Evidence map›Paper›PMID 39998766›Full record

ArticleAnnals of biomedical engineering2025

Transient Lymphatic Remodeling Follows Sub-Ablative High-Frequency Irreversible Electroporation Therapy in a 4T1 Murine Model.

Savieay Esparza, Edward Jacobs, Jennifer H Hammel, Sharon K Michelhaugh, Nastaran Alinezhadbalalami, Margaret Nagai-Singer, Khan Mohammad Imran, Rafael V Davalos, Irving C Allen, Scott S Verbridge and 1 more

Abstract read
In one paragraph

Article in Annals of biomedical engineering, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Article
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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.

Savieay EsparzaFralin Biomedical Research Institute at Virginia Tech-Carilion, Room 1210, 4 Riverside Circle, Roanoke, VA, 24016, USA.
Edward JacobsDepartment of Biomedical Engineering & Mechanics, Virginia Tech-Wake Forest School of Biomedical Engineering & Sciences, Blacksburg, VA, USA.
Jennifer H HammelFralin Biomedical Research Institute at Virginia Tech-Carilion, Room 1210, 4 Riverside Circle, Roanoke, VA, 24016, USA.
Sharon K MichelhaughFralin Biomedical Research Institute at Virginia Tech-Carilion, Room 1210, 4 Riverside Circle, Roanoke, VA, 24016, USA.
Nastaran AlinezhadbalalamiDepartment of Biomedical Engineering & Mechanics, Virginia Tech-Wake Forest School of Biomedical Engineering & Sciences, Blacksburg, VA, USA.
Margaret Nagai-SingerDepartment of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA, USA.
Khan Mohammad ImranDepartment of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA, USA.
Rafael V DavalosDepartment of Biomedical Engineering & Mechanics, Virginia Tech-Wake Forest School of Biomedical Engineering & Sciences, Blacksburg, VA, USA.
Irving C AllenDepartment of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA, USA.
Scott S VerbridgeDepartment of Biomedical Engineering & Mechanics, Virginia Tech-Wake Forest School of Biomedical Engineering & Sciences, Blacksburg, VA, USA.
Jennifer M MunsonFralin Biomedical Research Institute at Virginia Tech-Carilion, Room 1210, 4 Riverside Circle, Roanoke, VA, 24016, USA. Jm4kt@vt.edu.ORCID http://orcid.org/0000-0002-9477-1505

Funding

A spatially organized microphysiological model of a human lymph nodeU01EB029127 · NIBIB · UNIVERSITY OF VIRGINIA · PI POMPANO, REBECCA R · 2019 to 2023
$3.3M
Optimization of High Frequency Irreversible Electroporation (H-FIRE) for tumor ablation and immune system activation in pancreatic cancer applicationsR01CA274439 · NCI · VIRGINIA POLYTECHNIC INST AND ST UNIV · PI Irving C Allen · 2023 to 2026
$2.1M
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
Nanoparticle-mediated Histotripsy (NMH) for Noninvasive and Targeted Ablation of Metastatic Breast CancerR21EB027979 · NIBIB · VIRGINIA POLYTECHNIC INST AND ST UNIV · PI VLAISAVLJEVICH, ELI · 2020 to 2022
$603k
NCATS NIH HHS U01EB029127NCI NIH HHS R01 CA213423NCI NIH HHS R01CA213423NCI NIH HHS R01 CA274439NCI NIH HHS R01CA274439NIBIB NIH HHS R21 EB027979NIBIB NIH HHS R21EB027979NIBIB NIH HHS U01 EB029127
6 · The paper itself

Abstract

High-frequency irreversible electroporation (H-FIRE) is a minimally invasive local ablation therapy known to activate the adaptive immune system and reprogram the tumor microenvironment. Its predecessor, irreversible electroporation (IRE), transiently increases microvascular density and immune cell infiltration within the surviving non-ablated and non-necrotic tumor region, also known as the viable tumor region. However, the impact of pulse electric field therapies on lymphatic vessels, crucial for T-cell fate and maturation, remains unclear. This study investigates how sub-ablative H-FIRE (SA-HFIRE) affects lymphatic and blood microvascular remodeling in the 4T1 mammary mouse model. We conducted a temporal and spatial analysis to evaluate vascular changes in the viable tumor, peritumoral fat pad, and tumor-draining lymph node post-treatment. Histological examination showed a transient increase in blood vessel density on Day 1 post-treatment, followed by a spike in lymphatic vessel density in the viable tumor region on Day 3 post-treatment, increased lymphatic vessel density in the peripheral fat pad, and minimal remodeling of the tumor-draining lymph node within 3 days following treatment. Gene expression analysis indicated elevated levels of CCL21 and CXCL2 on Day 1 post-treatment, while VEGFA and VEGFC did not appear to contribute to vascular remodeling. Likewise, CCL21 protein content in tumor-draining axillary lymph nodes correlated with gene expression data from the viable tumor region. These findings suggest a dynamic shift in lymphatic and blood microvascular structures post-SA-HFIRE, potentially enhancing the adaptive immune response through CCL21-mediated lymphatic homing and subsequent lymph node microvascular remodeling. Future work will assess the immune and transport function of the microvasculature to inform experiments aimed at the application of adjuvant therapies during scenarios of tumor partial ablation.

Indexed as

ElectroporationLymphatic VesselsMammary Neoplasms, ExperimentalAnimalsCell Line, TumorFemaleIrreversible Electroporation TherapyLymph NodesMiceMice, Inbred BALB C4T1Breast cancerCCL21High-frequency irreversible electroporationLymphangiogenesisMicrovasculatureSub ablationTumor-draining lymph nodeVEGFC

Identifiers

PMID39998766
PMCPMC12006248

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Registered trials

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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.