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Bleomycin ElectroScleroTherapy (BEST): mechanistic parallels to electrochemotherapy, experimental models, and unresolved questions Cover

Bleomycin ElectroScleroTherapy (BEST): mechanistic parallels to electrochemotherapy, experimental models, and unresolved questions

Radiology and Oncology
Volume 60 (2026): Issue 1 (March 2026)
By: Barbara Lisec,  Maja Cemazar,  Tobian Muir,  Masa Omerzel,  Tanja Jesenko,  Bostjan Markelc,  Ales Groselj,  Rok Dezman,  Miha Stabuc,  Dimitrij Kuhelj and  Gregor Sersa  
Open Access
|Mar 2026

Figures & Tables

FIGURE 1.

Shared and distinct endothelial phenotypes in (venous) VMs and tumors. Created in BioRender. Cemazar, M. (2026) https://BioRender.com/wo8u8ja VEGF = vascular endothelial growth factor

FIGURE 2.

Schematic comparison of the key phenotypic and structural differences between normal venous vessels and venous malformations. Created in BioRender. Cemazar, M. (2026) https://BioRender.com/7nzewhx EC = endothelial cell; ECM = extracellular matrix

FIGURE 3.

A schematic overview of shared signaling pathways in VMs and tumor angiogenesis associated with aberrant angiogenesis and/or abnormalities in vessels development and maturation. Asterisks (*) highlight mutations associated with (venous) vascular malformations (VM)s. Created in BioRender. Cemazar, M. (2026) https://BioRender.com/kfngg58 ECM = extracellular matrix; EGF = epidermal growth factor; Eph = ephrin; FGF = fibroblast growth factor; HGF = hepatocyte growth factor; IGF = insulin-like growth factor; KITLG = KIT ligant, stem cell factor; NOTCH receptors = highly conserved transmembrane proteins; PDGF = plateletderived growth factor; TGF-β = transforming growth factor-beta; TIE receptors = type of receptor tyrosine kinases that include Tie1 and Tie2; VEGF = vascular endothelial growth factor

FIGURE 4.

Mechanisms of bleomycin on endothelial cells (ECs). In experimental endothelial systems, bleomycin induces DNA damage, oxidative stress, inflammatory activation, apoptosis, and junctional disruption. After BEST, electroporation markedly increases intracellular bleomycin delivery, and similar injury mechanisms are presumed to happen; however, the extent and hierarchy of these mechanisms in treated vascular malformations (VMs) remain to be defined. Created in BioRender. Cemazar, M. (2026) https://BioRender.com/vyht6ij Bcl-2 = B-cell lymphoma 2; BLM = bleomycin; EndoMT = endothelial-to-mesenchymal transition; GSDMD = gasdermin D; ICAM-1 = intercellular adhesion molecule-1; IL-8 = interleukin 8; MCP-1 = monocyte chemoattractant protein-1; mTOR = mechanistic target of rapamycin; NLRP3 = NOD-like receptor protein 3; ROS = reactive oxygen species; TNF = tumor necrosis factor; VCAM-1 = vascular cell adhesion molecule-1

FIGURE 5.

Experimental models for studying vascular malformations (VMs) and mechanisms of BEST. These models differ in complexity, throughput capacity, and physiological relevance, as well as in their ability to recapitulate native vascular structure, hemodynamics, and immune context. Simple systems are well suited for mechanistic analyses, whereas microphysiological and in vivo models are required to investigate flow disruption and tissue remodeling. Strategic integration of complementary model systems is essential to dissect the cellular and vascular disrupting mechanisms underlying BEST. Created in BioRender. Cemazar, M. (2026) https://BioRender.com/spmxuwa
DOI: https://doi.org/10.2478/raon-2026-0017 | Journal eISSN: 1581-3207 | Journal ISSN: 1318-2099
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Language: English
Page range: 1 - 14
Submitted on: Feb 26, 2026
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Accepted on: Mar 5, 2026
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Published on: Mar 24, 2026
Published by: Association of Radiology and Oncology
In partnership with: Paradigm Publishing Services
Publication frequency: 4 issues per year
Keywords:
vascular malformations,
bleomycin electrosclerotherapy,
BEST,
electrochemotherapy
Related subjects:
Medicine,
Clinical medicine,
Internal medicine,
Haematology, oncology,
Radiology

© 2026 Barbara Lisec, Maja Cemazar, Tobian Muir, Masa Omerzel, Tanja Jesenko, Bostjan Markelc, Ales Groselj, Rok Dezman, Miha Stabuc, Dimitrij Kuhelj, Gregor Sersa, published by Association of Radiology and Oncology
This work is licensed under the Creative Commons Attribution 4.0 License.

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