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公开(公告)号：US08168568B1
公开(公告)日：2012-05-01
申请号：US12581019
申请日：2009-10-16
IPC分类号： C40B30/06
CPC分类号： G01N33/5041
摘要： A method for selecting combinations of drugs for treatment of diseases that arise from deranged signaling pathways is disclosed. The method involves measuring the activity states for signaling proteins in a diseased cell and determining whether the activity states are different from the activity states observed for a reference cell such as a normal cell. Based on the observed differences, combinations of two or more drugs are selected to reduce these differences. Treatment of a subject with the combinations restores the activity states of the signaling proteins of the deranged disease-associated signaling pathways toward the activity states observed in the reference cell. Since the diseased cell and the reference cell can both be obtained from the same subject, combinations of drugs that specifically target patient-specific signaling derangements is possible.
摘要翻译： 公开了一种用于选择用于治疗由紊乱信号传导途径引起的疾病的药物组合的方法。 该方法包括测量患病细胞中的信号蛋白的活性状态，并确定活性状态是否与观察到的参考细胞例如正常细胞的活性状态不同。 基于观察到的差异，选择两种或更多种药物的组合以减少这些差异。 用组合治疗受试者恢复了与参考细胞中观察到的活动状态相关的紊乱疾病相关信号通路的信号蛋白的活性状态。 由于患病细胞和参照细胞都可以从相同的受试者获得，所以特别针对患者特异性信号紊乱的药物的组合是可能的。
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12.发明申请SIGNAL PATHWAY ALTERATIONS AND DRUG TARGET ELEVATIONS IN PRIMARY METACHRONOUS METASTATIC COLORECTAL CANCER COMPARED TO NON-METASTATIC DISEASE 审中-公开与非分子性疾病相比，主要METACHRUSOUS METASTATIC COLORECTAL CANCER中的信号途径改变和药物目标高度公开(公告)号：US20110200597A1
公开(公告)日：2011-08-18
申请号：US13057409
申请日：2009-08-05
IPC分类号： A61K39/395 , C12Q1/48 , C12Q1/37 , C40B30/04 , C12Q1/02 , G01N33/53 , G01N33/573 , A61K31/415 , A61K31/365 , A61K31/439 , A61K31/517 , A61K31/5377 , A61K31/506 , A61K31/404 , A61K31/4164 , A61P35/00 , A61P35/04 , G06F19/00
CPC分类号： G01N33/57419 , G01N2800/60
摘要： The present invention relates to the identification and diagnostic use of biomarkers in primary colorectal cancer tumors whose activation level are predictive of the likelihood of the onset of metastatic disease. These biomarkers may be used to determine the suitability of a patient for aggressive and/or targeted treatments. Kits and compositions of the invention are also provided.
摘要翻译： 本发明涉及生物标志物在原发性结肠直肠癌肿瘤中的鉴定和诊断用途，其活化水平预示出转移性疾病发病的可能性。 这些生物标志物可用于确定患者对侵袭性和/或靶向治疗的适合性。 还提供了本发明的试剂盒和组合物。
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公开(公告)号：US20100074895A1
公开(公告)日：2010-03-25
申请号：US12513040
申请日：2007-10-31
IPC分类号： A61K39/395 , G01N33/48 , A61K31/497 , A61K31/517
CPC分类号： G01N33/57419 , A61K31/506 , A61K39/39558 , C07K16/22 , G01N33/57438 , G01N2800/52
摘要： Methods are provided for treating cancer metastasis by administering a therapeutic composition targeting a kinase substrate cascade.
摘要翻译： 提供了通过施用靶向激酶底物级联的治疗组合来治疗癌症转移的方法。
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公开(公告)号：US20080255243A1
公开(公告)日：2008-10-16
申请号：US12081290
申请日：2008-04-14
IPC分类号： A61K31/135 , G01N33/574 , A61P35/04
CPC分类号： G01N33/57415 , G01N2800/52
摘要： This invention relates, e.g., to a method for predicting the response of a subject having estrogen-receptor-positive breast cancer to an inhibitor of the estrogen signaling pathway (e.g. tamoxifen), comprising measuring in a cancer sample from the subject the level of phosphorylation, compared to a baseline value, of one or more of the following members of an interconnected intracellular signaling pathway: (a) 4EBP1, and/or (b) p70S6, and/or (c) STAT3, and/or (d) FAK, wherein a significantly elevated level of phosphorylation of 4EBP1, and/or p70S6 and/or STAT3, and/or a significantly decreased level of phosphorylation of FAK, compared to the baseline value, indicates that the subject is likely to be a non-responder to the inhibitor and/or has a poor prognosis. Additional members of the intracellular signaling pathway whose phosphorylation can be measured are also described. Also described is a method for treating breast cancer in a subject in need thereof, wherein the subject exhibits an elevated level of phosphorylation of these markers, comprising administering to the subject an effective amount of one or more inhibitors of members of the interconnected intracellular signaling pathway.
摘要翻译： 本发明涉及例如用于预测具有雌激素受体阳性乳腺癌的受试者对雌激素信号通路抑制剂（例如他莫昔芬）的反应的方法，包括在受试者的癌症样品中测量磷酸化水平 （a）4EBP1和/或（b）p70S6和/或（c）STAT3和/或（d）FAK的一个或多个以下成员的基线值; 其中与基线值相比，4EBP1和/或p70S6和/或STAT3的磷酸化水平显着升高和/或FAK的磷酸化水平显着降低，表明受试者可能是非应答者 对抑制剂和/或预后不良。 还描述了可以测量其磷酸化的细胞内信号传导途径的其他成员。 还描述了在有需要的受试者中治疗乳腺癌的方法，其中所述受试者表现出这些标志物的磷酸化水平升高，包括向受试者施用有效量的一种或多种互连的细胞内信号传导途径的成员抑制剂 。
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公开(公告)号：US09335328B2
公开(公告)日：2016-05-10
申请号：US10182354
申请日：2001-02-02
IPC分类号： G01N33/558 , G01N33/68
CPC分类号： G01N33/6842 , G01N33/5014 , G01N33/502 , G01N33/6803 , G01N33/6845
摘要： An assay device for determining the presence of analytes in a cell lysate comprises a porous support member and a plurality of binding reagents arranged and immobilized at multiple reaction sites on the support member. The binding reagents are selected and arranged to assess the status of a selected cellular signal transduction pathway/protein-protein interactive network. In a further aspect, a method for assessing the status of a signal transduction pathway comprises generating a lysate of cells, the lysate retaining one or more pathway molecules present in one or more states and the pathway molecules reflecting signal transduction events taking place in the cells. The method further includes applying the lysate to an immobilized series of binding reagents which can discriminate the pathway molecules and their states. Binding events between the pathway molecules and the binding reagents are identified and the state of the selected signal pathway is determined.
摘要翻译： 用于确定细胞裂解物中分析物的存在的测定装置包括多孔支撑构件和多个结合试剂，其布置并固定在支撑构件上的多个反应位点处。 选择和排列结合试剂以评估所选择的细胞信号转导途径/蛋白质 - 蛋白质相互作用网络的状态。 在另一方面，用于评估信号转导途径的状态的方法包括产生细胞的裂解物，保留一个或多个状态中存在的一种或多种途径分子的裂解物和反映发生在细胞中的信号转导事件的途径分子 。 该方法还包括将裂解物应用于可以区分途径分子及其状态的固定化的一系列结合试剂。 鉴定途径分子和结合试剂之间的结合事件，并确定所选信号通路的状态。
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公开(公告)号：US20100003247A1
公开(公告)日：2010-01-07
申请号：US12446910
申请日：2007-10-29
IPC分类号： A61K39/395 , C12Q1/02 , A61K31/4545 , A61K31/496 , A61K31/404 , A61K31/517 , A61K31/34 , A61K31/415 , A61P35/00
CPC分类号： G01N33/57419 , C12Q1/485 , G01N2333/90245
摘要： This invention relates, e.g., to a method for predicting the prognosis, the likelihood of metastasis in, or the desirability of administering an aggressive therapy to, a subject with colorectal cancer, comprising determining, in a sample from the subject, the level of phosphorylation compared to a positive and/or negative reference standard, of one or more of: (a) AKT (S473); (b) BAD (S112); (c) cABL (T735); (d) ERK (T42/44); (e) MARCKS (S152-156); (0 p38MAPK (T180-182): (g) STAT 1 (Y701 ); (h) PTEN (S380); (i) EGFR (Y992); (j) PAK 1/2 (S 1 19/204); or (k) PKC zeta/lambda (T410-403); or the total amount of (1) COX-2 protein; wherein if the level of phosphorylation of one or more of a-i or the total amount of COX-2 protein (1) is elevated compared to the negative reference standard, and/or if the level of phosphorylation of j or k is decreased compared to the positive reference standard, the subject has poor prognosis, is likely to undergo metastasis, and/or is a good candidate for aggressive therapy. Also described are methods for treating subjects likely to develop metastatic colorectal carcinoma, and pharmaceutical compositions and kits for implementing methods of the invention.
摘要翻译： 本发明涉及例如用于预测具有结肠直肠癌的受试者的预后，转移的可能性或对其进行侵袭性治疗的可行性的方法，其包括在受试者的样品中测定磷酸化水平 与正和/或负参考标准相比，以下一个或多个：（a）AKT（S473）; （b）BAD（S112）; （c）cABL（T735）; （d）ERK（T42 / 44）; （e）MARCKS（S152-156）; （0 p38MAPK（T180-182）：（g）STAT1（Y701）;（h）PTEN（S380）;（i）EGFR（Y992）;（j）PAK 1/2（S 19/204）;或 （k）PKCζ/λ（T410-403）;或（1）COX-2蛋白的总量;其中如果ai中的一种或多种或COX-2蛋白（1）的总量的磷酸化水平， 与阴性参考标准相比升高，和/或如果j或k的磷酸化水平与阳性参照标准相比降低，则受试者的预后不良，可能经历转移，和/或是 还描述了治疗可能产生转移性结直肠癌的受试者的方法，以及用于实施本发明方法的药物组合物和试剂盒。
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公开(公告)号：US08834873B2
公开(公告)日：2014-09-16
申请号：US12513040
申请日：2007-10-31
IPC分类号： A61K39/395 , C07K16/22 , G01N33/574
CPC分类号： G01N33/57419 , A61K31/506 , A61K39/39558 , C07K16/22 , G01N33/57438 , G01N2800/52
摘要： Methods are provided for treating cancer metastasis by administering a therapeutic composition targeting a kinase substrate cascade.
摘要翻译： 提供了通过施用靶向激酶底物级联的治疗组合来治疗癌症转移的方法。
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18.发明申请SIGNAL PATHWAY ALTERATIONS AND DRUG TARGET ELEVATIONS IN PRIMARY METACHRONOUS METASTATIC COLORECTAL CANCER COMPARED TO NON-METASTATIC DISEASE 审中-公开与非分子性疾病相比，主要METACHRUSOUS METASTATIC COLORECTAL CANCER中的信号途径改变和药物目标高度公开(公告)号：US20140030254A1
公开(公告)日：2014-01-30
申请号：US13851644
申请日：2013-03-27
IPC分类号： G01N33/574
CPC分类号： G01N33/57419 , G01N2800/60
摘要： The present invention relates to the identification and diagnostic use of biomarkers in primary colorectal cancer tumors whose activation level are predictive of the likelihood of the onset of metastatic disease. These biomarkers may be used to determine the suitability of a patient for aggressive and/or targeted treatments. Kits and compositions of the invention are also provided.
摘要翻译： 本发明涉及生物标志物在原发性结肠直肠癌肿瘤中的鉴定和诊断用途，其活化水平预示出转移性疾病发病的可能性。 这些生物标志物可用于确定患者对侵袭性和/或靶向治疗的适合性。 还提供了本发明的试剂盒和组合物。
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公开(公告)号：US08628931B2
公开(公告)日：2014-01-14
申请号：US12083866
申请日：2006-10-18
CPC分类号： G01N33/6842 , G01N2800/52
摘要： This invention relates, e.g., to a method for predicting a subject's response to a chemotherapeutic agent and/or the subject's prognosis, comprising measuring the phosphorylation state of at least one member of the mTOR pathway, and/or of at least one member of an interconnected polypeptide pathway (e.g. a member of the Akt pathway or a member of the IRS pathway), compared to a baseline value, in a cancer tissue or cancer cell sample from the subject, wherein an elevated level of the phosphorylation state compared to the baseline value indicates that the subject is a non-responder to the chemotherapeutic agent and/or has a poor prognosis. Also described is a method for treating a cancer in a subject in need thereof, wherein the subject exhibits an elevated level of the phosphorylation state, comprising administering one or more inhibitors of the mTOR and/or an interconnected pathway.
摘要翻译： 本发明涉及例如用于预测受试者对化学治疗剂和/或受试者预后的反应的方法，包括测量mTOR途径的至少一个成员的磷酸化状态和/或至少一种成员 相互作用的多肽途径（例如Akt途径的成员或IRS途径的成员）与来自受试者的癌症组织或癌细胞样品中的基线值相比，其中与基线相比提高了磷酸化水平 值表明受试者是化疗药物的无反应者和/或预后不良。 还描述了在有需要的受试者中治疗癌症的方法，其中所述受试者表现出升高的磷酸化状态水平，包括施用一种或多种mTOR抑制剂和/或互连途径。
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公开(公告)号：US08460859B2
公开(公告)日：2013-06-11
申请号：US12447773
申请日：2007-10-26
申请人： Virginia A. Espina , Lance A. Liotta , David Geho
发明人： Virginia A. Espina , Lance A. Liotta , David Geho
IPC分类号： A01N1/00
摘要： This invention relates, e.g., to a composition that, at room temperature, when contacted with a sample comprising phosphoproteins, can fix and stabilize cellular phosphoproteins, preserve cellular morphology, and allow the sample to be frozen to generate a cryostat frozen section suitable for molecular analysis. The composition comprises (1) a fixative that is effective to fix the phosphoproteins, and that has a sufficient water content to be soluble for a stabilizer and/or a permeability enhancing agent); (2) a stabilizer, comprising (a) a kinase inhibitor and (b) a phosphatase inhibitor and, optionally, (c) a protease (e.g., proteinase) inhibitor; and (3) a permeability enhancing agent (e.g. PEG). Methods are described for preserving phosphoproteins, using such a composition. Also described are endogenous surrogate markers for monitoring protein degradation, including the loss of posttranslational modifications (such as phosphorylation), e.g. the following removal of a cell or tissue from a subject; and exogenous molecular sentinels (e.g. phosphoproteins attached to magnetic nanoparticles) that allow one to evaluate the processing history of a cellular or tissue population sample.
摘要翻译： 本发明涉及例如在室温下与包含磷蛋白的样品接触时可以固定和稳定细胞磷酸蛋白的组合物，保留细胞形态，并允许样品冷冻以产生适于分子的低温恒温器冷冻切片 分析。 组合物包含（1）固定磷酸蛋白有效的固定剂，并且其具有足够的水含量可溶于稳定剂和/或渗透性增强剂）; （2）稳定剂，其包含（a）激酶抑制剂和（b）磷酸酶抑制剂和任选的（c）蛋白酶（例如蛋白酶）抑制剂; 和（3）渗透性增强剂（例如PEG）。 描述了使用这种组合物来保存磷蛋白的方法。 还描述了用于监测蛋白质降解的内源替代标记，包括翻译后修饰（例如磷酸化）的丧失，例如， 以下从受试者中除去细胞或组织; 和外源性分子前哨蛋白（例如连接到磁性纳米颗粒的磷酸蛋白），其允许评价细胞或组织群体样品的加工历史。
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