Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

At the Orthopaedic University Hospital Vienna, neoadjuvant chemotherapy with high-dose methotrexate (MTX) has been applied since 1975 in patients with osteosarcoma. Since 1977 the hospital has been a participant in the Cooperative German-Austrian Study on Osteosarcoma (COSS, 77, 80, 82, 85, 86). Therapeutic results and incidence of side effects are reviewed at regular intervals. Over a 2-year period (1/86 to 12/87), a total of 1999 g MTX were given to 15 patients in 102 therapeutic cycles. In patients treated with MTX in our hospital, only minor intolerance phenomena occurred, owing to careful leucovorin monitoring. Intoxications of up to grade III (modified WHO-score) have been seen in only a few patients. The management of the administration of leucovorin (leucovorin calcium, calcium folinate, INN; citrovorum factor) which is directly dependent on the serum level of MTX, is exactly shown in the discussion.
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PMID:[Management of the administration of leucovorin calcium in high-dose methotrexate therapy]. 278 50

The soft tissue uptake of 99mTc-hydroxymethylene diphosphonate (99mTc-HMDP) due to subcutaneous injections of heparin calcium is reported in two patients with osteosarcoma. This uptake occurs in an unusual site, i.e. the shoulders and the anterior and posterior compartments of the upper arms.
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PMID:Unusual site of extraosseous uptake of Tc 99m-HMDP due to subcutaneous heparin injections. Report of two cases. 280 30

We have used a monoclonal antibody (9A7) against the purified avian 1,25-dihydroxyvitamin D3 receptor to develop an immunocytochemical technique for visualization of the protein in fixed tissues and cultured cells. In Bouin's-fixed, chick intestine, 1,25-dihydroxyvitamin D3 receptor-like immunoreactivity was localized mainly in nuclei of epithelial cells and was more abundant in the crypt than in the villar cells. Receptor staining was low or undetectable in liver hepatocytes but was present in nuclei of cells lining the hepatic sinusoids. In rat brain, receptor-like immunoreactivity was abundant and widely distributed, but did not always coincide with the presence of vitamin D-dependent calcium-binding protein; 1,25-dihydroxyvitamin D3 receptor was absent from cerebellar Purkinje cells that contained abundant calcium-binding protein. In disaggregated rat bone cells, receptor immunoreactivity was present in mononuclear cells including osteoblasts and fibroblasts but was absent from osteoclasts. Two separate clones of osteoblast-like, rat osteosarcoma cells, shown in previous studies to be either receptor positive (17/2.8) or negative (24.1), demonstrated nuclear immunoreactivity in exact concordance with receptor levels as determined by ligand binding. The phenomenon of hormone-induced up-regulation of receptor was visualized in receptor-positive 3T6 fibroblasts by demonstration of markedly enhanced nuclear reactivity in cells treated with 10(-7) M 1,25-dihydroxyvitamin D3 for 48 h. Our studies demonstrate the feasibility of the immunocytochemical approach to visualize the 1,25-dihydroxyvitamin D3 receptor in target tissues and show that it is predominantly a nuclear protein in the relatively unoccupied and fully activated states. Moreover, the vitamin D-dependent calcium binding is not a universal marker for 1,25-dihydroxyvitamin D3 action. Rather, our observations suggest that the expression of the 1,25-dihydroxyvitamin D3 receptor may be connected with the state of cellular differentiation.
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PMID:Immunocytochemical localization of the 1,25-dihydroxyvitamin D3 receptor in target cells. 283 Oct 24

This new bioassay for parathyrin (PTH) in plasma (bio-PTH) combines immunoextraction on affinity columns [goat anti-hPTH (1-44) conjugated to Sepharose 4B] and a receptor assay involving an osteosarcoma cell line. The mean extraction efficacy ranges from 87% (as determined with immunopurified 125I-labeled PTH) to 62% for hPTH bioactivity. The assay is standardized with synthetic hPTH (1-84) and can detect as little as 0.9 pmol/L of PTH in 2 mL of plasma. In 100 healthy adults, the 95% reference interval for bio-PTH was less than 0.9 to 6.1 pmol/L (median, 2.0 pmol/L). In 185 patients with surgically confirmed hyperparathyroidism, bio-PTH concentrations ranged from 1.0 to greater than 120 pmol/L (median, 12.9 pmol/L); 80% of values were greater than 6.1 pmol/L. In 50 patients with both preoperative and postoperative determinations, the mean (+/--SD) concentrations of calcium in serum were 113 +/- 10 and 89 +/- 6 mg/L, respectively; the median bio-PTH concentrations were 13.6 and 2.0 pmol/L, respectively. In 22 patients with nonparathyroid-mediated hypercalcemia, the concentration of bio-PTH ranged from less than 0.9 to 5.3 pmol/L (median, 1.8 pmol/L). This bio-PTH assay is slightly less sensitive than our GP235 immunoreactive PTH (iPTH) immunoassay for detecting hyperparathyroidism (Clin Chem 1982;28:69-74); however, the bioassay is more specific and detected some cases missed by the iPTH assay. Overall, 95% of the hyperparathyroid patients had an increased test result for either the bio-PTH or the iPTH assay.
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PMID:Bioassay of parathyrin: analytical characteristics and clinical performance in patients with hypercalcemia. 283 99

Human cDNA clones encoding the extracellular calcium-binding, acidic glycoprotein known as SPARC, osteonectin, or BM-40 were isolated from a placental cDNA library. Two polyadenylated transcripts of 2.2 and 3.0 kb were detected in human tissues and cultured cells by Northern blot analysis, and cDNAs for both transcripts were characterized. The 2133-bp sequence of the more abundant (major) transcript contains an open reading frame for 303 amino acids. The deduced polypeptide has extensive amino acid sequence identity with mouse SPARC. The larger and minor 3.0-kb cDNA has an identical coding region but utilizes a downstream polyadenylation signal. Gene localization studies have revealed a single chromosomal site at 5q31-q33 by somatic cell hybrid analysis and in situ chromosomal hybridization. Furthermore, pulsed-field gel electrophoresis of human genomic DNA cleaved with different rare-cutting restriction enzymes and hybridized with SPARC cDNA probes revealed single or double fragments of less than 50 to about 150 kb. The evidence is consistent with a single locus for SPARC in humans. The gene was found to be differentially expressed in many human tissues and in an osteogenic sarcoma, but not in other transformed cells.
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PMID:Molecular analysis of the cDNA for human SPARC/osteonectin/BM-40: sequence, expression, and localization of the gene to chromosome 5q31-q33. 283 12

The effect of prostaglandins (PG) on free cytosolic calcium concentrations [( Ca2+]i) and cAMP levels was studied in the osteosarcoma cell line UMR-106. PGF2 alpha and PGE2, but not 6-keto-PGF1 alpha, induced an increase in [Ca2+]i which was mainly due to Ca2+ release from intracellular stores. The EC50 for PGF2 alpha was approximately 7 nM, whereas that for PGE2 was approximately 1.8 microM. Maximal doses of PGF2 alpha increased [Ca2+]i to higher levels than PGE2. Both active PGs also stimulated phosphatidylinositol turnover in UMR-106 cells. The effects of the two PGs were independent of each other and appear to involve separate receptors for each PG. PGE2 was a very potent stimulator of cAMP production and increased cAMP by approximately 80-fold with an EC50 of 0.073 microM. PGF2 alpha was a very poor stimulator of cAMP production; 25 microM PGF2 alpha increased cAMP by 5-fold. The increase in cellular cAMP levels activated a plasma membrane Ca2+ channel which resulted in a secondary, slow increase in [Ca2+]i. High concentrations of both PGs (10-50 microM) inhibited this channel independent of their effect on cAMP levels. Pretreatment of the cells with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate inhibited the PG-mediated increase in phosphatidylinositol turnover and the increase in [Ca2+]i. However, pretreatment with 12-O-tetradecanoyl-13-acetate had no effect on the PGE2-mediated increase in cAMP. The latter finding, together with the dose responses for PGE2-mediated increases in [Ca2+]i and cAMP levels, suggests the presence of two subclasses of PGE2 receptors: one coupled to adenylate cyclase and the other to phospholipase C. With respect to osteoblast function, the cAMP signaling system is antiproliferative, whereas the Ca2+ messenger system, although having no proliferative effect by itself, tempers cAMP's antiproliferative effect.
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PMID:Relationship of cAMP and calcium messenger systems in prostaglandin-stimulated UMR-106 cells. 283 4

The role of cAMP and calcium in the induction of ornithine decarboxylase (ODC, E.C.4.1.1.17) activity in the osteogenic sarcoma cell line, UMR 106-01, was studied, with particular interest for parathyroid hormone (PTH). PTH and forskolin dose-dependently induced the ODC activity and the cAMP production. Protein synthesis is involved in the effect of PTH and forskolin on ODC activity but not on cAMP production. Using quin2 we showed that 20 nM PTH and 10 microM forskolin increased the intracellular ionized calcium concentration ([Ca2+]i), thereby offering the possibility for calcium to play a role as cellular mediator in the action of PTH and forskolin in bone. Data obtained with A23187 showed that solely an increase of the [Ca2+]i is not sufficient to stimulate basal or potentiate PTH- and forskolin-induced ODC activity. However, the effects of calcium channel blockers and EGTA on basal and PTH- and forskolin-induced ODC activity point to a specific role for calcium. Moreover, the effects of calcium channel blockers and EGTA on basal and PTH- and forskolin-induced cAMP production indicate that the involvement of calcium in the induction of ODC activity is primarily located at another site than the adenylate cyclase. These data indicate that calcium is involved in the control of basal ODC activity. Furthermore, these data suggest that both cAMP and calcium are involved in the induction of ODC activity by PTH and forskolin. More precisely, ODC activity in UMR 106-01 cells can be induced by PTH and forskolin via a calcium-dependent cAMP messenger system.
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PMID:Involvement of cAMP and calcium in the induction of ornithine decarboxylase activity in an osteoblast cell line. 284 Apr 35

While the stimulatory effect of parathyroid hormone (PTH) on osteoblast-like cell adenylate cyclase is well known, the effect of PTH on cytosolic calcium ion ([Ca2+]i) mobilization is controversial, one group finding no effect but others reporting various increases. We investigated the effects on [Ca2+]i of synthetic rat PTH fragment 1-34 (rPTH(1-34)) and two bovine PTH analogues that inhibit PTH's stimulation of adenylate cyclase (bovine 8,18Nle, 34Tyr-PTH(3-34) and 34Tyr-PTH(7-34]. [Ca2+]i was measured before, during, and after exposure to PTH analogues in perifused, attached osteoblast-like rat osteosarcoma cells (ROS 17/2.8) that had been scrape-loaded with the luminescent photoprotein aequorin. Resting [Ca2+]i was 0.094 +/- 0.056 microM (mean +/- S.D., n = 103) and rose in a time- and dose-specific way after exposure to rPTH(1-34). At 10(-10) M rPTH(1-34), [Ca2+]i rose 100% within 30 s to a plateau; higher concentrations of PTH yielded increasing initial peaks of [Ca2+]i followed by lower plateaus. At 10(-6) M, the initial peak was 5-fold basal, or 0.64 +/- 0.07 microM. Both analogues of PTH were at least partial agonists for [Ca2+]i mobilization and did not reduce peak [Ca2+]i when co-perifused with rPTH(1-34). However, the analogues did reduce significantly rPTH(1-34)-induced cAMP accumulation and did not increase cAMP accumulation by themselves. Thus, rPTH(1-34) strongly mobilizes [Ca2+]i in ROS 17/2.8 cells, at near-physiologic concentrations. Failure of the PTH analogues to block the effect of PTH on [Ca2+]i while inhibiting the effect on cAMP accumulation suggests separate pathways for PTH activation of adenylate cyclase and mobilization of calcium.
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PMID:Differential effects of parathyroid hormone and its analogues on cytosolic calcium ion and cAMP levels in cultured rat osteoblast-like cells. 284 23

We compared the bioactivities of a synthetic truncated NH2-terminal fragment of the human (h) PTH-like peptide (PLP) associated with malignancies [hPLP-(3-34)], an intact NH2-terminal fragment [hPLP-(1-34)], and an NH2-terminal fragment of PTH [hPTH-(1-34)]. Although hPLP-(1-34) was less potent than hPTH-(1-34) in stimulating adenylate cyclase in rat renal membranes, hPLP-(1-34) and hPTH-(1-34) were equipotent in stimulating adenylate cyclase in OK renal cells as well as in UMR 108 osteosarcoma cells in vitro. In osteosarcoma cells, each of these peptides could desensitize adenylate cyclase responses to itself and to the other peptide, but could not reduce stimulation by prostaglandin E2. Renal membranes of vitamin D-deficient rats with secondary hyperparathyroidism had a reduced PLP-stimulated as well as PTH-stimulated adenylate cyclase response. The truncated analog hPLP-(3-34) was only a weak partial agonist and an antagonist in vitro, produced equivalent inhibition of hPLP-(1-34) and hPTH-(1-34) in renal and osseous cells, and could not desensitize agonist responses. In thyroparathyroidectomized rats in vivo, hPLP-(1-34) and hPTH-(1-34) increased cAMP excretion, enhanced phosphaturia, maintained plasma calcium, and reduced calciuria. Equimolar concentrations of hPLP-(3-34) produced no increases above control levels; however, high concentrations of this peptide mimicked PTH actions on renal and plasma ion handling while modestly augmenting cAMP excretion. These results demonstrate the importance of the first two residues of PLP for bioactivity, indicate that PLP and PTH interact at common receptor sites in vivo as well as in vitro, suggest that PLP may not be less potent than PTH in renal target cells, and indicate that the net result of interaction of these peptides with their common receptor in target tissues may reflect both activation and desensitization of receptor-mediated events.
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PMID:Influence of the amino-terminus on in vitro and in vivo biological activity of synthetic parathyroid hormone-like peptides of malignancy. 284 83

The properties of phospholipase C (PL-C) in the plasma membranes (PM) and the cytosol of osteoblast-like osteosarcoma cells, UMR-106, were analyzed to see if separate enzymes or similar enzymes were involved in signalling, transduction, and arachidonate release. The cytosolic PL-C displayed substrate affinities in the order of phosphatidylinositol (PI) greater than phosphatidylinositol-4-phosphate (PIP) or phosphatidylinoisitol-4, 5-bisphosphate (PIP2). Hydrolysis of PI, PIP, and PIP2 by cytosolic PL-C was not affected by GTP or GTP gamma S and other nucleotides. PI hydrolysis by PM and cytosolic PL-C was undetectable in the presence of 500 microM EGTA and displayed two activity plateaus at various concentrations of Ca2+. The Km for Ca2+ in the PL-C activity of the first plateau was 0.08 microM. Significant hydrolysis of PIP2 by cytosolic PL-C was observed in the absence of Ca2+. In contrast to the enzyme(s) predominant in the cytosol, the order of substrate affinities for PM PL-C was PIP2 greater than PIP greater than PI. Only PIP2 hydrolysis by PM PL-C was stimulated by both GTP and GTP gamma S in a dose-dependent manner. PIP2 hydrolysis by PL-C of the PM was not observed in the absence of Ca2+, serving to further discriminate this enzyme activity from that of the cytosol. PIP2 hydrolysis by PL-C of the PM also was biphasic in the dependence on Ca2+. At resting cytosolic Ca2+ levels, the Vmax of the high affinity activity already had been achieved. Guanine nucleotide stimulation of PIP2 hydrolysis by PM PL-C was characterized by increased maximum activity with an unchanged Km for Ca2+ or for PIP2. The pH optimum of PIP2 hydrolysis was similar between cytosolic and PM forms of PL-C. PIP2 hydrolysis with production of IP3 (PL-C activity) in UMR-106 cells treated with [2-3H]-myoinositol was stimulated by PTH, and this stimulation was not inhibited by pertussis toxin. These data suggest that UMR-106 cells possess at least two distinct PL-C activities, one predominant in the cytosol and activated by increasing cytosolic Ca2+ with PI as the substrate. The second enzyme, a GTP-activated PIP2-specific PL-C in the plasma membranes may play an important role in hormone-induced PIP2 hydrolysis mediated through guanine nucleotide regulatory proteins and may participate in the hormonal regulation of osteoblast cytosolic Ca2+ and bone remodeling functions.
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PMID:Characterization of phospholipase C activity of the plasma membrane and cytosol of an osteoblast-like cell line. 292 33


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