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dc.contributor.authorSerganova, I
dc.contributor.authorDoubrovin, M
dc.contributor.authorVider, J
dc.contributor.authorPonomarev, V
dc.contributor.authorSoghomonyan, S
dc.contributor.authorBeresten, T
dc.contributor.authorAgeyeva, L
dc.contributor.authorSerganov, A
dc.contributor.authorCai, SD
dc.contributor.authorBalatoni, J
dc.contributor.authorBlasberg, R
dc.contributor.authorGelovani, J
dc.date.accessioned2012-04-11
dc.date.accessioned2012-07-12T23:44:38Z
dc.date.accessioned2017-03-01T22:52:02Z
dc.date.available2017-03-01T22:52:02Z
dc.date.issued2004
dc.date.modified2012-07-12T23:44:38Z
dc.identifier.issn0008-5472
dc.identifier.doi10.1158/0008-5472.CAN-04-0842
dc.identifier.urihttp://hdl.handle.net/10072/45851
dc.description.abstractTumor 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.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherAmerican Association for Cancer Research
dc.publisher.placeUnited States of America
dc.relation.ispartofpagefrom6101
dc.relation.ispartofpageto6108
dc.relation.ispartofissue17
dc.relation.ispartofjournalCancer Research
dc.relation.ispartofvolume64
dc.subject.fieldofresearchOncology and carcinogenesis
dc.subject.fieldofresearchCancer cell biology
dc.subject.fieldofresearchcode3211
dc.subject.fieldofresearchcode321101
dc.titleMolecular imaging of temporal dynamics and spatial heterogeneity of hypoxia-inducible factor-1 signal transduction activity in tumors in living mice.
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codec1x
gro.facultyGriffith Health Faculty
gro.date.issued2004
gro.hasfulltextNo Full Text
gro.griffith.authorVider, Jelena


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