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    METHOD FOR SCREENING INHIBITORS TARGETING ANTI-APOPTOTIC SURVIVAL PATHWAYS
    2.
    发明申请
    METHOD FOR SCREENING INHIBITORS TARGETING ANTI-APOPTOTIC SURVIVAL PATHWAYS 审中-公开
    筛选靶向抗凋亡存活途径的抑制剂的方法

    公开(公告)号：WO2017087810A1

    公开(公告)日：2017-05-26

    申请号：PCT/US2016/062789

    申请日：2016-11-18

    Applicant: MEMORIAL SLOAN-KETTERING CANCER CENTER

    Inventor： CHENG, Emily, H. ,  HSIEH, James

    IPC: G01N33/50 ,  G01N33/574

    CPC classification number: G01N33/5011 ,  A61K31/00 ,  G01N2510/00

    Abstract: A method of identifying inhibitors of the anti-apoptotic survival pathway in cancer cells is disclosed. The method comprises the steps of (a) exposing cultured wild-type cells to a candidate inhibitor at a predetermined concentration for a predetermined period of time and determining cell viability after the exposure to the candidate inhibitor; (b) exposing two or more cell lines of specifically MCL-1 or BCL-2 or BCL-X L addicted cells to the candidate inhibitor at the predetermined concentration for the predetermined period of time and determining cell viability after the exposure to the candidate inhibitor; and (c) identifying the candidate inhibitor as a MCL-1 or BCL-2 or BCL-X L inhibitor if the cell viability in step (a) is significantly higher than the cell viability in step (b). The disclosed method provides a way to identify inhibitors which selectively inhibit specific members of the BCL-2 family ( e.g ., MCL-1) by screening two or more cell lines with addictions to different and specific members of the BCL-2 family of proteins.

    Abstract translation: 公开了一种鉴定癌细胞中抗凋亡存活途径抑制剂的方法。 该方法包括以下步骤：（a）将培养的野生型细胞暴露于预定浓度的候选抑制剂达预定时间段，并测定暴露于候选抑制剂后的细胞活力; （b）将特定MCL-1或BCL-2或BCL-XL嗜中性细胞的两种或更多种细胞系暴露于预定浓度的候选抑制剂达预定时间段并测定细胞活力 暴露于候选抑制剂后; 和（c）如果步骤（a）中的细胞活力显着高于步骤（b）中的细胞活力，则鉴定候选抑制剂为MCL-1或BCL-2或BCL-XL抑制剂 ）。 所公开的方法提供了一种通过筛选两种或更多种细胞系选择性抑制BCL-2家族的特定成员（例如，MCL-1）的抑制剂的方法，所述细胞系对不同的和特定成员 BCL-2家族蛋白质。

    PRIMING OF CANCER CELLS WITH LOW DOSE NALTREXONE
    4.
    发明申请
    PRIMING OF CANCER CELLS WITH LOW DOSE NALTREXONE 审中-公开
    用低剂量NALTREXONE预处理癌细胞

    公开(公告)号：WO2015189597A1

    公开(公告)日：2015-12-17

    申请号：PCT/GB2015/051686

    申请日：2015-06-09

    Applicant: CANCER VACCINE INSTITUTE

    Inventor： DALGLEISH, Angus ,  LIU, Wai

    IPC: A61K31/436 ,  A61P35/00

    CPC classification number: A61K31/485 ,  A61K31/282 ,  A61K31/436 ,  A61K31/664 ,  A61K31/7068 ,  A61K45/06 ,  G01N33/57484 ,  G01N2333/4703 ,  G01N2510/00

    Abstract: The present invention provides a pharmaceutical composition comprising naltrexone or an analogue thereof for use in the treatment of a subject having a tumour/cancer; wherein the naltrexone or the analogue thereof is to be administered to the subject in a first treatment phase, followed by a recovery phase; wherein, following the recovery phase, a small molecule signalling inhibitor selected from the group consisting of PI3-kinase inhibitors, AKT inhibitors, taxanes, antimetabolites, alkylating agents and cell cycle inhibitors is to be administered to the subject in a second treatment phase; the recovery phase being characterised by the absence of administration of the naltrexone or the analogue thereof and the small molecule signalling inhibitor. Also envisaged are a diagnostic test to assess the response of a subject to the first treatment phase, an in vitro method of testing the efficacy of a small molecule signalling inhibitor when for use in combination with naltrexone, and the use of naltrexone in such a method when in vivo.

    Abstract translation: 本发明提供包含纳曲酮或其类似物的药物组合物，用于治疗患有肿瘤/癌症的受试者; 其中纳曲酮或其类似物将在第一治疗阶段施用于受试者，随后是恢复期; 其中，在恢复阶段之后，在第二处理阶段向对象施用选自PI3-激酶抑制剂，AKT抑制剂，紫杉烷类，抗代谢物，烷化剂和细胞周期抑制剂的小分子信号传导抑制剂。 恢复期的特征在于不给予纳曲酮或其类似物和小分子信号传导抑制剂。 还设想了用于评估受试者对第一治疗阶段的反应的诊断测试，用于与纳曲酮组合使用时测试小分子信号传导抑制剂的功效的体外方法，以及在这种方法中使用纳曲酮 当体内。

    ANTIBODIES AND METHODS FOR THE DETECTION OF CELL DEATH
    5.
    发明申请
    ANTIBODIES AND METHODS FOR THE DETECTION OF CELL DEATH 审中-公开
    用于检测细胞死亡的抗体和方法

    公开(公告)号：WO2015143277A1

    公开(公告)日：2015-09-24

    申请号：PCT/US2015/021678

    申请日：2015-03-20

    Applicant: WELLSTAT DIAGNOSTICS, LLC

    Inventor： MILLER, Jeffrey, Allan ,  JEFFRIES, Eddie, Phillip

    IPC: C07K16/18 ,  G01N33/53 ,  G01N33/58

    CPC classification number: G01N33/6893 ,  C07K16/18 ,  C07K2317/33 ,  C07K2317/34 ,  C07K2317/56 ,  C07K2317/72 ,  G01N33/54333 ,  G01N2333/4742 ,  G01N2510/00 ,  G01N2800/085 ,  G01N2800/7033

    Abstract: Disclosed herein are antibodies having binding specificity to the amino acid sequences Ala Ser Ser Gly Leu Thr Val Glu Val Asp (SEQ ID NO:1 ) and Thr Val Glu Val Asp (SEQ ID NO:14), and methods of detecting cell death in a sample, comprising contacting the sample with a first antibody specific for a C-terminal amino acid sequence Ala Ser Ser Gly Leu Thr Val Glu Val Asp (SEQ ID NO:1 ) or Thr Val Glu Val Asp (SEQ ID NO:14) of a CK18 protein fragment having a C-terminal amino acid sequence of Val Glu Val Asp (SEQ ID NO:2) and a second antibody that specifically binds an epitope that is present in both full-length CK18 and the CK18 protein fragment, and that does not overlap with SEQ ID NO:1 or SEQ ID NO:14, under conditions such that the CK1 8 protein fragment present in the sample specifically binds to the first antibody and the second antibody, wherein one of the antibodies is bound to a solid support and the other antibody is bound to a detection moiety capable of producing a signal; optionally removing any unbound or excess material; and detecting the signal from the detection moiety, wherein the signal is positively correlated with the presence of the CK18 protein fragment in the sample.

    Abstract translation: 本文公开了对氨基酸序列Ala Ser Ser Gly Leu Thr Val Glu Val Asp（SEQ ID NO：1）和Thr Val Glu Val Asp（SEQ ID NO：14）具有结合特异性的抗体，以及检测细胞死亡的方法 包括使样品与C末端氨基酸序列Ala Ser Ser Gly Leu Thr Val Glu Val Asp（SEQ ID NO：1）或Thr Val Glu Val Asp（SEQ ID NO：14）特异的第一抗体接触， 的具有Val Glu Val Asp（SEQ ID NO：2）的C末端氨基酸序列的CK18蛋白片段和特异性结合存在于全长CK18和CK18蛋白片段中的表位的第二抗体，以及 其不与SEQ ID NO：1或SEQ ID NO：14重叠，使得样品中存在的CK1 8蛋白片段特异性结合第一抗体和第二抗体，其中一种抗体结合于 固体支持物和另一抗体结合到能产生信号的检测部分; 任选地去除任何未结合或多余的材料; 并检测来自检测部分的信号，其中该信号与样品中CK18蛋白片段的存在呈正相关。

    APOPTOSIS BIOMARKERS
    8.
    发明申请
    APOPTOSIS BIOMARKERS 审中-公开
    杀虫剂生物标志物

    公开(公告)号：WO2013192298A1

    公开(公告)日：2013-12-27

    申请号：PCT/US2013/046554

    申请日：2013-06-19

    Applicant: THE SCRIPPS RESEARCH INSTITUTE ,  DIX, Melissa ,  SIMON, Gabriel, M. ,  CRAVATT, Benjamin, F.

    Inventor： DIX, Melissa ,  SIMON, Gabriel, M. ,  CRAVATT, Benjamin, F.

    IPC: C07K7/08 ,  G01N33/68

    CPC classification number: G01N33/6848 ,  C07K14/4747 ,  G01N2333/96413 ,  G01N2510/00

    Abstract: The present invention provides novel biomarkers for apoptosis. The apoptosis biomarkers comprise a polypeptide with a caspase cleaved terminus and also a phosphotylaCed amino acid residue located close to the terminus (e.g., within about 15 residues). The invention also provides methods of using such biomarkers to monitor apoptotic activities and methods for identifying apoptosis biomarkers in various cellular systems.

    Abstract translation: 本发明提供新的凋亡生物标志物。 凋亡生物标志物包含具有胱天蛋白酶切割末端的多肽，以及位于接近末端（例如，约15个残基）内的磷酸羟化Ced氨基酸残基。 本发明还提供使用这样的生物标志物来监测凋亡活性的方法和用于鉴定各种细胞系统中的凋亡生物标志物的方法。

    ANASTASIS BIOSENSOR
    10.
    发明申请
    ANASTASIS BIOSENSOR 审中-公开
    ANASTASIS生物传感器

    公开(公告)号：WO2013134499A1

    公开(公告)日：2013-09-12

    申请号：PCT/US2013/029594

    申请日：2013-03-07

    Applicant: THE JOHNS HOPKINS UNIVERSITY ,  MONTELL, Denise ,  TANG, Ho Lam

    Inventor： MONTELL, Denise ,  TANG, Ho Lam

    IPC: G01N33/68 ,  C12Q1/68 ,  G01N33/58 ,  A61K51/00

    CPC classification number: G01N33/5091 ,  A01K67/0275 ,  A01K2227/105 ,  A01K2267/0393 ,  G01N33/582 ,  G01N33/6872 ,  G01N2510/00

    Abstract: The present invention relates to the field of anastasis, i.e., the process of reversal of apoptosis. More specifically, the present invention provides methods and compositions useful for studying anastasis. In one embodiment, the present invention provides an in vivo biosensor comprising (a) a transcription factor complex comprising the Gal4 transcription factor linked to an enzyme cleavable linker, wherein the transcription factor complex is tethered to the plasma membrane via a transmembrane domain; and (b) a reporter system comprising (1) a first nucleic acid encoding flippase operably linked to the upstream activating sequence that binds Gal4; and (2) a second nucleic acid comprising an FRT-flanked stop codon cassette separating a constitutive promoter and a fluorescent protein open reading frame.

    Abstract translation: 本发明涉及转移的领域，即逆转细胞凋亡的过程。 更具体地，本发明提供了用于研究静息的方法和组合物。 在一个实施方案中，本发明提供了一种体内生物传感器，其包含（a）转录因子复合物，其包含与酶切割接头连接的Gal4转录因子，其中所述转录因子复合物通过跨膜结构域连接于所述质膜; 和（b）报告系统，其包括（1）编码翻转酶的第一核酸，其与上游激活序列结合，其与Gal4结合; 和（2）包含分离组成型启动子和荧光蛋白质开放阅读框的FRT侧翼终止密码子盒的第二核酸。

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