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.

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.

[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.

The effect of electromagnetic field and local inductive hyperthermia on nonlinear dynamics of the growth of transplanted animal tumors.

AIM: To examine the effects of electromagnetic field with amplified magnetic component and local inductive hyperthermia (IH) on nonlinear dynamics of the growth of animal tumors. MATERIALS AND METHODS: Guerin carcinoma, Lewis lung carcinoma, sarcoma 45, Walker 256 carcinosarcoma and Pliss lymphosarcoma were studied. The animal tumors were exposed inside of loop aerial, 3 cm in diameter locally for 30 min. Parameters of electromagnetic irradiation (EI): frequency 40 MHz, magnetic intensity 72 A/m, electric intensity 200 V/m and the output power 50 W. The temperature measured by immersion of thermocouple inside the center of the tumor didn't exceed 38.5-39.5 degrees C. Nonlinear dynamics of the growth of animal tumors was analyzed by autocatalytic equation. The heterogeneity of ultrasonic image of the tumor was analyzed by Moran spatial autocorrelation. RESULTS: The strongest inhibition effect under the influence of EI was in Pliss lymphosarcoma and sarcoma 45. The growth stimulation of animal tumors after EI was recorded in Walker 256 carcinosarcoma. The use of mild IH increased the blood flow in the tumor of Guerin carcinoma. CONCLUSION: These results are important for clinical application because they testify the necessity of optimization of schemes for local EI during anticancer neoadjuvant therapy with the use of drugs or magnetic nanoparticles. The use of mild IH as a basis for the monotherapy of malignant tumors is not expedient.

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.

Effects of mechanochemically activated doxorubicin and 40 MHz frequency irradiation on human A-549 lung carcinoma cells.

AIM: To study in vitro influence of mechanochemically activated (MA) doxorubicin (DOXO) and electromagnetic irradiation (EMI) on human lung carcinoma A-549 cells. METHODS: Solid state DOXO was MA by input energy 20 W/g during 5 min. Tumor cells were exposed to 40 MHz EMI with power density 2 W/cm(2) at temperature 37 degrees C. RESULTS: Particles of MA DOXO have sizes 10 time smaller than officinal DOXO, high performance liquid chromatography analysis showed that parameters of officinal and MA DOXO were quantitatively equal. Mechanochemical activation initiated in the drug formation of free radicals with g = 2.005, g = 2.003 and g = 1.97. LD(50) values of MA DOXO were 5 times lower than that of officinal drug. Cell survival decreased in the following way after effects EMI --> officinal DOXO --> MA DOXO --> officinal DOXO + EMI --> MA DOXO + EMI. CONCLUSION: Treatment by MA DOXO and drug with EMI at 37 degrees C showed better targeting of drug in human lung carcinoma A-549 cells outcomes than officinal DOXO.

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.

Mechanoluminescence: lymphocyte analysis after exposure to ionizing radiation.

Lymphocyte mechanoluminescence (ML) develops as a result of mechanochemical activation of cells. This paper describes devices (tribogenerators) and techniques for lymphocyte mechanoluminescence analysis. At different stages of the cellular cycle the ML of non-irradiated peripheral blood lymphocytes (PBL) showed characteristic differences. After (60)Co gamma -irradiation of PBL in vitro at 0.25 Gy and 1 Gy an alteration of ML was observed with a relationship between ML values of lymphocytes, and also of mitochondria (MT), and the dose of ionizing radiation used. By using bioluminescence techniques it was shown that gamma-irradiation reduces the amount of ATP synthesized by PBL in the stationary phase.

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.

[Singlet oxygen therapy]. / Singletnaia kislorodnaia terapiia.

Physico-chemical concept of the singlet oxygen therapy application using photochemically sensibilized air or drinking a water, already barbaturized by an activated singlet oxygen of air, is adduced. Therapy technology and examples of its clinical application in the treatment of several pathologic processes for the free-radicals correction are depicted.

[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.

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.

[Physical and technical aspects of research on mechanical blood emission]. / Fiziko-tekhnicheskie printsipy issledovaniia mekhanoémissii krovi.

Mechanic emission is an effect observed in dissipation of mechanical energy due to mechanochemical reactions and electrophysic processes at tension, deformation or friction of blood samples dried on the chromatographic paper. The effect is accompanied by electron emission and electromagnetic radiation. The physical principles of mechanic emission were technically realized while developing and designing a microcomputer approximate analyzer (MPA) for spectral analysis of blood mechanic emission when it was recorded in the optical, electric, and radio channels of information conversion. The arrangement of MPA and analytical methods for its technical parameters are given in the paper. MPA may be useful in supplementary non-invasive differential diagnosis of cancer and inflammatory diseases, as well as in the solution of some diagnostic goals of radiology and cardiology.

[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.

Mechanoluminescence: an assay for lymphocyte analysis in neoplasia.

We have studied the mechano-electrochemical activation of optical emission (mechanoluminescence, ML) from the surface of lymphocytes. In C57BL/6 mice with B16 melanoma at the terminal stage of tumour growth and after immunotherapy with thymic agents, there is a correlation between light emission and the value of lymphocyte surface charge and titres of thymic serum factor (FTS).