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| SPATIAL AND TEMPORAL CONTROL OF GENE-THERAPY USING IONIZING-RADIATION |
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| Author(s): HALLAHAN DE, MAUCERI HJ, SEUNG LP, DUNPHY EJ, WAYNE JD, HANNA NN, TOLEDANO A, HELLMAN S, KUFE DW, WEICHSELBAUM RR |
| Source: NATURE MEDICINE Volume: 1 Issue: 8 Pages: 786-791 Published: AUG 1995 |
| Times Cited: 236 References: 34 |
| Abstract: Activation of transcription of the Egr-1 gene by X-rays is regulated by the promoter region of this gene. We linked the radiation-inducible promoter region of the Egr-1 gene to the gene encoding the radiosensitizing and tumoricidal cytokine, tumour necrosis factor-alpha (TNF-alpha) and used a replication-deficient adenovirus to deliver the Egr-TNF construct to human tumours growing in nude mice. Combined treatment with AdS.EgrTNF and 5,000 cGy (rad) resulted in increased intratumoral TNF-a production and increased tumour control compared with treatment with Ad5.Egr-TNF alone or with radiation alone. The increase in tumour control was achieved without an increase in normal tissue damage when compared to tissue injury from radiation alone. Control of gene transcription by ionizing radiation in vivo represents a novel method of spatial and temporal regulation of gene-based medical treatments. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV CHICAGO, DEPT RADIAT & CELLULAR ONCOL, CHICAGO, IL 60637 USA
2. UNIV CHICAGO, PRITZKER SCH MED, CHICAGO, IL 60637 USA
3. UNIV CHICAGO, DEPT SURG, CHICAGO, IL 60637 USA
4. UNIV CHICAGO, DEPT ANESTHESIA & CRIT CARE, CHICAGO, IL 60637 USA
5. DANA FARBER CANC INST, DIV CANC PHARMACOL, BOSTON, MA 02115 USA |
| Publisher: NATURE PUBLISHING CO, 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental |
| IDS Number: RM635 |
| ISSN: 1078-8956 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |