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Publications

Enhanced Detection of Cancer Biomarkers in Blood-Borne Extracellular Vesicles Using Nanodroplets and Focused Ultrasound

Cancer Res. 2017 Jan 1;77(1):3-1

Paproski RJ, Jovel J, Wong GK, Lewis JD, Zemp RJ.

Abstract

The feasibility of personalized medicine approaches will be greatly improved by the development of noninvasive methods to interrogate tumor biology. Extracellular vesicles shed by solid tumors into the bloodstream have been under recent investigation as a source of tumor-derived biomarkers such as proteins and nucleic acids. We report here an approach using submicrometer perfluorobutane nanodroplets and focused ultrasound to enhance the release of extracellular vesicles from specific locations in tumors into the blood. The released extracellular vesicles were enumerated and characterized using micro flow cytometry. Only in the presence of nanodroplets could ultrasound release appreciable levels of tumor-derived vesicles into the blood. Sonication of HT1080-GFP tumors did not increase the number of circulating tumor cells or the metastatic burden in the tumor-bearing embryos. A variety of biological molecules were successfully detected in tumor-derived extracellular vesicles, including cancer-associated proteins, mRNAs, and miRNAs. Sonication of xenograft HT1080 fibrosarcoma tumors released extracellular vesicles that contained detectable RAC1 mRNA with the highly tumorigenic N92I mutation known to exist in HT1080 cells. Deep sequencing serum samples of embryos with sonicated tumors allowed the identification of an additional 13 known heterozygous mutations in HT1080 cells. Applying ultrasound to HT1080 tumors increased tumor-derived DNA in the serum by two orders of magnitude. This work is the first demonstration of enhanced extracellular vesicle release by ultrasound stimulation and suggests that nanodroplets/ultrasound offers promise for genetic profiling of tumor phenotype and aggressiveness by stimulating the release of extracellular vesicles.

PubMed

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The Calgary Prostate Cancer Centre has the highest accrual for a novel ultrasound study in prostate cancer

“We have enrolled over 400 patients at our site, reaching our enrollment goal much faster than all other sites across North America. We are now planning on adding in 250 more patients to this trial because of the encouraging results found with the first arm of the trial. Our site tied with the highest accrual goal and surpassed all other sites to meet our enrollment goal.”

The study is a “Multi-Center trial of high-resolution transrectal ultrasound versus standard low-resolution transrectal ultrasound for the identification of clinically significant prostate cancer”

The only definitive method for diagnosing prostate cancer is through a prostate biopsy. This procedure includes the use of an ultrasound machine to guide both freezing needles and biopsy needles into the prostate. The ultrasound machine that is currently in use is a low-resolution ultrasound machine which means that although it is good at seeing the entire prostate gland to guide the needles, it is often unable to visualize the prostate in enough detail to be able to see different lesions and areas of concern within it. Thus, many biopsy samples are taken systematically with two samples from each section of the prostate. Recently a new ultrasound machine has been created that gives images of the prostate with much higher resolution, allowing the radiologist performing the biopsy to see details within the prostate that were previously inaccessible. A study using this new high-resolution ultrasound machine is being completed at the Prostate Cancer Centre to compare the adequacy of this new machine to detect prostate cancer over the standard low-resolution machine. Over 650 patients will be enrolled in this study!

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- Eric Hyndman