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Biomedical subjects

M W Ghilchik

Publications and source records attributed to M W Ghilchik.

At least 55 records · Page 3Linked to original sources
PubMed1989

The effect of breast tumour and normal breast tissue cytosols on oestradiol 17 beta-hydroxysteroid dehydrogenase activity.

We have prepared cytosols of normal breast tissue and breast tumour tissue and examined their effect on 17 beta-oestradiol dehydrogenase (E2DH) activity in cultured normal breast fibroblasts and on the MCF-7 breast cancer cell line. Tumour cytosol increased the activity of E2DH in the reductive (E1----E2) direction in both MCF-7 cells and normal breast fibroblasts. E2DH activity in the oxidative (E2----E1) direction did not change. Increasing the amount of tumour cytosol progressively raised E2DH activity in the E1----E2 direction in MCF-7 cells, whereas equivalent amounts of cytosol from normal tissue had no effect. No change was seen in the oxidative direction. These findings suggest that a factor present in breast tumours may influence E2DH activity and consequently, the hormonal environment and growth of tumours.

17-Hydroxysteroid Dehydrogenases↗
PubMed1989

Relationship between epidermal growth factor and dehydroepiandrosterone and its sulphate in breast cyst fluid.

Gross cystic breast disease is a common condition. Women with apocrine breast cysts may be at higher risk of breast cancer than women with cysts which are lined by flattened epithelium. Apocrine cysts have been shown to be associated with higher intracystic levels of dehydroepiandrosterone sulphate and intracystic sodium to potassium ratios of less than 3. In this study we measured the concentrations of epidermal growth factor, dehydroepiandrosterone and its sulphate in breast cyst fluid. The concentrations of all three analytes were significantly higher in cysts with intracystic Na+/K+ ratios of less than 3 than in cysts with electrolyte ratios of greater than or equal to 3 (P less than 0.001). The higher levels of EGF in cysts with low intracystic electrolyte ratios may provide an explanation of why women with apocrine cysts may be at greater risk of breast cancer. Positive correlations were obtained between concentrations of EGF and DHAS and between EGF and DHA, compatible with the view that intracystic EGF levels may be androgen-modulated. A positive correlation was also obtained between DHA and DHAS concentrations which supports the view that DHA in cyst fluid may be derived from the metabolism of DHAS in the breast cyst wall.

Dehydroepiandrosterone↗
PubMed1988

The effects of androgens and cortisol on the in vivo metabolism of oestradiol.

We have examined the effect of co-administration of dehydroepiandrosterone sulphate, 5-androstenediol or cortisol on the metabolic clearance rate of oestradiol (MCR-E2) and conversion of oestradiol to oestrone (CRE2E1). Previous studies have shown that these androgens influence the metabolism of oestradiol in vitro while cortisol alters the distribution of oestradiol in plasma. The MCR-E2 and CRE2E1 were measured after 2.5 and 5 h of [3H]oestradiol infusion with co-infusion of androgen or cortisol starting after 2.5 h of tracer infusion. For one subject who did not receive co-infusion of another steroid no significant change in MCR-E2 or CRE2E1 occurred over the 5-h period. For other subjects, however, the MCR-E2 decreased by 18 +/- 7% (mean +/- SD) while the CRE2E1 increased by 45 +/- 12%. It is possible that these results are due to: changes in the distribution of oestradiol in plasma; differences in the metabolism of oestradiol bound to albumin or SHBG, or an effect of androgens or cortisol on the uptake of [3H]oestradiol by the liver.

Aged↗
PubMed1988

Postirradiation angiosarcoma of the breast--a case report.

Angiosarcoma of the breast is an uncommon neoplasm but coincident angiosarcoma with infiltrating ductal carcinoma is not yet reported. This paper describes a case of angiosarcoma which developed after 4 years of a wide excision and adjuvant radiotherapy for a ductal carcinoma of the breast. Due to latent period of only 4 years radiotherapy cannot be blamed as an aetiological factor in this case but neither is it possible to exclude it as a causative factor.

Aged↗
PubMed1986

A comparison of the in vivo uptake and metabolism of 3H-oestrone and 3H-oestradiol by normal breast and breast tumour tissues in post-menopausal women.

After infusion of 3H-oestradiol or 3H-oestrone into post-menopausal women with breast cancer, there was a significant uptake of both steroids by breast tumour and normal tissue. The proportion of oestrogen present in tumour tissue as 3H-oestradiol after infusion of 3H-oestradiol (89.4 +/- 3.5%, mean +/- SD, n = 4) was significantly higher (p less than 0.001) than in normal breast tissue (72.8 +/- 3.3%) obtained from the same women. Similarly, after infusion of 3H-oestrone, the proportion of oestrogen present as 3H-oestradiol (48.4 +/- 14.4%) was significantly higher than in normal breast tissue (19.1 +/- 6.4%). These results suggest that conversion of oestrone to oestradiol is enhanced in breast tumour tissue with little metabolism of oestradiol. This would account for the higher concentrations of oestradiol reported in breast tumour tissue in the presence of increased oestradiol 17 beta-hydroxysteroid dehydrogenase activity.

Aged↗
PubMed1986

The regulation of the biologically available fractions of oestradiol and testosterone in plasma.

The albumin bound fractions of oestradiol and testosterone have been measured in samples of plasma obtained over a 24 h period from women with breast cancer or polycystic ovarian disease and from pre- and postmenopausal control subjects and related to plasma levels of free fatty acids. For most subjects changes in the fraction of oestradiol bound to albumin were related to changes in plasma levels of free fatty acids. A significant decrease in the albumin bound testosterone fraction during the night was associated with increased plasma levels of cortisol.

Biological Availability↗
PubMed1986

Metabolism of [3H]oestradiol in vivo by normal breast and tumour tissue in postmenopausal women.

Tumour and normal breast tissue was obtained from postmenopausal breast cancer patients following [3H]oestradiol infusion (50 mu Ci over a 12 h period). The fraction of radioactivity present as oestradiol or oestrone was measured and the results expressed both as the ratio of oestradiol-oestrone and as the percentage oestrogen present as oestrone, and the findings compared with in vitro measurements of 17 beta-hydroxysteroid dehydrogenase activity. Concentrations of 5-androstene-3 beta, 17 beta-diol, dehydroepiandrosterone and its sulphate and testosterone were measured and related to oestradiol metabolism. The study demonstrated that tumour tissue is less able to metabolise oestradiol to oestrone than is normal breast tissue and indicated that the ability of the tissue to detoxify oestradiol may be dependent on cofactor availability. The results also supported the possibility that increased tissue concentrations of adrenal androgens inhibit oestradiol and thus increase tissue exposure to oestradiol.

Aged↗
PubMed1986

Estrogen production and metabolism in normal postmenopausal women and postmenopausal women with breast or endometrial cancer.

The metabolic clearance rates of estradiol in postmenopausal women with breast cancer (1269 +/- 370 1/24 hr, mean +/- S.D.) or endometrial cancer (1320 +/- 238 1/24 hr) were significantly higher than in normal postmenopausal women (922 +/- 238 1/24 hr). The metabolic clearance rates of estrone were elevated in women with endometrial cancer (2012 +/- 749 1/24 hr) or with conditions associated with an increased risk for breast or endometrial cancer (1830 +/- 413 1/24 hr) compared with values for normal postmenopausal women (1321 +/- 301 1/24 hr). The production rate of estradiol was only increased in women with breast cancer. Significant correlations were found between subjects' percentage of ideal body wt and the metabolic clearance rates of estrone and estradiol and also the production rate of estrone. The increased clearance rates may reflect differences in either the binding of estrogens to plasma proteins or the tissue metabolism of estrogens in cancer patients.

Aged↗
PubMed1986

The effect of epidermal growth factor, transforming growth factor and breast tumour homogenates on the activity of oestradiol 17 beta hydroxysteroid dehydrogenase in cultured adipose tissue.

The effect of epidermal growth factor (EGF), transforming growth factor (TGF alpha) and breast tumour homogenates on oestradiol 17 beta hydroxysteroid dehydrogenase (E2DH) activity has been examined using cultured human breast adipose tissue. EGF (100-1000 ng/ml) inhibited E2DH activity (E1----E2) in a dose dependent manner. TGF alpha (250 and 500 ng/ml) stimulated E2DH activity, with conversion of E1----E2 increasing to a greater degree than E2----E1 activity. Breast tumour homogenates (2-10% w/v) also influenced E2DH activity. It is concluded that growth factors, produced by breast tumours, may modulate E2DH activity in tissues surrounding the tumour and thereby influence tumour growth.

17-Hydroxysteroid Dehydrogenases↗
PubMed1985

The relationship between 17 beta hydroxysteroid dehydrogenase and breast tumour site and size.

The activity of 17 beta hydroxysteroid dehydrogenase (170HSD) was measured in adipose tissue adjacent to benign or malignant breast tumours. 170HSD activity was significantly correlated with tumour size in malignant tumours (r = 0.75) but not with benign tumours (r = 0.28). Enzyme activity was reduced in adipose tissue adjacent to tumours obtained from inferior breast quadrants.

17-Hydroxysteroid Dehydrogenases↗
PubMed1985

The distribution of oestradiol in plasma from postmenopausal women with or without breast cancer: relationships with metabolic clearance rates of oestradiol.

The distribution of oestradiol in plasma from postmenopausal women with or without breast cancer has been measured and related to the metabolic clearance rates of oestradiol (MCR-E2). All measurements were carried out preoperatively. No difference in the free fraction of oestradiol was found between women with breast cancer (1.8 +/- 0.4%, mean +/- SD) and normal women (1.6 +/- 0.3%). Approximately 40% of oestradiol in plasma was bound to albumin with 60% bound to sex hormone binding globulin (SHBG), but values were similar for women with or without breast cancer. Concentrations of total unconjugated oestradiol and free oestradiol (2.4 +/- 0.5 ng/100 ml and 44 +/- 12 pg/100 ml respectively, mean +/- SD, n = 9) were significantly higher in plasma from postmenopausal women with breast cancer compared with levels in plasma from normal postmenopausal women (1.8 +/- 0.5 ng/100 ml and 27 +/- 10 pg/100 ml, n = 8). A significant correlation was found between the free oestradiol fraction and MCR-E2 (r = 0.53, p less than 0.05). Correlations were also found between the fractions of oestradiol bound to albumin and MCR-E2 (r = 0.45). From correlations between the binding capacity of SHBG and MCR-E2 it appears that, for a given level of SHBG, MCR-E2 may be higher in women with breast cancer.

Body Weight↗
PubMed1985

Conversion of estrone to estradiol and estradiol to estrone in postmenopausal women.

The conversion of estrone to estradiol and metabolism of estradiol to estrone have been measured in postmenopausal women to examine factors that influence these conversions. Transfer constants for the conversion of estrone to estradiol and estradiol to estrone were not significantly correlated with age (r = -.01 and r = .1, respectively) or subjects' percentage of ideal body weight (r = -.25 and r = -.22, respectively). There was a significant negative correlation between the transfer constants for the conversion of estradiol to estrone and plasma levels of dehydroepiandrosterone sulphate (r = -.45, P less than .05) but not plasma levels of progesterone. Transfer constants for the conversion of estrone to estradiol and metabolism of estradiol to estrone in women with breast or endometrial disease were similar to values in normal women, but metabolism of estradiol to estrone was elevated in two women with primary biliary cirrhosis.

Aged↗
PubMed1984

17 Beta-hydroxysteroid dehydrogenase and aromatase activity in breast fat from women with benign and malignant breast tumours.

The activity of 17 beta-hydroxysteroid dehydrogenase and aromatase was studied in adipose tissue taken from women aged between 22 and 83 years with benign or malignant breast lesions. The benign and malignant groups showed no significant differences in the mean activities of either of the enzymes studied. Under the experimental conditions used, the rate of conversion of oestrone to oestradiol varied markedly between subjects (6-169 ng oestradiol/mg protein/h), and there was a positive correlation between oestrone reduction and the total body weight of the tissue donor. In contrast, although the apparent Km for oestradiol (0.1-2.6 mumol/l) was lower than that for oestrone (9-14 mumol/l) the maximum velocity for oestrone production was very low (10-50 pmol/mg protein/h), and there was no obvious correlation with the age or body weight of the tissue donor. Aromatase activity in breast fat was at the lower end of the normal range of activity previously reported for abdominal adipose tissue, and there was no correlation between oestrone production and age or body weight.

17-Hydroxysteroid Dehydrogenases↗
PubMed1971

Abnormal insulin response in patients with small-vessel disease.

The insulin response to a glucose load has been investigated in twenty-five patients with small-vessel disease (ischaemic lesions of toes or feet in the presence of foot pulses). The clinical presentation was similar to that of juvenile diabetic microangiopathy, but in small-vessel disease there was no glucose intolerance. Unexpectedly in the patients with small-vessel disease there was no striking insulin secretion response to the stimulus of a glucose load. Controls increased their circulating insulin levels on average sixfold over fasting levels after 50 g. oral glucose: all the small-vessel-disease patients had increases of less than three times their fasting levels, and nine of them had completely flat curves throughout the test. Tolbutamide also did not stimulate insulin secretion. The refractory state of these patients' responses to the normal stimulus of insulin output has similarities to the picture in juvenile diabetes mellitus and may be important in the aetiology of the small-vessel lesions.

Diabetic Angiopathies↗