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    COMPOSITIONS FOR GENERATING AN ANTIGEN SPECIFIC IMMUNE RESPONSE
    1.
    发明申请
    COMPOSITIONS FOR GENERATING AN ANTIGEN SPECIFIC IMMUNE RESPONSE 审中-公开
    用于产生抗原特异性免疫应答的组合物

    公开(公告)号：US20120251579A1

    公开(公告)日：2012-10-04

    申请号：US13386590

    申请日：2010-07-30

    申请人： Lars Zender

    发明人： Lars Zender

    IPC分类号： A61K35/12 ,  C12N5/071 ,  C12N5/10 ,  C12P21/02 ,  C07F9/00 ,  A61K39/00 ,  A61K31/496 ,  C07D403/04 ,  A61K31/555 ,  A61P35/00 ,  C12N15/85

    CPC分类号： A61K39/0011 ,  A61K31/00 ,  A61K35/12 ,  A61K2039/5152 ,  C12N5/0693

    摘要： The present invention provides for the purposeful utilisation of the induction of senescence in eukaryotic cells for induction of an antigen specific immune response. Such cells can be normal cells, pre-malignant and malignant cells as well as virally or bacterially infected cells, for the generation of an immune response, preferably a cellular or humoral immune response comprising T-cells and/or B-cells, whose immune response is directed specifically against antigens from those cells in which senescence was induced and then comprises an immune response against the senescent cells itself as well as to the non-senescent counterparts harbouring the same antigens.

    摘要翻译： 本发明提供了有目的地利用真核细胞中的衰老诱导来诱导抗原特异性免疫应答。 这样的细胞可以是正常细胞，恶性前和恶性细胞以及病毒或细菌感染的细胞，用于产生免疫应答，优选包含T细胞和/或B细胞的细胞或体液免疫应答，其免疫 响应特异性针对诱导衰老的那些细胞的抗原，然后包含针对衰老细胞本身以及含有相同抗原的非衰老对应物的免疫应答。

    Orthotopic and genetically tractable non-human animal model for liver cancer and the uses thereof
    2.
    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
    3.
    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。

    Development and use of a new orthotopic, genetically tractable non-human animal model for liver cancer
    4.
    发明申请
    Development and use of a new orthotopic, genetically tractable non-human animal model for liver cancer 审中-公开
    开发和使用新的原位，遗传易感的非人动物肝癌模型

    公开(公告)号：US20060162000A1

    公开(公告)日：2006-07-20

    申请号：US11325218

    申请日：2006-01-03

    申请人： Lars Zender ,  Scott Lowe ,  Mona Spector

    发明人： Lars Zender ,  Scott Lowe ,  Mona Spector

    IPC分类号： A01K67/027 ,  C12N15/87

    CPC分类号： A01K67/0271 ,  A01K2227/105 ,  A01K2267/0331 ,  C07K14/4747 ,  C12N2510/04 ,  C12N2517/02 ,  C12N2799/027 ,  G01N33/57438 ,  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.

    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。

    ONCOGENOMICS-BASED RNAi SCREEN AND USE THEREOF TO IDENTIFY NOVEL TUMOR SUPPRESSORS
    8.
    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。