Evidence map›Paper›PMID 25853661›Full record

ArticlePloS one2015

Dose-dependent ATP depletion and cancer cell death following calcium electroporation, relative effect of calcium concentration and electric field strength.

Emilie Louise Hansen, Esin Bengisu Sozer, Stefania Romeo, Stine Krog Frandsen, P Thomas Vernier, Julie Gehl

Erratum issued Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT03051269 (Calcium Electroporation for Head and Neck Cancer), which is not on this map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
10.1field-weighted citation impact, top 2% of its field
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.

NCT03051269 phase1unknown statusnot on this mapstarted 2016, after this paper: background citation

Calcium Electroporation for Head and Neck Cancer

TypeinterventionalSponsorRigshospitalet, DenmarkRan2016 to 2019Enrolled6ConditionsHead Neck CancerArmsCalcium chloride, Electroporation
3 · Its place in the literature

Who cites it

54 citing papers in PubMed, 94 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 3 countries.

Emilie Louise HansenCenter for Experimental Drug and Gene Electrotransfer, Department of Oncology, Copenhagen University Hospital Herlev, Copenhagen, Denmark.
Esin Bengisu SozerFrank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, Virginia, United States of America.
Stefania RomeoInstitute for Electromagnetic Sensing of the Environment (IREA), Italian National Research Council, Naples, Italy.
Stine Krog FrandsenCenter for Experimental Drug and Gene Electrotransfer, Department of Oncology, Copenhagen University Hospital Herlev, Copenhagen, Denmark.
P Thomas VernierFrank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, Virginia, United States of America.
Julie GehlCenter for Experimental Drug and Gene Electrotransfer, Department of Oncology, Copenhagen University Hospital Herlev, Copenhagen, Denmark.
Copenhagen University Hospital · DKOld Dominion University · USIstituto per il Rilevamento Elettromagnetico dell'Ambiente · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundElectroporation, a method for increasing the permeability of membranes to ions and small molecules, is used in the clinic with chemotherapeutic drugs for cancer treatment (electrochemotherapy). Electroporation with calcium causes ATP (adenosine triphosphate) depletion and cancer cell death and could be a novel cancer treatment. This study aims at understanding the relationship between applied electric field, calcium concentration, ATP depletion and efficacy.

methodsIn three human cell lines--H69 (small-cell lung cancer), SW780 (bladder cancer), and U937 (leukaemia), viability was determined after treatment with 1, 3, or 5 mM calcium and eight 99 μs pulses with 0.8, 1.0, 1.2, 1.4 or 1.6 kV/cm. Fitting analysis was applied to quantify the cell-killing efficacy in presence of calcium. Post-treatment intracellular ATP was measured in H69 and SW780 cells. Post-treatment intracellular ATP was observed with fluorescence confocal microscopy of quinacrine-labelled U937 cells.

resultsBoth H69 and SW780 cells showed dose-dependent (calcium concentration and electric field) decrease in intracellular ATP (p<0.05) and reduced viability. The 50% effective cell kill was found at 3.71 kV/cm (H69) and 3.28 kV/cm (SW780), reduced to 1.40 and 1.15 kV/cm (respectively) with 1 mM calcium (lower EC50 for higher calcium concentrations). Quinacrine fluorescence intensity of calcium-electroporated U937 cells was one third lower than in controls (p<0.0001).

conclusionsCalcium electroporation dose-dependently reduced cell survival and intracellular ATP. Increasing extracellular calcium allows the use of a lower electric field. GENERAL SIGNIFICANCE: This study supports the use of calcium electroporation for treatment of cancer and possibly lowering the applied electric field in future trials.

Indexed as

ElectroporationAdenosine TriphosphateAnimalsApoptosisCalciumCell DeathCell Line, TumorCell SurvivalHumansMiceNeoplasmsAdenosine TriphosphateCalcium

Identifiers

PMID25853661
PMCPMC4390219
OpenAlexW1998742674

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Registered trials

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.