Biophysical aspect of cancer - Electromagnetic mechanism

Terrific paper, read it!
"Frohlich assumed that disturbances of electromagnetic states lead to evasion of cancer cells from control and regulation in tissue"
https://pdfs.semanticscholar.org/a2c4/b18613b739828b9c6ddcc94367a00211c803.pdf

In vitro stimulation with a strongly pulsed electromagnetic field on rat basophilic leukemia cells

In this study, the effects of pulsed electromagnetic field stimulation with a strong magnetic field on rat basophilic leukemia (RBL-2H3) cells were investigated to confirm the efficacy of the magnetic stimulator for biomedical applications. The maximum intensity of the magnetic field generated from the stimulation coil was 0.203 T, and the transition time was 126 μs$126\mu \text{s}$. The oscillation time and frequency of the pulsed field were almost 0.1 ms and 8 kHz, respectively. The cell count as well as the mRNA expression and DNA sequenceof the cytokine genes, such as the tumor necrosis factor-α$\alpha$ (TNF-α$\alpha$) and interleukin-4 (IL-4), of the stimulated RBL-2H3 cells were analyzed with a hemocytometer and via reverse transcriptase polymerase chain reaction to determine the physiological response under a strong pulse field. After 12 h stimulation, cell death was observed at an increasing scale with the increase in the stimulation time. On the other hand, the cells that were stimulated for 10 min almost doubled as the interval time between the stimulations was extended.
https://aip.scitation.org/doi/10.1063/1.3357349

Synergic effect of retinoic acid and extremely low frequency magnetic field exposure on human neuroblastoma cell line BE(2)C

The aim of the present study was to assess whether exposure to a sinusoidal extremely low frequency magnetic field (ELF-MF; 50 Hz, 1 mT) can affect proliferation and differentiation in the human neuroblastoma cell line BE(2)C, which is representative of high risk neuroblastomas. Cells were subjected to ELF-MF exposure in the presence or absence of a neuronal differentiating agent (all-trans-retinoic acid, ATRA) for 24–72 h. In each experiment, ELF-MF-exposed samples were compared to sham-exposed samples. Cells exposed to ELF-MF combined with retinoic treatment showed a decreased cellular proliferation and an increased proportion of G0/G1 phase cells compared to cells exposed to either treatment alone. Moreover, ELF-MF- and ATRA-treated cells showed more differentiated morphological traits (a higher neurite number/cell, an increased neurite length), together with a significant increase of mRNA levels of p21WAF1/CIP1 and cdk5 genes, both involved in neuronal differentiation. In addition, the expression of cyp19 gene, which is involved both in neuronal differentiation and stress response, was evaluated; cyp19 gene expression was enhanced by ATRA treatment and significantly enhanced further by ELF-MF exposure combined with ATRA. In conclusion, our data suggest that ELF-MF exposure can strengthen ATRA effects on neuroblastoma cells.
http://onlinelibrary.wiley.com/doi/10.1002/bem.20581/abstract

Pulsed electromagnetic field with Temozolomide can elicit an epigenetic pro-Apoptotic effect on Glioblastoma T98G Cells

Treatment with pulsed electromagnetic fields (PEMFs) is emerging as an interesting therapeutic option for patients with cancer. The literature has demonstrated that low-frequency/low-energy electromagnetic fields do not cause predictable effects on DNA; however, they can epigenetically act on gene expression. The aim of the present work was to study a possible epigenetic effect of a PEMF, mediated by miRNAs, on a human glioblastoma cell line (T98G). We tested a PEMF (maximum magnetic induction, 2 mT; frequency, 75 Hz) that has been demonstrated to induce autophagy in glioblastoma cells. In particular, we studied the effect of PEMF on the expression of genes involved in cancer progression and a promising synergistic effect with temozolomide, a frequently used drug to treat glioblastoma multiforme. We found that electromagnetic stimulation in combination with temozolomide can elicit an epigenetic pro-Apoptotic effect in the chemo-and radioresistant T98G glioblastoma cell line.
https://moh-it.pure.elsevier.com/en/publications/pulsed-electromagnetic-field-with-temozolomide-can-elicit-an-epig

Mechanisms and therapeutic effectiveness of pulsed electromagnetic field therapy in oncology

PEMFs have also an immunomodulatory effect, as supported by in vivo evidence showing an increase in tumor necrosis factor alpha levels that induce an anti-tumoral response, leading to the activation of a proapoptotic pathway induced by caspase-8 interaction with Fas-associated death domain, in the spleen of the murine melanoma mouse model after a 16-day therapy [78]. Changes in blood pressure, skin electrical resistance, and pulse amplitude in 163 oncology patients exposed to tumor-specific PEMF frequencies have also been reported suggesting that PEMF therapy does not only target neoplastic cells, but may also have systemic effects [15]. However, long-term PEMF treatment in HCC patients is not toxic, confirming the safety of PEMF therapy that employs 100,000 times lower frequencies if compared with radiofrequency ablation that is also employed for treatment of HCC
http://onlinelibrary.wiley.com/doi/10.1002/cam4.861/full

Electromagnetic field effects on cells of the immune system: The role of calcium signalling

During the past decade considerable evidence has accumulated demonstrating the exposures of cells of the immune system to relatively weak extremely-low-frequency (ELF) electromagnetic fields (< 300 Hz) can elicit cellular changes which might be relevant to in-vivo immune activity. However, knowledge about the underlying biological mechanisms by which weak fields induce cellular changes is still very limited. It is generally believed that the cell membrane and Ca{sup 2+} regulated activity is involved in bioactive ELF field-coupling to living systems. This article begins with a short review of the current state of knowledge concerning the effects of nonthermal levels of ELF electromagnetic fields on the biochemistry and activity of immune cells, and then closely examines new results which suggest a role for Ca{sup 2+} in the induction of these cellular field effects. Based on these findings it is proposed that membrane-mediated Ca{sup 2+} signalling processes are involved in the mediation of field effects on the immune system
https://www.osti.gov/biblio/5261345

Therapeutic Effects of Low Frequency Pulsed Electromagnetic Fields on Rat Liver Cancer

Abstract - The attempts made to treat invasive liver cancer have failed so far at an alarming rate. 

One effective strategy used recently is low frequency pulsed magnetic field therapy. 

Coil A of intensity 13-42 gauss; 2-3 Hz and Coil B of 0.6 Tesla <1 Hz were evaluated on diethylnitrosamine-induced rat liver cancer. 

Furthermore, an exposure system was designed to provide a safe, selective and a noninvasive therapeutic device designed according to the international safety standards of therapeutic devices. 

The histopathology and ultra-structure of liver tissues suggest a selective anticancer activity of these magnetic fields through incorporating three main strategies. 

These strategies consist of apoptosis, necrosis and the inflammatory infiltration of the malignant carcinoma. 

These results simulate the gene therapy and immunogenic therapy of liver cancer. 

Finally, it can be concluded that the exposure system coil A of 3 Hz and coil B 0.9 Hz will contribute to magnetic therapy. 

http://www.researchinventy.com/papers/v2i9/C029017018.pdf

Low Frequency Magnetic Fields Enhance Antitumor Immune Response against Mouse H22 Hepatocellular Carcinoma

Objective

Many studies have shown that magnetic fields (MF) inhibit tumor growth and influence the function of immune system. However, the effect of MF on mechanism of immunological function in tumor-bearing mice is still unclear.

Methods

In this study, tumor-bearing mice were prepared by subcutaneously inoculating Balb/c mice with hepatocarcinoma cell line H22. The mice were then exposed to a low frequency MF (0.4 T, 7.5 Hz) for 30 days. Survival rate, tumor growth and the innate and adaptive immune parameters were measured.

Results

MF treatment could prolong survival time (n = 28, p<0.05) and inhibit tumor growth (n = 9, p<0.01) in tumor-bearing mice. Moreover, this MF suppressed tumor-induced production of cytokines including interleukin-6 (IL-6), granulocyte colony- stimulating factor (G-CSF) and keratinocyte-derived chemokine (KC) (n = 9–10, p<0.05 or 0.01). Furthermore, MF exposure was associated with activation of macrophages and dendritic cells, enhanced profiles of CD4+ T and CD8+ T lymphocytes, the balance of Th17/Treg and reduced inhibitory function of Treg cells (n = 9–10, p<0.05 or 0.01) in the mice model.

Conclusion

The inhibitory effect of MF on tumor growth was related to the improvement of immune function in the tumor-bearing mice.

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0072411

Effect of low frequency magnetic fields on melanoma: tumor inhibition and immune modulation

LF-MF inhibited the growth and metastasis of melanoma cancer cells and improved immune function of tumor-bearing mice. This suggests that the inhibition may be attributed to modulation of LF-MF on immune function and LF-MF may be a potential therapy for treatment of melanoma.
https://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-13-582

The Effects of Hypoxia, Metabolic Restriction and Magnetic Fields on Chromosome Instability and Karyotype Contraction in Cancer Cell Lines

This is an exhaustive thesis from the University of McGill Montreal:

A biological assay based on chromosome counts in human cancer cells was developed as an
index of metabolic state. The assay is then used to describe the action of a variety of metabolic
agents: oxygen, melatonin, vitamin C, the drugs oligomycin and imatinib, as well as extra-low
frequency (ELF) magnetic fields (MFs). This led us to uncover a basic mechanism of interaction
between ELF MFs and biological materials. The action of MFs is through an alteration in the
structure of water, originally described by Russian physicists at Lomonosov University in
Moscow, in the early 1980s.


Biological effects of ELF MFs have lacked a credible mechanism of interaction between fields
and living material. The karyotype changes produced by 6-day exposures to ELF MFs between
25 nT and 5 µT were evaluated in our five human cancer cell lines. Similar to the chemical
metabolic restrictors, all cancer cells lines lost chromosomes from all MF exposures, with a
mostly flat dose-response. Continued MF exposures for three weeks allow a rising return to the
baseline, unperturbed karyotypes. From this point, small MF increases or decreases are again
capable of inducing KCs. 
Our data suggests that the KCs are caused by MF interference with mitochondria’s ATP synthase
(ATPS), compensated by the action of AMP-activated protein kinase (AMPK). The effects of
MFs are similar to those of the ATPS inhibitor oligomycin. They are amplified by metformin, an
AMPK stimulator, and attenuated by resistin, an AMPK inhibitor. Over environmental MFs,
KCs of various cancer cell lines show exceptionally wide and flat dose-responses, except for
those of erythro-leukemia cells, which display a progressive rise from 25 nT to 0.4 µT. 

https://arxiv.org/ftp/arxiv/papers/1404/1404.3604.pdf

Combined effects of electromagnetic field and low-level laser increase proliferation and alter the morphology of human adipose tissue-derived mesenchymal stem cells

In recent years, electromagnetic field (EMF) and low-level laser (LLL) have been found to affect various biological processes, the growth and proliferation of cells, and especially that of stem cells. The aim of this study was to investigate the effects of EMF and LLL on proliferation of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) and thus to examine the impact of these therapeutic physical modalities on stem cell engraftment. hAT-MSCs were isolated from subcutaneous adipose tissue of six persons ranging in age from 21 to 56 years. EMF was applied for a period of 7 days, once a day for 30 min, via a magnetic cushion surface at a frequency of 50 Hz and an intensity of 3 mT. LLL was applied also for 7 days, once a day for 5 min, at radiation energies of 3 J/cm2, with a wavelength of 808 nm, power output of 200 mW, and power density of 0.2 W/cm2. Nonexposed cells (control) were cultivated under the same culture conditions. Seven days after treatment, the cells were examined for cell viability, proliferation, and morphology. We found that after 7 days, the number of EMF-treated hAT-MSCs was significantly higher than the number of the untreated cells, LLL-treated hAT-MSCs were more numerous than EMF-treated cells, and hAT-MSCs that were treated with the combination of EMF and LLL were the most numerous. EMF and/or LLL treatment did not significantly affect hAT-MSC viability by itself. Changes in cell morphology were also observed, in terms of an increase in cell surface area and fractal dimension in hAT-MSCs treated with EMF and the combination of EMF and LLL. In conclusion, EMF and/or LLL treatment accelerated the proliferation of hAT-MSCs without compromising their viability, and therefore, they may be used in stem cell tissue engineering.
https://link.springer.com/article/10.1007/s10103-016-2097-2

Effects of Sinusoidal Magnetic Field Observed on Cell Proliferation, Ion Concentration, and Osmolarity in Two Human Cancer Cell Lines

Low frequency magnetic fields have previously been shown to affect cell functions. In this article, the effects of 20 mT, 50 Hz sinusoidal magnetic field on cell proliferation, ion concentration, and osmolarity in two human cancer cell lines (HL-60 and SK-Hep-1) were investigated. Inhibition of cell growth was observed. On the other hand, the exposure also increased the Na+, K+ ion concentration and osmolarity in cell supernatant compared to the control group. To our knowledge, this is the first study on cancer cells where magnetic fields affect osmolarity in cell supernatant. In addition, a model of cells exposed to the oscillating magnetic field is described as well as the characteristics of ions in and out of cells. The experimental data appears to be consistent with the theoretical analysis. The results are also discussed in terms of the relationships among cell growth, ion concentration, and osmolarity. Magnetic field inhibitions of cell growth in vitro may relate to changes in cell ion concentration and osmolarity.
https://www.tandfonline.com/doi/full/10.1080/15368370600719067

Ion Cyclotron Resonance interactions in living systems

The interaction of weak magnetic fields, with intensities on the order of the geomagnetic field, is a very interesting subject that only recently, in the last few decades, has received much scientific attention. In the late 1970s a number of independent studies showed, counter to scientific prediction, that magnetic fields on the order of the geomagnetic field (GMF) appeared capable of interacting with living things. The first of these was the impressive data on bird sensitivity brought to the fore by husband-and-wife Wolfgang and Roswitha Wiltschko, by Beason and Semm, and by other ornithologists. Quite independently, an epidemiological study by Wertheimer and Leeper found that leukemia in children increased with proximity to the 60 Hz frequencies emitted by power lines, implicating magnetic intensities below 5µT, ten times less than maximum geomagnetic levels. Most critically, an experiment designed by Adey (Fig. 1) and Bawin studying radiofrequency effects on chick brain (Bawin et al, 1978), later modified by Blackman, discovered that calcium transport is profoundly affected when the radiofrequency was modulated by specific extremely low frequencies (ELF).
https://emmind.net/openpapers_repos/Applied_Fields-Experimental/ELF_LF_Effects/ELF-EMF/2013_Ion_Cyclotron_Resonance_interactions_in_living_systems.pdf

Remotely and Noninvasively Controlling Genes and Cells in Living Animals

One of the two components of the new system is a natural iron storage particle called ferritin. This particle is tethered to a temperature-sensitive channel protein that controls the flow of calcium into a cell. Together, the two molecules work as a nano-machine that can be used to trigger gene activity, or expression, in cells. When the ferritin particle is exposed to radio waves or a magnetic field, it opens the channel, activating a gene engineered to respond to calcium.

The researchers found that radio waves and magnets may have different ways of causing the calcium channel to open. Low-frequency radio waves cause mild heating of the ferritin’s iron core, tripping a switch that opens the channel, while the tug of a magnetic field most likely causes the ferritin particles to move slightly and nudge the channel open. Calcium then flows into the cell and turns on the calcium-responsive gene.

As proof of principle, the team, led by Jeffrey Friedman  at Rockefeller University and Jonathan Dordick  at Rensselaer Polytechnic Institute, showed that they could use their system to turn on insulin production and thereby lower blood sugar in diabetic mice. The researchers used genetic techniques to introduce the ferritin-tethered channels into mice along with a calcium-responsive version of the insulin gene.
https://biobeat.nigms.nih.gov/2015/02/remotely-and-noninvasively-controlling-genes-and-cells-in-living-animals/

Ephaptic Coupling of Cortical Neurons: Possible Contribution of Astroglial Magnetic Fields?

The close anatomical and functional relationship between neuronal circuits and the astroglial network in the neocortex has been demonstrated at several organization levels supporting the idea that neuron-astroglial crosstalk can play a key role in information processing. In addition to chemical and electrical neurotransmission, other non-synaptic mechanisms called ephaptic interactions seem to be important to understand neuronal coupling and cognitive functions. 

Recent interest in this issue comes from the fact that extra-cranial electric and magnetic field stimulations have shown therapeutic actions in the clinical practice. 

The present paper reviews the current knowledge regarding the ephaptic effects in mammalian neocortex and proposes that astroglial bio-magnetic fields associated with Ca2+ transients could be implicated in the ephaptic coupling of neurons by a direct magnetic modulation of the intercellular local field potentials.
https://www.sciencedirect.com/science/article/abs/pii/S0306452217305584

Electromagnetic homeostasis and the role of low-amplitude electromagnetic fields on life organization

https://www.ncbi.nlm.nih.gov/pubmed/27399207
The appearance of endogenous electromagnetic fields in biological systems is a widely debated issue in modern science. The electrophysiological fields have very tiny intensities and it can be inferred that they are rapidly decreasing with the distance from the generating structure, vanishing at very short distances. This makes very hard their detection using standard experimental methods. However, the existence of fast-moving charged particles in the macromolecules inside both intracellular and extracellular fluids may envisage the generation of localized electric currents as well as the presence of closed loops, which implies the existence of magnetic fields. Moreover, the whole set of oscillatory frequencies of various substances, enzymes, cell membranes, nucleic acids, bioelectrical phenomena generated by the electrical rhythm of coherent groups of cells, cell-to-cell communication among population of host bacteria, forms the increasingly complex hierarchies of electromagnetic signals of different frequencies which cover the living being and represent a fundamental information network controlling the cell metabolism. From this approach emerges the concept of electromagnetic homeostasis: that is, the capability of the human body to maintain the balance of highly complex electromagnetic interactions within, in spite of the external electromagnetic noisy environment. This concept may have an important impact on the actual definitions of heal and disease.