Development of a large-animal human brain tumor xenograft model in immunosuppressed cats.
A large-animal model was developed to facilitate the noninvasive investigation of the effect on the human glioma-derived D-54 MG (glioblastoma multiforme) continuous cell line of a variety of therapeutic regimens. Twenty random-bred male cats were inoculated intracerebrally with 1 x 10(7) D-54 MG tumor cells after being initiated on one of three preparatory regimens of cyclosporin A p.o. Reproducible success of D-54 MG xenotransplantation (100%, 6 of 6 cats) was achieved only after pretreatment with 120 mg cyclosporin A p.o. (24-30 mg/kg) daily for greater than or equal to 10 days prior to tumor implantation. High-performance liquid chromatography-derived whole blood cyclosporin A 12-h trough levels of greater than or equal to 640 ng/ml were seen in successful implants. Lesions ranging from 2 to 20 mm in diameter were seen in cats sacrificed 27-44 days after implantation with no growth seen in control animals. Histopathological examination revealed the tumors to be well-circumscribed anaplastic intracerebral tumors with some invasion into surrounding host parenchyma. Perivascular lymphocytic cuffing was observed, but intratumoral lymphocytic infiltration was minimal. Gadolinium-EDTA-enhanced nuclear magnetic resonance imaging provided accurate tumor localization in T1-weighted images (TE 26 ms; TR 600 ms). Biochemical tests of kidney, liver, and hematological function were within normal limits, although 10% (2 of 20) of the animals developed gingival hyperplasia, and 5% (1 of 20) developed intussusception. The reproducible growth of the D-54 MG human glioblastoma cell line in a large-animal model eliminates many of the limitations associated with the standard nude mouse/rat model, thereby providing a novel test bed for a variety of imaging modalities as well as for drug immunoconjugate localization and toxicity studies.
Krushelnycky
B W
BW
Department of Surgery, University of Alberta, Edmonton, Canada.
Farr-Jones
M A
MA
Mielke
B
B
McKean
J D
JD
Weir
B K
BK
Petruk
K C
KC
D000818:Animals; D001932:Brain Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D002415:Cats; D003524:Cyclosporins; D004195:Disease Models, Animal; D005910:Glioma / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007108:Immune Tolerance; D007621:Karyotyping; D008279:Magnetic Resonance Imaging; D008297:Male; D009368:Neoplasm Transplantation; D012208:Rhabdomyosarcoma / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000473:pathology
D003524:Cyclosporins