title: Regression of glioma tumor growth in F98 and U87 rat glioma models by the Nitrone OKN-007.
abstract: BACKGROUND
  Glioblastoma multiforme, a World Health Organization grade IV glioma, has a poor prognosis in humans despite current treatment options. Here, we present magnetic resonance imaging (MRI) data regarding the regression of aggressive rat F98 gliomas and human U87 glioma xenografts after treatment with the nitrone compound OKN-007, a disulfonyl derivative of α-phenyl-tert-butyl nitrone.
  
  
  METHODS
  MRI was used to assess tumor volumes in F98 and U87 gliomas, and bioluminescence imaging was used to measure tumor volumes in F98 gliomas encoded with the luciferase gene (F98(luc)). Immunohistochemistry was used to assess angiogenesis (vascular endothelial growth factor [VEGF] and microvessel density [MVD]), cell differentiation (carbonic anhydrase IX [CA-IX]), hypoxia (hypoxia-inducible factor-1α [HIF-1α]), cell proliferation (glucose transporter 1 [Glut-1] and MIB-1), proliferation index, and apoptosis (cleaved caspase 3) markers in F98 gliomas. VEGF, CA-IX, Glut-1, HIF-1α, and cleaved caspase 3 were assessed in U87 gliomas.
  
  
  RESULTS
  Animal survival was found to be significantly increased (P < .001 for F98, P < .01 for U87) in the group that received OKN-007 treatment compared with the untreated groups. After MRI detection of F98 gliomas, OKN-007, administered orally, was found to decrease tumor growth (P < .05). U87 glioma volumes were found to significantly decrease (P < .05) after OKN-007 treatment, compared with untreated animals. OKN-007 administration resulted in significant decreases in tumor hypoxia (HIF-1α [P < .05] in both F98 and U87), angiogenesis (MVD [P < .05], but not VEGF, in F98 or U87), and cell proliferation (Glut-1 [P < .05 in F98, P < .01 in U87] and MIB-1 [P < .01] in F98) and caused a significant increase in apoptosis (cleaved caspase 3 [P < .001 in F98, P < .05 in U87]), compared with untreated animals.
  
  
  CONCLUSIONS
  OKN-007 may be considered as a promising therapeutic addition or alternative for the treatment of aggressive human gliomas.
authors: Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, 825 NE 13th St., Oklahoma City, OK 73104, USA. rheal-towner@omrf.org
authors: Rheal A
authors: RA
authors: Towner
authors: David L
authors: DL
authors: Gillespie
authors: Andrea
authors: A
authors: Schwager
authors: Debra G
authors: DG
authors: Saunders
authors: Nataliya
authors: N
authors: Smith
authors: Charity E
authors: CE
authors: Njoku
authors: Richard S
authors: RS
authors: Krysiak
authors: Chelsea
authors: C
authors: Larabee
authors: Henna
authors: H
authors: Iqbal
authors: Robert A
authors: RA
authors: Floyd
authors: David W A
authors: DW
authors: Bourne
authors: Osama
authors: O
authors: Abdullah
authors: Edward W
authors: EW
authors: Hsu
authors: Randy L
authors: RL
authors: Jensen
mesh_terms: D000818:Animals; D017209:Apoptosis; D001557:Benzenesulfonates / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D005910:Glioma / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D007097:Imines / Q000494:pharmacology*; D007124:Immunoenzyme Techniques; D008163:Luminescent Measurements; D008279:Magnetic Resonance Imaging; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D051381:Rats; D011916:Rats, Inbred F344; D011923:Rats, Nude; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D001557:Benzenesulfonates; D007097:Imines; C552724:OKN 007