Molecular imaging and mathematical modeling approaches to interrogate the liquid phase of cancer
Abstract/Contents
- Abstract
- Metastasis, the cause for 90% of cancer mortality, is a complex and poorly understood process, often involving the invasion of blood vessels by circulating tumor cells (CTCs). CTCs can be detected and harvested from a blood sample and are potentially ideal candidates for a real-time "liquid biopsy" of cancer. How and when these cells are circulating in the blood, on their way to potentially give rise to metastasis, is a question that remains largely unanswered. To address this issue, in this thesis, we developed new mathematical and molecular imaging approaches to interrogate CTCs and characterize their dynamics in an orthotopic mouse model of breast cancer metastasis. We summarize current approaches and major findings in the field of CTC research. We then describe a 1-compartment mathematical model describing how a metastasizing cancer is giving rise to CTCs in the bloodstream. Next, we describe how we developed a simple bioluminescence imaging assay to detect and quantify CTCs in any cancer mouse model. We demonstrate how this method allows to uncover the dynamics of CTCs during cancer progression and provide in vivo measurements of the mathematical model parameters. We then show the first reported use of a miniature mountable intravital microscopy setup for in vivo imaging of CTCs in awake animals. This novel technology will become a useful technique for the precise characterization of the long-term dynamics of CTCs in vivo. Finally, we present our early results in investigating the metabolomics of CTCs, a promising avenue to characterize the properties of a cancer using the "liquid biopsy". This approach could lead to the identification of metastasis-initiating cells among CTCs, as well as provide critical information for the prediction of response to therapy.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2014 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Sasportas, Laura Sarah |
|---|---|
| Associated with | Stanford University, Department of Bioengineering. |
| Primary advisor | Gambhir, Sanjiv Sam |
| Thesis advisor | Gambhir, Sanjiv Sam |
| Thesis advisor | Graves, Edward (Edward Elliot), 1974- |
| Thesis advisor | Pelc, Norbert J |
| Advisor | Graves, Edward (Edward Elliot), 1974- |
| Advisor | Pelc, Norbert J |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Laura Sarah Sasportas. |
|---|---|
| Note | Submitted to the Department of Bioengineering. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2014. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2014 by Laura Sarah Sasportas
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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