Metabolic effects of accompanying activation therapy in oncopathology

Federal State Budgetary Institution “National Medical Research Center of Oncology” of the Ministry of Health of the Russian Federation, Rostov-on-Don, Russia

At present, there is a primacy of molecular and genetic concepts on the mechanism of the appearance and development of cancer. Much less attention is paid to an attention and an understanding of the metabolic features of malignant cells as a result of transformation at the genetic level. One of the trigger points in the pathogenesis of a malignant neoplasm is energy homeostasis in tumor cells and its microenvironment. Moreover, the pathways of energy metabolism are actually based on similar mechanisms of satisfying energy hunger with normal cells [1].

It is necessary to take into account that energy supply serves as the most important part of the global mechanism of the adaptive activity of the organism

16 | Cardiometry | Issue 33. November 2024

and its integral central control of nonspecific resistance, including antitumor resistance. As a result from the discovery by H. Selye (1936), L.Kh. Garkavi, M.A. Ukolova, E.B. Kvakina (1975) known are 4 archetypes of the body’s response to the action of stimuli of varying intensity: the adaptational reaction of training to relatively weak stimulation, the reaction of activation (including 2 types of the reaction, namely, calm and elevated activation) to medium-scale intensity stimulation, and stress as the reaction to strong stimulation. These main types of the organism’s response create the primary structure of the general nonspecific adaptational reactions (GNAR), which repeats at different levels of reactivity with increasing (decreasing) of intensity of applied stimulation, building in such a manner the periodic system of GNARs. The GNARs qualitatively differ from each other in the symptom complex of nervous, endocrine, immune changes and metabolic resources, including energy supply. Medicine, with oncology included, has acquired literally an appropriate control system for integrative regulation of nonspecific adaptational capabilities [2].

Due to the multilevel organization of GNAR (the presence of a pattern of periodic repetition at different levels of reactivity), wide opportunities for accompanying cancer therapy are opened, including scientifically substantiated approaches to the implementation of metabolic effects from the standpoint of a dual control approach: the central control and the peripheral one. The development of this approach has been based on data on the state of energy processes in the brain of animals without tumors against those as tumor carriers that was obtained in close scientific cooperation with the Institute of Biophysics at the Russian Academy of Sciences in Pushchino. The processes of respiration and oxidative phosphorylation, oxaloacetic limitation, a low-energy shift, levels of endogenous succinic acid and adenosine triphosphate have been studied. Physiological adaptive reactions have been induced by an exponential algorithm of doses of adrenaline or succinic acid, or eleutherococcus, or weak ULF MF on the brain: this is a strategy of central genesis of GNAR of the anti-stress physiological type (training, activation of calm and elevated reactions). The induction of these GNARs has made it possible to control the protective potential of the organism as a whole.

At the same time, against the background of experimental chemotherapy, we added to the central effect a local one produced on the tumor by peritumoral injections of large doses of ATP or diphenhydramine along the tumor perimeter, taking into account the logical effect of inhibition of energy processes. The antitumor effect by metabolic therapy in the experiment was manifested in the form of full or partial regression of sarcoma 45. Under the clinical conditions, during chemotherapy of locally advanced breast cancer against the background of inversion of local energy metabolism along the tumor periphery, it has been possible to achieve complete (17%) or partial (66.7) regression of the primary process and transfer the latter to an operable status [3].

We expanded later the spectrum of activation metabolic therapy, including programmed algorithms for dosing energy substrates (cAMP, succinic acid), neurotropic substances (adrenaline, noradrenaline, cellex), factors of electrical and electromagnetic nature (SCENAR, ultra-low frequency magnetic fields – ULF MF) and inert gas xenon. In the framework of translational therapy, an accompanying metabolic therapy was carried out under the control of AR in patients with lung cancer, bowel cancer, bladder cancer, high-grade brain tumors, mediated by central and local use of ULF MF, breast cancer and genital cancer.

The technology of central (hypothalamic projection) electromagnetic exposure took into account the features of the magnetic map of the brain obtained with SQUID imaging technique according to H. Delgado, W.B.Reidi, Yu.A. Kholodov (1989). Based on the coordination of the endogenous brain rhythms and the exogenous frequencies induced by the Gradient medical device with an algorithm 0.03-0.3-3.0-9.0-12 Hz with an exponential decrease in induction from 5 to 0.8 mT and an increase in time from 3 to 8 min., under monitoring of GNAR signal indicators, a controlled increase in nonspecific antitumor resistance was achieved. The local action of ULF MF or SCENAR was carried out within the area of the surgical field with enhanced parameters, and in some cases with polymodal complexation with cAMP or SA in the double exponential mode. In the complex treatment of colorectal cancer, polymodal metabolic correction made it possible to increase the two-year survival rate after radical surgery from 66% to 100%, and an increase in the average life expectancy after palliative surgery by 2 times compared to the reference. Metabolic effects of activation magnetic therapy in the early postoperative period in lung cancer were manifested in a decrease in the level of cortisol, catecholamines, normalization of immune parameters, circadian rhythmicity of the pineal gland by determining the level of 6-SOM. One of the highly effective types of metabolic therapy based on activation technologies has become an innovative approach to correcting neurohormonal disorders and adaptive status using xenon therapy in patients of reproductive age diagnosed with cervical cancer and breast cancer after hormone-reducing operations. Dose regimens are also of fundamental importance when implementing activation therapy with pulsed ultra-low frequency electromagnetic fields, contributing to the normalization of disorders of the electrophysiological, neurological, cognitive and adaptive status after the stages of surgical and radiation treatment of glioblastomas of the brain. The metabolic component of such effects is a natural link in the complex integral adaptive response of the physiological type. Thus, when discussing the controlled metabolic therapy, it is necessary to take into account the integrity and the nature of GNAR first of all, depending on the intensity of the presented functional load, whatever quality is, but at the same time, the selection of a means for correcting metabolism should also take into account the specifics of its influence to achieve a harmonious state of the body.