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    • 1. 发明申请
    • INHIBITORS OF USP1 DEUBIQUITINATING ENZYME COMPLEX
    • USP1去糖基化酶复合物的抑制剂
    • WO2007149484A9
    • 2008-03-20
    • PCT/US2007014378
    • 2007-06-20
    • DANA FARBER CANCER INST INCD ANDREA ALAN
    • D ANDREA ALAN
    • C12Q1/37
    • G01N33/57496C12Q1/37G01N33/5011G01N2500/00
    • The invention provides compositions and methods used to inhibit USP1 deubiquitinase activity and to identify new inhibitors of USP1 deubiquitinase. The inhibitors can be used to treat or prevent cancer, bone marrow failure, and damage to cells or DNA resulting from genotoxic agents such as antineoplasic agents, including chemotherapeutic agents and radiation. The inhibitors include siRNA directed at inhibiting the expression of USP1 or UAF1, a protein which forms a heterodimeric complex with USP1. The inhibitors can be used to enhance cell survival if administered either before or after radiation exposure. Methods are also provided to enhance chemotherapy or radiotherapy of cancer and to enhance DNA repair. Transgenic knockout animals and knockdown cells are provided, whose USP1 expression is impaired.
    • 本发明提供了用于抑制USP1去泛素酶活性并鉴定USP1去泛素化酶的新抑制剂的组合物和方法。 这些抑制剂可用于治疗或预防癌症,骨髓衰竭,以及由遗传毒性剂(例如抗肿瘤剂,包括化学治疗剂和辐射)导致的细胞或DNA的损伤。 抑制剂包括针对抑制USP1或UAF1(一种与USP1形成异二聚体复合物的蛋白质)表达的siRNA。 如果在辐射暴露之前或之后施用,抑制剂可用于增强细胞存活。 还提供了增强癌症化疗或放疗和增强DNA修复的方法。 提供转基因敲除动物和敲低细胞,其USP1表达受损。
    • 2. 发明申请
    • INHIBITORS OF USP1 DEUBIQUITINATING ENZYME COMPLEX
    • USP1 DEBIQUITINATING ENZYME复合物的抑制剂
    • WO2007149484A3
    • 2008-07-24
    • PCT/US2007014378
    • 2007-06-20
    • DANA FARBER CANCER INST INCD ANDREA ALAN
    • D ANDREA ALAN
    • C12N9/64
    • G01N33/57496C12Q1/37G01N33/5011G01N2500/00
    • The invention provides compositions and methods used to inhibit USP1 deubiquitinase activity and to identify new inhibitors of USP1 deubiquitinase. The inhibitors can be used to treat or prevent cancer, bone marrow failure, and damage to cells or DNA resulting from genotoxic agents such as antineoplasic agents, including chemotherapeutic agents and radiation. The inhibitors include siRNA directed at inhibiting the expression of USP1 or UAF1, a protein which forms a heterodimeric complex with USP1. The inhibitors can be used to enhance cell survival if administered either before or after radiation exposure. Methods are also provided to enhance chemotherapy or radiotherapy of cancer and to enhance DNA repair. Transgenic knockout animals and knockdown cells are provided, whose USP1 expression is impaired.
    • 本发明提供用于抑制USP1去泛素酶活性并鉴定USP1去泛素酶的新抑制剂的组合物和方法。 抑制剂可用于治疗或预防癌症,骨髓衰竭,以及由遗传毒性因子如抗肿瘤药物(包括化学治疗剂和辐射)引起的细胞或DNA的损伤。 抑制剂包括用于抑制USP1或UAF1表达的siRNA,这是与USP1形成异二聚体复合物的蛋白质。 如果在辐射暴露之前或之后施用,抑制剂可用于增强细胞存活。 还提供了增强癌症化学疗法或放射疗法并增强DNA修复的方法。 提供转基因敲除动物和敲低细胞,其USP1表达受损。
    • 4. 发明申请
    • METHOD FOR DETERMINATION AND QUANTIFICATION OF RADIATION OR GENOTOXIN EXPOSURE
    • 辐射或生殖毒素暴露的测定和定量方法
    • WO2005081783A3
    • 2006-10-19
    • PCT/US2005003344
    • 2005-01-28
    • DANA FARBER CANCER INST INCD ANDREA ALAN
    • D ANDREA ALAN
    • G01N33/53C07K14/47C07K16/18C12Q1/68G01N33/50G01N33/52G01N33/533G01N33/574
    • C07K14/47C07K16/18G01N33/5014G01N2800/52
    • The present invention discloses methods for detecting exposure of a living subject to genotoxic agents, testing sensitivity to a genotoxic agent, and determining DNA damage caused by exposure to an agent, comprising detecting the presence of FANCD2-containing foci from a sample collected from said subject. The presence of concentrated foci is indicative of DNA damage, and the degree of foci formation is correlated with degree of exposure. Diagnostic reagents contain a ligand that binds to human FANC~2 associated with a detectable label, Kits for detecting DNA damage in a biological sample contain such diagnostic reagents and signal detection components. The invention further discloses methods for identifying agents which modulate the ability of ~ANCD2-containing foci to form. Among other things, such agents are potentially useful chemosensitizing agents or may confer protection against damage caused by genotoxic agents.
    • 本发明公开了一种用于检测活体受体对基因毒物的暴露的方法,检测对遗传毒性试剂的敏感性,以及确定由暴露于药剂引起的DNA损伤的方法,包括从所述受试者收集的样品中检测含FANCD2的病灶的存在 。 浓缩灶的存在表明DNA损伤,并且病灶形成程度与暴露程度相关。 诊断试剂含有与可检测标记物相关的人FANC〜2结合的配体,用于检测生物样品中DNA损伤的试剂盒含有此类诊断试剂和信号检测组分。 本发明还公开了用于鉴定调节含有〜ANCD2的灶的形成能力的试剂的方法。 除此之外,这些试剂是潜在有用的化学增感剂或可以赋予针对由遗传毒性剂引起的损伤的保护。