Evolution of Using the Electric Field in Medical Applications

Qusay Kh. Al-Dulamey, Rana Hesham Mahmood, Mahmoud A M Fakhri, Marwan Zhuhair

Volume 6, Issue 4 2022

Page: 23-35

Abstract

Direct-current electric fields and exogenous alternating electric fields have long been examined for their biological effects, which vary from implications for embryonic development to influences on wound healing. The employ electric fields to cure tumors is the main topic of this essay. This article focuses on the clinical effects of tumor treating fields, a type of AEF, on the therapy of cancers including glioblastoma and mesothelioma. We give a summary of TT Fields' typical mode of action, which is their capacity to interfere with specifically dividing cells generate and segregate their mitotic spindles. Even if the operation of TT Fields can be largely explained by this common mechanism, it is by no means all-inclusive. The direct impact of exogenously applied AEFs on DNA as well as their Mainstream theory does not take into account the ability to alter the permeability and functionality of cancer cell membranes.. In order to give readers a more thorough understanding of how AEFs affect cell membranes, this review provides a summary of the most recent research. It provides a summary of three mechanical theories that possibly explain the more recent observations on the effects of AEFs made using the gated ion channel voltage, bio electrorheological, and electroporation model. There were inconsistencies between TTFields for all three proposed models' effective frequency range and field strength. Through theoretical investigations into how different electric fields affect cellular membranes depending on the presence or absence of a disease, the external microenvironment, and the structure of the tissue or cell, we resolved these differences. Finally, potential experimental approaches to confirm these results are described. Clinical advantages will eventually materialize.

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References

  • Bresadola, M. Medicine and science in the life of Luigi Galvani (1737–1798). Brain Res. Bull. 1998, 46, 367–380.
  • Funk, R.H.; Monsees, T.; Özkucur, N. Electromagnetic effects—From cell biology to medicine. Prog. Histochem. Cytochem. 2009, 43, 177–264.
  • Levin, M. Bioelectromagnetic in morphogenesis. Bioelectromagnetic 2003, 24, 295–315.
  • McCaig, C.D.; Zhao, M. Physiological electrical fields modify cell behaviour. BioEssays 1997, 19, 819– 826.
  • Karanam, N.K.; Story, M.D. An overview of potential novel mechanisms of action underlying Tumor Treating Fields-induced cancer cell death and their clinical implications. Int. J. Radiat. Biol. 2020, 1– 11.
  • Fueredi, A.A.; Ohad, I. Effects of high-frequency electric fields on the living cell. I. Behaviour of human erythrocytes in high- frequency electric fields and its relation to their age. Biochim. Biophys. Acta 1964, 79, 1–8.
  • Novickij, V.; Ruzgys, P.; Grainys, A.; Å atkauskas, S. High frequency electroporation efficiency is under control of membrane capacitive charging and voltage potential relaxation. Bioelectrochemistry 2018, 119, 92–97.
  • Giladi, M.; Schneiderman, R.S.; Voloshin, T.; Porat, Y.; Munster, M.; Blat, R.; Sherbo, S.; Bomzon, Z.; Urman, N.; Itzhaki, A.; et al. Mitotic Spindle Disruption by Alternating Electric Fields Leads to Improper Chromosome Segregation and Mitotic Catastrophe in Cancer Cells. Sci. Rep. 2016, 5, 18046.
  • Kirson, E.D.; Gurvich, Z.; Schneiderman, R.; Dekel, E.; Itzhaki, A.; Wasserman, Y.; Schatzberger, R.; Palti, Y. Disruption of Cancer Cell Replication by Alternating Electric Fields. Cancer Res. 2004, 64, 3288– 3295.
  • Kirson, E.D.; Schneiderman, R.S.; Dbalý, V.; TovaryÅ¡, F.; Vymazal, J.; Itzhaki, A.; Mordechovich, D.; Gurvich, Z.; Shmueli, E.; Goldsher, D.; et al. Chemotherapeutic treatment efficacy and sensitivity are increased by adjuvant alternating electric fields (TTFields). BMC Med. Phys. 2009, 9, 1–13.
  • Stupp, R.; Taillibert, S.; Kanner, A.A.; Kesari, S.; Steinberg, D.M.; Toms, S.A.; Taylor, L.P.; Lieberman, F.; Silvani, A.; Fink, K.L.; et al. Maintenance Therapy with Tumor-Treating Fields Plus Temozolomide vs. Temozolomide Alone for Glioblastoma. JAMA 2015, 314, 2535–2543.
  • Stupp, R.; Taillibert, S.; Kanner, A.; Read, W.; Steinberg, D.M.; Lhermitte, B.; Toms, S.; Idbaih, A.; Ahluwalia, M.S.; Fink, K.; et al. Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs. Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma. JAMA 2017, 318, 2306– 2316.
  • Ceresoli, G.L.; Aerts, J.G.; Dziadziuszko, R.; Ramlau, R.; Cedres, S.; van Meerbeeck, J.P.; Mencoboni, M.; Planchard, D.; Chella, A.; Crinò, L.; et al. Tumour Treating Fields in combination with pemetrexed and cisplatin or carboplatin as first-line treatment for unresectable malignant pleural mesothelioma (STELLAR): A multicentre, single-arm phase 2 trial. Lancet Oncol. 2019, 20, 1702–1709.
  • Vogelzang, N.J.; Rusthoven, J.J.; Symanowski, J.; Denham, C.; Kaukel, E.; Ruffie, P.; Gatzemeier, U.; Boyer, M.; Emri, S.; Manegold, C.; et al. Phase III Study of Pemetrexed in Combination With Cisplatin Versus Cisplatin Alone in Patients With Malignant Pleural Mesothelioma. J. Clin. Oncol. 2003, 21, 2636– 2644.
  • Zalcman, G.; Mazieres, J.; Margery, J.; Greillier, L.; Audigier-Valette, C.; Moro-Sibilot, D.; Molinier, O.; Corre, R.; Monnet, I.; Gounant, V.; et al. Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): A randomised, controlled, open-label, phase 3 trial. Lancet 2016, 387, 1405–1414.
  • Hottinger, A.F.; Stupp, R.; Homicsko, K. Standards of care and novel approaches in the management of glioblastoma multiforme. Chin. J. Cancer 2014, 33, 32–39.
  • Davies, A.M.; Weinberg, U.; Palti, Y. Tumor treating fields: A new frontier in cancer therapy. Ann. N. Y. Acad. Sci. 2013, 1291, 86–95.
  • Hottinger, A.F.; Pacheco, P.; Stupp, R. Tumor treating fields: A novel treatment modality and its use in brain tumors. Neuro Oncol. 2016, 18, 1338–1349.
  • Tuszynski, J.A.; Wenger, C.; Friesen, D.E.; Preto, J. An Overview of Sub-Cellular Mechanisms Involved in the Action of TTFields. Int. J. Environ. Res. Public Heal. 2016, 13, 1128.
  • Chaudhry, A.; Benson, L.; Varshaver, M.; Farber, O.;Weinberg, U.; Kirson, E.D.; Palti, Y. NovoTTFâ„¢- 100A System [or eating Fields] transducer array layout planning for glioblastoma: A NovoTALâ„¢ system user study. World J. Surg. Oncol. 2015, 13, 1–7.
  • Stupp, R.; Wong, E.T.; Kanner, A.A.; Steinberg, D.; Engelhard, H.; Heidecke, V.; Kirson, E.D.; Taillibert, S.; Liebermann, F.; Dbalý, V.; et al. NovoTTF-100A versus physician’s choice chemotherapy in recurrent glioblastoma: A randomised phase III trial of a novel treatment modality. Eur. J. Cancer 2012, 48, 2192– 2202.
  • Mrugala, M.M.; Engelhard, H.H.; Tran, D.D.; Kew, Y.; Cavaliere, R.; Villano, J.L.; Bota, D.A.; Rudnick, J.; Sumrall, A.L.; Zhu, J.-J.; et al. Clinical Practice Experience With NovoTTF-100Aâ„¢ System for Glioblastoma: The Patient Registry Dataset (PRiDe). Semin. Oncol. 2014, 41, S4–S13.
  • Gallego, O. Nonsurgical Treatment of Recurrent Glioblastoma. Curr. Oncol. 2015, 22, 273–281.
  • Wong, E.T.; Lok, E.; Swanson, K.D. Alternating Electric Fields Therapy for Malignant Gliomas: From Bench Observation to Clinical Reality. Prog. Neurol. Surg. 2018, 32, 180–195.
  • Gera, N.; Yang, A.; Holtzman, T.S.; Lee, S.X.; Wong, E.T.; Swanson, K.D. Tumor Treating Fields Perturb the Localization of Septins and Cause Aberrant Mitotic Exit. PLoS ONE 2015, 10, e0125269.
  • Chang, E.; Pohling, C.; Beygui, N.; Patel, C.B.; Rosenberg, J.; Ha, D.H.; Gambhir, S.S. Synergistic inhibition of glioma cell proliferation by Withaferin A and tumor treating fields. J. Neuro Oncol. 2017, 134, 259–268.
  • Chang, E.; Patel, C.B.; Pohling, C.; Young, C.; Song, J.; Flores, T.A.; Zeng, Y.; Joubert, L.-M.; Arami, H.; Natarajan, A.; et al. Tumor treating fields increases membrane permeability in glioblastoma cells. Cell Death Discov. 2018, 4, 1–13.
  • Lobikin, M.; Chernet, B.; Lobo, D.; Levin, M. Resting potential, oncogene-induced tumorigenesis, and metastasis: The bioelectric basis of cancer in vivo. Phys. Biol. 2012, 9, 065002.
  • Marino, A.A.; Iliev, I.G.; Schwalke, M.A.; González, E.; Marler, K.C.; Flanagan, C.A. Association between Cell Membrane Potential and Breast Cancer. Tumor Biol. 1994, 15, 82–89.
  • Tokuoka, S.; Morioka, H. The membrane potential of the human cancer and related cells. I. Gan 1957, 48, 353–354.
  • Yang, M.; Brackenbury, W.J. Membrane potential and cancer progression. Front. Physiol. 2013, 4, 185.
  • Barnes, J.M.; Nauseef, J.T.; Henry, M.D. Resistance to Fluid Shear Stress Is a Conserved Biophysical Property of Malignant Cells. PLoS ONE 2012, 7, e50973.
  • Huang, Q.; Hu, X.; He, W.; Zhao, Y.; Hao, S.; Wu, Q.; Li, S.; Zhang, S.; Shi, M. Fluid shear stress and tumor metastasis. Am. J. Cancer Res. 2018, 8, 763–777.
  • Sok, M.; Å entjurc, M.; Schara, M.; Stare, J.; Rott, T. Cell membrane fluidity and prognosis of lung cancer. Ann. Thorac. Surg. 2002, 73, 1567–1571.
  • Lastraioli, E.; Iorio, J.; Arcangeli, A. Ion channel expression as promising cancer biomarker. Biochim. Biophys. Acta (BBA) Biomembr. 2015, 1848, 2685–2702.
  • Wenger, C.; Giladi, M.; Bomzon, Z.; Salvador, R.; Basser, P.J.; Miranda, P.C. Modeling Tumor Treating Fields (TTFields) application in single cells during metaphase and telophase. In Proceedings of the 2015 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), Milan, Italy, 25–29 August 2015; Institute of Electrical and Electronics Engineers (IEEE): Piscataway, NJ, USA, 2015; Volume 2015, pp. 6892–6895.
  • Wong, E.T.; Lok, E.; Swanson, K.D. An Evidence-Based Review of Alternating Electric Fields Therapy for Malignant Gliomas. Curr. Treat. Options Oncol. 2015, 16, 40.
  • Hering, S.; Beyl, S.; Stary, A.; Kudrnac, M.; Hohaus, A.; Guy, R.H.; Timin, E.; Beyl, S.; Guy, H.R. Pore stability and gating in voltage-activated calcium channels. Channels 2008, 2, 61–69.
  • Hering, S.; Zangerl-Plessl, E.-M.; Beyl, S.; Hohaus, A.; Andranovits, S.; Timin, E.N. Calcium channel gating. Pflüger Arch. Für Die Gesammte Physiol. Des Menschen Tiere 2018, 470, 1291–1309.
  • ]PawÅ‚owski, P.; Fikus, M. Bioelectrorheological model of the cell. Analysis of the extensil deformation of cellular membrane in alternating electric field. Biophys. J. 1993, 65, 535–540.
  • López-Alonso, B.; Hernáez, A.; Sarnago, H.; Naval, A.; Güemes, A.; Junquera, C.; Burdío, J.M.; Castiella, T.; Monleón, E.; Gracia-Llanes, J.; et al. Histopathological and Ultrastructural Changes after Electroporation in Pig Liver Using Parallel-Plate Electrodes and High-Performance Generator. Sci. Rep. 2019, 9, 2647.
  • Tenforde TS, Kaune WT. Interaction of extremely low frequency electric and magnetic fields with humans. Health Physics 1987; 53(6):585–606.
  • Takuma T, et al. at a symposium entitled. Evaluation of electric field and current in a human body induced by electromagnetic fields. 1-S6-1 ∼ 1-S6-8 (in Japanese), Annual Meeting of the IEEJ, at Tokushima (2005-3).
  • ICNIRP. Guidelines for limiting exposure to time-varying electric, magnetic, and electromagnetic fields (up to 300 GHz). Health Physics 1998; 74(4):494–522.
  • IEEE C 95.6–2002. Standards for safety levels with respect to human exposure to electromagnetic fields, 0 to 3 kHz, 2002.
  • Joshi RP, Schoenbach KH. Electroporation dynamics in biological cells subjected to ultrafast electrical pulses: A numerical simulation study. Physical Review E 2000; 62:1025–1033.
  • Weaver JC. Electroporation of biological membranes from multicellular to nano scales. IEEE Transactions on Dielectrics and Electrical Insulation 2003; 10(5):754–768.

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