HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: 2482071674v1 248/2/485    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Poff, J. A. Articles by Frenkel, V. PubMed PubMed Citation Articles by Poff, J. A. Articles by Frenkel, V.

Pulsed High-Intensity Focused Ultrasound Enhances Apoptosis and Growth Inhibition of Squamous Cell Carcinoma Xenografts with Proteasome Inhibitor Bortezomib¹

¹ From the Diagnostic Radiology Department, Clinical Center (J.A.P., B.T., A.C., J.X., B.J.W., K.C.P.L., V.F.) and Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders (NIDCD) (C.T.A., Z.C., C.V.W.), National Institutes of Health (NIH), 9000 Rockville Pike, Bethesda, MD 20892. Received September 21, 2007; revision requested November 15; revision received January 7, 2008; final version accepted February 1. Supported in part by Howard Hughes Medical Institute NIH Research Scholars Program (J.A.P.), NIDCD Intramural Research Project DC-00016 (C.V.W., Z.C., C.T.A.), NIH Clinical Center, and a Materials Cooperative Research and Development Agreement with Millennium Pharmaceuticals (C.V.W.). Address correspondence to V.F. (e-mail: vfrenkel{at}cc.nih.gov).

Purpose: To investigate whether combining pulsed high-intensity focused ultrasound (HIFU) with the chemotherapeutic drug bortezomib could improve antitumor activity against murine squamous cell carcinoma (SCC) tumors.

Materials and Methods: All experiments were conducted with animal care and use committee approval. Murine SCC cells were implanted subcutaneously in C3H mice. When tumors reached 100 mm³, mice were randomized to one of three groups for twice weekly intraperitoneal injections of 1.5 mg of bortezomib per kilogram of body weight, a proteasome inhibitor (n = 10); 1.0 mg/kg bortezomib (n = 11); or a control vehicle (n = 12). Within each group, half of the mice received pulsed HIFU exposure to their tumors immediately prior to each injection. The time for tumors to reach 650 mm³ was compared among groups. Additional tumors were stained with terminal deoxynucledotidyl transferase-mediated dUTP nick end labeling and CD31 to assess apoptotic index and blood vessel density, respectively.

Results: Tumors in the control group, pulsed HIFU and control group, and 1.0 mg/kg of bortezomib alone group reached the size end point in 5.2 days ± 0.8 (standard deviation), 5.3 days ± 0.8, and 5.6 days ± 1.1, respectively. However, pulsed HIFU and 1.0 mg/kg bortezomib increased the time to end point to 9.8 days ± 2.9 (P < .02), not significantly different from the 8.8 days ± 2.1 in tumors treated with 1.5 mg/kg bortezomib alone (P > .05). Combination therapy was also associated with a significantly higher apoptotic index (P < .05).

Conclusion: Treatment of tumors with pulsed HIFU lowered the threshold level for efficacy of bortezomib, resulting in significant tumor cytotoxicity and growth inhibition at lower dose levels.

© RSNA, 2008