Publications

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

Download PDF

Stay Informed

To stay up to date on all the latest news and publications, subscribe to our newsletter!

Working to include Yukoners in APCaRI

APCaRI, represented by John Lewis and Catalina Vasquez, met with many Yukoners in Whitehorse recently to discuss the potential of including the North of 60 men in the registry and their samples in the biorepository. Sean Secord (photographed with John and Catalina), formerly with the Yukon Hospitals Foundation, talked with John on CBC Whitehorse radio about the challenges that Yukoners with cancer, and their families, have to manage and overcome to get testing and treatment. They are formidable; a recent article by Simkin et al., 2017 evaluated cancer mortality rates in the Yukon from 1999 to 2013 and found that they were elevated for prostate, female breast and lung, and colorectal cancers compared to both urban and rural populations in Canada South of the Yukon. The authors suggested that the high Yukon rates are, in part, due to the high percentage of Yukoners living in rural and very remote communities, making it necessary for patients to have to travel long distances for diagnoses and treatment. But even if the cancer patient lives in Whitehorse, (Yukon capital, population 25 085), cancer care options are limited due in part to a lack of oncologists and the specialized equipment needed.
John and Catalina met and had stimulating discussions with many people dedicated to improving cancer care in the North including the Yukon Ride for Dad organizers, representatives from the medical and laboratory communities and people living with cancer, and their families.
APCaRI is determined to find a way to include the Yukon men in the registry so that their valuable medical information and samples can be added to the prostate cancer research initiative and be an important part of improving prostate cancer diagnosis, treatment and care.

- Perrin Beatty