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Biomedical subjects

V F Semiglazov

Publications and source records attributed to V F Semiglazov.

At least 19 recordsLinked to original sources

Genotoxic factors associated with the development of receptor-negative breast cancer: potential role of the phenomenon of switching of estrogen effects.

AIM: 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. MATERIALS AND METHODS: 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. RESULTS: As it was shown, smokers and diabetics carry more frequently (p = or < 0.05) 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. CONCLUSION: 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.

8-Hydroxy-2'-Deoxyguanosine↗

[Testosterone's role in regulating expression of genes of several proliferation factors].

This research work focuses on an important topic--the study of cause and effect links between partial androgen deficiency of ageing men (PADAM) and an increased expression of genes of a series of factors that make proliferate activity. The results of this research show that an increased expression of genes of several proliferation factors, and a decreased expression of the gene of the insulin receptor among men of older age groups are all connected to PADAM. The given changes are directed at compensation for testicular inadequacy, and are a particular expression of metabolic syndrome (X-syndrome); their effect can be inversed however by androgen-replacement therapy.

Actins↗

[The influence of partial androgen deficiency of aging men (PADAM) on the impulse regime of incretion of several hormones and mitotic activity].

This research work is devoted to an important subject--study of the impulse regime of the incretion of a series of hormones among men with partial androgen deficience of aging men (PADAM). The results of this study suggest that PADAM leads to a breakdown of the impulse regime of incretion of a series of hormones, including luteinizing hormone (LH), follicle stimulating hormone (FSH), and somatotropic hormones (STH), as well as cortisol and insulin among men of older age groups. These changes accompany the development of metabolic syndrome (X-syndrome); their development can be inversed through androgen-replacement therapy.

Adult↗

[Hormonal and progenotoxic properties of mammary fat in pre- and postmenopausal cancer patients].

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.

Adiponectin↗

[Correlation of hormone-metabolic status in breast cancer and effectiveness of adjuvant hormone therapy].

Hormono-metabolic status was assayed before and after month 6, 12, 24, 36, 48, 54 and 60 of therapy in 72 patients with receptor-positive tumors of the breast who completed 5 years of adjuvant tamoxifen (20 mg/24 hrs) or letrozole (2.5 mg/24 hrs). Eleven patients were not followed up, 11 relapsed and had metastases while 50 completed therapy. Significant fall in body mass (Ketle's index), in C-peptide concentration after an insignificant rise and C-peptide/insulin ratio 129 min after glucose loading, low basal blood level of estradiol as well as stable estradiolemia throughout treatment were characteristic of cases of pre-treatment recurrence and metastastic spread. Insulin resistance status, basal serum-estradiol level and fasting its course of development during hormonotherapy should be the subject of further research in criteria for adjuvant hormonotherapy efficacy.

Aged↗

[Breast cancer receptor status in smoking and diabetic patients].

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, p < 0.05) as well as among the diabetics (t = 2.01, p < 0.05). In reproductive diabetics, the share of PR- tumors was significantly higher than in diabetes-free patients (t = 2.17, p < 0.05). 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.

Adult↗

[Investigation of the drug "Mamoclam" for the treatment of patients with fibroadenomatosis of the breast].

The clinical trial of a new drug "mamoclam" was carried out in patients with benign breast disease. The drug contains omega-3 polyunsaturated fatty acids, iodine and chlorophyll derivatives and is produced from the brown sea alga laminaria. The study involved 33 patients (mean age 42.5 +/- 1.1 yrs). Two tablets were administered thrice a day for three months. Examination included clinical evaluation of symptoms of mastopathy and dysalgomenorrhea, breast sonography and mammography. Therapeutic response presented as reduced mastalgia, premenopausal syndrome, dysmenorrhea and algomenorrhea, breast cyst regression as well as attenuated pain associated with benign breast disease and palpation. Positive response was reported in 94%. The drug should be recommended for benign breast disease treatment.

Adult↗

[Prognostic and predictive factors in breast cancer].

Recent data on prognostic and predictive significance of breast cancer-associated molecular markers are presented and their clinical value in making individual prognosis and choosing adequate therapy is discussed. Markers of tumor proliferation, steroid hormone receptors, factors of epidermal cell growth, plasminogen activators and inhibitors, factors influencing angiogenesis and apoptosis and genome characteristics are considered. It is concluded that only Ki-67, ER, PR and Her-2/neu may be recommended for clinical use.

Biomarkers, Tumor↗

[Changes in the expression of receptors of steroid hormones in the development of partial androgen deficiency of aging men (PADAM)].

This work is devoted to the vital topic of the influence of partial androgen deficiency of aging men (PADAM) on the development of cells with androgen receptors. The results obtained in this study suggest a conclusion that the production of testosterone by some tumors and tissues of the peritumorous zone, which is accompanied by increased proliferative activity and disturbance of the regulation of the cell cycle, is caused by PADAM. The given changes are directed at compensating for testicular deficiency (in particular at overcoming the androgen-dependent stage of development of androgen-sensitive cells). These changes are a partial manifestation of metabolic syndrome (X-syndrome). The atypical cells, which unavoidably develop during metabolic syndrome, are dealt with by means of the immune system, whose capabilities become less and less adequate in the given circumstances.

Aged↗

[Effect of testosterone concentration on the intensity of 5alpha-dihydrotestosterone and 17beta-oestradiol formation].

The culture of human male foreskin fibroblasts was incubated with various concentrations of testosterone in the medium. It has been shown that the minimum formation of 17beta-oestradiol and 5alpha-dihydrotestosterone occurs at physiological testosterone concentrations. Any deviation of testosterone concentration, both up and down, was accompanied by an increase in the formation of 17beta-oestradiol and 5alpha-dihydrotestosterone.

17-Ketosteroids↗

Expression of estrogen receptors-alpha and -beta in primary breast neoplasms and tumors exposed to neoadjuvant hormonal therapy.

We studied the content and expression of mRNA for estrogen receptors-alpha and -beta in breast tumors before and after 3-month neoadjuvant hormone therapy with antiestrogen tamoxifen and/or aromatase inhibitors. Expression of estrogen receptors-alpha and -beta was most often detected in ER+PR+ tumors and most significantly decreased in these neoplasms after exemestane therapy. Immunocytochemical and radioligand assays showed that tamoxifen and anastrozole have little effect on the number of estrogen receptors-alpha. The number of progesterone receptors in tumors decreased by the end of anastrozole therapy. Estrogen receptors-beta were immunocytochemically revealed in 50% primary breast tumors. Anastrozole slightly decreased, while tamoxifen increased the incidence of these receptors. Interruption of signaling through estrogen receptors and suppression of estrogen biosynthesis had different effects on the receptor status of neoplasms and distribution of estrogen receptors-alpha and -beta.

Anastrozole↗

[Gail's coefficient in breast cancer patients with respect to menstrual status, body mass and estrogen receptor pattern of tumor].

Groups at high risk for breast cancer are generally identified using Gail's coefficient (GC) which is calculated on the basis of up-to-date age, recorded menarche, at primapara age, having kinswomen with breast cancer, number of biopsy examinations and morphological evidence of atypical hyperplasia of the breast in case history. We established GC versus estrogen receptor pattern of tumor and body weight in 108 cancer patients. Estimated mean GC values for the next 5 years and survival time did not differ significantly from those in healthy subjects (n=60). They were lower than in the US population which is likely to be due to a number of ethnic, hormonal and screening-related factors. GC tended to grow in RE+ tumor bearers, particularly at reproductive age, and in obese postmenopausal patients. Further study is expected to throw light on the relationships of GC, on the one hand, and certain hormono-metabolic characteristics and clinical course of breast cancer, on the other. This in turn may prove useful in designing therapeutic strategies and, in particular, administration of antisteroid and antimetabolic drugs for prophylaxis in groups at high risk.

Adult↗

[Study of an antioxidant dietary supplement "Karinat" in patients with benign breast disease].

A randomized double blind placebo-controlled trial of efficiency of a dietary supplement "Karinat" in patients with benign breast disease was carried out. Karinat contains beta-carotene 2.5 mg, alpha-tocopherol 5 mg, ascorbic acid 30 mg and garlic powder 150 mg per one tablet. Out of 66 patients, 33 patients were given karinat, 33 were given placebo. The patients reccived a tablet of karinal or placebo twice a day during 6 months. Examinations of the patients included clinical estimation of symptoms of mastopathy and dysalgomenorrhea, breast sonography and mammography. It was found that karinat reduced the severity of mastalgia, premenstrual syndrome, dysmenorrhea and algomenorrhea and caused regression of palpable symptoms of the breast fibromatosis. On the whole karinat had positive action in 75.8% that was significantly greater by 45.5% as compared with placebo. Karinat may be useful for the treatment of patients with benign breast disease.

Adult↗