公开(公告)号：WO2007089731A2

公开(公告)日：2007-08-09

申请号：PCT/US2007/002452

申请日：2007-01-29

申请人： GEORGE MASON UNIVERSITY ,  LIOTTA, Lance ,  ZHOU, Weidong ,  ESPINA, Virginia ,  PETRICOIN, Emanuel

发明人： LIOTTA, Lance ,  ZHOU, Weidong ,  ESPINA, Virginia ,  PETRICOIN, Emanuel

IPC分类号： A61K31/56

CPC分类号： G01N33/6842 ,  C12Q1/485 ,  G01N33/68 ,  G01N2800/164 ,  Y02A90/24

摘要： The present invention relates to the analysis and monitoring of ocular fluids for determining the physiological state of an organism, to monitor drug efficacy and dynamics, for early disease detection, as well as to certain molecular markers and fingerprints of identified molecules or molecule fragments in such analysis.

摘要翻译： 本发明涉及用于确定生物体的生理状况，监测药物功效和动力学，用于早期疾病检测的眼液的分析和监测，以及鉴定的分子或分子片段的某些分子标记和指纹 分析。

公开(公告)号：WO2010148397A1

公开(公告)日：2010-12-23

申请号：PCT/US2010/039357

申请日：2010-06-21

申请人： LIOTTA, Lance ,  ESPINA, Virginia ,  LUCHINI, Alessandra ,  TAMBURRO, Davide

发明人： LIOTTA, Lance ,  ESPINA, Virginia ,  LUCHINI, Alessandra ,  TAMBURRO, Davide

IPC分类号： C07D265/34

CPC分类号： C07D311/82 ,  B01J20/3253 ,  B01J20/3255 ,  C07D251/50 ,  C07D279/20 ,  C07D403/04 ,  C07D471/22

摘要： This invention describes the identification of novel organic dye chemistries that can be used as affinity baits to capture proteins and other biomolecules useful in the fields of medical diagnostics, environmental science, toxicology, and infectious disease. Incorporation of unique affinity dye compounds within hydrogel capture particles improves analyte yield and preanalytical precision, and stabilizes the analyte against degradation, while increasing measurement sensitivity. The particles in this invention can be used for routine clinical testing as well as for discovery of low abundance disease biomarkers. Example hydrogel particles containing new high affinity bait chemistries were used to identify a new set of human serum biomarkers.

摘要翻译： 本发明描述了可用作捕获蛋白质和其它可用于医学诊断学，环境科学，毒理学和传染病领域的其他生物分子的亲和诱饵的新型有机染料化学物质的鉴定。 在水凝胶捕获颗粒中引入独特的亲和染料化合物可提高分析物的产率和分析前精度，并稳定分析物以防止降解，同时提高测量灵敏度。 本发明中的颗粒可用于常规临床测试以及发现低丰度疾病生物标志物。 使用含有新的高亲和力诱饵化学物质的示例性水凝胶颗粒来鉴定新的一组人血清生物标志物。

公开(公告)号：WO2010117715A1

公开(公告)日：2010-10-14

申请号：PCT/US2010/029034

申请日：2010-03-29

申请人： GEORGE MASON INTELLECTUAL PROPERTIES, INC. ,  ESPINA, Virginia ,  LIOTTA, Lance

发明人： ESPINA, Virginia ,  LIOTTA, Lance

IPC分类号： A61K39/00

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。

公开(公告)号：WO2010025190A1

公开(公告)日：2010-03-04

申请号：PCT/US2009/055060

申请日：2009-08-26

申请人： LIOTTA, Lance, A. ,  LUCHINI, Alessandra ,  PETRICOIN, Emanuel, F. ,  ESPINA, Virginia

发明人： LIOTTA, Lance, A. ,  LUCHINI, Alessandra ,  PETRICOIN, Emanuel, F. ,  ESPINA, Virginia

IPC分类号： B82B1/00

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对样品预处理的要求。 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材料制成，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。

公开(公告)号：WO2010006027A1

公开(公告)日：2010-01-14

申请号：PCT/US2009/049903

申请日：2009-07-08

申请人： GEORGE MASON INTELLECTUAL PROPERTIES, INC. ,  PETRICOIN, Emanuel, III ,  LIOTTA, Lance ,  ESPINA, Virginia ,  WULFKUHLE, Julia

发明人： PETRICOIN, Emanuel, III ,  LIOTTA, Lance ,  ESPINA, Virginia ,  WULFKUHLE, Julia

IPC分类号： G01N33/574

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。

公开(公告)号：WO2008070579A3

公开(公告)日：2009-03-19

申请号：PCT/US2007086177

申请日：2007-11-30

申请人： UNIV LOMA LINDA MED ,  UNIV GEORGE MASON ,  STONY BROOK UNIVERSITY ,  UNIV CALIFORNIA ,  KIRSCH WOLFF ,  LIOTTA LANCE A ,  VAN NOSTRAND WILLIAM E ,  VINTERS HARRY V ,  ESPINA VIRGINIA

发明人： KIRSCH WOLFF ,  LIOTTA LANCE A ,  VAN NOSTRAND WILLIAM E ,  VINTERS HARRY V ,  ESPINA VIRGINIA

IPC分类号： A61K31/409 ,  A61K31/713 ,  A61P25/28 ,  A61P27/00 ,  C12N15/113

CPC分类号： C12N15/1137 ,  A61K31/409 ,  C12N2310/14 ,  C12N2320/32 ,  C12Y114/99003

摘要： A method of treating or inhibiting progress of dementia and/or macular degeneration in a mammal involves administering compositions containing siRNA to heme oxygenase- 1 (HO-I) or heme oxygenase-2 (HO-2), a matrix metalloproteinase (MMP) inhibitor, a caspase inhibitor, or a metalloporphyrin in a manner that permits access to brain sites and/or the macula of the patient.

摘要翻译： 治疗或抑制哺乳动物痴呆和/或黄斑变性进程的方法包括给含有血红素加氧酶-1（HO-1）或血红素加氧酶-2（HO-2），基质金属蛋白酶（MMP）抑制剂 ，胱天蛋白酶抑制剂或金属卟啉以允许接近患者的脑部位和/或黄斑的方式。

公开(公告)号：WO2011091438A1

公开(公告)日：2011-07-28

申请号：PCT/US2011/022463

申请日：2011-01-25

申请人： GEORGE MASON INTELLECTUAL PROPERTIES, INC. ,  ESPINA, Virginia ,  LIOTTA, Lance, A. ,  MUELLER, Claudius

发明人： ESPINA, Virginia ,  LIOTTA, Lance, A. ,  MUELLER, Claudius

IPC分类号： A01N1/02 ,  G01N33/48

CPC分类号： G01N1/30 ,  A01N1/00

摘要： The invention relates to a one-step chemical composition that preserves animal tissue, cells, and biomolecules, such as human tissue, human cells, and biomolecules therein. It improves the fidelity and morphologic structure of cells, organelles, and nuclear chromatin, and maintains and enhances the cellular antigenicity for immunohistochemistry and flow cytometry, while preserving proteins, post-translational modifications of proteins, and nucleic acids. In one embodiment, the composition comprises a) a non-aldehyde precipitating fixative at a concentration below 25% (volume/volume), b) a reversible/cleavable protein cross-linker that targets lipid-associated molecules, and c) a c reversible/cleavable protein cross-linker that targets water soluble molecules. In another embodiment, the composition further includes a kinase inhibitor, a phosphatase inhibitor, and a permeation enhancer. In still another embodiment, the compositions further include lactic acid at a concentration sufficient to maintain cellular nuclear volume at a level equivalent to aldehyde fixation of the same type of cell. In a further embodiment, the composition comprises: a) a precipitating fixative, b) a reversible/cleavable cross-linker, c) a permeation enhancer, d) a kinase inhibitor, e) a phosphatase inhibitor, and f) a carboxylic acid. In a still further embodiment, the invention comprises method for preserving a biological sample by contacting the sample with the composition of the invention under conditions effective for the preservation of the sample.

摘要翻译： 本发明涉及保留动物组织，细胞和生物分子的一步化学组合物，例如人组织，人细胞和生物分子。 它提高细胞，细胞器和核染色质的保真度和形态结构，并保持和增强免疫组织化学和流式细胞术的细胞抗原性，同时保留蛋白质，蛋白质的翻译后修饰和核酸。 在一个实施方案中，组合物包含a）浓度低于25％（体积/体积）的非醛沉淀固定剂，b）靶向脂质相关分子的可逆/可切割蛋白质交联剂，以及c）可逆可逆/ 可裂解的蛋白质交联剂，其靶向水溶性分子。 在另一个实施方案中，组合物还包含激酶抑制剂，磷酸酶抑制剂和渗透增强剂。 在另一个实施方案中，组合物还包括浓度足以将细胞核体积保持在与相同类型细胞的醛固定相当的水平的乳酸。 在另一个实施方案中，组合物包括：a）沉淀固定剂，b）可逆/可切割交联剂，c）渗透促进剂，d）激酶抑制剂，e）磷酸酶抑制剂，和f）羧酸。 在又一个实施方案中，本发明包括通过在有效保存样品的条件下使样品与本发明的组合物接触来保存生物样品的方法。

公开(公告)号：WO2010019227A1

公开(公告)日：2010-02-18

申请号：PCT/US2009/004608

申请日：2009-08-12

申请人： GEORGE MASON INTELLECTUAL PROPERTIES, INC. ,  ESPINA, Virginia ,  LIOTTA, Lance ,  PETRICOIN, Emanuel, F.

发明人： ESPINA, Virginia ,  LIOTTA, Lance ,  PETRICOIN, Emanuel, F.

IPC分类号： G01N33/48

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。

公开(公告)号：WO2008073187A3

公开(公告)日：2009-12-23

申请号：PCT/US2007022744

申请日：2007-10-26

申请人： GEORGE MASON INTELLECTUAL PROP ,  LIOTTA LANCE A ,  PETRICOIN EMANUEL F ,  GEHO DAVID ,  ESPINA VIRGINIA A

发明人： LIOTTA LANCE A ,  PETRICOIN EMANUEL F ,  GEHO DAVID ,  ESPINA VIRGINIA A

IPC分类号： A01N1/00 ,  G01N1/30

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部分 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。

公开(公告)号：WO2008115707A3

公开(公告)日：2009-04-16

申请号：PCT/US2008056038

申请日：2008-03-06

申请人： GEORGE MASON INTELLECTUAL PROP ,  POPOV SERGUEI G ,  POPOVA TAISSIA ,  ESPINA VIRGINIA ,  BAILEY CHARLES ,  LIOTTA LANCE A ,  PETRICOIN EMANUEL

发明人： POPOV SERGUEI G ,  POPOVA TAISSIA ,  ESPINA VIRGINIA ,  BAILEY CHARLES ,  LIOTTA LANCE A ,  PETRICOIN EMANUEL

IPC分类号： A61K31/496 ,  A61K45/06 ,  A61P31/04

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 1/4, 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。 实施例提供了使用菌株和模型系统进行差异谱分析的材料和方法，例如蛋白质组学分析，例如分化磷酸化分析，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，所述疾病包括降低半胱天冬酶1/4的活性的试剂，例如YVAD，和/或增加AKT磷酸化的试剂， 例如IB-MECA或Cl-IB-MECA，以及在具体实施方案中，抗生素，如环丙沙星。 还提供了包括其的套件，以及其他。