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 Gupta, V. K. Articles by Posner, M. C. Search for Related Content PubMed PubMed Citation Articles by Gupta, V. K. Articles by Posner, M. C. Related Collections Molecular biology

Combined Gene Therapy and Ionizing Radiation Is a Novel Approach To Treat Human Esophageal Adenocarcinoma

From the Departments of Surgery (VKG, JOP, NTJ, MCP) and Radiation & Cellular Oncology (HJM, SS, RRW), The University of Chicago, Chicago, Illinois.

Correspondence: Address correspondence and reprint requests to: Mitchell C. Posner, MD, Department of Surgery, University of Chicago, 5841 South Maryland Ave., MC 5031, Chicago, IL 60637; Fax: 773-702-4444; E-mail: mposner@ surgery.bsd.uchicago.edu.

Background: The ability to infect tumor cells limits the antitumor effects of gene therapy. The addition of radiotherapy to treatment with Ad.Egr.TNF.11D, a replication-deficient adenovirus containing a radiation-inducible promoter, early growth response-1, and the tumor necrosis factor- (TNF) complementary DNA may enhance the therapeutic ratio.

Methods: Seg-1 human esophageal adenocarcinoma cells were treated with Ad.Egr.TNF.11D with or without radiation. TNF levels were quantified with enzyme-linked immunosorbent assay. Athymic nude mice bearing Seg-1 tumors were randomized to buffer, ionizing radiation, Ad.Egr.TNF.11D, and combination therapy. Tumor growth delay was used to compare treatment regimens. TNF levels were measured in tumor homogenates and plasma.

Results: Seg-1 cells treated with Ad.Egr.TNF.11D and ionizing radiation demonstrated increased TNF levels at 72 hours compared with cells exposed to vector alone (124 ± 0 pg/mL vs. 31.11 ± 22 pg/mL; P = .008). In vivo, Ad.Egr.TNF.11D-treated tumors expressed low TNF levels (151.5 ± 107.11 pg/mg protein) compared with tumors receiving combined treatment (793.92 ± 489.13 pg/mg protein; P = .067). Increased TNF levels were associated with increased tumor growth delay after combined treatment (P < .05).

Conclusions: Radiotherapy enables focal stimulation of TNF expression in Ad.Egr.TNF.11D-infected cells and thus improves local tumor control.

Key Words: Tumor necrosis factor- • Esophageal cancer • Ionizing radiation • Gene therapy

This article has been cited by other articles:

				M. Goblirsch, P. Zwolak, M. L. Ramnaraine, W. Pan, C. Lynch, P. Alaei, and D. R. Clohisy Novel Cytosine deaminase fusion gene enhances the effect of radiation on breast cancer in bone by reducing tumor burden, osteolysis, and skeletal fracture. Clin. Cancer Res., May 15, 2006; 12(10): 3168 - 3176. [Abstract] [Full Text] [PDF]

				C. A. Lopez, E. T. Kimchi, H. J. Mauceri, J. O. Park, N. Mehta, K. T. Murphy, M. A. Beckett, S. Hellman, M. C. Posner, D. W. Kufe, et al. Chemoinducible gene therapy: A strategy to enhance doxorubicin antitumor activity Mol. Cancer Ther., September 1, 2004; 3(9): 1167 - 1175. [Abstract] [Full Text] [PDF]

				A. J. Mundt, S. Vijayakumar, J. Nemunaitis, A. Sandler, H. Schwartz, N. Hanna, T. Peabody, N. Senzer, K. Chu, C. S. Rasmussen, et al. A Phase I Trial of TNFerade Biologic in Patients with Soft Tissue Sarcoma in the Extremities Clin. Cancer Res., September 1, 2004; 10(17): 5747 - 5753. [Abstract] [Full Text] [PDF]