PMID- 31851698 OWN - NLM STAT- MEDLINE DCOM- 20200330 LR - 20200330 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 14 IP - 12 DP - 2019 TI - Ultrasound microbubble potentiated enhancement of hyperthermia-effect in tumours. PG - e0226475 LID - 10.1371/journal.pone.0226475 [doi] LID - e0226475 AB - It is now well established that for tumour growth and survival, tumour vasculature is an important element. Studies have demonstrated that ultrasound-stimulated microbubble (USMB) treatment causes extensive endothelial cell death leading to tumour vascular disruption. The subsequent rapid vascular collapse translates to overall increases in tumour response to various therapies. In this study, we explored USMB involvement in the enhancement of hyperthermia (HT) treatment effects. Human prostate tumour (PC3) xenografts were grown in mice and were treated with USMB, HT, or with a combination of the two treatments. Treatment parameters consisted of ultrasound pressures of 0 to 740 kPa, the use of perfluorocarbon-filled microbubbles administered intravenously, and an HT temperature of 43 degrees C delivered for various times (0-50 minutes). Single and multiple repeated treatments were evaluated. Tumour response was monitored 24 hours after treatments and tumour growth was monitored for up to over 30 days for a single treatment and 4 weeks for multiple treatments. Tumours exposed to USMB combined with HT exhibited enhanced cell death (p<0.05) and decreased vasculature (p<0.05) compared to untreated tumours or those treated with either USMB alone or HT alone within 24 hours. Deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining and cluster of differentiation 31 (CD31) staining were used to assess cell death and vascular content, respectively. Further, tumours receiving a single combined USMB and HT treatment exhibited decreased tumour volumes (p<0.05) compared to those receiving either treatment alone when monitored over the duration of 30 days. Additionally, tumour response monitored weekly up to 4 weeks demonstrated a reduced vascular index and tumour volume, increased fibrosis and lesser number of proliferating cells with combined treatment of USMB and HT. Thus in this study, we characterize a novel therapeutic approach that combines USMB with HT to enhance treatment responses in a prostate cancer xenograft model in vivo. FAU - Sharma, Deepa AU - Sharma D AUID- ORCID: 0000-0002-0475-1755 AD - Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada. AD - Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada. AD - Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada. AD - Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada. FAU - Giles, Anoja AU - Giles A AD - Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada. FAU - Hashim, Amr AU - Hashim A AD - Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada. FAU - Yip, Jodi AU - Yip J AD - Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada. FAU - Ji, Yipeng AU - Ji Y AD - Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada. FAU - Do, Natalie Ngoc Anh AU - Do NNA AD - Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada. FAU - Sebastiani, Juliana AU - Sebastiani J AD - Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada. FAU - Tran, William Tyler AU - Tran WT AUID- ORCID: 0000-0002-0733-7234 AD - Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada. AD - Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada. AD - Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada. FAU - Farhat, Golnaz AU - Farhat G AD - Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada. FAU - Oelze, Michael AU - Oelze M AUID- ORCID: 0000-0002-3099-7425 AD - Department of Electrical and Computer Engineering, University of Illinois, Urbana-Champaign, IL, United States of America. FAU - Czarnota, Gregory J AU - Czarnota GJ AD - Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada. AD - Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada. AD - Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada. AD - Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada. LA - eng PT - Journal Article DEP - 20191218 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Platelet Endothelial Cell Adhesion Molecule-1) SB - IM MH - Animals MH - Combined Modality Therapy MH - Humans MH - *Hyperthermia, Induced MH - In Situ Nick-End Labeling MH - Male MH - Mice MH - Mice, SCID MH - Microbubbles/*therapeutic use MH - Platelet Endothelial Cell Adhesion Molecule-1/metabolism MH - Prostatic Neoplasms/*therapy MH - *Ultrasonic Therapy MH - Xenograft Model Antitumor Assays PMC - PMC6919613 COIS- The authors have declared that no competing interests exist. EDAT- 2019/12/19 06:00 MHDA- 2020/03/31 06:00 PMCR- 2019/12/18 CRDT- 2019/12/19 06:00 PHST- 2019/05/23 00:00 [received] PHST- 2019/11/27 00:00 [accepted] PHST- 2019/12/19 06:00 [entrez] PHST- 2019/12/19 06:00 [pubmed] PHST- 2020/03/31 06:00 [medline] PHST- 2019/12/18 00:00 [pmc-release] AID - PONE-D-19-14627 [pii] AID - 10.1371/journal.pone.0226475 [doi] PST - epublish SO - PLoS One. 2019 Dec 18;14(12):e0226475. doi: 10.1371/journal.pone.0226475. eCollection 2019.