Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1522083 (Osteosarcoma)
 2,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Osteosarcoma arising on the periosteal aspect of bone comprises a biologically heterogeneous group of neoplasms. The group as a whole may be referred to by a single descriptive term that emphasizes their common site of origin and underscores their malignant osteogenic potential: surface osteosarcoma. Its biologic heterogeneity may be approached via a number of avenues. Detailed description of individual tumors and grading are frequently employed. However, implementation of a classification system based upon reproducible clinical, roentgenographic, macroscopic, and histologic parameters is advantageous. The suggested classification system serves to clearly define parosteal and periosteal osteosarcoma, as well as recognize unusual variants. Most important, it defines therapeutic strategy. The classification system identifies low-grade, biologically indolent forms (i.e., parosteal osteosarcoma and periosteal osteosarcoma) that are best treated by surgery alone. At the same time, it recognizes high-grade forms with significant potential for life-threatening behavior (i.e., 'dedifferentiated' parosteal osteosarcoma and high-grade surface osteosarcoma) that are best managed by multimodality therapy incorporating chemotherapy and surgery.
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PMID:Surface osteosarcoma. 188 33

An osteosarcoma of the talus occurred in a 21-year-old man. The tumor had been mistaken for a fibrosarcoma, but its osteogenic nature was demonstrated by multiple sectioning of the entire talus. Nineteen months after amputation the patient died from pulmonary metastases. Osteosarcoma in the talus seems not to have been previously reported.
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PMID:An unusual case of primary osteosarcoma of the talus. 693 30

An unusual osteogenic anaplastic carcinoma of the thyroid developed in a 68-year-old man and showed follicular and osteosarcomatous components. Seven months after surgery and 70 mCi 131I treatment, a local tumor recurrence was found and showed an intense uptake of 99mTc-MDP on the bone scan. After a second operation, pathologic and immunostaining analysis revealed no more thyroid carcinoma but only osteosarcomatous cells. Chemotherapy was ineffective and the patient died with diffuse pulmonary metastases 26 months after the diagnosis. The importance of osteogenic sarcomatous differentiation is proven by the bone scan. Osteosarcoma of the thyroid is a rare but well known tumor. Usually these tumors do not contain any cells originating from the thyroid epithelium and only comprise sarcomatous components. Ten cases of undifferentiated carcinoma of thyroid origin with osteogenic component have been reported. These tumors have been recently included in undifferentiated carcinomas in the second edition of the WHO classification. The evolution and pathologic findings favor the hypothesis of a transdifferentiation of the thyroid cell into osteogenic cells.
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PMID:Osteogenic anaplastic carcinoma of the thyroid. 811 26

Alterations in the p53 tumor suppressor gene have been implicated in the genesis and/or progression of the majority of human cancers, including osteosarcoma. Stabilization of the protein by mutation or interaction with other proteins prolongs its half-life, rendering it detectable by immunohistochemistry. Osteosarcoma is the most common primary canine bone tumor and is characterized by frequent early metastases. Multilobular tumors of bone involve primarily flat bones of the head and are low-grade malignancies with lower metastatic potential. The objectives of this study were to determine the prevalence of p53 protein overexpression in 106 osteogenic tumors of dogs using an indirect immunohistochemical method and to compare p53 overexpression between tumors with different clinical behavior. A polyclonal p53 antibody (CM-1) served as the primary antibody. Tumors were scored based upon an estimate of the percentage of tumor cells stained. Significant differences in the prevalence of overexpression were observed between osteosarcomas (72%) and multilobular tumors of bone (20%, P = 0.0020). Osteosarcomas of the appendicular skeleton had a significantly higher prevalence of p53 overexpression (84%) than did osteosarcomas of the axial skeleton (56%, P = 0.0060). Our results show that p53 tumor suppressor protein is overexpressed in the majority of canine osteosarcomas. The higher prevalence of overexpression in osteosarcomas versus multilobular tumors of bone and in osteosarcomas of the appendicular skeleton versus those of the axial skeleton suggests that alterations in p53 expression correlate with highly aggressive tumor behavior.
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PMID:p53 tumor suppressor protein overexpression in osteogenic tumors of dogs. 880 15

Osteosarcomas are malignant tumors arising from skeletal tissue and occur most frequently during childhood and adolescence. Osteosarcoma was once fatal in more than 80% of patients who presented with apparently localized disease. Chemotherapy, better surgical techniques, and improved staging methods now allow most patients to be treated with limb-sparing surgery and to be cured of their disease. However, many patients still die of metastatic disease and new approaches are still needed. The lung is the most frequent metastatic site and is treated with chemotherapy and surgical resections. Multiple resections for repeated recurrences that are limited to the lung are not uncommon but are limited by the amount of lung tissue that can be removed and become futile as recurrences become more frequent. Although a main component of initial therapy, chemotherapy has not been shown to be of benefit for recurrent disease. Direct introduction of therapeutic genes into malignant cells in vivo may provide effective treatment of solid tumors. The proposed study will use the adenoviral vector Ad-OC-E1a (OCaP1), which contains a murine osteocalcin (OC) promoter to regulate the production of the adenoviral E1a protein to allow for restricted viral replication and subsequent lysis of tumor cells. The OC promoter is developmentally regulated, with peak expression in the neonate. It functions primarily in osteoblasts found in growing bone and is highly expressed in osteogenic sarcomas. Because adenovirus is quickly cleared by normal tissues, especially the liver, systemic administration has been problematic. Although bioavailability would be decreased following exposure to the liver, the OcaP1 construct should not be hepatotoxic due to OC-restricted tissue expression of the Ela protein. Metastatic disease to the lung is a major problem and often is the cause of death for patients with osteogenic sarcoma. Treatment of pulmonary metastases could potentially be accomplished using intravenously administered OcaP1 since the material would pass through the lung prior to reaching the systemic circulation. In animal models using OC expressing tumors, OCaP1 has been effective at reducing lung metastases following intravenous injection. This protocol is a phase I/II investigational study of bolus intravenous injections of Ad-OC-E1a for the treatment of chemotherapy-refractory osteogenic sarcoma that has metastasized to the lungs. Initially patients will receive one injection of 1 x 10(10), 1 X 10(11), 1 X 10(12), or 5 x 10(12) viral particles of Ad-OC-E1a using a standard Phase I dose escalation design that studies 3 to 6 patients per dose group. After safety has been established in the first part of the trial, we will evaluate the anti-tumor activity of OCaP1. Because the matrix associated with osteogenic sarcoma may not change despite tumor necrosis, radiographic evaluation alone has not been considered sufficient to evaluate response in this disease. Histologic criteria that assess the amount of necrosis have been shown to have prognostic significance and are a key component of the anti-tumor response assessment. Therefore, the anti-tumor assessments will be carried out in patients for whom resection of their pulmonary metastases is clinically indicated. These patients will receive one injection of OCaP1 and 28 to 42 days later undergo their planned pulmonary resection. Responses will be graded using radiographic and histologic objective response criteria that are considered standard for osteogenic sarcoma. A total of 14 to 25 patients, depending upon whether objective anti-tumor responses occur, will be studied in this part of the protocol.
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PMID:A phase I/II dose escalation and activity study of intravenous injections of OCaP1 for subjects with refractory osteosarcoma metastatic to lung. 1152 47

Osteosarcoma is the most common form of primary bone cancer. In this study, we established a human osteosarcoma cell line (OS 99-1) from a highly aggressive primary tumor. G-banding karyotype analysis demonstrated a large number of clonal abnormalities, as well as extensive intercellular heterogeneity. Through the use of immunologic, molecular, and biochemical analyses, we characterized protein and gene expression profiles confirming the osteogenic nature of the cells. Further evaluation indicated that OS 99-1 cells maintain the capacity to differentiate in an in vitro mineralization assay as well as form tumors in the in vivo chicken embryo model. This cell line provides a useful tool to investigate the molecular mechanisms contributing to osteosarcoma and may have the potential to serve as a culture system for studies involving bone physiology.
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PMID:Establishment and characterization of OS 99-1, a cell line derived from a highly aggressive primary human osteosarcoma. 1824

Osteosarcoma is the most common nonhematologic malignancy of bone in children and adults. The peak incidence occurs in the second decade of life, with a smaller peak after age 50. Osteosarcoma typically arises around the growth plate of long bones. Most osteosarcoma tumors are of high grade and tend to develop pulmonary metastases. Despite clinical improvements, patients with metastatic or recurrent diseases have a poor prognosis. Here, we reviewed the current understanding of human osteosarcoma, with an emphasis on potential links between defective osteogenic differentiation and bone tumorigenesis. Existing data indicate osteosarcoma tumors display a broad range of genetic and molecular alterations, including the gains, losses, or arrangements of chromosomal regions, inactivation of tumor suppressor genes, and the deregulation of major signaling pathways. However, except for p53 and/or RB mutations, most alterations are not constantly detected in the majority of osteosarcoma tumors. With a rapid expansion of our knowledge about stem cell biology, emerging evidence suggests osteosarcoma should be regarded as a differentiation disease caused by genetic and epigenetic changes that interrupt osteoblast differentiation from mesenchymal stem cells. Understanding the molecular pathogenesis of human osteosarcoma could ultimately lead to the development of diagnostic and prognostic markers, as well as targeted therapeutics for osteosarcoma patients.
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PMID:Osteosarcoma development and stem cell differentiation. 1856 7

Immortalized cells are often used to model the behavior of osteogenic cells on orthopaedic and dental biomaterials. In the current study we compared the adhesive behavior of two osteosarcoma cell lines, MG-63 and Saos-2, with that of mesenchymal stem cells (MSCs) on hydroxyapatite (HA). It was found that osteosarcoma cells demonstrated maximal binding to fibronectin-coated HA, while MSCs alternately preferred HA coated with collagen-I. Interesting, the binding of MG-63 and Saos-2 cells to fibronectin was mediated by both alpha5 and alphav-containing integrin heterodimers, whereas only alphav integrins were used by MSCs. Cell spreading was also markedly different for the three cell types. Osteosarcoma cells exhibited optimal spreading on fibronectin, but poor spreading on HA disks coated with fetal bovine serum. In contrast, MSCs spread very well on serum-coated surfaces, but less extensively on fibronectin. Finally, we evaluated integrin expression and found that MSCs have higher levels of alpha2 integrin subunits relative to MG-63 or Saos-2 cells, which may explain the enhanced adhesion of MSCs on collagen-coated HA. Collectively our results suggest that osteosarcoma cells utilize different mechanisms than MSCs during initial attachment to protein-coated HA, thereby calling into question the suitability of these cell lines as in vitro models for cell/biomaterial interactions.
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PMID:Comparison of mesenchymal stem cell and osteosarcoma cell adhesion to hydroxyapatite. 1862 47

Osteosarcoma (OS) is the most common primary malignancy of bone. Here, we investigated a possible role of defective osteoblast differentiation in OS tumorigenesis. We found that basal levels of the early osteogenic marker alkaline phosphatase (ALP) activity were low in OS lines. Osteogenic regulators Runx2 and OSX, and the late marker osteopontin (OPN) expressed at low levels in most OS lines, indicating that most OS cells fail to undergo terminal differentiation. Furthermore, OS cells were refractory to osteogenic BMP-induced increases in ALP activity. Osteogenic BMPs were shown to upregulate early target genes, but not late osteogenic markers OPN and osteocalcin (OC). Furthermore, osteogenic BMPs failed to induce bone formation from human OS cells, rather effectively promoted OS tumor growth in an orthotopic OS model. Exogenous expression of early target genes enhanced BMP-stimulated OS tumor growth, whereas osteogenic BMP-promoted OS tumor growth was inhibited by exogenous Runx2 expression. These results suggest that alterations in osteoprogenitors may disrupt osteogenic differentiation pathway. Thus, identifying potential differentiation defects in OS tumors would allow us to reconstruct the tumorigenic events in osteoprogenitors and to develop rational differentiation therapies for clinical OS management.
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PMID:Osteogenic BMPs promote tumor growth of human osteosarcomas that harbor differentiation defects. 1883 62

Osteosarcoma is the most common malignant bone tumour, with a peak incidence in children and young adolescents, suggesting a role of rapid bone growth in its pathogenesis. The Wnt/beta-catenin pathway plays a crucial role in skeletal development and is indispensable for osteoblasts' lineage determination. Previous studies suggesting an oncogenic role for the Wnt/beta-catenin pathway in osteosarcoma were based on cytoplasmic staining of beta-catenin or the detection of one component of this pathway. However, those approaches are inappropriate to address whether the Wnt/beta-catenin pathway is functionally active. Therefore, in this study, we examined nuclear beta-catenin expression in 52 human osteosarcoma biopsies, 15 osteoblastomas (benign bone tumours), and four human osteosarcoma cell lines by immunohistochemistry. Furthermore, we modulated Wnt/beta-catenin pathway activity using a GIN (GSK3beta inhibitor) and evaluated its effect on cell growth and osteogenic differentiation. Absence of nuclear beta-catenin staining was found in 90% of the biopsies and all osteosarcoma cell lines, whereas strong nuclear beta-catenin staining was observed in all osteoblastomas. Wnt-luciferase activity was comparable to the negative control in all osteosarcoma cell lines. GIN stimulated the Wnt/beta-catenin pathway, as shown by translocation of beta-catenin into the nucleus and increased Wnt-luciferase activity as well as mRNA expression of AXIN2, a specific downstream target gene. Stimulation of the Wnt/beta-catenin pathway by GIN significantly reduced cell proliferation in the cell lines MG-63 and U-2-OS and enhanced differentiation in the cell lines HOS and SJSA-1, as shown by an increase in alkaline phosphatase (ALP) activity and mineralization. In contrast with the oncogenic role of the Wnt/beta-catenin pathway in osteosarcoma as previous studies suggested, here we demonstrate that this pathway is inactivated in osteosarcoma. Moreover, activation of the Wnt/beta-catenin pathway inhibits cell proliferation or promotes osteogenic differentiation in osteosarcoma cell lines. Our data suggest that loss of Wnt/beta-catenin pathway activity, which is required for osteoblast differentiation, may contribute to osteosarcoma development.
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PMID:Inactive Wnt/beta-catenin pathway in conventional high-grade osteosarcoma. 1989 Aug 90


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