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Showing papers by "Michael B. Sporn published in 1999"


Journal Article
TL;DR: The results suggest that CDDO needs further study in vivo, for either chemoprevention or chemotherapy of malignancy as well as for neuroprotection.
Abstract: The new synthetic oleanane triterpenoid 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) is a potent, multifunctional molecule. It induces monocytic differentiation of human myeloid leukemia cells and adipogenic differentiation of mouse 3T3-L1 fibroblasts and enhances the neuronal differentiation of rat PC12 pheochromocytoma cells caused by nerve growth factor. CDDO inhibits proliferation of many human tumor cell lines, including those derived from estrogen receptor-positive and -negative breast carcinomas, myeloid leukemias, and several carcinomas bearing a Smad4 mutation. Furthermore, it suppresses the abilities of various inflammatory cytokines, such as IFN-gamma, interleukin-1, and tumor necrosis factor-alpha, to induce de novo formation of the enzymes inducible nitric oxide synthase (iNos) and inducible cyclooxygenase (COX-2) in mouse peritoneal macrophages, rat brain microglia, and human colon fibroblasts. CDDO will also protect rat brain hippocampal neurons from cell death induced by beta-amyloid. The above activities have been found at concentrations ranging from 10(-6) to 10(-9) M in cell culture, and these results suggest that CDDO needs further study in vivo, for either chemoprevention or chemotherapy of malignancy as well as for neuroprotection.

329 citations


Journal Article
TL;DR: This is the first report of the use of a ligand for peroxisome proliferator-activated receptor-gamma to prevent experimental breast cancer.
Abstract: We have tested a new ligand for peroxisome proliferator-activated receptor-gamma, GW7845, as an inhibitor of experimental mammary carcinogenesis, using the classic rat model with nitrosomethylurea as carcinogen. Rats were first treated with a single dose of nitrosomethylurea (50 mg/kg body weight, i.p.). Starting 1 week later, they were fed GW7845, at either 60 or 30 mg/kg of diet, for 2 months. This agent significantly reduced tumor incidence, tumor number, and tumor weight at both doses. This is the first report of the use of a ligand for peroxisome proliferator-activated receptor-gamma to prevent experimental breast cancer.

232 citations



Journal ArticleDOI
TL;DR: Novel oleanane triterpenoids with modified rings A and C showed similar high inhibitory activity to 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO), which has been synthesized previously, against production of nitric oxide induced by interferon-gamma in mouse macrophages.

113 citations


Journal ArticleDOI
TL;DR: The history of transforming growth factor-beta as a bifunctional agent in the immune system is briefly described and the importance of cellular context in understanding the role of TGF-β in regulating immune response is emphasized.

56 citations


Journal ArticleDOI
TL;DR: In this article, new derivatives with electron-withdrawing substituents at the C-2 position of 3-oxoolean-1-en-28-oic acid were synthesized.
Abstract: New derivatives with electron-withdrawing substituents at the C-2 position of 3-oxoolean-1-en-28-oic acid were synthesized. Among them, 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) was 400 times more potent than previous compounds we have made as an inhibitor of production of nitric oxide induced by interferon-gamma in mouse macrophages (IC50, 0.4 nM). The potency of CDDO was similar to that of dexamethasone, although CDDO does not act through the glucocorticoid receptor.

20 citations


Journal ArticleDOI
TL;DR: The development of a new system for quantitating the process of prostatic carcinogenesis in an experimental animal is described and this system is used to demonstrate that the retinoid, 4-hydroxyphenylretinamide, the deltanoid, Ro24-5531, and the estrogen analog, tamoxifen, all are effective agents for prevention of experimental prostate cancer.

17 citations


Patent
18 Jun 1999
TL;DR: In this article, the authors present a list of compounds and methods useful for chemopreventive treatment of diseases such as cancer, Alzheimer's disease, Parkinson disease, inflammatory bowel diseases and multiple sclerosis.
Abstract: Compounds and methods useful for chemopreventative treatment of diseases such as cancer, Alzheimer's disease, Parkinson's disease, inflammatory bowel diseases, and multiple sclerosis.

5 citations


Journal ArticleDOI
Peter Ekman, Yves Fradet, François Meyer, Isabelle Bairati, Ramak Shadmani, Lynne Moore, Donna M. Peehl, Judd W. Moul, Helmut Klocker, Zoran Culig, Iris E. Eder, Claudia Nessler-Menardi, Alfred Hobisch, Thomas Putz, Georg Bartsch, Heike Peterziel, Andrew C.B. Cato, Michael B. Sporn, Peter Whelan, Fouad K. Habib, Margaret Ross, Colin W. Bayne, K. Griffiths, M.S. Morton, L. Denis, Maarten C. Bosland, David L. McCormick, K.V.N. Rao, Wael Sakr, Junqi Qian, Robert B. Jenkins, Ronald A. Lubet, Levy Kopelovitch, Winfred A. Malone, James A. Crowell, Caroline C. Sigman, R.K. Ross, G.A. Coetzee, C.L. Pearce, J.K.V. Reichardt, P. Bretsky, L.N. Kolonel, B.E. Henderson, E. Lander, D. Altshuler, G. Daley, Charles E. Myers, Jagat Ghosh, Marion J.G. Bussemakers, D. Urban, R. Myers, U. Manne, H. Weiss, J. Mohler, D. Perkins, M. Markiewicz, R. Lieberman, G. Kelloff, M. Marshall, W. Grizzle, David J. Waters, David G. Bostwick, Peter H. Bartels, Rodolfo Montironi, Vinicius Duval da Silva, Peter W. Hamilton, Deborah Thompson, Linda Vaught, Hubert G. Bartels, Roxann M. Neumann, Liang Cheng, Ferran Algaba, Don W. W. Newling, T.H. Van Der Kwast, F. Labrie, B. Têtu, E.D. Crawford, Richard Sylvester, Laurence Collette, W. Horninger, A. Reissigl, H. Rogatsch, H. Volgger, M. Studen, H. Klocker, G. Bartsch, C.A. Coltman, Ian M. Thompson, Polly Feigl, Nina N. Nupponen, Tapio Visakorpi, Peter Boyle, Gianluca Severi, Marina Scarpelli, Fritz H. Schröder, Ries Kranse, John Rietbergen, Robert F. Hoedemaeker, Wim J. Kirkels, Gary J. Kelloff, Ronald Lieberman, Vernon E. Steele, Charles W. Boone, Adrian P.M. van der Meijden, A.R. Zlotta, C.C. Schulman 

1 citations


Patent
18 Jun 1999
TL;DR: In this article, the present invention relates to a compound having formula: "premature" where either A or B is a double-bond such that when A was a double bond, C 11 has substituted thereon =X, and when B was an inorganic moiety selected from amino, thiol, and hydroxyl (tantamount to =X being =NH, =S, or =O).
Abstract: The present invention relates to a compound having formula: wherein (a) either A or B is a double bond such that when A is a double bond, C 11 has substituted thereon =X, and when B is a double bond, C 12 has substituted thereon =X, X being an inorganic moiety selected from amino, thiol, and hydroxyl (tantamount to =X being =NH, =S, or =O); (b) R 1 is an electron-withdrawing moiety selected from cyano, -COOH, and halogen; (c) R x is methyl; and (d) Y is hydrogen, an inorganic moiety selected from halogen, amino, and hydroxyl, or an organic moiety selected from alkyl, alkylamino, alkoxy, and aryl.