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Radical surgical treatment with and without radiation often induces symptoms of premature menopause in cervical cancer (CC) patients. Few retrospective studies seem to suggest that hormonal replacement therapy (HRT) is not detrimental for patients with CC and can improve life quality in this group of women. To investigate the effect of HRT on menopausal symptoms inpatients with С C history, 85 patients after CC treatment, 22-51 years old, were included into this research. In 59 patients HRT was carried out to overcomepostovariectomic syndrome (POES). Severity of menopausal symptoms, serum estradiol, FSH and lipid profiles were evaluated. The research showed high therapeutic effect as to reducing the frequency of postovariectomic frustration in HRT application. No recurrences of CC were observed in this group of patients. HRT side effects were extremely rare. HRT can effectively cure climacteric symptoms in women with surgical menopause induced by CC treatment.

We present an original method for recognition of different types of hydrodynamic discontinuities such as shock fronts and tangential discontinuities, smooth types of flows such as rarefaction waves, and their intensities simultaneously. The method is based on invariants of a strain velocity tensor of hydrodynamic flow. We demonstrate the advantages of this new technique by way of giving an example of a supersonic turbulence produced by a blast wave from a point explosion propagating in a ‘cloudy’ inhomogeneous medium.

We discuss an idea whether spherical blast waves can amplify by a non-local resonant hydrodynamic mechanism inhomogeneities formed by turbulence or phase segregation in the interstellar medium. We consider the problem of a blast-wave-turbulence interaction in the Linear Interaction Approximation. Mathematically, this is an eigenvalue problem for finding the structure and amplitude of eigenfunctions describing the response of the shock-wave flow to forced oscillations by external perturbations in the ambient interstellar medium. Linear analysis shows that the blast wave can amplify density and vorticity perturbations for a wide range of length scales with amplification coefficients of up to 20, with amplification the greater, the larger the length. There also exist resonant harmonics for which the gain becomes formally infinite in the linear approximation. Their orbital wavenumbers are within the range of macro- ($l \sim 1$), meso- ($l \sim 20$) and microscopic ($l > 200$) scales. Since the resonance width is narrow: typically, $��l, 11 pages, 6 figures

The current concept of obesity as a heterogeneous condition is discussed. Such interpretation provides a basis for distinguishing a group of obese subjects without metabolic disturbances (metabolically healthy obese (MHO) subjects) and another one including subjects with normal body weight and signs of hormonal and metabolic disorders (metabolically obese normal weight (MONW) subjects). A separate subgroup is represented by obese patients with deficit of muscular mass and force (sarcopenic obesity). Potential mechanisms underlying development of these conditions are considered along with selected applied aspects of this problem.

The evolution of a supernova remnant in a cloudy medium as a function of the volume filling factor of the clouds is studied in a three-dimensional axially symmetrical model. The model includes the mixing of heavy elements (metals) ejected by the supernova and their contribution to radiative losses. The interaction of the supernova envelope with the cloudy phase of the interstellar medium leads to nonsimultaneous, and on average earlier, onsets of the radiative phase in different parts of the supernova envelope. Growth in the volume filling factor $f$ leads to a decrease in the time for the transition of the envelope to the radiative phase and a decrease in the envelope's mean radius, due to the increased energy losses by the envelope in the cloudy medium. When the development of hydrodynamical instabilities in the supernova envelope is efficient, the thermal energy falls as $E_t\sim t^{-2.3}$, for the propagation of the supernova remnant through either a homogeneous or a cloudy medium. When the volume filling factor is $f\simgt 0.1$, a layer with excess kinetic energy andmomentumforms far behind the global shock front from the supernova, which traps the hot gas of the cavity in the central part of the supernova remnant. Metals ejected by the supernova are also enclosed in the central region of the remnant, where the initial (high) metallicity is essentially preserved. Thus, the interaction of the supernova envelope with the cloudy interstellar medium appreciably changes the dynamics and structure of the distribution of the gas in the remnant. This affects the observational characteristics of the remnant, in particularly, leading to substantial fluctuations of the emission measure of the gas with $T>10^5$~K and the velocity dispersion of the ionized gas., 23 pages, 9 figures

An exact solution is obtained to the three-dimensional problem of thermoelectroelasticity for a piezoceramic body with a spheroidal cavity. The solutions of static thermoelectroelastic problems are represented in terms of harmonic functions. Far from the cavity, the body is in a uniform heat flow perpendicular to the axis of symmetry of the cavity

The effect of the biguanide siofor (metformin) on the menstrual function of the endometrium and on hormonal and metabolic parameters was studied in 27 patients with ovarian polycystosis (OPC), of them 15 patients (mean age 30.7±1.7 years) were treated with the antidiabetic biguanide siofor (Berlin-Chemi) for 3 months. Siofor (metformin) used alone in patients with OPC was effective in restoring a regular menstrual cycle in 60% of cases and concurrently showed a moderate decrease in body weight. There was a significant reduction in the blood level of luteinizing hormone (LH) in most siofor-treated patients with OPC (more frequently in obese patients), which is indicative of that it is important to correct the states of central parts of the reproductive system, which are involved (along with insulin resistance and impaired steroidogenesis) in the development and formation of a clinical picture of the disease. The elevated concentration of C-peptide was found in the blood, which might be one of the manifestations of overcoming insulin resistance.

Female rats (aged three months at the start of the study) were kept for four months on drinking water (group 1) or 5% ethanol. Rats drinking ethanol were additionally divided into six groups (groups 2–7). During the next two months of the experiment, animals of group 2 continued to drink only ethanol, while rats of group 3 additionally received N-acetylcysteine, those of group 4 received ascorbic acid (vitamin C) and α-tocopherol (vitamin E), those of group 5 received melatonin, those of group 6 received carnosine, and those of group 7 swam in the so-called training regime for five days a week. All animals underwent bilateral ovariectomy 2.5 weeks before experiments ended, and were given daily i.m. estradiol (2 μg) during the 11 days before the last experimental day. After treatments, blood estradiol and cholesterol levels were measured, along with progesterone receptor levels, peroxidase activity, the index of proliferation, the proportions of cells in the S and G2/M phases, the thickness of the endometrium, and the extent of DNA damage (using the “comet” technique) in uterine tissue. Liver estradiol 2-hydroxylase activity was also measured. The results led to the conclusion that drinking of 5% ethanol in combination with administration of estrogens was accompanied by induction of genotoxic (G) changes in the uterus and that this was prevented by administration of N-acetylcysteine and melatonin. The combination of vitamins C and E increased some of the manifestations of the hormonal (H) effect of estrogens (uterine weight and induction of progesterone receptors), but weakened others (the index of proliferation). As a result, the combination of N-acetylcysteine and optimum doses of ascorbic acid and α-tocopherol can be recommended for preventing the estrogen effect-switching phenomenon (increases in the G component on the background of weakening of the H component), which is seen particularly in patients consuming excessive amounts of alcohol, increasing the risk that the genotoxic version of hormonal cancerogenesis will develop.

We present results of 2-dimensional calculations of a supernova remnant expansion into a cloudy medium. We use direct single fluid simulation of a multiphase interstellar medium. We find some disagreements between our numerical results and theoretical predictions by White and Long (1991): the X-ray map does not reveal the property of centrally peaked luminosity of the remnant.

We studied the influence of various methods for correction of age-related changes (administration of N-acetyl-L-cysteine, vitamins C and E, melatonin, and carnosine and swimming training) on the realization of estrogens effects in ovariectomized rats. The proliferation index in the endometrium decreased in 12-14-month-old control animals. The weight of the uterus, percentage of "comets", and average length of their tail in estradiol-treated rats far surpassed the corresponding parameters in control animals. Administration of melatonin and N-acetyl-L-cysteine and swimming training corrected these genotoxic abnormalities. Our results indicate that aging induces incomplete variant of the phenomenon for switching of estrogen's effects (increase in the severity of genotoxic damage without facilitation of the hormonal effect). These methods for correction of age-related changes have not only common, but also distinguishing characteristics compared to correction of changed induced by drinking of ethanol in various concentrations, whole body γ-irradiation, and exposure to tobacco smoke.

We present a resonant description of hydrodynamic instabilities of shock waves in inhomogeneous media. This approach (1) allows us to clarify the physical mechanisms of instabilities; (2) provides a natural classification of all hydrodynamic instabilities; (3) allows us to simplify the search and prediction of instabilities, reducing the analysis to studying the coefficients of transformation (reflection) of perturbations at the shock front. We apply the developed formalism to the analysis of the resonance characteristics of a model of an accelerating shock wave in an exponential atmosphere and a model of a galactic shock wave. Analysis shows that instability in these models is caused by the effect of spontaneous emission of waves by the shock front while the true resonant effects are insignificant. Finally, we predict that the standing shock wave in an accretion flow on to a point mass must be unstable for the same reasons.

We examine the spatial stability of spherical adiabatic Bondi accretion on to a point gravitating mass against external perturbations. Both transonic critical and subsonic subcritical accretion are shown to be stable against purely radial acoustic, vortex or entropy perturbations. In the case of non-radial perturbations the amplitude of the perturbations grows without limit with smaller radii. Instability manifests itself only if the size of the accreting body is much less than the Bondi radius so that the inflow is highly supersonic or highly subsonic at the surface of the accretor in the case of critical or subcritical accretion respectively. These asymptotics hold and consequently the instability may develop for adiabatic index of accreting gas γ

The stability of the shocked and the shock-free gas flows in the gaseous galactic disc is discussed. It is shown that the periodic shock-free supersonic flow between the spiral gravitational potential wells is unstable due to the parametric instability and thus should be re-organized into the shocked flow. The steady-state shock at the rear side of the well (relative to the flow) is subject to the local instability. This instability is suppressed if the shock is at the front side of the well.

Mammographic breast density (MBD) value is currently one of the strong predictors for mammary carcinoma development. There are also other conditions predisposing to MBD increase with hormone-related markers different from those used in breast cancer, while pharmacological methods for MBD reduction are few and still considered experimental. In the current study 25 postmenopausal women received daily for a median 10.5 months 1-1.5 g of antidiabetic biguanide metformin (siofor) (n = 14) or 400-600 mg of antigenotoxic drug N-acetylcysteine (n = 11). In both groups MBD was measured before and after treatment. The effects of both drugs were quite similar. Metformin use lead to lower MBD in 4 of 14 (28.5%) women with mean MBD decrease of -1,24% (absolute dynamics) and -5.03% (relative value). In N-acetylcysteine group this effect was observed in 27.3% of cases, with -2.0% absolute dynamics and -6.1% relative dynamics. In metformin group the most evident absolute and relative dynamics was observed in patients with no signs of metabolic syndrome, -10.86% compared to -2.45%. In 7 women the metformin use also lead to decrease of dense and increase of non-dense areas on digital scans, leading to decrease in dense to non-dense area volume ratio. Therefore, the similar effects of metformin and N-acetylcysteine are probably explained mostly not by insulin resistance elimination by metformin, but by altered cell proliferation, apoptosis and DNA repair.

Our study involving healthy postmenopausal females established that mammographic breast tissue density was lower in cases of more intensive stimulation by glucose of reactive insulinemia and glucose-induced glyoxalase I activity in bood mononuclears as well as in women with higher concentrations of circulating CD90+stem cells. Conversely, the density tended to increase in those with higher ratio of glucose-induced generation of reactive oxygen species in mononuclears. Our data point to possible mechanisms of increased density as a breast cancer factor when concomitant with relative predominance of progenotoxic effect of glucose and lower CD90+stem cells levels which are believed by some authors to be capable of suppressing the growth of certain tumors.

Our study involved 25 postmenopausal patients (endometrial carcinoma--16, breast (6) and colorectal (3) cancer, aged 56.8 +/- 0.9). All patients were in clinical remission. None had received any specific therapy for at least 12 months. After a laboratory endocrine-genotoxic switch evaluation, 17 patients were given an antidiabetic drug--biguanide metformin--or N-acetylcysteine as antioxidant (8) for 3 months. A checkup was carried out on completion of the course. As a result, hormonal and progenotoxic effects of glucose were found to be inhibited significantly. Much less pronounced was the impact on relevant effects of estradiol which were investigated vis-a-vis nature of blood mononuclear response in vitro. Both isolated and combined administration of said drugs used for endocrine-metabolic rehabilitation is justified.

An original multiple‐vector representation of a composite quantum system’s state is suggested. For this purpose a decomposition of the density matrix of a quantum system is carried out on the basis of algebra SU(n1)⊗ ...⊗SU(nk), possessing separable (tensor product of local states) and non‐separable components. In the case of two qubits the latter one is described by a vector. Such a vector representation is possible in the cases of no more than two qubits and no more than six qutrits.The vectors being introduced that way should be considered to be additional, different from entanglement, nonlocality characteristics of a composite quantum system’s state. Being unique such decomposition possesses the full nonlocality characteristic of a quantum system’s state.The formalism discussed is applied to the situation of two‐qubit register [1, 2]. In this case there occurs an explicit multiple‐vector representation. In the case of two‐qubits these vectors are three‐dimensional, and there exists a suitable geometrical interpretation dealing with Bloch’s sphere.

Poly(ADP-ribosyl)ation polymerase-1 (PARP-1) is a major factor of DNA repair. Age-related parameters such as body weight and blood cholesterol in knockout male mice PARP-1 were more pronounced as compared with controls. Mean life span was shorter (486 +/- 31.7 and 723 +/- 22.6 days, respectively, (p = 0.000005) while initial risk of death (beta) was 8 times as high as in mice PARP-1(+/+). Mean latency of all tumors in knockout and control mice was 656 +/- 43.5 and 782 +/- 33.8 days, respectively, (p0.05). Among the most frequent neoplasms were tumors of the liver (experimental--22% and control--8%, respectively) (p = 0.03) and lungs (8% and 12%, respectively). Hence, mice PARP-1(-/-) revealed certain typical charhacteristics of accelerated aging, shorter life span, earlier carcinogenesis and higher rates of liver tumor incidence as compared with mice PARP-1(+/+). Our evidence highlights the role of DNA repair in carcinogenesis and aging.

A relationship was studied between generation of glucose-induced reactive oxygen species capable of causing damage to DNA (genotoxic or G-effect) and insulin secretion (endocrine or hormonal effect - H-effect) in primary menopausal patients with endomrnetrial carcinoma (EC) (32) or colonic cancer (CC) (16). The study group was compared with healthy menopausal women (25) and patients with an impaired glucose tolerance (IGT) (21). Besides, we examined 32 menopausal patients (CC--6 and EC--26) more than 12 months after surgery. The following basic patterns were established: (1) H-effect was reported in EC-1 and 1GT groups nmore often than in healthy peers and those with EC-2: (2) G-effect tended to prevail in CC patients and those with EC-2 and in patients with EC-1 twelve months after operation; (3) G-effect occurred more often in primary EC patients, particularly, those with EC-2 (71%) and IGT (58%) (as compared with CC patients (33%) and healthy females (por = 0.001). It is suggested that a comparison of the two effects might provide a criterion for use of relevant means of prevention of certain malignancies or correction of disorders in cancer patients following radical treatment.

The hydrodynamics of a spherical cloud, surrounded by hot intercloud gas or exposed by heating radiation, is investigated. Two principal types of hydrodynamical flows are shown to exist simultaneously: an outflow of gas from the outer layer of the cloud that corresponds to the cloud's evaporation, and cumulative compression of the cloud's interior. The cause of such flows is a pressure excess in the outer layers of the cloud created by heating of the cloud's gas by thermal conductivity or by radiation, which is assumed to be absorbed by the surface layers. The qualitative features of the dynamics of evaporating and compressing gas are described. In particular, an amplifying of the magnitude of compression of the cloud's interior in models with a dominating role of electronic conductivity and volume cooling is shown. The importance of these effects for the physics of interstellar matter is discussed.

Relation was studied between generation of glucose-induced reactive oxygen species (ROS), which appear to be related to DNA damage (genotoxic effect, G), and insulin secretion (endocrine or hormonal effect, H) in women of different ages (one group under 45 and the other one over 45; n=25 and n=14, respectively). The healthy women in those two groups were compared with patients in whom we had found an impaired glucose tolerance (IGT) or type 2 diabetes mellitus (DM) (n=17, mean age 57.3 +/- 2.7). The hormonal effect of glucose was more pronounced in the senior group, and especially in group with IGT, if compared with the younger group. Genotoxic effect of glucose was discovered more frequently in the younger group, mainly in smoking women. Comparison of G/H effects showed that the evaluation of glucose-induced genotoxity (GIGT) was more frequent in the IGT group than in the senior group (p0.05). No difference was detected in the GIGT frequency values in the two healthy groups. It may therefore be concluded that GIGT did not increase within the ambit of ageing studied in this work, while it increased in the IGT group. It is possible that the high frequency of the G effect in the IGT group could be a marker of oxidative stress and/or predisposition to complications in DM. The dual (joker) function of glucose and the prevalence of G effects over H effects may be of use in choosing the method of correction for each particular case.

Peculiarities of the incidence and spread of main non-infectious diseases (MNID) are in one or another way connected with the conception of "normal" and "successful" aging. The age-related increase in the frequency of MNID, associated with estrogen deficiency or excess, can be explained by the presence of estrogen effect switching phenomenon. The increase in the genotoxic effect of estrogens, isolated or combined with the weakening of the hormonal effect, can worsen the clinical course of MNID (including malignant tumors of hormone-dependent tissues). The effects of two other endocrine-genotoxic switchings (the joker function of glucose and adipogenotoxicosis) may realize in the same direction. The three mentioned phenomena form the so called basic triad, separate elements of which can interact. Endocrine-genotoxic switchings and their inductors are targets for prophylactic measures and, possibly, therapeutic ones. Both approaches may be divided into several groups with different points of application, whereas their ultimate goal is optimal balance between hormonal and DNA-damaging effects of estrogens, glucose, and adipose tissue-associated factors.

Breast cancer course may be influenced by a profile of steroids and peptides produced by mammary fat. The study was concerned with assessment of hormonal (leptin and adiponectin production, adipocyte diameter and aromatase level) and progenotoxic factors which characterize DNA damage (8-OHdG) and such cancer promoters as tumor necrosis (TNF-alpha), interleukin-6 (IL-6), nitric oxide (NO), thiobarbiturate reactive products (TRP), macrophage/histiocyte infiltration, estrogen 4-hydroxylase expression (CYP1B1) in mammary fat located 1.5-2 cm or not less than 5 cm away from tumor edge. Thirty-three pairs of mammary fat samples from 23 menopausal and 10 cycling patients were used. Closer proximity of mammary fat involved intensified biosynthesis of estrogens (as shown by aromatase level) and their conversion to catechol derivatives (as shown by CYP1B1 concentration) as well as accumulation of 8-OH-dG. Smoking and hyperglycemic patients and those with considerable mammary fat volume revealed accumulations of anti-inflammatory and progenotoxic cytokines (IL-6 or TNF-alpha). Hence, hormonal/progenotoxic ratio in mammary fat can be identified both by topographic, systemic and environmental factors.

Since breast cancer may emerge both before and after menopause onset, relevant forms of the disease show marked biological and clinical differences. Intrinsic properties of mammary fat located in the vicinity of tumor, which play a definitive role in stromal-epithelial interactions, are an important factor of development of such differences. The DNA damage promoting hormonal (leptin and adiponectin production, aromatase activity) and progenotoxic. The properties of mammary fat such as formation of tumor necrosis factor, interleukin-6, nitric oxide, malonic aldehyde, macrophage/histiocyte infiltration and estrogen 4-hydroxylase expression, were studied in mammary fat tissue of 95 patients with receptor-positive or receptor-negative breast tumors (reproductive--25, menopausal--70). It was found that progenotoxic properties might somewhat predominate, as far as differences in parameters and pathways are concerned, both in menopausal and still cycling patients. Hence, progenotoxic damage which represents mammary fat tissue status is perhaps modified by a number of genetic and mitochondrial factors. It may exert unfavorable effect on the course of the disease within a fairly wide period.

About 30-40% of breast cancers lack steroid receptors (ER and/or PR) at diagnosis that worsen prognosis and limit the usage of hormone therapy. The aim of this paper has been to study the role of DNA-damaging factors as the potential modifiers of the receptor-negative tumors incidence.The investigation consisted of two principal parts. In one of them ER and PR content was measured in breast cancer samples from 2284 primary patients (350 of them - current or previous smokers). In separately studied subgroup of 1010 patients 95 suffered with diabetes mellitus type II.As it was shown, smokers and diabetics carry more frequently (p = or0.05) tumors with phenotypes ER+PR- and PR- only in the group of women with conserved menstrual cycle that is in case of relatively higher estrogenic stimulation. In another part of the investigation immunohistochemical study of DNA damage marker - 8-hydroxy-2-deoxyguanosine (8-OH-dG) in 16 R(-) and 18 R(+) breast cancer specimens demonstrated more frequent positive staining in the former group of samples (p = 0.05). Besides, as it was revealed in breast cancer cell line MCF-7 the combination of estradiol with aryl hydrocarbonic receptors agonist beta-naphtoflavone induced pronounced genotoxic damage (by 8-OH-dG content) in association with the loss of ER.Thus, pro-genotoxic status (smoking, diabetes) and direct signs of genotoxic injury, in accordance with regularities of the phenomenon of switching of estrogen effects can be reckoned among the factors promoting the development of receptor-negative breast cancer.

Estrogen (ER) and progesterone (PR) receptor levels were assayed in 2,284 primary breast cancer patients who either smoked (350) or suffered diabetes mellitus type 2 (1997-2003). In a group of 1010, 95 patients had diabetes mellitus type 2 whereas 393--such signs of cardiovascular pathology as atherosclerosis, arterial hypertension and ischemic heart disease (2000-2003). Among the premenopausal smokers, the ER+PR-phenotype predominated (t = 2.18, p0.05) as well as among the diabetics (t = 2.01, p0.05). In reproductive diabetics, the share of PR- tumors was significantly higher than in diabetes-free patients (t = 2.17, p0.05). There was no correlation between diabetes and the tumor receptor phenotype in the menopausal group, while ER + tumors--occurred more frequently in smokers (t = 2.33, p = 0.02). There was no link between cardiovascular pathology and receptor status in either of the age groups. Hence, the increasing proportion of ER + PR--tumors in smokers and diabetes mellitus patients occurs in a random manner in menstruating women, which is associated with elevated estrogenemia. This indicates the phenomenon of switching of estrogen effects involving disturbed transduction of estrogen signals.

Cognitive dysfunction may be associated with the presence of an array of hormono-metabolic factors of risk for certain basic noninfectious diseases, supposedly, including cancer. The investigation was concerned with an appraisal of such cognitive functions as verbal and eye memory and ability to concentrate in endometrial and colorectal cancer patients versus hormonometabolic status and relevant parameters in menopausal women. The indices of short-term memory and concentration in endometrial carcinoma were significantly higher than both in colorectal cancer and osteoporotic patients. However, they were not among healthy women of the same age. A whole range of relationships between said indices and glucose- and estradiol levels in blood serum of patients was studied. No link was established between blood-serum cholesterol, b-lipoproteide and insulin concentration in patients, on the one hand, and cognitive function, on the other. Further research is expected to disclose the ties of the latter with other hormono-metabolic factors as well as tumor-related stress.

Objectives: To study the frequency of insulin resistance (IR) in endometrial cancer patients, its relation to the clinical course of the disease and DNA damage, and to evaluate possible approaches to the pharmacological correction of IR in the patients studied. Methods: The signs of insulin resistance syndrome and its association with the clinical and pathological features of the disease and DNA damage in somatic cells (micronucleus frequency in peripheral blood lymphocytes) and endometrial normal and tumor tissue (alkaline unwinding) were determined in 99 endometrial cancer patients. Results: The frequency of insulin resistance syndrome counted on the basis of fasting plasma glucose and insulin concentrations according to Duncan et al. is equal to 0.35 (95% CI 0.24-0.46), or 35%, in endometrial cancer patients who do not have a history of diabetes mellitus. Patients with well- or moderately differentiated endometrial adenocarcinomas (mostly type 1) had statistically significantly higher basal and stimulated plasma insulin and C-peptide concentrations than patients with poorly differentiated endometrial adenocarcinomas or rarely encountered tumors of the endometrium (primarily type 11). Interestingly, the level of fasting insulinemia positively correlates with disease stage and with local and regional tumor dissemination only in the group of patients with well- or moderately differentiated endometrial adenocarcinomas. On the other hand, hyperinsulinemia and other hormonal-metabolic disturbances typical of insulin resistance syndrome do not increase the probability of DNA damage of somatic cells (according to the data of micronucleus test). In addition, no association between hormonal-metabolic disturbances and the degree of DNA unwinding in tumor and visually unchanged endometrium was found. Conclusion: Thus, insulin resistance/ hyperinsulinemia is associated with a more aggressive course of the disease in certain groups of the patients but-in contrast to excessive estrogenic stimulation-does not result in increased genotoxic damage in tumor and normal tissues. The data obtained once more confirm the need for treatment and prevention measures aimed at correcting hormonal-metabolic disturbances in endometrial cancer patients and groups at risk of this disease. Such an approach might include use of antidiabetic biguanides, thiazolidinediones (glitazones), and statins.

Data are summarized on experimental means of induction of PSEE and its modification/prevention with the aim to achieve optimal ratio of estrogenic effects (as low as possible genotoxicity in combination with satisfactory and excessive hormonal action). Among studied agents were ethanol, tobacco smoke, irradiation, aging (as PSEE inductors) and carnosine, N-acetylcystein, vit. E and C, melatonin, swimming and antiestrogen ICI 182780 (as PSEE modificators).

2,429 breast cancer patients and 478 patients with endometrial carcinoma were examined. It was suggested that the absence of estrogen receptors (ER) and/or progesterone receptors (PR) should be accounted for by peculiar endocrine features (including those of reproductive function) of the patients' medical history and/or hormonal metabolic status (body weight, estrogenemia, insulinemia, etc.) at clinical detection of tumor. The differences between breast and endometrial cancer in receptor-negative (R-) incidence were related to age (decade of lifespan) and menstrual cycle. Indices describing hormone-metabolic status were used for identification of receptor-negative or receptor-positive status of tumor (reliability of 65-70% for breast cancer and 75-80%--endometrial carcinoma) when it was not feasible under laboratory conditions.

We studied the influence of various methods for correction of age-related changes (administration of N-acetyl-L-cysteine, vitamins C and E, melatonin, and carnosine and swimming training) on the realization of estrogens effects in ovariectomized rats. The proliferation index in the endometrium decreased in 12-14-month-old control animals. The weight of the uterus, percentage of "comets", and average length of their tail in estradiol-treated rats far surpassed the corresponding parameters in control animals. Administration of melatonin and N-acetyl-L-cysteine and swimming training corrected these genotoxic abnormalities. Our results indicate that aging induces incomplete variant of the phenomenon for switching of estrogen's effects (increase in the severity of genotoxic damage without facilitation of the hormonal effect). These methods for correction of age-related changes have not only common, but also distinguishing characteristics compared to correction of changed induced by drinking of ethanol in various concentrations, whole body gamma-irradiation, and exposure to tobacco smoke.

Late-onset of menopause is a marker of risk factor for neoplasia in the reproductive system and, conversely, anti-risk for certain non-infectious diseases, such as cardio-vascular disease or osteoporosis. We studied 118 postmenopausal patients with early endometrial and breast cancers. The investigation was particularly concerned with hormonal-metabolic status versus age at menopause age at. While a Quetelet index/age was irrelevant, blood cholesterol and insulin (120 min) concentrations and tumor estrogen/progesterone receptor ratios were relatively higher in the late-onset group ((52 yrs). This group showed a correlation with age at menopause while the other one--with its duration. Insulin/body weight ratios were higher in the late-onset group while LH/FSH--lower. Hence, patients of the same age but differing in age at menopause age at may show differences in hormonal-metabolic status as well. This feature may be significant in identifying both biological distinctions of associated tumors and their clinical course.

Initiation and/or promotion of endometrial carcinoma is considered to be associated with estrogens and androgens (androstendione) excess as well as hyperinsulinemia and resistance to insulin. It is possible that certain polymorphisms of the genes involved in steroidogenesis or steroid metabolism contribute to carcinoma susceptibility. In the current study, we compared the role of CYP17 biallelic MspA1) polymorphism in 114 endometrial carcinoma patients and 182 healthy women. According to our data, A2/A2 CYP17 genotype traditionally regarded as "unfavorable" was less frequent in cancer patients than in control which confirmed the results of two previous publications. For the first time, carriers of the genotype were shown to have relatively low levels of blood insulin and C-peptide. No significant difference was found between mean concentrations of testosterone, dehydroepiandrosterone sulfate and those of estradiol in the carriers of various CYP17 genotypes with endometrial cancer. Hence, CYP17 polymorphism which is represented by the "normal" A1/A1 genotype might be a factor of risk for endometrial carcinoma. Since this genetic variety may develop through an unconventional (nonsteroid) pathway, taking relevant preventive measures in high-risk groups should be recommended.

Female rats (aged three months at the start of the study) were kept for four months on drinking water (group 1) or 5% ethanol. Rats drinking ethanol were additionally divided into six groups (groups 2-7). During the next two months of the experiment, animals of group 2 continued to drink only ethanol, while rats of group 3 additionally received N-acetylcysteine, those of group 4 received ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E), those of group 5 received melatonin, those of group 6 received carnosine, and those of group 7 swam in the so-called training regime for five days a week. All animals underwent bilateral ovariectomy 2.5 weeks before experiments ended, and were given daily i.m. estradiol (2 microg) during the 11 days before the last experimental day. After treatments, blood estradiol and cholesterol levels were measured, along with progesterone receptor levels, peroxidase activity, the index of proliferation, the proportions of cells in the S and G2/M phases, the thickness of the endometrium, and the extent of DNA damage (using the "comet" technique) in uterine tissue. Liver estradiol 2-hydroxylase activity was also measured. The results led to the conclusion that drinking of 5% ethanol in combination with administration of estrogens was accompanied by induction of genotoxic (G) changes in the uterus and that this was prevented by administration of N-acetylcysteine and melatonin. The combination of vitamins C and E increased some of the manifestations of the hormonal (H) effect of estrogens (uterine weight and induction of progesterone receptors), but weakened others (the index of proliferation). As a result, the combination of N-acetylcysteine and optimum doses of ascorbic acid and alpha-tocopherol can be recommended for preventing the estrogen effect-switching phenomenon (increases in the G component on the background of weakening of the H component), which is seen particularly in patients consuming excessive amounts of alcohol, increasing the risk that the genotoxic version of hormonal cancerogenesis will develop.

Endometrial cancer (EC) is estrogen-dependent tumor in the hormonal treatment of which mostly progestins are used. During last 5-7 years feasibility of aromatase inhibitors use in EC is discussed without any special practical move in this direction. To evaluate possible biological response of tumor and patients to such treatment, we conducted a short pilot study involving 10 primary postmenopausal EC patients, mostly stage Ia,b (average age 59) who received letrozole (Femara, Novartis) 2.5 mg/day during 14 days before operation. Clinical, sonographical, morphological, cytological and hormonal-metabolic (blood estradiol, FSH, LH, glucose, lipid fractions by RIA or enzyme-colorimetric methods; tumor progesterone receptors by LBA and aromatase activity by 3H-water release assay) studies were included into the protocol before and after treatment. Tolerability of letrozole was satisfactory in all patients. 2 patients reported decrease of pain and pathological secretions from uterine cavity. In 3 patients, decrease in M-sonographical endometrial signal was registered; average value after treatment was 31.1% lower than before it. Tendency to the decrease in estrogenicity of vaginal smears was revealed. Average decrease in blood estradiol was 37.8% and in progesterone receptor level and aromatase activity 34.4% and 17.5% respectively. Decrease of aromatase activity in tumor tissue was registered mostly in normal weight patients. A more detailed and longer randomized study of aromatase inhibitors in EC performed in neoadjuvant setting deserves consideration.

Twenty seven breast cancer patients with receptor-positive tumors stage IIb-IIIa (TNM) were treated with an aromatase inhibitor--letrozole, 2.5 mg/day, or an antiestrogen--tamoxifen, 20 mg/day, 4 months before surgery. Complete or partial response (CP + PR) was recorded in patients older than those with stabilization or progression of the disease. Moreover, the former group tended to show higher of suppression of blood-estradiol and progesterone receptors levels in tumor and lower suppression of serum-FSH concentration after treatment. These, practically, first findings of the kind suggest that the search for hormonal markers to predict the efficiency of neoadjuvant hormonal therapy for breast cancer should be continued.

Drinking of 5% ethanol in combination with estradiol induced genotoxic (G) changes in the rat uterine tissue. The changes could be prevented by N-acetylcysteine or melatonin. The data obtained suggest that ascorbic acid and alpha-tocopherol may be recommended in combination with N-acetylcysteine for repair of estrogen effect switching phenomenon.

The effect of gamma-irradiation on the realization of the effects of estrogens was studied on rats treated with N-acetylcysteine, vitamins C and E, melatonin, and carnosine or subjected to forced swimming in a training mode. Irradiation (0.2 Gy) in combination with estrogens and without correction therapy induced genotoxic changes in the uterus, while irradiation in a higher dose (2 Gy) predominantly potentiated the hormonal effect of estrogens. Correction of the revealed abnormalities was achieved mainly with carnosine. The peculiarities of "estrogen toggle (re-targeting) effect" under the effect of gamma-irradiation and its elimination differed from those induced by ethanol intake or tobacco smoking, which is important for understanding the mechanisms of hormone-induced carcinogenesis.

The levels of estradiol-2-hydroxylase were assayed in patients with breast (17) and endometrial (30) tumors. In the latter group, the findings were compared with normal endometrium and the enzyme was found in it, too. A direct correlation was established between age and said level in tumor tissue in nonsmokers, particularly, in breast cancer cases. Smokers revealed relatively higher levels both in tumor tissue and normal endometrium. No relationship between estradiol-2-hydroxylase and steroid hormone receptor concentrations was found in either endometrial or breast tumors. The role of estrogen metabolism and conversion of classical estrogens to catecholestrogens in hormone-related carcinogenesis is discussed.

Standard glucose-tolerance test (SGTT) was carried out in 73 patients with endometrial tumors. Elevated concentrations of plasma insulin and C-peptide were established in endometrial carcinoma patients (irrespective of age and reproductive status) after night fast and 120 min after SGTT start, as compared to healthy subjects and breast cancer patients. Obese (BMI index 28 kg/m2) reproductive endometrial carcinoma patients showed pronounced hyperinsulinemia and resistance to insulin. Menopausal patients with endometrial tumors (BMI index= 28) were characterized by a much faster metabolic clearance of insulin, as compared with all other patients. Therefore, degree of insulin resistance in endometrial carcinoma is determined by both enhanced secretion of insulin and lowered metabolic clearance of this hormone which in turn is associated with obesity.

Tobacco smoke induced no changes in the rat uterus weight or in oestrus cycle but decreased estradiol (E2) concentration in the uterus tissue and increased and later decreased the proliferation index and percentage of the cells in the S-phase. The data obtained suggest a phasic character of changes in the reproductive system under the effect of tobacco smoke and corroborate the concept of the role of smoking in the shifting the type of hormonal carcinogenesis from promotional to genotoxic one.

Body weight, body mass index, body fat, lean body mass, blood-glucose, cholesterol, HDL-cholesterol, triglyceride, beta-lipoproteins, insulin, gonadotropin, estradiol, testosterone, SHBG, T3, T4 and TSH levels as well as estradiol and progesterone receptor levels in excised tumor were studied in 40 patients with breast cancer prior to conservative treatment. Said anthropometric, metabolic and hormonal parameters were compared with the index of lymphocytic infiltration of tumor selected as a prognostic factor. A significant correlation between high lymphocytic infiltration (2.5 points), low body mass and fat was identified. Also, smoking contributed to loss of body mass and fat; however, it caused lymphocytic infiltration to rise. Moderate body mass, relatively low fat level and positive receptor status are among factors of good prognosis in breast cancer of early stages.

Nonlinear evolution of one-dimensional planar perturbations in an optically thin radiatively cooling medium in the long-wavelength limit is studied numerically. The accepted cooling function generates in thermal equilibrium a bistable equation of state $P(\rho)$. The unperturbed state is taken close to the upper (low-density) unstable state with infinite compressibility ($dP/d\rho= 0$). The evolution is shown to proceed in three different stages. At first stage, pressure and density set in the equilibrium equation of state, and velocity profile steepens gradually as in case of pressure-free flows. At second stage, those regions of the flow where anomalous pressure (i.e. with negative compressibility) holds, create velocity profile more sharp than in pressure-free case, which in turn results in formation of a very narrow (short-wavelength) region where gas separates the equilibrium equation of state and pressure equilibrium sets in rapidly. On this stage, variation in pressure between narrow dense region and extended environment does not exceed more than 0.01 of the unperturbed value. On third stage, gas in the short-wavelength region reaches the second (high-density) stable state, and pressure balance establishes through the flow with pressure equal to the one in the unperturbed state. In external (long-wavelength) regions, gas forms slow isobaric inflow toward the short-wavelength layer. The duration of these stages decreases when the ratio of the acoustic time to the radiative cooling time increases. Limits in which nonlinear evolution of thermally unstable long-wavelength perturbations develops in isobaric regime are obtained., Comment: 21 pages with 7 figures, Revtex, accepted in Physics of Plasmas

Lymphocytes were isolated from 43 surgical samples of breast cancer after tumor enzyme digestion and Ficoll/Verographine procedure. In all, 23 specimens from lymphocytic-tissue infiltrates were analyzed (in some cases, material from 2 or 3 patients was combined). The ability of tumor-infiltrating lymphocytes (TIL) to convert androstenedione was demonstrated, as evaluated by hard-water release from the androgenic precursor 3H-1beta-androstenedione. In material obtained from menopausal women this ability was higher than in the women of reproductive age. A positive correlation was revealed between the level of androstenedione conversion in TIL and aromatase activity in tumor tissue, while no correlation was shown between androstenedione conversion in TIL and percentage of tumor cells in lymphocytic suspension. The data obtained suggest that factors secreted by a neoplasm are able to induce aromatase gene expression in TIL.

Blood-glucose and insulin were assayed by administering 40 g/sq.m glucose (per os) and 0.08 unit/kg body weight in 113 patients with early-stage breast tumors (glucose-tolerance test) and in 62 patients (insulin-sensitivity test). Sensitivity to insulin was assessed versus age, reproductive status, body size and smoker/non-smoker status. A direct correlation between high level of reactive insulinemia and obesity and an inverse one--between sensitivity to insulin and age were established on the basis of insulin test data and the insulin resistance factor. Smokers showed, on the average, lowered basal insulin levels and increased sensitivity to insulin (depending on age and number of cigarettes consumed). Smoking was found to influence prolactin reaction to hypoglycemia and to upset the correlation between age and progesterone receptor concentration in tumor which may account for certain peculiarities of the course of the disease in smokers with breast tumors.