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1. 发明申请

WO2005081783A3 METHOD FOR DETERMINATION AND QUANTIFICATION OF RADIATION OR GENOTOXIN EXPOSURE 审中-公开
标题翻译：辐射或生殖毒素暴露的测定和定量方法
公开(公告)号：WO2005081783A3
公开(公告)日：2006-10-19
申请号：PCT/US2005003344
申请日：2005-01-28
申请人： DANA FARBER CANCER INST INC , D ANDREA ALAN
发明人： D ANDREA ALAN
IPC分类号： G01N33/53 , C07K14/47 , C07K16/18 , C12Q1/68 , G01N33/50 , G01N33/52 , G01N33/533 , G01N33/574
CPC分类号： C07K14/47 , C07K16/18 , G01N33/5014 , G01N2800/52
摘要： 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.
摘要翻译：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。

2. 发明申请

WO2008066624A3 DNA DAMAGE REPAIR INHIBITORS AND METHODS FOR TREATING CANCER 审中-公开
标题翻译： DNA损伤修复抑制剂和治疗癌症的方法
公开(公告)号：WO2008066624A3
公开(公告)日：2008-08-14
申请号：PCT/US2007022439
申请日：2007-10-22
申请人： DANA FARBER CANCER INST INC , DNAR INC , UNIV OREGON HEALTH & SCIENCE , D ANDREA ALAN , WEAVER DAVID T , GROMPE MARKUS
发明人： D ANDREA ALAN , WEAVER DAVID T , GROMPE MARKUS
IPC分类号： C12Q1/68
CPC分类号： C12N15/1137 , A61K31/713 , A61K45/06 , C12N2310/14 , C12N2320/30 , C12N2320/31 , C12Q1/6886 , C12Q2600/106 , C12Q2600/136 , C12Q2600/158 , G01N33/57496 , G01N2333/4716
摘要： This present invention relates compositions and methods of treating cancer and methods of accessing/monitoring the responsiveness of a cancer cell to a therapeutic compound, specific for a DNA repair pathway. A method for treating cancer is provided, which includes: a) determining whether the cancer cell is deficient in a DNA repair pathway (eg. Fanconi anemia) and b) administering a DNA damaging agent or inhibitor specific for at least one different DNA repair pathway than that identified in step (a) (eg. mismatch repair or non-homologous endjoining repair pathways).
摘要翻译：本发明涉及治疗癌症的组合物和方法以及获取/监测癌细胞对治疗性化合物的反应性的方法，其特异于DNA修复途径。提供了一种治疗癌症的方法，其包括：a）确定癌细胞是否缺乏DNA修复途径（例如范可尼贫血症），和b）施用对至少一种不同DNA修复途径特异的DNA损伤剂或抑制剂比步骤（a）中所确定的（例如错配修复或非同源终止修复途径）。

3. 发明申请

WO2007149484A9 INHIBITORS OF USP1 DEUBIQUITINATING ENZYME COMPLEX 审中-公开
标题翻译： USP1去糖基化酶复合物的抑制剂
公开(公告)号：WO2007149484A9
公开(公告)日：2008-03-20
申请号：PCT/US2007014378
申请日：2007-06-20
申请人： DANA FARBER CANCER INST INC , D ANDREA ALAN
发明人： D ANDREA ALAN
IPC分类号： C12Q1/37
CPC分类号： G01N33/57496 , C12Q1/37 , G01N33/5011 , G01N2500/00
摘要： 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.
摘要翻译：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。

4. 发明申请

WO2007149484A3 INHIBITORS OF USP1 DEUBIQUITINATING ENZYME COMPLEX 审中-公开
标题翻译： USP1 DEBIQUITINATING ENZYME复合物的抑制剂
公开(公告)号：WO2007149484A3
公开(公告)日：2008-07-24
申请号：PCT/US2007014378
申请日：2007-06-20
申请人： DANA FARBER CANCER INST INC , D ANDREA ALAN
发明人： D ANDREA ALAN
IPC分类号： C12N9/64
CPC分类号： G01N33/57496 , C12Q1/37 , G01N33/5011 , G01N2500/00
摘要： 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.
摘要翻译：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。

5. 发明公开

EP1728077A4 METHOD FOR DETERMINATION AND QUANTIFICATION OF RADIATION OR GENOTOXIN EXPOSURE 审中-公开
标题翻译：法确定和量化辐射或GENOTOXINBELASTUNG
公开(公告)号：EP1728077A4
公开(公告)日：2008-11-05
申请号：EP05756419
申请日：2005-01-28
申请人： DANA FARBER CANCER INST INC
发明人： D ANDREA ALAN
IPC分类号： G01N33/53 , C07K14/47 , C07K16/18 , C12Q1/68 , G01N33/50
CPC分类号： C07K14/47 , C07K16/18 , G01N33/5014 , G01N2800/52
摘要： 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.

6. 发明专利

CA2703006A1 COMPOSITIONS AND METHODS FOR TREATING CANCER 未知
公开(公告)号：CA2703006A1
公开(公告)日：2008-06-05
申请号：CA2703006
申请日：2007-10-22
申请人： DANA FARBER CANCER INST INC , DNAR INC , UNIV OREGON HEALTH & SCIENCE
发明人： D ANDREA ALAN , WEAVER DAVID T , GROMPE MARKUS , KENNEDY RICHARD
IPC分类号： C12Q1/68
摘要： This present invention relates compositions and methods of treating cancer and methods of accessing/monitoring the responsiveness of a cancer cell to a therapeutic compound, specific for a DNA repair pathway. A method for treating cancer is provided, which includes: a) determining whether the cancer cell is deficient in a DNA repair pathway (eg. Fanconi anemia) and b) administering a DNA damaging agent or inhibitor specific for at least one different DNA repair pathway than that identified in step (a) (eg. mismatch repair or non-homologous endjoining repair pathways).

7. 发明专利

CA2552351A1 METHOD FOR DETERMINATION AND QUANTIFICATION OF RADIATION OR GENOTOXIN EXPOSURE 未知
公开(公告)号：CA2552351A1
公开(公告)日：2005-09-09
申请号：CA2552351
申请日：2005-01-28
申请人： DANA FARBER CANCER INST INC
发明人： D ANDREA ALAN
IPC分类号： C12N15/62 , C07K14/435 , C07K14/47 , C07K16/18 , C07K19/00 , C12N1/21 , C12N5/10 , C12N15/12 , C12N15/13 , C12N15/63 , C12N15/65 , C12Q1/02 , C12Q1/68 , G01N33/50 , G01N33/53 , G01N33/533 , G01N33/566
摘要： 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. Diagnost ic reagents contain a ligand that binds to human FANC~2 associated with a detectable label, Kits for detecting DNA damage in a biological sample conta in 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.

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