Science News -- April 28, 2022: Noninvasive sound technology created at the University of Michigan breaks down liver tumors in rats, kills cancer cells, and stimulates the immune system to prevent further spread — a breakthrough that could improve human cancer outcomes.
The immune systems of the rats were able to clear away the remaining after only killing 50 percent to 75 percent of the liver tumor volume, with no evidence of recurrence or metastasis in more than 80 percent of the animals.
"Even if we don't target the entire tumor, we can still induce it to regress and minimize the chance of future metastasis," said Zhen Xu, a professor of biomedical engineering at the University of Michigan and the study's corresponding author.
The medication also activated the rats' immunological responses, which may have contributed to the final regression of the untargeted area of the tumor and the prevention of cancer spread.
Histotripsy is a noninvasive treatment that uses ultrasonic pulses to mechanically damage target tissue with millimeter precision. In the United States and Europe, the relatively new method is now being employed in a human liver cancer trial.
For a variety of reasons, including the size, location, and stage of a malignant tumor, it is not possible to treat the entire tumor directly in many clinical scenarios. This current study targeted only a section of each mass, leaving a viable entire tumor, to evaluate the consequences of partially eliminating cancers using sound. It also allowed the team, which included researchers from Michigan Medicine and the Ann Arbor VA Hospital, to demonstrate the approach's efficacy in less-than-ideal circumstances.
"Histotripsy is a promising option that can overcome the limitations of currently available ablation modalities and provide safe and effective noninvasive liver tumor ablation," said Tejaswi Worlikar, a doctoral student in biomedical engineering. "We hope that our learnings from this study will motivate future preclinical and clinical histotripsy investigations toward the ultimate goal of clinical adoption of histotripsy treatment for liver cancer patients."
Rather than producing images of the body's interior with sound waves, U-M engineers have pioneered the use of those waves for treatment. And their method is free of the negative side effects associated with existing techniques like radiation and chemotherapy.
"Our transducer, designed and built at U-M, delivers high amplitude microsecond-length ultrasound pulses -- acoustic cavitation -- to focus on the tumor specifically to break it up," Xu said. "Traditional ultrasound devices use lower amplitude pulses for imaging."
Microbubbles are created within the targeted tissues by the microsecond long pulses from UM's transducer — bubbles that swiftly swell and collapse. The tumor's structure is broken up and cancer cells are killed by these severe but extremely confined mechanical forces.
Since 2001, Xu's team at U-M has pioneered the use of histotripsy in cancer research, resulting to the #HOPE4LIVER clinical study sponsored by HistoSonics, a U-M spinoff firm. More recently, the group's research on histotripsy treatment of brain therapy and immunotherapy has yielded encouraging results.
The National Institutes of Health, the Focused Ultrasound Foundation, the VA Merit Review, the Forbes Institute for Discovery at U-M, and the Michigan Medicine-Peking University Health Sciences Center Joint Institute for Translational and Clinical Research all contributed to the research.
Wnctimes by Marjorie Farrington
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The University of Michigan donated the materials for this project. Please keep in mind that content may be altered for style and length.
Tejaswi Worlikar, Man Zhang, Anutosh Ganguly, Timothy L. Hall, Jiaqi Shi, Lili Zhao, Fred T. Lee, Mishal Mendiratta-Lala, Clifford S. Cho, Zhen Xu, Tejaswi Worlikar, Man Zhang, Anutosh Ganguly, Timothy L. Hall, Jiaqi Shi, Lili Zhao, Fred T. Lee, Mishal Mendiratta-Lala, Cliffor In a rodent liver tumor model, the effect of histotripsy on the development of intrahepatic metastases. Cancers, 14 (7), 1612, 2022. Cancers14071612 (DOI: 10.3390/cancers14071612)
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University of Michigan MLA APA Chicago "Tumors that have been largely eliminated by sound do not reappear." ScienceDaily. www.sciencedaily.com/releases/2022/04/220418093955.htm>, ScienceDaily, 18 April 2022.