VITAMIN D ANALOGS AS ADJUVANTS IN CHEMOTHERAPY

维生素 D 类似物作为化疗佐剂

• 批准号: 2633794
• 负责人: George P Studzinski
• 金额: $ 21.82万
• 依托单位: UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-06-01 至 1998-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2633794
• 关键词: 1,25 dihydroxycholecalciferol; antileukemic agent; apoptosis; calcium flux; calcium metabolism; calcium transporting ATPase; cell cycle; cell differentiation; combination cancer therapy; cytosine arabinoside; drug resistance; etoposide; gene expression; guanine nucleotide binding protein; lipid metabolism; myeloid stem cell; neoplasm /cancer pharmacology; northern blottings; phosphorylation; protein kinase C; sphingomyelins; tissue /cell culture; vitamin analog; vitamin therapy; western blottings

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.

描述：（改编自申请人的描述）。 这 本申请提出研究维生素D3的类似物，（1，25D3）， 与抗白血病剂如阿拉伯胞嘧啶或 依托泊苷和相关化合物。细胞对D3的反应 将监测类似物和药物组合在细胞中的变化 循环遍历和控制循环遍历的基因的表达 通过信号转导进行生长，分化， 和程序性细胞死亡 研究的基因将包括那些 编码细胞周期依赖性蛋白激酶的调节亚基 复合物，即，细胞周期蛋白D、E、A和B及其抑制剂 活性，蛋白质p16和p21。信号转导启动于 这些类似物也将通过测定细胞内 钙，通过改变钙的表达和活性， 磷脂活化蛋白激酶C，并通过评估 PKC的能力，以增加活性和上调 质膜钙泵的表达。 这些方法 旨在增加对细胞活动的理解， VD3类似物，并为更好地设计临床 现在正在启动试验。