TY - JOUR
T1 - Prostaglandins, cancer and bone
T2 - Pharmacological considerations
AU - Martin, T. J.
AU - Partridge, N. C.
N1 - Funding Information:
Acknowledgements : Supported by grants from the Victorian Anti-Cancer Council and the Australian Government, Department of Veterans' Affairs. T.J. Martin is William Buckland Fellow of the Victorian Anti-Cancer Council for 1979.
PY - 1980
Y1 - 1980
N2 - Prostaglandins are potent bone resorbing agents, the most potent of those tested being prostaglandin E2. The labile prostanofd, prostacylin, is also capable of resorbing bone, but its potency is not known. The responsiveness of rat bone and bone tumour cell adenylate cyclase has been used to assess the relative efficacies of a wide range of stable and labile prostaglandins, their metabolites and analogues upon bone. Prostaglandins may be important local regulators in bone, and it will be critical, therefore, to define the precise action of prostaglandin-like molecules on bone cells. There is ample evidence for a role for prostaglandins in the pathogenesis of malignant hypercalcaemia in a number of animal tumour models. Evidence is also accumulating in human cancers, suggesting that prostaglandin production may be important in the establishment of osseous metastases, and in generating excessive resorption adjacent to metastatic deposits in bone, particularly in breast and renal cortical carcinomas. The nature of the responsible proslaglandin-like molecules is undetermined, and this needs to be investigated by defining the pathways of arachidonic acid metabolism in tumours. When this has been achieved, drug therapy can be directed at the appropriate enzyme activities. The current application of cyclo-oxygenase inhibitors in these clinical syndromes is of little benefit.
AB - Prostaglandins are potent bone resorbing agents, the most potent of those tested being prostaglandin E2. The labile prostanofd, prostacylin, is also capable of resorbing bone, but its potency is not known. The responsiveness of rat bone and bone tumour cell adenylate cyclase has been used to assess the relative efficacies of a wide range of stable and labile prostaglandins, their metabolites and analogues upon bone. Prostaglandins may be important local regulators in bone, and it will be critical, therefore, to define the precise action of prostaglandin-like molecules on bone cells. There is ample evidence for a role for prostaglandins in the pathogenesis of malignant hypercalcaemia in a number of animal tumour models. Evidence is also accumulating in human cancers, suggesting that prostaglandin production may be important in the establishment of osseous metastases, and in generating excessive resorption adjacent to metastatic deposits in bone, particularly in breast and renal cortical carcinomas. The nature of the responsible proslaglandin-like molecules is undetermined, and this needs to be investigated by defining the pathways of arachidonic acid metabolism in tumours. When this has been achieved, drug therapy can be directed at the appropriate enzyme activities. The current application of cyclo-oxygenase inhibitors in these clinical syndromes is of little benefit.
KW - Bone Resorption
KW - Cancer
KW - Prostaglandin Synthetase Inhibitors
KW - Prostaglandins
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U2 - 10.1016/0221-8747(80)90024-7
DO - 10.1016/0221-8747(80)90024-7
M3 - Article
AN - SCOPUS:0005925620
SN - 0221-8747
VL - 2
SP - 167
EP - 171
JO - Metabolic Bone Disease and Related Research
JF - Metabolic Bone Disease and Related Research
IS - 3
ER -