AYMEN I. IDRIS MSC. PH.D.

Transcription

1 AYMEN I. IDRIS MSC. PH.D. SENIOR LECTURER UNIVERSITY OF SHEFFIELD ORIGINAL RESEARCH ARTICLES Sophocleous A, Sims AH, Aymen I. Idris, Ralston SH. Genetic Background Modifies the Effects of Type 2 Cannabinoid Receptor Deficiency on Bone Mass and Bone Turnover. CTI : Sophocleous A, Aymen I. Idris, Ralston SH. Modulation of Strain-Specific Differences in Gene Expression by Cannabinoid Type 2 Receptor Deficiency. CTI : Logan J. G., Sophocleous,A, Marino S, Muir M., Brunton V.G., and Aymen I. Idris. Selective tyrosine kinase inhibition of insulin-like growth factor-1 receptor inhibits human and mouse breast cancer induced bone cell activity, bone remodelling and osteolysis. J. Bone Miner. Res. 2013; 165: Frantzias J, Logan G.J, Mollat P, Sparatore A, Del Soldato P, Ralston S.H and Aymen I. Idris. Hydrogen sulfide releasing diclofenac derivatives inhibit breast cancer-induced osteoclastogenesis in vitro and prevent osteolysis ex vivo. Br J Pharmacol. 2012; 165(6), Sophocleous A, Landao-Bassonga E, Van't Hof RJ, Aymen I. Idris, Ralston S.H. The Type 2 Cannabinoid Receptor Regulates Bone Mass and Ovariectomy-Induced Bone Loss by Affecting Osteoblast Differentiation and Bone Formation. Endocrinology. 2011; 152(6): Aymen I. Idris, Krishnan M, Simic P, Landao-Bassonga E, Mollat P, Vukicevic S, and Ralston S.H. Small molecule inhibitors of IKK signalling inhibit osteoclast formation in vitro and ovariectomy induced bone loss in vivo. FASEB J. 2010; 24: Aymen I. Idris, Coste E, Greig I.R, Ralston S.H and van t Hof, R.J. The orally active biphenyl carboxylic acid derivative ABD328 prevents ovariectomy bone loss in vivo. CTI. 2010; 87(6): Aymen I. Idris, Landao-Bassonga E, Ralston S.H. The TRPV1 receptor antagonist capsazepine inhibits osteoclast and osteoblast differentiation in vitro and ovariectomy induced bone loss in vivo. Bone. 2010; 46: Aymen I. Idris, Sophocleous A, Landao-Bassonga E, Canals M, Milligan G, Baker D, vant Hof R.J, Ralston S.H. Cannabinoid receptor type 1 protects against age-related bone loss by regulating osteoblast and adipocyte differentiation of bone marrow stromal cells. Cell Metabolism. 2009; 10(2): Aymen I. Idris, Libouban H, Nyangoga H, Landao-Bassonga E, Chappard D, Ralston S.H. Pharmacological inhibitors of IKK suppress growth and migration of mammary carcinosarcoma cells in vitro and prevent osteolytic bone metastasis in vivo. Molecular Cancer Therapeutics : Aitken S, Landao-Bassonga E, Ralston S.H and Aymen I. Idris. Beta-2 adrenoreceptor ligands regulate osteoclast differentiation by direct and indirect mechanisms. Arch Biochem Biophys. 2009; 482: Aymen I. Idris, Ralston SH and van t Hof RJ. The nitrosylated Flurbiprofen derivative HCT1026 inhibits bone resorption by suppressing RANKL signalling. Eur J Pharmacol (2-3): Aymen I. Idris, Greig I.R, Ralston S.H and van t Hof R.J. Identification of Novel Biphenyl Carboxylic Acid Derivatives as Novel Antiresorptive Agents that Do Not Impair Parathyroid Hormone-Induced Bone Formation. Endocrinology. 2009; 150:5-13. Aymen I. Idris, Sophocleous A, Landao-Bassonga E, van t Hof R.J, Ralston S.H. Role of CNR2 in regulating bone mass osteoclast function and ovariectomy. Endocrinology. 2008; 149(11): Aymen I. Idris, Mrak E, Greig I.R, Guidobonoc F, Ralston S.H and van t Hof R.J. ABD56 causes osteoclast apoptosis by inhibiting the NFκB and ERK pathways. BBRC. 2008; 371 (1): Aymen I. Idris, Greig I.R, van t Hof R.J, and Ralston S.H. Aminobisphosphonates cause osteoblast apoptosis and inhibit bone nodule formation in vitro. CTI. 2008; 82:

2 Alun Hughes, Rogers M.J, Aymen I. Idris and Crockett J.C. A Comparison between the Effects of Hydrophobic and Hydrophilic Statins on Osteoclast Function in vitro and Ovariectomy-Induced Bone Loss in vivo. CTI. 2007; 81: Greig I.R, Aymen I. Idris, Ralston S.H and van t Hof R.J. Identification of biphenyl-carboxylic acid derivatives as a novel class of bone resorption inhibitors. J Med Chem. 2006; 14;49 (25): Aymen I. Idris, van t Hof R.J, Greig I.R, Ridge S, Ross R and Ralston S.H. Regulation of bone mass, bone loss and osteoclast activity by cannabinoid receptors. Nat Med. 2005; 11(6): Aymen I. Idris*, van t Hof R.J*, Greig I.R, Ridge S, Dunford J, Ralston S.H. Identification of biphenylcarboxylic acid derivatives as a novel class of bone resorption inhibitors. JBMR. 2004;19: *Authors contributed equally to manuscript. Aymen I. Idris, van t Hof R.J, Del Soldato P, Ralston S.H. The NO-NSAID HCT1026 inhibits bone resorption by a novel mechanism independent of COX inhibition and NO production. Bone. 2004; 35: REVIEWS Aymen I. Idris. The promise and dilemma of cannabinoid therapy: lessons from animal studies of bone disease. IBMS BoneKEy. 2011; 8(2): Aymen I. Idris. Cannabinoid receptors as target for treatment of osteoporosis: a tale of two therapies. Current Neuropharmacology. 2010; 8: Aymen I. Idris and Stuart H. Ralston. Cannabinoids and bone: Friend or Foe?. CTI. 2010; 87(4): Aymen I. Idris. Role of cannabinoid receptors in bone disorders: alternatives for treatment. Drug News Perspect. 2008; 21(10): BOOK CHAPTERS Aymen I. Idris. Analysis of Signalling Pathways in Bone Cells. Bone Research Protocols. 2 nd ed. Totowa, NJ: Humana Press. 2012;816: Aymen I. Idris. Ovariectomy and Orchidectomy in Rodents. Bone Research Protocols. 2 nd ed. Totowa, NJ: Humana Press. 2012;816: PATENTS I.R Greig, Aymen I. Idris, S.H. Ralston, R.J. van t Hof. Aryl Alkyl Sulfonamides as therapeutic agents for the treatment of bone conditions, PCT/GB2005/002043, I.R Greig, Aymen I. Idris, S.H. Ralston, and R.J. van t Hof. Ketones and reduced ketones as therapeutic agents for the treatment of bone conditions, PCT/GB2004/001958, I.R Greig, Aymen I. Idris, S.H. Ralston, R. Ross and R.J. van t Hof. Cannabinoid receptor inverse agonists as therapeutic agents for the treatment of bone disorders, PCT/GB2004/000858, Two patent applications describing the next generation of reduced ketones are under preparation. SELECTED ORAL PRESENTATIONS AND ABSTRACTS 1. S. Marino, J.G Logan, P. Mollat, B. Mognetti, S.H. Ralston and Aymen I. Idris. Regulation of osteolysis by IKKβ. Bone, Oral presentation at the Cancer Induced Bone Disease meeting, Lyon, France (May 2013).

3 2. S. Marino, J.G Logan, P. Mollat, B. Mognetti, S.H. Ralston and Aymen I. Idris. Genetic inactivation and pharmacological inhibition of IKKβ activity in cancer cells inhibits breast cancer-induced osteoclastogenesis, promotes osteoblast differentiation and prevents osteolysis. Bone, 2012: 50(S1); P S51. Oral presentation at the European Symposium on Calcified Tissues, Stockholm, Sweden (May 2012). 3. P. Peramuhendige, S. Marino2, A. Unciti-Broceta, S.H. Ralston and Aymen I. Idris. A novel small molecule inhibitor of TRAF-dependent signaling inhibits breast cancer-induced osteoclastogenesis and prevents osteolysis. Bone, 2012, 50(S1), Page S61. Oral presentation at the European Symposium on Calcified Tissues, Stockholm, Sweden (May 2012). 4. J.G. Logan, A. Sophocleous, E. Landao-Bassonga, V.G. Brunton and Aymen I Idris. The novel and selective insulin-like growth factor-1 receptor kinase inhibitor pqip suppresses bone cell function and osteoclast- breast cancer cell cross-talk. Bone, Volume 48, Page S257. Oral presentation and winner of best presentation by New Investigator (J.G. Logan) at European Symposium on Calcified Tissues, Athens, Greece (May 2011). 5. A. Sophocleous, J.G. Logan, E. A. Mackintosh, Landao-Bassonga, S.H. Ralston and Aymen I Idris. The CB2 receptor regulates osteoclast formation, breast cancer cell migration and osteoclast/tumour cell interaction via the PI3 Kinase/AKT pathway. Bone, Volume 48, Page S73. Oral presentation at European Symposium on Calcified Tissues, Athens, Greece (May 2011). 6. Joseph Frantzias, Patrick Mollat, Anna Sparatore, Piero Del Soldato, Stuart H. Ralston and Aymen I. Idris. Identification of hydrogen sulfide releasing compounds as novel antiresorptive and antitumour agents. Poster presentation at Cancer Induced Bone Disease, Sheffield, UK (July 2011). 7. A. Sophocleous, Landao-Bassonga, Robert J van t Hof, S.H. Ralston and Aymen I Idris. The type 2 cannabinoid receptor protects against age-related bone loss and ovariectomy. Bone, Volume 48, Page S73. Oral presentation at European Symposium on Calcified Tissues, Glasgow, Scotland (June 2010). 8. Antonia Sophocleous, Euphemie Landao-Bassonga, Robert J van t Hof, Stuart H Ralston and Aymen I Idris. The type 2 cannabinoid receptor s (CB2) protects against age-related bone loss by affecting bone formation and CB2 agonists exhibit anabolic activity. Bone, Volume 42 (Supplement 2), Page S219. Oral presentation at European Symposium on Calcified Tissues, Vienna, Austria (May 2009). 9. Aymen I Idris, Antonia Sophocleous, Euphemie Landao-Bassonga, Meritxell Canals, Graeme I Milligan, David Baker, Robert J van t Hof, Stuart H Ralston. Cannabinoid receptor type 1 protects against age-related bone loss by regulating osteoblast and adipocyte differentiation of bone marrow stromal cells. Bone, Volume 42 (Supplement 2), Page S222. Oral presentation at European Symposium on Calcified Tissues, Vienna, Austria (May 2009). 10. Aymen I. Idris, Petra Simic, Maala Krishnan, Slobodan Vukicevic and Stuart Ralston. Small molecule inhibitors of IKK-dependent signalling inhibit osteoclast formation in vitro and ovariectomy-induced bone loss in vivo. Calcif Tissue Int, Volume 82 (Supplement 1), Page S Aymen I. Idris, Antonia Sophocleous, Euphemie Landao-Bassonga, Robert van t Hof and Stuart H Ralston. Bidirectional regulation of peak bone mass and age-related bone loss by the type 1 cannabinoid receptor. Calcif Tissue Int, Volume 82 (Supplement 1), Page S Aymen I. Idris, Helene Libouban, Hervé Nyangoga, Euphemie Landao-Bassonga, Daniel Chappard and Stuart Ralston. The IKK inhibitors Celastrol and Parthenolide inhibit breast cancer cell proliferation and migration in vitro and osteolytic bone metastasis in vivo. Calcif Tissue Int, Volume 82 (Supplement 1), Page S49.

4 13. Antonia Sophocleous, Euphemie Landao-Bassonga, Robert van t Hof, Stuart H Ralston and Aymen I. Idris. Cannabinoid receptor antagonists inhibit osteoclast formation in vitro and ovariectomy-induced bone loss in vivo through the CB1 and CB2 receptors. Calcif Tissue Int, Volume 82 (Supplement 1), Page S Antonia Sophocleous, Euphemie Landao-Bassonga, Robert van t Hof, Aymen I. Idris and Stuart H Ralston. Cannabinoid receptor 2 selective agonists stimulate osteoclast formation in vitro but act as anabolic agents in vivo by stimulating bone formation. Calcif Tissue Int, Volume 82 (Supplement 1), Page S Aymen I. Idris, Helene Libouban, Hervé Nyangoga, Euphemie Landao-Bassonga, Daniel Chappard and Stuart Ralston. The IKK inhibitors Celastrol and Parthenolide inhibit breast cancer cell proliferation and migration in vitro and osteolytic bone metastasis in vivo. Cancer Metastases Reviews, Volume 34 (Supplement 1), Page S Sarah Aitken, Euphemie Landao-Bassonga, Stuart H. Ralston and Aymen I. Idris. Beta-2 adrenoreceptor ligands regulate osteoclast differentiation in vitro by direct and indirect mechanisms. Bone, Volume 42 (Supplement 1), Page S34 - S35 Oral presentation at IBMS Workshops: Bone Biology & Therapeutics, Switzerland (March 2008) 17. Antonia Sophocleous, Euphemie Landao, Rob vant Hof, Aymen I. Idris and Stuart H. Ralston. Cannabinoid receptor 2 selective agonists stimulate osteoclast formation in vitro but act as anabolic agents in vivo by stimulating bone formation. Bone, Volume 42 (Supplement 1), Page S31 Oral presentation at IBMS Davos Workshops: Bone Biology & Therapeutics, Switzerland (2008) 18. Aymen I. Idris, Greig IR, Mohini Gray, Ralston SH, van t Hof, RJ. Small molecule inhibitors of TRAFdependent signaling as anti resorptive and anti-rheumatic drugs. Calcif Tissue Int, 80 (supplement 1), S Aymen I. Idris, Greig IR, Ralston SH, van t Hof, RJ. Biphenylcarboxylates inhibit bone resorption in vitro and ovariectomy induced bone loss in vivo without impairing PTH induced bone formation. Calcif Tissue Int, 80 (supplement 1), S Antonia Sophocleous, Euphemie Landao-Bassonga, van t Hof, RJ, Aymen I. Idris, Ralston SH. Cannabinoid receptor agonists are potential bone anabolic agents which stimulate bone formation in vitro and increase bone mass in vivo. Calcif Tissue Int, 80 (supplement 1), S Aymen I. Idris, Greig IR, Ralston SH, van t Hof, RJ. Cannabinoid Receptor 2 antagonists are potent inhibitors of bone resorption in vitro and ovariectomy-induced bone loss in vivo. Oral presentation at European Symposium on Calcified Tissues, Prague, Czech Republic (June 2006). 22. Aymen I. Idris, Robert J. van 't Hof, Iain R. Greig, Susan A. Ridge, David Baker, Ruth A. Ross, Stuart H. Ralston. (2005) Cannabinoid Receptor 1 Knockout mice have increased bone mass and are protected from ovariectomy induced bone loss. Oral presentation at Presented at European Symposium on Calcified Tissues, Switzerland (June 2005). 23. Aymen I. Idris, Robert J. van 't Hof, Iain R. Greig, Susan A. Ridge, Ruth A. Ross, Stuart H. Ralston. (2004) Cannabinoid receptor antagonists inhibit bone resorption and prevent ovariectomy induced bone loss, Calcif Tissue Int, 74 (supplement 1), S34. Oral presentation at Frontiers of Skeletal Biology, Switzerland and European Symposium on Calcified Tissues, France (2004). 24. Aymen I. Idris, Iain R. Greig, Stuart H. Ralston and Robert J. van 't Hof. (2004) ABD56 a potent inhibitor of bone resorption induces osteoclast apoptosis via NFκB and ERK inhibition in vitro, Calcif Tissue Int, 74 (supplement 1), S35.

5 Oral presentation at European Symposium on Calcified Tissues, Niece, France (June 2004). 25. Aymen I. Idris, P. Del Soldato, S.H. Ralston, R.J. van t Hof. NO-NSAIDs induce apoptosis in macrophages and mature osteoclasts but not primary osteoblasts, Calcif Tissue Int, 233, 369 (2003). 26. Aymen I. Idris, S.H. Ralston, R.J. van t Hof. Butanediol esters as novel inhibitors of bone resorption, Calcif Tissue Int, 233, 369 (2003). 27. Aymen I. Idris, I.R Greig, S.H. Ralston, R.J. van t Hof. The anti-resorptive effects of NO-NSAIDs are not dependent on COX-inhibition or Nitric oxide, Bone, 30 (sup 3), 19S (2002). Oral presentation at Frontiers of Skeletal Biology, Davos, Switzerland (March 2002). 28. Aymen I. Idris, P. Del Soldato, S.H. Ralston, R.J. van t Hof. Nitrosylated-NSAIDs are potent inhibitors of bone resorption in vitro, Calcif Tissue Int, 233, 369 (2001). Oral presentation at Bone and Tooth Society, Warwick, UK (July 2001).