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Frequency of separate malignancies and diabetes tends to an increase. This is one of the reasons that diabetes is more often attracting attention as a potential risk factor for cancer. At the same time, in general, relatively less attention is paid to the analysis of the question of whether the presence of diabetes is able to influence on features of neoplasm, inherent at the diagnosis, as well as on the clinical course of the tumor process and its outcomes. In this paper, exactly this aspect of the problem is considered on example of such common and characterized by undoubted specificity of tumors of the female reproductive system as breast cancer and uterine cancer.

Metabolism and information between cells is the basis of the existence of any multicellular organism. Malfunction of the intercellular communication play an important and sometimes decisive role in the pathogenesis of the most diseases, including cancer. According to traditional views, functional integration of individual cells in tissues, organs and organ systems is mediated by the efficient work of regulatory systems: nervous, immune, endocrine. Over the past few years the attention of scientists is attracted the ability of cells to "communicate" with the help of nanoscale vesicular formations, or so-called exosomes. There are accumulated data that the cells of the most tissues secrete exosomes into the intercellular environment, after which, by means of stream of blood or lymph, exosomes transferred to anatomically distant sites where they are accepted by the other cells. It is showed that the content of exosomes are not random and that vesicular transport may be targeted and to play a significant physiological and even "pathophysiological" role. The aim of this review is the analysis and integration of modern scientific data on the role of exosomes in the process of tumor progression and presentation of possible ways and methods of using these data in the practice of oncology.

The paper presents the results of a study of the ovarian reserve in young women who received treatment for malignant tumors in childhood and adolescence and are in complete clinical remission. The function of the reproductive system was evaluated by serum concentrations of gonadotropins, estradiol, anti-Müllerian hormone (AMH) and inhibin B. The results were compared to the treatment, patients' age at the beginning of therapy and at the time of the examination. AMH level in serum was the most informative indicator of ovarian reserve in patients treated for malignant tumors.

The state of the viscosity of erythrocyte membranes in breast cancer patients (68--in menopause and 32--with menstrual cycle) was studied in comparison with the content of steroid hormone receptors in the tumor tissue and the age of patients. It is showed that the less hormone dependence of the tumor the higher viscosity of erythrocyte membranes that manifested by a decrease in the coefficient of eximerization (CE) of pyrene in the protein/lipid and in particular, lipid/lipid membrane layers. Increasing CE of pyrene in lipid/lipid layer of erythrocyte membranes above 1.7 units, reflecting a decline in their microviscosity, could be considered as an additional extra-tumor criterion for identification of the tumor as of hormone dependent type.

Simultaneously with keeping one of the leading positions in the structure of oncogynecological morbidity, endometrial cancer (EC) presents for many decades 'the food for brains' of cancer endocrinologists. Step by step development of contemporary ideas and collecting the data on mechanisms of hormonal carcinogenesis, the role of excessive estrogenic stimulation and metabolic syndrome/insulin resistance as risk factors for EC, very probable gradual changing of the disease phenotype and significance of genetic damages (with PTEN-mutations as one of the examples), as a consequence point at potential perspectives in the usage of preventive and therapeutic approaches in this important area.

In order to assess the effectiveness of compression elastography of the thyroid gland as a method for differential diagnosis to studies conducted in the pre-operative period, there were involved 34 patients with a mean age 46.6 +/- 2.7 years. Elastography in the real time was characterized, according to the method of estimating, by a relatively high sensitivity (85.2-92.5%) and accuracy (70.6-79.4%), but low (30%) specificity. The specificity of the method, as it turned out, could be improved by taking into account the level of thyroid stimulating hormone (TSH) in the blood or body mass index (BMI) of the patients and, therefore, reducing the number of false-positive findings. Further improvement in the pre-operative diagnosis of malignant tumors of the thyroid gland and the formation of appropriate risk groups could be based on a combination of cytologic, hormonal, genetic and instrumental methods, including the so-called shear wave elastography.

Metformin (MF) belongs to the most popular andidiabetic medicines and is considered to possess a selective antineoplastic action. This selectivity at least partly may be explained by the certain features of MF pharmacogenetics. More than 150 postmenopausal females divided into 4 groups (cancer +diabetes type 2 (DM2); cancer without DM2; DM2 without cancer, and healthy) were studied. Genetic polymorphisms of the two groups of genes--entitled on the basis of the relation to potential MF effect as a 'standard' (S) or 'associated' (A)--were under investigation. Among S-markers a most informative in regard of MF response prediction appeared to be polymorphisms of OCT1-R61C organic cation transporter protein 1 gene and serin/threonine kinase STK11. In the group of A-polymorphisms the GC genotype of oxidized lipoprotein receptor OLR1_G501C demonstrated tendency to the combination with 'MF-positive' variant of OCT1_R61C. The carriers of the latter were characterized with insulin resistance while carriers of STK11 variants--with lower blood estradiol level. Postmenopausal diabetics with as well as without cancer, differ in genetic markers of potential response to metformin less than they differ from cancer patients without DM2.

Preliminary data are confirmed on the more rare prevalence of family history of diabetes mellitus (DM) in cancer patients, mainly females, with diabetes in comparison with diabetics without cancer pathology. Familial diabetes does not worsen additionally tumor characteristics against the same in patients with non-familial diabetes. More than that, familial diabetes in diabetics with breast cancer goes together with lesser size of tumor and demonstrates an inclination to the rarer distant metastases in breast and endometrial cancer patients. The signs of systemic DNA damage (evaluated, in particular, on the basis of 8-OH-dG serum levels) are pronounced in postmenopausal diabetic cancer patients with familial diabetes in lesser degree than in non-familial variant of DM. In toto, this allows to consider family history of DM in patients with type-2 diabetes as a particular factor of tumor growth containment, which mechanisms and causes, warrant further studies.

The group (totally 156 postmenopausal women) used for the study of 'standard' (S) and 'associated' (A) genetic markers of potential sensitivity to metformin (MF) consisted of 37 healthy females, 32--with diabetes (DM) without cancer, 64 cancer patients with DM, and 23 cancer patients without DM. No significant difference in carrying of S-polymorphisms was found between DM patients without and with cancer. In cancer patients without DM most characteristic data regarding potential MF-response were detected with polymorphisms of STK11 gene while data on OCT1_rs622342 and OCT1_R61C variants showed opposite trends. In regard of A-markers, the tendency to the more often finding of GC genotype of OLR1_GS01C in DM patients carrying 'MF-positive' variant of OCT1_R61C deserves to be underlined. In patients with new-onset diabetes who carried S-markers of potential response to MF higher insulin resistance (OCT1_R61C and OCT1_rs622342) as well as lower estradiolemia (STK11 and C11orf65) were discovered. Thus, according to genetic S-criteria of sensitivity to MF, DM patients with and without cancer differ in lesser degree than they differ from cancer patients without DM. It can not be excluded, that The efficiency of such criteria might be increased due to combination with A-markers and certain hormonal-metabolic indices.

85 females were studied, 35 females had new onset of diabetes (DM2) and in 50 women DM2 was associated with recently diagnosed cancer (C+DM2). Group C+DM2 was characterized by higher levels ofbody mass index, insulinemia, estradiolemia, interleukin 6 in serum, and glyoxalase I activity in mononuclears. At the same time patients in C+DM2 group who had familial predisposition to DM2 were characterized by lower body mass index, body fat content, waist circumference, insulinemia, serum interleukin 6, viscosity of erythrocyte membranes and percent of comets in mononuclears in comparison with patients without familial predisposition to DM2. These trends were mostly opposite to the data of subgroups comparison (with or without relatives with DM2) in females with DM2 without cancer. The conclusion is made that the hereditary load with DM2 is differently realized in diabetics with higher or lower predisprosition to cancer that deserves further study.

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.

High level of thyroglobulin (Tg) after thyroidectomy has been shown to be an early marker of either metastases or local recurrence of differentiated thyroid cancer (DTC). The aim of this study was to evaluate the relation between Tg level estimated on the third week after thyroidectomy and clinic-pathologic characteristics of DTC as a possible prognostic criterion used to mark the patients with radioiodine therapy indications. Research data on 45 patients (39 women, 6 men, age 22-75 years) with DTC and without high level of Tg autoantibodies have been included in the study. Eleven patients underwent surgical treatment due to disease recurrence. In all patients Tg and thyroid hormones levels were measured before the thyroidectomy and on the third week after it. The postoperative level of Tg as TTM coefficient (ratio of postoperative Tg to daily L-thyroxin dose in mcg to body weight in kg) was higher in patients with unfavorable prognosis: (a) capsular invasion, (b) cervical lymph nodes metastases, (c) advanced disease stage, (d) high risk of recurrence. The postoperative serum Tg levels were similar in primary disease patients and patients with DTC recurrence. There was no relation between preoperative Tg level and any prognostic factors although there was a tendency to higher (more than 2 ng/ml) Tg levels in patents with high preoperative Tg levels. Finally, the serum Tg level on the third week after thyroidectomy is a valuable prognostic criterion and can be used in DTC to determine the radioiodine therapy indications.

Of examined 37 breast cancer patients (average age 42,3 +/- 1,2 years) 25 had not had any specific therapy by the date of investigation and the rest 12 had received in average 5,3 +/- 0,6 cycles of neoadjuvant chemotherapy mainly TAC and FAC. It was revealed that such kind of treatment conformed to valid decrease of both testosterone level and ratio value [(testosterone concentration/follicle stimulating hormone concentration, FSH) x 100] in blood serum. Testosterone level in blood of patients in fact decreased to similar values both in amenorrhea induced by adjuvant chemotherapy and saving menorrhea. This is a confirmation that maintenance of menorrhea does not mean intactness of ovarian function (ovarian reserve) and indicates that evaluation of testosteronemia in these circumstance at least does not give in estimation of estradiol and FSH's content in blood. Further attention could be paid to study testosteronemia before and after neoadjuvant chemotherapy as a potential additional prognostic factor of efficacy of this treatment for breast cancer patients.

In this mini-review the basic evidence about anticancer properties of ursolic acid (UA), the compound belonging to the class of triterpenoids, is given. Beside inhibiting tumor cell growth in vitro and in vivo and activating of apoptosis, UA (as well as some other related and not related compounds) is capable to induce PTEN (a tumor suppressor mutation of which is rather often discovered in human tumors including endometrial cancer type I) and amount/activity of brown fat. The latter action may explain obesity-preventing capacity of UA that also may lead to an additional antiblastomogenic effect.

Although there is data suggesting the in vitro inhibition of aromatase in cell lines by antidiabetic biguanide metformin (MF), there is no data on the intratumoral breast cancer (BC) aromatase expression in patients already receiving therapy for type II diabetes. Paraffinized tumor samples obtained from 57 BC pts aged 48-77 yrs, >80% of pts had stage T1-2N0-3M0 BC. Thirteen of the pts didn't have diabetes, 44 pts were previously diagnosed type II diabetes and reseaved the following therapy for at least 1 year: diet only (n=14), sulphonylurea (SU, n=14), metformin (MF, n=9) or MF with SU (n=7). Tumor samples were deparaffinized in xylene and treated with the monoclonal aromatase antibody 677. The rate and intensity of tissue staining was then analyzed by semi-quantitative method using conventional scores. Negative controls were processed with 0.01 M PBS instead of the specific antibody. For positive control paraffin-embedded human placenta samples were used. By conventional scores method the following values were obtained: 1.31 (pts without diabetes), 1.47 (all diabetic patients), 2.22 (MF), 1.50 (SU), 1.29 (MF+SU), 1.81 (MF and MF+SU), 1.07 (diet). Allred scores for progesterone receptor (PR) were the highest in the samples from pts treated with MF or MF+SU and the lowest in the samples obtained from SU-treated pts. Thus, in contrast to previous findings suggesting the suppressive effect of MF on aromatase in vitro, no such trend was discovered for aromatase expression in tumor samples from diabetic patients treated with MF. Although the investigated patients population is still small, this data combined with clinical data (higher PR levels) may suggest the better responses to hormonal therapy in MF-treated diabetic patients.

Although type 2 diabetes contributes to the risk of development of certain tumors; factors which modify this relationship need to be further examined. Familial diabetes frequency was followed in (a) diabetes-free cancer patients (132), aged 60.3 +/- 1.2; (b) cancer patients with apparent (62.3 +/- 0.4; n=371) or occult type 2 diabetes (61.6 +/- 1.2; n=65) and (c) cancer-free patients with type 2 diabetes (61.8 +/- 0.4; n=237); the latter group (172 females and 65 males) featured almost identical diabetes frequencies: 30.8 +/- 3.5% and 30.8 +/- 5.7%, respectively. They significantly exceeded a relevant index occurring in families free from cancer concomitant with diabetes (6.1 +/- 2.1%). Significantly lower frequencies of familial diabetes were reported in cancer patients as compared with cancer-free patients (12.9 +/- 2.1% females, p < or = 0.01; 19.4 +/- 3.8% - males, p=0.1). To sum up, it cannot be ruled out that familial diabetes is a marker of relative decrease in potential risk of cancer rather than that of increase. The causes of this phenomenon and its possible dependence on gender need to be explored.

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.

We compared the efficacy of endometrial cancer neoadjuvant treatment in 38 patients receiving nonsteroid (letrozol, anastrozol) or steroid (ekzemestan) aromatase inhibitors and 12 patients receiving metformin. The changes in glucose metabolism were revealed in 26.3% of patients treated with aromatase inhibitors and 16.7% of patients treated with metformin. However, comparison of endometrial thickness (M-echo signal) data, postoperative data on favorable differentiation grade changes rate and proliferative activity (Ki-67 expression) revealed the superiority of 2-4 weeks aromatase inhibitors course in comparison with 2-9 (average 5.3 +/- 0.7) weeks metformin treatment.

According to some existing data, unlike sulphonylurea (SU) and insulin derivatives, treatment with biguanide metformin, for reasons still unknown, may diminish breast cancer (BC) morbidity in diabetic females. For its part, diabetes is known to worsen survival of BC patients although there is no evidence of a pathway by which antidiabetic therapy might influence the key prognostic feature of BC tissue--the tumor receptor phenotype. Combination of BC and diabetes (n=90) was studied. SU drugs were received for at least 12 months by 22 patients, biguanide metformin alone or in conjunction with SU by 15, insulin by 5, and dietary treatment alone--by 48 pts. Percentage of estrogen receptor-positive tumors did not vary significantly from group to group. However, progesterone receptor-positive (PR+) tumors in metformin-treated patients were revealed more often than in those receiving SU alone (p = 0.43) or with insulin (p = 0.041), respectively. Hence, previous treatment with metformin is expected lead to higher incidence of PR+ tumors which in turn may stimulate efficiency of hormonal therapy only in relevant group of diabetic BC patients.

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 (p < or = 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.

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.

Peculiar features of human morbidity and their changes in time are registered chronologically starting from the XVII-VYIIIth centuries. After the period of predominantly infectious diseases, chronic and non-communicable conditions continued to gain momentum in the last 3-5 decades. Side by side with AIDS, accidents, effects of smoking etc, the global epidemics of diabetes mellitus and obesity comes up to take a leading place in the general population morbidity. In this communication, possible causes of this situation and its possible association with cancer are considered based on the results of original studies. Measures for the prevention and treatment of these diseases are discussed.

Polymorphisms in genes involved in steroidogenesis as well as sensitivity to insulin as potential cancer risk factors have received constantly-growing attention over this decade. The peculiarities of endocrine and metabolic features of cancer identified earlier in BRCA1 mutation carriers prompted an investigation of the frequency of polymorphisms in the genes of IRS-1 and enzymes of estrogen biosynthesis and metabolism, such as aromatase (CYP19), estrogen 4-hydroxylase and catechol-O-methyl transferase (COMT) in 12 BRCA1 mutation carriers and in 22 non-carriers. The results were compared with the earlier data from the patients with the same diagnosis (n = 110 and n = 295, respectively) but untested for BRCA1 mutation. BRCA1 mutation carriers tended to show increasing fractions of heterozygotes for AG (COMT Vall58Met p = 0.24) and active allele A6 featuring 11 TTTA repeats in the 4-th introne [corrected] of CYP19 gene (p 0.09). [corrected] The frequency of co-occurring CC (CYP1B1) Arg48Gly), AG (COMT Vall58Met ) and A6 (CYP19) in BRCA1 mutation carriers (5 out of 12, 41.6% ) was significantly higher than that in non-carriers (2 out of 22, 9.1% ) (p = 0.03). Immunohistochemical assay showed aromatase expression levels to be the highest among cases of BRCA1 mutation and A6 (CYP19) while CYP1B1 expression was the highest in those of combination of BRCA1 mutation and low-activity AA genotype (COMT Vall58Mer). Our results warrant further large-scale cooperative studies of the problem.

Clinical and experimental effects of neoadjuvant treatment of endometrial cancer patients with non-steroidal aromatase inhibitors: letrozole (femara, n=10, 2.5 mg/day, 14 days), anastrozole (arimidex, n=15,1 mg/day, 28 days) and exemestane (aromazine, n=13, 25 mg/day, 14 days) were compared. Administration of anastrozole was mostly frequently followed by pain relief in the lower abdomen and/or decreased rates of uterine discharge. Endometrial wall thickness (M-echo signal) decreased significantly in 60% of patients receiving anastrozole, exemestane - 58.3% and letrozole - 40%. Substantial drop in intratumoral aromatase and blood estradiol levels occurred more frequently after anastrozole and letrozole while progesterone receptor levels in tumor were markedly lower after exemestane administration. Assay of blood LH (except letrozole), FSH and cholesterol appeared to be of less relevance. On the contrary, significance of assessment of marker Ki-67 expression, which, in the case of anastrozole, dropped in 6 out of 12 patients after a 28-day course, could hardly be underestimated.

The group of main noncommunicable diseases (NCDs) includes cardio- and cerebrovascular pathology, cancer, chronic nonspecific respiratory states, diabetes mellitus, osteoporosis, unipolar depression, obesity, etc. Tumors of hormone dependent tissues compose about 35-45% of the whole cancer morbidity. The attempts to understand place of these tumors among other NCDs and analyze their interrelationships with regard to age and aging represent a vital task of contemporary oncoendocrinology. On the ground of accumulated data one can conclude that although principal NCDs are diagnosed mainly in the course of second half of human life, the maturing of their hormonal and metabolic bases is extended in time, rather often starts several decades before clinical appearance and demonstrates diverse character of the associations with different constituents of this group of diseases. As a result it may give rise for the absence of parallelism in age-specific incidence of several main NCDs, especially at concluding stages of ontogenesis.

Breast cancer in germline BRCA1 mutation carriers features a peculiar endocrine and metabolic profile which is yet to be studied properly in clinical settings. We used a novel immunohistochemical method to compare expression levels of aromatase, estrogen 4-hydroxylase (CYP1B1) and fatty acid synthetase in breast cancer tissues from 12 BRCA1 mutation carriers and 22 non-carriers. Rates of aromatase in carriers were significantly higher than in control (p=0.04) to match the data obtained earlier in cell lines employed in down-regulation of the wild BRCA1 gene. These findings make a case for use of aromatase inhibitors in such patients. No differences in CYP1B1 and fatty acid synthetase expression levels were found between the mutation and the wild BRCA1 gene groups. Further search is warranted for manifestations of excess genotoxic effects of estrogens and enhanced lipogenesis in BRCA1 mutation carriers.

Glucose intolerance and insulin resistance belong to the group of leading risk factors for breast (BC) and endometrial cancer (EC). Differences in the intensity of association of these endocrine disturbances with BC and EC may at least partly be explained by non-identity in polygenic nature of the mentioned hormone-metabolic shifts and oncological diseases themselves as well. In this study, which included 105 healthy postmenopausal women and 301 female cancer patients (110 BC and 191 EC) without overt diabetes mellitus, we compared the frequency of the following genetic polymorphisms: insulin receptor substrate-1, IRS Gly972Arg; leptin receptor, LEPR Lys109Arg and Gln223Arg; mitochondrial uncoupling protein-2, UCP2&#95;866G/A; and gene ND3 of mitochondrial DNA, mtDNA 10398A/G. Genotyping was performed with allele-specific real-time PCR. According to data received, certain genetic markers associated with impaired glucose tolerance and/or insulin resistance (namely, leptin receptor genotypes 223 Gln/Arg and Gln/Gln) are revealed in oncological patients more often than in females without cancer. Other markers (like genotype UCP2 866AA and polymorphism mtDNA 10398A) appeared to be relatively more frequent in EC than in BC providing one of the interpretations for the lower insulin sensitivity and higher incidence of carbohydrate metabolism disturbances in the first of these two diseases.

Gail coefficient (GC) generally used in breast cancer predictions for the next 5 year--or entire survival was determined in both patients and healthy controls of the same age, residents of St. Petersburg. Simultaneously, a correlation was established with hormono-metabolic indices, receptor pattern, tumor stage and size and some other characteristics. GC in cancer patients with age <50 was significantly higher than in control. In menopausal cancer patients, greater GC correlated with such parameters as body mass, weight index, glucose, total cholesterol and low density lipoproteids after fasting. The latter group showed a tendency towards enhanced estradiol and testosterone in blood serum. In reproductive patients with elevated GC, estradiol level rise was significantly lower and most tumors were receptor-negative. However, involvement of regional nodes was relatively rare. To summarize, GC determination characterizes risk and certain clinico-morphological features of distinction between reproductive and menopausal patients.

Our investigation included 158 women, aged 23-73: patients with tumors of the ovary, breast and endometrium--117 and subjects without oncological pathology--41. Autoantibodies to microsomal fraction of follicular ovarian cells (> 500 Unit/ml) in healthy subjects were revealed 8.3% while in patients with ovarian, breast and endometrial malignancies (without significant differences between benign and malignant tumors) in 33.30%, 45.60% and 25.0%, respectively. Higher level of anti-ovarian autoantibodies involved an inverse correlation between blood levels of FSH and estradiol in ovarian and endometrial carcinoma patients. It also co-occurred with a tendency of increasing levels of autoantibodies to thyroglobulin. Whatever apparent predictive accuracy in oncological clinic, high concentrations of anti-ovarian autoantibodies point to certain shifts taking place in the formation of reproductive system pathology. Besides, they may have considerable prognostic significance.

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.

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 (p < 0.05). 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.

Twenty-four patients with thyroid carcinoma receiving thyroxine were examined. The thyroid gland had been extirpated in 20; hemithyreoidectomy (4). Tests with ethinyl estradiol (50 mcg, per os, 6 days) (8), estradiol valerate (2 mg, per os, 12 days) (10), and tamoxifen (40 mg, per os, 14 days) (6) were carried out on the assumption of normal and neoplastic thyroid epithelium sensitivity to estrogen stimulation. Blood thyroglobulin, TSH and estradiol levels were assayed before and after loading. Thyroglobulin concentrations increased in 5 out of 24 patients (ethinyl estradiol--1 out of 8, estradiol valerate--2 out of 10 and tamoxifen--2 out of 6); those of TSH--in 6 out 24 (3 out of 8, 2 out of 10 and 1 out of 6, respectively). Enhanced thyroglobulin correlated with higher levels of TSH in 2 out of 5 and with blood-estradiol--in 4 out of 5. It was suggested that at least, in some patients, the preparations might produce a direct stimulating effect on thyroglobulin biosynthesis in the thyroid tissue remnants. Further research is suggested or on whether tamoxifen exerts pro- or antiestrogenic influence on thyroid epithelium.

Data are presented on a randomized study (stage II) which was undertaken to assess the efficacy of neoadjuvant chemotherapy (doxorubicin+paclitaxel) vis-a-vis endocrine therapy with aromatase inhibitors (anastrazole or exemestane) in postmenopausal women with ER-positive and/or PgR-positive tumors. Preoperative neoadjuvant chemotherapy was well tolerated and showed similar rates of overall response as compared with the latter regimen.

Blood levels of sex hormone-binding globulin (SHBG), transcortin and pregnancy-related alpha2-glycoprotein (PalphaGP) were assayed using commercial kits for alpha-protein analysis in 223 breast cancer patients and 180 healthy women. Elevated concentration of SHBG was characteristic of both the luteal stage of menstrual cycle and menopause. It occurred chiefly in patients under 59 whereas at older age no differences from control were observed. Blood- transcortin in tumor patients was significantly lower than in control; conversely, PalphaGP concentration was higher irrespective of age. Since steroid-binding protein levels in the blood of breast cancer patients appeared to differ from those in healthy women, relevant data should be considered when hormone-metabolic status of reproductive and menopausal patients is identified.

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.

Neoplasia was established in 5.4% out of 15,813 patients with diabetes mellitus registered at the City Population-Based Cancer Register and Territorial Diabetic Center, St. Petersburg. Gender-unrelated decreasing order of tumor sites was as follows: breast, skin, uterus, colon and stomach. Broncho-pulmonary and gastric cancer incidence in male patients with diabetes was higher than in females (3.5 and 2.2 times, respectively). The relationship was reversed with thyroid cancer and skin melanoma (4.4 and 2.3 times, respectively). In patients with type 1 diabetes mellitus (10.3%), the cancer incidence pattern differed significantly from that in the whole diabetes-associated cohort of cancer patients: the former tended to involve such sites as pancreas, urinary bladder, stomach, cervix uteri, lung and skin. Data on age at diagnosis of cancer or diabetes, insulin therapy intensity and body mass were evaluated. The value of timely screening for both cancer and diabetes mellitus in such cohorts was confirmed.