A non-invasive way to treat brain tumours

After treating 300 cancer patients from across the world over the past decade, Bengaluru-based SBF Healthcare & Research Centre (SHRC) has formally announced a treatment based on a new technology called SPMF (Sequentially Programmed Magnetic Field) therapy.

SHRC has received the US Patent and CE as well as ISO 9001:2008 and ISO 13485 certification for this technology.

Pioneered by Wg Cdr (Retd) Dr Vasishta, SHRC was founded in 2006 and claims to be the first in the world to use SPMF therapy in the treatment of cancer.

Based on MRI technology, the therapy is delivered by the AKTIS SOMA device invented by Dr Vasishta, which resembles an MRI machine but, unlike one, allows for a lot more breathing space for the patient without making him or her claustrophobic.

SPMF produces highly complex sequentially programmed magnetic fields, which are computer controlled and can be precisely focused on the cancerous tissues with the help of laser guides.

“The only available mode of treatment today anywhere in the world is surgery followed by radiation and chemotherapy. We have treated GBM (glioblastoma multiforme), a very common form of brain tumour with very little or no chance of survival, very successfully and patients have gone back to their normal routine,” Dr Vasishta told BusinessLine. The patients are evaluated using MRI and the Karnofsky performance score, which are considered gold standards for evaluating the efficacy of a therapy.

No side-effects

SPMF therapy is performed for one hour every day for 28 consecutive days as an outpatient treatment and costs ₹1.5 lakh. The treatment is non-invasive, has no side-effects and asks for no dietary restrictions.

http://www.thehindubusinessline.com/news/a-noninvasive-way-to-treat-brain-tumours/article9795713.ece

Endogenous Bioelectric Signaling Networks: Exploiting Voltage Gradients for Control of Growth and Form

Living systems exhibit remarkable abilities to self-assemble, regenerate, and remodel complex shapes. How cellular networks construct and repair specific anatomical outcomes is an open question at the heart of the next-generation science of bioengineering. Developmental bioelectricity is an exciting emerging discipline that exploits endogenous bioelectric signaling among many cell types to regulate pattern formation. We provide a brief overview of this field, review recent data in which bioelectricity is used to control patterning in a range of model systems, and describe the molecular tools being used to probe the role of bioelectrics in the dynamic control of complex anatomy. We suggest that quantitative strategies recently developed to infer semantic content and information processing from ionic activity in the brain might provide important clues to cracking the bioelectric code. Gaining control of the mechanisms by which large-scale shape is regulated in vivo will drive transformative advances in bioengineering, regenerative medicine, and synthetic morphology, and could be used to therapeutically address birth defects, traumatic injury, and cancer.
http://www.annualreviews.org/doi/full/10.1146/annurev-bioeng-071114-040647

BETSE (BioElectric Tissue Simulation Engine) is an open-source cross-platform finite volume simulator for 2D computational multiphysics problems in the life sciences

BETSE (BioElectric Tissue Simulation Engine) is an open-source cross-platform finite volume simulator for 2D computational multiphysics problems in the life sciences – including electrodiffusion, electro-osmosis, galvanotaxis, voltage-gated ion channels, gene regulatory networks, and biochemical reaction networks (e.g., metabolism). BETSE is associated with the Paul Allen Discovery Center at Tufts University and supported by a Paul Allen Discovery Center award from the Paul G. Allen Frontiers Group.
https://pypi.python.org/pypi/betse/0.6.1

Everything you ever wanted to know about Bioelectricity

Wow, great resource with alot of scientific references:
Modern Bioelectricity
http://cassandrapublishing.net/MB/ModernBioelectricity.pdf

For anyone doing research: Fractional Calculus Based FDTD Modeling of Layered Biological Media Exposure to Wideband Electromagnetic Pulses

Fractional Calculus Based FDTD Modeling of Layered Biological Media Exposure to Wideband Electromagnetic Pulses

Contains math to determine the penetration of electromagnetic fields in elements of the body:
PDF Here: file:///E:/Downloads/electronics-06-00106%20(1).pdf

Molecular mechanisms underlying antiproliferative and differentiating responses of hepatocarcinoma cells to subthermal electric stimulation.

Abstract

Capacitive Resistive Electric Transfer (CRET) therapy applies currents of 0.4-0.6 MHz to treatment of inflammatory and musculoskeletal injuries. Previous studies have shown that intermittent exposure to CRET currents at subthermal doses exert cytotoxic or antiproliferative effects in human neuroblastoma or hepatocarcinoma cells, respectively. It has been proposed that such effects would be mediated by cell cycle arrest and by changes in the expression of cyclins and cyclin-dependent kinase inhibitors. The present work focuses on the study of the molecular mechanisms involved in CRET-induced cytostasis and investigates the possibility that the cellular response to the treatment extends to other phenomena, including induction of apoptosis and/or of changes in the differentiation stage of hepatocarcinoma cells. The obtained results show that the reported antiproliferative action of intermittent stimulation (5 m On/4 h Off) with 0.57 MHz, sine wave signal at a current density of 50 µA/mm(2), could be mediated by significant increase of the apoptotic rate as well as significant changes in the expression of proteins p53 and Bcl-2. The results also revealed a significantly decreased expression of alpha-fetoprotein in the treated samples, which, together with an increased concentration of albumin released into the medium by the stimulated cells, can be interpreted as evidence of a transient cytodifferentiating response elicited by the current. The fact that this type of electrical stimulation is capable of promoting both, differentiation and cell cycle arrest in human cancer cells, is of potential interest for a possible extension of the applications of CRET therapy towards the field of oncology.

https://www.ncbi.nlm.nih.gov/pubmed/24416255

Unraveling the mechanistic effects of electric field stimulation towards directing stem cell fate and function: A tissue engineering perspective

Abstract

Electric field (EF) stimulation can play a vital role in eliciting appropriate stem cell response. Such an approach is recently being established to guide stem cell differentiation through osteogenesis/neurogenesis/cardiomyogenesis. Despite significant recent efforts, the biophysical mechanisms by which stem cells sense, interpret and transform electrical cues into biochemical and biological signals still remain unclear. The present review critically analyses the variety of EF stimulation approaches that can be employed to evoke appropriate stem cell response and also makes an attempt to summarize the underlying concepts of this notion, placing special emphasis on stem cell based tissue engineering and regenerative medicine. This review also discusses the major signaling pathways and cellular responses that are elicited by electric stimulation, including the participation of reactive oxygen species and heat shock proteins, modulation of intracellular calcium ion concentration, ATP production and numerous other events involving the clustering or reassembling of cell surface receptors, cytoskeletal remodeling and so on. The specific advantages of using external electric stimulation in different modalities to regulate stem cell fate processes are highlighted with explicit examples, in vitro and in vivo.
http://www.sciencedirect.com/science/article/pii/S0142961217306300

The use of electric, magnetic, and electromagnetic field for directed cell migration and adhesion in regenerative medicine

Directed cell migration and adhesion is essential to embryonic development, tissue formation and wound healing. For decades it has been reported that electric field (EF), magnetic field (MF) and electromagnetic field (EMF) can play important roles in determining cell differentiation, migration, adhesion, and even wound healing. Combinations of these techniques have revealed new and exciting explanations for how cells move and adhere to surfaces; how the migration of multiple cells are coordinated and regulated; how cells interact with neighboring cells, and also to changes in their microenvironment. In some cells, speed and direction are voltage dependent. Data suggests that the use of EF, MF and EMF could advance techniques in regenerative medicine, tissue engineering and wound healing.
http://onlinelibrary.wiley.com/doi/10.1002/btpr.2371/full

Low Frequency Magnetic Fields Induce Autophagy-associated Cell Death in Lung Cancer through miR-486-mediated Inhibition of Akt/mTOR Signaling Pathway

Low frequency magnetic fields (LF-MFs) can affect cell proliferation in a cell-type and intensity-dependent way. Previous study has reported the anti-tumor effect of LF-MFs in lung cancers. Our previous study also optimized the intensity and duration of LF-MFs to effectively inhibit the proliferation of lung cancer cells. However, the anti-tumor mechanism of LF-MFs remains unclear, which limit the clinical application of LF-MFs in anti-tumor therapy. Here, in a well-established Lewis Lung Cancer (LLC) mouse model, we found that LF-MFs inhibit tumor growth and induce an autophagic cell death in lung cancer. We also found that LF-MFs could up-regulate the expression level of miR-486, which was involved in LF-MFs activated cell autophagy. Furthermore, we found B-cell adaptor for phosphatidylinositol 3-kinase (BCAP) is a direct target of miR-486. miR-486 inhibit AKT/mTOR signaling through inhibiting expression of BCAP. Moreover, a decreased expression of miR-486 and an increased expression of BCAP were found in tumor tissues of lung cancer patients. Taken together, this study proved that LF-MFs can inhibit lung cancers through miR-486 induced autophagic cell death, which suggest a clinical application of LF-MFs in cancer treatment.
https://www.nature.com/articles/s41598-017-10407-w

Magnetic Fields and Reactive Oxygen Species

Abstract

Reactive oxygen species (ROS) ubiquitously exist in mammalian cells to participate in various cellular signaling pathways. The intracellular ROS levels are dependent on the dynamic balance between ROS generation and elimination. In this review, we summarize reported studies about the influences of magnetic fields (MFs) on ROS levels. Although in most cases, MFs increased ROS levels in human, mouse, rat cells, and tissues, there are also studies showing that ROS levels were decreased or not affected by MFs. Multiple factors could cause these discrepancies, including but not limited to MF type/intensity/frequency, exposure time and assay time-point, as well as different biological samples examined. It will be necessary to investigate the influences of different MFs on ROS in various biological samples systematically and mechanistically, which will be helpful for people to get a more complete understanding about MF-induced biological effects. In addition, reviewing the roles of MFs in ROS modulation may open up new scenarios of MF application, which could be further and more widely adopted into clinical applications, particularly in diseases that ROS have documented pathophysiological roles
http://www.mdpi.com/1422-0067/18/10/2175

Enhancing cold atmospheric plasma treatment of cancer cells by static magnetic field

Abstract

It has been reported since late 1970 that magnetic field interacts strongly with biological systems. Cold atmospheric plasma (CAP) has also been widely studied over the past few decades in physics, biology, and medicine. In this study, we propose a novel idea to combine static magnetic field (SMF) with CAP as a tool for cancer therapy. Breast cancer cells and wild type fibroblasts were cultured in 96-well plates and treated by CAP with or without SMF. Breast cancer cells MDA-MB-231 showed a significant decrease in viability after direct plasma treatment with SMF (compared to only plasma treatment). In addition, cancer cells treated by the CAP-SMF-activated medium (indirect treatment) also showed viability decrease but was slightly weaker than the direct plasma-SMF treatment. By integrating the use of SMF and CAP, we were able to discover their advantages that have yet to be utilized. Bioelectromagnetics. 38:53–62, 2017. © 2016 Wiley Periodicals, Inc.

• Enhanced PDF
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INTRODUCTION

In the past few decades, cold atmospheric plasma (CAP) has been widely used in various fields such as material processing [Zelzer et al., 2012], bacterial inactivation [Deng et al., 2007], wound healing, cut coagulation [Isbary et al., 2012], cancer therapy [Shashurin et al., 2008; Keidar et al., 2011; Barekzi and Laroussi, 2012; Walk et al., 2013], and viral destruction [Shi et al., 2012]. The temperature of heavy species in CAP is usually close to room temperature, allowing its application to living tissue treatment [Keidar, 2015].
It has been reported since the late 1970s that a magnetic field (MF) appears to have a strong effect on biological systems [Bawin and Sabbot, 1978; Liboff, 1985; Halle, 1988; Liboff and McLeod, 1988]. Research on the electromagnetic field effect on biological systems advanced after Wertheimer and Leeper [1979] found that the likelihood of developing leukemia in children increased as they were present in 60 Hz frequency electromagnetic field. As the research progressed, it appeared as though vibrational energy levels in the ion–protein complex were pumping into the system, which was creating parametric resonance. This occurs when the atoms shake slightly [Lednev, 1991]. This “shaking” is an anomaly that can change ion flux through the cell membrane [Liboff et al., 1987] or cell mobility [McLeod et al., 1987; Smith et al., 1987]. Santoro et al. [1997] showed that extremely low frequency (ELF) MFs influence physiological processes in different organisms, such as plasma membrane structure modification and initiation of signal cascade pathways interference. Cell membrane morphology modification by ELF was again reaffirmed by Ikehara et al. [2003], who found that exposure to the ELF MF has reversible effects on NH inplane bending and CN stretching vibrations of peptide linkages, and changes the secondary structures of α-helix and β-sheet in cell membrane proteins.
Link to Publication

Quantum Information Medicine: Bit as It—The Future Direction of Medical Science: Antimicrobial and Other Potential Nontoxic Treatments

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 anti-microbial 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.
https://www.researchgate.net/publication/305343138_Quantum_Information_Medicine_Bit_as_It-The_Future_Direction_of_Medical_Science_Antimicrobial_and_Other_Potential_Nontoxic_Treatments

Power frequency magnetic field promotes a more malignant phenotype in neuroblastoma cells via redox-related mechanisms

In accordance with the classification of the International Agency for Research on Cancer, extremely low frequency magnetic fields (ELF-MF) are suspected to promote malignant progression by providing survival advantage to cancer cells through the activation of critical cytoprotective pathways. Among these, the major antioxidative and detoxification defence systems might be targeted by ELF-MF by conferring cells significant resistance against clinically-relevant cytotoxic agents. We investigated whether the hyperproliferation that is induced in SH-SY5Y human neuroblastoma cells by a 50 Hz, 1 mT ELF magnetic field was supported by improved defence towards reactive oxygen species (ROS) and xenobiotics, as well as by reduced vulnerability against both H 2 O 2 and anti-tumor ROS-generating drug doxorubicin. ELF-MF induced a proliferative and survival advantage by activating key redox-responsive antioxidative and detoxification cytoprotective pathways that are associated with a more aggressive behavior of neuroblastoma cells. This was coupled with the upregulation of the major sirtuins, as well as with increased signaling activity of the erythroid 2-related nuclear transcription factor 2 (NRF2). Interestingly, we also showed that the exposure to 50 Hz MF as low as 100 µT may still be able to alter behavior and responses of cancer cells to clinically-relevant drugs.
https://www.researchgate.net/publication/319678929_Power_frequency_magnetic_field_promotes_a_more_malignant_phenotype_in_neuroblastoma_cells_via_redox-related_mechanisms

Theoretical framework for a fundamental understanding of the effects of magnetic gradient forces on intracellular processes

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.

To identify the intracellular targets and molecular effectors of magnetic fields and to reveal the underlying mechanisms, many complex multidisciplinary problems must be solved. As is often the case when multiple disciplines address a complex scientific problem, theoretical models and mathematical equations can provide a unifying platform to synergize the efforts. We present a theoretical framework for a fundamental understanding of the effects of magnetic gradient forces on intracellular processes, highlighting new directions of the study of living cell machinery affected by magneto-mechanical forces.

https://www.nature.com/articles/srep37407?WT.feed_name=subjects_physical-sciences

The informational magnecule: the role of aqueous coherence and information in biological dynamics and morphology.

This is really indepth, to the point you may not think it is applicable here, however, if you are educated and informed, what this paper presents is key to a non invasive cure for cancer:

Biological systems are dependent upon and intertwined with aqueous systems. We will present empirically derived evidence of the unique properties of water and demonstrate the efficacious role of molecular electromagnetic informational encoding as mediated through aqueous dynamics and mnemic properties. Working theory will then be articulated from quantum, thermodynamic and Hadronic aspects. An aqueous molecular species of dynamic magnecule will then be defined. Implications are drawn which point to a possible nontoxic, purely informational potential for future medical and pharmacological science. Magnecules and aqueous informational magnecular dynamics may one day redefine energy storage and production, as well as medical practice.
The informational magnecule: the role of aqueous coherence and information in biological dynamics and morphology. *. Available from: https://www.researchgate.net/publication/312578881_The_informational_magnecule_the_role_of_aqueous_coherence_and_information_in_biological_dynamics_and_morphology [accessed Sep 15, 2017].

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/