Acute vascular response to cediranib treatment in human non-small-cell lung cancer xenografts with different tumour stromal architecture

Lung Cancer : Journal of the International Association for the Study of Lung Cancer
Yanyan JiangAnderson J Ryan

Abstract

Tumours can be categorised based on their stromal architecture into tumour vessel and stromal vessel phenotypes, and the phenotypes have been suggested to define tumour response to chronic treatment with a VEGFR2 antibody. However, it is unclear whether the vascular phenotypes of tumours associate with acute vascular response to VEGFR tyrosine kinase inhibitors (TKI), or whether the early changes in vascular function are associated with subsequent changes in tumour size. This study was sought to address these questions by using xenograft models of human non-small cell lung cancer (NSCLC) representing stromal vessel phenotype (Calu-3) and tumour vessel phenotype (Calu-6), respectively. For dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), nude mice bearing established Calu-3 or Calu-6 xenografts were treated with a potent pan-VEGFR TKI, cediranib (6 mg/kg), at 0 h and 22 h. DCE-MRI was performed 2h before the first dose and 2h after the second dose of cediranib to examine acute changes in tumour vessel perfusion. Tumours were harvested for hypoxia detection by CA9 immunohistochemistry. For tumour growth study, mice carrying established Calu-3 or Calu-6 tumours were treated with cediranib once daily for 5 days. Twen...Continue Reading

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Citations

Mar 30, 2016·International Journal of Radiation Oncology, Biology, Physics·Yanyan JiangAnderson J Ryan
Dec 22, 2016·European Surgical Research. Europäische Chirurgische Forschung. Recherches Chirurgicales Européennes·Elodie MelsensWim Ceelen
May 17, 2019·Science Translational Medicine·Alanna R KaplanPeter M Glazer
Jul 10, 2019·Mutagenesis·Alanna R Kaplan, Peter M Glazer

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Methods Mentioned

BETA
xenograft
xenografts
biopsies

Software Mentioned

SNAP
Matlab
SPSS
ITK

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