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Biomedical subjects

A A Larionov

Publications and source records attributed to A A Larionov.

At least 19 recordsLinked to original sources
PubMed2003

Aromatase in skeletal muscle.

Aromatase gene expression and activity have been studied in human skeletal muscle. Using two separate rounds of RT-nested PCR, transcripts from the coding region of aromatase mRNA were detected in 32 of 34 samples. In terms of the non-coding exon I, PCR product for I.4 was detected in 13 cases (38%), I.3 in 10 cases (29%), P.II in 6 cases (18%) and I.1 was not detected in any case. No transcripts for any studied variants of exon I were detected in 18 samples (53%). Aromatase activity was assessed using two different methodologies: in 19 cases by definitive product isolation (DPI) and in 42 cases by tritium-release assay (TRA). Using both methods detectable activity was present in 52% of cases. Average values for the cases with detectable activity were 2.2 fmol/mg protein/h for DPI and 6.5 fmol/mg protein/h for TRA. In the cohort studied by TRA, a positive correlation of aromatase activity with age of the donor was observed (r=0.34, P=0.03). In six cases paired comparison of aromatase activity in muscle and associated fat tissue were performed by DPI. When expressed per milligram of protein the activity was always higher in fat. However, this difference disappeared when activity was based on the gram of wet tissue. Taking into account bulk in the body it is concluded that muscle can be an important source of estrogens in men and post-menopausal women and its contribution to the circulating pool of estrogens may be comparable to that of adipose tissue. The nature of mRNA transcripts in muscle suggests that estrogen formation may be controlled by glucocorticoid- as well as cAMP-dependent promoters of the aromatase gene.

Adipose Tissue↗
PubMed2003

[Esophagoplasty with the colon in flap patients with burn strictures of the esophagus].

Results of coloesophagoplasty in 366 patients with long burn strictures of the esophagus are presented. The lesion was total in 74 (21.2%) of them. Inefficacy of bougieurage was indication for plastic surgery in 133 (36.3%) patients, complete obliteration of esophagus--in 53 (14.5%). Left half of the colon was used in 296 (80.9%) cases, transverse colon--in 48 (13.1%), right half of the colon--in 22 (6.0%) cases. Retrosternal shunting esophagoplasty was performed in 247 (67.5%) patients. Complications were in 84 (34.0%), necrosis of the transplant--in 4 (1.6%) patients. Extirpation of the esophagus with posteriormediastinoplasty was performed in 16 (4.4%) patients, in 14 of them--transhiatally. Complications occurred in 7 patients coloesophagopharyngoplasty was carried out in 52 (14.2%) patients with combined stricture of the esophagus and the pharynx, in 23 of them--simultaneously. Complications were in 28 (53.8%) patients. Intrapleural of coloesophagoplasty was performed in 51 patients. General hospital lethality was 3.3%. Long-term results were studied in 259 patients. Good results of esophagoplasty were seen in 135 (52.1%) patients, satisfactory--in 65 (25.1%), unsatisfactory--in 59 (22.8%) patients. Dysfunction of the artificial esophagus was seen in 22.0% patients, 12.7% patients underwent repeated reconstructive surgeries.

Adolescent↗
PubMed2002

Aromatase (CYP19) expression in tumor-infiltrating lymphocytes and blood mononuclears.

PURPOSE: To clarify the role of lymphocytes as a possible source of estrogens. METHODS: In the present study, lymphocytes were isolated from 11 surgical samples of breast cancer after tumor enzyme digestion and Ficoll/Verographine procedure. Simultaneously, using the latter procedure, mononuclears were separated from the blood of 15 female volunteers. RESULTS: Expression of the aromatase (CYP19) gene was readily demonstrated by standard RT-PCR in blood mononuclears cultivated in the presence of 10% fetal calf serum for 48 h. In the tumor-infiltrating lymphocytes (TIL) of breast cancer patients, CYP19 expression was discovered only with the aid of nested PCR. CONCLUSIONS: The data obtained suggest that aromatase gene expression is presented in TIL at a rather low level. Nevertheless, this can have some functional significance for the estrogen-dependent growth of breast cancer tissue.

Adult↗
PubMed2002

Local uptake and synthesis of oestrone in normal and malignant postmenopausal breast tissues.

Uptake and local formation of oestrone (E1) were studied in vivo by a double isotopic technique in normal and malignant breast tissues from 24 postmenopausal women with breast cancer. Active uptake of radio-labelled E1 beyond plasma was found both in normal and malignant tissue, the effect being significantly greater in non-malignant compared with cancer tissue. The presence of local E1 formation was also demonstrated in most samples. Both uptake and synthesis positively correlated with total amount of radioactive E1 found in the tissues. Uptake appeared to make a greater contribution to E1 levels within the breast than in situ synthesis, although there were marked variations between specimens from different patients and the relative proportion of synthesis to uptake was higher in tumour compared with non-malignant tissue. These results demonstrate quantitative differences in the different compartments by which postmenopausal breasts obtain oestrogen and highlight variations between individual breasts. This may be important in optimising oestrogen deprivation therapy for postmenopausal patients with hormone-dependent cancers.

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↗
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↗
PubMed1999

[Aromatase gene expression and its modifying factors in breast tumor tissue].

Aromatase (CYP 19) gene expression was studied in 70 breast tumors. When RNA-dot-blot or rt-polymerase chain reaction were used expression frequency was 60.4 and 91.7%, respectively. An analysis of individual variants of non-coding exon of aromatase gene confirmed that, unlike normal mammary tissue, tumor switched from activation of exon I.4 ("sensitive" to glucocorticoids) to exons II ("sensitive" to cAMP) or I.3. This difference was relatively somewhat more pronounced in the Russian material. Direct correlation between aromatase enzymatic activity and expression of exons II and I.3 in tumor tissue appeared more significant than that of aromatase gene coding site. An evaluation of the expression of adenylate cyclase G-protein alpha-subunit genes established an inverse correlation between expression of Gi2a and exon I.3. Breast tumors with elevated basal aromatase activity were more sensitive to aromatase inhibitors (letrozole, 4-OHA) in vitro although no relationship between use of CYP19 (aromatase) 5' exon variant and in vitro inhibition of aromatase was detected. A correlation was observed between expression of aromatase gene and variants of its 5' exon, on the one hand, and age, tumor grade, steroid receptor presence and tumor lymphocytic infiltration, on the other. To summarize, local estrogen production in breast tumor tissue is regulated by a wide range of factors expression both aromatase gene influencing and its enzymatic activity, thus providing leverage on both.

Adult↗
PubMed1998

Ability of lymphocytes infiltrating breast-cancer tissue to convert androstenedione.

Lymphocytes were isolated from 43 surgical samples of breast cancer after tumor enzyme digestion and Ficoll/Verographine procedure. In all, 23 specimens from lymphocytic-tissue infiltrates were analyzed (in some cases, material from 2 or 3 patients was combined). The ability of tumor-infiltrating lymphocytes (TIL) to convert androstenedione was demonstrated, as evaluated by hard-water release from the androgenic precursor 3H-1beta-androstenedione. In material obtained from menopausal women this ability was higher than in the women of reproductive age. A positive correlation was revealed between the level of androstenedione conversion in TIL and aromatase activity in tumor tissue, while no correlation was shown between androstenedione conversion in TIL and percentage of tumor cells in lymphocytic suspension. The data obtained suggest that factors secreted by a neoplasm are able to induce aromatase gene expression in TIL.

Androstenedione↗
PubMed1998

[Aromatase activity and its gene expression in tumor tissue of smokers and non-smokers with breast cancer].

Tissue was sampled from 121 tumors of the breast. The activity of aromatase (estrogen synthetase) was assessed by radiobiochemical means in 61 cases; gene expression was evaluated with the aid of polymerase chain reaction in 14 and the same--by the dot-blot procedure in 46 patients. Inveterate smokers (15 years and more) made up 16.5%. The smokers revealed a distinct tendency towards aromatase activity decreasing in tumor tissue (chiefly in menopausal patients) as well as lower intensity of aromatase gene expression assessed in terms of polymerase chain reaction. Alongside with other evidence, our finding point to long-term-smoking-related sensitivity of intratissular estrogen synthesis being higher than in general circulation. It also demonstrated local aromatization inhibition in tumor tissue, the latter being a possible mechanism which causes tumor tissue hormone sensitivity to change in smokers and affects course of disease.

Adult↗
PubMed1998

[Metabolism of the androgenic precursor androstenedione and effects of aromatase inhibitors in cultured blood lymphocytes].

Blood lymphocytes from 26 women were cultivated in RPMI-1640 for 72 hrs with or without dexamethasone, dbcAMP, and TPA. Androstenedione conversion was most often activated by the dbcAMP, then by Dex and TPA. Response to dbcAMP was most obvious in women under 50, whereas response to Dex--in women over 50. Aromatase inhibitor fadrosol displayed a tendency towards prevention of the activation of androstenedione conversion in cultivated lymphocytes. A possibility of aromatase gene induction in cultivated lymphocytes cannot be completely excluded and demands further investigation with the aid of molecular-genetic methods.

Adolescent↗
PubMed1998

[Correlation between tumor tissue aromatase, histological pattern and reproductive status in patients with breast cancer].

Aromatase levels were measured in tumor tissue vis-a-vis clinico-morphological patterns of tumor, menopausal status and sex hormone concentration in blood in 50 patients with breast tumors. The test was based on heavy water release from 1 beta-3H-androstenedione. Direct correlation was established between aromatase concentration, on the one hand, and tumor size, cell differentiation status and blood-testosterone on the other. The data point to the role of aromatase concentration in situ during breast tumor genesis, its dependence on hormonal environment of tumor and its presence in breast tumor cells.

Adult↗
PubMed1998

[Distraction osteosynthesis in occlusive diseases of the limb arteries].

The method of distraction osteosynthesis was used in 265 patients with arterial occlusions of the upper and lower limbs, which developed due to obliterative thromboangiitis and atherosclerosis. Surgical treatment of patients with distal type of occlusive disease of the arteries was followed by steady compensation of ischemic disturbances after bone chip formation and its dosage across transfer with formation of distraction regenerate transforming into mature osseous tissue. Favourable results of the treatment were observed in 236 patients (88.9%). They persisted during 3 years in 86% of patients. Analysis of outcomes after treatment demonstrated the best results in patients with grade II ischemia. Distraction osteosynthesis ensured protracted remission of the disease and elimination of its symptoms.

Adult↗
PubMed1996

Aromatase in breast cancer tissue--localization and relationship with reproductive status of patients.

The precise place of local estrogen production in mammary cancer is still controversial. In this investigation localization of aromatase (the key enzyme of estrogen biosynthesis) was studied in breast cancer tissue by immunohistochemical method using polyclonal rabbit antibodies. The cytoplasmic staining was found in different cell types, but the most intensive specific staining was found in malignant cells and it was stronger (P < 0.01) in postmenopausal patients than in patients of reproductive age.

Animals↗
PubMed1996

[Correlation of lymphocytic infiltration of tumor tissue with the hormonal and metabolic state in patients with breast cancer].

Lymphocyte infiltration of tumor was studied vis-a-vis hormone metabolic status, tumor tissue hormone sensitivity and tobacco smoking, in 113 breast cancer patients, aged 25-77. On the average, no correlation was established between degree of lymphocyte infiltration in breast tumor and age and menopause onset. In smoking menopausal patients, lymphocyte infiltration was found to be higher than in non-smokers (p < 0.05). There was a direct correlation between the rate of lymphocyte infiltration and the level of progesterone receptors in tumor. Some subgroups displayed a direct correlation between infiltration and sex-binding globulin, cholesterol, luteinizing hormone in blood, and lean body mass. It was matched by an inverse correlation between lymphocyte infiltration and blood-thyroid hormone concentration, urine catecholamines and free cortisol excretion and fat/lean body mass ratio. Considering the abovesaid as well as the lymphocyte ability to perform the dual function of immunocytes and hormonocytes, it is suggested that the results may be used in both the study of lymphocyte infiltration and research in means of its control.

Adult↗