[Diabetes mellitus and cancer: a system of insulin-like growth factors].

Diabetes mellitus and malignant tumors are among the most common and complex diseases. Epidemiological studies have shown a strong relationship between these pathologies. The causality of this relationship has not yet been unambiguously established, but a number of probable biological mechanisms have been proposed to explain it through the effects of hyperglycemia, hyperinsulinemia on the process of oncogenesis. An important role in this is played by the axis of insulin-like growth factors, their receptors and binding proteins (IGF / IGFR / IGFBP). The review provides data on the structural elements of the insulin / IGF / IGFR / IGFBP signaling axis and their internal relationships in diabetes mellitus and in the development of malignant tumors. Significant changes in the axis that occur during the formation of the diabetic environment prepare the background, which, under certain conditions, can lead to the stimulation or inhibition of tumor development. The considered signaling system, playing a significant role in the physiology of normal cells, often functions as a decisive factor in the survival of tumor cells, providing fine context-dependent regulation of many cellular processes associated with oncogenesis. However, despite many years of in-depth studies of the pathogenesis of diabetes mellitus and malignant tumors, the molecular mechanisms of the relationship between these pathologies are still largely unclear, and the internal heterogeneity of pathologies complicates research and interpretation of the results, leaving many questions.

Method to Create Multiple Primary Malignant Neoplasms with Stimulation of Tumor Growth under Conditions of Primary Immunodeficiency in Experiment.

The experimental model of synchronous multiple primary malignant tumors (MPMT) was created. B16/F10 melanoma (0.5 ml of suspension diluted 1:20 in saline) and sarcoma 45 (0.5 million tumor cells in 0.5 ml saline) were simultaneously subcutaneously inoculated to male BALB/c nude mice. In the model of synchronous MPMT, the tumors appeared faster by 2.4 times and had greater volumes: melanoma by 2.2 times and sarcoma by 3.2 times; melanoma metastasized into sarcoma in 71.4% cases; the survival of mice with MPMT was lower. The altered dynamics of malignant growth in the MPMT model is based on the mutual influence of tumors, which results in the exchange of "structural information".

Experimental Modeling of Multiple Primary Malignant Processes with One Tumor Suppressed by Another under Conditions of Primary Immunodeficiency.

The phenomenon of multiple primary malignant tumors (MPMT) is characterized by the presence of several primary neoplasms in the same patient. An experimental model of MPMT with one dominating tumor was developed. Female BALB/c nude mice received simultaneous subcutaneous inoculation of Guerin's carcinoma (5×105 tumor cells in 0.5 ml saline) and B16/F10 melanoma (0.5 ml suspension diluted 1:20 with saline). Control females received transplantation of either melanoma or carcinoma alone in the same doses and volumes. In animals with MPMT model, tumors appeared 3-fold faster than after isolated transplantation of melanoma or Guerin's carcinoma and were larger by 7.5 and 2.2 times, respectively; the survival of mice with MPMT was lower. Guerin's carcinoma in the MPMT model metastasized to melanoma and almost completely suppressed its growth. Thus, a MPMT model was created with carcinoma suppressing the malignant growth of melanoma.

[Influence of malignant growth and chronic neurogenic pain on neurosteroid levels in rat brain]. / Vliianie zlokachestvennogo rosta i khronicheskoi neirogennoi boli na uroven' neirosteroidov v mozge krys.

The aim of the study was to determine the level of sex steroid hormones in white matter of the brain of rats with tumors combined with chronic neurogenic pain (CNP), which was modeled by bilateral sciatic nerve ligation. The study included albino male rats (n=74). In the main group, M1 sarcoma was transplanted subcutaneously (n=11) or into the subclavian vein (n=11) 45 days after CNP modeling. Two comparison groups (n=13 each) included sham operated animals (without CNP) with M1 sarcoma transplanted subcutaneously and intravenously. Control groups included animals with CNP and sham operated animals. Rats were euthanized on day 21 of the carcinogenesis. Levels of total and free testosterone (T), estrone (E1), estradiol (E2), estriol (E3) and progesterone (P4) in the brain white matter were measured using ELISA kits ("Cusabio", China). CNP caused a decrease in the total and free T by 1.5 times (p<0.05), E2 and P4 by 1.9 and 3 times, respectively, E3 by 1.6 times (p<0.05), as well as an increase in E1 by 1.4 times (p<0.05) as compared to the corresponding levels in the brain white matter of rats without CNP. CNP stimulated M1 sarcoma growth in both subcutaneous and intravenous transplantation. Regardless of the tumor site, the dynamics of total T, E2 and E3 in the brain had similar features, but the dynamics of free T, P4 and E1 differed. Thus, changes in the level of neurosteroids in the white matter of rat brain with CNP and tumor growth alone or associated with CNP are a reaction to stress.

[The activity of redox-regulatory systems in the primary and recurrence tumors in vulvar cancer]. / Aktivnost' redoks-reguliruiushchikh sistem v pervichnykh i retsidivnykh opukholiakh vul'vy.

The activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GR), glutathione transferase (GST), the content of reduced glutathione (GSH) and malondialdehyde (MDA) were investigated in the samples of the tumor, peritumoral zone and healthy tissue, taken at the line of resection, were obtained from 14 patients with primary squamous cell carcinoma of the vulva, and 13 patients with local recurrence appeared in the period from 3 months to 7 years. by conventional spectrophotometric methods. The content of GSH and the activity of SOD, GPx, GR, GST were significantly increased, while MDA was decreased in the tissue of the primary carcinoma of the vulva in compared with the healthy tissue. Differences in the functioning of the investigated system of enzymes in the peritumoral zone were also revealed in the primary and recurrent tumoral process. Similar but much less pronounced changes were also observed in the recurrent tumor. It is suggested that such dynamics of activity of the studied system with the progression of cancer process can be the result of adaptation to changes in the local biochemical status of healthy (nonmalignant) tissue of the organ carrying the tumor and reflect the metabolic features of the recurrent tumor.

[The level of endogenous intoxication iт oncologic gynecologic patients.]

The leading role of syndrome of endogenous intoxication in structure of clinical manifestations of tumor disease conditions actuality of studying components determining its development, in dynamics of malignant process and under anti-tumor therapy. Among all studied groups of oncogynecological patients, the most expressed decreasing of functional activity of albumin binding toxic compounds is observed under ascitic form of ovary cancer. In the group of patients with ovary cancer of stage I-II and also in condition of remission of process in patients with ovary cancer of stage III, the values of total and effective concentration of albumin and its binding capacity, on the contrary, are approaching to donor values. Under cervical carcinoma and vulva cancer the statistically significant decreasing of effective concentration of albumin and its binding capacity was established. However, thisdecreasing is manifested in minor degree than in patients with ascitic form of ovary cancer.

Experimental study of structural, functional, and biochemical changes in immune organs under conditions of antitumor activity of copper nanoparticles.

The effects of copper nanoparticles on the structure and function of the immune system organs (thymus and spleen) and intensity of free radical processes in the spleens of rats with sarcoma 45 were studied. A relationship between morphological and biochemical changes and antitumor efficiency of copper nanoparticles was demonstrated.

[Structural-functional changes in lymphocyte ans erythrocyte membranes after exposure to alternating magnetic field]. / Strukturno-funktsional'nye izmeneniia membran limfotsitov i éritrotsitov pod vozdeistviem peremennogo magnitnogo polia.

The lymphocyte membrane fluidity, membrane potential, isoenzyme spectrum of superoxide dismutase (SOD) and catabolic product level of blood cell receptors in rats, healthy volunteers and patients with ovary and skin tumors were studied under the influence of low frequency electromagnetic field (EMF). The increase of fluidity of rat blood lymphocyte membranes was observed at 20 and 40 min exposure of the lymphocyte suspension to EMF. The increase of ANS fluorescence observed after 20 min exposure to EMF suggested a decrease of cell membrane potential. EMF exerted opposite changes of lymphocyte membrane fluidity of healthy volunteers and the effect depended on the initial level of this parameter. Study of SOD isoenzyme spectrum revealed that Cu,Zn-dependent SOD can account for the superoxide dismutase catalytic activity of supernatant and lymphocytes. The EMF exposure for 20 min caused 2-fold increase of SOD activity. The EMF exposure for 40 min caused the further increase of SOD activity but only in lymphocytes. At the same time the EMF exposure did not influence the actual SOD-activity in erythrocytes. However, there was clear anti-R-reagent-sensitive SOD-activity which was not abolished by DDC. The reasons and possible consequences of these changes of feuidity and SOD-activity under EMF effect are discussed.

[Level of monoamines during hypobaric hypoxia and protective effect of pyrazidol]. / Soderzhanie monoaminov pri gipobaricheskoi i zashchitnom éffekte pirazidola.

The effects of single acute hypoxia (9000 m above the sea level, 3h) and intermittent hypoxia (5000 m 4 h daily during 3 and 10 days) were studied. Acute hypoxia was characterized by the increase in the content of brain serotonin, dopamine and norepinephrine accompanied by a decrease of deaminated product. The increase of monoamine contents in hypothalamus and adrenals during initial stage caused to considerable extent by their deamination and the monoamine decrease under 10-day hypoxia were typical for intermittent hypoxia. The administration of MAO a inhibitor pyrazidol promoted the increase in brain serotonin content, normalized brain catecholamine contents and demonstrated positive effect on the animal state.