Radiotherapy local irradiation with immune therapy have been demonstrated to induce anti-tumor immunity

Radiotherapy (RT) primarily aims to locally destroy the tumor via the induction of DNA damage in the tumor cells. However, the so-called abscopal, namely systemic and immune–mediated, effects of RT move over more and more in the focus of scientists and clinicians since combinations of local irradiation with immune therapy have been demonstrated to induce anti-tumor immunity. 

We here summarize changes of the phenotype and microenvironment of tumor cells after exposure to irradiation, chemotherapeutic agents, and immune modulating agents rendering the tumor more immunogenic. The impact of therapy-modified tumor cells and damage-associated molecular patterns on local and systemic control of the primary tumor, recurrent tumors, and metastases will be outlined. Finally, clinical studies affirming the bench-side findings of interactions and synergies of radiation therapy and immunotherapy will be discussed. Focus is set on combination of radio(chemo)therapy (RCT) with immune checkpoint inhibitors, growth factor inhibitors, and chimeric antigen receptor T-cell therapy. Well-deliberated combination of RCT with selected immune therapies and growth factor inhibitors bear the great potential to further improve anti-cancer therapies.

https://www.researchgate.net/publication/282867189_Radio-Immunotherapy-Induced_Immunogenic_Cancer_Cells_as_Basis_for_Induction_of_Systemic_Anti-Tumor_Immune_Responses_-_Pre-Clinical_Evidence_and_Ongoing_Clinical_Applications

Low-frequency pulsed electromagnetic field pretreated bone marrow-derived mesenchymal stem cells promote the regeneration of crush-injured rat mental nerve

Bone marrow-derived mesenchymal stem cells (BMSCs) have been shown to promote the regeneration of injured peripheral nerves. Pulsed electromagnetic field (PEMF) reportedly promotes the proliferation and neuronal differentiation of BMSCs. Low-frequency PEMF can induce the neuronal differentiation of BMSCs in the absence of nerve growth factors. This study was designed to investigate the effects of low-frequency PEMF pretreatment on the proliferation and function of BMSCs and the effects of low-frequency PEMF pre-treated BMSCs on the regeneration of injured peripheral nerve using in vitro and in vivo experiments. In in vitro experiments, quantitative DNA analysis was performed to determine the proliferation of BMSCs, and reverse transcription-polymerase chain reaction was performed to detect S100 (Schwann cell marker), glial fibrillary acidic protein (astrocyte marker), and brain-derived neurotrophic factor and nerve growth factor (neurotrophic factors) mRNA expression. In the in vivo experiments, rat models of crush-injured mental nerve established using clamp method were randomly injected with low-frequency PEMF pretreated BMSCs, unpretreated BMSCs or PBS at the injury site (1 × 10⁶ cells). DiI-labeled BMSCs injected at the injury site were counted under the fluorescence microscope to determine cell survival. One or two weeks after cell injection, functional recovery of the injured nerve was assessed using the sensory test with von Frey filaments. Two weeks after cell injection, axonal regeneration was evaluated using histomorphometric analysis and retrograde labeling of trigeminal ganglion neurons. In vitro experiment results revealed that low-frequency PEMF pretreated BMSCs proliferated faster and had greater mRNA expression of growth factors than unpretreated BMSCs. In vivo experiment results revealed that compared with injection of unpretreated BMSCs, injection of low-frequency PEMF pretreated BMSCs led to higher myelinated axon count and axon density and more DiI-labeled neurons in the trigeminal ganglia, contributing to rapider functional recovery of injured mental nerve. These findings suggest that low-frequency PEMF pretreatment is a promising approach to enhance the efficacy of cell therapy for peripheral nerve injury repair. 

http://www.nrronline.org/article.asp?issn=1673-5374;year=2018;volume=13;issue=1;spage=145;epage=153;aulast=Seo

Protective effect of 1950 MHz electromagnetic field in human neuroblastoma cells challenged with menadione

This study aims to assess whether a 1950 MHz radiofrequency (RF) electromagnetic field could protect human neuroblastoma SH-SY5Y cells against a subsequent treatment with menadione, a chemical agent inducing DNA damage via reactive oxygen species formation. Cells were pre-exposed for 20 h to specific absorption rate of either 0.3 or 1.25 W/kg, and 3 h after the end of the exposure, they were treated with 10 µM menadione (MD) for 1 h. No differences were observed between sham- and RF-exposed samples. A statistically significant reduction in menadione-induced DNA damage was detected in cells pre-exposed to either 0.3 or 1.25 W/kg (P < 0.05). Moreover, our analyses of gene expression revealed that the pre-exposure to RF almost inhibited the dramatic loss of glutathione peroxidase-based antioxidant scavenging efficiency that was induced by MD, and in parallel strongly enhanced the gene expression of catalase-based antioxidant protection. In addition, RF abolished the MD-dependent down-regulation of oxoguanine DNA glycosylase, which is a critical DNA repairing enzyme. Overall, our findings suggested that RF pre-exposure reduced menadione-dependent DNA oxidative damage, most probably by enhancing antioxidant scavenging efficiency and restoring DNA repair capability. Our results provided some insights into the molecular mechanisms underlying the RF-induced adaptive response in human neuroblastoma cells challenged with menadione.
https://www.nature.com/articles/s41598-018-31636-7

Epidermal Growth Factor Receptor (EGFR) can be directly inhibited by static magnetic field.

With the development of modern appliances, including MRI machines in the hospitals, concerns to the potential impact of magnetic fields on human health have arisen. It is found that static magnetic field can affect cell proliferation in a cell-type and intensity-dependent way, of which the mechanism, however, remains unclear.

Researchers in the High Magnetic Field Laboratory of the Chinese Academy of Sciences (CHMFL) found that Epidermal Growth Factor Receptor (EGFR), a protein that is over expressed and highly activated in multiple cancers, can be directly inhibited by static magnetic field.

Using Liquid-phase Scanning Tunneling Microscopy and molecular dynamics simulation, they found that the alignment of EGFR kinase domain can be affected by 1-9 T static magnetic fields in an intensity-dependent manner, which may interrupt inter-molecular interactions between EGFR monomers that are critical for their activation. Correspondingly, ultra-strong 9 T magnet evidently inhibited EGFR-expressing cancer cell growth.

Besides, researchers found that 1 T static magnetic field can affect microtubules in cells that are the fundamental components in mitotic spindle and play essential roles in cell division. Combining static magnetic field with chemodrugs, they found that SMFs can increase the antitumor efficacy of 5-FU or 5-FU/Taxol in four different cancer cell lines.

In addition, due to the feedback reactivation of other signaling components, the clinical effects of the most mTOR inhibitors are limited. The study found that 1 T static magnetic field could increase the inhibition efficiency on mTOR substrates and repress mTOR inhibitor-induced feedback reactivation of EGFR and Akt, thus increase the antitumor efficacy of mTOR inhibitor Torin 2.

These findings show that static magnetic fields not only inhibit the growth of cancer cells, but also increase the antitumor efficacy of some chemodrugs. Further studies are expected to reveal the clinical potentials of static magnetic fields in cancer treatment.

This work was jointly done by Dr. XIN Zhang’s group, Dr. LU Qingyou’s group and LI Guohui’ group. And the findings were published in Oncotarget with title Moderate and strong static magnetic fields directly affect EGFR kinase domain orientation to inhibit cancer cell proliferation, Bioelectrochemistry with title Moderate intensity static magnetic fields affect mitotic spindles and increase the antitumor efficacy of 5-FU and Taxol. and Science Bulletin with title 1 T moderate intensity static magnetic field affects Akt/mTOR pathway and increases the antitumor efficacy of mTOR inhibitors in CNE-2Z cells.

The work was funded by “Hundred Talent Program” of the Chinese Academy of Sciences and the National Natural Science Foundation of China.

http://english.cas.cn/newsroom/research_news/201606/t20160622_164712.shtml

Weak power frequency magnetic fields induce microtubule cytoskeleton reorganization depending on the epidermal growth factor receptor and the calcium related signaling

OK, I'm not a scientist.  When I read this was scratching my head, as it is VERY in depth.  The abstract mentions them using 50Hz, which, from my reading, indicates negative connotations (the frequency is key).  However, whether this article indicates such a force is positive, or negative, the fact remains; they elaborate on the subject in great detail, hoping that it may spark ideas in any researchers reading this:

We have shown previously that a weak 50 Hz magnetic field (MF) invoked the actin-cytoskeleton, and provoked cell migration at the cell level, probably through activating the epidermal growth factor receptor (EGFR) related motility pathways. However, whether the MF also affects the microtubule (MT)-cytoskeleton is still unknown. In this article, we continuously investigate the effects of 0.4 mT, 50 Hz MF on the MT, and try to understand if the MT effects are also associated with the EGFR pathway as the actin-cytoskeleton effects were. Our results strongly suggest that the MF effects are similar to that of EGF stimulation on the MT cytoskeleton, showing that 1) the MF suppressed MT in multiple cell types including PC12 and FL; 2) the MF promoted the clustering of the EGFR at the protein and the cell levels, in a similar way of that EGF did but with higher sensitivity to PD153035 inhibition, and triggered EGFR phosphorylation on sites of Y1173 and S1046/1047; 3) these effects were strongly depending on the Ca²⁺ signaling through the L-type calcium channel (LTCC) phosphorylation and elevation of the intracellular Ca²⁺ level. Strong associations were observed between EGFR and the Ca²⁺ signaling to regulate the MF-induced-reorganization of the cytoskeleton network, via phosphorylating the signaling proteins in the two pathways, including a significant MT protein, tau. These results strongly suggest that the MF activates the overall cytoskeleton in the absence of EGF, through a mechanism related to both the EGFR and the LTCC/Ca²⁺ signaling pathways.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0205569

The addition of TTFields to standard treatment results in improved survival

The addition of TTFields (...Tumor Treating Fields) to standard treatment with temozolomide for patients with glioblastoma results in improved survival 

https://jamanetwork.com/journals/jamaoncology/fullarticle/2670704

On possible role of DNA electrodynamics in chromatin regulation

In spite of extensive research, modeling and predictive ability of gene regulation networks are very limited. This difficulty is likely caused not only by the complexity of gene regulation and but also by an incomplete understanding of gene regulation mechanisms. It is suggested that a major gene regulation mechanism has been missing, the one which is mediated by resonances of electron clouds in chromatin structure. Specifically, polynucleosomal models are proposed for macromolecular electron cloud oscillations in chromatin. It is suggested that these oscillations could be the basis for resonances between polynucleosomal structures in the nucleus. These resonances could serve as a basis for the proposed mechanism of natural gene regulation. Understanding this mechanism would help improving the modeling of gene regulation networks and enable the development of new tools for manipulation of gene expression.
https://www.researchgate.net/publication/322150016_On_possible_role_of_DNA_electrodynamics_in_chromatin_regulation

Magnetic isotope and magnetic field effects on the DNA synthesis

The abstract does not give justice to this great publication, read the publication in it's hard to read entirety,  for facts, observations, and a unique hypothesis:
https://academic.oup.com/nar/article/41/17/8300/2411006

Modeling the Electric Potential across Neuronal Membranes: The Effect of Fixed Charges on Spinal Ganglion Neurons and Neuroblastoma Cells

We present a model for the electric potential profile across the membranes of neuronal cells. We considered the resting and action potential states, and analyzed the influence of fixed charges of the membrane on its electric potential, based on experimental values of membrane properties of the spinal ganglion neuron and the neuroblastoma cell. The spinal ganglion neuron represents a healthy neuron, and the neuroblastoma cell, which is tumorous, represents a pathological neuron. We numerically solved the non-linear Poisson-Boltzmann equation for the regions of the membrane model we have adopted, by considering the densities of charges dissolved in an electrolytic solution and fixed on both glycocalyx and cytoplasmic proteins. Our model predicts that there is a difference in the behavior of the electric potential profiles of the two types of cells, in response to changes in charge concentrations in the membrane. Our results also describe an insensitivity of the neuroblastoma cell membrane, as observed in some biological experiments. This electrical property may be responsible for the low pharmacological response of the neuroblastoma to certain chemotherapeutic treatments.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0096194

Cells Membrane Vibration s as a Mechanism of Endogenous ELF Magnetic Field Generation in Biosystems

The proposed model attempts to bring more details into explanation of an intricate mechanism of endogenous ELF magnetic fields generation in living cells. 

It is based on hypothesis that ELF endogenous magnetic fields are initiated by cells as an integral part of their living activities, including selective ion transport and intercellular communications. 

Dynamic variations in length of cytoskeleton microtubules, attached to membrane microdomains were identified in (Cifra, et al., 2007) as a driving force of cells membrane mechanical vibrations. 

Resultant normal to surface vibrations of electrically polarized microdomains is the second part of this mechanism, in which microdomains function as elementary magnetic antennas radiating locally biologically significant ELF magnetic field. 

Besides cell-to-cell synchronization, the resultant endogenous magnetic field is employed by cells for selective ion transport through specific ion channels associated with the microdomain. 

For this, microdomain mechanical vibrations and associated magnetic field are tuned to cyclotron resonance frequency of specific ion type, and facilitates this ion type dehydration. 

The ions dehydration enables their energy-lossless penetration into channels, while the ion-selective channels mimic natural electrical environment of hydrated ion in aqueous solutions (MacKinnon, 2003). 

Remarkable susceptibility of ion channels to exogenous weak ELF magnetic fields tuned to specific ion resonance frequencies, observed in numerous experiments, may be considered an indirect indication of existing build-in magnetic field sensing mechanism employed by living cells routinely for ion traffic regulation and corporative operation.

https://www.researchgate.net/publication/314284442_Cells_Membrane_Vibrations_as_a_Mechanism_of_Endogenous_ELF_Magnetic_Field_Generation_in_Biosystems

TheraBionic approved for use in Liver cancer treatment in Eurpoe

https://www.therabionic.com/press-releases/

Tumor-Treating Fields: A Fourth Modality in Cancer Treatment

Despite major advances in therapy, cancer continues to be a leading cause of mortality. In addition, toxicities of traditional therapies pose a significant challenge to tolerability and adherence. TTFields, a noninvasive anticancer treatment modality, utilizes alternating electric fields at specific frequencies and intensities to selectively disrupt mitosis in cancerous cells. TTFields target proteins crucial to the cell cycle, leading to mitotic arrest and apoptosis. TTFields also facilitate an antitumor immune response. Clinical trials of TTFields have proven safe and efficacious in patients with glioblastoma multiforme (GBM), and are FDA approved for use in newly diagnosed and recurrent GBM. Trials in other localized solid tumors are ongoing. 
http://clincancerres.aacrjournals.org/content/24/2/266

Tubulin's response to external electric fields by molecular dynamics simulations

Tubulin heterodimers are the building blocks of microtubules and disruption of their dynamics is exploited in the treatment of cancer. 

Electric fields at certain frequencies and magnitudes are believed to do the same. 

Here, the tubulin dimer's response to external electric fields was determined by atomistic simulation. 

External fields from 50 to 750 kV/cm, applied for 10 ns, caused significant conformational rearrangements that were dependent upon the field's directionality. 

Charged and flexible regions, including the α:H1-B2 loop, β:M-loop, and C-termini, were susceptible. 

Closer inspection of the α:H1-B2 loop in lower strength fields revealed that these effects were consistent and proportional to field strength, and the findings indicate that external electric fields modulate the stability of microtubules through conformational changes to key loops involved in lateral contacts. 

We also find evidence that tubulin's curvature and elongation are affected, and external electric fields may bias tubulin towards depolymerization.

https://www.researchgate.net/publication/327755624_Tubulin%27s_response_to_external_electric_fields_by_molecular_dynamics_simulations