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)

Preoperative chemotherapy before limb-sparing surgery for osteosarcoma is used to reduce the size of the tumour, facilitate removal and prevent distant metastases. Fifteen patients with osteosarcoma were treated with six different protocols. Assessment of the clinical and radiological size of the lesion, of the histology of the resected specimen and of serum alkaline phosphatase levels were done. Greatest control of the tumour was obtained with the intravenous use of cisplatin, three times at intervals of three weeks before surgery, compared to the use of adriamycin or methotrexate in other protocols. Prompt surgery after preoperative chemotherapy and postoperative chemotherapy are advised.
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PMID:Evaluation of chemotherapy before limb-sparing surgery for osteosarcoma. 157 73

Transforming growth factor beta (TGF beta) and 1,25-dihydroxyvitamin D3 (1,25D3), when added simultaneously to a human osteosarcoma cell line, MG-63, induce alkaline phosphatase activity 40-70-fold over basal levels, 6-7-fold over 1,25D3 treatment alone, and 15-20-fold over TGF beta treatment alone. TGF beta and 1,25D3 synergistically increased alkaline phosphatase specific activity in both matrix vesicles and plasma membrane isolated from the cultures, but the specific activity was greater in and targeted to the matrix vesicle fraction. Inhibitor and cleavage studies proved that the enzymatic activity was liver/bone/kidney alkaline phosphatase. Preincubation of MG-63 cells with TGF beta for 30 min before addition of 1,25D3 was sufficient for maximal induction of enzyme activity. Messenger RNA for liver/bone/kidney alkaline phosphatase was increased 2.1-fold with TGF beta, 1.7-fold with 1,25D3, and 4.8-fold with the combination at 72 h. Human alkaline phosphatase protein as detected by radioimmunoassay was stimulated only 6.3-fold over control levels with the combination. This combination of factors was tested for their effect on production of three other osteoblast cell proteins: collagen type I, osteocalcin, and fibronectin. TGF beta inhibited 1,25D3-induced osteocalcin production, whereas both factors were additive for fibronectin and collagen type I production. TGF beta appears to modulate the differentiation effects of 1,25D3 on this human osteoblast-like cell and thereby retain the cell in a non-fully differentiated state.
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PMID:Effects of combining transforming growth factor beta and 1,25-dihydroxyvitamin D3 on differentiation of a human osteosarcoma (MG-63). 157 31

After demonstrating the presence of matrix vesicles in three osteosarcoma cell lines, MG-63, ROS 17/2.8 and MC-3T3-E1, we sought to determine whether two major enzymes localized to matrix vesicles, alkaline phosphatase and phospholipase A2, could be regulated by 1,25(OH)2D3 and/or TGF beta. Intravesicular calcification is probably dependent on these two enzymes. Alkaline phosphatase is essential for hydrolysis of phosphate-containing substrates and phospholipase A2 hydrolyzes diacylphosphatides in a calcium-mediated manner at lipid-aqueous interfaces leading to changes in membrane fluidity and possibly breakdown of the matrix vesicle. The 1,25(OH)2D3 induced increase of alkaline phosphatase in bone cells is localized to the matrix vesicle. TGF beta also increased alkaline phosphatase activity in two of the cell lines, MG-63 and ROS 17/2.8 but to a greater degree than 1,25(OH)2D3. Matrix vesicle alkaline phosphatase activity exhibited a greater response than that in the plasma membrane. TGF beta increased phospholipase A2 activity in both matrix vesicles and plasma membranes, therefore, no targeting was observed with respect to this enzyme. When TGF beta was combined with 1,25(OH)2D3, 1,25(OH)2D3 had no effect on phospholipase A2 and did not interfere with TGF beta stimulation of phospholipase A2 activity. When 1,25(OH)2D3 and TGF beta were combined, a tremendous synergy was observed in alkaline phosphatase specific activity in both plasma membranes and matrix vesicles with targeting to matrix vesicles. Therefore, TGF beta not only plays an important role in matrix formation and differentiation, but works in conjunction with 1,25(OH)2D3 to greatly potentiate the effects seen with 1,25(OH)2D3 alone.
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PMID:Stimulation of matrix vesicle enzyme activity in osteoblast-like cells by 1,25(OH)2D3 and transforming growth factor beta (TGF beta). 161 Dec 99

Nearly all models of skeleton, cartilage, and dentin mineralization evoke a specific role for matrix vesicles (MV) and alkaline phosphatase (ALP). Nevertheless, the mechanism underlying MV production, mineralization, and the pivotal role of ALP is largely unknown. Previous studies in this laboratory demonstrated that ALP in a human osteosarcoma cell line (SAOS-2) is of the tissue nonspecific ('bone') isoenzyme and lipid-anchored to the plasma membrane in ecto-orientation [1], thus reminiscent of osteoblasts in vivo [2]. Herein, we show that these cells spontaneously release ALP-rich structures (MVs) with the capacity to mineralize. MVs from SAOS-2 cells are 100-200 nm in diameter with characteristic trilaminar membranes. ALP in these vesicles is hydrophobic and lipid-anchored in ecto-orientation in a manner similar to the ALP in the parent SAOS-2 cells. 5'-Nucleotidase, another plasma membrane enzyme, is also abundant in MVs; adenylate cyclase is relatively deficient. Analysis of plasma membrane and MV proteins by 2-D gel electrophoresis reveals many common constituents; nevertheless, MVs contain several unique (or greatly enriched) proteins indicating that SAOS-2 MVs originate from specialized regions of the plasma membrane and are released in the same orientation as the plasma membrane. MVs, unlike plasma membrane vesicles, can cause the formation of insoluble calcium and phosphate in a manner that i) requires ALP substrates; ii) is blocked by ALP inhibition or inactivation; and iii) is not dependent on intact MVs. SAOS-2 derived MVs contain at least 3 protein kinases and their substrates. ALP does not, however, have a major role in regulating the phosphorylation state of these phosphoproteins.
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PMID:Human osteosarcoma cells spontaneously release matrix-vesicle-like structures with the capacity to mineralize. 161

A new cell line (SARG) was established from a human radiation-induced osteosarcoma (OSA). It showed an epithelial-like morphology with polymorphous and sometimes bizarre nuclei. SARG had an osteoblastic differentiation pattern: almost 100% of the cells were positive for alkaline phosphatase, type I and III collagens and osteonectin. The expression of class I HLA antigens was detectable even after 40 in vitro passages. The expression of MHC antigens was greatly increased after in vitro treatment with interferon gamma (IFN-gamma), whereas interferon alpha (IFN-alpha) and tumor necrosis factor alpha (TNF-alpha) increased the expression of class I antigens, but not of class II antigens. SARG was tumorigenic after subcutaneous injection in nude mice. Experimental metastases were never detected.
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PMID:SARG: a new human osteosarcoma cell line. Expression of bone markers and of major histocompatibility antigens. 162 59

During continuous culture with serial passage, the human osteosarcoma cell line SaOS-2 showed a time-dependent decrease in skeletal alkaline phosphatase (ALP) activity. Because this was indicative of heterogeneity, subpopulations of SaOS-2 cells were isolated from replicate low-density cultures. The subpopulations were less heterogeneous and more stable (with respect to ALP) than the parent population. ALP specific activity in the subpopulations ranged from 0.05 to 2.3 U/mg protein, and cytochemical analyses indicated multiple steady-state levels of ALP activity per cell. The amount of ALP activity in SaOS-2 subpopulations was proportional to collagen production ([3H]proline incorporation into collagenase-digestible protein; r = .84, P less than .005), and to parathyroid hormone (PTH)-linked synthesis of cyclic adenosine monophosphate (cAMP) (r = .88, P less than .01). From these data, we inferred that ALP activity in SaOS-2 cells can provide a useful index of the osteoblastic phenotype, and that ALP activity, collagen production, and PTH-linked adenylate cyclase were coordinately regulated in these osteoblast-like osteosarcoma cells (ie, selection of subpopulations for ALP activity coselected for collagen synthesis and PTH-linked synthesis of cAMP). Further comparative studies showed that micromolar fluoride concentrations stimulated cell proliferation ([3H]thymidine incorporation into DNA) in low-ALP SaOS-2 subpopulations, but not in high-ALP cells (P less than .001), and that this differential sensitivity to fluoride was associated with an inverse correlation between fluoride-sensitive acid phosphatase and ALP activities (r = -.91, P less than .001).
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PMID:Skeletal alkaline phosphatase specific activity is an index of the osteoblastic phenotype in subpopulations of the human osteosarcoma cell line SaOS-2. 165 38

Bone tumors were categorized into alkaline phosphatase (ALPase)-positive (2 ossifying fibromas, 1 benign osteoblastoma and 16 osteosarcomas) and negative (2 chondromas, 2 chondrosarcomas, 3 non-ossifying fibromas, 2 malignant fibrous histiocytomas and 6 giant cell tumors of bone) groups. Production and distribution of matrix vesicles (MVs) in the tumor tissues were examined to clarify their role in neoplastic bone formation. Four distinct types of MV were isolated primarily in ALPase positive bone tumors: empty, amorphous, crystalline and ruptured MVs. They were formed by budding off from the cytoplasmic projections of the osteoblastic tumor cells. The significance of differences in the production rate of MVs between ALPase-positive and negative bone tumors was investigated in view of the predominantly high production of MVs in ALPase-positive bone tumors. Many more mature MVs (crystalline and ruptured) were observed in the osteoblastic lesions of osteosarcoma than in the fibroblastic and MFH-like lesions, suggesting an intimate relationship with maturation and differentiation of the osteoblastic tumor cells. The above findings indicate that production of MVs is one of the diagnostic parameters for osteoblast-derived bone tumors, as well as ALPase activity, and that vesicle-induced mineralization is a major mineralization mechanism in neoplastic bone formation.
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PMID:Matrix vesicles in bone tumors. Ultrastructural analysis and their significance in neoplastic bone formation. 166 Oct 59

A newly established human osteosarcoma cell line, HS-Os-1, from an osteoblastic tumor arising in the left humerus of an 11-year-old girl was morphologically characterized in vitro and in vivo. HS-Os-1 cells in a monolayer have been maintained for more than 2 years since the initial cultivation, and were round or polygonal in shape with marked pleomorphism. Their cytoplasm was strongly positive for specific markers of osteoblasts, such as alkaline phosphatase and osteocalcin. Tumors induced in nude mice by HS-Os-1 cell inoculation at passage 12 or 23 revealed typical histological features of osteoblastic osteosarcoma, similar to those observed in the original tumor, producing prominent osteoid matrix with calcification. Ultrastructurally, HS-Os-1 cells in vitro and tumor cells in vivo showed similar well-developed, markedly dilated rough endoplasmic reticulum, polysomes and microfilaments in their cytoplasm. Additionally, many collagen fibers associated with deposition of electron-dense material were detected in the stroma featuring osteoid matrix. Thus, the HS-Os-1 cell line was shown to exhibit its osteoblastic nature in vitro and in vivo, and therefore might become an extremely useful tool for various pathomorphological investigations on human osteosarcomas.
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PMID:Morphological characterization of a newly established human osteosarcoma cell line, HS-Os-1, revealing its distinct osteoblastic nature. 167 69

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

The bone, liver, and kidney isozyme of alkaline phosphatase (ALP) has been measured in MG-63 human osteosarcoma cells after treatment with ascorbic acid (AA) and/or 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. Both compounds were required to achieve maximum ALP activity. When grown in the absence of 1,25-(OH)2D3 cells had low basal ALP activity regardless of whether media contained AA. In AA-free medium, 1,25-(OH)2D3 (10 nM) increased ALP activity fourfold. Addition of AA further increased levels of ALP activity induced by 1,25-(OH)2D3 to 10-15 times those found in -AA controls. The earliest effects of 1,25-(OH)2D3 were seen after 24-48 h, and ALP activity continued to increase for 6-8 days. AA and 1,25-(OH)2D3 had similar effects on ALP activity in ROS 17/2.8 rat osteosarcoma cells. In MG-63 cells the effects of AA and 1,25-(OH)2D3 could not be simply explained by the ability of these compounds to inhibit cell growth because another mitotic inhibitor, hydroxyurea, had a minimal effect on ALP activity. 1,25-(OH)2D3-specific induction of ALP +/- AA was totally blocked by inhibitors of protein and RNA synthesis. Maximal ALP induction was obtained when cells were plated at low density. Consistent with our previous report (Franceschi et al. 1988 J Biol Chem 263:18938-18945), 1,25-(OH)2D3 rapidly stimulated type I collagen synthesis and acid-precipitable hydroxyproline production in MG-63 cells and this stimulation was further increased by AA. These results suggest that induction of the osteoblast marker, ALP, is directly or indirectly coupled to collagen matrix synthesis and/or accumulation.
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PMID:Regulation of alkaline phosphatase by 1,25-dihydroxyvitamin D3 and ascorbic acid in bone-derived cells. 170 22


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