The DOI matches its Crossref record; 24 of the 25 references it cites were found in a registry or an index; 5 of the 18 sources its claims cite were checked for support.
Disruption of Cancer Cell Replication by Alternating Electric Fields
Open accessAbstract
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.
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58 Own result · 17 Own interpretation · 7 No basis given · 4 No full text of the sources · 3 Sources not found · 3 Own method · 2 Partly supported · 1 Supported · 1 Supported so far · accuracy not yet measured
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“This effect resembles the whole-cell rotation previously described during exposure to intermediate-frequency alternating electric fields (7,8).”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > The Effects of TTFields on Cellular and Molecular Processes in Proliferating Cells.
What the sources say
- Supportedcites [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 Abstract reports that suspended cells rotated in an alternating electric field, and the Results give resonance frequencies of 20–180 kHz for several cell types. The comparison with nuclear rotation is the citing authors’ own framing; this source supports the cited description of whole-cell rotation. (LLM, conf=0.92)
- Not checked — no full text of the sourcecites [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
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“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).”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > DISCUSSION
What the sources say
- Supportedcites [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
The citation supports the comparison to cultured human corneal epithelial cells, not the citing paper’s finding about TTFields. In Results and Discussion, the source reports that cells exposed to a constant electric field aligned their division axes parallel to the field vector, while their cleavage planes were perpendicular to it. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“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).”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [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
- Not checked — no full text of the sourcecites [19] Rowinsky EK, Donehower RC Paclitaxel (Taxol). N Engl J Med, 332: 1004-14, 1995. source
- Not checked — no full text of the sourcecites [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
- Partly supportedcites [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. sourceExperimental — accuracy not yet measured
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)
- Partly supportedcites [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. sourceExperimental — accuracy not yet measured
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)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“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.”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“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.”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: Dividing cells contain highly polar, spatially oriented microtubules and develop a directional, hourglass-shaped morphology during cytokinesis.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These fields act in two modes: arrest of cell proliferation and destruction of cells while undergoing division.”
- Also stated in: § INTRODUCTION · boosted
“We demonstrate that applying these fields to cancerous cells leads to proliferation arrest and cell destruction.”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > Abstract
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Also stated in: § INTRODUCTION · boosted
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“These fields act in two modes: arrest of cell proliferation and destruction of cells while undergoing division.”
- Also stated in: § INTRODUCTION · boosted
“We demonstrate that applying these fields to cancerous cells leads to proliferation arrest and cell destruction.”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > Abstract
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Also stated in: § INTRODUCTION · boosted
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When applied to syngeneic mice tumor models, these tumor treating fields (TTFields) cause a significant reduction in tumor growth rate without any significant side effects.”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > INTRODUCTION
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“In all cell lines tested, 24-h exposure to TTFields at 100 kHz (at an intensity of 1.0 -1.4 V/cm) caused significant inhibition of cell proliferation (TER range, 0.14 -0.96; P Ͻ 0.05; Fig. 1C).”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > Effect of TTFields on Cells in Culture.
plaindirect- Asserted: passes — The authors put it forward as true.
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- Probably not a substantial claim. 4
- It may state two separate claims as one. 23
- The quote only partly states this claim. 1
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“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).”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > INTRODUCTION
What the sources say
- Not checked — no full text of the sourcecites [6] Takashima S, Schwan HP Alignment of microscopic particles in electric fields and its biological implications. Biophys J, 47: 513-8, 1985. source
- Partly supportedcites [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. sourceExperimental — accuracy not yet measured
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)
- Not checked — no full text of the sourcecites [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
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This effect, shown to be nonthermal, selectively affects dividing cells while quiescent cells are left intact.”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Both effects are demonstrated when such fields are applied for 24 h to cells undergoing mitosis that is oriented roughly along the field direction.”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > Abstract
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“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.”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > Effect of TTFields on Cells in Culture.
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“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.”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > The Effects of TTFields on Cellular and Molecular Processes in Proliferating Cells.
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“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).”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > Effect of TTFields on Tumors in Vivo.
plaindirectn = 14- Asserted: passes — The authors put it forward as true.
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In the paper
“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).”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > Effect of TTFields on Cells in Culture.
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“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.”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: The finite element simulations accurately represent the electric field distribution and forces inside real dividing cells.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > DISCUSSION
plaindirectn = 7 ·- Asserted: passes — The authors put it forward as true.
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In the paper
“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).”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > The Effects of TTFields on Cellular and Molecular Processes in Proliferating Cells.
plainn = 53- Asserted: passes — The authors put it forward as true.
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In the paper
“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.”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > The Effects of TTFields on Cellular and Molecular Processes in Proliferating Cells.
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“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.”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > DISCUSSION
plaindirectSingle case- Asserted: passes — The authors put it forward as true.
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In the paper
“Complete proliferation arrest (TER ϭ 1) is seen at 1.35 and 2.25 V/cm in melanoma and glioma cells, respectively.”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > The Effects of TTFields on Cellular and Molecular Processes in Proliferating Cells.
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“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.”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > DISCUSSION
plaindirectSingle case- Asserted: passes — The authors put it forward as true.
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In the paper
“Destructive effects were observed only in mitotic cells, whereas quiescent cells remained morphologically and functionally intact.”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > The Effects of TTFields on Cellular and Molecular Processes in Proliferating Cells.
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A window effect is seen with maximal inhibition by TTFields at 120 kHz in melanoma cells and at ϳ200 kHz in glioma cells.”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > The Effects of TTFields on Cellular and Molecular Processes in Proliferating Cells.
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In the treated cells, mitosis seemed to begin normally but was prolonged for variable periods of time before completing cleavage into two daughter cells.”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > The Effects of TTFields on Cellular and Molecular Processes in Proliferating Cells.
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“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.”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > Effect of TTFields on Cells in Culture.
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We have demonstrated that two main processes occur at the cellular level during exposure to TTFields: arrest of proliferation and cell destruction.”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > DISCUSSION
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The voltage drop on this resistor was linearly correlated to the field intensity (r 2 ϭ 0.96).”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > Electric Field Measurement.
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Such fields of low to moderate intensities are commonly considered to have no biological effect (4).”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > INTRODUCTION
What the sources say
- Not matchedcites [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.
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
- Not matched
In the paper
“At very low frequencies (under 1 kHz), alternating electric fields stimulate excitable tissues through membrane depolarization (1).”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > INTRODUCTION
What the sources say
- Not matchedcites [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.
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“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).”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > INTRODUCTION
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“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.”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > Electric Field Measurement.
plain- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > DISCUSSION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The finite element simulations accurately represent the electric field distribution and forces inside real dividing cells.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > DISCUSSION
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The absence of local histopathological damage and observed acute effects in mice indicates no general side effects of TTFields.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > DISCUSSION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The finite element simulations accurately represent the electric field distribution and forces inside real dividing cells.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > DISCUSSION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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.”
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“TTFields are low intensity, intermediate frequency alternating electric fields that were shown to disrupt cancer cell replication in vitro and to slow tumor progression in animal cancer models and patients with recurrent and newly diagnosed glioblastoma [18–20].”
From Alternating electric fields (TTFields) inhibit metastatic spread of solid tumors to the lungs (2009) · cites this paper as [19]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Treatment efficacy was found to be positively correlated with TTFields intensities, as previously described (data not shown).6,7”
In the citing paper
“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]
In the citing paper
“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].”
From Tumor Treating Fields (TTFields) Hinder Cancer Cell Motility through Regulation of Microtubule and Actin Dynamics (2020) · cites this paper as [1]
In the citing paper
“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.”
From Tumor Treating Fields (TTFields) Hinder Cancer Cell Motility through Regulation of Microtubule and Actin Dynamics (2020) · cites this paper as [1]
In the citing paper
“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”
From Tumor treating fields: A novel treatment modality and its use in brain tumors (2016) · cites this paper as [7]
In the citing paper
“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.”
From Tumor treating fields: A novel treatment modality and its use in brain tumors (2016) · cites this paper as [7]
In the citing paper
“The optimal frequency to maximize the antitumor effect is inversely correlated with cell size and when the incident angle of the electrical field is perpendicular to the mitotic plate.7”
From Tumor treating fields: A novel treatment modality and its use in brain tumors (2016) · cites this paper as [7]
In the citing paper
“In telophase, during cytokinesis the hourglass shape taken by the daughter cells that are about to separate induces a nonuniform electric field that is strongly enhanced at the level of the furrow region (→ fig. 1). This results in dielectrophoretic forces that may attract charged molecules from the cytosol and compromise normal cytokinesis.7”
From Tumor treating fields: A novel treatment modality and its use in brain tumors (2016) · cites this paper as [7]
In the citing paper
“the inhibitory effect increases with an increasing electric field intensity, resulting in a complete proliferation arrest of rat glioma cells after 24 h exposure to a field intensity of 2.25 V/cm.”
From An Overview of Sub-Cellular Mechanisms Involved in the Action of TTFields (2016) · cites this paper as [2]
In the citing paper
“A significant prolongation of mitosis was predicted, where treated cells remain stationary at metaphase for several hours, which was accompanied by abnormal mitotic figures as well as membrane rupture and blebbing leading to apoptosis [2,3].”
From An Overview of Sub-Cellular Mechanisms Involved in the Action of TTFields (2016) · cites this paper as [2]
In the citing paper
“Kirson et al. [2] reported the discovery that low-intensity (1–3 V/cm), intermediate frequency (100–300 kHz) electric fields have a profoundly inhibitory effect on the growth rate of various mammalian tumor cell lines [2,3,4].”
From An Overview of Sub-Cellular Mechanisms Involved in the Action of TTFields (2016) · cites this paper as [2]
In the citing paper
“the optimal frequency for the inhibitory effect of TTFields is inversely related to cell size [2,44]”
From An Overview of Sub-Cellular Mechanisms Involved in the Action of TTFields (2016) · cites this paper as [2]
In the citing paper
“These organelles can move at velocities up to 30 μm/s and, as a result, they could pile up at the cleavage furrow within a few minutes, interfering with cytokinesis, which may lead to cell destruction.”
From An Overview of Sub-Cellular Mechanisms Involved in the Action of TTFields (2016) · cites this paper as [2]
In the citing paper
“As a consequence, the TTField-generated forces acting on these organelles may reach values up to 60 pN resulting in their movement toward the cleavage furrow.”
From An Overview of Sub-Cellular Mechanisms Involved in the Action of TTFields (2016) · cites this paper as [2]
In the citing paper
“It was determined that cytoplasmic organelles are electrically polarized by the field within dividing cells.”
From An Overview of Sub-Cellular Mechanisms Involved in the Action of TTFields (2016) · cites this paper as [2]
In the citing paper
“Another potential member of the cytoskeleton that has been found affected by TTFields [2] is the protein called septin”
From An Overview of Sub-Cellular Mechanisms Involved in the Action of TTFields (2016) · cites this paper as [2]
In the citing paper
“we have recently demonstrated (9) that 100 KHz to 1 MHz ac fields have significant specific effects on dividing cells.”
From Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors (2007) · cites this paper as [9]
In the citing paper
“We have recently shown that low intensity, intermediate frequency, electric fields inhibit by an anti-microtubule mechanism of action, cancerous cell growth in vitro.”
From Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors (2007) · cites this paper as [9]
In the citing paper
“The basis of these effects during cytokinesis was shown to be the unidirectional forces induced by the inhomogeneous fields at the bridge separating the daughter cells (Fig. 1B) that interfere with spindle tubulin orientation and induce dielectrophoresis.”
From Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors (2007) · cites this paper as [9]
In the citing paper
“Using implanted electrodes, these fields were also shown to inhibit the growth of dermal tumors in mice.”
From Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors (2007) · cites this paper as [9]
In the citing paper
“This result is consistent with the previously reported effects on malignant melanoma cells (9).”
From Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors (2007) · cites this paper as [9]
In the citing paper
“An exception, are the TTFields described in ref. 9.”
From Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors (2007) · cites this paper as [9]
In the citing paper
“it shows the same frequency dependency as the dependence of cultured B16F1 cells reported in ref. 9, which supports the conclusion that this is the optimum frequency.”
From Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors (2007) · cites this paper as [9]
In the citing paper
“The tumor inhibitory effect of TTFields has been attributed previously to two separate mechanisms (9): interference with the formation of the mitotic spindle microtubules and physical destruction of cells during cleavage, both of which are strongly dependant on the orientation of mitosis axis versus the field vectors.”
From Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors (2007) · cites this paper as [9]
In the citing paper
“Tumor-treating fields (TTFields) are lowintensity, intermediate-frequency alternating electric fields that disrupt proper spindle microtubule arrangement, thereby leading to mitotic arrest and ultimately to cell death.”
In the citing paper
“TTFields have demonstrated effectiveness in the treatment of solid tumors in vitro and in vivo.[6][7][8][9][10]”
In the citing paper
“TTFields forces act on the dipole moment of tubulin chains, leading to misalignment of mitotic spindle filaments 6 and paclitaxel stabilizes the link between individual tubulin dimers, subsequently increasing the length and average dipole moment of the tubulin filaments.This, in turn, could increase the TTFields-induced forces and sensitize cells to TTFields.”
In the citing paper
“This effect is possibly explained by the different stages of mitosis at which the two treatment modalities putatively operate: Pemetrexed inhibits three enzymes responsible for purine and pyrimidine synthesis, thereby acting on the G1 and S phases of the cell cycle, 16 and TTFields therapy predominantly acts on cells in the M phase.6,7,9”
In the citing paper
“TTFields are low intensity, intermediate frequency alternating electric fields that were shown to disrupt cancer cell replication in vitro and to slow tumor progression in animal cancer models and patients with recurrent and newly diagnosed glioblastoma [18–20].”
From Alternating electric fields (TTFields) inhibit metastatic spread of solid tumors to the lungs (2009) · cites this paper as [19]
In the citing paper
“Such a 0.5 V/cm field intensity measured in the rabbit’ lungs is below the threshold required for cancerous cell growth inhibition [19].”
From Alternating electric fields (TTFields) inhibit metastatic spread of solid tumors to the lungs (2009) · cites this paper as [19]
In the citing paper
“Specifically, under cell culture conditions, these forces affected cells during division in a way that resulted in the induction of violent plasma membrane contractions during mitosis and cell death [38, 43].”
From Tumor Treating Fields Perturb the Localization of Septins and Cause Aberrant Mitotic Exit (2015) · cites this paper as [38]
In the citing paper
“It has recently been demonstrated that alternating electric fields referred to here as Tumor Treating Fields (TTFields), are able to disrupt cells during mitosis within a narrow range of frequencies with peak activity between 100 and 200 kHz; such fields have little measureable effect on cell biology at frequencies of 500 kHz or above, [38].”
From Tumor Treating Fields Perturb the Localization of Septins and Cause Aberrant Mitotic Exit (2015) · cites this paper as [38]
In the citing paper
“Similar to other studies [38], we noted a small increase in mitotic cells at later time points in the TTFields-treated cultures relative to control cultures demonstrating an increase in time in mitosis.”
From Tumor Treating Fields Perturb the Localization of Septins and Cause Aberrant Mitotic Exit (2015) · cites this paper as [38]
In the citing paper
“Previous studies showed that cells exposed to TTFields exhibited violent plasma membrane contractions during mitosis, increased time in mitosis and decreased cellular accumulation in exposed cultures [38].”
From Tumor Treating Fields Perturb the Localization of Septins and Cause Aberrant Mitotic Exit (2015) · cites this paper as [38]
In the citing paper
“Previous studies showed that TTFields perturbed cells in mitosis resulting in plasma membrane contractions and the formation of dynamic blebs on the cell surface. [38, 43].”
From Tumor Treating Fields Perturb the Localization of Septins and Cause Aberrant Mitotic Exit (2015) · cites this paper as [38]
In the citing paper
“TTFields are able to affect cellular physiology through their effects on proteins that both possess high dipole moments and are also critical to specific cellular functions, in this case mitosis [38].”
From Tumor Treating Fields Perturb the Localization of Septins and Cause Aberrant Mitotic Exit (2015) · cites this paper as [38]
In the citing paper
“These specially tuned fields have no effect on quiescent cells while having an anti-mitotic effect on dividing cells.”
From Chemotherapeutic treatment efficacy and sensitivity are increased by adjuvant alternating electric fields (TTFields) (2009) · cites this paper as [2]
In the citing paper
“A new physical cancer treatment modality termed Tumor Treating Fields, or TTFields, has recently been demonstrated to be highly effective when applied to cell cultures, animal cancer models, as well as to patients suffering from locally advanced and or metastatic solid tumors [1-3].”
From Chemotherapeutic treatment efficacy and sensitivity are increased by adjuvant alternating electric fields (TTFields) (2009) · cites this paper as [2]
In the citing paper
“In the specific case of Paclitaxel, one of the most commonly used treatments for late-stage human breast cancer [20], the combined effect may be attributed to their similar site of action – the spindle microtubules [1,2,21].”
From Chemotherapeutic treatment efficacy and sensitivity are increased by adjuvant alternating electric fields (TTFields) (2009) · cites this paper as [2]
In the citing paper
“One of the mechanisms of action of TTFields is the misalignment of mitotic spindle filaments as a result of TTFields forces on tubulin chains [2].”
From Chemotherapeutic treatment efficacy and sensitivity are increased by adjuvant alternating electric fields (TTFields) (2009) · cites this paper as [2]
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.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > DISCUSSION
“Contrary to normal mitosis, the duration of which is less than 1 h”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > The Effects of TTFields on Cellular and Molecular Processes in Proliferating Cells.
“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).”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > MATERIALS AND METHODS
“These included human melanoma (Patricia), glioma (U-118, U-87), Lung (H-1299), prostate (PC3), and breast (MDA231) cancerous cell lines as well as mouse melanoma (B16F1), rat glioma (F-98, C-6, and RG2), and mouse adenocarcinoma (CT-26) cell lines”
§ Disruption of Cancer Cell Replication by Alternating Electric Fields > DISCUSSION
“In all four animal cell lines (Ⅺ) and seven human cell lines (f) tested”
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Metadata
- 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)
- ORCID
- Palti, Yoram
- Venue
- Cancer research
- Published
- 2004-05-01
- Volume
- 64
- Issue
- 9
- Pages
- 3288-3295
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2098950184
- Semantic Scholar
- 57d3f1baa7124bd17ab9dd3344010122c2f2d644
- 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
- bronze
- doi.org
- 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 › Agricultural and Biological Sciences › Agronomy and Crop Science › 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.
A language model drew the claims from the paper on 2026-10-11, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-11 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
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