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Endothelial cells • glucocorticoids • leukemia • osteonecrosis • genetics
My research focuses on the vascular complication of cancer therapy, mainly high dose glucocorticoids. Synthetic glucocorticoids are often administered in high doses to kill cancer cells in young patients with leukemia and lymphoma. A devastating side effect is the death of healthy cells lining the small vessels in bone. This results in bone death, or osteonecrosis, and collapse of the hip joint. The only treatment to alleviate the pain is to surgically replace the dead bone with a synthetic one, which may have to be replaced more than once in the lifetime of a young recipient. As survival rates continue to rise, osteonecrosis is likely to become more prevalent and have greater impact upon the quality of life of survivors. Early detection would be a major advancement. I am currently investigating potential biomarkers, used in conjunction with magnetic resonance imaging, to screen for susceptibility to osteonecrosis in young patients affected with acute lymphoblastic leukemia and treated with high dose glucocorticoid therapy. My translational research program aims to identify a potential pathway for new therapeutic targets and identify a biomarker for early osteonecrosis. The long-term goal is to transform patient care and improve the quality of life of cancer survivors.
Carli A, Harvey EJ, Gao C, Li Y, Li A, Azeddine B, Sayegh M, Wang H, Nayal A, Michel RP, Henderson JE, Séguin C. Substrain-specific differences in bone parameters, alpha-2- macroglobulin circulating levels and osteonecrosis incidence in a rat model. J Orthop Res. 2016 Feb 19. doi: 10.1002/jor.23199. [Epub ahead of print] PMID:26895739.
Albers A, Carli A, Routy B, Harvey EJ, Séguin C. Treatment with acetylsalicylic acid prevents short-to-mid-term radiographic progression of non-traumatic osteonecrosis of the femoral head: a pilot study Can J Surg 2015 Jun; 58(3):198-205 PMID: 26011853.
Kerachian MA, Harvey EJ, Cournoyer D, Chow TY, Nayal A, Séguin C. A rat model of glucocorticoid-induced osteonecrosis. J Orthop Surg Res. 2011 Dec 21;6:62. doi: 10.1186/1749-799X-6-62. PMID: 22189040.
Kerachian MA, Cournoyer D, Harvey EJ, Chow TY, Bégin LR, Nayal A, Séguin C. New insights into the pathogenesis of glucocorticoid-induced avascular necrosis: microarray analysis of gene expression in a rat model. Arthritis Res Ther. 2010;12(3):R124. doi: 10.1186/ar3062. Epub 2010 Jun 25 PMID: 20579363.
Séguin C, Kassis J, Busque L, Theodoropoulos T, Bestawros A, Alonso ML, Harvey EJ. Non-traumatic necrosis of bone (osteonecrosis) is associated with endothelial cell activation but not thrombophilia. Rheumatology. (Oxford). 2008 Aug;47(8):1151-5 PMID: 18524806.