PubMed HealthSearch

Biomedical subjects

T J Powles

Publications and source records attributed to T J Powles.

31 records · Page 2Linked to original sources

Calcium metabolism in breast cancer.

Patients with breast cancer and bone destruction were found to have a pattern of calcium metabolism which was broadly similar to that found in other malignancies, but different from that in primary hyperparathyroidism. Thus, they tended to have reduced absorption of calcium from the intestine, elevated endogenous faecal calcium and normal or reduced urinary cyclic AMP excretion. Since prostaglandin synthetase inhibitors have been shown to inhibit breast cancer-induced osteolysis in vitro we have attempted to reduce bone destruction and serum calcium in patients with hypercalcaemia complicating breast cancer using these agents. High doses failed to reduce the serum calcium or the urinary hydroxyproline: creatinine ratio in ten patients with skeletal metastases, four of whom had hypercalcaemia.

Adult

Breast-cancer osteolysis, bone metastases, and anti-osteolytic effect of aspirin.

23 (60%) of 38 human breast carcinomas had significant in-vitro osteolytic activity. All patients presenting with bone metastases or hypercalcaemia had active tumours. Over a subsequent three-year follow-up period, bone metastases did not develop in any of the 15 patients with inactive tumours, and metastases at other sites developed in only 2. Of the 23 patients with active tumours, 7 either had, or have since developed bone metastases; in 4 of these hypercalcaemia also developed. 14 tumours, chosen at random, were tested for in-vitro osteolytic activity in the presence and absence of aspirin, which inhibits prostaglandin synthetase. The activity of 8 of the 9 osteolytically active tumours was significantly, though not completely inhibited by aspirin. Although the number of patients is limited, these results indicate that the in-vitro osteolysis assay may detect substances, perhaps including prostaglandins, produced by breast tumours which affect prognosis and contribute to the subsequent formation of bone metastases.

Animals

Early morning hydroxyproline excretion in patients with breast cancer.

The hydroxyproline/creatinine excretion ratios have been measured in half-hour fasting morning urine specimens from breast cancer patients and compared with corresponding values measured in 24 hour urine collections. Both parameters show a close correlation. The value of the half-hour test in predicting the presence of early bone metastases, in monitoring the response of patients to therapy and in eliminating unwanted effects of dietary Hydroxyproline intake are discussed.

Bone Neoplasms

Human breast tumour-induced osteolysis and prostaglandins.

Osteolysis effected in vitro by breast carcinomas can be inhibited by aspirin. Some prostaglandins stimulate in vitro bone resorption. Our results indicate that whilst osteolytically active PGE and PGF are released by the carcinomas in most cases, some other osteolytic principle is released as well.

Aspirin

Failure of indomethacin to reduce hypercalcemia in patients with breast cancer.

Prostaglandin synthetase inhibitors have, in the past, been shown to inhibit osteolysis caused by breast carcinoma tissue in vitro. We therefore assessed the effect of Indomethacin and aspirin on some parameters of calcium metabolism in patients with breast cancer. Neither drug reduced the serum calcium in pateints with hypercalcemia, nor reduced skeletal destruction as measured by the urinary hydroxy proline: creatinine ratio and urinary calcium in normocalcemic or hypercalcemic patients with osteolytic metastases. A possible reason for the discrepancy between results obtained in vitro and in vivo is that there are two phases of bone destruction in breast cancer; the early phase dependent and the late phase independent of prostaglandin synthesis.

Aspirin

Hydroxyproline excretion in patients with breast cancer and response to treatment.

The urinary excretion of hydroxyproline, measured as the hydroxyproline: creatinine ratio, was useful in monitoring the progression of metastatic cancer of the breast. After new treatment was started changes in the hydroxyproline excretion occurred earlier than other clinically observable responses. The test could therefore be used for predicting the response to treatment and early detection of the sensitivity of the tumour to hormone therapy.

Antineoplastic Agents

Nucleoside excretion in breast cancer: comparison with other biochemical tumour-index-substances.

[We have measured four urinary nucleosides (dimethylguanosine, 1-methylinosine, pseudouridine and beta-aminoisobutyric acid)in patients with benign breast disease and patients with early and advanced breast cancer in order to assess their value as tumour-index-substances. We compared the results with other biochemical indices of breast cancer and sought and correlations between these indices. The results indicate that few abnormalities occurred in patients without overt metastases and these did not predict early relapse. In those with metastatic disease, dimethylguanosine excretion was most frequently elevated. Correlations were observed between some of the nucleosides and lysozyme and alpha1-antirypsin.

Aminoisobutyric Acids