Eliason J F, Inoue T, Kubota A, Teelmann K, Horii I, Hartmann D
Department of Oncology, Nippon Roche Research Center, Kanagawa Prefecture, Japan.
Int J Cancer. 1993 Sep 30;55(3):492-7. doi: 10.1002/ijc.2910550328.
The arotinoid Ro 40-8757 is a novel compound that has significant therapeutic activity against chemically induced breast tumors in rats. The results of combination therapy with cyclophosphamide, plus the arotinoid showed that the anti-tumor effects were additive. However, all of the rats given CPA alone died between week 6 and week 10 of treatment. None of the animals in the group treated with the combination died. Administration of a single dose of Ro 40-8757 to non-tumor bearing mice resulted in a transient increase in bone-marrow-progenitor cells after 2 days and a decrease in splenic progenitors at day 4. Treatment of mice with the combination demonstrated that the marrow progenitors were protected from the toxic effects of CPA by the arotinoid. Direct addition of Ro 40-8757 to mouse bone-marrow cells in clonogenic assay cultures containing WEHI-3-conditioned medium plus erythropoietin showed no significant enhancement by the arotinoid. The results suggest that this compound may exert its protective effect through the hemopoietic micro-environment.
芳维甲酸Ro 40 - 8757是一种新型化合物，对化学诱导的大鼠乳腺肿瘤具有显著的治疗活性。环磷酰胺与芳维甲酸联合治疗的结果表明，抗肿瘤作用是相加的。然而，所有单独给予环磷酰胺的大鼠在治疗的第6周和第10周之间死亡。联合治疗组的动物均未死亡。给未患肿瘤的小鼠单次注射Ro 40 - 8757，2天后骨髓祖细胞短暂增加，第4天脾祖细胞减少。用该联合方案治疗小鼠表明，芳维甲酸可保护骨髓祖细胞免受环磷酰胺的毒性作用。在含有WEHI - 3条件培养基和促红细胞生成素的克隆形成试验培养物中，将Ro 40 - 8757直接添加到小鼠骨髓细胞中，芳维甲酸未显示出显著增强作用。结果表明，该化合物可能通过造血微环境发挥其保护作用。
