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)

Type V collagen from FBJ virus-induced osteosarcoma of mice has a high content of saccharide as has been noted for type V collagens from different sources. In the present study, this collagen was found to contain significant amounts of mannose and hexosamine. Three alpha chains of this collagen were electrophoretically separated and cleaved by cyanogen bromide. The cyanogen bromide peptides, following their separation by SDS-polyacrylamide gel electrophoresis, were transferred onto nitrocellulose paper and stained with concanavalin A. Several bands derived only from alpha 3(V) stained positively, but this was inhibited by the presence of alpha-methylmannoside. Thus, at least one of these three chains appears to have an asparagine-linked oligosaccharide.
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PMID:The staining of type V collagen obtained from FBJ virus-induced osteosarcoma with concanavalin A. 345 58

The chondroblastic component of a human osteosarcoma was established as a transplantable tumor in nude athymic mice for the first time. The collagen biosynthetic production of the excised tumor was studied in organ culture. The majority of the collagen secreted in the culture media was pro-Type II as identified by diethylaminoethyl cellulose (DEAE cellulose) chromatography, gel electrophoresis, and cyanogen bromide cleavage. This system should be useful for producing large quantities of human pro-Type II collagen and for studying neoplastic cell switching of collagen synthesis.
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PMID:Synthesis of pro-collagen type II by a xenotransplanted human chondroblastic osteosarcoma. 694 12

This study characterizes the actions of insulin and parathyroid hormone (PTH) on the glucose transport system in the rat osteogenic sarcoma cell line UMR 106-01, which expresses a number of features of the osteoblast phenotype. Using [1,2-3H]2-deoxyglucose (2-DOG) as a label, UMR 106-01 cells were shown to possess a glucose transport system which was enhanced by insulin. In contrast, PTH influenced glucose transport in a biphasic manner with a stimulatory effect at 1 h and a more potent inhibitory effect at 16 h on basal and insulin-stimulated 2-DOG transport. To explore the mechanism of PTH action, a direct agonist of cAMP-dependent protein kinase (PKA) was tested. 8-Bromo-cAMP had no acute stimulatory effect but inhibited basal and insulin-stimulated 2-DOG transport at 16 h. This result suggested that the prolonged, but not the acute, effect of PTH was mediated by the generation of cAMP. Further studies with the cell line UMR 4-7, a UMR 106-01 clone stably transfected with an inducible mutant inactive regulatory subunit of PKA, confirmed that the inhibitory but not the stimulatory effect of PTH was mediated by the PKA pathway. Northern blot data indicated that the prolonged inhibitory effects of PTH and 8-bromo-cAMP on glucose transport were likely to be mediated in part by reduction in the levels of GLUT1 (HepG2/brain glucose transporter) mRNA.
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PMID:Modulation of glucose transport by parathyroid hormone and insulin in UMR 106-01, a clonal rat osteogenic sarcoma cell line. 761 14

We have examined the contribution of the mitochondrial genome to the tumorigenic phenotype expressed by human cell lines derived from an ovarian and a cervical carcinoma and from an osteogenic sarcoma. All these continuous cell lines are anchorage-independent in soft agar and form tumors in athymic nude mice. Long-term exposure of the cells to ethidium bromide, an intercalating agent which inhibits mitochondrial DNA replication, gave rise to subclones depleted of mitochondrial DNA and RNA molecules and displaying either anchorage independence or dependence. These respiratory-deficient subclones contain disorganized and enlarged mitochondria, are auxotrophic for uridine and pyruvate, and grow in vitro at a rate nearly identical or moderately slower than their respective parent. The tumor-forming ability of both anchorage-independent and -dependent cell lines was tested by s.c. and intramuscular implantation of the cells in nude mice. We found that the tumorigenic capacity was influenced by the route of inoculation. Subcutaneously, mitochondrial DNA-less cell lines are either poorly or nontumorigenic, while all but one cell line form tumors when implanted into the hind leg muscle. The relative in vivo growth rate of the parent and the mitochondrial DNA-less subclones reflects their respective in vitro rate of growth. All intramuscular tumors introduced into culture mimic the molecular and phenotypic traits of the injected cells, with the exception of the anchorage-dependent cell lines which give rise to anchorage-independent tumor cell lines. The present observations indicate that human cells without mitochondrial DNA have the capacity to proliferate and form tumors in vivo.
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PMID:Tumor-forming ability in athymic nude mice of human cell lines devoid of mitochondrial DNA. 803 12

The chemosensitivity of 43 human sarcoma tissues, including 18 osteosarcomas, 16 leiomyosarcomas and 9 liposarcomas, was compared with that of 28 adenocarcinomas of the stomach, using the in vitro succinate dehydrogenase inhibition (SDI) test. These tissues were exposed for 3 days to each antitumor drug, including adriamycin (ADM), 5-fluorouracil (5-FU), mitomycin C (MMC), cisplatin (CDDP), aclacinomycin A (ACR) and carboquone (CQ), them the cell viability was estimated based on the succinate dehydrogenase (SD) activity, determined using [3-(4,5-dimethyl-2-thiazolyl) -2,5-diphenyl-2H tetrazolium bromide] (MTT). SD activity was significantly lower in the osteosarcoma as compared to that in the adenocarcinoma, for ADM, MMC, CDDP, ACR and CQ (p < 0.01), and was higher for ADM (p < 0.05) in cases of leiomyosarcoma and for CDDP (p < 0.01) and ACR (p < 0.05) in cases of liposarcoma. The sensitivity rate was higher in osteosarcoma than in adenocarcinoma for ADM, MMC and CDDP. These findings suggest that patients with osteosarcoma will probably show a fairly good response to antitumor drugs, and that when liposarcoma or leiomyosarcoma tumors show resistance to antitumor drugs, then resection at the time of initial exploration and combined modalities, including radiation and hyperthermia, should be considered.
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PMID:Antitumor chemosensitivity differs between clinical sarcoma and adenocarcinoma tissues. 816 44

The differentiating and antitumor activities of 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3) in vitro and 1 alpha-hydroxyvitamin D3 (1 alpha(OH)D3) in vivo were studied with a human osteosarcoma cell line (OST strain). Anti-tumor activity was estimated with the use of 3-(4,5-dimethylthiazol)-2, 5-diphenyltetrazolium bromide (MTT) assay, colony-forming assay, and athymic mouse assay. The intracellular alkaline phosphatase (ALP) activity of tumor cells and production of bone Gla protein (BGP) in culture media were measured to mark osteoblastic differentiation. In addition, the combination of 1 alpha,25(OH)2D3 and cis-dichlorodiammineplatinum(II) (CDDP) was tested by the colony-forming assay and the measurement of ALP activity and BGP production for differentiating and antitumor effects. The assays revealed that 1 alpha,25(OH)2D3 exerted a dose-related, growth-inhibitory influence. In the colony-forming assay, the 1 alpha,25(OH)2D3-treated colonies were smaller than the untreated colonies. The ALP activity and the BGP production also increased in relation to dose. In the assay in athymic mice, the relative weight of tumors treated with 1 alpha(OH)D3 at 2.5 nmol/kg was significantly smaller than that of the controls, and no side effects were observed in the 1 alpha(OH)D3-treated mice. Marked tumor chondrogenesis was observed in human osteosarcoma treated with 1 alpha(OH)D3 in athymic mice. The combination of 1 alpha,25(OH)2D3 at 10(-8) M and CDDP at 2 micrograms/ml significantly enhanced both the differentiation and the growth inhibition in vitro. Our study apparently is the first demonstration that vitamin D3 metabolites have an antitumor and differentiating effect on human osteosarcoma cells in vitro and in athymic mice.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differentiating and antitumor activities of 1 alpha,25-dihydroxyvitamin D3 in vitro and 1 alpha-hydroxyvitamin D3 in vivo on human osteosarcoma. 842 14

1 alpha,25-Dihydroxycholecalciferol [1,25-(OH)2D3] is a potent differentiating agent in a variety of tumor cell lines. However, the induction of severe hypercalcemia has limited its clinical use. Several analogs have been synthesized that retain the antiproliferative differentiating effects of 1,25-(OH)2D3, but do not have the calcitropic effect of the parent compound. One such analog, 1 alpha,25(OH)2-16-ene-23-yne-26,27-hexafluorocholecalciferol (Ro24-5531), can induce differentiation in HL-60 cells and does not induce hypercalcemia in animal models. We, therefore, evaluated the effect of Ro24-5531 on a human osteosarcoma cell line, MG-63. Compared with 1,25-(OH)2D3, the analog Ro24-5531 is 10-100 times more potent as an inhibitor of MG-63 cell proliferation, as determined by [3H]thymidine incorporation and/or 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The inhibition in cell growth is accompanied by a decrease in the expression of p34cdc2 (> 4-fold), a protein critically involved in cell cycle regulation. Ro24-5531 treatment of MG-63, at a concentration of 10(-8) mol/L, induced expression of the bone differentiation markers biglycan and osteocalcin, as determined by Northern analysis. These data suggest that Ro24-5531 treatment induces growth arrest coupled with differentiation. To begin to evaluate the mechanisms by which Ro24-5531 may exert an effect, we evaluated the effect of Ro24-5531 on components of the insulin-like growth factor I (IGF-I) signaling pathway, an important regulator of normal bone growth and differentiation. The expression of IGF-binding protein (IGFBP), IGFBP-3 messenger ribonucleic acid, and protein levels are increased 20-fold after 72 h of treatment with Ro24-5531 and are associated with a marked increase in detectable binding of ligand to binding protein, as measured by RRA. These data suggest an association between Ro24-5531-induced growth arrest and increased expression of IGFBP-3.
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PMID:1 alpha, 25-dihydroxy-16-ene-23-yne-26,27-hexafluorocholecalciferol (Ro24-5531) modulation of insulin-like growth factor-binding protein-3 and induction of differentiation and growth arrest in a human osteosarcoma cell line. 855 Aug 1

The pericellular proteoglycan biglycan is among the major secretory products of osteoblasts and articular chondrocytes but the regulatory agents and signal transduction pathways that ultimately lead to alterations in biglycan gene expression are poorly defined. We report here on the transcriptional up-regulation of biglycan in MG-63 osteosarcoma cells by agents that increase intracellular cAMP levels. Transfection of these cells with biglycan promoter luciferase reporter fusion genes and subsequent treatment with forskolin or the cAMP analog 8-Bromo-cAMP resulted in an up to 3.8-fold stimulation of biglycan promoter activity. This effect could be prevented with the compound KT5720, a specific inhibitor of the cAMP-dependent protein kinase. Up-regulation of transcription is also reflected at the level of mRNA expression, since biglycan mRNA steady state levels in MG-63 cells increased approximately 2-fold after 24 hours of forskolin treatment. These data suggest that elevated levels of intracellular cAMP increase transcription from the biglycan promoter in bone cells and implicate for the first time the cAMP/protein kinase A signal transduction pathway in the regulation of biglycan gene expression.
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PMID:Biglycan gene promoter activity in osteosarcoma cells is regulated by cyclic AMP. 919 8

The effects of recombinant human bone morphogenetic protein-2 (rhBMP-2) on cell growth were studied in three human osteosarcoma cell lines, NOS-1, HuO9, and HuO-3N1; one human prostate cancer cell line, PC-3; and one human breast cancer cell line, OCUB-1M. The growth of these cell lines was not promoted by rhBMP-2 at concentrations of 50, 100, 250, and 500 ng/ml, as evaluated by colorimetric 3 (4,5-dimethyl-thiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) assay. Furthermore, the protein induced osteogenic differentiation, characterized by increased alkaline phosphatase activity, and increased production of type I collagen and gamma-carboxylated osteocalcin in NOS-1 cells. The results of this study may suggest the feasibility of using rhBMP-2 for the reconstruction of bone defects caused by malignant tumors, although the data are still preliminary and require further investigation.
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PMID:Effects of bone morphogenetic protein-2 on human tumor cell growth and differentiation: a preliminary report. 1118 Sep 25

There is now conclusive evidence that extracellular nucleotides acting via cell surface P2 receptors are important local modulators of bone cell function. Multiple subtypes of P2 receptors have been localized to bone, where their activation modulates multiple processes including osteoblast proliferation, osteoblast-mediated bone formation, and osteoclast formation and resorptive capacity. Locally released nucleotides also have been shown to sensitize surrounding cells to the action of systemic factors such as parathyroid hormone (PTH). In nonskeletal tissue recent attention has focused on one particular P2 receptor, the P2X7 receptor (previously termed P2Z), and its ability to form nonselective aqueous pores in the plasma membrane on prolonged stimulation. Expression of this receptor originally was thought to be restricted to cells of hemopoietic origin, in which it has been implicated in cell fusion, apoptosis, and release of proinflammatory cytokines. However, recent reports have indicated expression of this receptor in cells of stromal origin. In this study, we investigated the expression of the P2X7 receptor in two human osteosarcoma cell lines, as well as several populations of primary human bone-derived cells (HBDCs) at the levels of messenger RNA (mRNA) and protein. We found that there is a subpopulation of osteoblasts that expresses the P2X7 receptor and that these receptors are functional as assessed by monitoring ethidium bromide uptake following pore formation. Inhibition of delayed lactate dehydrogenase (LDH) release in response to the specific agonist 2',3'-(4-benzoyl)-benzoyl-adenosine triphosphate (BzATP) by the nonspecific P2X receptor antagonist PPADS confirmed a receptor-mediated event. After treatment with BzATP SaOS-2 cells exhibited dramatic morphological changes consistent with those observed after P2X7-mediated apoptosis in hemopoietic cells. Dual staining with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) and a P2X7-specific monoclonal antibody confirmed the induction of apoptosis in osteoblasts expressing the P2X7 receptor. These data show for the first time the expression of functional P2X7 receptors in a subpopulation of osteoblasts, activation of which can result in ATP-mediated apoptosis.
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PMID:Expression of a P2X7 receptor by a subpopulation of human osteoblasts. 1134 29


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