公开(公告)号：US20070292948A1

公开(公告)日：2007-12-20

申请号：US10570116

申请日：2004-08-27

申请人： Joerg Heyer ,  Murray Robinson ,  William Rideout ,  Ronald Depinho ,  Steven Clark ,  Yinghui Zhou ,  Tyler Jacks

发明人： Joerg Heyer ,  Murray Robinson ,  William Rideout ,  Ronald Depinho ,  Steven Clark ,  Yinghui Zhou ,  Tyler Jacks

IPC分类号： C12N5/06 ,  A01K67/00 ,  C12N15/00

CPC分类号： A01K67/0276 ,  A01K67/0271 ,  A01K2217/05 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/0331 ,  C07K14/82 ,  C12N15/8509 ,  C12N2830/003

摘要： Chimeric nonhuman mammals useful as inducible spontaneous cancer models are disclosed. The nonhuman mammals are obtained by introducing one or more genetically modified embryonic stem (ES) cells into an early stage embryo, and then implanting the manipulated embryo into a surrogate mother. The ES cells contain a recombinant oncogene, and also may contain a genetic mutation that deletes or inactivates a tumor suppressor gene. Models of different types of cancer are produced by introducing different combinations of genetic mutations into the ES cells that are introduced into the early stage embryo.

摘要翻译： 公开了可用作诱导型自发癌症模型的嵌合非人哺乳动物。 通过将一个或多个经遗传修饰的胚胎干细胞（ES）细胞引入早期胚胎，然后将操作的胚胎植入替代母体中获得非人类哺乳动物。 ES细胞含有重组癌基因，并且还可能含有遗传突变，其删除或灭活肿瘤抑制基因。 不同类型癌症的模型是通过将遗传突变的不同组合引入引入早期胚胎的ES细胞来产生的。

公开(公告)号：US07622630B2

公开(公告)日：2009-11-24

申请号：US10570116

申请日：2004-08-27

申请人： Joerg Heyer ,  Murray Robinson ,  William Rideout, III ,  Ronald Depinho ,  Steven C. Clark ,  Yinghui Zhou ,  Tyler Jacks ,  Ronan C. O'Hagan

发明人： Joerg Heyer ,  Murray Robinson ,  William Rideout, III ,  Ronald Depinho ,  Steven C. Clark ,  Yinghui Zhou ,  Tyler Jacks ,  Ronan C. O'Hagan

IPC分类号： C12N15/00 ,  A01K67/00 ,  C12N5/06

CPC分类号： A01K67/0276 ,  A01K67/0271 ,  A01K2217/05 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/0331 ,  C07K14/82 ,  C12N15/8509 ,  C12N2830/003

摘要： Chimeric nonhuman mammals useful as inducible spontaneous cancer models are disclosed. The nonhuman mammals are obtained by introducing one or more genetically modified embryonic stem (ES) cells into an early stage embryo, and then implanting the manipulated embryo into a surrogate mother. The ES cells contain a recombinant oncogene, and also may contain a genetic mutation that deletes or inactivates a tumor suppressor gene. Models of different types of cancer are produced by introducing different combinations of genetic mutations into the ES cells that are introduced into the early stage embryo.

摘要翻译： 公开了可用作诱导型自发癌症模型的嵌合非人哺乳动物。 通过将一个或多个经遗传修饰的胚胎干细胞（ES）细胞引入早期胚胎，然后将操作的胚胎植入替代母体中获得非人类哺乳动物。 ES细胞含有重组癌基因，并且还可能含有遗传突变，其删除或灭活肿瘤抑制基因。 不同类型癌症的模型是通过将遗传突变的不同组合引入引入早期胚胎的ES细胞来产生的。

公开(公告)号：US20090165150A1

公开(公告)日：2009-06-25

申请号：US11963358

申请日：2007-12-21

申请人： Yinghui Zhou ,  William Rideout, III ,  Joerg Heyer ,  Murray Robinson

发明人： Yinghui Zhou ,  William Rideout, III ,  Joerg Heyer ,  Murray Robinson

IPC分类号： A01K67/027 ,  C12N15/87

CPC分类号： C12N15/85 ,  A01K67/0271 ,  A01K67/0275 ,  A01K2217/05 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/0331 ,  C07K14/82 ,  C12N15/8509 ,  C12N2799/027 ,  G01N2500/10

摘要： The invention provides an improved directed complementation method for generating a conditionally tumorigenic mouse cell. In a directed complementation method, the tumorigenicity of a conditionally tumorigenic mouse cell depends on either the expression of an inducible recombinant oncogene or the expression of a recombinant gene of interest that functionally complements an uninduced recombinant oncogene. The invention provides a method of producing a tumorigenic mouse cell containing an uninduced oncogene, a recombinant gene of interest that functionally complements the uninduced oncogene, and a Cre-ER system capable of excising the recombinant gene of interest. When the Cre-ER system is activated, the recombinant gene of interest is excised. From the effect on the mouse cell it is possible to determine whether the recombinant gene of interest is a tumor maintenance gene.

摘要翻译： 本发明提供了一种用于产生有条件致瘤性小鼠细胞的改进的定向互补方法。 在定向互补方法中，条件致瘤小鼠细胞的致瘤性取决于可诱导的重组癌基因的表达或功能上补充未诱导的重组癌基因的重组感兴趣的基因的表达。 本发明提供了一种产生致瘤性小鼠细胞的方法，所述致瘤性小鼠细胞含有未诱导的癌基因，功能上补充未诱导的致癌基因的重组基因，以及能够切除感兴趣的重组基因的Cre-ER系统。 当Cre-ER系统被激活时，切除感兴趣的重组基因。 从对小鼠细胞的作用可以确定感兴趣的重组基因是否是肿瘤维持基因。

公开(公告)号：US07556796B2

公开(公告)日：2009-07-07

申请号：US11398171

申请日：2006-04-05

申请人： Murray Robinson ,  Ronan O'Hagan ,  Karuppiah Kannan ,  Ti Cai ,  Maria Isabel Chiu ,  Lorena Lerner ,  Jie Lin ,  Yinghui Zhou

发明人： Murray Robinson ,  Ronan O'Hagan ,  Karuppiah Kannan ,  Ti Cai ,  Maria Isabel Chiu ,  Lorena Lerner ,  Jie Lin ,  Yinghui Zhou

IPC分类号： A61K49/00 ,  A61K35/12

CPC分类号： A01K67/0271 ,  A01K2217/05 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/0331 ,  C07K14/82 ,  C12N15/8509 ,  C12N2830/002

摘要： A method of producing a tumorigenic mouse cell, the tumorigenicity of which depends on a recombinant gene of interest is disclosed. The method involves: (a) providing a conditionally tumorigenic mouse cell containing a recombinant oncogene operably linked to an inducible promoter, wherein (i) expression of the recombinant oncogene is necessary and sufficient for the tumorigenicity of the tumorigenic mouse cell, and (ii) the inducible promoter is in the uninduced state; and (b) introducing into the cell a recombinant gene of interest that functionally complements the oncogene, thereby restoring tumorigenicity without expression of the inducible recombinant oncogene. Also disclosed is a method of testing a compound for anti-tumor effects. The method includes producing tumorigenic mouse cells the tumorigenicity depends on expression of a recombinant gene of interest, implanting the cells in mice and obtaining tumors from the implanted cells, administering test compounds to the mice, and determining anti-tumor effects, if any, of the compounds.

摘要翻译： 公开了一种致瘤性小鼠细胞的产生方法取决于感兴趣的重组基因的方法。 该方法包括：（a）提供含有可操作地连接到诱导型启动子的重组癌基因的条件致瘤小鼠细胞，其中（i）重组癌基因的表达对于致瘤性小鼠细胞的致瘤性是必要和足够的，以及（ii） 诱导型启动子处于未诱导状态; 和（b）在细胞中引入功能上补充致癌基因的重组基因，从而恢复致瘤性而不表达可诱导的重组癌基因。 还公开了测试化合物抗肿瘤作用的方法。 该方法包括产生致瘤性小鼠细胞，其致瘤性取决于感兴趣的重组基因的表达，将细胞植入小鼠中并从植入的细胞中获得肿瘤，向小鼠施用测试化合物，并测定抗肿瘤作用（如果有的话） 化合物。

公开(公告)号：US20120302572A1

公开(公告)日：2012-11-29

申请号：US13455972

申请日：2012-04-25

申请人： Julie Kan ,  Stuart Thomson ,  Gretchen M. Argast ,  Matthew E. O'Connor ,  Murray Robinson ,  Bin Feng ,  Joerg Heyer ,  Maria I. Chiu ,  Richard Nicoletti

发明人： Julie Kan ,  Stuart Thomson ,  Gretchen M. Argast ,  Matthew E. O'Connor ,  Murray Robinson ,  Bin Feng ,  Joerg Heyer ,  Maria I. Chiu ,  Richard Nicoletti

IPC分类号： A61K31/517 ,  A61P35/00 ,  C40B30/04 ,  A61K31/4985

CPC分类号： C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/112 ,  C12Q2600/158

摘要： The present invention provides diagnostic methods for assessing the EMT status of tumor cells, and for predicting the effectiveness of treatment of a cancer patient with an EGFR or IGF-1R kinase inhibitor, utilizing an EMT gene signature index score. The present invention further provides methods for treating patients with cancer that incorporate these methods.

摘要翻译： 本发明提供用于评估肿瘤细胞的EMT状态的诊断方法，并且利用EMT基因特征指数评分来预测用EGFR或IGF-1R激酶抑制剂治疗癌症患者的有效性。 本发明还提供了用于治疗纳入这些方法的癌症患者的方法。

公开(公告)号：US09896730B2

公开(公告)日：2018-02-20

申请号：US13455972

申请日：2012-04-25

申请人： Julie Kan ,  Stuart Thomson ,  Gretchen M. Argast ,  Matthew E. O'Connor ,  Murray Robinson ,  Bin Feng ,  Joerg Heyer ,  Maria I. Chiu ,  Richard Nicoletti

发明人： Julie Kan ,  Stuart Thomson ,  Gretchen M. Argast ,  Matthew E. O'Connor ,  Murray Robinson ,  Bin Feng ,  Joerg Heyer ,  Maria I. Chiu ,  Richard Nicoletti

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/112 ,  C12Q2600/158

摘要： The present invention provides diagnostic methods for assessing the EMT status of tumor cells, and for predicting the effectiveness of treatment of a cancer patient with an EGFR or IGF-1R kinase inhibitor, utilizing an EMT gene signature index score. The present invention further provides methods for treating patients with cancer that incorporate these methods.

公开(公告)号：US20060228302A1

公开(公告)日：2006-10-12

申请号：US11398171

申请日：2006-04-05

申请人： Murray Robinson ,  Ronan O'Hagan ,  Karuppiah Kannan ,  Ti Cai ,  Maria Chiu ,  Lorena Lerner ,  Jie Lin ,  Yinghui Zhou

发明人： Murray Robinson ,  Ronan O'Hagan ,  Karuppiah Kannan ,  Ti Cai ,  Maria Chiu ,  Lorena Lerner ,  Jie Lin ,  Yinghui Zhou

IPC分类号： A61K49/00 ,  C12N5/06 ,  C12N15/09

CPC分类号： A01K67/0271 ,  A01K2217/05 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/0331 ,  C07K14/82 ,  C12N15/8509 ,  C12N2830/002

摘要： A method of producing a tumorigenic mouse cell, the tumorigenicity of which depends on a recombinant gene of interest is disclosed. The method involves: (a) providing a conditionally tumorigenic mouse cell containing a recombinant oncogene operably linked to an inducible promoter, wherein (i) expression of the recombinant oncogene is necessary and sufficient for the tumorigenicity of the tumorigenic mouse cell, and (ii) the inducible promoter is in the uninduced state; and (b) introducing into the cell a recombinant gene of interest that functionally complements the oncogene, thereby restoring tumorigenicity without expression of the inducible recombinant oncogene. Also disclosed is a method of testing a compound for anti-tumor effects. The method includes producing tumorigenic mouse cells the tumorigenicity depends on expression of a recombinant gene of interest, implanting the cells in mice and obtaining tumors from the implanted cells, administering test compounds to the mice, and determining anti-tumor effects, if any, of the compounds.

公开(公告)号：US09345788B2

公开(公告)日：2016-05-24

申请号：US11170338

申请日：2005-06-28

申请人： Min Wu ,  Charlotte Kuperwasser ,  Murray Robinson

发明人： Min Wu ,  Charlotte Kuperwasser ,  Murray Robinson

IPC分类号： A01K67/027 ,  A61K49/00

CPC分类号： A61K49/0008 ,  A01K67/0271 ,  A01K2227/105 ,  A01K2267/0331 ,  C12N2510/04 ,  C12N2799/027

摘要： A reconstituted human breast tumor model is disclosed. The model, which is incorporated into mice, provides actual tumors that arise spontaneously, thereby mimicking naturally occurring breast cancer. The tumors are genetically human, because they arise from human mammary tissues that develop from human mammary epithelial cells implanted into host mice. Prior to implantation, the mammary epithelial cells are genetically modified to contain a recombinant human oncogene and an SV40 early region.

公开(公告)号：US20050282150A1

公开(公告)日：2005-12-22

申请号：US11192450

申请日：2005-07-28

申请人： Steven Coats ,  Michael Bass ,  Murray Robinson

发明人： Steven Coats ,  Michael Bass ,  Murray Robinson

IPC分类号： C12N15/09 ,  A61K48/00 ,  C07K14/47 ,  C12N1/15 ,  C12N1/19 ,  C12N1/21 ,  C12N5/10 ,  C12N15/12 ,  C12P21/02 ,  C12Q1/00 ,  C12Q1/02 ,  C12Q1/48 ,  C12Q1/68 ,  G01N33/573 ,  G01N33/574

CPC分类号： C12Q1/485 ,  A61K48/00 ,  C07K14/4738 ,  G01N33/573 ,  G01N33/57407 ,  G01N2333/91215 ,  G01N2500/02 ,  G01N2510/00

摘要： Disclosed are nucleic acid molecules encoding novel cyclin E2 polypeptides. Also disclosed are methods of preparing the nucleic acid molecules and polypeptides, and methods of using these molecules.

公开(公告)号：US20120231478A1

公开(公告)日：2012-09-13

申请号：US13502476

申请日：2010-06-03

申请人： Jie Lin ,  Bin Feng ,  Murray Robinson ,  Feng Jiang ,  Xiaojian Sun

发明人： Jie Lin ,  Bin Feng ,  Murray Robinson ,  Feng Jiang ,  Xiaojian Sun

IPC分类号： G01N33/566

CPC分类号： G01N33/57492 ,  C12Q1/6886 ,  G01N33/57407 ,  G01N2333/70596 ,  G01N2800/52

摘要： A diagnostic method for predicting whether a human tumor will be sensitive or resistant to treatment with tivozanib (AV-951) is disclosed. The method is based on measurement of macrophage content in a tissue sample from a tumor. Measurement of macrophage content can be based on analysis of macrophage marker gene expression, e.g., by RNA analysis or immunohistochemistry.

摘要翻译： 公开了一种诊断方法，用于预测人肿瘤是否敏感或对利托那尼治疗有抗药性（AV-951）。 该方法基于来自肿瘤的组织样品中巨噬细胞含量的测量。 巨噬细胞含量的测定可以基于巨噬细胞标记基因表达的分析，例如通过RNA分析或免疫组织化学。