title: Effect of Notch expression in glioma stem cells on therapeutic response to chemo-radiotherapy in recurrent glioblastoma.
abstract: Glioma stem cells (GSCs) have the capacity to repopulate tumors and mediate resistance to radiotherapy and chemotherapy. The Notch signaling pathway is important in proliferation, stem cell maintenance, cell differentiation, and tumorigenesis in GSCs. In this study, we compared CD133, Notch, and VEGF expressions in histological sections of primary and recurrent glioblastomas after radiotherapy and chemotherapy. In vitro study, the γ-secretase inhibitor inhibited NICD, Hes1 and pVEGFR2 expressions in GSCs. GSCs cultured under endothelial conditions undergo endothelial differentiation. Tumor samples were collected from 27 patients at the time of tumor recurrence. We used immunohistochemical techniques to compare expression of CD133, Notch-1 and VEGF. Expressions of CD133-, Notch-1-, and VEGF-positive glioma cells were higher in recurrent glioblastoma after radiotherapy and chemotherapy. To determine the clinical importance of Notch-1 expression in glioblastoma, we analyzed 15 patients who had received bevacizumab therapy followed by a second surgery at recurrence. OS was significantly longer in cases with Notch-1 negativity (8.8 months) than in those with I Notch-1 positivity (6.8 months). We noted that GSCs have the potential for endothelial differentiation with Notch activity. We believe that Notch-1 is a potential target and/or biomarker for antiangiogenic treatments.
authors: Department of Neurosurgery, Toho University Ohashi Medical Center, 2-17-6, Ohashi, Meguro, Tokyo, Japan, bsaitob@med.toho-u.ac.jp.
authors: Norihiko
authors: N
authors: Saito
authors: Kazuya
authors: K
authors: Aoki
authors: Nozomi
authors: N
authors: Hirai
authors: Satoshi
authors: S
authors: Fujita
authors: Junya
authors: J
authors: Iwama
authors: Yu
authors: Y
authors: Hiramoto
authors: Masashi
authors: M
authors: Ishii
authors: Kenichiro
authors: K
authors: Sato
authors: Haruo
authors: H
authors: Nakayama
authors: Junichi
authors: J
authors: Harashina
authors: Morito
authors: M
authors: Hayashi
authors: Hideaki
authors: H
authors: Izukura
authors: Hitoshi
authors: H
authors: Kimura
authors: Keisuke
authors: K
authors: Ito
authors: Takatoshi
authors: T
authors: Sakurai
authors: Yuki
authors: Y
authors: Yokouchi
authors: Toshiaki
authors: T
authors: Oharazeki
authors: Kei
authors: K
authors: Takahashi
authors: Satoshi
authors: S
authors: Iwabuchi
mesh_terms: D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D015703:Antigens, CD / Q000235:genetics; D000068258:Bevacizumab / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000235:genetics* / Q000628:therapy*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D059248:Chemoradiotherapy; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D005909:Glioblastoma / Q000235:genetics* / Q000628:therapy*; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D014411:Neoplastic Stem Cells / Q000473:pathology; D010455:Peptides / Q000235:genetics; D051881:Receptor, Notch1 / Q000235:genetics*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D055815:Young Adult
chemical_list: D000071916:AC133 Antigen; D020533:Angiogenesis Inhibitors; D015703:Antigens, CD; D006023:Glycoproteins; C497761:NOTCH1 protein, human; C000606023:PROM1 protein, human; D010455:Peptides; D051881:Receptor, Notch1; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab