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    Stat3 as a theranostic indicator
    61.
    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

    申请人： Emanuel F. Petricoin ,  Lance A. Liotta ,  Julia D. Wulfkuhle

    发明人： Emanuel F. Petricoin ,  Lance A. Liotta ,  Julia D. Wulfkuhle

    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 。

    Methods for the isolation and analysis of cellular protein content
    62.
    发明授权
    Methods for the isolation and analysis of cellular protein content 有权
    分离和分析细胞蛋白质含量的方法

    公开(公告)号：US06969614B1

    公开(公告)日：2005-11-29

    申请号：US09913667

    申请日：2000-02-16

    申请人： Lance A. Liotta ,  Nicole Simone ,  Michael Emmert-Buck ,  Emmanuel F. Petricoin III

    发明人： Lance A. Liotta ,  Nicole Simone ,  Michael Emmert-Buck ,  Emmanuel F. Petricoin III

    IPC分类号： G01N1/18 ,  G01N1/28 ,  G01N1/30 ,  G01N21/00 ,  G01N21/75 ,  G01N33/53 ,  G01N33/68

    CPC分类号： G01N33/6803 ,  G01N2001/284 ,  Y10T436/25375 ,  Y10T436/255

    摘要： The present invention describes devices and methods for performing protein analysis on laser capture microdissected cells, which permits proteomic analysis on cells of different populations. Particular disclosed examples are analysis of normal versus malignant cells, or a comparison of differential protein expression in cells that are progressing from normal to malignant. The protein content of the microdissected cells may be analyzed using techniques such as immunoassays, 1D and 2D gel electrophoresis characterization, Western blotting, liquid chromatography quadrapole ion trap electrospray (LCQ-MS), Matrix Assisted Laser Desorption Ionization/Time of Flight (MALDI/TOF), and Surface Enhanced Laser Desorption Ionization Spectroscopy (SELDI). In addition to permitting direct comparison of qualitative and quantitative protein content of tumor cells and normal cells from the same tissue sample, the methods also allow for investigation of protein characteristics of tumor cells, such as binding ability and amino acid sequence, and differential expression of proteins in particular cell populations in response to drug treatment. The present methods also provide, through the use of protein fingerprinting, a rapid and reliable way to identify the source tissue of a tumor metastasis.

    摘要翻译： 本发明描述了用于对激光捕获显微切割细胞进行蛋白质分析的装置和方法，其允许对不同群体的细胞进行蛋白质组学分析。 特别公开的实例是正常与恶性细胞的分析，或从正常到恶性进展的细胞中差异蛋白表达的比较。 可以使用免疫测定，1D和2D凝胶电泳表征，Western印迹，液相色谱四极离子阱电喷雾（LCQ-MS），基质辅助激光解吸电离/飞行时间（MALDI / TOF）和表面增强激光解吸电离光谱（SELDI）。 除了允许直接比较来自相同组织样品的肿瘤细胞和正常细胞的定性和定量蛋白质含量之外，该方法还允许研究肿瘤细胞的蛋白质特征，例如结合能力和氨基酸序列，以及差异表达 蛋白质在特定的细胞群体响应药物治疗。 本方法还通过使用蛋白质指纹图谱提供了一种快速可靠的方法来鉴定肿瘤转移的源组织。

    Method for inhibiting angiogenesis
    67.
    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

    申请人： Elise C. Kohn ,  Lance A. Liotta ,  Riccardo Alessandro

    发明人： Elise C. Kohn ,  Lance A. Liotta ,  Riccardo Alessandro

    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
    69.
    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

    申请人： Lance A. Liotta ,  William Stetler-Stevenson ,  Henry Krutzsch

    发明人： Lance A. Liotta ,  William Stetler-Stevenson ,  Henry Krutzsch

    IPC分类号： G01N33/53 ,  A61K9/08 ,  A61K38/55 ,  A61P19/02 ,  A61P35/00 ,  A61P43/00 ,  C07H21/04 ,  C07K7/06 ,  C07K7/08 ,  C07K14/00 ,  C07K14/81 ,  C07K16/00 ,  C07K16/38 ,  C07K17/00 ,  C12N5/10 ,  C12N9/99 ,  C12N15/09 ,  G01N33/573 ,  A61K37/547 ,  C07K17/02

    CPC分类号： C07K14/8146 ,  G01N33/573 ,  Y10S530/806 ,  Y10S530/81

    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
    70.
    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

    申请人： Lance A. Liotta ,  William Stetler-Stevenson ,  Henry Krutzsch

    发明人： Lance A. Liotta ,  William Stetler-Stevenson ,  Henry Krutzsch

    IPC分类号： C07K14/81 ,  G01N33/573 ,  A61K37/02 ,  C12N11/08

    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。