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At least 235 records · Page 13Linked to original sources
PubMed2000

Platelet-osteosarcoma cell interaction is mediated through a specific fibrinogen-binding sequence located within the N-terminal domain of thrombospondin 1.

Approximately 20% of patients with osteosarcoma have metastatic disease in lungs or bones at diagnosis. The requirement of platelets in hematogenous dissemination of metastatic cells is now well established. Tumor cells interact with platelets and induce platelet aggregation. In this respect, metastatic potential of tumor cells correlates with their capacity to aggregate platelets in vitro. We have previously shown that thrombospondin 1 (TSP-1) is synthesized and expressed on the surface of MG-63 osteosarcoma cells and mediates platelet-osteosarcoma cell interaction. However, active sites mimicking the function of TSP-1 during platelet-osteosarcoma cell interaction are not known. In this study, a panel of antibodies directed against the N-terminal and C-terminal domains and type 1, type 2, and type 3 repeats of TSP-1 were first used to delineate the structural requirement for the binding of osteosarcoma cell surface-associated TSP-1 to platelets. A drastic inhibition of the platelet-aggregating activity of MG-63 cells was obtained in the presence of a monoclonal antibody directed against the N-terminal domain of TSP-1. Among a series of 16 synthetic peptides spanning the whole N-terminal domain of TSP-1, only synthetic peptide N12/I encompassing amino acid residues 151-164 of the N-terminal domain of TSP-1 inhibited the platelet-aggregating activity of MG-63 cells. Electron microscopy studies showed that peptide N12/I strongly inhibited platelet-osteosarcoma cell interaction. A polyclonal antibody directed against peptide N12/I specifically bound to the surface of MG-63 cells, recognized TSP-1 and drastically inhibited the platelet-aggregating activity of MG-63 cells. In addition, peptide N12/I specifically bound to fibrinogen and inhibited TSP-1/fibrinogen interaction. Overall, our results provide evidence that a fibrinogen-binding sequence located within the N-terminal domain of TSP-1 mediates the binding of osteosarcoma cell surface-associated TSP-1 to platelet-bound fibrinogen.

Amino Acid Sequence↗
PubMed2001

Imaging findings in pseudocystic osteosarcoma.

OBJECTIVE: Our purpose was to describe four female patients with osteosarcoma whose clinical and imaging findings primarily suggested either simple or aneurysmal bone cyst. All lesions were osteolytic, intracompartmental, and expanded bone without periosteal reaction. None of the patients presented during the peak age incidence for osteosarcoma. From imaging to histologic diagnosis, the discovery of osteosarcoma ranged from 1 week to 3 years. CONCLUSION: Atypical osteosarcoma may rarely mimic simple or aneurysmal bone cyst radiologically and may show a nonmalignant rate of growth. It may be more frequently encountered in females and may not present during the peak age incidence for osteosarcoma. Microscopically, the tumors were not cystic, necrotic, or telangiectatic but were conventional osteosarcoma and osteoclast-rich osteosarcoma.

Adult↗
PubMed2000

In vitro retinoid-induced growth inhibition and morphologic differentiation of canine osteosarcoma cells.

OBJECTIVE: To determine differentiation and growth inhibition effects of retinoids on canine osteosarcoma cells. SAMPLE POPULATION: 3 osteosarcoma cell lines established from osteosarcomas in dogs. PROCEDURE: Osteosarcoma cells were incubated with various concentrations of all-trans-retinoic acid and 9-cis-retinoic acid or control medium, counted daily for 10 days, and evaluated for morphologic changes. Synthesis of DNA was measured by use of a cell proliferation ELISA. To analyze effect of retinoids on colony formation on plastic dishes, cells were cultured for 14 days, fixed, and stained; number of colonies was counted. RESULTS: In a dose-dependent manner, both retinoids induced morphologic differentiation and growth inhibition in the 3 osteosarcoma cell lines and inhibited each cell's ability to form anchorage-dependent colonies. CONCLUSION AND CLINICAL RELEVANCE: Retinoids induced differentiation of osteosarcoma cells of dogs, resulting in altered expression of their malignant phenotype. Induction of differentiation by retinoids may have potential as an adjunctive treatment for osteosarcoma in dogs.

Alitretinoin↗
PubMedDate not supplied

Studies of the RB1 gene and the p53 gene in human osteosarcomas.

We analyzed 14 native osteosarcoma tissue samples for alterations of the tumor suppressor genes RB1 and p53 on the DNA level, and as far as possible, the RNA level. Southern blot analyses concerning both tumor suppressor genes were carried out in all osteosarcomas. In two cases we could demonstrate a deletion within the RB1 gene. DNA analysis of a third osteosarcoma patient revealed a rearrangement of the p53 gene. We had the opportunity of performing corresponding northern analyses in eight native osteosarcoma specimens. The RB1 gene expression was significantly decreased or completely absent in six tumor samples. In two of these tissue probes the expression of both tumor suppressor genes was missing. We determined coexistence of decreased expression of both tumor suppressor genes in one additional case. In summary, 7/14 or 6/8 cases of osteosarcomas (including only those cases which allowed both analyses) showed RB1 gene alteration. In 3/14 or 3/8 osteosarcomas we could determine p53 gene abnormalities. This may indicate that either loss of p53 function is etiologically important only for the development of some osteosarcomas, or a major part of p53 gene mutations are subtle ones and their detection requires more sophisticated techniques, which are currently under development.

Bone Neoplasms↗
PubMed2000

[Poor prognosis of osteosarcoma of pelvis; 39 years of registration by the Netherlands Commission on Bone Tumors].

OBJECTIVE: To evaluate the results of treatment in patients with osteosarcoma of the pelvis. DESIGN: Retrospective. PATIENTS AND METHODS: Sixty-five patients with pelvic osteosarcoma registered in the files of the Netherlands Committee on Bone Tumours over 1957-1995 were reviewed. Complete information was obtained on 62 cases: 27 males and 35 females, median age was 31 years (range: 12-83). Distant metastases were present in 11 patients (stage IIIB; 18%), while 50 patients had stage IIB osteosarcoma (81%) and 1 patient stage IB osteosarcoma (2%). The results of treatment and survival were determined. RESULTS: Median survival was 14 months (2-177), the 5-year survival 15%. Distant metastases developed in 27 of 42 (64%) patients with curatively treated stage IIB osteosarcoma, with prolonged metastasis-free survival after chemotherapy treatment (p < 0.0012). Survival in patients with stage IIB pelvic osteosarcoma was better after surgical resection of the primary tumour than after no operation (p < 0.0054); (neo)adjuvant chemotherapy gave no longer survival than surgery alone (p < 0.083). CONCLUSION: The prognosis of pelvic osteosarcoma was poor, despite modern multimodality treatment regimens, including surgical resection and chemotherapy.

Adolescent↗
PubMed2001

The expression of the urokinase plasminogen activator system in metastatic murine osteosarcoma: an in vivo mouse model.

The role of urokinase plasminogen activator (uPA) in osteosarcoma is poorly understood. We examined the importance of uPA, its receptor, uPAR, and its inhibitor, PAI-1, in our in vivo model of metastatic osteosarcoma. Rodent osteosarcoma cells (UMR 106-01) were inoculated into the tibia of athymic mice. Animals were sacrificed and autopsied at 4 days to 5 weeks after inoculation. Tibiae and lungs were excised, fixed, and examined histologically and by in situ hybridization. Osteosarcoma development was associated with tibial swelling and lameness, and radiographic changes included osteolysis and new bone formation. Lung metastases developed spontaneously. In the tibial tumors, uPAR mRNA was expressed early (4 days), whereas uPA and PAI-1 mRNA increased as the tumor invaded the surrounding tissue (3 weeks). There was also an increase in the mRNA expression of the osteoblast-related genes, alpha1(I) procollagen and osteopontin, but not matrix Gla protein. Lung metastases also expressed mRNA for the uPA system and the bone-related proteins. We have produced a model of metastatic osteosarcoma, which typifies the characteristics of the human tumor. Our results suggest that the uPA system plays a role in the local aggressiveness and metastasis of osteosarcoma and, in particular, indicates a possible therapeutic role for uPAR antagonists in the treatment of osteosarcoma.

Animals↗
PubMedDate not supplied

The role of fine needle aspiration biopsy in the diagnosis and management of osteosarcoma.

We retrospectively reviewed our experience with fine needle aspiration biopsy (FNAB) in the diagnosis and management of skeletal osteosarcoma. The bi-institutional study sample involved 30 consecutive aspirates from 29 patients (28 primary tumors, 1 pulmonary metastasis, 1 local recurrence). There were 17 children and 12 adults. Two aspirates were unsatisfactory for diagnosis. Of the adequate primary osteosarcoma cases analyzed by FNAB, 24 of 26 were diagnosed as osteosarcoma. All pediatric cases were correctly interpreted as osteosarcoma and treated appropriately. There were 2 incomplete diagnoses. A secondary osteosarcoma arising within an otherwise clinically, radiologically, and histologically typical giant cell tumor (malignant giant cell tumor) was not diagnosed preoperatively on FNAB due to nonrepresentative sampling. Chronologically, the first patient with osteosarcoma analyzed by FNAB was diagnosed simply as "spindle cell neoplasm." No complications resulted from the procedure. With adequate clinical and radiologic correlation, FNAB represents a technically, easily performed, cost-effective, and accurate procedure for establishing the diagnosis of skeletal osteosarcoma. Immediate interpretation of aspirated material allows for therapy planning and oncologic consultation at the initial clinic visit.

Adult↗
PubMed1999

[Expression and regulation of p16 in osteosarcoma].

OBJECTIVE: To study the expression and regulation of p16 and related factors in osteosarcoma. METHODS: The levels of p16 protein and related factors were explored by Western blot analysis in 12 cases of osteosarcoma tissues and in cells of different phases of osteosarcoma cell line OS732. The status of p16 protein in osteosarcoma cells was revealed by immunofluorescence analysis. RESULTS: p16 protein was detected in 10 of 12 osteosarcoma tissues. pRb was found in all of the specimens, but 8 of them were hyperphosphorylated. p16 protein was the least in G1 phase. Localized in cytoplasm during G1 phase, p16 protein gathered around nuclear envelope in S phase and entered the nucleus in G2 phase. CONCLUSIONS: The expression rate of p16 protein was 83.3% in osteosarcoma tissues. The expression of p16 protein was unable to inhibit the phosphorylation of pRb in most osteosarcomas; p16 protein was extremely low in G1 phase, presumably it was sufficient to inhibit the phosphorylation of pRb, causing abnormal proliferation of the cells.

Adolescent↗
PubMed2002

Methylthioadenosine phosphorylase gene deletions are common in osteosarcoma.

PURPOSE: Methylthioadenosine phosphorylase (MTAP) is an enzyme essential in the salvage of cellular adenine and methionine synthesis. The MTAP gene is located in the 9p21 chromosomal region and its loss is frequently associated with deletion of the tumor suppressor genes p15(INK4b) and p16(INK4a). The aim of this study was to investigate the frequency of molecular alterations in MTAP in osteosarcoma. EXPERIMENTAL DESIGN: Samples from patients with high-grade osteosarcoma (n = 96) and three osteosarcoma cell lines (HOS, SaOS-2, and U2OS) were analyzed. Genomic DNA was analyzed for MTAP gene deletions by PCR, RNA expression was measured by semiquantitative reverse transcription-PCR, and the protein levels were measured by immunohistochemistry. RESULT: Deletion of at least one MTAP exon was found in 36 of 96 (37.5%) osteosarcoma patient samples and in one of the three cell lines (HOS). In all cases in which an MTAP gene deletion was observed, there was absence of detectable mRNA and protein. Furthermore, in four osteosarcoma patients, an MTAP deletion which was not evident at diagnosis was detected in subsequent tumor samples. CONCLUSIONS: The MTAP gene is commonly deleted in osteosarcoma patient samples, leading to an absence of mRNA and protein expression; these results indicate that inhibitors of de novo purine synthesis or methionine depletion may be effective as treatments for osteosarcoma patients whose tumors fail to express MTAP.

Adolescent↗
PubMed2002

Nuclear receptor agonists as potential differentiation therapy agents for human osteosarcoma.

PURPOSE: This study was designed to investigate whether nuclear receptor agonists can be used as potential differentiation therapy agents for human osteosarcoma. EXPERIMENTAL DESIGN: Four osteosarcoma cell lines (143B, MNNG/HOS, MG-63, and TE-85) were treated with proliferator-activated receptor (PPAR)gamma agonists, troglitazone and ciglitazone, and a retinoid X receptor (RXR) ligand, 9-cis retinoic acid. The proliferation and induction of apoptosis in the treated cells were assessed, as was the induction of alkaline phosphatase, a differentiation marker of osteoblasts. RESULTS: The expression of PPARgamma was readily detected in all tested osteosarcoma lines. On treatment with the PPARgamma and RXR ligands, all four osteosarcoma lines exhibited a significantly reduced proliferation rate and cell viability. Among the four lines, 143B and MNNG/HOS were shown to be more sensitive to ligand-induced apoptosis, as demonstrated by the Crystal Violet and Hoechst staining assays. Of the three tested ligands, troglitazone was shown to be the most effective in inducing cell death, followed by 9-cis retinoic acid. Moreover, a strong synergistic effect on the induction of cell death was observed when both troglitazone and 9-cis retinoic acid or ciglitazone and 9-cis retinoic acid were administered to osteosarcoma cells. Troglitazone was shown to effectively induce alkaline phosphatase activity, a well-characterized hallmark for osteoblastic differentiation. CONCLUSIONS: Our findings suggest that PPARgamma and/or RXR ligands may be used as efficacious adjuvant therapeutic agents for primary osteosarcoma, as well as potential chemopreventive agents for preventing the recurrence and metastasis of osteosarcoma after the surgical removal of the primary tumors.

Alitretinoin↗
PubMed2002

Inhibition of platelet-derived growth factor-mediated proliferation of osteosarcoma cells by the novel tyrosine kinase inhibitor STI571.

PURPOSE: Osteosarcoma is an aggressive primary bone cancer characterized by expression of platelet-derived growth factor (PDGF) and its cognate receptor. Coexpression of the growth factor and receptor suggests their role in autocrine or paracrine growth mechanisms. It has been reported previously that STI571 has specific activity in inhibiting select tyrosine kinase receptors, including PDGF and c-Kit. Osteosarcomas express low levels of c-Kit but abundant levels of PDGF receptor (PDGFR). EXPERIMENTAL DESIGN: To investigate the potential of STI571 as therapy for osteosarcoma, we studied its effects on PDGF-mediated cell growth in vitro and in an in vivo mouse model. RESULTS: PDGF acted as a potent mitogen in a dose-dependent manner in two osteosarcoma cell lines. STI571 (1.0 micro M) inhibited both PDGFR-alpha and PDGFR-beta phosphorylation and the downstream phosphorylation targets extracellular signal-regulated kinase and Akt. STI571 also inhibited PDGF-mediated growth and induced apoptosis in vitro as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and terminal deoxynucleotidyl transferase-mediated nick end labeling staining. To study the effect of STI571 alone or in combination with Taxol in an in vivo model, an osteosarcoma cell line (KRIB) was transplanted into the tibia of athymic nude mice. Mice were treated with STI571 (50 mg/kg p.o. q M-F), Taxol (8 mg/kg i.p. weekly), or STI571 plus Taxol for 6 weeks. There was no significant difference in tumor size between treatment and control mice. Aberrant signaling pathways downstream of the PDGFR in the v-Ki-ras oncogene-transformed KRIB cell line may in part explain this finding. CONCLUSIONS: Our data demonstrate that STI571 inhibits PDGF-mediated growth and leads to apoptosis of osteosarcoma cells in vitro by selective inhibition of the PDGFR tyrosine kinase. The effectiveness of STI571 in our studies suggests targeting of PDGFRs as a novel treatment for osteosarcoma.

Animals↗
PubMed2003

[Expression of multidrug resistance-associated protein 1 in osteosarcoma and its relationship with clinicopathologic characteristics].

OBJECTIVE: To detect the expression of multidrug resistance-associated protein 1 (MRP1) in human ostesarcoma and to explore its relationship with clinicopathologic characteristics. METHODS: Six normal bone specimens and 45 osteosarcomas from patients were analysed for MRP1 expression by immunohistochemistry. The expression levels of MRP1 with the clinicopathologic parameters of the patients were examined using Chisquare test. RESULTS: The expression of MRP1 was observed in 32 (71.11%) osteosarcoma specimens. More(P < 0.05) specimens expressed MRP1 in high-grade osteosarcomas(30/38, 78.95%) than in low-grade osteosarcomas (2/7, 28.57%). The correlation coefficient between expression of MRP1 and grade of pathology was 0.844. In a limited number of patients, the expression of MRP1 was not related to the the age and sex of the patients, Enneking surgical stage, osteosarcoma size, serum concentration of ALP and duration before diagnosis. No expression of MRP1 in 6 normal bone specimens was observed. CONCLUSION: MRP1 is expressed in osteosarcoma and its expression is positively correlated with the malignancy of osteosarcoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2003

A fully human antimelanoma cellular adhesion molecule/MUC18 antibody inhibits spontaneous pulmonary metastasis of osteosarcoma cells in vivo.

PURPOSE: The melanoma cellular adhesion molecule, also known as MUC18, is highly expressed on several tumors, including bone sarcomas. The level of MUC18 expression has been found to correlate directly with tumor progression and metastatic potential. These observations have established MUC18 as a candidate mediator of tumor growth and metastasis, and suggest that blockade of MUC18 might be a potential target for immunotherapy against several MUC18-expressing tumors, including human bone sarcomas. EXPERIMENTAL DESIGN: To investigate whether blockade of MUC18 might be a potential target for immunotherapy against osteosarcoma, we have recently developed a fully human anti-MUC18 antibody, ABX-MA1. We studied the effect of ABX-MA1 on growth, adhesion, invasion, and metastasis of human osteosaroma cells both in vitro and in vivo. RESULTS: MUC18 was widely expressed on both osteosarcoma and Ewing's sarcoma cells. ABX-MA1 had no effect on the proliferation of osteosarcoma cells in vitro, nor did it significantly inhibit the growth of KRIB human osteosarcoma cells when they were orthotopically implanted into the tibias of nude mice. However, after 6 weeks, significantly fewer ABX-MA1-treated mice developed spontaneous pulmonary metastases than did IgG-treated control mice. Additionally, ABX-MA1 decreased the invasion of osteosarcoma cells through Matrigel-coated filters and disrupted homotypic adhesion between osteosarcoma cells and their heterotypic interaction with human vascular endothelial cells. CONCLUSIONS: Our findings demonstrate that MUC18 plays a central role in the metastasis of osteosarcoma and suggest that targeted inhibition of this antigen by ABX-MA1 may be a novel immunotherapeutic approach in the management of this tumor.

Animals↗
PubMed2003

[Relationship between expression of BLCAP protein and malignancy of osteosarcoma].

AIM: To study the relationship between expression of bladder cancer-associated protein (BLCAP) and malignancy of osteosarcoma. METHODS: SABC method was applied to study the expression of BLCAP protein in osteosarcoma, according to clinical results, to analyze the prognosis value of BLCAP protein in osteosarcoma. RESULTS: The positive rate of BLCAP protein in primary osteosarcoma was 65.6%,much higher than that in recurrent osteosarcoma, which was 25.0%. CONCLUSION: It may be helpful for evaluating the prognosis of osteosarcoma to study the relationship between expression of BLCAP protein and malignancy of osteosarcoma.

Bone Neoplasms↗
PubMed2004

Quantitative assessment of HER2/neu expression by real-time PCR and fluorescent in situ hybridization analysis in low-grade osteosarcoma.

Low-grade osteosarcoma is a rare variant of osteosarcoma. Although malignant, it must be distinguished from conventional osteosarcomas because of its excellent prognosis. Numerous published papers have described the expression of HER2/neu oncogene in osteosarcoma as a poor prognostic factor; however their results are discordant. To address the expression of HER2/neu and to validate the assessment methods of amplification of the HER2/neu oncogene, the authors have employed quantitative real-time PCR and fluorencent in situ hybridization analysis (FISH) in 21 low-grade osteosarcomas. We calculated the quantification of HER2/neu oncogene amplification as the ratio of measured HER2/neu gene/beta-globin reference gene in real-time PCR. All 21 cases had amplified signals in the quantitative real-time PCR. However, in the FISH analysis, HER2/neu oncogene amplification was only identified in 26% (5/19). The exact reasons for the discordance between these two methods are unknown; however, variable histological features might play a potential role. In conclusion, as our study showed amplification of HER2/neu oncogene in low-grade osteosarcoma, we assume that expression of HER2/neu is not a poor prognostic factor in low-grade osteosarcoma.

Base Sequence↗
PubMedDate not supplied

Characterization of osteosarcoma cell lines MG-63, Saos-2 and U-2 OS in comparison to human osteoblasts.

BACKGROUND: Osteosarcomas are malignant bone tumors consisting of cells with abnormal cellular functions. Although osteosarcoma-derived cells are commonly used for osteoblastic models, the molecular composition of the osteosarcoma extracellular matrix (ECM) is not well characterized. MATERIALS AND METHODS: We compared three osteosarcoma cell lines (MG-63, Saos-2 and U-2 OS) with normal human osteoblasts by immunocytochemistry. Cellular characteristics were assessed by morphometric analysis and proliferation kinetics. RESULTS: All investigated osteosarcoma cell lines exhibited very heterogeneous labelling profiles and each differed significantly from that of normal osteoblasts. Saos-2 cells revealed the most mature osteoblastic labelling profile while U-2 OS cells were negative for most of the investigated osteoblastic markers. CONCLUSION: We conclude that each osteosarcoma cell line exhibits a characteristic labelling profile and thus produces a differently composed extracellular matrix. This can be used in attempts to better characterize osteosarcoma, a as well as for their diagnosis.

Aged↗
PubMed1991

Surface osteosarcoma.

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.

Bone Neoplasms↗
PubMed1977

Virus-induced animal model of osteosarcoma in the rat: Morphologic and biochemical studies.

Osteosarcomas were produced by the intratibial inoculation of New Zealand black rats with Moloney sarcoma virus (MSV) at 1 day and 4 days of age. Radiographic evidence of osteosarcoma development was first demonstrated at 10 to 15 days postinoculation in both groups. Subsequent radiographic and light and electron microscopic evaluation of tumor-bearing rats demonstrated that osteosarcomas in rats inoculated at Day 4 of age were more osteoproliferative osteosarcomas than those in rats inoculated on Day 1. Rats inoculated at 4 days of age lived longer, had more slowly growing osteosarcomas, and developed a consistent tumor-associated cachexia compared to tumor-bearing rats inoculated at Day 1. Both groups of rats had a 93% metastasis rate involving either sublumbar lymph nodes, lungs, or both. Tumor-bearing rats inoculated at 4 days of age had consistent elevations in both urinary hydroxyproline excretion (HOP/CR) and serum alkaline phosphatase levels, and in serum calcium levels at some time points. The high tumor incidence after a short latent period and the morphologic and biochemical similarities between the MSV-induced murine osteosarcoma and the osteosarcoma in human beings makes this discrete tumor and a valuable animal model for the evaluation of new therapeutic regimens.

Animals↗