公开(公告)号：US20060166257A1

公开(公告)日：2006-07-27

申请号：US11389062

申请日：2006-03-27

申请人： Bert Vogelstein ,  Kenneth Kinzler ,  Nickolas Papadopoulos ,  Hai Yan

发明人： Bert Vogelstein ,  Kenneth Kinzler ,  Nickolas Papadopoulos ,  Hai Yan

IPC分类号： C12Q1/68 ,  C12N5/06 ,  C12N15/87

CPC分类号： C12N5/166 ,  C12Q1/6886 ,  C12Q2600/156

摘要： Detection of mutations associated with hereditary diseases is complicated by the diploid nature of mammalian cells. Mutations present in one allele are often masked by the wild-type sequence of the other allele. Individual alleles can be isolated from every chromosome within somatic cell hybrids generated from a single fusion. Nucleic acids from the hybrids can be analyzed for mutations in an unambiguous manner. This approach was used to detect two cancer-causing mutations that had previously defied genetic diagnosis. One of the families studied, Warthin Family G, was the first kindred with a hereditary colon cancer syndrome described in the biomedical literature.

公开(公告)号：US20050079157A1

公开(公告)日：2005-04-14

申请号：US10495116

申请日：2002-11-21

申请人： Long Dang ,  Kenneth Kinzler ,  Bert Vogelstein

发明人： Long Dang ,  Kenneth Kinzler ,  Bert Vogelstein

IPC分类号： A61K31/475 ,  A61K35/74 ,  A61K35/742 ,  A61K41/00 ,  A61K45/06 ,  C12N1/21 ,  A61K48/00

CPC分类号： C12R1/145 ,  A61K31/475 ,  A61K35/742 ,  A61K38/193 ,  A61K41/00 ,  A61K45/06 ,  C12N1/36 ,  A61K2300/00

摘要： Current chemotherapeutic approaches for cancer are in part limited by the inability of drugs to destroy neoplastic cells within poorly vascularized compartments of tumors. We have here systematically assessed anaerobic bacteria for their capacity to grow expansively within avascutar compartments of transplanted tumors. Among 26 different strains tested, one (Clostridium novyi) appeared particularly promising. We created a strain of C. novyi devoid of its lethal toxin (C. novyi-NT) and showed that intravenously injected C. novyi-NT spores germinated within the avascular regions of tumors in mice and destroyed surrounding viable tumor cells. When C. novyi-NT spores were administered together with conventional chemotherapeutic drugs, extensive hemorrhagic necrosis of tumors often developed within 24 hours, resulting in significant and prolonged anti-tumor effects. This strategy, called combination bacteriolytic therapy (COBALT), has the potential to add a valuablle dimension to the treatment of cancer.

摘要翻译： 目前用于癌症的化学治疗方法在一定程度上受到药物不能破坏肿瘤不良血管化区域内的肿瘤细胞的作用。 我们在这里系统地评估了厌氧细菌在移植肿瘤的avascutar区域内扩大生长的能力。 在测试的26种不同菌株中，1种（Clostridium novyi）出现特别有前途。 我们创建了一种没有其致死毒素（C. novyi-NT）的C. novyi菌株，并且显示在小鼠的肿瘤的无血管区域内静脉内注射C.novyi-NT孢子，并破坏周围的活的肿瘤细胞。 当与常规化疗药物一起施用C.novyi-NT孢子时，广泛的肿瘤出血性坏死通常在24小时内发展，导致显着的和长期的抗肿瘤效应。 这种称为组合溶菌治疗（COBALT）的策略有可能为治疗癌症增加一个价值。

公开(公告)号：US6114124A

公开(公告)日：2000-09-05

申请号：US450582

申请日：1995-05-25

申请人： Hans Albertsen ,  Rakesh Anand ,  Mary Carlson ,  Joanna Groden ,  Philip John Hedge ,  Geoff Joslyn ,  Kenneth Kinzler ,  Alexander Fred Markham ,  Yusuke Nakamura ,  Andrew Thliveris ,  Bert Vogelstein ,  Raymond L. White

发明人： Hans Albertsen ,  Rakesh Anand ,  Mary Carlson ,  Joanna Groden ,  Philip John Hedge ,  Geoff Joslyn ,  Kenneth Kinzler ,  Alexander Fred Markham ,  Yusuke Nakamura ,  Andrew Thliveris ,  Bert Vogelstein ,  Raymond L. White

IPC分类号： C07K14/47 ,  C07K14/82 ,  C07K16/32 ,  C12N5/12 ,  C12N15/12 ,  C12Q1/68 ,  G01N33/53 ,  G01N33/48 ,  G01N33/574

CPC分类号： C07K14/47 ,  C07K14/82 ,  C12Q1/68 ,  C12Q1/6827 ,  C12Q1/6886 ,  A01K2217/05 ,  C12Q2600/112 ,  C12Q2600/156 ,  C12Q2600/158 ,  C12Q2600/172 ,  Y10S530/828

摘要： A human gene termed APC is disclosed. Methods and kits are provided for assessing mutations of the APC gene in human tissues and body samples. APC mutations are found in familial adenomatous polyposis patients as well as in sporadic colorectal cancer patients. APC is expressed in most normal tissues. These results suggest that APC is a tumor suppressor.

摘要翻译： 公开了一种称为APC的人类基因。 提供了用于评估人类组织和身体样品中APC基因突变的方法和试剂盒。 家族性腺瘤性息肉病患者以及散发性结肠直肠癌患者发现APC突变。 APC在大多数正常组织中表达。 这些结果表明APC是肿瘤抑制因子。

公开(公告)号：US5519118A

公开(公告)日：1996-05-21

申请号：US283911

申请日：1994-08-04

申请人： Bert Vogelstein ,  Kenneth Kinzler

发明人： Bert Vogelstein ,  Kenneth Kinzler

IPC分类号： C12N15/09 ,  A61K38/00 ,  A61K38/17 ,  A61K48/00 ,  C07H21/04 ,  C07K14/47 ,  C07K16/18 ,  C12N1/19 ,  C12Q1/68 ,  G01N33/50 ,  G01N33/574 ,  G01N33/68

CPC分类号： G01N33/57484 ,  A61K38/1709 ,  C07K14/47 ,  C07K16/18 ,  C12Q1/6886 ,  C12Q1/6897 ,  G01N33/5011 ,  G01N33/57407 ,  G01N33/68 ,  G01N33/6872 ,  A61K48/00 ,  C12Q2600/136 ,  G01N2500/10 ,  Y10S436/813

摘要： A human gene has been discovered which is genetically altered in human tumor cells. The genetic alteration is gene amplification and leads to a corresponding increase in gene products. Detecting that the gene, designated hMDM2, has become amplified or detecting increased expression of gene products is diagnostic of tumorigenesis. Human MDM2 protein binds to human p53 and appears to allow the cell to escape from p53-regulated growth.

摘要翻译： 已经发现人类基因在人类肿瘤细胞中被遗传改变。 遗传改变是基因扩增，导致基因产物相应增加。 检测到称为hMDM2的基因已经被扩增或检测到基因产物的增加的表达是肿瘤发生的诊断。 人类MDM2蛋白与人类p53结合，似乎允许细胞从p53调节的生长中逃逸。

公开(公告)号：US20130323167A1

公开(公告)日：2013-12-05

申请号：US13880608

申请日：2011-10-20

申请人： Bert Vogelstein ,  Yuan Qiao ,  Xin Huang ,  Kenneth Kinzler ,  Shibin Zhou ,  Luis Diaz

发明人： Bert Vogelstein ,  Yuan Qiao ,  Xin Huang ,  Kenneth Kinzler ,  Shibin Zhou ,  Luis Diaz

IPC分类号： A61K51/10

CPC分类号： A61K51/1045 ,  A61K9/1271 ,  A61K39/395 ,  A61K45/06 ,  A61K51/1009 ,  C07K16/2887 ,  C07K16/40 ,  A61K2300/00

摘要： Several agents capable of inducing vascular responses akin to those observed in inflammatory processes enhance the accumulation of nanoparticles in tumors. Exemplary vascular-active agents include a bacterium, a pro-inflammatory cytokine, and microtubule-destabilizing drugs. Such agents can increase the tumor to blood ratio of radioactivity by more than 20-fold compared to nanoparticles alone. Moreover, vascular-active agents dramatically improved the therapeutic effect of nanoparticles containing radioactive isotopes or chemotherapeutic agents.

摘要翻译： 能够诱导与炎症过程中观察到的血管反应类似的几种药物增强纳米颗粒在肿瘤中的积累。 示例性的血管活性剂包括细菌，促炎细胞因子和微管不稳定药物。 与单独的纳米颗粒相比，这样的药物可以将放射性的肿瘤与血液的比例增加20倍以上。 此外，血管活性剂显着改善了含有放射性同位素或化学治疗剂的纳米颗粒的治疗效果。

公开(公告)号：US07829338B2

公开(公告)日：2010-11-09

申请号：US11907338

申请日：2007-10-11

申请人： Nicholas Nicolaides ,  Bert Vogelstein ,  Kenneth Kinzler

发明人： Nicholas Nicolaides ,  Bert Vogelstein ,  Kenneth Kinzler

IPC分类号： C12N15/00 ,  C12N5/00 ,  C12N5/02 ,  C12N15/74 ,  C12Q1/68

CPC分类号： C12N15/1024 ,  A01K2217/05 ,  C07K14/47

摘要： Dominant negative alleles of human mismatch repair genes can be used to generate hypermutable cells and organisms. By introducing these genes into cells and transgenic animals, new cell lines and animal varieties with novel and useful properties can be prepared more efficiently than by relying on the natural rate of mutation.

摘要翻译： 人类错配修复基因的主要阴性等位基因可用于产生超可变细胞和生物体。 通过将这些基因引入细胞和转基因动物，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动物品种。

公开(公告)号：US20090010844A1

公开(公告)日：2009-01-08

申请号：US11629607

申请日：2005-06-20

申请人： Martin G. Pomper ,  Chetan Bettegowda ,  Catherine Foss ,  Shibin Zhou ,  Kenneth Kinzler ,  Bert Vogelstein

发明人： Martin G. Pomper ,  Chetan Bettegowda ,  Catherine Foss ,  Shibin Zhou ,  Kenneth Kinzler ,  Bert Vogelstein

IPC分类号： A61K51/06 ,  A61K49/04 ,  A61K101/02

CPC分类号： A61K51/1241 ,  A61K51/0491 ,  A61K51/1231

摘要： The instant invention provides a method for diagnosing an infection in a subject by administering to the subject a compound suitable for imaging which binds to a thymidine kinase present in the infecting organism, and obtaining an image of the subject to determine the presence and location of the compound, wherein a localization of the compound is indicative that the subject has an infection.

摘要翻译： 本发明提供了一种用于通过向受试者施用适合于与感染生物体中存在的胸腺嘧啶激酶结合的成像的化合物并且获得受试者的图像来确定受试者的感染的存在和位置的方法， 化合物，其中化合物的定位表明受试者具有感染。

公开(公告)号：US20060019277A1

公开(公告)日：2006-01-26

申请号：US11138912

申请日：2005-05-27

申请人： Carlo Traverso ,  Kenneth Kinzler ,  Bert Vogelstein

发明人： Carlo Traverso ,  Kenneth Kinzler ,  Bert Vogelstein

IPC分类号： C12Q1/68 ,  C12P19/34

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.

公开(公告)号：US20050188428A1

公开(公告)日：2005-08-25

申请号：US10873114

申请日：2004-06-23

申请人： Nicholas Nicolaides ,  Philip Sass ,  Luigi Grasso ,  Bert Vogelstein ,  Kenneth Kinzler

发明人： Nicholas Nicolaides ,  Philip Sass ,  Luigi Grasso ,  Bert Vogelstein ,  Kenneth Kinzler

IPC分类号： C07K14/47 ,  C12N15/01 ,  C12N15/10 ,  A01K67/027 ,  C12N15/85

CPC分类号： C12N15/1024 ,  C07K14/47 ,  C12N15/01 ,  C12N15/102

摘要： Dominant negative alleles of human mismatch repair genes can be used to generate hypermutable cells and organisms. By introducing these genes into cells and transgenic animals, new cell lines and animal varieties with novel and useful properties can be prepared more efficiently than by relying on the natural rate of mutation. The enhanced rate of mutation can be further augmented using mutagens. Moreover, the hypermutability of mismatch repair deficient cells can be remedied to stabilize cells or mammals with useful mutations.

摘要翻译： 人类错配修复基因的主要阴性等位基因可用于产生超可变细胞和生物体。 通过将这些基因引入细胞和转基因动物，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动物品种。 使用诱变剂可以进一步增强突变率的增强。 此外，错配修复缺陷细胞的高度易失性可以补救以稳定具有有用突变的细胞或哺乳动物。

公开(公告)号：US20050142138A1

公开(公告)日：2005-06-30

申请号：US10979159

申请日：2004-11-03

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

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

IPC分类号： G01N33/50 ,  A61K35/12 ,  A61K38/00 ,  A61K39/00 ,  A61K39/395 ,  A61K48/00 ,  A61P9/10 ,  A61P13/12 ,  A61P17/06 ,  A61P19/02 ,  A61P29/00 ,  A61P35/00 ,  C07K14/46 ,  C07K14/47 ,  C07K16/18 ,  C07K16/30 ,  C12N1/15 ,  C12N1/19 ,  C12N1/21 ,  C12N5/10 ,  C12N15/09 ,  C12P21/08 ,  C12Q1/02 ,  C12Q1/68 ,  G01N33/15 ,  G01N33/53 ,  G01N33/566

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。