Comparisons of the efficacy of a Jak1/2 inhibitor (AZD1480) with a VEGF signaling inhibitor (Cediranib) and sham treatments in mouse tumors using DCE-MRI, DW-MRI, and histology

Mary E. Loveless, Deborah Lawson, Michael Collins, Murali V. Prasad Nadella, Corinne Reimer, Dennis Huszar, Jane Halliday, John C. Waterton, John C. Gore, Thomas E. Yankeelov

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Jak1/2 inhibition suppresses STAT3 phosphorylation that is characteristic of many cancers. Activated STAT3 promotes the transcription of factors that enhance tumor growth, survival, and angiogenesis. AZD1480 is a novel small molecule inhibitor of Jak1/2,which is a key mediator of STAT3 activation. This study examined the use of diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) biomarkers in assessing early tumor response to AZD1480. Cediranib (AZD2171), a vascular endothelial growth factor signaling inhibitor, was used as a comparator. Thirty mice were injected with Calu-6 lung cancer cells and randomized into the three treatment groups: AZD1480, cediranib, and sham. DWMRI and DCE-MRI protocols were performed at baseline and at days 3 and 5 after treatment. The percent change from baseline measurements for K trans, ADC, and v e were calculated and compared with hematoxylin and eosin (H&E), CD31, cParp, and Ki-67 histology data. Decreases in K trans of 29% (P
    Original languageEnglish
    Pages (from-to)54-64
    Number of pages10
    JournalNeoplasia
    Volume14
    Issue number1
    DOIs
    Publication statusPublished - Jan 2012

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