the efficacy of BCG vaccine by increasing peptide presentation in mouse dendritic cells
    Chinnaswamy Jagannath
    Department of Pathology and Laboratory Medicine, University of Texas Health Sciences Center UTHSC, 6431, Fannin, Houston, Texas 77030, USA
    Nat Med 15:267-76. 2009
    ..Finally, overexpression of Ag85B in BCG induced autophagy in APCs and enhanced immunogenicity in mice, suggesting that vaccine efficacy can be enhanced by augmenting autophagy-mediated antigen presentation...
  89. pmc Enhanced bioavailability of sirolimus via preparation of solid dispersion nanoparticles using a supercritical antisolvent process
    Min Soo Kim
    College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea
    Int J Nanomedicine 6:2997-3009. 2011
    The aim of this study was to improve the physicochemical properties and bioavailability of poorly water-soluble sirolimus via preparation of a solid dispersion of nanoparticles using a supercritical antisolvent (SAS) process.
  90. ncbi Multicenter phase II study of everolimus in patients with previously treated metastatic gastric cancer
    Toshihiko Doi
    National Cancer Center Hospital East, 5 1, Kashiwanoha 6 chome, Kashiwa shi, Chiba 277 8577, Japan
    J Clin Oncol 28:1904-10. 2010
    ..Adverse events are consistent with the reported safety profile of everolimus. These results warrant further evaluation in patients with advanced gastric cancer...
  91. pmc The efficacy of the novel dual PI3-kinase/mTOR inhibitor NVP-BEZ235 compared with rapamycin in renal cell carcinoma
    Daniel C Cho
    Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
    Clin Cancer Res 16:3628-38. 2010
    ....
  92. pmc mTOR mediates Wnt-induced epidermal stem cell exhaustion and aging
    Rogerio M Castilho
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
    Cell Stem Cell 5:279-89. 2009
    ....
  93. pmc Quantifying pharmacologic suppression of cellular senescence: prevention of cellular hypertrophy versus preservation of proliferative potential
    Zoya N Demidenko
    Oncotarget, Buffalo, NY 14263, USA
    Aging (Albany NY) 1:1008-16. 2009
    ..When p21 was switched off, competent cells, by resuming proliferation, became progressively less hypertrophic. Preservation of proliferative potential is a sensitive and quantitative measure of suppression of mTOR-driven senescence...
  94. pmc Pharmacological inhibition of the mammalian target of rapamycin pathway suppresses acquired epilepsy
    Xiaoxing Huang
    Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, NY 12208, USA
    Neurobiol Dis 40:193-9. 2010
    ..Finally, mTOR inhibition also significantly suppresses mossy fiber sprouting. Our findings suggest the possibility for a much broader window for intervention for some acquired epilepsies by targeting the mTOR pathway...
  95. ncbi Inhibition of mammalian target of rapamycin or apoptotic pathway induces autophagy and radiosensitizes PTEN null prostate cancer cells
    Carolyn Cao
    Department of Radiation Oncology, Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    Cancer Res 66:10040-7. 2006
    ..Together, these data highlight the emerging importance of mTOR as a molecular target for therapeutic intervention, and lend support to the idea that nonapoptotic modes of cell death may play a crucial role in improving tumor cell kill...
  96. ncbi Mammalian target of rapamycin (mTOR) inhibition activates phosphatidylinositol 3-kinase/Akt by up-regulating insulin-like growth factor-1 receptor signaling in acute myeloid leukemia: rationale for therapeutic inhibition of both pathways
    Jerome Tamburini
    Institut Cochin, Departement d Hematologie, Centre National de la Recherche Scientifique Unite Mixte de Recherche 8104, Paris
    Blood 111:379-82. 2008
    ..Our results suggest that dual inhibition of the mTORC1 complex and the IGF-1/IGF-1R/PI3K/Akt pathway in AML may enhance the efficacy of mTOR inhibitors in treatment of this disease...
  97. ncbi Comparison of zotarolimus-eluting stents with sirolimus- and paclitaxel-eluting stents for coronary revascularization: the ZEST (comparison of the efficacy and safety of zotarolimus-eluting stent with sirolimus-eluting and paclitaxel-eluting stent for cor
    Duk Woo Park
    Department of Cardiology, Center for Medical Research and Information, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
    J Am Coll Cardiol 56:1187-95. 2010
    ..aim of this study was to evaluate the relative efficacy and safety of zotarolimus-eluting stents (ZES) in comparison with the established and widely used sirolimus- (SES) and paclitaxel-eluting stents (PES) in routine clinical practice.
  98. ncbi Comparison of inflammatory response after implantation of sirolimus- and paclitaxel-eluting stents in porcine coronary arteries
    Gregory J Wilson
    Department of Laboratory Medicine and Pathobiology, University of Toronto, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada
    Circulation 120:141-9, 1-2. 2009
    Although both sirolimus (CYPHER) and paclitaxel (TAXUS) drug-eluting stents have demonstrated efficacy and safety in clinical trials, human autopsy data have raised concerns about long-term healing and the potential for local ..
  99. pmc Molecular interplay between mammalian target of rapamycin (mTOR), amyloid-beta, and Tau: effects on cognitive impairments
    Antonella Caccamo
    Department of Physiology, University of Texas Health Science Center, San Antonio, Texas 78245, USA
    J Biol Chem 285:13107-20. 2010
    ..The results presented here provide a molecular basis for the Abeta-induced cognitive deficits and, moreover, show that rapamycin, an FDA approved drug, improves learning and memory and reduces Abeta and Tau pathology...
  100. pmc Suppression of PTEN function increases breast cancer chemotherapeutic drug resistance while conferring sensitivity to mTOR inhibitors
    L S Steelman
    Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA
    Oncogene 27:4086-95. 2008
    ..Mutations in the key residues which control PTEN lipid and protein phosphatase may act as dominant-negative mutants to suppress endogenous PTEN and alter the sensitivity of breast cancer patients to chemo- and targeted therapies...
  101. ncbi Aging-suppressants: cellular senescence (hyperactivation) and its pharmacologic deceleration
    Mikhail V Blagosklonny
    Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
    Cell Cycle 8:1883-7. 2009
    ..How can growth inhibitors suppress senescence? May these aging-suppressants decelerate organismal aging? To answer these questions, we need to reconsider the meaning of aging...

Research Grants65

  1. STATISITICAL DESIGN, MONITORING &COORD. OF VISION CLINICAL TRIALS &EPIDEMIOLOGY
    Keri Hammel; Fiscal Year: 2013
    ..Title: A Phase I Study to Investigate Subconjunctival Sirolimus for the Treatment of Active Autoimmune Non-Necrotizing Anterior Scleritis Number: 12-EI-0057 Background: - ..
  2. STATISITICAL DESIGN, MONITORING &COORD. OF VISION CLINICAL TRIALS &EPIDEMIOLOGY
    Keri Hammel; Fiscal Year: 2012
    ..Title: A Phase I Study to Investigate Subconjunctival Sirolimus for the Treatment of Active Autoimmune Non-Necrotizing Anterior Scleritis Number: 12-EI-0057 Background: - ..
  3. Improved Adventitial Sirolimus Therapy for Peripheral Artery Restenosis
    KIRK SEWARD; Fiscal Year: 2010
    ..We propose to deliver sirolimus, a well-known anti-restenotic agent in a novel nanoparticle formulation, directly into the vascular adventitia ..
  4. Donor Stem Cells, Campath, T/B Cell Regulation In HLA-Identical Renal Transplants
    Joshua Miller; Fiscal Year: 2010
    ..This is to be accompanied by a temporary course of therapy with Tacrolimus converted to Sirolimus (Tacro-Siro conversion) to be withdrawn at 12 months, and mycophenolate mofetil (MMF) to be withdrawn by 18 ..
  5. Renal and Cardiovascular Events in Patients with Chronic Kidney Disease
    Akinlolu O Ojo; Fiscal Year: 2013
    ..funded research projects namely: (a) The Chronic Renal Insufficiency Cohort Study (CRIC);and (b) The Sirolimus-based, Steroid Avoidance Immunosuppression in Black de novo Kidney Transplant Recipients...
  6. Improved Therapeutics for Drug Eluting Stents
    Alyssa Panitch; Fiscal Year: 2013
    ..The DESs used in clinical application deliver an anti-proliferative agent, such as sirolimus or paclitaxel (PTX), which inhibits not only smooth muscle cells (SMCs) proliferation, but also prevents ..
  7. Fibrocytes in human pulmonary fibrosis
    C Edward Rose; Fiscal Year: 2013
    ..chemokine receptor expressed on human fibrocytes, and its expression is down-regulated by the mTOR inhibitor, sirolimus;and 5) in an animal model of pulmonary fibrosis, administration of sirolimus results in reduced number of blood ..
  8. The role of hypoxia in venous neointimal hyperplasia in hemodialysis grafts
    Sanjay Misra; Fiscal Year: 2013
    ..using commercially available anti-VEGF-A antibodies (Avastin (Bevacizumab)) and MMP inhibitors (Simvastatin or Sirolimus) which can be delivered using catheter based technology...
  9. Targeting Wnt and mTOR to expand hematopoietic stem cells
    Peter S Klein; Fiscal Year: 2012
    ..vivo and ex vivo using currently available FDA-approved agents, including lithium to inhibit GSK-3 and rapamycin/sirolimus to inhibit mTOR...
  10. Clinical Refinement of islet transplantation
    NICOLE ANN TURGEON; Fiscal Year: 2011
    ..Current data from centers performing islet transplantation worldwide indicates that in the presence of sirolimus-based, steroid-free, low-dose tacrolimus therapy, usually more than one donor pancreas graft is required to ..
  11. Regulation of Vascular Smooth Muscle Cell Proliferation
    Hana Totary Jain; Fiscal Year: 2010
    ..Drug-eluting stents (rapamycin-sirolimus) was a major advance in the treatment of CAD, causing significant reduction in the incidence of restenosis...
  12. The mTOR pathway in neuronal death and epileptogenesis
    Yunfei Huang; Fiscal Year: 2011
    ..Rapamycin (Sirolimus) has been used as immunosuppressant for organ transplantation and was recently put on clinical trial in patients ..
  13. Targeting the mTOR signaling pathway in Autoimmune Lymphoproliferative Syndrome
    David T Teachey; Fiscal Year: 2011
    ..We have treated both mice and children with sirolimus, an mTOR inhibitor (MTI), and found rapid, complete, and durable resolution of disease...
  14. Phase 2 Study of Belatacept, Alemtuzumab, and Sirolimus in Renal Transplantation
    Allan D Kirk; Fiscal Year: 2013
    ..It investigated off-label use of approved drugs: alemtuzumab, belatacept and sirolimus. It has shown that use of a single intraoperative dose of alemtuzumab, followed by maintenance treatment with ..
  15. Development of a new Imaging Platform for Pharmaceutical and Biomedical applicati
    Lynne S Taylor; Fiscal Year: 2012
    ..combined with oral delivery polymers), dexamethasone and naltrexone (combined with biodegradable polymers), and sirolimus and paclitaxel (combined with device coating polymers)...
  16. Regulation of NHE3 by the mTOR/autophagy pathways in diarrheal diseases
    Xinjun Zhu; Fiscal Year: 2013
    ..b>Sirolimus (rapamycin) is frequently used as an immunosuppressant in organ transplantations...
  17. Solving the elusive mechanism of rapamycin action in lymphocytes
    David A Fruman; Fiscal Year: 2013
    ..of T and B lymphocytes profoundly blocks proliferation triggered by antigen and other mitogens, and rapamycin (sirolimus;Rapamune(R)) is an FDA-approved immunosuppressant...
  18. mTOR Signaling and Vascular Repair in an Experimental Model of Diabetes Mellitus
    ALOKE VIRMANI FINN; Fiscal Year: 2013
    ..The majority of DES using in clinical practice are designed to elute pharmacologic agents such as sirolimus that inhibit the mammalian target of rapamycin (mTOR), a member of the phosphatidylinositol kinase-related ..
  19. Layer by layer assembly for making drug-eluting stents
    Kinam Park; Fiscal Year: 2009
    ..The DESs in clinical applications deliver an anti-proliferative agent, such as paclitaxel, sirolimus, or zotarolimus...
  20. ProHealing Drug Alternative for Coronary Drug Eluting Stents
    PATRICK SL WONG; Fiscal Year: 2012
    ..PRM-100 will be compared to drugs currently used on DES, specifically, sirolimus or a sirolimus analogue such as everolimus. Aim 2. In vivo efficacy using a DES platform. Milestone...
  21. Localized Delivery of Sirolimus to Vascular Grafts
    Ronald J Shebuski; Fiscal Year: 2012
    ..primate studies, completed at the Oregon National Primate Research Center, showing that very low doses of sirolimus, locally infused through ePTFE grafts, can effectively and safely abolish the tissue ingrowth that would ..
  22. Targeting Akt signaling in Autoimmune Lymphoproliferative Syndrome
    David T Teachey; Fiscal Year: 2013
    ..We recently demonstrated that targeting mTOR signaling with the mTORC1 inhibitor sirolimus is effective in preclinical models and in children with ALPS...
  23. Paper Spray Ionization Mass Spectrometry Device for Direct Analysis of Biofluid S
    Zheng Ouyang; Fiscal Year: 2011
    ..A representative set of therapeutic drugs including the chemotherapeutic imatinib, the immunosuppressive drugs sirolimus and cyclosporine A, the antiepileptic oxcarbazepine, and the antibiotic gentamicin will be used in this study...
  24. Paper Spray Ionization Mass Spectrometry Device for Direct Analysis of Biofluid S
    Zheng Ouyang; Fiscal Year: 2012
    ..A representative set of therapeutic drugs including the chemotherapeutic imatinib, the immunosuppressive drugs sirolimus and cyclosporine A, the antiepileptic oxcarbazepine, and the antibiotic gentamicin will be used in this study...
  25. Prevention of neointimal thickening by Mst1
    Junichi Sadoshima; Fiscal Year: 2006
    ..Current first- generation DES, such as sirolimus-or taxol-ES, target proliferative changes after stenting, but have several problems, including increased ..
  26. Totally Bioresorbable Drug-eluting Peripheral Polymer Stents
    HOCK SENG TAN; Fiscal Year: 2012
    ..The commonly used anti-inflammatory and anti-proliferative drug, rapamycin (sirolimus), and amorphous bioabsorbable polymer, poly-D,L-lactide, will be applied as drug/polymer coating in this phase I ..
  27. Intramural drug infusion balloon for preventing vascular restenosis
    RON SAHATJIAN; Fiscal Year: 2011
    ..Drugs such as Paclitaxel and Sirolimus are known to inhibit some of the processes that lead to restenosis, if cellular uptake occurs...
  28. Modulation of innate immunity in lung transplantation
    Sadis Matalon; Fiscal Year: 2005
    ..Healthcare, Inc, was planned to compare the efficacy of treating lung transplant patients with tacrolimus and sirolimus versus tacrolimus and azathioprine in reducing the incidence of acute rejection during the first twelve months ..
  29. Development of Second Generation Tissue Engineered Vascular Grafts
    CHRISTOPHER KANE BREUER; Fiscal Year: 2010
    ..of neointimal hyperplasia in tissue engineered vascular grafts in vivo, 2) Determining if controlled release of sirolimus (rapamycin) from the scaffold used to construct tissue engineered vascular conduits can inhibit the development ..
  30. Mixed Chimerism in Haploidentical Non-human Primates
    Bernhard Hering; Fiscal Year: 2006
    ..It is hypothesized that the correct use of anti-CD40L mAb, preferably combined with sirolimus and donor I;ellular antigen, allows, via initial contraction of the alloreactive T cell clone size, induction of ..
  31. PHASE III TRIAL FO SIROLIMUS IN LYMPHANGIOLEIOMYLMATOSIS
    Francis McCormack; Fiscal Year: 2009
    ..Patients with LAM may also develop lymphangitic spread through axial lymph nodes. Sirolimus is a specific inhibitor of Akt signaling that acts at the same point in the pathway as the tuberin/hamartin ..
  32. Effects of Immunosuppressants on Cell Metabolism
    Uwe Christians; Fiscal Year: 2006
    ..With the target-of-rapamycin (TOR) inhibitor sirolimus, an equally potent immunosuppressant that itself is lacking the most important side effects of Cls, such as ..
  33. Pharmacodynamic Thresholds of Immunosuppression
    Rakesh Sindhi; Fiscal Year: 2004
    ..During our studies with regimens of (SRL) sirolimus+cyclosporine/tacrolimus (CsA/TAC), cytokine and costimulatory cell surface proteins (biomarkers), have ..
  34. New NAPRTCS Trials in Steroid-Free Immunosuppression
    Oscar Salvatierra; Fiscal Year: 2007
    ..and mycophenalate mofetit (MMF) and (2) the other, a new protocol with half-dose tacrolimus and substitution of sirolimus for MMF...
  35. Induction of Tolerance to Allografts
    Anthony Monaco; Fiscal Year: 2004
    ..We have utilized non-radiation based lymphoablation with antilymphocyte serum (ALS), rapamycin (sirolimus) and donor bone marrow (BM) to induce indefinite tolerance to fully MHC incompatible murine skin allografts...
  36. Early Growth Response-1 (Egr-1), PKC Beta and Restenosis
    Shi Fang Yan; Fiscal Year: 2007
    ..With the advent of sirolimus-coated stents, the risk of restenosis after angioplasty has been strikingly reduced...
  37. Novel A2A Adenosine Agonists in Vascular Protection
    Jayson Rieger; Fiscal Year: 2005
    ..The results will be compared to commercially available stents containing sirolimus as a gold standard...
  38. Mechanisms of GVHD
    Joseph Antin; Fiscal Year: 2007
    ..Studies of the synergistic combination of sirolimus and tacrolimus in URD transplantation, and the evaluation of CD8 T cell depletion will provide the clinical ..
  39. ISLET TRANSPLANTATION IN NON UREMIC DIABETIC PATIENTS
    Paul Gores; Fiscal Year: 2001
    ..application) The recent development of a steroid-free protocol of immunosuppression by Shapiro, et al, based on sirolimus and tacrolimus, has been a major advance in the field of islet transplantation...
  40. CELLULAR MECHANISMS OF PTLD IN TRANSPLANT RECIPIENTS
    OLIVIA MARTINEZ; Fiscal Year: 2002
    ..We also established that the immunosuppressive sirolimus (RAPA) can directly inhibit the growth of EBV-infected B cells...
  41. OPTIMAL TREATMENT OF FOCAL SEGMENTAL GLOMERULOSCLEROSIS
    Richard Fine; Fiscal Year: 2007
    ..The Specific Aims of this proposal are to compare two regimens: (a) low-dose CS and sirolimus, and (b) intravenous methylprednisolone and cyclophosphamide in patients with SRFSGS who do not respond with a ..
  42. Prediction and assessment of response to targated therapy in pancreatic cancer
    Soner Altiok; Fiscal Year: 2007
    ..incorporate the developed methodology in a phase l/ll clinical study of an mTOR inhibitor rapamycin (Rapamune, Sirolimus, Wyeth) and a Raf/MEK/ERK inhibitor Sorafenib (BAY-439006, Bayer Pharmaceuticals) in second line pancreatic ..
  43. Engineering metabolic flow for rapamycin production
    J Weber; Fiscal Year: 2005
    Rapamycin (sirolimus) has recently been approved for clinical use in transplantation medicine and improved derivatives are already under development...
  44. UCLA IPF Clinical Research Network
    Joseph Lynch; Fiscal Year: 2009
    ..We propose two projects. The first project aims to determine the safety and efficacy of sirolimus combined with interferon gamma-1b (IFN-y lb) in 138 patients with idiopathic pulmonary fibrosis (IPF)...
  45. In Vitro correlates of rapamycin therapy in MS patients
    David Hafler; Fiscal Year: 2004
    ..abstract_text> ..
  46. Systematic Integration POR into Clinical Pathway of HCC
    Myron Schwartz; Fiscal Year: 2006
    ..Secondary prevention after transplantation- "Sirolimus vs Tacrolimus as the Primary Immunosuppressive Agent after Liver Transplantation for HCC"; and 5...
  47. PHARMACOLOGY OF CYCLOSPORINE BASED IMMUNOSUPPRESSION
    Barry Kahan; Fiscal Year: 2004
    ....
  48. FLT PET imaging for evaluating molecular therapeutics
    Jann Sarkaria; Fiscal Year: 2005
    ..abstract_text> ..
  49. DNA Replication Fork: Pausing, Recombination and Disease
    John Bissler; Fiscal Year: 2007
    ..By understanding the effects of these sequences on the fidelity of DNA replication, therapeutic inroads into delaying disease onset can be made. ..
  50. Early prediction of response to combined modality therapy by functional imaging
    Jann Sarkaria; Fiscal Year: 2008
    ..If successful, this approach would facilitate the selection of the most efficacious therapies for individual patients. [unreadable] [unreadable] [unreadable]..
  51. Utility of Rapamycin for the Treatment of Renal Angiomy*
    John Bissler; Fiscal Year: 2004
    ..Successful completion of the aim of this study will help to establish tuberous sclerosis as a valuable model for targeted molecular therapy for neoplasia. ..
  52. Rapamycin as an Antineoplastic Agent
    Ezra Cohen; Fiscal Year: 2006
    ..At the conclusion of the trial RAPA toxicity and effect on p-S6K will be defined over a range of doses as well as the MTD for use in future studies that will develop this agent. ..
  53. S6K and mTOR as targets for tuberous sclerosis
    Kun Liang Guan; Fiscal Year: 2003
    ..To validate S6K as a key downstream effector of TSC1/ TSC2. Biochemical, molecular and cell biological approaches will be used to accomplish these specific aims. ..
  54. Plaque Progression, Apoptosis and Inflammation
    Renu Virmani; Fiscal Year: 2005
    ..abstract_text> ..
  55. ITEM BANKING AND CAT FOR QUALITY OF LIFE OUTCOMES
    David Cella; Fiscal Year: 2008
    ..We will also monitor treatment/management changes, and evaluate acceptability of computer assessments and the perceived benefits of the recommendations. ..
  56. CHOLESTEROL & PLAQUE RUPTURE--WOMEN AND PLAQUE EROSION
    Renu Virmani; Fiscal Year: 2001
    ..In addition, analysis of plaque morphology in the animal model proposed in Project 4 will be carried out in project 1. ..
  57. Functional Infrared Imaging Predicts Radiation Mucositis
    Ezra Cohen; Fiscal Year: 2008
    ..Such a tool would have wide applicability in this patient population and would have tremendous impact on their treatment. [unreadable] [unreadable] [unreadable]..
  58. MTOR as a Therapeutic Target in Childhood Cancer
    Peter Houghton; Fiscal Year: 2005
    ..abstract_text> ..
  59. Phase II Study of 44Gy from 131I-81C6 for CNS Tumors
    David Reardon; Fiscal Year: 2004
    ..To further define the toxicity of this approach and Specific Aim 3.To determine the impact of this therapy on quality of life. ..
  60. ISLET OF LANGERHANS GRAFT MONITORING BY MAGNETIC RESONANCE IMAGING
    Thierry Berney; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  61. Lymphangioleiomyomatosis Research Project
    Francis McCormack; Fiscal Year: 2003
    ..abstract_text> ..
  62. WILD DERIVED MOUSE STOCKS--NEW MODELS FOR AGING RESEARCH
    Richard Miller; Fiscal Year: 2004
    ....
  63. TRANSGENIC MICE, AGING, CANCER, AND OXIDATIVE DAMAGE
    Arlan Richardson; Fiscal Year: 2001
    ..4. To measure parameters of mitochondrial function (e.g., mitochondrial respiration, hydrogen peroxide generation, and permeability transition) in tissues of wild type, Sod2+/-, and Sod2+/-XGpx1+/-F1 mice at 5, 14 and 26 moths of age. ..
  64. Indoleamine 2,3-dioxygenase protective role in lung transplantation
    Gary A Visner; Fiscal Year: 2010
    ....
  65. TOLERANCE TO ISLET ALLOGRAFTS IN TYPE I DIABETES
    Bernhard Hering; Fiscal Year: 2005
    ....