Pediatric Focus - Vol. 1, Issue 2

• Letter from Chairman

• New Director of Pediatric
Cardiology

• Hospital Receives Lounge

• Pediatric Hypertension

• Ewing's Sarcoma Family
of Tumors

• New Physician Profiles

Spotlight on Research: Study Seeks to Improve Survival Rate of ESFT Patients

Jeffrey Toretsky, M.D., assistant professor of pediatrics at the University of Maryland School of Medicine, is currently researching Ewing's Sarcoma Family of Tumors (ESFT), which affects individuals between the ages of 3 and 40. The most common age group affected by ESFT is teenagers. Currently, patients who develop ESFT undergo intensive chemotherapy for approximately one year.

Despite an excellent initial response to therapy, 30 to 40 percent of patients with a single lesion and 80 to 90 percent of patients with initial metastasis contract the disease a second time, which is almost always fatal. Dr. Toretsky describes his research: In seeking a greater understanding of ESFT, two challenges must be confronted. The first challenge involves improving the survival rate in patients with ESFT and identifying risk factors in patients with single lesions. The second challenge entails the development of new treatment methods to combat repeat occurrences of the disease. Our laboratory and research program is hard at work addressing both of these challenges.

Ewing's sarcoma contains a genetic abnormality that rearranges part of chromosome 11 with part of chromosome 22. This rearrangement forms a new protein, called EWS/FL11, which is critical for Ewing's Sarcoma cell survival. Laboratory studies show that the elimination of EWS/FL11 causes Ewing's Sarcoma tumor death. Since eliminating EWS/F11 has the potential to destroy tumor cells while leaving normal cells intact, our laboratory researchers are attempting to identify drugs that will disrupt EWS/F11 function. Unfortunately, current laboratory techniques cannot yet be applied to humans.

In order to identify proteins that interact with EWS/FL11, we have prepared recombinant EWS/FL11 in bacterial cells. We have mixed the recombinant EWS/FL11 with a bacterial virus that has a random library of protein fragments on its surface. The virus particles, which stick to the EWS/FL11, are likely to contain fragments of proteins that will interact with EWS/FL11 inside patient tumors. We already have assembled a large collection of viruses that stick to EWS/FL11 and are now in the process of identifying the protein fragments.

Once we identify the protein fragments, the next step will involve determining whether the entire protein interacts with EWS/FL11. Once we find out which proteins are critical for EWS/FL11 to cause Ewing's Sarcoma, we will begin to identify drugs that could potentially interrupt this interaction. Our long-term plan involves screening large collections of compounds that could possibly serve as future ESFT therapy techniques.

For more information about UMHC or to make an appointment, call the University Physicians Consultation and Referral Service at:
1-800-492-5538 (patients) or 1-800-373-4111 (physicians).

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