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)

BK virus (BKV), a human papovavirus, was inoculated iv into 3-week-old Syrian golden hamsters. Between 2 1/2 and 9 months after inoculation, 82% of the animals developed tumors. The induced neoplasms were ependymoma, carcinoma of the pancreatic islets, osteosarcoma, adenocarcinoma, angiosarcoma, angioma, lymphoma, and seminoma. Hypersecretion of insulin, glucagon, C-peptide, and calcitonin was detected in tumors of pancreatic islets. BKV etiology of tumors was supported by the following evidence: 1) No tumors with BKV-specific markers appeared in animals given injections of buffer, animals inoculated with BKV neutralized by anti-BKV-specific serum, or uninoculated controls; 2) BKV tumor (T) antigen was detected by immunofluorescence and complement fixation tests in tumors of animals inoculated with infectious BKV and in transplanted tumors; 3) antibodies to BKV T-antigen were detected in sera of animals bearing primary or transplanted tumors; 4) BKV could be activated by Sendai virus-mediated fusion of neoplastic cells with susceptible Vero cells; and 5) no endogenous hamster oncornaviruses were found in tumors.
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PMID:Ependymomas, malignant tumors of pancreatic islets, and osteosarcomas induced in hamsters by BK virus, a human papovavirus. 21 Dec 43

Histological and biochemical changes during calcitonin treatment have been studied in 15 patients with Paget's disease of bone. For each patient, osteoclast counts were made by the same observer on serial needle biopsies of diseased bone from the posterosuperior iliac spine. Serial estimations were also made of the serum alkaline phosphatase and urinary hydroxyproline excretion. A total of 66 biopsies was examined (ranging from two to seven per patient). Osteoclast populations and the biochemical measurements were log normally distributed. During calcitonin treatment there was a statistically significant decrease in: (1) the total osteoclast count per square millimetre; (2) the number per square millimetre of osteoclasts in resorption cavities on the trabecular surface; (3) the relative proportion of osteoclasts sited in resorption cavities compared with total osteoclasts; (4) the serum alkaline phosphatase level; (5) 24-hour urinary hydroxyproline excretion. On stopping treatment there was a statistically significant increase in all of these histological and biochemical values except that the proportion of osteoclasts in resorption cavities remained low. The trabecular cement line pattern remained abnormal during and after treatment in all biopsies examined, and complete suppression of osteoclast activity was not observed. One of the patients developed a Paget's osteosarcoma while on calcitonin therapy.
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PMID:Effect of calcitonin treatment on osteoclast counts in Paget's disease of bone. 74 91

The results of two experiments are reported in which the formation of an osteosarcoma was induced in mice by the intraosseous injection of Moloney's virus. In the first group of fifty mice, a complete diaphyseal fracture was carried out nine days later at the site of the tumour. In the second group of 200 mice, a partial fracture was produced at the time of injection so that immobilisation was assured. The effects of cyclophosphamide and calcitonin administration were also studied in this group. The course of the repair processes of the bone was studied in both groups, and showed that, even in the presence of an osteosarcoma, these begin and can reach completion, though obstructed and delayed by the tumour.
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PMID:A study of the development of fracture callus in the presence of an experimentally induced osteosarcoma. 107 75

The UMR 106-06 rat osteosarcoma osteoblast-like cell line possesses calcitonin (CT) receptors in addition to expressing PTH receptors and a highly osteoblast-like phenotype, and may represent an intermediate developmental stage between early osteoblast precursors and mature osteoblasts. Therefore, we examined the effects of CT and PTH on second messenger generation and osteoblastic function in these cells. In UMR-106-06 cells, 10-1000 nM CT produced a dose-dependent stimulation of intracellular free calcium concentration ([Ca2+]i), which reached a plateau between 2-3 min. This stimulatory effect was abolished in the absence of extracellular Ca2+ ([Ca2+]o) and was mimicked by forskolin and (Bu)2cAMP. One hundred nanomolar CT also produced a slight but significant increase in inositol triphosphate production (13%, P less than 0.05) but did not produce a rapid, transient increase in [Ca2+]i. In contrast, PTH produced a rapid, transient increase in [Ca2+]i, which reached a maximum within 30 sec. This stimulatory effect of PTH on [Ca2+]i signal was dose-dependent and accompanied by a parallel stimulation of inositol triphosphate production. PTH, forskolin, and (Bu)2cAMP all produced a marked dose-related suppression of both DNA and collagen synthesis, which paralleled their stimulatory effects on intracellular cAMP levels. In marked contrast, CT only minimally reduced DNA and collagen synthesis despite producing comparable increases in intracellular cAMP. One hundred nanomolar CT also stimulated alkaline phosphatase specific activity by 33% (P less than 0.05). Thus, CT stimulates cAMP, [Ca2+]i, and inositol phosphate second messengers in UMR 106-06 cells. However, in contrast to other agents which elevate intracellular cAMP levels, CT does not suppress DNA synthesis. These results suggest that the linkage of CT receptor second messengers to effects on cell function differ from those of PTH and/or that CT may produce additional second messenger(s) which antagonize the antiproliferative effect of increased cAMP levels in UMR-106-06 cells.
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PMID:Effects of calcitonin on 3',5'-cyclic adenosine monophosphate and calcium second messenger generation and osteoblast function in UMR 106-06 osteoblast-like cells. 130 38

Parathyroid hormone (PTH), a major regulator of mineral ion metabolism, and PTH-related peptide (PTHrP), which causes hypercalcemia in some cancer patients, stimulate multiple signals (cAMP, inositol phosphates, and calcium) probably by activating common receptors in bone and kidney. Using expression cloning, we have isolated a cDNA clone encoding rat bone PTH/PTHrP receptor from rat osteosarcoma (ROS 17/2.8) cells. The rat bone PTH/PTHrP receptor is 78% identical to the opossum kidney receptor; this identity indicates striking conservation of this receptor across distant mammalian species. Additionally, the rat bone PTH/PTHrP receptor has significant homology to the secretin and calcitonin receptors but not to any other G protein-linked receptor. When expressed in COS cells, a single cDNA clone, expressing either rat bone or opossum kidney PTH/PTHrP receptor, mediates PTH and PTHrP stimulation of both adenylate cyclase and phospholipase C. These properties could explain the diversity of PTH action without the need to postulate other receptor subtypes.
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PMID:Expression cloning of a common receptor for parathyroid hormone and parathyroid hormone-related peptide from rat osteoblast-like cells: a single receptor stimulates intracellular accumulation of both cAMP and inositol trisphosphates and increases intracellular free calcium. 131 66

The effect of four different neuropeptides and norepinephrine (NE) on cyclic AMP formation in four different osteoblastic cell lines and in isolated neonatal mouse calvarial bone cells has been examined. In the rat osteosarcoma cell line UMR-106-01, vasoactive intestinal polypeptide (VIP, 0.001-1 microM), calcitonin gene-related peptide (CGRP, 0.3-30 nM), and NE (0.1-300 microM), but not neuropeptide Y (NPY, 0.001-1 microM) or substance P (SP, 0.1-10 microM), caused a dose-dependent stimulation of cyclic AMP formation. The stimulatory effects were synergistically potentiated by forskolin (0.1-3 microM). The effects of NE and VIP were time dependent, with an optimal effect seen at 5 minutes. The amount of cyclic AMP accumulated in cells stimulated with NE and VIP was in the same range. The amplitude of the cyclic AMP response induced by CGRP was smaller than that caused by VIP and NE. In the human osteosarcoma cell line Saos-2, NE (0.1 microM) and VIP (0.3 microM) stimulated cyclic AMP formation, and the effect was synergistically potentiated by forskolin. In the absence of forskolin, no effect of CGRP (30 nM) could be seen in the Saos-2 cells, but in the presence of forskolin (3 microM) a stimulatory effect was observed. SP and NPY did not change basal cyclic AMP levels in Saos-2 cells. In the osteoblastic osteosarcoma cell line of rat, ROS 17/2.8, NE (0.1 microM) caused a significant stimulatory action on cyclic AMP formation that was synergistically potentiated by forskolin (3 microM), VIP, CGRP, and SP did not affect the cellular content of cyclic AMP in ROS 17/2.8.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neuroendocrine regulation of cyclic AMP formation in osteoblastic cell lines (UMR-106-01, ROS 17/2.8, MC3T3-E1, and Saos-2) and primary bone cells. 138 76

Authors report on the results of treatment of 52 primary and 16 secondary aneurysmal bone cysts (ABC). ABC grow rapidly; 84% of them have already destroyed more than the half of the bone width at recognition. En bloc resection is preferred when the ABC is growing superficially and eccentrically and more than half of the bone width is intact. Careful curettage and bone grafting still remains the surgical method of choice in the majority of cases, when the ABC is more destructive and affects the subchondral bone of the joints. Segmental resection is only indicated when removal of the affected bone does not influence the function of the extremity. Superselective embolization of the cyst was performed in seven cases with excellent results. This method is suggested for ABC in certain locations inaccessible to surgical intervention, e.g., the pelvis, or to avoid excessive bleeding in hypervascularized tumors. In one case, however, an incomplete rebuilding of the ABC could only be achieved by the administration of calcitonin. The 16 cases of secondary ABC were observed mostly in association with osteoblastomas, giant-cell tumors, and osteosarcomas. The incidence of the secondary ABC was 23% in the whole ABC group but not more than 2-4% among the osteosarcomas and giant-cell tumors. Secondary ABC may confuse the histological and clinical diagnoses and that, especially in cases of osteosarcoma, may have fatal consequences.
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PMID:Aneurysmal bone cyst. A review of 52 primary and 16 secondary cases. 144 39

The osteoinductive effects of bone morphogenetic protein (BMP, derived from murine osteosarcoma) were studied with regard to its use combined with beta-tricalcium phosphate (beta-TCP). BMP and beta-TCP were molded into pellets by the "pressure method", originated by us and transplanted to ddY mice. Control mice received interdorsal muscular implantations of either the BMP or beta-TCP pellets. The animals were sacrificed 1, 2 and 3 weeks after grafting, for radiological, histochemical, and ultrastructural observations. The BMP-beta-TCP compound pellets induced faster cartilage and bone formation, whereas these activities were slower when pellets made solely of BMP were used. The beta-TCP pellets demonstrated no osteoinductive properties. Observations revealed two types of beta-TCP resorbing multinuclear giant cells. One was osteoclastic, expressing calcitonin receptors, having numerous mitochondria and ruffled border-like structures; the other was not osteoclastic in nature. In animals grafted with the compound pellets, a great number of osteoclastic cells gathered on the pellets, much earlier than those grafted with the pellets made of BMP alone. Then, osteoblastic bone formation over the cement lines followed an osteoclastic resorption of both beta-TCP and newly formed bone. In contrast, BMP induced few osteoclastic cells, resulting in slower bone coupling. Furthermore, the faster bone formation induced by the compound pellets seemed to be associated with the presence of beta-TCP. Porous by nature, beta-TCP would entrap BMP within its micropores, and thus, the intrinsically diffusible BMP is retained and its action consequently prolonged. In addition, the compound pellet offered increased surface contact between BMP and mesenchymal cells. Therefore, BMP-beta-TCP compound pellets induce cartilage and bone formation more rapidly than does BMP alone.
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PMID:Enhanced osteoinduction by intramuscular grafting of BMP-beta-TCP compound pellets into murine models. 158 74

Parathyroid hormone (PTH) and PTH-related protein (PTHrP) act via PTH receptors in bone to stimulate bone resorption. Bone resorption is also stimulated by certain cytokines, which are produced in bone and bone marrow. The effects of such cytokines on the PTH-receptor system were studied in the osteoblast-like osteosarcoma cell line UMR 106-06. 125I-labelled PTHrP-(1-84)-peptide bound specifically to the cells, and PTHrP-(1-34) and -(1-84) competed with equimolar affinity for binding to UMR 106-06 cells. The specific binding of 125I-PTHrP-(1-84) could be completely blocked by PTH. Therefore 125I-PTHrP-(1-84) bound to a classical receptor in UMR 106-06 cells. Preincubation for 3 days with either tumour necrosis factor alpha (TNF alpha) or retinoic acid (RA) both decreased the specific binding of 125I-PTHrP-(1-84) to about 40% of control levels. These effects were specific for PTH binding, since there was little effect on 125I-salmon-calcitonin binding. Both TNF alpha and RA required 24 h exposure to cells to produce a measurable effect. The decrease in 125I-PTHrP-(1-84) binding was due to a reduced number of binding sites, with little apparent change in affinity. Half-maximal effects were seen with 1 ng of TNF alpha/ml, whereas 1 microM-RA was needed to observe the loss of PTH receptors. Combinations of RA and TNF alpha produced a greater effect than that of either agonist alone. The loss of PTH receptors was accompanied by a specific loss of PTH-stimulated cyclic AMP production. Preincubation with TNF alpha increased the basal plasminogen activator (PA) activity in the cells and decreased the amplitude of the response of PA activity to PTH compared with control cells. Furthermore TNF alpha decreased sensitivity to PTH (50% stimulation of PA activity with 0.1 nM-PTH in control cells versus 50% stimulation with 0.3 nM-PTH in TNF alpha-treated cells). In contrast, TNF alpha pretreatment increased the amplitude of the response of PA activity to calcitonin, whereas sensitivity to calcitonin was not altered. These data are consistent with a specific down-regulation of PTH receptors in osteoblast-like UMR 106-06 cells after exposure to TNF alpha or RA. The loss of PTH receptors is accompanied by a decreased responsiveness to PTH, as measured with the PA system in these cells. A loss of PTH receptors could modulate PTH responses in osteoblasts, either in the local control of bone formation and resorption, or in pathological conditions such as humoral hypercalcaemia of malignancy.
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PMID:Specific down-regulation of parathyroid hormone (PTH) receptors and responses to PTH by tumour necrosis factor alpha and retinoic acid in UMR 106-06 osteoblast-like osteosarcoma cells. 166 Jul 13

Proteolytic enzymes acting at physiologic pH (neutral proteases) are involved in both the formation and modeling of new bone and the remodeling of mature bone. In endochondral ossification systems such as growth-plate calcification, fracture healing, osteophyte formation, and demineralized bone matrix-induced osteogenesis, neutral proteases are predominantly involved in modifying proteins and proteoglycans in the extracellular matrix in preparation for calcification. These enzymes are of low molecular weight (below 30,000 Mr), are poorly charged, metal ion dependent, and appear to become active only after being released from chondrocytes. These neutral proteases may be distributed to the extracellular matrix in association with matrix vesicles that are derived from chondrocyte plasma membranes. A similar mechanism of calcification may also exist during malignant osteogenesis in an osteosarcoma; however, the cell producing the neutral protease in this lesion is the osteoblast and the matrix being synthesized is osteoid. In remodeling bone, osteoblasts secrete neutral collagenase (as an inactive enzyme) and produce not only additional proteases capable of activating the collagenase but also a collagenase inhibitor. Osteoblast collagenase or neutral protease may act to remove unmineralized osteoid from bone surfaces, thus facilitating its subsequent degradation by osteoclasts. The production of all these factors by osteoblasts appears to be regulated by calciotropic hormones (e.g., parathyroid hormone, 1,25-dihydroxyvitamin D, and calcitonin), possibly in a concerted fashion. Other possible functions of neutral proteases involve direct actions on cells or on specific molecules (growth factors) residing in the extracellular matrix.
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PMID:Neutral proteases in regenerating bone. 184 59


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