M-HIFU inhibits tumor growth, suppresses STAT3 activity and enhances tumor specific immunity in a transplant tumor model of prostate cancer.


OBJECTIVE: In this study, we explored the use of mechanical high intensity focused ultrasound (M-HIFU) as a neo-adjuvant therapy prior to surgical resection of the primary tumor. We also investigated the role of signal transducer and activator of transcription 3 (STAT3) in M-HIFU elicited anti-tumor immune response using a transplant tumor model of prostate cancer. METHODS: RM-9, a mouse prostate cancer cell line with constitutively activated STAT3, was inoculated subcutaneously in C57BL/6J mice. The tumor-bearing mice (with a maximum tumor diameter of 5∼6 mm) were treated by M-HIFU or sham exposure two days before surgical resection of the primary tumor. Following recovery, if no tumor recurrence was observed in 30 days, tumor rechallenge was performed. The growth of the rechallenged tumor, survival rate and anti-tumor immune response of the animal were evaluated. RESULTS: No tumor recurrence and distant metastasis were observed in both treatment groups employing M-HIFU + surgery and surgery alone. However, compared to surgery alone, M-HIFU combined with surgery were found to significantly inhibit the growth of rechallenged tumors, down-regulate intra-tumoral STAT3 activities, increase cytotoxic T cells in spleens and tumor draining lymph nodes (TDLNs), and improve the host survival. Furthermore, M-HIFU combined with surgery was found to significantly decrease the level of immunosuppression with concomitantly increased number and activities of dendritic cells, compared to surgery alone. CONCLUSION: Our results demonstrate that M-HIFU can inhibit STAT3 activities, and when combined synergistically with surgery, may provide a novel and promising strategy for the treatment of prostate cancers.





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Publication Info

Huang, Xiaoyi, Fang Yuan, Meihua Liang, Hui-Wen Lo, Mari L Shinohara, Cary Robertson and Pei Zhong (2012). M-HIFU inhibits tumor growth, suppresses STAT3 activity and enhances tumor specific immunity in a transplant tumor model of prostate cancer. PLoS One, 7(7). p. e41632. 10.1371/journal.pone.0041632 Retrieved from https://hdl.handle.net/10161/14230.

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Mari L. Shinohara

Professor of Integrative Immunobiology

Shinohara Lab Website

Immune responses against pathogens are essential for host protection, but excessive and uncontrolled immune reactions can lead to autoimmunity. How does our immune system keep the balance fine-tuned? This is a central question being asked in my laboratory.

The immune system needs to detect pathogens quickly and effectively. This is performed by the innate immune system, which includes cells such as macrophages and dendritic cells (DCs). Pathogens are recognized by pattern recognition receptors (PRRs) and may be cleared in the innate immune system. However, when pathogens cannot be eliminated by innate immunity, the adaptive immune system participates by exploiting the ability of T cells and B cells. The two immune systems work together not only to clear pathogens effectively but also to avoid collateral damages by our own immune responses. 

In my lab, we use mouse models for infectious and autoimmune diseases to understand the cellular and molecular mechanisms of; pathogen recognition by PRRs in macrophages and DCs, initiation of inflammatory responses in the innate immune system, and the impact of innate immune inflammation on the development and regulation of T cell-mediated adaptive immune responses. 

Several projects are ongoing in the lab. They are to study (1) the roles of PRR in EAE (an animal model of multiple sclerosis), (2) the interplay between immune cells and CNS (central nervous system)-resident cells during EAE and fungal infection, (3) protective and pathogenic mechanisms of immune cells in the lung during fungal infection and inflammation, and (4) the roles of a protein termed osteopontin (OPN), as both secreted (sOPN) and intracellular (iOPN) isoforms, in regulation of immune responses . Although we are very active in EAE to study autoimmunity, other mouse models, such as graft-versus-host disease (GvHD) is ongoing. Cell types we study are mainly DCs, macrophagesneutrophils, and T cells


Cary Nobles Robertson

Associate Professor of Urology

1. High Intensity Focused Ultrasound Therapy of Prostate Cancer
2. Surgical Technique Improvement in Prostate Cancer
3. Clinical Predictors of Outcome in Prostate Cancer
4. Molecular Imaging and Genomics of Genitourinary Malignancies
5. Quality of Life measures in Genitourinary Malignancies


Pei Zhong

Professor in the Thomas Lord Department of Mechanical Engineering and Materials Science

My research focuses on engineering and technology development with applications in the non-invasive or minimally invasive treatment of kidney stone disease via shock wave and laser lithotripsy, high-intensity focused ultrasound (HIFU) and immunotherapy for cancer treatment, acoustic and optical cavitation, and ultrasound neuromodulation via sonogenetics. 

We are taking an integrated and translational approach that combines fundamental research with engineering and applied technology development to devise novel and enabling ultrasonic, optical, and mechanical tools for a variety of clinical applications. We are interested in shock wave/laser-fluid-bubble-solid interaction, and resultant mechanical and thermal fields that lead to material damage and removal.  We also investigate the stress response of biological cell and tissue induced by cavitation and ultrasound exposure, mediated through mechanosensitive ion channels, such as Piezo 1. Our research activities are primarily supported by NIH and through collaborations with the medical device industry.

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