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 |
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Rok vydání: | 2018 |
Předmět: |
CD31
Indoles medicine.medical_treatment Hydrostatic pressure Cetuximab Mice Nude Pharmaceutical Science 02 engineering and technology Pharmacology Mice 03 medical and health sciences Antineoplastic Agents Immunological 0302 clinical medicine Interstitial fluid Cell Line Tumor medicine Animals Neovascularization Pathologic business.industry Benzenesulfonates Head and neck cancer Neoplasms Experimental 021001 nanoscience & nanotechnology medicine.disease Vascular Endothelial Growth Factor Receptor-2 Cytokine Chemotherapy Adjuvant Head and Neck Neoplasms 030220 oncology & carcinogenesis Immunohistochemistry Female 0210 nano-technology business Adjuvant medicine.drug |
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 |
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