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¹ Division of Pediatrics and ² Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX

Requests for Reprints: Eugenie S. Kleinerman, Division of Pediatrics, Unit 87, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. Phone: (713) 792-8110; Fax: (713) 794-5042. E-mail: ekleiner{at}mail.mdanderson.org

We assessed vascular endothelial growth factor (VEGF) expression in four different human Ewing's sarcoma cell lines (TC71, SK-ES, RD, and A4573) and in tumors in nude mice induced following s.c. injection of TC71 cells. Three of the four cell lines (TC71, SK-ES, and A4573) expressed significantly higher levels of VEGF than did normal human osteoblasts. Transfection of the adenovirus type 5 early region 1A (E1A) gene into TC71 cells down-regulated VEGF expression in vitro. In the mice bearing TC71 cell tumors, intratumoral injections of an adenoviral vector containing the E1A gene (Ad-E1A) decreased VEGF expression, inhibited tumor growth, and increased the survival rates in comparison with the mice given injections of PBS or an adenoviral vector containing ß-galactosidase (Ad-ß-gal). E1A gene therapy also significantly reduced blood vessel density and induced cell apoptosis in the tumors. These results demonstrate that E1A gene therapy inhibits angiogenesis, most likely by suppression of VEGF expression. Thus, E1A gene therapy may be a new therapeutic approach for Ewing's sarcoma.

Key Words: Ewing's sarcoma • angiogenesis • VEGF • E1A • gene therapy

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Grant support: National Cancer Institute grant CA 82606 (E.S.K.); the Elliot Kayton Memorial Fund; a grant from the Ladies Auxiliary for Ewing's Sarcoma Research; and National Institutes of Health core grant CA16672.

Received 7/15/03; revised 9/10/03; accepted 9/15/03.

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