Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0279530 (bone cancer)
 1,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two new forms of BRP-2, a previously described bone resorptive protein, were purified from ascites fluids obtained from patients with hypercalcemia and metastatic bone cancer. The apparent molecular weights of BRP-2 and of these two proteins were 52,000, 48,000, and 46,000, respectively, as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The three proteins have essentially the same amino acid compositions but differ with respect to their carbohydrate moieties. The amino-terminal amino acid sequences of the three glycoproteins were identical to each other as well as to human serum alpha 2HS-(human serum) glycoprotein. The relationship of the three forms of BRP-2 to alpha 2HS was also established immunochemically. The ascites proteins, as well as alpha 2HS, on a molar basis, were approximately one-tenth as potent as bovine parathyroid hormone fragment (1-34) in their abilities to stimulate calcium release from bone in vitro. This study describes for the first time a possible function for human serum alpha 2HS.
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PMID:Three forms of BRP-2 (bone resorptive proteins) from human cancer ascites fluid and their relationship to human serum alpha-2 HS-glycoprotein. 311 44

The mobilization of calcium from the bone to the extracellular fluid proceeds in parallel with the dissolution of bone matrix, and is subject to the same influences. The role of circulating hormones has been discussed, and the importance of the skeleton as a store of calcium, even though skeletal calcium release is a relatively slow process in maturity. The major circulating hormones stimulating the processes are parathyroid hormone, 1,25-dihydroxyvitamin D3, and epidermal growth factor related substances. These represent three different classes of hormone with respect to their initial mechanisms of action. The most potent known hormonal inhibitor of bone resorption is the peptide, calcitonin, which acts directly upon the osteoclasts to inhibit their activity and generation. Local factors are undoubtedly important in the regulation of bone resorption, especially the prostaglandins. Prostaglandin E2 is the most potent bone resorber of the arachidonic acid metabolites, and is much more likely to be important locally than as a circulating factor especially in disease states such as metastatic bone cancer and arthritis. In understanding the ways in which drugs can influence bone mineral release it is important to appreciate how bone cells interact to resorb mineral and matrix. In this review the view is presented that cells of the osteoblast lineage (perhaps at the stage of osteocytes, or 'lining' cells) are the prime target of the resorbing hormones. Once having been acted upon, they initiate events which result in activation of osteoclasts. If this involves the passage of a message from osteoblast/osteocyte to osteoclast, it will be important to define this in further research.
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PMID:Drug and hormone effects on calcium release from bone. 635 42

Fischer 344 rats (60/sex/group) were given daily subcutaneous injections of recombinant human parathyroid hormone (PTH)(1-34) for 2 years at doses of 0, 5, 30, or 75 microg/kg. Treatment caused substantial increases in bone mass consistent with the known pharmacologic effects of once-daily administration. As determined by quantitative computed tomography (QCT) and histomorphometry, bone mass was markedly increased. Substantial new bone formation resulted in a large decrease in marrow space accompanied by altered bone architecture. Bone proliferative lesions were observed in all PTH( 1-34)-treated groups. Osteosarcoma occurred in 3, 21, and 31 male rats and in 4, 12, and 23 female rats in the 5-, 30-, and 75-microg/kg treatment groups, respectively. Focal osteoblast hyperplasia, osteoma, and osteoblastoma were much less frequent. Although the specific cellular or molecular mechanisms responsible for the rat bone tumors have not been fully elucidated, the data suggest that these lesions resulted from the long duration of treatment and the exaggerated pharmacologic response of the rat skeleton to daily treatment with PTH(1-34). Important differences between the rat study and clinical use in adult humans suggest that the increased incidence of bone neoplasia in rats treated for 2 years is likely not predictive of an increased risk of bone cancer in skeletally mature adult humans being given PTH(1-34) for a limited period of time in the treatment of osteoporosis.
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PMID:Skeletal changes in rats given daily subcutaneous injections of recombinant human parathyroid hormone (1-34) for 2 years and relevance to human safety. 1205 48