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)

Bone-seeking radionuclides have been used to treat bone pain due to metastatic bone disease for over 40 years. More than 10 clinical studies using radiostrontium (Sr-89) have shown benefit in about 70-80% of patients having refractory bone pain from prostate, breast and other metastatic bone cancers, with minimal hematological toxicity. Other radionuclides, such as, radiophosphate (P-32), Yttrium-90, lodine-131, Rhenium-186, have also been used. Tumor necrosis has been found within the range of beta irradiation from the surrounding shell of bone incorporating the radionuclide. New strategies using radionuclides may be able to provide more effective methods of treatment, perhaps, beyond palliation. For example, the effect of low dose continuous radiation can be potentiated by hypoxic cell sensitizers. In addition, the kinetics of radionuclide uptake and retention can be modulated to increase the dose of radiation delivered to osteoblastic metastatic lesions, such as osteosarcoma.
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PMID:A new look at radionuclides therapy in metastatic disease of bone (review and prospects). 246 20

The clinical features, radiographic and histopathological findings, treatment, and results are described for eleven patients who were managed for an extracranial osteoma at our medical center between 1980 and 1993. Ten of the patients were initially seen because of dull, aching bone pain that had been present for two weeks to thirty years. Radiographs demonstrated single or multiple homogeneous, well defined, radiodense foci with smooth round or lobulated margins. The histopathological features consistently included uniformly dense, compact, cortical-like, mature lamellar bone. The preoperative diagnosis was unclear for all patients, and osteoma was rarely considered in the differential diagnosis. For four patients, a tentative diagnosis of osteosarcoma was made, and a wide excision was carried out in two of these patients. Marginal excision with less than three millimeters of normal tissue around the lesion was performed in most patients. None of the osteomas recurred, and ten patients had relief of the pain. Awareness of the clinical, radiographic, and histopathological features of osteoma, as described, is valuable for making a differential diagnosis and for distinguishing osteomas from other lesions.
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PMID:Osteoma of the long bones and the spine. A study of eleven patients and a review of the literature. 875 9

Methotrexate is commonly used in the treatment of rheumatoid arthritis. An osteopathy has been described in children treated with methotrexate for leukaemia, consisting of bone pain, osteoporosis and fractures. Animals given short-term high-dose and long-term low-dose methotrexate have both reduced bone formation and increased resorption on histomorphometry. As patients with rheumatic diseases have numerous risk factors for osteoporosis, possible additional risk from low-dose methotrexate is of relevance to the rheumatologist. To investigate further the mechanism of osteoporosis in animals and man, in vitro studies were carried out on an osteoblast cell line, using concentrations found in patients with rheumatic disease. UMR 106 rat osteoblast-like osteosarcoma cells were incubated with methotrexate, and also with sulphasalazine, an anti-rheumatic drug with no known effect on bone, for comparison. A dose-dependent toxic effect of methotrexate on the cell line was observed using concentrations found in patients with rheumatic disease. This was not observed with sulphasalazine. The reduced bone formation observed in animals and man may be due to a direct effect of methotrexate on the osteoblast.
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PMID:Effect of methotrexate and sulphasalazine on UMR 106 rat osteosarcoma cells. 913 25

Paget's disease of bone is a common condition characterized by bone pain, deformity, pathological fracture, and an increased incidence of osteosarcoma. Genetic factors play a role in the pathogenesis of Paget's disease but the molecular basis of the disease remains unclear. Previous genetic linkage studies have mapped the rare Paget's disease-like bone dysplasia familial expansile osteolysis (FEO) to chromosome 18q21-22, and recent work has shown evidence of linkage between this locus and Paget's disease in one family. Here we studied the relationship between the 18q21-22 locus and Paget's disease in eight large multiplex families from diverse ethnic backgrounds with inherited Paget's disease. Paget's disease was inherited as an autosomal dominant trait in all families, with high penetrance by the sixth decade. Analysis of seven highly polymorphic markers from chromosome 18q21-22 showed positive summated two-point log10 odds ratio (lodscores) of +2.97 with the marker D18S42 at a recombination fraction (theta) = 0.05, and of +2.95 with the marker D18S60 at theta = 0.00, values which are close to the cut-off of +3.0, which is generally accepted as evidence of linkage. Segregation analysis of the haplotypes and formal statistical analysis using the HOMOG program provided evidence for genetic heterogeneity, however, with evidence for linkage in five families and against linkage in the remaining three families (chi square 8.82; df = 2; p < 0.025). Multipoint linkage analysis in the five linked families showed lodscores of above +3.5 across the whole susceptibility region and a maximum summated lodscore of 3.89 at the marker D18S465. In the three nonlinked families, negative multipoint results were obtained for the whole region, with lodscores below -2.0 in one family, excluding this as a candidate locus for the disease. Our studies demonstrate the importance of hereditary factors in the pathogenesis of Paget's disease and confirm evidence of linkage between Paget's disease and chromosome 18q21-22 in some families. This raises the possibility that Paget's disease and FEO may share a common molecular basis, perhaps due to different mutations in the same gene or family of genes. Data from three families did not support evidence of linkage to 18q21-22 however, indicating that Paget's disease is genetically heterogeneous and suggests the presence of at least one additional locus which remains to be discovered.
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PMID:Paget's disease of bone: evidence for a susceptibility locus on chromosome 18q and for genetic heterogeneity. 962 21

Nine dogs with primary bone tumours were treated with Samarium-153-EDTMP (Sm-153-EDTMP). Conventional treatment protocols were precluded by the size of the dogs and the owners' refusal of limb amputation. All the tumours were of the appendicular skeleton; 4 were confirmed osteosarcomas. The other 5 tumours were radiologically suspect for osteosarcoma. Bone scans were performed on all dogs using Technetium-99m-methylene diphosphonate (Tc-99m-MDP) before administration of Sm-153-EDTMP. Regions of interest were identified over the contralateral limb at the same site as the tumour and counts per pixel were recorded for the tumour and contralateral limb and expressed as a ratio. The dogs were given 1 injection of 37 MBq/kg (1 mCi/kg) of Sm-153-EDTMP intravenously. Thoracic and primary tumour site radiographs were taken at monthly or 2-monthly intervals to monitor progression of the primary tumour and search for evidence of metastasis. Two dogs showed no response to treatment, with an increase in bone pain, and were euthanased within 1 month. In 1 dog, a tumour of the scapula underwent complete involution and the dog is considered free of disease at 20 months post Sm-153-EDTMP treatment. The overall tumourcidal effect of a single dose of Sm-153-EDTMP on primary bone tumours was difficult to evaluate in this group of dogs, as, with one exception, all the primary tumours progressed over time and the dogs were euthanased. Pain control, for which Sm-155-EDTMP is used in man, was not evident, except in the dog that responded completely to treatment.
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PMID:Targeted radiotherapy with Sm-153-EDTMP in nine cases of canine primary bone tumours. 964 55

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

Paget's disease of bone is a common condition characterized by bone pain, deformity, pathological fracture, and an increased incidence of osteosarcoma. Genetic factors play a role in the pathogenesis of Paget's disease but the molecular basis remains largely unknown. Susceptibility loci for Paget's disease of bone have been mapped to chromosome 6p21.3 (PDB1) and 18q21.1-q22 (PDB2) in different pedigrees. We have identified a large pedigree of over 250 individuals with 49 informative individuals affected with Paget's disease of bone; 31 of whom are available for genotypic analysis. The disease is inherited as an autosomal dominant trait in the pedigree with high penetrance by the sixth decade. Linkage analysis has been performed with markers at PDB1; these data show significant exclusion of linkage with log10 of the odds ratio (LOD) scores < -2 in this region. Linkage analysis of microsatellite markers from the PDB2 region has excluded linkage with this region, with a 30 cM exclusion region (LOD score < -2.0) centered on D18S42. These data confirm the genetic heterogeneity of Paget's disease of bone. Our hypothesis is that a novel susceptibility gene relevant to the pathogenesis of Paget's disease of bone lies elsewhere in the genome in the affected members of this pedigree and will be identified using a microsatellite genomewide scan followed by positional cloning.
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PMID:Familial Paget's disease of bone: nonlinkage to the PDB1 and PDB2 loci on chromosomes 6p and 18q in a large pedigree. 1114 87

Paget's disease of bone (PDB) is one of the most common bone disorders in the western world. PDB is characterized by focal areas of increased osteoclastic bone resorption and bone formation, which leads to the formation of poorly structured bone. These abnormalities of bone turnover and structure predispose affected individuals to various complications including bone pain, deformity, pathological fracture, and an increased risk of osteosarcoma. One of the main mechanisms of osteoclast formation and activation involves the receptor activator of nuclear factor -kappaB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) pathway, where binding of RANKL to RANK results in the differentiation of osteoclast precursors. OPG, on the other hand, acts as an inhibitor of osteoclastogenesis by serving as a decoy receptor for RANKL. Recently, mutations in the RANK gene have been shown to cause familial expansile osteolysis, a rare bone disorder showing great similarity to PDB. We performed mutation analysis in the RANK and OPG genes in 28 PDB patients to investigate whether mutations in these genes could be responsible for PDB. Our data suggest that RANK is not directly involved in PDB in our set of patients, as no mutations in the RANK coding region could be identified and allele frequencies of RANK polymorphisms did not differ in PDB patients as compared with the random population. Also, in the OPG gene, we could not detect PDB-causing mutations. However, of the several polymorphisms identified, one (400 + 4 C/T in intron 2), showed a statistically significant increased frequency for the C allele in PDB patients, suggesting that individuals harboring this allele may be more susceptible for developing PDB.
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PMID:Evaluation of the role of RANK and OPG genes in Paget's disease of bone. 1116 49

Paget's disease of bone (PDB) is a common disorder characterized by focal areas of increased and disorganized osteoclastic bone resorption, leading to bone pain, deformity, pathological fracture, and an increased risk of osteosarcoma. Genetic factors play an important role in the pathogenesis of Paget's disease. In some families, the disease has been found to be linked to a susceptibility locus on chromosome 18q21-22, which also contains the gene responsible for familial expansile osteolysis (FEO)--a rare bone dysplasia with many similarities to Paget's disease. Insertion mutations of the TNFRSF11A gene encoding Receptor Activator of NF kappa B (RANK) have recently been found to be responsible for FEO and rare cases of early onset familial Paget's disease. Loss of heterozygosity (LOH) affecting the PDB/FEO critical region has also been described in osteosarcomas suggesting that TNFRSF11A might also be involved in the development of osteosarcoma. In order to investigate the possible role of TNFRSF11A in the pathogenesis of Paget's disease and osteosarcoma, we conducted mutation screening of the TNFRSF11A gene in patients with familial and sporadic Paget's disease as well as DNA extracted from Pagetic bone lesions, an osteosarcoma arising in Pagetic bone and six osteosarcoma cell lines. No specific abnormalities of the TNFRSF11A gene were identified in a Pagetic osteosarcoma, the osteosarcoma cell lines, DNA extracted from Pagetic bone lesions, or DNA extracted from peripheral blood in patients with familial or sporadic Paget's disease including several individuals with early onset Paget's disease. These data indicate that TNFRSF11A mutations contribute neither to the vast majority of cases of sporadic or familial PDB, nor to the development of osteosarcoma.
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PMID:Mutation screening of the TNFRSF11A gene encoding receptor activator of NF kappa B (RANK) in familial and sporadic Paget's disease of bone and osteosarcoma. 1135 98

The medical applications of lanthanides are diverse: MRI contrast agents, hypophosphatemic agents for kidney dialysis patients, luminescent probes in cell studies, and for palliation of bone pain in osteosarcoma.
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PMID:Editorial: lanthanide compounds for therapeutic and diagnostic applications. 1672 43


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