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143 条记录 (耗时 0.043 秒)

    SAFE SEQUENCING SYSTEM
    92.
    发明授权
    SAFE SEQUENCING SYSTEM 有权
    安全分级制度

    公开(公告)号：EP2697397B1

    公开(公告)日：2017-04-05

    申请号：EP12772013.4

    申请日：2012-04-12

    申请人： The Johns Hopkins University

    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.

    IMPROVED COMBINATION BACTERIOLYTIC THERAPY FOR THE TREATMENT OF TUMORS
    98.
    发明公开
    IMPROVED COMBINATION BACTERIOLYTIC THERAPY FOR THE TREATMENT OF TUMORS 有权
    改进的溶菌联合治疗肿瘤的治疗

    公开(公告)号：EP1675465A2

    公开(公告)日：2006-07-05

    申请号：EP04809987.3

    申请日：2004-10-21

    申请人： THE JOHNS HOPKINS UNIVERSITY

    发明人： DANG, Long ,  BETTEGOWDA, Chetan ,  KINZLER, Kenneth, W. ,  VOGELSTEIN, Bert

    IPC分类号： A01N63/00

    CPC分类号： A61K35/742 ,  A61K31/337 ,  A61K31/427 ,  A61K45/06 ,  Y10S435/842 ,  A61K2300/00

    摘要： Current approaches for treating cancer are limited, in part, by the inability of drugs to affect the poorly vascularized regions of tumors. We have found that spores of anaerobic bacteria in combination with agents which interact with microtubules can cause the destruction of both the vascular and avascular compartments of tumors. Two classes of microtubule inhibitors were found to exert markedly different effects. Some agents that inhibited microtubule synthesis, such as vinorelbine, caused rapid, massive hemorrhagic necrosis when used in combination with spores. In contrast, agents that stabilized microtubules, such as the taxane docetaxel, resulted in slow tumor regressions that killed most neoplastic cells. Remaining cells in the poorly perfused regions of tumors could be eradicated by sponzlated bacteria. Mechanistic studies showed that the microtubule destabilizers, but not the microtubule stabilizers, radically reduced blood flow to tumors, thereby enlarging the hypoxic niche in which spores could germinate. A single intravenous injection of spores plus selected microtubule-interacting agents was able to cause regressions of several tumors in the absence of excessive toxicity.

    ENDOTHELIAL CELL EXPRESSION PATTERNS
    99.
    发明公开
    ENDOTHELIAL CELL EXPRESSION PATTERNS 有权
    内皮细胞表达模式

    公开(公告)号：EP1572867A2

    公开(公告)日：2005-09-14

    申请号：EP02728495.9

    申请日：2002-04-10

    申请人： THE JOHNS HOPKINS UNIVERSITY

    发明人： CARSON-WALTER, Eleanor ,  ST. CROIX, Brad ,  KINZLER, Kenneth, W. ,  VOGELSTEIN, Bert

    IPC分类号： C12N1/00

    CPC分类号： C07K14/705 ,  A61K2039/505 ,  C07K14/4748 ,  C07K16/28 ,  G01N33/5023 ,  G01N33/68 ,  G01N2333/4703 ,  G01N2500/04 ,  G01N2800/7014 ,  G01N2800/7028

    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（EC）和评估基因表达模式的新技术。 当将来自正常和恶性结直肠组织的EC的转录物与来自非内皮细胞的转录物进行比较时，鉴定了主要在内皮中表达的170多种基因。 正常和肿瘤来源的内皮细胞之间的比较显示79个差异表达的基因，包括46个在肿瘤相关内皮中特异性升高的基因。 来自该组的代表性基因的实验证明，大多数在原发性肺癌，乳腺癌，脑癌和胰腺癌的内皮中以及在肝脏的转移性病变中类似地表达。 这些结果表明，人类中的肿瘤和正常内皮在分子水平上是不同的，并且对于未来抗血管生成治疗的发展具有重要意义。