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INVESTIGATING THE MECHANISMS OF ACTION AND SCREENING UTILITY OF AMPLITUDE-MODULATED RADIOFREQUENCY ELECTROMAGNETIC FIELDS FOR HEPATOCELLULAR CARCINOMA

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title
INVESTIGATING THE MECHANISMS OF ACTION AND SCREENING UTILITY OF AMPLITUDE-MODULATED RADIOFREQUENCY ELECTROMAGNETIC FIELDS FOR HEPATOCELLULAR CARCINOMA
author
McGrath, Callum
abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide, largely due to limited systemic treatment options and the lack of broad, cost-effective screening modalities. Amplitude-modulated radiofrequency electromagnetic fields (AM RF EMF) are an FDA-approved, athermal, noninvasive cancer treatment that suppresses the proliferation of primary and metastatic HCC lesions. Additionally, AM RF EMF treatment induces hemodynamic responses selectively in cancer patients. This dissertation investigates both the mechanism of action and diagnostic potential of AM RF EMF to address these clinical challenges. AM RF EMF inhibits cancer proliferation through activation of the IP3/DAG signaling pathway resulting from calcium influx via the Cav3.2 calcium channel. Given the tumor- and tissue-specific frequency dependence of AM RF EMF, we hypothesized AM RF EMF-induced calcium influx was mediated by a resonance mechanism. To evaluate this, we exposed HCC cells to AM RF EMF shifted from base treatment frequencies ranging from +0.1 to +0.0001 Hz, with the expectation that small shifts (+0.0001 Hz and +0.001 Hz) would not change treatment efficacy while larger shifts (+0.1 Hz) would abrogate treatment efficacy. Each frequency shift significantly reduced treatment efficacy, indicating that the antiproliferative effect of AM RF EMF is not driven by resonance, but remains highly sensitive to even small changes in frequency.
subject
AM RF EMF
CNN
HCC
Machine Learning
contributor
Pasche, Boris (advisor)
Davalos, Rafael (committee member)
Watabe, Kounosuke (committee member)
Weis, Jared (committee member)
Whitlow, Christopher (committee member)
Zhang, Wei (committee member)
date
2025-06-24T08:36:36Z (accessioned)
2025 (issued)
degree
Biomedical Engineering (discipline)
embargo
2026-06-23 (terms)
2026-06-23 (liftdate)
identifier
http://hdl.handle.net/10339/111037 (uri)
language
en (iso)
publisher
Wake Forest University
type
Dissertation

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