公开(公告)号：US07087583B2

公开(公告)日：2006-08-08

申请号：US09813824

申请日：2001-03-22

申请人： Bert Vogelstein ,  Kenneth W. Kinzler ,  Michael I. Sherman

发明人： Bert Vogelstein ,  Kenneth W. Kinzler ,  Michael I. Sherman

IPC分类号： A61K31/711

CPC分类号： G01N33/5008 ,  C07K14/4746 ,  C12Q1/6811 ,  C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/136 ,  C12Q2600/154 ,  G01N33/5011 ,  G01N33/57496 ,  G01N33/68

摘要： Specific sequences in the human genome are the sites of strong binding of wild-type p53 protein, but not mutant forms of the protein. These sequences are used diagnostically to detect cells in which the amount of wild-type p53 is diminished. The sequences can also be used to screen for agents which correct for loss of wild-type p53 to DNA in cancer cells.

公开(公告)号：US07026119B2

公开(公告)日：2006-04-11

申请号：US09780675

申请日：2001-02-12

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 ,  C12N15/74 ,  C12N1/20

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

摘要： Bacteria are manipulated to create desirable output traits using dominant negative alleles of mismatch repair proteins. Enhanced hypermutation is achieved by combination of mismatch repair deficiency and exogenously applied mutagens. Stable bacteria containing desirable output traits are obtained by restoring mismatch repair activity to the bacteria.

公开(公告)号：USRE38916E1

公开(公告)日：2005-12-06

申请号：US09442489

申请日：1999-11-18

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

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

IPC分类号： C07K14/47 ,  C07K16/32 ,  C12N5/12 ,  C12N15/12

CPC分类号： C07K14/47

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：US06746845B2

公开(公告)日：2004-06-08

申请号：US10096596

申请日：2002-03-14

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

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

IPC分类号： C12Q168

CPC分类号： C12N15/1096 ,  C12Q1/6809 ,  C12Q1/6869 ,  C12Q2539/103

摘要： Serial analysis of gene expression, SAGE, a method for the rapid quantitative and qualitative analysis of transcripts is provided. Short defined sequence tags corresponding to expressed genes are isolated and analyzed. Sequencing of over 1,000 defined tags in a short period of time (e.g., hours) reveals a gene expression pattern characteristic of the function of a cell or tissue. Moreover, SAGE is useful as a gene discovery tool for the identification and isolation of novel sequence tags corresponding to novel transcripts and genes.

摘要翻译： 提供基因表达的串行分析，SAGE，一种用于快速定量和定性分析转录本的方法。 分离并分析与表达基因相对应的短定义序列标签。 在短时间（例如，小时）内测定超过1,000个定义的标签显示了细胞或组织功能特征的基因表达模式。 此外，SAGE可用作用于鉴定和分离对应于新转录物和基因的新序列标签的基因发现工具。

公开(公告)号：US06432640B1

公开(公告)日：2002-08-13

申请号：US09154750

申请日：1998-09-17

申请人： Kornelia Polyak ,  Bert Vogelstein ,  Kenneth W. Kinzler

发明人： Kornelia Polyak ,  Bert Vogelstein ,  Kenneth W. Kinzler

IPC分类号： C12Q168

CPC分类号： C12Q1/6809 ,  C12Q1/6886 ,  C12Q1/6897 ,  C12Q2539/103 ,  C12Q2600/136 ,  C12Q2600/142

摘要： The most well-documented biochemical property of p53 is its ability to transcriptionally activate genes. Many of the genes which are activated by p53 expression prior to the onset of apoptosis are predicted to encode proteins which could generate or respond to oxidative stress, including one that is implicated in apoptosis within plant meristems. p53 may result in apoptosis through a three-step process: (I) the transcriptional induction of specific redox-related genes; (ii) the formation of reactive oxygen species (ROS); and (iii) the oxidative degradation of mitochondrial components, rapidly leading to cell death. Transcription of other genes is decreased by p53. Examination of the level of transcription of p53-induced or repressed genes can be used to determine p53 status, to diagnose cancer, and to evaluate cytotoxicity or carcinogenicity of a test agent.

摘要翻译： 最有说明的p53生物化学性质是其转录激活基因的能力。 预计在细胞凋亡发生之前由p53表达激活的许多基因可以编码可产生或响应氧化应激的蛋白质，包括与植物分生组织内凋亡相关的蛋白质。 p53可能通过三步过程导致凋亡：（I）特异性氧化还原相关基因的转录诱导; （ii）形成活性氧（ROS）; 和（iii）线粒体成分的氧化降解，迅速导致细胞死亡。 其他基因的转录通过p53降低。 检测p53诱导或抑制基因的转录水平可用于确定p53状态，诊断癌症，并评估测试药物的细胞毒性或致癌性。

公开(公告)号：US06333152B1

公开(公告)日：2001-12-25

申请号：US09081646

申请日：1998-05-20

申请人： Bert Vogelstein ,  Kenneth W. Kinzler ,  Lin Zhang ,  Wei Zhou

发明人： Bert Vogelstein ,  Kenneth W. Kinzler ,  Lin Zhang ,  Wei Zhou

IPC分类号： C12Q168

CPC分类号： C12Q1/6809 ,  C12Q1/6886 ,  C12Q2600/118 ,  C12Q2600/136 ,  C12Q2600/158 ,  G01N33/574

摘要： As a step towards understanding the complex differences between normal and cancer cells, gene expression patterns were examined in gastrointestinal tumors. More than 300,000 transcripts derived from at least 45,000 different genes were analyzed. Although extensive similarity was noted between the expression profiles, more than 500 transcripts that were expressed at significantly different levels in normal and neoplastic cells were identified. These data provide insights into the extent of expression differences underlying malignancy and reveal genes that are useful as diagnostic or prognostic markers.

摘要翻译： 作为理解正常和癌细胞之间复杂差异的一步，在胃肠道肿瘤中检查基因表达模式。 分析来自至少45,000个不同基因的超过30万个转录物。 虽然在表达谱之间注意到广泛的相似性，但是鉴定了在正常和肿瘤细胞中以显着不同水平表达的500多个转录物。 这些数据提供了对恶性肿瘤的表达差异程度的了解，并揭示了可用作诊断或预后标志物的基因。

公开(公告)号：US06255464B1

公开(公告)日：2001-07-03

申请号：US08840767

申请日：1997-04-16

申请人： Bert Vogelstein ,  Kenneth W. Kinzler ,  Gregory R. Riggins ,  Sam Thiagalingam

发明人： Bert Vogelstein ,  Kenneth W. Kinzler ,  Gregory R. Riggins ,  Sam Thiagalingam

IPC分类号： C07H2102

CPC分类号： C07K14/4703 ,  A61K38/00

摘要： Five human genes related to the Mad gene of Drosophila were identified. One of these genes (Smad2) was found to reside at chromosome 18q21, adjacent to a previously described member of this family called DPC4 (Smad4). Smad2 was found to be somatically mutated in two of eighteen human colorectal cancers. Smad2 and Smad4 are important in the suppression of neoplasia by mediating the growth inhibitory effects of TGF-&bgr;-like ligands.

摘要翻译： 鉴定了与果蝇Mad基因相关的五个人类基因。 发现这些基因之一（Smad2）位于染色体18q21处，与该家族之前称为DPC4（Smad4）的成员相邻。 发现Smad2在十八个人结肠直肠癌中的两个中被体细胞突变。 Smad2和Smad4通过介导TGF-β样配体的生长抑制作用来抑制肿瘤是重要的。

公开(公告)号：US5922576A

公开(公告)日：1999-07-13

申请号：US31917

申请日：1998-02-27

申请人： Tong-Chuan He ,  Bert Vogelstein ,  Kenneth W. Kinzler

发明人： Tong-Chuan He ,  Bert Vogelstein ,  Kenneth W. Kinzler

IPC分类号： C07K14/075 ,  C12N15/861 ,  C12N15/64 ,  C07H21/04 ,  C12N1/21 ,  C12N15/70

CPC分类号： C12N15/86 ,  C07K14/005 ,  C12N2710/10322 ,  C12N2710/10343 ,  C12N2830/38

摘要： Recombinant adenoviruses provide a versatile system for gene expression studies and therapeutic applications. This invention describes a strategy which simplifies the generation and production of such viruses. A recombinant adenoviral plasmid is generated with a minimum of enzymatic manipulations, employing homologous recombination in bacteria rather than in eucaryotic cells. Following transfections of such plasmids into a mammalian packaging cell line, viral production can be conveniently followed with the aid of green fluorescent protein, encoded by a gene incorporated into the viral backbone. Homogeneous viruses can be obtained from this procedure without plaque purification. This system expedites the process of generating and testing recombinant adenoviruses.

摘要翻译： 重组腺病毒为基因表达研究和治疗应用提供了多功能的系统。 本发明描述了一种简化这种病毒生成和生产的策略。 通过最少的酶操作产生重组腺病毒质粒，在细菌中而不是在真核细胞中使用同源重组。 在将这些质粒转染到哺乳动物包装细胞系之后，可以方便地利用由掺入病毒骨架的基因编码的绿色荧光蛋白来辅助病毒生产。 可以从该程序获得均一的病毒，无需进行噬斑纯化。 该系统加速了重组腺病毒的产生和检测过程。

公开(公告)号：US5910418A

公开(公告)日：1999-06-08

申请号：US370235

申请日：1995-01-09

申请人： David E. Hill ,  Karen A. Johnson ,  Kenneth W. Kinzler ,  Bert Vogelstein

发明人： David E. Hill ,  Karen A. Johnson ,  Kenneth W. Kinzler ,  Bert Vogelstein

IPC分类号： G01N33/574 ,  C07K14/47 ,  C07K16/18 ,  C07K16/22 ,  C07K16/30 ,  C12N5/10 ,  C12N5/20 ,  C12N15/02 ,  C12P21/08 ,  C12R1/91 ,  G01N33/577 ,  G01N33/53 ,  G01N33/532 ,  G01N33/537

CPC分类号： C07K16/18 ,  C07K14/47 ,  C07K16/22 ,  C07K2319/00

摘要： Antibodies and assays employing them are taught which are useful for detecting the bulk of mutations which occur in the APC gene in familial adenomatous polyposis. The antibodies are specific for epitopes in the amino terminal or carboxy terminal portion of the protein. A variety of immunoassay formats are described which are all based on the observation that the bulk of the APC mutations which occur in familial adenomatous polyposis and sporadic colorectal carcinomas result in truncated APC proteins. Generally, either the size of APC proteins is determined or the relative binding of amino terminal-binding antibodies to carboxy terminal-binding antibodies is determined.

摘要翻译： 教导了使用它们的抗体和测定法，其可用于检测在家族性腺瘤性息肉病中发生在APC基因中的大部分突变。 抗体对蛋白质的氨基末端或羧基末端部分的表位是特异性的。 描述了各种免疫测定形式，其全部基于观察到家族性腺瘤性息肉病和散发性结肠直肠癌中发生的大部分APC突变导致截短的APC蛋白。 通常，确定APC蛋白的大小或确定氨基末端结合抗体与羧基末端结合抗体的相对结合。

公开(公告)号：US5882865A

公开(公告)日：1999-03-16

申请号：US781201

申请日：1997-01-10

申请人： Bert Vogelstein ,  Todd Waldman ,  Christoph Lengauer ,  Kenneth W. Kinzler

发明人： Bert Vogelstein ,  Todd Waldman ,  Christoph Lengauer ,  Kenneth W. Kinzler

IPC分类号： C12N5/08 ,  C12Q1/68 ,  G01N33/50

CPC分类号： G01N33/5044 ,  C12Q1/6841 ,  C12Q1/6886 ,  G01N33/5008 ,  G01N33/5011 ,  C12Q2600/136 ,  G01N2510/00

摘要： Checkpoint gene-defective human cells are useful for screening potential anti-tumor agents. Potential therapeutic agents are screened for the ability to cause DNA accumulation or cell death in a checkpoint gene-defective human cell.