[Influence of metformin and N-acetylcysteine on hormonal and genotoxic effects of estrogens and glucose in convalescent cancer patients].

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.

[Progenotoxic shift in mammary adipose tissue (adipogenotoxicosis): association with clinical and biological characteristics of breast cancer].

The study is concerned with identification of a relationship between levels of production and accumulation of compounds capable of hormonal and progenotoxic effects in mammary fat, on the one hand, and characteristics of tumor tissue in breast cancer, on the other. Mammary fat was sampled at a distance of 1.5-2 cm from tumor edge (79 pts.). Case histories were used to provide data on clinical stage, size, grade and regional lymph node involvement. Levels were assayed of leptin, adiponectin, tumor necrosis factor (TNF-alpha), interleukin-6 (IL-6), nitric oxide (NO), thiobarbiturate-reactive products (TBRP) and DNA oxidative damage marker (8-OH-dG) from 4hr-incubates of fat tissue culture. Mammary fat aromatase was assayed by radiometrical means while macrophage-assisted fat infiltration (CD68) and estrogen-4-hydroxylase (CYP1B1) expression were evaluated immunohistochemically. Radio-competitive and immunohistochemical methods were used to assay estrogen (ER) and progesterone (PR) receptor levels in tumor and tumor-related expression of cytokeratins 5/6 ("basal") and 7/8 ("luminal" epithelium), respectively. As far as hormonal properties of mammary fat were concerned, there were direct correlations between aromatase concentration, on the one hand, and tumor stage and size, on the other, and adiponectin secretion and CK7 expression in tumor. Besides, an inverse correlation was found between mammary fat-mediated release of leptin and adiponectin, on the one hand, and stage and regional lymph node involvement, on the other. The following main relationships were identified by comparison of the clinico-biological characteristics of tumor and markers of proinflammatory/progenotoxic properties of mammary adipose tissue: tendency toward direct correlation with IL-6 and 8-OH-dG in fat (tumor progress stage); direct correlation with TNF-alpha secretion rate (malignancy grade); lymph node involvement--tendency toward direct correlation with NO generation; CK5 expression in tumor--tendency toward direct correlation with 8-OH-dG, TBRP and CD68 fat infiltration; CK7 expression in tumor--tendency toward inverse correlation with NO generation in adipose tissue; ER-negative phenotype of tumor--tendency toward higher generation of TBRP, NO and TNF/leptin in fat. Hence, shift toward predominance of proinflammatory/progenotoxic properties of mammary adipose tissue (adipogenotoxicosis) is associated with signs of less favorable course of tumor process in the mammary gland which calls for working out adequate measures.

[Bcl-2 tumor suppressor as a possible mediator between genotoxic stress and disturbance in hormonal homeostasis]. / Onkosupressor bcl-2 kak vozmozhnyi posrednik mezhdu genotoksicheskim stressom i narusheniem gormonal'nogo gomeostaza.

Overexpression of tumor suppressor gene bcl-2 plays an important role in cellular resistance to apoptosis caused by various factors including glucocorticoids. In this study, the role of bcl-2 in glucocorticoid-mediated negative feedback regulation has been investigated. Transient transfection of bcl-2 into murine corticotrope AtT-20 cells resulted in significant resistance of proopiomelanocortin gene expression and ACTH secretion to down-regulation by dexamethasone. Bcl-2 revealed its activity mostly in the presence of saturating concentrations of dexamethasone (100 nM-1 mM). Overexpression of bcl-1 interfered with the receptor-mediated glucocorticoid activity and appeared to be relatively specific towards expression of proopiomelanocortin/ACTH. The data suggest a novel function of bcl-2 as a factor capable of regulating hormonal homeostasis. Thus, bcl-2 may be involved in hormonal and metabolic response to genotoxic stress, the phenomenon which was earlier defined as carcinogenic aging.

[Multifactorial analysis of the effect of metabolic and endocrine factors on cellular immunity in patients with cancer of the uterine body]. / Mnogofaktornyi analiz vliianiia metabolicheskikh i éndokrinnykh faktorov na kletochnyi immunitet u bol'nykh rakom tela matki.

Multifactorial analysis of effects of metabolic and endocrine determinants of the host and morphology of the tumor on cellular immunity has been undertaken in 29 patients with cancer of the corpus uteri. Several regression models obtained using the Hocking-Leslie method demonstrated significant effects of age, obesity, triglyceride levels, morphologic differentiation of the tumor and magnitude of invasion on various levels of cellular immunity, presenting as an increase in T-helper and decrease in suppressor counts. The multifactorial analysis depicted additive effects of endocrine homeostatic determinants and the tumor on different aspects of cellular immunity in cancer of the corpus uteri.

[Cyclic adenosine monophosphate content in the lymphocytes of cancer patients]. / Soderzhanie tsiklicheskogo adenozinmonofosfata v limfotsitakh onkologicheskikh bol'nykh.

Examinations have been carried out on 83 cancer patients (aged 34-72), 24 patients with atherosclerosis (aged 38-68) and 34 healthy persons (aged 20-69). The cAMP concentration decrease with age in lymphocytes of healthy persons is confirmed. This index in patients with lung carcinoma, breast carcinoma in remission and in patients with atherosclerosis was identical with that of healthy persons, but in patients with breast and corpus uteri carcinomas without metastases it was higher than in healthy persons of the similar age. The amount of cAMP in lymphocytes is compared with the magnitude of the blast transformation and with the amount of cholesterol in blood and lymphocytes in examined persons. The cAMP level in lymphocytes is observed to increase in the process of hyperlipidemia disappearance in cancer patients and in those with atherosclerosis.