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1. 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.

2. 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。

3. 发明申请

WO2004005883A2 SECRETED AND CYTOPLASMIC TUMOR ENDOTHELIAL MARKERS 审中-公开
标题翻译：分泌和肿瘤肿瘤内皮标记
公开(公告)号：WO2004005883A2
公开(公告)日：2004-01-15
申请号：PCT/US2003/016250
申请日：2003-07-02
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： G01N
CPC分类号： G01N33/5011 , A61K38/00 , G01N33/5091 , G01N33/57484
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 from 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 many differentially expressed genes, including a large nujber of genes that were specifically elevated in tumor-associated endothelium. Experiments with representative genes from this group demonstrated that most were similarly expressed in the endothelium of primary lung, breast, brain, and pancreatic cancers as well as in metastatic lesions fo the liver. Theses 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.
摘要翻译：为了更好地了解肿瘤血管生成，开发了分离内皮细胞（ECs）和评估基因表达模式的新技术。将来自正常和恶性结肠直肠组织的ECs的转录物与来自非内皮细胞的转录物进行比较，鉴定了主要在内皮中表达的170个以上的基因。正常和肿瘤衍生的内皮的比较显示许多差异表达的基因，包括在肿瘤相关内皮中特异性升高的大量基因。来自该组的代表性基因的实验表明，大多数类似地在原发性肺，乳腺，脑和胰腺癌的内皮以及肝脏的转移性损伤中表达。这些结果表明，人类的肿瘤和正常内皮在分子水平上是不同的，对抗血管生成的发展具有重要意义。

4. 发明申请

WO2002083874A3 ENDOTHELIAL CELL EXPRESSION PATTERNS 审中-公开
公开(公告)号：WO2002083874A3
公开(公告)日：2002-10-24
申请号：PCT/US2002/008253
申请日：2002-04-10
申请人： THE JOHNS HOPKINS UNIVERSITY , CARSON-WALTER, Eleanor , ST. CROIX, Brad , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
发明人： CARSON-WALTER, Eleanor , ST. CROIX, Brad , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
IPC分类号： A61K39/395
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 from 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 the 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.

5. 发明申请

WO2004001004A2 MEMBRANE ASSOCIATED TUMOR ENDOTHELIUM MARKERS 审中-公开
标题翻译：膜相关肿瘤内皮标记
公开(公告)号：WO2004001004A2
公开(公告)日：2003-12-31
申请号：PCT/US2003/019544
申请日：2003-06-23
申请人： JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE , ST. CROIX, Brad , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
发明人： ST. CROIX, Brad , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
IPC分类号： C12N
CPC分类号： C07K14/705 , A61K38/00 , A61K2039/505 , C12Q1/6886 , C12Q2600/136 , C12Q2600/158
摘要： To gain a better understanding of tumor angiogenesis endothelial cells (Ecs) were isolated and gene expression patterns were evaluated. When transcripts from Ecs derived from 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 differentially expressed genes, including many that were specifically elevated in tumor-associated endothelium. Experiments with representative genes from this group demonstrated that most were similarly expressed in the 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.
摘要翻译：为了更好地了解肿瘤血管生成，分离内皮细胞（Ecs），评估基因表达模式。将来自正常和恶性结肠直肠组织的Ecs的转录物与来自非内皮细胞的转录物进行比较，鉴定出在内皮中主要表达的170个以上的基因。正常和肿瘤衍生的内皮的比较显示差异表达的基因，包括在肿瘤相关内皮中特异性升高的许多基因。来自该组的代表性基因的实验证明，大多数类似物在原发性肺癌，乳腺癌，脑癌和胰腺癌的内皮以及肝转移灶中均表达。这些结果表明，人类的肿瘤和正常内皮在分子水平上是不同的。

6. 发明申请

WO2005062812A3 A rAAV-BASED SYSTEM FOR SOMATIC CELL GENE DISRUPTION 审中-公开
公开(公告)号：WO2005062812A3
公开(公告)日：2005-07-14
申请号：PCT/US2004/042597
申请日：2004-12-21
申请人： THE JOHNS HOPKINS UNIVERSITY , VOGELSTEIN, Bert , KINZLER, Kenneth, W. , KOHLI, Manu , RAGO, Carlo
发明人： VOGELSTEIN, Bert , KINZLER, Kenneth, W. , KOHLI, Manu , RAGO, Carlo
IPC分类号： C12N15/63
摘要： Emerging evidence suggests that recombinant adeno-associated viral (rAAV) vectors can be used for specific gene targeting in human somatic cells. We have developed an rAAV vector construction procedure employing fusion PCR and a single cloning step that considerably simplifies the knockout process. We demonstrate its utility by disrupting genes at specific positions within human colon cancer cells as well as within immortalized normal epithelial cells. This technology should be broadly applicable to in vitro studies that require the manipulation of the human genome.

7. 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.

8. 发明申请

WO2003065870A2 DIGITAL AMPLIFICATION FOR DETECTION OF MISMATCH REPAIR DEFICIENT TUMOR CELLS 审中-公开
标题翻译：用于检测缺陷修复缺血性肿瘤细胞的数字放大
公开(公告)号：WO2003065870A2
公开(公告)日：2003-08-14
申请号：PCT/US2003/001062
申请日：2003-01-29
申请人： THE JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE , VOGELSTEIN, Bert , TRAVERSO, Giovanni, C. , KINZLER, Kenneth, W.
发明人： VOGELSTEIN, Bert , TRAVERSO, Giovanni, C. , KINZLER, Kenneth, W.
IPC分类号： A61B
CPC分类号： C12Q1/6886 , C12Q1/6851 , C12Q1/686 , C12Q2600/156 , C12Q2549/119 , C12Q2527/143
摘要： The detection of mutations in fecal DNA represents a promising, non-invasive approach for detecting colorectal cancers in average risk populations. One of the first practical applications of this technology involves the examination of microsatellite markers to sporadic cancers with mismatch repair deficiencies. As such cancers nearly always occur in the proximal colon, this test is useful as an adjunct to sigmoidoscopy, which detects only distal colorectal lesions.
摘要翻译：检测粪便DNA中的突变代表了一种有希望的非侵入性方法，用于检测平均危险人群中的结肠直肠癌。该技术的第一个实际应用之一涉及将微卫星标记物检查到具有错配修复缺陷的散发性癌症。因为这样的癌症几乎总是发生在近端结肠，这个测试是有用的乙状结肠镜检查的附件，只检测远端结肠直肠病变。

9. 发明申请

WO2003022863A1 SECRETED AND CELL SURFACE GENES EXPRESSED IN BENIGN AND MALIGNANT COLORECTAL TUMORS 审中-公开
标题翻译：分泌和细胞表面基因表达于胆管和恶性色素性肿瘤
公开(公告)号：WO2003022863A1
公开(公告)日：2003-03-20
申请号：PCT/US2002/028518
申请日：2002-09-09
申请人： THE JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE , BUCKHAULTS, Phillip , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
发明人： BUCKHAULTS, Phillip , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
IPC分类号： C07H21/04
CPC分类号： C07K14/495 , C07K14/47 , C07K14/705
摘要： Serial analysis of gene expression (SAGE) was used to identify transcripts encoding secreted or cell-surface proteins that were expressed in benign and malignant tumors of the colorectum. A total of 290,394 tags were analyzed from normal, adenomatous and cancerous colonic epithelium. Of the 21,343 different transcripts observed, 957 were found to be differentially expressed between normal and adenoma or between normal and cancer. Forty-nine transcripts were elevated ≥ 20-fold in adenomas, 40 transcripts were elevated ≥ 20-fold in cancers, and nine transcripts were elevated ≥ 20-fold in both. Product of six these nine transcripts (TGFBI, LYS, RDP, MIC-1, REGA, and DEHL) were predicted to be secreted or to reside on the cell surface and these were analyzed in more detail. The abnormal expression levels predicted by SAGE were confirmed by quantitative PCR analyses of each of these six genes. Moreover, the cell types responsible for the elevated expression were identified by in situ hybridization and by PCR analyses of epithelial cells immunoaffinity purified from primary tumors.
摘要翻译：基因表达（SAGE）的序列分析用于鉴定在结肠直肠癌和恶性肿瘤中表达的编码分泌的或细胞表面蛋白的转录物。从正常，腺瘤和癌性结肠上皮分析总共290,394个标签。在观察到的21,343种不同的转录物中，957被发现在正常和腺瘤之间或在正常和癌症之间差异表达。在腺瘤中，49个转录本升高了20倍，40个转录物在癌症中升高了20倍，而9个转录物在两者中升高了20倍。预计这六种转录本（TGFBI，LYS，RDP，MIC-1，REGA和DEHL）的六种产物被分泌或驻留在细胞表面上，并且更详细地分析这些转录物的产物。通过对这6种基因中的每一种进行定量PCR分析证实SAGE预测的异常表达水平。此外，通过原位杂交和通过从原发性肿瘤纯化的上皮细胞免疫亲和素的PCR分析来鉴定负责升高的表达的细胞类型。

10. 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.

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