Adjuvant anti-angiogenic therapy enhances chemotherapeutic uptake in a murine model of head and neck cancer

Autor: Andrew C. Prince, Eben L. Rosenthal, Christopher D. Willey, Jason M. Warram, Lindsay S. Moore, Neel Patel, William R. Carroll, Andrew S. McGee, John C. Ahn
Rok vydání: 2018
Předmět:
Zdroj: Journal of Drug Targeting. 27:193-200
ISSN: 1029-2330
1061-186X
DOI: 10.1080/1061186x.2018.1497040
Popis: Intratumoural metabolic demands result in excessive angiogenic cytokine release leading to unorganised vasculature. Resultant fluid dynamics oppose blood flow and drug penetration due to a marked increase in interstitial fluid hydrostatic pressure. It is hypothesised that anti-angiogenic therapy may function to 'prune' vasculature and lead to improved chemotherapeutic penetration. Subcutaneous, OSC19 tumour bearing mice (n = 5/dose/agent) were administered varying doses of an anti-mouse VEGFR2 (DC101) or an anti-mouse VEGFR3 (31C1) -3 d, -1 d, 0 d, +1 d and +3 d prior to 200 µg of cetuximab fluorescently labelled with IRDye800CW. Fluorescence imaging of tumours was performed 10 d post cetuximab-IRDye800CW dose to monitor therapeutic uptake. Co-administration of dual anti-angiogenic agents at 50-50%, 75-25% and 25-75% using optimal dose and time (-1 d 10 mg/kg anti-VEGFR2 and -1 d 40 mg/kg anti-VEGFR3) was also evaluated. In order to establish vessel normalisation, NG2 (pericyte marker) and CD31 (endothelial cells) ratios were assessed during immunohistochemical staining of tumour sections. Twenty-mg/kg anti-VEGFR3 + 5 mg/kg anti-VEGFR2 significantly (p
Databáze: OpenAIRE