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    • 2. 发明申请
    • CELLULAR ARRAYS FOR RAPID MOLECULAR PROFILING
    • 细胞阵列用于快速分子分析
    • WO9944062B1
    • 1999-11-04
    • PCT/US9904000
    • 1999-02-24
    • US HEALTHKALLIONIEMI OLLIKONONEN JUHALEIGHTON STEPHEN BSAUTER GUIDO
    • KALLIONIEMI OLLIKONONEN JUHALEIGHTON STEPHEN BSAUTER GUIDO
    • G01N33/48B01L3/00C12Q1/04C12Q1/24C12Q1/28C12Q1/68G01N1/08G01N1/28G01N1/31G01N1/36G01N33/50G01N33/543G01N33/566G01N33/574G01N37/00G02B21/34
    • G02B21/34B01J2219/00659B01J2219/00702B01L3/5085C12Q1/6811G01N1/08G01N1/312G01N1/36G01N33/5005G01N33/54306G01N2001/282G01N2001/368G06F19/20G06F19/24
    • A method is disclosed for rapid molecular profiling of tissue or other cellular specimens by placing a donor specimen in an assigned location in a recipient array, providing copies of the array, and performing a different biological analysis of each copy. In one embodiment, the copies of the array are formed by placing elongated specimens in a three dimensional matrix, and cutting sections from the matrix to form multiple copies of a two dimensional array that can then be subjected to the different biological analyses. Alternatively, the array can be formed from cell suspensions such that identical multiple copies of an array are formed, in which corresponding positions in the copies of the array have samples from the same or similar specimen. The results of the different biological analyses are compared to determine if there are correlations between the results of the different biological analyses at each assigned location. In some embodiments, the specimens may be tissue specimens from different tumors, which are subjected to multiple parallel molecular (including genetic and immunological) analyses. The results of the parallel analyses are then used to detect common molecular characteristics of the tumor type, which can subsequently be used in the diagnosis or treatment of the disease. The biological characteristics of the tissue can be correlated with clinical or other information, to detect characteristics associated with the tissue, such as susceptibility or resistance to particular types of drug treatment. Other examples of suitable tissues which can be placed in the matrix include tissue from transgenic or model organisms, or cellular suspensions (such as cytological preparations or specimens of liquid malignancies or cell lines).
    • 公开了一种方法,用于通过将供体样本放置在受体阵列中的指定位置,提供阵列的拷贝以及对每个拷贝进行不同的生物学分析来对组织或其他细胞样本进行快速分子谱分析。 在一个实施例中,通过将细长样本放置在三维矩阵中形成阵列的副本,并且从该矩阵切割部分以形成二维阵列的多个副本,然后可以对这些副本进行不同的生物分析。 或者,阵列可以由细胞悬浮液形成,从而形成阵列的相同多个拷贝,其中阵列拷贝中的对应位置具有来自相同或相似样本的样本。 对不同生物学分析的结果进行比较,以确定每个指定地点的不同生物学分析结果之间是否存在相关性。 在一些实施方案中,标本可以是来自不同肿瘤的组织标本,其经历多个平行分子(包括遗传和免疫学)分析。 平行分析的结果然后用于检测肿瘤类型的常见分子特征,其随后可用于疾病的诊断或治疗。 组织的生物学特征可以与临床或其他信息相关联,以检测与组织相关的特征,例如对特定类型的药物治疗的敏感性或抗性。 可以放置在基质中的合适组织的其他例子包括来自转基因或模型生物体的组织,或细胞悬浮液(例如细胞学制剂或液体恶性肿瘤或细胞系的样本)。
    • 6. 发明申请
    • ONCOGENES USEFUL FOR THE IDENTIFICATION OF URINARY BLADDER CANCER
    • 关于泌尿系癌症的鉴定有用的依据
    • WO2004010848A3
    • 2005-01-20
    • PCT/US0323555
    • 2003-07-25
    • DIOMEDA LIFE SCIENCES INCSCHRAML PETERTOMOVSKA SANJASAUTER GUIDOSIMON RONALDKONONEN JUHA
    • SCHRAML PETERTOMOVSKA SANJASAUTER GUIDOSIMON RONALDKONONEN JUHA
    • A61B20060101A61K38/00C12Q1/68
    • C12Q1/6886A61K38/00C07K14/4748C12Q2600/112C12Q2600/118C12Q2600/136
    • Studies by Comparative Genome Hybridization (CGH) have shown that 6p22 is frequently amplified in invasive urinary bladder cancer. The E2F3 gene maps to 6p22 and encodes a transcription factor important for cell cycle regulation and DNA replication. To determine whether E2F3 resides in the 6p22 amplicon, 7 primary tumors and 3 cell lines known to have 6p22 amplification by CGH were examined by fluorescence in situ hybridization (FISH) using an E2F3-specific probe. All ten 6p22 amplified tumors showed E2F3 amplification. To further investigate the role of E2F3 in bladder cancer, a tissue microarray containing samples from 2317 bladder tumors was used for FISH and immunohistochemical expression analysis. E2F3 amplification was strongly associated with invasive tumor phenotype and high tumor grade (p
    • 比较基因组杂交(CGH)的研究表明6p22在侵袭性膀胱癌中经常被扩增。 E2F3基因映射到6p22,编码重要的细胞周期调节和DNA复制的转录因子。 为了确定E2F3是否位于6p22扩增子中,通过使用E2F3特异性探针的荧光原位杂交(FISH)检查已知具有6p22扩增的7个原发肿瘤和3个细胞系。 全部10个6p22扩增肿瘤显示E2F3扩增。 为了进一步研究E2F3在膀胱癌中的作用,将含有来自2317膀胱肿瘤的样品的组织微阵列用于FISH和免疫组织化学表达分析。 E2F3扩增与侵袭性肿瘤表型和高肿瘤分级密切相关(p <0.0001)。 398例pTaG1 / G2肿瘤(1%)中只有4例,489例pT1-4癌中有110例(22%)具有E2F3扩增。 高E2F3表达水平与高等级,晚期和E2F3基因扩增相关(p <0.0001)。 为了评估E2F3表达是否与肿瘤增殖相关,分析了每个肿瘤的Ki67标记指数(LI)。 高Ki67 LI和E2F3表达(p <0.0001)之间存在强烈的联系,与成绩和阶段无关。 我们得出结论,E2F3经常在膀胱癌侵袭性膀胱癌(pT1-4期)中被扩增并过度表达。 E2F3表达似乎通过在膀胱肿瘤的子集中激活细胞增殖而为肿瘤细胞提供增长优势。
    • 7. 发明申请
    • ONCOGENES USEFUL FOR THE IDENTIFICATION OF URINARY BLADDER CANCER
    • 可用于鉴别尿路膀胱癌的肿瘤
    • WO2004010848A8
    • 2004-10-28
    • PCT/US0323555
    • 2003-07-25
    • DIOMEDA LIFE SCIENCES INCSCHRAML PETERTOMOVSKA SANJASAUTER GUIDOSIMON RONALDKONONEN JUHA
    • SCHRAML PETERTOMOVSKA SANJASAUTER GUIDOSIMON RONALDKONONEN JUHA
    • A61B20060101A61K38/00C12Q1/68A61B
    • C12Q1/6886A61K38/00C07K14/4748C12Q2600/112C12Q2600/118C12Q2600/136
    • Studies by Comparative Genome Hybridization (CGH) have shown that 6p22 is frequently amplified in invasive urinary bladder cancer. The E2F3 gene maps to 6p22 and encodes a transcription factor important for cell cycle regulation and DNA replication. To determine whether E2F3 resides in the 6p22 amplicon, 7 primary tumors and 3 cell lines known to have 6p22 amplification by CGH were examined by fluorescence in situ hybridization (FISH) using an E2F3-specific probe. All ten 6p22 amplified tumors showed E2F3 amplification. To further investigate the role of E2F3 in bladder cancer, a tissue microarray containing samples from 2317 bladder tumors was used for FISH and immunohistochemical expression analysis. E2F3 amplification was strongly associated with invasive tumor phenotype and high tumor grade (p
    • 通过比较基因组杂交(CGH)的研究已经显示6p22经常在侵入性膀胱癌中扩增。 E2F3基因定位于6p22并编码对细胞周期调控和DNA复制重要的转录因子。 为了确定E2F3是否存在于6p22扩增子中,使用E2F3特异性探针通过荧光原位杂交(FISH)检查已知具有由CGH扩增6p22的7个原发性肿瘤和3个细胞系。 所有10个6p22扩增的肿瘤显示E2F3扩增。 为了进一步研究E2F3在膀胱癌中的作用,将含有来自2317个膀胱肿瘤的样品的组织微阵列用于FISH和免疫组织化学表达分析。 E2F3扩增与侵袭性肿瘤表型和高肿瘤等级强烈相关(各自p <0.0001)。 398个pTaG1 / G2肿瘤中仅有4个(1%),而489个pT1-4癌中有110个(22%)具有E2F3扩增。 高E2F3表达水平与高年级,晚期和E2F3基因扩增相关(各自p <0.0001)。 为了评估E2F3表达是否与肿瘤增殖相关,分析每种肿瘤的Ki67标记指数(LI)。 高Ki67L1和E2F3表达之间存在强相关性(p <0.0001),其与级别和阶段无关。 我们得出这样的结论:E2F3在侵入性生长的膀胱癌(阶段pT1-4)中经常被放大并过度表达。 E2F3表达似乎通过激活膀胱肿瘤亚群中的细胞增殖而为肿瘤细胞提供生长优势。
    • 8. 发明申请
    • ONCOGENES USEFUL FOR THE IDENTIFICATION OF URINARY BLADDER CANCER
    • 关于泌尿系癌症的鉴定有用的依据
    • WO2004010848A2
    • 2004-02-05
    • PCT/US2003/023555
    • 2003-07-25
    • DIOMEDA LIFE SCIENCES, INC.SCHRAML, PeterTOMOVSKA, SanjaSAUTER, GuidoSIMON, RonaldKONONEN, Juha
    • SCHRAML, PeterTOMOVSKA, SanjaSAUTER, GuidoSIMON, RonaldKONONEN, Juha
    • A61B
    • C12Q1/6886A61K38/00C07K14/4748C12Q2600/112C12Q2600/118C12Q2600/136
    • Studies by Comparative Genome Hybridization (CGH) have shown that 6p22 is frequently amplified in invasive urinary bladder cancer. The E2F3 gene maps to 6p22 and encodes a transcription factor important for cell cycle regulation and DNA replication. To determine whether E2F3 resides in the 6p22 amplicon, 7 primary tumors and 3 cell lines known to have 6p22 amplification by CGH were examined by fluorescence in situ hybridization (FISH) using an E2F3-specific probe. All ten 6p22 amplified tumors showed E2F3 amplification. To further investigate the role of E2F3 in bladder cancer, a tissue microarray containing samples from 2317 bladder tumors was used for FISH and immunohistochemical expression analysis. E2F3 amplification was strongly associated with invasive tumor phenotype and high tumor grade (p
    • 比较基因组杂交(CGH)的研究表明6p22在侵袭性膀胱癌中经常被扩增。 E2F3基因映射到6p22,编码重要的细胞周期调节和DNA复制的转录因子。 为了确定E2F3是否位于6p22扩增子中,通过使用E2F3特异性探针的荧光原位杂交(FISH)检查已知具有6p22扩增的7个原发肿瘤和3个细胞系。 全部10个6p22扩增肿瘤显示E2F3扩增。 为了进一步研究E2F3在膀胱癌中的作用,将含有来自2317膀胱肿瘤的样品的组织微阵列用于FISH和免疫组织化学表达分析。 E2F3扩增与侵袭性肿瘤表型和高肿瘤分级密切相关(p <0.0001)。 398例pTaG1 / G2肿瘤(1%)中只有4例,489例pT1-4癌中有110例(22%)具有E2F3扩增。 高E2F3表达水平与高等级,晚期和E2F3基因扩增相关(p <0.0001)。 为了评估E2F3表达是否与肿瘤增殖相关,分析了每个肿瘤的Ki67标记指数(LI)。 高Ki67 LI和E2F3表达(p <0.0001)之间存在强烈的联系,与成绩和阶段无关。 我们得出结论,E2F3经常在膀胱癌侵袭性膀胱癌(pT1-4期)中被扩增并过度表达。 E2F3表达似乎通过在膀胱肿瘤的子集中激活细胞增殖而为肿瘤细胞提供增长优势。