公开(公告)号：US09896730B2

公开(公告)日：2018-02-20

申请号：US13455972

申请日：2012-04-25

Applicant: Julie Kan ,  Stuart Thomson ,  Gretchen M. Argast ,  Matthew E. O'Connor ,  Murray Robinson ,  Bin Feng ,  Joerg Heyer ,  Maria I. Chiu ,  Richard Nicoletti

Inventor： Julie Kan ,  Stuart Thomson ,  Gretchen M. Argast ,  Matthew E. O'Connor ,  Murray Robinson ,  Bin Feng ,  Joerg Heyer ,  Maria I. Chiu ,  Richard Nicoletti

IPC: C12Q1/68

CPC classification number: C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/112 ,  C12Q2600/158

Abstract: The present invention provides diagnostic methods for assessing the EMT status of tumor cells, and for predicting the effectiveness of treatment of a cancer patient with an EGFR or IGF-1R kinase inhibitor, utilizing an EMT gene signature index score. The present invention further provides methods for treating patients with cancer that incorporate these methods.

公开(公告)号：US08383357B2

公开(公告)日：2013-02-26

申请号：US11787044

申请日：2007-04-13

Applicant: John D. Haley ,  Stuart Thomson ,  Filippo Petti

Inventor： John D. Haley ,  Stuart Thomson ,  Filippo Petti

IPC: G01N33/574

CPC classification number: G01N33/6893 ,  G01N33/5011 ,  G01N33/57407 ,  G01N33/57484 ,  G01N2800/52

Abstract: The present invention provides diagnostic and prognostic methods for predicting the effectiveness of treatment of a cancer patient with an EGFR kinase inhibitor. Methods are provided for predicting the sensitivity of tumor cell growth to inhibition by an EGFR kinase inhibitor, comprising assessing whether the tumor cell has undergone an epithelial to mesenchymal transition (EMT), by determining the expression level of epithelial and/or mesenchymal biomarkers, wherein tumor cells that have undergone an EMT are substantially less sensitive to inhibition by EGFR kinase inhibitors. Improved methods for treating cancer patients with EGFR kinase inhibitors that incorporate the above methodology are also provided. Additionally, methods are provided for the identification of new biomarkers that are predictive of responsiveness of tumors to EGFR kinase inhibitors. Furthermore, methods for the identification of agents that restore the sensitivity of tumor cells that have undergone EMT to inhibition by EGFR kinase inhibitors are also provided.

Abstract translation: 本发明提供用于预测EGFR激酶抑制剂治疗癌症患者的有效性的诊断和预后方法。 提供了用于预测肿瘤细胞生长对EGFR激酶抑制剂抑制的敏感性的方法，包括通过测定上皮和/或间质生物标志物的表达水平来评估肿瘤细胞是否经历了上皮间质转化（EMT），其中 已经经历EMT的肿瘤细胞对EGFR激酶抑制剂的抑制基本上较不敏感。 还提供了用于治疗结合上述方法的EGFR激酶抑制剂的癌症患者的改进方法。 另外，提供了用于鉴定预测肿瘤对EGFR激酶抑制剂的反应性的新生物标志物的方法。 此外，还提供了用于鉴定恢复已经经历EMT的肿瘤细胞对EGFR激酶抑制剂抑制的敏感性的药剂的方法。

公开(公告)号：US07951549B2

公开(公告)日：2011-05-31

申请号：US12381082

申请日：2009-03-06

Applicant: John D. Haley ,  Stuart Thomson ,  Julie Kan ,  Salam A. Shaaban

Inventor： John D. Haley ,  Stuart Thomson ,  Julie Kan ,  Salam A. Shaaban

IPC: G01N33/574 ,  C12Q1/02

CPC classification number: G01N33/5011 ,  G01N2333/475 ,  G01N2333/485 ,  G01N2333/495 ,  G01N2333/525

Abstract: The present invention provides tumor cell preparations for use as models of the EMT process for use in the identification of anti-cancer agents, wherein said tumor cell preparations comprise cells of the epithelial tumor cell line H358, which are stimulated by receptor ligands to induce EMT, or which have been engineered to inducibly express a protein that stimulates EMT. The present invention also provides methods of identifying potential anti-cancer agents by using such tumor cell preparations to identify agents that inhibit EMT, stimulate MET, or inhibit the growth of mesenchymal-like cells. Such agents should be particularly useful when used in conjunction with other anti-cancer drugs such as EGFR and IGF-1R kinase inhibitors, which appear to be less effective at inhibiting tumor cells that have undergone an EMT.

Abstract translation: 本发明提供用作鉴定抗癌剂的EMT方法的模型的肿瘤细胞制剂，其中所述肿瘤细胞制剂包含受体配体刺激以诱导EMT的上皮肿瘤细胞系H358的细胞 ，或已被设计成可诱导地表达刺激EMT的蛋白质。 本发明还提供了通过使用这样的肿瘤细胞制剂鉴定潜在的抗癌剂的方法来鉴定抑制EMT，刺激MET或抑制间充质细胞生长的药剂。 当与其它抗癌药物如EGFR和IGF-1R激酶抑制剂联合使用时，这些药剂应该特别有用，对于抑制已经发生EMT的肿瘤细胞来说，这些药物似乎效果较差。

公开(公告)号：US20070212738A1

公开(公告)日：2007-09-13

申请号：US11787044

申请日：2007-04-13

Applicant: John Haley ,  Stuart Thomson ,  Filippo Petti

Inventor： John Haley ,  Stuart Thomson ,  Filippo Petti

IPC: G01N33/574

CPC classification number: G01N33/6893 ,  G01N33/5011 ,  G01N33/57407 ,  G01N33/57484 ,  G01N2800/52

Abstract: The present invention provides diagnostic and prognostic methods for predicting the effectiveness of treatment of a cancer patient with an EGFR kinase inhibitor. Methods are provided for predicting the sensitivity of tumor cell growth to inhibition by an EGFR kinase inhibitor, comprising assessing whether the tumor cell has undergone an epithelial to mesenchymal transition (EMT), by determining the expression level of epithelial and/or mesenchymal biomarkers, wherein tumor cells that have undergone an EMT are substantially less sensitive to inhibition by EGFR kinase inhibitors. Improved methods for treating cancer patients with EGFR kinase inhibitors that incorporate the above methodology are also provided. Additionally, methods are provided for the identification of new biomarkers that are predictive of responsiveness of tumors to EGFR kinase inhibitors. Furthermore, methods for the identification of agents that restore the sensitivity of tumor cells that have undergone EMT to inhibition by EGFR kinase inhibitors are also provided.

Abstract translation: 本发明提供用于预测EGFR激酶抑制剂治疗癌症患者的有效性的诊断和预后方法。 提供了用于预测肿瘤细胞生长对EGFR激酶抑制剂抑制的敏感性的方法，包括通过测定上皮和/或间质生物标志物的表达水平来评估肿瘤细胞是否经历了上皮与间质转化（EMT），其中 已经经历EMT的肿瘤细胞对EGFR激酶抑制剂的抑制基本上较不敏感。 还提供了用于治疗结合上述方法的EGFR激酶抑制剂的癌症患者的改进方法。 另外，提供了用于鉴定预测肿瘤对EGFR激酶抑制剂的反应性的新生物标志物的方法。 此外，还提供了用于鉴定恢复已经经历EMT的肿瘤细胞对EGFR激酶抑制剂抑制的敏感性的药剂的方法。

公开(公告)号：US20060224732A1

公开(公告)日：2006-10-05

申请号：US11349018

申请日：2006-02-07

Applicant: Bruce Gilmour ,  Donald Scobbie ,  Gavin Lauchlan ,  Stuart Thomson

Inventor： Bruce Gilmour ,  Donald Scobbie ,  Gavin Lauchlan ,  Stuart Thomson

IPC: G06F15/173

CPC classification number: H04L41/0631 ,  H04L41/00 ,  H04L43/12 ,  H04W24/00 ,  H04W24/04

Abstract: A method and apparatus for monitoring telecommunications network elements, especially where direct access to those network elements is not available. The invention allows a network manager to build and maintain significant relationship information, as well as model the state of network elements with a high degree of accuracy, but based only on the information contained within the transactions built from the network traffic which is being monitored. In particular, it allows the network manager to obtain the same results that would previously have required direct access to an operator's network elements.

Abstract translation: 一种用于监视电信网络元件的方法和装置，特别是在对这些网络元件的直接访问不可用的情况下。 本发明允许网络管理器构建和维护重要的关系信息，以及以高精确度对网络元素的状态进行建模，而仅基于包含在正在被监视的网络流量构建的事务中的信息。 特别地，它允许网络管理器获得先前需要直接访问运营商的网络元件的相同结果。