title: Enhanced antitumor efficacy of ultrasonic cavitation with up-sized microbubbles in pancreatic cancer.
abstract: Ultrasonic cavitation is a novel potential approach for cancer treatment. We optimized the techniques of ultrasonic cavitation to enhance antitumor efficacy in a mouse model with human pancreatic cancer. A polydisperse MB contrast agent formulation (TS-P) with a mean number diameter of 1.9 μm was depleted in small diameter particles by differential centrifugation, producing an "up-sized" size distribution (TS-PL) possessing a mean diameter of 2.9 μm. Mice bearing the XPA-1-RFP pancreatic tumor were treated daily for 3 consecutive days with either up-sized or standard MB. Both treatment cohorts exhibited a significant reduction in tumor volume relative to the untreated control cohort (P < 0.05), and TS-PL group has significantly reduction in tumor volume (1215.1± 324.7 mm3) compared with standard TS-P group (2131.2±753.4 mm3) (P < 0.05). The treatment with TS-PL resulted in more tumor cell necrosis and apoptosis than with TS-P. Decreased expression of CD31 and MVD was observed histologically in tumors treated with TS-PL relative to TS-P. This study demonstrates that tuning the size distribution of existing contrast agent products, specifically to reduce the concentration of small MB, is required for enhanced anti-tumor cavitation activity.
authors.affiliation: Department of Ultrasonography, The Second Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou, Zhejiang Province, P. R. China.
authors.forename: Pintong
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of Ultrasonography, The Second Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou, Zhejiang Province, P. R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Surgery, The Second Affiliated Hospital Zhejiang University College of Medicine, Hangzhou, Zhejiang Province, P. R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Ultrasonography, The Second Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou, Zhejiang Province, P. R. China.
authors.forename: Weihui
authors.initials: W
authors.lastname: Shentu
authors.affiliation: Origin Biosciences Inc., Nanjing, Jiangsu Province, P. R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Origin Biosciences Inc., Nanjing, Jiangsu Province, P. R. China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Surgery, The Second Affiliated Hospital Zhejiang University College of Medicine, Hangzhou, Zhejiang Province, P. R. China.
authors.forename: Tingbo
authors.initials: T
authors.lastname: Liang
authors.affiliation: Baylor Research Institute, Baylor University Medical Center at Dallas, Dallas, Texas, USA.
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Ultrasonography, The Second Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou, Zhejiang Province, P. R. China.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Pu
mesh_terms: D000818:Animals; D017209:Apoptosis; D006801:Humans; D051379:Mice; D045423:Microbubbles / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology*; D014465:Ultrasonics / Q000379:methods*; D014463:Ultrasonography
keywords: microbubbles; pancreatic cancer; therapy; tumor vasculature; ultrasonic cavitation