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Generation of an Orthotopic Xenograft of Pancreatic Cancer Cells by Ultrasound-Guided Injection
Published on: November 1, 2021
Radiosensitizing Pancreatic Cancer Xenografts by an Implantable Micro-Oxygen Generator
Ning Cao1,2, Seung Hyun Song3, Teimour Maleki4
1Schools of a Health Sciences.
Abstract:
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.
Insights
A novel implantable micro-oxygen generator (IMOG) successfully produced oxygen within pancreatic tumors. This in situ oxygenation enhanced tumor radiosensitivity, improving radiation therapy response.
Area of Science:
- Oncology
- Biomedical Engineering
- Radiation Oncology
Background:
- Pancreatic cancer has extremely low survival rates, with tumor hypoxia contributing to aggressive behavior and reduced treatment efficacy.
- Hypoxia in pancreatic tumors impedes conventional radiation and chemotherapy effectiveness.
- Developing strategies to overcome hypoxia is crucial for improving pancreatic cancer treatment outcomes.
Purpose of the Study:
- To evaluate the efficacy of a novel implantable micro-oxygen generator (IMOG) for in situ tumor oxygenation in pancreatic cancer.
- To assess the potential of IMOG-generated oxygen to radiosensitize pancreatic tumors.
- To determine if IMOG can enhance the response to single-dose radiation therapy.
Main Methods:
- Human pancreatic xenograft tumors were implanted subcutaneously in athymic rats and nude mice.
- The IMOG device was implanted and wirelessly powered using ultrasonic waves to electrolyze water and produce oxygen.
- Oxygen levels were monitored using a NeoFox oxygen sensor.
- Tumor growth was monitored after irradiation of tumors with or without a functional IMOG.
Main Results:
- The IMOG successfully produced significant amounts of oxygen within the tumor microenvironment.
- Tumors treated with a functional IMOG and 5 Gy radiation showed tumor growth inhibition comparable to tumors receiving 7 Gy radiation without an IMOG.
- The study demonstrated the feasibility and effectiveness of the IMOG for in situ tumor oxygenation.
Conclusions:
- The activated IMOG effectively generates oxygen within pancreatic tumors, addressing tumor hypoxia.
- IMOG-mediated oxygenation significantly radiosensitizes pancreatic tumors, enhancing the efficacy of radiation therapy.
- This novel approach holds promise for improving treatment outcomes in pancreatic cancer patients by overcoming hypoxia-induced resistance.
