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Adjuvant anti-angiogenic therapy enhances chemotherapeutic uptake in a murine model of head and neck cancer
- Source :
- Journal of Drug Targeting. 27:193-200
- Publication Year :
- 2018
- Publisher :
- Informa UK Limited, 2018.
-
Abstract
- 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
- Subjects :
- 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
Subjects
Details
- ISSN :
- 10292330 and 1061186X
- Volume :
- 27
- Database :
- OpenAIRE
- Journal :
- Journal of Drug Targeting
- Accession number :
- edsair.doi.dedup.....12b581405674a350c65a2de39b679e78