Pulsed high-intensity focused ultrasound enhances apoptosis and growth inhibition of squamous cell carcinoma xenografts with proteasome inhibitor bortezomib

Jason A. Poff, Clint T Allen, Bryan Traughber, Aric Colunga, Jianwu Xie, Zhong Chen, Bradford J. Wood, Carter Van Waes, King C P Li, Victor Frenkel

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)485-491
Number of pages7
JournalRadiology
Volume248
Issue number2
DOIs
StatePublished - Aug 2008

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Proteasome Inhibitors
Heterografts
Squamous Cell Carcinoma
Apoptosis
Growth
Neoplasms
Animal Care Committees
Control Groups
Bortezomib
Inbred C3H Mouse
Transferases
Intraperitoneal Injections
Blood Vessels
Body Weight
Injections
Therapeutics

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology

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Pulsed high-intensity focused ultrasound enhances apoptosis and growth inhibition of squamous cell carcinoma xenografts with proteasome inhibitor bortezomib. / Poff, Jason A.; Allen, Clint T; Traughber, Bryan; Colunga, Aric; Xie, Jianwu; Chen, Zhong; Wood, Bradford J.; Van Waes, Carter; Li, King C P; Frenkel, Victor.

In: Radiology, Vol. 248, No. 2, 08.2008, p. 485-491.

Research output: Contribution to journalArticle

Poff, Jason A. ; Allen, Clint T ; Traughber, Bryan ; Colunga, Aric ; Xie, Jianwu ; Chen, Zhong ; Wood, Bradford J. ; Van Waes, Carter ; Li, King C P ; Frenkel, Victor. / Pulsed high-intensity focused ultrasound enhances apoptosis and growth inhibition of squamous cell carcinoma xenografts with proteasome inhibitor bortezomib. In: Radiology. 2008 ; Vol. 248, No. 2. pp. 485-491.
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abstract = "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.",
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T1 - Pulsed high-intensity focused ultrasound enhances apoptosis and growth inhibition of squamous cell carcinoma xenografts with proteasome inhibitor bortezomib

AU - Poff, Jason A.

AU - Allen, Clint T

AU - Traughber, Bryan

AU - Colunga, Aric

AU - Xie, Jianwu

AU - Chen, Zhong

AU - Wood, Bradford J.

AU - Van Waes, Carter

AU - Li, King C P

AU - Frenkel, Victor

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N2 - 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.

AB - 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.

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