利索-全球专利检索

  1. 登录
  2. 注册

搜索结果

239 条记录 (耗时 0.042 秒)

    Safe sequencing system
    62.
    发明授权
    Safe sequencing system 有权
    安全排序系统

    公开(公告)号：US09476095B2

    公开(公告)日：2016-10-25

    申请号：US14111715

    申请日：2012-04-12

    申请人： Bert Vogelstein ,  Kenneth W. Kinzler ,  Nickolas Papadopoulos ,  Isaac Kinde

    发明人： Bert Vogelstein ,  Kenneth W. Kinzler ,  Nickolas Papadopoulos ,  Isaac Kinde

    IPC分类号： C12Q1/68 ,  C07H21/02

    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片段是真实的突变体（“超突变体”），如果其≥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。

    Integrated analyses of breast and colorectal cancers
    63.
    发明授权
    Integrated analyses of breast and colorectal cancers 有权
    乳腺癌和结肠直肠癌的综合分析

    公开(公告)号：US08709723B2

    公开(公告)日：2014-04-29

    申请号：US13461268

    申请日：2012-05-01

    申请人： Bert Vogelstein ,  Kenneth W. Kinzler ,  Rebecca J. Leary ,  Victor E. Velculescu

    发明人： Bert Vogelstein ,  Kenneth W. Kinzler ,  Rebecca J. Leary ,  Victor E. Velculescu

    IPC分类号： C12Q1/66 ,  C12P19/34 ,  C07H21/02

    CPC分类号： C12Q1/6886 ,  C12Q2600/156

    摘要： Genome-wide analysis of copy number changes in breast and colorectal tumors used approaches that can reliably detect homozygous deletions and amplifications. The number of genes altered by major copy number changes—deletion of all copies or amplification of at least twelve copies per cell—averaged thirteen per tumor. These data were integrated with previous mutation analysis of the Reference Sequence genes in these same tumor types to identify genes and cellular pathways affected by both copy number changes and point alterations. Pathways enriched for genetic alterations include those controlling cell adhesion, intracellular signaling, DNA topological change, and cell cycle control. These analysis provide an integrated view of copy number and sequencing alterations on a genome-wide scale and identify genes and pathways that are useful for cancer diagnosis and therapy.

    摘要翻译： 使用可以可靠地检测纯合缺失和扩增的方法对乳腺和结肠直肠肿瘤的拷贝数变化进行全基因组分析。 通过主要拷贝数变化改变的基因数量 - 全部拷贝的缺失或每个细胞至少12个拷贝的扩增，平均每个肿瘤13个。 这些数据与以前相同肿瘤类型的参考序列基因的突变分析结合起来，以鉴定受拷贝数变化和点变化影响的基因和细胞途径。 富含遗传改变的途径包括控制细胞粘附，细胞内信号转导，DNA拓扑变化和细胞周期控制的途径。 这些分析提供了在全基因组范围内的拷贝数和测序改变的综合视图，并确定了可用于癌症诊断和治疗的基因和途径。

    Method for Generating Hypermutable Plants
    65.
    发明申请
    Method for Generating Hypermutable Plants 有权
    生成超可变植物的方法

    公开(公告)号：US20110055964A1

    公开(公告)日：2011-03-03

    申请号：US12728958

    申请日：2010-03-22

    申请人： Nicholas C. Nicolaides ,  Luigi Grasso ,  Phillip M. Sass ,  Ken Kinzler ,  Bert Vogelstein

    发明人： Nicholas C. Nicolaides ,  Luigi Grasso ,  Phillip M. Sass ,  Ken Kinzler ,  Bert Vogelstein

    IPC分类号： C12N15/87 ,  C12Q1/68

    CPC分类号： C12N15/1024 ,  C07K14/415 ,  C12N15/8216 ,  C12N15/8241

    摘要： Blockade of mismatch repair in a plant can lead to hypermutation and a new genotype and/or phenotype. One approach used to generate hypermutable plants is through the expression of dominant negative alleles of mismatch repair genes in transgenic plants or derived cells. By introducing these genes into cells and transgenic plants, new cell lines and plant varieties with novel and useful properties can be prepared more efficiently than by relying on the natural rate of mutation. Moreover, methods to inhibit the expression and activity of endogenous plant MMR genes and their encoded products are also useful to generate hypermutable plants.

    摘要翻译： 植物中错配修复的阻断可导致超突变和新的基因型和/或表型。 用于产生超可变植物的一种方法是通过在转基因植物或衍生细胞中表达错配修复基因的显性负等位基因。 通过将这些基因引入细胞和转基因植物，可以比通过依赖于突变的自然速率更有效地制备具有新颖和有用性质的新细胞系和植物品种。 此外，抑制内源植物MMR基因及其编码产物的表达和活性的方法也可用于产生高可变性植物。

    HUMAN TRANSCRIPTOMES
    66.
    发明申请
    HUMAN TRANSCRIPTOMES 审中-公开
    人物代码

    公开(公告)号：US20110033466A1

    公开(公告)日：2011-02-10

    申请号：US12858717

    申请日：2010-08-18

    申请人： Victor E. Velculescu ,  Bert Vogelstein ,  Kenneth W. Kinzler

    发明人： Victor E. Velculescu ,  Bert Vogelstein ,  Kenneth W. Kinzler

    IPC分类号： C12Q1/68 ,  C07H21/00 ,  C12N5/071 ,  C12N15/00 ,  A61K31/7088 ,  A61K39/395 ,  A61P35/00 ,  A61P43/00

    CPC分类号： C12Q1/6886 ,  C12Q2600/136

    摘要： Global gene expression patterns have been characterized in normal and cancerous human cells using serial analysis of gene expression (SAGE). Cancer cell-specific, cell-type specific, and ubiquitously expressed genes have been identified. This information can be used to provide combinations of cell type- and cancer-specific gene probes, as well as methods of using these probes to identify particular cell types, screen for useful drugs, reduce cancer-specific gene expression, standardize gene expression, and restore function to a diseased cell or tissue.

    摘要翻译： 使用基因表达（SAGE）的连续分析，在正常和癌性人类细胞中表征全球基因表达模式。 已经鉴定了癌细胞特异性，细胞型特异性和普遍表达的基因。 该信息可用于提供细胞类型和癌症特异性基因探针的组合，以及使用这些探针来鉴定特定细胞类型，筛选有用药物，降低癌症特异性基因表达，标准化基因表达的方法，以及 恢复功能到病变细胞或组织。

    Phosphatase associated with metastasis
    67.
    发明授权
    Phosphatase associated with metastasis 有权
    与转移相关的磷酸酶

    公开(公告)号：US07745165B2

    公开(公告)日：2010-06-29

    申请号：US10868658

    申请日：2004-06-16

    申请人： Bert Vogelstein ,  Kenneth W. Kinzler ,  Saurabh Saha ,  Alberto Bardelli

    发明人： Bert Vogelstein ,  Kenneth W. Kinzler ,  Saurabh Saha ,  Alberto Bardelli

    IPC分类号： C12Q1/48 ,  G01N33/567

    CPC分类号： C12N9/16 ,  A61K39/00 ,  C12Q1/6886 ,  C12Q2600/112 ,  C12Q2600/136 ,  C12Q2600/158

    摘要： Among the genes identified, in a comparison of the global gene expression profile of metastatic colorectal cancer to that of primary cancers, benign colorectal tumors, and normal colorectal epithelium, the PRL-3 protein tyrosine phosphatase gene was of particular interest. It was expressed at high levels in each of 18 cancer metastases studied but at lower levels in non-metastatic tumors and normal colorectal epithelium. In three of twelve metastases examined, multiple copies of the PRL-3 gene were found within a small amplicon located at chromosome 8q24.3. These data suggest that the PRL-3 gene is important for colorectal cancer metastasis and provides a new therapeutic target for these intractable lesions.

    摘要翻译： 在确定的基因中，在转移性结肠直肠癌与原发性癌症，良性结肠直肠肿瘤和正常结肠直肠上皮的全球基因表达谱比较中，PRL-3蛋白酪氨酸磷酸酶基因特别引人关注。 在所研究的18个癌症转移中的每一个中表达高水平，但在非转移性肿瘤和正常结肠直肠上皮中的水平较低。 在检查的十二个转移中的三个中，在位于染色体8q24.3的小扩增子中发现了PRL-3基因的多个拷贝。 这些数据表明，PRL-3基因对结肠直肠癌转移很重要，为这些难治性病变提供了新的治疗靶点。

    Methods for generating hypermutable yeast
    68.
    发明授权
    Methods for generating hypermutable yeast 有权
    产生超可变酵母的方法

    公开(公告)号：US07514216B2

    公开(公告)日：2009-04-07

    申请号：US11188743

    申请日：2005-07-26

    申请人： Nicholas C. Nicolaides ,  Philip M. Sass ,  Luigi Grasso ,  Bert Vogelstein ,  Kenneth W. Kinzler

    发明人： Nicholas C. Nicolaides ,  Philip M. Sass ,  Luigi Grasso ,  Bert Vogelstein ,  Kenneth W. Kinzler

    IPC分类号： C12Q1/68

    CPC分类号： C12N15/81

    摘要： Yeast cells are mutagenized to obtain desirable mutants. Mutagenesis is mediated by a defective mismatch repair system which can be enhanced using conventional exogenously applied mutagens. Yeast cells with the defective mismatch repair system are hypermutable, but after selection of desired mutant yeast strains, they can be rendered genetically stable by restoring the mismatch repair system to proper functionality.

    摘要翻译： 酵母细胞被诱变以获得所需的突变体。 诱变由缺陷错配修复系统介导，可以使用常规的外源应用诱变剂进行增强。 具有缺陷错配修复系统的酵母细胞是可超过可变的，但是在选择所需的突变酵母菌株之后，可以通过将错配修复系统恢复到适当的功能来使它们变得遗传稳定。

    Endothelial Cell Expression Patterns
    69.
    发明申请
    Endothelial Cell Expression Patterns 审中-公开
    内皮细胞表达模式

    公开(公告)号：US20090017030A1

    公开(公告)日：2009-01-15

    申请号：US11930528

    申请日：2007-10-31

    申请人： Brad St.Croix ,  Bert Vogelstein ,  Kenneth W. Kinzler

    发明人： Brad St.Croix ,  Bert Vogelstein ,  Kenneth W. Kinzler

    IPC分类号： A61K39/395 ,  C07K16/18 ,  C12N5/00 ,  G01N33/567 ,  A61K38/16 ,  C12Q1/68 ,  C07H21/04 ,  C07K14/435 ,  A61K39/00 ,  C07K17/00

    CPC分类号： C07K16/30 ,  A61K2039/505

    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.

    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。 正常和肿瘤来源的内皮的比较显示79个差异表达基因，其中46个在肿瘤相关内皮特异性升高。 来自该组的代表性基因的实验表明，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性损伤中都表达。 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，对未来抗血管生成疗法的发展具有重要意义。