期刊
CANCERS
卷 14, 期 7, 页码 -出版社
MDPI
DOI: 10.3390/cancers14071612
关键词
histotripsy; hepatocellular carcinoma; tumor ablation; immunomodulation; metastases
类别
资金
- National Institutes of Health (NIH) [R01 CA211217, K08 CA234222]
- Focused Ultrasound Foundation
- VA Merit Review [1I01BX001619-05]
- Michigan Medicine-Peking University Health Sciences Center Joint Institute for Translational and Clinical Research
- University of Michigan Forbes Institute for Discovery
Histotripsy treatment has been shown to have significant effects on reducing tumor growth, improving survival outcomes, and preventing local recurrence and metastasis in an in vivo orthotopic, immunocompetent rat HCC model.
Histotripsy has been used for tumor ablation, through controlled, non-invasive acoustic cavitation. This is the first study to evaluate the impact of partial histotripsy ablation on immune infiltration, survival outcomes, and metastasis development, in an in vivo orthotopic, immunocompetent rat HCC model (McA-RH7777). At 7-9 days post-tumor inoculation, the tumor grew to 5-10 mm, and similar to 50-75% tumor volume was treated by ultrasound-guided histotripsy, by delivering 1-2 cycle histotripsy pulses at 100 Hz PRF (focal peak negative pressure P- >30 MPa), using a custom 1 MHz transducer. Complete local tumor regression was observed on MRI in 9/11 histotripsy-treated rats, with no local recurrence or metastasis up to the 12-week study end point, and only a <1 mm residual scar tissue observed on histology. In comparison, 100% of untreated control animals demonstrated local tumor progression, developed intrahepatic metastases, and were euthanized at 1-3 weeks. Survival outcomes in histotripsy-treated animals were significantly improved compared to controls (p-value < 0.0001). There was evidence of potentially epithelial-to-mesenchymal transition (EMT) in control tumor and tissue healing in histotripsy-treated tumors. At 2- and 7-days post-histotripsy, increased immune infiltration of CD11b(+), CD8(+) and NK cells was observed, as compared to controls, which may have contributed to the eventual regression of the untargeted tumor region in histotripsy-treated tumors.
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