Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aromatase inhibition is an established endocrine treatment modality in postmenopausal breast cancer and is currently considered as an interesting experimental treatment approach in other malignant conditions such as endometrial carcinomas and prostatic cancer. While the 'classic' aromatase inhibitor aminoglutethimide causes many adverse effects that makes it unfit for use in elderly patients, several novel aromatase inhibitors with minimal adverse effects are currently being investigated. These drugs may provide important new tools in the endocrine treatment of malignant diseases in aging patients.
 ...
PMID:Aromatase inhibitors in malignant diseases of aging. 149 56

Endocrine therapy is important in the treatment of advanced breast cancer. The prototype antiestrogen tamoxifen and the prototype aromatase inhibitor aminoglutethimide have been in clinical use for more than 2 decades, as have synthetic progestin derivatives. Currently, several novel antiestrogens and aromatase inhibitors are used to treat breast cancer. This paper reviews the present knowledge of the clinical pharmacokinetics of these drugs. Drug monitoring in plasma and other body fluids has been improved over recent years by the introduction of sensitive and specific high performance liquid chromatography and gas chromatography-mass spectrometry methods. However, we still lack information on such basic pharmacokinetic parameters as the bioavailability of several of these drugs. It is important to study not only plasma but also tissue drug concentrations.
 ...
PMID:Clinical pharmacokinetics of endocrine agents used in advanced breast cancer. 150 41

Patients (186) with locally advanced or metastatic breast cancer were treated with the aromatase inhibitor 4-hydroxyandrostenedione given parenterally at 3 different doses. 21% of patients responded to treatment, 93% of objective responders whose oestrogen receptor (ER) status was known had ER positive tumours. The drug was well-tolerated particularly at a dose of 250 mg i.m. every fortnight. At this dose, only 4/96 (4%) patients had to discontinue treatment. We conclude that 4-hydroxyandrostenedione is a well-tolerated form of endocrine treatment for postmenopausal patients with breast cancer.
 ...
PMID:4-Hydroxyandrostenedione treatment for postmenopausal patients with breast cancer. 152 56

The effectiveness in reducing oestrogen exposure, of an aromatase inhibitor, and a sulphatase inhibitor, as measured by in vivo studies in breast cancer patients, has been investigated. 4-Hydroxyandrostenedione (4HA) was shown to diminish plasma oestrogen levels, to inhibit peripheral and local aromatization and to cause a concomitant decrease in the activity of DNA-polymerase-alpha, measured as an indicator of cellular proliferation. The source of oestrone sulphate in breast tissues was examined, and it was shown that the tissue content of this conjugate derived from circulating oestrone, but no evidence could be found for the direct accumulation of conjugate from the plasma. Administration of Danazol was found to cause a fall in plasma oestrone levels, and to diminish the conversion ratio of oestrone sulphate to oestrone in some patients. It also inhibited tissue sulphatase activity. Although it is concluded that this drug is only a weak sulphatase inhibitor, these observations indicate the potential value of developing more efficient sulphatase inhibitors. Enzyme inhibition is now a proven effective treatment for breast cancer and the development of more efficient inhibitors is an important objective.
 ...
PMID:Inhibition of oestrogen synthesis in postmenopausal women with breast cancer. 152 57

Plasma insulin-like growth factor-I (IGF-I) was measured in breast cancer patients before and during treatment with tamoxifen, goserelin or aminoglutethimide. 24 out of 27 postmenopausal women treated with tamoxifen 20 or 30 mg daily experienced a decrease in plasma IGF-I levels (mean levels before treatment 14.8 nM, during treatment 10.2 nM, P less than 0.001). In 8 out of 12 premenopausal breast cancer patients there was a reduction in plasma IGF-I during treatment with goserelin (mean levels before treatment 23.3 nM, during treatment 19.4 nM, P = 0.052). Contrary, 15 out of 17 postmenopausal women treated with the aromatase inhibitor aminoglutethimide had an increase in plasma IGF-I level (mean level before treatment 17.0 nM, during treatment 21.1 nM, P less than 0.01). These preliminary results indicate that different forms of endocrine treatment of breast cancer may influence plasma IGF-I levels in different directions.
 ...
PMID:Influence of tamoxifen, aminoglutethimide and goserelin on human plasma IGF-I levels in breast cancer patients. 153 4

Currently there is much interest in the role that growth factors may play in the development of human breast tumours. We have shown previously that growth factors secreted by breast tumours may influence the activity of oestradiol hydroxysteroid dehydrogenase, the enzyme which catalyses the interconversion of oestrone (E1) and oestradiol. As the formation of E1 from its sulphate (E1S) by oestrone sulphatase may be quantitatively more important than production from androstenedione via aromatase, we have studied the effect of insulin-like growth factor-1 (IGF-I) and basic fibroblast growth factor (bFGF) on oestrone sulphatase activity in the hormone-dependent MCF-7 and the hormone-independent MDA-MB-231 breast cancer cell lines. In both these cell types, bFGF (1-200 ng/ml) and IGF-I (25-200 ng/ml) significantly stimulated oestrone sulphatase activity in a dose-dependent manner (by 8-60%) after 48 h. Additionally, cycloheximide significantly inhibited (by 90-120%) this stimulation of oestrone sulphatase activity by the two growth factors in both MCF-7 and MDA-MB-231 cells. Basal oestrone sulphatase activity was higher in the oestrogen receptor, ER-ve MDA-MB-231 cells than in the ER + ve MCF-7 breast cancer cells. We conclude that these growth factors, believed to be secreted by breast tumours, may induce enzymes of oestrogen synthesis and hence increase local production of oestrogens.
 ...
PMID:Modulation of oestrone sulphatase activity in breast cancer cell lines by growth factors. 156 28

Peripheral aromatase activity was measured in 24 postmenopausal women suffering from advanced breast cancer. The % conversion of androstenedione to oestrone was then assessed for a significant correlation with age, weight, height, Quetelets index (weight/height2, Q.I.) and length of menopause. Serum oestradiol (E2) levels were measured in 22 of the subjects and compared with the same indices. There was no correlation between E2 or aromatase activity with the length of menopause (P = 0.3 and P = 0.5, respectively). In our data aromatase activity did not correlate with age (P greater than 0.5, n = 22). Serum E2 levels (P = 0.07, n = 20) expressed a negative correlation (i.e. decreased) with age. There was also a poor correlation between aromatase activity and weight of Quetelets index (P = 0.3, n = 20 for both). Serum E2 levels showed a statistically significant correlation with weight (P = 0.01, n = 21), but the relationship with Quetelets index just failed to attain statistical significance (P = 0.07, n = 20). In both cases the regression line was positive. When aromatase activity was correlated with serum E2 levels the regression line was positive but not statistically significant (P = 0.4, n = 22). The data indicate that aromatase activity is only one factor determining the differences in serum E2 levels between postmenopausal women.
 ...
PMID:Aromatase activity, serum oestradiol and their correlation with demographic indices. 156 52

Gross cystic breast disease is a common benign disease which may be associated with an increased risk for breast cancer. Breast cyst fluid (BCF) contains many steroids, peptide growth factors and proteins. We have now identified interleukin-1 (IL-1) and IL-6 in BCF by specific radioimmunoassays. Concentrations of IL-1 were similar in BCF with low or high Na+/K+ ratios (ratio less than 3 vs greater than 3; 357 +/- 72 pg/ml vs 308 +/- 126 pg/ml). In contrast, IL-6 concentrations were significantly higher (P less than 0.01) in BCF with a Na+/K+ ratio greater than 3 (2.75 +/- 2.34 ng/ml) compared with BCF with a low electrolyte ratio (0.21 +/- 0.09 ng/ml). BCF (10%, v/v) stimulated aromatase activity when added to dexamethasone stimulated breast tumour-derived fibroblasts and there was a significant correlation between the stimulation of aromatase activity and BCF Na+/K+ ratio (r = 0.95, P less than 0.001). A significant correlation was also found between stimulation of aromatase activity and concentration of IL-6 in BCF (r = 0.80, P less than 0.01) but not IL-1 concentration (r = -0.39, not significant). Addition of IL-1 or IL-6 (50 ng/ml) to fibroblasts stimulated aromatase activity but was associated with a small (20%) decrease in cell growth. It is concluded that IL-6 may have an important role in regulating aromatase activity in breast cancer cells.
 ...
PMID:Interleukin-1 and interleukin-6 in breast cyst fluid: their role in regulating aromatase activity in breast cancer cells. 156 16

Of the total number of breast cancers approx. 30-50% are hormone-dependent and estradiol is one of the main factors of cancerization. Consequently, the control of this hormone inside the cancer cell is of capital importance because it is well established that the inhibition of estradiol biosynthesis can have a positive effect on the evolution of the disease. The blockage of estradiol can be obtained by the action of anti-aromatases, anti-sulfatases, the control of the 17 beta-hydroxysteroid dehydrogenase activity or by the stimulation of the sulfotransferase which converted the estrogens in their sulfates. In breast cancer tissue estrone sulfate is quantitatively the most important source of estradiol. In the intact cell, estrone sulfatase activity is very intense in the hormone-dependent cell lines (e.g. MCF-7, T-47D) but very small activity is observed in the hormone-independent (e.g. MDA-MB-231, MDA-MB-436) cell lines. However, this activity became very strong after homogenization in the hormone-independent cells, suggesting the presence of repressive factor(s) for this enzyme or its sequestering in an inactive form, in the intact cells of these cell lines. In a series of previous studies it was found that in hormone-dependent cell lines different anti-estrogens: tamoxifen and derivatives, ICI 164,384, very significantly decrease the estradiol concentration originated from estrone sulfate, and recently it was observed that Decapeptyl (D-Trp6-gonadotropin-releasing hormone) in the presence of heparin can also decrease the conversion of estrone sulfate into estradiol. No significant effect was obtained in the presence of heparin or Decapeptyl alone. The estrone sulfatase activity can be inhibited by progesterone, the progestagen R-5020, and testosterone. In another series of recent studies the presence of very strong estrogen sulfotransferase activity has been shown in one breast cancer cell line, the MDA-MB-468. We can conclude that: (1) the control of estradiol concentration can be carried out in the breast cancer tissue itself; (2) estrone sulfate can play an important role in the bioavailability of estradiol in the breast cancer cell; and (3) as is the case for the aromatase, the control of: the estrogen sulfatase, estrogen sulfotransferase, and 17 beta-hydroxysteroid dehydrogenase can be new targets for therapeutic applications in breast cancer.
 ...
PMID:Recent data on estrogen sulfatases and sulfotransferases activities in human breast cancer. 158 Sep 21

43 postmenopausal breast cancer patients were treated orally with the aromatase inhibitor formestane (4-hydroxyandrostenedione) at daily doses of 62.5, 125, 250 or 500 mg for 4 weeks followed by 250 mg daily for a further 4 weeks. For some patients, 62.5 mg did not suppress serum oestradiol levels maximally. The doses of 250 and 500 mg did not differ in their effectiveness. Oestrone levels were suppressed by all doses of formestane but no consistent changes of aldosterone, cortisol or 17-hydroxyprogesterone occurred. Serum levels of sex hormone binding globulin fell by about 15% during treatment with 250 mg formestane reflecting its minor androgenic activity. The maximum concentration and area under the curve of serum formestane levels after the first dose varied in an approximately linear manner with dose. It is concluded that formestane is an effective, specific suppressant of oestradiol levels via the oral route requiring no more than 250 mg to be given daily.
 ...
PMID:An endocrine and pharmacokinetic study of four oral doses of formestane in postmenopausal breast cancer patients. 159 Oct 54


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>