Translational strategies exploiting TNF-α that sensitize tumors to radiation therapy
| Autor: | Donald Kufe, Elena V. Efimova, Nikolai N. Khodarev, Eva Galka, Sean P. Pitroda, M.A. Beckett, Helena J. Mauceri, C R King, Samuel Hellman, Mitchell C. Posner, Hua Liang, Thomas E. Darga, Ralph R. Weichselbaum, Harold G. Sutton |
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| Rok vydání: | 2008 |
| Předmět: |
Radiation-Sensitizing Agents
Cancer Research Pathology medicine.medical_specialty Endothelium medicine.medical_treatment Melanoma Experimental Apoptosis X-Ray Therapy Biology Receptors Tumor Necrosis Factor Article Etanercept Mice Cell Line Tumor Pancreatic cancer medicine Animals Humans Receptors Tumor Necrosis Factor Type II Radiosensitivity Receptor Molecular Biology Tumor Necrosis Factor-alpha Melanoma Endothelial Cells Genetic Therapy medicine.disease Radiation therapy medicine.anatomical_structure Receptors Tumor Necrosis Factor Type I Cell culture Immunoglobulin G Cancer research Molecular Medicine Tumor necrosis factor alpha Immunosuppressive Agents Neoplasm Transplantation |
| Zdroj: | Cancer Gene Therapy. 16:373-381 |
| ISSN: | 1476-5500 0929-1903 |
| DOI: | 10.1038/cgt.2008.86 |
| Popis: | TNFerade is a radioinducible adenoviral vector expressing tumor necrosis factor-alpha (TNF-alpha) (Ad.Egr-TNF) currently in a phase III trial for inoperable pancreatic cancer. We studied B16-F1 melanoma tumors in TNF receptor wild-type (C57BL/6) and deficient (TNFR1,2-/- and TNFR1-/-) mice. Ad.Egr-TNF+IR inhibited tumor growth compared with IR in C57BL/6 but not in receptor-deficient mice. Tumors resistant to TNF-alpha were also sensitive to Ad.Egr-TNF+IR in C57BL/6 mice. Ad.Egr-TNF+IR produced an increase in tumor-associated endothelial cell apoptosis not observed in receptor-deficient animals. Also, B16-F1 tumors in mice with germline deletions of TNFR1,2, TNFR1 or TNF-alpha, or in mice receiving anti-TNF-alpha exhibited radiosensitivity. These results show that tumor-associated endothelium is the principal target for Ad.Egr-TNF radiosensitization and implicate TNF-alpha signaling in tumor radiosensitivity. |
| Databáze: | OpenAIRE |
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