Discovery of adaptational reactions: a new milestone in the development of oncology

National Medical Research Centre for Oncology

Russia, Rostov-on-Don

The celebration of the 90th anniversary of the National Medical Research Centre for Oncology at the Ministry of Health of the Russian Federation in the past 2021 expanded its time frame due to other anniversaries that are inextricably linked with the scientific activities of the Rostov Cancer Centre. First of all, this is the 115th anniversary of the birth of M.A. Ukolova, the founder of fundamental research at the Centre for Oncology, the 65th anniversary of the establishment of the experimental department, and the 45th anniversary of the discovery of "Pattern of development of qualitatively differing general nonspecific adaptational reactions of the organism” made by Garkavi L.Kh., Ukolova E. B. and Kvakina E.B. [1].

The intellectual power of Lyubov Garkavi, the fantastic expertise and talent of Elena Kvakina, the brilliant, top leader and top organizer Maria Ukolova have contributed to expand the boundaries of the knowledge and offered to the world a discovery of the patterns of development of adaptational reactions depending on the intensity of a stimulus. It was a breakthrough, a new philosophy in biology and medicine, based on the ideas of the nervism theory by I.P. Pavlov, the laws of dialectics, synergetics, self-organization of complex systems, phase transitions and, of course, the theoretical heritage by the titans of thought: Selye, Anokhin, Simonov, Lazarev, Kavetsky, Arshavsky, Kryzhanovsky, Dilman and many other outstanding scientists of the 20th century. It is destined by fate that the Rostov Cancer Research Institute (today referred to as the National Medical Research Centre for Oncology) has become a platform and a trigger centre that launches the process of the emergence and development of the theory of adaptational reactions.

It would seem difficult to imagine how they succeeded in the identification of the subtle mechanism responsible for an integral control of the organism as a whole in presence of a tumor progression. But nothing helps to get closer to the truth as much as the obstacles which appeared at the Cancer Research Institute in their experiments, starting from the fact that at the beginning of the establishment of the experimental department there were no appropriate conditions for keeping tumor-bearing animals, there was no diagnostic and therapeutic equipment, there was no bank of tumor cell strains available. But there were bright minds of young scientists, their observation ability and full dedication to research, who dared to penetrate into the Holy of Holies of the neuroendocrine regulation: the hypothalamus, in order to discover the relationship between the quantity (strength, measure) of a direct or remote impact on this command centre of the system control and the integral qualitative response by the body, namely, the development of a general adaptational reaction of nonspecific nature.

The discovery of the patterns of development of adaptational reactions of the body, the theory and practice of managing complex systems based on the principles of activation therapy have become the visiting card of the scientific team and fundamental research of the National Medical Research Centre for Oncology in Rostov-on-Don, which has accumulated over several decades unique experience in experimental oncology and in the transfer of developed technologies to clinical practice. Those developments have been well in advance of the officially formulated idea of translational medicine. Completed governmental assignments, defended candidate and doctoral dissertations and theses, patents, hundreds of articles on solving problems of increasing nonspecific antitumor resistance, - all these works have become an integral part of the Russian national oncology, offering a new view of considering the relationship between the tumor and the body from the standpoint of the theory of adaptational reactions [2].

When presenting the basics of this theory, it is necessary to return to the prototype of those generally accepted simple true statements, according to which our genotype is not a chaotic set of molecular genetic structures, but it is a unique algorithm for the periodic repetition of the four nitrogenous bases only: guanine, cysteine, uracil and adenine. No matter how the level of selforganization rises, the principle of discreteness of the particular and the integration of the whole remains applicable. The outer shell of an atom of various chemical elements is filled with electrons and, according to the criteria of the outer shell electrons, the periodic system of chemical elements with different properties is formed. At the level of the organism and its response to effects produced by the external and internal environment, a mechanism of periodic repetition of several, similarly named, general nonspecific adaptational reactions (GNAR) is implemented at different levels of reactivity.

The discovery of the archetype of the stress response by Hans Selye is one of the most outstanding achievements in biology and medicine. The implementation of such an archetype of reaction in response to a strong and dangerous impact is carried out with the participation of the command systems of the brain, regulatory influences of the pituitary gland regarding the release of ACTH, suppression of the executive endocrine and immune organs, at high energy expenses and the dominance of catabolism processes over anabolism. As a result, the resistance decreases and, with prolonged exposure to a stressor, an unfavorable outcome may occur.

The stress program is only a part of the adaptational response that forms the nonspecific basis for pathology, including cancers. To ensure health and increase resistance, including the antitumor resistance, there are other regulatory programs in a human organism available, involving the use of the same CNS structures and the regulatory systems (the neuroendocrine and the immune systems), which are sensitive and respond appropriately to physiological, middle-intensity or even weak influences and stimulation. These programs are the core and the essence of the opened by L.Kh. Garkavi, M.A. Ukolova, E.B. Kvakina discrete archetypes of the physiological adaptational responses of training (to a relatively weak stimulus), calm and elevated activation (medium strength, intermediate between the weak and strong stimulation). These latter are distinguished by the most harmonious and synchronized increase in the functional activity of all organism systems. Thus, the targeted design of the intensity of stimulation applied to the body shall be based on the control of the desired response that should lead to a rise in its nonspecific resistance.

The human brain, like the entire organism as a whole, has the ability to generate more than just the four adaptational reactions. Obeying the laws of self-organization of complex systems in an environment, where and when the intensity of influencing factors can vary in the widest range, a living organism is furnished with a multi-level periodic system of adaptive reactions. The alternation of reactions of the same name in the sequence T, CA, EA, S at one level of reactivity and the transition to another level (lower or higher) occurs with a mandatory entry into the interlevel zone of AREACTIVITY, where the systems seem to be silent, giving no response. Such a zone of areactivity is of great biological importance for maintaining negentropy and homeostasis under transitional conditions.

The theory of adaptational reactions is based on the description of the features of the development of each existing biological archetype of nonspecific adaptational reactions and the unique natural periodic system of their repetition that offers ample opportunities for the selection of the desired reaction at the required level of reactivity, taking into account age, sex, nosology and the stage of a specific treatment. Over the years of work, the researchers of the Rostov Centre for Oncology have developed the strategy, tactics and principles of activation therapy, defined simple signal criteria for assessing adaptational reactions, as well as mathematically justified programmed modes of dose 3 Cardiometry, Issue 24, November 2022

variation of different stimulating factors (weak electromagnetic fields from ultra-low frequencies to EHF range, pharmacological neurotropic gas mixtures with xenon, herbal medicines, metabolic support products based on succinic acid, cAMP, selenium, and much more).

Despite the genuine interest of scientists from America, Japan, Israel and other countries, this powerful store of knowledge has found its port of destination primarily in Russia. For more than 30 years, our Oncology Centre has been promoting the accompanying therapy for various cancers at the stages of combination treatment. It has been shown that the inclusion of accompanying activation therapy in the form of central, local, extracorporeal or other actions and effects significantly improves the indicators of the state of the central nervous system, the hormonal and immune status in cancer patients, improves the quality of life and survival and also contributes to the effectiveness of special antitumor treatment. It is a transparent system of regulation of homeostasis.

At present, great importance is prioritized to the functional rehabilitation of cancer patients: international congresses are held, rehabilitation measures are being developed in various countries, the International Model of Rehabilitation in Oncology is presented in a versatile and qualified way [3], but however the mechanisms of integral response patterns cannot be found in these high technologies and unique systems. Behind the simplicity of the theory of health, the strategic keys to practical health remain unnoticed, the acquisition of which will open the path to a long and healthy life.