PubMed Health⌕ Search

Biomedical subjects

H Braunsberg

Publications and source records attributed to H Braunsberg.

At least 19 recordsLinked to original sources
PubMed1990

Hormone and cytotoxic drug responsiveness of cultured human breast cancer cells resistant to specific hormones.

Attempts have been made to develop sublines of MCF-7 cells resistant to the growth-inhibitory actions of medroxyprogesterone acetate (MPA), dexamethasone (DEX), anti-oestrogens or high-dose oestradiol (E2) by prolonged exposure to high hormone concentrations. While high degrees of resistance to MPA, DEX and E2 were achieved, cells remained anti-oestrogen-sensitive after prolonged treatment with 4 microM tamoxifen (TAM) or the anti-oestrogen LY 117018 (LY). Cells resistant to DEX were also resistant to MPA, while cells resistant to high-dose E2 remained sensitive to TAM. Cells resistant to MPA and E2 appeared to be less responsive to cytotoxic drugs than wild-type cells, while resistance to DEX was associated with increased sensitivity. The responses of tumours to cytotoxic drugs may be affected by prior endocrine therapy.

Breast Neoplasms↗
PubMed1989

Adriamycin action on human breast cancer cells: enhancement by medroxyprogesterone acetate.

Exposure of cultured human breast cancer cells (MCF-7) to medroxyprogesterone acetate (MPA) prior to treatment with adriamycin (ADR) enhanced the effect of the cytotoxic drug on cell yield after further growth of viable cells. Pretreatment with oestradiol (E2) produced similar synergism, but no such effect was observed using dexamethasone. Exposure to ADR before MPA led to an additive effect, but not to synergism. When cells resistant to the growth-inhibitory action of MPA were examined, progestogen/drug synergism could still be demonstrated. We conclude that the effects of ADR, like those of methotrexate and vincristine, can be enhanced by pre-treatment with MPA and that further clinical trials of such a regimen are needed.

Antineoplastic Agents↗
PubMed1989

Actions of medroxyprogesterone acetate on the efficacy of cytotoxic drugs: studies with human breast cancer cells in culture.

Human breast cancer cells (MCF-7) showed increased responses to methotrexate and vincristine after a 48-hr pre-treatment with medroxyprogesterone acetate. The effect of the hormone, which was detectable at concentrations of between 10 and 100 nM, was independent of its growth-inhibitory action. These findings confirm a previous clinical study and have important implications with regard to the management of advanced breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

The effects of sequential treatment with ethynyloestradiol and medroxyprogesterone acetate on oestrogen and progestogen receptors in breast cancer.

As part of a clinical study designed to modulate oestrogen and progestogen receptor (ER and PR) binding site concentrations prior to chemotherapy ER and PR levels have been estimated immediately before treatment, after ethynyloestradiol (EE, 10 micrograms/day, 1 week) and after medroxyprogesterone acetate (MPA, 500 mg/day i.m., 2 weeks) in tumour tissue from 14 women with advanced breast cancer. There was no consistent change after EE treatment. MPA tended to decrease ER and PR levels, though some increases were also seen. Responses (10 complete and 3 partial remissions) to sequential cyclical hormono-chemotherapy were not related to ER or PR levels prior to chemotherapy.

Aged↗
PubMed1988

Paracrine influence of human breast stromal fibroblasts on breast epithelial cells: secretion of a polypeptide which stimulates reductive 17 beta-oestradiol dehydrogenase activity.

We have previously shown that a stroma-associated paracrine influence may occur in the human breast. In particular, human breast fibroblasts secrete a factor which stimulates reductive 17 beta-oestradiol dehydrogenase (HSD) activity, thereby regulating tissue concentrations of 17 beta-oestradiol. We report here the results of experiments designed to establish the nature of the enzyme activity stimulating factor. In vitro cell culture techniques were used, in which human breast fibroblast-conditioned medium was used to grow the human breast cancer cell line, MCF-7, for 6 days, after which the reductive HSD activity of the monolayers was assessed. The fibroblastic reductive HSD stimulating factor was found to be a trypsin-sensitive polypeptide. The polypeptide eluted from a Sephadex G-75 column as a peak corresponding to a molecular weight of about 50 kDa. The polypeptide exerts its effects by altering the Vmax of 2 of the cytosolic forms of HSD within MCF-7 cells. This is achieved by a protein-synthesis-dependent but calmodulin-independent mechanism. These results provide further evidence of a paracrine effect by stromal tissue within the human breast and have important implications with respect to the aetiology and treatment of breast cancer.

17-Hydroxysteroid Dehydrogenases↗
PubMed1988

Effects of human breast fibroblasts on growth and 17 beta-estradiol dehydrogenase activity of MCF-7 cells in culture.

The effect of conditioned medium from human breast fibroblasts on growth and 17 beta-estradiol dehydrogenase (E2DH) activity of the MCF-7 human breast cancer cell line has been investigated. Fibroblasts were derived from normal and tumorous (benign and malignant) breast tissue. Conditioned medium from normal derived fibroblasts inhibited the growth of MCF-7 cells, the effect being statistically significant by day 3 of culture. In contrast, conditioned medium from benign and malignant derived fibroblasts significantly enhanced the growth of MCF-7 cells by day 9 of culture. When added to MCF-7 cells for three days, conditioned medium from all three types of fibroblasts increased E2DH activity in the reductive direction (estrone (E1)----estradiol (E2] 2-3 fold. There was little or no effect on the oxidative direction (E2----E1). After 12 days, enzyme activity in the reductive direction was still markedly increased, the effect being greatest in conditioned medium from fibroblasts derived from malignant breast tissue, and least in conditioned medium from fibroblasts derived from benign breast tumors. These results demonstrate that human breast fibroblasts may have paracrine influences on neighboring epithelial cells in vivo.

17-Hydroxysteroid Dehydrogenases↗
PubMed1988

Relationships between polyamine, deoxyribonucleic acid and oestrogen receptor binding site concentrations in human breast tumours.

Concentrations of polyamines, DNA and oestrogen receptor (ER) binding sites have been estimated in 23 malignant and 2 benign breast tumours. Polyamine and DNA concentrations, expressed per unit wet weight of tissue, were significantly higher in ER-poor (less than 10 fmol/mg cytosol protein) than in ER-rich tumours. Spermidine/spermine ratios were similar in ER-poor and ER-rich tumours. There was a relationship between polyamine and DNA levels and when polyamine concentrations were expressed per unit weight of DNA those in ER-poor tumours did not differ from those in ER-rich tumours. Possible reasons for these findings are discussed.

Breast Neoplasms↗
PubMed1987

Actions of a progestogen on human breast cancer cells: mechanisms of growth stimulation and inhibition.

Medroxyprogesterone acetate (MPA) reduced the proliferation of MCF-7 cells with a maximal response at 100 nM. A subline ('M' cells) resistant to this action remained responsive to antioestrogen but showed a poor response to dexamethasone (DEX). Experiments with mixtures of MPA and DEX showed that MPA acts on wild-type MCF-7 cells through a glucocorticoid as well as a progestogen mechanism. The growth of 'M' cells was stimulated by MPA at 100 nM or greater and the drug increased polyamine concentrations in 'wild-type' as well as 'M' cells. It is suggested that both progestogen and glucocorticoid receptors may mediate the effects of high-dose MPA therapy in breast cancer. The possible stimulation of the growth of some cell types by MPA requires further investigation.

Antineoplastic Agents↗
PubMed1984

Application of high performance liquid chromatography to the analysis of cytoplasmic and nuclear oestrogen receptors.

Soluble and nuclear preparations of fresh human endometrium have been analysed by HPLC on a gel permeation column. With high ionic strength eluants recoveries of receptor binding were less than 40% while low ionic strength eluants gave recoveries of 70% or greater. Non-specific binding by endometrial and plasma proteins was largely lost at both high and low ionic strength. Soluble binding components saturable by diethylstilboestrol (DES) were resolved into two components differing in heat lability and response to variations in ionic strength. Molybdate appears to alter the receptor protein rather than the activity of inactivating enzymes. At low ionic strength nuclear binding components saturable by DES could be resolved into two components.

Cell Nucleus↗
PubMed1975

Urinary total oestrogen values determined by an automated method in normal and abnormal pregnancies.

Urinary total oestrogen values in late pregnancy have been determined by an automated, fluorimetric method based on the Kober reaction and Ittrich extraction. The normal range was obtained from 360 samples from 56 patients. The mean value at 40 weeks gestation was 52.6 mg/24 h and the 95 per cent probability bounds were 29.1 and 95.3 mg/24 h, obtained after initial calculations on logarithm values. "Small for dates" foetuses in good condition at birth were associated with oestrogen values generally below the normal mean. They were usually well discriminated from foetuses that died in the uterus. These were always associated with oestrogen values below or approaching 10 mg/24 h before death except when growth had been normal and death was due to mechanical complications at delivery.

Autoanalysis↗