Development of Spectroscopic Biomarkers of Bone Quality in Metastatic Disease

转移性疾病骨质量光谱生物标志物的开发

• 批准号: 7872307
• 负责人: Xiaohong Bi
• 金额: $ 10.58万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7872307
• 关键词: Aging; Animal Model; Apatites; Award; Biological; Biological Markers; Bioluminescence; Biomedical Research; Bone Matrix; Bone Pain; Bone Tissue; Bone neoplasms; Bone remodeling; Breast; Cancer Biology; Cardiac; Categories; Chemistry; Clinic; Collaborations; Collagen; Data; Development; Diagnosis; Diagnostic; Diagnostic radiologic examination; Discrimination; Disease; Educational workshop; Evaluation; Extracellular Matrix; Extramural Activities; Factor Analysis; Fiber Optics; Fracture; Funding; Future; Goals; Hand; Histology; Hypercalcemia; Image; Immunohistochemistry; In Situ; In Vitro; Injection of therapeutic agent; Knowledge; Laboratories; Malignant Neoplasms; Malignant neoplasm of prostate; Maps; Measurement; Measures; Mentors; Metastatic Neoplasm to the Bone; Methodology; Methods; Modeling; Molecular; Molecular Structure; Monitor; Morbidity - disease rate; Nature; Neoplasm Metastasis; Operative Surgical Procedures; Optics; Orthopedics; Osteoblasts; Osteoclasts; Osteolytic; Paralysed; Pathologic; Pathological fracture; Pattern Recognition; Primary Neoplasm; Principal Investigator; Property; Raman Spectrum Analysis; Research; Research Personnel; Research Project Grants; Resolution; Resources; Risk; Running; Sampling; Serum; Site; Spatial Distribution; Spectrum Analysis; Statistical Models; Structure; Surgeon; System; Techniques; Testing; Therapeutic; Time; Tissue Harvesting; Tissues; Training; Treatment Cost; Tumor Burden; Universities; Woman; anticancer research; base; bone; bone cell; bone quality; bone turnover; cancer cell; cancer diagnosis; career; career development; environmental change; experience; improved; in vivo; interest; malignant breast neoplasm; medical specialties; men; mineralization; mouse model; non-invasive system; novel; novel strategies; outcome forecast; photonics; programs; public health relevance; response; skills; statistics; therapy development; tool; tumor; tumor progression; two-dimensional

DESCRIPTION (provided by applicant): The PI's long term career goal is to become an independent investigator in quantitative cancer research specializing in bone metastasis. The main research interest is to develop novel optical methodologies for cancer diagnosis or surgical guidance, and to develop/evaluate therapeutic treatments for bone metastasis. The immediate goals for the PI over the next four years are to obtain necessary trainings, gain experience in cancer photonics, establish independent research and build collaborations with the fellow colleagues. These goals will be achieved by realizing the following objectives 1) to enrich her knowledge in cancer biology, 2) to expand her specialty in the field of biomedical optics, 3) to pursue a serious research project from which she will gain experience in biomedical research and obtain preliminary data for future extramural funding, and 5) to establish collaborations and obtain other necessary trainings in career development through the research and educational resources at Vanderbilt University. The K25 award will allow the PI protected time to accomplish these goals by following a detailed training plan including hands on laboratory training in biological skills, several courses/workshop over the first two years, and a mentored research plan. For the proposed research project, the PI seeks to develop a statistical model that can be used in combination with Raman fiber optic probe, providing real-time quantitative assessment on the quality of metastatic bone in situ.This goal will be realized in three aims. Aim 1) Characterize the temporal alterations of metastatic bone in breast and prostate cancers using Raman spectroscopy. This aim will prove the overall hypothesis of the study that that the alterations in the quality of metastatic bone can be detected by Raman spectroscopy. Both lyitc and blastic metastases will be studied in an intra-cardiac and an intra-tibial injection mouse model for breast and prostate cancers, respectively. The structural and compositional properties of the bone matrix will be assessed for intact non-tumor and tumor-bearing bones using a fiber optic probe interfaced Raman spectroscopy. These Raman-derived bone quality measurements will be correlated with bone structure (by X-ray imaging and Micro-CT analysis), tumor burden (assessed by bioluminescence imaging in vivo), bone turnover (by serum biomarkers) and bone cell activities (by bone histomorphometry). Statistics evaluation will test whether bone quality is changed with the progression of tumor, and how the osteoblast/osteoclast activities and pathological bone turnover are related to the alterations in the quality of metastatic bone. Aim 2) Develop a statistical model that can provide real-time automated assessment on the quality of metastatic bone in situ. The full range of spectral data collected in Aim 1 will be analyzed using statistical pattern recognition method for extracting the diagnostic features and classifying them into corresponding categories of bone quality. Aim 3) Correlate Raman spectral biomarkers to the microenvironment of metastatic bone. This aim seeks to identify the biological contributors of the apparent spectral signatures (biomarkers) for metastatic bone. Two-Dimensional Raman maps will be acquired at the marked sites where Raman probe measurements are performed using conventional confocal Raman micro-spectroscopy with a spatial resolution at the cellular level. Multivariate factor analysis on the Raman maps can extract the spectrum and spatial distribution of each component (factor) in the sample. The molecular nature of each component will be identified by comparing its spectrum with that of model compounds. Additional guidance is available by comparing the image of factors with the immunohisto chemistry and bone histology images. Upon completion of this project, a quantitative spectral scoring system will be developed, which will enable in situ assessment for bone quality in metastasis when used in combination with Raman spectroscopy. This will provide the PI tools to establish her independent research in bone metastasis. The results will serve as preliminary data for the PI's future extramural funding application. PUBLIC HEALTH RELEVANCE: In this project, the PI seeks to develop a novel Raman spectroscopy method that can assess bone quality in metastatic disease in real time non-destructively. In clinics the correct assessment of bone quality is crucial to help orthopaedic surgeons evaluate bone damage caused by bone metastasis, while for treatment development, bone quality is an important determinant to evaluate the response of bone to therapy. Thus this project in the long run will help improve the diagnosis and prognosis of bone metastasis and limit treatment costs by avoidance of unnecessary tests.

描述（由申请人提供）：PI的长期职业目标是成为一名独立的定量癌症研究人员，专门研究骨转移。主要研究方向是开发新的光学方法用于癌症诊断或手术指导，以及开发/评估骨转移的治疗方法。PI在未来四年的直接目标是获得必要的培训，获得癌症光子学方面的经验，建立独立研究并与同事建立合作关系。这些目标将通过实现以下目标来实现：1)丰富她在癌症生物学方面的知识；2)扩展她在生物医学光学领域的专业领域；3)从事一个认真的研究项目，从而获得生物医学研究的经验，并为未来的校外资助获得初步数据；5)通过范德比尔特大学的研究和教育资源建立合作关系并获得职业发展所需的其他培训。K25奖励将允许PI通过遵循详细的培训计划来完成这些目标，包括生物技能的实验室实践培训，前两年的几门课程/研讨会，以及指导研究计划。