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)

Various agents have caused osteosarcoma in several experimental animal systems. These agents or initiators may be classified as chemicals, radiation, viruses, and miscellaneous. Zinc beryllium silicate with beryllium oxide in rabbits and FBJ virus in mice are two such initiating agents. The relevance of these animal experiments to the human situation is not known, but recent reports regarding a transmissible agent obtained from human osteosarcoma tissue suggest that a virus may be implicated. There is a theoretic indication that the various etiologic agents, including viruses, may affect the DNA of normal cells in such a way that further evolution and differentiation through several cell divisions may result in the clinical appearance of cancer.
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PMID:The etiology of osteosarcoma. A review of current considerations. 5 Aug 94

Serum copper level (SCL), serum zinc level (SZL), and SCL/SZL ratio were measured in 18 patients with biopsy-proven osteogenic sarcoma. Measurements were made on sequentially collected serum samples beginning prior to the institution of therapy and continuing periodically until documented relapse. All patients were treated by curative resection and adjuvant therapy consisting of high dose methotrexate (with leucovorin rescue) with or without BCG immunotherapy. The SCL, SZI, and SCL/SZL determinations were made using proton-induced x-ray fluorescence spectrometry. SCL was significantly elevated (p less than .0001) in the 18 patients with primary untreated osteogenic sarcoma )173 +/- 30 microgram/dl) compared with a sex and age-matched normal group (115 +/- 16 microgram/dl). A significantly different SZL was not found, however, so that an elevated SCL/SZL ratio in the osteogenic sarcoma patients was primarily due to the altered SCL. SCL and SCL/SZL did not change significantly following curative surgery or become more abnormal in those patients who developed recurrent disease. The SCL and SCL/SZL were noted to be markedly elevated in those patients receiving BCG therapy, raising concern regarding the specificity of these tests as markers of tumor activity. SCL, SZL, and SCL/SZL did not appear useful as markers of tumor activity in patients with osteogenic sarcoma.
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PMID:Serum copper and zinc measurement in patients with osteogenic sarcoma. 30 81

Serum copper levels (SCL) and serum zinc levels (SZL) were evaluated in 19 patients with sarcomas, 12 of which were osteosarcomas at various stages. Patients with primary or metastatic osteosarcoma had elevated SCL, whereas amputated osteosarcoma patients who were clinically tumor-free had nearly normal SCL. Patients with primary osteosarcoma had elevated SZL, those with metastases had depressed zinc levels, and amputated patients who were clinically tumor-free and nearly normal SZL. Thus, the ratio of SCL:SZL in metastatic osteosarcoma patients is higher than in patients with primary osteosarcoma. SCL and SZL are compared to clinical histories for selected patients. Patients with the more advanced disease and poorest prognoses had the most elevated SCL and highest SCL:SZL ratios. It appears that the determination of SCL and SZL in osteosarcoma patients may be of value in prognosis and therapy evaluation; furthermore, the ratio of SCL:SZL may be useful in discriminating between patients with primary and metastatic osteosarcoma.
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PMID:Copper and zinc levels in serum from human patients with sarcomas. 76 64

The local intra-osseous injection of double zinc beryllium silicate into the tibial or femoral epiphysis of a rabbit causes an osteogenic sarcoma in 70 p. 100 of cases. These experimental conditions make it possible to reveal early non specific radiological alterations, later on secondary alterations corresponding to the development of the sarcoma and finally to follow the spontaneous evolution of the tumor. Moreover, this experimental process of induction of an osteogenic sarcoma by means of a local intra-osseous injection is vastly better than an intra-venous injection which causes straight-away multiple visceral lesions.
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PMID:[Experimental production of bone sarcomas in the rabbit by a single local injection of beryllium]. 106 48

Trains of long-duration "action potentials" were induced by Ba2+ in osteoblast-like rat osteosarcoma cells (ROS 17/2.8), under current clamp and voltage clamp. Large depolarizing pulses were seen in microelectrode measurements at 37 degrees C following the addition of 10 or 20 mM Ba2+ to physiological bathing medium. Application of BAY K 8644 resulted in the onset of the pulses at earlier times and at more negative potentials. The pulses were blocked by nifedipine and Cd2+, but not by Ni2+. Large inward current pulses were seen in whole-cell patch technique voltage-clamp measurements at 37 degrees C in the presence of from 10 to 110 mM Ba2+ in the bathing medium. The current pulses were not seen at 22 degrees C in the presence of 110 mM Ba2+, but could be induced by BAY K 8644. These pulses were not blocked by TTX, but were blocked by nifedipine, Cd2+, Zn2+, Co2+, and by an increase in bathing [Ca2+]. The shape and frequency of the current pulses were the same as for voltage pulses under current clamp. A model that can explain these observations involves opening of L-type Ca2+ channels in a voltage-independent manner by cytosolic Ba2+ via a screening of Ca2+ from sites that produce either inactivation or a lower probability of opening in the activated state. There would be a closing of these channels at higher [Ba2+] as Ba2+ is forced onto these sites. A refractory period is also required to give repeated pulses of openings.
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PMID:Ba(2+)-induced action potentials in osteoblastic cells. 174 4

PTH activates multiple acute intracellular signals within responsive target cells, but the importance of cAMP vs. other second messenger signals in mediating different biological responses to PTH is not known. To address these questions, we developed a genetic approach to block activation of the cAMP-dependent protein kinase (PK-A) in PTH-responsive cell lines. Clonal rat osteosarcoma cells (UMR 106-01) were stably transfected with REV-I, a plasmid that directs synthesis of a mutant cAMP-resistant form of the type I regulatory subunit of PK-A. In the transfected bone cells, most of the catalytic subunits of PK-A were associated with the mutant regulatory subunit, and activation of PK-A by cAMP was correspondingly inhibited. We have characterized one such mutant (UMR 4-7) that expressed large amounts of mutant mRNA and exhibited inducible blockade of PK-A via the REV-1 metallothionein promoter. In the absence of metallothionein induction, these cells exhibited nearly normal PTH responsiveness, but after REV-1 induction by Zn2+, they were resistant to PTH-induced activation of PK-A and regulation of membrane phospholipid synthesis by both PTH and cAMP analogs. The mutant UMR 4-7 cell provides a model system in which the consequences of cAMP production by PTH or other agonists that activate adenylate cyclase in osteoblasts may be specifically inhibited by brief exposure to Zn2+. Such mutant cell lines will facilitate further investigation of the linkage between early signalling events and subsequent biological responses in the action of PTH and other agonists on target cells in bone.
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PMID:Inhibition of parathyroid hormone responsiveness in clonal osteoblastic cells expressing a mutant form of 3',5'-cyclic adenosine monophosphate-dependent protein kinase. 253 93

Human interferon was prepared by superinduction of cultures of either diploid embryonic skin and muscle cells or of the osteosarcoma cell line MG-63. The interferon so obtained was concentrated and partially purified by adsorption to controlled pore glass (CPG) beads at neutral pH and desorption by glycine-HCl buffer at pH 2. After neutralization, this interferon was applied to a column of zinc chelate which was eluted with buffers of decreasing pH. Most of the proteins eluted ahead of the interferon activity, which itself eluted in two distinct peaks. The first peak occurred in the effluent fractions around pH 5.9, and the second one in fractions around pH 5.2. The interferon found in fractions of pH 5.9 contained 5% of the original contaminating proteins. In contrast, the amount of total protein in the pH 5.2 peak was so small that it could not accurately be assayed by the fluorescamine method. Consequently, the interferon in the peak fraction was estimated to have a specific activity of about 2 x 10(9) units/mg. This material was radiolabelled and analysed by electrophoresis. A major peak of about 22000 mol. wt. with only minor contaminating proteins appeared on the autoradiographs. The total recovery of the zinc chelate chromatographical procedure was nearly 100%, and the interferon recovered from each peak behaved consistently on rechromatography. Fibroblast interferon produced by most diploid cells contained less than 10% of the variant eluting at pH 5.9. MG-63 cells and high-passage cultures of some diploid cell strains produced up to 50% of this variant.
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PMID:Purification of human fibroblast interferon by zinc chelate chromatography. 616 89

Morbidity rates for osteogenic sarcoma in the Armenian SSR within 10 years (1970-1979) were studied. The climatic, geographic and geochemical peculiarities of low and high morbidity rate regions of the Republic were compared. The rates were high in areas where the soil is rich in boron and poor in silicon, cobalt and zinc and where, as a rule, calcium level in irrigating and drinking water is high.
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PMID:[Analytical epidemiology of osteogenic sarcoma in the Armenian SSR]. 622 25

The concentrations of calcium and magnesium, and of the trace elements iron, copper, manganese and zinc were determined in the amputation specimen of a 25-year-old patient with osteosarcoma and compared with the tumor-free, normal bone tissue. Not only the concentrations of calcium and magnesium, but also those of the trace elements were significantly higher in the osseous portion of the tumor. The periosseous concentrations of trace elements iron, copper and zinc were also significantly higher in the tumor than in the normal bone tissue.
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PMID:[Mineral and trace element determination in human osteosarcoma. Case report]. 659 3

Previous studies have shown that the actions of insulin-like growth factor-II (IGF-II) in bone are determined by both its concentration and the concentrations of the IGF-binding proteins (IGFBPs). As IGFBP concentrations may be regulated not only at the level of production, but also at the level of degradation, IGFBP proteases may be an important component of the IGF-II regulatory system. In this study, we have identified IGFBP-4 and IGFBP-5 protease activity in the conditioned medium (CM) of the human osteosarcoma U2 cell line (U2OS) and untransformed normal human bone cell (HBC) derived from skull. Proteolysis of the 29-kilodalton (kDa) [125I]IGFBP-5 produced an 18- to 20-kDa fragment of IGFBP-5, and 25 kDa [125I]IGFBP-4 yielded two lower mol wt fragments in the presence of IGF-II. CM from IGF-II-treated U2OS and normal HBC cultures exhibited decreased IGFBP-5 proteolytic activity compared to control cultures. In contrast, CM from IGF-II-treated HBC cultures had increased proteolytic activity against IGFBP-4. To determine the mechanisms by which IGF-II modulates IGFBP-4 and -5 proteolytic activity, CM from control U2OS cell culture was incubated with [125I]IGFBP-4 or -5 in the presence of various concentrations of IGF-II and IGF analogs under cell-free conditions. It was found that exogenous IGF-II stimulated IGFBP-4 proteolysis, but IGF analogs that had no or extremely low affinity to IGFBP-4 failed to induce IGFBP-4 proteolysis. On the contrary, exogenous IGF-II had no effect on IGFBP-5 proteolysis in cell-free U2OS CM. Both IGFBP-4 and IGFBP-5 proteolytic activities were inhibited by aprotinin, zinc chloride, and EDTA and eluted as a single major peak between mol wt markers of 160 and 67 kDa upon gel filtration. Based on the findings that HBCs in culture produce a protease(s) capable of cleaving both IGFBP-4 and IGFBP-5 and that IGF-II can promote or inhibit proteolytic degradation of IGFBP-4 and IGFBP-5, respectively, it is proposed that IGFBP protease(s) may be an important modulator of IGF activity in bone.
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PMID:Evidence that human bone cells in culture produce insulin-like growth factor-binding protein-4 and -5 proteases. 750 11


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