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Electrochemotherapy by pulsed electromagnetic field treatment (PEMF) in mouse melanoma B16F10 in vivo

Simona Kranjc

Simona Kranjc

Department of Experimental Oncology, Institute of Oncology LjubljanaLjubljana, Slovenia
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Kranjc, Simona
, 
Matej Kranjc

Matej Kranjc

University of Ljubljana, Faculty of Electrical EngineeringLjubljana, Slovenia
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Kranjc, Matej
, 
Janez Scancar

Janez Scancar

Jozef Stefan InstituteLjubljana, Slovenia
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Scancar, Janez
, 
Jure Jelenc

Jure Jelenc

Iskra Medical LLCLjubljana, Slovenia
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Jelenc, Jure
, 
Gregor Sersa

Gregor Sersa

Department of Experimental Oncology, Institute of Oncology LjubljanaLjubljana, Slovenia
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Sersa, Gregor
 and 
Damijan Miklavcic

Damijan Miklavcic

University of Ljubljana, Faculty of Electrical EngineeringLjubljana, Slovenia
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Miklavcic, Damijan
  
Feb 16, 2016
Electrochemotherapy by pulsed electromagnetic field treatment (PEMF) in mouse melanoma B16F10 in vivo's Cover Image
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Article Category: Research Article
Published Online: Feb 16, 2016
Page range: 39 - 48
Received: Oct 30, 2015
Accepted: Jan 20, 2016
DOI: https://doi.org/10.1515/raon-2016-0014
Keywords
© 2016 Radiol Oncol
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Figure 1. (A)

Illustrated lateral view of multi-turn coil (colored orange) and the treated tumor (colored blue). Tumor was located in the center of the coil, i.e. 31 mm and 42 mm from the inner (r1) and outer boundary (r2) of the coil, respectively. The number of turns (N) in coil was 72. Due to the casing of the applicator the coil was placed 23 mm above the tumor (h). (B) Illustrated view from above.
Illustrated lateral view of multi-turn coil (colored orange) and the treated tumor (colored blue). Tumor was located in the center of the coil, i.e. 31 mm and 42 mm from the inner (r1) and outer boundary (r2) of the coil, respectively. The number of turns (N) in coil was 72. Due to the casing of the applicator the coil was placed 23 mm above the tumor (h). (B) Illustrated view from above.

Figure 2.

Sequence of bipolar electric pulses where tp is a duration of the pulse, lp is a pulse amplitude, tint is an interval between pulses and fp is a repetition frequency.
Sequence of bipolar electric pulses where tp is a duration of the pulse, lp is a pulse amplitude, tint is an interval between pulses and fp is a repetition frequency.

Figure 3.

Antitumor effectiveness of electrochemotherapy with CDDP mediated by PEMF in mouse melanoma B16F10. Data were collected from two individual experiments and each point on graph represents mean and standard error of the mean (AM ± SE). Each group consisted at least of 8 animals.
Antitumor effectiveness of electrochemotherapy with CDDP mediated by PEMF in mouse melanoma B16F10. Data were collected from two individual experiments and each point on graph represents mean and standard error of the mean (AM ± SE). Each group consisted at least of 8 animals.

Figure 4.

Platinum (Pt) accumulation in tumor and serum after electroporation induced by PEMF. Each group consisted from 3–8 animals. Data represent mean and standard error of the mean (AM ± SE).CDDP = intravenously injection of cisplatin (4 mg/ kg); PEMF = pulsed electromagnetic field treatment; PEMF + CDDP = PEMF after intravenously injection of CDDP. * = p < 0.05 statistically significant difference; ** = p < 0.05 statistically significant difference to measured Patinum (Pt) content in the whole tumor
Platinum (Pt) accumulation in tumor and serum after electroporation induced by PEMF. Each group consisted from 3–8 animals. Data represent mean and standard error of the mean (AM ± SE).CDDP = intravenously injection of cisplatin (4 mg/ kg); PEMF = pulsed electromagnetic field treatment; PEMF + CDDP = PEMF after intravenously injection of CDDP. * = p < 0.05 statistically significant difference; ** = p < 0.05 statistically significant difference to measured Patinum (Pt) content in the whole tumor

Figure 5.

Platinum (Pt) bound to the DNA in tumor cells representing intracellular fraction and Pt content in extracellular fractions after electroporation induced by PEMF. Data represent mean and standard error of the mean (AM ± SE). Each group consisted from 3–8 animals.CDDP = intravenously injection of cisplatin (4 mg/kg); PEMF = pulsed electromagnetic field treatment; PEMF + CDDP = PEMF after intravenously injection of CDDP. *** = p < 0.05 statistically significant difference
Platinum (Pt) bound to the DNA in tumor cells representing intracellular fraction and Pt content in extracellular fractions after electroporation induced by PEMF. Data represent mean and standard error of the mean (AM ± SE). Each group consisted from 3–8 animals.CDDP = intravenously injection of cisplatin (4 mg/kg); PEMF = pulsed electromagnetic field treatment; PEMF + CDDP = PEMF after intravenously injection of CDDP. *** = p < 0.05 statistically significant difference

Figure 6. (A)

Evaluation surfaces (Ωxy, Ωyz, Ωzx) in three different planes (xy, yz, zx) where electric field distribution and magnetic flux density were simulated by means of numerical modelling. (B) Distribution of induced electric field in evaluation surfaces when it reached its peak at tE. (C) Time course of magnetic flux density and induced electric field at evaluation point Pev. Time points when magnetic flux density and induced electric field reached its maximum are marked with tE and tB, respectively. (D) Distribution of magnetic flux density in evaluation surfaces when it reached its peak at tB.
Evaluation surfaces (Ωxy, Ωyz, Ωzx) in three different planes (xy, yz, zx) where electric field distribution and magnetic flux density were simulated by means of numerical modelling. (B) Distribution of induced electric field in evaluation surfaces when it reached its peak at tE. (C) Time course of magnetic flux density and induced electric field at evaluation point Pev. Time points when magnetic flux density and induced electric field reached its maximum are marked with tE and tB, respectively. (D) Distribution of magnetic flux density in evaluation surfaces when it reached its peak at tB.

Tumor doubling times of melanoma B16F10 tumors after treatment with CDDP or combined with electroporation induced by PEMF_

GroupnDT (Mean ± SE)GDP (<0.05)
Control*121.5 ± 0.1
CDDP*4 mg/kg122.2 ± 0.20.7
PEMF91.9 ± 0.10.4
PEMF + CDDP103.8 ± 0.12.3<0.001 (to PEMF)
EP*122.2 ± 0.30.7
ECT CDDP*84.5 ± 0.23.0<0.009 (to PEMF + CDDP)
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