New xenograft model for assessing experimental therapy of central nervous system tumors: human glioblastoma in the intrathecal compartment of the nude mouse.
Ten congenitally athymic "nude" mice and 10 immunocompetent mice underwent intrathecal inoculation with a human glioblastoma cell line (U87MG) via percutaneous lumbar puncture (5 x 10(5) cells/animal). All of the nude mice developed paraplegia with or without incontinence at 2 weeks and routinely died of inanition 3 weeks postimplantation. Histological examination confirmed extensive proliferation of neoplastic cells within the intrathecal space. A second group of animals was inoculated with 5 x 10(4) cells/animal: 20 nude mice, 10 cyclosporine A-immunosuppressed animals, and 10 immunocompetent control mice. The 20 mice were further divided into four subsets. Subset A did not receive chemotherapy, Subset B received 200 mg of carmustine (BCNU) per m2 by intraperitoneal injection, Subset C received a single dose of 4 mg of methotrexate (MTX) per m2 by intrathecal injection 4 hours after tumor inoculation, and Subset D received 12 mg of intrathecal MTX per m2. Decreasing the concentration of cells per animal by 1 log doubled the time interval required for the development of paralysis and incontinence to 4 weeks. Treatment with intrathecal MTX at a dose of 4 mg/m2 extended the symptom-free period by an additional week (to 5 weeks postinoculation), and a dose of 12 mg/m2 allowed an average of 6 weeks before the onset of neurological impairment. The xenografts did not grow in the immunocompetent control mice, the BCNU-treated group, or the cyclosporine A-immunosuppressed animals. An intrathecal xenograft model of central nervous system malignancies allows a novel approach to the evaluation of experimental chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Abernathey
C D
CD
Department of Neurosurgery, Mayo Clinic, Rochester, Minnesota.
Kooistra
K L
KL
Wilcox
G L
GL
Laws
E R
ER
D000818:Animals; D002330:Carmustine / Q000008:administration & dosage / Q000627:therapeutic use; D002460:Cell Line; D004195:Disease Models, Animal; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D007274:Injections, Intraperitoneal; D007278:Injections, Spinal; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D009380:Neoplasms, Nerve Tissue / Q000188:drug therapy*; D013116:Spinal Cord / Q000502:physiology*; D013997:Time Factors; D014183:Transplantation, Heterologous
D002330:Carmustine; D008727:Methotrexate