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11. 发明申请

WO2004082458A3 TYROSINE KINOME 审中-公开
公开(公告)号：WO2004082458A3
公开(公告)日：2004-09-30
申请号：PCT/US2004/004452
申请日：2004-02-18
申请人： THE JOHNS HOPKINS UNIVERSITY , BARDELLI, Alberto , PARSONS, Will , VELCULESCU, Victor , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
发明人： BARDELLI, Alberto , PARSONS, Will , VELCULESCU, Victor , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
IPC分类号： C12Q1/68
摘要： Protein kinases are important signaling molecules involved in tumorigenesis. Mutational analysis of the human tyrosine kinase gene family (98 genes) identified somatic alterations in -20% of colorectal cancers, with the majority of mutations occurring in NTRK3, FES, GUCY2F and a previously uncharacterized tyrosine kinase gene called MCCK/MLK4. Most alterations were in conserved residues affecting key regions of the kinase domain. These data represent a paradigm for the unbiased analysis of signal transducing genes in cancer and provide useful targets for therapeutic intervention.

12. 发明申请

WO2002076383A3 SECURIN IS REQUIRED FOR CHROMOSOMAL STABILITY IN HUMAN CELLS 审中-公开
公开(公告)号：WO2002076383A3
公开(公告)日：2002-10-03
申请号：PCT/US2002/006643
申请日：2002-03-20
申请人： THE JOHNS HOPKINS UNIVERSITY , VOGELSTEIN, Bert , KINZLER, Kenneth, W. , JALLEPALLI, Prasad , LENGAUER, Christoph
发明人： VOGELSTEIN, Bert , KINZLER, Kenneth, W. , JALLEPALLI, Prasad , LENGAUER, Christoph
IPC分类号： C12N5/08
摘要： Securin-deficient cells and their securin-proficient counterparts are useful for screening potential anti-tumor agents. Potential therapeutic agents are screened for the ability to preferentially inhibit or kill a securin-deficient cell. The association of securin deficiency and chromosomal instability leading to aneuploidy, renders securin an excellent target for chemotherapeutic drug development.

13. 发明申请

WO2002010217A3 ENDOTHELIAL CELL EXPRESSION PATTERNS 审中-公开
公开(公告)号：WO2002010217A3
公开(公告)日：2002-02-07
申请号：PCT/US2001/024031
申请日：2001-08-01
申请人： THE JOHNS HOPKINS UNIVERSITY , ST. CROIX, Brad , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
发明人： ST. CROIX, Brad , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
IPC分类号： C12N15/12
摘要： To gain a better understanding of tumor angiogenesis, new techniques for isolating endothelial cells (ECs) and evaluating gene expression patterns were developed. When transcripts from ECs derived f rom normal and malignant colorectal tissues were compared with transcripts from non-endothelial cells, over 170 genes predominantly expressed in the endothelium were identified. Comparison between normal- and tumor-derived endothelium revealed 79 differentially expressed genes, including 46 that were specifically elevated in tumor-associated endothelium. Experiments with representative genes from this group demonstrated that most were similarly expressed in teh endothelium of primary lung, breast, brain, and pancreatic cancers as well as in metastatic lesions of the liver. These results demonstrate that neoplastic and normal endothelium in humans are distinct at the molecular level, and have significant implications for the development of anti-angiogenic therapies in the future.

14. 发明申请

WO2010118016A2 DIGITAL QUANTIFICATION OF DNA METHYLATION 审中-公开
标题翻译： DNA甲基化的数字量化
公开(公告)号：WO2010118016A2
公开(公告)日：2010-10-14
申请号：PCT/US2010/030084
申请日：2010-04-06
申请人： THE JOHNS HOPKINS UNIVERSITY , CASE WESTERN RESERVE UNIVERSITY , VOGELSTEIN, Bert , KINZLER, Kenneth, W. , LI, Meng , DIAZ, Luis , PAPADOPOULOS, Nickolas , MARKOWITZ, Sanford
发明人： VOGELSTEIN, Bert , KINZLER, Kenneth, W. , LI, Meng , DIAZ, Luis , PAPADOPOULOS, Nickolas , MARKOWITZ, Sanford
IPC分类号： C12Q1/68 , C12N15/11 , G01N33/52
CPC分类号： C12Q1/6816 , C12Q1/6886 , C12Q2600/154 , C12Q2565/501 , C12Q2527/125 , C12Q2523/125
摘要： Abnormal DNA methylation can be used as a biomarker in cancer patients. For such purposes, it is important to determine precisely the fraction of methylated molecules in an analyzed sample. A technology we term Methyl-BEAMing achieves this goal. Individual bisulfite-treated DNA molecules can be PCR-amplified within aqueous nanocompartments containing beads, resulting in a population of beads each containing thousands of copies of the template molecule. After hybridization with probes specific for methylated sequences, the beads can be analyzed by flow cytometry. This approach enables detection and enumeration of one methylated molecule in a population of ~5000 unmethylated molecules. Methyl-BEAMing provides digital quantification of rare methylation events and is generally applicable to the assessment of methylated genes in clinical samples.
摘要翻译： DNA甲基化异常可用作癌症患者的生物标志物。为此目的，重要的是精确测定分析样品中甲基化分子的分数。我们称之为甲基BEAMing的技术实现了这一目标。单独的亚硫酸氢盐处理的DNA分子可以在含有珠粒的含水纳米间隔内进行PCR扩增，导致每个珠粒群含有数千份拷贝的模板分子。与特异于甲基化序列的探针杂交后，可以通过流式细胞术分析珠粒。这种方法能够检测和计数一个约5000个非甲基化分子的一个甲基化分子。甲基BEAMing提供罕见甲基化事件的数字量化，通常适用于临床样品中甲基化基因的评估。

15. 发明申请

WO2007149433A2 TUMOR-SPECIFIC DELIVERY OF THERAPEUTIC AGENTS VIA LIPOSOMASE 审中-公开
标题翻译：通过脂质体的肿瘤特异性递送治疗药物
公开(公告)号：WO2007149433A2
公开(公告)日：2007-12-27
申请号：PCT/US2007/014274
申请日：2007-06-19
申请人： THE JOHNS HOPKINS UNIVERSITY , CHEONG, Ian , ZHOU, Shibin , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
发明人： CHEONG, Ian , ZHOU, Shibin , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
IPC分类号： A61K48/00
CPC分类号： A61K38/465 , A61K9/1271 , A61K9/1278 , A61K31/4545 , A61K31/4745 , A61K31/704 , A61K31/713 , A61K35/742 , A61K39/39558 , A61K47/64 , C12N9/20 , C12Y301/01003 , A61K2300/00
摘要： Clostridium novyi is an obligate anaerobe that can infect hypoxic regions within experimental tumors. We found that mice bearing large, established tumors were often cured when treated with C. novyi plus a single dose of liposomal doxorubicin. The secreted factor responsible for this phenomenon was identified and, surprisingly, proved to be a member of the lipase family. The gene encoding this protein, called liposomase, has the potential to be incorporated into diverse therapeutic methods to deliver specifically a variety of chemotherapeutic agents to tumors.
摘要翻译： Clostridiu

16. 发明申请

WO2006127607A2 PI3K PATHWAY MUTATIONS IN CANCER 审中-公开
标题翻译：癌症中PI3K路径突变
公开(公告)号：WO2006127607A2
公开(公告)日：2006-11-30
申请号：PCT/US2006/019748
申请日：2006-05-23
申请人： THE JOHNS HOPKINS UNIVERSITY , PARSONS, Donald, William , WANG, Tian-li. Ph.D. , SAMUELS, Yardena , BARDELLI, Alberto , LENGAUER, Christopher , VELCULESCU, Victor , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
发明人： PARSONS, Donald, William , WANG, Tian-li. Ph.D. , SAMUELS, Yardena , BARDELLI, Alberto , LENGAUER, Christopher , VELCULESCU, Victor , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6883 , C12Q1/485 , C12Q2600/136 , C12Q2600/156 , G01N33/5044 , G01N33/57419
摘要： Given the important role of protein kinases in pathways affecting cellular growth and invasion, we have analyzed 340 serine/threonine kinases for genetic mutations in colorectal cancers. Mutations in eight genes were identified, including three members of the phosphatidylinositol-3- kinase (PI3K) pathway; the alterations in the latter genes each occurred in different tumors and did not overlap with mutations in PIK3CA or other non-serine-threonine kinase (STK) members of the PI3K pathway, suggesting that mutations in any of these genes had equivalent tumorigenic effects. These data demonstrate that the PI3K pathway is a major target for mutational activation in colorectal cancers and provide new opportunities for therapeutic intervention.
摘要翻译：鉴于蛋白激酶在影响细胞生长和侵袭的途径中的重要作用，我们已经分析了340个丝氨酸/苏氨酸激酶在结肠直肠癌中的遗传突变。鉴定出8个基因的突变，包括磷脂酰肌醇-3-激酶（PI3K）通路的3个成员; 后一种基因的改变各自发生在不同的肿瘤中，并且不与PIK3CA或PI3K途径的其他非丝氨酸 - 苏氨酸激酶（STK）成员的突变重叠，这表明任何这些基因中的突变具有相等的致瘤作用。这些数据表明，PI3K途径是结肠直肠癌突变激活的主要靶标，为治疗干预提供新的机会。

17. 发明申请

WO2006034191A2 TEM17 BINDS TO CORTACTIN 审中-公开
标题翻译： TEM17为CORTACTIN
公开(公告)号：WO2006034191A2
公开(公告)日：2006-03-30
申请号：PCT/US2005/033479
申请日：2005-09-20
申请人： THE JOHNS HOPKINS UNIVERSITY , ST. CROIX, Brad , VOGELSTEIN, Bert , KINZLER, Kenneth, W. , NANDA, Akash , BUCKHAULTS, Philip, W.
发明人： ST. CROIX, Brad , VOGELSTEIN, Bert , KINZLER, Kenneth, W. , NANDA, Akash , BUCKHAULTS, Philip, W.
IPC分类号： C07K14/82
CPC分类号： C07K14/4748
摘要： Tumor Endothelial Marker 17 (TEM17) was recently identified as an mRNA transcript overexpressed in the endothelium of vessels in human solid tumors. We have identified several new variants of TEMI7, derived by alternative splicing, that are intracellular (TEM17-I), secreted (TEM17-S), and on the cell surface membrane (TEM17-M) of tumor endothelium. We identified cortactin as a protein capable of binding to the extracellular region of both TEM17 and its closest homologue, TEM3, which is also expressed in tumor endothelium. The binding domain of cortactin is a 9-amino acid residue region in its plexin-like domain. These provide targets for the delivery of therapeutic and imaging agents to the vessels of solid tumors.
摘要翻译：肿瘤内皮标记17（TEM17）最近被鉴定为人类实体瘤血管内皮中过表达的mRNA转录物。我们已经确定了通过选择性剪接（细胞内（TEM17-I），分泌型（TEM17-S））和肿瘤内皮的细胞表面膜（TEM17-M）衍生的几种新的变体TEMI7。我们鉴定了皮质激素作为能够结合TEM17及其最近同源物TEM3的细胞外区域的蛋白质，TEM3也在肿瘤内皮中表达。皮质激素的结合结构域是其plexin样结构域中的9-氨基酸残基区域。这些为将实施肿瘤的血管递送治疗和显像剂提供了目标。

18. 发明申请

WO2005017182A2 MULTI-COLOR IN VITRO TRANSLATION 审中-公开
标题翻译：多色翻译
公开(公告)号：WO2005017182A2
公开(公告)日：2005-02-24
申请号：PCT/US2004/019097
申请日：2004-07-21
申请人： THE JOHNS HOPINKS UNIVERSITY SCHOOL OF MEDICINE , TRAVERSO, Carlo, Giovanni , DIEHL, Frank , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
发明人： TRAVERSO, Carlo, Giovanni , DIEHL, Frank , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
IPC分类号： C12Q
CPC分类号： G01N33/6845 , G01N33/542
摘要： In vitro translation is a widely used tool for both analytical and preparative purposes. For analytical purposes, small amounts of proteins are synthesized and visualized through labeled amino acids incorporated during translation. The radioactively labeled amino acids originally used, such as [ 35 S]methionine or [ 14 C]leucine, have been superceded by the addition of antigenic tags or the incorporation of biotin-labeled or fluorescently-labeled amino acids. Such non-radioactive tags are simpler to visualize following translation and do not pose a radiation hazard. Among the non-radioactive tags, fluorescently labeled-lysine is the most convenient, as proteins that have incorporated this amino acid can be directly visualized following gel electrophoresis. Multiple fluorophores introduced into proteins significantly extend their utility, particularly for the comparison of in vitro translated proteins from related sources. This methodology can be employed for several purposes, including the simplified detection of rare truncating mutations in clinical samples from cancer patients.
摘要翻译：体外翻译是用于分析和制备目的的广泛使用的工具。为了分析的目的，通过在翻译过程中并入的标记氨基酸合成少量蛋白质并使其可视化。最初使用的放射性标记的氨基酸，例如[35 S]甲硫氨酸或[[14 C]亮氨酸）已经通过加入抗原标签或引入生物素标记或荧光标记的氨基酸而被替代。这种非放射性标签更容易可视化翻译，并且不会造成辐射危害。在非放射性标签中，荧光标记的赖氨酸是最方便的，因为结合了该氨基酸的蛋白质可以在凝胶电泳后直接显现。引入蛋白质的多种荧光团显着扩展其效用，特别是用于比较来自相关来源的体外翻译蛋白质。该方法可用于多种目的，包括简化检测癌症患者临床样品中罕见的截短突变。

19. 发明申请

WO2005010145A2 METHOD AND COMPOSITIONS FOR DETECTION AND ENUMERATION OF GENETIC VARIATIONS 审中-公开
标题翻译：用于检测和产生遗传变异的方法和组合物
公开(公告)号：WO2005010145A2
公开(公告)日：2005-02-03
申请号：PCT/US2004/015587
申请日：2004-06-09
申请人： THE JOHNS HOPKINS UNIVERSITY , DRESSMAN, Devin , YAN, Hai , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
发明人： DRESSMAN, Devin , YAN, Hai , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
IPC分类号： C12N
CPC分类号： C12Q1/6858 , C07H21/04 , C12N15/1075 , C12Q1/686 , C12Q2565/537 , C12Q2563/149 , C12Q2563/143
摘要： Many areas of biomedical research depend on the analysis of uncommon variations in individual genes or transcripts. Here we describe a method that can quantify such variation at a scale and ease heretofore unattainable. Each DNA molecule in a collection of such molecules is converted into a single particle to which thousands of copies of DNA identical in sequence to the original are bound. This population of beads then corresponds to a one-to-one representation of the starting DNA molecules. Variation within the original population of DNA molecules can then be simply assessed by counting fluorescently-labeled particles via flow cytometry. Millions of individual DNA molecules can be assessed in this fashion with standard laboratory equipment. Moreover, specific variants can be isolated by flow sorting and employed for further experimentation. This approach can be used for the identification and quantification of rare mutations as well as to study variations in gene sequences or transcripts in specific populations or tissues.
摘要翻译：生物医学研究的许多领域取决于对个别基因或转录本中不常见变异的分析。在这里，我们描述一种可以量化这种变化的方法，其规模和容易度迄今为止是无法实现的。将这样的分子的集合中的每个DNA分子转化成单个颗粒，其中与原始序列顺序相同的数千个拷贝的DNA被结合。这种珠子群对应于起始DNA分子的一对一表示。然后可以通过流式细胞术对荧光标记的颗粒进行计数，简单地评估原始DNA分子群体内的变异。可以用标准实验室设备以这种方式评估数百万个单独的DNA分子。此外，可以通过流动分选分离特定的变体并用于进一步的实验。该方法可用于鉴定和定量稀有突变，并研究特定群体或组织中基因序列或转录本的变异。

20. 发明申请

WO2002066684A2 GENOME-BASED PERSONALIZED MEDICINE 审中-公开
标题翻译：基于基因的个人化医学
公开(公告)号：WO2002066684A2
公开(公告)日：2002-08-29
申请号：PCT/US2002/004686
申请日：2002-02-19
申请人： THE JOHNS HOPKINS UNIVERSITY , VOGELSTEIN, Bert , KINZLER, Kenneth, W. , YAN, Hai , PAPADOPOULOS, Nickolas
发明人： VOGELSTEIN, Bert , KINZLER, Kenneth, W. , YAN, Hai , PAPADOPOULOS, Nickolas
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6876 , C12N2503/00 , C12Q2600/106 , C12Q2600/156
摘要： Individual alleles can be isolated from every chromosome within somatic cell hybrids generated from a single fusion event. Nucleic acids or proteins from the hybrids can be analyzed for polymorphisms to provide unambiguous determinations. Information thus obtained can be used to develop and implment personalized medical interventions for individuals having particular polymorphic markers.
摘要翻译：可以从单个融合事件产生的体细胞杂交体内的每个染色体分离个体等位基因。可以分析来自杂交体的核酸或蛋白质的多态性以提供明确的测定。由此获得的信息可用于为具有特定多态性标记的个体开发和隐含个性化医疗干预。

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