title: Liquid-solid phase-inversion PLGA implant for the treatment of residual tumor tissue after HIFU ablation.
abstract: BACKGROUND
  HIFU has been shown to be a more suitable alternative for the treatment of primary solid tumors and metastatic diseases than other focal heat ablation techniques due to its noninvasive and extracorporeal nature. However, similar to other focal heat ablation techniques, HIFU is still in need of refinements due to tumor recurrence.
  
  
  METHODS
  In this work, we investigated the effectiveness of an adjunct treatment regimen using doxorubicin (DOX)-loaded, injectable, in situ-forming, and phase-inverting PLGA as the second line of defense after HIFU ablation to destroy detrimental residual tumors and to prevent tumor recurrence. All of the statistical analyses were performed using the Statistical Package for the Social Sciences 18.0 (SPSS, Inc., Chicago, IL, USA), and p<0.05 was considered statistically significant. All of the results are presented as the means ± STDEV (standard deviation). For multiple comparisons, ANOVA (differences in tumor volumes, growth rates, apoptosis, proliferation indexes, and Bcl-2 and Bax protein levels) was used when the data were normally distributed with homogenous variance, and rank sum tests were used otherwise. Once significant differences were detected, Student-t tests were used for comparisons between two groups.
  
  
  RESULTS
  Our results revealed that DOX diffused beyond the ablated tissue regions and entered tumor cells that were not affected by the HIFU ablation. Our results also show that HIFU in concert with DOX-loaded PLGA led to a significantly higher rate of tumor cell apoptosis and a lower rate of tumor cell proliferation in the areas beyond the HIFU-ablated tissues and consequently caused significant tumor volume shrinkage (tumor volumes:0.26±0.1,1.09±0.76, and 1.42±0.9 cm3 for treatment, sham, and no treatment control, respectively).
  
  
  CONCLUSIONS
  From these results, we concluded that the intralesional injection of DOX-loaded PLGA after HIFU ablation is significantly more effective than HIFU alone for the treatment of solid tumors.
authors.affiliation: Second Affiliated Hospital and Ultrasound Imaging Institute, Chongqing Medical University, Chongqing, 400010, P. R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: Radiology Department, Stanford University, Stanford, California, United States of America.
authors.forename: Tianyi
authors.initials: T
authors.lastname: Krupka
authors.affiliation: Second Affiliated Hospital and Ultrasound Imaging Institute, Chongqing Medical University, Chongqing, 400010, P. R. China.
authors.forename: Jinpeng
authors.initials: J
authors.lastname: Yao
authors.affiliation: Second Affiliated Hospital and Ultrasound Imaging Institute, Chongqing Medical University, Chongqing, 400010, P. R. China.
authors.forename: Ronghui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Second Affiliated Hospital and Ultrasound Imaging Institute, Chongqing Medical University, Chongqing, 400010, P. R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Second Affiliated Hospital and Ultrasound Imaging Institute, Chongqing Medical University, Chongqing, 400010, P. R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Second Affiliated Hospital and Ultrasound Imaging Institute, Chongqing Medical University, Chongqing, 400010, P. R. China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Zuo
authors.affiliation: College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, P. R. China.
authors.forename: Zhibiao
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Second Affiliated Hospital and Ultrasound Imaging Institute, Chongqing Medical University, Chongqing, 400010, P. R. China.
authors.forename: Lili
authors.initials: L
authors.lastname: Dai
authors.affiliation: Second Affiliated Hospital and Ultrasound Imaging Institute, Chongqing Medical University, Chongqing, 400010, P. R. China.
authors.forename: Jianli
authors.initials: J
authors.lastname: Ren
authors.affiliation: Second Affiliated Hospital and Ultrasound Imaging Institute, Chongqing Medical University, Chongqing, 400010, P. R. China.
authors.forename: Yuanyi
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Ultrasound, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, 400014, P. R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry; D017209:Apoptosis; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D057086:High-Intensity Focused Ultrasound Ablation; D019344:Lactic Acid / Q000737:chemistry*; D045423:Microbubbles; D018365:Neoplasm, Residual / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011817:Rabbits; D012878:Skin Neoplasms / Q000473:pathology; D016896:Treatment Outcome; D014463:Ultrasonography; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004317:Doxorubicin