Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

5,5-diphenylhydantoin (Phenytoin, PHT), a widely used anticonvulsant, is also a vitamin K antagonist and disrupts bone metabolism, leading to osteomalacia. The vitamin K-dependently synthesized protein, osteocalcin, has been implicated as a key regulatory protein in bone resorption. The purpose of the present study was to determine whether PHT had an effect on osteocalcin secretion. Cells were grown to confluence in Ham's F-12 nutrient mixture, and treated with 1,25 (OH)2 vitamin D3 (2.6 microM to 2.6 pM) or PHT (5-100 micrograms/mL) for either 24 or 48 h of pretreatment. The media were then discarded, replaced with fresh media and test reagents, and quantitated for osteocalcin by radioimmunoassay at 0, 4, and 8 h secretion time points. Results were statistically analyzed by the Student's two-tailed t test. Controls showed a nearly linear secretion rate of osteocalcin, reaching 8-9 ng/10(6) cells by 8 h. Vitamin D3 (2.6 nM) maximally stimulated secretion nearly two-fold after 24 or 48 h of pretreatment in comparison to controls. PHT alone (25-100 micrograms/mL) exerted an inhibitory effect, which appeared dose-dependent and was most evident at 4 and 8 h. PHT (50 micrograms/mL) had a significant effect, in the presence of a range of vitamin D3 concentrations (2.6 microM to 2.6 pM), after 48 h of pretreatment. A maximal PHT dose of 100 micrograms/mL had no effect on either the viability or the numbers of cultured cells. These data indicate that PHT affects osteocalcin secretion from osteoblastic rat osteosarcoma (ROS 17/2.8) cells.
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PMID:Phenytoin affects osteocalcin secretion from osteoblastic rat osteosarcoma 17/2.8 cells in culture. 225 8

Aluminum-induced osteomalacia is a frequent complication observed in patients on maintenance hemodialysis. However, it is not known whether there are direct effects of aluminum on osteoblasts, or alternatively, whether the observed changes are due to changes in PTH or other factors. We sought to determine the effect of micromolar levels of aluminum on osteoblasts using a well-defined cell line derived from a 32P induced osteosarcoma of rat, UMR 106-01, which is alkaline-phosphatase positive, responds to PTH, and synthesizes type I collagen. Aluminum exposure was controlled using tissue culture media with [Al ] less than 1 microgram/liter (40 nM), produced by precipitation of aluminum salts at pH 8.5. The effect of defined [Al ], from 20 to 800 micrograms/liter (0.7 to 30 microM), was then determined by adding back aluminum while measuring DNA and protein synthesis. We found that aluminum depressed DNA synthesis, as determined by 3H-thymidine incorporation, by 60%, with half maximal effect at 20 micrograms/liter (740 nM) in cells at a density of 20,000/cm2. Alternatively, protein synthesis, as determined by 3H-leucine incorporation, did not decline, and in some cases increased. However, qualitative analysis of matrix proteins produced with and without 800 micrograms/liter (30 mM) [Al ] showed no differences. Direct measurements of cell number and protein synthesis confirmed these findings. Al does not alter the PTH-induced cAMP response of these cells. Thus, aluminum has a direct effect on cell division, and probably on protein synthesis, in this osteoblast-like cell line. These effects occur at levels of aluminum below those commonly contaminating tissue culture media, and thus are seen reproducibly only in media of defined [Al ].(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Micromolar aluminum levels reduce 3H-thymidine incorporation by cell line UMR 106-01. 254 94

Tumour extracts from two patients with humoral hypercalcaemia of malignancy contained material which stimulated adenylate cyclase in chick renal membranes and in rat osteosarcoma cells. Adenylate cyclase-stimulating activity in each system was inhibited by a specific parathyroid hormone (PTH) antagonist. Studies in two HPLC systems suggested that the adenylate cyclase-stimulating factors extracted from these tumours differed from each other and from synthetic human parathyroid hormone 1-34. The presence of similar PTH-like adenylate cyclase stimulating material(s) in oncogenic osteomalacia suggests that adenylate cyclase stimulating factor(s) may not be the direct or the sole cause of hypercalcaemia.
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PMID:Humoral hypercalcaemia of malignancy: report of two further patients with biochemical studies on tumour extracts. 301 3

Hypertrophic osteoarthropathy and hypophosphatemic osteomalacia are both associated with neoplasm and unusual clinical syndromes. Although the etiologies of these conditions are unknown, their clinical courses are interesting, so we are reporting two cases of these conditions separately. Case 1: A 20-year-old man had an osteogenic sarcoma originating in the 2nd thoracic vertebra which was developing in the mediastinal region. He had complained of numbness and swelling in the left arm and of clubbing of the fingers of both hands. A chest radiograph showed a billiard-ball-sized, round opacity in the left upper mediastinal region. Periosteal new bone formation was demonstrated symmetrically in both humeri, radii, ulnae, femurs, tibiae, fibulae and metacarpals. Case 2: A 30-year-old man had complained of lower back, hip, knee and ankle pain and muscle weakness of five years' duration and was admitted to the National Yokosuka Hospital. Surum phosphorus was 0.7 mg/dl, alkaline phosphatase was 24.9 K.A. and glucosuria was noted. He had a fibrous xanthoma on the right thigh, and after removal of the tumor, his symptoms improved dramatically and pertinent laboratory data returned to normal. However, ossification of the ligaments of the spine subsequently developed.
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PMID:[Hypertrophic osteoarthropathy and hypophosphatemic osteomalacia associated with tumor]. 345 94

A case of vitamin D resistant hypophosphatemic osteomalacia associated with osteosarcoma of the mandible is presented. The patient complained of lumbar, knee and foot pain and muscle weakness of two years' duration. Serum phosphorous was 1.0-1.6 mg/dl, tubular reabsorption of phosphorus was 47 to 58%, TmPO4/GFR was o.7-1.2 mg/dl. Aminoaciduria was noted. Bone biopsy confirmed the diagnosis of osteomalacia. He partially responded to the treatment with 1 alpha()H) D3 and sodium phosphate. After removal of sarcoma of the mandible, symptoms remitted and pertinent laboratory data became normal except serum alkaline phosphatase for more than one year without treatment. It is suggested that an impaired response of the tubule and bone to active vitamin D3, caused in some way by the osteosarcoma might be one of the causes of osteomalacia in this case.
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PMID:Vitamin D resistant hypophosphatemic osteomalacia associated with osteosarcoma of the mandible: report of a case. 627 44

Oncogenic osteomalacia is an unusual and rare clinicopathologic syndrome characterized by mesenchymal tumors that apparently produce osteomalacia and biochemical abnormalities consisting of hypophosphatemia, normocalcemia, and increased levels of alkaline phosphatase. We collected from the Mayo Clinic files and from our consultation files the records for 17 cases of osteomalacia associated with bone lesions. There were five cases of fibrous dysplasia, three of hemangiopericytoma, and two of phosphaturic mesenchymal tumor. There was one case each of osteosarcoma, chondroblastoma, chondromyxoid fibroma, malignant fibrous histiocytoma, giant cell tumor, metaphyseal fibrous defect, and hemangioma. In this study we can figure out that the most common characteristic histologic features of our cases were hemangiopericytomatous vascular proliferation, fine lace-like stromal calcification, and stromal giant cells. In most of the cases, the clinical and biochemical symptoms and signs resolved soon after complete resection of the lesion. When the lesion recurred or metastasized, the symptoms and signs also recurred.
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PMID:Oncogenic osteomalacia: a clinicopathologic study of 17 bone lesions. 784 76

Oncogenic osteomalacia is a condition where renal phosphate wasting occurs causing defective mineralisation, in the presence of a tumor. Cultures of cells were established from a hemangiopericytoma resected from a patient with oncogenic osteomalacia. Conditioned media from the cells inhibited phosphate uptake in opossum kidney cells and stimulated of cAMP in rat osteosarcoma cells, a standard parathyroid hormone (PTH)-like assay. This cAMP stimulation was suppressed by the PTH analogue, 3-34 bPTH and also by heat and trypsin treatment of the media. Tests of conditioned media for PTH and parathyroid hormone related protein (PTHrP) immunoreactivity were negative, however, and no hybridisation to probes for PTH, PTHrP or human stanniocalcin was detected in tumor cell RNA on Northern blot. These data support the hypothesis that tumors responsible for oncogenic osteomalacia produce a humoral substance that reduces renal phosphate reabsorption and provide evidence that the factor may act via PTH/PTHrP receptors.
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PMID:Characteristics of tumor cell bioactivity in oncogenic osteomalacia. 902 20

Oncogenic osteomalacia is a rare paraneoplastic syndrome. It is characterized by bone pain, muscle weakness, gait disturbance, fractures and skeletal deformities. Hypophosphatemia, diminished renal phosphate reabsorption, decreased 1,25 dihydroxy Vitamin D and elevated alkaline phosphatase are the biochemical hallmarks of this disorder. Most tumors are of mesenchymal origin. We report the case of a 39-year-old woman with oncogenic osteomalacia caused by osteosarcoma of the right scapula which was unrecognized for several years. She subsequently developed tertiary hyperparathyroidism after treatment with oral phosphate and Vitamin D. This case illustrates that oncogenic osteomalacia may persist for many years before the tumor is discovered. This is because the tumors are frequently very small and are in obscure locations. The uniqueness of this case is the coexistence of hyperparathyroidism and oncogenic osteomalacia. Five other cases have been reported up to date. All patients had received phosphate supplement, ranging from 10 to 14 years prior to their diagnosis. Interestingly, our patient was on the treatment for only 2 years. The proposed mechanism is that exogenous phosphate stimulates parathyroid activity through sequestration of calcium.
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PMID:Development of tertiary hyperparathyroidism after phosphate supplementation in oncogenic osteomalacia. 1085 15

Oncogenic osteomalacia (OO) is a rare paraneoplastic syndrome of osteomalacia due to phosphate wasting. The phosphaturic mesenchymal tumor (mixed connective tissue variant) (PMTMCT) is an extremely rare, distinctive tumor that is frequently associated with OO. Despite its association with OO, many PMTMCTs go unrecognized because they are erroneously diagnosed as other mesenchymal tumors. Expression of fibroblast growth factor-23 (FGF-23), a recently described protein putatively implicated in renal tubular phosphate loss, has been shown in a small number of mesenchymal tumors with known OO. The clinicopathological features of 32 mesenchymal tumors either with known OO (29) or with features suggestive of PMTMCT (3) were studied. Immunohistochemistry for cytokeratin, S-100, actin, desmin, CD34, and FGF-23 was performed. The patients (13 male, 19 female) ranged from 9 to 80 years in age (median 53 years). A long history of OO was common. The cases had been originally diagnosed as PMTMCT (15), hemangiopericytoma (HPC) (3), osteosarcoma (3), giant cell tumor (2), and other (9). The tumors occurred in a variety of soft tissue (21) and bone sites (11) and ranged from 1.7 to 14 cm. Twenty-four cases were classic PMTMCT with low cellularity, myxoid change, bland spindled cells, distinctive "grungy" calcified matrix, fat, HPC-like vessels, microcysts, hemorrhage, osteoclasts, and an incomplete rim of membranous ossification. Four of these benign-appearing PMTMCTs contained osteoid-like matrix. Three other PMTMCTs were hypercellular and cytologically atypical and were considered malignant. The 3 cases without known OO were histologically identical to the typical PMTMCT. Four cases did not resemble PMTMCT: 2 sinonasal HPC, 1 conventional HPC, and 1 sclerosing osteosarcoma. Three cases expressed actin; all other markers were negative. Expression of FGF-23 was seen in 17 of 21 cases by immunohistochemistry and in 2 of 2 cases by RT-PCR. Follow-up (25 cases, 6-348 months) indicated the following: 21 alive with no evidence of disease and with normal serum chemistry, 4 alive with disease (1 malignant PMTMCT with lung metastases). We conclude that most cases of mesenchymal tumor-associated OO, both in the present series and in the reported literature, are due to PMTMCT. Improved recognition of their histologic spectrum, including the presence of bone or osteoid-like matrix in otherwise typical cases and the existence of malignant forms, should allow distinction from other mesenchymal tumors. Recognition of PMTMCT is critical, as complete resection cures intractable OO. Immunohistochemistry and RT-PCR for FGF-23 confirm the role of this protein in PMTMCT-associated OO.
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PMID:Most osteomalacia-associated mesenchymal tumors are a single histopathologic entity: an analysis of 32 cases and a comprehensive review of the literature. 2021 75

Matrix extracellular phosphoglycoprotein (MEPE) is an extracellular matrix protein that was first detected in tumor-induced osteomalacia (TIO). Investigations in mice revealed that MEPE is expressed in bone and teeth in a maturation-dependent manner, reaching its maximum during mineralization. However, from knockout experiments, although it has become clear that MEPE might function as a mineralization inhibitor, the exact mechanism of action is still unclear. Even less is known about the regulation of MEPE in men. Therefore, we have studied the time- and maturation-dependent expression of MEPE in two human osteoblast culture systems, the osteosarcoma cell line HOS 58 and primary trabecular osteoblasts. Cells were cultured for up to 29 days, and the influence of beta-glycerophosphate (bGP), ascorbate, transforming growth factor beta (TGF-beta), BMP-2, and dexamethasone was studied. HOS 58 cells showed no significant effect on MEPE gene expression up to 5.0 mM, but a significant inhibition was revealed at 10 and 20 mM, when osteocalcin (OC) expression was maximal. Under the same conditions, primary human osteoblasts showed no effect on MEPE gene expression. However, when cultured in the presence of 5 mM beta-glycerophosphate, ascorbate, and dexamethasone for 29 days, which are similar conditions to those described by Owen in his differentiation model in rat osteoblasts, a progressive inhibition of MEPE gene expression to 20% of the maximum was observed. Increasing osteocalcin expression indicated advancing differentiation. In conclusion, in contrast to the results in mice, when MEPE was maximally expressed during mineralization, in the human system, this factor seems to be maximally active in the proliferation and early matrix maturation phase. It was, however, strongly suppressed, associated with the mineralization phase.
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PMID:Evidence of downregulation of matrix extracellular phosphoglycoprotein during terminal differentiation in human osteoblasts. 1526 10


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