Electron paramagnetic resonance study of tumor affected bone marrow.

To study the mechanism of interaction of tumor cells with bone marrow cells continuous wave electron paramagnetic resonance (EPR) experiments at 9 GHz including a spin trapping of superoxide were carried out. The common features of the EPR spectra in healthy and tumor affected tissues of donors and rats as well as their difference are presented and discussed. It is proposed that labile iron pool plays a significant role in mechanisms of tumor invasion. We hope that the observed EPR features could be used to study the mechanisms of invasion and progression of tumor in different organs.

[Metabolic changes in cells under electromagnetic radiation of mobile communication systems].

Review is devoted to the analysis of biological effects of microwaves. The results of last years' researches indicated the potential risks of long-term low-level microwaves exposure for human health. The analysis of metabolic changes in living cells under the exposure of microwaves from mobile communication systems indicates that this factor is stressful for cells. Among the reproducible effects of low-level microwave radiation are overexpression of heat shock proteins, an increase of reactive oxygen species level, an increase of intracellular Ca2+, damage of DNA, inhibition of DNA reparation, and induction of apoptosis. Extracellular-signal-regulated kinases ERK and stress-related kinases p38MAPK are involved in metabolic changes. Analysis of current data suggests that the concept of exceptionally thermal mechanism of biological effects of microwaves is not correct. In turn, this raises the question of the need to revaluation of modern electromagnetic standards based on thermal effects of non-ionizing radiation on biological systems.

[Prognostic value of the androgenic function state of patients with lung cancer].

The authors have studied interconnection between daily excretion of androgenous metabolites and life-span of patients with lung cancer of different histological gradation. Positive correlation was found between life-span of patients with lung cancer and index of androsterone daily excretion. The patients with lung cancer of high differentiation had their androgenous fractions daily excretion compared with those of healthy persons, and patients with the lung cancer of middle and low degree of differentiation had their androgenous fractions daily excretion considerably lower than those of healthy persons.

O2*- and NO-associated mechanisms of selective action of redox-active cobalt complexes on tumor tissue.

AIM: To study the influence of redox-active cobalt(III) complex with tetradentate Schiff base and nicotinamide as an axial ligand on the rate of superoxide radical-anions generation and levels of NO in tumor and normal tissues of Lewis lung carcinoma bearing mice as well as activity of matrix metalloproteinases 2 and 9 (MMPs) in tumor. METHODS: The superoxide radical-anions formation and NO level in tissues were assessed by EPR method with the use of 1-hydroxy-2,2,6,6-tetramethyl-4-oxopiperidin and diethyldithiocarbomate spin traps, respectively. MMPs activities were determined by zymography in polyacrylamide gel. RESULTS: It was observed that the rate of superoxide radical-anions generation was selectively increased in tumor tissue (by a factor of 6-7) accompanied with the decrease of NO level (by a factor of 2) due to tested complex administration. Activities of MMPs in tumor were significantly decreased. CONCLUSION: It is supposed that the one of mechanisms of detected earlier antimetastatic effect of complex is based on its ability to induce the formation of high level of superoxide radical-anions selectively in the tumor tissue that results in the damage of its regulatory functions, in particular alteration in the regulation of NO-synthase, decrease of NO generation as well as activities of MMPs.

Effects of radical oxygen species and NO: formation of intracellular hypoxia and activation of matrix metalloproteinases in tumor tissues.

AIM: To establish the association between the radical oxygen species (ROS) and NO levels in the tumor cells mitochondria, between cell hypoxia development and activation of matrix metalloproteinases-2 and -9. MATERIALS AND METHODS: Electron paramagnetic resonance (EPR) at room temperature and at the temperature of liquid nitrogen (77 degrees K), spin traps technology, enzymography in polyacrylamide gel were applied. RESULTS: Redox-centers in the respiration cascade of mitochondria have been revealed, multiple oxidative damage of which in breast and liver cancer tissues of experimental animals as well as in tumor tissue from patients with gastric cancer promote the development of cell hypoxia. Involvement of ROS and NO in activation of latent forms of matrix metalloproteinases in gastric tumor tissues has been shown. CONCLUSION: We hypothesize that superoxide radical-anions participate in development of cell hypoxia in tumors and surrounding normal tissues inducing activation of latent forms of matrix metalloproteinases.

High formation of superoxide anion and nitric oxide, and matrix metalloproteinases activity in vascular wall of rectal carcinoma vessels.

AIM: To study the relationship between the level of generation of reactive oxygen species (ROS) and nitric oxide (NO) and activity of matrix metalloproteinases (MMPs) MMP-2 and MMP-9 in the vessels isolated from rectal tumors and Arteria rectalis superior. METHODS: EPR at the room temperature and 77 degrees K, Spin Traps technology and zymography in polyacrylamide gels were applied. RESULTS: In the vessels isolated from rectal tumors and Arteria rectalis superior high levels of ROS, NO and formation of complexes of NO with FeS-proteins at the sites of electron-transporting chain of mitochondria have been detected. High activities of MMP-2 and MMP-9 in vascular wall were also observed. The direct positive correlation between the rate of NO generation and formation of complexes of NO with FeS-proteins as well as between ROS and NO formation and MMPs activities have been revealed. CONCLUSION: Altered oxidative equilibrium in mitochondria of cells in vascular wall promotes formation of cell hypoxia and its autocatalytic potentiation accompanied with activation of MMPs.

[Modulating effect of helium-neon laser radiation on the state of antioxidant and hydroxylation systems of quail liver under X-ray irradiation and chemical intoxication]. / Moduliruiushchee vliianie izlucheniia gelii-neonovogo lazera na sostoianie antioksidantnoi i gidroksiliruiushchei sistem pecheni u perepelov pri rentgenovskom obluchenii i khimicheskoi intoksikatsii.

Red laser light (lambda = 633 nm) in a dose of 9.5 mJ/cm2 defends quail's embryo from X-ray irradiation (8.5 Gr). It is expressed in the 1.9 times decrease of embryo mortality on early term of incubation and 1.6 times increase of hatch in a group of embryos, which were affected by X-rays and laser radiation compared with an embryo, irradiated only by X-rays. Repeated laser irradiation of adult quails (dose 21 J) after CCl4-intoxication led to normalization of hydroxylation and antioxidant systems functions.

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 combined chemotherapy with platinum of patients with inoperable non-small cell lung cancer]. / Kombinirovannaia khimioterapiia s paltinom neoperabel'nykh bol'nykh nemelkokletochnym rakom legkogo.

Combination chemotherapy with cyclophosphamide, 5-fluorouracil, adriamycin and platinum was performed in 122 patients with stage III-IV squamous-cell cancer and adenocarcinoma of the lung. Control group included 84 cases of non-small-cell lung cancer treated with the same drugs except platinum. Ten patients with stage III disease received platinum-based combination chemotherapy and split-course radiotherapy in the total dose of 65-70 Gy. Complete or partial remission was obtained in 48.6 +/- 11.74% of stage III patients following three cycles of chemotherapy, with mean survival reaching 8.6 +/- 3.2 months. Survival in responders was 10.6 +/- 2.1 months. Chemoradiation treatment was associated with even higher survival (14.6 +/- 2.16 months). It is concluded that platinum be used in combination chemotherapy and chemoradiation treatment of the above categories of patients.

[Role of protein receptors of Vitamin A in the mechanism of antitumor action of retinoids]. / Rol' belkovykh retseptorov vitamina A v mekhanizmakh protivoopukholevogo deistviia retinoidov.

Data on protein receptors of vitamin A participating in retinoid metabolism, storage, transport and action are presented. Information about cytosolic protein receptors of vitamin A exerting hormone-like action on the cell proliferation and differentiation is considered in detail. Data concerning the presence of protein receptors in normal and tumour tissues, correlation between protein receptors and biological retinoid effect are analyzed. A hypothetic model of the binding protein mode of action in target cells related to the action model of steroid hormones is described. The authors' own data on action of vitamin A and steroid hormones on the level of estrogen and progesterone receptors in the rate of mammary cancer are reviewed.

[The effect of age-related changes on the hypophyseo-adrenal and sympathetico-adrenal systems in patients with cancer of the digestive tract and lungs]. / Vliianie vozrastnykh izmenenii na gipofizarno-nadpochechnikovuiu i simpato-adrenalovuiu sistemy u bol'nykh rakom pishchevaritel'nogo kanala i legkikh.

An analysis of the activity of pituitary-adrenal and sympathetic-adrenal systems in patients with cancer of the digestive canal and lungs with consideration of age, sex and stage of the disease indicates that not age but the development of the tumour process is the leading factor in disorders of the neuroendocrine homeostasis. Therapeutic measures are discussed.

[Anti-carcinogenic and anti-blastic effect of vitamin A in various modes of its administration to random-bred rats during carcinogenesis of the mammary gland, induced by 7,12-dimethylbenz(a)anthracene]. / Antikantserogennoe i antiblasticheskoe deistvie vitamina A pri razlichenykh rezhimakh ego vvedeniia nelineinym krisam v period kantserogeneza molochnoi zhelezy, indutsirovannogo 7,12-dimetil- benz(a)antratsenom.

The dependence of the anticarcinogenic and antiblastic effect of retinoid on the regime of its inoculation and on the process stage has been established using the 7,12 dimethylbenz(a)anthracene-induced mammary carcinogenesis of rats. The prophylactic administration of retinoid alone and its therapeutic inoculation against a background of hormonal correction resulted in the most expressed effect that was estimated by the elongation of the latent period, incidence and growth rate of tumours, lifespan of treated animals as well as by the distribution of malignant and benign tumours.

[Structural dynamic properties of the cell membranes of Ehrlich ascites tumor associated with a polyamine deficiency caused by DL-difluoromethylornithine]. / Strukturno-dinamicheskie svoistva membran kletok astsitnogo raka Erhlikha pri defitsite poliaminov, vyzvannom DL-diftormetilornitinom.

The blocking of polyamine synthesis in cancer cell by a specific inhibitor (DFMO) results in an increase in membrane viscosity and in significant changes in cell deformability as determined by cell penetration through a nuclear filter with given porosity. Almost two-fold reduction of the penetration rate through the filter pores was registered for the DFMO-treated cells in spite of the fact that the cell size decreases after such a treatment. The number of cells penetrating through the filter after DFMO treatment is diminished due to an increasing resistance to penetration. The addition of putrescine to the incubation medium at physiological concentration restores all these parameters to the initial values. The possible association of these changes with differential sensitivity of cancer cells towards the inhibitor action depending on the stage of cell cycles is discussed.

[The role of membranes in the mechanisms of the anti-carcinogenic effect of retinoids]. / Rol' membran v mekhanizmakh antikantserogennogo deistviia retinoidov.

The role of cell membrane structures in the mechanism of anticarcinogenic and antiblastic action of retinoids was reviewed on the basis of the authors' results and data from literature. The retinoid action induced a delay and prevention of malignant neoplasms development, which is shown by various experimental models of carcinogenesis and tumour growth. The regulatory effect of retinoids on the membrane-bound enzymic processes was analyzed as very important in the clarification of the retinoid action mechanisms not only as antipromotor agents, but also as those influencing immediately the initiation stage of the tumour process. Improvement of the A-vitamin status of the organism is an important step in realization of the prophylactic programme of the tumor growth.

[The state of the molecular electron carriers of the cell energy system at early periods following irradiation]. / Sostoianie molekuliarnykh perenoschikov élektronov énergeticheskoi sistemy kletki na rannykh étapakh posle radiatsionnogo vozdeistviia.

The content of non-heme iron-sulfur proteins and free radicals in the liver, cardiac muscle, and brain was studied during the period from 10 min to 7 days following X-irradiation with doses of 11.0, 7.5, and 4.5 Gy. Ionizing radiation caused substantial changes in the function of electron-transport chains of mitochondria. The change rating was a function of dose while their character depended, in addition, upon the structural and functional characteristics of the organ.

[Effect of preparations of unsaturated fatty acids on the lipid component of the endoplasmic reticulum membranes of liver cells in rats following administration of N-nitrosodiethylamine]. / Vliianie preparatov nenasyshchennykh zhirnykh kislot na lipidnyi komponent membran éndoplazmaticheskogo retikuluma kletok pecheni krys pri vvedenii N-nitrozodiétilamina.

The effect of drugs, including unsaturated fatty acids and antioxidants, on the lipid composition of the endoplasmic reticulum membranes was studied at early stages of NDEA-induced hepatocarcinogenesis. The complexes containing oleic, linoleic, and arachidonic acids and biological antioxidants prevent changes in the fatty acid composition and the lipid bilayer organization of the both membrane fractions of endoplasmic reticulum which are observed after the injection of NDEA alone, and they inhibit the appearance and growth in the liver of gamma-glutamyltranspeptidase positive hyperplastic nodules.

[Development and application of an "IR-spectrophotometer-minicomputer" system for determination of steroid hormones in patients with malignant neoplasms]. / Razrabotka i primenenie avtomatizirovannoi sistemy "IK-spektrofotometr-mini-EVM" dlia opredeleniia steroidnykh gormonov u bol'nykh so zlokachestvennymi novoobrazovaniiami.

An automated IR-spectrophotometer-mini-computer system was designed for assay of steroid hormone level. Its application obviates a clinical analysis of urine. The ratio of 17-ketogenic steroids to androsterone was found to be significantly higher in patients with lung cancer than in healthy controls. The system may be used for identification of groups at high risk both during screenings and in oncological clinic.

[Molecular electron carriers in mouse tissues during development of sarcomas induced by 3-methylcholanthrene and Moloney virus]. / Molekuliarnye perenoschiki élektronov v tkaniakh myshei pri razvitii sarkom, indutsirovannykh 3-metilkholantrenom i virusom Moloni.

Regular changes are revealed in electron-transport chains of the energy and detoxifying systems. The changes occur mainly in iron-sulphur centres and cytochrome P-450 under chemical and viral blastomogenesis in the muscular tissue induced by 3-methyl cholanthrene and Moloney oncornavirus. In the tissue of developing Moloney tumour and spleen kinetics of the formation of triplet signal of nitrosyl complexes is recorded in the region of g-factor of free radicals of semiquinone type and its transformation into singlet signal of EPR with the Moloney sarcoma regression.

[Fatty acid content in the muscles and liver of mice developing sarcomas induced by 3-methylcholanthrene and Moloney murine sarcoma virus]. / Soderzhanie zhirnykh kislot v myshtsakh i pecheni myshei pri razvitii sarkom, indutsirovannykh 3-metilkholantrenom i virusom sarkomy myshei Moloni.

A comparative analysis was made for the fatty acid composition of lipids in the malignant muscular tissue, muscle and liver under blastomogenesis induced in mice by the Moloney sarcoma virus and 3-methylcholanthrene. The relation of the found changes in the fatty acid composition to the blastomogenesis stages is shown. The development of the tumour node is accompanied by a decrease of the fatty acid amount in the animal tissues and by its increase in the tumour. A spontaneous regression of the Moloney sarcoma results in increased level of the fatty acid content in the animal tissues followed by its normalization.

[Prospects for using platinum coordination compounds possessing antitumor activity]. / Perspektivy primeneniia koordinatsionnykh soedinenii platiny, obladaiushchikh protivoopukholevoi aktivnost'iu.

The review presents a complete analysis of studies on experimental and clinical application of platinum complexes with special reference to cis-dichlorodiamminoplatinum, both separately and in combination with other chemotherapeutic preparations. Platinum complexes show their highest antiblastic activity in treatment of ovarian, testicular, lung tumours and those located in the head and neck regions as well as of the bladder cancer and tumours of the other localizations resistant to the action of alkylating agents and other preparations. The clinical material is systematized so that it is possible on the basis of the analysis performed to choose an optimum regime for treating different tumours by platinum complexes.