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Biomedical subjects

W R Miller

Publications and source records attributed to W R Miller.

At least 217 records · Page 12Linked to original sources
PubMed1990

Oestrogen receptor expression and the effects of oestrogen and tamoxifen on the growth of human ovarian carcinoma cell lines.

To assess the role of oestrogen regulation in the growth of ovarian cancer, we examined the effects of an oestrogen, 17 beta-oestradiol, and an anti-oestrogen, tamoxifen, on oestrogen receptor (ER) -positive and -negative human ovarian carcinoma cell lines. As measured by a dextran-coated charcoal adsorption assay, cell lines PEO1, PEO4 and PEO6 possessed moderate concentrations of ER (96-132 fmol mg-1 protein), PEA1 and PEA2 had low values (12-23 fmol mg-1 protein) and PEO14, TO14, PEO23 and PEO16 were ER-negative. Addition of 17 beta-oestradiol (10 nM or 0.1 nM) to the ER +ve cell line, PEO4, increased the growth rate. This oestrogen stimulation could be blocked by 1 microM tamoxifen. In contrast, the growth rate of the ER -ve cell line PEO14 was unaffected by the addition of 17 beta-oestradiol or tamoxifen. Concentrations of tamoxifen in excess of 8 microM were required to produce complete cytostasis in all lines. This concentration of tamoxifen over 72 hours also inhibited 50% colony formation when cells were plated on plastic. These data indicate that some ovarian carcinoma cell lines contain ER and their growth can be sensitive to oestrogen and anti-oestrogen modulation.

Cell Division↗
PubMed1990

Cyclic AMP binding proteins and prognosis in breast cancer.

Cyclic AMP binding proteins were measured in the primary tumour from 100 patients with non-disseminated breast cancer selected on the basis that sufficient tumour material was available for analysis. These measurements have been related to factors of established prognostic value and to the patients' disease-free interval and survival. There was a wide variation in amounts of binding proteins in different tumours. Values were significantly higher (P less than 0.05) in oestrogen receptor-negative tumours but no statistically significant correlations were apparent between levels and tumour grade or whether the patients had lymph node metastasis or adjuvant treatment. However, levels were significantly higher in patients whose disease recurred within 3 years of primary treatment as compared with those who remained disease-free. Using a retrospectively determined cut off point of 8 pmol mg-1 cytosol protein, it was shown that patients with tumour cyclic AMP binding in excess of this value had a significantly greater chance of developing recurrent disease and poorer survival rates (P less than 0.001 by Cox analysis) than those with lower levels. This remained true when other prognostic factors were taken into account in a multivariate analysis. It is suggested that the level of tumour cyclic AMP binding may be an independent prognostic factor for patients with early breast cancer.

Breast Neoplasms↗
PubMed1989

Quantification of epidermal growth factor in human breast cyst fluids: correlation with dehydroepiandrosterone-sulphate and electrolyte concentrations.

Epidermal growth factor (EGF), dehydroepiandrosterone (DHA)-sulphate and [Na+] and [K+] were assayed in 78 cyst fluids from patients with a palpable breast cyst. Epidermal growth factor was detected in all but 2 cysts, the mean value +/- SEM being 506.2 +/- 39.3 ng/ml, with a range of 0-1,599 ng/ml. When the cyst fluids were sub-divided according to their [Na+]:[K+] ratio, group A cyst fluids ( [Na+]:[K+] less than 3) had a significantly higher (p less than 0.001) level of EGF than group B cyst fluids ([Na+]:[K+] greater than 3). Furthermore, the relationship between EGF and [Na+] and [K+] and between EGF and DHA-sulphate seemed to differ between the 2 cyst types and each cyst type was therefore analyzed separately.

Aged↗
PubMed1989

Thrombospondin in malignant and non-malignant breast tissue.

Cytosols of malignant breast tissue contained significantly higher levels of thrombospondin (TSP) and von Willebrand factor (vWF) than non-malignant breast. TSP and vWF content of human breast were significantly correlated whereas there was no correlation between TSP and the platelet-specific protein beta-thromboglobulin (beta TG). Whilst TSP in pre-menopausal breast cancer was slightly lower than in post-menopausal breast cancer, it did not correlate with oestrogen receptors (ER) or progesterone receptors (PR), but was negatively correlated with tissue-type plasminogen activator (tPA), an oestradiol-inducible enzyme. Secretion of TSP by MCF-7 cells was low and refractory to hormones. High levels of TSP appeared to be associated with the centre of the tumour mass. It is suggested that activation of the endothelium may be responsible, at least in part, for the high levels of TSP found in malignant breast tissue and could be a factor in the growth and spread of breast cancer.

Breast↗
PubMed1989

Variations associated with the DNA analysis of multiple fine needle aspirates obtained from breast cancer patients.

The present study was carried out to determine the variation in DNA content between multiple fine needle aspirates (FNA) of the same tumour from patients with breast cancer. Analysis of different aliquots of the same FNA showed good reproducibility in terms of cell cycle distribution and DNA index. Duplicate FNAs taken from different sites in nine of 11 excised tumours showed similar reproducibility. However, two of the aneuploid tumours displayed substantial variations in the distribution of cell populations between the duplicate samples. Sequential FNAs with no intervening therapy were obtained from the same tumour in 17 patients; one at the time of diagnosis and the other at biopsy 1-3 weeks later. Only five cases showed no variation between the sequential FNAs; the remaining 12 displayed different DNA profiles. A further 13 patients were studied before and during systemic therapy. While there was no variation between sequential FNAs in four patients, marked differences in the DNA profile were observed in the remaining nine patients undergoing treatment, the changes not necessarily being associated with clinical response to therapy. It is concluded that the monitoring of cellular changes by DNA analysis of sequential FNAs may be complex and subject to problems associated with heterogenecity.

Biopsy, Needle↗
PubMed1989

Expression of glutathione S-transferase B1, B2, Mu and Pi in breast cancers and their relationship to oestrogen receptor status.

The concentrations of glutathione S-transferase (GST) B1 and B2 (Alpha), Pi and Mu have been measured by radioimmunoassay in cytosols from 28 oestrogen receptor (ER) rich an 30 ER-poor breast tumours. GST B1, B2 and Pi was detected in all 58 breast tumour cytosols whilst GST Mu was found in only 28. Of the GSTs, Pi was expressed most strongly in all cytosols and the concentration was significantly higher in ER-poor tumour cytosols than in ER-rich tumours (P less than 0.01). As with GST Pi, the highest levels of GST B1 and GST B2 were found in ER-poor tumour cytosols; the levels of GST B1 and GST B2 were positively correlated (r = 0.66, P less than 0.001). No quantitative or qualitative association was found between ER status and GST Mu which was expressed in 46% of ER-rich and 50% of ER-poor tumour cytosols. No relationship could be found between GST expression and age, menopausal status, lymph node involvement or tumour T stage in the subgroup of patients in whom this information was available. These data suggest that a common mechanism is responsible for GST induction in ER-poor tumours and that the nulled Mu phenotype has no increased susceptibility to developing breast cancer.

Breast Neoplasms↗
PubMed1989

Oral contraceptive steroids and breast secretions.

Breast secretions were obtained by nipple aspiration from 164 (44.7%) of 368 consecutive premenopausal non-pregnant women volunteers attending family planning clinics. Women currently taking oral contraceptive steroids were significantly less likely to yield breast secretions than women who had never taken such preparations. The effect was confined to parous women of whom 94% not taking oral contraceptives yielded breast secretions compared with only 51% currently using the pill and 60% of those with a previous history of use. The percentage of nulliparous women yielding breast secretions (30%) was significantly less than that in parous women and was not affected by a present or previous history of contraceptive steroid use. These results provide further evidence of the difference in hormone responsiveness of parous and nulliparous breasts and the potential of oral contraceptive steroids to influence breast function.

Breast↗
PubMed1988

Aromatase activity in adipose tissue from breast quadrants: a link with tumour site.

To determine the importance of local oestrogen biosynthesis within the breast, aromatase activity was measured in adipose tissue from the breast quadrants of 12 consecutive mastectomies from patients with breast cancer. Activity was detected in all samples (range 3.6-35.0 fmol oestrogen/mg protein/h) but varied considerably not only among different patients but also among the quadrants of individual breasts. The highest activity in a breast was always found in a quadrant that contained tumour, whereas quadrants with the lowest activity were never associated with the presence of tumour. These results provide evidence of a significant relation between breast adipose tissue and breast cancer. Whether such an association occurs because breast tumours are more likely to develop in areas with enhanced oestrogen biosynthesis or because they secrete into their local environment factors capable of stimulating oestrogen biosynthesis remains to be determined.

Adipose Tissue↗
PubMed1988

Urokinase and tissue-type plasminogen activators are present in breast cyst fluids.

Breast cyst fluids obtained by needle aspiration from 20 patients were analysed for the presence of urokinase-like (u-PA) and tissue-type (t-PA) plasminogen activators. Plasminogen, the natural substrate for these PAs, was also measured. u-PA activity was detected in 18 samples (mean +/- S.D. = 1.11 +/- 1.08 IU ml-1) and t-PA activity in 16 samples (0.35 +/- 0.28 IU ml-1). Plasminogen was detected in 10 samples (mean = 37 micrograms ml-1), range 28-85 micrograms ml-1) and was below the assay detection limit in the other samples. While both u-PA and t-PA specific activities were greater in the 10 cyst fluids categorized as Group A (Na+ to K+ concentration ratio less than 4) than in the 10 samples categorized in Group B (Na+ to K+ concentration ratio greater than 4), the differences were not statistically significant. Nevertheless, this is the first evidence that u-PA and t-PA are present in active forms in breast cyst fluids. The significance of such activities must be hypothetical, but it is possible that a study of factors influencing the levels of u-PA and t-PA within the breast may yield information about pathophysiology of cystic and other diseases of the breast.

Enzyme Precursors↗
PubMed1988

Breast gross cystic disease protein 15 in human breast cancer in culture.

Media from explants of 120 human breast cancers cultured for 24 h were analysed for breast gross cystic disease protein 15 (GCDFP-15). The protein was detected in media from 94 tumours (73%) in concentrations varying from 1.5 to 2100 ng/ml. Levels were not related to menopausal status of the patient, disease stage, tumour oestrogen receptors or the derivation of tumour material. However, concentrations were significantly related to the degree of apocrine differentiation of the tumour and, in a subset of the cancers, capacity to release GCDFP-15 was positively correlated with incidence of progestogen and androgen receptors. There was also a negative quantitative correlation between production of GCDFP-15 and glycoprotein hormone alpha subunit (but no relationship with CEA). In 10 tumours culture was continued for 48 h. Values for GCDFP-15 were always considerably lower in the 24-48 h media compared with those from 0-24 h and cytosols from post-culture explants contained no detectable GCDFP-15. In contrast, CEA levels were often comparable in 0-24 and 24-48 h media and explants after culture frequently contained substantial amounts of CEA. The high proportion of breast carcinomas producing GCDF-15 in relatively large amounts and its rapid release make it an interesting marker by which the in vitro activity of human breast cancers may be monitored.

Apolipoproteins↗
PubMed1987

Prognostic significance of the expression of a ras protein with a molecular weight of 21,000 by human breast cancer.

Expression of the cellular ras Mr 21,000 protein (p21) has been measured in tumors from breast cancer patients who at time of presentation had no evidence of metastatic disease. Western blotting analysis revealed that 37 of 54 (69%) tumors contained p21 levels 2- to 10-fold greater than those of control breast tissues. An excessive increase of p21 (5- to 10-fold over the control value) occurred more frequently in tumors of T3 and T4 stages [15 of 25 (60%)] than in tumors at T2 stage [6 of 29 (21%)], suggesting a correlation between advancement of disease and high p21 levels. p21 levels were positively related to the involvement of axillary lymph nodes at the time of primary treatment. As no correlations were detected between p21 levels and a gross pathological parameter, tumor grade, it is possible that p21 levels may reflect the degree of cellular malignancy. This is supported by data on tumor recurrence; 13 of 16 patients (81%) with tumors expressing low p21 levels were disease free for greater than or equal to 4 years after primary treatment, whereas only 5 of 9 patients (56%) with high p21 tumors remained disease free. These results suggested that a quantitative enhancement of p21 oncogene protein is associated with both the progression and prognosis of breast cancer.

Breast Neoplasms↗
PubMed1987

Prognostic significance of oestrogen and progestogen receptor activities in breast cancer.

The prognostic significance of the tumour activities of 2 steroid receptors, those for oestrogen (ER) and for progestogen (PgR), has been studied in 372 patients with breast cancer, in whom follow-up was available for 2-6 years (median 41 months). Of 252 patients with operable disease, 75.8 per cent had ER-positive tumours and 46.4 per cent had PgR-positive tumours, though a small additional fraction (6.3 per cent) had an equivocal PgR assay result. For the 236 patients with unequivocal receptor status, the relationships between disease-free interval or overall survival and receptor activity and other factors were evaluated by univariate and multivariate analyses. The latter revealed that only tumour size, node status, menstrual status and ER status related significantly to both disease-free interval and survival, though adjuvant therapy also related to disease-free interval, and tumour grade related to survival. It is concluded that measurements of PgR activity do not add to the prognostic significance of ER status.

Breast Neoplasms↗