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Biomedical subjects

B G Mobbs

Publications and source records attributed to B G Mobbs.

At least 37 records · Page 2Linked to original sources
PubMed1986

Role and mechanism of action of tamoxifen in premenopausal women with metastatic breast carcinoma.

Tamoxifen was evaluated as initial hormone therapy for metastatic breast cancer in 85 premenopausal patients. Tamoxifen responders continued on tamoxifen, while tamoxifen failures and initial responders who later progressed were to receive ovarian ablation next. Of 74 evaluable patients, 5 had complete responses (CR) and 15 had partial responses (PR) while 12 remained stable (ST), giving response rates of 27% (CR + PR) or 43% (CR + PR + ST). Of the 23 patients who initially responded (CR + PR + ST) to tamoxifen but then progressed and received ovarian ablation alone, 15 are assessable. Nine (60%) responded (CR + PR + ST) to ovarian ablation. Sixteen patients who failed tamoxifen had ovarian ablation alone, and of 14 assessable patients 2 had ST while 12 progressed. Thus response to tamoxifen strongly predicted response to ovarian ablation (P = 0.021). Serial follicle stimulating hormone, prolactin, and estradiol levels suggested that tamoxifen does not act by induction of a "medical ovariectomy" or by alteration of prolactin levels in premenopausal patients.

Breast Neoplasms↗
PubMed1985

Characterization of estrogen-induced progestin binding in cytosol of the R3327 prostatic carcinoma of the rat.

High affinity binding of the synthetic steroids methyltrienolone (R1881) and promegestone (R5020) to cytosol protein from the Dunning (R3327) experimental prostatic carcinoma of the rat was investigated. Animals bearing tumours of approx 1.5 cm mean diameter were either left untreated, or were administered diethylstilbestrol diphosphate (DESP) in the drinking water in doses close to those used clinically for the treatment of human prostatic carcinoma. Tumours were excised after 10-40 days, and binding of [3H]R1881 and [3H]R5020 to tumour cytosol was characterized using Scatchard analysis, sucrose density gradient centrifugation, and steroid competition, under conditions optimal for the conservation and assay of progesterone receptor. Both ligands were bound in much higher concentrations by cytosol from DESP-treated tumours than from untreated tumours. Binding was of high affinity (Kd congruent to 1 nM), was specific for progestins, and sedimented in peaks at approximately 8S and approximately 4S in sucrose density gradients. We conclude the DESP treatment of rats bearing the R3327 prostatic carcinoma induces synthesis of progesterone receptor in this tumour.

Adenocarcinoma↗
PubMed1985

Inter-laboratory quality control of estrogen and progesterone receptor assays in breast cancer tissue using lyophilised cytosols.

In 1981 a quality control (QC) program for estrogen and progesterone receptor assays was organized among six laboratories in Ontario, Canada. Twenty-three vials of lyophilised cytosol prepared from human breast tumor tissues were analysed by each laboratory over a two-year period. Samples of each batch of QC material were analysed at least twice: either in the same batch or on separate occasions. The present study demonstrates the stability of the QC material, defines the relative accuracy of the receptor assays, and provides estimates of within-batch and between-batch precision of the receptor assays.

Breast Neoplasms↗
PubMed1984

Clinical applications and value of receptor levels in treatment of prostate cancer.

Factors affecting the validity and interpretation of androgen receptor (AR) assays on prostatic carcinoma tissue are discussed, and attempts to relate AR concentration with response of the patient to hormonal manipulation are reviewed. It is concluded that nuclear AR content may be useful in evaluating prognosis and likely response to hormonal therapy, and that, owing to the heterogeneity of many prostatic carcinoma specimens, a reliable histochemical method for the assessment of androgen sensitivity would be a valuable supplement to the biochemical assay.

Androgens↗
PubMed1983

Concentration and cellular distribution of androgen receptor in human prostatic neoplasia: can estrogen treatment increase androgen receptor content?

The concentration of androgen receptor in cytosol (free and total sites) and nuclear fractions from benign (28 specimens) and malignant prostatic tissue from treated (16 specimens) and untreated patients (10 specimens) were assayed using [3H]methyltrienolone (3H R-1881) as ligand under conditions which stabilize AR and prevent binding of 3H R-1881 to progesterone receptor. It was found that optimum results were obtained when sodium molybdate (10 mM) was added after separation of the nuclear pellet rather than during tissue homogenization; when cytosol and nuclear exchange assays were carried out at 15 degrees C rather than at 0 degrees C; and when hydroxylapatite was used to separate free and bound steroid in the nuclear assay. Although AR values were variable in both BPH and carcinoma tissue, certain patterns of concentration, occupancy, and cellular distribution were observed in different patient groups. In BPH and untreated carcinoma tissue, the mean occupancy of cytosol AR by endogenous androgens was high, but the mean nuclear AR concentration was higher in BPH than in carcinoma tissue. Androgen receptor concentrations in tissue from orchiectomized patients were consistent with the effects of androgen deprivation: total cell AR was depleted, and a higher proportion was present as free cytosol AR. However, in tissue from most patients who had been treated with diethylstilbestrol (DES) on a long-term basis, total cell AR values were high. Although most of the AR was present as free cytosol AR, in three of four patients who had been treated with both orchiectomy and DES, the concentrations of bound cytosol AR and nuclear AR were similar to those in untreated patients.

Castration↗
PubMed1983

Close correlation between progesterone receptor concentration and hormonal sensitivity in DMBA-induced mammary tumours of the rat.

Cyclic administration of oestrogen alone and with progesterone to ovariectomized rats bearing DMBA-induced tumours resulted in more uniform cytosol oestrogen and progesterone receptor (ER and PgR) concentrations in the uteri and a stronger correlation between ER and PgR concentrations in the the tumours than in a group of naturally cycling animals. Using this model, the concentration of PgR was a better indicator of tumour response to ovariectomy and hormonal restimulation than the concentration of ER. In ten unequivocally responsive adenocarcinomas receptor values, expressed as fmol/mg cytosol protein, were: ER 47 +/- S.D. 19, PgR 246 +/- 134, PgR:ER 5.9 +/- 3.0, compared with ER 18 +/- 2, PgR 33 +/- 8 and PgR:ER 1.8 +/- 0.3 in three autonomous adenocarcinomas. All 3 parameters were significantly different between the two groups (0.02 less than P less than 0.05), but there was overlap in the ER values, whereas no overlap occurred in the PgR values or the PgR:ER ratios. Ten other adenocarcinomas showed a different sensitivity to restimulation than to ovariectomy and six tumours were fibroadenomas or of mixed histopathology. For the whole tumour population the response to hormonal restimulation at the time of excision suggested that a PgR concentration greater than 60 fm/mg protein combined with an ER concentration greater than 20 fm/mg protein is necessary for the maintenance of hormonal sensitivity. Using these criteria, response was related to receptor concentrations in 93% of the tumours.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1982

Effect of time and therapy on the hormone receptor status of breast carcinomas.

To determine whether the hormone receptor status of a breast carcinoma can change during the course of the disease or its treatment, the results of estrogen receptor assays in two or more biopsy specimens from 68 patients were examined; progesterone receptors had been assayed in approximately 40% of the specimens, too few to permit statistical analysis of the results. The patients fell into four groups: A, those with at least two primary breast carcinomas, and B to D, those with at least two breast carcinomas, at least one of which was a secondary tumour (usually of lymph node, skin or soft tissue) excised on the same occasion (B), 1 to 76 months later, after no intervening therapy (C), or 3 to 73 months later, after intervening chemotherapy (usually adjuvant), regional irradiation or hormonal therapy, or a combination of these (D). The small numbers in the subgroups precluded statistical analysis of the results for groups A and D. The degree of concordance of the hormone receptor status of the primary and secondary tumours in groups B and C was significant, at 87% (P less than 0.01) and 80% (P congruent to 0.01) respectively. Chemotherapy and regional irradiation did not appear to reduce the degree of concordance. All primary tumours in the same breast removed on the same occasion had the same hormone receptor status, but bilateral primary tumours appeared to have an independent status, which suggests that local tissue factors, as well as the systemic hormonal environment, play a role in establishing the hormone receptor status of breast carcinomas.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1982

Cellular localization of estrogen binding sites in human breast cancer.

Biopsy specimens from 52 consecutive cases of primary human breast cancer were collected over a period of seven months and included in a study for histochemical localization of estrogen binding sites (EBS), using a fluorescein labelled Estradiol conjugate. Cryostat frozen sections from each tumor were examined to determine the localization of the tracer and to evaluate the percentage of positive cells in a given tumor. Results are correlated with the values of the biochemical assay for the estrogen receptor (ER) protein done on the same tumor. The localization of EBS by a tracer is a simple technique that can be done and interpreted in any surgical pathology laboratory. It was concluded that this method could be a valuable supplementary technique to the biochemical assay; allowing more accurate selection of patients and prediction of their response to endocrine therapy. Clinical follow-ups are extremely necessary to evaluate the suitability and the accuracy of the technique in choosing breast cancer patients for endocrine manipulation.

Breast Neoplasms↗
PubMed1980

The effect of therapy on the concentration and occupancy of androgen receptors in human prostatic cytosol.

With a protamine sulphate precipitation method, total and free cytosol AR was assayed in BPH and prostatic carcinoma tissue, in order to investigate possible differences in AR concentration that might relate to the histo-pathology of the tissue or to endocrine manipulation of the patients. Similar ranges of total cytosol AR concentrations were observed in BPH and untreated prostatic carcinoma, but the latter tended to have a higher proportion of apparently free sites. Moreover, the proportion of "free" sites in the untreated carcinoma tissue appeared to be related to the proportion of poorly differentiated carcinoma in the specimen. In patients whose endogenous androgen levels had been lowered by treatment, the proportion of free sites tended to be higher, but a considerable proportion of sites appeared to be still occupied. Carcinoma tissue from some estrogen-treated patients had high cytosol AR concentrations. It is suggested that, in some treated patients, androgens of adrenal origin may occupy some AR sites and that some carcinomas may contain a considerable concentration of nonfunctional AR.

Castration↗
PubMed1976

In vitro estrogen-binding by human breast carcinomas.

Patients whose breast carcinomas possess only low concentrations of a receptor molecule that binds estrogens with high affinity are unlikely to respond to hormonal manipulative therapy when the disease recurs. The estrogen-binding capacity of 106 breast carcinomas was measured by an in vitro method and was expressed per milligram wet weight and in some cases related to the concentration of deoxyribonucleic acid (DNA) of the tumours. The ability of tumors to bind 3H-estradiol ranged from 0 to 1.3 fm/mg in pre- and perenopausal women, and from 0 to 16.8 fm/mg in postmenopausal women. Menopausal status or serum concentrations of endogenous estrogen, or both, should therefore be considered when tumours are classified into low and high estrogen-binding capacity. It is not necessary to carry out Scatchard analysis for every tumour, and expressing estradiol binding on the basis of DNA concentration may be preferable to expressing in on a wet-weight basis.

Adenofibroma↗