Research Project
Grant-in-Aid for Young Scientists (B)
The Notch signaling is an evolutionarily conserved pathway that plays an important role in multiple cellular processes. We investigated the effects of Notch inhibition in glioma stem cell (GSC) populations using γ secretase inhibitors. Drug cytotoxicity testing showed differential growth responses to the inhibitors. Responder GSCs had an enriched proneural gene signature in comparison to nonresponders. Analysis of TCGA dataset identified a group (43.9%) of tumors with proneural signature showing high Notch pathway activation. Inhibition of Notch pathway by γ secretase inhibitor treatment attenuated proliferation and self-renewal of responder GSCs and induces both neuronal and astrocytic differentiation. Our results suggest that proneural GBM characterized by high Notch pathway activation may exhibit greater sensitivity to γ secretase inhibitor treatment, holding a promise to improve the efficiency of current glioma therapy.
All 2016 2015 Other
All Presentation (9 results) (of which Int'l Joint Research: 3 results) Remarks (2 results)
http://www.ohashi-neurosurgery.com/
http://www.lab.toho-u.ac.jp/med/ohashi/neurosurgery/
