TUMOR MARKERS TO PREDICT TREATMENT RESPONSE

肿瘤标志物可预测治疗反应

• 批准号: 6790615
• 负责人: LYNN Gail DRESSLER
• 金额: $ 27.94万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-10 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6790615
• 关键词: CD34 molecule; antineoplastics; breast neoplasm /cancer diagnosis; breast neoplasms; cadherins; cooperative study; diagnosis design /evaluation; enzyme activity; enzyme induction /repression; estrogen receptors; female; flow cytometry; focal adhesion kinase; human old age (65+); neoplasm /cancer chemotherapy; neoplasm /cancer genetics; oncogenes; p53 gene /protein; pentosyltransferase; progesterone receptors; receptor expression; thymidylate synthase; tumor antigens; vascular endothelial growth factors; women' s health

DESCRIPTION (Applicant?s Description): This revised application for funding is part of a multidisciplinary CALGB research project targeting elderly women with breast cancer. This study is a laboratory companion to the clinical trial proposed by the CALGB, entitled," A Randomized Trial of Adjuvant Chemotherapy with Standard Regimens, Cyclophosphamide, Methotrexate and Fluorouracil- "CMF" or Cyclophosphamide and Doxorubicin -"AC" versus Capecitabine in Women 65 Years and Older with Early?? Stage Breast cancer. The primary aim of the clinical trial is to compare the effectiveness of standard chemotherapy regimens (CMF or AC) with a less toxic, single agent (Capecitabine), with respect to five-year relapse free survival in women 65 years and older with early stage breast cancer. The laboratory companion is designed to evaluate tumor specimens (formalin-fixed paraffin-embedded, FFPE) that are collected as part of the CALGB clinical trial to examine the relationships between biological markers of tumor progression and clinical outcome in elderly women with early stage breast cancer. We have selected tumor markers that are associated with metabolic pathways of chemotherapy action as well as those associated with common pathways of tumor progression. We will evaluate whether specific markers of capecitabine metabolism, thymidylate synthetase, thymidine phosphorylase and dihyodropyrimidine dehydrogenase gene expression (mRNA) can predict recurrence and survival in patients treated with capecitabine. We will also determine whether local regional or distant failure can be predicted in this population based on a tumor marker profile that reflects markers of genetic instability/proliferation in the primary tumors, (protein expression of p53, erbB2/HER2, and KI-67 (MIB-1) as well as markers of invasion and metastasis (angeogenesis, focal adhesion kinase, VEGF and e-cadherin). The expression of these markers will be correlated with conventional markers of tumor size, histologic and nuclear grade, and estrogen and progesterone receptor status. In addition, comparisons of tumor marker expression between elderly and younger populations with node positive breast cancer (patients from this adjuvant chemotherapy trial and CALGB 8541) will be performed. It will also be possible to compare tumor marker expression between elderly patients with stage I and stage II breast cancer (patients from this adjuvant chemotherapy trial and CALGB 9343). Two subcontracts are included in this proposal, one to support the CALGB Pathology Coordinating Office functions at OSU relevant to this study and the other in support of the molecular studies being performed by USC.

描述（申请人的描述）： 此修订的资金申请是多学科的一部分 针对老年乳腺癌妇女的研究项目。这项研究是 Calgb提出的临床试验的实验室伴侣，标题为“ A 用标准方案的辅助化疗随机试验， 环磷酰胺，甲氨蝶呤和氟尿嘧啶 - “ CMF”或环磷酰胺以及 阿霉素 - 年龄在65岁及以上的女性中，“ AC”与卡皮替滨（Capecitabine）早。 阶段乳腺癌。临床试验的主要目的是比较 具有毒性较小的标准化疗方案（CMF或AC）的有效性 关于五年的无复发生存 在早期乳腺癌65岁及以上的女性中。实验室 伴侣旨在评估肿瘤标本（福尔马林固定石蜡包裹， FFPE）是作为CALB临床试验的一部分收集到的 检查肿瘤进展的生物学标记与 早期乳腺癌老年妇女的临床结果。我们有 与代谢途径相关的选定肿瘤标记 化学疗法作用以及与肿瘤的常见途径相关的作用 进展。我们将评估Capecitabine的特定标记 代谢，胸苷酸合成酶，胸苷磷酸化酶和 二羟基嘧啶脱氢酶基因表达（mRNA）可以预测复发性 以及用卡捷他滨治疗的患者的生存。我们还将确定 在该人群中是否可以预测当地区域或遥远的失败 基于反映遗传标记的肿瘤标记谱 原发性肿瘤中的不稳定性/增殖（p53的蛋白质表达， ERBB2/HER2和KI-67（MIB-1）以及入侵和转移的标记 （Angeogeny，局灶性粘附激酶，VEGF和E-钙粘蛋白）。表达 这些标记将与肿瘤大小的常规标记相关， 组织学和核等级以及雌激素和孕酮受体状态。 另外，老年人和老年人表达的比较 乳腺癌阳性阳性阳性乳腺癌的年轻人群（来自此的患者 将进行辅助化疗试验和CALGB 8541）。也将是 可以比较老年患者之间的肿瘤标志物表达 I期和II期乳腺癌（该辅助化疗的患者 试验和CALGB 9343）。该提案中包括两个分包合同，一个 支持与OSU的CALGB病理协调办公室功能有关 这项研究，另一项支持分子研究 由南加州大学。