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Biomedical subjects

A Howell

Publications and source records attributed to A Howell.

At least 199 records · Page 11Linked to original sources
PubMed1989

Serum bioactive lactogenic hormone levels in women with familial breast cancer and their relatives.

Serum levels of bioactive lactogenic hormone (BLH), immunoreactive prolactin and growth hormone (ir-PRL and ir-GH) were measured in a group of familial breast cancer patients and their first degree female relatives and compared to those found in normal healthy women. The ratio of BLH to the sum of ir-PRL and ir-GH was slightly but significantly decreased in the familial breast cancer group (P = 0.018 by the Mann-Whitney U test) although there were no significant differences in the levels of BLH, ir-PRL and ir-GH between the two groups. No differences in the levels of the lactogenic hormones could be detected when the pre-menopausal women were considered separately or when 20 women from the familial group were compared to normal controls matched for age, parity, weight and menopausal status. The levels of BLH were highly correlated with the sum of ir-PRL and ir-GH in both the familial breast cancer group and the controls (P less than 0.001 for both groups by Spearman's rank correlation test). These findings are not indicative of the presence of an additional species of bioactive, but not immunoreactive, lactogen in the sera of women with or at high risk of breast cancer. However, the presence of different, but equipotent, forms of lactogen cannot be excluded in these women.

Adolescent↗
PubMed1989

Epidermal and transforming growth factor alpha in patients with breast tumours.

Measurements of transforming growth factor alpha (TGF-alpha) in cancer patients have produced variable results. We have now used a specific radioimmunoassay (RIA) and a mitogenic assay to evaluate TGF-alpha content of tumour and urine samples separated by an analytical HPLC system. Urine samples from patients with breast tumours and from age matched controls gave TGF-alpha amounts ranging from 0 to 61.5 ng 24 h-1 compared to urogastrone epidermal growth factor figures of 3.0-26.2 micrograms 24 h-1. The quantities of TGF-alpha in patient and control groups were not significantly different. The majority of breast tumour extracts contained mitogenic material eluting from the HPLC system at the TGF-alpha calibration point. Measurement by RIA of combined samples from each group showed that steroid receptor positive tumours had a mean figure of 14.8 ng g-1 tissue and steroid receptor negative 7.4 ng g-1. Receptor positive tumours from patients treated with an antioestrogen, tamoxifen citrate (Nolvadex), had 0.16 ng g-1. Thus TGF-alpha is found in tumours as a biologically active entity and in quantities sufficient to promote cell division. In addition the observation that tamoxifen causes a significant reduction in the content of TGF-alpha may be an additional beneficial action.

Breast Neoplasms↗
PubMed1989

The use of granulocyte colony-stimulating factor to increase the intensity of treatment with doxorubicin in patients with advanced breast and ovarian cancer.

Granulocyte colony stimulating factor (G-CSF) was given to 17 patients with advanced breast and ovarian cancer in order to increase the intensity and effectiveness of chemotherapy. Treatment with doxorubicin, at doses of 75 mg m-2 (n = 4 patients), 100 mg m-2 (n = 5), 125 mg m-2 (n = 6) and 150 mg m-2 (n = 2), was followed by infusion of G-CSF for 11 days. G-CSF administration resulted in a return of the absolute neutrophil count to normal or above normal levels within 12-14 days at all dose levels of doxorubicin used and allowed the administration of up to three cycles of high dose chemotherapy at 14 day intervals. An absolute neutrophil count greater than 2.5 x 10(9)l-1 was not reached until day 19-21 after 75 mg m-2 of doxorubicin given without G-CSF. At doses of doxorubicin of 125 mg m-2 and 150 mg m-2 all tumours regressed rapidly, although there was marked epithelial toxicity. The overall response rate in patients with advanced breast cancer was 80% with a median time to progression of 6 months. Two months after doxorubicin-G-CSF therapy there was a pronounced improvement of symptoms compared with before treatment. Thus the effectiveness of chemotherapy may be enhanced and treatment duration shortened by the use of G-CSF infusions. Further studies of this promising approach are warranted.

Adult↗
PubMed1989

West Midlands Oncology Association trials of adjuvant chemotherapy in operable breast cancer: results after a median follow-up of 7 years. I. Patients with involved axillary lymph nodes.

The aim of this study was to test the effectiveness of a regimen of combination chemotherapy known to be active in advanced breast cancer when given as an adjuvant treatment after mastectomy. A total of 569 patients with cancer of the breast and involvement of axillary lymph nodes were randomised, after simple mastectomy with axillary sampling, to receive either no adjuvant treatment or intravenous adriamycin 50 mg, vincristine 1 mg, cyclophosphamide 250 mg, methotrexate 150 mg and fluorouracil 250 mg (AVCMF) every 21 days for eight cycles. Randomisation was stratified according to menopausal status and tumour size. Treatment was started within 14 days of surgery in 94% of patients. Eighty-eight per cent of patients received at least seven cycles of chemotherapy with no dose reduction. The median relapse-free survival was prolonged by 14 months in patients treated with AVCMF (chi2 1 = 11.7; P = 0.0006). In the premenopausal group this period was 17 months (chi2 1 = 8.8; P = 0.003) compared with 8 months in the post-menopausal group (chi2 1 = 3.3; P = 0.07). Neither overall survival nor survival in these subgroups was significantly influenced by treatment.

Adult↗
PubMed1989

West Midlands Oncology Association trials of adjuvant chemotherapy in operable breast cancer: results after a median follow-up of 7 years. II. Patients without involved axillary lymph nodes.

The aim of this study was to test the effectiveness of a regimen of combination chemotherapy when given as an adjuvant treatment after mastectomy to patients with histologically negative axillary lymph nodes. A total of 574 patients with cancer of the breast and no involvement of axillary lymph nodes were randomised, after simple mastectomy with axillary sampling, to receive either no adjuvant treatment or oral fluorouracil 500 mg, methotrexate 25 mg and chlorambucil 10 mg p.o. on day 1 and fluorouracil 500 mg and chlorambucil 10 mg p.o. on day 2 (LMF) every 21 days for eight cycles. Randomisation was stratified according to menopausal status and tumour size. Treatment was started within 14 days of surgery in 97% of patients. Ninety per cent of patients received eight cycles of chemotherapy with no dose reduction. At a median follow-up of 7 years, there was no evidence that relapse-free or overall survival time were influenced by treatment.

Adult↗
PubMed1989

The kinetics of human granulopoiesis following treatment with granulocyte colony-stimulating factor in vivo.

Cell proliferation in the bone marrow and blood of two patients with metastatic breast cancer who were treated with granulocyte colony-stimulating factor was studied by using [3H]thymidine labeling and autoradiography. Additionally, the fate of neutrophils labeled with 99mTc-hexamethylpropyleneamineoxime was observed following granulocyte colony-stimulating factor infusion. Proliferation increased in all stages of granulopoiesis, but a significant amount of the increased production stemmed from a greater input to the myeloblast compartment. Changes in the myelogram combined with the increased labeling indicated a faster throughput of cells, which resulted in labeled cells appearing in the circulation within 1 day compared to the normal 4 or 5 days. The 99mTc studies demonstrated no sequestration of circulating neutrophils by spleen, lungs, or liver. The half-life of the circulating neutrophils was not significantly changed, and calculations from the flow of labeled cells to the peripheral blood indicated an increase of 3.2 extra amplification divisions during neutrophil development. The dramatic neutrophil response to granulocyte colony-stimulating factor can therefore be accommodated by a relatively modest increase in granulopoietic activity.

Adult↗
PubMed1989

The relationship between age and the effect of adjuvant therapies in women with primary breast cancer.

Apparent differences in the effectiveness of adjuvant therapies according to age, has led to controversy concerning the optimum treatment for women with breast cancer above and below 50 years of age. The data upon which this controversy is based and the possible reasons why chemotherapy appears more active in young women, whilst endocrine therapy appears more active in older women, is examined.

Adult↗
PubMed1988

Expression of differentiation antigens within human mammary tumours is related to response to endocrine therapy and survival.

Human mammary tumours which are histologically well differentiated are more likely to synthesize receptors for estrogen (ER) and progesterone (PR) and to respond to systemic endocrine therapy. The aim of this study was to explore the relationship between differentiation, receptors and endocrine responsiveness in more detail by relating the expression of putative differentiation antigens within tumours to ER, PR and response to treatment. Sections of the primary tumours of 160 patients with advanced evaluable breast cancer were immunostained with 2 monoclonal antibodies (MAbs) (HMFG1 and HMFG2) raised against putative differentiation antigens found on the membranes which surround the milk fat globule. Tumours were highly heterogeneous with respect to antigen expression. However, the number of cells which expressed the antigens was highly correlated with ER and PR concentrations and with response to endocrine therapy. In tumours where greater than or equal to 20% of cells expressed the antigen recognized by HMFG1, 73% responded to endocrine therapy; this was similar to the response predicted by ER (67%) and PR (73%). Expression of HMFG1 was correlated with survival from the start of endocrine therapy (p less than 0.0001) to the same degree as ER and PR. Patients with tumours which expressed ER, PR and HMFG1 had the highest response rate (87%) and survival (median 49 months); the response in tumours which expressed none of these phenotypes was 13% and the median survival of these patients was 9 months. These results suggest that cells which express differentiation antigens also express ER and PR. Differentiated cells within mammary tumours may therefore be the target cells for systemic hormone, and also the source of factors which control tumour growth.

Adult↗
PubMed1988

Single dose versus daily intravenous aminohydroxypropylidene biphosphonate (APD) for the hypercalcaemia of malignancy.

Thirty patients with hypercalcaemia and known malignant disease were randomly allocated to receive 60 mg 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (APD) intravenously as a single dose or as consecutive daily doses of 30 mg (two days) or 15 mg (four days). The rate of infusion was the same for each regimen (7.5 mg/hour). Calcium concentrations fell in all patients and returned to normal in all but two. Relapse of hypercalcaemia occurred after a mean of 21 days in each group. Urinary calcium excretion fell in all groups and symptoms were greatly improved. After relapse patients were retreated with APD (30 mg as a single infusion) and normocalcaemia maintained by regular infusions at two to three week intervals. APD given as a single 60 mg infusion over eight hours together with rehydration is recommended as the initial management of the hypercalcaemia of malignancy, followed by 30 mg APD roughly every two to three weeks to maintain normal or near normal serum calcium concentrations.

Calcium↗
PubMed1988

The definition of the 'no change' category in patients treated with endocrine therapy and chemotherapy for advanced carcinoma of the breast.

In the criteria used for assessment of response to treatment for advanced breast cancer the definition of no change (NC) is clear; however, there is no indication of the duration of stabilization required for patients to qualify for this category of response. We have made the assumption that NC is a worthwhile category of response if the overall time to progression (TTP) and survival of this group is not significantly different from patients with partial remissions (PR). Two hundred and sixty-three evaluable patients treated with endocrine therapy and 302 evaluable chemotherapy-treated patients were studied and the TTP and survival curves for PR and periods of NC from 1 to 6 months compared. For the endocrine-treated patients the TTP and survival curves for NC became non-significantly different from the PR curves after 4 and 5 months respectively. For chemotherapy-treated patients the TTP curves became non-significantly different from PR at 4 months and for survival the period was 3 months. In order to define NC as a useful category of response and to eliminate the possibility that NC taken for a shorter period could simply represent a slowly progressive tumour, we suggest that the minimum period of disease stabilization be taken as 5 months for both endocrine- and chemotherapy-treated patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Cellular aspects of breast cancer: workshop report.

It has not been possible in this review to cover all the submitted posters nor indeed all the points discussed during the workshop session. It is hoped, however, that major points of interest have been presented and that areas where there is consensus and areas where controversy remains concerning the clinical value of particular investigations have been highlighted. It is also hoped that some new potential growth areas for investigation of tumour biology have been defined.

Animals↗
PubMed1988

The effect of age and menstrual cycle upon proliferative activity of the normal human breast.

The aim of this study was to determine the proliferative activity within the epithelial cells of the normal human breast in 122 patients (6 reduction mammoplasties and 116 fibroadenoma excisions) in relation to age and the phase of the menstrual cycle. Thirty three of the patients were on oral contraceptives and 33 were parous. Thin tissue slices were incubated with tritiated thymidine and processed for autoradiography. Other samples were fixed directly and prepared for histology. The labelling, mitotic and apoptotic indices (LI, MI and AI) were determined and all illustrated considerable variability. The labelling indices are significantly (P less than 0.05) influenced by both patient age and stage during the menstrual cycle and ranged from 0-11.5%. Maximum LI values were obtained on the 20.8th day of the cycle. A square root transformation of the data was used to reduce the skewness of the data to a more normal distribution. The square root of the LI declined by 0.22 per decade. The mitotic data showed similar significant (P less than 0.05) correlations against age and day of cycle with a peak on the 21.5th day of the cycle, a decline by 0.072 per decade and a range from 0-0.6%. The data for apoptotic cells were less clearly influenced by the stage of the menstrual cycle but showed a significant (P less than 0.5) decline with age. The AI in parous patients was significantly higher than that in non-parous patients. There was no significant effect of oral contraceptives on any of the parameters measured when age and stage of cycle were taken into account. The considerable variability in the data could not be fully accounted for by either technical factors, the age of the patients, or the day of the cycle. We conclude that proliferation is negatively related to age and is influenced by the menstrual cycle but that additional as yet unknown factors must account for a large part of the variability seen in the data.

Adolescent↗
PubMed1988

The relationship of body weight to response to endocrine therapy, steroid hormone receptors and survival of patients with advanced cancer of the breast.

High body weight is associated with increased production of oestrogens which may influence the clinical behaviour of breast cancer. We have examined the influence of body weight on the response to endocrine therapy, steroid hormone receptor content and survival in 227 women who either presented with or developed advanced cancer of the breast. One hundred and thirty-three (59%) patients presented with operable disease and 94 (41%) with locally advanced tumours. Two hundred (88%) were treated by tamoxifen and 27 (12%) by ovarian ablation. High body weight was correlated with advanced tumour stage (P = 0.002) and progesterone receptor (PR) positivity (P = 0.01), but not with the presence of oestrogen receptor (ER P = 0.21). The association between high body weight and PR positivity was particularly noticeable among ER positive tumours. There was no significant relationship between the nature of the response to therapy and weight (P = 0.57). There was no significant difference in survival from the start of endocrine therapy (P = 0.95), nor the time to progression of disease (P = 0.29) between patients above and below the median weight of 64 kg. Among the patients with operable disease, there was no difference in overall survival (P = 0.42), relapse free survival (P = 0.69), and survival from the start of endocrine therapy (P = 0.85) according to body weight.

Body Weight↗
PubMed1988

In situ hybridisation and S1 mapping show that the presence of infiltrating plasma cells is associated with poor prognosis in breast cancer.

In order to identify potential markers of prognosis in breast cancer, representative cDNA libraries were constructed using RNA isolated from primary breast tumour tissue associated with good and poor prognosis. Cross-screening of these libraries repeatedly identified cloned mRNA species associated with the immune system, in particular B-cells, in libraries derived from tumours of poor prognosis. We have used one of these a kappa IV light chain cDNA probe, in two complementary studies to investigate the relationship between immunoglobin gene expression and prognosis. The results obtained using a combination of S1 mapping, RNA blotting and in situ hybridisation demonstrate that the presence of plasma cells, as defined by infiltrating cells which express high levels of immunoglobulin kappa-chain mRNA, is associated with a poor prognosis.

Adult↗