dc.contributor.author | Serganova, I | |
dc.contributor.author | Doubrovin, M | |
dc.contributor.author | Vider, J | |
dc.contributor.author | Ponomarev, V | |
dc.contributor.author | Soghomonyan, S | |
dc.contributor.author | Beresten, T | |
dc.contributor.author | Ageyeva, L | |
dc.contributor.author | Serganov, A | |
dc.contributor.author | Cai, SD | |
dc.contributor.author | Balatoni, J | |
dc.contributor.author | Blasberg, R | |
dc.contributor.author | Gelovani, J | |
dc.date.accessioned | 2012-04-11 | |
dc.date.accessioned | 2012-07-12T23:44:38Z | |
dc.date.accessioned | 2017-03-01T22:52:02Z | |
dc.date.available | 2017-03-01T22:52:02Z | |
dc.date.issued | 2004 | |
dc.date.modified | 2012-07-12T23:44:38Z | |
dc.identifier.issn | 0008-5472 | |
dc.identifier.doi | 10.1158/0008-5472.CAN-04-0842 | |
dc.identifier.uri | http://hdl.handle.net/10072/45851 | |
dc.description.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 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.peerreviewed | Yes | |
dc.description.publicationstatus | Yes | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | American Association for Cancer Research | |
dc.publisher.place | United States of America | |
dc.relation.ispartofpagefrom | 6101 | |
dc.relation.ispartofpageto | 6108 | |
dc.relation.ispartofissue | 17 | |
dc.relation.ispartofjournal | Cancer Research | |
dc.relation.ispartofvolume | 64 | |
dc.subject.fieldofresearch | Oncology and carcinogenesis | |
dc.subject.fieldofresearch | Cancer cell biology | |
dc.subject.fieldofresearchcode | 3211 | |
dc.subject.fieldofresearchcode | 321101 | |
dc.title | Molecular imaging of temporal dynamics and spatial heterogeneity of hypoxia-inducible factor-1 signal transduction activity in tumors in living mice. | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dc.type.code | c1x | |
gro.faculty | Griffith Health Faculty | |
gro.date.issued | 2004 | |
gro.hasfulltext | No Full Text | |
gro.griffith.author | Vider, Jelena | |