Over the past decades, little progress has been made to improve the extremely low survival rates in pancreatic cancer patients. Extreme hypoxia observed in pancreatic tumors contributes to the aggressive and metastatic characteristics of this tumor and can reduce the effectiveness of conventional radiation therapy and chemotherapy. In an attempt to reduce hypoxia-induced obstacles to effective radiation treatment, we used a novel device, the implantable micro-oxygen generator (IMOG), for in situ tumor oxygenation. After subcutaneous implantation of human pancreatic xenograft tumors in athymic rats, the IMOG was wirelessly powered by ultrasonic waves, producing 30 μA of direct current (at 2.5 V), which was then utilized to electrolyze water and produce oxygen within the tumor. Significant oxygen production by the IMOG was observed and corroborated using the NeoFox oxygen sensor dynamically. To test the radiosensitization effect of the newly generated oxygen, the human pancreatic xenograft tumors were subcutaneously implanted in nude mice with either a functional or inactivated IMOG device. The tumors in the mice were then exposed to ultrasonic power for 10 min, followed by a single fraction of 5 Gy radiation, and tumor growth was monitored thereafter. The 5 Gy irradiated tumors containing the functional IMOG exhibited tumor growth inhibition equivalent to that of 7 Gy irradiated tumors that did not contain an IMOG. Our study confirmed that an activated IMOG is able to produce sufficient oxygen to radiosensitize pancreatic tumors, enhancing response to single-dose radiation therapy.
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1 April 2016
SHORT COMMUNICATION|
March 22 2016
Radiosensitizing Pancreatic Cancer Xenografts by an Implantable Micro-Oxygen Generator
Ning Cao;
Schools ofaHealth Sciences,
dDepartment of Radiation Oncology, University of Washington Medical Center, Seattle, Washington; Departments of
1Address for correspondence: Department of Radiation Oncology, University of Washington Medical Center, 1959 NE Pacific Street, Box 356043, Seattle, WA 98195; email: ningcao@uw.edu.
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Seung Hyun Song;
Seung Hyun Song
2
bElectrical and Computer Engineering and
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Teimour Maleki;
Teimour Maleki
cBirck Nanotechnology Center, Purdue University, W. Lafayette, Indiana;
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Michael Shaffer;
Michael Shaffer
Schools ofaHealth Sciences,
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Keith M. Stantz;
Keith M. Stantz
Schools ofaHealth Sciences,
eRadiology,
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Minsong Cao;
Minsong Cao
fRadiation Oncology and
hRadiation Oncology, UCLA Medical Center, Los Angeles, California; and
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Chinghai Kao;
Chinghai Kao
gUrology, Indiana University School of Medicine, Indianapolis, Indiana;
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Marc S. Mendonca;
Marc S. Mendonca
fRadiation Oncology and
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Babak Ziaie;
Babak Ziaie
bElectrical and Computer Engineering and
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Song-Chu Ko
Song-Chu Ko
fRadiation Oncology and
iRadiation Oncology, IU Health Arnett Hospital, Lafayette, Indiana
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Radiat Res (2016) 185 (4): 431–437.
Article history
Received:
May 25 2015
Accepted:
December 22 2015
Citation
Ning Cao, Seung Hyun Song, Teimour Maleki, Michael Shaffer, Keith M. Stantz, Minsong Cao, Chinghai Kao, Marc S. Mendonca, Babak Ziaie, Song-Chu Ko; Radiosensitizing Pancreatic Cancer Xenografts by an Implantable Micro-Oxygen Generator. Radiat Res 1 April 2016; 185 (4): 431–437. doi: https://doi.org/10.1667/RR14149.1
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