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Lombardi research teams hone in on treatments for osteosarcoma and Ewing's sarcoma
Date:4/20/2010

disrupt a key protein-protein interaction, leading to decreased cancer growth. Using state-of-the art tools, we screened 3000 compounds and found one, YK-4-279, that significantly inhibited this protein-protein binding. We have now demonstrated that YK-4-279 has a detrimental effect on Ewing's sarcoma both in vitro and in vivo, providing us with an oncogenic target and a lead compound for therapeutic testing." Jeffrey Toretsky

Authors: Jeffrey A. Toretsky, Hayriye V. Erkizan, Yali Kong, Julie S. Barber-Rotenberg, Milton L. Brown, and Aykut ren, of Georgetown Lombardi Comprehensive Cancer Center; Melinda Merchant, of Pediatric Oncology Branch, National Institutes of Health

To be presented: Tuesday, April 20, 9:00 am -12:00 pm; Exhibit Hall A-C, Poster Section 18; Board 12


EWS-FLI1 is regulated by acetylation (Abstract # 3897)

EMBARGO: Tuesday, April 20, 2010; 2:00 pm ET

Author's summary: "EWS-FLI1 is a protein specific to Ewing's Sarcoma Family of Tumors (ESFT). EWS-FLI1 is a transcription factor and thereby a central regulator of ESFT cell survival and tumor growth. The mechanisms controlling its function and stability are not well understood. We show, for the first time, that EWS-FLI1 is modified by acetylation, a process that can in fact regulate both stability and function of proteins. Drugs called Histone Deacetylase Inhibitors (HDI) inhibit the reverse process, the deacetylation of proteins, and are promising in the treatment of a variety of cancers. HDI act mainly (but not solely) by deacetylating histone protein, and are very active in inducing cell death of ESFT cells. We investigate how acetylation regulates EWS-FLI1 and the possibility of EWS-FLI1 being a specific target for the activity of HDI in ESFT cells." Silke Schlottmann

Authors: Silke Schlottmann, Hayriye V. Erkizan, Julie Barber-Rotenberg, Aykut Uren, Maria L. Avantaggiati, and Jeffrey A. Toretsky. Georgetown Lombardi Comp. Cancer Ctr.
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Contact: Karen Mallet
km463@georgetown.edu
215-514-9751
Georgetown University Medical Center
Source:Eurekalert

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