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1. 发明授权

US07983850B2 Diagnosis, prognosis, identification, and classification of multiple myeloma based on gene expression profiling 有权
标题翻译：基于基因表达谱的多发性骨髓瘤的诊断，预后，鉴定和分类
公开(公告)号：US07983850B2
公开(公告)日：2011-07-19
申请号：US12012302
申请日：2008-02-01
申请人： John D. Shaughnessy , Bart Barlogie , Fenghuang Zhan
发明人： John D. Shaughnessy , Bart Barlogie , Fenghuang Zhan
IPC分类号： G01N33/48 , C12Q1/68 , G06G7/58
CPC分类号： C12Q1/6886 , C12Q1/6837 , C12Q2600/112 , C12Q2600/118 , C12Q2600/136 , C12Q2600/158 , Y02A90/26
摘要： Provided herein is a method for gene expression profiling multiple myeloma patients into distinct subgroups via DNA hybridization and hierarchical clustering analysis of the hybridization data where the results may further be used to identify therapeutic gene targets. Also provided is a method for controlling bone loss in an individual via pharmacological inhibitors of DKK1 protein. In addition provided herein is a method for diagnosing multiple myeloma using a 15-gene model that classifies myeloma into groups 1-7.
摘要翻译：本文提供了通过DNA杂交和杂交数据的分层聚类分析将多发性骨髓瘤患者分类为不同亚组的基因表达方法，其中结果可进一步用于鉴定治疗性基因靶标。还提供了通过DKK1蛋白的药理学抑制剂来控制个体骨丢失的方法。此外，本文提供了使用将骨髓瘤分为1-7组的15-基因模型来诊断多发性骨髓瘤的方法。

2. 发明授权

US07741035B2 Use of gene expression profiling to predict survival in cancer patient 有权
标题翻译：使用基因表达谱来预测癌症患者的存活
公开(公告)号：US07741035B2
公开(公告)日：2010-06-22
申请号：US11147829
申请日：2005-06-08
申请人： John D. Shaughnessy , Bart Barlogie , Fenghuang Zhan
发明人： John D. Shaughnessy , Bart Barlogie , Fenghuang Zhan
IPC分类号： C12Q1/68 , G01N33/48
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/112 , C12Q2600/118 , C12Q2600/136 , C12Q2600/178
摘要： Gene expression profiling in multiple myeloma patients identifies genes that distinguish between patients with subsequent early death or long survival after treatment. Poor survival is linked to over-expression of genes such as ASPM, OPN3 and CKS1B which are located in chromosome 1q. Given the frequent amplification of 1q in many cancers, it is possible that these genes can be used as powerful prognostic markers and therapeutic targets for multiple myeloma and other cancer.
摘要翻译：在多发性骨髓瘤患者中进行基因表达谱分析鉴定了随后早期死亡或治疗后长期存活的患者之间区分的基因。差的存活与位于染色体1q的基因如ASPM，OPN3和CKS1B的过表达有关。鉴于许多癌症中1q的频繁扩增，这些基因可能被用作多种骨髓瘤和其他癌症的强大的预后标志物和治疗靶点。

3. 发明授权

US07371736B2 Gene expression profiling based identification of DKK1 as a potential therapeutic targets for controlling bone loss 失效
标题翻译：基因表达谱基于DKK1的鉴定作为控制骨丢失的潜在治疗靶点
公开(公告)号：US07371736B2
公开(公告)日：2008-05-13
申请号：US10931780
申请日：2004-09-01
申请人： John D. Shaughnessy , Bart Barlogie , Fenghuang Zhan
发明人： John D. Shaughnessy , Bart Barlogie , Fenghuang Zhan
IPC分类号： A61K39/00 , C12Q1/68 , A01N43/04 , A01N57/00
CPC分类号： C12Q1/6886 , C12Q1/6837 , C12Q2600/112 , C12Q2600/118 , C12Q2600/136 , C12Q2600/158 , Y02A90/26
摘要： Gene expression profiling reveals four distinct subgroups of multiple myeloma that have significant correlation with various clinical characteristics. Diagnosis for multiple myeloma (and possibly monoclonal gammopathy of undetermined significance) based on differential expression of 14 genes, as well as prognosis for the four subgroups of multiple myeloma based on the expression of 24 genes are established. A 15-gene model that classifies myeloma into 7 groups is also reported. Gene expression profiling also allows placing multiple myeloma into a developmental schema parallel to that of normal plasma cell differentiation. Development of a gene expression- or developmental stage-based classification system for multiple myeloma would lead to rational design of more accurate and sensitive diagnostics, prognostics and tumor-specific therapies for multiple myeloma.
摘要翻译：基因表达分析显示与各种临床特征有显着相关性的多个骨髓瘤的四个不同亚组。基于14个基因的差异表达的多发性骨髓瘤的诊断（可能是未确定的意义的单克隆丙种球蛋白病），以及基于24个基因的表达的多发性骨髓瘤的四个亚组的预后。还报道了将骨髓瘤分为7组的15基因模型。基因表达谱也允许将多发性骨髓瘤放置在与正常浆细胞分化平行的发育模式中。开发基因表达或基于发育阶段的多发性骨髓瘤分类系统将导致对多发性骨髓瘤的更准确和敏感的诊断，预后和肿瘤特异性治疗的合理设计。

4. 发明授权

US07308364B2 Diagnosis of multiple myeloma on gene expression profiling 有权
标题翻译：多发性骨髓瘤诊断基因表达谱
公开(公告)号：US07308364B2
公开(公告)日：2007-12-11
申请号：US10454263
申请日：2003-06-04
申请人： John D. Shaughnessy , Fenghuang Zhan , Bart Barlogie
发明人： John D. Shaughnessy , Fenghuang Zhan , Bart Barlogie
IPC分类号： G01N33/48 , C12Q1/68 , C12P19/34 , C07H21/04
CPC分类号： C12Q1/6886 , C12Q1/6837 , C12Q2600/112 , C12Q2600/158 , Y02A90/24
摘要： Gene expression profiling between normal B cells/plasma cells and multiple myeloma cells revealed four distinct subgroups of multiple myeloma plasma cells that have significant correlation with clinical characteristics known to be associated with poor prognosis. Diagnosis for multiple myeloma (and possibly monoclonal gammopathy of undetermined significance) based on differential expression of 14 genes, as well as prognostics for the four subgroups of multiple myeloma based on the expression of 24 genes were also established. Gene expression profiling also allows placing multiple myeloma into a developmental schema parallel to that of normal plasma cell differentiation. The development of a gene expression- or developmental stage-based classification system for multiple myeloma would lead to rational design of more accurate and sensitive diagnostics, prognostics and tumor-specific therapies for multiple myeloma.
摘要翻译：在正常B细胞/浆细胞和多发性骨髓瘤细胞之间的基因表达谱显示与已知与不良预后相关的临床特征具有显着相关性的多个骨髓瘤浆细胞的四个不同亚组。还建立了基于14个基因的差异表达的多发性骨髓瘤的诊断（以及可能的未确定意义的单克隆丙种球蛋白病），以及基于24个基因的表达的多发性骨髓瘤的四个亚组的预后。基因表达谱也允许将多发性骨髓瘤放置在与正常浆细胞分化平行的发育模式中。开发基因表达或发育阶段的多发性骨髓瘤分类系统将导致对多发性骨髓瘤的更准确和敏感的诊断，预后和肿瘤特异性治疗的合理设计。

5. 发明授权

US08843320B2 Use of gene expression profiling to predict survival in cancer patient 有权
标题翻译：使用基因表达谱来预测癌症患者的存活
公开(公告)号：US08843320B2
公开(公告)日：2014-09-23
申请号：US11133937
申请日：2005-05-20
申请人： John D. Shaughnessy , Fenghuang Zhan , Bart Barlogie
发明人： John D. Shaughnessy , Fenghuang Zhan , Bart Barlogie
IPC分类号： G01N33/50 , C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/118 , C12Q2600/158
摘要： Gene expression profiling in multiple myeloma patients identifies genes that distinguish between patients with subsequent early death or long survival after treatment. Poor survival is linked to over-expression of genes such as ASPM, OPN3 and CKS1B which are located in chromosome 1q. Given the frequent amplification of 1q in many cancers, it is possible that these genes can be used as powerful prognostic markers and therapeutic targets for multiple myeloma and other cancer.
摘要翻译：在多发性骨髓瘤患者中进行基因表达谱分析鉴定了随后早期死亡或治疗后长期存活的患者之间区分的基因。差的存活与位于染色体1q的基因如ASPM，OPN3和CKS1B的过表达有关。鉴于许多癌症中1q的频繁扩增，这些基因可能被用作多种骨髓瘤和其他癌症的强大的预后标志物和治疗靶点。

6. 发明申请

US20110319470A1 Diagnosis, prognosis and identification of potential therapeutic targets of multiple myeloma based on gene expression profiling 审中-公开
标题翻译：基于基因表达谱的多发性骨髓瘤的潜在治疗靶点的诊断，预后和鉴定
公开(公告)号：US20110319470A1
公开(公告)日：2011-12-29
申请号：US13135574
申请日：2011-07-08
申请人： John D. Shaughnessy , Bart Barlogie , Fenghuang Zhan
发明人： John D. Shaughnessy , Bart Barlogie , Fenghuang Zhan
IPC分类号： A61K31/713 , A61P35/00 , G01N33/574 , C12Q1/68 , C40B30/04
CPC分类号： C12Q1/6886 , C12Q1/6837 , C12Q2600/112 , C12Q2600/118 , C12Q2600/136 , C12Q2600/158 , Y02A90/26
摘要： Provided herein is a method for gene expression profiling multiple myeloma patients into distinct subgroups via DNA hybridization and hierarchical clustering analysis of the hybridization data where the results may further be used to identify therapeutic gene targets. Also provided is a method for controlling bone loss in an individual via pharmacological inhibitors of DKK1 protein. In addition provided herein is a method for diagnosing multiple myeloma using a 15-gene model that classifies myeloma into subtypes 1-7.
摘要翻译：本文提供了通过DNA杂交和杂交数据的分层聚类分析将多发性骨髓瘤患者分类为不同亚组的基因表达方法，其中结果可进一步用于鉴定治疗性基因靶标。还提供了通过DKK1蛋白的药理学抑制剂来控制个体骨丢失的方法。此外，本文提供了使用将骨髓瘤分类为亚型1-7的15-基因模型来诊断多发性骨髓瘤的方法。

7. 发明授权

US07935679B2 Gene expression profiling based identification of CKS1B as a potential therapeutic target in multiple myeloma 有权
标题翻译：基因表达谱鉴定CKS1B作为多发性骨髓瘤的潜在治疗靶点
公开(公告)号：US07935679B2
公开(公告)日：2011-05-03
申请号：US11110209
申请日：2005-04-20
申请人： John D. Shaughnessy , Bart Barlogie , Fenghuang Zhan
发明人： John D. Shaughnessy , Bart Barlogie , Fenghuang Zhan
IPC分类号： A01N43/04 , C12Q1/68 , G01N33/48
CPC分类号： C12Q1/6886 , C12Q1/6809 , C12Q1/6837 , C12Q2600/112 , C12Q2600/118 , C12Q2600/136 , Y02A90/26 , C12Q2565/501
摘要： Gene expression profiling is a powerful tool that has varied utility. It enables classification of multiple myeloma into subtypes and identifing genes directly involved in disease pathogensis and clinical manifestation. The present invention used gene expression profiling in large uniformly treated population of patients with myeloma to identify genes associated with poor prognosis. It also demonstrated that over-expression of CKS1B gene, mainly due to gene amplification that was determined by Fluorescent in-situ hybridization to impart a poor prognosis in multiple myleoma. It is further contemplated that therapeutic strategies that directly target CKS1B or related pathways may represent novel, and more specific means of treating high risk myeloma and may prevent its secondary evolution.
摘要翻译：基因表达谱是一种功能多样的强大工具。它可以将多发性骨髓瘤分类为亚型，并确定直接参与疾病病理和临床表现的基因。本发明在大量均匀治疗的骨髓瘤患者群中使用基因表达谱来鉴定与预后不良相关的基因。它还表明CKS1B基因的过表达，主要是由于通过荧光原位杂交确定的基因扩增，以在多种myleoma中预后不良。进一步预期，直接靶向CKS1B或相关途径的治疗策略可以代表治疗高风险骨髓瘤的新颖和更具体的手段，并且可以防止其二次进化。

8. 发明授权

US07894992B2 Diagnosis and classification of multiple myeloma 有权
标题翻译：多发性骨髓瘤的诊断和分类
公开(公告)号：US07894992B2
公开(公告)日：2011-02-22
申请号：US10409004
申请日：2003-04-08
申请人： John D. Shaughnessy , Bart Barlogie , Fenghuang Zhan
发明人： John D. Shaughnessy , Bart Barlogie , Fenghuang Zhan
IPC分类号： G01N33/48 , C12Q1/68 , C12M1/34 , C07H21/04
CPC分类号： C12Q1/6886 , C12Q1/6837 , C12Q2600/112 , C12Q2600/158
摘要： Gene expression profiling between normal B cells/plasma cells and multiple myeloma cells revealed four distinct subgroups of multiple myeloma plasma cells that have significant correlation with clinical characteristics known to be associated with poor prognosis. Diagnosis for multiple myeloma (and possibly monoclonal gammopathy of undetermined significance) based on differential expression of 14 genes, as well as prognostics for the four subgroups of multiple myeloma based on the expression of 24 genes were also established. Gene expression profiling also allows placing multiple myeloma into a developmental schema parallel to that of normal plasma cell differentiation. The development of a gene expression- or developmental stage-based classification system for multiple myeloma would lead to rational design of more accurate and sensitive diagnostics, prognostics and tumor-specific therapies for multiple myeloma.
摘要翻译：在正常B细胞/浆细胞和多发性骨髓瘤细胞之间的基因表达谱显示与已知与不良预后相关的临床特征具有显着相关性的多个骨髓瘤浆细胞的四个不同亚组。还建立了基于14个基因的差异表达的多发性骨髓瘤的诊断（以及可能的未确定意义的单克隆丙种球蛋白病），以及基于24个基因的表达的多发性骨髓瘤的四个亚组的预后。基因表达谱也允许将多发性骨髓瘤放置在与正常浆细胞分化平行的发育模式中。开发基因表达或发育阶段的多发性骨髓瘤分类系统将导致对多发性骨髓瘤的更准确和敏感的诊断，预后和肿瘤特异性治疗的合理设计。

9. 发明授权

US07668659B2 Diagnosis and classification of multiple myeloma 有权
标题翻译：多发性骨髓瘤的诊断和分类
公开(公告)号：US07668659B2
公开(公告)日：2010-02-23
申请号：US10289746
申请日：2002-11-07
申请人： John D. Shaughnessy , Bart Barlogie , Fenghuang Zhan
发明人： John D. Shaughnessy , Bart Barlogie , Fenghuang Zhan
IPC分类号： G01N33/48 , C12Q1/68 , C07H21/04
CPC分类号： C12Q1/6886 , C12Q1/6837 , C12Q2600/158
摘要： Gene expression profiling between normal B cells/plasma cells and multiple myeloma cells revealed four distinct subgroups of multiple myeloma plasma cells that have significant correlation with clinical characteristics known to be associated with poor prognosis. Diagnosis for multiple myeloma (and possibly monoclonal gammopathy of undetermined significance) based on differential expression of 14 genes, as well as prognostics for the four subgroups of multiple myeloma based on the expression of 24 genes were also established. Gene expression profiling also allows placing multiple myeloma into a developmental schema parallel to that of normal plasma cell differentiation. The development of a gene expression- or developmental stage-based classification system for multiple myeloma would lead to rational design of more accurate and sensitive diagnostics, prognostics and tumor-specific therapies for multiple myeloma.
摘要翻译：在正常B细胞/浆细胞和多发性骨髓瘤细胞之间的基因表达谱显示与已知与不良预后相关的临床特征具有显着相关性的多个骨髓瘤浆细胞的四个不同亚组。还建立了基于14个基因的差异表达的多发性骨髓瘤的诊断（以及可能的未确定意义的单克隆丙种球蛋白病），以及基于24个基因的表达的多发性骨髓瘤的四个亚组的预后。基因表达谱也允许将多发性骨髓瘤放置在与正常浆细胞分化平行的发育模式中。开发基因表达或发育阶段的多发性骨髓瘤分类系统将导致对多发性骨髓瘤的更准确和敏感的诊断，预后和肿瘤特异性治疗的合理设计。

10. 发明申请

US20080234139A1 Diagnosis, prognosis and identification of potential therapeutic targets of multiple myeloma based on gene expression profiling 审中-公开
标题翻译：基于基因表达谱的多发性骨髓瘤的潜在治疗靶点的诊断，预后和鉴定
公开(公告)号：US20080234139A1
公开(公告)日：2008-09-25
申请号：US12001110
申请日：2007-12-10
申请人： John D. Shaughnessy , Bart Barlogie , Fenghuang Zhan
发明人： John D. Shaughnessy , Bart Barlogie , Fenghuang Zhan
IPC分类号： C40B30/04 , C12Q1/68 , G01N33/53
CPC分类号： C12Q1/6886 , C12Q1/6837 , C12Q2600/112 , C12Q2600/158 , Y02A90/24
摘要： Provided herein are methods for diagnosing and treating multiple myeloma based on statistical analysis of and subsequent increasing/inhibiting expression of subgroups of plasma cells and B cell genes. Also provided are methods for a developmental stage-based classification for multiple myeloma using hierarchical clustering analysis of plasma cell and B cell nucleic acids and for discriminating among normal, hyperplastic and malignant using gene expression array data and statistical analysis thereof. In addition methods for determining the risk of developing bone disease in a test individual by examining expression levels of a WNT signaling antagonist, such as DKK1, are provided. A kit comprising anti-DKK1 antibodies and detection reagents for measuring DKK1 protein levels also is provided.
摘要翻译：本文提供了基于浆细胞和B细胞基因亚组的统计分析和随后增加/抑制表达来诊断和治疗多发性骨髓瘤的方法。还提供了使用等离子体聚集分析血浆细胞和B细胞核酸并用于使用基因表达阵列数据和其统计分析区分正常，增生和恶性的多发性骨髓瘤的基于发育阶段的分类的方法。另外提供了通过检查WNT信号传导性拮抗剂如DKK1的表达水平来测定测试个体发生骨疾病风险的方法。还提供了包含抗DKK1抗体的试剂盒和用于测量DKK1蛋白质水平的检测试剂。

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