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61. 发明授权

US06344322B1 Subtle mitochondrial mutations as tumor markers 失效
公开(公告)号：US06344322B1
公开(公告)日：2002-02-05
申请号：US09377856
申请日：1999-08-20
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 , C12Q2600/156
摘要： The accumulation of homoplasmic somatic mutations has been observed in the mitochondrial DNA of certain tumor cells. The presence or recurrence of a tumor can be detected by determining the presence of single basepair mutations in the mitochondrial genome from a cell sample of a patient.

62. 发明授权

US06300059B1 Cancer diagnosis and WAF1 失效
标题翻译：癌症诊断和WAF1
公开(公告)号：US06300059B1
公开(公告)日：2001-10-09
申请号：US08456297
申请日：1995-06-01
申请人： Bert Vogelstein , Kenneth W. Kinzler
发明人： Bert Vogelstein , Kenneth W. Kinzler
IPC分类号： C12Q168
CPC分类号： C12N15/1135 , A61K38/00 , C07K14/4703 , C12N2310/15 , C12N2310/53
摘要： A human gene, WAF1, has been identified which is induced by wild-type but not mutant p53 in human brain tumor cells. The gene is located on chromosome 6p21.2 and directs the synthesis of an 18.1 kd protein. Introduction of WAF1 cDNA suppresses growth of human brain and colon tumor cells. The WAF1 gene and protein are useful inter alia for diagnosis and treatment of human tumors.
摘要翻译：已经鉴定了人基因WAF1，其在人脑肿瘤细胞中由野生型但不突变的p53诱导。该基因位于染色体6p21.2上，并指导18.1kd蛋白的合成。引入WAF1 cDNA抑制人脑和结肠肿瘤细胞的生长。 WAF1基因和蛋白质特别用于人类肿瘤的诊断和治疗。

63. 发明授权

US06214616B1 Homozygous p53 gene-defective human colonic cell line 有权
标题翻译：纯合p53基因缺陷型人结肠细胞系
公开(公告)号：US06214616B1
公开(公告)日：2001-04-10
申请号：US09298822
申请日：1999-04-26
申请人： Bert Vogelstein , Todd Waldman , Kenneth W. Kinzler
发明人： Bert Vogelstein , Todd Waldman , Kenneth W. Kinzler
IPC分类号： C12N508
CPC分类号： G01N33/5044 , C12Q1/6841 , C12Q1/6886 , C12Q2600/136 , G01N33/5008 , G01N33/5011 , G01N2510/00 , C12Q2563/173
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.
摘要翻译：检查点基因缺陷的人细胞可用于筛选潜在的抗肿瘤剂。筛选潜在的治疗剂在检查点基因缺陷型人细胞中引起DNA积累或细胞死亡的能力。

64. 发明授权

US6140052A cMYC is regulated by Tcf-4 有权
标题翻译： C-MYC受TCF-4监管
公开(公告)号：US6140052A
公开(公告)日：2000-10-31
申请号：US136605
申请日：1998-08-20
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： C12N15/09 , A61K31/711 , A61K38/00 , A61K45/00 , A61K48/00 , A61P35/00 , C07K14/47 , C12N15/12 , C12Q1/02 , C12Q1/68 , G01N33/15 , G01N33/50 , C12N5/10
CPC分类号： C07K14/47 , C07K14/4705 , C12Q1/6897 , A61K38/00 , A61K48/00
摘要： The APC tumor suppressor protein binds to .beta.-catenin, a protein recently shown to interact with Tcf/Lef transcription factors. Here, the gene encoding a Tcf family member that is expressed in colonic epithelium (hTcf-4) was cloned and characterized. hTcf-4 transactivates transcription only when associated with .beta.-catenin. Nuclei of APC.sup.-/- colon carcinoma cells were found to contain a stable .beta.-catenin-hTCF-4 complex that was constitutively active, as measured by transcription of a Tcf reporter gene. Reintroduction of APC removed .beta.-catenin from hTcf4 and abrogated the transcriptional transactivation. Constitutive transcription of TCF target genes, caused by loss of APC function, may be a crucial event in the early transformation of colonic epithelium. It is also shown here that the products of mutant APC genes found in colorectal tumors are defective in regulating .beta.-catenin/Tcf-4 transcriptional activation. Furthermore, colorectal tumors with intact APC genes were shown to contain subtle activating mutations of .beta.-catenin that altered functionally significant phosphorylation sites. These results indicate that regulation of .beta.-catenin is critical to APC's tumor suppressive effect and that this regulation can be circumvented by mutations in either APC or .beta.-catenin.
摘要翻译： APC肿瘤抑制蛋白结合β-连环蛋白，最近显示出与Tcf / Lef转录因子相互作用的蛋白质。这里，克隆并表征编码在结肠上皮（hTcf-4）中表达的Tcf家族成员的基因。 hTcf-4仅在与β-连环蛋白相关时才转录转录。发现APC - / - 结肠癌细胞的核含有稳定的β-联蛋白-hTCF-4复合物，其通过Tcf报道基因的转录测量而具有组成型活性。重新引入APC从hTcf4中除去β-连环蛋白，并废除转录反式激活。由APC功能丧失引起的TCF靶基因的组成转录可能是结肠上皮早期转化的关键事件。这里还显示，在结肠直肠肿瘤中发现的突变APC基因的产物在调节β-连环蛋白/ Tcf-4转录激活中是缺陷的。此外，具有完整APC基因的结肠直肠肿瘤显示含有改变功能显着磷酸化位点的β-连环蛋白的微妙活化突变。这些结果表明，β-连环蛋白的调节对于APC的肿瘤抑制作用至关重要，并且该调节可以通过APC或β-连环蛋白的突变来规避。

65. 发明授权

US6100032A Human Smad3 and Smad4 are sequence-specific transcription activators 失效
标题翻译：人Smad3和Smad4是序列特异性转录激活因子
公开(公告)号：US6100032A
公开(公告)日：2000-08-08
申请号：US41675
申请日：1998-03-13
申请人： Scott Eliot Kern , Leigh Zawel , Jia Le Dai , Bert Vogelstein , Kenneth W. Kinzler
发明人： Scott Eliot Kern , Leigh Zawel , Jia Le Dai , Bert Vogelstein , Kenneth W. Kinzler
IPC分类号： C07K14/47 , C12N15/12 , C12Q1/68
CPC分类号： C07K14/4702 , C12Q1/6897
摘要： Two human Smad proteins (Smad3 and Smad4) specifically recognize an identical 8 bp palindromic sequence (GTCTAGAC) (SEQ ID NO: 1). Tandem repeats of this palindrome confer striking TGF-.beta. responsiveness to a minimal promoter. This responsiveness is abrogated by targeted deletion of the cellular Smad4 gene. DNA molecules comprising the 8 bp palindromic sequence can be used in assays for drug screening and diagnostically.
摘要翻译：两个人Smad蛋白（Smad3和Smad4）特异性识别相同的8bp回文序列（GTCTAGAC）（SEQ ID NO：1）。这种回文的串联重复赋予了对最小启动子的明显的TGF-β响应性。这种反应性被细胞Smad4基因的靶向删除所消除。包含8bp回文序列的DNA分子可用于药物筛选和诊断测定。

66. 发明授权

US6048701A Antibody detection of mismatch repair proteins 失效
标题翻译：抗体检测错配修复蛋白
公开(公告)号：US6048701A
公开(公告)日：2000-04-11
申请号：US709784
申请日：1996-09-09
申请人： Kenneth W. Kinzler , Bert Vogelstein , Marilee Burrell , David E. Hill , Fredrick S. Leach
发明人： Kenneth W. Kinzler , Bert Vogelstein , Marilee Burrell , David E. Hill , Fredrick S. Leach
IPC分类号： G01N33/53 , C12Q1/06 , G01N33/574 , G01N33/68
CPC分类号： G01N33/574 , G01N33/57484 , G01N33/6893 , G01N2800/52
摘要： Antibodies directed to human protein mismatch repair proteins can be used diagnostically to discriminate between proliferating and non-proliferating cells. In addition, they can be used to determine whether cells have a mismatch repair defect caused by a mutation in e.g., hMSH2, hMLH1, or hPMS2. They can also be used to monitor the efficacy of anti-neoplastic therapies.
摘要翻译：针对人类蛋白质错配修复蛋白的抗体可用于诊断性地区分增殖细胞和非增殖细胞。此外，它们可以用于确定细胞是否具有由例如hMSH2，hMLH1或hPMS2中的突变引起的错配修复缺陷。它们也可用于监测抗肿瘤治疗的疗效。

67. 发明授权

US5910407A Method for detection of target nucleic acid by analysis of stool 失效
标题翻译：通过粪便分析检测靶核酸的方法
公开(公告)号：US5910407A
公开(公告)日：1999-06-08
申请号：US297265
申请日：1994-08-26
申请人： Bert Vogelstein , Kenneth W. Kinzler
发明人： Bert Vogelstein , Kenneth W. Kinzler
IPC分类号： C12N15/09 , C07H21/04 , C12Q1/34 , C12Q1/68 , G01N33/50 , C12N15/00 , C12P19/34
CPC分类号： G01N33/50 , C12Q1/6806 , C12Q1/6886 , C12Q2600/156 , Y10S435/81 , Y10T436/143333
摘要： Method for detecting target nucleic acid from a stool specimen.
摘要翻译：从粪便样本中检测靶核酸的方法。

68. 发明授权

US5888735A Cancer drug screen based on cell cycle uncoupling 失效
公开(公告)号：US5888735A
公开(公告)日：1999-03-30
申请号：US781200
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.

69. 发明授权

US5874235A Screening assays for cancer chemopreventative agents 失效
标题翻译：癌症化学预防剂的筛选试验
公开(公告)号：US5874235A
公开(公告)日：1999-02-23
申请号：US896462
申请日：1997-07-18
申请人： Timothy A. Chan , Patrice J. Morin , Bert Vogelstein , Kenneth W. Kinzler
发明人： Timothy A. Chan , Patrice J. Morin , Bert Vogelstein , Kenneth W. Kinzler
IPC分类号： G01N33/50 , C12Q1/34 , C12Q1/00 , C12Q1/42
CPC分类号： G01N33/5011
摘要： Nonsteroidal anti-inflammatory drugs cause a dramatic increase in intracellular ceramide, which induces apoptosis. The ceramide increase is likely mediated by cyclooxygenase inhibition, which elevates arachidonic acid, which stimulates sphingomyelinase, which produces ceramide. Contacting members of this pathway with test compounds and observing their effects provides a method of screening for potential cancer chemopreventative agents.
摘要翻译：非甾体抗炎药引起细胞内神经酰胺的剧烈增加，诱导细胞凋亡。神经酰胺增加可能由环氧合酶抑制介导，其升高花生四烯酸，其刺激产生神经酰胺的鞘磷脂酶。将该途径与测试化合物接触并观察其作用提供了筛选潜在的癌症化学预防剂的方法。

70. 发明授权

US5858976A Methods for inhibiting interaction of human MDM2 and p53 失效
标题翻译：抑制人MDM2和p53相互作用的方法
公开(公告)号：US5858976A
公开(公告)日：1999-01-12
申请号：US801718
申请日：1997-02-14
申请人： Marilee Burrell , David E. Hill , Kenneth W. Kinzler , Bert Vogelstein
发明人： Marilee Burrell , David E. Hill , Kenneth W. Kinzler , Bert Vogelstein
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 , C07K14/435
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 allows 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MDM2蛋白与人p53结合并使细胞从p53调节的生长中逃逸。

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