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Repetitive Bleomycin-Based Electrochemotherapy Improves Antitumor Effectiveness in 3D Tumor Models of Conjunctival Melanoma

Background: Conjunctival melanoma (CM) is associated with a high rate of local recurrence and poor survival rate. Novel therapeutic options are needed to reduce recurrence rate. The objective of the study was to demonstrate the improved effectiveness of electrochemotherapy (ECT) on CM using repetiti...

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Autores principales: Heinzelmann, Joana, Hecht, Sabine, Vogt, Alexander Ruben, Siebolts, Udo, Kaatzsch, Peter, Viestenz, Arne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917688/
https://www.ncbi.nlm.nih.gov/pubmed/36769736
http://dx.doi.org/10.3390/jcm12031087
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author Heinzelmann, Joana
Hecht, Sabine
Vogt, Alexander Ruben
Siebolts, Udo
Kaatzsch, Peter
Viestenz, Arne
author_facet Heinzelmann, Joana
Hecht, Sabine
Vogt, Alexander Ruben
Siebolts, Udo
Kaatzsch, Peter
Viestenz, Arne
author_sort Heinzelmann, Joana
collection PubMed
description Background: Conjunctival melanoma (CM) is associated with a high rate of local recurrence and poor survival rate. Novel therapeutic options are needed to reduce recurrence rate. The objective of the study was to demonstrate the improved effectiveness of electrochemotherapy (ECT) on CM using repetitive application. Methods: Tumor spheroids of three CM cell lines (CRMM1, CRMM2, CM2005.1) were treated repetitively with ECT using the chemotherapeutic agent bleomycin on days 3, 5, and 7 of culture. Application of bleomycin alone and electroporation alone served as controls. The cytotoxic effect was analyzed on day 10 compared to untreated control using an independent t-test. The spheroid outgrowth rate was measured. Result: CM tumor spheroid size (median value: 78%, SD: 32%) and viability (median value: 11%, SD: 11%) were dramatically reduced after repetitive ECT treatment (p-value < 0.001). Decreased proliferation capacity (down to 8%) and an increase of apoptotic cells were observed. In most repetitive ECT-treated spheroids, no viable or proliferating cells were detected. Only 33–40% of repetitive ECT-treated spheroids exhibited single outgrowing cells with a delay of time up to 38 days. Conclusion: Repetitive ECT application effectively induces cytotoxic effects in CM spheroids by inducing apoptosis, inhibiting proliferation and decreasing the percentage of surviving tumor cells. Thus, repetitive ECT results in improved antitumor effectiveness in CM and could be an alternative therapy option.
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spelling pubmed-99176882023-02-11 Repetitive Bleomycin-Based Electrochemotherapy Improves Antitumor Effectiveness in 3D Tumor Models of Conjunctival Melanoma Heinzelmann, Joana Hecht, Sabine Vogt, Alexander Ruben Siebolts, Udo Kaatzsch, Peter Viestenz, Arne J Clin Med Article Background: Conjunctival melanoma (CM) is associated with a high rate of local recurrence and poor survival rate. Novel therapeutic options are needed to reduce recurrence rate. The objective of the study was to demonstrate the improved effectiveness of electrochemotherapy (ECT) on CM using repetitive application. Methods: Tumor spheroids of three CM cell lines (CRMM1, CRMM2, CM2005.1) were treated repetitively with ECT using the chemotherapeutic agent bleomycin on days 3, 5, and 7 of culture. Application of bleomycin alone and electroporation alone served as controls. The cytotoxic effect was analyzed on day 10 compared to untreated control using an independent t-test. The spheroid outgrowth rate was measured. Result: CM tumor spheroid size (median value: 78%, SD: 32%) and viability (median value: 11%, SD: 11%) were dramatically reduced after repetitive ECT treatment (p-value < 0.001). Decreased proliferation capacity (down to 8%) and an increase of apoptotic cells were observed. In most repetitive ECT-treated spheroids, no viable or proliferating cells were detected. Only 33–40% of repetitive ECT-treated spheroids exhibited single outgrowing cells with a delay of time up to 38 days. Conclusion: Repetitive ECT application effectively induces cytotoxic effects in CM spheroids by inducing apoptosis, inhibiting proliferation and decreasing the percentage of surviving tumor cells. Thus, repetitive ECT results in improved antitumor effectiveness in CM and could be an alternative therapy option. MDPI 2023-01-30 /pmc/articles/PMC9917688/ /pubmed/36769736 http://dx.doi.org/10.3390/jcm12031087 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Heinzelmann, Joana
Hecht, Sabine
Vogt, Alexander Ruben
Siebolts, Udo
Kaatzsch, Peter
Viestenz, Arne
Repetitive Bleomycin-Based Electrochemotherapy Improves Antitumor Effectiveness in 3D Tumor Models of Conjunctival Melanoma
title Repetitive Bleomycin-Based Electrochemotherapy Improves Antitumor Effectiveness in 3D Tumor Models of Conjunctival Melanoma
title_full Repetitive Bleomycin-Based Electrochemotherapy Improves Antitumor Effectiveness in 3D Tumor Models of Conjunctival Melanoma
title_fullStr Repetitive Bleomycin-Based Electrochemotherapy Improves Antitumor Effectiveness in 3D Tumor Models of Conjunctival Melanoma
title_full_unstemmed Repetitive Bleomycin-Based Electrochemotherapy Improves Antitumor Effectiveness in 3D Tumor Models of Conjunctival Melanoma
title_short Repetitive Bleomycin-Based Electrochemotherapy Improves Antitumor Effectiveness in 3D Tumor Models of Conjunctival Melanoma
title_sort repetitive bleomycin-based electrochemotherapy improves antitumor effectiveness in 3d tumor models of conjunctival melanoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917688/
https://www.ncbi.nlm.nih.gov/pubmed/36769736
http://dx.doi.org/10.3390/jcm12031087
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