Convection-enhanced delivery of a hydrophilic nitrosourea ameliorates deficits and suppresses tumor growth in experimental spinal cord glioma models

Shogo Ogita, Toshiki Endo, Shinichiro Sugiyama, Ryuta Saito, Tomoo Inoue, Akira Sumiyoshi, Hiroi Nonaka, Ryuta Kawashima, Yukihiko Sonoda, Teiji Tominaga

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Background: 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. Objective: To evaluate the utility of nimustine hydrochloride (ACNU) CED in controlling tumor progression in an experimental spinal cord glioma model. Methods: 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. Results: 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). Conclusions: 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.

Original languageEnglish
Pages (from-to)939-946
Number of pages8
JournalActa neurochirurgica
Volume159
Issue number5
DOIs
Publication statusPublished - 2017 May 1

Keywords

  • Convection-enhanced delivery
  • Glioma
  • Nitrosourea
  • Spinal cord

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

Fingerprint Dive into the research topics of 'Convection-enhanced delivery of a hydrophilic nitrosourea ameliorates deficits and suppresses tumor growth in experimental spinal cord glioma models'. Together they form a unique fingerprint.

Cite this