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公开(公告)号:US5888735A
公开(公告)日:1999-03-30
申请号:US781200
申请日:1997-01-10
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.
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公开(公告)号:US5874235A
公开(公告)日:1999-02-23
申请号:US896462
申请日:1997-07-18
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。
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公开(公告)号:US5858976A
公开(公告)日:1999-01-12
申请号:US801718
申请日:1997-02-14
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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公开(公告)号:US5851775A
公开(公告)日:1998-12-22
申请号:US821355
申请日:1997-03-20
申请人: Nick Barker , Hans Clevers , Kenneth W. Kinzler , Vladimer Korinek , Patrice J. Morin , Andrew B. Sparks , Bert Vogelstein
发明人: Nick Barker , Hans Clevers , Kenneth W. Kinzler , Vladimer Korinek , Patrice J. Morin , Andrew B. Sparks , Bert Vogelstein
IPC分类号: G01N33/50 , A61K31/711 , A61K38/00 , A61K48/00 , A61P35/00 , C07K14/47 , C12N15/09 , C12N15/12 , C12Q1/68 , G01N33/15 , G01N33/53
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 transcrpitional 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跨刺激激活中是有缺陷的。 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。
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公开(公告)号:US5843757A
公开(公告)日:1998-12-01
申请号:US518862
申请日:1995-08-24
CPC分类号: C07K14/47
摘要: The hPMS2 gene encodes a protein which is involved in DNA mismatch repair and is mutated in a subset of patients with hereditary nonpolyposis colon cancer (HNPCC). The previously published hPMS2 cDNA sequence lacks an upstream in-frame stop codon preceding the presumptive initiating methionine. To further evaluate the 5' terminus of the hPMS2 coding region, we isolated additional cDNA clones, RT-PCR products, and the corresponding 5' genomic segment of the hPMS2 locus. The hPMS2 gene transcripts were found to have heterogeneous but collinear 5' termini, one of which contained an in-frame termination codon preceding the initiating methionine. In addition, a novel gene encoding a 34.5 kDa polypeptide was found to transcriptionally initiate within hPMS2 from the opposite strand.
摘要翻译: hPMS2基因编码参与DNA错配修复的蛋白质,并在遗传性非息肉性结肠癌(HNPCC)患者的亚组中突变。 以前发表的hPMS2 cDNA序列在推定的起始甲硫氨酸之前缺少上游的内切终止密码子。 为了进一步评估hPMS2编码区的5'末端,我们分离了另外的cDNA克隆,RT-PCR产物和hPMS2基因座的相应的5'基因组片段。 发现hPMS2基因转录物具有异源但共线的5'末端,其中之一包含起始甲硫氨酸之前的框内终止密码子。 另外,发现编码34.5kDa多肽的新基因在相反链的hPMS2内转录起始。
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公开(公告)号:US5807692A
公开(公告)日:1998-09-15
申请号:US574043
申请日:1995-12-18
IPC分类号: A61K38/00 , A61P35/00 , C07K14/47 , C12N15/113 , C12N15/12 , G01N33/567 , C07H21/04 , C12N5/00 , C12N15/63
CPC分类号: C12N15/1135 , C07K14/4703 , A61K38/00 , C12N2310/15 , C12N2310/53
摘要: The striking compartmentalization of p21.sup.WAF1 expression found in normal tissues is completely abrogated in neoplastic tissues. Methods are provided for using p21.sup.WAF1 expression as a tool to assess neoplasia and to discover new drugs. A truncated p21.sup.WAF1 protein is more active than full-length p21.sup.WAF1 protein in inhibiting tumor cell growth.
摘要翻译: 正常组织中发现的p21WAF1表达的显着区别在肿瘤组织中被完全消除。 提供了使用p21WAF1表达作为评估肿瘤并发现新药物的工具的方法。 截短的p21WAF1蛋白在抑制肿瘤细胞生长中比全长p21WAF1蛋白更具活性。
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公开(公告)号:US5736389A
公开(公告)日:1998-04-07
申请号:US446919
申请日:1995-05-22
IPC分类号: G01N33/566 , A61K38/00 , C07K14/47 , C07K16/18 , C12N1/21 , C12N15/09 , C12N15/12 , C12P21/02 , C12P21/08 , C12Q1/68 , G01N33/577 , C12N15/11 , C12N15/63
CPC分类号: C07K14/47 , A61K38/00 , C07K2319/00
摘要: Inactivation of the APC minor suppressor gene plays an important role in the development of both sporadic and familial forms of colorectal cancers. The majority of these mutations result in the loss of the carboxyl terminus of the APC protein. A cellular protein, EB1, that associates with the carboxyl terminus of APC both in vitro and in vivo has been identified. The EB1 gene is predicted to encode a 268 amino acid protein without significant homology to any protein with known function.
摘要翻译: APC次要抑制基因的失活在结肠直肠癌的散发和家族形式的发展中起重要作用。 这些突变中的大多数导致APC蛋白的羧基末端的损失。 已经鉴定了在体外和体内与APC的羧基末端缔合的细胞蛋白质EB1。 EB1基因被预测编码268个氨基酸的蛋白质,而与具有已知功能的任何蛋白质没有显着的同源性。
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公开(公告)号:US5695937A
公开(公告)日:1997-12-09
申请号:US527154
申请日:1995-09-12
CPC分类号: C12N15/1096 , C12Q1/6809 , C12Q1/6869
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。
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公开(公告)号:US08444963B2
公开(公告)日:2013-05-21
申请号:US12304178
申请日:2007-06-19
申请人: Ian Cheong , Shibin Zhou , Kenneth W. Kinzler , Bert Vogelstein
发明人: Ian Cheong , Shibin Zhou , Kenneth W. Kinzler , Bert Vogelstein
CPC分类号: A61K38/465 , A61K9/1271 , A61K9/1278 , A61K31/4545 , A61K31/4745 , A61K31/704 , A61K31/713 , A61K35/742 , A61K39/39558 , A61K47/64 , C12N9/20 , C12Y301/01003 , A61K2300/00
摘要: Clostridium novyi is an obligate anaerobe that can infect hypoxic regions within experimental tumors. We found that mice bearing large, established tumors were often cured when treated with C. novyi plus a single dose of liposomal doxorubicin. The secreted factor responsible for this phenomenon was identified and, surprisingly, proved to be a member of the lipase family. The gene encoding this protein, called liposomase, has the potential to be incorporated into diverse therapeutic methods to deliver specifically a variety of chemotherapeutic agents to tumors.
摘要翻译: 梭菌(Clostridium novyi)是可以感染实验性肿瘤内的缺氧区域的专性厌氧菌。 我们发现,用C.novyi加单次剂量的脂质体多柔比星治疗时,承担大的,建立的肿瘤的小鼠经常被治愈。 鉴定了造成这种现象的分泌因子,令人吃惊的是,它被证明是脂肪酶家族的成员。 编码这种蛋白质的基因,称为脂质体,有可能并入多种治疗方法,以特异性递送多种化疗药物到肿瘤中。
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公开(公告)号:US20110250258A1
公开(公告)日:2011-10-13
申请号:US12304178
申请日:2007-06-19
申请人: Ian Cheong , Shibin Zhou , Kenneth W. Kinzler , Bert Vogelstein
发明人: Ian Cheong , Shibin Zhou , Kenneth W. Kinzler , Bert Vogelstein
IPC分类号: A61K9/127 , C12N15/85 , C12N15/86 , A61P35/00 , A61K39/395 , C12N9/96 , C07H21/04 , C12N9/20 , A61K35/74
CPC分类号: A61K38/465 , A61K9/1271 , A61K9/1278 , A61K31/4545 , A61K31/4745 , A61K31/704 , A61K31/713 , A61K35/742 , A61K39/39558 , A61K47/64 , C12N9/20 , C12Y301/01003 , A61K2300/00
摘要: Clostridium novyi is an obligate anaerobe that can infect hypoxic regions within experimental tumors. We found that mice bearing large, established tumors were often cured when treated with C. novyi plus a single dose of liposomal doxorubicin. The secreted factor responsible for this phenomenon was identified and, surprisingly, proved to be a member of the lipase family. The gene encoding this protein, called liposomase, has the potential to be incorporated into diverse therapeutic methods to deliver specifically a variety of chemotherapeutic agents to tumors.
摘要翻译: 梭菌(Clostridium novyi)是可以感染实验性肿瘤内的缺氧区域的专性厌氧菌。 我们发现,用C.novyi加单次剂量的脂质体多柔比星治疗时,承担大的,建立的肿瘤的小鼠常常被治愈。 鉴定了造成这种现象的分泌因子,令人吃惊的是,它被证明是脂肪酶家族的成员。 编码这种蛋白质的基因,称为脂质体,有可能并入多种治疗方法,以特异性递送多种化疗药物到肿瘤中。
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