title: Evaluation of the antiangiogenic effect of Kringle 1-5 in a rat glioma model.
abstract: BACKGROUND
  Kringle 1-5 (K1-5) is a potent antiangiogenesis factor for treating breast cancer and hepatocellular carcinoma. However, its use in treating brain tumors has not been studied.
  
  
  OBJECTIVE
  To evaluate whether K1-5 is effective at treating gliomas.
  
  
  METHODS
  The effects of K1-5 on cell morphology and cytotoxicity with or without lipopolysaccharide were tested in primary mixed neuronal-glial cultures. The antiglioma activity of K1-5 was evaluated by intra-arterial administration of K1-5 at 4 days after implantation of C6 glioma cells into the rat hippocampus. In 1 group of animals, tumor size, tumor vasculature, and tumor histology were evaluated on day 12. Animal survival was assessed in the other group.
  
  
  RESULTS
  In vitro studies showed that K1-5 did not induce cytotoxicity in neurons and glia. In vivo studies demonstrated that K1-5 reduced vessel length and vessel density and inhibited perivascular tumor invasion. In addition, K1-5 normalized vessel morphology, decreased expression of hypoxia-inducible factor-1α and vascular endothelial growth factor, decreased tumor hypoxia, and decreased pseudopalisading necrosis. The average tumor volume was smaller in the treated than in the untreated group. Furthermore, animals treated with K1-5 survived significantly longer.
  
  
  CONCLUSIONS
  Kringle 1-5 effectively reduces the growth of malignant gliomas in the rat. Although still far from translation in humans, K1-5 might be a possible future alternative treatment option for patients with gliomas.
authors.affiliation: Neural Regeneration Laboratory, Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Yi-Lo
authors.initials: YL
authors.lastname: Lin
authors.forename: May-Jywan
authors.initials: MJ
authors.lastname: Tsai
authors.forename: Ming-Jei
authors.initials: MJ
authors.lastname: Lo
authors.forename: Shao-En
authors.initials: SE
authors.lastname: Chang
authors.forename: Yang-Hsin
authors.initials: YH
authors.lastname: Shih
authors.forename: Meng-Jen
authors.initials: MJ
authors.lastname: Lee
authors.forename: Huai-Sheng
authors.initials: HS
authors.lastname: Kuo
authors.forename: Wen-Chun
authors.initials: WC
authors.lastname: Kuo
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Huang
authors.forename: Henrich
authors.initials: H
authors.lastname: Cheng
authors.forename: Ming-Chao
authors.initials: MC
authors.lastname: Huang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D007150:Immunohistochemistry; D018082:Kringles; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D020533:Angiogenesis Inhibitors