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)

The exercretion of urinary total glycosaminoglycans (GAG) in a case of Rothmund Thomson syndrome associated with osteosarcoma was increased about 2--3 times that of normal control. Since the excretion of urinary total GAG in two cases of osteosarcoma was within normal range, the increased excretion of total GAG might be on account of the metabolic disorder of GAG in Rothmund Thomson syndrome. The prominent fractions obtained by Dowex 1 column chromatography from this syndrome were 0.75 M Fr and 1.0 M Fr, in which the major GAG were indicated to be partially degraded forms of heparan sulfate and chondroitin sulfate, respectively.
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PMID:Increased excretion of urinary glycosaminoglycans in a case of Rothmund Thomson syndrome. 28 5

Twenty patients with osteogenic sarcoma of the distal portion of the femur and the proximal portion of the tibia received chemotherapy (vincristine sulfate, methotrexate with leucovorin calcium rescue, [citrovorum factor; folinade calcium], and doxorubicin hydrochloride [Adriamycin]), followed by radical en bloc resection and prosthetic bone replacement. Histologic examination of surgical specimens obtained after chemotherapy showed variable degrees of tumor destruction and, in some cases, massive tumor necrosis, attesting to the profound effects of vigorous chemotherapy. This new therapeutic regimen, when feasible, may prove to be the treatment of choice in osteogenic sarcoma.
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PMID:Primary osteogenic sarcoma: pathologic aspects in 20 patients after treatment with chemotherapy en bloc resection, and prosthetic bone replacement. 29 12

Two protein inhibitors of metalloproteinases (TIMP) were isolated from medium conditioned by the clonal rat osteosarcoma line UMR 106-01. Initial purification of both a 30-kDa inhibitor and a 20-kDa inhibitor was accomplished using heparin-Sepharose chromatography with dextran sulfate elution followed by DEAE-Sepharose and CM-Sepharose chromatography. Purification of the 20-kDa inhibitor to homogeneity was completed with reverse-phase high-performance liquid chromatography. The 20-kDa inhibitor was identified as rat TIMP-2. The 30-kDa inhibitor, although not purified to homogeneity, was identified as rat TIMP-1. Amino terminal amino acid sequence analysis of the 30-kDa inhibitor demonstrated 86% identity to human TIMP-1 for the first 22 amino acids while the sequence of the 20-kDa inhibitor was identical to that of human TIMP-2 for the first 22 residues. Treatment with peptide:N-glycosidase F indicated that the 30-kDa rat inhibitor is glycosylated while the 20-kDa inhibitor is apparently unglycosylated. Inhibition of both rat and human interstitial collagenase by rat TIMP-2 was stoichiometric, with a 1:1 molar ratio required for complete inhibition. Exposure of UMR 106-01 cells to 10(-7) M parathyroid hormone resulted in approximately a 40% increase in total inhibitor production over basal levels.
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PMID:Purification and sequence analysis of two rat tissue inhibitors of metalloproteinases. 130 71

ROS17/2.8 cells, a cell line derived from a rat osteosarcoma, have abundant receptors for parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP). A particulate membrane fraction was prepared from these cells and it was solubilized using relatively mild conditions with digitonin (0.25%), a nonionic detergent. When radioligands of both PTH and PTHrP were incubated with this membrane fraction in the absence of any protease inhibitor at 15 degrees C, approximately 75% of these radioligands were degraded within 2 hours. This degradative activity was inhibited more effectively by bacitracin than by any of several other protease inhibitors tested. The digitonin-solubilized PTH/PTHrP receptors were radiolabeled in the presence of bacitracin using radioiodinated [Tyr36]PTHrP(1-36) amide (PTHrP(1-36)) and N-hydroxysuccinimidyl-4-azidobenzoate (HSAB), as cross-linker. When an aliquot of the reaction solution was subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and autoradiography, a broad band was observed that had an apparent molecular size of 90,000 daltons (M(r) = 90 kD). This band was no longer seen when the binding was conducted in the presence of 10(-6) M of unlabeled PTHrP(1-36), and it was decreased in density when binding was conducted in the presence of 10(-6) M of unlabeled [Nle8,18, Tyr34] bovine PTH(1-34) amide (NlePTH). The solubilized receptors retained their capacity to bind the radioligand after partial purification by wheat-germ agglutinin affinity-chromatography. The use of relatively mild detergent conditions thus offers a means to solubilize receptors that retain their capacity to bind PTH and PTHrP.
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PMID:Solubilization of functional receptors for parathyroid hormone and parathyroid hormone-related peptide from clonal rat osteosarcoma cells, ROS17/2.8. 133 76

Polyacrylamide gel electrophoresis utilizing sodium dodecyl sulfate followed by specific staining for alkaline phosphatase was accomplished using sera from patients with osteosarcoma, polyostotic fibrous dysplasia, metastatic bone tumor, and idiopathic hyper-alkalinephosphatasemia. Alkaline phosphatase activity of the sera was uniformly demonstrated at a molecular weight of 60,000. L-homoarginine more strongly inhibited the alkaline phosphatase activity than did L-phenylalanine. Alkaline phosphatase activity was markedly inactivated by heating. Regarding substrate specificity, the hydrolysis of p-nitro-phenylphosphate occurred at a lower rate than did that of phenylphosphate. By contrast, the hydrolysis of alpha- and beta-glycerophosphate occurred at a higher rate than did that of phenylphosphate. As seen from the data presented here, the serum alkaline phosphatase samples obtained from these patients with skeletal disorders have several common characteristics.
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PMID:[Identification of serum alkaline phosphatase from human bone]. 169 Jul 86

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

An activity isolated from bovine bone was previously shown to stimulate proteoglycan synthesis by several connective tissue cell lines from normal tissues (Matrigenin activity). The effect of this activity on glycoconjugate synthesis by two osteoblastic cell lines, ROS 17/2 and UMR-106, derived from rat osteogenic sarcoma, was examined after labelling of the cells with [3H]glucosamine and [35S]sulfate. The glycoconjugates from the cell layers and the media were separated by DEAE-Sephacel chromatography and the anionic glycoconjugates of the media were further analyzed by chromatography on Sepharose CL-2B and enzymatic digestion of the papain-released glycosaminoglycans. The ROS 17/2 cells secreted at least two distinct species of proteoglycan (one heparan sulfate rich and the other chondroitin sulfate rich), whereas the UMR-106 secreted primarily an anionic glycoprotein. The addition of Matrigenin activity to the ROS 17/2 cells resulted in stimulation of incorporation of radioactivity into the proteoglycan and hyaluronic acid, but in UMR-106 cultures it resulted in decreased incorporation into the anionic glycoprotein. The decrease in incorporation into the anionic glycoprotein from the medium was shown, by alkaline beta-elimination, to have occurred mainly in the oligosaccharide fraction, relative to control cultures.
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PMID:Newly synthesized glycoconjugates from two cell lines derived from rat osteogenic sarcoma: effects of Matrigenin activity from bone. 190 48

Micromolar concentrations of aluminum sulfate consistently stimulated [3H]thymidine incorporation into DNA and increased cellular alkaline phosphatase activity (an osteoblastic differentiation marker) in osteoblast-line cells of chicken and human. The stimulations were highly reproducible, and were biphasic and dose-dependent with the maximal stimulatory dose varied from experiment to experiment. The mitogenic doses of aluminum ion also stimulated collagen synthesis in cultured human osteosarcoma TE-85 cells, suggesting that aluminum ion might stimulate bone formation in vitro. The effects of mitogenic doses of aluminum ion on basal osteocalcin secretion by normal human osteoblasts could not be determined since there was little, if any, basal secretion of osteocalcin by these cells. 1,25 Dihydroxyvitamin D3 significantly stimulated the secretion of osteocalcin and the specific activity of cellular alkaline phosphatase in the human osteoblasts. Although mitogenic concentrations of aluminum ion potentiated the 1,25 dihydroxyvitamin D3-dependent stimulation of osteocalcin secretion, they significantly inhibited the hormone-mediated activation of cellular alkaline phosphatase activity. Mitogenic concentrations of aluminum ion did not stimulate cAMP production in human osteosarcoma TE 85 cells, indicating that the mechanism of aluminum ion does not involve cAMP. The mitogenic activity of aluminum ion is different from that of fluoride because (a) unlike fluoride, its mitogenic activity was unaffected by culture medium changes; (b) unlike fluoride, its mitogenic activity was nonspecific for bone cells; and (c) aluminum ion interacted with fluoride on the stimulation of the proliferation of osteoblastic-line cells, and did not share the same rate-limiting step(s) as that of fluoride. PTH interacted with and potentiated the bone cell mitogenic activity of aluminum ion, and thereby is consistent with the possibility that the in vivo osteogenic actions of aluminum ion might depend on PTH. In summary, low concentrations of aluminum ion could act directly on osteoblasts to stimulate their proliferation and differentiation by a mechanism that is different from fluoride.
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PMID:Aluminum stimulates the proliferation and differentiation of osteoblasts in vitro by a mechanism that is different from fluoride. 192 12

We showed recently that the initial peak cytosolic ionized calcium ([Ca2+]i) response to PTH (2-min exposure) is preserved relative to the cAMP response in osteoblast-like rat osteosarcoma cells (ROS 17/2.8) desensitized by 72-h exposure to PTH. We attempted in the present studies to determine the mechanisms for preservation of the [Ca2+]i response and to explore the effects of longer PTH rechallenges. The [Ca2+]i response to a 20-min perifusion with rat PTH [rPTH-(1-34)] was monitored by aequorin luminescence in both naive and PTH-desensitized ROS 17/2.8 cells. The responses of both naive and desensitized cells consisted of two phases: an initial peak, followed by an intermediate plateau that was sustained in the presence of PTH. We observed in the naive cell populations synchronous oscillations in [Ca2+]i concentration during this second phase (amplitude, 10-60 nM; frequency, 1-3/100 sec). These oscillations were maintained through extracellular calcium (EC Ca2+) entry; the initial peak was the result of Ca2+ release from intracellular stores. In desensitized cells, these two phases could not be clearly separated with respect to Ca2+ source, but, as we showed before, exhibited an enhanced dependence on EC Ca2+ entry for the response to PTH. Nevertheless, in the desensitized cells, the sustained [Ca2+]i response was diminished in magnitude and showed little oscillatory behavior. Brief exposure to neomycin sulfate, an inhibitor of phosphoinositide turnover, attenuated the PTH-induced [Ca2+]i rise in both naive and desensitized cells. Protein kinase-C activity did not appear to be required for either phase of the PTH-induced [Ca2+]i response. Exposure to cholera toxin attenuated the [Ca2+]i response to hormone in both naive and desensitized cells, more markedly in the latter. Cholera toxin treatment dramatically increased basal cAMP levels in both cell preparations; PTH-stimulated cAMP production was unchanged in naive cells, but increased nearly 4-fold in desensitized cells. We propose that the preserved PTH-induced peak [Ca2+]i rise in desensitized cells results primarily from the diminished regulation of EC Ca2+ entry by the cAMP response limb. The attenuated sustained oscillatory behavior observed in desensitized cells upon rechallenge with hormone may be the result of reduced phosphoinositide turnover and reduced Ca2+-stimulated Ca2+ release. Thus, the [Ca2+]i response to PTH in osteoblast-like cells is complex and modulable and seems to provide a number of ways to regulate intracellular metabolism under various conditions. We speculate that this plasticity of the [Ca2+]i response to PTH is related to the pleiotropic actions of the hormone on cells of the osteoblast lineage.
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PMID:Parathyroid hormone (PTH)-induced intracellular Ca2+ signalling in naive and PTH-desensitized osteoblast-like cells (ROS 17/2.8): pharmacological characterization and evidence for synchronous oscillation of intracellular Ca2+. 195 83

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


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