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1. 发明申请

US20090286276A1 METHODS FOR PREDICTING A PATIENT'S RESPONSE TO EGFR INHIBITORS 审中-公开
标题翻译：方法预防患者对EGFR抑制剂的反应
公开(公告)号：US20090286276A1
公开(公告)日：2009-11-19
申请号：US12466129
申请日：2009-05-14
申请人： Stacey L. BROWER , Shara D. RICE , Heather M. BUECHEL , Lauren M. HANCHER
发明人： Stacey L. BROWER , Shara D. RICE , Heather M. BUECHEL , Lauren M. HANCHER
IPC分类号： C12Q1/02
CPC分类号： G01N33/574 , G01N33/5011 , G01N2333/485 , G01N2800/52
摘要： The present invention provides methods for individualizing chemotherapy for cancer treatment, and particularly for evaluating a patient's responsiveness to one or more epidermal growth factor receptor (EGFR) inhibitors prior to treatment with such agents. Particularly, the invention provides an in vitro chemoresponse assay for predicting a patient's response to an EGFR inhibitor, such as an EGFR tyrosine kinase inhibitor or a molecule targeting the extracellular domain of EGFR. The method generally comprises culturing malignant cells from a patient's specimen (e.g., biopsy specimen), contacting the cultured cells with an EGFR inhibitor that is a candidate treatment for the patient, and evaluating the cultured cells for a response to the drug. In certain embodiments, monolayer(s) of malignant cells are cultured from explants prepared by mincing tumor tissue, and the cells of the monolayer are suspended and plated for chemosenstivity testing. The in vitro response to the drug as determined by the method of the invention is correlative with the patient's in vivo response upon receiving the EGFR inhibitor during chemotherapeutic treatment (e.g., in combination with other standardized or individualized chemotherapeutic regimen).
摘要翻译：本发明提供了用于个体化癌症治疗化学疗法的方法，特别是用于评估患者在用这些药物治疗之前对一种或多种表皮生长因子受体（EGFR）抑制剂的反应性。特别地，本发明提供了用于预测患者对EGFR抑制剂（例如EGFR酪氨酸激酶抑制剂或靶向EGFR细胞外结构域的分子）的反应的体外化学应答测定。该方法通常包括从患者标本（例如活检标本）培养恶性细胞，使培养的细胞与作为患者候选治疗的EGFR抑制剂接触，并评价培养细胞对药物的应答。在某些实施方案中，从通过切割肿瘤组织制备的外植体培养恶性细胞的单层，并将单层细胞悬浮并铺板以进行化学敏感性测试。通过本发明的方法确定的药物的体外应答与在化疗期间接受EGFR抑制剂（例如，与其他标准化或个体化化学治疗方案组合）时患者的体内反应相关。

2. 发明申请

US20110130302A1 BIOLOGICAL PATHWAYS ASSOCIATED WITH CHEMOTHERAPY OUTCOME FOR BREAST CANCER 审中-公开
标题翻译：与乳腺癌化疗相关的生物学途径
公开(公告)号：US20110130302A1
公开(公告)日：2011-06-02
申请号：US12957608
申请日：2010-12-01
申请人： Kui SHEN , Nan Song , Shara D. Rice , Dakun Wang , David A. Gingrich , Zhenyu Ding , Chunqiao Tian , Stacey L. Brower , Paul R. Ervin , Michael Gabrin
发明人： Kui SHEN , Nan Song , Shara D. Rice , Dakun Wang , David A. Gingrich , Zhenyu Ding , Chunqiao Tian , Stacey L. Brower , Paul R. Ervin , Michael Gabrin
IPC分类号： C40B30/04 , C12Q1/68 , C40B40/06
CPC分类号： C12Q1/6886 , C12Q2600/106
摘要： The present invention provides methods for preparing drug response and/or resistance profiles for breast tumor specimens, or cells derived therefrom. The drug response and/or resistance profiles are useful for determining effective chemotherapeutic agents for treatment of the tumor or cell to thereby individualize patient therapy. In other aspects, the invention provides a method for identifying a pathway or gene expression signature indicative of a breast cancer cell's sensitivity to a chemotherapeutic agent, which is useful for identifying a population response rate, or patient sub-population likely to respond to the drug candidate.
摘要翻译：本发明提供了用于制备用于乳腺肿瘤标本或由其衍生的细胞的药物反应和/或抗性谱的方法。药物反应和/或抗性谱可用于确定用于治疗肿瘤或细胞的有效化学治疗剂，从而个体化患者治疗。在其它方面，本发明提供了一种用于鉴定指示乳腺癌细胞对化学治疗剂的敏感性的途径或基因表达特征的方法，其可用于鉴定群体应答率，或可能对药物有反应的患者亚群候选人。

3. 发明申请

US20110129822A1 MULTI DRUG RESPONSE MARKERS FOR BREAST CANCER CELLS 审中-公开
标题翻译：多种药物对乳腺癌细胞的反应标记
公开(公告)号：US20110129822A1
公开(公告)日：2011-06-02
申请号：US12957604
申请日：2010-12-01
申请人： Kui SHEN , Nan Song , Shara D. Rice , Dakun Wang , David A. Gingrich , Zhenyu Ding , Chunqiao Tian , Stacey L. Brower , Paul R. Ervin , Michael Gabrin
发明人： Kui SHEN , Nan Song , Shara D. Rice , Dakun Wang , David A. Gingrich , Zhenyu Ding , Chunqiao Tian , Stacey L. Brower , Paul R. Ervin , Michael Gabrin
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/112 , C12Q2600/158
摘要： The present invention provides methods for preparing a gene expression profile of a breast cancer cell, tumor, or cell line, where the gene expression profile may be evaluated for one or more gene expression signatures indicative of multidrug resistance. The signature may be indicative of resistance to one or more chemotherapeutic agents selected from a Taxol (e.g., Docetaxel or Paclitaxel), an antibiotic (e.g., Doxorubicin or Epirubicin), an antimetabolite (e.g., Fluorouracil and/or Gemcitabine), and an alkylating agent (e.g., Cyclophosphamide). Generally, the gene expression profile contains the level of expression for a plurality of genes listed in FIGS. 3, 4, and/or 5. Gene expression profiles for evaluating multidrug resistance for ER positive and ER negative breast cancers are also provided.
摘要翻译：本发明提供了制备乳腺癌细胞，肿瘤或细胞系的基因表达谱的方法，其中基因表达谱可被评估表示多药耐药性的一种或多种基因表达特征。签名可以指示对一种或多种选自紫杉醇（例如多西紫杉醇或紫杉醇），抗生素（例如多柔比星或表柔比星），抗代谢药（例如氟尿嘧啶和/或吉西他滨）和化学治疗剂药剂（如环磷酰胺）。通常，基因表达谱包含图1和2中列出的多个基因的表达水平。还提供了评估ER阳性和ER阴性乳腺癌多药耐药性的基因表达谱。

4. 发明申请

US20100311084A1 METHODS FOR PREDICTING A PATIENT'S RESPONSE TO EGFR INHIBITORS 审中-公开
标题翻译：方法预防患者对EGFR抑制剂的反应
公开(公告)号：US20100311084A1
公开(公告)日：2010-12-09
申请号：US12795286
申请日：2010-06-07
申请人： Stacey Brower , Shara D. Rice , Theresa R. Cassino , Lahari Sakhamuri , Heather M. Buechel , Lauren M. Hancher
发明人： Stacey Brower , Shara D. Rice , Theresa R. Cassino , Lahari Sakhamuri , Heather M. Buechel , Lauren M. Hancher
IPC分类号： G01N33/574
CPC分类号： G01N33/5091 , G01N33/574 , G01N2333/485 , G01N2800/52
摘要： The present invention provides methods for individualizing chemotherapy for cancer treatment, and particularly for evaluating a patient's responsiveness to one or more epidermal growth factor receptor (EGFR) inhibitors prior to treatment with such agents. Particularly, the invention provides an in vitro chemoresponse assay for predicting a patient's response to a monoclonal EGFR antibody, such as cetuximab. The method generally comprises culturing malignant cells from a patient's specimen (e.g., biopsy specimen), contacting the cultured cells with a monoclonal EGFR antibody that is a candidate treatment for the patient, and evaluating the cultured cells for a response to the drug. In certain embodiments, monolayer(s) of malignant cells are cultured from explants prepared by mincing tumor tissue, and the cells of the monolayer are suspended and plated for chemosenstivity testing. The in vitro response to the drug as determined by the method of the invention is correlative with the patient's in vivo response upon receiving the monoclonal EGFR antibody during chemotherapeutic treatment (e.g., in combination with other standardized or individualized chemotherapeutic regimen).
摘要翻译：本发明提供了用于个体化癌症治疗化学疗法的方法，特别是用于评估患者在用这些药物治疗之前对一种或多种表皮生长因子受体（EGFR）抑制剂的反应性。特别地，本发明提供了用于预测患者对单克隆EGFR抗体如西妥昔单抗的应答的体外化学应答测定。该方法通常包括从患者标本（例如活检标本）培养恶性细胞，使培养的细胞与作为患者候选治疗的单克隆EGFR抗体接触，并评价培养细胞对药物的应答。在某些实施方案中，从通过切割肿瘤组织制备的外植体培养恶性细胞的单层，并将单层细胞悬浮并铺板以进行化学敏感性测试。通过本发明的方法确定的对药物的体外应答与在化疗期间接受单克隆EGFR抗体（例如，与其他标准化或个体化化学治疗方案组合）时患者体内应答相关。

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