A joint project of the Graduate School, Peabody College, and the Jean & Alexander Heard Library

Title page for ETD etd-03262012-143254

Type of Document Master's Thesis
Author Walsh, Alexandra Jule
Author's Email Address alex.walsh@vanderbilt.edu
URN etd-03262012-143254
Title Optical imaging of metabolism in HER2 overexpressing cells
Degree Master of Science
Department Biomedical Engineering
Advisory Committee
Advisor Name Title
Melissa C. Skala Committee Chair
E. Duco Jansen Committee Member
  • fluorescence
  • NADH
  • FAD
  • optical redox ratio
  • breast cancer
  • cellular metabolism
  • resistance
Date of Defense 2012-03-26
Availability unrestricted
The optical redox ratio (fluorescence intensity of NADH divided by that of FAD), was acquired for a panel of breast cancer cell lines to investigate how overexpression of human epidermal growth factor receptor 2 (HER2) affects tumor cell metabolism, and how tumor metabolism may be altered in response to clinically used HER2-targeted therapies. Confocal fluorescence microscopy was used to acquire NADH and FAD auto-fluorescent images. The optical redox ratio was highest in cells overexpressing HER2 and lowest in triple negative breast cancer (TNBC) cells, which lack HER2, progesterone receptor, and estrogen receptor (ER). The redox ratio in ER-positive/HER2-negative cells was higher than what was seen in TNBC cells, but lower than that in HER2 overexpressing cells. Importantly, inhibition of HER2 using trastuzumab significantly reduced the redox ratio in HER2 overexpressing cells. Furthermore, the combinatorial inhibition of HER2 and ER decreased the redox ratio in ER+/HER2+ breast cancer cells to a greater extent than inhibition of either receptor alone. Interestingly, trastuzumab had little impact upon the redox ratio in a cell line selected for acquired resistance to trastuzumab. Taken together, these data indicate that the optical redox ratio measures changes in tumor metabolism that reflect the oncogenic effects of HER2 activity within the cell, as well as the response of the cell to therapeutic inhibition of HER2. Therefore, optical redox imaging holds the promise of measuring response and resistance to receptor-targeted breast cancer therapies in real time, which could potentially impact clinical decisions and improve patient outcome.
  Filename       Size       Approximate Download Time (Hours:Minutes:Seconds) 
 28.8 Modem   56K Modem   ISDN (64 Kb)   ISDN (128 Kb)   Higher-speed Access 
  Alex_Walsh_MS_thesis.pdf 729.80 Kb 00:03:22 00:01:44 00:01:31 00:00:45 00:00:03

Browse All Available ETDs by ( Author | Department )

If you have more questions or technical problems, please Contact LITS.