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)

Chicken parathyroid hormone (cPTH) has been reported to stimulate adrenal steroidogenesis and to have unusual potency on traditional PTH target tissues. To evaluate these properties, chicken PTH-(1-88) has been expressed in Escherichia coli using a plasmid encoding a fusion protein which links together growth hormone, a factor Xa recognition site, and chicken PTH-(1-88). The growth hormone-cPTH fusion protein required the presence of 0.02% sodium dodecyl sulfate to remain in solution and be cleaved by factor Xa. The high performance liquid chromatography-purified recombinant cPTH-(1-88) and chemically synthesized cPTH-(1-34) had similar potency in rat osteosarcoma (ROS 17/2.8) cells, opossum kidney (OK) cells, and dispersed primary chicken kidney cells. The biologic potencies of cPTH-(1-34) and cPTH-(1-88) in radioreceptor binding and cAMP generation in both bone- and kidney-derived cell lines were less than those of human (h)PTH-(1-34). In dispersed chicken kidney cells, cAMP production by cPTH-(1-34) and cPTH-(1-88) was similar to that stimulated by human PTH-(1-34). No stimulation of steroidogenesis could be detected when recombinant chicken PTH-(1-88) was added to dispersed chicken adrenal cells. The biologic activity of recombinant chicken PTH-(1-88) purified from E. coli was comparable with that of chicken PTH-(1-88) expressed by mammalian COS cells. Thus, the full-length chicken PTH did not exhibit enhanced potency, when compared with human PTH in ROS 17/2.8, OK cell lines, and dispersed chicken kidney cells and did not demonstrate the novel steroidogenic action previously reported in adrenal cells. The successful production of chicken PTH-(1-88) will enhance our understanding of the structure-activity relationships for PTH, particularly the sequence-dependent metabolism of the hormone.
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PMID:Full-length chicken parathyroid hormone. Biosynthesis in Escherichia coli and analysis of biologic activity. 184 86

These studies were undertaken to characterize the physiological fate of the insulin-like growth factor-I (IGF-I)-type I receptor complex in MG-63, an IGF-responsive human osteosarcoma cell line. To investigate this, a photoreactive iodinated derivative of IGF-I [5-azido-2-nitrobenzoyl-125I-IGF-I (ANBz-125I-IGF-I)] was synthesized. This derivative retained biological activity and photolabeled a cell surface component on MG-63 cells with the size and binding specificity characteristic of the type I IGF receptor. To assess the stability of the photoaffinity-labeled IGF-I receptor complex, quiescent monolayers of MG-63 cells were incubated with ANBz-125I-IGF-I at 2 C, photolyzed, and then warmed to 37 C. At various times the monolayers were solubilized and the receptor complex was identified by quantitative autoradiography after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Under these conditions the photoaffinity-labeled IGF-I receptor complex was relatively stable, with a half-life of 11 +/- 2 h in five experiments. To determine if the complex undergoes internalization, its susceptibility to hydrolysis by trypsin at 2 C was measured. When cells that were labeled at 2 C were warmed to 37 C, a trypsin-insensitive band appeared within 20 min, reached a maximum by 1 h, and declined thereafter; however, an average of only 7% (5-8% in four experiments) of the total labeled receptor pool was present intracellularly at 1 h, and this declined to less than 1% by 4 h. A similar distribution of receptors was observed in cells photolabeled after incubation with ANBz-125I-IGF-I at 37 C, indicating that this distribution was not the result of altered metabolism of the photolabeled receptor complex. Lysosomotropic agents inhibited degradation of the complex, but did not alter its distribution between the cell surface and interior. These results indicated that the IGF-I-type I receptor complex is relatively stable and does not undergo rapid ligand-induced down-regulation and degradation. These observations suggest a model in which the IGF-receptor complex functions while present at or near the cell surface.
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PMID:Metabolism of photoaffinity-labeled insulin-like growth factor-I receptors by human cells in vitro. 215 97

The metabolism of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] by a human osteoblastic sarcoma cell line, U-2 OS, and by primary cultures of human bone-derived cells was examined at physiologic (5 x 10(-11) M) and pharmacologic (3.5 x 10(-7) M) substrate concentrations. For metabolite identification purposes, cells nearing confluency were incubated for 18 h with 3.5 x 10(-7) M 1,25-(OH)2D3 in serum-free medium. The putative vitamin D metabolites produced during this incubation were isolated from a total lipid extract of cells and medium. Identification of the metabolites was achieved by comigration with authentic standards on three high-performance liquid chromatography systems, UV spectral analysis, mass spectrometry, and chemical modification by sodium borohydride and sodium metaperiodate. The identified metabolites produced from 1,25-(OH)2D3 by the human osteosarcoma cells include 1,24,25-trihydroxyvitamin D3; 24-oxo-1,25-dihydroxyvitamin D3; 24-oxo-1,23,25-trihydroxyvitamin D3; and 24,25,26,27-tetranor-1,23-dihydroxyvitamin D3. Evidence is presented that (1) 1,25-(OH)2D3 metabolism occurs constitutively in U-2 OS osteosarcoma cells at a physiologic substrate concentration (5 x 11(-11) M), (2) the pathway can be further induced by pharmacologic 1,25-(OH)2D3 concentrations (10(-7) M), and (3) this pathway is present in primary cultures of normal human bone-derived cells.
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PMID:1,25-Dihydroxyvitamin D3 metabolism in a human osteosarcoma cell line and human bone cells. 216 23

Eleven patients with primary osteosarcoma were treated by intra-arterial infusion of cisplatin. Cisplatin (50-100 mg/m2) was infused slowly into tumor feeding artery or proximal-to-the-lesion artery. An antidote, sodium thiosulfate, was also administered intravenously in 10 cases and angiotensin II was simultaneously used in 2 cases. Symptoms of heat sensation and local pain were decreased or disappeared in almost all cases and histopathologic changes were observed in 7 cases. No viable tumor cells were seen in 3 cases.
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PMID:[A clinical study of intraarterial infusion therapy with CDDP for primary osteosarcoma]. 229 38

Measurements of cytosolic pH (pHi) 36Cl fluxes and free cytosolic Ca2+ concentration ([Ca2+]i) were performed in the clonal osteosarcoma cell line UMR-106 to characterize the kinetic properties of Cl-/HCO3- (OH-) exchange and its regulation by pHi and [Ca2+]i. Suspending cells in Cl(-)-free medium resulted in rapid cytosolic alkalinization from pHi 7.05 to approximately 7.42. Subsequently, the cytosol acidified to pHi 7.31. Extracellular HCO3- increased the rate and extent of cytosolic alkalinization and prevented the secondary acidification. Suspending alkalinized and Cl(-)-depleted cells in Cl(-)-containing solutions resulted in cytosolic acidification. All these pHi changes were inhibited by 4',4',-diisothiocyano-2,2'-stilbene disulfonic acid (DIDS) and H2DIDS, and were not affected by manipulation of the membrane potential. The pattern of extracellular Cl- dependency of the exchange process suggests that Cl- ions interact with a single saturable external site and HCO3- (OH-) complete with Cl- for binding to this site. The dependencies of both net anion exchange and Cl- self-exchange fluxes on pHi did not follow simple saturation kinetics. These findings suggest that the anion exchanger is regulated by intracellular HCO3- (OH-). A rise in [Ca2+]i, whether induced by stimulation of protein kinase C-activated Ca2+ channels, Ca2+ ionophore, or depolarization of the plasma membrane, resulted in cytosolic acidification with subsequent recovery from acidification. The Ca2+-activated acidification required the presence of Cl- in the medium, could be blocked by DIDS, and H2DIDS and was independent of the membrane potential. The subsequent recovery from acidification was absolutely dependent on the initial acidification, required the presence of Na+ in the medium, and was blocked by amiloride. Activation of protein kinase C without a change in [Ca2+]i did not alter pHi. Likewise, in H2DIDS-treated cells and in the absence of Cl-, an increase in [Ca2+]i did not activate the Na+/H+ exchanger in UMR-106 cells. These findings indicate that an increase in [Ca2+]i was sufficient to activate the Cl-/HCO3- exchanger, which results in the acidification of the cytosol. The accumulated H+ in the cytosol activated the Na+/H+ exchanger. Kinetic analysis of the anion exchange showed that at saturating intracellular OH-, a [Ca2+]i increase did not modify the properties of the extracellular site. A rise in [Ca2+]i increased the apparent affinity for intracellular OH- (or HCO3-) of both net anion and Cl- self exchange. These results indicate that [Ca2+]i modifies the interaction of intracellular OH- (or HCO3-) with the proposed regulatory site of the anion exchanger in UMR-106 cells.
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PMID:Cytosolic pH regulation in osteoblasts. Regulation of anion exchange by intracellular pH and Ca2+ ions. 229 28

Occurrence of osteogenic sarcoma in the craniofacial bones is limited. The case presented here is only the second reported case of osteogenic sarcoma of the frontal sinus, occurring in an 80-year-old woman who presented with proptosis and developed neurologic symptoms. The radiographic appearance was of a diffuse opacity with thickening of the calvaria. Tumor tissue was adherent to the dura, and there was a fairly good initial response with the methotrexate sodium-cisplatin combination chemotherapy used, but the outcome was fatal.
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PMID:Osteogenic sarcoma of the frontal sinus. 235 Jan 35

The effects of gossypol were examined in several cell lines including hamster V79 lung fibroblasts, WB-344 rat liver oval cells, human osteosarcoma cells and LC540 rat Leydig cells. Gossypol had little cytotoxic effects in these cell lines except at high concentrations. Plasma membrane integrity was maintained in LC540 except at high concentrations of gossypol. Gossypol did not increase mutational frequency as examined by the hypoxanthine guanine phosphoribosyl transferase and Na+,K(+)-ATPase loci in V79 cells. Gossypol inhibited gap junctional intercellular communication in some but not all of the cell lines. This selectivity might be the basis for the sensitivity of certain tissues or organs to gossypol. For example, the Leydig cell, which is the component of a target organ system for toxicity, was sensitive to gossypol. Modulation of gap junctional functions might play a significant role in both pharmacological and toxicological effects of gossypol.
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PMID:The modulation of gap junctional communication by gossypol in various mammalian cell lines in vitro. 236 80

A human osteosarcoma cell line derived from cells obtained from a patient with Paget's disease is shown to synthesize and secrete bone Gla protein (BGP); (osteocalcin), a noncollagenous bone matrix protein. Using a human BGP-specific RIA, we show that the human osteosarcoma cells synthesize significant amounts of BGP without any prior induction of BGP synthesis by 1,25-dihydroxyvitamin D. After specific immunoprecipitation of poly-A+ RNA in vitro translation products with antibodies to BGP, we found that BGP is synthesized as a precursor with an apparent mol wt of 13.5K, as demonstrated on 15% sodium dodecyl sulfate-polyacrylamide gels. Finally, pulse labeling of the osteosarcoma cells with [3H]proline reveals that the cells synthesize mature BGP of 12,000 mol wt as well as a higher mol wt precursor (13,500) of the protein.
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PMID:Constitutive biosynthesis of bone Gla protein in a human osteosarcoma cell line. 241 Feb 38

In previous studies we showed that human sarcoma and melanoma cell lines synthesize and secrete into culture medium a glycoprotein, migrating in urea sodium dodecyl sulfate-polyacrylamide gel electrophoresis at Mr 140,000. It is not detected in cultures of the corresponding normal cells. Conditioned medium of the melanoma cell line HMB-2, producing among the cell lines tested the largest amounts of this glycoprotein, has now been used as a source for purification of the protein. NH2-terminal amino-acid sequence determination of the purified glycoprotein showed that it is identical to human alpha 2-macroglobulin (alpha 2M). Rabbit antibodies raised against the glycoprotein specifically reacted in immunoblotting and immunodiffusion tests with alpha 2M present in human plasma. Likewise, these antibodies immunoprecipitated from the conditioned media of 35S-methionine-labelled melanoma and osteosarcoma cell lines the protein which had a molecular weight corresponding to alpha 2M. alpha 2M was also synthesized and secreted by 2 strains of fetal lung fibroblasts but not by fetal skin fibroblasts or adult skin fibroblasts autologous to the osteosarcoma cell line.
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PMID:Human tumor cells synthesize and secrete alpha-2-macroglobulin in vitro. 241

A clonal line of osteoblastic cells from a rat osteogenic sarcoma (UMR 106-06), known to possess parathyroid hormone (PTH)-responsive adenylate cyclase, has been shown to increase its rate of K+ uptake mediated by a Na+/K+ pump after exposure to the hormone. The increase in pump activity was not associated with significant changes in K+ efflux or Na+ influx and would therefore be expected to alter intracellular levels of both Na+ and K+. The maximal (75%) increase in pump activity was noted at a PTH concentration of 100 micrograms/l and half-maximal stimulation at 1.9 micrograms/l. The effect appeared to be independent of the adenylate cyclase system, since a synthetic peptide antagonist of PTH activation of adenylate cyclase failed to prevent stimulation of the Na+/K+ pump. Similarly, prostaglandin E2, an alternative agonist of adenylate cyclase in these cells, had no effect on the Na+/K+ pump. This novel action of PTH on monovalent cation transport in osteoblast-like cells should provide a clearer insight into the mechanisms of hormone-induced bone resorption.
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PMID:Parathyroid hormone stimulation of the Na+/K+ pump in rat clonal osteosarcoma cells. 243 Oct 89


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