VEGFR2 Expression and TGF-β Signaling in Initial and Recurrent High-Grade Human Glioma
| Autor: | Steven G. Patten, Elizabeth A. Kuczynski, Brenda L. Coomber |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Cancer Research genetic structures Bevacizumab Angiogenesis Smad2 Protein Vascular endothelial growth inhibitor Disease-Free Survival Recurrence Transforming Growth Factor beta Glioma medicine Humans Aged biology Brain Neoplasms business.industry General Medicine Transforming growth factor beta Middle Aged medicine.disease Vascular Endothelial Growth Factor Receptor-2 Vascular endothelial growth factor B Vascular endothelial growth factor A Oncology Vascular endothelial growth factor C Immunology Cancer research biology.protein Female Neoplasm Grading Neoplasm Recurrence Local business Signal Transduction medicine.drug |
| Zdroj: | Oncology. 81:126-134 |
| ISSN: | 1423-0232 0030-2414 |
| DOI: | 10.1159/000332849 |
| Popis: | Objective: Bevacizumab has promising activity against glioma, although reasons for poor efficacy and variable response rates in certain patients are unclear. Vascular endothelial growth factor receptor 2 (VEGFR2) is heterogeneously expressed within the microvasculature of various malignancies. Moreover, transforming growth factor β (TGF-β), a negative prognostic factor for glioma, is intimately involved in angiogenesis including VEGFR2 regulation. Our objective was to associate expression of VEGFR2 and TGF-β activity with clinicopathological features of human glioma. Methods: Expression patterns determined by immunohistochemistry for VEGFR2 and phosphorylated Smad2 in human gliomas were compared to overall survival, progression-free survival (PFS), initial versus recurrent tumors and tumor grade. Results: Endothelial VEGFR2 expression was low or undetectable in normal tissue but the proportion of VEGFR2-positive vessels increased with tumor grade. Decreased PFS was associated with tumors whose vessels had increased proportions of VEGFR2 at recurrence. Neither parenchymal nor endothelial cell p-Smad2 was associated with tumor grade; however, the former was negatively correlated with overall survival in glioblastoma multiforme. Conclusions: The molecular phenotype of the vasculature based on the status of VEGFR2 but not p-Smad2 is related to aspects of glioma progression and patient response. Changes in VEGFR2-positive vessels may account for variable therapeutic efficacy of anti-angiogenic agents. |
| Databáze: | OpenAIRE |
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