Gene expression profiles, histologic analysis, and imaging of squamous cell carcinoma model treated with focused ultrasound beams.

Abstract

OBJECTIVE:

The purpose of our study was to evaluate the effect of short-pulse high-intensity focused ultrasound (HIFU) on inducing cell death in a head and neck cancer model (SCCVII [squamous cell carcinoma]) compared with continuous HIFU to get a better understanding of the biologic changes caused by HIFU therapy.

MATERIALS AND METHODS:

HIFU was applied to 12 SCCVII tumors in C3H/Km mice using a dual sonography system (imaging, 6 MHz; therapeutic, 1 MHz). A continuous HIFU mode (total time, 20 seconds; intensity, 6,730.6 W/cm2) and a short-pulse HIFU mode (frequency, 0.5 Hz; pulse duration, 50 milliseconds; total time, 16.5 minutes; intensity, 134.4 W/cm2) was applied. Three hours later, MR images were obtained on a 1.5-T scanner. After imaging, the treated and untreated control tumor tissue samples were taken out for histology and oligonucleotide microarray analysis.

RESULTS:

Prominent changes were observed in the MR images in the continuous HIFU mode, whereas the short-pulse HIFU mode showed no discernible changes. Histology (H and E, TUNEL [terminal deoxynucleotidyl transferase-mediated dUTP {deoxyuridine triphosphate} nick-end labeling], and immunohistochemistry) of the tumors treated with the continuous HIFU mode revealed areas of significant necrosis. In the short-pulse HIFU mode, the H and E staining showed multifocal areas of coagulation necrosis. TUNEL staining showed a high apoptotic index in both modes. Gene expression analysis revealed profound differences. In the continuous HIFU mode, 23 genes were up-regulated (> twofold change) and five genes were down-regulated (< twofold change), and in the short-pulse HIFU mode, 32 different genes were up-regulated and 16 genes were down-regulated.

CONCLUSION:

Genomic analysis might be included when investigating tissue changes after interventional therapy because it offers the potential to find molecular targets for imaging and therapeutic applications.

• Authors: Walter Hundt, Esther L Yuh, Mark D Bednarski, Samira Guccione
• Journal: AJR. American journal of roentgenology (AJR Am J Roentgenol) Vol. 189 Issue 3 Pg. 726-36 (Sep 2007) ISSN: 1546-3141 [Electronic] United States
• PMID: 17715123 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Neoplasm Proteins

Topics

• Animals
• Biomarkers, Tumor (metabolism)
• Carcinoma, Squamous Cell (diagnosis, metabolism, pathology, therapy)
• Cell Line, Tumor
• Gene Expression Profiling
• Mice
• Mice, Inbred C3H
• Neoplasm Proteins (metabolism)
• Treatment Outcome
• Ultrasonic Therapy (methods)