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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Osteoporosis is a known complication of diabetes mellitus, suggesting a role for insulin in bone homeostasis. We studied insulin receptors and insulin action in the osteoblast-like rat osteogenic sarcoma cell line ROS 17/2.8. These cells share many common features with the osteoblast, such as 1,25-dihydroxyvitamin D3 receptors, PTH receptors, and 1,25-dihydroxyvitamin D3-induced modulation of alkaline phosphatase activity and osteocalcin. Competition binding studies revealed high affinity insulin receptors, with an ED50 for insulin of 1 nM. The receptors were highly specific for insulin, with 60% inhibition of insulin binding by an antireceptor antibody, no competition by epidermal growth factor, and an ED50 of 300 nM for proinsulin. Steady state maximal insulin binding was obtained by 40 min at 37 C, and insulin degradation, as measured by trichloroacetic acid solubility, was 1%/h at 37 C. ROS cells readily internalized insulin, and under steady state binding conditions at 37 C, 56% of the cell-associated radioactivity consisted of intracellular material. Chloroquine (100 microM) inhibited intracellular processing of insulin, leading to a 300% increase in cell-associated insulin by 2 h (37 C). Photoaffinity labeling of the insulin receptor with the photosensitive analog of insulin, B2 (2-nitro-4-azidophenyl-acetyl)des-pheB1-insulin, followed by solubilization and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, revealed specific bands of 125K and 430K mol wt under reducing and nonreducing conditions, respectively. Thus, the structure of insulin receptors in ROS cells appears comparable to that of insulin receptors of known target tissues. Insulin action was also examined. Insulin did not stimulate [2-3H]deoxyglucose uptake or [1-14C]leucine incorporation into protein. In contrast, physiological concentrations of insulin inhibited alkaline phosphatase activity in nonconfluent cells. After exposure to insulin for 24 h, alkaline phosphatase activity was decreased compared to basal by 39.5% and 50% with 5 and 50 ng/ml insulin, respectively. In conclusion, ROS cells bind insulin to specific receptors that are similar to insulin receptors on other target tissues; receptors internalize insulin, which is then processed through a chloroquine-sensitive pathway; insulin does not affect membrane substrate transport; and insulin does inhibit the activity of an enzyme that is important in bone metabolism. ROS cells represent a model for studying insulin effects on bone.
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PMID:Demonstration of insulin receptors and modulation of alkaline phosphatase activity by insulin in rat osteoblastic cells. 353 Jul 24

Although acute alterations in Ca2+ fluxes may mediate the skeletal responses to certain humoral agents, the processes subserving those fluxes are not well understood. We have sought evidence for Ca2+-dependent ATPase activity in isolated osteoblast-like cells maintained in primary culture. Two Ca2+-dependent ATPase components were found in a plasma membrane fraction: a high affinity component (half-saturation constant for Ca2+ of 280 nM, Vmax of 13.5 nmol/mg per min) and a low affinity component, which was in reality a divalent cation ATPase, since Mg2+ could replace Ca2+ without loss of activity. The high affinity component exhibited a pH optimum of 7.2 and required Mg2+ for full activity. It was unaffected by potassium or sodium chloride, ouabain or sodium azide, but was inhibited by lanthanum and by the calmodulin antagonist trifluoperazine. This component was prevalent in a subcellular fraction which was also enriched in 5'-nucleotidase and adenylate cyclase activities, suggesting the plasma membrane as its principal location. Osteosarcoma cells, known to resemble osteoblasts in their biological characteristics and responses to bone-seeking hormones, contained similar ATPase activities. Inclusion of purified calmodulin in the assay system caused small non-reproducible increases in the Ca2+-dependent ATPase activity of EGTA-washed membranes. Marked, consistent calmodulin stimulation was demonstrated in membranes exposed previously to trifluoperazine and then washed in trifluoperazine-free buffer. These results indicate the presence of a high affinity, calmodulin-sensitive Ca2+-dependent ATPase in osteoblast-like bone cells. As one determinant of Ca2+ fluxes in bone cells, this enzyme may participate in the hormonal regulation of bone cell function.
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PMID:A high affinity, calmodulin-responsive (Ca2+ + Mg2+)-ATPase in isolated bone cells. 613 20

A case of vitamin D resistant hypophosphatemic osteomalacia associated with osteosarcoma of the mandible is presented. The patient complained of lumbar, knee and foot pain and muscle weakness of two years' duration. Serum phosphorous was 1.0-1.6 mg/dl, tubular reabsorption of phosphorus was 47 to 58%, TmPO4/GFR was o.7-1.2 mg/dl. Aminoaciduria was noted. Bone biopsy confirmed the diagnosis of osteomalacia. He partially responded to the treatment with 1 alpha()H) D3 and sodium phosphate. After removal of sarcoma of the mandible, symptoms remitted and pertinent laboratory data became normal except serum alkaline phosphatase for more than one year without treatment. It is suggested that an impaired response of the tubule and bone to active vitamin D3, caused in some way by the osteosarcoma might be one of the causes of osteomalacia in this case.
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PMID:Vitamin D resistant hypophosphatemic osteomalacia associated with osteosarcoma of the mandible: report of a case. 627 44

The expression of a cell surface antigen defined by an anti-human osteogenic sarcoma monoclonal antibody was analysed by flow cytofluorometry using fluorescein-labelled antibody. Quantitative absorption tests established that the antigen was associated with plasma membranes, whereas cytosol, cellular lipids and nuclei were largely devoid of activity. Single-phase aqueous butanol solutions at non-cytolytic concentrations failed to solubilize the antigen, although treatment of cells with papain virtually abolished antigenic activity. The antigen was shown to be solubilized by the non-ionic detergent Nonidet P-40, and following lactoperoxidase-catalysed radioiodination of viable cells, extraction with detergent, immunoprecipitation of antigen with monoclonal antibody and Sepharose-Protein A, the molecular weight of antigen was determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The findings indicate that this human osteogenic sarcoma antigen is a monomeric integral membrane protein with an apparent molecular weight of 72,000, which is predominantly expressed at the external face of the tumour cell plasma membrane.
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PMID:Characteristics of a cell surface antigen defined by an anti-human osteogenic sarcoma monoclonal antibody. 634 92

An anti-human osteogenic sarcoma monoclonal antibody (mouse IgG2b) termed 791T/36 was found to exert complement-dependent cytotoxicity against phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear (PBMN) cells. This reaction was examined by flow cytofluorimetry using indirect membrane immunofluorescence to detect cell-bound antibody and by measurement of the binding of fluorescein-isothiocyanate-conjugated 791T/36 antibody to cells. The antibody reacted strongly with peripheral blood blast cells induced by PHA, and there was negligible reactivity with resting lymphocytes. Maximum binding was observed after 3 days' culture with PHA, coinciding with maximum DNA synthesis, and this represented of the order of 2 X 10(5) antibody molecules bound per cell. After cell surface radioiodination of PHA-stimulated PBMN cells, detergent lysis and immunoprecipitation of antigen with 791T/36 antibody and Sepharose-protein A, the apparent molecular weight of this antigen was determined to be 72,000 by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. This is identical to that of the 791T/36-defined antigen expressed on various osteogenic sarcoma cell lines [3, 17], and by this criterion the antigen is distinguishable from other cell surface markers of activated human lymphocytes.
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PMID:Identification of an anti-human osteogenic sarcoma monoclonal-antibody-defined antigen on mitogen-stimulated peripheral blood mononuclear cells. 635 72

Intracellular microelectrode measurements were made on a well-characterized osteoblast-like clonal cell line isolated from a rat osteosarcoma. In serum-free medium, stable membrane potentials of -42 +/- 9 mV (SD, n = 190) were recorded. Ion substitution experiments suggested that this membrane potential is primarily a Na+/K+ diffusion potential. Input resistance was correlated strongly with colony size, ranging from 49 +/- 18 M omega (SD, n = 14) for colonies of 1-3 cells, to 4 +/- 4 M omega (SD, n = 164) for colonies of 100 or more cells. These results are consistent with the existence of low resistance intercellular junctions. Application of the carboxylic calcium ionophore A23187 by pressure microejection onto the cell surface resulted in a transient hyperpolarization and concomitant decrease in input resistance. Both these effects are consistent with an increased K+ conductance. Ion substitution experiments demonstrated that the degree of hyperpolarization was dependent on the external concentration of both K+ and Ca2+. Quinine, a blocker of Ca2+-activated K+ channels, inhibited the ionophore-induced hyperpolarization in a dose-dependent manner. It was concluded that these cells exhibit a Ca2+-activated K+ conductance.
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PMID:Electrophysiology of a clonal osteoblast-like cell line: evidence for the existence of a Ca2+-activated K+ conductance. 643 42

A bone-inducing substance (osteogenic factor) from a murine osteosarcoma was found to be soluble in 1% sodium lauryl sulfate (SDS), 1% deoxycholate, 1% Triton X-100, and 1% Nonidet P-40. A precipitate formed on removal of the detergents by dialysis against phosphate buffer, and this precipitate induced ectopic bone formation when implanted into allogeneic mice. The insoluble residue left after extraction with SDS or deoxycholate did not evoke new bone formation, indicating that the substance was solubilized completely. The bone-inducing substance was also partially solubilized with weak acids (pH, 2.6-3.0) but not with acidic solutions of lower or higher pH. These findings indicate that the solubility of the substance depends on the hydrogen ion concentration of the solution. The substance was not solubilized with EDTA or 6 M urea.
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PMID:Solubility of a bone-inducing substance from a murine osteosarcoma. 658 84

1,25 Dihydroxyvitamin D3 suppressed colony formation in soft agar and increased alkaline phosphatase activity in clonal rat osteosarcoma cells. Sodium butyrate enhanced these effects of the hormone partly through a mechanism involving an alteration of nuclear binding of the hormone. It is suggested that 1,25 dihydroxyvitamin D3 in conjunction with sodium butyrate might be able to regulate differentiation and proliferation of neoplastic cells.
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PMID:Sodium butyrate (SB) augments the effects of 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) on neoplastic and osteoblastic phenotype in clonal rat osteosarcoma cells. 658 71

Insulin-like growth factor I (IGF-I) stimulates multiplication of the human osteosarcoma cell line, MG-63. by acting through the IGF-I receptor. We have characterized IGF-I stimulated phosphorylation of the IGF-I receptor in this cell line. Serum starved MG-63 cells were metabolically labeled with [32P]orthophosphoric acid and the cells were treated with IGF-I. Phosphotyrosine containing proteins were immunoprecipitated from the cell lysates with antiphosphotyrosine-Agarose and eluted with phenyl phosphate. Further immunoprecipitation with IGF-I receptor monoclonal antibodies (alpha IR-3, 18E9) and analysis by sodium dodecylsulfate polyacrylamide gel electrophoresis and autoradiography demonstrated IGF-I dependent autophosphorylation of the IGF-I receptor. Phosphoamino acid analysis of the IGF-I receptor beta subunit and the observation that antiphosphotyrosine-Agarose did not immunoprecipitate [35S]methionine-labeled receptor from unstimulated cells, demonstrated that in the absence of IGF-I, the receptor was not phosphorylated on tyrosine residues. Western blotting of cell lysates with a monoclonal phosphotyrosine antibody did not identify the IGF-I receptor or pp185 but demonstrated IGF-I dependent phosphorylation on tyrosine residues in three other proteins, p110, p70 and p40.
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PMID:Insulin-like growth factor-I (IGF-I) dependent phosphorylation of the IGF-I receptor in MG-63 cells. 750 67

Decorporation therapy is the only known effective method of reducing the radiation dose to persons following accidental internal contamination with transportable radionuclides. Deposits of actinides in bone should be minimized because development of osteosarcoma appears to be related to internal exposure. In contrast with other actinides, such as plutonium or americium where chelating agent treatment is efficient, the therapeuric approaches used for cases of uranium contamination are widely ineffective. This is the first report on in vivo efficacy of a chelating agent, a siderophore analogue code named 3,4,3-LIHOPO, after systematic exposure to natural uranium in the rat. Using the classical antidotal therapy (sodium bicarbonate) for comparison, this ligand has been investigated for its ability to remove uranium from rats after intravenous or intramuscular injection as nitrate. Following an immediate single intramuscular or intravenous injection of 3,4,3-LIHOPO (30 mumol.kg-1) urinary excretion of uranium was greatly enhanced with a corresponding reduction 24 h later in kidney and bone uranium content (to about 20 and 50% of the control rat respectively). Under identical experimental conditions, sodium bicarbonate (640 mumol.kg-1) reduced the uranium content in kidney in kidney and bone only to about 90 and 70% of controls respectively, and there was less enhancement of uranium excretion. However, when treatment was delayed by 30 min and administered intraperitoneally, there was no marked difference in retention and excretion of uranium between the two compounds. As this ligand showed no apparent irreversible toxicity at effective dosages, it is concluded that the administration of the 3,4,3-LIHOPO chelating agent represents potentially a most significant advance for prompt treatment of uranium contamination, while a more detailed investigation is necessary on the possible advantage when treatment delayed.
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PMID:Efficacy of 3,4,3-LIHOPO for reducing the retention of uranium in rat after acute administration. 759 63


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