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    IMPROVED COMBINATION BACTERIOLYTIC THERAPY FOR THE TREATMENT OF TUMORS
    4.
    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.

    TERT PROMOTER MUTATIONS IN GLIOMAS AND A SUBSET OF TUMORS
    6.
    发明公开
    TERT PROMOTER MUTATIONS IN GLIOMAS AND A SUBSET OF TUMORS 审中-公开
    在胶质瘤TERT启动子突变和部分量的肿瘤

    公开(公告)号：EP2956556A1

    公开(公告)日：2015-12-23

    申请号：EP14751900.3

    申请日：2014-02-18

    申请人： Duke University ,  The Johns Hopkins University

    发明人： YAN, Hai ,  VOGELSTEIN, Bert ,  PAPADOPOULOS, Nickolas ,  KINZLER, Kenneth W. ,  JIAO, Yuchen ,  BETTEGOWDA, Chetan ,  BIGNER, Darell D.

    IPC分类号： C12Q1/68 ,  C12N15/12

    CPC分类号： C12Q1/6886 ,  C12Q2600/112 ,  C12Q2600/156

    摘要： We surveyed 1,230 tumors of 60 different types and found that tumors could be divided into types with low ( TERT promoter mutations. The nine TERT-high tumor types almost always originated in tissues with relatively low rates of self renewal, including melanomas, liposarcomas, hepatocellular carcinomas, urothelial carcinomas, squamous cell carcinomas of the tongue, medulloblastomas, and subtypes of gliomas (including 83% of primary glioblastoma, the most common brain tumor type).
    TERT and
    ATRX mutations were mutually exclusive, suggesting that these two genetic mechanisms confer equivalent selective growth advantages. In addition to their implications for understanding the relationship between telomeres and tumorigenesis,
    TERT mutations provide a biomarker for the early detection of urinary tract and liver tumors and aid in the classification and prognostication of brain tumors.

    OLIGODENDROGLIOMA DRIVER GENES
    10.
    发明授权
    OLIGODENDROGLIOMA DRIVER GENES 有权
    OLIGODENDROGLIOM-TREIBERGENE

    公开(公告)号：EP2734644B1

    公开(公告)日：2016-12-21

    申请号：EP12814956.4

    申请日：2012-07-18

    申请人： The Johns Hopkins University ,  Duke University

    发明人： VOGELSTEIN, Bert ,  KINZLER, Kenneth W. ,  BETTEGOWDA, Chetan ,  AGRAWAL, Nishant ,  PAPADOPOULOS, Nickolas ,  BIGNER, Darell ,  YAN, Hai ,  MCLENDON, Roger

    IPC分类号： C12Q1/68 ,  A61K39/00

    CPC分类号： C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/112 ,  C12Q2600/118 ,  C12Q2600/156 ,  C12Q2600/158

    摘要： Oligodendrogliomas are the second most common malignant brain tumor in adults. These tumors often contain a chromosomal abnormality involving a pericentromeric fusion of chromosomes 1 and 19, resulting in losses of the entire short arm of the former and the long arm of the latter. To identify the molecular genetic basis for this alteration, we performed exomic sequencing of seven anaplastic oligodendrogliomas with chromosome 1p and 19q losses. Among other changes, we found that that CIC (homolog of the Drosophila gene capicua) on chromosome 19q was somatically mutated in six of the seven cases and that FUBP1 (far upstream element (FUSE) binding protein) on chromosome 1p was somatically mutated in two of the seven cases. Examination of 27 additional oligodendrogliomas revealed 12 and 3 more tumors with mutations of CIC and FUBP1, respectively, 58% of which were predicted to result in truncations of the encoded proteins. These results suggest a critical role for these genes in the biology and pathology of oligodendrocytes.

    摘要翻译： 少突胶质瘤是成人中第二常见的恶性脑肿瘤。 这些肿瘤通常含有染色体异常，涉及染色体1和染色体1的周期性融合，导致前者的整个短臂和后者的长臂的损失。 为了鉴定这一改变的分子遗传基础，我们对染色体1p和19q损失进行了7个分离性少突胶质细胞瘤的外切测序。 在其他变化中，我们发现在七种病例中的六种中，染色体19q上的CIC（果蝇基因capicua的同系物）被体细胞突变，并且染色体1p上的FUBP1（远上游元件（FUSE）结合蛋白）在两个体系中被体细胞突变 的七例。 另外27例少突胶质细胞瘤的检查显示，分别有12例和3例具有CIC和FUBP1突变的肿瘤，其中58％预计会导致编码蛋白的截短。 这些结果表明这些基因在少突胶质细胞的生物学和病理学中的关键作用。