2023 iTHRIV Pilot: Tumor and circulating extracellular vesicle characterization following mechanical, high-intensity focused ultrasound (histotripsy) in soft tissue sarcoma
Extracellular vesicles (EVs) are particles that transfer genes and protein between cells, and are implicated in cancer progression and metastasis, but also with potential for novel biomarker discovery. Challenges in EV research include quantity, clinical relevance of models, extraction from tissue, and standards in the conduct and reporting of research. Focused ultrasound (FUS) is a focal therapy that leverages sound waves to yield bioeffects in tissues. Low-intensity, sublethal FUS augments EVs in circulation and shifts EV size and cargo profiles. Histotripsy is a high-intensity FUS regimen that disintegrates tissue.
The impact of high-intensity FUS on EVs has never been evaluated. Clinical trials in pet dogs with cancer play a key role in translational research. Histotripsy is safe and effectively kills cancer cells in pet dogs with soft tissue sarcoma (STS), with early evidence of alterations in immune cells and gene expression in the tumor microenvironment. Histotripsy has potential to augment EV release and modify cargo profile, as well as become a method for evaluating vesicles.
This study aims to characterize the vesicles that are released following histotripsy treatment of naturally-occurring soft tissue sarcoma. The data generated by this study will advance knowledge and techniques used in the EV-cancer and EV-FUS clinical and research arenas.
| Keywords | immune cell alterations, focused ultrasound, ev size and cargo profiles, fus, pet dogs with cancer, cancer progression, ev research challenges, gene transfer, gene expression, evs, tumor microenvironment, biomarker discovery, tissue disintegration, metastasis, translational research, extracellular vesicles, low-intensity fus, ev-cancer, ev-fus, ev circulation, clinical trials, histotripsy, protein transfer, high-intensity fus, sts, soft tissue sarcoma, bioeffects in tissues, ev release augmentation, vesicle characterization, ithriv pilot |
| Storage Organization | University of Virginia |
| Partner Institution(s) | Virginia Tech, University of Virginia |
| Funding Source(s) | NCATS Award UL1TR003015 iTHRIV CTSA |