M-HIFU inhibits tumor growth, suppresses STAT3 activity and enhances tumor specific immunity in a transplant tumor model of prostate cancer.
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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.
Cell Line, Tumor
Disease Models, Animal
High-Intensity Focused Ultrasound Ablation
Mice, Inbred C57BL
STAT3 Transcription Factor
Published Version (Please cite this version)10.1371/journal.pone.0041632
Publication InfoHuang, Xiaoyi; Yuan, Fang; Liang, Meihua; Lo, Hui-Wen; Shinohara, Mari L; Robertson, Cary; & Zhong, Pei (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). pp. e41632. 10.1371/journal.pone.0041632. Retrieved from https://hdl.handle.net/10161/14230.
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Associate Professor of Surgery
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
Associate Professor of Immunology
Shinohara Lab WebsiteImmune 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 mac
Professor in the Department of Mechanical Engineering and Materials Science
My research focuses on four broad and interconnected areas in the emerging field of therapeutic ultrasound, which is located at the interface of engineering, biology and clinical medicine. Current research interests in my group include: Ultrasound-targeted gene delivery and activation Synergistic combination of high-intensity focused ultrasound (HIFU) and immunotherapy for cancer treatment Innovations in shock wave lithotripsy (SWL) technology</l
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