利索-全球专利检索

  1. 登录
  2. 注册

搜索结果

24 条记录 (耗时 0.043 秒)

    ONCOGENOMICS-BASED RNAi SCREEN AND USE THEREOF TO IDENTIFY NOVEL TUMOR SUPPRESSORS
    14.
    发明申请
    ONCOGENOMICS-BASED RNAi SCREEN AND USE THEREOF TO IDENTIFY NOVEL TUMOR SUPPRESSORS 审中-公开
    基于ONCOGENOMICS的RNAi筛选及其用于鉴定新型肿瘤抑制剂

    公开(公告)号：US20100273660A1

    公开(公告)日：2010-10-28

    申请号：US12617624

    申请日：2009-11-12

    申请人： Lars Zender ,  Wen Xue ,  Scott Powers ,  Scott W. Lowe

    发明人： Lars Zender ,  Wen Xue ,  Scott Powers ,  Scott W. Lowe

    IPC分类号： C40B20/06 ,  C07K16/00 ,  C40B50/04 ,  C40B40/06 ,  C12N5/09 ,  C12Q1/68 ,  G01N33/574

    CPC分类号： A01K67/0271 ,  A01K2217/058 ,  A01K2267/0331 ,  C07K14/4747 ,  C12N15/1079 ,  C12N15/8509 ,  C12N2510/04 ,  C12N2517/02 ,  C12N2799/027 ,  C12Q1/6886 ,  C12Q2600/154 ,  C12Q2600/178 ,  G01N33/5044 ,  G01N33/5067 ,  G01N33/5088 ,  G01N33/57415 ,  G01N33/57438 ,  G01N2500/00 ,  G01N2800/50 ,  G01N2800/52

    摘要： In some aspects, the invention provides a genetically tractable in situ non-human animal model for hepatocellular carcinoma. The model is useful, inter alia, in understanding the molecular mechanisms of liver cancer, in understanding the genetic alterations that lead to chemoresistance or poor prognosis, and in identifying and evaluating new therapies against hepatocellular carcinomas. The liver cancer model of this invention is made by altering hepatocytes to increase oncogene expression, to reduce tumor suppressor gene expression or both and by transplanting the resulting hepatocytes into a recipient non-human animal.The present invention also provides methods for identifying and validating tumor suppressor genes by screening pools of shRNAs that target genomic regions deleted in human cancers, such as human hepatocellular carcinomas. The present invention also provides validated tumor suppressor genes, and methods of inhibiting cell proliferation and/or tumor growth, for example by expression of such tumor suppressor genes.

    摘要翻译： 在一些方面，本发明提供了用于肝细胞癌的遗传易处的非人动物模型。 该模型除其他外，有助于理解肝癌的分子机制，了解导致化学耐药性或预后不良的遗传改变，以及鉴定和评估针对肝细胞癌的新疗法。 本发明的肝癌模型通过改变肝细胞以增加癌基因表达，减少肿瘤抑制基因表达或两者并通过将所得肝细胞移植到受体非人动物中来制备。 本发明还提供了通过筛选靶向人类癌症中缺失的基因组区域（例如人肝细胞癌）的shRNA的鉴定和验证肿瘤抑制基因的方法。 本发明还提供了经过验证的肿瘤抑制基因，以及例如通过表达这种肿瘤抑制基因来抑制细胞增殖和/或肿瘤生长的方法。

    Orthotopic and genetically tractable non-human animal model for liver cancer and the uses thereof
    16.
    发明授权
    Orthotopic and genetically tractable non-human animal model for liver cancer and the uses thereof 有权
    肝癌的原位和遗传易感性非人动物模型及其用途

    公开(公告)号：US08137907B2

    公开(公告)日：2012-03-20

    申请号：US12072115

    申请日：2008-02-21

    申请人： Lars Zender ,  Scott W. Lowe ,  Mona S. Spector

    发明人： Lars Zender ,  Scott W. Lowe ,  Mona S. Spector

    IPC分类号： C12Q1/68 ,  C07H21/04 ,  C07K16/00 ,  C12P19/34

    CPC分类号： A01K67/0271 ,  A01K2217/058 ,  A01K2267/0331 ,  C07K14/4747 ,  C12N15/8509 ,  C12N2510/04 ,  C12N2517/02 ,  C12N2799/027 ,  G01N33/5067 ,  G01N33/57438 ,  G01N2500/00 ,  G01N2800/52

    摘要： This invention provides a genetically tractable in situ non-human animal model for hepatocellular carcinoma. The model is useful, inter alia, in understanding the molecular mechanisms of liver cancer, in understanding the genetic alterations that lead to chemoresistance or poor prognosis, and in identifying and evaluating new therapies against hepatocellular carcinomas. The liver cancer model of this invention is made by altering hepatocytes to increase oncogene expression, to reduce tumor suppressor gene expression or both and by transplanting the resulting hepatocytes into a recipient non-human animal.This invention also relates to the use of RNA interference (RNAi) technology in vivo to efficiently identify genes associated with liver cancer, in particular those encoding tumor suppressors, by knocking out candidate genes using RNAi and observing whether tumors would develop.

    摘要翻译： 本发明提供了用于肝细胞癌的遗传易处理的非人动物模型。 该模型除其他外，有助于理解肝癌的分子机制，了解导致化学耐药性或预后不良的遗传改变，以及鉴定和评估针对肝细胞癌的新疗法。 本发明的肝癌模型通过改变肝细胞以增加癌基因表达，减少肿瘤抑制基因表达或两者并通过将所得肝细胞移植到受体非人动物中来制备。 本发明还涉及RNA干扰（RNAi）技术在体内有效地鉴定与肝癌相关的基因，特别是编码肿瘤抑制因子的基因，通过使用RNAi敲除候选基因并观察肿瘤是否会发展。

    METHODS FOR TREATING FIBROSIS BY MODULATING CELLULAR SENESCENCE
    17.
    发明申请
    METHODS FOR TREATING FIBROSIS BY MODULATING CELLULAR SENESCENCE 审中-公开
    通过调节细胞感觉治疗纤维化的方法

    公开(公告)号：US20100310504A1

    公开(公告)日：2010-12-09

    申请号：US12679835

    申请日：2008-09-25

    申请人： Scott W. Lowe ,  Valery Krizhanovsky ,  Lars Zender

    发明人： Scott W. Lowe ,  Valery Krizhanovsky ,  Lars Zender

    IPC分类号： A61K38/20 ,  A61K38/21 ,  A61K38/18 ,  A61K35/12 ,  A61K31/7052 ,  A61K39/395 ,  C12Q1/02 ,  A61P1/16

    CPC分类号： A61K38/18 ,  A61K35/17 ,  A61K38/1774 ,  A61K38/19 ,  G01N33/5061 ,  G01N2510/00 ,  Y02A50/465

    摘要： Fibrosis arises as part of a wound healing response that maintains organ integrity following catastrophic tissue damage, but can also contribute to a variety of human pathologies, including liver cirrhosis. The invention demonstrates that cellular senescence acts to limit the fibrogenic response to tissue damage, thereby establishing a role for the senescence program in pathophysiological settings beyond cancer. Accordingly, the methods of the invention relate to modulating cellular senescence in disease tissue that have elevated numbers of senescent cells, such as in fibrotic tissues.

    摘要翻译： 纤维化是伤口愈合反应的一部分，其在灾难性组织损伤后维持器官完整性，但也可能导致多种人类病理，包括肝硬化。 本发明证明细胞衰老起限制对组织损伤的纤维形成反应，从而在衰老程序在癌症以外的病理生理环境中建立起一种作用。 因此，本发明的方法涉及调节具有升高的衰老细胞数量的疾病组织中的细胞衰老，例如在纤维组织中。

    Model for studying the role of genes in chemoresistance
    18.
    发明申请
    Model for studying the role of genes in chemoresistance 审中-公开
    研究基因在化学耐药性中的作用的模型

    公开(公告)号：US20090186839A1

    公开(公告)日：2009-07-23

    申请号：US11893540

    申请日：2007-08-15

    申请人： Scott W. Lowe ,  Hans G. Wendel ,  Jerry Pelletier ,  Marie-Eve Bordeleau ,  Francis Robert

    发明人： Scott W. Lowe ,  Hans G. Wendel ,  Jerry Pelletier ,  Marie-Eve Bordeleau ,  Francis Robert

    IPC分类号： A61K31/704 ,  A61K49/00 ,  C12Q1/02 ,  A61K31/335

    CPC分类号： G01N33/5088 ,  A01K67/0271 ,  A01K2227/105 ,  A01K2267/0331 ,  C12N15/8509 ,  G01N33/5011 ,  G01N33/57426 ,  G01N2800/52

    摘要： The invention provides novel inhibitors of protein translation initiation and inhibitors of eIF4F activity that can increase chemosensitivity or diminish or reverse chemoresistance in growth transformed cells and thereby reduce hyperproliferative conditions, such as cancer progression, in select patient populations having particular tumor genotypes. The invention also provides methods which target translation initiation controls in growth-transformed cells, such as tumor subtypes with altered expression of a gene activity, including the human akt, bcl-2, eIF4E, eIF4A or PTEN activities, to restore drug sensitivity in vivo in a genotype selective manner. In one aspect, the inhibitors of translation initiation of the invention are rocaglates, i.e., cyclopenta[b]benzofurons, which increases chemosensitivity or diminishes or reverses chemoresistance either alone or in combination, additively or synergistically, with other agents that alter growth or death. Preferably, the rocaglate is silvestrol, which is used alone or in combination with doxorubicin to reverses chemoresistance in PTEN-deficient lymphomas or eIF4E-over-expressing lymphomas and to promote cancer remission.

    摘要翻译： 本发明提供蛋白质翻译起始的新型抑制剂和eIF4F活性的抑制剂，其可以在具有特定肿瘤基因型的选定患者群体中增加化学敏感性或降低或逆转生长转化细胞中的化学抗性，从而降低过度增殖状况，例如癌症进展。 本发明还提供了靶向生长转化细胞中的翻译起始对照的方法，例如具有改变的基因活性表达的肿瘤亚型，包括人类akt，bcl-2，eIF4E，eIF4A或PTEN活性，以恢复体内药物敏感性 以基因型选择性方式。 在一个方面，本发明的翻译起始抑制剂是环戊二烯并[b]苯并呋喃，其可以增加化学敏感性，或者单独地或组合地降低或逆转化学抗性，与改变生长或死亡的其它试剂相加或协同地。 优选地，罗卡非特是silvestrol，其单独使用或与多柔比星组合使用以逆转PTEN缺陷型淋巴瘤或eIF4E过表达淋巴瘤中的化学抗性并促进癌症缓解。

    Lymphoma-susceptible transgenic mice and methods for studying drug sensitivity of lymphomas
    20.
    发明授权
    Lymphoma-susceptible transgenic mice and methods for studying drug sensitivity of lymphomas 失效
    淋巴瘤敏感转基因小鼠和研究淋巴瘤药物敏感性的方法

    公开(公告)号：US06583333B1

    公开(公告)日：2003-06-24

    申请号：US09076776

    申请日：1998-05-12

    申请人： Scott W. Lowe ,  Rachel R. Wallace-Brodeur

    发明人： Scott W. Lowe ,  Rachel R. Wallace-Brodeur

    IPC分类号： G01N3300

    CPC分类号： C12N15/8509 ,  A01K67/0271 ,  A01K67/0275 ,  A01K67/0276 ,  A01K2217/05 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/0331 ,  A61K49/0008 ,  C12N2517/02 ,  C12N2800/30

    摘要： A mouse expressing myc in B cells, because of defective function of one or more tumor suppressor genes, is useful for the testing of anti-lymphoma agents and for the testing of genes which may have an effect on the apoptotic pathway. Preferred embodiments include mice of genotypes E&mgr;-myc/p53+/−, E&mgr;-myc/Rb+/− and E&mgr;-myc/p16+/−, and cells derived from lymphomas arising in these mice, wherein the cells may have undergone further genetic alteration. Mouse strains, lymphoma cells and cell lines of the invention can be used in methods to discover new anti-lymphoma agents, methods to characterize tumors, and to characterize genes which may affect the development of resistance to anti-tumor agents. Such methods are also part of the invention.

    摘要翻译： 由于一个或多个肿瘤抑制基因的功能缺陷，在B细胞中表达myc的小鼠可用于抗淋巴瘤试剂的测试和可能对凋亡途径有影响的基因的测试。 优选的实施方案包括基因型Emu-myc / p53 +/-，Emu-myc / Rb +/-和Emu-myc / p16 +/-的小鼠，以及源自这些小鼠中产生的淋巴瘤的细胞，其中细胞可能已经经历进一步的遗传改变。 本发明的小鼠品系，淋巴瘤细胞和细胞系可用于发现新的抗淋巴瘤药物，表征肿瘤的方法，以及表征可能影响抗肿瘤剂抗性发展的基因的方法。 这些方法也是本发明的一部分。