King W A, Black K L, Ikezaki K, Conklin S, Becker D P
Brain Research Institute, Jonsson Cancer Center, Los Angeles, California.
J Neurosurg. 1991 Jan;74(1):112-5. doi: 10.3171/jns.1991.74.1.0112.
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.
在大鼠脑肿瘤模型中评估了U - 74006F和U - 78517F治疗血肿瘤屏障通透性及肿瘤相关神经功能障碍的疗效。U - 74006F是一种21 - 氨基类固醇，U - 78517F是一种2 - 甲基氨基苯并二氢吡喃。在植入Walker 256肿瘤后的第6至10天，对立体定向植入肿瘤的大鼠给予甲泼尼龙、U - 74006F、U - 78517F或赋形剂（0.05 N盐酸）治疗。在第10天评估神经功能和血管通透性。与对照组相比，甲泼尼龙和U - 74006F在预防神经功能障碍方面同样有效（p小于0.01）；U - 78517F在预防神经功能障碍方面比U - 74006F和甲泼尼龙稍差，但明显优于赋形剂。给予甲泼尼龙导致肿瘤血管通透性显著降低（p小于0.006），而U - 74006F和U - 78517F对通透性无影响。这表明U - 74006F和U - 78517F通过降低肿瘤毛细血管通透性以外的机制预防肿瘤相关神经功能障碍，并且U - 74006F或U - 78517F可能在脑肿瘤治疗中有用。
