公开(公告)号：US20140242602A1

公开(公告)日：2014-08-28

申请号：US14131423

申请日：2012-07-06

申请人： Gabriela Chiosis ,  Tony Taldone ,  Mary L. Alpaugh ,  Erica M. Gomes-Dagama ,  Monica L. Guzman ,  Hongliang Zong

发明人： Gabriela Chiosis ,  Tony Taldone ,  Mary L. Alpaugh ,  Erica M. Gomes-Dagama ,  Monica L. Guzman ,  Hongliang Zong

IPC分类号： G01N33/574

CPC分类号： A61K51/0459 ,  A61K31/52 ,  G01N33/5011 ,  G01N33/5017 ,  G01N33/5044 ,  G01N33/574 ,  G01N33/57407 ,  G01N33/57426 ,  G01N2500/04 ,  G01N2800/52

摘要： The disclosure provides evidence that the abundance of this particular “oncogenic HSP90” species, which is not dictated by HSP90 expression alone, predicts for sensitivity to HSP90 inhibition therapy, and thus is a biomarker for HSP90 therapy. The disclosure also provides evidence that identifying and measuring the abundance of this oncogenic HSP90 species in tumors predicts of response to HSP90 therapy. “Oncogenic HSP90” is defined herein as the HSP90 fraction that represents a cell stress specific form of chaperone complex, that is expanded and constitutively maintained in the tumor cell context, and that may execute functions necessary to maintain the malignant phenotype. Such roles are not only to regulate the folding of overexpressed (i.e. HER2), mutated (i.e. mB-Raf) or chimeric proteins (i.e. Bcr-Abl), but also to facilitate scaffolding and complex formation of molecules involved in aberrantly activated signaling complexes (i.e. STATS, BCL6).

摘要翻译： 该公开提供了证据表明，单独HSP90表达不规定的特定“致癌HSP90”物种的丰度预测对HSP90抑制疗法的敏感性，因此是HSP90治疗的生物标志物。 本公开还提供了证据，确定和测量肿瘤中这种致癌HSP90物种的丰度预测了对HSP90治疗的反应。 “致癌HSP90”在本文中被定义为代表分子伴侣复合物的细胞应激特异性形式的HSP90级分，其在肿瘤细胞环境中被扩增和组成型维持，并且可以执行维持恶性表型所需的功能。 这样的作用不仅是调节过表达（即HER2），突变（即mB-Raf）或嵌合蛋白（即Bcr-Abl）的折叠，而且还促进涉及异常激活的信号传导复合体的分子的支架和复合物形成 即STATS，BCL6）。

公开(公告)号：US09555137B2

公开(公告)日：2017-01-31

申请号：US14131423

申请日：2012-07-06

申请人： Gabriela Chiosis ,  Tony Taldone ,  Mary L. Alpaugh ,  Erica M. Gomes-Dagama ,  Monica L. Guzman ,  Hongliang Zong

发明人： Gabriela Chiosis ,  Tony Taldone ,  Mary L. Alpaugh ,  Erica M. Gomes-Dagama ,  Monica L. Guzman ,  Hongliang Zong

IPC分类号： G01N33/574 ,  A61K31/52 ,  A61K51/04 ,  G01N33/50

CPC分类号： A61K51/0459 ,  A61K31/52 ,  G01N33/5011 ,  G01N33/5017 ,  G01N33/5044 ,  G01N33/574 ,  G01N33/57407 ,  G01N33/57426 ,  G01N2500/04 ,  G01N2800/52

摘要： The disclosure provides evidence that the abundance of this particular “oncogenic HSP90” species, which is not dictated by HSP90 expression alone, predicts for sensitivity to HSP90 inhibition therapy, and thus is a biomarker for HSP90 therapy. The disclosure also provides evidence that identifying and measuring the abundance of this oncogenic HSP90 species in tumors predicts of response to HSP90 therapy. “Oncogenic HSP90” is defined herein as the HSP90 fraction that represents a cell stress specific form of chaperone complex, that is expanded and constitutively maintained in the tumor cell context, and that may execute functions necessary to maintain the malignant phenotype. Such roles are not only to regulate the folding of overexpressed (i.e. HER2), mutated (i.e. mB-Raf) or chimeric proteins (i.e. Bcr-Abl), but also to facilitate scaffolding and complex formation of molecules involved in aberrantly activated signaling complexes (i.e. STATS, BCL6).

摘要翻译： 该公开提供了证据表明，单独HSP90表达不规定的特定“致癌HSP90”物种的丰度预测对HSP90抑制疗法的敏感性，因此是HSP90治疗的生物标志物。 本公开还提供了证据，确定和测量肿瘤中这种致癌HSP90物种的丰度预测了对HSP90治疗的反应。 “致癌HSP90”在本文中被定义为代表分子伴侣复合物的细胞应激特异性形式的HSP90级分，其在肿瘤细胞环境中被扩增和组成型维持，并且可以执行维持恶性表型所需的功能。 这样的作用不仅是调节过表达（即HER2），突变（即mB-Raf）或嵌合蛋白（即Bcr-Abl）的折叠，而且还促进涉及异常激活的信号传导复合体的分子的支架和复合物形成 即STATS，BCL6）。

公开(公告)号：US20140294725A1

公开(公告)日：2014-10-02

申请号：US14131420

申请日：2012-07-06

申请人： Gabriela Chiosis ,  Nagavarakishore Pillarsetty ,  Jason S. Lewis ,  Steven M. Larson ,  Tony Taldone ,  Mary L. Alpaugh ,  Erica M. Gomes

发明人： Gabriela Chiosis ,  Nagavarakishore Pillarsetty ,  Jason S. Lewis ,  Steven M. Larson ,  Tony Taldone ,  Mary L. Alpaugh ,  Erica M. Gomes

IPC分类号： A61K51/04 ,  G01N33/574

CPC分类号： A61K51/0459 ,  A61K31/52 ,  G01N33/5011 ,  G01N33/5017 ,  G01N33/5044 ,  G01N33/574 ,  G01N33/57407 ,  G01N33/57426 ,  G01N2500/04 ,  G01N2800/52

摘要： The invention concerns various methods of using labeled HSP90 inhibitors to improve treatment of cancer patients with HSP90 inhibitors, including ex vivo and in vivo methods for determining whether a tumor will likely respond to therapy with an HSP90 inhibitor. The disclosure provides a method for determining whether a tumor will likely respond to therapy with an HSP90 inhibitor which comprises the following steps: (a) contacting the tumor or a sample containing cells from the tumor with a detectably labeled HSP90 inhibitor which binds preferentially to a tumor-specific form of HSP90; (b) measuring the amount of labeled HSP90 inhibitor bound to the tumor or the tumor cells in the sample; and (c) comparing the amount of labeled HSP90 inhibitor bound to the tumor or the tumor cells in the sample measured in step (b) to the amount of labeled-HSP90 inhibitor bound to a reference.

摘要翻译： 本发明涉及使用标记的HSP90抑制剂改善用HSP90抑制剂治疗癌症患者的各种方法，包括用于确定肿瘤是否可能对HSP90抑制剂治疗有反应的离体和体内方法。 本公开提供了一种用于确定肿瘤是否可能响应于HSP90抑制剂治疗的方法，该方法包括以下步骤：（a）使来自肿瘤的肿瘤或含有细胞的样品与优先结合于肿瘤的可检测标记的HSP90抑制剂接触 肿瘤特异性形式的HSP90; （b）测量与样品中的肿瘤或肿瘤细胞结合的标记的HSP90抑制剂的量; 和（c）将在步骤（b）中测量的样品中与肿瘤或肿瘤细胞结合的标记HSP90抑制剂的量与结合参考物的标记的HSP90抑制剂的量进行比较。

公开(公告)号：US06455027B1

公开(公告)日：2002-09-24

申请号：US09153564

申请日：1998-09-15

申请人： Sanford H. Barsky ,  Susan M. Love ,  Mary L. Alpaugh

发明人： Sanford H. Barsky ,  Susan M. Love ,  Mary L. Alpaugh

IPC分类号： A61B500

CPC分类号： A61K49/0058 ,  A61K49/0013 ,  A61K49/0043 ,  A61K49/006

摘要： Methods, kits, and apparatus for locating, labelling, and accessing breast ducts are described. An orifice to one or more ductal networks is marked to enhance visibility. In a first embodiment, the orifice is labelled using a specific binding substance, typically an antibody, specific for a tissue marker present on the orifice. Exemplary tissue markers include those present on the ductal epithelium, such as cytokeratins, including cytokeratin 8 and cytokeratin 18; cadhedrins, such as E cadhedrin; and epithelial membrane antigens. In a second embodiment, a dye is injected into the base of the nipple and preferentially accumulates at at least some of the orifices. Other marking techniques are also described. Marking of the ductal orifices permits reliable identification and access to each of the multiple ductal networks which may be present in an individual breast.

摘要翻译： 描述了用于定位，标记和访问乳房导管的方法，套件和装置。 标记到一个或多个导管网络的孔口以增强可视性。 在第一个实施方案中，使用特定的结合物质（通常是针对存在于孔口上的组织标记物的抗体）标记孔。 示例性组织标志物包括存在于导管上皮上的那些，例如细胞角蛋白，包括细胞角蛋白8和细胞角蛋白18; 院士，如E小学生; 和上皮膜抗原。 在第二实施方案中，将染料注入到乳头的基部中，并且优选地在至少一些孔口处积聚。 还描述了其他标记技术。 导管孔的标记允许可靠地识别和进入可能存在于单独乳房中的多个导管网络中的每一个。

公开(公告)号：US06998513B1

公开(公告)日：2006-02-14

申请号：US09856104

申请日：2000-09-15

申请人： Sanford H. Barsky ,  Mary L. Alpaugh ,  James S. Tomlinson

发明人： Sanford H. Barsky ,  Mary L. Alpaugh ,  James S. Tomlinson

IPC分类号： A01K67/00 ,  A01K67/033 ,  A61K49/00 ,  C12N5/00 ,  C12N5/08

CPC分类号： A01K67/0271 ,  A01K2227/105 ,  A01K2267/0331 ,  A61K49/0008 ,  A61K2039/505 ,  C07K16/18 ,  C07K16/30 ,  C12N5/0693 ,  C12N2503/00

摘要： The present invention provides human transplantable inflammatory breast carcinoma xenografts. Such xenografts exhibit a number of unique characteristics which allows their use in experimental models of inflammatory carcinoma in order to dissect out the molecular basis of this phenotype. This experimental model of inflammatory carcinoma can be used to identify molecular targets for therapeutic intervention and to assess the efficacy of a broad spectrum of diagnostic and therapeutic agents. Specific animal models of inflammatory breast cancer are described as well as methods for evaluating diagnostic and therapeutic agents for treating inflammatory breast cancer. Methods for identifying molecules whose expression is modulated in inflammatory breast cancer are provided. In addition, methods for diagnosing and inhibiting the growth of inflammatory breast cancer metastases in vivo are provided.

摘要翻译： 本发明提供人类可移植的炎性乳腺癌异种移植物。 这种异种移植物表现出许多独特的特征，允许它们在炎性癌的实验模型中使用，以便剖析该表型的分子基础。 这种炎性癌的实验模型可用于鉴定治疗性干预的分子靶点，并评估广谱诊断和治疗药物的功效。 描述了炎性乳腺癌的具体动物模型以及用于评估用于治疗炎性乳腺癌的诊断和治疗剂的方法。 提供了用于鉴定表达在炎性乳腺癌中调节的分子的方法。 另外，提供了用于诊断和抑制体内炎性乳腺癌转移生长的方法。

公开(公告)号：US20170336392A1

公开(公告)日：2017-11-23

申请号：US15584593

申请日：2017-05-02

申请人： Emmanuel A. Theodorakis ,  Mary L. Alpaugh

发明人： Emmanuel A. Theodorakis ,  Mary L. Alpaugh

IPC分类号： G01N33/50

CPC分类号： G01N33/5011

摘要： The present invention relates to imaging methods to assess the efficacy of anticancer drugs in vitro using spontaneously-forming spheroids.

公开(公告)号：US06514695B1

公开(公告)日：2003-02-04

申请号：US09488464

申请日：2000-01-20

申请人： Sanford H. Barsky ,  Mary L. Alpaugh

发明人： Sanford H. Barsky ,  Mary L. Alpaugh

IPC分类号： C12Q168

CPC分类号： C12N15/86 ,  A61K38/57 ,  A61K48/00 ,  C12N2710/10343 ,  C12N2750/14143 ,  C12N2810/6018

摘要： The present invention provides methods for the selective transduction of a cell in a ductal system in a mammary gland by contacting, via ductal cannulation, the cell with a vector that selectively targets the cell. In this context, the invention provides prophylactic and therapeutic methods of treating the ductal epithelium of the breast, for disease, in particular cancer. The present invention further provides diagnostic methods of determining the presence of disease in the ductal epithelium of the breast, in particular cancer.

摘要翻译： 本发明提供了通过导管插管将细胞与选择性靶向细胞的载体接触来选择性转导乳腺导管系统中的细胞的方法。 在本文中，本发明提供了治疗乳腺导管上皮，特别是癌症的预防和治疗方法。 本发明还提供了确定乳腺导管上皮，特别是癌症中疾病存在的诊断方法。