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)

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

Osteosarcoma is a frequently fatal complication of Paget's disease of bone typically manifesting radiographically as a lytic lesion with soft tissue extension. A clinically worrisome, but benign manifestation of Paget's disease simulating malignancy because of an extraosseous mass is reported.
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PMID:Benign tumefactive soft tissue extension from Paget's disease of bone simulating malignancy. 1135 54

Pagetoid osteosarcoma is a complication of Paget's disease of bone. Sarcomatous transformation is most often seen in severe, long-standing Paget's disease. Familial clustering of Paget's disease has been described with apparent autosomal dominant inheritance with high penetrance by the sixth decade. Although definitive proof of the specific gene involved remains elusive, some researchers have shown loss of heterozygosity in a region of chromosome 18q in a relatively high percentage of studied patients affected with either Paget's disease alone, in Pagetoid osteosarcoma, and in uncomplicated osteosarcoma. Our patient was diagnosed with Pagetoid osteosarcoma and had a first-degree relative with history of the same. We hypothesized that our patient's tumor samples might contain a similar genetic abnormality. Our analysis of several polymorphic markers from the chromosome 18q21-22 region showed loss of maternally inherited alleles throughout the region. This finding is similar to those described previously and provides further evidence of a susceptibility region relating to this disease. This report describes a father and son, their young ages at diagnosis of Pagetoid sarcoma, the identical sites of disease involvement, and a loss of heterozygosity study illustrating the inheritance of the presumed defective gene.
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PMID:Inheritance of osteosarcoma and Paget's disease of bone: a familial loss of heterozygosity study. 1168 1

Although the prognosis and quality of life of patients with osteosarcoma were improved significantly during the past decades, the pathogenesis and etiology of this disease remain obscure. Significant interest and effort in this cancer led to the identification of numerous etiologic agents. Several chemical agents such as beryllium, viruses such as FBJ, subsequently found to contain the src-oncogene, and radiation were shown to be potent inducers of osteosarcoma. Paget's disease, electrical burn, or trauma all are thought to be other factors that may contribute to the pathogenesis. More recently, patients with hereditary diseases such as Rothmund-Thomson syndrome, Bloom syndrome, and Li-Fraumeni syndrome were found to have an increased risk of having osteosarcoma develop. During the past few years, the molecular analysis brought a wealth of new information with numerous genes that were associated with osteosarcoma and its clinical disease progression. They can be categorized into self-sufficiency in growth signals, insensitivity to growth inhibitory signals, evasion of apoptosis, limitless replicative potential, sustained angiogenesis, and tissue evasion and metastasis. Although the understanding of these processes in osteosarcoma still is incomplete, it may have the potential to significantly affect the patient care in the future.
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PMID:Etiology of osteosarcoma. 1195 94

Associated chemotherapy (adjuvant or neoadjuvant) means the association of systemic pharmacological therapy to local therapy in the treatment of tumors that, although appearing to still be localized at the time of diagnosis, have a high probability of having already given systemic micrometastases. The purpose of this kind of treatment is that of controlling the micrometastases present, even if they can't be documented, in many tumors. These neoplasms, although still apparently localized, do not achieve healing with the simple removal of the primary tumor, precisely because of the presence of these micrometastases. The current treatment of osteosarcoma (OS) commonly makes use of these therapies. There are different types of OS and they are not indicated in all associated therapies, nor do they provide the same results. We may begin by distinguishing between "high-grade" forms, which have a considerable tendency to early metastasis (about 96% of cases) and "low-grade" forms, generally characterized by local malignancy alone (about 4% of cases). Based on the site on which they occur, OS may be "primary," that is, occurring on apparently normal bone (about 95% of cases) and "secondary," that instead occur on bone that is in some way already changed (as a result of radiation, infarction, Paget's disease, etc.). Based on the site and on the staging, OS can be subdivided into forms of the limbs (75% of cases) and "forms of the axile skeleton" (25% of cases) and in forms that are "still localized" at the time of diagnosis (80% of cases) and in forms "with metastases that are documented at the onset (20% of cases). The present review only concerns primary high-grade OS of the limbs that were not metastatic on diagnosis, representing about 60% of all OS, and it is based on the experience of the Rizzoli Orthopaedic Institute where, between 1983 and 1996, a total of 731 patients were treated by neoadjuvant chemotherapy using five different protocols that were subsequently activated (Table I).
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PMID:Adjuvant and neoadjuvant chemotherapy in osteosarcoma. 1205 42

Prostate cancer coexisting with asymptomatic Paget's disease (osteitis deformans) may be difficult to stage. The skeletal lesions of both prostate cancer and Paget's disease may closely resemble each other, as appearing on imaging. A case of clinically localized prostate cancer coexisting with incidental Paget's disease is herein reported. Prostate cancer and coexisting incidental Paget's disease both need careful evaluation and close follow-up of the skeleton by imaging, because there is a risk of the former involving the skeleton at low clinical stages and low PSA serum levels, as well as the latter developing osteosarcoma.
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PMID:Prostate cancer and coexisting incidental Paget's disease--report on a case. 1223 Feb 80

The European Musculo Skeletal Oncology Society (EMSOS) has carried out a retrospective review of patients over the age of 40 years with osteosarcoma. 481 patients from 12 centres or multicentric groups were included. 42 patients had osteosarcoma arising in Paget's disease, median survival was 9 months. Patients with axial or metastatic tumours also did badly whilst 41 patients with radiation-induced osteosarcoma had a prognosis paralleling conventional osteosarcoma matched for patient age and site of the tumour. 238 patients had high grade non-metastatic osteosarcoma and had a survival of 46% at 5 years. Older patients had less chemotherapy and fared worse. Osteosarcoma in the elderly is a curable condition and warrants intensive treatment with chemotherapy and surgical resection.
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PMID:Osteosarcoma over the age of forty. 1250 46

Although osteosarcoma is a well-known complication of Paget's disease of bone, it uncommonly develops in the jaw bones. We present an osteosarcoma arising in Paget's disease of the mandible with unique features of a normal serum alkaline phosphatase level, and histologic features of telangiectatic change in the osteosarcoma and association with cemento-osseous dysplasia. Sixteen reported cases of osteosarcoma arising in Paget's disease of the jaw bones (OPJ) are also reviewed and compared to osteosarcoma arising in Paget's disease occurring in the entire skeleton (OPS) and osteosarcoma arising de novo in the jaw bones (OJ). Females are more commonly involved in OPJ in contrast to a male predominance in OPS and OJ. OPJ also has a distinctively higher percentage involving blacks compared to OPS. The prognosis of OPJ is poor, with 69% of patients dying within two years after diagnosis. Early recognition, early and aggressive treatment are important to improve the prognosis and are hence emphasized.
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PMID:Osteosarcoma arising in Paget's disease of the mandible. 1257 58


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