|
Preclinical Verification of Modulated Electro-Hyperthermia
|
Abstract:
The modulated electro-hyperthermia (mEHT) method is a unique approach that utilizes all the essential apoptotic pathways through an external radiofrequency (RF) signal. The high-frequency RF is amplitude-modulated and coupled capacitively to the target. The provided energy triggers the death receptors and FAS-FADD complexes in the malignant cells. Multi-pathway apoptosis produces immunogenic cell death (ICD). This ICD provides intracellular information about cancer cells by releasing damage-associated molecular patterns (DAMP), including membrane expression of calreticulin (CRT) and extracellular ATP, HMGB1, and HSP70, executing tumor-specific antigen presentation. The antigen-presenting cells (APCs) play a crucial role in reestablishing immune surveillance and hampering the tumor cells’ ability to hide, thereby evading immune attacks. The matured DCs (generally APCs) produce tumor-specific killer and helper T-cells, which have the potential to be active in distant metastases from the treated location. This unique mechanism of action underscores its potential in cancer treatment and extends the local mEHT treatment to the whole body anticancer therapy with an abscopal effect.
[1] | Raff, M.C. (1992) Social Controls on Cell Survival and Cell Death. Nature, 356, 397-400. https://doi.org/10.1038/356397a0 |
[2] | Ferrarelli, L.K. (2014) Focus Issue: Refining the War on Cancer. Science Signaling, 7, eg2. https://doi.org/10.1126/scisignal.2005276 |
[3] | 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 |
[4] | Szasz, A. and Szigeti, G.P. (2024) Exploring Biocomplexity in Cancer: A Comprehensive Review. Open Journal of Biophysics, 14, 154-238. https://doi.org/10.4236/ojbiphy.2024.142009 |
[5] | Lee, S., Fiorentini, G., Szasz, A.M., Szigeti, G., Szasz, A. and Minnaar, C.A. (2020) Quo Vadis Oncological Hyperthermia (2020)? Frontiers in Oncology, 10, Article 1690. https://doi.org/10.3389/fonc.2020.01690 |
[6] | Szasz, A. (2024) Pulsing Addition to Modulated Electro-Hyperthermia. Part I. In vitro Research. International Journal of Clinical Medicine. |
[7] | Szasz, A. (2024) Pulsing Addition to Modulated Electro-Hyperthermia. Part II. In vivo Research. International Journal of Clinical Medicine. |
[8] | Lee, S. and Szasz, A. (2022) Immunogenic Effect of Modulated Electro-Hyperthermia (mEHT) in Solid Tumors. In: Interdisciplinary Cancer Research, Springer. https://doi.org/10.1007/16833_2022_74 |
[9] | Krenacs, T., Meggyeshazi, N., Forika, G., Kiss, E., Hamar, P., Szekely, T., et al. (2020) Modulated Electro-Hyperthermia-Induced Tumor Damage Mechanisms Revealed in Cancer Models. International Journal of Molecular Sciences, 21, Article 6270. https://doi.org/10.3390/ijms21176270 |
[10] | 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 |
[11] | Szasz, A. and Szasz, O. (2020) Time-Fractal Modulation of Modulated Electro-Hyperthermia (mEHT). Oncothermia Journal, 24, 318-332. |
[12] | The Physical Sciences—Oncology Centers Network, Staunton, J.R., et al. (2008) A Physical Sciences Network Characterization of Non-Tumorigenic and Metastatic Cells. Scientific Reports, 3, Article No. 1449. |
[13] | Szasz, A. (2022) Heterogeneous Heat Absorption Is Complementary to Radiotherapy. Cancers, 14, Article 901. https://doi.org/10.3390/cancers14040901 |
[14] | Lee, S., Kim, J., Han, Y. and Cho, D. (2018) The Effect of Modulated Electro-Hyperthermia on Temperature and Blood Flow in Human Cervical Carcinoma. International Journal of Hyperthermia, 34, 953-960. https://doi.org/10.1080/02656736.2018.1423709 |
[15] | Szasz, O. (2019) Bioelectromagnetic Paradigm of Cancer Treatment—Modulated Electro-Hyperthermia (mEHT). Open Journal of Biophysics, 9, 98-109. https://doi.org/10.4236/ojbiphy.2019.92008 |
[16] | Szasz, O., Andocs, G., Kondo, T., Rehman, M.U., Papp, E., Vancsik, T., et al. (2015) Heating of Membrane Rafts of Cancer-Cells. Journal of Clinical Oncology, 33, e22176. https://doi.org/10.1200/jco.2015.33.15_suppl.e22176 |
[17] | Obeid, M., Tesniere, A., Ghiringhelli, F., Fimia, G.M., Apetoh, L., Perfettini, J., et al. (2006) Calreticulin Exposure Dictates the Immunogenicity of Cancer Cell Death. Nature Medicine, 13, 54-61. https://doi.org/10.1038/nm1523 |
[18] | Kepp, O., Senovilla, L., Galluzzi, L., Panaretakis, T., Schlemmer, F., Madeo, F., et al. (2009) Viral Subversion of Immunogenic Cell Death. Cell Cycle, 8, 860-869. https://doi.org/10.4161/cc.8.6.7939 |
[19] | Krysko, D.V., Ravichandran, K.S. and Vandenabeele, P. (2018) Macrophages Regulate the Clearance of Living Cells by Calreticulin. Nature Communications, 9, Article No. 4644. https://doi.org/10.1038/s41467-018-06807-9 |
[20] | Kwon, M.S., Park, C.S., Choi, K., Park, C., Ahnn, J., Kim, J.I., et al. (2000) Calreticulin Couples Calcium Release and Calcium Influx in Integrin-Mediated Calcium Signaling. Molecular Biology of the Cell, 11, 1433-1443. https://doi.org/10.1091/mbc.11.4.1433 |
[21] | Andocs, G., Rehman, M.U., Zhao, Q., Tabuchi, Y., Kanamori, M. and Kondo, T. (2016) Comparison of Biological Effects of Modulated Electro-Hyperthermia and Conventional Heat Treatment in Human Lymphoma U937 Cells. Cell Death Discovery, 2, Article No. 16039. https://doi.org/10.1038/cddiscovery.2016.39 |
[22] | Klune, J.R., Dhupar, R., Cardinal, J., Billiar, T.R. and Tsung, A. (2008) HMGB1: Endogenous Danger Signaling. Molecular Medicine, 14, 476-484. https://doi.org/10.2119/2008-00034.klune |
[23] | Kang, R., Chen, R., Zhang, Q., Hou, W., Wu, S., Cao, L., et al. (2014) HMGB1 in Health and Disease. Molecular Aspects of Medicine, 40, 1-116. https://doi.org/10.1016/j.mam.2014.05.001 |
[24] | Kazama, H., Ricci, J., Herndon, J.M., Hoppe, G., Green, D.R. and Ferguson, T.A. (2008) Induction of Immunological Tolerance by Apoptotic Cells Requires Caspase-Dependent Oxidation of High-Mobility Group Box-1 Protein. Immunity, 29, 21-32. https://doi.org/10.1016/j.immuni.2008.05.013 |
[25] | Li, C., Zhang, Y., Cheng, X., Yuan, H., Zhu, S., Liu, J., et al. (2018) PINK1 and PARK2 Suppress Pancreatic Tumorigenesis through Control of Mitochondrial Iron-Mediated Immunometabolism. Developmental Cell, 46, 441-455.e8. https://doi.org/10.1016/j.devcel.2018.07.012 |
[26] | Yu, Y., Tang, D. and Kang, R. (2015) Oxidative Stress-Mediated HMGB1 Biology. Frontiers in Physiology, 6, Article 93. https://doi.org/10.3389/fphys.2015.00093 |
[27] | Galluzzi, L., Buqué, A., Kepp, O., Zitvogel, L. and Kroemer, G. (2016) Immunogenic Cell Death in Cancer and Infectious Disease. Nature Reviews Immunology, 17, 97-111. https://doi.org/10.1038/nri.2016.107 |
[28] | Medina, C.B. and Ravichandran, K.S. (2016) Do Not Let Death Do Us Part: ‘Find-Me’ Signals in Communication between Dying Cells and the Phagocytes. Cell Death & Differentiation, 23, 979-989. https://doi.org/10.1038/cdd.2016.13 |
[29] | Michaud, M., Martins, I., Sukkurwala, A.Q., Adjemian, S., Ma, Y., Pellegatti, P., et al. (2011) Autophagy-Dependent Anticancer Immune Responses Induced by Chemotherapeutic Agents in Mice. Science, 334, 1573-1577. https://doi.org/10.1126/science.1208347 |
[30] | Vega, V.L., Rodríguez-Silva, M., Frey, T., Gehrmann, M., Diaz, J.C., Steinem, 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 |
[31] | Shevtsov, M., Balogi, Z., Khachatryan, W., Gao, H., Vígh, L. and Multhoff, G. (2020) Membrane-Associated Heat Shock Proteins in Oncology: From Basic Research to New Theranostic Targets. Cells, 9, Article 1263. https://doi.org/10.3390/cells9051263 |
[32] | Multhoff, G., Botzler, C., Jennen, L., Schmidt, J., Ellwart, J. and Issels, R. (1997) Heat Shock Protein 72 on Tumor Cells: A Recognition Structure for Natural Killer Cells. The Journal of Immunology, 158, 4341-4350. https://doi.org/10.4049/jimmunol.158.9.4341 |
[33] | Kumar, S., Deepak, P., Kumar, S., Kishore, D. and Acharya, A. (2009) Autologous Hsp70 Induces Antigen Specific Th1 Immune Responses in a Murine T-Cell Lymphoma. Immunological Investigations, 38, 449-465. https://doi.org/10.1080/08820130902802673 |
[34] | Calderwood, S.K. and Gong, J. (2016) Heat Shock Proteins Promote Cancer: It’s a Protection Racket. Trends in Biochemical Sciences, 41, 311-323. https://doi.org/10.1016/j.tibs.2016.01.003 |
[35] | Albakova, Z., Siam, M.K.S., Sacitharan, P.K., Ziganshin, R.H., Ryazantsev, D.Y. and Sapozhnikov, A.M. (2021) Extracellular Heat Shock Proteins and Cancer: New Perspectives. Translational Oncology, 14, Article ID: 100995. https://doi.org/10.1016/j.tranon.2020.100995 |
[36] | Jolesch, A., Elmer, K., Bendz, H., Issels, R.D. and Noessner, E. (2012) Hsp70, a Messenger from Hyperthermia for the Immune System. European Journal of Cell Biology, 91, 48-52. https://doi.org/10.1016/j.ejcb.2011.02.001 |
[37] | Hickman-Miller, H.D. and Hildebrand, W.H. (2004) The Immune Response under Stress: The Role of HSP-Derived Peptides. Trends in Immunology, 25, 427-433. https://doi.org/10.1016/j.it.2004.05.011 |
[38] | Binder, R.J. (2014) Functions of Heat Shock Proteins in Pathways of the Innate and Adaptive Immune System. The Journal of Immunology, 193, 5765-5771. https://doi.org/10.4049/jimmunol.1401417 |
[39] | Krenacs, T. and Benyo, Z. (2017) Tumor Specific Stress and Immune Response Induced by Modulated Electrohyperthermia in Relation to Tumor Metabolic Profiles. Oncothermia Journal, 20, 264-272. |
[40] | Beachy, S.H. and Repasky, E.A. (2011) Toward Establishment of Temperature Thresholds for Immunological Impact of Heat Exposure in Humans. International Journal of Hyperthermia, 27, 344-352. https://doi.org/10.3109/02656736.2011.562873 |
[41] | Andocs, G., Meggyeshazi, N., Balogh, L., Spisak, S., Maros, M.E., Balla, P., et al. (2015) 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 |
[42] | Vancsik, T., Kovago, C., Kiss, E., Papp, E., Forika, G., Benyo, Z., 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 |
[43] | Tsang, Y., Huang, C., Yang, K., Chi, M., Chiang, H., Wang, Y., 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 |
[44] | Vancsik, T., Máthé, D., Horváth, I., Várallyaly, A.A., Benedek, A., Bergmann, R., 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 590764. https://doi.org/10.3389/fonc.2021.590764 |
[45] | Qin, W., Akutsu, Y., Andocs, G., Suganami, A., Hu, X., Yusup, 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 |
[46] | Kuo, I., Lee, J., Wang, Y., Chiang, H., Huang, C., Hsieh, P., et al. (2020) Potential Enhancement of Host Immunity and Anti-Tumor Efficacy of Nanoscale Curcumin and Resveratrol in Colorectal Cancers by Modulated Electro-Hyperthermia. BMC Cancer, 20, Article No. 603. https://doi.org/10.1186/s12885-020-07072-0 |
[47] | Besztercei, B., Vancsik, T., Benedek, A., Major, E., Thomas, M.J., Schvarcz, C.A., et al. (2019) Stress-Induced, P53-Mediated Tumor Growth Inhibition of Melanoma by Modulated Electrohyperthermia in Mouse Models without Major Immunogenic Effects. International Journal of Molecular Sciences, 20, Article 4019. https://doi.org/10.3390/ijms20164019 |
[48] | Danics, L., Schvarcz, C.A., Viana, P., Vancsik, T., Krenács, T., Benyó, Z., 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, Article 2581. https://doi.org/10.3390/cancers12092581 |
[49] | Danics, L. (2021) Antitumor Effects of Modulated Electro-Hyperthermia in 4T1 Triple-Negative Breast Cancer Models. Ph.D. Thesis, Semmelweis University. |
[50] | Danics, L., Schvarcz, C.S. and Zolcsak, Z. (2018) Modulated Electro Hyperthermia Inhibits Tumor Progression in a Triple Negative Mouse Breast Cancer Model. Oncothermia Journal, 24, 442-454. |
[51] | Wang, S. and Wang, Y.-S. (2019) Immunotherapy in Combination with Modulated Electro-Hyperthermia. 37th Conference of the International Clinical Hyperthermia Society, Thessaloniki, 19-21 September 2019. |
[52] | Chi, K.H. (2018) Tumor-Directed Immunotherapy: Combined Radiotherapy and Oncothermia. Oncothermia Journal, 24, 196-235. |
[53] | Thomas, M.J., Major, E., Benedek, A., Horváth, I., Máthé, D., Bergmann, R., et al. (2020) Suppression of Metastatic Melanoma Growth in Lung by Modulated Electro-Hyperthermia Monitored by a Minimally Invasive Heat Stress Testing Approach in Mice. Cancers, 12, Article 3872. https://doi.org/10.3390/cancers12123872 |
[54] | Szász, A.M., Lóránt, G., Szász, A. and Szigeti, G. (2023) The Immunogenic Connection of Thermal and Nonthermal Molecular Effects in Modulated Electro-hyperthermia. Open Journal of Biophysics, 13, 103-142. https://doi.org/10.4236/ojbiphy.2023.134007 |
[55] | Dank, M., Meggyeshazi, N., Szigeti, G. and Andocs, G. (2016) Immune Effects by Selective Heating of Membrane Rafts of Cancer-Cells. Journal of Clinical Oncology, 34, e14571. https://doi.org/10.1200/jco.2016.34.15_suppl.e14571 |
[56] | Vancsik, T., Kiss, E, Kovago, C.S., Meggyeshazi, N., Forika, G. and Krenacs, T. (2017) Inhibition of Proliferation, Induction of Apoptotic Cell Death and Immune Response by Modulated Electro-Hyperthermia in C26 Colorectal Cancer Allografts. Thermometry Oncothermia Journal, 20, 277-292. |
[57] | Minnaar, C.A. and Szasz, A. (2022) Forcing the Antitumor Effects of HSPs Using a Modulated Electric Field. Cells, 11, Article 1838. https://doi.org/10.3390/cells11111838 |
[58] | 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 |
[59] | Szasz, O. (2020) Local Treatment with Systemic Effect: Abscopal Outcome. In: Szasz, A., Ed., Challenges and Solutions of Oncological Hyperthermia, Cambridge Scholars, 192-205. |
[60] | Szasz, A. (2018) Local Oncothermia Treatment Fights against Systemic Malignancy. Oncothermia Journal, 22, 58-84. |
[61] | Andocs, G., Meggyeshazi, N., Okamoto, Y., Balogh, L. and Szasz, O. (2013) Bystander Effect of Oncothermia. Conference Papers in Medicine, 2013, Article ID: 953482. https://doi.org/10.1155/2013/953482 |
[62] | Volker, S. (2017) A New Strategy of Cancer Immunotherapy Combining Hyperthermia/oncolytic Virus Pretreatment with Specific Autologous Anti-Tumor Vaccination—A Review. Austin Oncology Case Reports, 2, Article 1006. https://doi.org/10.26420/austinoncolcaserep.1006.2017 |
[63] | Van Gool, S., Makalowski, J. and Feyen, O. (2019) Can We Monitor Immunogenic Cell Death (ICD) Induced with Modulated Electrohyperthermia and Oncolytivc Virus Injections? Oncothermia Journal, 26, 120-125. |
[64] | Yang, K., Huang, C., Chi, M., Chiang, H., Wang, Y., Hsia, C., et al. (2016) In Vitro Comparison of Conventional Hyperthermia and Modulated Electro-hyperthermia. Oncotarget, 7, 84082-84092. https://doi.org/10.18632/oncotarget.11444 |
[65] | Balogh, A. (2018) mEHT as an Effective Treatment Modality for Melanoma. 36th Annual Conference of the International Clinical Hyperthermia Society (ICHS), Budapest, 28-29 September 2018. |
[66] | Andocs, G., Meggyeshazi, N., Galfi, P., Balogh, L., Fonyad, L., Muller, L., Szasz, O. and Szasz, A. (2010) Experimental Oncothermia in Nude Mice Xenograft Tumor Models. Oncothermia Journal, 1, 30. https://oncotherm.com/sites/oncotherm/files/2017-07/Experimental_oncothermia_in_nude_mice_xenograft_tumor_models.pdf |
[67] | Andocs, G., Meggyeshazi, N., Okamoto, Y., Balogh, L., Kovago, C. and Szasz, O. (2013) Oncothermia Treatment Induced Immunogenic Cancer Cell Death. Oncothermia Journal, 9, 28-37. https://oncotherm.com/sites/oncotherm/files/2017-07/Oncothermia_treatment_induced_immunogenic_cancer_cell_death.pdf |
[68] | Meggyeshazi, N. (2015) Studies on Modulated Electrohyperthermia Induced Tumor Cell Death in a Colorectal Carcinoma Model. Master’s Thesis, Semmelweis University. http://repo.lib.semmelweis.hu/handle/123456789/3956 |
[69] | Tomeh, M.A., Hadianamrei, R. and Zhao, X. (2019) A Review of Curcumin and Its Derivatives as Anticancer Agents. International Journal of Molecular Sciences, 20, Article 1033. https://doi.org/10.3390/ijms20051033 |
[70] | Ko, J., Sethi, G., Um, J., Shanmugam, M.K., Arfuso, F., Kumar, A.P., et al. (2017) The Role of Resveratrol in Cancer Therapy. International Journal of Molecular Sciences, 18, Article 2589. https://doi.org/10.3390/ijms18122589 |
[71] | Lukácsi, S., Munkácsy, G. and Győrffy, B. (2024) Harnessing Hyperthermia: Molecular, Cellular, and Immunological Insights for Enhanced Anticancer Therapies. Integrative Cancer Therapies, 23, 1-17. https://doi.org/10.1177/15347354241242094 |
[72] | Simson, L., Ellyard, J.I., Dent, L.A., Matthaei, K.I., Rothenberg, M.E., Foster, P.S., et al. (2007) Regulation of Carcinogenesis by IL-5 and CCL11: A Potential Role for Eosinophils in Tumor Immune Surveillance. The Journal of Immunology, 178, 4222-4229. https://doi.org/10.4049/jimmunol.178.7.4222 |
[73] | Cormier, S.A., Taranova, A.G., Bedient, C., Nguyen, T., Protheroe, C., Pero, R., et al. (2006) Pivotal Advance: Eosinophil Infiltration of Solid Tumors Is an Early and Persistent Inflammatory Host Response. Journal of Leukocyte Biology, 79, 1131-1139. https://doi.org/10.1189/jlb.0106027 |
[74] | Carretero, R., Sektioglu, I.M., Garbi, N., Salgado, O.C., Beckhove, P. and Hämmerling, G.J. (2015) Eosinophils Orchestrate Cancer Rejection by Normalizing Tumor Vessels and Enhancing Infiltration of CD8+ T Cells. Nature Immunology, 16, 609-617. https://doi.org/10.1038/ni.3159 |
[75] | Takeuchi, E., Ogino, H., Kondo, K., Okano, Y., Ichihara, S., Kunishige, M., et al. (2023) An Increased Relative Eosinophil Count as a Predictive Dynamic Biomarker in Non-Small Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors. Thoracic Cancer, 15, 248-257. https://doi.org/10.1111/1759-7714.15191 |
[76] | Akutsu, Y., Tamura, Y., Murakami, K., Qin, W., Hu, X., Suganami, A., Suito, H. and Matsubara, H. (2014) Can Modulated Electro-Hyperthermia (mEHT) Elicit Immune Reaction?—From Basic and Clinical Research. Oncothermia Journal, 11, 94. |
[77] | Holtmeier, W. and Kabelitz, D. (2005) γδT Cells Link Innate and Adaptive Immune Responses. In: Kabelitz, D., Schröder, J.M. and Karger, A.G., Eds., Chemical Immunology and Allergy, KARGER, 151-183. https://doi.org/10.1159/000086659 |
[78] | Zhang, H., Hu, H., Jiang, X., He, H., Cui, L. and He, W. (2005) Membrane HSP70: The Molecule Triggering γδT Cells in the Early Stage of Tumorigenesis. Immunological Investigations, 34, 453-468. https://doi.org/10.1080/08820130500265349 |
[79] | Fisher, J.P., Heuijerjans, J., Yan, M., Gustafsson, K. and Anderson, J. (2014) γδT Cells for Cancer Immunotherapy: A Systematic Review of Clinical Trials. OncoImmunology, 3, e27572. https://doi.org/10.4161/onci.27572 |
[80] | Liu, Y. and Zhang, C. (2020) The Role of Human γδT Cells in Anti-Tumor Immunity and Their Potential for Cancer Immunotherapy. Cells, 9, Article 1206. https://doi.org/10.3390/cells9051206 |
[81] | Roth, J. and Blatteis, C.M. (2014) Mechanisms of Fever Production and Lysis: Lessons from Experimental LPS Fever. Comprehensive Physiology, 4, 1563-1604. |
[82] | Szasz, A. (2020) Preface. In: Szasz, A., Ed., Challenges and Solutions of Oncological Hyperthermia, Cambridge Scholars, 8-13. |
[83] | Barich, A.J., Daniilidis, L. and Marangos, M. (2018) Oncothermia and the Paradigm Shift in Integrative Oncology. Oncothermia Journal, 24, 373-404. |
[84] | Szigeti, G.P., Lee, D.Y. and Hegyi, G. (2017) What Is on the Horizon for Hyperthermic Cancer Therapy? Journal of Traditional Medicine and Clinical Naturopathy, 6, Article ID: 1000217. |
[85] | Minnaar, C.A., Szigeti, G.P., Szasz, A.M. and Kotzen, J.A. (2022) Review on the Use of Modulated Electro-Hyperthermia as a Stand-Alone Therapy in a Palliative Setting: Potential for Further Research? Journal of Cancer Therapy, 13, 362-377. https://doi.org/10.4236/jct.2022.136032 |
[86] | Szasz, A.M., Minnaar, C.A., Szentmártoni, G., Szigeti, G.P. and Dank, M. (2019) Review of the Clinical Evidences of Modulated Electro-Hyperthermia (mEHT) Method: An Update for the Practicing Oncologist. Frontiers in Oncology, 9, Article 1012. https://doi.org/10.3389/fonc.2019.01012 |
[87] | Lee, S., Lorant, G., Grand, L. and Szasz, A.M. (2023) The Clinical Validation of Modulated Electro-Hyperthermia (mEHT). Cancers, 15, Article 4569. https://doi.org/10.3390/cancers15184569 |
[88] | Minnaar, C.A., Kotzen, J.A., Ayeni, O.A., Vangu, M. and Baeyens, A. (2020) Potentiation of the Abscopal Effect by Modulated Electro-Hyperthermia in Locally Advanced Cervical Cancer Patients. Frontiers in Oncology, 10, Article 376. https://doi.org/10.3389/fonc.2020.00376 |
[89] | Chi, M., Mehta, M.P., Yang, K., Lai, H., Lin, Y., Ko, H., et al. (2020) Putative Abscopal Effect in Three Patients Treated by Combined Radiotherapy and Modulated Electrohyperthermia. Frontiers in Oncology, 10, Article 254. https://doi.org/10.3389/fonc.2020.00254 |