Development of a large-animal human brain tumor xenograft model in immunosuppressed cats.

Abstract

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.

• Authors: B W Krushelnycky, M A Farr-Jones, B Mielke, J D McKean, B K Weir, K C Petruk
• Journal: Cancer research (Cancer Res) Vol. 51 Issue 9 Pg. 2430-7 (May 01 1991) ISSN: 0008-5472 [Print] United States
• PMID: 2015604 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclosporins

Topics

• Animals
• Brain Neoplasms (diagnosis, genetics, pathology)
• Cats
• Cyclosporins
• Disease Models, Animal
• Glioma (diagnosis, genetics, pathology)
• Humans
• Immune Tolerance
• Karyotyping
• Magnetic Resonance Imaging
• Male
• Neoplasm Transplantation
• Rhabdomyosarcoma (diagnosis, genetics, pathology)
• Tumor Cells, Cultured (pathology)