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Biomedical subjects

L M Bershteĭn

Publications and source records attributed to L M Bershteĭn.

At least 19 recordsLinked to original sources
PubMed2006

[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↗
PubMed2006

[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↗
PubMed2005

[The joker function of glucose in the development of main non-communicable human diseases].

Glucose is one of the basic components of the internal milieu; it fulfills two principal functions: an endocrine one (the ability to induce insulin secretion) and another function, consisting in DNA-damaging associated with forming of reactive oxygen species. The joker glucose function, determined by individual balance between the mentioned functions, can be an important modifier of human pathology and, at the same time, a target for correcting measures implying the combination of insulin-sensitizing and antigenotoxic measures. The "glucose problem" and the "estrogenic problem" show some resemblance; the latter is based on the shifting of estrogen effects in the direction of genotoxicity domination in the course of aging and under the influence of some exogenic/environmental agents. Thus, both problems should be taken into account when discussing mechanisms of appearance of main non-communicable human diseases and the measures for their prevention.

Adult↗
PubMed2005

[Comparison of letrozole and exemestane used in non-adjuvant therapy of endometrial carcinoma].

The clinical and endocrine-related effects of 2-week preoperative treatment of endometrial carcinoma patients with a non-steroid inhibitor of letrozole aromatase (femara 2.5 mg/day, n=10) and a steroid inactivator of the enzyme (exemestane 25 mg/day, n=13) were compared. In the first group, pain relief in the lower part of the belly and/or decreased uterine discharge were reported in two cases, as well as a 31% drop in the mean endometrial M-echo (ultrasound) signal. In the exemestane group, two patients revealed moderate uterine discharge decrease matched by a 15.6% decrease in M-signal intensity; no tumor was detected in another patient on completion of the course. Letrozole effect was relatively greater when such parameters as tumor-tissue aromatase level, estrogen concentration in vaginal smear and blood-cholesterol, FSH and LH levels were taken into consideration. However, exemestane therapy involved a relatively sharper drop in the levels of tumor receptors of progesterone and a significantly higher estrogen/progesterone receptor ratio. Hence, no matter how short treatment duration was, both steroid and non-steroid aromatase inhibitors induced effects predominantly associated with lowering estrogen production in endometrial carcinoma patients. This makes a case for further clinical trials of these drugs to deal with the pathology.

Androstadienes↗
PubMed2004

[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↗
PubMed2003

[Switching off the estrogen effect and approaches to its correction].

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).

Acetylcysteine↗
PubMed2001

[Metabolic effect of tobacco smoke and "switching" the estrogen effect: mechanism of increased genotoxicity].

Earlier studies demonstrated dynamic changes in the hormonal and genotoxic effects of estrogens and a decrease in estradiol concentrations and/or aromatase (estrogen synthetase) activity in the uterine tissue in rats exposed to tobacco smoke (TS) and in endometrial and breast tumor tissues of female smokers. This study was the first to reveal an elevation in the excretion of 2- and 4-hydroxyestrogens in smoking postmenopausal women receiving estrogen-replacement therapy, an increase in estrogen-2-hydroxylase activity in the breast and endometrial tumors of the smokers, and no signs of higher aneuploidy frequency in the cervicovaginal epithelium of mice exposed to TS + estrogens. Thus, it can be concluded that there are different stages of endocrine and genotoxic effects of a TS + estrogen combination which may be related to the specific mechanisms and types of hormonal carcinogenesis. A combination of estrogens and smoking induces such variants of DNA damage, which are mediated mainly through the metabolism of catecholestrogens/free radical formation and not through increased or incorrect (aneuploidy) proliferation.

Adult↗
PubMed2001

[Age, environmental factors, and hormonal carcinogenesis].

In this paper modern concepts of hormonal carcinogenesis are discussed. Distinguishing of the latter into 2 principal types (promotional and genotoxic) is supported. The role of age, aging and effect of environmental factors in the choice of hormonal carcinogenesis type (as well as for the creation of "estrogenic effect switching/overtargeting phenomenon") is underlined. Mentioned phenomenon is manifested by the weakening of endocrine (hormonal) effects of estrogens together with intensification of genotoxic (DNA-damaging) effect of their metabolites. Conclusion is made that both the conditions favoring hormone-dependent tumors development and the direct mechanisms of hormonal carcinogenesis may be considerably modulated on different stages of ontogenesis and by the influence of environmental factors that is to be taken into considerations while choosing methods for oncological diseases prevention.

Aging↗
PubMed2001

[Effect of neoadjuvant therapy with neovir on the level of steroid hormone receptors in endometrial cancer tissue].

The effects of neoadjuvant therapy with neovir, provera and their combinations on endometrial tumor morphology, progesterone (PR) and estradiol (ER) receptor levels were studied in 50 patients, aged 40-78, with primary tumors stage I-III, and without concomitant pathology. A 19-day course of neovir did not alter tumor morphological status but was followed by a significant rise in PR and ER concentrations. After neoadjuvant therapy in combination with provera, which generally lowers cytoplasmic receptor levels, mean values of receptors dropped in PR+ tumors while, in PR- tumors, they increased significantly. Our findings suggest that neovir may be used in clinic to stimulate endometrial tumor sensitivity to specific hormonal therapy, particularly, for hormone-independent neoplasia.

Acridines↗
PubMed2001

[Induction by ethanol of 'phenomenon of switching estrogen effect' and its correction].

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.

Acetylcysteine↗
PubMed2001

[Interrelationship between response to neoadjuvant hormone therapy and hormonal-metabolic status in breast cancer patients].

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.

Aged↗
PubMed2001

[Neoadjuvant use of the aromatase inhibitor letrozole in uterine cancer: endocrine and clinical effects].

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.

Antineoplastic Agents↗
PubMed2001

[Peroxidase activity in human uterine tissue: connection with clinico-morphological features of endometrial cancer].

Peroxidase activity was determined in 98 patients with endometrial cancers. In 34 patients with endometrial cancers, the activity of the enzyme was also detected in the neighbouring unchanged (normal) tissues. It was shown that in tumor tissues the level of peroxidase activity was higher than in normal ones. The peroxidase activity increased both in tumor and normal endometrium when clinical and morphological characteristics of tumor were unfavourable, i.e. at later stages of the disease, deeper invasion to myometrium, lower levels of differentiation of tumors. The peroxidase activity was somewhat higher in post-menopausal women; however, no direct was found between the activity of this enzyme in malignant and normal tissues, on the one hand, and the menstrual status of patients with different clinical and morphological characteristics of endometrial cancer, on the other relationship. The level of peroxidase activity in normal and malignant tissues was more pronounced in advanced and poorly-differentiated tumors. It seems important to use peroxidase activity as a prognostic factor and as a possible marker of endometrial cancer hormone-dependence that needs further investigation.

Endometrial Neoplasms↗
PubMed2000

[Aromatase (estrogen synthetase) gene expression in human leukocytes].

Extragonadal aromatization plays an important role in many physiological and pathological conditions. It has been found that incubation of the peripheral blood mononuclears in the RPMI-1640 medium with 10% fetal calf serum during 48 hrs is able to induce the aromatase gene expression. The latter did not occur in 11 samples of mononuclears of the intra-tissue leukocyte infiltration which finding needs further investigation. The data obtained suggest that the possibility of the aromatase gene induction in leukocytes is associated with the cellular fraction capable of the substrate adhesion.

Adult↗
PubMed2000

[A polymorphism study of the CYP19 gene in endometrial cancer patients].

A strong connection is known to exist between initiation/promotion of endometrial cancer and excess of estrogens. Therefore, participation of certain alleles of genetic polymorphisms in steroid biosynthesis or metabolism may be responsible for predisposition to the disease. The present study, comparing CYP19 (aromatase) gene polymorphism in 85 patients and 110 healthy females, pointed to a more frequent occurrence of relatively longer alleles (A6 and A7) of the CYP19 gene in the former group. Furthermore, precisely those genotypes co-occurred more frequently with elevated blood levels of estradiol and testosterone in postmenopausal patients. Hence, CYP19 gene polymorphism may be regarded as a factor of genetic risk for endometrial carcinoma.

Adult↗
PubMed2000

[Estradiol-2-hydroxylase activity in tumors of the corpus uteri and breast: the effect of smoking].

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.

Adult↗