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    NICHE TARGETING OF QUIESCENT CANCER STEM CELLS
    11.
    发明申请
    NICHE TARGETING OF QUIESCENT CANCER STEM CELLS 审中-公开
    静脉癌干细胞的靶向治疗

    公开(公告)号：WO2013070807A1

    公开(公告)日：2013-05-16

    申请号：PCT/US2012/064000

    申请日：2012-11-07

    Applicant: THE REGENTS OF THE UNIVERSITY OF CALIFONIA

    Inventor： JAMIESON, Catriona, H. ,  GOFF, Daniel ,  SMITH, Kristen

    IPC: C12Q1/02 ,  C12N5/095 ,  G01N33/68 ,  C12Q1/68 ,  A61K35/12

    CPC classification number: G01N33/5748 ,  A61K31/166 ,  A61K31/506 ,  A61K45/06 ,  C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/158 ,  G01N33/57426 ,  G01N2510/00 ,  G01N2800/52

    Abstract: The disclosure provides methods for determining the self-renewal potential of a cancer stem cell (CSC), or for predicting the drugability (susceptibility to a drug) of a CSC, and/or for predicting the progression of a cancer that corresponds to the CSC. In alternative embodiments, the disclosure provides methods for determining whether a CSC in a niche is more pro-apoptotic or more anti-apoptotic in relation to a normal stem cell or a CSC from another niche. In alternative embodiments, the disclosure provides methods for determining the prognosis or malignant potential of a cancer. In alternative embodiments, the disclosure provides methods determining the anti-apoptotic versus a pro-apoptotic potential of a cancer stem cell (CSC).

    Abstract translation: 本公开提供了用于确定癌症干细胞（CSC）的自我更新潜力或用于预测CSC的可药用性（对药物的易感性）和/或用于预测进展的方法 对应于CSC的癌症。 在可选的实施方案中，本公开内容提供了用于确定相对于正常干细胞或来自另一个生态位的CSC，生态位中的CSC是否更加促凋亡或更多抗凋亡的方法。 在可选实施方式中，本公开提供了用于确定癌症的预后或恶性潜能的方法。 在可选的实施方案中，本公开提供了确定抗凋亡相对于癌症干细胞（CSC）的促凋亡潜力的方法。

    METHOD AND KIT FOR ASSESSING VIABLE CELLS
    18.
    发明申请
    METHOD AND KIT FOR ASSESSING VIABLE CELLS 审中-公开
    用于评估可变细胞的方法和工具包

    公开(公告)号：WO2010006615A3

    公开(公告)日：2010-06-10

    申请号：PCT/DK2009050173

    申请日：2009-07-13

    Applicant: CHEMOMETEC AS ,  SKINDERSOE METTE ELENA ,  SOERENSEN HELLE FROBOESE ,  KJAERULFF SOEREN

    Inventor： SKINDERSOE METTE ELENA ,  SOERENSEN HELLE FROBOESE ,  KJAERULFF SOEREN

    IPC: A01N1/02 ,  G01N15/14 ,  G01N21/64 ,  G01N33/50

    CPC classification number: G01N33/582 ,  C09B15/00 ,  C09B57/00 ,  C09B57/02 ,  G01N21/6428 ,  G01N33/502 ,  G01N33/583 ,  G01N2021/6439 ,  G01N2201/06113 ,  G01N2201/062 ,  G01N2510/00

    Abstract: The present invention provides simple, rapid methods and procedures for analyzing cells, hereunder quantitative and qualitative assessment of cells, such as viability. The present invention relates to the use of various optionally substituted reporter compounds particularly detectable upon their reaction with thiol-containing species present in higher concentrations in intact (e.g., living) cells than in non-intact (e.g., dead, stressed and apoptotic) cells. The present invention also relates to the use of various optionally substituted reporter compounds particularly detectable upon their reaction with species present in intact and/or non-intact cells. Moreover, the present invention relates to the use of measuring techniques and/or instruments coupled with the use of various optionally substituted reporter compounds. The invention further relates to compositions used in methods for analyzing cells, such as a composition comprising N-(7-dimethylamino-4-methyl-3-coumarinyl)-maleimide (DACM).

    Abstract translation: 本发明提供用于分析细胞的简单，快速的方法和程序，在此对细胞进行定量和定性评估，例如活力。 本发明涉及各种任选取代的报告化合物在完整（例如，活的）细胞中与在非完整（例如死亡，应激和凋亡）细胞中比较高的浓度存在的硫醇类物质反应时特别可检测的用途） 。 本发明还涉及各种任选取代的报告化合物在与完整和/或未完整细胞中存在的物质反应时特别可检测的用途。 此外，本发明涉及与使用各种任选取代的报告化合物的测量技术和/或仪器的用途。 本发明还涉及用于分析细胞的方法中使用的组合物，例如包含N-（7-二甲基氨基-4-甲基-3-香豆素基） - 马来酰亚胺（DACM）的组合物。

    DISCOVERY OF CANDIDATE BIOMARKERS OF IN VIVO APOPTOSIS BY GLOBAL PROFILING OF CASPASE CLEAVAGE SITES
    19.
    发明申请
    DISCOVERY OF CANDIDATE BIOMARKERS OF IN VIVO APOPTOSIS BY GLOBAL PROFILING OF CASPASE CLEAVAGE SITES 审中-公开
    通过CASPASE切割位点的全球分布发现体内细胞凋亡的候选生物标志物

    公开(公告)号：WO2010021822A3

    公开(公告)日：2010-06-03

    申请号：PCT/US2009052297

    申请日：2009-07-30

    Applicant: UNIV CALIFORNIA ,  WELLS JAMES A ,  MAHRUS SAMI

    Inventor： WELLS JAMES A ,  MAHRUS SAMI

    IPC: C07K14/47 ,  C07K1/00 ,  G01N33/574 ,  G01N33/68

    CPC classification number: C07K14/47 ,  C07K14/4747 ,  C12Q1/37 ,  G01N33/573 ,  G01N33/574 ,  G01N33/6848 ,  G01N2333/96466 ,  G01N2510/00

    Abstract: The present invention relates to the discovery of novel biomarkers of in vivo apoptosis based on a large number of caspase-like cleavage sites. These biomarkers are useful for detection and quantification of apoptosis in a biological sample. The invention also provides synthetic peptides and proteins corresponding to neo-epitopes created by proteolytic processing of these cleavage sites. The synthetic peptides can be used as standards to enable identification and quantitation of these biomarkers using mass spectrometry. The synthetic proteins can be used to generate antibodies and other binding reagents specific for these biomarkers. Methods for detecting apoptosis as well as for diagnosing or for providing a prognosis for a disease or disease state characterized by apoptosis are also provided herein. Finally, the invention provides compositions and kits for performing the methods of the invention.

    Abstract translation: 本发明涉及基于大量胱天蛋白酶样切割位点发现体内凋亡的新型生物标志物。 这些生物标志物可用于检测和量化生物样品中的细胞凋亡。 本发明还提供了对应于通过蛋白水解加工这些切割位点产生的新表位的合成肽和蛋白质。 可以使用合成肽作为标准物，以使用质谱法鉴定和定量这些生物标志物。 合成蛋白质可用于生成特异于这些生物标志物的抗体和其他结合试剂。 本文还提供了用于检测细胞凋亡以及用于诊断或提供以细胞凋亡为特征的疾病或疾病状态的预后的方法。 最后，本发明提供了用于实施本发明方法的组合物和试剂盒。

    GENERATION OF MITOTIC PHASE REPORTER FOR IN VIVO BIOLUMINESCENCE IMAGING IN LIVING ANIMALS
    20.
    发明申请
    GENERATION OF MITOTIC PHASE REPORTER FOR IN VIVO BIOLUMINESCENCE IMAGING IN LIVING ANIMALS 审中-公开
    生物动物生物相容性生物识别的生成

    公开(公告)号：WO2010042333A1

    公开(公告)日：2010-04-15

    申请号：PCT/US2009/058515

    申请日：2009-09-28

    Applicant: MERCK SHARP & DOHME CORP. ,  ZHANG, Guy-Jun ,  SUR, Cyrille

    Inventor： ZHANG, Guy-Jun ,  SUR, Cyrille

    IPC: C12N15/00 ,  C12P21/06 ,  C12P21/04 ,  A61K39/00

    CPC classification number: G01N33/5011 ,  G01N2333/4739 ,  G01N2333/90241 ,  G01N2510/00

    Abstract: Disclosed herein is a fusion protein comprising of 173 amino acid residues of the N terminus of cyclin B1 (including the Destruction Box and Cytoplasmic Retention Signal) fused in-frame with the luciferase reporter gene. Expression of the fusion protein is driven by the cyclin B1 promoter and mimics expression of the endogenous cyclin B1 gene. Following addition of the substrate luciferin, increased levels of the luciferase reporter gene can be used to monitor cell cycle arrest at the G2/M phase. Importantly, this invention may be used in vivo to monitor luciferase expression and G2/M cell cycle arrest in living animals. A broad aspect of the invention provides a method of detecting cell death in a target cell comprising transfecting the target cell with a nucleic acid construct that encodes a cyclinB1-Luciferase fusion protein under conditions favoring expression of the fusion protein; introducing the target cell with a substrate specific for the fusion protein for a period of time sufficient to detect a signal, wherein the generation of a signal indicates that the cell has arrested at the G2/M transition; and detecting a signal.

    Abstract translation: 本文公开了一种融合蛋白，其包含与萤光素酶报告基因框架融合的细胞周期蛋白B1（包括破坏盒和细胞质保留信号）的N末端的173个氨基酸残基。 融合蛋白的表达由细胞周期蛋白B1启动子驱动并模拟内源性细胞周期蛋白B1基因的表达。 添加底物萤光素后，荧光素酶报告基因的增加可用于监测G2 / M期的细胞周期停滞。 重要的是，本发明可以在体内用于监测活的动物中的荧光素酶表达和G2 / M细胞周期停滞。 本发明的广泛方面提供了一种检测靶细胞中的细胞死亡的方法，包括在有利于融合蛋白表达的条件下用编码细胞周期蛋白B1荧光素酶融合蛋白的核酸构建体转染靶细胞; 将具有融合蛋白特异性底物的靶细胞引入足以检测信号的时间段，其中信号的产生指示细胞在G2 / M转变处已经停止; 并检测信号。

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