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  • Molecular imaging of temporal dynamics and spatial heterogeneity of hypoxia-inducible factor-1 signal transduction activity in tumors in living mice.

    Author(s)
    Serganova, I
    Doubrovin, M
    Vider, J
    Ponomarev, V
    Soghomonyan, S
    Beresten, T
    Ageyeva, L
    Serganov, A
    Cai, SD
    Balatoni, J
    Blasberg, R
    Gelovani, J
    Griffith University Author(s)
    Vider, Jelena
    Year published
    2004
    Metadata
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    Abstract
    Tumor hypoxia is a spatially and temporally heterogeneous phenomenon, which results from several tumor and host tissue-specific processes. To study the dynamics and spatial heterogeneity of hypoxia-inducible factor-1 (HIF-1)-specific transcriptional activity in tumors, we used repetitive noninvasive positron emission tomography (PET) imaging of hypoxia-induced HIF-1 transcriptional activity in tumors in living mice. This approach uses a novel retroviral vector bearing a HIF-1-inducible "sensor" reporter gene (HSV1-tk/GFP fusion) and a constitutively expressed "beacon" reporter gene (DsRed2/XPRT). C6 glioma cells transduced ...
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    Tumor hypoxia is a spatially and temporally heterogeneous phenomenon, which results from several tumor and host tissue-specific processes. To study the dynamics and spatial heterogeneity of hypoxia-inducible factor-1 (HIF-1)-specific transcriptional activity in tumors, we used repetitive noninvasive positron emission tomography (PET) imaging of hypoxia-induced HIF-1 transcriptional activity in tumors in living mice. This approach uses a novel retroviral vector bearing a HIF-1-inducible "sensor" reporter gene (HSV1-tk/GFP fusion) and a constitutively expressed "beacon" reporter gene (DsRed2/XPRT). C6 glioma cells transduced with this multireporter system revealed dose-dependent patterns in temporal dynamics of HIF-1 transcriptional activity induced by either CoCl2 or decreased atmospheric oxygen concentration. Multicellular spheroids of C6 reporter cells developed a hypoxic core when >350 microm in diameter. 18F-2'-fluoro-2'deoxy-1beta-D-arabionofuranosyl-5-ethyl-uracil (FEAU) PET revealed spatial heterogeneity of HIF-1 transcriptional activity in reporter xenografts in mice as a function of size or ischemia-reperfusion injury. With increasing tumor diameter (>3 mm), a marked increase in HIF-1 transcriptional activity was observed in the core regions of tumors. Even a moderate ischemia-reperfusion injury in small C6 tumors caused a rapid induction of HIF-1 transcriptional activity, which persisted for a long time because of the inability of C6 tumors to rapidly compensate acute changes in tumor microcirculation.
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    Journal Title
    Cancer Research
    Volume
    64
    Issue
    17
    DOI
    https://doi.org/10.1158/0008-5472.CAN-04-0842
    Subject
    Cancer Cell Biology
    Oncology and Carcinogenesis
    Publication URI
    http://hdl.handle.net/10072/45851
    Collection
    • Journal articles

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