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1. 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.

2. 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.

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

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。

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

WO2021163546A1 METHODS AND MATERIALS FOR ASSESSING NUCLEIC ACIDS 审中-公开
公开(公告)号：WO2021163546A1
公开(公告)日：2021-08-19
申请号：PCT/US2021/017937
申请日：2021-02-12
申请人： THE JOHNS HOPKINS UNIVERSITY , PAPADOPOULOS, Nickolas , KINZLER, Kenneth W. , VOGELSTEIN, Bert , COHEN, Joshua David
发明人： PAPADOPOULOS, Nickolas , KINZLER, Kenneth W. , VOGELSTEIN, Bert , COHEN, Joshua David
IPC分类号： C12Q1/686
摘要： Provided herein are systems, kits, compositions and methods for sequencing library preparation and sequencing workflow (e.g., for the identification of mutations). In certain embodiments, provides herein systems and methods to identically barcode both strands of templates, and PCR-based enrichment of each strand that does not require hybridization capture.

7. 发明申请

WO2012142213A2 SAFE SEQUENCING SYSTEM 审中-公开
标题翻译：安全排序系统
公开(公告)号：WO2012142213A2
公开(公告)日：2012-10-18
申请号：PCT/US2012/033207
申请日：2012-04-12
申请人： THE JOHNS HOPKINS UNIVERSITY , VOGELSTEIN, Bert , KINZLER, Kenneth W. , PAPADOPOULOS, Nickolas , KINDE, Isaac
发明人： VOGELSTEIN, Bert , KINZLER, Kenneth W. , PAPADOPOULOS, Nickolas , KINDE, Isaac
IPC分类号： C12Q1/68 , C12N15/11
CPC分类号： C12Q1/6874 , C12Q1/6806 , C12Q1/6869 , C12Q1/6876 , C12Q2563/179 , C12Q2600/158 , C12Q2535/122 , C12Q2565/514
摘要： The identification of mutations that are present in a small fraction of DNA templates is essential for progress in several areas of biomedical research. Though massively parallel sequencing instruments are in principle well-suited to this task, the error rates in such instruments are generally too high to allow confident identification of rare variants. We here describe an approach that can substantially increase the sensitivity of massively parallel sequencing instruments for this purpose. One example of this approach, called "Safe-SeqS" for (Safe-Sequencing System) includes (i) assignment of a unique identifier (UID) to each template molecule; (ii) amplification of each uniquely tagged template molecule to create UID-families; and (iii) redundant sequencing of the amplification products. PCR fragments with the same UID are truly mutant ("super-mutants") if ≥95% of them contain the identical mutation. We illustrate the utility of this approach for determining the fidelity of a polymerase, the accuracy of oligonucleotides synthesized in vitro , and the prevalence of mutations in the nuclear and mitochondrial genomes of normal cells.
摘要翻译：存在于DNA模板的一小部分中的突变的鉴定对于在几个生物医学研究领域的进展是必不可少的。尽管大规模并行测序仪器原则上非常适合于此任务，但是这些仪器中的错误率通常太高，无法确定罕见的变体。我们在这里描述了一种可以显着增加大规模并行测序仪器对此目的的灵敏度的方法。这种方法的一个例子是（Safe-Sequencing System），称为“Safe-SeqS”，包括（i）将唯一标识符（UID）分配给每个模板分子; （ii）每个唯一标记的模板分子的扩增以产生UID家族; 和（iii）扩增产物的冗余测序。具有相同UID的PCR片段是真正的突变体（“超突变体”），如果其中95％含有相同的突变。我们说明了这种方法用于确定聚合酶的保真度，体外合成的寡核苷酸的准确性以及正常细胞的核和线粒体基因组中突变的流行率的效用。

8. 发明申请

WO2012071096A2 ARID1A AND PPP2R1A MUTATIONS IN CANCER 审中-公开
标题翻译： ARID1A和PPP2R1A突变在癌症中
公开(公告)号：WO2012071096A2
公开(公告)日：2012-05-31
申请号：PCT/US2011/050487
申请日：2011-09-06
申请人： THE JOHNS HOPKINS UNIVERSITY , VOGELSTEIN, Bert , KINZLER, Kenneth W. , VELCULESCU, Victor , PAPADOPOULOS, Nickolas , JONES, Sian
发明人： VOGELSTEIN, Bert , KINZLER, Kenneth W. , VELCULESCU, Victor , PAPADOPOULOS, Nickolas , JONES, Sian
IPC分类号： C12Q1/68 , C12N5/09 , G01N33/68 , A61K31/7088 , C12N15/11
CPC分类号： C12Q1/6886 , A61K31/7088 , A61K31/711 , C12Q2600/156 , G01N33/5011
摘要： Two genes, ARID1A (AT-rich interactive domain-containing protein 1A) and PPP2R1A (protein-phosphatase 2, regulatory subunit 1, alpha), can be used in methods which are useful for detecting cancer, diagnosing cancer, contributing to a diagnosis of cancer, confirming a diagnosis of cancer, identifying appropriate treatments for cancer, monitoring treatment of cancer, and evaluating treatment protocols for cancer, including ovarian clear cell carcinoma, breast cancer, colon cancer, gastric cancer, lung cancer, medulloblastoma, pancreatic cancer, and prostate cancer.
摘要翻译：在可用于检测癌症的方法中可以使用两种基因，即ARID1A（富含AT的交互结构域的蛋白质1A）和PPP2R1A（蛋白质磷酸酶2，调节亚基1，α）诊断癌症，有助于诊断癌症，确认癌症的诊断，鉴别癌症的适当治疗，监测癌症的治疗，以及评估癌症的治疗方案，包括卵巢透明细胞癌，乳腺癌，结肠癌，胃癌，肺癌癌症，成神经管细胞瘤，胰腺癌和前列腺癌。

9. 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.

10. 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.

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