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Stephanie Bachar Matt Luchette

Isolation of Rare Circulating Tumor Cells in Cancer Patients by Microchip Technology Toner, et al. 2007. Stephanie Bachar Matt Luchette. Background: Circulating Tumor Cells. CTCs: tumor cells shed into the blood stream Motivation for detection Study biology of metastasis

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Stephanie Bachar Matt Luchette

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  1. Isolation of Rare Circulating Tumor Cells in Cancer Patients by Microchip TechnologyToner, et al. 2007 Stephanie Bachar Matt Luchette

  2. Background: Circulating Tumor Cells • CTCs: tumor cells shed into the blood stream • Motivation for detection • Study biology of metastasis • Diagnose, detect, monitor cancer in patients without invasive biopsy The bone marrow niche: habitat to hematopoietic and mesenchymal stem cells, and unwitting host to molecular parasites Y Shiozawa, A M Havens, K J Pienta and R S Taichman

  3. Motivation for the “CTC-Chip” • Shortcomings prior to “CTC-Chip” • Accuracy: 20-60% • Purity: 0.1% • Non-viable cells Photoacoustic detection of CTCs. Viator lab at University of Missouri http://web.missouri.edu/~viatorj/tumor.htm

  4. How to use the “CTC Chip" • Flow sample through CTC Chip • EpCAM coated microposts • Verify with markers Pressure Control Blood on Rocker CTC Chip Toner 2007 EpCAM Non-CTCs CTCs Micropost Cytokeratin CD45

  5. Instrument Design: in silico • Maximize CTCs detected • Flow Velocity • Shear Force • Vary micropost characteristics • Theoretical capture efficiency of 65% Toner 2007

  6. Laboratory Results • 1 target cell/10^9 blood cells • Purity of capture ~60% (competitors = 0.1%) •  Efficiency of capture ~65% (competitors = 35%) • Captured cells were viable and could be further manipulated Capture purity per type of cancer Toner 2007

  7. Clinical Results • Identified CTCs in 99% cancer pts (competitors =  20-60%) • no false positives • Change in number of CTCs correlated with clinical path • No pre-processing required Change in CTCs captured per mL (red) with lung cancer patient mirrors change in tumor size (blue) Toner 2007

  8. Concerns and next steps • How cells used afterwards? • How to mass produce chips? • Financially viable? • How reliable is EpCAM as a caner cell marker? • FDA approval Paper tree-branch glucose and protein assay for urine technologyreview.com

  9. Recap/Applications • New diagnostic and prognostic tool for cancer patients • Provide alternative to biopsies for areas with low resources • Use to isolate and further study CTCs MRI of 67-year old patient with pancreatic cancer with the pancreatic tumor indicated imagingeconomics.com

  10. Works Cited --imagingeconomics.com --technologyreview.com --http://web.missouri.edu/~viatorj/tumor.htm --The bone marrow niche: habitat to hematopoietic and mesenchymal stem cells, and unwitting host to molecular parasites Y Shiozawa, A M Havens, K J Pienta and R S Taichman

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