UMLS:C0029463 - FACTA Search

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Query: UMLS:C0029463 (osteosarcoma)
16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclic adenosine monophosphate (cAMP) is an important second messenger in the hormonal regulation of bone metabolism. cAMP is inactivated by the cyclic nucleotide phosphodiesterases (PDEs), a superfamily of enzymes divided into 11 known families, designated PDE1-11. Interference with the cAMP signaling pathway has been suggested as one mechanism causing glucocorticoid induced osteoporosis. We speculated that glucocorticoids could affect the cAMP pathway by a down-regulation of PDE-mediated cAMP hydrolysis. The main cAMP hydrolysing enzyme families of human MG-63 and SaOS-2 osteosarcoma cells were identified as PDE1 and PDE4 by assaying the PDE activity of Q-sepharose fractions and cell homogenates with selective inhibitors. Treatment with the glucocorticoid dexamethasone (Dex) decreased cAMP-PDE activity by up to 50%, without affecting cGMP-PDE activity. Dex treatment reduced the sensitivity of the total cAMP-PDE activity towards the PDE4 selective PDE inhibitor rolipram. Forskolin stimulated cAMP accumulation was increased 30-60-fold in the presence of rolipram. Treatment with Dex did not affect the basal or forskolin stimulated cAMP accumulation, but treatment resulted in a reduced effect of rolipram on cAMP accumulation. Expression of the following cAMP-PDE subtypes were detected by reverse transcriptase PCR (RT-PCR): PDE1A, PDE1C, PDE2A, PDE3A, PDE4A, PDE4B, PDE4C, PDE4D, PDE7A, PDE7B, PDE8A, PDE10A and PDE11A. Using semi-quantitative RT-PCR, we detected a 50-70% decrease in the mRNA of PDE4A and PDE4B subtypes following Dex treatment. Further analysis revealed that Dex reduced the PDE4A4 and PDE4B1 isoforms. PDE4A1 PDE4A, PDE4A7, PDE4A10, PDE4B2 were also expressed, but Dex did not affect the transcription of these isoforms. We conclude that Dex treatment could affect the cAMP signaling pathway of human osteosarcoma cells by reducing type 4 cAMP-phosphodiesterase (PDE4).
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PMID:Dexamethasone down-regulates cAMP-phosphodiesterase in human osteosarcoma cells. 1562 79

CTLA-4 (CD152) is a cell surface receptor that behaves as a negative regulator of the proliferation and the effector function of T cells. We have previously shown that CTLA-4 is also expressed on neoplastic lymphoid and myeloid cells, and it can be targeted to induce apoptosis. In our study, we have extended our analysis and have discovered that surface expression of CTLA-4 is detectable by flow cytometry on 30 of 34 (88%) cell lines derived from a variety of human malignant solid tumors including carcinoma, melanoma, neuroblastoma, rhabdomyosarcoma and osteosarcoma (but not in primary osteoblast-like cultures). However, by reverse transcriptase-PCR, CTLA-4 expression was detected in all cell lines. We have also found, by immunohistochemistry, cytoplasmic and surface expression of CTLA-4 in the tumor cells of all 6 osteosarcoma specimens examined and in the tumour cells of all 5 cases (but only weakly or no positivity at all in neighbouring nontumor cells) of ductal breast carcinomas. Treatment of cells from CTLA-4-expressing tumor lines with recombinant forms of the CTLA-4-ligands CD80 and CD86 induced apoptosis associated with sequential activation of caspase-8 and caspase-3. The level of apoptosis was reduced by soluble CTLA-4 and by anti-CTLA-4 scFvs antibodies. The novel finding that CTLA-4 molecule is expressed and functional on human tumor cells opens up the possibility of antitumor therapeutic intervention based on targeting this molecule.
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PMID:CTLA-4 is constitutively expressed on tumor cells and can trigger apoptosis upon ligand interaction. 1591 38

The roles of insulin-like growth factors (IGFs) in regulating growth and their modulation by six IGF binding proteins (IGFBP) are well established. IGFBP-5, the most abundant IGFBP stored in bone, is an important regulator of bone formation via IGF-dependent and -independent mechanisms. Two new proteins, four and a half lim (FHL)-2, a transcription modulator that interacts with IGFBP-5, and a disintegrin and metalloprotease (ADAM)-9, an IGFBP-5 protease, have been identified as potential regulators of IGFBP-5 action in bone. We tested the hypothesis that agents which modulate bone formation by regulating IGFBP-5 expression would also regulate FHL-2 and ADAM-9 expression in a coordinated manner. We evaluated the expression of IGFBP-5, FHL-2, and ADAM-9 by real-time reverse transcriptase (RT)-PCR during differentiation of mouse bone marrow stromal cells into osteoblasts and in response to treatment with bone formation modulators in the LSaOS human osteosarcoma cell line. IGFBP-5 and FHL-2 increased 4.3- and 3.0-fold (P < or = 0.01), respectively, during osteoblast differentiation. Dexamethasone (Dex), an inhibitor of bone formation, decreased IGFBP-5 and FHL-2 and increased ADAM-9 in LSaOS cells (P < or = 0.05). Bone morphogenic protein (BMP)-7, a stimulator of bone formation, increased IGFBP-5 and decreased ADAM-9 (P<0.01). To determine if BMP-7 would eliminate Dex inhibition of IGFBP-5, cells were treated with Dex+BMP-7. The BMP-7-induced increase in IGFBP-5 was reduced, but not eliminated, in the presence of Dex (P < or = 0.01), indicating that BMP-7 and Dex may regulate IGFBP-5 via different mechanisms. Transforming growth factor (TGF)-beta, a stimulator of bone formation, increased IGFBP-5 and FHL-2 expression (P < or = 0.01). IGF-I and TNF-alpha decreased expression of ADAM-9 (P<0.05). In conclusion, our findings are consistent with the hypothesis that FHL-2 and ADAM-9 are important modulators of IGFBP-5 actions and are, in part, regulated in a coordinated manner in bone.
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PMID:Regulation of insulin-like growth factor binding protein-5, four and a half lim-2, and a disintegrin and metalloprotease-9 expression in osteoblasts. 1631 Oct 53

Dedifferentiated chondrosarcoma is a rare, highly malignant variant of chondrosarcoma in which a high-grade sarcoma coexists with a low-grade chondroid tumor. We herein review a case of dedifferentiated chondrosarcoma with an osteosarcoma omit component that occurred in the distal femur of a 38-year-old man. We established the cell line (NDCS-1) from a pleural effusion of the metastatic lung tumor. The cell line was characterized by a the G-banded karyotype, polymerase chain reaction (PCR) single-strand conformation polymorphism analysis, spectral karyotyping, and reverse transcriptase PCR (RT-PCR). The tumor exhibited complex karyotypes and a high frequency of chromosomal amplication with p53 mutation. This tumor revealed an osteoblastic and chondroblastic character in vitro and in severe combined immunodeficiency mice. The expression and phosphorylation of platelet-derived growth factor receptor-beta, which seemed to play a major role in the malignant phenotype of chondrosarcoma, was confirmed by RT-PCR and Western blotting. To our knowledge, this is the first report of the establishment of a human dedifferentiated chondrosarcoma.
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PMID:Establishment of novel human dedifferentiated chondrosarcoma cell line with osteoblastic differentiation. 1765 62

Osteosarcoma is the most frequent malignant bone tumor with a poor survival rate for patients with metastasis. Previous studies have shown that beside other proteases, distinct sets of cathepsins are involved in the process of metastasis of different tumors. In this study we investigated the expression of cathepsin proteases in human osteosarcoma metastasis. First, the mRNA expression of 14 human cathepsins was studied in SAOS-2 osteosarcoma cells and the highly metastatic LM5 and LM7 sublines by reverse transcriptase (RT)-polymerase chain reaction (PCR). The expression of cathepsin D, K, and L mRNA was found upregulated and that of cathepsin F, H, and V downregulated in the highly metastatic LM5 and LM7 cells. A subgroup of the cathepsin proteases was further studied at the protein level by Western blot analysis of cell extracts. The expression of cathepsin B and H was decreased and that of cathepsin D, K, and L was increased in the highly metastatic cell lines as compared to the SAOS-2 cell line. Diagnostic relevance of cathepsin K expression in osteosarcoma was revealed upon correlation of survival and metastasis with immunohistochemical cathepsin K staining of biopsies collected from 92 patients prior to chemotherapy. Patients with metastatic high-grade osteosarcoma and low cathepsin K expression at diagnosis had a better prognosis than those with high expression. Thus, it appears that cathepsin K expression is of predictive prognostic value for patients with high-grade tumors and metastasis at diagnosis.
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PMID:Cathepsins and osteosarcoma: Expression analysis identifies cathepsin K as an indicator of metastasis. 1768 65

Ezrin is a cytoskeleton linker protein that is actively involved in the metastatic process of cancer cells. We have searched for a prognostic value of ezrin and some of its partners: alpha-smooth muscle actin and CD44H in 37 patients with an osteosarcoma. Automate immunohistochemistry (IHC) with anti-ezrin, alpha-smooth muscle actin and CD44H antibodies was performed in 66 specimens: 37 biopsies before chemotherapy, 16 resected tumours of "poor" responders and 13 metastases. The messenger RNA (mRNA) levels of ezrin of 13 frozen biopsies and 4 metastases were evaluated by real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR). All results were correlated to the following clinical data. Ezrin expression by IHC was found in 62% of 37 biopsies in the different histological subtypes. A good correlation was found between positive or negative samples by IHC and mRNA levels. Ezrin expression was recorded in 84.5% of metastastic samples. The mean expression of ezrin was higher in metastases than biopsies (p = 0.024). In multivariate analysis, ezrin was an independent prognostic marker for event-free survival and overall survival (OS) with p < 0.001 and p = 0.003, respectively, and alpha-smooth muscle actin for OS only (p = 0.024). Our findings suggest that ezrin and alpha-smooth muscle actin are predictive IHC prognostic markers for patients with an osteosarcoma.
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PMID:Ezrin and alpha-smooth muscle actin are immunohistochemical prognostic markers in conventional osteosarcomas. 1778 74

An understanding of differential gene expression in highly metastatic osteosarcoma could provide gene targets for treatment of metastases. We compared gene expression profiles of high- (LM7) and low- (LM2) metastatic SaOS2-derived cell lines in an in vitro tissue culture model and examined several differentially regulated genes in vivo in a murine orthotopic xenograft model. We hypothesized an orthotopic inoculation of LM2 and LM7 cells would establish a primary lesion and the gene expression profile of cells grafted in this fashion would resemble the gene expression profile observed in an in vitro model. Thirty-five days after inoculation, animals were euthanized and both tibiae were harvested and rapidly frozen in liquid nitrogen. Human-specific GAPDH mRNA was present in two of four tibias inoculated with LM2 cells and three of four tibias inoculated with LM7 cells. Tibiae displaying the presence of human cells were assayed by semiquantitative reverse transcriptase polymerase chain reaction. We observed poor correspondence of in vitro to in vivo gene expression for either cell line. Accordingly, in vitro osteosarcoma gene expression data must be interpreted with caution until confirmed in vivo. Our orthotopic injection model allowed in vivo study of differential gene expression between these two cell lines but did not show radiographic evidence of an established primary lesion.
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PMID:Metastatic osteosarcoma gene expression differs in vitro and in vivo. 1851 56

MicroRNA (miRNA) dysregulation frequently occurs in cancer. Analysis of whole blood miRNA in tumor models has not been widely reported, but could potentially lead to novel assays for early detection and monitoring of cancer. To determine whether miRNAs associated with malignancy could be detected in the peripheral blood, we used real-time reverse transcriptase-PCR to determine miRNA profiles in whole blood obtained from transgenic mice with c-MYC-induced lymphoma, hepatocellular carcinoma and osteosarcoma. The PCR-based assays used in our studies require only 10 nanograms of total RNA, allowing serial mini-profiles (20 - 30 miRNAs) to be carried out on individual animals over time. Blood miRNAs were measured from mice at different stages of MYC-induced lymphomagenesis and regression. Unsupervised hierarchical clustering of the data identified specific miRNA expression profiles that correlated with tumor type and stage. The miRNAs found to be altered in the blood of mice with tumors frequently reverted to normal levels upon tumor regression. Our results suggest that specific changes in blood miRNA can be detected during tumorigenesis and tumor regression.
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PMID:A quantitative PCR method to detect blood microRNAs associated with tumorigenesis in transgenic mice. 1882 39

Arthritis is one of the most prevalent chronic inflammatory diseases, and it is characterized by structural and biochemical changes in major tissues of the joint, including degradation of the cartilage matrix, insufficient synthesis of extracellular matrix (ECM). Ecklonia cava (EC) is a member of the family of Laminariaceae, which is an edible marine brown alga with various bioactivities. In this study of the methanol extract of brown alga EC, the dieckol (1) and 1-(3',5'-dihydroxyphenoxy)-7-(2'',4'',6''-trihydroxyphenoxy) 2,4,9-trihydroxydibenzo-1,4,-dioxin (2) were isolated and characterized by NMR techniques with high yield. Phlorotannin derivatives (1, 2) promoted osteosarcoma differentiation by increasing alkaline phosphatase (ALP) activity, mineralization, total protein and collagen synthesis in human osteosarcoma cell (MG-63 cells), respectively. Furthermore, these phlorotannin derivatives (1, 2) inhibited mRNA gene and protein levels of matrix metalloproteinase (MMP-1, MMP-3, and MMP-13), iNOS and COX-2 in casein zymography, Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR) assays. In addition, it was observed that the phlorotannins inhibited phosphorylation of JNK and p38 MAPK in human osteosarcoma cell. These results suggested the phlorotannin derivatives (1, 2) could promote cell differentiation, attenuate MMP-1, MMP-3, MMP-13 expressions, and inflammatory response via MAPK pathway in chronic articular diseases.
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PMID:Differentiation of human osteosarcoma cells by isolated phlorotannins is subtly linked to COX-2, iNOS, MMPs, and MAPK signaling: implication for chronic articular disease. 1933 Aug 80

Gene hypomethylation and hypermethylation can lead to a loss of genetic imprinting in malignancies. The mechanism responsible for overexpression of the imprinted insulin-like growth factor II (IGF2) gene has not been investigated in osteosarcoma. In this study, the expression levels, imprinting status, and the extent of cytosine methylation of the IGF2 gene was evaluated in 20 of 24 cases of osteosarcoma using immunohistochemistry, reverse transcriptase polymerase chain reaction, restriction fragment length polymorphism, and bisulfite genomic sequencing. Promoter use analysis indicated that P3- and P4-derived messenger RNAs were more highly expressed than P1 transcripts in the osteosarcoma samples. Loss of imprinting of IGF2 was observed in 3 of 20 of the osteosarcoma samples, but this was not associated with IGF2-specific transcripts. Methylation analysis revealed that the methylation patterns of the differentially methylated region of IGF2 were not uniform, regardless of IGF2-P3 expression. However, the average degree of methylation of the 14 CpG sites in the IGF2-P3 promoter was significantly lower in osteosarcoma samples with P3 transcripts than in osteosarcoma samples without P3 expression (P < .05). This observation was also observed in nontumor samples. These data suggest that hypomethylation of the IGF2-P3 promoter correlates with expression of P3 transcripts in osteosarcoma. Furthermore, elevated IGF2-P3 expression in osteosarcoma tissues is due to P3 promoter hypomethylation, which may represent an early event in progression of osteosarcoma.
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PMID:Hypomethylation of the P3 promoter is associated with up-regulation of IGF2 expression in human osteosarcoma. 1942 70

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