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1. 发明申请

WO2011046807A3 MULTI-MODALITY CONTRAST AND BRIGHTFIELD CONTEXT RENDERING FOR ENHANCED PATHOLOGY DETERMINATION AND MULTI-ANALYTE DETECTION IN TISSUE 审中-公开
标题翻译：多模式对比度和亮度上下文呈现用于增强病理学确定和组织多分析检测
公开(公告)号：WO2011046807A3
公开(公告)日：2011-09-01
申请号：PCT/US2010051857
申请日：2010-10-07
申请人： VENTANA MED SYST INC , GARSHA KARL , PESTANO GARY , OTTER MICHAEL , NAGY ALEXANDRA DEA , NAGLE RAY B , MILLER PHILLIP , FROEHLICH JAN , DAY WILLIAM
发明人： GARSHA KARL , PESTANO GARY , OTTER MICHAEL , NAGY ALEXANDRA DEA , NAGLE RAY B , MILLER PHILLIP , FROEHLICH JAN , DAY WILLIAM
IPC分类号： G01N33/483
CPC分类号： G01N21/6456
摘要： Multiple modality contrast can be used to produce images that can be combined and rendered to produce images similar to those produced with wavelength absorbing stains viewed under transmitted white light illumination. Images obtained with other complementary contrast modalities can be presented using engineered color schemes based on classical contrast methods used to reveal the same anatomical structures and histochemistry, thereby providing relevance to medical training and experience. Dark-field contrast images derived from refractive index and fluorescent DAPI counterstain images are combined to produce images similar to those obtained with conventional H&E staining for pathology interpretation. Such multi-modal image data can be streamed for live navigation of histological samples, and can be combined with molecular localizations of genetic DNA probes (FISH), sites of mRNA expression (mRNA-ISH), and immunohistochemical (IHC) probes localized on the same tissue sections, used to evaluate and map tissue sections prepared for imaging mass spectrometry.
摘要翻译：可以使用多种形式的对比度来产生可以组合和渲染的图像，以产生与在透射白光照明下观察到的吸收波长的污渍产生的图像类似的图像。用其他互补对比方式获得的图像可以使用基于经典对比方法的工程颜色方案来呈现，该方法用于揭示相同的解剖结构和组织化学，从而提供与医学训练和经验的相关性。将来自折射率和荧光DAPI复染图像的暗场对比图像组合以产生与用常规H＆E染色获得的用于病理解释的图像相似的图像。这种多模式图像数据可以流式传输组织样本的实时导航，并且可以与基因DNA探针（FISH），mRNA表达位点（mRNA-ISH）和免疫组织化学（IHC）探针位于相同的组织切片，用于评估和映射为成像质谱准备的组织切片。

2. 发明申请

WO2012152747A3 SPECTRAL IMAGING FOR MEASUREMENT OF NUCLEAR PATHOLOGY FEATURES IN CANCER CELLS PREPARED FOR IN SITU ANALYSIS 审中-公开
标题翻译：用于测量原位分析中准备的癌细胞中核型病理特征的光谱成像
公开(公告)号：WO2012152747A3
公开(公告)日：2013-01-24
申请号：PCT/EP2012058356
申请日：2012-05-07
申请人： VENTANA MED SYST INC , HOFFMANN LA ROCHE , UNIV CORNELL , DEMICHELIS FRANCESCA , GARSHA KARL , MILLER PHILLIP C , NAGLE RAY B , OTTER MICHAEL , PESTANO GARY ANTHONY , RUBIN MARK A
发明人： DEMICHELIS FRANCESCA , GARSHA KARL , MILLER PHILLIP C , NAGLE RAY B , OTTER MICHAEL , PESTANO GARY ANTHONY , RUBIN MARK A
IPC分类号： C12Q1/68 , G01N33/574
CPC分类号： G01N33/57407 , C12Q1/6841 , C12Q1/6886 , C12Q2600/156
摘要： In general, the presently disclosed technology relates to identification of cancer subtypes. More specifically, the technology relates to methods for determining molecular drivers of cancer and/or progression using a multivariate image data and statistical analysis of in-situ molecular markers and morphological characteristics in the same cells of a biological sample suspected of cancer. This analysis takes place after a single acquisition that obtains the molecular and anatomic morphology data in parallel. The analysis compares specific morphological and molecular markers to known samples exhibiting particular genetic drivers of the cancer. This method provides statistical information that allows for an increased confidence in the identification of specific molecular drivers of the cancer.
摘要翻译：一般来说，目前公开的技术涉及癌症亚型的鉴定。更具体地说，该技术涉及使用多变量图像数据确定癌症和/或进展的分子驱动因素的方法，以及在怀疑患有癌症的生物样品的相同细胞中的原位分子标记物和形态特征的统计分析。这种分析是在单次采集后并行获得分子和解剖形态数据进行的。该分析将特定的形态学和分子标记与展示癌症的特定遗传驱动因子的已知样品进行比较。该方法提供统计信息，可以增加对癌症特异性分子驱动因子的识别的信心。

3. 发明申请

WO2009036427A2 PROSTATE CANCER BIOMARKERS 审中-公开
标题翻译：前列腺癌生物标志物
公开(公告)号：WO2009036427A2
公开(公告)日：2009-03-19
申请号：PCT/US2008076407
申请日：2008-09-15
申请人： VENTANA MED SYST INC , PESTANO GARY , SATHYANARAYANA UBARADKA G , RILEY JANICE , NAGLE RAY B
发明人： PESTANO GARY , SATHYANARAYANA UBARADKA G , RILEY JANICE , NAGLE RAY B
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/118 , C12Q2600/16 , G01N33/57434 , G01N2800/60
摘要： Disclosed are biomarkers, at least, useful for the diagnosis and/or prognosis of cancer and for making treatment decisions in cancer, for example prostate cancer.
摘要翻译：公开的生物标志物至少可用于癌症的诊断和/或预后以及用于在癌症例如前列腺癌中作出治疗决定。

4. 发明申请

WO2006119265A3 XENOGRAFT TISSUE CONTROL FOR HISTOLOGY 审中-公开
标题翻译：异体组织的XENOGRAFT组织控制
公开(公告)号：WO2006119265A3
公开(公告)日：2006-12-21
申请号：PCT/US2006016766
申请日：2006-05-01
申请人： VENTANA MED SYST INC , HARDY MARGARET , GROGAN THOMAS M , NAGLE RAY B
发明人： HARDY MARGARET , GROGAN THOMAS M , NAGLE RAY B
IPC分类号： G01N33/50 , G01N33/567 , G01N33/577
CPC分类号： G01N33/5005 , G01N1/30 , G01N1/312 , G01N2001/2893 , G01N2015/1018
摘要： An embodiment of the invention is a method of using a xenograft as a control tissue for histology, comprising staining both a patient and a xenograft-derived control sample under substantially similar staining conditions, and assessing the staining outcomes of the two to determine whether the stain was effective for the patient sample. A xenograft has never been used before in histology as a control, as far as the inventors know. The result of using a xenograft as a control is surprisingly advantageous. First, the cell lines grow and differentiate similarly to a human, taking on the general morphology of a real tissue sample. Second, because the same transformed cell line can be grown limitless times in SCID mice, the xenograft control is highly reproducible, leading to a consistent artificial control that is highly manufacturable and subject to genetic manipulation so that antigens or genetic elements may be embedded in the tissue. Another embodiment of the invention is directed generally to a method of making a tissue control substrate, comprising growing a xenograft from a mammalian transformed cell line in a host animal, removing the xenograft from the host animal, processing the xenograft thereby embedding the xenograft tissue in an embedding medium, and finally affixing the embedded xenograft sample onto a substrate. The substrate is generally a microscope slide. The xenograft control slide can then be stained side-by-side with a specimen sample in an automated slide stainer, and act as a control against which the staining quality can be compared. The xenograft control can also be used as a manual staining control. Determining whether the staining was effective for the patient specimen comprises judging the staining intensity of the xenograft control sample to determine if the expected degree and type of staining were realized in the control. If the expected type (nuclear, membranous, or cytoplasmic) and degree (0-4 scale) of staining are realized during the run, then the xenograft control indicates the staining process and reagents are working properly, and so the result in the patient specimen can be trusted. A further embodiment of the invention is a xenograft-derived control slide for histochemical use, comprising at least one xenograft control sample prepared for histological use, and a sample slide upon which the at least one xenograft control sample is affixed.
摘要翻译：本发明的一个实施方案是使用异种移植物作为组织学对照组织的方法，包括在基本相似的染色条件下对患者和异种移植物衍生的对照样品进行染色，并评估两者的染色结果以确定染色剂对患者样本有效。据发明人所知，异种移植物在组织学之前从未用作对照。使用异种移植物作为对照的结果出人意料地是有利的。首先，细胞系与人类相似地生长和分化，呈现真实组织样本的一般形态。其次，因为相同的转化细胞系可以在SCID小鼠中无限生长，所以异种移植物对照是高度可重复的，导致一致的人工对照，其是高度可制造的且经历基因操作，使得抗原或遗传元件可以嵌入组织。本发明的另一个实施方案通常涉及制备组织对照底物的方法，包括在宿主动物中从哺乳动物转化的细胞系生长异种移植物，从宿主动物移除异种移植物，处理异种移植物，由此将异种移植组织包埋入包埋介质，并最终将嵌入的异种移植物样品固定到基底上。底物通常是显微镜载玻片。然后可以将异种移植物对照载玻片与自动载玻片染色器中的样本样本并排染色，并作为对照来对比染色质量。异种移植物控制也可以用作手动染色控制。确定染色是否对患者样本有效包括判断异种移植对照样本的染色强度以确定在对照中是否实现了期望的染色程度和类型。如果在运行过程中实现了期望的染色类型（核，膜或胞质）和程度（0-4标度），则异种移植物控制指示染色过程并且试剂正常工作，因此患者标本中的结果可以信任。本发明的另一个实施方案是用于组织化学用途的异种移植物衍生的对照载玻片，其包含至少一种为组织学使用而制备的异种移植对照样品和其上附着有至少一种异种移植对照样品的样品载玻片。

5. 发明公开

EP2488860A4 MULTI-MODALITY CONTRAST AND BRIGHTFIELD CONTEXT RENDERING FOR ENHANCED PATHOLOGY DETERMINATION AND MULTI-ANALYTE DETECTION IN TISSUE 审中-公开
标题翻译： MULTIMODALITÄTSKONTRAST和增强的病理学测定的BREITFELD背景和MEHRANALYTERKENNUNG组织
公开(公告)号：EP2488860A4
公开(公告)日：2015-12-16
申请号：EP10823858
申请日：2010-10-07
申请人： VENTANA MED SYST INC
发明人： GARSHA KARL , PESTANO GARY , OTTER MICHAEL , NAGY ALEXANDRA DEA , NAGLE RAY B , MILLER PHILLIP , FROEHLICH JAN , DAY WILLIAM
IPC分类号： G01N33/483 , G01N21/64
CPC分类号： G01N21/6456

6. 发明专利

ES2589507T3 Obtención de imágenes espectrales para la medición de características patológicas nucleares en células de cáncer preparadas para el análisis in situ 未知
公开(公告)号：ES2589507T3
公开(公告)日：2016-11-14
申请号：ES12725639
申请日：2012-05-07
申请人： VENTANA MED SYST INC , UNIV CORNELL
发明人： DEMICHELIS FRANCESCA , GARSHA KARL , MILLER PHILLIP C , NAGLE RAY B , OTTER MICHAEL , PESTANO GARY ANTHONY , RUBIN MARK A
IPC分类号： C12Q1/68 , G01N33/574
摘要： Método diagnóstico del cáncer multivariante, comprendiendo el método: a. obtener datos de marcadores moleculares de una única muestra de un sujeto que comprende una única célula o población de células procedente de un tejido, en el que el marcador molecular es una reorganización genética, b. obtener datos cuantitativos de la morfología celular de la misma célula individual o población de células utilizada en la etapa (a), en la que los datos de marcadores de la morfología celular son el tamaño nuclear, la forma nuclear y el contenido de ADN, c. llevar a cabo un análisis multivariable de dicha muestra única para generar un conjunto de datos de análisis multivariable que comprende datos cuantitativos de marcadores de la morfología celular de la etapa (b) y datos de marcadores moleculares de la etapa (a), d. comparar los datos de análisis multivariable obtenidos en la etapa (c) con un conjunto de datos de análisis multivariable de referencia creado mediante la obtención de tanto datos de marcadores moleculares como datos cuantitativos de morfología celular de muestras celulares de cáncer y de no cáncer obtenidas de individuos con resultado clínico conocido, en el que el marcador molecular es una reorganización genética y los datos de marcadores de la morfología celular son el tamaño nuclear, la forma nuclear y el contenido de ADN, y e. predecir un resultado clínico definido por combinaciones específicas de datos de marcadores de la morfología celular y datos de marcadores moleculares asociados estadísticamente con la progresión, incidencia y metástasis del cáncer u otro determinante de resultado clínico observado en el conjunto de datos de análisis multivariable de referencia.

7. 发明专利

CA2699385A1 PROSTATE CANCER BIOMARKERS 未知
公开(公告)号：CA2699385A1
公开(公告)日：2009-03-19
申请号：CA2699385
申请日：2008-09-15
申请人： VENTANA MED SYST INC
发明人： PESTANO GARY , SATHYANARAYANA UBARADKA G , RILEY JANICE , NAGLE RAY B
IPC分类号： C12Q1/68
摘要： Disclosed are biomarkers, at least, useful for the diagnosis and/or prognosis of cancer and for making treatment decisions in cancer, for example prostate cancer.

8. 发明专利

CA2774422C MULTI-MODALITY CONTRAST AND BRIGHTFIELD CONTEXT RENDERING FOR ENHANCED PATHOLOGY DETERMINATION AND MULTI-ANALYTE DETECTION IN TISSUE 未知
公开(公告)号：CA2774422C
公开(公告)日：2017-08-29
申请号：CA2774422
申请日：2010-10-07
申请人： VENTANA MED SYST INC
发明人： GARSHA KARL , PESTANO GARY , OTTER MICHAEL , NAGY ALEXANDRA DEA , NAGLE RAY B , MILLER PHILLIP , FROEHLICH JAN , DAY WILLIAM
IPC分类号： G01N33/483
摘要： Multiple modality contrast can be used to produce images that can be combined and rendered to produce images similar to those produced with wavelength absorbing stains viewed under transmitted white light illumination. Images obtained with other complementary contrast modalities can be presented using engineered color schemes based on classical contrast methods used to reveal the same anatomical structures and histochemistry, thereby providing relevance to medical training and experience. Dark-field contrast images derived from refractive index and fluorescent DAPI counterstain images are combined to produce images similar to those obtained with conventional H&E staining for pathology interpretation. Such multi-modal image data can be streamed for live navigation of histological samples, and can be combined with molecular localizations of genetic DNA probes (FISH), sites of mRNA expression (mRNA-ISH), and immunohistochemical (IHC) probes localized on the same tissue sections, used to evaluate and map tissue sections prepared for imaging mass spectrometry.

9. 发明专利

AU2012252532B2 Spectral imaging for measurement of nuclear pathology features in cancer cells prepared for in situ analysis 未知
公开(公告)号：AU2012252532B2
公开(公告)日：2016-03-03
申请号：AU2012252532
申请日：2012-05-07
申请人： UNIV CORNELL , VENTANA MED SYST INC
发明人： DEMICHELIS FRANCESCA , GARSHA KARL , MILLER PHILLIP C , NAGLE RAY B , OTTER MICHAEL , PESTANO GARY ANTHONY , RUBIN MARK A
IPC分类号： C12Q1/68 , G01N33/574
摘要： In general, the presently disclosed technology relates to identification of cancer subtypes. More specifically, the technology relates to methods for determining molecular drivers of cancer and/or progression using a multivariate image data and statistical analysis of in-situ molecular markers and morphological characteristics in the same cells of a biological sample suspected of cancer. This analysis takes place after a single acquisition that obtains the molecular and anatomic morphology data in parallel. The analysis compares specific morphological and molecular markers to known samples exhibiting particular genetic drivers of the cancer. This method provides statistical information that allows for an increased confidence in the identification of specific molecular drivers of the cancer.

10. 发明专利

AU2008298560A1 Prostate cancer biomarkers 未知
公开(公告)号：AU2008298560A1
公开(公告)日：2009-03-19
申请号：AU2008298560
申请日：2008-09-15
申请人： VENTANA MED SYST INC
发明人： SATHYANARAYANA UBARADKA G , PESTANO GARY , RILEY JANICE , NAGLE RAY B
IPC分类号： C12Q1/68
摘要： Disclosed are biomarkers, at least, useful for the diagnosis and/or prognosis of cancer and for making treatment decisions in cancer, for example prostate cancer.

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