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公开(公告)号：US20120077843A1
公开(公告)日：2012-03-29
申请号：US13258119
申请日：2010-03-29
CPC分类号： G01N33/502 , A61K31/00 , A61K31/138 , A61K31/4706 , A61K35/12 , C12N5/0695 , G01N33/5044 , G01N2800/52
摘要： Described herein are progenitor cancer cells and cell lines isolated from human breast ductal carcinoma in situ (DCIS) lesions and the uses of these cells or cell lines in drug design, drug screening, and monitoring in vivo therapy. The DCIS malignant precursor cells or cell lines are epithelial in origin, are positive for markers of autophagy, show at least one genetic difference from normal cells of said fragment, form 3-D tube-like structures or ball aggregates, or are inhibited in formation of 3-D structures and migration by treatment with chloroquine.
摘要翻译： 本文描述了从人乳腺导管原位癌（DCIS）病变分离的祖细胞癌细胞和细胞系，以及这些细胞或细胞系在药物设计，药物筛选和体内治疗监测中的用途。 DCIS恶性前体细胞或细胞系起源于上皮，对自噬标志物呈阳性，与所述片段的正常细胞呈现至少一个遗传差异，形成3-D管状结构或球聚集体，或形成抑制 的3-D结构和通过用氯喹处理的迁移。
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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：US20110046039A1
公开(公告)日：2011-02-24
申请号：US12530538
申请日：2008-03-06
申请人： Serguei G. Popov , Taissia Popov , Virginia Espina , Charles Bailey , Lance A. Liotta , Emanuel Petricoin
发明人： Serguei G. Popov , Taissia Popov , Virginia Espina , Charles Bailey , Lance A. Liotta , Emanuel Petricoin
CPC分类号： A61K45/06 , A61K31/496 , A61K2300/00
摘要： The invention provides methods and materials for identifying agents for preventing and/or treating anthrax and similar diseases. Embodiments provide strains and model systems for studying non-lethal and lethal exposure to anthrax and similar disease vectors. Embodiments provide materials and methods for using the strains and model systems for differential profiling, such as proteomic profiling, such as differentiation phosphorylation profiling, to target identification and therapeutics discovery and development. Embodiments provide pharmaceutically acceptable compositions, and methods for using them to prevent and/or treat anthrax and similar diseases comprising an agent that decreases the activity of caspase ¼, such as YVAD, and/or an agent that increases the phosphorylation of AKT, such as IB-MECA or Cl-IB-MECA, together with, in particular embodiments, an antibiotic, such as ciprofloxacin. Kits comprising the same are provided as well, among other things.
摘要翻译： 本发明提供用于鉴定用于预防和/或治疗炭疽和类似疾病的药剂的方法和材料。 实施例提供用于研究非致死和致死性暴露于炭疽和类似疾病载体的菌株和模型系统。 实施例提供了用于使用菌株和模型系统进行差异分析的材料和方法，例如蛋白质组学分析，例如分化磷酸化分析，以靶向鉴定和治疗发现和发展。 实施方案提供了药学上可接受的组合物，以及使用它们来预防和/或治疗炭疽和类似疾病的方法，其包括降低半胱天冬酶（例如YVAD）的活性的试剂和/或增加AKT磷酸化的试剂，例如 在特定实施方案中，IB-MECA或Cl-IB-MECA，以及抗生素，如环丙沙星。 还提供了包括其的套件，以及其他。
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4.发明授权Phosphorylated C-ErbB2 as a superior predictive theranostic marker for the diagnosis and treatment of cancer 有权磷酸化的C-ErbB2作为癌症诊断和治疗的优越预测因素公开(公告)号：US09086414B2
公开(公告)日：2015-07-21
申请号：US13003206
申请日：2009-07-08
IPC分类号： A61K39/395 , A01N43/48 , G01N33/53 , G01N33/543 , G01N33/574 , C12Q1/68 , A61K31/517 , G01N1/30 , A61K39/00
CPC分类号： G01N33/57492 , A61K31/517 , A61K39/39558 , A61K2039/505 , C12Q1/6841 , C12Q1/6886 , C12Q2600/106 , C12Q2600/112 , G01N1/30 , G01N33/54366 , G01N33/574 , G01N33/57415 , G01N2033/57403 , G01N2333/71 , G01N2800/52
摘要： The present invention provides reliable methods to identify subsets of subjects with a cancer of epithelial origin characterized by a high level of phosphorylated c-erbB2 which does not correlate with the over-expression of total c-erbB2 as measured by IHC or FISH, for selection and inclusion for c-erbB2-direct treatment and therapy. Furthermore, the present invention provides a reliable method to determine whether a subject with a cancer of epithelial origin who has been determined to be c-erbB2 positive by IHC and by FISH should be excluded from c-erbB2-direct treatment because of a non-significant level of phosphorylated c-erbB2 in epithelial tumor tissue.
摘要翻译： 本发明提供了可靠的方法来鉴定具有上皮起源癌症的受试者的亚群，其特征在于高水平的磷酸化c-erbB2，其与通过IHC或FISH测量的总c-erbB2的过表达不相关，用于选择 并包括c-erbB2直接治疗和治疗。 此外，本发明提供了一种可靠的方法，用于确定由IHC和FISH确定为c-erbB2阳性的具有上皮起源癌症的受试者是否应从c-erbB2直接治疗中排除， 磷酸化c-erbB2在上皮肿瘤组织中的显着水平。
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公开(公告)号：US09012240B2
公开(公告)日：2015-04-21
申请号：US13061507
申请日：2009-08-26
IPC分类号： G01N33/549 , G01N33/53 , G01N33/544 , G01N33/558 , G01N33/52 , G01N33/543
CPC分类号： G01N33/521 , G01N33/54333 , G01N33/54346
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。
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6.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
CPC分类号： G01N33/56972 , G01N33/5011 , G01N2333/70596 , G01N2510/00 , G01N2800/52
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。
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7.发明申请PHOSPHORYLATED C-ErbB2 AS A SUPERIOR PREDICTIVE THERANOSTIC MARKER FOR THE DIAGNOSIS AND TREATMENT OF CANCER 有权磷酸化C-ErbB2作为诊断和治疗癌症的高级预测性治疗标记公开(公告)号：US20110189173A1
公开(公告)日：2011-08-04
申请号：US13003206
申请日：2009-07-08
IPC分类号： A61K39/395 , C40B30/00 , G01N33/574 , A61K31/517 , C12Q1/48 , A61P35/00
CPC分类号： G01N33/57492 , A61K31/517 , A61K39/39558 , A61K2039/505 , C12Q1/6841 , C12Q1/6886 , C12Q2600/106 , C12Q2600/112 , G01N1/30 , G01N33/54366 , G01N33/574 , G01N33/57415 , G01N2033/57403 , G01N2333/71 , G01N2800/52
摘要： The present invention provides reliable methods to identify subsets of subjects with a cancer of epithelial origin characterized by a high level of phosphorylated c-erbB2 which does not correlate with the over-expression of total c-erbB2 as measured by IHC or FISH, for selection and inclusion for c-erbB2-direct treatment and therapy. Furthermore, the present invention provides a reliable method to determine whether a subject with a cancer of epithelial origin who has been determined to be c-erbB2 positive by IHC and by FISH should be excluded from c-erbB2-direct treatment because of a non-significant level of phosphorylated c-erbB2 in epithelial tumor tissue.
摘要翻译： 本发明提供了可靠的方法来鉴定具有上皮起源癌症的受试者的亚群，其特征在于高水平的磷酸化c-erbB2，其与通过IHC或FISH测量的总c-erbB2的过表达不相关，用于选择 并包括c-erbB2直接治疗和治疗。 此外，本发明提供了一种可靠的方法，用于确定由IHC和FISH确定为c-erbB2阳性的具有上皮起源癌症的受试者是否应从c-erbB2直接治疗中排除， 磷酸化c-erbB2在上皮肿瘤组织中的显着水平。
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公开(公告)号：US20100159486A1
公开(公告)日：2010-06-24
申请号：US12513032
申请日：2007-11-01
申请人： Lance A. Liotta , Wediong Zhou , Wolff Kirsch , Virginia Espina , Emanuel Petricoin, III , Mark Ross , Claudius Mueller , Shino Magaki
发明人： Lance A. Liotta , Wediong Zhou , Wolff Kirsch , Virginia Espina , Emanuel Petricoin, III , Mark Ross , Claudius Mueller , Shino Magaki
IPC分类号： G01N33/53 , C12Q1/02 , G01N33/566 , G01N33/00 , C07K16/18
CPC分类号： G01N33/6896 , G01N2800/2821 , G01N2800/2871
摘要： Low molecular weight (LMW) peptides have been discovered that are indicative of neurological conditions, such as Alzheimer's Disease (AD), cognitive impairment and brain microhemmorhages. Evaluating patient samples for the presence of such LMW peptides is an effective means of detecting neurological conditions and monitoring the progression of the disease. The LMW peptides are particularly useful in detecting neurological conditions during the early stages without invasive procedures.
摘要翻译： 已经发现了低分子量（LMW）肽，其指示诸如阿尔茨海默氏病（AD），认知障碍和脑微血管损伤之类的神经病学状况。 评估患者样本中存在这样的LMW肽是检测神经系统疾病和监测疾病进展的有效手段。 LMW肽特别可用于在早期阶段检测神经系统疾病而无侵入性手术。
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公开(公告)号：US20110236999A1
公开(公告)日：2011-09-29
申请号：US13061507
申请日：2009-08-26
IPC分类号： G01N33/543 , B82Y15/00
CPC分类号： G01N33/521 , G01N33/54333 , G01N33/54346
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。
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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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