Development of Spectroscopic Biomarkers of Bone Quality in Metastatic Disease

Summary

Principal Investigator: Xiaohong Bi
Abstract: 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.
Funding Period: 2010-06-01 - 2014-12-31
more information: NIH RePORT

Top Publications

  1. pmc Prostate cancer metastases alter bone mineral and matrix composition independent of effects on bone architecture in mice--a quantitative study using microCT and Raman spectroscopy
    Xiaohong Bi
    Department of Biomedical Engineering, Vanderbilt University, VU Station B 351631, 2301 Vanderbilt Place, Nashville, TN 37235, USA
    Bone 56:454-60. 2013
  2. pmc Evaluating HER2 amplification status and acquired drug resistance in breast cancer cells using Raman spectroscopy
    Xiaohong Bi
    Vanderbilt University, Department of Biomedical Engineering, VU Station B 351631, 2301 Vanderbilt Place, Nashville, Tennessee 37235bUniversity of Texas Health Science Center at Houston, Department of Nanomedicine and BioMedical Engineering, CABIR 3SCR 46
    J Biomed Opt 19:025001. 2014
  3. pmc Development of Raman spectral markers to assess metastatic bone in breast cancer
    Hao Ding
    University of Texas Health Science Center at Houston, Department of Nanomedicine and BioMedical Engineering, 1881 East Road, Houston, Texas 77054
    J Biomed Opt 19:111606. 2014

Research Grants

  1. Signaling in Inflammation, Stress, and Tumorigenesis
    GEORGE ROBERT STARK; Fiscal Year: 2013
  2. Orchestration of breast cancer osteolytic bone metastasis by MIF
    Jessica M Grunda; Fiscal Year: 2013
  3. Mechanisms of GVHD
    Joseph H Antin; Fiscal Year: 2013

Detail Information

Publications3

  1. pmc Prostate cancer metastases alter bone mineral and matrix composition independent of effects on bone architecture in mice--a quantitative study using microCT and Raman spectroscopy
    Xiaohong Bi
    Department of Biomedical Engineering, Vanderbilt University, VU Station B 351631, 2301 Vanderbilt Place, Nashville, TN 37235, USA
    Bone 56:454-60. 2013
    ..Raman spectroscopy may provide a new avenue of investigation into interactions between tumor and bone microenvironment. ..
  2. pmc Evaluating HER2 amplification status and acquired drug resistance in breast cancer cells using Raman spectroscopy
    Xiaohong Bi
    Vanderbilt University, Department of Biomedical Engineering, VU Station B 351631, 2301 Vanderbilt Place, Nashville, Tennessee 37235bUniversity of Texas Health Science Center at Houston, Department of Nanomedicine and BioMedical Engineering, CABIR 3SCR 46
    J Biomed Opt 19:025001. 2014
    ..Enhanced lipid content and decreased proteome were observed in HER2+ cells. With lapatinib treatment, lapatinib-resistant breast cancer cells demonstrated sustained lipogenesis compared with the sensitive cells...
  3. pmc Development of Raman spectral markers to assess metastatic bone in breast cancer
    Hao Ding
    University of Texas Health Science Center at Houston, Department of Nanomedicine and BioMedical Engineering, 1881 East Road, Houston, Texas 77054
    J Biomed Opt 19:111606. 2014
    ....

Research Grants30

  1. Signaling in Inflammation, Stress, and Tumorigenesis
    GEORGE ROBERT STARK; Fiscal Year: 2013
    ..abstract_text> ..
  2. Orchestration of breast cancer osteolytic bone metastasis by MIF
    Jessica M Grunda; Fiscal Year: 2013
    ..Additionally, information gleaned from this work may be used in the generation of therapeutic interventions for other diseases associated with osteoclast-mediated bone loss, such as osteoporosis and diabetes-associated bone disease. ..
  3. Mechanisms of GVHD
    Joseph H Antin; Fiscal Year: 2013
    ..Ultimately we envision an integrated genomic profile that will determine the type of GVHD prophylaxis that will be most effective. ..