Cited by 832Electromagnetic Fields and Biological EffectsMicrobial Inactivation MethodsMagnetic and Electromagnetic Effects

Disruption of cancer cell replication by alternating electric fields

Open access
Kirson, Eilon D., Gurvich, Zoya, Schneiderman, Rosa, Dekel, Erez, Itzhaki, Aviran, Wasserman, Yoram, Schatzberger, Rachel, Palti, Yoram·2004·Cancer research

Abstract

Low-intensity, intermediate-frequency (100-300 kHz), alternating electric fields, delivered by means of insulated electrodes, were found to have a profound inhibitory effect on the growth rate of a variety of human and rodent tumor cell lines (Patricia C, U-118, U-87, H-1299, MDA231, PC3, B16F1, F-98, C-6, RG2, and CT-26) and malignant tumors in animals. This effect, shown to be nonthermal, selectively affects dividing cells while quiescent cells are left intact. These fields act in two modes: arrest of cell proliferation and destruction of cells while undergoing division. Both effects are demonstrated when such fields are applied for 24 h to cells undergoing mitosis that is oriented roughly along the field direction. The first mode of action is manifested by interference with the proper formation of the mitotic spindle, whereas the second results in rapid disintegration of the dividing cells. Both effects, which are frequency dependent, are consistent with the computed directional forces exerted by these specific fields on charges and dipoles within the dividing cells. In vivo treatment of tumors in C57BL/6 and BALB/c mice (B16F1 and CT-26 syngeneic tumor models, respectively), resulted in significant slowing of tumor growth and extensive destruction of tumor cells within 3-6 days. These findings demonstrate the potential applicability of the described electric fields as a novel therapeutic modality for malignant tumors.

Integrity signals

Registry

Crossref · 10.1158/0008-5472.can-04-0083

Cites

24 of 24 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

5 of 18 cited sources checked · 2 supported · 0 flagged · accuracy not yet measured

  • Interpretationcitation

    The nuclear rotation effect resembles the whole-cell rotation previously described during exposure to intermediate-frequency alternating electric fields.

    “This effect resembles the whole-cell rotation previously described during exposure to intermediate-frequency alternating electric fields (7,8).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [7] Zimmermann U, Vienken J, Pilwat G Rotation of cells in an alternating electric field: the occurrence of a resonance frequency. Z Naturforsch C, 36: 173-7,  1981. source
    • cites [8] Holzapfel C, Vienken J, Zimmermann U Rotation of cells in an alternating electric field: theory and experimental proof. J Membr Biol, 67: 13-26,  1982. source
  • Findingcitation

    TTFields caused dividing cells to orient in the direction of the applied field.

    “Also, TTFields caused the dividing cells to orient in the direction of the applied field in a manner similar to that described in cultured human corneal epithelial cells exposed to constant electric fields (17).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [17] Zhao M, Forrester JV, McCaig CD A small, physiological electric field orients cell division. Proc Natl Acad Sci USA, 96: 4942-6,  1999. source
  • Interpretationcitation

    The abnormal mitotic configurations seen after TTFields exposure are similar to morphological abnormalities seen in cells treated with agents that interfere directly or indirectly with microtubule polymerization (e.g., Taxol).

    “TTFields are similar to the morphological abnormalities seen in cells treated with agents that interfere directly (18,19) or indirectly (20 -22) with microtubule polymerization (e.g., Taxol).”
    Quote in the paperNot a substantial claim2 of 5 sources checked
    • cites [18] Jordan MA, Thrower D, Wilson L Effects of vinblastine, podophyllotoxin and nocodazole on mitotic spindles: implications for the role of microtubule dynamics in mitosis. J Cell Sci, 102: 401-16,  1992. source
    • cites [19] Rowinsky EK, Donehower RC Paclitaxel (Taxol). N Engl J Med, 332: 1004-14,  1995. source
    • cites [20] Kline-Smith SL, Walczak CE The microtubule-destabilizing kinesin XKCM1 regulates microtubule dynamic instability in cells. Mol Biol Cell, 13: 2718-31,  2002. source
    • cites [21] Kapoor TM, Mayer TU, Coughlin ML, Mitchison TJ Probing spindle assembly mechanisms with monastrol, a small molecule inhibitor of the mitotic kinesin, Eg5. J Cell Biol, 150: 975-88,  2000. source

      The Results section (‘Monastrol Inhibits Centrosome Separation Not Duplication’; page unavailable) reports that monastrol produces abnormal monoastral spindles by inhibiting centrosome separation. The Discussion (‘Monastrol Is a Reversible and Specific Probe for Eg5-dependent Mitotic Processes’; page unavailable) says monastrol does not affect tubulin polymerization in vitro, so the paper supports the morphological example but not the characterization of monastrol as interfering with microtubule polymerization. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [22] Maiato H, Sampaio P, Lemos CL, et al MAST/Orbit has a role in microtubule-kinetochore attachment and is essential for chromosome alignment and maintenance of spindle bipolarity. J Cell Biol, 157: 749-60,  2002. source

      The Results sections on MAST RNAi report abnormal mitotic configurations, including monopolar spindles and misaligned chromosomes. The Discussion proposes that MAST/Orbit may affect microtubule plus-end stabilization, but treats that mechanism as uncertain. The paper does not compare these abnormalities with TTFields exposure; it supports the cited example of abnormal spindle morphology, not the comparison or a definite effect on polymerization. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
  • Findingreasoning

    Both effects of TTFields are frequency dependent.

    “Both effects, which are frequency dependent, are consistent with the computed directional forces exerted by these specific fields on charges and dipoles within the dividing cells.”
    Quote in the paperSubstantial claim
  • Findingreasoning

    The first mode of TTField action is manifested by interference with the proper formation of the mitotic spindle.

    “The first mode of action is manifested by interference with the proper formation of the mitotic spindle, whereas the second results in rapid disintegration of the dividing cells.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Dividing cells contain highly polar, spatially oriented microtubules and develop a directional, hourglass-shaped morphology during cytokinesis.
  • Classified as probably not a substantial claim. 4
  • May combine two claims. 23
  • The quote only partly states this claim. 1
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A number of nonthermal effects of minor biological consequence have been reported even at low field intensities, including microscopic particle alignment and cell rotation.

    “However, a number of nonthermal effects of minor biological consequence have been reported even at low field intensities.These include microscopic particle alignment (i.e., the pearl chain effect; Ref. 6) and cell rotation (7,8).”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [6] Takashima S, Schwan HP Alignment of microscopic particles in electric fields and its biological implications. Biophys J, 47: 513-8,  1985. source
    • cites [7] Zimmermann U, Vienken J, Pilwat G Rotation of cells in an alternating electric field: the occurrence of a resonance frequency. Z Naturforsch C, 36: 173-7,  1981. source

      The Results (page not provided) report cell rotation in an alternating electric field and conclude that thermal effects are not its primary cause. They specify a threshold of 300–500 V/cm, however, and do not characterize rotation as occurring at low field intensities or as having minor biological consequence. The pearl-chain effect is cited separately in the citing sentence, so it is not the basis of this verdict. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [8] Holzapfel C, Vienken J, Zimmermann U Rotation of cells in an alternating electric field: theory and experimental proof. J Membr Biol, 67: 13-26,  1982. source
  • May combine two claims.

    Findingown data

    TTFields selectively affect dividing cells while quiescent cells are left intact.

    “This effect, shown to be nonthermal, selectively affects dividing cells while quiescent cells are left intact.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    Both the arrest and destruction effects are demonstrated when TTFields are applied for 24 h to cells undergoing mitosis oriented roughly along the field direction.

    “Both effects are demonstrated when such fields are applied for 24 h to cells undergoing mitosis that is oriented roughly along the field direction.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    Under control conditions, most of the cell lines had doubling times of less than 24 h (range 17-24 h), except PC-3 for which the doubling time was 73 h.

    “Because under control conditions, most of the cell lines had doubling times of less than 24 h (range, 17-24 h; except for PC-3 for which the doubling time was 73 h), treatment duration was at least 24 h.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    TTField treatment produced abnormal mitotic forms including polypoid cells in prophase, ill-separated, multi-spindled and single-spindled cells in metaphase, asymmetric anaphases, and a large proportion of metaphase cells (>20%) with rosette-shaped chromosome assemblies.

    “These included polypoid cells in prophase, ill-separated, multi-spindled and single-spindled cells in metaphase, asymmetric anaphases, and a large proportion of cells in metaphase (Ͼ20%) with rosette shaped chromosome assemblies.”
    Quote in the paperSubstantial claim
  • The quote only partly states this claim.

    Findingown data

    In BALB/c mice with intradermal adenocarcinomas treated with the same field parameters, the average treated tumor size was 73% of control tumor size at the end of treatment (n = 14 mice).

    “The average effect of TTFields on adenocarcinoma carrying mice was less dramatic than that seen for malignant melanoma (average treated tumor size was 73% of control tumor size at the end of treatment; n ϭ 14 mice).”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    The inhibitory effect of TTFields lasted beyond the exposure time; in some experiments (e.g., malignant melanoma), culture growth was stunted for as long as 72 h after TTField exposure was terminated.

    “This effect lasted beyond the exposure time of the cells to TTFields.In fact in some experiments (e.g., malignant melanoma), culture growth was stunted for as long as 72 h after TTField exposure was terminated (Fig. 2A).”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    In simulations, the electric field within quiescent cells is homogenous, whereas the field inside mitotic cells during cytokinesis is not homogenous.

    “As seen in the simulations depicted in Fig. 7B, the electric field within quiescent cells is homogenous, whereas the field inside mitotic cells, during cytokinesis, is not homogenous.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The finite element simulations accurately represent the electric field distribution and forces inside real dividing cells.
  • May combine two claims.

    Findingown data

    In all four animal cell lines and seven human cell lines tested, TTFields (100 kHz, 1-1.4 V/cm) inhibited growth rate compared with temperature-matched controls, and all effects were statistically significant (P < 0.05; Student's t test).

    “In all four animal cell lines (Ⅺ) and seven human cell lines (f) tested, the ratio is greater than 0, indicating an inhibition in the growth rate of the treated cultures compared with temperature matched controls.All effects were statistically significant (P Ͻ 0.05; Student's t test).”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    In TTField-treated cultures, mitosis lasted on average 124 ± 91 min (mean ± SD, n=53; range 40-541 min), whereas under control conditions average mitosis duration was 62 ± 8 min (mean ± SD, n=12; range 47-78 min).

    “Due to this proliferation arrest, in treated cultures, mitosis lasted on average 124 Ϯ 91 min (mean Ϯ SD, n ϭ 53; range, 40 -541 min), whereas under control conditions, average mitosis duration was 62 Ϯ 8 min from cell rounding to cytokinesis (mean Ϯ SD, n ϭ 12; range, 47-78 min).”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    In TTField-treated cultures, nuclear rotation occurred in early mitosis after cell rounding, with a full rotation lasting on average 15 min.

    “The third phenomenon, seen only in TTField-treated cultures, was nuclear rotation.In early mitosis, after cell rounding, nuclei could be seen rotating within the cell.A full rotation lasted on average 15 min.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    A cell in mitosis was arrested by TTFields; contrary to normal mitosis, which lasts less than 1 h, the depicted cell was stationary at mid-cytokinesis for 3 h.

    “A, an example of a cell in mitosis arrested by TTFields.Contrary to normal mitosis, the duration of which is less than 1 h, the depicted cell is seen to be stationary at mid-cytokinesis for 3 h.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    Complete proliferation arrest (TER = 1) is seen at 1.35 V/cm in melanoma cells and 2.25 V/cm in glioma cells.

    “Complete proliferation arrest (TER ϭ 1) is seen at 1.35 and 2.25 V/cm in melanoma and glioma cells, respectively.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    After 4 days of TTFields treatment at 100 kHz, no tumor could be discerned on the treated side, whereas on the untreated side a large tumor had grown.

    “After 4 days of TTFields treatment (at 100 kHz), no tumor can be discerned on the treated side, whereas on the untreated side a large tumor has grown.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    Destructive effects of TTFields were observed only in mitotic cells, whereas quiescent cells remained morphologically and functionally intact.

    “Destructive effects were observed only in mitotic cells, whereas quiescent cells remained morphologically and functionally intact.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    A window effect is seen with maximal inhibition by TTFields at 120 kHz in melanoma cells and at approximately 200 kHz in glioma cells.

    “A window effect is seen with maximal inhibition by TTFields at 120 kHz in melanoma cells and at ϳ200 kHz in glioma cells.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    In treated cells, mitosis seemed to begin normally but was prolonged for variable periods before completing cleavage into two daughter cells.

    “In the treated cells, mitosis seemed to begin normally but was prolonged for variable periods of time before completing cleavage into two daughter cells.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    The inhibitory effect of TTFields on proliferation of B16F1 melanoma and F-98 glioma cells increased as intensity was raised from 1 to 2.5 V/cm until complete proliferation arrest was achieved at 1.4 V/cm in melanoma and 2.25 V/cm in glioma cells.

    “The inhibitory effect of TTFields on cell proliferation increased as intensity was raised (Fig. 2B) until complete proliferation arrest was achieved at intensities of 1.4 and 2.25 V/cm in melanoma and glioma cells, respectively.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    Two main processes occur at the cellular level during exposure to TTFields: arrest of proliferation and cell destruction.

    “We have demonstrated that two main processes occur at the cellular level during exposure to TTFields: arrest of proliferation and cell destruction.”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The voltage drop across a 100Ω resistor in series with a field-generating wire was linearly correlated to the field intensity (r2=0.96).

    “The voltage drop on this resistor was linearly correlated to the field intensity (r 2 ϭ 0.96).”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim.

    Premisecitation

    Intermediate-frequency electric fields of low to moderate intensities are commonly considered to have no biological effect.

    “Such fields of low to moderate intensities are commonly considered to have no biological effect (4).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [4] Elson E Biologic effects of radiofrequency and microwave fields: in vivo and in vitro experimental results Bronzino JD eds. . The biomedical engineering handbook, p. 1417-23, CRC Press, Inc. Boca Raton, FL  1995.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    At very low frequencies (under 1 kHz), alternating electric fields stimulate excitable tissues through membrane depolarization.

    “At very low frequencies (under 1 kHz), alternating electric fields stimulate excitable tissues through membrane depolarization (1).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] Polk C Therapeutic applications of low-frequency sinusoidal and pulsed electric and magnetic fields Bronzino JD eds. . The biomedical engineering handbook, p. 1404-16, CRC Press, Inc. Boca Raton, FL  1995.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisenone given

    Intermediate-frequency electric fields (tens of kilohertz to megahertz) alternate too fast for causing nerve-muscle stimulation and involve only minute dielectric losses (heating).

    “Intermediate-frequency electric fields (i.e., tens of kilohertz to megahertz) alternate too fast for causing nerve-muscle stimulation and involve only minute dielectric losses (heating).”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Study design and conductown data

    Electromagnetic radiation in the 100-300-kHz range within incubators containing treated culture dishes was 10^-12 Tesla and within animal cages containing TTField-treated mice was 10^-14 Tesla, i.e., negligible.

    “The electromagnetic radiation in the 100 -300-kHz range within the incubators containing treated culture dishes was found to be 10 Ϫ12 Tesla and within animal cages containing TTField-treated mice, 10 Ϫ14 Tesla, i.e., negligible.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Interpretationreasoning

    Cytoplasmic organelles are polarized by the field within dividing cells; once polarized, forces acting on such particles may reach values up to 60 pN, resulting in movement toward the furrow at velocities approaching 0.03 m/s.

    “With regard to other particles such as cytoplasmatic organelles, they are polarized by the field within dividing cells.Once polarized, the forces acting on such particles may reach values up to an order of 60 pN resulting in their movement toward the furrow at velocities that may approach 0.03 m/s.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The finite element simulations accurately represent the electric field distribution and forces inside real dividing cells.
  • May combine two claims.

    Interpretationown data

    TTFields inhibit both the proliferation of malignant cells in culture and the growth of tumors in mice while showing no general side effects or local histopathological damage.

    “In conclusion, we have demonstrated that TTFields inhibit both the proliferation of malignant cells in culture and the growth of tumors in mice while showing no general side effects or local histopathological damage.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The absence of local histopathological damage and observed acute effects in mice indicates no general side effects of TTFields.
  • May combine two claims.

    Interpretationown data

    The mechanism of action of TTFields is, at least in part, dependent on disruption of the microtubules of the mitotic spindle and the electric forces resulting from focusing of the field in the dividing cells.

    “The mechanism of action of the fields is, at least in part, dependent on disruption of the microtubules of the mitotic spindle and the electric forces resulting from focusing of the field in the dividing cells.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The finite element simulations accurately represent the electric field distribution and forces inside real dividing cells.
  • May combine two claims.

    Interpretationreasoning

    At such velocity, cytoplasmic organelles would pile up at the cleavage furrow within a few minutes, interfering with cytokinesis and possibly leading to cell destruction.

    “At such velocity, cytoplasmatic organelles would pile up at the cleavage furrow within a few minutes, interfering with cytokinesis and possibly leading to cell destruction.”
    Quote in the paperSubstantial claim
28 of 28
  • The authors state this as an assumption.

    At the relatively low frequencies used (100 kHz), the complex dielectric constant of the particle is greater than that of the cytoplasm, so the Clausius-Mossotti factor is always positive.

    “K() in this case is always positive at the relatively low frequencies used (i.e., 100 kHz), assuming that at these frequencies, ‫ء⑀‬ p Ͼ ‫ء⑀‬ m .”
  • The paper relies on this without support.

    Dividing cells contain highly polar, spatially oriented microtubules and develop a directional, hourglass-shaped morphology during cytokinesis.

    “One is that the latter contain highly polar, spatially oriented microtubules and that they develop a directional, hourglass-shaped cell morphology during the cytokinesis phase.”
  • The paper relies on this without support.

    The force exerted by an electric field on a dipole is maximal when the dipole is oriented in the direction of the field.

    “With regard to the latter, the force exerted by the field is maximal when the dipole is oriented in the direction of the field.”
  • The authors state this as an assumption.

    The simplified description of cell morphology used in the finite element calculations adequately represents the cells.

    “The calculations of the electric field within the cells are based on finite element mesh (11), using a simplified description of the cell morphology (see Fig. 7).”
  • The paper relies on this without support.

    The absence of local histopathological damage and observed acute effects in mice indicates no general side effects of TTFields.

    “In conclusion, we have demonstrated that TTFields inhibit both the proliferation of malignant cells in culture and the growth of tumors in mice while showing no general side effects or local histopathological damage.”
  • The paper relies on this without support.

    The finite element simulations accurately represent the electric field distribution and forces inside real dividing cells.

    “To explain how TTFields cause orientation-dependent damage to dividing cancerous cells and disrupt the proper formation of the mitotic spindle, we modeled the forces exerted by TTFields on intracellular charges and polar particles using finite element simulations (see”
  • The paper relies on this without support.

    The effects of TTFields on cultured cancer cell lines and mouse tumor models are predictive of effects in human cancer patients.

    “The highly specific effects of these fields on dividing cells, together with the relative ease of applying them, focusing them, and screening from them, make them an attractive candidate to serve as a novel treatment modality for cancer.”
7 of 7

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • TTFields-induced mitotic spindle perturbations lead to abnormal chromosomal segregation, mitotic cell death, and perhaps apoptosis from cells that are able to exit mitosis.

    “Such perturbations lead to abnormal chromosomal segregation, mitotic cell death, and perhaps apoptosis from cells that are able to exit mitosis [8,9,19].”

    From Permeabilizing Cell Membranes with Electric Fields (2021) · cites this paper as [9]

  • Induction of TTFields anti-mitotic effects requires electric field intensities above 1 V/cm RMS.

    “Noteworthy, the duration of the invasion experiments and the applied electric fields intensities were shorter and lower than the duration and the intensities (above 1 V/cm RMS) required for induction of TTFields anti-mitotic effects [1,2].”
  • Tumor Treating Fields (TTFields) are noninvasive alternating electric fields in the intermediate frequency range (100-300 kHz) used as an antimitotic cancer treatment.

    “Tumor Treating Fields (TTFields) are noninvasive, alternating electric fields within the intermediate frequency range (100–300 kHz) that are utilized as an antimitotic cancer treatment.”
  • In initial experiments, exposure of a variety of tumor cell lines to TTFields exerted a profound growth inhibitory effect by inducing cell cycle arrest and apoptosis, while no effect was induced on non-dividing cells.

    “In initial experiments, exposure of a variety of tumor cell lines to TTFields was shown to exert a profound growth inhibitory effect by inducing cell cycle arrest and apoptosis, while no effect was induced on non-dividing cells.7”
  • Tumor treating fields (TTFields) are low-intensity electric fields alternating at an intermediate frequency (200 kHz) that block cell division and interfere with organelle assembly.

    “Tumor treating fields (TTFields) are low-intensity electric fields alternating at an intermediate frequency (200kHz), which have been demonstrated to block cell division and interfere with organelle assembly.”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Claimed normal mitosis duration conflicts with control measurements

    Minor

    The figure caption says normal mitosis lasts less than one hour, whereas the reported control mean is 62 minutes and the range extends to 78 minutes.

  • Human and animal cell-line counts are reversed

    Minor

    The listed cell lines comprise six human and five animal lines, but the figure caption reports seven human and four animal lines.

2 of 2

Cites

Flagged first, then by citations

1 of the 25 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. Pohl AH . Dielectrophoresis, Cambridge University Press Cambridge, UK  1978.

Cited by

Sorted by citations

Authors
Kirson, E. D., Gurvich, Z., Schneiderman, R., Dekel, E., Itzhaki, A., Wasserman, Y., Schatzberger, R., & Palti, Y.
Affiliations
  • 1Department of Biomedical Engineering, NovoCure Ltd., Haifa, Israel;
  • Technion – Israel Institute of Technology (IL)
  • Weizmann Institute of Science (IL)
  • Elisha Hospital (IL)
Venue
Cancer research
Published
2004-05-01
Volume
64
Issue
9
Pages
3288-3295
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
OpenAlex
W2098950184
Cited by
827
References
25
Citations by year
2026: 45 · 2025: 57 · 2024: 66 · 2023: 88 · 2022: 87 · 2021: 52 · 2020: 63 · 2019: 46 · 2018: 56 · 2017: 44 · 2016: 50 · 2015: 34 · 2014: 33 · 2013: 24 · 2012: 23
FWCI
1.48
Type
journal article
Language
en
Open access
Locations
  • Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Electromagnetic Fields and Biological Effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Microbial Inactivation Methods
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Magnetic and Electromagnetic Effects
Keywords
AC electric field, tumor cell growth inhibition, non-thermal effects, mitotic spindle disruption, cell division arrest, frequency dependence, tumor growth in mice, B16F1 melanoma cells, CT26 cells, tumor cell quiescence
MeSH terms
Animals, Cell Division, Electric Stimulation Therapy, Humans, Neoplasms, Cell Line, Tumor, Mice, Rats

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-11.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-11.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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