The malignant processes deviate from the healthy homeostatic control, and various “tricks” enable malignant cells to avoid the healthy regulation. Consequently, the malignant structures miss the apoptosis and proliferate without restriction, and without the formation of communication networks in the newly formed cells. The modulation supports the homeostatic control to rearrange the health regulation processes in various ways. The modulation acts with stochastic processes, using stochastic resonances for molecular excitations, supporting the regulative enzymatic processes. The number of stochastic resonant frequencies is as many as the number of enzymatic reactions. The malignant cells differ structurally and dynamically in their connections and interactions from their healthy host tissues. The radiofrequency carrier is modulated with an appropriate time-fractal (1/f) noise to select the autonomic cancer-cells, destroy them, or force the precancerous, semi-individual cells to participate in the networking connections. The modulation in this way limits the cellular autonomy of malignant cells and boosts the healthy control. The resonant energy triggers apoptotic processes and helps immunogenic actions deliver extracellular genetic information for antigen-presentation. The modulation is applied in clinical practice. The therapy (modulated electro-hyperthermia, mEHT) is intensively used in oncology in complementary applications and for palliative stages, and occasionally even as a monotherapy.
References
[1]
Trigos, A.S., Pearson, R.B., Papenfuss, A.T., et al. (2016) Altered Interactions between Unicellular and Multicellular Genes Drive Hallmarks of Transformation in a Diverse Range of Solid Tumors. PNAS, 114, 6406-6411. https://doi.org/10.1073/pnas.1617743114
Balmain, A., Gray, J. and Ponder, B. (2014) The Genetics and Genomics of Cancer. Nature Genetics Supplement, 33, 238-244. https://doi.org/10.1038/ng1107
[4]
Szigeti, G.P., Szasz, O. and Hegyi, G. (2017) Connections between Warburg’s and Szentgyorgyi’s Approach about the Causes of Cancer. Journal of Neoplasm, 1, 1-13.
[5]
Hanahan, D. and Weinberg, R.A. (2000) The Hallmarks of Cancer. Cell, 100, 57-70. https://doi.org/10.1016/S0092-8674(00)81683-9
[6]
Hanahan, D. and Weinberg, R.A. (2011) Hallmarks of Cancer: The Next Generation. Cell, 144, 646-674. https://doi.org/10.1016/j.cell.2011.02.013
[7]
Dyas, F.G. (1928) Chronic Irritation as a Cause of Cancer. JAMA, 90, 457. https://doi.org/10.1001/jama.1928.92690330003008c
[8]
Dvorak, H.F. (1986) Tumors: Wounds That Do Not Heal, Similarities between Tumor Stroma Generation and Wound Healing. The New England Journal of Medicine, 315, 1650-1659. https://doi.org/10.1056/NEJM198612253152606
[9]
Platz, E.A. and Marzo, A.M. (2004) Epidemiology of Inflammation and Prostate Cancer. The Journal of Urology, 171, S36-S40. https://doi.org/10.1097/01.ju.0000108131.43160.77
[10]
Punyiczki, M. and Fesus, L. (1998) Heat Shock and Apoptosis: The Two Defense Systems of the Organisms May Have Overlapping Molecular Elements. Annals of the New York Academy of Sciences, 951, 67-74. https://doi.org/10.1111/j.1749-6632.1998.tb08978.x
[11]
Aktipis, C.A., Bobby, A.M., Jansen, G., et al. (2015) Cancer across the Tree of Life: Cooperation and Cheating in Multicellularity. Philosophical Transactions of the Royal Society B, 370, Article ID: 20140219. https://doi.org/10.1098/rstb.2014.0219
[12]
Varma, R. and Selman, J.S., (1991) Techniques for Characterisation of Electrodes and Electrochemical Processes. John Wiley & Sons, New York.
[13]
Jacobsen, T. and West, K. (1995) Diffusion Impedance for Planar, Cylindrical, and Spherical Geometry. Electrochimica Acta, 40, 255-262. https://doi.org/10.1016/0013-4686(94)E0192-3
Goldup, A., Ohki, S. and Danielli, J.F. (1970) Black Lipid Films. Recent Progress in Surface Science, 3, 193-261. https://doi.org/10.1016/B978-0-12-571803-5.50013-4
[16]
Goldman, D.E. (1943) Potential, Impedance, and Rectification in Membranes. Journal of General Physiology, 27, 37-60. https://doi.org/10.1085/jgp.27.1.37
[17]
Ramachandran, S., Blick, R.H. and van der Weide, D.W. (2010) Radio-Frequency Rectification on Membrane Bound Pores. Nanotechnology, 1, 75201. https://doi.org/10.1088/0957-4484/21/7/075201
[18]
Tanaka, A. and Tokimasa, T. (1999) Theoretical Background for Inward Rectification. Tokai Journal of Experimental and Clinical Medicine, 24, 147-153.
[19]
Szendro, P., Vincze, G. and Szasz, A. (2001) Bio-Response to White Noise Excitation. Electro- and Magnetobiology, 20, 215-229. https://doi.org/10.1081/JBC-100104145
[20]
Kerr, W.T., Anderson, A., Lau, E.P., et al. (2012) Automated Diagnosis of Epilepsy Using EEG Power Spectrum. Epilepsia, 53, e189-e192.
[21]
Dave, K., Davtyan, A., Papoian, G.A., et al. (2015) Environmental Fluctuations and Stochastic Resonance in Protein Folding. ChemPhysChem, 17, 1341-1348. https://doi.org/10.1002/cphc.201501041
[22]
Astumian, R.D., Weaver, J.C. and Adair, R.K. (1995) Rectification and Signal Averaging of Weak Electric Fields by Biological Cells. Proceedings of the National Academy of Sciences of the United States of America, 92, 3740-3743. https://doi.org/10.1073/pnas.92.9.3740
[23]
Vincze, Gy., Szasz, A. and Szasz, N. (2005) On the Thermal Noise Limit of Cellular Membranes. Bioelectromagnetics, 26, 28-35. https://doi.org/10.1002/bem.20051
[24]
Winfree, A.T. (1984) The Prehistory of the Belousov-Zhabotinsky Oscillator. Journal of Chemical Education, 61, 661-663. https://doi.org/10.1021/ed061p661
[25]
Hudson, J.L. and Mankin, J.C. (1981) Chaos in the Belousov-Zhabotinskii Reaction. The Journal of Chemical Physics, 74, 6171-6177. https://doi.org/10.1063/1.441007
[26]
Matsumoto, K. and Tsuda, I. (1983) Noise-Induced Order. Journal of Statistical Physics, 31, 87-106. https://doi.org/10.1007/BF01010923
[27]
Taylor, A.F., Tinsley, M.R., Wang, F., et al. (2009) Dynamical Quorum Sensing and Synchronization in Large Populations of Chemical Oscillators. Science, 323, 614-617. https://doi.org/10.1126/science.1166253
[28]
Hunt, T. and Schooler, J.W. (2019) The Easy Part of the Hard Problem: A Resonance Theory of Consciousness. Frontiers in Human Neuroscience, 13, Article No. 378. https://doi.org/10.3389/fnhum.2019.00378
[29]
Voss, R.F. and Clarke, J. (1975) “1/f Noise” in Music and Speech, Nature, 28, 317-318. https://doi.org/10.1038/258317a0
[30]
Colley, I.D. and Dean, R.T. (2019) Origins of 1/f Noise in Human Music Performance from Short-Range Autocorrelations Related to Rhythmic Structures. PLoS ONE, 1, e0216088. https://doi.org/10.1371/journal.pone.0216088
[31]
Chorvatova, A. and Chorvat Jr., D. (2011) Coherent Resonant Properties of Cardiac Cells. In: Min, M., Ed., Cardiac Pacemakers—Biological Aspects, Clinical Applications and Possible Complications, IntechOpen, London, 25-45. https://doi.org/10.5772/23292
[32]
Schrödinger, E. (1951) Science and Humanism. Cambridge University Press, Cambridge.
[33]
Raff, M.C. (1992) Social Controls on Cell Survival and Death. Nature, 356, 397-400. https://doi.org/10.1038/356397a0
[34]
Von Neumann, J. (1959) The Computer and the Brain. Yale University Press, London.
[35]
Szendro, P., Vincze, G. and Szasz, A. (2001) Pink Noise Behaviour of the Bio-Systems. European Biophysics Journal, 30, 227-231. https://doi.org/10.1007/s002490100143
[36]
Goldenfeld, N. and Woese, C. (2010) Life Is Physics: Evolution as a Collective Phenomenon Far from Equilibrium.
[37]
West, B.J. and West, D. (2011) Are Allometry and Macroevolution Related? Physica A: Statistical Mechanics and Its Applications, 390, 1733-1736. https://doi.org/10.1016/j.physa.2010.11.031
[38]
West, G.B. and Brown, J.H. (2005) The Origin of Allometric Scaling Laws in Biology from Genomes to Ecosystems: Towards a Quantitative Unifying Theory of Biological Structure and Organization. Journal of Experimental Biology, 208, 1575-1592. https://doi.org/10.1242/jeb.01589
[39]
Häusser, M. (2001) Synaptic Function: Dendritic Democracy. Current Biology, 11, R10-R12. https://doi.org/10.1016/S0960-9822(00)00034-8
[40]
Das, Neves, R.P., Jones, N.S. andreu, L., Gupta, R., Enver, T. and Iborra, F.J. (2010) Connecting Variability in Global Transcription Rate to Mitochondrial Variability. PLOS Biology, 8, e1000560. https://doi.org/10.1371/journal.pbio.1000560
[41]
Johnston, I.G., Gaal, B., das, Neves, R.P., Enver, T., Iborra, F.J. and Jones, N.S. (2012) Mitochondrial Variability as a Source of Extrinsic Cellular Noise. PLOS Computational Biology, 8, e1002416. https://doi.org/10.1371/journal.pcbi.1002416
[42]
Alberts, B., Alexander, J., Julian, L., Martin, R., Keith, R. and Peter, W. (1994). Molecular Biology of the Cell. Garland Publishing Inc., New York.
[43]
Dawkins, R. (1976) The Selfish Gene. Oxford University Press, Oxford.
[44]
McAvoy, A. and Hauert, C. (2016) Autocratic Strategies for Iterated Games with Arbitrary Action Spaces. PNAS, 113, 3573-3578. https://doi.org/10.1073/pnas.1520163113
[45]
McAvoy, A. and Hauert, C. (2016) Autocratic Strategies for Alternating Games. Theoretical Population Biology, 113, 13-22. https://doi.org/10.1016/j.tpb.2016.09.004
[46]
Nowak, M.A. and Sigmund, K. (1994) The Alternating Prisoner’s Dilemma. Journal of Theoretical Biology, 168, 219-226. https://doi.org/10.1006/jtbi.1994.1101
[47]
Ross-Gillespie, A. and Kümmerli, R. (2014) Collective Decision-Making in Microbes. Frontiers in Microbiology, 5, Article No. 54. https://doi.org/10.3389/fmicb.2014.00054
[48]
Bhardway, N., Yan, K.K. and Gerstein, M.B. (2010) Analysis of Diverse Regulatory Networks in a Hierarchical Context Shows Consistent Tendencies for Collaboration in the Middle Levels. PNAS, 107, 6841-6846. https://doi.org/10.1073/pnas.0910867107
[49]
Dissado, L.A. (1990) A Fractal Interpretation of the Dielectric Response of Animal Tissues. Physics in Medicine & Biology, 35, 1487-1503. https://doi.org/10.1088/0031-9155/35/11/005
[50]
El-Lakkani, A. (2001) Dielectric Response of Some Biological Tissues. Bioelectromagnetics, 22, 272-279. https://doi.org/10.1002/bem.50
[51]
Chigira, M., Noda, K. and Watanabe, H. (1990) Autonomy in Tumor Cell Proliferation. Medical Hypotheses, 32, 249-254. https://doi.org/10.1016/0306-9877(90)90101-J
[52]
Ngo, S., Liang, J., Su, Y.H. and O’Brien, L.E. (2020) Tumor Establishment Requires Tumor Autonomous and Non-Autonomous Deregulation of Homeostatic Feedback Control. https://doi.org/10.1101/541912
[53]
Li, J., Cheng, L. and Jiang, H. (2019) Cell Shape and Intercellular Adhesion Regulate Mitotic Spindle Orientation. Molecular Biology of the Cell, 30, 2458-2468. https://doi.org/10.1091/mbc.E19-04-0227
[54]
Szentgyorgyi, A. (1978) The Living State and Cancer. Marcel Dekker Inc., New York.
[55]
Jeanes, A., Gottardi, C.J. and Yap, A.S. (2008) Cadherins and Cancer: How Does Cadherin Dysfunction Promote Tumor Progression? Oncogene, 27, 6920-6929. https://doi.org/10.1038/onc.2008.343
[56]
Mendonsa, A.M., Na, T.Y. and Gumbiner, B.M. (2018) E-Cadherin in Contact Inhibition and Cancer. Oncogene, 37, 4769-4780. https://doi.org/10.1038/s41388-018-0304-2
[57]
Szasz, O., Szasz, A.M., Minnaar, C. and Szasz, A. (2017) Heating Preciosity—Trends in Modern Oncological Hyperthermia. Open Journal of Biophysics, 7, 116-144. https://doi.org/10.4236/ojbiphy.2017.73010
[58]
Szentgyorgyi, A. (1960) Introduction to a Submolecular Biology. Academic Press, New York. https://doi.org/10.1016/B978-0-12-395612-5.50005-1
[59]
Szasz, A. (1991) An Electrically Driven Instability: The Living-State (Does the Room Temperature Superconductivity Exist?). Physiological Chemistry and Physics and Medical NMR, 23, 43-50.
[60]
Alfarouk, K.O., Shayoub, M.E.A., Muddathir, A.K., Elhassan, G.O. and Bashir, A.H.H. (2011) Evolution of Tumour Metabolism Might Reflect Carcinogenesis as a Reverse Evolution Process (Dismantling of Multicellularity). Cancers, 3, 3002-3017. https://doi.org/10.3390/cancers3033002
[61]
Weinberg, R.A. (1999) One Renegade Cell. How Cancer Begins. Basic Books, New York.
[62]
Szigeti, Gy.P., Szasz, A.M. and Szasz, A. (2020) The Growth of Healthy and Cancerous Tissues. Open Journal of Biophysics, 10, 113-128. https://doi.org/10.4236/ojbiphy.2020.103010
[63]
Willmer, P. (2009) Environmental Physiology of Animals. Wiley, Hoboken.
[64]
West, G.B., Brown, J.H. and Enquist, B.J. (1997) A General Model for the Origin of Allometric Scaling Laws in Biology. Science, 276, 122-126. https://doi.org/10.1126/science.276.5309.122
[65]
Dodds, P.S., Rothman, D.H. and Weitz, J.S. (2001) Re-Examination of the “3/4-Law” of Metabolism. Journal of Theoretical Biology, 209, 9-27. https://doi.org/10.1006/jtbi.2000.2238
[66]
Rothman, D.H. and Weitz, J.S. (2005) Beyond the “3/4-Power Law”: Variation in the Intra- and Interspecific Scaling of Metabolic Rate in Animals. Biological Reviews, 80, 611-662. https://doi.org/10.1017/S1464793105006834
[67]
Kozlowski, J. and Konarzewski, M. (2004) Is West, Brown and Enquist’s Model of Allometric Scaling Mathematically Correct and Biologically Relevant? Function Ecology, 18, 283-289. https://doi.org/10.1111/j.0269-8463.2004.00830.x
[68]
Beckman, R.A. and Loeb, L.A. (2005) Genetic Instability in Cancer: Theory and Experiment. Seminars in Cancer Biology, 15, 423-435. https://doi.org/10.1016/j.semcancer.2005.06.007
[69]
Ferguson, L.R., Chen, H., Collins, A.R., Connel, M., Damia, G., Dasgupta, S., et al. (2015) Genomic Instability in Human Cancer: Molecular Insights and Opportunities for Therapeutic Attack and Prevention through Diet and Nutrition. Seminars in Cancer Biology, 35, S5-S24. https://doi.org/10.1016/j.semcancer.2015.03.005
[70]
Colotta, F., Allavena, P., Sica, A., Garlanda, C. and Mantovani, A. (2009) Cancer-Related Inflammation, the Seventh Hallmark of Cancer: Links to Genetic Instability. Carcinogenesis, 30, 1073-1081. https://doi.org/10.1093/carcin/bgp127
[71]
Luoto, K.R., Kumareswaran, R. and Bristow, R.G. (2013) Tumor Hypoxia as a Driving Force in Genetic Instability. Genome Integrity, 4, 5. https://doi.org/10.1186/2041-9414-4-5
[72]
Loewenstein, W.R. (1999) The Touchstone of Life, Molecular Information, Cell Communication and the Foundations of the Life. Oxford University Press, Oxford, New York, 298-304.
[73]
Szasz, O. (2020) Ch. 11. Local Treatment with Systemic Effect: Abscopal Outcome. In: Szasz, A., Ed., Challenges and Solutions of Oncological Hyperthermia, Cambridge Scholars Publishing, Newcastle upon Tyne District, Publishing, Newcastle upon Tyne District, 192-205.
[74]
Schwan, H.P. and Takashima, S. (1991) Dielectric Behavior of Biological Cells and Membranes. Bulletin of the Institute for Chemical Research, Kyoto University, 69, 459-475.
[75]
Cole, K.S. (1972) Membranes, Ions and Impulses. University of California Press, Berkeley.
Pethig, R.R. (1979) Dielectric and Electronic Properties of Biological Materials. Wiley, Hoboken.
[78]
Schwan, H.P. (1957) Electrical Properties of Tissue and Cell Suspensions. Advances in Biological and Medical Physics, 5, 147. https://doi.org/10.1016/B978-1-4832-3111-2.50008-0
[79]
Martinsen, O.G., Grimnes, S. and Mirtaheri, P. (2000) Non-Invasive Measurements of Post Mortem Changes in Dielectric Properties of Haddock Muscle—A Pilot Study. Journal of Food Engineering, 43, 189-192. https://doi.org/10.1016/S0260-8774(99)00151-X
[80]
Grant, E.H., Sheppard, R.J. and South, S.P. (1978) Dielectric Behavior of Biological Molecules in Solution. Clarendon Press, Oxford.
[81]
Schwarz, G. and Seelig, J. (1968) Kinetic Properties and the Electric Field Effect of Life Helix-Coil Transition of Poly(y-benzyl L-glutamate) Determined from Dielectric Relaxation Measurements. Biopolymers, 6, 1263-1277. https://doi.org/10.1002/bip.1968.360060904
[82]
Debye, F. (1928) Dispersion of the Conductivity and Dielectric Constants of Strong Electrolytes. Physikalische Zeitschrift, 29, 121-401.
[83]
Pennock, B.E. and Schwan, H.P. (1969) Further Observations on the Electrical Properties of Hemoglobin Bound Water. The Journal of Physical Chemistry, 73, 2600-2610. https://doi.org/10.1021/j100842a024
[84]
Kirkwood, J.G. and Shumaker (1952) Forces between Protein Molecules in Solution Arising from Fluctuations in Proton Charge and Configuration. Proceedings of the National Academy of Sciences of the United States of America, 38, 863-871. https://doi.org/10.1073/pnas.38.10.863
[85]
South, G.P. and Grant, E.H. (1972) Dielectric Dispersion and Dipole Moment of Myoglobin in Water. Proceedings of the Royal Society A, 328, 371. https://doi.org/10.1098/rspa.1972.0083
[86]
Pethig, R.R. (2017) Dielectrophoresis: Theory, Methodology and Biological Applications. John Wiley & Sons, Hoboken. https://doi.org/10.1002/9781118671443
[87]
Asami, K. (2002) Characterization of Biological Cells by Dielectric Spectroscopy. Journal of Non-Crystalline Solids, 305, 268-277. https://doi.org/10.1016/S0022-3093(02)01110-9
[88]
Pauly, H. and Schwan, H.P. (1959) Uber die Impedanzeiner Suspension von Kugelformigen Teilchenmiteiner Schale. Zeitschrift für Naturforschung B, 14, 125-131. https://doi.org/10.1515/znb-1959-0213
[89]
Stoy, R.D., Foster, K.R. and Schwan, H.P. (1982) Dielectric Properties of Mammalian Tissues from 0.1 to 100 MHz: A Summary of Recent Data. Physics in Medicine & Biology, 27, 501-513. https://doi.org/10.1088/0031-9155/27/4/002
[90]
Gotz, M., Karsch, L. and Pawelke, J. (2017) A New Model for Volume Recombination in Plane-Parallel Chambers in Pulsed Fields of High Dose-per-Pulse. Physics in Medicine & Biology, 62, 8634-8654. https://doi.org/10.1088/1361-6560/aa8985
[91]
Pethig, R. (1984) Dielectric Properties of Biological Materials: Biophysical and Medical Application. IEEE Transactions on Electrical Insulation, E1-19, 453-474. https://doi.org/10.1109/TEI.1984.298769
[92]
Schwan, H.P. (1963) Determination of Biological Impedances. In: Physical Techniques in Biological Research, Vol. 6, Academic Press, New York, 323-406. https://doi.org/10.1016/B978-1-4831-6743-5.50013-7
[93]
Stubbe, M. and Gimsa, J. (2015) Maxwell’s Mixing Equation Revisited: Characteristic Impedance Equations for Ellipsoidal Cells. Biophysical Journal, 109, 194-208. https://doi.org/10.1016/j.bpj.2015.06.021
[94]
Papp, E., Vancsik, T., Kiss, E. and Szasz, O. (2017) Energy Absorption by the Membrane Rafts in the Modulated Electro-Hyperthermia (mEHT). Open Journal of Biophysics, 7, 216-229. https://doi.org/10.4236/ojbiphy.2017.74016
[95]
Vincze, Gy., Szigeti, Gy. andocs, G. and Szasz, A. (2015) Nanoheating without Artificial Nanoparticles. Biology and Medicine, 7, 249.
[96]
Megyesshazi, N. (2015) Studies on Modulated Electrohyperthermia Induced Tumor Cell Death in a Colorectal Carcinoma Model. Ph.D. Theses, Pathological Sciences Doctoral School, Semmelweis University, Budapest.
[97]
Waldhauer, I. and Steinle, A. (2008) NK Cells and Cancer Immunosurveillance. Oncogene, 27, 5932-5943. https://doi.org/10.1038/onc.2008.267
[98]
Zamai, L., Ponti, C., Mirandola, P., et al. (2007) NK Cells and Cancer. The Journal of Immunology, 178, 4011-4016. https://doi.org/10.4049/jimmunol.178.7.4011
[99]
Hu, W., Wang, G., Huang, D., et al. (2019) Cancer Immunotherapy Based on Natural Cell Killer Cells: Current Progress and New Opportunities. Frontiers in Immunology, 10, Article No. 1205. https://doi.org/10.3389/fimmu.2019.01205
[100]
Bassani, B., Baci, D. and Gallazzi, M. (2019) Natural Killer Cells as Key Players of Tumor Progression and Angiogenesis: Old and Novel Tools to Divert Their Pro-Tumor Activities into Potent Anti-Tumor Effects. Cancers, 11, 461. https://doi.org/10.3390/cancers11040461
[101]
Betten, A., Dahlgren, C., Mellqvist, U.H., et al. (2004) Oxygen Radical-Induced Natural Killer Cell Dysfunction: Role of Myeloperosicase and Regulation by Serotonin. Journal of Leukocyte Biology, 75, 1111-1115. https://doi.org/10.1189/jlb.1103595
[102]
Rosado, M.M., Simko, M., Mattsson, M.O. and Pioli, C. (2018) Immune-Modulating Perspectives for Low Frequency Electromagnetic Fields in Innate Immunity. Frontiers in Public Health, 6, Article No. 85. https://doi.org/10.3389/fpubh.2018.00085
[103]
Reindl, L.M., Albinger, N., Bexte, T., et al. (2020) Immunotherapy with NK Cells: Recent Developments in Gene Modification Open Up New Avenues. OncoImmunology, 9, Article ID: 1777651. https://doi.org/10.1080/2162402X.2020.1777651
[104]
Vancsik, T., Mathe, D., Horvath, I., et al. (2021) Modulated Electro-Hyperthermia Facilitates NK-Cell Infiltration and Growth Arrest of Human A2058 Melanoma in a Xenograft Model. Frontiers in Oncology, 11, Article ID: 590764. https://doi.org/10.3389/fonc.2021.590764
[105]
Damele, L., Ottonello, S., Mingari, M.C., Pietra, G. and Vitale, C. (2020) Targeted Therapies: Friends or Foes for Patient’s NK Cell-Mediated Tumor Immune-Surveillance? Cancers, 12, 774. https://doi.org/10.3390/cancers12040774
[106]
Meggyeshazi, N. andocs, G., Balogh, L., Balla, P., Kiszner, G., Teleki, I., Jeney, A. and Krenacs, T. (2014) DNA Fragmentation and Caspase-Independent Programmed Cell Death by Modulated Electrohyperthermia. Strahlentherapie und Onkologie, 190, 815-822. https://doi.org/10.1007/s00066-014-0617-1
[107]
Yang, K.L., Huang, C.C., Chi, M.S., Chiang, H.C., Wang, Y.S. andocs, G., et al. (2016) In Vitro Comparison of Conventional Hyperthermia and Modulated Electro-Hyperthermia. Oncotarget, 7, 84082-84092. https://doi.org/10.18632/oncotarget.11444
[108]
Andocs, G., Meggyeshazi, N., Balogh, L., Spisak, S., Maros, M.E., Balla, P., Kiszner, G., Teleki, I., Kovago, Cs. and Krenacs, T. (2014) Upregulation of Heat Shock Proteins and the Promotion of Damage-Associated Molecular Pattern Signals in a Colorectal Cancer Model by Modulated Electrohyperthermia. Cell Stress and Chaperones, 20, 37-46. https://doi.org/10.1007/s12192-014-0523-6
[109]
Jeon, T.W., Yang, H., Lee, C.G., et al. (2016) Electro-Hyperthermia Up-Regulates Tumour Suppressor Septin 4 to Induce Apoptotic Cell Death in Hepatocellular Carcinoma. International Journal of Hyperthermia, 7, 1-9. https://doi.org/10.1080/02656736.2016.1186290
[110]
Vancsik, T., Kovago, Cs., Kiss, E., et al. (2018) Modulated Electro-Hyperthermia Induced Loco-Regional and Systemic Tumor Destruction in Colorectal Cancer Allografts. Journal of Cancer, 9, 41-53. https://doi.org/10.7150/jca.21520
[111]
Szasz, A. (2019) Immune-Effects with Local Hyperthermia. Oncothermia Journal, 26, 139-148.
[112]
Qin, W., Akutsu, Y. andocs, G., et al. (2014) Modulated Electro-Hyperthermia Enhances Dendritic Cell Therapy through an Abscopal Effect in Mice. Oncology Reports, 32, 2373-2379. https://doi.org/10.3892/or.2014.3500
[113]
Tsang, Y.W., Huang, C.C., Yang, K.L., et al. (2015) Improving Immunological Tumor Microenvironment Using Electro-Hyperthermia Followed by Dendritic Cell Immunotherapy. BMC Cancer, 15, Article No. 708. https://doi.org/10.1186/s12885-015-1690-2
[114]
Wust, P., Kortum, B., Strauss, U., Nadobny, J., Zschaeck, S., Beck, M., et al. (2020) Nonthermal Effects of Radiofrequency Electromagnetic Fields. Scientific Reports, 10, Article No. 13488. https://doi.org/10.1038/s41598-020-69561-3
[115]
Wust, P., Ghadjar, P., Nadobny, J., et al. (2019) Physical Analysis of Temperature-Dependent Effects of Amplitude-Modulated Electromagnetic Hyperthermia. International Journal of Hygiene and Environmental Health, 36, 1246-1254. https://doi.org/10.1080/02656736.2019.1692376
[116]
Wust, P., Nadobny, J., Zschaeck, S. and Ghadjar, P. (2020) Ch. 16. Physics of Hyperthermia—Is Physics Really against Us? In: Szasz, A., Ed., Challenges and Solutions of Oncological Hyperthermia, Cambridge Scholars Publishing, Newcastle upon Tyne District, 346-376.
[117]
Szasz, A. (2019) Thermal and Nonthermal Effects of Radiofrequency on Living State and Applications as an Adjuvant with Radiation Therapy. Journal of Radiation and Cancer Research, 10, 1-17. https://doi.org/10.4103/jrcr.jrcr_25_18
[118]
West, B.J. (1990) Fractal Physiology and Chaos in Medicine. World Scientific, Singapore, London. https://doi.org/10.1142/1025
[119]
Goldberger, A.L., Amaral, L.A., Hausdorff, J.M., et al. (2002) Fractal Dynamics in Physiology: Alterations with Disease and Aging. PNAS Colloquium, 99, 2466-2472. https://doi.org/10.1073/pnas.012579499
[120]
Stehlik, M., Hermann, P. and Nicolis, O. (2016) Fractal Based Cancer Modelling. REVSTAT—Statistical Journal, 14, 139-155.
[121]
Deisboeck, T.S., Guiot, C., Delsanto, P.P., et al. (2006) Does Cancer Growth Depend on Surface Extension? Medical Hypotheses, 67, 1338-1341. https://doi.org/10.1016/j.mehy.2006.05.029
[122]
Stehlik, M., Wartner, F. and Minarova, M. (2013) Fractal Analysis for Cancer Research: Case Study and Simulation of Fractals. Pliska Studia Mathematica Bulgarica, 22, 195-206.
[123]
Waliszewski, P., Molski, M. and Konarski, J. (2011) Self-Similarity, Collectivity, and Evolution of Fractal Dynamics during Retinoid-Induced Differentiation of Cancer Cell Population. Fractals, 7, 139-149. https://doi.org/10.1142/S0218348X99000165
[124]
Baish, J.W. and Jain, R.K. (2000) Fractals and Cancer. Cancer Research, 60, 3683-3688.
[125]
Liu, S., Wang, Y., Xu, K., Wang, Z., Fan, X., Zhang, C., Li, S., Qiu, X. and Jiang, T. (2017) Relationship between Necrotic Patterns in Glioblastoma and Patient Survival: Fractal Dimension and Lacunarity Analyses Using Magnetic Resonance Imaging. Scientific Reports, 7, Article No. 8302. https://doi.org/10.1038/s41598-017-08862-6
[126]
Szasz, A. (2021) The Capacitive Coupling Modalities for Oncological Hyperthermia. Open Journal of Biophysics, 11, 252-313. https://doi.org/10.4236/ojbiphy.2021.113010
[127]
Zbilut, J.P. and Marwan, N. (2008) The Wiener-Khinchin Theorem and Recurrence Quantification. Physics Letters A, 372, 6622-6626. https://doi.org/10.1016/j.physleta.2008.09.027
[128]
Petrova, Y.I., Schecterson, L. and Gumbiner, B.M. (2016) Roles for E-cadherin Cell Surface Regulation in Cancer. Molecular Biology of the Cell, 27, 3233-3244. https://doi.org/10.1091/mbc.E16-01-0058
[129]
Beavon, I.R. (2000) The E-cadherin-catenin Complex in Tumour Metastasis: Structure, Function and Regulation. European Journal of Cancer, 36, 1607-1620. https://doi.org/10.1016/S0959-8049(00)00158-1
[130]
Pećina-Šlaus, N. (2003) Tumor Suppressor Gene E-cadherin and Its Role in Normal and Malignant Cells. Cancer Cell International, 3, 17. https://doi.org/10.1186/1475-2867-3-17
[131]
Cavallaro, U., Schaffhauser, B. and Christofori, G. (2002) Cadherins and the Tumour Progression: Is It All in a Switch? Cancer Letters, 176, 123-128. https://doi.org/10.1016/S0304-3835(01)00759-5
[132]
Szentgyorgyi, A. (1968) Bioelectronics: A Study on Cellular Regulations, Defence and Cancer. Academic Press, New York, London.
[133]
Lowenstein, W.R. and Kanno, Y. (1967) Intercellular Communication and Tissue Growth, I. Cancerous Growth. The Journal of Cell Biology, 33, 225-234. https://doi.org/10.1083/jcb.33.2.225
[134]
Lowenstein, W.R. and Penn, R.D. (1967) Intercellular Communication and Tissue Growth, II. Tissue Regeneration. The Journal of Cell Biology, 33, 235-242. https://doi.org/10.1083/jcb.33.2.235
[135]
Alimperti, S. and Andreadis, S.T. (2015) CDH2 and CDH11 Act as Regulators of Stem Cell Fate Decisions. Stem Cell Research, 14, 270-282. https://doi.org/10.1016/j.scr.2015.02.002
[136]
Szentgyorgyi, A. (1965) Cell Division and Cancer. Science, 149, 34-37. https://doi.org/10.1126/science.149.3679.34
[137]
Lugano, R., Ramachandran, M. and Dimberg, A. (2020) Tumor Angiogénesis: Causes, Consequences, Challenges and Opportunities. Cellular and Molecular Life Sciences, 77, 1745-1770. https://doi.org/10.1007/s00018-019-03351-7
[138]
Szasz, O. and Szasz, A. (2018) Modulated Electro-Hyperthermia, (mEHT) from LAB to Clinic. Oncothermia Journal, 23, 24-61.
[139]
Ritossa, F. (1962) A New Puffing Pattern Induced by Temperature Shock and DNP in Drosophila. Experimental, 18, 571-573. https://doi.org/10.1007/BF02172188
[140]
Csermely, P. (1998) Stress of Life from Molecules to Man. Annals of the New York Academy of Sciences, 851, 547. https://doi.org/10.1111/j.1749-6632.1998.tb08965.x
[141]
Soti, C. and Csermely, P. (2007) Protein Stress and Stress Proteins: Implications in Aging and Disease. Journal of Biosciences, 32, 511-515. https://doi.org/10.1007/s12038-007-0050-z
[142]
Vega, V.L., Rodriguez, Silva, M., Frey, T., Gehrmann, M., Diaz, J.C., et al. (2008) Hsp70 Translocates into the Plasma Membrane after Stress and Is Released into the Extracellular Environment in a Membrane-Associated form That Activates Macrophages. The Journal of Immunology, 180, 4299-4307. https://doi.org/10.4049/jimmunol.180.6.4299
[143]
Juhasz, K., Lipp, A.M., Nimmervoll, B., Sonnleitner, A., et al. (2013) The Complex Function of Hsp70 in Metastatic Cancer. Cancers, 6, 42-66. https://doi.org/10.3390/cancers6010042
[144]
Ohtsuka, K., Kawashima, D. and Asai, M. (2007) Dual Functions of Heat Shock Proteins: Molecular Chaperones Inside of Cells and Danger Signals Outside of Cells. Thermal Medicine, 23, 11-22. https://doi.org/10.3191/thermalmedicine.23.11
[145]
Soti, Cs., Nagy, E., Giricz, Z., Vigh, L., Csermely, P. and Ferdinandy, P. (2005) Heat Shock Proteins as Emerging Therapeutic Targets. British Journal of Pharmacology, 146, 679-780. https://doi.org/10.1038/sj.bjp.0706396
[146]
Torok, Z.S., Crul, T., Maresca, B., Schutz, G.J., Viana, F., et al. (2014) Plasma Membranes as Heat Stress Sensors: From Lipid-Controlled Molecular Switches to Therapeutic Applications. Biochimica et Biophysica Acta, 1838, 1594-1618. https://doi.org/10.1016/j.bbamem.2013.12.015
[147]
Shevtsov, M., Balogi, Z.S., Khachatryan, W., Gao, H., Vigh, L. and Multhof, F.G. (2020) Membrane-Associated Heat Shock Proteins in Oncology: From Basic Research to New Theranostic Targets. Cells, 9, 1263. https://doi.org/10.3390/cells9051263
[148]
Andocs, G., Rehman, M.U., Zhao, Q.L., Papp, E., Kondo, T. and Szasz, A. (2015) Nanoheating without Artificial Nanoparticles Part II. Experimental Support of the Nanoheating Concept of the Modulated Electro-Hyperthermia Method, Using U937 Cell Suspension Model. Biology and Medicine, 7, 1-9. https://doi.org/10.4172/0974-8369.1000247
[149]
Danics, L., Schvarcz, Cs., Viana, P., et al. (2020) Exhaustion of Protective Heat Shock Response Induces Significant Tumor Damage by Apoptosis after Modulated Electro-Hyperthermia Treatment of Triple Negative Breast Cancer Isografts in Mice. Cancers, 12, 2581. https://doi.org/10.3390/cancers12092581
[150]
Wang, X.Y., Li, Y., Yang, G. and Subjeck, J.R. (2005) Current Ideas about Applications of Heat Shock Proteins in Vaccine Design and Immunotherapy. International Journal of Hyperthermia, 21, 717-722. https://doi.org/10.1080/02656730500226407
[151]
Calderwood, S.K., Mambula, S.S. and Gray Jr., P.J. (2007) Extracellular Heat Shock Proteins in Cell Signalling and Immunity. Annals of the New York Academy of Sciences, 1113, 28-39. https://doi.org/10.1196/annals.1391.019
[152]
Pederson, T. (2003) Historical Review: An Energy Reservoir for Mitosis, and Its Productive Wake. Trends in Biochemical Sciences, 28, 125-129. https://doi.org/10.1016/S0968-0004(03)00030-6
[153]
Warburg, O. (1996) Oxygen, The Creator of Differentiation, Biochemical Energetics. Academic Press, New York.
[154]
Szentgyorgyi, A. (1998) Electronic Biology and Cancer. Marcel Dekker, New York.
[155]
Sengupta, A., Gupta, S., Sharda, A., et al. (2021) Effect of Low Frequency Electrical Current on the Biophysical and Molecular Properties of Cancer Cells. International Journal of Cancer and Clinical Research, 8, 145. https://doi.org/10.23937/2378-3419/1410145
[156]
Lanouette, W. and Silard, B. (1992) Genius in the Shadows. Macmillan Publishing Co., New York.
[157]
Meng, X. and Riordan, N.H. (2006) Cancer Is a Functional Repair Tissue. Medical Hypotheses, 66, 486-490. https://doi.org/10.1016/j.mehy.2005.09.041
[158]
McCarthy-Morrogh, L. and Martin, P. (2020) The Hallmarks of Cancer Are Also Hallmarks of Wound Healing. Science Signaling, 13, eaay8690. https://doi.org/10.1126/scisignal.aay8690
[159]
Deyell, M., Garris C.S. and Laughney, A.M. (2021) Cancer Metastasis as a Non-Healing Wound. British Journal of Cancer, 124, 1491-1502. https://doi.org/10.1038/s41416-021-01309-w
[160]
Sundaram, G.M., Quah, S. and Sampath, P. (2018) Cancer: The Dark Side of Wound Healing. The FEBS Journal, 285, 4516-4534. https://doi.org/10.1111/febs.14586
[161]
Shin, B.J. and Ching, S.S. (2003) A Case of Limbal Stem Cell Deficiency in a Patient with Chronic Mucocutaneous Candiddiasis. Investigative Ophthalmology & Visual Science, 44, 1359.
[162]
Houghton, J., Stoicov, C., Nomura, S., et al. (2004) Gastric Cancer Originating from Bone Marrow-Derived Cells. Science, 306, 1568-1571. https://doi.org/10.1126/science.1099513
[163]
Ouahes, N., Phillips, T.J. and Park, H.Y. (1998) Expression of c-fos and c-Ha-ras Protooncogenes Is Induced in Human Chronic Wounds. Dermatologic Surgery, 24, 1354-1357. https://doi.org/10.1111/j.1524-4725.1998.tb00014.x
[164]
Huang, S., Trujillo, J.M. and Chakrabarty, S. (1992) Proliferation of Human Colon Cancer Cells: Role of Epidermal Growth Factor and Transforming Growth Factor. International Journal of Cancer, 52, 978-986. https://doi.org/10.1002/ijc.2910520625
[165]
Dahiya, R., Lee, C., Haughney, P.C., et al. (1996) Differential Gene Expression of Transforming Growth Factors Alpha and Beta, Epidermal Growth Factor, Keratinocyte Growth Factor, and Their Receptors in Fetal and Adult Human Prostatic Tissues and Cancer Cell Lines. Urology, 48, 963-970. https://doi.org/10.1016/S0090-4295(96)00376-7
[166]
Mizuno, K., Sone, S., Orino, E., et al. (1994) Autonomous Expressions of Cytokine Genes by Human Lung Cancer Cells and Their Paracrine Regulation. Japanese Journal of Cancer and Oncology Research, 85, 179-186. https://doi.org/10.1111/j.1349-7006.1994.tb02080.x
[167]
Zhang, H., Vutskits, L., Pepper, M.S., et al. (2003) VEGF Is a Chemoattractant for FGF-2-Stimulated Neural Progenitors. Journal of Cell Biology, 163, 1375-1384. https://doi.org/10.1083/jcb.200308040
[168]
Cicuttini, F.M., Begley, C.G. and Boyd, A.W. (1992) The Effect of Recombinant Stem Cell Factor (SCF) on Purified CD34-Positive Human Umbilical Cord Blood Progenitor Cells. Growth Factors, 6, 31-39. https://doi.org/10.3109/08977199209008869
[169]
Lovelady, D.C., Richmond, T.C., Maggi, A.N., Lo, C.M. and Rabson, D.A. (2007) Distinguishing Cancerous from Non-Cancerous Cells through Analysis of Electrical Noise. Physical Review E, 76, Article ID: 041908. https://doi.org/10.1103/PhysRevE.76.041908
[170]
Lovelady, D.C., Friedman, J., Patel, S., et al. (2009) Detecting Effects of Low Levels of Cytochalasin B in 3T3 Fibroblast Cultures by Analysis of Electrical Noise Obtained from Cellular Micromotion. Biosensors and Bioelectronics, 24, 2250-2254. https://doi.org/10.1016/j.bios.2008.09.033
[171]
Lineweaver, C.H., Davies, P.C.W. and Vincent, M.D. (2014) Targeting Cancer’s Weaknesses (Not Its Strengths): Therapeutic Strategies Suggested by the Atavistic Model. Bioessays, 36, 827-835. https://doi.org/10.1002/bies.201400070
[172]
Jezequel, P. and Campone, M. (2018) Comment on “How the Evolution of Multicellularity Set the Stage for Cancer”. British Journal of Cancer, 119, 133-134. https://doi.org/10.1038/s41416-018-0091-0
[173]
Andocs, G., Szasz, O. and Szasz, A. (2009) Oncothermia Treatment of Cancer: From the Laboratory to Clinic. Electromagnetic Biology and Medicine, 28, 148-165. https://doi.org/10.1080/15368370902724633
[174]
Wust, P., Ghadjar, P., Nadobny, J. and Beck, M. (2019) Physical Potentials of Radiofrequency Hyperthermia with Amplitude Modulation. Oncothermia Journal, 26, 128-137.
[175]
Vincze, Gy. and Szasz, A. (2018) Similarities of Modulation by Temperature and by Electric Field. Ojbiphy, 8, 95-103. https://doi.org/10.4236/ojbiphy.2018.83008
[176]
Andocs, G., Renner, H., Balogh, L., Fonyad, L., Jakab, C. and Szasz, A. (2009) Strong Synergy of Heat and Modulated Electro-Magnetic Field in Tumor Cell Killing, Study of HT29 Xenograft Tumors in a Nude Mice Model. Strahlentherapie und Onkologie, 185, 120-126. https://doi.org/10.1007/s00066-009-1903-1
[177]
Nagy, G., Meggyeshazi, N. and Szasz, O. (2013) Deep Temperature Measurements in Oncothermia Processes. Conference Papers in Medicine, 2013, Article ID: 685264. https://doi.org/10.1155/2013/685264
[178]
Hossain, M.T., Prasad, B., Park, K.S., et al. (2016) Simulation and Experimental Evaluation of Selective Heating Characteristics of 13, 56 MHz Radiofrequency Hyperthermia in Phantom Models. International Journal of Precision Engineering and Manufacturing, 17, 253-256. https://doi.org/10.1007/s12541-016-0033-9
[179]
Orczy-Timko, B. (2020) Ch. 18. Phantom Measurements with the EHY-2030 Device. In: Szasz, A., Ed., Challenges and Solutions of Oncological Hyperthermia, Cambridge Scholars Publishing, Newcastle upon Tyne District, 416-428.
[180]
Szasz, O. and Szasz, A. (2021) Approaching Complexity: Hyperthermia Dose and Its Possible Measurement in Oncology. Ojbiphy, 11, 68-132. https://doi.org/10.4236/ojbiphy.2021.111002
[181]
Szasz, A. and Vincze, Gy. (2006) Dose Concept of Oncological Hyperthermia: Heat-Equation Considering the Cell Destruction. Journal of Cancer Research and Therapeutics, 2, 171-181. https://doi.org/10.4103/0973-1482.29827
[182]
Lee, S.Y., Szigeti, G.P. and Szasz, A.M. (2019) Oncological Hyperthermia: The Correct Dosing in Clinical Applications. International Journal of Oncology, 54, 627-643. https://doi.org/10.3892/ijo.2018.4645
[183]
Szasz, A., Vincze, Gy., Szasz, O. and Szasz, N. (2003) An Energy Analysis of Extracellular Hyperthermia. Magneto- and Electro-Biology, 22, 103-115. https://doi.org/10.1081/JBC-120024620
[184]
Vincze, Gy. and Szasz, A. (2015) Effect of Cellular Membrane Resistivity Inhomogeneity on the Thermal Noise-Limit. Journal of Advances in Physics, 11, 3170-3183. https://doi.org/10.24297/jap.v11i3.6859
[185]
Vincze, Gy. and Szasz, A. (2015) Reorganization of Actin Filaments and Microtubules by Outside Electric Field. Journal of Advances in Biology, 8, 1514-1518.
[186]
Lee, S.Y., Fiorentini, G., Szasz, A.M., Szigeti, Gy., Szasz, A. and Minnaar, C.A. (2020) Quo Vadis Oncological Hyperthermia (2020)? Frontiers in Oncology, 10, Article No. 1690. https://doi.org/10.3389/fonc.2020.01690
[187]
Szasz, O. and Szasz, A. (2014) Oncothermia—Nano-Heating Paradigm. Journal of Cancer Science and Therapy, 6, 4. https://doi.org/10.4172/1948-5956.1000259
[188]
Szasz, A. (2013) Chapter 4. Electromagnetic Effects in Nanoscale Range. In: Shimizu, T. and Kondo, T., Eds., Cellular Response to Physical Stress and Therapeutic Applications, Nova Science Publishers, Hauppauge, 55-81.
[189]
Andocs, G., Rehman, M.U., Zhao, Q.L., Tabuchi, Y., Kanamori, M. and Kondo, T. (2016) Comparison of Biological Effects of Modulated Electro-Hyperthermia and Conventional Heat Treatment in Human Lymphoma U937 Cell. Cell Death Discovery, 2, 16039. https://doi.org/10.1038/cddiscovery.2016.39
[190]
Szasz, A. (2020) Towards the Immunogenic Hyperthermic Action: Modulated Electro-Hyperthermia. Clinical Oncology and Research, Science Repository, 3, 5-6. https://doi.org/10.31487/j.COR.2020.09.07
[191]
Kim, J.K., Prasad, B. and Kim, S. (2017) Temperature Mapping and Thermal Dose Calculation in Combined Radiation Therapy and 13.56 MHz Radiofrequency Hyperthermia for Tumor Treatment. Proceedings SPIE 10047, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXVI, Volume 10047, Article ID: 1004718. https://doi.org/10.1117/12.2253163
[192]
Prasad, B., Kim, S., Cho, W., et al. (2019) Quantitative Estimation of the Equivalent Radiation Dose Escalation Using Radiofrequency Hyperthermia in Mouse Xenograft Models of Human Lung Cancer. Scientific Reports, 9, Article No. 3942. https://doi.org/10.1038/s41598-019-40595-6
[193]
Forika, G., Balogh, A., Vancsik, T., Zalatnai, A., et al. (2020) Modulated Electro-Hyperthermia Resolves Radioresistance of Panc1 Pancreas Adenocarcinoma and Promotes DNA Damage and Apoptosis in Vitro. International Journal of Molecular Sciences, 21, 5100. https://doi.org/10.3390/ijms21145100
[194]
Vancsik, T., Forika, G., Balogh, A., et al. (2019) Modulated Electro-Hyperthermia Induced p53 Driven Apoptosis and Cell Cycle Arrest Additively Support Doxorubicin Chemotherapy of Colorectal Cancer in Vitro. Cancer Medicine, 8, 4292-4303. https://doi.org/10.1002/cam4.2330
[195]
Tsang, Y.W., Chi, K.H., Huang, C.C., et al. (2019) Modulated Electro-Hyperthermia-Enhanced Liposomal Drug Uptake by Cancer Cells. International Journal of Nanomedicine, 14, 1269-1579. https://doi.org/10.2147/IJN.S188791
[196]
Krenacs, T., Meggyeshazi, N., Forika, G., et al. (2020) Modulated Electro-Hyperthermia-Induced Tumor Damage Mechanisms Revealed in Cancer Models. International Journal of Molecular Sciences, 21, 6270. https://doi.org/10.3390/ijms21176270
[197]
Wismeth, C., Dudel, C., Pascher, C., et al. (2010) Transcranial Electro-Hyperthermia Combined with Alkylating Chemotherapy in Patients with Relapsed High-Grade Gliomas—Phase I Clinical Results. Journal of Neuro-Oncology, 98, 395-405. https://doi.org/10.1007/s11060-009-0093-0
[198]
Sahinbas, H., Groenemeyer, D.H.W., Boecher, E. and Szasz, A. (2007) Retrospective Clinical Study of Adjuvant Electro-Hyperthermia Treatment for Advanced Brain-Gliomas. Deutsche Zeitschriftfuer Onkologie, 39, 154-160. https://doi.org/10.1055/s-2007-986020
[199]
Fiorentini, G., Sarti, D., Milandri, C., et al. (2018) Modulated Electrohyperthermia in Integrative Cancer Treatment for Relapsed Malignant Glioblastoma and Astrocytoma: Retrospective Multicenter Controlled Study. Integrative Cancer Therapies, 18, 1-11. https://doi.org/10.1177/1534735418812691
[200]
Fiorentini, G., Sarti, D., Casadei, V., et al. (2020) Ch. 6. Modulated Electro-Hyperthermia for the Treatment of Relapsed Brain Gliomas. In: Szasz, A., Ed., Challenges and Solutions of Oncological Hyperthermia, Cambridge Scholars Publishing, Newcastle upon Tyne District, 110-125.
[201]
Ou, J., Zhu, X., Lu, Y., et al. (2017) The Safety and Pharmacokinetics of High Dose Intravenous Ascorbic Acid Synergy with Modulated Electrohyperthermia in Chinese Patients with Stage III-IV Non-Small Cell Lung Cancer. European Journal of Pharmaceutical Sciences, 109, 412-418. https://doi.org/10.1016/j.ejps.2017.08.011
[202]
Ou, J., Zhu, X., Chen, P., et al. (2020) A Randomized Phase II Trial of Best Supportive Care with or without Hyperthermia and Vitamin C for Heavily Pretreated, Advanced, Refractory Non-Small-Cell Lung Cancer. Journal of Advanced Research, 24, 175-182. https://doi.org/10.1016/j.jare.2020.03.004
[203]
Roussakow, S. (2017) Clinical and Economic Evaluation of Modulated Electrohyperthermia Concurrent to Dose-Dense Temozolomide 21/28 Days Regimen in the Treatment of Recurrent Glioblastoma: A Retrospective Analysis of a Two-Centre German Cohort Trial with Systematic Comparison and Effect-to-Treatment Analysis. BMJ Open, 7, e017387. https://doi.org/10.1136/bmjopen-2017-017387
[204]
Roussakow, S.V. (2016) Pharmacoeconomic Study of Oncothermia (Modulated Electro-Hyperthermia) in the Treatment of Lung Cancer. Oncothermia Journal, 18, 116-138.
[205]
Ranieri, G., Laface, C., Laforgia, M., et al. (2020) Bevacizumab plus FOLFOX-4 Combined with Deep Electro-Hyperthermia as First-Line Therapy in Metastatic Colon Cancer: A Pilot Study. Frontiers in Oncology, 10, Article ID: 590707. https://doi.org/10.3389/fonc.2020.590707
[206]
Kim, S., Lee, J.H., Cha, J. and You, S.H. (2021) Beneficial Effects of Modulated Electro-Hyperthermia during Neoadjuvant Treatment for Locally Advanced Rectal Cancer. International Journal of Hyperthermia, 38, 144-151. https://doi.org/10.1080/02656736.2021.1877837
[207]
Gadaleta-Caldarola, G., Infusino, S., Galise, I., et al. (2014) Sorafenib and Locoregional Deep Electro-Hyperthermia in Advanced Hepatocellular Carcinoma. A Phase II Study. Oncology Letters, 8, 1783-1787. https://doi.org/10.3892/ol.2014.2376
[208]
Fiorentini, G., Sarti, D., Casadei, V., et al. (2019) Modulated Electro-Hyperthermia as Palliative Treatment for Pancreas Cancer: A Retrospective Observational Study on 106 Patients. Integrative Cancer Therapies, 18, 1-8. https://doi.org/10.1177/1534735419878505
[209]
Volovat, C., Volovat, S.R., Scripcaru, V., et al. (2014) Second-Line Chemotherapy with Gemcitabine and Oxaliplatin in Combination with Loco-Regional Hyperthermia (EHY-2000) in Patients with Refractory Metastatic Pancreatic Cancer—Preliminary Results of a Prospective Trial. Romanian Reports in Physics, 66, 166-174.
[210]
Yoo, H.J., Lim, M.C., Seo, S.S., et al. (2019) Phase I/II Clinical Trial of Modulated Electro-Hyperthermia Treatment in Patients with Relapsed, Refractory or Progressive Heavily Treated Ovarian Cancer. Japanese Journal of Clinical Oncology, 49, 832-838. https://doi.org/10.1093/jjco/hyz071
[211]
Lee, S.Y., Lee, N.R., Cho, D.H., et al. (2017) Treatment Outcome Analysis of Chemotherapy Combined with Modulated Electro-Hyperthermia Compared with Chemotherapy Alone for Recurrent Cervical Cancer, Following Irradiation. Oncology Letters, 14, 73-78. https://doi.org/10.3892/ol.2017.6117
[212]
Minnaar, C.A., Kotzen, J.A., Ayeni, O.A., et al. (2019) The Effect of Modulated Electro-Hyperthermia on Local Disease Control in HIV-Positive and -Negative Cervical Cancer Women in South Africa: Early Results from a Phase III Randomized Controlled Trial. PLoS ONE, 14, e0217894. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584021 https://doi.org/10.1371/journal.pone.0217894
[213]
Minnaar, C.A., Kotzen, J.A., Naidoo, T., et al. (2020) Analysis of the Effects of mEHT on the Treatment-Related Toxicity and Quality of Life of HIV-Positive Cervical Cancer Patients. International Journal of Hyperthermia, 37, 263-272. https://doi.org/10.1080/02656736.2020.1737253
[214]
Jeung, T.S., Ma, S.Y., Choi, J., et al. (2015) Results of Oncothermia Combined with Operation, Chemotherapy and Radiation Therapy for Primary, Recurrent and Metastatic Sarcoma. Case Reports in Clinical Medicine, 4, 157-168. https://doi.org/10.4236/crcm.2015.45033
[215]
Volovat, C., Volovat, S.R., Scripcaru, V., et al. (2014) The Results of Combination of Ifosfamid and Locoregional Hyperthermia (EHY 2000) in Patients with Advanced Abdominal Soft-Tissue Sarcoma after Relapse of First Line Chemotherapy. Romanian Reports in Physics, 66, 175-181.
[216]
Van, Gool, S.W., Makalowski, J., Feyen, O., Prix, L., Schirrmacher, V. and Stuecker, W. (2018) The Induction of Immunogenic Cell Death (ICD) during Maintenance Chemotherapy and Subsequent Multimodal Immunotherapy for Glioblastoma (GBM). Austin Oncology Case Reports, 3, 1010.
[217]
Chi, M.S., Mehta, M.P., Yang, K.L., et al. (2020) Putative Abscopal Effect in Three Patients Treated by Combined Radiotherapy and Modulated Electrohyperthermia. Frontiers in Oncology, 10, Article No. 254. https://doi.org/10.3389/fonc.2020.00254
[218]
Minnaar, C.A., Kotzen, J.A., Ayeni, O.A., et al. (2020) Potentiation of the Abscopal Effect by Modulated Electro-Hyperthermia in Locally Advanced Cervical Cancer Patients. Frontiers in Oncology, 10, Article No. 376. https://doi.org/10.3389/fonc.2020.00376
[219]
Chi, K.H. (2020) Ch. 12. Tumour-Directed Immunotherapy: Clinical Results of Radiotherapy with Modulated Electro-Hyperthermia. In: Szasz, A., Ed., Challenges and Solutions of Oncological Hyperthermia, Cambridge Scholars Publishing, Newcastle upon Tyne District, 206-226. https://www.cambridgescholars.com/challenges-and-solutions-of-oncological-hyperthermia
[220]
Van, Gool, S.W., Makalowski, J., Domogalla, M.P., et al. (2020) Ch. 7. Personalised Medicine in Glioblastoma Multiforme. In: Szasz, A., Ed., Challenges and Solutions of Oncological Hyperthermia, Cambridge Scholars Publishing, Newcastle upon Tyne District, 126-158.
[221]
Pang, C.L.K., Zhang, X., Wang, Z., et al. (2017) Local Modulated Electro-Hyper-thermia in Combination with Traditional Chinese Medicine vs. Intraperitoneal Chemoinfusion for the Treatment of Peritoneal Carcinomatosis with Malignant Ascites: A Phase II Randomized Trial. Molecular and Clinical Oncology, 6, 723-732. https://doi.org/10.3892/mco.2017.1221
[222]
Szasz, A.M., Minnaar, C.A., Szentmartoni, Gy., et al. (2019) Review of the Clinical Evidences of Modulated Electro-Hyperthermia (mEHT) Method: An Update for the Practicing Oncologist. Frontiers in Oncology, 9, Article No. 1012. https://doi.org/10.3389/fonc.2019.01012
[223]
Szasz, A.M., Arkosy, P., Arrojo, E.E., et al. (2020) Ch. 2. Guidelines for Local Hyperthermia Treatment in Oncology. In: Szasz, A., Ed., Challenges and Solutions of Oncological Hyperthermia, Cambridge Scholars Publishing, Newcastle upon Tyne District, 32-71.
[224]
Van, Gool, S.W., Makalowski, J., Fiore, S., et al. (2021) Randomized Controlled Immunotherapy Clinical Trials for GBM Challenged. Cancers, 13, 32. https://doi.org/10.3390/cancers13010032
[225]
Szasz, A., Szasz, N. and Szasz, O. (2010) Oncothermia—Principles and Practices. Springer Science, Heidelberg. https://doi.org/10.1007/978-90-481-9498-8
[226]
Parmar, G., Rurak, E., Elderfield, M., et al. (2020) Ch. 13. 8-Year Observational Study on Naturopathic Treatment with Modulated Electro-Hyperthermia (mEHT): A Single-Centre Experience. In: Szasz, A., Ed., Challenges and Solutions of Oncological Hyperthermia, Cambridge Scholars Publishing, Newcastle upon Tyne District, 227-266.
[227]
Hager, E.D., Sahinbas, H., Groenemeyer, D.H., et al. (2008) Prospectivephase II Trial for Recurrent High-Grade Malignant Gliomas with Capacitive Coupled Low Radiofrequency (LRF) Deep Hyperthermia. ASCO, Journal of Clinical Oncology, Annual Meeting Proceedings (Post-Meeting Edition), 26, 2047. https://doi.org/10.1200/jco.2008.26.15_suppl.2047
[228]
Renner, H. and Albrecht, I. (2007) Analyseder überlebenszeiten von Patineten mit Pankreastumoren mit erfolgterkapazitativer Hyperthermiebehandlung, (Erstellt: Mr. Mirko Friedrich; May & STM.
[229]
Dani, A., Varkonyi, A., Magyar, T. and Szasz, A. (2008) Clinical Study for Advanced Pancreas Cancer Treated by Oncothermia. Forum Hyperthermie, 1, 13-20.
[230]
Parmar, G. (2018) Naturopathic Anti-Tumoral Treatment & 8 Year Survival Benefit Statistics: A Single-Centre Experience. 36th Conference of the International Clinical Hyperthermia Society, Budapest, 28-29 September 2018.
[231]
SEER (Surveillance, Epidemiology, and End Result Program) Database. https://seer.cancer.gov/data
[232]
Szasz, O. and Szasz, A. (2020) Parametrization of Survival Measures, Part I: Consequences of Self-Organizing. International Journal of Clinical Medicine, 11, 316-347. https://doi.org/10.4236/ijcm.2020.115031
[233]
Szasz, O., Szasz, A.M., Szigeti, G.P. and Szasz, A. (2020) Chapter 2. Data Mining and Evaluation of Single Arm Clinical Studies. In: Yong, X., Ed., Recent Developments in Engineering Research, Vol. 3, GAN Publishing, London, 15-74.
[234]
Szasz, A., Szigeti, G.P. and Szasz, A.M. (2020) Parametrization of Survival Measures, Part II: Single Arm Studies. International Journal of Clinical Medicine, 11, 348-373. https://doi.org/10.4236/ijcm.2020.115032
[235]
Szasz, A., Szigeti, G.P. and Szasz, A.M. (2020) Parametrization of Survival Measures, Part III: Clinical Evidences in Single Arm Studies with Endpoint of Overall Survival. International Journal of Clinical Medicine, 11, 389-419. https://doi.org/10.4236/ijcm.2020.116034
