- Oral presentation
- Open Access
High intensity focused ultrasound-induced bubbles stimulate the release of nucleic acid cancer biomarkers
© Khokhlova et al; licensee BioMed Central Ltd. 2015
Published: 30 June 2015
Prostate biopsy for prostate cancer (PCa) is invasive with associated morbidity and several diagnostic limitations, suggesting the need for a new approach. Recently, several nucleic acid cancer biomarkers (e.g., microRNA and mutant DNA) have been identified and shown promise for improving cancer diagnostics. However, the abundance of these biomarker classes in the circulation is low, impeding reliable detection and adoption into clinical practice. In order to stimulate the release of these intracellular biomarkers, the exposures optimized for mechanical disruption of cells may be desirable.
Here, two approaches based on HIFU-induced bubble activity were tested for their ability to stimulate release of cancer-associated microRNAs in a heterotopic syngeneic rat prostate cancer model. In the first approach, tumor tissue was locally liquefied with boiling histotripsy (BH) - a HIFU technique utilizing millisecond-long pulses to create boiling bubbles via rapid shockwave heating. The interaction of shocks with the ensuing vapor cavity fractionates tissue with negligible thermal effect. In the second approach HIFU-induced inertial cavitation was used for permeabilization of tumor tissue and vasculature.
Putative miRNA biomarkers were identified using RT-PCR array profiling of the syngeneic MatLyLu rat PCa cell line. Adult intact male Copenhagen rats were then subcutaneously grafted with the MatLyLu cells. When the tumors were >1cm, the rats were assigned to one of two HIFU treatment groups: HIFU optimized for inertial cavitation activity (focal peak negative pressure 16 MPa, 1 ms pulses, duty factor 0.001, N=6), BH (intensity ~20kW/cm2, 1% duty factor, N=8) or a to a control group (N=6) that received sham treatment. Treatments were performed in a heated water tank using a single-element 1.5 MHz HIFU transducer (45 mm radius of curvature, 64 mm aperture) under ultrasound image guidance. Blood samples were collected immediately prior to treatment and serially over a 24-hour time course. Specimens were immediately processed into plasma and miRNAs extracted. Plasma concentrations of candidate tumor-derived miRNAs were measured via quantitative RT-PCR and compared with ANOVA and the Mann-Whitney test.
Results and conclusions
Work supported by NIH 1K01EB015745, R01CA154451, R01DK085714.
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