Faculty Collaboration Database

Tumor necrosis factor-alpha-based gene therapy enhances radiation cytotoxicity in human prostate cancer. Cancer Gene Ther 1998;5(6):344-9

Date

01/23/1999

Pubmed ID

9917088

Scopus ID

2-s2.0-0032199393 (requires institutional sign-in at Scopus site)   70 Citations

Abstract

The purpose of the present study was to determine the therapeutic potential of combining radiotherapy with tumor necrosis factor (TNF)-alpha-based gene therapy in the human prostate cancer PC-3 xenograft. PC-3 cells are highly resistant to TNF-alpha-induced cytotoxicity in vitro. A modest enhancement of radiation killing was observed with the addition of TNF-alpha in clonogenic survival assays. Combined treatment with Ad.Egr-TNF, a replication-deficient adenovirus modified to express TNF-alpha following the exposure of infected cells to ionizing radiation (40 Gy administered at 5 Gy per fraction) in vivo, resulted in increased tumor control, as defined by a reduction of tumor volume, when compared with treatment with Ad.Egr-TNF alone or with radiation alone (P < .03). The improvement in tumor control was achieved without increasing acute normal tissue damage when compared with tissue injury from radiation alone. The results of these studies support further development and clinical application of genetic radiotherapy for human prostate cancer.

Author List

Chung TD, Mauceri HJ, Hallahan DE, Yu JJ, Chung S, Grdina WL, Yajnik S, Kufe DW, Weichselbaum RR

Author

Santosh Yajnik MD Associate Professor in the Radiation Oncology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenoviridae
Animals
Cell Survival
Combined Modality Therapy
Dose-Response Relationship, Drug
Female
Genetic Therapy
Humans
Male
Mice
Neoplasm Transplantation
Prostatic Neoplasms
Transfection
Transplantation, Heterologous
Tumor Cells, Cultured
Tumor Necrosis Factor-alpha