VITAMIN D ANALOGS AS ADJUVANTS IN CHEMOTHERAPY

描述：(改编自申请人的描述)。这 应用建议研究维生素D3，(1，25D3)的类似物 与抗白血病药物的组合，如阿拉伯胞嘧啶或 依托泊苷及其相关化合物。细胞对D3的反应 类似物和药物组合将被监测细胞的变化 循环遍历及其调控基因的表达 通过传递信号来实现生长、分化、 以及程序性细胞死亡。所研究的基因将包括那些 编码细胞周期依赖性蛋白激酶调节亚基 复合体，即周期蛋白D、E、A和B及其抑制剂 活性，蛋白p16和p21。由基因启动的信号传导 这些类似物也将通过细胞内的测定进行评估 钙，通过钙的表达和活性的变化， 磷脂激活的蛋白激酶C，并通过评估 PKC的活性增加和上调的能力 质膜钙泵的表达。这些方法 旨在增加对细胞活动的理解 VD3模拟，为临床更好的设计提供了依据 现在正在启动小径。

DESCRIPTION: (Adapted from the applicant's description). This application proposes to investigate analogs of vitamin D3, (1,25D3) in combinations with antileukemia agents such as arabinocytosine or etoposide and related compounds. The cellular responses to D3 analogs and drug combinations will be monitored for changes in the cell cycle traverse and the expression of genes which control this traverse by transduction of signals for growth, differentiation, and programmed cell death. The genes studied will include those encoding the regulatory subunits of cell cycle dependent protein kinase complexes, i.e., cyclins D, E, A, and B, and inhibitors of this activity, proteins p16 and p21. Transduction of signals initiated by these analogs will also be assessed by determinations of intracellular calcium, by changes in the expression and activity of calcium, phospholipid-activated protein kinase C, and by evaluation of the ability of PKC to increase the activity and upregulated the expression of the plasma membrane calcium pump. These approaches are intended to increase the understanding of the cellular actions of VD3 analogs, and to provide a basis for better design of clinical trails now being initiated.