Comments on ‘Search for tumor-specific frequencies of amplitude modulated 27 MHz electromagnetic fields in mice with hepatocarcinoma xenografted tumors’

Dear Editor, In the recent publication titled ‘Search for tumor-specific frequencies of amplitude-modulated 27MHz electromagnetic fields in mice with hepatocarcinoma xenografted tumors’, Veyret et al. investigated the physiological effects of tumorspecific electromagnetic field frequencies in mice carrying a human hepatocellular carcinoma (HCC) cell line xenograft. The purpose was to validate our previously reported findings, wherein human patients, with a clinical diagnosis of cancer, exhibited changes in pulse pressure upon exposure to radiofrequency electromagnetic fields, when amplitudemodulated with tumor-specific modulation frequencies (Jimenez et al. 2019). Administration of tumor-specific frequencies by means of a spoon-shaped antenna has led to tumor shrinkage and long-term responses in patients with breast cancer and hepatocellular carcinoma (Barbault et al. 2009; Costa et al. 2011; Jimenez et al. 2019; Sharma et al. 2019). The overall findings of Veyret et al. concluded that they were unable to detect tumor-related frequencies based off of their model system using either a systemic scan of frequencies or the published frequencies as identified by the Pasche group (Zimmerman et al. 2012). First, we would like to compliment Veyret et al. for designing and conducting state of the art experiments. However, upon review of the experimental methods we noticed that the investigators used ketamine/xylazine during recording of plethysmographic waveforms. This is likely to explain why no change in plethysmographic waveforms were observed. Indeed, we recently discovered that Cav 3.2 (gene name: CACNA1H), an isoform of the T-type voltage gated calcium channel, is the necessary and sufficient mediator of the anti-cancer effect of both hepatocellular carcinoma – and breast cancer-specific AM RF EMF (Jimenez et al. 2019; Sharma et al. 2019). This effect was identified by knockdown of Cav 3.2 and Cav 3.2 blockade with ethosuximide (panT-type calcium channel blocker), which fully abrogate the anti-cancer effect in both breast cancer and hepatocellular carcinoma (Jimenez et al. 2019; Sharma et al. 2019). Ketamine is a potent inhibitor of L-type voltage gated calcium channels, the same calcium channel type that blood pressure medications, such as nifedipine/amlodipine, affect in order to decrease blood pressure in patients (Hatakeyama et al. 2001; Striessnig et al. 2015). Moreover, while blood pressure medications are generally selective for the L-type channels, some analogs are capable of blocking T-type channels (Perez-Reyes 2003; Ge and Ren 2009). For example, amlodipine is 12 fold more selective for cardiac L-type channels (IC50 1⁄4 0.5 lM), blocking T-type channels with an apparent IC50 of 5.7 lM. Since amlodipine serum concentrations are 14 nM, approximately 3% of T-type channels will be blocked during therapy, and the fraction might be higher in depolarized cells (Perez-Reyes 2003). Additionally, xylazine has been shown to both decrease and increase blood pressure (Ruiz-Colon et al. 2014). Overall, this letter is meant as a token of appreciation as these results combined with our most recent publications have made us realize that we need to consider what biochemical entities [i.e. pain killers (propofol; Olcese et al. 1994), ascorbate (vitamin C; Todorovic and JevtovicTodorovic 2011), blood pressure medications (nifedipine/ amlodipine; Striessnig et al. 2015)] potentially can or will inhibit T-type voltage gated calcium channels in addition to L-type channels. Moving forward, we need to consider that common drugs may have secondary or off target effects on the T-type voltage gated calcium channels altering or possibly negating the therapeutic effect of tumor-specific AM RF EMF. The publication by Veyret et al. together with our two recent publications (Jimenez et al. 2019; Sharma et al. 2019) illuminate the important connection related to the mechanism of action of various drugs, medications, vitamins, and/or anesthetics (ketamine/xylazine) and their impact on AM RF EMF therapeutic effects.