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Cancers 2016, 8(1), 11; doi:10.3390/cancers8010011

Preclinical Activity of the Vascular Disrupting Agent OXi4503 against Head and Neck Cancer

1
Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
2
College of Osteopathic Medicine, University of New England, Biddeford, ME 04005, USA
3
Department of Molecular and Cellular Biophysics and Biochemistry, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
4
Department of Oral Medicine/Head and Neck Surgery, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Dirk Rades
Received: 24 October 2015 / Revised: 28 December 2015 / Accepted: 4 January 2016 / Published: 7 January 2016
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Abstract

Vascular disrupting agents (VDAs) represent a relatively distinct class of agents that target established blood vessels in tumors. In this study, we examined the preclinical activity of the second-generation VDA OXi4503 against human head and neck squamous cell carcinoma (HNSCC). Studies were performed in subcutaneous and orthotopic FaDu-luc HNSCC xenografts established in immunodeficient mice. In the subcutaneous model, bioluminescence imaging (BLI) along with tumor growth measurements was performed to assess tumor response to therapy. In mice bearing orthotopic tumors, a dual modality imaging approach based on BLI and magnetic resonance imaging (MRI) was utilized. Correlative histologic assessment of tumors was performed to validate imaging data. Dynamic BLI revealed a marked reduction in radiance within a few hours of OXi4503 administration compared to baseline levels. However, this reduction was transient with vascular recovery observed at 24 h post treatment. A single injection of OXi4503 (40 mg/kg) resulted in a significant (p < 0.01) tumor growth inhibition of subcutaneous FaDu-luc xenografts. MRI revealed a significant reduction (p < 0.05) in volume of orthotopic tumors at 10 days post two doses of OXi4503 treatment. Corresponding histologic (H&E) sections of Oxi4503 treated tumors showed extensive areas of necrosis and hemorrhaging compared to untreated controls. To the best of our knowledge, this is the first report, on the activity of Oxi4503 against HNSCC. These results demonstrate the potential of tumor-VDAs in head and neck cancer. Further examination of the antivascular and antitumor activity of Oxi4503 against HNSCC alone and in combination with chemotherapy and radiation is warranted. View Full-Text
Keywords: head and neck squamous cell carcinomas; angiogenesis; vascular disrupting agents; bioluminescence imaging; magnetic resonance imaging head and neck squamous cell carcinomas; angiogenesis; vascular disrupting agents; bioluminescence imaging; magnetic resonance imaging
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MDPI and ACS Style

Bothwell, K.D.; Folaron, M.; Seshadri, M. Preclinical Activity of the Vascular Disrupting Agent OXi4503 against Head and Neck Cancer. Cancers 2016, 8, 11.

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