Breast Cancer Bone Metastasis

乳腺癌骨转移

基本信息

批准号：
8435146
负责人：
LARRY J. SUVA
金额：
$ 30.05万
依托单位：
UNIV OF ARKANSAS FOR MED SCIS
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-03-01 至 2018-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8435146
关键词：
Biochemical Markers Biochemistry Bioinformatics Biological Biological Assay Biological Markers Biological Process Blinded Blood Circulation Breast Cancer Detection Breast Cancer Early Detection Breast Cancer Treatment Cancer Burden Cancer Patient Cellular biology Clinical Clinical Oncology Data Set Development Diagnosis Diagnostic Disease Distant Evaluation Event Fingerprint Genetic Goals Human IL8 gene Individual Interleukin-8 Liquid substance Malignant Neoplasms Measures Metastatic Neoplasm to the Bone Methodology Monitor Mus Neoplasm Metastasis Osteoclasts Outcome Patients Pattern Peptides Performance Phenotype Plasma Plasma Proteins Positioning Attribute Positron-Emission Tomography Probability Process Protein Fingerprints Protein Fragment Proteins Proteomics Publishing Qualifying Quality of life Regulation Research Role Sensitivity and Specificity Serum Severities Signal Pathway Site Specimen Stress TNFSF11 gene Technology Testing Time Transgenic Mice Tumor Burden Tumor-Derived United States United States National Institutes of Health Woman bone bone cell bone imaging bone metabolism breast cancer diagnosis chemokine clinically relevant cohort improved in vivo insight interest malignant breast neoplasm neoplastic cell novel novel strategies null mutation osteoclastogenesis parathyroid hormone-related protein protein profiling protein purification public health relevance research study skeletal success tool tumor tumor progression

项目摘要

DESCRIPTION (provided by applicant): Our application entitled "Breast Cancer Bone Metastasis" is focused on the characterization of specific biomarkers (PTHrP(12-48) and IL-8) that we have identified in the circulation of breast cancer patients with bone metastasis. Currently, a barrier to understanding and treating diseases of interest to NIH/NCI, such as breast cancer bone metastasis, is the paucity of sensitive and specific biomarkers. The biomarker profile we have identified and validated contains PTHrP(12-48) and IL-8 and discriminates breast cancer patients with and without bone metastasis with a sensitivity and specificity of (98% and 82% respectively). These molecules have the potential to increase the accuracy of bone metastasis diagnosis in the clinical setting, provide new mechanistic insight into tumor-induced changes in bone metabolism and possibly even improve the assessment of breast cancer bone metastasis patient outcomes. Aim 1 will improve our existing assay and measure PTHrP(12-48) and IL-8 in patient plasma and human breast cancer specimens. Aim 2 will explore the mechanism of action of tumor-derived IL-8 in the regulation of osteoclastogenesis. Importantly, we will also obtain genetic evidence for direct effects of IL-8 on osteoclast formation in vivo and determine if IL-8 expression can rescue the osteopetrotic bone phenotype of RANKL-/- mice. Aim 3 will correlate other clinically relevant parameters such as survival, tumor burden and time-to-next SRE with our existing proteomic dataset, and then independently validate and identify the correlated biomarkers using untested archival patient plasma. The studies proposed will significantly impact the field by providing new information regarding the progression of breast cancer bone metastasis. If successful clinically, PTHrP(12-48) and IL-8 have the potential to be utilized as biochemical markers for the evaluation of breast cancer bone metastasis that may predict breast cancer burden and possibly even patient survival.

描述（由申请人提供）：我们的申请题为“乳腺癌骨转移”，重点是我们在患有骨转移的乳腺癌患者的循环中鉴定出的特定生物标志物（PTHrP（12-48）和IL-8）的表征。目前，理解和治疗 NIH/NCI 感兴趣的疾病（例如乳腺癌骨转移）的障碍是缺乏敏感和特异性的生物标志物。我们已鉴定和验证的生物标志物谱包含 PTHrP(12-48) 和 IL-8，并以敏感性和特异性（分别为 98% 和 82%）区分有骨转移和无骨转移的乳腺癌患者。这些分子有可能提高临床环境中骨转移诊断的准确性，为肿瘤引起的骨代谢变化提供新的机制见解，甚至可能改善对乳腺癌骨转移患者预后的评估。目标 1 将改进我们现有的检测方法并测量患者血浆和人类乳腺癌样本中的 PTHrP(12-48) 和 IL-8。目标 2 将探索肿瘤源性 IL-8 在调节破骨细胞生成中的作用机制。重要的是，我们还将获得 IL-8 直接影响的遗传证据体内破骨细胞形成并确定 IL-8 表达是否可以挽救 RANKL-/- 小鼠的骨硬化骨表型。目标 3 将把其他临床相关参数（例如生存率、肿瘤负荷和下次 SRE 时间）与我们现有的蛋白质组数据集相关联，然后使用未经测试的存档患者血浆独立验证和识别相关生物标志物。拟议的研究将通过提供有关乳腺癌骨转移进展的新信息对该领域产生重大影响。如果在临床上取得成功，PTHrP(12-48) 和 IL-8 有潜力用作评估乳腺癌骨转移的生化标记物，从而可以预测乳腺癌负担，甚至可能预测患者的生存率。