目的:尽管急性髓细胞性白血病(AML)传统上被认为是一种肿瘤急症,开始治疗被认为是降低疾病相关发病率和死亡率的关键,也有人提出,治疗的一定延迟在反应方面没有负面影响,早期死亡,或生存。我们的目的是确定服用酪蛋白酸钠(SC)的效果,酪蛋白的盐,主要的牛奶蛋白质,阿糖胞苷或柔红霉素对白血病小鼠的存活率。
方法:为了测定骨髓中白血病的建立时间,Balb/c小鼠接种2.5×105个WEHI-3细胞/小鼠,并在3、6和9天后安乐死。获得股骨的骨髓单核细胞(BM-MNC),并在有或没有rmIL-3的情况下培养120小时,并通过结晶紫技术评估细胞增殖。然后,测定了SC-阿糖胞苷或SC-柔红霉素对已确诊白血病小鼠存活率的影响.用WEHI-3细胞接种另一组Balb/c小鼠,10天后用SC-阿糖胞苷或SC-柔红霉素处理小鼠40天。每天记录存活小鼠的存活率,用结晶紫技术检测治疗后骨髓增生的发生率。
结果:对白血病建立时间的测定表明,在没有生长因子的情况下,白血病细胞在骨髓中积累了足够的数量,以维持体外培养。而我们,因此,将其用作公认的白血病的标准。当白血病细胞负荷超过9天的小鼠用SC-阿糖胞苷或SC-柔红霉素治疗时,这两种治疗方法都有55%的存活率,增殖实验表明,骨髓保留了其正常的增殖能力。
结论:SC-阿糖胞苷或SC-柔红霉素治疗可延长Balb/c小鼠的生存率,对骨髓功能没有负面影响;然而,需要寻求SC-阿糖胞苷或SC-柔红霉素组合选择以增加超过40天的存活。
OBJECTIVE: Although acute myeloid leukemia (AML) has traditionally been considered an oncological emergency and initiation of therapy is believed to be crucial to minimizing disease-related morbidity and mortality, it has also been suggested that a certain delay in treatment has no negative consequences in terms of response, early mortality, or survival. We aimed to determine the effect of administration of sodium caseinate (SC), a salt of casein, the main milk protein, with cytarabine or with daunorubicin on survival in mice with well-established leukemia.
METHODS: To assay the time of establishment of leukemia in the bone marrow, Balb/c mice were inoculated with 2.5×10 5 WEHI-3 cells/mouse and after 3, 6 and 9 days were euthanized. Bone marrow mononuclear cells (BM-MNCs) of the femur were obtained and cultured for 120 h with or without rmIL-3 and cell proliferation was evaluated by the crystal violet technique. Then, the effect of administrating SC-cytarabine or SC-daunorubicin on survival rates of mice with well-established leukemia was assayed. Another group of Balb/c mice was inoculated with WEHI-3 cell and after 10 days mice were treated with SC-cytarabine or SC-daunorubicin for 40 days. Survival rates were recorded daily and in surviving mice, the prevalence of bone marrow proliferation after treatment was assayed by the crystal violet technique.
RESULTS: The assay on the time of establishment of leukemia shows that in 9 days leukemia cells accumulate in the bone marrow in sufficient quantities to sustain an in vitro culture in the absence of growth factors, and we, thus, used this as a criterion of well-established leukemia. When mice with a burden of leukemic cells of more than 9 days were treated with SC-cytarabine or SC-daunorubicin, this resulted in 55% survival for both treatments, and the proliferation assays showed that the bone marrow retained its normal proliferation capacity.
CONCLUSIONS: SC-cytarabine or SC-daunorubicin treatment prolonged the survival rate of Balb/c mice with a burden of well-established leukemia, and there was no negative impact on bone marrow functionality; however, SC-cytarabine or SC-daunorubicin combination options need to be sought to increase survival beyond 40 days.