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1.
Vopr Onkol ; 59(3): 352-7, 2013.
Article in Russian | MEDLINE | ID: mdl-23909037

ABSTRACT

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.


Subject(s)
Breast Neoplasms/epidemiology , Breast Neoplasms/pathology , DNA Damage , Diabetes Mellitus, Type 2/genetics , Endometrial Neoplasms/epidemiology , Endometrial Neoplasms/pathology , 8-Hydroxy-2'-Deoxyguanosine , Aged , Biomarkers, Tumor/blood , Breast Neoplasms/blood , Breast Neoplasms/genetics , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/blood , Endometrial Neoplasms/blood , Endometrial Neoplasms/genetics , Female , Humans , Incidence , Male , Middle Aged , Postmenopause
2.
Vestn Ross Akad Med Nauk ; (2): 29-34, 2013.
Article in Russian | MEDLINE | ID: mdl-23819326

ABSTRACT

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.


Subject(s)
Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/metabolism , Neoplasms/genetics , Aged , Body Fat Distribution , Body Mass Index , Coffee , Erythrocyte Membrane , Female , Genetic Predisposition to Disease , Humans , Interleukin-6/blood , Lactoylglutathione Lyase/blood , Lipid Metabolism , Middle Aged , Neoplasms/diagnosis , Postmenopause , Testosterone/blood , Waist Circumference
3.
Vopr Onkol ; 58(2): 194-8, 2012.
Article in Russian | MEDLINE | ID: mdl-22774523

ABSTRACT

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.


Subject(s)
Aromatase/metabolism , Breast Neoplasms/enzymology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/pharmacology , Metformin/pharmacology , Aged , Aromatase/biosynthesis , Aromatase/immunology , Breast Neoplasms/complications , Female , Gene Expression Regulation, Enzymologic/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Humans , Hypoglycemic Agents/therapeutic use , Immunohistochemistry , Metformin/therapeutic use , Middle Aged , Receptors, Progesterone/metabolism
4.
Vopr Onkol ; 58(1): 45-9, 2012.
Article in Russian | MEDLINE | ID: mdl-22629827

ABSTRACT

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.


Subject(s)
Acetylcysteine/pharmacology , Breast Neoplasms/pathology , Breast/drug effects , Breast/pathology , Hypoglycemic Agents/pharmacology , Mammography , Metformin/pharmacology , Neoplasms, Hormone-Dependent/pathology , Postmenopause , Aged , Apoptosis/drug effects , Breast Neoplasms/epidemiology , Breast Neoplasms/metabolism , Cell Proliferation/drug effects , DNA Repair/drug effects , Female , Humans , Insulin Resistance , Middle Aged , Neoplasms, Hormone-Dependent/epidemiology , Neoplasms, Hormone-Dependent/metabolism , Risk Assessment , Risk Factors
5.
Vopr Onkol ; 57(6): 737-41, 2011.
Article in Russian | MEDLINE | ID: mdl-22416390

ABSTRACT

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.


Subject(s)
Antineoplastic Agents/therapeutic use , Aromatase Inhibitors/therapeutic use , Endometrial Neoplasms/drug therapy , Glucose/metabolism , Hypoglycemic Agents/therapeutic use , Metformin/therapeutic use , Neoadjuvant Therapy/methods , Adult , Aged , Anastrozole , Androstadienes/administration & dosage , Antineoplastic Agents, Hormonal/therapeutic use , Biomarkers, Tumor/analysis , Endometrial Neoplasms/surgery , Female , Humans , Ki-67 Antigen/analysis , Letrozole , Middle Aged , Neoplasm Grading , Nitriles/administration & dosage , Treatment Outcome , Triazoles/administration & dosage
6.
Vopr Onkol ; 56(6): 664-70, 2010.
Article in Russian | MEDLINE | ID: mdl-21395121

ABSTRACT

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.


Subject(s)
Acetylcysteine/therapeutic use , Estrogens/metabolism , Free Radical Scavengers/therapeutic use , Glucose/metabolism , Hypoglycemic Agents/therapeutic use , Metformin/therapeutic use , Neoplasms/metabolism , Acetylcysteine/administration & dosage , Acetylcysteine/pharmacology , Aged , Blood Glucose/drug effects , Blood Glucose/metabolism , Body Mass Index , Breast Neoplasms/metabolism , Colonic Neoplasms/metabolism , Drug Administration Schedule , Endometrial Neoplasms/metabolism , Female , Free Radical Scavengers/administration & dosage , Free Radical Scavengers/pharmacology , Humans , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/pharmacology , Interleukin-6/blood , Metformin/administration & dosage , Metformin/pharmacology , Middle Aged , Neoplasms/blood , Postmenopause , Treatment Outcome , Tumor Necrosis Factor-alpha/blood
7.
Adv Gerontol ; 21(2): 204-11, 2008.
Article in Russian | MEDLINE | ID: mdl-18942362

ABSTRACT

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.


Subject(s)
Aging/metabolism , Glucose Intolerance/metabolism , Glucose , Adult , Aged , Aging/blood , Aging/genetics , Blood Glucose/metabolism , Comet Assay , DNA Damage , Glucose/metabolism , Glucose/physiology , Glucose Intolerance/blood , Glucose Intolerance/genetics , Glucose Tolerance Test , Humans , Insulin/blood , Leukocytes, Mononuclear/metabolism , Middle Aged , Reactive Oxygen Species/blood , Young Adult
8.
Vopr Onkol ; 54(1): 25-30, 2008.
Article in Russian | MEDLINE | ID: mdl-18416053

ABSTRACT

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.


Subject(s)
Biomarkers, Tumor/blood , Breast Neoplasms/blood , Breast Neoplasms/pathology , Models, Statistical , Risk Assessment/methods , Adult , Age Factors , Aged , Blood Glucose/metabolism , Case-Control Studies , Cholesterol/blood , Estradiol/blood , Female , Humans , Hydrocortisone/blood , Insulin/blood , Lipoproteins, LDL/blood , Lymphatic Metastasis , Menopause , Middle Aged , Neoplasm Staging , Predictive Value of Tests , Premenopause , Prognosis , Risk Factors , Testosterone/blood , Triglycerides/blood
9.
Vopr Onkol ; 50(3): 311-5, 2004.
Article in Russian | MEDLINE | ID: mdl-15318704

ABSTRACT

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.


Subject(s)
Body Weight , Breast Neoplasms/physiopathology , Menstruation , Receptors, Estrogen/metabolism , Adult , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Case-Control Studies , Female , Humans
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