This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Thomas, S. M. Articles by Grandis, J. R. Search for Related Content PubMed PubMed Citation Articles by Thomas, S. M. Articles by Grandis, J. R.

Abrogation of Head and Neck Squamous Cell Carcinoma Growth by Epidermal Growth Factor Receptor Ligand Fused to Pseudomonas Exotoxin Transforming Growth Factor -PE38

Departments of ¹ Otolaryngology, ² Pharmacology, ³ Radiation Oncology, and ⁴ Biostatistics, University of Pittsburgh and the University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania; and ⁵ Laboratory of Molecular Biology, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, Maryland

Purpose: This study was undertaken to determine whether low intratumoral doses of the epidermal growth factor receptor ligand-transforming growth factor (TGF-) fused to Pseudomonas exotoxin (TGF-–PE38)-abrogated head and neck squamous cell carcinoma (HNSCC) tumor growth in vitro and in vivo.

Experimental Design: In vitro cytotoxicity assays were carried out to determine the sensitivity of HNSCC cells to TGF-–PE38. TGF-–PE38-treated HNSCC cells were examined by immunoblotting for cleaved poly(ADP-ribose) polymerase to evaluate apoptosis. Nude mice bearing established HNSCC xenografts were treated with several doses of TGF-–PE38 to evaluate the antitumor efficacy in vivo. Tumor sections were stained with terminal deoxynucleotidyl transferase-mediated nick end labeling for apoptosis. To determine the effect of oral administration of TGF-–PE38, gavage injections of TGF-–PE38 were administered, and the esophagus and surrounding soft tissue were then stained for apoptotic cells.

Results: HNSCC cell lines examined were sensitive to low doses of TGF-–PE38 (EC₅₀ in the range of 1.6 to 10 ng/mL). HNSCC cells treated with TGF-–PE38 undergo apoptosis. Antitumor effects were observed using 0.1 and 0.03 µg of TGF-–PE38 administered intratumorally. At these doses, the treatment was well tolerated. Tumors treated with the toxin had a higher number of apoptotic cells compared with the control tumors. No apoptotic cells were observed in the pharyngoesophageal tissues of the mice after gavage administration of the toxin suggesting that the toxin could be orally administered without toxicity.

Conclusions: These results indicate that topical or intratumoral administration of low doses of TGF-–PE38 may demonstrate antitumor effects in HNSCC without associated systemic toxicity.

This article has been cited by other articles:

				A. Lopez-Albaitero and R. L. Ferris Immune Activation by Epidermal Growth Factor Receptor Specific Monoclonal Antibody Therapy for Head and Neck Cancer Arch Otolaryngol Head Neck Surg, December 1, 2007; 133(12): 1277 - 1281. [Abstract] [Full Text] [PDF]