Molecular Analysis of Breast Cancer Utilizing Tumor Targeting Ultrasound Mechanical Contrast Agents - Jason Haruo Sakamoto

Molecular Analysis of Breast Cancer Utilizing Tumor Targeting Ultrasound Mechanical Contrast Agents

By Jason Haruo Sakamoto

  • Release Date - Published: 2013-05-19
  • Book Genre: Medical
  • Author: Jason Haruo Sakamoto
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Molecular Analysis of Breast Cancer Utilizing Tumor Targeting Ultrasound Mechanical Contrast Agents Jason Haruo Sakamoto read online review & book description:

This study was structured to challenge the hypothesis that nano-sized particulates could be molecularly targeted and bound to the prognostic and predictive HER-2/neu cell membrane receptor to elicit detectable changes in ultrasound response from human breast cancer cells. This study first utilized an agarose tissue phantom model to embed nanoparticles throughout its matrix to simulate cell conjugation of contrast agents to evaluate the sensitivity of the ultrasound modality. SKBR-3 human cancer cells were then enlisted to test the efficacy of the particle conjugation strategy used in this study and ultimately, to provide conclusive remarks regarding the validity of the stated hypothesis. A characterization-mode ultrasound (CMUS) system was used to apply a continuum mechanics based, two-step inversion algorithm to reconstruct the mechanical material properties of agarose tissue phantoms with the sensitivity to statistically distinguish particle concentration data from samples containing 4.56 x 1013 particles/sample, 4.56 x 1012 particles/sample, 4.56 x 1011 particles/sample, and 0.00 particles/sample. This ability to statistically differentiate particle concentrations by measured density was then maintained throughout the CMUS testing of SKBR-3 cells treated with molecularly targeted conjugated iron oxide nanoparticles. The statistical analysis of these ultrasound results supported the ability to differentiate between 3+ HER-2/neu positive SKBR-3 cells that have been successfully tagged with Herceptin conjugated iron oxide particles to those that have not demonstrated particle binding. Furthermore, the secondary objectives of this study were also completed. C-scan images suggest that molecularly targeted iron oxide particles were successfully bound to the surface of 3+ HER-2/neu positive breast cancer tissue. Insufficient data was collected to decisively establish conclusive evidence regarding the ability to quantify HER-2/neu expression upon human tissue; however, this finding serves as proof-of-concept data for the development of a quantitative histopathologic evaluation tool. The ultimate goal of this research is to exploit the molecular expression of the HER-2/neu protein to offer quantitative ultrasound information concerning the malignancy rating of human breast tissue biopsies. When fully developed, this could potentially help 32,000-63,000 women efficiently find their proper treatment strategy to fight and win their battle against breast cancer.

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