Calcium Electroporation versus Electrochemotherapy with Bleomycin in an In Vivo CAM-Based Uveal Melanoma Xenograft Model

Despite recent advancements in the diagnosis and treatment of uveal melanoma (UM), its metastatic rate remains high and is accompanied by a highly dismal prognosis, constituting an unmet need for the development of novel adjuvant therapeutic strategies. We established an in vivo chick chorioallantoi...

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Main Authors: Theodora Tsimpaki, Ralitsa Anastasova, Hongtao Liu, Berthold Seitz, Nikolaos E. Bechrakis, Utta Berchner-Pfannschmidt, Miriam M. Kraemer, Miltiadis Fiorentzis
Format: Article
Language:English
Published: MDPI AG 2024-01-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/25/2/938
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author Theodora Tsimpaki
Ralitsa Anastasova
Hongtao Liu
Berthold Seitz
Nikolaos E. Bechrakis
Utta Berchner-Pfannschmidt
Miriam M. Kraemer
Miltiadis Fiorentzis
author_facet Theodora Tsimpaki
Ralitsa Anastasova
Hongtao Liu
Berthold Seitz
Nikolaos E. Bechrakis
Utta Berchner-Pfannschmidt
Miriam M. Kraemer
Miltiadis Fiorentzis
author_sort Theodora Tsimpaki
collection DOAJ
description Despite recent advancements in the diagnosis and treatment of uveal melanoma (UM), its metastatic rate remains high and is accompanied by a highly dismal prognosis, constituting an unmet need for the development of novel adjuvant therapeutic strategies. We established an in vivo chick chorioallantoic membrane (CAM)-based UM xenograft model from UPMD2 and UPMM3 cell lines to examine its feasibility for the improvement of selection of drug candidates. The efficacy of calcium electroporation (CaEP) with 5 or 10 mM calcium chloride (Ca) and electrochemotherapy (ECT) with 1 or 2.5 µg/mL bleomycin in comparison to monotherapy with the tested drug or electroporation (EP) alone was investigated on the generated UM tumors. CaEP and ECT showed a similar reduction of proliferation and melanocytic expansion with a dose-dependent effect for bleomycin, whereas CaEP induced a significant increase of the apoptosis and a reduction of vascularization with varying sensitivity for the two xenograft types. Our in vivo results suggest that CaEP and ECT may facilitate the adequate local tumor control and contribute to the preservation of the bulbus, potentially opening new horizons in the adjuvant treatment of advanced UM.
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spelling doaj.art-2c75eac2ca324c81af317080e7e094972024-01-29T13:55:41ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-01-0125293810.3390/ijms25020938Calcium Electroporation versus Electrochemotherapy with Bleomycin in an In Vivo CAM-Based Uveal Melanoma Xenograft ModelTheodora Tsimpaki0Ralitsa Anastasova1Hongtao Liu2Berthold Seitz3Nikolaos E. Bechrakis4Utta Berchner-Pfannschmidt5Miriam M. Kraemer6Miltiadis Fiorentzis7Department of Ophthalmology, University Hospital Essen, University of Duisburg-Essen, Hufeland Str. 55, 45147 Essen, GermanyDepartment of Ophthalmology, University Hospital Essen, University of Duisburg-Essen, Hufeland Str. 55, 45147 Essen, GermanyDepartment of Ophthalmology, University Hospital Essen, University of Duisburg-Essen, Hufeland Str. 55, 45147 Essen, GermanyDepartment of Ophthalmology, Saarland University Medical Center, Kirrberger Str. 100, 66421 Homburg, GermanyDepartment of Ophthalmology, University Hospital Essen, University of Duisburg-Essen, Hufeland Str. 55, 45147 Essen, GermanyDepartment of Ophthalmology, University Hospital Essen, University of Duisburg-Essen, Hufeland Str. 55, 45147 Essen, GermanyDepartment of Ophthalmology, University Hospital Essen, University of Duisburg-Essen, Hufeland Str. 55, 45147 Essen, GermanyDepartment of Ophthalmology, University Hospital Essen, University of Duisburg-Essen, Hufeland Str. 55, 45147 Essen, GermanyDespite recent advancements in the diagnosis and treatment of uveal melanoma (UM), its metastatic rate remains high and is accompanied by a highly dismal prognosis, constituting an unmet need for the development of novel adjuvant therapeutic strategies. We established an in vivo chick chorioallantoic membrane (CAM)-based UM xenograft model from UPMD2 and UPMM3 cell lines to examine its feasibility for the improvement of selection of drug candidates. The efficacy of calcium electroporation (CaEP) with 5 or 10 mM calcium chloride (Ca) and electrochemotherapy (ECT) with 1 or 2.5 µg/mL bleomycin in comparison to monotherapy with the tested drug or electroporation (EP) alone was investigated on the generated UM tumors. CaEP and ECT showed a similar reduction of proliferation and melanocytic expansion with a dose-dependent effect for bleomycin, whereas CaEP induced a significant increase of the apoptosis and a reduction of vascularization with varying sensitivity for the two xenograft types. Our in vivo results suggest that CaEP and ECT may facilitate the adequate local tumor control and contribute to the preservation of the bulbus, potentially opening new horizons in the adjuvant treatment of advanced UM.https://www.mdpi.com/1422-0067/25/2/938uveal melanomaelectroporationelectrochemotherapycalcium electroporationchick chorioallantois membrane assayuveal melanoma xenografts
spellingShingle Theodora Tsimpaki
Ralitsa Anastasova
Hongtao Liu
Berthold Seitz
Nikolaos E. Bechrakis
Utta Berchner-Pfannschmidt
Miriam M. Kraemer
Miltiadis Fiorentzis
Calcium Electroporation versus Electrochemotherapy with Bleomycin in an In Vivo CAM-Based Uveal Melanoma Xenograft Model
International Journal of Molecular Sciences
uveal melanoma
electroporation
electrochemotherapy
calcium electroporation
chick chorioallantois membrane assay
uveal melanoma xenografts
title Calcium Electroporation versus Electrochemotherapy with Bleomycin in an In Vivo CAM-Based Uveal Melanoma Xenograft Model
title_full Calcium Electroporation versus Electrochemotherapy with Bleomycin in an In Vivo CAM-Based Uveal Melanoma Xenograft Model
title_fullStr Calcium Electroporation versus Electrochemotherapy with Bleomycin in an In Vivo CAM-Based Uveal Melanoma Xenograft Model
title_full_unstemmed Calcium Electroporation versus Electrochemotherapy with Bleomycin in an In Vivo CAM-Based Uveal Melanoma Xenograft Model
title_short Calcium Electroporation versus Electrochemotherapy with Bleomycin in an In Vivo CAM-Based Uveal Melanoma Xenograft Model
title_sort calcium electroporation versus electrochemotherapy with bleomycin in an in vivo cam based uveal melanoma xenograft model
topic uveal melanoma
electroporation
electrochemotherapy
calcium electroporation
chick chorioallantois membrane assay
uveal melanoma xenografts
url https://www.mdpi.com/1422-0067/25/2/938
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