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On the Thermal Distribution in Oncological Hyperthermia Treatments

Open Journal of Biophysics 2024年第2期14卷 239-263页

作者： andras szasz Department of Biotechnics Hungarian University of Agriculture and Life Sciences G&#246d&#246ll&#337 Hungary

The temperature is one of the principal controlling parameters of oncological hyperthermia. However, local heating forms a complicated thermal distribution in space and has developed over time, too. The decisional factors are the heterogeneity of the targeted volume, the electrolyte perfusions controlled by thermal homeostasis, and the spreading of the heat energy with time. A further complication is that the energy absorption sharply changes by depth, so the spatiotemporal development of the temperature distribution requires specialized methods to control. Most of the temperature imaging facilities (thermography, radiometry, electric impedance tomography, etc.) are less precise than the medical practice needs. In contrast, precise point sensing (like thermocouples, thermistors, and fluoroptical methods) is invasive and measures only a discrete point in the robustly changing thermal map. The two most precise thermal imaging methods, computer tomography, and magnetic resonance are expensive and have numerous technical complications. Our objective is to show the complexity of the temperature distribution inside the human body, and offer a relatively simple and cheap method to visualize its spatiotemporal development. A novel emerging technology, the application of ultrasound microbubble contrast agents is a promising method for solving complicated tasks of thermal distribution deep inside the living body. Noteworthy, the temperature distribution does not determine the full hyperthermia process, nonthermal effects make considerable impact, too. Additionally to the difficulties to measure the thermal heterogeneity during hyperthermia in oncology, numerous nonthermal processes, molecular and structural changes are triggered by the incoming electromagnetic energy, which presently has no spatiotemporal visualization technique. Microbubble imaging has a suitable spatiotemporal thermal resolution, and also it is sensitive to nonthermal effects. Its application for characteri

关键词： Microbubbles Thermal Heterogeneity Electric Heterogeneity Bloodstream Thermal and Nonthermal Synergy Temperature Distribution Temperature Measurements

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Preclinical Verification of Modulated Electro-Hyperthermia—Part III. Immunogenic Effects

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International Journal of Clinical Medicine 2024年第7期15卷 335-364页

作者： andras szasz Department of Biotechnics Hungarian University of Agriculture and Life Sciences Gdll Hungary

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.

关键词： mEHT Cancer Thermal Nonthermal Immunogenic ICD DAMP Tumor-Specific Immune

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Preclinical Verification of Modulated Electro-Hyperthermia —Part I. In Vitro Research

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International Journal of Clinical Medicine 2024年第7期15卷 257-298页

作者： andras szasz Department of Biotechnics Hungarian University of Agriculture and Life Sciences Gdll Hungary

Modulated electro-hyperthermia (mEHT) targets tissue’s natural electric and thermal heterogeneities to heat the cancer cells selectively. The applied 13.56 MHz radiofrequency (RF) is a carrier of the low-frequency modulation. The high-frequency part was chosen to select the malignant lesion using the specialties of the tumor: the higher conductivity and dielectric constant of the tumor than its host. The electric field selects the tumor, and the low-frequency amplitude modulation polarizes and excites the transmembrane proteins of the malignant cells. The dominant absorption of the energy by the microscopic clusters of the membrane rafts acts like nanoparticle heating. Exciting the membrane produces various apoptotic signals. The processes were modeled using silico and phantom experiments, which proved the concept. The preclinical verification was made in vitro and in vivo, and in the end, clinical proofs validated the method. Our objective is to follow all the development steps from the laboratory to the clinics in a trilogy of articles. This present is the first part, which deals with in silico, phantom, and in vitro research.

关键词： Modulated Electro-Hyperthermia mEHT In Silico Calculations Phantom Measurement In Vitro Experiments Thermal Effects Nonthermal Processes Apoptosis

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Exploring Biocomplexity in Cancer: A Comprehensive Review

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Open Journal of Biophysics 2024年第2期14卷 154-238页

作者： andras szasz Gyula Peter Szigeti Department of Biotechnics Hungarian University of Agriculture and Life Sciences G&#246d&#246ll&#337 Hungary John von Neumann Faculty of Informatics O&#769buda University Budapest Hungary

Living objects have complex internal and external interactions. The complexity is regulated and controlled by homeostasis, which is the balance of multiple opposing influences. The environmental effects finally guide the self-organized structure. The living systems are open, dynamic structures performing random, stationary, stochastic, self-organizing processes. The self-organizing procedure is defined by the spatial-temporal fractal structure, which is self-similar both in space and time. The system’s complexity appears in its energetics, which tries the most efficient use of the available energies;for that, it organizes various well-connected networks. The controller of environmental relations is the Darwinian selection on a long-time scale. The energetics optimize the healthy processes tuned to the highest efficacy and minimal loss (minimalization of the entropy production). The organism is built up by morphogenetic rules and develops various networks from the genetic level to the organism. The networks have intensive crosstalk and form a balance in the Nash equilibrium, which is the homeostatic state in healthy conditions. Homeostasis may be described as a Nash equilibrium, which ensures energy distribution in a “democratic” way regarding the functions of the parts in the complete system. Cancer radically changes the network system in the organism. Cancer is a network disease. Deviation from healthy networking appears at every level, from genetic (molecular) to cells, tissues, organs, and organisms. The strong proliferation of malignant tissue is the origin of most of the life-threatening processes. The weak side of cancer development is the change of complex information networking in the system, being vulnerable to immune attacks. Cancer cells are masters of adaptation and evade immune surveillance. This hiding process can be broken by electromagnetic nonionizing radiation, for which the malignant structure has no adaptation strategy. Our objective is to review

关键词： Complexity Networks Small-World Genetic Mutations Self-Organizing Self-Symmetry Energetic Balance Entropy Nash Equilibrium Games Evolution Cancer Therapy

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Memristor Hypothesis in Malignant Charge Distribution

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Open Journal of Biophysics 2023年第4期13卷 51-92页

作者： andras szasz Department of Biotechnics St. Istvan University Budaors Hungary

Tissues in biological objects from the point of view of electromagnetic effects must be modeled not only for their conductivity. The ionic double layer induced by the electric field, built by electrolytic diffusion, must be counted. The micro (frequency dispersion phenomena) and macro (interfacial polarization), as well as more generalized by Nernst-Planck cells describe the biophysical aspects of this phenomena. The charge distribution depends on the processes and produces charge gradients in space. The dynamic feasibility of the-charge transition layer has memory and adaptability, working like a memristor in cancerous development. The memristor processes may complete the adaptation mechanisms of cancer cells to extremely stressful conditions. Our objective is to show the distribution and redistribution of space charges that generate memristors and internal currents like injury current (IC) in the development of cancer. We show some connected aspects of the modulated electrohyperthermia (mEHT) limiting the proliferation process in the micro-range like the macro-range electrochemotherapy (ECT) processes do. The internal polarization effects form space-charge, which characteristically differ in malignant and healthy environments. The electrical resistivity of the electrolytes depends on the distribution of the charges and concentrations of ions in the electrolytes, consequently the space-charge differences appear in the conductivity parameters too. The polarization heterogeneities caused by the irregularities of the healthy tissue induce a current (called injury current), which appears in the cancerous tumor as well. Due to the nonlinearity of the space-charge production and the differences of the relaxation time of the processes in various subunits. The tumor develops the space-charge which appears as an inductive component in the otherwise capacitive setting and forms a memristive behavior of the tumorous tissue. This continuously developing space-charge accommodat

关键词： Malignancy Tumors Memristor Imperfect Dielectrics Heterogeneity Charge Distribution Injury Current Nernst-Planck Cell

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Cancer-Specific Resonances

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Open Journal of Biophysics 2022年第4期12卷 185-222页

作者： andras szasz Department of Biotechnics Hungarian University of Agriculture and Life Sciences Godollo Hungary

The research of cancer-specific resonances started with Raymond R. Rife’s controversial results. The intensive debate began on the topic, and various interpretations of the results deepened after his death. This theme presently sparks desperate debates with extreme opinions, from the dangerous quackery to the brilliant discovery. A part of medical practices applies the resonance principle in various anticancer therapies and uses a variety of devices. Most medical experts refuse such “resonance therapies” due to their confidence in their quackery. I summarized some present problems and proposed a possible solution. My present article aims to discuss some aspects of the biological resonances, trying to clear some vague details of this subject and give a possible stochastic explanation of some resonances in cancer therapy. However, when considering the stochastic explanations of resonance frequencies, there are as many of these as there are enzymatic processes affecting the biological systems.

关键词： Rife Frequencies Pythagorean Mystics Resonances Noises Fluctuations Stochastic Processes Enzymatic Resonances

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Time-Fractal Modulation—Possible Modulation Effects in Human Therapy

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Open Journal of Biophysics 2022年第1期12卷 38-87页

作者： andras szasz Department of Biotechnics Szent Istvan University Budaors Hungary

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.

关键词： Pink-Noise Homeostasis Amplitude-Modulation Cellular-Communication Antigen-Presentation Stochastic Resonances Resonance Frequencies Cellular Networking

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Time-Fractal in Living Objects

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Open Journal of Biophysics 2022年第1期12卷 1-26页

作者： andras szasz Department of Biotechnics Szent Istvan University Buda&ouml rs Hungary

Homeostasis creates self-organized synchrony of the body’s reactions, and despite the energetically open system with intensive external and internal interactions, it is robustly stable. Importantly the self-organized system has scaling behaviors in its allometry, internal structures, and dynamic processes. The system works stochastically. Deterministic reductionism has validity only by the great average of the probabilistic processes. The system’s dynamics have a characteristic distribution of signals, which may be characterized by their frequency distribution, creating a particular “noise” 1/f of the power density. The stochastic processes produce resonances pumped by various noise spectra. The chemical processes are mostly driven by enzymatic processes, which also have noise-dependent resonant optimizing. The resonance frequencies are as many as many enzymatic reactions exist in the target.

关键词： Homeostasis Self-Organizing Feedbacks Complexity Resonance Stochastic Processes 1/f Noise Dissipation Enzymatic Reactions

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Stimulation and Control of Homeostasis

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Open Journal of Biophysics 2022年第2期12卷 89-131页

作者： andras szasz Department of Biotechnics Szent Istvan University Budaors Hungary

Healthy homeostasis is a principal driving force of the dynamic equilibrium of living organisms. The dynamical basis of homeostasis is the complex and interconnected feedback mechanisms, which are fundamentally governed by the nervous system, mainly the balance of the sympathetic and parasympathetic controlling actions. The balancing regulation is well presented in the heart’s sinus node and can be measured by the time-domain heart-rate variation (HRV) of its frequency domain to analyze the constitutional frequencies of the variation. This last is a fluctuation that shows 1/f time fractal arrangement (f is the composing frequency). The time-fractal arrangement could depend on the structural fractal of the His-Purkinje system of the heart and personally modify the HRV. The cancers gradually destroy the homeostatic harmony, starting locally and finishing systemically. The controlling activity of vagus-nerve changes the HRV or the power density spectrum of the signal fluctuations in malignant development, presenting an appropriate control of the cancerous processes. The modified spectrum by a non-invasive radiofrequency treatment could arrest the tumor growth. An appropriate modulation could support the homeostatic control and force reconstructing of the broken complexity.

关键词： Homeostasis Vagus Stimulation Heart-Rate Variability Immune-Stimuli Cancer Time-Fractal Modulation Bifurcations 1/f Noise mEHT Personalized Therapy

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Supportive and Palliative Care in Cancer Therapies—Path from Tumor-Driven Therapies to Patient-Driven Ones

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International Journal of Clinical Medicine 2022年第7期13卷 287-359页

作者： Carrie Anne Minnaar andras szasz Sun Young Lee Gyula Peter Szigeti Attila Marcell szasz Domokos Mathe Wits Donald Gordon Medical Center Department of Radiation Oncology Johannesburg South Africa Department of Radiation Sciences University of the Witwatersrand Gauteng South Africa Biotechnics Department Hungarian University of Agriculture and Life Sciences Godollo Hungary Department of Radiation Oncology Jeonbuk National University Medical School Jeonbuk Republic of Korea Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital Jeonju Republic of Korea Semmelweis University Innovation Center Budapest Hungary Division of Oncology 1st Department of Internal Medicine and Oncology Semmelweis University Budapest Hungary Department of Biophysics and Radiation Biology Faculty of Medicine Semmelweis University Budapest Hungary

Cancer patients frequently report a set of symptoms including fatigue, pain, and physiological and social distress. Families and other personal lay relations give proposals to take supportive drugs and supplemental nutrients, without professional knowledge about their actions. Internet search engines and social networks serve up most of the treatment proposals, opening wide possibilities for quackeries and predatory money-making practices. Medical professionals have a responsibility to clear this field and concentrate on patients’ well-being and personal needs. According to our approach, the integration of supportive and palliative care with conventional therapies needs a change of paradigm from tumour-driven to patient-driven treatment actions. Supportive/palliative care includes a broad spectrum of applied methods, including medications, nourishments, electrical effects, and psycho and social supports. Our goal is to discuss the possibilities for combining conventional oncotherapies with additional supportive/palliative care and to give suggestions on a professional basis.

关键词： Cancer Vitamins Minerals Fungi Immune Phytomedicine Complexity Electric-Stimuli Hyperthermia mEHT

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