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Abstract:
Circulating tumor cells (CTC) in patient blood samples correlate with poor disease-free
survival. The objective was to develop a peripheral blood CTC detection method using
microfluidic confocal flow cytometry to discriminate cell types based on differences in
backscattered light intensity. Cultured breast cancer cells scattered in a unique,
intermediate space relative to the two ... read moremajor leukocyte classes of mononuclear cells and
granulocytes. To discriminate native CTCs, green fluorescent protein-expressing (GFP+)
human breast cancer cells were implanted orthotopically in mice. This animal work was
conducted in collaboration with a therapeutic target project investigating ADAM8. Mice
implanted with ADAM8-knockdown cells had significantly reduced CTC concentrations and
brain metastases. Further, anti-ADAM8 antibody treatment of resected tumors decreased
metastases and significantly increased a rare population of autofluorescent leukocytes
implicated in an immune response. Optimizations in signal processing and blood sample
preparation are ongoing efforts to enhance the sensitivity and specificity
performance.
Thesis (M.S.)--Tufts University,
2014.
Submitted to the Dept. of Biomedical
Engineering.
Advisor: Irene
Georgakoudi.
Committee: David Kaplan, and Gail
Sonenshein.
Keywords: Biomedical engineering,
Biophysics, and Cellular biology.read less
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