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Adenovirus-E1A gene therapy enhances the in vivo sensitivity of Ewing's sarcoma to VP-16

Cancer Gene Therapy volume 9, pages 407–413 (2002)Cite this article

Abstract

This study determined the effect of Ad-E1A gene therapy in vivo. TC71 cells (2×106) injected subcutaneously into nude mice resulted in tumor development (1–3 mm) 6 days later. Animals were then treated with Ad-E1A or Ad-β-gal (5×109 plaque-forming units) by intratumoral injection twice weekly for 2 weeks. Animals received 8 mg/kg VP-16 given by intraperitoneal injection daily for 5 days following the first week of treatment with Ad-E1A or Ad-β-gal. Control animals received no therapy or VP-16 only after tumor cells were injected. When tumors exceeded 2×2 cm, the mice were sacrificed and the tumors underwent histologic and immunohistochemical analysis. Tumors from mice treated with Ad-E1A plus VP-16 were 9.6-fold smaller than those treated with VP-16 alone and 6.3-fold smaller than those treated with Ad-E1A alone. HER2/neu p185 protein expression decreased in all tumors that received Ad-E1A therapy. TUNEL fluorescence staining revealed more apoptosis in the tumors from animals treated with Ad-E1A plus VP-16 than in those from animals treated with Ad-E1A alone, Ad-β-gal plus VP-16, or VP-16 alone. These data demonstrated that Ad-E1A gene therapy down-regulated HER2/neu expression, increased tumor cell apoptosis induced by VP-16, and enhanced tumor cell sensitivity to VP-16. Ad-E1A may have potential in the treatment of relapsed drug-resistant Ewing's sarcoma.

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Authors and Affiliations

  1. Division of Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston, 77030, Texas, USA

    Rong-Rong Zhou, Shu-Fang Jia, Zhichao Zhou & Eugenie S Kleinerman

  2. Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, 77030, Texas, USA

    Yunfang Wang & Corazon D Bucana

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  1. Rong-Rong Zhou
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  2. Shu-Fang Jia
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  3. Zhichao Zhou
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  4. Yunfang Wang
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  5. Corazon D Bucana
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  6. Eugenie S Kleinerman
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Correspondence to Eugenie S Kleinerman.

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Zhou, RR., Jia, SF., Zhou, Z. et al. Adenovirus-E1A gene therapy enhances the in vivo sensitivity of Ewing's sarcoma to VP-16. Cancer Gene Ther 9, 407–413 (2002). https://doi.org/10.1038/sj.cgt.7700449

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