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    • 102. 发明申请
    • P53-MEDIATED APOPTOSIS
    • P53介导的APOPTOSIS
    • WO1995011301A1
    • 1995-04-27
    • PCT/US1994011923
    • 1994-10-19
    • THE REGENTS OF THE UNIVERSITY OF MICHIGAN
    • THE REGENTS OF THE UNIVERSITY OF MICHIGANCLARKE, Michael, F.RYAN, James, JosephNUNEZ, GabrielWICHA, Max, S.
    • C12N15/12
    • A61K38/1709A61K48/00C07K14/4746C07K14/82C12N2799/022
    • The invention is directed to methods of reducing the viability of a proliferating mammalian cells such as cancer cells. In one method cells deficient in p53 activity and in p53 suppressor activity of one or more p53-interacting regulatory proteins cell viability is reduced by increasing the level or activity of p53 in the cell. In another method viability of cells exhibiting p53 activity and p53 suppressor activity of one or more p53-interacting regulatory proteins is reduced by reducing the suppressor activity of the one or more p53-interacting regulatory proteins. Further, cell viability is reduced in cells deficient in p53 activity and exhibiting p53 suppressor activity of one or more p53-interacting regulatory proteins by a method that includes: (a) increasing the level or activity of p53 in the cell, and (b) reducing the suppressor activity of the one or more p53-interacting regulatory proteins. Also, included are methods of selectively reducing the viability of proliferating cancer cells compared to nonproliferating normal cells within a mixed population of cells and to methods of selectively reducing the viability of chronic granulocytic leukemia cells within a sample of proliferating bone marrow cells.
    • 本发明涉及减少增殖的哺乳动物细胞如癌细胞的活力的方法。 在一种方法中,一种或多种p53相互作用的调节蛋白的p53活性和p53抑制活性缺乏的细胞通过增加细胞中p53的水平或活性来降低细胞活力。 在另一种方法中,通过降低一种或多种p53相互作用的调节蛋白的抑制活性来降低表现出一种或多种p53相互作用调节蛋白的p53活性和p53抑制活性的细胞的存活力。 此外,通过包括以下方法的一种或多种p53相互作用的调节蛋白的p53抑制活性表现出p53活性缺陷的细胞的细胞活力降低,(a)增加细胞中p53的水平或活性,(b) 降低一种或多种p53相互作用的调节蛋白的抑制活性。 此外,包括与混合细胞群体内的非增殖性正常细胞相比选择性降低增殖性癌细胞的存活力的方法以及选择性降低增殖性骨髓细胞样品内慢性粒细胞白血病细胞活力的方法。