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111. 发明公开

EP2988760A4 C. NOVYI FOR THE TREATMENT OF SOLID TUMORS IN HUMANS 无效
标题翻译： C.诺氏实体瘤治疗人的
公开(公告)号：EP2988760A4
公开(公告)日：2016-10-05
申请号：EP14774988
申请日：2014-03-28
申请人： BIOMED VALLEY DISCOVERIES INC , UNIV JOHNS HOPKINS
发明人： SAHA SAURABH , ZHOU SHIBIN , VOGELSTEIN BERT , KINZLER KENNETH W
IPC分类号： A61K35/66 , A61P35/00
CPC分类号： A61K35/74 , A61K31/65 , A61K35/742 , A61K45/06 , A61K2035/11 , A61N5/10

112. 发明公开

EP2536854A4 PERSONALIZED TUMOR BIOMARKERS 有权
标题翻译：个性化肿瘤生物标志物
公开(公告)号：EP2536854A4
公开(公告)日：2013-08-07
申请号：EP11745196
申请日：2011-02-17
申请人： UNIV JOHNS HOPKINS
发明人： VOGELSTEIN BERT , KINZLER KENNETH W , VELCULESCU VICTOR , DIAZ LUIS , LEARY REBECCA J
IPC分类号： C12Q1/68 , C12N15/11 , C40B40/06
CPC分类号： C12Q1/6886 , C12Q2600/156
摘要： Clinical management of human cancer is dependent on the accurate monitoring of residual and recurrent tumors. We have developed a method, called personalized analysis of rearranged ends (PARE), which can identify translocations in solid tumors. Analysis of four colorectal and two breast cancers revealed an average of nine rearranged sequences (range 4 to 15) per tumor. Polymerase chain reaction with primers spanning the breakpoints were able to detect mutant DNA molecules present at levels lower than 0.001% and readily identified mutated circulating DNA in patient plasma samples. This approach provides an exquisitely sensitive and broadly applicable approach for the development of personalized biomarkers to enhance the clinical management of cancer patients.
摘要翻译：人类癌症的临床管理取决于对残留和复发性肿瘤的准确监测。我们开发了一种称为重排末端（PARE）的个性化分析方法，可以识别实体瘤易位。对4例结直肠癌和2例乳腺癌的分析显示，每个肿瘤平均有9个重排序列（范围4至15）。聚合酶链反应与穿过断点的引物能够检测出存在于低于0.001％水平的突变DNA分子，并且容易鉴定出患者血浆样品中突变的循环DNA。这种方法为个体化生物标志物的开发提供了一种非常灵敏和广泛适用的方法，以加强癌症患者的临床管理。

113. 发明公开

EP2417268A4 DIAGNOSTIC METHOD USING PALB2 有权
标题翻译：与PALB2诊断步骤
公开(公告)号：EP2417268A4
公开(公告)日：2012-07-11
申请号：EP10749365
申请日：2010-03-05
申请人： UNIV JOHNS HOPKINS
发明人： VOGELSTEIN BERT , KINZLER KENNETH W , PARSONS D WILLIAMS , JONES SIAN , KERN SCOTT , HRUBAN RALPH , ESHLEMAN JAMES R , GOGGINS MICHAEL , KLEIN ALISON , HIDALGO MANUEL , VELCULESCU VICTOR E
IPC分类号： C12Q1/68 , G01N33/574 , G01N33/68
CPC分类号： C12Q1/6886 , A61K31/407 , C12Q2600/106 , C12Q2600/156 , C12Q2600/158 , G01N33/57438 , G01N2333/47

114. 发明公开

EP2038427A4 SINGLE-MOLECULE PCR ON MICROPARTICLES IN WATER-IN-OIL EMULSIONS 审中-公开
标题翻译：单分子PCR微粒的水包油乳液
公开(公告)号：EP2038427A4
公开(公告)日：2010-07-07
申请号：EP07809665
申请日：2007-06-19
申请人： UNIV JOHNS HOPKINS
发明人： DIEHL FRANK , KINZLER KENNETH W , VOGELSTEIN BERT
IPC分类号： C12Q1/68 , C07H21/02
CPC分类号： C12Q1/686 , C12Q1/6876 , C12Q2600/16 , C12Q2527/125 , C12Q2527/153 , C12Q2565/537

115. 发明公开

EP1675465A4 IMPROVED COMBINATION BACTERIOLYTIC THERAPY FOR THE TREATMENT OF TUMORS 有权
标题翻译：改进的溶菌联合治疗肿瘤的治疗
公开(公告)号：EP1675465A4
公开(公告)日：2008-07-30
申请号：EP04809987
申请日：2004-10-21
申请人： UNIV JOHNS HOPKINS
发明人： DANG LONG , BETTEGOWDA CHETAN , KINZLER KENNETH W , VOGELSTEIN BERT
IPC分类号： A61K35/74 , A01N63/00 , A61K20060101 , A61K31/337 , A61K31/427 , A61K45/06 , A61P35/00
CPC分类号： A61K35/742 , A61K31/337 , A61K31/427 , A61K45/06 , Y10S435/842 , A61K2300/00
摘要： Current approaches for treating cancer are limited, in part, by the inability of drugs to affect the poorly vascularized regions of tumors. We have found that spores of anaerobic bacteria in combination with agents which interact with microtubules can cause the destruction of both the vascular and avascular compartments of tumors. Two classes of microtubule inhibitors were found to exert markedly different effects. Some agents that inhibited microtubule synthesis, such as vinorelbine, caused rapid, massive hemorrhagic necrosis when used in combination with spores. In contrast, agents that stabilized microtubules, such as the taxane docetaxel, resulted in slow tumor regressions that killed most neoplastic cells. Remaining cells in the poorly perfused regions of tumors could be eradicated by sponzlated bacteria. Mechanistic studies showed that the microtubule destabilizers, but not the microtubule stabilizers, radically reduced blood flow to tumors, thereby enlarging the hypoxic niche in which spores could germinate. A single intravenous injection of spores plus selected microtubule-interacting agents was able to cause regressions of several tumors in the absence of excessive toxicity.

116. 发明公开

EP1534331A4 MEMBRANE ASSOCIATED TUMOR ENDOTHELIUM MARKERS 有权
标题翻译：膜相关肿瘤内皮MARKER
公开(公告)号：EP1534331A4
公开(公告)日：2006-12-13
申请号：EP03742108
申请日：2003-06-23
申请人： UNIV JOHNS HOPKINS MED
发明人： ST CROIX BRAD , KINZLER KENNETH W , VOGELSTEIN BERT
IPC分类号： C07K16/28 , G01N33/50 , A61K38/00 , A61K38/17 , A61K39/00 , A61K39/395 , A61K48/00 , A61P9/00 , A61P13/12 , A61P17/02 , A61P17/06 , A61P19/02 , A61P27/00 , A61P35/00 , A61P43/00 , C07K14/705 , C12N15/09 , C12P21/08 , C12Q1/02 , C12Q1/68 , G01N33/15 , G01N33/53 , G01N33/566 , G01N33/68
CPC分类号： C07K14/705 , A61K38/00 , A61K2039/505 , C12Q1/6886 , C12Q2600/136 , C12Q2600/158

117. 发明公开

EP1523573A4 DISEASE DETECTION BY DIGITAL PROTEIN TRUNCATION ASSAYS 有权
标题翻译：疾病检测与DIGITAL蛋白减少试验
公开(公告)号：EP1523573A4
公开(公告)日：2006-03-08
申请号：EP02808038
申请日：2002-12-04
申请人： UNIV JOHNS HOPKINS MED
发明人： TRAVERSO C GIOVANNI , KINZLER KENNETH W , VOGELSTEIN BERT
IPC分类号： G01N33/483 , C12N15/09 , C12Q1/68 , G01N27/447 , G01N33/574 , G01N33/68 , C07H21/02 , C07H21/04 , C12P19/34
CPC分类号： C12Q1/6886 , C12Q2600/156 , G01N33/68
摘要： Genetic diseases can be diagnosed by detection of mutations in causative genes. Protein truncation assays can be used to detect gene products of truncation-type mutations. However, the sensitivity of the assays is often insufficient to detect mutations present in a sample of DNA at a low frequency. Sensitivity can be increased by dividing samples so that the signal generated by a mutant allele comprises a larger fraction of the total alleles than prior to dividing. Thus a previously undetectable signal generated by the mutant allele can become detectable in the assay. Such increased sensitivity permits detection at early stages and in samples having high levels of other alleles.

118. 发明公开

EP0761822A3 Method for serial analysis of gene expression 失效
标题翻译：基因表达的序列分析方法
公开(公告)号：EP0761822A3
公开(公告)日：1998-08-05
申请号：EP96306634
申请日：1996-09-12
申请人： UNIV JOHNS HOPKINS MED
发明人： KINZLER KENNETH W , VELCULESCU VICTOR E , VOGELSTEIN BERT , ZHANG LIN
IPC分类号： C12N15/09 , C12M1/00 , C12N15/10 , C12Q1/68 , C40B40/02 , C40B50/06 , G06F17/30
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.

119. 发明申请

WO9841631A3 BETA -CATENIN, TCF-4, AND APC INTERACT TO PREVENT CANCER 审中-公开
标题翻译： BETA-CATENIN，TCF-4和APC相互作用以预防癌症
公开(公告)号：WO9841631A3
公开(公告)日：1998-12-03
申请号：PCT/US9805506
申请日：1998-03-20
申请人： UNIV JOHNS HOPKINS , UNIV UTRECHT
发明人： BARKER NICK , CLEVERS HANS , KINZLER KENNETH W , KORINEK VLADIMIR , MORIN PATRICE J , SPARKS ANDREW B , VOGELSTEIN BERT
IPC分类号： G01N33/50 , A61K31/711 , A61K38/00 , A61K48/00 , A61P35/00 , C07K14/47 , C12N15/09 , C12N15/12 , C12Q1/68 , G01N33/15 , A61K38/17
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.

120. 发明申请

WO9832847A3 CHARACTERIZATION OF THE YEAST TRANSCRIPTOME 审中-公开
标题翻译： YEAST转录物的表征
公开(公告)号：WO9832847A3
公开(公告)日：1998-11-26
申请号：PCT/US9801216
申请日：1998-01-22
申请人： UNIV JOHNS HOPKINS MED
发明人： VELCULESCU VICTOR E , VOGELSTEIN BERT , KINZLER KENNETH W
IPC分类号： C12N15/09 , C07K14/395 , C12Q1/02 , C12Q1/68 , C12R1/85 , C12N15/10 , C12N15/31
CPC分类号： C07K14/395
摘要： Yeast genes which are differentially expressed during the cell cycle are described. They can be used to study, affect, and monitor the cell cycle of a eukaryotic cell. They can be used to obtain human homologs involved in cell cycle regulation. They can be used to identify antifungal agents. They can be formed into arrays on solid supports for interrogation of a cell's transcriptome under various conditions.

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