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HIF-1{alpha} and HI...
HIF-1{alpha} and HIF-2{alpha} Are Differentially Regulated In vivo in Neuroblastoma: High HIF-1{alpha} Correlates Negatively to Advanced Clinical Stage and Tumor Vascularization.
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Noguera, Rosa (author)
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- Fredlund, Erik (author)
- Lund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Department of Translational Medicine,Faculty of Medicine
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Piqueras, Marta (author)
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- Pietras, Alexander (author)
- Lund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Department of Translational Medicine,Faculty of Medicine
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- Beckman, Siv (author)
- Lund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Department of Translational Medicine,Faculty of Medicine
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Navarro, Samuel (author)
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- Påhlman, Sven (author)
- Lund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Department of Translational Medicine,Faculty of Medicine
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(creator_code:org_t)
- 2009
- 2009
- English.
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In: Clinical Cancer Research. - 1078-0432. ; 15:23, s. 7130-7136
- Related links:
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http://www.ncbi.nlm....
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
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- PURPOSE: Hypoxia is considered to be a major driving force behind tumor angiogenesis. The stabilization and activation at hypoxia of the hypoxia-inducible factors HIF-1alpha and HIF-2alpha and the concomitant induction of expression of vascular endothelial growth factor (VEGF) and other proangiogenic factors provide a molecular frame for hypoxia-driven tumor angiogenesis. This study has investigated how HIF and VEGF protein levels relate to each other with regard to vascularization, tumor stage, and overall survival in neuroblastoma. EXPERIMENTAL DESIGN: Tissue cores taken from tumor specimens representing 93 children with neuroblastoma were arranged on a microarray and stained for HIF-1alpha, HIF-2alpha, VEGF, and CD31 proteins. Both fraction of positive cells and staining intensity were evaluated and protein levels were correlated with each other and with clinical variables. RESULTS: Although high levels of both HIF-1alpha (P < 0.001) and HIF-2alpha (P < 0.001) correlated positively to VEGF expression, they did not fully correlate with each other. Moreover, HIF-1alpha (P = 0.002) and VEGF (P < 0.001), but not HIF-2alpha, correlated negatively to vascularization as determined by CD31 staining abundance. VEGF expression or degree of vascularization did not correlate with tumor stage or overall survival. High HIF-1alpha levels correlated with low tumor stage (P < 0.001) and were associated with a favorable patient prognosis (P = 0.08). CONCLUSIONS: The discordant results on expression of HIF-1alpha and HIF-2alpha suggest that these two proteins are differentially regulated in vivo, thus reflecting distinctive protein expression/stabilization mechanisms. The association between HIF-1alpha and favorable outcome stresses the importance of discriminating HIF-2alpha from HIF-1alpha expression and has implications for using HIFs as treatment targets. (Clin Cancer Res 2009;15(23):OF1-7).
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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