Mitochondria in Lewis lung carcinoma cells under the effect of magnetosensitive nanocomplex and radiofrequency hyperthermia.

Electron microscopic study of Lewis lung carcinoma cell mitochondria after intravenous injection of a magnetosensitive nanocomplex based on ferric oxide (Fe3O4) nanoparticles and doxorubicin followed by radiofrequency hyperthermia showed that a common increase of the electron density of the cytoplasm was paralleled by mitochondrial edema in comparison with organelles of animals receiving doxorubicin alone. These changes were accompanied by virtually total lysis of the cristae and sharp clarification of mitochondrial matrix, which was seen from appreciable increase in mitochondria image brightness. Morphometric analysis showed lesser perimeter, area, and mean radius of the tumor cell mitochondria in animals receiving the injection of magnetosensitive nanocomplex and exposed to radiofrequency hyperthermia in comparison with those injected with doxorubicin alone. Histograms of distribution of the perimeter, area, and mean radius of the mitochondria after combined exposure to the nanocomplex and hyperthermia showed bimodal asymmetrical distribution. Injection of the magnetosensitive nanocomplex followed by radiosensitive hyperthermia led to more significant impairment of the tumor cell mitochondrial ultrastructure than doxorubicin alone.

[About the impact of the dendritic cell autovaccine on the results of treatment of non-small-cell lung cancer patients].

In thoracic department of the National Cancer Institute studied the effectiveness of dendritic cell autovaccine in the postoperative period in non-small-cell lung cancer patients. The results, showing good tolerance dendritic cell autovaccine. Shows the formation of the expressed antigen immune response after repeated injections dendritic cell autovaccine, as manifested after 4 revaccination. Results of survival patients non-small-cell lung cancer who received postoperative dendritic cell autovaccines demonstrate the high efficiency of the method and its applicability with a minimum of side effects. Further study of survival of patients non-small-cell lung cancer who received immunotherapy treatment, monitoring of compliance with the best mode of repeated injections.

[Diagnostic and prognostic significance of the level of IgM antibodies to myelin basic protein in children with traumatic brain injury]. / Diagnosticheskoe i prognosticheskoe znachenie urovnya antitel k osnovnomu belku mielina v krovi detei s cherepno-mozgovoi travmoi.

OBJECTIVE: To study the content of antibodies to the basic protein of myelin IgM in the blood of children with traumatic brain injury for a comprehensive assessment of the severity and prediction of outcomes of TBI. MATERIAL AND METHODS: 81 children with traumatic brain injury (TBI) of varying severity and 29 children of the comparison group aged 2 months to 18 years were examined, in whom the content of IgM antibodies in blood plasma was determined. RESULTS: In groups of children with different severity of TBI, the average content of IgM antibodies in the blood is higher than in children of the comparison group, and the values of IgM antibodies correlate with the severity of TBI. In children with moderate TBI, the average level of IgM antibodies in the blood is significantly higher than in children with mild TBI, and in children with severe TBI, the average level of IgM antibodies in the blood is significantly higher than in children with moderate TBI. A repeated study found a significant decrease in the average content of IgM antibodies in severe TBI in children without post-traumatic epilepsy compared to their average content in children with post-traumatic epilepsy. CONCLUSION: Normalization (elimination) of IgM antibodies in children in the late period of TBI is associated with a prognostically favorable course of the autoimmune process in the brain; its absence indicates a prolonged autoimmune process. After TBI, it is recommended to include in the examination of children an immunological study of the content of antibodies to the basic protein of myelin IgM in the blood, the indicators of which, in combination with other data, make it possible to predict the outcomes of TBI.

Magnetically sensitive nanocomplex enhances antitumor efficacy of dendritic cell-based immunotherapy.

BACKGROUND: One of the major factors restricting in vivo efficacy of dendritic cells (DCs) based immunotherapy is the inefficient migration of these cells to the lymphoid tissue, wherein DCs activate antigen-specific T cells. A fundamentally new approach for the possibility of enhancing the antitumor effects of DC-based immunotherapy may be the use of magnetically sensitive nanocomplexes to increase the target delivery of DCs to the lymph nodes of the recipient. AIM: To study the antitumor and immunomodulatory effects of the DC-nanovaccine with magnetosensitive properties and its influence on the immunosuppressive tumor microenvironment in mice with sarcoma 37. MATERIALS AND METHODS: The antitumor, antimetastatic and immunomodulatory effects of DCs loaded with magnetic nanocomplex under magnetic field (MF) control in mice with sarcoma 37 have been investigated. RESULTS: Combined therapy contributed to a significant reduction in tumor volume and weight compared to the control group of mice and mice that received the DC vaccine without MF. Therapy with magnetically sensitive DC nanovaccine with and without the addition of the MF was accompanied by a significant down-regulation of the level of FoxP3, transforming growth factor ß, interleukin (IL)-10 and vascular endothelial growth factors, mRNA expression in tumor tissues. A significant increase in interferon-γ and IL-4 mRNA expression was found in mice treated with the magnetically sensitive DC nanovaccine under MF control. CONCLUSION: A significant increase in the antitumor efficacy of the DC vaccine can be achieved using magnetosensitive nanocarriers of tumor antigens under MF control.

[Effect of doxorubicine and heterogenous electromagnetic and thermal fields on the nonlinear dynamics of carcinoma Guerin development].

While local hyperthermia application the intratumoral blood flow is enhancing, leading to oxygenation and vascular permeability for antitumoral medicines. The work objective was to investigate the dependence of the development kinetics in carcinoma Gereni (CG) from combined action of doxorubicin (DR) and the kind of thermal impact, a contact one--due to a contact delivery of heat from a water heater and without contact - due to the tumor electromagnetic irradiation (EMI) using heterogenous electromagnetic field (EMF). DR was injected to the animals in a mass concentration of 1,5 mg on 1 kg of their body mass. The DR injection, a contact heating and EMI were started on the 8th day after the tumor reinoculation and kept on conducting once a 2 days. The course had included 5 injections and/or 5 seances of a contact heating and/or EMF. The combined action of DR and EMI, using spatially heterogenous EMF of applicator in environment of physiological hyperthermia, have had influenced mostly the inhibition of a nonlinear dynamics in CG development. Antitumoral action of DR in the animals with CG was influenced by thermal and nonthermal effects, which were initiated by spatially heterogenous EMF. Nonlinear dynamics of a CG development in animals did not depend from horizontal direction of isolines of a spatially heterogenous EMF of inductive applicator towards the tumor and duration of the irradiation procedure (15 or 30 minutes) after DR injection. The data obtained were exploited in clinical practice for the inductothermy optimal regimes elaboration while conducting complex treatment of patients, suffering oncological diseases.

Drag reducing polymers attenuate adverse effects of ischemia-reperfusion upon resection of liver metastases modeled by MC38 mouse colon adenocarcinomama.

BACKGROUND: The resection of metastases within healthy parenchyma improves significantly the long-term outcome in metastatic colorectal cancer. Until now, the resection technique involves Pringle maneuver, which allows reducing blood loss during transsection of liver parenchyma. However, the classical Pringle maneuver has restrictions due to ischemia/reperfusion (I/R) effect, in particular increasing risk of tumor recurrence after liver surgery. AIM: To study the pathological impact of surgical intervention and I/R effect on healthy liver tissue in the experimental setting by evaluating the markers of redox-homeostasis and oxidatively induced mutage-nesis, and also to assess the current possibilities of their correction by application of drag-reducing polymers (DRPs). MATERIALS AND METHODS: MC38 mouse colon adenocarcinoma cells were transplanted intrahepatically to C57Bl/6 mice. The influence of warm ischemia on metastatic potential of MC38 cells, the speed of superoxide radicals (SR) generation and 8-hydroxydeoxyguanosine content were studied. RESULTS: In case of modeled liver metastases, the surgery initiates an increase in the rate of SR generation into the remaining liver tissue and, consequently, provokes its ischemic injury. The application of DRPs protects liver tissue under I/R conditions. CONCLUSIONS: The warm I/R can promotes metastatic lesions in the healthy part of the organ with underlying increase in the rate of SR generation and oxidatively induced damage of guanine in DNA. The hemorheological effects of DRPs ensure increase of microcirculatory perfusion and oxygenation of liver tissues with the reduction of the rate of SR generation and decrease of 8-hydroxydeoxyguanosine as a marker of oxidatively induced mutations in DNA of hepatocytes. The intraperitoneal administration of nanomolar doses of DRPs prevents the activation of the growth of dormant metastatic MC38 cells in the liver. Further experimental and clinical study of these substances will allow reducing the risks of activation of uncontrolled tumor growth in the liver due to the pathological effect of post-operative I/R.

Non-linear dynamics theory and malignant melanoma.

Chaos theory (nonlinear dynamics) defines cancer as a complex adaptive system in which each cyclic point corresponds to the bifurcation at which changes in signaling pathways emerge. Quantitative assessment of chaos in digital medical images such as electron microscopy, histology and cytology sections collected from patients with malignant cutaneous melanoma employed the following calculation parameters: the irregularity of external contours, internal heterogeneity based on brightness distribution of macromo-lecules, chromosomes, organelles, inclusion bodies, cells and tissues, kurtosis, entropy and the asymmetry coefficient. The present study undertook a nonlinear analysis of the chaotic hierarchy of malignant melanoma. However, considerably more studies will need to be carried out to determine the exact interrelationship between different levels of the hierarchy in the biological system. Multidisciplinary collaborations are therefore essential to find evidence to answer questions that remain open to researchers and oncologists.

Heterogeneity of hypoxia in solid tumours and mechanochemical reactions with oxygen nanobubbles.

Tumour hypoxia leads to radio and chemotherapy resistance among cancer patients. The aim of this paper is to formulate a hypothesis on the heterogeneity of hypoxia in solid tumours. Tumour vasculature is known to be significantly variable. The great structural and functional abnormalities of tumour microcirculation cause spatial and temporal heterogeneity in its perfusion. Tumours have constantly been under the influence of pulsatile blood perfusion with variable pressure that initiates inhomogeneous erythrocyte deformation and following impact on oxygen disorder release from red blood cells into plasma within the blood vessel. Furthermore, stochastically released oxygen in tumour vessel, plasma and interstitial fluid may lead to heterogeneity of hypoxia. Under the influence of increased heterogeneity of hemodynamic force, the oxygen molecules dissolved in blood plasma are inclined to form nanobubbles (NBs) in tumour vessels. Considering the fact that tumour interstitial fluid pressure is increased compared to normal tissues, we assume that oxygen NBs may burst under the impact of shear stress. During the course of mechanochemical reaction, when a nanobubble (NB) bursts, both reactive oxygen species and ions form in various charged states. In consequence of a chain reaction, free radical oxygen molecules bind to proteins and lipids, thus reducing oxygen molecules in a chaotic manner within the tumour. The proposed hypothesis should be used as a methodical approach based on the simultaneous ultrasound imaging diagnostic techniques and therapy, regarding the mechanochemical effect on NB conglomerates with drugs in the tumour.

Mechanochemically activated doxorubicin nanoparticles in combination with 40 MHz frequency irradiation on A-549 lung carcinoma cells.

Targeting of mechanochemically activated doxorubicin (MA DOXO) nanoparticles, conventional doxorubicin, and electromagnetic irradiation (EMI) at A-549 lung carcinoma cells in vitro was investigated. Conventional DOXO was micronized using an input energy of 20 W/g for 5 min resulting in positively charged MA DOXO particles 10 times smaller than conventional DOXO. Mechanochemical activation gives rise to additional free quinone radicals. High performance liquid chromatograph analyses demonstrate that conventional and MA DOXO are quantitatively similar. Tumor cells were exposed to 40 MHz electromagnetic irradiation at a power density of 2 W/cm2. The lethal dose LD50 values of MA DOXO were 5 times greater than conventional doxorubicin. MA DOXO in combination with EMI at 37 degrees C demonstrates improved drug delivery to A-549 human lung carcinoma and greater cell kill than does conventional DOXO.

Mechanochemiemission and atherogenesis.

Haemodynamic factors activate mechanochemiemission between the surfaces of vessels and blood cells, i.e. optical, acoustic, heat and radioemissions which initiate formation of lipid peroxide radicals causing vascular wall damage. Subsequent development of mechanochemiemission reactions in lipids results in formation of atherosclerotic plaques in the arterial intima.

The device and algorithm for estimation of the mechanoemisson chaos in blood of patients with gastric cancer.

The mechanoemission (ME) of blood is developed as a result of mechanochemical activation of a sample which is layered onto chromatographic paper. This paper describes computer-controlled device, aimed for generation, detection and analysis of ME data in the blood of the persons investigated. The original algorithm for estimation of ME chaos in blood is developed. For gastric cancer patients an increase of ME chaos is observed in comparison with healthy individuals and patients with inflammation of gastric mucosa. The concept of deterministic chaos is biohierarchical for the host of a cancer patient. In the light of this we have calculated that spatial chaos for gastric cancer patients is also increased in the geometrical structure of tumor cells and magnetic resonance imaging of the stomach. The concept of deterministic chaos may find an application in the development of new multi-computer organizations for medical diagnostic equipment.

Physical dosimetry and biological indicators of carcinogenic risk in a cohort of persons exposed to unhealthy ecological factors following the Chernobyl Nuclear Power Plant accident.

The April 1986 Chernobyl Nuclear Power Plant accident caused ecological changes in the Ovruch State forests in the Zhytomir oblast in the Ukraine. The highest radioactivity existed in moss, followed by the pine-forest substrate and soil. During 1984-1985, the pine needles were primarily surface contaminated, whereas during 1986-1988, they were contaminated secondarily. Radioactivity in air was highest (1.07+/-0.185 Bq/l) during dry and sunny weather and when trees were felled; the lowest levels (0.196+/-0.044 Bq/l) occurred during periods of stable snow coverage. Between 1987 and 1989 (i.e., after the Chernobyl accident), the caesium levels in forestry employees exceeded by 13.9-fold the average levels found in the Ukrainian Polessje population. Ovruch forest guards and woodcutters had the highest effective equivalent doses of radiation, and they therefore exhibited the highest carcinogenic risk.

[The effect of gamma irradiation on lymphocyte mechanical emission in rats at different stages of the cell cycle]. / Vliianie gamma-oblucheniia ba mekhanoémissiiu limfotsitov krys v razkykh stadiiakh kletochnogo tsikla.

Mechanoemission (ME) of rat peripheral blood lymphocytes (PBL) over the radio-frequency range has characteristic peculiarities in various stages of the cell cycle, both in unirradiated cells and in cells exposed to 0.25 or 1 Gy of gamma radiation. After 52 h incubation of irradiated and unirradiated lymphocytes, ME PBL indices take values equivalent to initial ones in the G0 phase. Increase of radiation dose from 0.25 to 1 Gy was followed by a decrease of the value of the ME PBL kinetic parameter after 24, 40 and maximum 48 h incubation.

[Chemiluminescence and triboluminescence of the endothelium of the thoracic aorta in gamma-irradiated rabbits with experimental hypercholesterolemia]. / Khemi- i triboliuminestsentsiia éndoteliia grudnoi aorty gamma-obluchennykh krolikov s éksperimental'noi giperkholesterinemiei.

A comparative study of chemiluminescence and triboluminescence of endothelium of the thoracic aorta in the intact rabbits and in ones with experimental hypercholesterolemia 3, 6, 24 hours after single total influence of low doses of ionizing radiation allowed us to conclude that higher fluctuation of the examined parameters is characteristic feature of the rabbits with hypercholesterolemia. At the same time it was found that the changes in chemiluminescence and triboluminescence of endothelium of the thoracic aorta three hours after irradiation with a dose of 0.25 Gy were different in the experiments in vitro and in vivo.

[Lymphocyte mechanoluminescence]. / Mekhanoliuminestsentsiia limfotsitov.

A unique installation and an original investigation method are described for studying mechanoluminescence of lymphocytes. The spectral content of mechanoluminescence of lymphocytes of human peripheral blood showed maxima of optical emission at 262, 291, 335 and 412 nm. Intraperitoneal administration of hydrocortisone in mice enhances thymocyte mechanoluminescence intensity after 2 and 3 days by 33 and 62%, resp. It is shown that Acridine orange, reacting with murine thymocytes and their nucleoids, affects intensity of their mechanoluminescence, depending on the value of concentration of the injected intercalator.

[The effect of nitrogen and oxygen on triboluminescence generated by blood]. / Vliianie azota i kisloroda na triboliuminestsentsiiu, generiruemuiu krov'iu.

The spectrum of triboluminescence by dried blood on a TPA-2 triboluminometer was shown to display four bands of emission with maximum levels at 262, 321, 422 and 649 nm, which are due to the processes of gas discharge in nitrogen and oxygen and to the luminescence of polytetrafluorochlorethylene probe, triboelectriating the samples under study. The intensity of triboluminescence of dried blood and its components depends on the value of pO2 in the liquid phase of the samples.

[Arterial impedance in transient modes of the performance of the circulation system]. / Arterial'nyi impedans pri perekhodnykh rezhimakh raboty apparata krovoobrashcheniia.

The authors consider transient processes for modifying arterial impedance, peripheral and elastic resistances of the arterial system, as well as some major hemodynamic parameters early in muscular performance. The analysis was made by applying experimental findings from 74 athletes. The transient processes were derived by using the mathematical modelling techniques on a computer. The termination of transient processes of arterial impedance and its determinants was shown to be asynchronous. Whether the values of arterial impedance at rest and during exercises of unlimited power are comparatively invariant is also discussed in the paper.

[Interaction of very low density lipoproteins (VLDL) with macrophages and their triboluminescence in hypercholesterolemia]. / Vzaimodeistvie lipoproteinov ochen' nizkoi plotnosti (LONP) s makrofagami i ikh triboliuminestsentsiia pri giperkholesterinemia.

Accumulation of cholesterol esters and triglycerides in peritoneal mice macrophages in the course of their interaction with lipoproteins of very low density (VLDL) is shown to grow considerably under conditions of hypercholesterolemia. A decrease of triboluminescence intensity characterizing the surface charge has been revealed at hypercholesterolemia both in VLDL and in the blood plasma. It is supposed that the triboluminescence method may be used for testing of the atherosclerotic process development.

[Effect of extreme factors and adaptation to high-altitude conditions on peroxidation indices of serum lipids]. / Deistvie ékstremal'nykh faktorov i adaptatsii k usloviiam vysokogor'ia na pokazateli perekisnogo okisleniia lipidov v syvorotke krovi.

High and low temperatures, physical exercises and acute hypoxia are studied for their effect on indices of peroxide lipid oxidation in highly trained persons under alpine conditions (2100-5600 m). Temperature effects (-15 degrees C and +100 degrees C, for 30 minutes) as well as their combination with acute hypoxy cause an increase (by 10-30%) of malonic dialdehyde and a decrease (by 46-70%) of spontaneous chemoluminescence of blood serum in nonadapted people. Adaptation to alpine conditions in combination with physical exercises and low-caloric diet decreases shifts of these indices, considerably increasing the organism stability to the action of such extreme stress agents as high and low temperatures and acute hypoxy.

[Spontaneous blood serum chemiluminescence in patients with cancer of the esophagus and proximal portion of the stomach]. / Spontannaia khemiliuminrstsentsiia syvorotki krovi bol'nykh rakom pishchevoda i proksimal'nogo otdela zheludka.

Based on the maternal pertaining to 193 patients with cancer of the esophagus and proximal gastric portion, 22 patients with non-tumor diseases of the stomach and esophagus, 19 donors (aged 18-25 years) and 10 practically healthy subjects aged 34-67 years, it was found that tumor invasion of the stomach body and the presence of such aggravating factors as grade IV dysphagia, inflammatory complications etc. are associated with a significantly increased intensity of serum chemiluminescence. Anesthesia and other factors as a concomitant of surgery reduce considerably the level of blood serum chemiluminescence during the operation, whereas an intensive postoperative therapy retains its initial level. The development of complications during the operation and after it is accompanied with 1.5--2 times or more increased luminescence. Radical surgical and combined treatment would condition the normalization of the luminescence. Radiation treatment first increases and then decreases the luminescence down to normal values.