Book - Fields of the Cell

In recent years, an increasing number of results from basic research support the view that biophysical, in particular bioelectromagnetic and photobiological factors are fundamental for the functional and structural organization of biosystems. 

Despite the relatively well-known and well researched bioelectromagnetic factors (endogenous currents, static and dynamic electric and magnetic fields as well as electromagnetic fields) in the context of biological function, photobiological factors (endogenous photon emissions) have become the focus of research as an additional entity influencing and guiding life processes. 

Are we heading towards a new paradigm in the understanding of life?

One of the manifestations of living system’s non-equilibrium behavior is the permanent production of electron excitation in biomolecules leading to ultra-weak photon emission. 

...

Based on solid experimental evidence, chapter six explains the generation of electron excited chemical species due to free radical and reactive oxygen species reactions. 

Biological ultra-weak photon emission is of very general nature. It is detectable from every metabolically active biological species under suitable conditions. 

Chapter seven focuses on ultraweak photon emission from multicellular organisms, namely plants, tumor tissues and humans. It relates photon emission to development and structure as well as to tumor and normal cells comparing them with reference to growth properties. 

The eighth chapter explains the peculiar phenomenon of non-chemical influences between cell cultures through glass barriers. It is suspected that the non-chemical interaction between cell cultures is mediated by photon emission generated by cells. A special emphasis is given on confounding effects and the method itself in order to gain understanding about the function. 

As statistical properties of biological ultra-weak photon emission have been a source of controversy in past decades; chapter nine assesses available experiments studying optical coherence, quantum states and signal properties of biological ultra-weak photon emission. 

Chapter ten aims to explain that the electrodynamic activity of living cells involves a broad range of frequencies, namely from kilohertz to terahertz. 

These frequency ranges are related to electromechanical vibrations of subcellular structures. It is hypothesized that electrodynamic fields generated by such sub-cellular coupled oscillations contribute significantly to biological self-organization

https://www.researchgate.net/profile/Daniel_Fels/publication/281409607_Fields_of_the_cell/links/5615216108aed47facefb302/Fields-of-the-cell.pdf

Effects of Ion Resonance Tuned Magnetic Fields on N-18 Murine Neuroblastoma Cells

Numerous experiments by various laboratories have demonstrated that the effects of ELF magnetic fields on living systems may be dependent upon resonance effects. Bawin and Adey (1976) and Blackman, et. al. (1984) observed such responses for calcium efflux from chick brains. Dutta, et. al. (1984) saw similar effects in neuroblastoma cells. Liboff (1985) suggested that these effects might be due to cyclotron resonance effects on transmembrane movement of ions. Since then, the theory has been expanded and refined a number of times, and the interested reader is directed to one of the recent theoretical papers by Liboff and McLeod (e.g. 1988) for an analytical discussion. In sum, the theory states that transport will be affected if the combined ac and static magnetic fields satisfy the cyclotron resonance conditions for a particular ion as given by the formula: 2πfc=(q/m)(B)$2\pi {\mathrm{f}}_{\mathrm{c}}=(\mathrm{q}/\mathrm{m})(\mathrm{B})$, where; fc = fundamental resonance frequency in Hz q/m = charge (Coulombs) to mass (Kg) ratio of the ion B = static magnetic field (Tesla {1 T = 1 × 104Gauss})
https://link.springer.com/chapter/10.1007/978-1-4615-9837-4_22

Electromagnetic Field Therapy Reduces Cancer Cell Radioresistance by Enhanced ROS Formation and Induced DNA Damage

Abstract

Each year more than 450,000 Germans are expected to be diagnosed with cancer subsequently receiving standard multimodal therapies including surgery, chemotherapy and radiotherapy. On top, molecular-targeted agents are increasingly administered. Owing to intrinsic and acquired resistance to these therapeutic approaches, both the better molecular understanding of tumor biology and the consideration of alternative and complementary therapeutic support are warranted and open up broader and novel possibilities for therapy personalization. Particularly the latter is underpinned by the increasing utilization of non-invasive complementary and alternative medicine by the population. One investigated approach is the application of low-dose electromagnetic fields (EMF) to modulate cellular processes. A particular system is the BEMER therapy as a Physical Vascular Therapy for which a normalization of the microcirculation has been demonstrated by a low-frequency, pulsed EMF pattern. Open remains whether this EMF pattern impacts on cancer cell survival upon treatment with radiotherapy, chemotherapy and the molecular-targeted agent Cetuximab inhibiting the epidermal growth factor receptor. Using more physiological, three-dimensional, matrix-based cell culture models and cancer cell lines originating from lung, head and neck, colorectal and pancreas, we show significant changes in distinct intermediates of the glycolysis and tricarboxylic acid cycle pathways and enhanced cancer cell radiosensitization associated with increased DNA double strand break numbers and higher levels of reactive oxygen species upon BEMER treatment relative to controls. Intriguingly, exposure of cells to the BEMER EMF pattern failed to result in sensitization to chemotherapy and Cetuximab. Further studies are necessary to better understand the mechanisms underlying the cellular alterations induced by the BEMER EMF pattern and to clarify the application areas for human disease.

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0167931

Mitotic Spindle Disruption by Alternating Electric Fields Leads to Improper Chromosome Segregation and Mitotic Catastrophe in Cancer Cells

Tumor Treating Fields (TTFields) are low intensity, intermediate frequency, alternating electric fields. TTFields are a unique anti-mitotic treatment modality delivered in a continuous, noninvasive manner to the region of a tumor. It was previously postulated that by exerting directional forces on highly polar intracellular elements during mitosis, TTFields could disrupt the normal assembly of spindle microtubules. However there is limited evidence directly linking TTFields to an effect on microtubules. Here we report that TTFields decrease the ratio between polymerized and total tubulin, and prevent proper mitotic spindle assembly. The aberrant mitotic events induced by TTFields lead to abnormal chromosome segregation, cellular multinucleation, and caspase dependent apoptosis of daughter cells. The effect of TTFields on cell viability and clonogenic survival substantially depends upon the cell division rate. We show that by extending the duration of exposure to TTFields, slowly dividing cells can be affected to a similar extent as rapidly dividing cells.
https://www.nature.com/articles/srep18046

How a High-Gradient Magnetic Field Could Affect Cell Life.

Abstract

The biological effects of high-gradient magnetic fields (HGMFs) have steadily gained the increased attention of researchers from different disciplines, such as cell biology, cell therapy, targeted stem cell delivery and nanomedicine. We present a theoretical framework towards a fundamental understanding of the effects of HGMFs on intracellular processes, highlighting new directions for the study of living cell machinery: changing the probability of ion-channel on/off switching events by membrane magneto-mechanical stress, suppression of cell growth by magnetic pressure, magnetically induced cell division and cell reprograming, and forced migration of membrane receptor proteins. By deriving a generalized form for the Nernst equation, we find that a relatively small magnetic field (approximately 1 T) with a large gradient (up to 1 GT/m) can significantly change the membrane potential of the cell and thus have a significant impact on not only the properties and biological functionality of cells but also cell fate.

https://www.ncbi.nlm.nih.gov/pubmed/27857227

The effects of tumor treating fields and temozolomide in MGMT expressing and non-expressing patient-derived glioblastoma cells.

Abstract

A recent Phase 3 study of newly diagnosed glioblastoma (GBM) demonstrated the addition of tumor treating fields (TTFields) to temozolomide (TMZ) after combined radiation/TMZ significantly increased survival and progression free survival. Preliminary data suggested benefit with both methylated and unmethylated O-6-methylguanine-DNA methyl-transferase (MGMT) promoter status. To date, however, there have been no studies to address the potential interactions of TTFields and TMZ. Thus, the effects of TTFields and TMZ were studied in vitro using patient-derived GBM stem-like cells (GSCs) including MGMT expressing (TMZ resistant: 12.1 and 22GSC) and non-MGMT expressing (TMZ sensitive: 33 and 114GSC) lines. Dose-response curves were constructed using cell proliferation and sphere-forming assays. Results demonstrated a ⩾10-fold increase in TMZ resistance of MGMT-expressing (12.1GSCs: IC50=160μM; 22GSCs: IC50=44μM) compared to MGMT non-expressing (33GSCs: IC50=1.5μM; 114GSCs: IC50=5.2μM) lines. TTFields inhibited 12.1 GSC proliferation at all tested doses (50-500kHz) with an optimal frequency of 200kHz. At 200kHz, TTFields inhibited proliferation and tumor sphere formation of both MGMT GSC subtypes at comparable levels (12.1GSC: 74±2.9% and 38±3.2%, respectively; 22GSC: 61±11% and 38±2.6%, respectively; 33GSC: 56±9.5% and 60±7.1%, respectively; 114 GSC: 79±3.5% and 41±4.3%, respectively). In combination, TTFields (200kHz) and TMZ showed an additive anti-neoplastic effect with equal efficacy for TTFields in both cell types (i.e., ± MGMT expression) with no effect on TMZ resistance. This is the first demonstration of the effects of TTFields on cancer stem cells. The expansion of such studies may have clinical implications.

https://www.ncbi.nlm.nih.gov/pubmed/27865821

Cancer is promoted by cellular states of electromagnetic decoherence and can be corrected by exposure to coherent non-ionizing electromagnetic fields A physical model about cell-sustaining and cell-decaying soliton eigen-frequencies

Abstract

Physical and biological evidence has been found for the hypothesis that carcinogenesis fits in a frequency pattern of electromagnetic (EM) waves, in which a gradual loss of cellular organization occurs. We find that cancer can be initiated and promoted at typical frequencies of electromagnetic waves positioned in decoherent soliton frequency zones. In contrast, the generation of cancer features can be inhibited and retarded by application of coherent soliton frequencies. This hypothesis has been substantiated by 200 different EM frequency data in 320 different published biomedical studies. All frequencies, ranging from sub Hz till Peta Hertz, could be normalized into 12 basic beneficial (anti-cancer) frequencies, and 12 basic detrimental (cancer promoting) frequencies, that exhibit a deviation from coherency and related geometry. Inhibiting of the cancer process, and even curing of the disease, could be further considered by exposure to coherent EM fields. Such coherent solitons frequency zones can, for instance, be implemented in man-made therapeutic radiation technology. Inhibition and retardation of the cancer process can take place through stabilization of the identified eigen-frequencies, characteristic for the proper functioning of living cells. The present hypothesis can be viewed upon as a further elaboration of the theory presented by Fröhlich in 1968 and his postulate that biological systems exhibit coherent longitudinal vibrations of electrically polar macromolecular structures. Fröhlich’s condensation of oscillators in vibration modes is usually compared with Bose–Einstein condensation and phenomena involving macroscopic quantum coherence. At the same time, Davydov discovered the related principle of longitudinal wave forms called solitons. Solitons with discrete wave frequencies can induce direct changes in DNA/RNA conformation and/or epigenetic changes, in addition to perturbation of protein folding and disturbance of intra and intercellular wave communication that is essential for the health ecology of cells. It is further hypothesized that such wave energies and eigen-frequencies can be optimally expressed by a toroidal geometry.

Cancer is promoted by cellular states of electromagnetic decoherence and can be corrected by exposure to coherent non-ionizing electromagnetic fields A physical model about cell-sustaining and cell-decaying soliton eigen-frequencies. Available from: https://www.researchgate.net/publication/316058728_Cancer_is_promoted_by_cellular_states_of_electromagnetic_decoherence_and_can_be_corrected_by_exposure_to_coherent_non-ionizing_electromagnetic_fields_A_physical_model_about_cell-sustaining_and_cell-de [accessed Jun 16, 2017].

Pulsed electromagnetic field (PEMF) prevents pro-oxidant effects of H 2 O 2 in SK-N-BE(2) human neuroblastoma cells

Some of us have recently reported that a pulsed EMF (PEMF) improves the antioxidant response of a drug-sensitive human neuroblastoma SH-SY5Y cell line to pro-oxidants. Since drug resistance may affect cell sensitivity to redox-based treatments, we wanted to verify whether drug-resistant human neuroblastoma SK-N-BE(2) cells respond to a PEMF in a similar fashion. Materials and methods SK-N-BE(2) cells were exposed to repeated 2 mT, 75 Hz PEMF (15 min each, repeated 3 times over 5 days), and ROS production, Mn-dependent superoxide dismutase (MnSOD)-based antioxidant protection and viability were assessed after 10 min or 30 min 1 mM hydrogen peroxide. Sham controls were kept at the same time in identical cell culture incubators. Results The PEMF increased the MnSOD-based antioxidant protection and reduced the ROS production in response to a pro-oxidant challenge. Conclusions Our work might lay foundation for the development of non-invasive PEMF-based approaches aimed at elevating endogenous antioxidant properties in cellular or tissue models. 
https://www.researchgate.net/publication/297605860_Pulsed_electromagnetic_field_PEMF_prevents_pro-oxidant_effects_of_H_2_O_2_in_SK-N-BE2_human_neuroblastoma_cells

How a High-Gradient Magnetic Field Could Affect Cell Life

This is the best scientific article yet that I've come across that details how magnetic fields affect living cells, packed with proof, theories, and data!
https://www.nature.com/articles/srep37407

The biological effects of high-gradient magnetic fields (HGMFs) have steadily gained the increased attention of researchers from different disciplines, such as cell biology, cell therapy, targeted stem cell delivery and nanomedicine. We present a theoretical framework towards a fundamental understanding of the effects of HGMFs on intracellular processes, highlighting new directions for the study of living cell machinery: changing the probability of ion-channel on/off switching events by membrane magneto-mechanical stress, suppression of cell growth by magnetic pressure, magnetically induced cell division and cell reprograming, and forced migration of membrane receptor proteins. By deriving a generalized form for the Nernst equation, we find that a relatively small magnetic field (approximately 1 T) with a large gradient (up to 1 GT/m) can significantly change the membrane potential of the cell and thus have a significant impact on not only the properties and biological functionality of cells but also cell fate.

Life Rhythm as a Symphony of Oscillatory Patterns: Electromagnetic Energy and Sound Vibration Modulates Gene Expression for Biological Signaling and Healing

Note: this article is very lengthy, but has many references to other pertinent papers:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010966/

Of particular interest to cell-cell communication with regard to EMF sensitivity is the messenger molecule nitric oxide (NO). NO diffuses freely and rapidly across cell membranes, plays key roles in the rapid regulation of microcirculation, inflammation, and the cell growth and repair process,118 and has been demonstrated to regulate chromatin folding dynamics, and thus gene expression, in human endothelial cells.119 The importance of transient NO signaling is underscored by the observation that Nature has evolved a remarkable sensitivity to subcellular, subsecond (100 ms) NO transients in the low picomolar range, as demonstrated in human embryonic kidney HEK 293T cell lines.120 A growing body of literature has demonstrated that NO signaling plays a significant role in biological EMF transduction, and effects on NO expression and NO-dependent pathways have been reported for a wide variety of nonthermal EMF amplitudes, frequencies, and signal shapes.121–137 Thus, modulation of NO signaling has been established as one means by which cells and tissues can respond rapidly to changes in the EMF environment and could interact with nuclear DNA through modulation of chromosome folding dynamics.119

Even within this narrow category, a large number of effects have been observed over a wide range of nonthermal EMF amplitudes, frequencies and waveform shapes, and the current rate of progress is rapidly increasing. Recent reports of such effects are displayed in the following list.

• Decreased proliferation, upregulation of neuronal differentiation marker (MAP2)157
• A decrease in filament protein Nestin in bone marrow derived mesenchymal stem cells157
• Increased filament protein NF-L, MAP2 and NeuroD1 in human bone marrow derived mesenchymal stem cells158,159
• Induction of rat bone mesenchymal stromal cells to differentiate into functional neurons160
• Significant up-regulation of early and late neuronal differentiation markers and significant down-regulation of the transforming growth factor-α (TGF-α) and the fibroblast growth factor-4 (FGF-4) in NT2 pluripotent human testicular embryonal carcinoma cells161
• Increased osteogenic gene expression, alkaline phosphate activity in adipose-derived stem cells162
• Enhanced chondrogenic gene expression (SOX-9, collagen type II, and aggrecan) in adipose-derived stem cells163
• Modulation of early (such as Runx-2 and osterix) and late (specifically, osteopontin and osteocalcin) osteogenic genes in adult human mesenchymal stem cells164
• Up-regulation of insulin factor genes, peroxisome proliferative activity, calcium channel gene, genes for mitochondrial ribosomal protein S, and uncoupling protein 2, down-regulation of tumor necrosis factor alpha and interleukin 6 in human embryonic stem cells165
• Enhanced expression of the collagen I gene in mouse bone marrow stromal cells166
• Increase in genetic markers for differentiation in human osteoprogenitor cells167
• Increased expression of Osterix and IGF-1 genes in rat bone marrow mesenchymal stem cells168
• Increased expression of osteogenic regulatory gene cbfa1 in human bone marrow mesenchymal stem cells169
• Up-regulation of cardiac markers such as troponin I and myosin heavy chain, decrease in angiogenic markers such as vascular endothelial growth factor and kinase domain receptor in cardiac stem cells170
• Up-regulation of expressions of Bmp1, Bmp7 mRNA and down-regulation of Egf, Egfr in murine bone marrow mesenchymal stem cells171
• Altered gene expression in human mesenchymal stem cells and chondrocytes172
• Alterations in transcript levels of the apoptosis-related bcl-2, bax, and cell cycle regulatory GADD45 genes in embryonic stem cell-derived neural progenitor cells173
• Up-regulation of c-jun, p21 and egr-1 mRNA gene expression levels in pluripotent embryonic stem cells174
• Alterations in gene expression through an EMF-activated free radical mechanism and175
• Increased expression of p21(WAF1/CIP1), cdk5 and cyp19 genes, involved in neuronal differentiation176
• Increased ALP gene expression and other osteogenic markers in bone marrow-derived human mesenchymal stem cells175
• Enhanced expression of ACTN2, alpha-actin and TNNT2 in rat bone marrow-derived mesenchymal stem cells178
• Induction of differentiation of mesenchymal stem cells into cardiomyocyte-like cells179
• Differentiation of rat bone marrow-derived mesenchymal stem cells into chondrocyte-like cells180
• Increased expression of GATA-4 and Nkx-2.5 cardiac lineage-promoting genes in embryonic stem cells181

Effect of pulsed electromagnetic field treatment on programmed resolution of inflammation pathway markers in human cells in culture

Abstract

Inflammation is a complex process involving distinct but overlapping biochemical and molecular events that are highly regulated. Pulsed electromagnetic field (PEMF) therapy is increasingly used to treat pain and edema associated with inflammation following surgery involving soft tissue. However, the molecular and cellular effects of PEMF therapy on pathways involved in the resolution of inflammation are poorly understood. Using cell culture lines relevant to trauma-induced inflammation of the skin (human dermal fibroblasts, human epidermal keratinocytes, and human mononuclear cells), we investigated the effect of PEMF on gene expression involved in the acute and resolution phases of inflammation. We found that PEMF treatment was followed by changes in the relative amount of messenger (m)RNAs encoding enzymes involved in heme catabolism and removal of reactive oxygen species, including an increase in heme oxygenase 1 and superoxide dismutase 3 mRNAs, in all cell types examined 2 hours after PEMF treatment. A relative increase in mRNAs encoding enzymes involved in lipid mediator biosynthesis was also observed, including an increase in arachidonate 12- and 15-lipoxygenase mRNAs in dermal fibroblasts and epidermal keratinocytes, respectively. The relative amount of both of these lipoxygenase mRNAs was elevated in mononuclear cells following PEMF treatment relative to nontreated cells. PEMF treatment was also followed by changes in the mRNA levels of several cytokines. A decrease in the relative amount of interleukin 1 beta mRNA was observed in mononuclear cells, similar to that previously reported for epidermal keratinocytes and dermal fibroblasts. Based on our results, we propose a model in which PEMF therapy may promote chronic inflammation resolution by mediating gene expression changes important for inhibiting and resolving inflammation.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346366/

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

NOTE: This article contains a lot of useful information.  A current trend in treating cancer is improving the body's immune system:

Abstract

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

The change of HCN1/HCN2 mRNA expression in peripheral nerve after chronic constriction injury induced neuropathy followed by pulsed electromagnetic field therapy.

Abstract

Neuropathic pain is usually defined as a chronic pain state caused by peripheral or central nerve injury as a result of acute damage or systemic diseases. It remains a difficult disease to treat. Recent studies showed that the frequency of action potentials in nociceptive afferents is affected by the activity of hyperpolarization-activated cyclic nucleotide-gated cation channels (HCN) family. In the current study, we used a neuropathy rat model induced by chronic constriction injury (CCI) of sciatic nerve to evaluate the change of expression of HCN1/HCN2 mRNA in peripheral nerve and spinal cord. Rats were subjected to CCI with or without pulsed electromagnetic field (PEMF) therapy. It was found that CCI induced neural cell degeneration while PEMF promoted nerve regeneration as documented by Nissl staining. CCI shortened the hind paw withdrawal latency (PWL) and hind paw withdrawal threshold (PWT) and PEMF prolonged the PWL and PWT. In addition, CCI lowers the expression of HCN1 and HCN2 mRNA and PEMF cannot restore the expression of HCN1 and HCN2 mRNA. Our results indicated that PEMF can promote nerve regeneration and could be used for the treatment of neuropathic pain.

https://www.ncbi.nlm.nih.gov/pubmed/27901476

Changes in cell death of peripheral blood lymphocytes isolated from children with acute lymphoblastic leukemia upon stimulation with 7 Hz, 30 mT pulsed electromagnetic field.

Abstract

Pulsed electromagnetic field (PEMF) influenced the viability of proliferating in vitro peripheral blood mononuclear cells (PBMCs) isolated from Crohn's disease patients as well as acute myeloblastic leukemia (AML) patients by induction of cell death, but did not cause any vital changes in cells from healthy donors. Experiments with lymphoid U937 and monocytic MonoMac6 cell lines have shown a protective effect of PEMF on the death process in cells treated with death inducers. The aim of the current study was to investigate the influence of PEMF on native proliferating leukocytes originating from newly diagnosed acute lymphoblastic leukemia (ALL) patients. The effects of exposure to PEMF were studied in PBMCs from 20 children with ALL. PBMCs were stimulated with three doses of PEMF (7 Hz, 30 mT) for 4 h each with 24 h intervals. After the last stimulation, the cells were double stained with annexin V and propidium iodide dye to estimate viability by flow cytometric analysis. The results indicated an increase of annexin V positive as well as double stained annexin V and propidium iodide positive cells after exposure to threefold PEMF stimulation. A low-frequency pulsed electromagnetic field induces cell death in native proliferating cells isolated from ALL patients. The increased vulnerability of proliferating PBMCs to PEMF-induced interactions may be potentially applied in the therapy of ALL. The analysis of expression of apoptosis-related genes revealed changes in mRNA of some genes engaged in the intrinsic apoptotic pathway belonging to the Bcl-2 family and the pathway with apoptosis-inducing factor (AIF) abundance upon PEMF stimulation of PBMCs.

https://www.ncbi.nlm.nih.gov/pubmed/26204398

Bioelectromagnetic Healing, its History and a Rationale for its Use

This paper gives an excellent historical account of Pulsed Electromagnetic Field therapy for cancer (and why it was rejected by the established medical sector), and technical aspects of it:

Abstract

Bioelectromagnetics (BEMs) is the study of the effect of electromagnetic fields on biological systems.1 Though electromagnetic fields have sometimes been associated with potential for harm to the body, there are many BEM instruments and devices re-emerging in the 21st century, based on high voltage Tesla coils, that apparently bring beneficial health improvements to human organisms. The Tesla coil class of therapy devices constitute pulsed electromagnetic fields (PEMF) that deliver broadband, wide spectrum, nonthermal photons and electrons deep into biological tissue. Electromedicine or electromagnetic healing are the terms applied to such developments in the ELF, RF, IR, visible or UV band. With short term, non-contacting exposures of several minutes at a time, such high voltage Tesla PEMF devices may represent the ideal, noninvasive therapy of the future, accompanied by a surprising lack of harmful side effects. A biophysical rationale for the benefits of BEM healing a wide variety of illnesses including cancer, proposes a correlation between a bioelectromagnetically restored transmembrane potential, and the electron transport across cell membranes by electroporation, with normal cell metabolism and immune system enhancement. The century-long historical record of these devices is also traced, revealing questionable behavior from the medical and public health institutions toward such remarkable innovations. This report also reviews the highlights of several BEM inventions but does not attempt to present an exhaustive nor comprehensive review of bioelectromagnetic healing devices. History of Bioelectromagnetic Healing Historically, as far back as 1890, the American Electro-Therapeutic Association conducted annual conferences on the therapeutic use of electricity and electrical devices by physicians on ailing patients. Some involved current flow through the patient, while others were electrically powered devices. At first, only direct current (DC) devices were utilized in the medical doctor's office for relieving pain and vibrating female patients who were routinely diagnosed with "hysteria."

https://www.researchgate.net/publication/237724829_Bioelectromagnetic_Healing_its_History_and_a_Rationale_for_its_Use

The Anti-Tumor Effect of A3 Adenosine Receptors Is Potentiated by Pulsed Electromagnetic Fields in Cultured Neural Cancer Cells

Abstract

A(3) adenosine receptors (ARs) play a pivotal role in the development of cancer and their activation is involved in the inhibition of tumor growth. The effects of pulsed electromagnetic fields (PEMFs) on cancer have been controversially discussed and the detailed mechanisms are not yet fully understood. In the past we have demonstrated that PEMFs increased A(2A) and A(3)AR density and functionality in human neutrophils, human and bovine synoviocytes, and bovine chondrocytes. In the same cells, PEMF exposure increased the anti-inflammatory effect mediated by A(2A) and/or A(3)ARs. The primary aim of the present study was to evaluate if PEMF exposure potentiated the anti-tumor effect of A(3)ARs in PC12 rat adrenal pheochromocytoma and U87MG human glioblastoma cell lines in comparison with rat cortical neurons. Saturation binding assays and mRNA analysis revealed that PEMF exposure up-regulated A(2A) and A(3)ARs that are well coupled to adenylate cyclase activity and cAMP production. The activation of A(2A) and A(3)ARs resulted in the decrease of nuclear factor-kappa B (NF-kB) levels in tumor cells, whilst only A(3)ARs are involved in the increase of p53 expression. A(3)AR stimulation mediated an inhibition of tumor cell proliferation evaluated by thymidine incorporation. An increase of cytotoxicity by lactate dehydrogenase (LDH) release and apoptosis by caspase-3 activation in PC12 and U87MG cells, but not in cortical neurons, was observed following A(3)AR activation. The effect of the A(3)AR agonist in tumor cells was enhanced in the presence of PEMFs and blocked by using a well-known selective antagonist. Together these results demonstrated that PEMF exposure significantly increases the anti-tumor effect modulated by A(3)ARs.

https://www.researchgate.net/publication/228116497_The_Anti-Tumor_Effect_of_A3_Adenosine_Receptors_Is_Potentiated_by_Pulsed_Electromagnetic_Fields_in_Cultured_Neural_Cancer_Cells

Effect of Pulsed Electromagnetic Field on MMP-9 and TIMP-1 Levels in Chondrosarcoma Cells Stimulated with IL-1β

Abstract

Chondrosarcoma, the second most common type of bone malignancy, is characterized by distant metastasis and local invasion. Previous studies have shown that treatment by pulsed electromagnetic field (PEMF) has beneficial effects on various cancer cells. In this study, we investigated the effects of PEMF applied for 3 and 7 days on the matrix metalloproteinase (MMP) levels in chondrosarcoma SW1353 cells stimulated with two different doses of IL-1β. SW1353 cells were treated with (0.5 and 5 ng/ml) IL-1β and PEMF exposure was applied either 3 or 7 days. MMP-9 and TIMP-1 levels were measured in conditioned media by enzyme-linked immunosorbent assay. The results were relative to protein levels. Statistical analyses were performed using one-way analysis of variance (ANOVA). P<0.05 was considered significant. PEMF treatment significantly decreased MMP-9 protein levels in human chondrosarcoma cells stimulated with 0.5 ng/ml IL-1β at day 7, whereas it did not show any effect on cells stimulated with 5 ng/ml IL-1β. There was no significant change in TIMP-1 protein levels either by IL-1β stimulation or by PEMF treatment. The results of this study showed that PEMF treatment suppressed IL-1β-mediated upregulation of MMP-9 protein levels in a dual effect manner. This finding may offer new perspectives in the therapy of bone cancer.

https://www.researchgate.net/publication/274726279_Effect_of_Pulsed_Electromagnetic_Field_on_MMP-9_and_TIMP-1_Levels_in_Chondrosarcoma_Cells_Stimulated_with_IL-1b

Electromagnetic effects-From cell biology to medicine

Abstract

In this review we compile and discuss the published plethora of cell biological effects which are ascribed to electric fields (EF), magnetic fields (MF) and electromagnetic fields (EMF). In recent years, a change in paradigm took place concerning the endogenously produced static EF of cells and tissues. Here, modern molecular biology could link the action of ion transporters and ion channels to the "electric" action of cells and tissues. Also, sensing of these mainly EF could be demonstrated in studies of cell migration and wound healing. The triggers exerted by ion concentrations and concomitant electric field gradients have been traced along signaling cascades till gene expression changes in the nucleus. Far more enigmatic is the way of action of static MF which come in most cases from outside (e.g. earth magnetic field). All systems in an organism from the molecular to the organ level are more or less in motion. Thus, in living tissue we mostly find alternating fields as well as combination of EF and MF normally in the range of extremely low-frequency EMF. Because a bewildering array of model systems and clinical devices exits in the EMF field we concentrate on cell biological findings and look for basic principles in the EF, MF and EMF action. As an outlook for future research topics, this review tries to link areas of EF, MF and EMF research to thermodynamics and quantum physics, approaches that will produce novel insights into cell biology.

https://www.researchgate.net/publication/23938298_Electromagnetic_effects-From_cell_biology_to_medicine

Modification of p21 level and cell cycle distribution by 50 Hz magnetic fields in human SH-SY5Y neuroblastoma cells

Abstract

Purpose: In our previous studies, exposure to extremely low frequency (ELF) magnetic fields (MFs) altered responses to DNA damage caused by menadione. The aim of this study was to evaluate possible ELF MF induced changes in proteins involved in DNA damage responses and in cell cycle distribution.
Materials and methods: Based on our previous studies, the exposure protocol included pre-exposure of human SH-SY5Y neuroblastoma cells to a 50 Hz, 100 µT MF for 24 h prior to a 3-h menadione treatment. As DNA damage responses are relatively fast processes, a 1-h menadione treatment was also included in the experiments. The menadione concentrations used were 1, 10, 15, 20, and 25 µM. Immunoblotting was used to assess the levels of DNA damage response-related proteins (γ-H2AX, Chk1, phospho-Chk1, p21, p27, and p53), while the level of DNA damage was assessed by the alkaline Comet assay. Cell cycle distribution was assayed by SYTOX Green staining followed by flow cytometry analysis.
Results: The main findings in MF-exposed cells were decreased p21 protein level after the 1-h menadione treatment, as well as increased proportion of cells in the G1 phase and decreased proportion of S phase cells after the 3-h menadione treatment. These effects were detectable also in the absence of menadione.
Conclusions: The results indicate that MF exposure can alter the G1 checkpoint response and that the p21 protein may be involved in early responses to MF exposure.

https://www.researchgate.net/publication/308387047_Modification_of_p21_level_and_cell_cycle_distribution_by_50_Hz_magnetic_fields_in_human_SH-SY5Y_neuroblastoma_cells

Electro-informational transfer of retinoic acid influencing human neuroblastoma cells and stem teratocarcinoma cells

ABSTRACT

Experimental evidence has accumulated to suggest that biologically efficacious informational effects can be derived mimicking active compounds solely through electromagnetic distribution upon aqueous systems affecting biological systems. Empirically rigorous demonstrations of antimicrobial agent associated electromagnetic informational inhibition of MRSA, Entamoeba histolytica, Trichomonas vaginalis, Candida albicans and a host of other important and various reported effects have been evidenced, such as the electro-informational transfer of retinoic acid influencing human neuroblastoma cells and stem teratocarcinoma cells. Cell proliferation and differentiation effects from informationally affected fields interactive with aqueous systems are measured via microscopy, statistical analysis, reverse transcription polymerase chain reaction and other techniques. Information associated with chemical compounds affects biological aqueous systems, sans direct systemic exposure to the source molecule. This is a quantum effect, based on the interactivity between electromagnetic fields, and aqueous ordered coherence domains. The encoding of aqueous systems and tissue by photonic transfer and instantiation of information rather than via direct exposure to potentially toxic drugs and physical substances holds clear promise of creating inexpensive non-toxic medical treatments.

http://www.scirp.org/journal/PaperInformation.aspx?paperID=68414

BEMER Electromagnetic Field Therapy Reduces Cancer Cell Radioresistance by Enhanced ROS Formation and Induced DNA Damage

Abstract

Each year more than 450,000 Germans are expected to be diagnosed with cancer subsequently receiving standard multimodal therapies including surgery, chemotherapy and radiotherapy. On top, molecular-targeted agents are increasingly administered. Owing to intrinsic and acquired resistance to these therapeutic approaches, both the better molecular understanding of tumor biology and the consideration of alternative and complementary therapeutic support are warranted and open up broader and novel possibilities for therapy personalization. Particularly the latter is underpinned by the increasing utilization of non-invasive complementary and alternative medicine by the population. One investigated approach is the application of low-dose electromagnetic fields (EMF) to modulate cellular processes. A particular system is the BEMER therapy as a Physical Vascular Therapy for which a normalization of the microcirculation has been demonstrated by a low-frequency, pulsed EMF pattern. Open remains whether this EMF pattern impacts on cancer cell survival upon treatment with radiotherapy, chemotherapy and the molecular-targeted agent Cetuximab inhibiting the epidermal growth factor receptor. Using more physiological, three-dimensional, matrix-based cell culture models and cancer cell lines originating from lung, head and neck, colorectal and pancreas, we show significant changes in distinct intermediates of the glycolysis and tricarboxylic acid cycle pathways and enhanced cancer cell radiosensitization associated with increased DNA double strand break numbers and higher levels of reactive oxygen species upon BEMER treatment relative to controls. Intriguingly, exposure of cells to the BEMER EMF pattern failed to result in sensitization to chemotherapy and Cetuximab. Further studies are necessary to better understand the mechanisms underlying the cellular alterations induced by the BEMER EMF pattern and to clarify the application areas for human disease.

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0167931

Effects of alternating magnetic field (12 gauss) on transplanted neuroblastoma

Abstract

Exposure of A/J animals bearing transplanted neuroblastoma (C1300) to a 12 Gauss, 60Hz magnetic field for 16 days, starting 3 days post transplant resulted in - (a) early slowing of tumor growth, (b) more free red blood cells in the tumor areas and (c) a tendency to focal tumor cell destruction suggesting that a small alternating magnetic field may affect transplanted tumor growth.
https://www.ncbi.nlm.nih.gov/pubmed/847289

Selective susceptibility to nanosecond pulsed electric field (nsPEF) across different human cell types.

Abstract

Tumor ablation by nanosecond pulsed electric fields (nsPEF) is an emerging therapeutic modality. We compared nsPEF cytotoxicity for human cell lines of cancerous (IMR-32, Hep G2, HT-1080, and HPAF-II) and non-cancerous origin (BJ and MRC-5) under strictly controlled and identical conditions. Adherent cells were uniformly treated by 300-ns PEF (0-2000 pulses, 1.8 kV/cm, 50 Hz) on indium tin oxide-covered glass coverslips, using the same media and serum. Cell survival plotted against the number of pulses displayed three distinct regions (initial resistivity, logarithmic survival decline, and residual resistivity) for all tested cell types, but with differences in LD₅₀ spanning as much as nearly 80-fold. The non-cancerous cells were less sensitive than IMR-32 neuroblastoma cells but more vulnerable than the other cancers tested. The cytotoxic efficiency showed no apparent correlation with cell or nuclear size, cell morphology, metabolism level, or the extent of membrane disruption by nsPEF. Increasing pulse duration to 9 µs (0.75 kV/cm, 5 Hz) produced a different selectivity pattern, suggesting that manipulation of PEF parameters can, at least for certain cancers, overcome their resistance to nsPEF ablation. Identifying mechanisms and cell markers of differential nsPEF susceptibility will critically contribute to the proper choice and outcome of nsPEF ablation therapies.

https://www.ncbi.nlm.nih.gov/pubmed/27986976

Relevant publication - Electron Spin Interactions in Chemistry and Biology

To understand how magnetic fields affect biological cells, consult this book:
Electron Spin Interactions in Chemistry and Biology
Gertz Likhtenshtein
Dept of Chemistry
Ben-Gurion University of the Negev
Beersheba
Israel
https://books.google.com/books?id=1CG8DAAAQBAJ&pg=PA204&lpg=PA204&dq=biological+cell+electron+spin+in+magnetic+field&source=bl&ots=VRkMgQFP8L&sig=z0qgBfowFz6iDS3zCjfjJ-j54Pk&hl=en&sa=X&ved=0ahUKEwjst9XcmoPRAhUo1oMKHWAJBfMQ6AEINjAE#v=onepage&q=biological%20cell%20electron%20spin%20in%20magnetic%20field&f=false

Bioeffects of Static Magnetic Fields: Oxidative Stress, Genotoxic Effects, and Cancer Studies

Abstract

The interaction of static magnetic fields (SMFs) with living organisms is a rapidly growing field of investigation. The magnetic fields (MFs) effect observed with radical pair recombination is one of the well-known mechanisms by which MFs interact with biological systems. Exposure to SMF can increase the activity, concentration, and life time of paramagnetic free radicals, which might cause oxidative stress, genetic mutation, and/or apoptosis. Current evidence suggests that cell proliferation can be influenced by a treatment with both SMFs and anticancer drugs. It has been recently found that SMFs can enhance the anticancer effect of chemotherapeutic drugs; this may provide a new strategy for cancer therapy. This review focuses on our own data and other data from the literature of SMFs bioeffects. Three main areas of investigation have been covered: free radical generation and oxidative stress, apoptosis and genotoxicity, and cancer. After an introduction on SMF classification and medical applications, the basic phenomena to understand the bioeffects are described. The scientific literature is summarized, integrated, and critically analyzed with the help of authoritative reviews by recognized experts; international safety guidelines are also cited.

https://www.hindawi.com/journals/bmri/2013/602987/

Synergistic inhibitory effect of static magnetic field and antitumor drugs on Hepa1-6 cells

Abstract

Chemotherapy as a routine method for clinical treatment of cancer has disadvantages such as significant toxicity and strong resistance. In order to improve the efficacy of the drugs and reduce the by-effects, we tried to combine static magnetic field (SMF) with cisplatin or adriamycin. The growth of Hepa1-6 cells treated with the static magnetic field (SMF) combined with cisplatin or adriamycin was significantly inhibited, as detected with MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) test. Combined treatment group cells underwent significant morphological changes as observed by HE (Hematoxylin and eosin) staining under optical microscope. Cell cycle analysis indicated that SMF increased the ratio of cells arrested in G2/M phase caused by cisplatin, and when treated with SMF combined with adriamycin, cells were almost arrested in G1 and G2/M phase. SCGE test showed that SMF can enhance the ability of cisplatin or adriamycin to promote cell DNA damage. Atomic force microscope observation found that the combination of antitumor drugs and magnetic field treatment induced larger and deeper holes on the cell membrane, and surface structure damage is serious. The combination of antitumor drugs and magnetic field technology effectively inhibits the growth of tumor cells, and reduces drug doses. The results implicate this method as potential cancer therapy.

https://www.ncbi.nlm.nih.gov/pubmed/26955714