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1. 发明申请

WO2003022863A1 SECRETED AND CELL SURFACE GENES EXPRESSED IN BENIGN AND MALIGNANT COLORECTAL TUMORS 审中-公开
标题翻译：分泌和细胞表面基因表达于胆管和恶性色素性肿瘤
公开(公告)号：WO2003022863A1
公开(公告)日：2003-03-20
申请号：PCT/US2002/028518
申请日：2002-09-09
申请人： THE JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE , BUCKHAULTS, Phillip , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
发明人： BUCKHAULTS, Phillip , KINZLER, Kenneth, W. , VOGELSTEIN, Bert
IPC分类号： C07H21/04
CPC分类号： C07K14/495 , C07K14/47 , C07K14/705
摘要： Serial analysis of gene expression (SAGE) was used to identify transcripts encoding secreted or cell-surface proteins that were expressed in benign and malignant tumors of the colorectum. A total of 290,394 tags were analyzed from normal, adenomatous and cancerous colonic epithelium. Of the 21,343 different transcripts observed, 957 were found to be differentially expressed between normal and adenoma or between normal and cancer. Forty-nine transcripts were elevated ≥ 20-fold in adenomas, 40 transcripts were elevated ≥ 20-fold in cancers, and nine transcripts were elevated ≥ 20-fold in both. Product of six these nine transcripts (TGFBI, LYS, RDP, MIC-1, REGA, and DEHL) were predicted to be secreted or to reside on the cell surface and these were analyzed in more detail. The abnormal expression levels predicted by SAGE were confirmed by quantitative PCR analyses of each of these six genes. Moreover, the cell types responsible for the elevated expression were identified by in situ hybridization and by PCR analyses of epithelial cells immunoaffinity purified from primary tumors.
摘要翻译：基因表达（SAGE）的序列分析用于鉴定在结肠直肠癌和恶性肿瘤中表达的编码分泌的或细胞表面蛋白的转录物。从正常，腺瘤和癌性结肠上皮分析总共290,394个标签。在观察到的21,343种不同的转录物中，957被发现在正常和腺瘤之间或在正常和癌症之间差异表达。在腺瘤中，49个转录本升高了20倍，40个转录物在癌症中升高了20倍，而9个转录物在两者中升高了20倍。预计这六种转录本（TGFBI，LYS，RDP，MIC-1，REGA和DEHL）的六种产物被分泌或驻留在细胞表面上，并且更详细地分析这些转录物的产物。通过对这6种基因中的每一种进行定量PCR分析证实SAGE预测的异常表达水平。此外，通过原位杂交和通过从原发性肿瘤纯化的上皮细胞免疫亲和素的PCR分析来鉴定负责升高的表达的细胞类型。

2. 发明申请

WO2003065870A2 DIGITAL AMPLIFICATION FOR DETECTION OF MISMATCH REPAIR DEFICIENT TUMOR CELLS 审中-公开
标题翻译：用于检测缺陷修复缺血性肿瘤细胞的数字放大
公开(公告)号：WO2003065870A2
公开(公告)日：2003-08-14
申请号：PCT/US2003/001062
申请日：2003-01-29
申请人： THE JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE , VOGELSTEIN, Bert , TRAVERSO, Giovanni, C. , KINZLER, Kenneth, W.
发明人： VOGELSTEIN, Bert , TRAVERSO, Giovanni, C. , KINZLER, Kenneth, W.
IPC分类号： A61B
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.
摘要翻译：检测粪便DNA中的突变代表了一种有希望的非侵入性方法，用于检测平均危险人群中的结肠直肠癌。该技术的第一个实际应用之一涉及将微卫星标记物检查到具有错配修复缺陷的散发性癌症。因为这样的癌症几乎总是发生在近端结肠，这个测试是有用的乙状结肠镜检查的附件，只检测远端结肠直肠病变。

3. 发明申请

WO2003065870A3 DIGITAL AMPLIFICATION FOR DETECTION OF MISMATCH REPAIR DEFICIENT TUMOR CELLS 审中-公开
公开(公告)号：WO2003065870A3
公开(公告)日：2003-08-14
申请号：PCT/US2003/001062
申请日：2003-01-29
申请人： THE JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE , VOGELSTEIN, Bert , TRAVERSO, Giovanni, C. , KINZLER, Kenneth, W.
发明人： VOGELSTEIN, Bert , TRAVERSO, Giovanni, C. , KINZLER, Kenneth, W.
IPC分类号： C12Q1/68
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.

4. 发明申请

WO2000011195A1 C-MYC IS ACTIVATED BY BETA-CATENIN AND TCF-4 审中-公开
标题翻译： C-MYC是由卡培他滨和TCF-4激活的
公开(公告)号：WO2000011195A1
公开(公告)日：2000-03-02
申请号：PCT/US1999/018774
申请日：1999-08-20
申请人： THE JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE , HE, Tong-Chuan , VOGELSTEIN, Bert , KINZLER, Kenneth, W.
发明人： HE, Tong-Chuan , VOGELSTEIN, Bert , KINZLER, Kenneth, W.
IPC分类号： C12N15/63
CPC分类号： C07K14/47 , A61K38/00 , A61K48/00 , C07K14/4705 , C12Q1/6897
摘要： The APC tumor suppressor protein binds to β-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 β-catenin. Nuclei of APC -/- colon carcinoma cells were found to contain a stable β-catenin-hTCF-4 complex that was constitutively active, as measured by transcription of a Tcf reporter gene. Reintroduction of APC removed β-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 β-catenin/Tcf-4 transcriptional activation. Furthermore, colorectal tumors with intact APC genes were shown to contain subtle activating mutations of β-catenin that altered functionally significant phosphorylation sites. These results indicate that regulation of β-catenin is critical to APC's tumor suppressive effect and that this regulation can be circumvented by mutations in either APC or β-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一个稳定的β-连环蛋白-hTCF-4复合物，其通过Tcf报告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。

5. 发明申请

WO2004010846A2 DESIGN AND SYNTHESIS OF RENAL DIPEPTIDASE INHIBITORS 审中-公开
标题翻译：肾脏双磷脂酶抑制剂的设计与合成
公开(公告)号：WO2004010846A2
公开(公告)日：2004-02-05
申请号：PCT/US2003/023363
申请日：2003-07-28
申请人： THE JOHNS HOPKINS SCHOOL OF MEDICINE , KHAN, Saeed, R. , VOGELSTEIN, Bert , KINZLER, Kenneth, W. , GURULINGAPPA, Hallur , BUCKHAULTS, Phillip
发明人： KHAN, Saeed, R. , VOGELSTEIN, Bert , KINZLER, Kenneth, W. , GURULINGAPPA, Hallur , BUCKHAULTS, Phillip
IPC分类号： A61B
CPC分类号： C07F9/303 , A61K51/0489 , C07B59/004 , C07B2200/05
摘要： Aminophosphinic acid derivatives were synthesized as potential inhibitors of renal dipeptidase, an enzyme overexpressed in benign and malignant colon tumors. Several compounds showed potent enzyme-inhibitory activity. These compounds can be used therapeutically and diagnostically for treatment and detection of tumors.
摘要翻译：氨基次膦酸衍生物作为肾二肽酶的潜在抑制剂合成，所述肾二肽酶是在良性和恶性结肠肿瘤中过表达的酶。几种化合物显示出有效的酶抑制活性。这些化合物可用于治疗和诊断治疗和检测肿瘤。

6. 发明申请

WO1993020235A1 METHODS OF DETECTING MAMMALIAN NUCLEIC ACIDS ISOLATED FROM STOOL SPECIMEN AND REAGENTS THEREFOR 审中-公开
标题翻译：检测从其样本和试剂中分离的MAMMALIAN核酸的方法
公开(公告)号：WO1993020235A1
公开(公告)日：1993-10-14
申请号：PCT/US1993002960
申请日：1993-03-31
申请人： THE JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE
发明人： THE JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE , VOGELSTEIN, Bert , KINZLER, Kenneth, W.
IPC分类号： C12Q01/68
CPC分类号： G01N33/50 , C12Q1/6806 , C12Q1/6886 , C12Q2600/156 , Y10S435/81 , Y10T436/143333 , C12Q2527/137
摘要： A method to isolate nucleic acids from stool specimen which is used to detect mutations associated with gastrointestinal neoplasia. An exemplary result obtained is shown in the Figure. Reagents used to carry out the isolation of nucleic acids are also disclosed.
摘要翻译：从粪便标本中分离核酸的方法，用于检测与胃肠道肿瘤相关的突变。获得的示例性结果示于图中。还公开了用于进行核酸分离的试剂。

7. 发明申请

WO1997010363A1 METHOD FOR SERIAL ANALYSIS OF GENE EXPRESSION 审中-公开
标题翻译：基因表达序列分析方法
公开(公告)号：WO1997010363A1
公开(公告)日：1997-03-20
申请号：PCT/US1996014638
申请日：1996-09-12
申请人： THE JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE
发明人： THE JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE , KINZLER, Kenneth, W. , VOGELSTEIN, Bert , VELVULESCU, Victor, E. , ZHANG, Lin
IPC分类号： C12Q01/68
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 analysed. 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。

8. 发明申请

WO2021163546A1 METHODS AND MATERIALS FOR ASSESSING NUCLEIC ACIDS 审中-公开
公开(公告)号：WO2021163546A1
公开(公告)日：2021-08-19
申请号：PCT/US2021/017937
申请日：2021-02-12
申请人： THE JOHNS HOPKINS UNIVERSITY , PAPADOPOULOS, Nickolas , KINZLER, Kenneth W. , VOGELSTEIN, Bert , COHEN, Joshua David
发明人： PAPADOPOULOS, Nickolas , KINZLER, Kenneth W. , VOGELSTEIN, Bert , COHEN, Joshua David
IPC分类号： C12Q1/686
摘要： Provided herein are systems, kits, compositions and methods for sequencing library preparation and sequencing workflow (e.g., for the identification of mutations). In certain embodiments, provides herein systems and methods to identically barcode both strands of templates, and PCR-based enrichment of each strand that does not require hybridization capture.

9. 发明申请

WO2012142213A2 SAFE SEQUENCING SYSTEM 审中-公开
标题翻译：安全排序系统
公开(公告)号：WO2012142213A2
公开(公告)日：2012-10-18
申请号：PCT/US2012/033207
申请日：2012-04-12
申请人： THE JOHNS HOPKINS UNIVERSITY , VOGELSTEIN, Bert , KINZLER, Kenneth W. , PAPADOPOULOS, Nickolas , KINDE, Isaac
发明人： VOGELSTEIN, Bert , KINZLER, Kenneth W. , PAPADOPOULOS, Nickolas , KINDE, Isaac
IPC分类号： C12Q1/68 , C12N15/11
CPC分类号： C12Q1/6874 , C12Q1/6806 , C12Q1/6869 , C12Q1/6876 , C12Q2563/179 , C12Q2600/158 , C12Q2535/122 , C12Q2565/514
摘要： The identification of mutations that are present in a small fraction of DNA templates is essential for progress in several areas of biomedical research. Though massively parallel sequencing instruments are in principle well-suited to this task, the error rates in such instruments are generally too high to allow confident identification of rare variants. We here describe an approach that can substantially increase the sensitivity of massively parallel sequencing instruments for this purpose. One example of this approach, called "Safe-SeqS" for (Safe-Sequencing System) includes (i) assignment of a unique identifier (UID) to each template molecule; (ii) amplification of each uniquely tagged template molecule to create UID-families; and (iii) redundant sequencing of the amplification products. PCR fragments with the same UID are truly mutant ("super-mutants") if ≥95% of them contain the identical mutation. We illustrate the utility of this approach for determining the fidelity of a polymerase, the accuracy of oligonucleotides synthesized in vitro , and the prevalence of mutations in the nuclear and mitochondrial genomes of normal cells.
摘要翻译：存在于DNA模板的一小部分中的突变的鉴定对于在几个生物医学研究领域的进展是必不可少的。尽管大规模并行测序仪器原则上非常适合于此任务，但是这些仪器中的错误率通常太高，无法确定罕见的变体。我们在这里描述了一种可以显着增加大规模并行测序仪器对此目的的灵敏度的方法。这种方法的一个例子是（Safe-Sequencing System），称为“Safe-SeqS”，包括（i）将唯一标识符（UID）分配给每个模板分子; （ii）每个唯一标记的模板分子的扩增以产生UID家族; 和（iii）扩增产物的冗余测序。具有相同UID的PCR片段是真正的突变体（“超突变体”），如果其中95％含有相同的突变。我们说明了这种方法用于确定聚合酶的保真度，体外合成的寡核苷酸的准确性以及正常细胞的核和线粒体基因组中突变的流行率的效用。

10. 发明申请

WO2012071096A2 ARID1A AND PPP2R1A MUTATIONS IN CANCER 审中-公开
标题翻译： ARID1A和PPP2R1A突变在癌症中
公开(公告)号：WO2012071096A2
公开(公告)日：2012-05-31
申请号：PCT/US2011/050487
申请日：2011-09-06
申请人： THE JOHNS HOPKINS UNIVERSITY , VOGELSTEIN, Bert , KINZLER, Kenneth W. , VELCULESCU, Victor , PAPADOPOULOS, Nickolas , JONES, Sian
发明人： VOGELSTEIN, Bert , KINZLER, Kenneth W. , VELCULESCU, Victor , PAPADOPOULOS, Nickolas , JONES, Sian
IPC分类号： C12Q1/68 , C12N5/09 , G01N33/68 , A61K31/7088 , C12N15/11
CPC分类号： C12Q1/6886 , A61K31/7088 , A61K31/711 , C12Q2600/156 , G01N33/5011
摘要： Two genes, ARID1A (AT-rich interactive domain-containing protein 1A) and PPP2R1A (protein-phosphatase 2, regulatory subunit 1, alpha), can be used in methods which are useful for detecting cancer, diagnosing cancer, contributing to a diagnosis of cancer, confirming a diagnosis of cancer, identifying appropriate treatments for cancer, monitoring treatment of cancer, and evaluating treatment protocols for cancer, including ovarian clear cell carcinoma, breast cancer, colon cancer, gastric cancer, lung cancer, medulloblastoma, pancreatic cancer, and prostate cancer.
摘要翻译：在可用于检测癌症的方法中可以使用两种基因，即ARID1A（富含AT的交互结构域的蛋白质1A）和PPP2R1A（蛋白质磷酸酶2，调节亚基1，α）诊断癌症，有助于诊断癌症，确认癌症的诊断，鉴别癌症的适当治疗，监测癌症的治疗，以及评估癌症的治疗方案，包括卵巢透明细胞癌，乳腺癌，结肠癌，胃癌，肺癌癌症，成神经管细胞瘤，胰腺癌和前列腺癌。

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