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In vitro and in vivo evaluation of electrochemotherapy with trans-platinum analogue trans-[PtCl2(3-Hmpy)2] Cover

In vitro and in vivo evaluation of electrochemotherapy with trans-platinum analogue trans-[PtCl2(3-Hmpy)2]

Radiology and Oncology
Volume 51 (2017): Issue 3 (September 2017)
By: Simona Kranjc,  Maja Cemazar,  Gregor Sersa,  Janez Scancar and  Sabina Grabner  
Open Access
|Sep 2017

Figures & Tables

Figure 1

Survival of SA-1 sarcoma (A), TBLCI2 sarcoma (B) and TBLCI2Pt sarcoma cells (C) after treatment with cisplatin (CDDP) or compound 2 or cisplatin electrochemotherapy (ECT CDDP) or compound 2 electrochemotherapy (ECT Compound 2), determined using a clonogenic assay. Data are presented as the arithmetic mean and standard error of the mean (AM±SE) of triplicates pooled from three independent experiments. The survival of cells treated with electrochemotherapy was normalized to the survival of cells treated with electric pulses alone. The survival of SA-1, TBLCl2 and TBLCl2Pt cells treated with electric pulses alone was 0.96 ± 0.05, 0.93 ± 0.09 and 0.92 ± 0.10, respectively.
Survival of SA-1 sarcoma (A), TBLCI2 sarcoma (B) and TBLCI2Pt sarcoma cells (C) after treatment with cisplatin (CDDP) or compound 2 or cisplatin electrochemotherapy (ECT CDDP) or compound 2 electrochemotherapy (ECT Compound 2), determined using a clonogenic assay. Data are presented as the arithmetic mean and standard error of the mean (AM±SE) of triplicates pooled from three independent experiments. The survival of cells treated with electrochemotherapy was normalized to the survival of cells treated with electric pulses alone. The survival of SA-1, TBLCl2 and TBLCl2Pt cells treated with electric pulses alone was 0.96 ± 0.05, 0.93 ± 0.09 and 0.92 ± 0.10, respectively.

Figure 2

Tumour growth and animal body weight change after cisplatin or compound 2 electrochemotherapy in mouse sarcoma tumours; SA-1, TBLCl2 and TBLCl2Pt. Mice (6-12 per group) were treated with intratumoural injection of cisplatin (CDDP, 13.3 mmol/kg) or compound 2 (13.3 mmol/kg) or with local application of electric pulses at 1 minute after drug injection (ECT CDDP; ECT Compound 2; 8 pulses, 1300 V/cm, 100 μs, 1 Hz). Data are presented as the arithmetic mean and standard error of the mean (AM±SE) of tumour volumes.*p (< 0.05) significant difference compared to treatment with cisplatin electrochemotherapy
Tumour growth and animal body weight change after cisplatin or compound 2 electrochemotherapy in mouse sarcoma tumours; SA-1, TBLCl2 and TBLCl2Pt. Mice (6-12 per group) were treated with intratumoural injection of cisplatin (CDDP, 13.3 mmol/kg) or compound 2 (13.3 mmol/kg) or with local application of electric pulses at 1 minute after drug injection (ECT CDDP; ECT Compound 2; 8 pulses, 1300 V/cm, 100 μs, 1 Hz). Data are presented as the arithmetic mean and standard error of the mean (AM±SE) of tumour volumes.*p (< 0.05) significant difference compared to treatment with cisplatin electrochemotherapy

Figure 3

Platinum amount in sarcoma SA-1 tumours (A), platinum amount in the serum (B) and platinum amount bound to DNA in the cells isolated from SA-1 tumours (C). Animals (8 per group) were treated with intratumoural injection of cisplatin (CDDP, 13.3 mM) alone or compound 2 (13.3 mM) alone or with local application of electric pulses 1 minute after intratumoural drug injection (ECT CDDP; ECT Compound 2; 8 pulses, 1300 V/cm, 100 μs, 1 Hz). The data are presented as the arithmetic mean and standard error of the mean (AM±SE) obtained from 8 samples. *p (< 0.05) under (A) and (C) statistically significant difference compared to corresponding drug treatment only; *p (< 0.05) under (B) statistically significant difference compared to cisplatin or cisplatin electrochemotherapy.
Platinum amount in sarcoma SA-1 tumours (A), platinum amount in the serum (B) and platinum amount bound to DNA in the cells isolated from SA-1 tumours (C). Animals (8 per group) were treated with intratumoural injection of cisplatin (CDDP, 13.3 mM) alone or compound 2 (13.3 mM) alone or with local application of electric pulses 1 minute after intratumoural drug injection (ECT CDDP; ECT Compound 2; 8 pulses, 1300 V/cm, 100 μs, 1 Hz). The data are presented as the arithmetic mean and standard error of the mean (AM±SE) obtained from 8 samples. *p (< 0.05) under (A) and (C) statistically significant difference compared to corresponding drug treatment only; *p (< 0.05) under (B) statistically significant difference compared to cisplatin or cisplatin electrochemotherapy.

Antitumour effectiveness of electrochemotherapy with cisplatin or compound 2 in mouse sarcoma tumours; SA-1, TBLCl2 and TBLCl2Pt

SA-1TBLCl2TBLCI2Pt
GroupnDT (days) (AM±SE)GD (days)CR (n, %)nDT (days) (AM±SE)GD (days)CR (n, %)nDT (days) (AM±SE)GD (days)CR (n, %)
Control101.7±0.2 082.8±0.3 063.1±0.2 0
EP103.1 ±0.31.4085.1±1.02.3064.2±0.91.10
CDDP105.2±1.0

p (< 0.05) significant difference compared to treatment with CDDP electrochemotherapy;

3.5085.3±0.7

p (< 0.05) significant difference compared to treatment with CDDP electrochemotherapy;

2.5063.4±0.5

p (< 0.05) significant difference compared to treatment with CDDP electrochemotherapy;

0.30
Compound 2122.3±0.3

p (< 0.05) significant difference compared to treatment with compound 2 electrochemotherapy.

0.6093.5±0.5

p (< 0.05) significant difference compared to treatment with compound 2 electrochemotherapy.

0.7063.2±0.3

p (< 0.05) significant difference compared to treatment with compound 2 electrochemotherapy.

0.10
ECT CDDP1215.8±2.2

p (< 0.05) significant difference compared to treatment with compound 2 electrochemotherapy.

14.10911.6±1.08.86, 66.667.6±0.9

p (< 0.05) significant difference compared to treatment with compound 2 electrochemotherapy.

4.50
ECT Compound 2125.1±0.43.4099.4±1.86.61, 11.165.1±0.62.00

IC50 values after electrochemotherapy with cisplatin or compound 2 in various mouse tumour cell lines

SA-1TBLCI2TBLCI2Pt
GroupIC50 (μM)EFIC50 (μM)EFIC50 (μM)EF
CDDP276.7

p (< 0.05) statistically significant difference compared to treatment with cisplatin electrochemotherapy (ECT CDDP);

 180.0

p (< 0.05) statistically significant difference compared to treatment with cisplatin electrochemotherapy (ECT CDDP);

 926.6

p (< 0.05) statistically significant difference compared to treatment with cisplatin electrochemotherapy (ECT CDDP);
Compound 2500.0

p (< 0.05) significant difference compared to treatment with compound 2 electrochemotherapy (ECT Compound 2)

 220.0

p (< 0.05) significant difference compared to treatment with compound 2 electrochemotherapy (ECT Compound 2)

 1066.6

p (< 0.05) significant difference compared to treatment with compound 2 electrochemotherapy (ECT Compound 2)
ECT CDDP28.3

p (< 0.05) statistically difference compared to treatment with compound 2 electrochemotherapy.

9.88.0

p (< 0.05) statistically difference compared to treatment with compound 2 electrochemotherapy.

22.512.0

p (< 0.05) statistically difference compared to treatment with compound 2 electrochemotherapy.

77.2
ECT Compound 280.06.341.05.4206.75.2
DOI: https://doi.org/10.1515/raon-2017-0034 | Journal eISSN: 1581-3207 | Journal ISSN: 1318-2099
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Language: English
Page range: 295 - 306
Submitted on: Jul 20, 2017
|
Accepted on: Aug 4, 2017
|
Published on: Sep 14, 2017
Published by: Association of Radiology and Oncology
In partnership with: Paradigm Publishing Services
Publication frequency: 4 issues per year
Keywords:
platinum analogue,
cisplatin,
3-Hmpy,
electroporation,
electrochemotherapy,
mouse sarcoma
Related subjects:
Medicine,
Clinical medicine,
Internal medicine,
Haematology, oncology,
Radiology

© 2017 Simona Kranjc, Maja Cemazar, Gregor Sersa, Janez Scancar, Sabina Grabner, published by Association of Radiology and Oncology
This work is licensed under the Creative Commons Attribution 4.0 License.

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