ミシガン大学がラットで開発した技術は、がんや神経疾患の治療成績を改善する可能性がある Technique pioneered in rats at the University of Michigan could improve outcomes for cancer and neurological conditions
ラット肝腫瘍モデルにおける肝内転移の発生に及ぼすヒストトリプシーの影響 Impact of Histotripsy on Development of Intrahepatic Metastases in a Rodent Liver Tumor Model
Tejaswi Worlikar,Man Zhang,Anutosh Ganguly,Timothy L. Hall,Jiaqi Shi,Lili Zhao,Fred T. Lee,Mishal Mendiratta-Lala,Clifford S. Cho and Zhen Xu
MDPI Published: 22 March 2022
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 ~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.