Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Enhancement of radiotherapy by hyperthermia-regulated gene therapy
Autore:
Lohr, F; Hu, K; Huang, Q; Zhang, L; Samulski, TV; Dewhirst, MW; Li, CY;
Indirizzi:
Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC USA Duke Univ Durham NCUSA Univ, Med Ctr, Dept Radiat Oncol, Durham, NC USA
Titolo Testata:
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
fascicolo: 5, volume: 48, anno: 2000,
pagine: 1513 - 1518
SICI:
0360-3016(200012)48:5<1513:EORBHG>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
FACILITATE TUMOR-REGRESSION; PROSTATE-CANCER; REGIONAL HYPERTHERMIA; IONIZING-RADIATION; PHASE-II; INTERLEUKIN-12; ADENOVIRUS; CELLS; ADENOCARCINOMA; DISSEMINATION;
Keywords:
interleukin 12 (IL-12); heat inducible gene therapy; immunotherapy; radiotherapy; multimodality therapy;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
26
Recensione:
Indirizzi per estratti:
Indirizzo: Lohr, F Univ Heidelberg, Dept Radiat Oncol, INF 400, D-69120 Heidelberg, Germany Univ Heidelberg INF 400 Heidelberg Germany D-69120 lberg, Germany
Citazione:
F. Lohr et al., "Enhancement of radiotherapy by hyperthermia-regulated gene therapy", INT J RAD O, 48(5), 2000, pp. 1513-1518

Abstract

Purpose: Interleukin 12 (IL-12) has shown strong antitumoral effects in numerous pre-clinical studies and appears to act synergistically with radiation in murine tumors. The major impediment to its clinical use has been its systemic toxicity. While using intratumorally injected viral gene therapy vectors encoding IL-12 reduces systemic side effects substantially, elevatedsystemic transgene levels are still observed because adenovirus can reach the circulation. Further restricting IL-12 expression in the tumor is therefore desirable in a combined radiation and adenovirus mediated cancer gene therapy regimen. Methods and Materials: Hyperthermia-regulated gene therapy was tested in anonimmunogenic B16.F10 melanoma line that is syngeneic with C57BL/6 mice. For hyperthermic gene therapy, an adenoviral vector coding for IL-12 under the control of the promoter of the human heat shock protein 70B (hsp70B) was used. One meek after transplantation (at a 5-7 mm diameter), tumors were irradiated with 3 x 11 Gy (mo-we-fri). Adenovirus was injected at 3 x 10(8)pfu/tumor 24 h before the last radiation fraction or 3 days afterwards. Hyperthermia was performed 24 h later at 42.5 degreesC. Growth delay to reaching 3 times initial tumor volume was chosen as the biologic endpoint. IL-12levels in tumor and serum were determined by using the enzyme-linked immunosorbant assay (ELISA). Results: Adenovirus mediated intratumoral expression of IL-12 under the control of a heat inducible promoter in combination with hyperthermia is almost as effective as that under the control of a constitutive cytomegaly virus (CMV) promoter while systemic transgene levels are substantially reduced with the heat inducible promoter. The response to radiotherapy is improved considerably when combined with heat inducible gene therapy without apparent systemic toxicity. When used as a single dose, applying IL-12 gene therapy after completion of radiotherapy appears to be beneficial. Conclusion: Hyperthermia-regulated gene therapy in combination with radiation is feasible and therapeutically effective in murine tumors,vith no apparent systemic toxicity. (C) 2000 Elsevier Science Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 16:23:34