Michael Sporn

Summary

Affiliation: Dartmouth Medical School
Country: USA

Publications

  1. pmc Retinoid X receptor and peroxisome proliferator-activated receptor-gamma agonists cooperate to inhibit matrix metalloproteinase gene expression
    Peter S Burrage
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
    Arthritis Res Ther 10:R139. 2008
  2. ncbi request reprint Role of raloxifene in breast cancer prevention in postmenopausal women: clinical evidence and potential mechanisms of action
    Michael B Sporn
    Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    Clin Ther 26:830-40. 2004
  3. ncbi request reprint New agents for chemoprevention of prostate cancer
    M B Sporn
    Department of Pharmacology, Dartmouth Medical School, Hanover, NH 03755, USA
    Eur Urol 35:420-3. 1999
  4. ncbi request reprint Dichotomies in cancer research: some suggestions for a new synthesis
    Michael B Sporn
    Department of Pharmacology, Dartmouth Medical School, Hanover, NH 03755, USA
    Nat Clin Pract Oncol 3:364-73. 2006
  5. ncbi request reprint Chemoprevention: an essential approach to controlling cancer
    Michael B Sporn
    Department of Pharmacology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    Nat Rev Cancer 2:537-43. 2002
  6. ncbi request reprint Arzoxifene: a promising new selective estrogen receptor modulator for clinical chemoprevention of breast cancer
    Michael B Sporn
    Department of Pharmacology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    Clin Cancer Res 10:5313-5. 2004
  7. pmc New synthetic triterpenoids: potent agents for prevention and treatment of tissue injury caused by inflammatory and oxidative stress
    Michael B Sporn
    Department of Pharmacology, Dartmouth Medical School, Hanover, New Hampshire 03755, United States
    J Nat Prod 74:537-45. 2011
  8. ncbi request reprint Prospects for prevention and treatment of cancer with selective PPARgamma modulators (SPARMs)
    M B Sporn
    Dept of Pharmacology, Dartmouth Medical School, Hanover, NH 03755, USA
    Trends Mol Med 7:395-400. 2001
  9. ncbi request reprint Design and synthesis of tricyclic compounds with enone functionalities in rings A and C: a novel class of highly active inhibitors of nitric oxide production in mouse macrophages
    Frank G Favaloro
    Department of Chemistry, 6128 Burke Laboratory, Dartmouth College, Hanover, New Hampshire 03755, USA
    J Med Chem 45:4801-5. 2002
  10. ncbi request reprint A new rexinoid, NRX194204, prevents carcinogenesis in both the lung and mammary gland
    Karen Liby
    Department of Pharmacology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    Clin Cancer Res 13:6237-43. 2007

Detail Information

Publications69

  1. pmc Retinoid X receptor and peroxisome proliferator-activated receptor-gamma agonists cooperate to inhibit matrix metalloproteinase gene expression
    Peter S Burrage
    Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA
    Arthritis Res Ther 10:R139. 2008
    ..The goals of this study were to evaluate the inhibition of IL-1-beta-induced expression of MMP-1 and MMP-13 by combinatorial treatment with RXR and PPARgamma ligands and to investigate the molecular mechanisms of this inhibition...
  2. ncbi request reprint Role of raloxifene in breast cancer prevention in postmenopausal women: clinical evidence and potential mechanisms of action
    Michael B Sporn
    Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    Clin Ther 26:830-40. 2004
    ..16; 95% ci, 0.09-0.30)...
  3. ncbi request reprint New agents for chemoprevention of prostate cancer
    M B Sporn
    Department of Pharmacology, Dartmouth Medical School, Hanover, NH 03755, USA
    Eur Urol 35:420-3. 1999
    ....
  4. ncbi request reprint Dichotomies in cancer research: some suggestions for a new synthesis
    Michael B Sporn
    Department of Pharmacology, Dartmouth Medical School, Hanover, NH 03755, USA
    Nat Clin Pract Oncol 3:364-73. 2006
    ..Finally, the importance of context in cancer biology is emphasized, as epitomized in Walt Whitman's famous quotation that "Nothing out of its place is good and nothing in its place is bad."..
  5. ncbi request reprint Chemoprevention: an essential approach to controlling cancer
    Michael B Sporn
    Department of Pharmacology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    Nat Rev Cancer 2:537-43. 2002
    ....
  6. ncbi request reprint Arzoxifene: a promising new selective estrogen receptor modulator for clinical chemoprevention of breast cancer
    Michael B Sporn
    Department of Pharmacology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    Clin Cancer Res 10:5313-5. 2004
  7. pmc New synthetic triterpenoids: potent agents for prevention and treatment of tissue injury caused by inflammatory and oxidative stress
    Michael B Sporn
    Department of Pharmacology, Dartmouth Medical School, Hanover, New Hampshire 03755, United States
    J Nat Prod 74:537-45. 2011
    ..Clinical investigation of a new SO (methyl 2-cyano-3,12-dioxooleana-1,9(11)dien-28-oate, "CDDO-Me", bardoxolone methyl, 13) is currently in progress...
  8. ncbi request reprint Prospects for prevention and treatment of cancer with selective PPARgamma modulators (SPARMs)
    M B Sporn
    Dept of Pharmacology, Dartmouth Medical School, Hanover, NH 03755, USA
    Trends Mol Med 7:395-400. 2001
    ....
  9. ncbi request reprint Design and synthesis of tricyclic compounds with enone functionalities in rings A and C: a novel class of highly active inhibitors of nitric oxide production in mouse macrophages
    Frank G Favaloro
    Department of Chemistry, 6128 Burke Laboratory, Dartmouth College, Hanover, New Hampshire 03755, USA
    J Med Chem 45:4801-5. 2002
    ....
  10. ncbi request reprint A new rexinoid, NRX194204, prevents carcinogenesis in both the lung and mammary gland
    Karen Liby
    Department of Pharmacology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    Clin Cancer Res 13:6237-43. 2007
    ....
  11. ncbi request reprint A novel dicyanotriterpenoid, 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-onitrile, active at picomolar concentrations for inhibition of nitric oxide production
    Tadashi Honda
    Department of Chemistry, Dartmouth College, Hanover, NH 03755, USA
    Bioorg Med Chem Lett 12:1027-30. 2002
    ..This potency is about 100 times and 30 times more potent than CDDO and dexamethasone, respectively...
  12. ncbi request reprint The synthetic triterpenoids CDDO-methyl ester and CDDO-ethyl amide prevent lung cancer induced by vinyl carbamate in A/J mice
    Karen Liby
    Department of Pharmacology, Dartmouth Medical School, Hanover, NH 03755, USA
    Cancer Res 67:2414-9. 2007
    ....
  13. pmc A novel acetylenic tricyclic bis-(cyano enone) potently induces phase 2 cytoprotective pathways and blocks liver carcinogenesis induced by aflatoxin
    Karen Liby
    Dartmouth Medical School, Hanover, NH 03755, USA
    Cancer Res 68:6727-33. 2008
    ....
  14. ncbi request reprint Prevention and treatment of experimental breast cancer with the combination of a new selective estrogen receptor modulator, arzoxifene, and a new rexinoid, LG 100268
    Nanjoo Suh
    Department of Pharmacology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    Clin Cancer Res 8:3270-5. 2002
    ....
  15. doi request reprint Prevention and treatment of experimental estrogen receptor-negative mammary carcinogenesis by the synthetic triterpenoid CDDO-methyl Ester and the rexinoid LG100268
    Karen Liby
    Department of Pharmacology, Dartmouth Medical School, Hanover, NH 03755, USA
    Clin Cancer Res 14:4556-63. 2008
    ....
  16. ncbi request reprint Triterpenoids and rexinoids as multifunctional agents for the prevention and treatment of cancer
    Karen T Liby
    Department of Pharmacology, Dartmouth Medical School, Hanover, NH 03755, USA
    Nat Rev Cancer 7:357-69. 2007
    ..Both classes of agents can prevent and treat cancer in experimental animals. These drugs have unique molecular and cellular mechanisms of action and might prove to be synergistic with standard anti-cancer treatments...
  17. ncbi request reprint Novel semisynthetic analogues of betulinic acid with diverse cytoprotective, antiproliferative, and proapoptotic activities
    Karen Liby
    Dartmouth Medical School, Hanover, NH 03755, USA
    Mol Cancer Ther 6:2113-9. 2007
    ..These results suggest that BA is a useful platform for drug development, and the enhanced potency and varied biological activities of CBA-Im make it a promising candidate for further chemoprevention or chemotherapeutic studies...
  18. ncbi request reprint The selective estrogen receptor modulator arzoxifene and the rexinoid LG100268 cooperate to promote transforming growth factor beta-dependent apoptosis in breast cancer
    Mara H Rendi
    Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    Cancer Res 64:3566-71. 2004
    ..The new protocol we have developed for chemoprevention allows the efficacious and safe administration of 268 and Arz, and these agents now should be considered for clinical use...
  19. pmc Novel tricyclic compounds having acetylene groups at C-8a and cyano enones in rings A and C: highly potent anti-inflammatory and cytoprotective agents
    Tadashi Honda
    Department of Chemistry, Dartmouth College, 6128 Burke Laboratory, Hanover, New Hampshire 03755, USA
    J Med Chem 50:1731-4. 2007
    ..Both in vitro and in vivo potencies are markedly higher than those of 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO), which is being evaluated as an anticancer drug in phase I clinical trials...
  20. ncbi request reprint Cancer chemoprevention: scientific promise, clinical uncertainty
    Michael B Sporn
    Department of Pharmacology, Dartmouth Medical School, Hanover, NH 03755, USA
    Nat Clin Pract Oncol 2:518-25. 2005
    ..The development of new drugs for the control of these targets that are both safe and effective will be important for the future of cancer chemoprevention...
  21. pmc Design, synthesis, and anti-inflammatory activity both in vitro and in vivo of new betulinic acid analogues having an enone functionality in ring A
    Tadashi Honda
    Department of Chemistry, Dartmouth College, Hanover, NH 03755, USA
    Bioorg Med Chem Lett 16:6306-9. 2006
    ..Analogue 10 is highly and orally active in vivo for induction of the anti-inflammatory and cytoprotective enzyme, heme oxygenase-1...
  22. ncbi request reprint The combination of the rexinoid, LG100268, and a selective estrogen receptor modulator, either arzoxifene or acolbifene, synergizes in the prevention and treatment of mammary tumors in an estrogen receptor-negative model of breast cancer
    Karen Liby
    Dartmouth Medical School, Hanover, NH 03755, USA
    Clin Cancer Res 12:5902-9. 2006
    ..We tested whether a selective estrogen receptor modulator (SERM) and a rexinoid are active for prevention and treatment in the mouse mammary tumor virus-neu mouse model of estrogen receptor-negative breast cancer...
  23. doi request reprint The rexinoid LG100268 and the synthetic triterpenoid CDDO-methyl amide are more potent than erlotinib for prevention of mouse lung carcinogenesis
    Karen Liby
    Department of Pharmacology, Dartmouth Medical School, Hanover, NH 03755, USA
    Mol Cancer Ther 7:1251-7. 2008
    ..Because rexinoids and triterpenoids signal through different biological pathways, they should be tested in combination for the prevention of lung cancer...
  24. pmc Synthetic triterpenoids prolong survival in a transgenic mouse model of pancreatic cancer
    Karen T Liby
    Department of Medicine, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    Cancer Prev Res (Phila) 3:1427-34. 2010
    ..These results suggest that oleanane triterpenoids and rexinoids have the potential to prevent pancreatic cancer...
  25. pmc 2-Cyano-3,10-dioxooleana-1,9(11)-dien-28-oic acid anhydride. A novel and highly potent anti-inflammatory and cytoprotective agent
    Tadashi Honda
    Department of Chemistry, Dartmouth College, Hanover, NH 03755, USA
    Bioorg Med Chem Lett 20:2275-8. 2010
    ..Notably, preliminary phamacokinetics studies show that CDDO anhydride levels are higher than CDDO levels in mouse tissues and blood. Further evaluation of CDDO anhydride is in progress...
  26. pmc Triterpenoids CDDO-methyl ester or CDDO-ethyl amide and rexinoids LG100268 or NRX194204 for prevention and treatment of lung cancer in mice
    Karen Liby
    Department of Pharmacology, Dartmouth Medical School, Hanover, NH 03755, USA
    Cancer Prev Res (Phila) 2:1050-8. 2009
    ..Triterpenoids and rexinoids are multifunctional, well-tolerated drugs that target different signaling pathways and are thus highly effective for prevention and treatment of experimental lung cancer...
  27. pmc CDDO-imidazolide induces DNA damage, G2/M arrest and apoptosis in BRCA1-mutated breast cancer cells
    Eun Hee Kim
    Department of Pharmacology, Dartmouth Medical School, Hanover, NH, USA
    Cancer Prev Res (Phila) 4:425-34. 2011
    ..The particular relevance of these findings to the chemoprevention of cancer is discussed. Cancer Prev Res; 4(3); 425-34. ©2011 AACR...
  28. ncbi request reprint Synthetic triterpenoids enhance transforming growth factor beta/Smad signaling
    Nanjoo Suh
    Dartmouth Medical School and Dartmouth College, Hanover, New Hampshire 03755, USA
    Cancer Res 63:1371-6. 2003
    ..These are the first studies to report enhancement of Smad signaling by synthetic triterpenoids and should further their optimal use for applications in prevention or treatment of diseases in which there is aberrant function of TGF-beta...
  29. ncbi request reprint The novel synthetic triterpenoid, CDDO-imidazolide, inhibits inflammatory response and tumor growth in vivo
    Andrew E Place
    Department of Pharmacology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    Clin Cancer Res 9:2798-806. 2003
    ..Moreover, CDDO-Im inhibits growth of B16 murine melanoma and L1210 murine leukemia cells in vivo. The potent effects of CDDO-Im, both in vitro and in vivo, suggest it should be considered for clinical use...
  30. ncbi request reprint Efficient synthesis of (-)- and (+)-tricyclic compounds with enone functionalities in rings A and C. A novel class of orally active anti-inflammatory and cancer chemopreventive agents
    Tadashi Honda
    Department of Chemistry, Dartmouth College, 6128 Burke Laboratory, Hanover, New Hampshire 03755, USA
    Org Biomol Chem 1:4384-91. 2003
    ..In contrast, (-)-3 inhibits proliferation of MCF-7 breast cancer cells, whereas (+)-3 does not...
  31. ncbi request reprint The synthetic triterpenoid CDDO-Imidazolide suppresses STAT phosphorylation and induces apoptosis in myeloma and lung cancer cells
    Karen Liby
    Dartmouth Medical School and Dartmouth College, Hanover, New Hampshire, USA
    Clin Cancer Res 12:4288-93. 2006
    ..It is, therefore, important to develop new drugs to control the STATs, particularly their phosphorylation state, which is required for their transcriptional activity...
  32. ncbi request reprint Peroxisome proliferator-activated receptor-gamma-independent repression of collagenase gene expression by 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid and prostaglandin 15-deoxy-delta(12,14) J2: a role for Smad signaling
    Kimberlee S Mix
    Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03756, USA
    Mol Pharmacol 65:309-18. 2004
    ..We conclude that CDDO represses MMP gene expression through a novel PPAR-gamma-independent mechanism that requires Smad signaling...
  33. ncbi request reprint Studies on the reactivity of CDDO, a promising new chemopreventive and chemotherapeutic agent: implications for a molecular mechanism of action
    Robin D Couch
    Department of Chemistry, Dartmouth College, Hanover, NH 03755, USA
    Bioorg Med Chem Lett 15:2215-9. 2005
    ..Spectroscopic evaluation with thiol nucleophiles illustrates that an addition does indeed occur, but this addition is selective and reversible...
  34. ncbi request reprint Design, synthesis, and biological evaluation of biotin conjugates of 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid for the isolation of the protein targets
    Tadashi Honda
    Department of Chemistry, Dartmouth College, 6128 Burke Laboratory, Hanover, New Hampshire 03755, USA
    J Med Chem 47:4923-32. 2004
    ..Consequently, 6 may be a very promising tool for the isolation of the protein targets of CDDO...
  35. doi request reprint Synthetic triterpenoids attenuate cytotoxic retinal injury: cross-talk between Nrf2 and PI3K/AKT signaling through inhibition of the lipid phosphatase PTEN
    Ian Pitha-Rowe
    Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire, USA
    Invest Ophthalmol Vis Sci 50:5339-47. 2009
    ....
  36. ncbi request reprint The synthetic triterpenoids, CDDO and CDDO-imidazolide, are potent inducers of heme oxygenase-1 and Nrf2/ARE signaling
    Karen Liby
    Dartmouth Medical School and Dartmouth College, Hanover, New Hampshire 03755, USA
    Cancer Res 65:4789-98. 2005
    ....
  37. ncbi request reprint The novel triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) potently enhances apoptosis induced by tumor necrosis factor in human leukemia cells
    Terrance A Stadheim
    Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    J Biol Chem 277:16448-55. 2002
    ....
  38. pmc The triterpenoid CDDO inhibits expression of matrix metalloproteinase-1, matrix metalloproteinase-13 and Bcl-3 in primary human chondrocytes
    Sarah Elliott
    Department of Medicine, Dartmouth Medical School, Hanover, New Hampshire, USA
    Arthritis Res Ther 5:R285-91. 2003
    ..Our data demonstrate that CDDO inhibits IL-1-induced MMP-1 and MMP-13 expression in human chondrocytes. CDDO also inhibits the expression of Bcl-3, an IL-1-responsive gene that preferentially contributes to MMP-1 gene expression...
  39. ncbi request reprint The synthetic triterpenoid 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole blocks nuclear factor-kappaB activation through direct inhibition of IkappaB kinase beta
    Mark M Yore
    Department of Pharmacology, Dartmouth Medical School, Hanover, NH 03755, USA
    Mol Cancer Ther 5:3232-9. 2006
    ..Furthermore, we show that Cys(179) on IKK is a target for CDDO-Im. This is the first report to show that this novel synthetic triterpenoid binds to and inhibits IKKbeta directly...
  40. ncbi request reprint Specific chemopreventive agents trigger proteasomal degradation of G1 cyclins: implications for combination therapy
    Konstantin H Dragnev
    Norris Cotton Cancer Center, and Department of Medicine, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
    Clin Cancer Res 10:2570-7. 2004
    ..G(1) arrest was triggered by cyclin D1 proteolysis via ubiquitin-dependent degradation. This study investigated which chemopreventive agents activated this degradation program and whether cyclin E was also degraded...
  41. ncbi request reprint Regulation of matrix metalloproteinase gene expression by a retinoid X receptor-specific ligand
    Peter S Burrage
    Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire 03756, USA
    Arthritis Rheum 56:892-904. 2007
    ....
  42. ncbi request reprint c-Jun NH2-terminal kinase-mediated up-regulation of death receptor 5 contributes to induction of apoptosis by the novel synthetic triterpenoid methyl-2-cyano-3,12-dioxooleana-1, 9-dien-28-oate in human lung cancer cells
    Wei Zou
    Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia, USA
    Cancer Res 64:7570-8. 2004
    ..Collectively, we conclude that CDDO-Me induces apoptosis via the JNK-mediated DR up-regulation in human lung cancer cells...
  43. ncbi request reprint The bortezomib/proteasome inhibitor PS-341 and triterpenoid CDDO-Im induce synergistic anti-multiple myeloma (MM) activity and overcome bortezomib resistance
    Dharminder Chauhan
    Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
    Blood 103:3158-66. 2004
    ..Together, these findings provide the framework for clinical evaluation of CDDO-Im, either alone or in combination with bortezomib, to overcome drug resistance and improve patient outcome in MM...
  44. ncbi request reprint The synthetic triterpenoid TP-222 inhibits RANKL stimulation of osteoclastogenesis and matrix metalloproteinase-9 expression
    Roy A Fava
    Research Service, Veterans Affairs Medical Center, White River Junction, Vermont, USA
    J Rheumatol 34:1058-68. 2007
    ..We therefore investigated the ability of the potent and bioavailable synthetic triterpenoid TP-222 to inhibit RANKL-induced osteoclast formation and MMP-9 expression from monocytic precursor cells...
  45. ncbi request reprint Pharmacodynamic characterization of chemopreventive triterpenoids as exceptionally potent inducers of Nrf2-regulated genes
    Melinda S Yates
    Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Room E7541, 615 North Wolfe Street, Baltimore, MD 21205, USA
    Mol Cancer Ther 6:154-62. 2007
    ..This pharmacodynamic characterization highlights the chemopreventive promise of several synthetic triterpenoids in multiple target organs...
  46. ncbi request reprint Hobson's choice and the need for combinations of new agents for the prevention and treatment of breast cancer
    Michael B Sporn
    J Natl Cancer Inst 94:242-3. 2002
  47. ncbi request reprint Synthetic triterpenoids cooperate with tumor necrosis factor-related apoptosis-inducing ligand to induce apoptosis of breast cancer cells
    Marc L Hyer
    The Burnham Institute, La Jolla, California 92037, USA
    Cancer Res 65:4799-808. 2005
    ..These data suggest that CDDO and CDDO-Im may be useful for selectively reversing the TRAIL-resistant phenotype in cancer but not normal cells...
  48. doi request reprint A dicyanotriterpenoid induces cytoprotective enzymes and reduces multiplicity of skin tumors in UV-irradiated mice
    Albena T Dinkova-Kostova
    The Lewis B and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 N Wolfe Street, WBSB Room 406, Baltimore, MD 21205, USA
    Biochem Biophys Res Commun 367:859-65. 2008
    ....
  49. ncbi request reprint c-FLIP downregulation contributes to apoptosis induction by the novel synthetic triterpenoid methyl-2-cyano-3, 12-dioxooleana-1, 9-dien-28-oate (CDDO-Me) in human lung cancer cells
    Wei Zou
    Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    Cancer Biol Ther 6:1614-20. 2007
    ..Collectively, these results indicate that c-FLIP downregulation contributes to CDDO-Me-initiated apoptosis and also to enhancement of TRAIL-induced apoptosis by CDDO-Me...
  50. ncbi request reprint The triterpenoid CDDO induces apoptosis in refractory CLL B cells
    Irene M Pedersen
    The Burnham Institute and University of California San Diego, La Jolla, CA 92037, USA
    Blood 100:2965-72. 2002
    ..These data suggest that the synthetic triterpenoid CDDO should be further explored as a possible therapeutic agent for treatment of chemo-resistant CLL...
  51. pmc The synthetic triterpenoid CDDO-methyl ester modulates microglial activities, inhibits TNF production, and provides dopaminergic neuroprotection
    Thi A Tran
    Department of Physiology, The University of Texas Southwestern Medical Center, Dallas, Texas, USA
    J Neuroinflammation 5:14. 2008
    ..Therefore, the aims of our study were to identify specific microglial activities modulated by CDDO-Me in vitro, and to determine the extent to which this modulation affords neuroprotection against inflammatory stimuli...
  52. doi request reprint Glycogen synthase kinase 3beta regulates cell death induced by synthetic triterpenoids
    Roberta Vené
    Molecular Oncology and Angiogenesis Laboratory, Istituto Nazionale per la Ricerca sul Cancro IST, Genova, Italy
    Cancer Res 68:6987-96. 2008
    ..These data suggest that modulation of GSK3beta activation is involved in the cell death pathway engaged by CDDO-Me in prostate cancer cells...
  53. ncbi request reprint Identification of a novel synthetic triterpenoid, methyl-2-cyano-3,12-dioxooleana-1,9-dien-28-oate, that potently induces caspase-mediated apoptosis in human lung cancer cells
    Kevin B Kim
    Department of Thoracic Head and Neck Medical Oncology, Box 432, University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Mol Cancer Ther 1:177-84. 2002
    ..Our results demonstrate that CDDO-Me may be a good candidate for additional evaluation as a potential therapeutic agent for human lung cancers and possibly other types of cancer...
  54. ncbi request reprint Treatment and prevention of intraepithelial neoplasia: an important target for accelerated new agent development
    Joyce A O'Shaughnessy
    Baylor Sammons Cancer Center, US Oncology, Collins 5, 3535 Worth Street, Dallas, TX 75246, USA
    Clin Cancer Res 8:314-46. 2002
    ..The IEN Task Force proposes several clinical trial designs that provide practical and feasible approaches to the rapid development of new agents to treat and prevent precancer...
  55. ncbi request reprint Novel triterpenoid CDDO-Me is a potent inducer of apoptosis and differentiation in acute myelogenous leukemia
    Marina Konopleva
    Department of Blood and Marrow Transplantation, Section of Molecular Hematology and Therapy, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Blood 99:326-35. 2002
    ..Differential effects of CDDO-Me on leukemic and normal progenitor cells suggest that CDDO-Me has potential as a novel compound in the treatment of hematologic malignancies...
  56. pmc Genetic or pharmacologic amplification of nrf2 signaling inhibits acute inflammatory liver injury in mice
    William O Osburn
    Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA
    Toxicol Sci 104:218-27. 2008
    ..Taken together, these results clearly illustrate that targeted cytoprotection of hepatocytes through Nrf2 signaling during inflammation prevents the amplification of inflammatory responses in the liver...
  57. pmc The synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid-imidazolide alters transforming growth factor beta-dependent signaling and cell migration by affecting the cytoskeleton and the polarity complex
    Ciric To
    Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario N6A 5C1, Canada
    J Biol Chem 283:11700-13. 2008
    ..Thus, the synthetic triterpenoid CDDO-Im interferes with TGFbeta receptor trafficking and turnover and disrupts cell migration by severing the link between members of the polarity complex and the microtubule network...
  58. pmc CDDO-Imidazolide inhibits growth and survival of c-Myc-induced mouse B cell and plasma cell neoplasms
    Seong Su Han
    Laboratory of Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
    Mol Cancer 5:22. 2006
    ....
  59. ncbi request reprint 2-cyano-3,12-dioxooleana-1,9(11)-diene-28-oic acid disrupts microtubule polymerization: a possible mechanism contributing to apoptosis
    Robin D Couch
    Department of Medicinal Chemistry, School of Pharmacy, University of Connecticut, 69 North Eagleville Rd, Storrs, CT 06269 3092, USA
    Mol Pharmacol 69:1158-65. 2006
    ..Unlike other known spindle poisons, CDDO does not result in a temporal increase in the mitotic index. Rather, CDDO seems to initiate apoptosis early in M phase...
  60. pmc Nrf2-dependent protection from LPS induced inflammatory response and mortality by CDDO-Imidazolide
    Rajesh K Thimmulappa
    Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
    Biochem Biophys Res Commun 351:883-9. 2006
    ..Activation of Nrf2-dependent compensatory antioxidative pathways by CDDO-Im protects from LPS induced inflammatory response and mortality...
  61. ncbi request reprint The tumour microenvironment as a target for chemoprevention
    Adriana Albini
    IRCCS Multimedica Science and Technology Park, Viale Fantoli 15 16, Milan, 20138, Italy
    Nat Rev Cancer 7:139-47. 2007
    ..Finally, we make suggestions for more effective clinical implementation of this knowledge in preventive strategies...
  62. pmc Extremely potent triterpenoid inducers of the phase 2 response: correlations of protection against oxidant and inflammatory stress
    Albena T Dinkova-Kostova
    The Lewis B and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, School of Medicine, Johns Hopkins University, 725 North Wolfe Street, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 102:4584-9. 2005
    ..91) over 6 orders of magnitude of concentration. Thus, in addition to blocking inflammation and promoting differentiation, these TP exhibit another very important protective property: the induction of the phase 2 response...
  63. pmc Human immunodeficiency virus type 1-induced macrophage gene expression includes the p21 gene, a target for viral regulation
    Nancy Vazquez
    National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA
    J Virol 79:4479-91. 2005
    ..These data implicate p21 as a pivotal macrophage facilitator of the viral life cycle. Moreover, regulators of p21, such as CDDO, may provide an interventional approach to modulate HIV-1 replication...
  64. ncbi request reprint The synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid induces caspase-dependent and -independent apoptosis in acute myelogenous leukemia
    Marina Konopleva
    Section of Molecular Hematology and Therapy and the Department of Blood and Marrow Transplantation at The University of Texas M D Anderson Cancer Center, Houston, Texas, USA
    Cancer Res 64:7927-35. 2004
    ..The direct modulation of mitochondrial-mediated, caspase-independent apoptosis by CDDO may be advantageous for overcoming chemoresistance in AML...
  65. pmc CDDO induces granulocytic differentiation of myeloid leukemic blasts through translational up-regulation of p42 CCAAT enhancer binding protein alpha
    Steffen Koschmieder
    Department of Medicine, Hematology and Oncology, University of Munster, Münster Germany
    Blood 110:3695-705. 2007
    ..Because AML is characterized by arrested differentiation, our data suggest the inclusion of CDDO in the therapy of AML characterized by dysfunctional CEBPA expression...
  66. pmc Preclinical evaluation of targeting the Nrf2 pathway by triterpenoids (CDDO-Im and CDDO-Me) for protection from LPS-induced inflammatory response and reactive oxygen species in human peripheral blood mononuclear cells and neutrophils
    Rajesh K Thimmulappa
    Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA
    Antioxid Redox Signal 9:1963-70. 2007
    ....
  67. ncbi request reprint Potent protection against aflatoxin-induced tumorigenesis through induction of Nrf2-regulated pathways by the triterpenoid 1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole
    Melinda S Yates
    Johns Hopkins University, Baltimore, Maryland, USA
    Cancer Res 66:2488-94. 2006
    ..The unparalleled potency of CDDO-Im in vivo highlights the chemopreventive promise of targeting Nrf2 pathways with triterpenoids...
  68. ncbi request reprint A new tumor suppressor gene, selective for lung cancer
    Michael B Sporn
    J Natl Cancer Inst 99:1654-5. 2007
  69. ncbi request reprint The synthetic oleanane triterpenoid, CDDO-methyl ester, is a potent antiangiogenic agent
    Nicola Vannini
    Multimedica IRCCS, Milan, Italy
    Mol Cancer Ther 6:3139-46. 2007
    ....

Research Grants21

  1. New Triterpenoids for Cancer Chemoprevention & Therapy
    Michael Sporn; Fiscal Year: 2007
    ..abstract_text> ..
  2. Chemoprevention of Estrogen Receptor Negative Breast Cancer
    Michael Sporn; Fiscal Year: 2007
    ..These studies on apoptosis will be supplemented by measuring effects of chemopreventive agents on Myc gene expression. ..
  3. New Triterpenoids for Chemoprevention and Therapy of Cancer
    Michael Sporn; Fiscal Year: 2009
    ..This grant application deals with the development and testing of new drugs to prevent lung, pancreatic, and liver cancer, with the eventual goal of using such drugs to prevent disease in men and women at high risk. ..
  4. New Triterpenoids for Chemoprevention and Therapy of Cancer
    Michael B Sporn; Fiscal Year: 2010
    ..This grant application deals with the development and testing of new drugs to prevent lung, pancreatic, and liver cancer, with the eventual goal of using such drugs to prevent disease in men and women at high risk. ..
  5. Conference on Roles of TGF-Beta in Disease Pathogenesis
    Michael Sporn; Fiscal Year: 2005
    ..The hope is that this meeting will both enhance our insights into pathogenetic mechanisms of action of TGF-Beta in disease and provide novel therapeutic approaches for clinical treatment of disease. ..
  6. New Triterpenoids for Chemoprevention and Therapy of Cancer
    Michael B Sporn; Fiscal Year: 2011
    ..This grant application deals with the development and testing of new drugs to prevent lung, pancreatic, and liver cancer, with the eventual goal of using such drugs to prevent disease in men and women at high risk. ..