title: Convection-enhanced delivery of a hydrophilic nitrosourea ameliorates deficits and suppresses tumor growth in experimental spinal cord glioma models.
abstract: Convection-enhanced delivery (CED) is a technique allowing local infusion of therapeutic agents into the central nervous system, circumventing the blood-brain or spinal cord barrier.
  
  
  
  To evaluate the utility of nimustine hydrochloride (ACNU) CED in controlling tumor progression in an experimental spinal cord glioma model.
  
  
  
  Toxicity studies were performed in 42 rats following the administration of 4 μl of ACNU CED into the mid-thoracic spinal cord at concentrations ranging from 0.1 to 10 mg/ml. Behavioral analyses and histological evaluations were performed to assess ACNU toxicity in the spinal cord. A survival study was performed in 32 rats following the implantation of 9 L cells into the T8 spinal cord. Seven days after the implantation, rats were assigned to four groups: ACNU CED (0.25 mg/ml; n = 8); ACNU intravenous (i.v.) (0.4 mg; n = 8); saline CED (n = 8); saline i.v. (n = 8). Hind limb movements were evaluated daily in all rats for 21 days. Tumor sizes were measured histologically.
  
  
  
  The maximum tolerated ACNU concentration was 0.25 mg/ml. Preservation of hind limb motor function and tumor growth suppression was observed in the ACNU CED (0.25 mg/ml) and ACNU i.v. groups. Antitumor effects were more prominent in the ACNU CED group especially in behavioral analyses (P < 0.05; log-rank test).
  
  
  
  ACNU CED had efficacy in controlling tumor growth and preserving neurological function in an experimental spinal cord tumor model. ACNU CED can be a viable treatment option for spinal cord high-grade glioma.
authors.affiliation: Department of Neurosurgery, Graduate School of Medicine, Tohoku University, 1-1 Seiryo Aoba, Sendai, Japan, 980-8574.
authors.forename: Shogo
authors.initials: S
authors.lastname: Ogita
authors.affiliation: Department of Neurosurgery, Graduate School of Medicine, Tohoku University, 1-1 Seiryo Aoba, Sendai, Japan, 980-8574. endo@nsg.med.tohoku.ac.jp.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Endo
authors.affiliation: Department of Neurosurgery, Graduate School of Medicine, Tohoku University, 1-1 Seiryo Aoba, Sendai, Japan, 980-8574.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Sugiyama
authors.affiliation: Department of Neurosurgery, Graduate School of Medicine, Tohoku University, 1-1 Seiryo Aoba, Sendai, Japan, 980-8574.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Saito
authors.affiliation: Department of Neurosurgery, Graduate School of Medicine, Tohoku University, 1-1 Seiryo Aoba, Sendai, Japan, 980-8574.
authors.forename: Tomoo
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Functional Brain Imaging, Institute of Development, Aging and Cancer, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Sumiyoshi
authors.affiliation: Department of Functional Brain Imaging, Institute of Development, Aging and Cancer, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Hiroi
authors.initials: H
authors.lastname: Nonaka
authors.affiliation: Department of Functional Brain Imaging, Institute of Development, Aging and Cancer, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Kawashima
authors.affiliation: Department of Neurosurgery, Graduate School of Medicine, Tohoku University, 1-1 Seiryo Aoba, Sendai, Japan, 980-8574.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Sonoda
authors.affiliation: Department of Neurosurgery, Graduate School of Medicine, Tohoku University, 1-1 Seiryo Aoba, Sendai, Japan, 980-8574.
authors.forename: Teiji
authors.initials: T
authors.lastname: Tominaga
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D018481:Convection; D016503:Drug Delivery Systems / Q000379:methods*; D005910:Glioma / Q000188:drug therapy*; D008297:Male; D015376:Nimustine / Q000008:administration & dosage* / Q000627:therapeutic use; D051381:Rats; D011916:Rats, Inbred F344; D013120:Spinal Cord Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D015376:Nimustine
keywords: Convection-enhanced delivery; Glioma; Nitrosourea; Spinal cord