Transforming growth factor- pathway activity in glioblastoma

Transforming growth factor (TGF)-� is a central molecule maintaining the malignant phenotype of glioblastoma. Anti-TGF-� strategies are currently being explored in early clinical trials. Yet, there is little contemporary data on the differential expression of TGF-� isoforms at the mRNA and protein level or TGF-�/Smad pathway activity in glioblastomas in vivo.Here we studied 64 newly diagnosed and 16 recurrent glioblastomas for the expression of TGF-�1-3, platelet-derived growth factor (PDGF)-B, and plasminogen activator inhibitor (PAI)-1 mRNA by RT-PCR and for the levels of TGF-�1-3 protein, phosphorylated Smad2 (pSmad2), pSmad1/5/8 and PAI-1 by immunohistochemistry.Among the TGF� isoforms, TGF-�1 mRNA was the most, whereas TGF-�3 mRNA was the least abundant. TGF-�1-3 mRNA expression was strongly correlated, as was the expression of TGF-�1-3 mRNA, and of the TGF�1-3 target genes, PDGF-B and PAI-1. TGF-�2 and TGF-�3 protein levels correlated well, whereas the comparison of the other TGF-�isoforms did not. Positive correlation was also observed between TGF-�1 and pSmad1/5/8 and between pSmad2 and pSmad1/5/8. Survival analyses indicated that a group of patients with high expression levels of TGF-�2 mRNA or pSmad1/5/8 protein have inferior outcome.We thus provide potential biomarkers for patient stratification in clinical trials of anti-TGF-� therapies in glioblastoma. DOI: 10.18632/oncotarget.3467 Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-110458 Published Version Originally published at: Frei, K; Gramatzki, D; Tritschler, I; Schroeder, J J; Espinoza, L; Rushing, E J; Weller, M (2015). Transforming growth factor-� pathway activity in glioblastoma. OncoTarget, 6(8):5963-5977. DOI: 10.18632/oncotarget.3467 Neurodegeneration in the Elderly – when the blood type matters An overview of the McLeod Syndrome with focus on hematological features B.M Frey, C. Gassner, H.H. Jung 1) Blood Transfusion Service SRK, 8952 Schlieren-Zurich, Switzerland 2) Department of Neurology, University Hospital Zurich, Zurich, Switzerland Corresponding author: Beat M. Frey, Blood Transfusion Service SRK, Rütistrasse 19, 8952 Schlieren-Zurich, Switzerland Tel: 0041 (0)58 272 52 52 Email: [email protected]