Tumour-specific amplitude-modulated radiofrequency electromagnetic fields induce differentiation of hepatocellular carcinoma via targeting Cav3.2 T-type voltage-gated calcium channels and Ca2+ influx
← Research streamIntrabuccal administration of amplitude-modulated 27.12 MHz RF EMF produced systemic, athermal exposure levels reported as lower than those generated by cell phones held close to the body. In mice with human HCC xenografts, exposure was associated with tumour…
Study snapshot
Abstract
Amplitude-modulated RF EMF blocks growth of hepatocellular carcinoma via voltage-gated calcium channels and calcium ion influx Jimenez H, Wang M, Zimmerman JW, et al. , Blackman CF, Pasche BC. Tumour-specific amplitude-modulated radiofrequency electromagnetic fields induce differentiation of hepatocellular carcinoma via targeting Cav3.2 T- type voltage-gated calcium channels and Ca2+ influx. EBioMedicine. 2019 May 24. pii: S2352-3964(19)30342-1. doi: 10.1016/j.ebiom.2019.05.034. Abstract BACKGROUND: Administration of amplitude modulated 27·12 MHz radiofrequency electromagnetic fields (AM RF EMF) by means of a spoon-shaped applicator placed on the patient's tongue is a newly approved treatment for advanced hepatocellular carcinoma (HCC). The mechanism of action of tumour-specific AM RF EMF is largely unknown. METHODS: Whole body and organ-specific human dosimetry analyses were performed. Mice carrying human HCC xenografts were exposed to AM RF EMF using a small animal AM RF EMF exposure system replicating human dosimetry and exposure time. We performed histological analysis of tumours following exposure to AM RF EMF. Using an agnostic genomic approach, we characterized the mechanism of action of AM RF EMF. FINDINGS: Intrabuccal administration results in systemic delivery of athermal AM RF EMF from head to toe at levels lower than those generated by cell phones held close to the body. Tumour shrinkage results from differentiation of HCC cells into quiescent cells with spindle morphology. AM RF EMF targeted antiproliferative effects and cancer stem cell inhibiting effects are mediated by Ca2+ influx through Cav3·2 T-type voltage-gated calcium channels (CACNA1H) resulting in increased intracellular calcium concentration within HCC cells only. INTERPRETATION: Intrabuccally-administered AM RF EMF is a systemic therapy that selectively block the growth of HCC cells. AM RF EMF pronounced inhibitory effects on cancer stem cells may explain the exceptionally long responses observed in several patients with advanced HCC. FUND: Research reported in this publication was supported by the National Cancer Institute's Cancer Centre Support Grant award number P30CA012197 issued to the Wake Forest Baptist Comprehensive Cancer Centre (BP) and by funds from the Charles L. Spurr Professorship Fund (BP). DWG is supported by R01 AA016852 and P50 AA026117. Open access paper: ebiomedicine.com
AI evidence extraction
Structured fields below were generated from the paper’s abstract and metadata to make the evidence easier to inspect. Automated extraction may be incomplete or incorrect; verify important details against the original paper.
Main findings
Intrabuccal administration of amplitude-modulated 27.12 MHz RF EMF produced systemic, athermal exposure levels reported as lower than those generated by cell phones held close to the body. In mice with human HCC xenografts, exposure was associated with tumour shrinkage and histological differentiation of HCC cells into quiescent spindle-morphology cells. The reported tumour-specific antiproliferative and cancer stem cell-inhibiting effects were mediated by Ca2+ influx through Cav3.2 (CACNA1H) channels, increasing intracellular calcium in HCC cells only.
Outcomes measured
- Human whole-body and organ-specific dosimetry (systemic delivery; athermal levels; comparison to cell phone exposure levels)
- Tumour shrinkage in HCC xenograft model
- Histological differentiation of HCC cells into quiescent spindle-morphology cells
- Mechanistic genomic characterization
- Ca2+ influx and intracellular calcium increase in HCC cells via Cav3.2 (CACNA1H) T-type voltage-gated calcium channels
- Antiproliferative effects and inhibition of cancer stem cell-related effects
Limitations
- Sample size not reported in abstract
- Human clinical outcomes are referenced as context ("several patients") but no clinical trial design or results are provided in the abstract
- Exposure duration and quantitative dosimetry metrics (e.g., SAR) not provided in abstract
View raw extracted JSON
{
"study_type": "other",
"exposure": {
"band": "RF",
"source": "intrabuccal applicator (spoon-shaped) placed on patient's tongue",
"frequency_mhz": 27.12,
"sar_wkg": null,
"duration": null
},
"population": "Patients with advanced hepatocellular carcinoma (treatment context); mice carrying human HCC xenografts (experimental model)",
"sample_size": null,
"outcomes": [
"Human whole-body and organ-specific dosimetry (systemic delivery; athermal levels; comparison to cell phone exposure levels)",
"Tumour shrinkage in HCC xenograft model",
"Histological differentiation of HCC cells into quiescent spindle-morphology cells",
"Mechanistic genomic characterization",
"Ca2+ influx and intracellular calcium increase in HCC cells via Cav3.2 (CACNA1H) T-type voltage-gated calcium channels",
"Antiproliferative effects and inhibition of cancer stem cell-related effects"
],
"main_findings": "Intrabuccal administration of amplitude-modulated 27.12 MHz RF EMF produced systemic, athermal exposure levels reported as lower than those generated by cell phones held close to the body. In mice with human HCC xenografts, exposure was associated with tumour shrinkage and histological differentiation of HCC cells into quiescent spindle-morphology cells. The reported tumour-specific antiproliferative and cancer stem cell-inhibiting effects were mediated by Ca2+ influx through Cav3.2 (CACNA1H) channels, increasing intracellular calcium in HCC cells only.",
"effect_direction": "benefit",
"limitations": [
"Sample size not reported in abstract",
"Human clinical outcomes are referenced as context (\"several patients\") but no clinical trial design or results are provided in the abstract",
"Exposure duration and quantitative dosimetry metrics (e.g., SAR) not provided in abstract"
],
"evidence_strength": "insufficient",
"confidence": 0.74,
"peer_reviewed_likely": "yes",
"keywords": [
"amplitude-modulated RF EMF",
"27.12 MHz",
"intrabuccal applicator",
"hepatocellular carcinoma",
"xenograft",
"dosimetry",
"athermal exposure",
"Cav3.2",
"CACNA1H",
"T-type calcium channels",
"Ca2+ influx",
"cancer stem cells",
"differentiation"
],
"suggested_hubs": []
}AI-extracted fields are generated from the abstract and metadata and may be incomplete or incorrect. This material is for informational purposes and is not medical advice.
Identifiers and source
DOI: 10.1016/j.ebiom.2019.05.034
PubMed: Not supplied
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