title: Efficacy of vincristine administered via convection-enhanced delivery in a rodent brainstem tumor model documented by bioluminescence imaging.
abstract: OBJECTIVE
  Brain stem gliomas account for 20% of childhood brain tumors. Presently, there is no effective treatment for these tumors, and the prognosis remains poor. One reason for this is that chemotherapeutic drugs cannot cross the blood-brain barrier. In this study, we used a rodent brainstem tumor model, monitored both qualitatively and quantitatively, to examine the effectiveness of vincristine (VCR) administered via convection-enhanced delivery (CED).
  
  
  METHODS
  C6 rat glioblastoma cells, transduced with an oncoretroviral plasmid containing a luciferase coding sequence, were inoculated into Fischer 344 rat brainstems. Tumor growth was monitored by bioluminescence intensity (BLI), and tumor volume was calculated from serial histopathologic sections. Therapeutic efficacy of VCR delivered via CED was assessed. Intravenous (I.V.) and intraperitoneal (I.P.) drug administration were used as a comparison for CED efficacy.
  
  
  RESULTS
  BLI monitoring revealed progressive tumor growth in inoculated rats. Symptoms caused by tumor burden were evident 16-18 days after inoculation. BLI correlated quantitatively with tumor volume (r(2) = 0.9413), established by histopathological analysis of tumor growth within the pons. VCR administered through CED was more effective than I.V. or I.P. administration in reducing tumor size and increasing survival times. TUNEL assay results suggest that VCR induced glioblastoma cell apoptosis.
  
  
  CONCLUSIONS
  VCR administered by CED was effective in reducing tumors and prolonging survival time.
authors.affiliation: Division of Pediatric Neurosurgery, Falk Brain Tumor Center, Children's Memorial Hospital, Northwestern University, Feinberg School of Medicine, Chicago, IL 60614, USA. gxi@childrensmemorial.org
authors.forename: Guifa
authors.initials: G
authors.lastname: Xi
authors.forename: Veena
authors.initials: V
authors.lastname: Rajaram
authors.forename: Babara
authors.initials: B
authors.lastname: Mania-Farnell
authors.forename: Chandra S
authors.initials: CS
authors.lastname: Mayanil
authors.forename: Marcelo B
authors.initials: MB
authors.lastname: Soares
authors.forename: Tadanori
authors.initials: T
authors.lastname: Tomita
authors.forename: Stewart
authors.initials: S
authors.lastname: Goldman
mesh_terms: D000818:Animals; D020295:Brain Stem Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D018481:Convection; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods*; D008163:Luminescent Measurements / Q000379:methods; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012377:Rodentia; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D014750:Vincristine