Matrix metalloproteinase peptides: role in diagnosis and therapy
    1.
    发明授权
    Matrix metalloproteinase peptides: role in diagnosis and therapy 失效
    基质金属蛋白酶肽:在诊断和治疗中的作用

    公开(公告)号:US5280106A

    公开(公告)日:1994-01-18

    申请号:US488460

    申请日:1990-02-26

    摘要: A family of metalloproteinases exist which cleave extracellular matrix molecules. These metalloproteinases are secreted in a latent inactive form and require activation in order to specifically cleave the preferred substrate. A series of peptides have been prepared based on the complete sequence analysis of type IV procollagenase. Peptide inhibitors were synthesized which correspond to cysteine repeat regions and histidine containing regions; the mechanism of action of these peptides involves inhibition of binding of the enzyme to the substrate. Peptide inhibitors were synthesized which correspond to the peptide cleaved off during activation, and constitute a novel class of metalloproteinase inhibitors. These inhibitors are members of a series of peptides which contain the core amino acid sequence RKPRC or analogs thereof. The cysteine residue is required for activity. Affinity purified antibodies directed against specific peptides can be used to a) detect any general metalloproteinase enzyme with the sequence in part VAAHE or PRCGNPD, and distinguish it from other known members of the metalloproteinase family, b) block functional domains resulting in the inhibition of enzyme activity, and c) distinguish latent from activated forms of the enzyme.

    摘要翻译: 存在切割细胞外基质分子的金属蛋白酶家族。 这些金属蛋白酶以潜伏活性形式分泌并需要活化以特异性切割优选的底物。 已经基于IV型原胶原酶的完整序列分析制备了一系列肽。 合成肽抑制剂,其对应于半胱氨酸重复区域和组氨酸区域; 这些肽的作用机理涉及抑制酶与底物的结合。 合成肽抑制剂,其对应于在活化期间切除的肽,并构成新型的金属蛋白酶抑制剂。 这些抑制剂是含有核心氨基酸序列RKPRC或其类似物的一系列肽的成员。 活性需要半胱氨酸残基。 针对特异性肽的亲和纯化抗体可用于a)用部分VAAHE或PRCGNPD中的序列检测任何一般金属蛋白酶,并将其与其他已知的金属蛋白酶家族成员区分开,b)阻断功能结构域,导致酶的抑制 活性,和c)区分潜在和酶的活化形式。

    Antigenic matrix metalloproteinase peptides
    2.
    发明授权
    Antigenic matrix metalloproteinase peptides 失效
    抗原基质金属蛋白酶肽

    公开(公告)号:US5372809A

    公开(公告)日:1994-12-13

    申请号:US830313

    申请日:1992-01-31

    摘要: A family of metalloproteinases exist which cleave extracellular matrix molecules. These metalloproteinases are secreted in a latent inactive form and require activation in order to specifically cleave the preferred substrate. A series of peptides have been prepared based on the complete sequence analysis of type IV procollagenase. Peptide inhibitors were synthesized which correspond to cysteine repeat regions and histidine containing regions; the mechanism of action of these peptides involves inhibition of binding of the enzyme to the substrate. Peptide inhibitors were synthesized which correspond to the peptide cleaved off during activation, and constitute a novel class of metalloproteinase inhibitors. These inhibitors are members of a series of peptides which contain the core amino acid sequence RKPRC or analogs thereof. The cysteine residue is required for activity. Affinity purified antibodies directed against specific peptides can be used to a) detect any general metalloproteinase enzyme with the sequence in part VAAHE or PRCGNPD, and distinguish it from other known members of the metalloproteinase family, b) block functional domains resulting in the inhibition of enzyme activity, and c) distinguish latent from activated forms of the enzyme.

    摘要翻译: 存在切割细胞外基质分子的金属蛋白酶家族。 这些金属蛋白酶以潜伏活性形式分泌并需要活化以特异性切割优选的底物。 已经基于IV型原胶原酶的完整序列分析制备了一系列肽。 合成肽抑制剂,其对应于半胱氨酸重复区域和组氨酸区域; 这些肽的作用机理涉及抑制酶与底物的结合。 合成肽抑制剂,其对应于在活化期间切除的肽,并构成新型的金属蛋白酶抑制剂。 这些抑制剂是含有核心氨基酸序列RKPRC或其类似物的一系列肽的成员。 活性需要半胱氨酸残基。 针对特异性肽的亲和纯化抗体可用于a)用部分VAAHE或PRCGNPD中的序列检测任何一般金属蛋白酶,并将其与其他已知的金属蛋白酶家族成员区分开,b)阻断功能结构域,导致酶的抑制 活性,和c)区分潜在和酶的活化形式。

    Metalloproteinase peptides: role in diagnosis and therapy
    3.
    发明授权
    Metalloproteinase peptides: role in diagnosis and therapy 失效
    金属蛋白酶肽:在诊断和治疗中的作用

    公开(公告)号:US5270447A

    公开(公告)日:1993-12-14

    申请号:US317407

    申请日:1989-03-01

    CPC分类号: C07K14/8146 G01N33/573

    摘要: A family of metalloproteinases exist which cleave extracellular matrix molecules. These metalloproteinases are secreted in a latent inactive form and require activation in order to specifically cleave the preferred substrate. A series of peptides have been prepared based on the complete sequence analysis of type IV Procollagenase. Peptide inhibitors were synthesized which correspond to cysteine repeat regions and histidine containing regions; the mechanism of action of these peptides involves inhibition of binding of the enzyme to the substrate. Peptide inhibitors were synthesized which correspond to the peptide cleaved off during activation, and constitute a novel class of metalloproteinase inhibitors. These inhibitors are members of a series of peptides which contain the core amino acid sequence PRCG. The cysteine residue is required for activity. Affinity purified antibodies directed against specific peptides can be used to a) detect any general metalloproteinase enzyme with the sequence in part VAAHE or PRCGNPD, and distinguish it from other known members of the metalloproteinase family, b) block functional domains resulting in the inhibition of enzyme activity, and c) distinguish latent from activated forms of the enzyme.

    摘要翻译: 存在切割细胞外基质分子的金属蛋白酶家族。 这些金属蛋白酶以潜伏活性形式分泌并需要活化以特异性切割优选的底物。 基于IV型原胶原酶的完整序列分析,已经制备了一系列肽。 合成肽抑制剂,其对应于半胱氨酸重复区域和组氨酸区域; 这些肽的作用机理涉及抑制酶与底物的结合。 合成肽抑制剂,其对应于在活化期间切除的肽,并构成新型的金属蛋白酶抑制剂。 这些抑制剂是含有核心氨基酸序列PRCG的一系列肽的成员。 活性需要半胱氨酸残基。 针对特异性肽的亲和纯化抗体可用于a)用部分VAAHE或PRCGNPD中的序列检测任何一般金属蛋白酶,并将其与其他已知的金属蛋白酶家族成员区分开,b)阻断功能结构域,导致酶的抑制 活性,和c)区分潜在和酶的活化形式。

    Hydrogel nanoparticle based immunoassay
    6.
    发明授权
    Hydrogel nanoparticle based immunoassay 有权
    基于水凝胶纳米颗粒的免疫测定

    公开(公告)号:US09012240B2

    公开(公告)日:2015-04-21

    申请号:US13061507

    申请日:2009-08-26

    摘要: An immunoassay device incorporating porous polymeric capture nanoparticles within either the sample collection vessel or pre-impregnated into a porous substratum within fluid flow path of the analytical device is presented. This incorporation of capture particles within the immunoassay device improves sensitivity while removing the requirement for pre-processing of samples prior to loading the immunoassay device. A preferred embodiment is coreshell bait containing capture nanoparticles which perform three functions in one step, in solution: a) molecular size sieving, b) target analyte sequestration and concentration, and c) protection from degradation. The polymeric matrix of the capture particles may be made of co-polymeric materials having a structural monomer and an affinity monomer, the affinity monomer having properties that attract the analyte to the capture particle. This device is useful for point of care diagnostic assays for biomedical applications and as field deployable assays for environmental, pathogen and chemical or biological threat identification.

    摘要翻译: 提供了在分析装置的流体流动路径内将多孔聚合物捕获纳米颗粒结合到样品采集容器中或预浸渍到多孔基质内的免疫测定装置。 这种在免疫测定装置内的捕获颗粒的并入提高了灵敏度,同时在加载免疫测定装置之前消除了样品预处理的要求。 优选的实施方案是含有捕获纳米颗粒的芯壳诱饵,其在一个步骤中在溶液中进行三个功能:a)分子筛分,b)目标分析物螯合和浓缩,以及c)防止降解。 捕获颗粒的聚合物基质可以由具有结构单体和亲和单体的共聚物制成,亲和单体具有将分析物吸引到捕获颗粒的性质。 该设备可用于生物医学应用的护理点诊断分析以及环境,病原体和化学或生物威胁鉴定的现场部署测定。

    Tissue preservation and fixation method
    7.
    发明授权
    Tissue preservation and fixation method 有权
    组织保存和固定方法

    公开(公告)号:US08460859B2

    公开(公告)日:2013-06-11

    申请号:US12447773

    申请日:2007-10-26

    IPC分类号: A01N1/00

    CPC分类号: G01N1/30 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。

    EX VIVO THERAPEUTICS SCREENING OF LIVING BONE MARROW CELLS FOR MULTIPLE MYELOMA
    8.
    发明申请
    EX VIVO THERAPEUTICS SCREENING OF LIVING BONE MARROW CELLS FOR MULTIPLE MYELOMA 审中-公开
    用于多发性骨髓瘤的生物骨髓细胞的筛查治疗

    公开(公告)号:US20110207627A1

    公开(公告)日:2011-08-25

    申请号:US13057978

    申请日:2009-08-12

    摘要: Methods of selecting a treatment for a patient with multiple myeloma are provided. Prior to commencing a treatment regime, bone marrow aspirates are isolated from a patient and incubated with one or more candidate therapeutics. The methods identify the therapy or combination of therapies most likely to yield the best results for a particular individual. In addition to improving clinical outcome, such theranostic evaluations dramatically reduce health care costs, by avoiding ineffective therapies. Screening assays for identifying treatments for multiple myeloma also are provided.

    摘要翻译: 提供了选择多发性骨髓瘤患者的治疗方法。 在开始治疗方案之前,从患者中分离骨髓抽吸物并与一种或多种候选治疗剂一起温育。 该方法确定最有可能为特定个体产生最佳结果的治疗或疗法组合。 除了改善临床结果之外,这种诊断性评估通过避免无效疗法,大大降低了医疗保健成本。 还提供了用于鉴定多发性骨髓瘤治疗的筛选试验。

    CALIBRATED RPMA ASSAY
    9.
    发明申请
    CALIBRATED RPMA ASSAY 审中-公开
    校准RPMA测定

    公开(公告)号:US20100203549A1

    公开(公告)日:2010-08-12

    申请号:US12676257

    申请日:2008-09-05

    IPC分类号: G01N33/53 C08B5/02

    CPC分类号: G01N33/96 G01N33/5005

    摘要: This invention relates, e.g., to a set of calibrants for determining the amount in a sample of an analyte (e.g., a protein, such as a protein that has been post-translationally modified), comprising a plurality of calibrants, which contain a range of amounts (e.g., defined amounts and/or serial dilutions) of the analyte, spanning the expected amount of the analyte in the sample. In each of the calibrants, a defined amount of the analyte is present in the same suitable, biological diluent (e.g., a cell or tissue lysate, or a bodily fluid). In one embodiment of the invention, the diluent reflects the same or a similar biological milieu (proteins, lipids, serum proteins, serum matrix proteins, etc.) as that in the sample in which the analyte to be measured is present. In embodiments of the invention, a single calibrant (e.g., a cell lysate) may comprise as many as hundreds of analytes, and can be used for the quantification of those hundreds of analytes in a sample. Methods are described for performing an assay (e.g. RPMA analysis), in which the calibrants of a set of calibrants of the invention are immobilized on each of the surfaces to which samples to be analyzed are immobilized, thereby providing an internal calibration curve for quantifying an RPMA assay.

    摘要翻译: 本发明涉及例如用于确定分析物样品中的量(例如蛋白质,例如经翻译后修饰的蛋白质)的一组校准剂,其包含多个校准物,其包含范围 的分析物的量(例如,定义的量和/或连续稀释度),跨越样品中分析物的预期量。 在每个校准中,一定量的分析物存在于相同的合适的生物稀释剂(例如,细胞或组织裂解液或体液)中。 在本发明的一个实施方案中,稀释剂反映与待测分析物存在的样品中相同或相似的生物环境(蛋白质,脂质,血清蛋白,血清基质蛋白等)。 在本发明的实施方案中,单个校准物(例如,细胞裂解物)可以包含多达数百种分析物,并且可以用于量化样品中数百种分析物。 描述了用于进行测定(例如RPMA分析)的方法,其中将本发明的一组校准物的校准物固定在固定有待分析样品的每个表面上,从而提供内部校准曲线,用于量化 RPMA测定。

    Diagnostic tests and personalized treatment regimes for cancer stem cells
    10.
    发明申请
    Diagnostic tests and personalized treatment regimes for cancer stem cells 审中-公开
    癌症干细胞的诊断测试和个性化治疗方案

    公开(公告)号:US20090275546A1

    公开(公告)日:2009-11-05

    申请号:US12386002

    申请日:2009-04-10

    IPC分类号: A61K31/395 C40B30/06 C12N5/02

    摘要: Provided are methods of identifying a metabolic target in a cancer stem cell that include using a microarray to identify intracellular signaling networks within a population of cancer stem cells that respond to a growth factor for the stem cell. Also provided are methods of determining a personalized therapeutic regime that include receiving metabolic information relating to a cancer stem cell in a patient, determining the patient's personal criteria relevant to the therapeutic regime, and combining the metabolic and personal criteria. Also provided are a diagnostic test for establishing a personalized therapeutic regime for a colon cancer patient and methods of reducing colon cancer stem cells/treating colon cancer.

    摘要翻译: 提供了确定癌症干细胞中的代谢靶标的方法,其包括使用微阵列来鉴定响应干细胞生长因子的癌干细胞群体内的细胞内信号传导网络。 还提供了确定个体化治疗方案的方法,其包括接收与患者中的癌干细胞相关的代谢信息,确定患者与治疗方案相关的个人标准,以及组合代谢和个人标准。 还提供了建立结肠癌患者的个性化治疗方案的诊断测试和减少结肠癌干细胞/治疗结肠癌的方法。