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Restriction of neuroblastoma angiogenesis and growth by interferon-alpha/beta

Streck, CJ; Zhang, Y; Miyamoto, R; Zhou, J; Ng, CYC; Nathwani, AC; Davidoff, AM; (2004) Restriction of neuroblastoma angiogenesis and growth by interferon-alpha/beta. In: SURGERY. (pp. 183 - 189). MOSBY, INC

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Abstract

Purpose. We tested the hypothesis that the antiangiogenic activity of the type I interferons (IFNs), could affect tumor engraftment and growth in marine xenograft models of neuroblastoma.Methods. Subcutaneous and retroperitoneal human neuroblastoma xenografts were established in SCID mice. Five days after tumor cell inoculation, daily subcutaneous injections of human IFN-alpha at several different doses were initiated and continued for 30 days. The effectiveness of continuous delivery of low-dose interferon was then tested using a gene therapy approach in which an adeno-associated virus vector encoding ITN-beta (rAAV-IFN-beta) was used to mediate expression prior to retroperitoneal tumor implantation.Results. Subcutaneous and retroperitoneal tumors were significantly smaller in IFN-alpha-treated mice, as compared with control mice. Intratumoral basic fibroblast growth factor and vascular endothelial growth factor expression were also decreased, as was mean intratumoral endothelial cell density. Interestingly, the lower doses of IFN-alpha were more effective than the higher dose. No tumors developed in any of the mice given rAAV-IFN-beta, whereas each of the mice that received control vector developed large tumors.Conclusions. Treatment with IFN had a significant impact on neuroblastoma engraftment and growth in mice, particularly when delivered continuously using a gene therapy approach. This activity appears to be mediated in part by inhibition of tumor-induced angiogenesis through the downregulation of tumor-elaborated factors, including basic fibroblast growth factor and vascular endothelial growth factor.

Type: Proceedings paper
Title: Restriction of neuroblastoma angiogenesis and growth by interferon-alpha/beta
Event: 65th Annual Meeting of the Society-of-University-Surgeons
Location: St Louis, MO
Dates: 2004-02-11 - 2004-02-14
DOI: 10.1016/j.surg.2004.04.014
Keywords: ADENOASSOCIATED VIRAL VECTORS, RENAL-CELL CARCINOMA, TUMOR ANGIOGENESIS, EXPRESSION, TRIAL, MELANOMA, THERAPY, CANCER, IMMUNOTHERAPY, SCHEDULE
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: http://discovery.ucl.ac.uk/id/eprint/1330929
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