TISSUE PRESERVATION AND FIXATION METHOD
    63.
    发明申请
    TISSUE PRESERVATION AND FIXATION METHOD 有权
    组织保存和固定方法

    公开(公告)号:US20100068690A1

    公开(公告)日:2010-03-18

    申请号:US12447773

    申请日:2007-10-26

    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。

    Stat3 as a theranostic indicator
    64.
    发明申请
    Stat3 as a theranostic indicator 审中-公开
    Stat3作为指标

    公开(公告)号:US20080255243A1

    公开(公告)日:2008-10-16

    申请号:US12081290

    申请日:2008-04-14

    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 。

    Method for inhibiting angiogenesis
    68.
    发明授权
    Method for inhibiting angiogenesis 失效
    抑制血管发生的方法

    公开(公告)号:US5744492A

    公开(公告)日:1998-04-28

    申请号:US209651

    申请日:1994-03-10

    IPC分类号: A61K31/41

    CPC分类号: A61K31/41

    摘要: Angiogenesis is a composite of regulated proliferation and regulated invasion occuring in a variety of normal and pathologic conditions. Compound 1 and related analogs are useful for inhibiting angiogenesis in a host and offer a novel approach to the treatment of cancer, diabetic retinopathy, hemangiomata, vasculidities and other diseases associated with angiogenesis.

    摘要翻译: 血管生成是在各种正常和病理状态下发生的调节性增殖和调节性侵袭的复合物。 化合物1和相关类似物可用于抑制宿主中的血管发生,并且提供了治疗癌症,糖尿病性视网膜病,血管瘤,血管炎和与血管生成相关的其它疾病的新方法。

    Antigenic matrix metalloproteinase peptides
    70.
    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。