A biosensor to detect ERE-binding proteins in cancer

检测癌症中 ERE 结合蛋白的生物传感器

• 批准号: 6832976
• 负责人: Judith L. Erb
• 金额: $ 11.36万
• 依托单位: IA, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-16 至 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6832976
• 关键词: antireceptor antibody; binding proteins; biomarker; biopsy; biosensor device; biotechnology; breast neoplasm /cancer diagnosis; breast neoplasms; clinical research; diagnosis design /evaluation; estradiol; estrogen receptors; gel mobility shift assay; genetic regulatory element; human therapy evaluation; human tissue; prognosis; rapid diagnosis; recombinant proteins; tamoxifen

DESCRIPTION (provided by applicant): Biosensors provide rapid data containing information on molecular interactions that are not easily available using equilibrium assays or histochemical methods. This study will be the first of a series with long-term objectives of developing rapid biosensor methods applied to extracts of breast cancer biopsies for (1) predicting risk of recurrence in both node negative and node positive breast cancers, (2) recognizing the presence of previously unidentified ERE-binding components in tumors, and (3) obtaining information leading to selection of effective therapeutic treatment modalities having a high likelihood of success for a given individual's breast cancer. As the first of the series, this study focuses primarily on establishing novel biosensor methods, which correlate with prognostic information for the cancer represented in extracts of tumor tissue biopsies. The proposed methods utilize IA, Inc.'s biosensor technology in conjunction with the extensive tumor bank and associated records, and resources for receptor preparation and assay at the University of Louisville. Specific aims are: (1) Use antibody-based sensors to assess established tumor markers in breast cancer biopsy extracts, (2) Assess capacity of selected tumor extracts of high risk and low risk node negative and node positive biopsies to compete with standardized hER preparation for binding to sensors bearing various EREs. ERE sequences found upstream of the promotor region of genes having known relevance to processes of tumorigenesis will be used. Included will be genes for proteins found in breast cancers, which have been associated with prognosis for patient response to Tamoxifen treatment, such as cathepsin D and pS2, and genes for transcription factors h-fos and jun. (3) Correlate the biosensor results with data from electrophoretic mobility shift and supershift assays and with retrospective analysis of patient characteristics and clinical follow-up. (4) Compare binding of tumor extract to ERE fibers with and without 4-OH-tamoxifen and correlate results with treatment outcome data. This novel approach with miniaturized biosensor techniques holds promise for rapid assessment of tumor markers and discovering new cancer associated regulatory proteins of clinical significance. It could reveal previously unrecognized ERE-binding proteins in tumors, and will lead to a biosensor product, which is an improved method for identifying treatment modalities most likely to produce a positive outcome for an individual cancer. Phase II studies will expand the sample base and will include a broader range of antibodies for tumor marker identifications. Co-activator and co-repressor interactions as well as ERE and other response element interactions will be included. Previously unidentified ERE binding-components will be characterized. If the 4-OH-tamoxifen sensor data correlates well with treatment outcome, additional therapeutic agents will be similarly assessed.

描述（由申请人提供）：生物传感器提供了快速数据，其中包含有关分子相互作用的信息，这些信息不容易使用平衡测定或组织化学方法获得。这项研究将是系列中的第一个，其长期目标是开发快速生物传感器方法，该方法应用于乳腺癌活检提取物，用于（1）预测节点阴性和节点阳性乳腺癌的复发风险，（2）认识到存在先前未识别的乳腺肿瘤中的乳腺肿瘤，以及在肿瘤中具有更高的乳腺疗法，以及（3）获得有效的A A A A A A A A A A A A A A A A A A A A A A A A A A A A Spection，（3） 癌症。作为系列的第一个，这项研究主要着重于建立新型的生物传感器方法，该方法与肿瘤组织活检提取物中所代表的癌症的预后信息相关。拟议的方法利用IA，Inc。与广泛的肿瘤库和相关记录以及路易斯维尔大学的受体制备和测定资源结合使用IA，Inc。的生物传感器技术。具体目的是：（1）使用基于抗体的传感器评估乳腺癌活检提取物中既定的肿瘤标志物，（2）评估所选肿瘤提取物的能力高风险和低风险节点阴性和节点阳性活检，以与标准化的她的准备工作，以使其与具有各种ERE的传感器结合。将使用与肿瘤发生过程相关的基因启动子区域的序列。其中包括在乳腺癌中发现的蛋白质基因，与患者对他莫昔芬治疗的反应有关，例如组织蛋白酶D和PS2，以及转录因子H-Fos和JUN的基因。 （3）将生物传感器的结果与电泳迁移率转移和超级速度测定的数据相关联，以及对患者特征和临床随访的回顾性分析。 （4）将肿瘤提取物与带有或没有4-OH氨基氧法的ERE纤维的结合与治疗结果数据相关联。这种新颖的方法用微型生物传感器技术有望快速评估肿瘤标志物，并发现与临床意义相关的新癌症调节蛋白。它可以揭示先前未识别的肿瘤中结合蛋白，并将导致生物传感器产物，这是一种改进的方法，用于鉴定最有可能对个体癌症产生积极结果的治疗方式。 第二阶段的研究将扩大样品基础，并将包括用于肿瘤标志物鉴定的更广泛的抗体。将包括共激活因子和共抑制剂相互作用以及ERE和其他响应元素相互作用。以前未识别的ERE结合组件将被表征。如果4-OH-Tamoxifen传感器数据与治疗结果良好相关，则将类似地评估其他治疗剂。