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Therapeutic Effects of Microbubbles Added to Combined High-Intensity Focused Ultrasound and Chemotherapy in a Pancreatic Cancer Xenograft Model

  • Yu, Mi Hye (Department of Radiology, Konkuk University Medical Center) ;
  • Lee, Jae Young (Department of Radiology, Seoul National University Hospital) ;
  • Kim, Hae Ri (Department of Pre-Dentistry, Gangneung-Wonju National University College of Dentistry) ;
  • Kim, Bo Ram (Department of Radiology, Seoul National University Hospital) ;
  • Park, Eun-Joo (Department of Radiology, Seoul National University Hospital) ;
  • Kim, Hoe Suk (Department of Radiology, Seoul National University Hospital) ;
  • Han, Joon Koo (Department of Radiology, Seoul National University Hospital) ;
  • Choi, Byung Ihn (Department of Radiology, Chung-Ang University Hospital)
  • 투고 : 2016.02.22
  • 심사 : 2016.06.15
  • 발행 : 2016.09.01

초록

Objective: To investigate whether high-intensity focused ultrasound (HIFU) combined with microbubbles enhances the therapeutic effects of chemotherapy. Materials and Methods: A pancreatic cancer xenograft model was established using BALB/c nude mice and luciferase-expressing human pancreatic cancer cells. Mice were randomly assigned to five groups according to treatment: control (n = 10), gemcitabine alone (GEM; n = 12), HIFU with microbubbles (HIFU + MB, n = 11), combined HIFU and gemcitabine (HIGEM; n = 12), and HIGEM + MB (n = 13). After three weekly treatments, apoptosis rates were evaluated using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay in two mice per group. Tumor volume and bioluminescence were monitored using high-resolution 3D ultrasound imaging and in vivo bioluminescence imaging for eight weeks in the remaining mice. Results: The HIGEM + MB group showed significantly higher apoptosis rates than the other groups (p < 0.05) and exhibited the slowest tumor growth. From week 5, the tumor-volume-ratio relative to the baseline tumor volume was significantly lower in the HIGEM + MB group than in the control, GEM, and HIFU + MB groups (p < 0.05). Despite visible distinction, the HIGEM and HIGEM + MB groups showed no significant differences. Conclusion: High-intensity focused ultrasound combined with microbubbles enhances the therapeutic effects of gemcitabine chemotherapy in a pancreatic cancer xenograft model.

키워드

과제정보

연구 과제 주관 기관 : National Research Foundation of Korea (NRF), NIPA (National IT Industry Promotion Agency), SNUH

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