Tumor-associated neurological dysfunction prevented by lazaroids in rats.
The efficacy of U-74006F and U-78517F in the treatment of blood-tumor barrier permeability and tumor-associated neurological dysfunction was evaluated in a brain-tumor model in rats. U-74006F is a 21-aminosteroid and U-78517F is a 2-methylamino chroman. Rats with stereotactically implanted Walker 256 tumors were treated with methylprednisolone, U-74006F, U-78517F, or vehicle (0.05 N HCl) on Days 6 through 10 following implantation. Neurological function and vascular permeability were assessed on Day 10. Methylprednisolone and U-74006F were equally effective at preventing neurological dysfunction compared to the control group (p less than 0.01); U-78517F was slightly less effective than U-74006F and methylprednisolone but was significantly better than vehicle in preventing neurological dysfunction. Delivery of methylprednisolone resulted in a significant decrease in tumor vascular permeability (p less than 0.006) while U-74006F and U-78517F had no effect on permeability. This suggests that U-74006F and U-78517F prevented tumor-associated neurological dysfunction by a mechanism other than decreasing permeability in tumor capillaries, and that U-74006F or U-78517F could prove useful in the treatment of brain tumors.
King
W A
WA
Brain Research Institute, Jonsson Cancer Center, Los Angeles, California.
Black
K L
KL
Ikezaki
K
K
Conklin
S
S
Becker
D P
DP
D000818:Animals; D001932:Brain Neoplasms / Q000098:blood supply / Q000503:physiopathology*; D002199:Capillary Permeability / Q000187:drug effects; D002279:Carcinoma 256, Walker / Q000150:complications*; D002839:Chromans / Q000494:pharmacology*; D004195:Disease Models, Animal; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors; D009422:Nervous System Diseases / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D010879:Piperazines / Q000494:pharmacology*; D011281:Pregnatrienes / Q000494:pharmacology*; D051381:Rats
D002839:Chromans; D008054:Lipid Peroxides; D010879:Piperazines; D011281:Pregnatrienes; C066382:U 78517F; C053355:tirilazad