UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

IMPROVED INTRATUMORAL OXYGENATION THROUGH VASCULAR NORMALIZATION INCREASES GLIOMA SENSITIVITY TO IONIZING RADIATION

McGee, MC; Hamner, JB; Williams, RF; Rosati, SF; Sims, TL; Ng, CY; Gaber, MW; ... Davidoff, AM; + view all (2010) IMPROVED INTRATUMORAL OXYGENATION THROUGH VASCULAR NORMALIZATION INCREASES GLIOMA SENSITIVITY TO IONIZING RADIATION. INT J RADIAT ONCOL , 76 (5) 1537 - 1545. 10.1016/j.ijrobp.2009.12.010.

Full text not available from this repository.

Abstract

Purpose: Ionizing radiation, an important component of glioma therapy, is critically dependent on tumor oxygenation. However, gliomas are notable for areas of necrosis and hypoxia, which foster radioresistance. We hypothesized that pharmacologic manipulation of the typically dysfunctional tumor vasculature would improve intratumoral oxygenation and, thus, the antiglioma efficacy of ionizing radiation.Methods and Materials: Orthotopic U87 xenografts were treated with either continuous interferon-beta (IFN-beta) or bevacizumab, alone, or combined with cranial irradiation (RT). Tumor growth was assessed by quantitative bioluminescence imaging; the tumor vasculature using immunohistochemical staining, and tumor oxygenation using hypoxyprobe staining.Results: Both IFN-beta and bevaziumab profoundly affected the tumor vasculature, albeit with different cellular phenotypes. IFN-beta caused a doubling in the percentage of area of perivascular cell staining, and bevacizumab caused a rapid decrease in the percentage of area of endothelial cell staining. However, both agents increased intratumoral oxygenation, although with bevacizumab, the effect was transient, being lost by 5 days. Administration of IFN-beta or bevacizumab before RT was significantly more effective than any of the three modalities as monotherapy or when RT was administered concomitantly with IFN-beta or bevacizumab or 5 days after bevacizumab.Conclusion: Bevacizumab and continuous delivery of IFN-beta each induced significant changes in glioma vascular physiology, improving intratumoral oxygenation and enhancing the antitumor activity of ionizing radiation. Additional investigation into the use and timing of these and other agents that modify the vascular phenotype, combined with RT, is warranted to optimize cytotoxic activity. (C) 2010 Elsevier Inc.

Type: Article
Title: IMPROVED INTRATUMORAL OXYGENATION THROUGH VASCULAR NORMALIZATION INCREASES GLIOMA SENSITIVITY TO IONIZING RADIATION
DOI: 10.1016/j.ijrobp.2009.12.010
Keywords: Vascular normalization, oxygenation, bevacizumab, interferon-beta, ionizing radiation, glioma, ENDOTHELIAL GROWTH-FACTOR, MEDIATED SYSTEMIC DELIVERY, INTERFERON-BETA, TUMOR ANGIOGENESIS, BLOOD-VESSELS, BRAIN-TUMORS, IN-VIVO, CANCER, MODEL, BEVACIZUMAB
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/1330949
Downloads since deposit
0Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item