公开(公告)号：US07338774B2

公开(公告)日：2008-03-04

申请号：US10074041

申请日：2002-02-14

申请人： Hideki Ishihara ,  Tomokazu Yoshida ,  Masatoshi Yamasaki ,  Sachiyo Tada

发明人： Hideki Ishihara ,  Tomokazu Yoshida ,  Masatoshi Yamasaki ,  Sachiyo Tada

IPC分类号： C12Q1/48

CPC分类号： C07K16/40 ,  C12N9/1205 ,  C12Q1/48 ,  C12Q1/485 ,  G01N33/57407 ,  G01N33/57484 ,  G01N33/581 ,  G01N33/582 ,  G01N2333/9121

摘要： A method for determining the activity of a cell cycle regulatory factor comprising the steps of: preparing a sample for measuring a cyclin-dependent kinase/cyclin complex from living cells; reacting adenosine 5′-O-(3-thiotriphosphate) (ATP-γS) with a substrate for the cyclin-dependent kinase in presence of the sample in order to introduce a monothiophosphate group into a serine or threonine residue of the substrate; labeling the substrate by coupling a labeling fluorophore or a labeling enzyme with a sulfur atom of the introduced monothiophosphate group; measuring the amount of fluorescence from the labeling fluorophore labeling the substrate, or reacting the labeling enzyme labeling the substrate with a substance which generates an optically detectable product by reaction with the labeling enzyme and optically measuring the amount of the generated product; and calculating the activity of the cyclin-dependent kinase from the measured amount of fluorescence or the measured amount of the generated product with reference to a pre-produced reference curve.

摘要翻译： 一种确定细胞周期调控因子活性的方法，包括以下步骤：制备用于从活细胞测量细胞周期蛋白依赖性激酶/细胞周期蛋白复合物的样品; 在样品存在下使腺苷5'-O-（3-硫代三磷酸酯）（ATP-γS）与用于细胞周期蛋白依赖性激酶的底物反应，以将一硫代磷酸酯基团引入底物的丝氨酸或苏氨酸残基中; 通过将标记的荧光团或标记酶与引入的一硫代磷酸酯基团的硫原子偶联来标记底物; 测量来自标记荧光团的荧光标记基质的荧光量，或使标记基质的标记酶与通过与标记酶反应产生可光学检测的产物并光学测量产生的产物的量的物质反应; 并且根据测量的荧光量或参考预先产生的参考曲线测量产生的产物的量计算细胞周期蛋白依赖性激酶的活性。

公开(公告)号：US20070264624A1

公开(公告)日：2007-11-15

申请号：US11747077

申请日：2007-05-10

申请人： Hideki Ishihara ,  Tomokazu Yoshida ,  Masatoshi Yamasaki ,  Sachiyo Tada

发明人： Hideki Ishihara ,  Tomokazu Yoshida ,  Masatoshi Yamasaki ,  Sachiyo Tada

IPC分类号： C12Q1/00

CPC分类号： C07K16/40 ,  C12N9/1205 ,  C12Q1/48 ,  C12Q1/485 ,  G01N33/57407 ,  G01N33/57484 ,  G01N33/581 ,  G01N33/582 ,  G01N2333/9121

摘要： A method for determining the activity of a cell cycle regulatory factor comprising the steps of preparing a sample for measuring a cyclin-dependent kinase/cyclin complex from living cells; reacting adenosine 5′-O-(3-thiotriphosphate) (ATP-γ S) with a substrate for the cyclin-dependent kinase in presence of the sample in order to introduce a monothiophosphate group into a serine or threonine residue of the substrate; labeling the substrate by coupling a labeling fluorophore or a labeling enzyme with a sulfur atom of the introduced monothiophosphate group; measuring the amount of fluorescence from the labeling fluorophore labeling the substrate, or reacting the labeling enzyme labeling the substrate with a substance which generates an optically detectable product by reaction with the labeling enzyme and optically measuring the amount of the generated product; and calculating the activity of the cyclin-dependent kinase from the measured amount of fluorescence or the measured amount of the generated product with reference to a pre-produced reference curve.

摘要翻译： 一种确定细胞周期调控因子活性的方法，包括以下步骤：制备用于从活细胞测量细胞周期蛋白依赖性激酶/细胞周期蛋白复合物的样品; 在样品存在下使腺苷5'-O-（3-硫代三磷酸）（ATP-γS）与用于细胞周期蛋白依赖性激酶的底物反应，以将一硫代磷酸酯基团引入底物的丝氨酸或苏氨酸残基中; 通过将标记的荧光团或标记酶与引入的一硫代磷酸酯基团的硫原子偶联来标记底物; 测量来自标记荧光团的荧光标记基质的荧光量，或使标记基质的标记酶与通过与标记酶反应产生可光学检测的产物并光学测量产生的产物的量的物质反应; 并且根据测量的荧光量或参考预先产生的参考曲线测量产生的产物的量计算细胞周期蛋白依赖性激酶的活性。

公开(公告)号：US20080090254A1

公开(公告)日：2008-04-17

申请号：US11905027

申请日：2007-09-27

申请人： Michitaka Notoya ,  Jun Sato ,  Tomoko Ohyama ,  Tomokazu Yoshida ,  Hideki Ishihara

发明人： Michitaka Notoya ,  Jun Sato ,  Tomoko Ohyama ,  Tomokazu Yoshida ,  Hideki Ishihara

IPC分类号： G01N33/53

CPC分类号： C12Q1/485 ,  G01N2333/9121 ,  G01N2500/00

摘要： A method for assessing the proliferation inhibiting effect of a receptor tyrosine kinase inhibitor is described. In the method, a cytoplasm is separated from a tumor cell to prepare a sample containing various receptor tyrosine kinases. The prepared sample is treated with the inhibitor. The receptor tyrosine kinases in the treated sample, and a substrate for at least two kinds of receptor tyrosine kinases are contacted. The phosphorylated substrate is detected, and the activity value of the receptor tyrosine kinases is measured based on the detection result. The proliferation inhibiting effect is assessed based on the resulting activity value.

摘要翻译： 描述了用于评估受体酪氨酸激酶抑制剂的增殖抑制作用的方法。 在该方法中，从肿瘤细胞分离细胞质以制备含有各种受体酪氨酸激酶的样品。 制备的样品用抑制剂处理。 处理的样品中的受体酪氨酸激酶和至少两种受体酪氨酸激酶的底物接触。 检测磷酸化底物，并根据检测结果测定受体酪氨酸激酶的活性值。 基于得到的活性值评估增殖抑制作用。

公开(公告)号：US20070238141A1

公开(公告)日：2007-10-11

申请号：US11729901

申请日：2007-03-30

申请人： Michitaka Notoya ,  Tomoko Ohyama ,  Shigeyuki Tamura ,  Tomokazu Yoshida ,  Hideki Ishihara

发明人： Michitaka Notoya ,  Tomoko Ohyama ,  Shigeyuki Tamura ,  Tomokazu Yoshida ,  Hideki Ishihara

IPC分类号： C12Q1/48 ,  G01N33/53

CPC分类号： C12Q1/485 ,  G01N33/573

摘要： A method for measuring the activity of a receptor kinase present in a cell membrane of a cell is described. The method comprises steps of preparing a sample containing the receptor kinase by separating a cytoplasm from the cell, contacting the receptor kinase in the sample with a substrate to phosphorylate the substrate with the activity of the receptor kinase, binding a labeling substance to the phosphorylated substrate, and measuring the activity of the receptor kinase based on a result of detection of the labeling substance bound to the phosphorylated substrate.

摘要翻译： 描述了测定存在于细胞的细胞膜中的受体激酶的活性的方法。 该方法包括以下步骤：通过从细胞分离细胞质来制备含有受体激酶的样品，使样品中的受体激酶与底物接触，以使受体激酶活性磷酸化底物，将标记物质结合到磷酸化底物 ，并且基于与磷酸化底物结合的标记物质的检测结果测量受体激酶的活性。

公开(公告)号：US20100250483A1

公开(公告)日：2010-09-30

申请号：US12569130

申请日：2009-09-29

申请人： Tomoko Ohyama ,  Masaki Shibayama ,  Hideki Ishihara ,  Tomokazu Yoshida ,  Keigo Gohda

发明人： Tomoko Ohyama ,  Masaki Shibayama ,  Hideki Ishihara ,  Tomokazu Yoshida ,  Keigo Gohda

IPC分类号： G06N5/02

CPC分类号： G16C20/30 ,  G16B25/00

摘要： An effect predicting apparatus for predicting an effect of anthracycline anticancer drugs, comprising: a display, a processor, and a memory, under control of said processor, including software instructions adapted to enable the processor to perform operations, comprising: acquiring a CDK parameter based on a first CDK parameter and a second CDK parameter; acquiring an expression level of glutathione; comparing the CDK parameter with a CDK threshold value, and the expression level of glutathione with a glutathione threshold value; predicting an effect of anthracycline anticancer drugs based on the result of the comparison; and displaying the result of the prediction. A computer program product and a method for predicting an effect are also disclosed.

摘要翻译： 一种用于预测蒽环类抗癌药物的效果的效果预测装置，包括：在所述处理器的控制下的显示器，处理器和存储器，包括适于使处理器执行操作的软件指令，包括：基于CDK参数获取 第一个CDK参数和第二个CDK参数; 获得谷胱甘肽的表达水平; 将CDK参数与CDK阈值进行比较，以及谷胱甘肽阈值的谷胱甘肽的表达水平; 基于比较结果预测蒽环类抗癌药物的作用; 并显示预测结果。 还公开了一种用于预测效果的计算机程序产品和方法。

公开(公告)号：US20110244497A1

公开(公告)日：2011-10-06

申请号：US13075673

申请日：2011-03-30

申请人： Tomoko Ohyama ,  Masaki Shibayama ,  Hideki Ishihara ,  Tomokazu Yoshida ,  Keigo Gohda

发明人： Tomoko Ohyama ,  Masaki Shibayama ,  Hideki Ishihara ,  Tomokazu Yoshida ,  Keigo Gohda

IPC分类号： C12Q1/48

CPC分类号： G01N33/57415 ,  G01N2333/91177 ,  G01N2333/9121 ,  G01N2800/44 ,  G01N2800/52

摘要： The present invention provides a method for judging susceptibility of cancer cells contained in a biological sample to an anthracycline anticancer agent comprising steps of: measuring expression levels of GST-π of cancer cells contained in a biological sample; and judging the susceptibility of cancer cells contained in a biological sample to an anthracycline anticancer agent as high when the expression level of GST-π obtained by the measuring process is high, and a computer program which makes a computer execute the method.

摘要翻译： 本发明提供了一种用于判断生物样品中包含的癌细胞对蒽环类抗癌剂的敏感性的方法，包括以下步骤：测量GST-和pgr的表达水平; 包含在生物样品中的癌细胞; 并且当GST-＆pgr的表达水平，判断生物样品中包含的癌细胞对蒽环类抗癌剂的敏感性高。 通过测量过程获得的计算机程序高，并且使计算机执行该方法。

公开(公告)号：US20090098582A1

公开(公告)日：2009-04-16

申请号：US12249417

申请日：2008-10-10

申请人： Tomoko OYAMA ,  Michitaka Notoya ,  Tomokazu Yoshida ,  Hideki Ishihara

发明人： Tomoko OYAMA ,  Michitaka Notoya ,  Tomokazu Yoshida ,  Hideki Ishihara

IPC分类号： G01N33/53 ,  G06F19/00

CPC分类号： G01N33/57484 ,  G01N2333/91205 ,  G01N2800/54 ,  G16H50/20 ,  Y02A90/26

摘要： The invention provides a method for determining a risk of cancer relapse comprising a step of determining the risk of cancer relapse on the basis of a comprehensive activity value of a transmembrane tyrosine kinase of a tumor cell, as well as a computer program product for determining a risk of a cancer relapse.

摘要翻译： 本发明提供了一种确定癌症复发风险的方法，该方法包括基于肿瘤细胞的跨膜酪氨酸激酶的综合活性值确定癌症复发的风险的步骤，以及用于确定 癌症复发的风险。

公开(公告)号：US20080003630A1

公开(公告)日：2008-01-03

申请号：US11819236

申请日：2007-06-26

申请人： Michitaka Notoya ,  Tomoko Ohyama ,  Tomokazu Yoshida ,  Hideki Ishihara

发明人： Michitaka Notoya ,  Tomoko Ohyama ,  Tomokazu Yoshida ,  Hideki Ishihara

IPC分类号： C12Q1/48 ,  C07K14/00

CPC分类号： C07K14/71 ,  C07K1/13 ,  C07K2319/00 ,  C12Q1/485

摘要： A tyrosine kinase substrate is described. The tyrosine kinase substrate comprises a fusion protein which comprises a protein for labeling and a specific peptide fused with the protein for labeling. The specific peptide has an amino acid sequence including a glutamic acid residue and a tyrosine residue. The tyrosine kinase substrate is capable of being phosphorylated by a plurality of kinds of tyrosine kinases.

摘要翻译： 描述了酪氨酸激酶底物。 酪氨酸激酶底物包含融合蛋白，其包含用于标记的蛋白质和与用于标记的蛋白质融合的特异性肽。 特定肽具有包含谷氨酸残基和酪氨酸残基的氨基酸序列。 酪氨酸激酶底物能够被多种酪氨酸激酶磷酸化。

公开(公告)号：US08131520B2

公开(公告)日：2012-03-06

申请号：US12286699

申请日：2008-10-01

申请人： Hideki Ishihara ,  Tomoko Matsushima

发明人： Hideki Ishihara ,  Tomoko Matsushima

IPC分类号： G06F7/60 ,  G06F19/00 ,  G06F15/00 ,  C12Q1/25

CPC分类号： G01N33/57484 ,  C12Q1/485 ,  G01N2333/9121 ,  G01N2800/52 ,  G06F19/20 ,  G06F19/24

摘要： A device for supporting a diagnosis of a cancer which provides information useful to decide whether or not an anthracycline anticancer drug should be administered to a cancer patient to be examined is disclosed. Concretely, the device is composed to be able to acquire an activity and an expression of two cyclin dependent kinases (CDK) from a malignant tumor of a cancer patient to be examined, and to acquire a CDK parameters from both of two CDKs. Furthermore the device determines sample data comprising predetermined CDK parameter, and display information of determined sample data. According to the above component, user is easily able to know whether or not a cancer of a cancer patient, whose tumor is similar to the tumor of the cancer patient to be examined, has been recurred in spite of an administration of an anthracycline anticancer drug.

摘要翻译： 公开了一种用于支持癌症诊断的装置，其提供用于决定是否向被检查的癌症患者施用蒽环类抗癌药物的信息。 具体地说，该装置构成为能够从要检查的癌症患者的恶性肿瘤获得两种细胞周期蛋白依赖性激酶（CDK）的活性和表达，并从两种CDK中获得CDK参数。 此外，设备确定包括预定CDK参数的样本数据，以及确定的样本数据的显示信息。 根据上述成分，使用者能够容易地知道尽管施用了蒽环类抗癌药物，癌肿瘤患者的肿瘤是否与待检查的癌症患者的肿瘤相似。 。

公开(公告)号：US20110246413A1

公开(公告)日：2011-10-06

申请号：US13074745

申请日：2011-03-29

申请人： Masaki SHIBAYAMA ,  Hideki Ishihara ,  Keigo Gohda ,  Satoshi Nakayama ,  Tadashi Kiniwa

发明人： Masaki SHIBAYAMA ,  Hideki Ishihara ,  Keigo Gohda ,  Satoshi Nakayama ,  Tadashi Kiniwa

IPC分类号： G06N5/04 ,  C12Q1/48

CPC分类号： G06F19/18 ,  G01N33/57496 ,  G01N2800/54

摘要： A method for judging a risk of cancer recurrence comprising: acquiring an activity value and expression level of a first cyclin dependent kinase (CDK) of a cell contained in tissues extracted from cancer patients, an activity value and expression level of a second CDK, and a number of Ki67-expressing cells or an expression level of Ki67; and judging a risk of cancer recurrence based on the acquired activity value and expression level of the first CDK, the activity value and expression level of the second CDK, and a percentage of Ki67-expressing cells or the expression level of Ki67. A computer program product and a computer system are also disclosed.

摘要翻译： 一种判断癌症复发风险的方法，包括：获得癌症患者提取的组织中含有的细胞的第一细胞周期蛋白依赖性激酶（CDK）的活性值和表达水平，第二CDK的活性值和表达水平，以及 多个Ki67表达细胞或Ki67表达水平; 根据获得的第一CDK的活性值和表达水平，第二CDK的活性值和表达量以及Ki67表达细胞的百分比或Ki67的表达水平来判断癌症复发的风险。 还公开了一种计算机程序产品和计算机系统。