title: Experimental study of intraoperative local chemotherapy with fibrin glue containing nitrosourea for malignant gliomas.
abstract: BACKGROUND
  Local control of the tumor bed after removal of a tumor is one of the most important points in the treatment of malignant gliomas. This study was designed to examine whether fibrin glue is useful as a vehicle for sustained release of intraoperative local chemotherapy with nitrosourea (ACNU).
  
  
  METHODS
  The growth-inhibiting activity of ACNU on C6 glioma cells and ACNU released into 5-mL supernatant saline from fibrin glue containing 5 mg/mL (10 mg) of ACNU was measured in vitro. C6 tumor inoculated in rat brains was covered with fibrin glue containing either 2 mg/mL or 5 mg/mL of ACNU for 5 days, and the histologic changes were examined.
  
  
  RESULTS
  ACNU inhibited the growth of C6 glioma cells in a dose-dependent manner, and the drug concentration required for 50% inhibition of cell growth (IC50) was about 4 micrograms/mL with 1 hour of treatment. Although about 50% of all ACNU included in the fibrin glue was released in the first hour, an effective concentration over the value of IC50 was sustained even after 12 hours. A histologic examination showed tumor cells damaged within a depth of about 2-3 mm from the tumor surface covered with fibrin glue containing ACNU.
  
  
  CONCLUSIONS
  Fibrin glue may be useful as a vehicle for sustained-release chemotherapy, and intraoperative local chemotherapy with fibrin glue containing anticancer agents such as nitrosourea may be helpful in the local control of malignant gliomas.
authors.affiliation: Department of Neurosurgery, Fukui Medical School, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kabuto
authors.forename: T
authors.initials: T
authors.lastname: Kubota
authors.forename: H
authors.initials: H
authors.lastname: Kobayashi
authors.forename: T
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Y
authors.initials: Y
authors.lastname: Arai
authors.forename: R
authors.initials: R
authors.lastname: Kitai
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004358:Drug Therapy / Q000379:methods*; D015718:Fibrin Tissue Adhesive / Q000494:pharmacology*; D005910:Glioma / Q000188:drug therapy*; D008297:Male; D015376:Nimustine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015718:Fibrin Tissue Adhesive; D015376:Nimustine