Role of Macrophages in Resistance to Anti-VEGF Drugs in Ovarian Cancer

巨噬细胞在卵巢癌抗 VEGF 药物耐药中的作用

• 批准号: 8731088
• 负责人: ROBERT C BAST
• 金额: $ 5万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-05 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8731088
• 关键词: Algorithms; Biological Assay; Biological Markers; CA-125 Antigen; Cancer Patient; Combination Drug Therapy; Computational algorithm; Conventional Surgery; Data; Detection; Diagnosis; Diagnostic; Diagnostic Neoplasm Staging; Disease; Early Diagnosis; Evaluation; Gene Expression; Goals; Grant; Instruction; Laparotomy; Malignant Neoplasms; Malignant neoplasm of ovary; Measures; Neoplasms; Operative Surgical Procedures; Participant; Patients; Performance; Pharmaceutical Preparations; Population; Postmenopause; Predictive Value; Prevalence; Principal Investigator; Proteomics; Resistance; Risk; Role; Rosa; Screening for Ovarian Cancer; Sensitivity and Specificity; Serum; Serum Markers; Site; Specificity; Staging; Techniques; Testing; Time; Tumor stage; Ultrasonography; United Kingdom; University of Texas M D Anderson Cancer Center; Validation; WFDC2 gene; Woman; advanced disease; base; bevacizumab; chemotherapy; disorder risk; macrophage; operation; pre-clinical; programs; screening; uncertain malignant potential neoplasm

PROJECT SUMMARY (See instructions): The goal of SPORE Project 1 is to develop effective strategies for earty detection of ovanan cancer in women at average risk for the disease. Given the prevalence of ovanan cancer among postmenopausal women, a diagnostic strategy must be moderately sensitive (>75%), but highly specific (>99.6%) to achieve a positive predictive value of 10%, i.e., 10 laparotomies for each case of ovarian cancer detected. One of the most promising approaches to early detection of this neoplasm is to use rising values of a serum marker such as CA 125 to prompt the performance of transvaginal sonography (TVS). Patients with abnormal TVS or a sufficiently rapid rise in CA 125 undergo exploratory surgery. During the last grant period, we have evaluated this strategy and found a positive predictive value of 30%. If one is to pursue a two-stage strategy for earty detection, the initial stage must be optimally sensitive. No single marker is likely to be adequately sensitive and multiple markers may be required to detect the full spectrum of ovarian cancers. Simple addition of multiple markers may increase sensitivity, but generally decreases specificity, posing a particular problem in a disease with the prevalence of ovarian cancer. We have identified a panel of four biomarkers (CA125, HE4, CEA and sVCAM-1) that detect 87% of early stage disease at 98% specificity. In this project, our aims are Aim 1: To evaluate the specificity and positive predictive value of an algorithm for early detection of ovarian cancer based on a panel of serum biomarkers measured annually. Multiple biomarkers promise to increase sensitivity for earty stage and preclinical disease, provided that specificity is maintained, permitting performance of TVS in a small fraction of participants. We will test the hypothesis that rising values of multiple biomarkers will prompt the referral of no more than 2% of women for TVS and achieve a positive predictive value >10%. Aim 2: To develop a "point of service" test for multiple serum biomarkers using a lab-on-a-chip sensor system that is performed on blood from a finger-stick. Screening could be simplified if results were immediately available and venipuncture was not required. We will test the hypothesis that measurement of the levels of the four biomarkers with a lab-on-a-chip.nanosystem will correlate with standard laboratory assays. Aim 3: To identify a panel of serum autoantibodies for eariy detection of ovarian cancer. Small volumes of ovanan cancer may not release sufficient antigen to be detected, but could evoke an antibody response. We will test the hypothesis that detection of autoantibodies to mutant and wild-type proteins will improve detection of ovarian cancers that do not elevate antigen levels.

项目总结（见说明）： SPORE项目1的目标是开发有效的策略，用于早期检测卵巢癌， 女性平均患病风险。考虑到绝经后妇女卵巢癌的患病率 对于女性，诊断策略必须是中等敏感性（>75%），但高度特异性（>99.6%），以实现 阳性预测值为10%，即，每发现一例卵巢癌，进行10次剖腹手术。之一 早期发现这种肿瘤最有希望的方法是使用血清标志物的升高值 例如CA 125，以促进经阴道超声检查（TVS）的执行。TVS异常患者 或者CA 125上升得足够快的病人接受了探查手术。在上一个资助期内， 评估了这一策略，发现阳性预测值为30%。如果要采取两阶段战略 对于早期检测，初始阶段必须具有最佳灵敏度。没有一个单一的标记可能足以 可能需要敏感的和多种标记物来检测卵巢癌的全部谱。简单 多个标记物的添加可增加灵敏度，但通常降低特异性，从而造成特定的 卵巢癌是一种常见的疾病。我们已经确定了一组四种生物标志物 （CA 125、HE 4、CEA和sVCAM-1），以98%的特异性检测87%的早期疾病。在本项目中， 我们的目标是目标1：评估一种算法的特异性和阳性预测值， 根据每年测量的一组血清生物标志物检测卵巢癌。多种生物标志物 有望增加对早期和临床前疾病的敏感性，只要保持特异性， 允许在一小部分参与者中进行TVS。我们将检验一个假设， 多个生物标志物的值将促使不超过2%的妇女转诊接受TVS， 阳性预测值> 10%。目的2：开发多种血清生物标志物的“服务点”检测 使用芯片实验室传感器系统，该系统对来自手指针刺的血液进行检测。筛查可能是 如果可以立即获得结果并且不需要静脉穿刺，则可以简化。我们将测试 假设用芯片实验室纳米系统测量四种生物标志物水平将 与标准的实验室化验相关联。目的3：鉴定一组早期抗甲状腺激素的血清自身抗体 卵巢癌的诊断小体积的卵巢癌可能不会释放足够的抗原， 检测到，但可以引起抗体反应。我们将检验检测自身抗体 突变型和野生型蛋白质将提高卵巢癌的检测，不提高抗原水平。