Evidence map›Paper›PMID 41294835›Full record

ArticleCells2025

High-Frequency Irreversible Electroporation Alters Proteomic Profiles and Tropism of Small Tumor-Derived Extracellular Vesicles to Promote Immune Cell Infiltration.

Kelsey R Murphy, Kenneth N Aycock, Spencer Marsh, Liping Yang, Jonathan Hinckley, Aubrie Selmek, Robert Gourdie, Shay Bracha, Rafael V Davalos, John H Rossmeisl and 1 more

Abstract read
In one paragraph

Article in Cells, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Kelsey R MurphyDepartment of Biomedical and Veterinary Sciences, Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA 24061, USA.ORCID 0000-0002-8834-1189
Kenneth N AycockDepartment of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA 24061, USA.ORCID 0000-0003-3885-6798
Spencer MarshFralin Biomedical Research Institute, Virginia Tech Carilion School of Medicine, Virginia Tech, Roanoke, VA 24016, USA.
Liping YangDepartment of Chemistry, Oregon State University, Corvallis, OR 97331, USA.
Jonathan HinckleyDepartment of Small Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA 24061, USA.ORCID 0000-0001-9868-1163
Aubrie SelmekDepartment of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
Robert GourdieDepartment of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA 24061, USA.ORCID 0000-0001-6021-0796
Shay BrachaDepartment of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.ORCID 0000-0002-0406-2079
Rafael V DavalosDepartment of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA 24061, USA.ORCID 0000-0003-1503-9509
John H RossmeislDepartment of Small Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA 24061, USA.ORCID 0000-0003-1655-7076
Nikolaos G DervisisDepartment of Small Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA 24061, USA.

Funding

Connexin-based Signaling in the Heart: Cellular and ExosomalR35HL161237 · NHLBI · VIRGINIA POLYTECHNIC INST AND ST UNIV · PI ROBERT G GOURDIE · 2022 to 2026
$4.4M
High-frequency Irreversible Electroporation (H-FIRE) combinatorial GBM treatmentR01CA213423 · NCI · VIRGINIA POLYTECHNIC INST AND ST UNIV · PI DAVALOS, RAFAEL VIDAL, VERBRIDGE, SCOTT S · 2017 to 2021
$1.7M
Orbitrap Elite with ETDS10OD020111 · OD · OREGON STATE UNIVERSITY · PI MAIER, CLAUDIA S · 2015 to 2015
$600k
Grayton Friedlander Memorial Fund N/ANCI NIH HHS R01 CA213423NCI NIH HHS R01CA213423NHLBI NIH HHS R35 HL161237NIH HHS 1S10OD020111-01NIH HHS S10 OD020111Virginia-Maryland College of Veterinary Medicine Internal Research Competition N/A
6 · The paper itself

Abstract

High-frequency irreversible electroporation (H-FIRE) is a nonthermal tumor ablation technique that disrupts the blood-brain barrier (BBB) in a focal and reversible manner. However, the mechanisms underlying this disruption remain poorly understood, particularly the role of small tumor-derived extracellular vesicles (sTDEVs) released from ablated tumor cells. In this study, we investigate the proteomic and functional alterations of sTDEVs released from F98 glioma and LL/2 Lewis lung carcinoma cells following H-FIRE ablation. Mass spectrometry analysis revealed 108 unique proteins in sTDEVs derived from ablative doses of H-FIRE, which are capable of disrupting the BBB in an in vitro model. Proteomic analysis of TDEVs highlights key changes in pathways related to integrin signaling, Platelet-derived growth factor receptor (PDGFR) signaling, and ubiquitination, which may underline their interactions with brain endothelial cells. These "disruptive" sTDEVs exhibit enhanced tropism for cerebral endothelial cells both in vitro and in vivo, where they persist in the brain longer than sTDEVs released after non-ablative H-FIRE doses. Notably, when introduced into a healthy Fischer rat model, disruptive sTDEVs are associated with increased recruitment of Iba1+ immune cells, suggesting a potential role in modulating post-ablation immune responses. However, despite their altered protein composition, these vesicles do not directly increase BBB permeability in vivo. This study is the first to demonstrate that electroporation-based tumor ablation significantly alters the composition and functionality of tumor-derived extracellular vesicles, potentially influencing the tumor microenvironment post-ablation. These findings have important implications for developing multimodal treatment strategies that combine H-FIRE with systemic therapies to enhance efficacy while managing the peritumoral microenvironment.

Indexed as

ElectroporationExtracellular VesiclesProteomeProteomicsTropismAnimalsBlood-Brain BarrierBrain NeoplasmsCell Line, TumorEndothelial CellsGliomaHumansMaleRatsRats, Inbred F344Proteomeblood–brain barrierbrain tumorcancerelectroporationexosomes 10extracellular vesiclesgliomaimmunomodulationtumor ablationtumor microenvironment

Identifiers

PMID41294835
PMCPMC12651280

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.