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A Syngeneic Pancreatic Cancer Mouse Model to Study the Effects of Irreversible Electroporation
Published on: June 8, 2018
Effects of different applied voltages of irreversible electroporation on prostate cancer in a mouse model
Hong Bae Kim1, Chu Hui Zeng2, Yunlim Kim3
1Department of Biosystems & Biomaterials Science and Engineering, Seoul National University, Seoul, 08826, Republic of Korea.
Abstract:
As a non-thermal ablation method, irreversible electroporation (IRE) has been widely investigated in the treatment of prostate cancer. However, no consensus has been achieved on the optimal parameters of IRE for prostate cancer. Since high voltage is known to carry risks of muscle contraction and patient discomfort, it is crucial to identify the minimum but effective and safer applied voltage to inhibit tumor growth. In this study, the effect of different applied voltages of IRE on prostate cancer was evaluated in BALB/c nude mice. Mathematical simulation and measurement of the actual ablation area revealed a larger ablation area at a higher voltage. In in vivo experiment, except for the three different voltages applied, all groups received identical electrical conditions: pulse number, 180 (20 groups × 9 pulses/group); pulse width, 100 µs; pulse interval, 2 ms; distance between the electrodes, 5 mm; and electrode exposure length, 15 mm. Whilst the tumor volume initially decreased in the 500 V (1000 V/cm) and 700 V (1400 V/cm) groups and subsequently increased, only a transient increase followed by a continuous decrease until the sacrifice was observed in the 900 V (1800 V/cm) group. This result demonstrated a lasting effect of a higher applied voltage on tumor growth inhibition. The histological, immunohistochemical, and western blot findings all confirmed IRE-induced apoptosis in the treatment groups. Taken together, 900 V seemed to be the minimum applied voltage required to reduce tumor growth, though subsequent studies are anticipated to further narrow the voltage intervals and lower the minimum voltage required for tumor inhibition.
Insights
Irreversible electroporation (IRE) shows promise for prostate cancer treatment. This study found 900 V to be the minimum effective voltage for inhibiting tumor growth, minimizing risks associated with higher voltages.
Area of Science:
- Oncology
- Biomedical Engineering
- Medical Physics
Background:
- Irreversible electroporation (IRE) is a non-thermal ablation technique explored for prostate cancer therapy.
- Optimal IRE parameters, particularly voltage, remain undetermined for effective and safe prostate cancer treatment.
- High voltages in IRE can cause adverse effects like muscle contraction and patient discomfort.
Purpose of the Study:
- To evaluate the impact of different applied voltages of IRE on prostate cancer growth in a murine model.
- To identify the minimum effective voltage for IRE in inhibiting prostate cancer tumor growth while considering safety.
- To correlate applied voltage with ablation area and tumor response.
Main Methods:
- Mathematical simulation and experimental measurement were used to assess ablation area in relation to voltage.
- An in vivo experiment utilized BALB/c nude mice with prostate cancer, applying varying IRE voltages (500 V, 700 V, 900 V) under controlled electrical conditions.
- Histological, immunohistochemical, and Western blot analyses were performed to confirm IRE-induced apoptosis.
Main Results:
- Mathematical simulation and ablation measurements indicated a larger ablation area with higher applied voltages.
- Tumor volume initially decreased in the 500 V and 700 V groups but subsequently increased.
- The 900 V group exhibited a transient increase followed by continuous tumor volume reduction, demonstrating lasting growth inhibition.
- IRE-induced apoptosis was confirmed across treatment groups via multiple analytical methods.
Conclusions:
- A minimum applied voltage of 900 V appears necessary for sustained prostate cancer tumor growth inhibition using IRE.
- Higher voltages correlate with larger ablation areas and more effective tumor suppression.
- Further research is needed to refine voltage intervals and potentially lower the minimum effective voltage for IRE in prostate cancer treatment.
