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

The realization that malignant tumors may grow not only due to proliferation but also because cells don't die when they should provides absolute new directions in basic and clinical tumor research. Thus, apoptosis, the programmed cell death is very hot now in the scientific community. In the center of interest are the regulation mechanisms of apoptosis and its significance in different tumor entities. Recently, numerous studies on apoptosis during embryogenesis, different stages of tissue development and in epithelial and hormone dependent tumors have been published. The data suggested an important role of bcl-2 in regulation of apoptosis. In this view the demonstration of bcl-2 oncogene expression in osteosarcoma, a mesenchymal tumor, is of potential great interest.
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PMID:[Apoptosis: bcl-2 as a key protein for programmed cell death]. 785 1

The relationship between the growth of tumors and the expression of the protooncogene Bcl-2 could be shown in epithelial tumors. A bcl-2 expression leads to a prolonged cell survival due to an inhibition of apoptosis. The potential meaning of bcl-2 expression in mesenchymal tumors remains still unknown. The fact, that the heterogenous group of osteosarcoma is not sufficiently characterized at present, suggested to investigate the bcl-2 expression in osteosarcoma. Thus, immunohistochemistry was used to analyze 47 specimens of different osteosarcomas of 36 patients. Sixteen cases (46%) showed a strong expression of bcl-2 and 13 cases (35%) were moderately positive for bcl-2. Seven cases (19%) were negative for bcl-2. The heterogenous, negative up to strong expression of bcl-2 yield clues, that the Bcl-2 controlled regulation of programmed cell death could be an important factor of cellular kinetics. Additionally the cellular proliferation rate was determined with the monoclonal antibody MIB 1, directed against the Ki-67 epitope. The data of bcl-2 expression and cellular proliferation rate lead to a classification correlating with the histological classification. To verify the importance of apoptosis in the genesis of mesenchymal tumors and whether Bcl-2 may play an important role as a predictive factor for the prognosis of osteosarcoma, further investigations will be needed.
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PMID:[Osteosarcoma--apoptosis and proliferation. Study of bcl-2 expression]. 785 2

A murine erythroleukemic cell line (1-2-3) which expresses only the temperature-sensitive mutant p53 gene (Ala-to-Val substitution at codon 135) was established. These cells showed typical characteristics of apoptosis, when they were cultured at 32 degrees C. In this process, p53 recovered the wild-type p53 function and the expression of the p21 (waf1/cip1/sdi1), cyclin G1 and gadd45 genes was increased. However, no significant changes were detected in the expression of the mdm2, bcl-2, bax, fas and fasl genes, suggesting the existence of other genes associated with apoptosis. Genes up-regulated by p53 were screened by the mRNA differential display method. One of the up-regulated genes was identified as the elongation factor 1 alpha (EF-1 alpha) gene. EF-1 alpha is also a microtubule-severing protein. Upon the temperature-shift, the cells developed the morphology and the localization of alpha-tubulin similar to those of the cells treated with vincristine, a drug that affects microtubules. The microtubule-severing associated with up-regulation of EF-1 alpha by p53 may be a cause of the cell death. On the other hand, the function of cyclin G1 is not so clear despite the fact that 1-2-3 cells showed a significant increase of the cyclin G1 gene during the early stage of apoptosis. The yeast two-hybrid system was used to identify cyclin G1-associated proteins. One is a cytochrome c (Cyt c) oxidase subunit II (COXII). Cyclin G1 and COXII were co-immunoprecipitated from an extract of human osteosarcoma cell line that expressed high levels of cyclin G1. COX activity was also increased by temperature-shift in this cell line. The pattern of changes in COX activity was closely reflected by the expression of the cyclin G1 gene. Cyclin G1 and COXII associate physically with each other in vivo and that activation of COXII by binding to cyclin G1 upregulated by p53 may be associated with apoptosis. These two new pathways, p53-EF-1 alpha-microtubule-severing (-distortion of cytoskeleton) and p53-cyclin G1-COXII (-CytC, ATP-caspase-3 activation), may cooperate to induce apoptosis in this cell line.
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PMID:The mechanisms of death of an erythroleukemic cell line by p53: involvement of the microtubule and mitochondria. 1019 36

Actinobacillus actinomycetemcomitans (A. actinomycetemcomitans) has been implicated in the etiology of localized juvenile periodontitis (LJP), and produces a multiplicity of tissue-damaging products. Among those products, the capsular-like polysaccharide antigen (CPA) from A. actinomycetemcomitans is a potent mediator of bone resorption. In fact, this CPA (serotype b) is known to promote osteoclast-like cell formation via interleukin (IL)-1alpha production in mouse marrow cultures. Although osteoblasts complete bone formation, there are few reports focusing on the effect of CPA in bone-forming activity of osteoblasts in inflammatory disease sites. We hypothesized that CPA plays a mediating role in osteoblastic cells. Therefore, the purpose of this study was to examine the effect of CPA from A. actinomycetemcomitans on the mouse osteoblastic cell line MC3T3-E1 and human osteosarcoma SaOS-2 cells. A. actinomycetemcomitans serotype c resulted in a potent dose-dependent inhibition of cell proliferation of both cell lines. Characterization of the antiproliferative activity in the CPA demonstrated that it was not cytotoxic for MC3T3-E1. A 20-hour incubation with CPA-c resulted in a significant increase in apoptotic cell death in the cells, as evaluated by both cellular DNA fragmentation ELISA and FACS analysis. In contrast to the results obtained with a cytokine mixture (tumor necrosis factor-alpha, IL-1beta, and interferon-gamma), no inducible nitric oxide (NO) synthase gene expression or NO release could be detected in MC3T3-E1 after incubation with CPA-c. Further, both CPA-b and -c caused potent induction of apoptosis-related modifiers, e.g., Fas mRNA, whereas bcl-2 mRNA levels were unchanged. Therefore, this study has shown that CPA from A. actinomycetemcomitans contains a potent antiproliferative polysaccharide whose activity is associated with apoptotic cell death in MC3T3-E1, and that CPA per se is an inducer of apoptosis mediated by the Fas system but not by NO.
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PMID:Anti-proliferative capsular-like polysaccharide antigen from Actinobacillus actinomycetemcomitans induces apoptotic cell death in mouse osteoblastic MC3T3-E1 cells. 1037 Dec 46

A stable transfectant (S2SN7) of p53-null SaOS-2 (human osteosarcoma) cells expressing wild-type p53 under the tight control of a tetracycline-responsive promoter was used to study the functional roles of p53 in cellular response to cisplatinum (CP). When cells were grown in media containing normal concentrations (10%) of serum, induction of p53 by tetracycline withdrawal resulted in an 8-fold decrease in sensitivity to CP. In contrast, when cells were grown in lower serum (1%) media, induction of p53 led to a 10-fold increase in sensitivity to CP. The p53-mediated sensitivity to CP under lower serum conditions was attributed, at least in part, to increased susceptibility of p53-mediated apoptosis. Under lower serum (0.1-1%) but not normal serum conditions, p53 induction correlated with selective down-regulation of bcl-2, an inhibitor of apoptosis. In addition, a host-cell reactivation assay showed that induction of p53 caused a significant increase in repair of CP-induced DNA damage under normal serum but not low serum conditions. These data suggest that growth conditions may modulate and possibly reverse p53-mediated CP sensitivity by altering p53-mediated gene regulation and, as a result, susceptibility to apoptosis. They also suggest that a combined effect of p53-mediated apoptosis and DNA repair may be the ultimate determinant in p53-mediated cellular resistance or sensitivity to chemotherapeutic drugs.
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PMID:Modulation of cisplatinum cytotoxicity by p53: effect of p53-mediated apoptosis and DNA repair. 1053 2

Progression through the cell cycle and redirection of cells towards programmed cell death (apoptosis) are tightly inter-related processes. However the requirement for tissue and cell type specificity suggests that a wide variety of mechanisms are used to achieve the same purpose. To examine this issue, we investigated cell cycle (c-myc, p53, p21/WAF) and apoptosis related (bcl-2, bcl-X(L), bax-alpha) gene expression in two cell lines of very different origin under proliferating and apoptosis-inducing conditions. Transformed human osteosarcoma cells (MG63) and non-transformed human kidney embryonal fibroblasts (293-0) were kept in culture in medium containing 10% FCS and growth arrest was induced by the addition of 50 ng/ml colcemid. Colcemid treatment caused growth arrest and elevated expression of cyclin B1 protein in both cell lines. Apoptosis was significantly elevated in both cell lines after colcemid exposure for at least one cell cycle. However the pattern of expression of cell cycle and apoptosis related genes, determined by RT-PCR, was quite different between the two cell lines during exponential growth and cell cycle arrest. Colcemid treatment did not markedly influence c-myc, p53 and p21/WAF expression in MG63 cells but did suppress c-myc and increase p21/WAF in 293-0 cells. Furthermore colcemid treated MG63 cells exhibited elevated bcl-2 and bax-alpha expression while similar treatment of 293-0 cells resulted in decreased bcl-X(L) and slightly increased bax-alpha expression. While growth arrest and apoptosis were induced in both MG63 and 293 cells following colcemid treatment, the differences in gene expression suggest that the mechanism by which these cells determine cell fate is quite different and may determine the sensitivity of different cell populations to anti-neoplastic drug therapy. The distinct patterns of gene expression should be carefully defined before mechanisms of apoptotic cell death are studied.
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PMID:Expression of apoptosis and cell cycle related genes in proliferating and colcemid arrested cells of divergent lineage. 1072 74

We recently obtained 3 cloned cell lines demonstrating the p53 mutation from a lung metastatic nodule of a rat transplantable osteosarcoma. In this study, we applied wild-type p53 gene transfer to the rat osteosarcoma cells by lipofection to investigate the effects on cell growth, expression of genes such as waf1/p21, bcl-2, and bax, and nucleosomal DNA fragmentation due to apoptosis. Reconstitution of the p53 gene inhibits cellular growth, and this growth-suppressive effect is partly due to apoptosis involving bcl-2 gene suppression in this tumor type. This rat osteosarcoma model is similar in biologic behavior to human cases and thus is very suitable for further investigation of tumorigenesis and gene therapy for osteosarcoma.
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PMID:Possible involvement of bcl-2 suppression in wild-type p53 gene-dependent cell growth repression in rat osteosarcoma cells. 1093 45

The cytotoxic activity of the imidazoacridinone C1311 was assessed on two ovarian cancer cell lines (A2780, OAW42) and one osteogenic sarcoma cell line (U2-OS) and their sublines (A2780Cp8, OAW42-MER and U2-OS-R) with experimentally induced resistance to cisplatin. A 1-h exposure to C1311 significantly inhibited the growth of all cell lines, with IC50 values ranging from 0.50 +/-0.11 to 4.10+/-0.36 microM. No or only partial cross-resistance was found between C1311 and cisplatin in the different cell lines. Treatment with equitoxic (IC50) C1311 concentrations consistently induced accumulation of cells in the G2M phase. The cyclin B1-associated p34(cdc2) kinase activity in cells arrested in G2M was superimposable to that of control cells in the OAW42-MER and U2-OS cell lines, whereas a reduction of cdc2 catalytic activity was observed in OAW42 and U2-OS-R cells. Exposure to C1311 (IC50) induced apoptosis in the U2-OS and U2-OS-R cell lines, whereas in the OAW42 and OAW42-MER cell lines there was a negligible percentage of apoptotic cells. In U2-OS, U2-OS-R and OAW42 cells, C1311 induced an increase in p53 expression and an increase in p21waf1 protein, whereas p53 failed to transactivate p21waf1 in OAW42-MER cells. An almost complete abrogation of bcl-2 was observed in U2-OS-R cells in correspondence with the peak of apoptosis induction. Our results indicate that C1311 is active against human ovarian cancer and osteogenic sarcoma cells and is not cross-resistant with CDDP. Moreover, C1311 blocks cells in the G2M phase and induces apoptosis in a small percentage of osteogenic sarcoma cells.
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PMID:Cell growth inhibition, G2M cell cycle arrest and apoptosis induced by the imidazoacridinone C1311 in human tumour cell lines. 1157 53

Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to produce an anti-proliferative and pro-apoptotic effect on different types of cancer cell lines. Previously, we demonstrated that high dose of NS-398 (100 microM), a selective cyclooxygenase-2 inhibitor, induced a cell cycle slowing or arrest and, in contrast to low dose (10 microM), a marked decrease in apoptosis in human 1547 osteosarcoma cells. In this study, we investigated particularly the effect of 100 microM NS-398 on p53 and p21 expression, caspase activities and nuclear factor-kappaB (NF-kappaB). We found a correlation between p53, p21 mRNA expression and NF-kappaB activation and, we observed an induction of heat shock protein 70 expression with a large decrease in caspase-3 activity after 100 microM NS-398 treatment. Moreover, the inhibition of apoptosis was correlated with an increase in bcl-2/bax ratio. Our new findings confirm the novel anti-apoptotic property of NS-398 at 100 microM, as we previously found, which contrasts to the described NS-398 pro-apoptotic effect on other cancer cell lines.
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PMID:The anti-apoptotic property of NS-398 at high dose can be mediated in part through NF-kappaB activation, hsp70 induction and a decrease in caspase-3 activity in human osteosarcoma cells. 1201 7

This study investigates cell growth and death (apoptosis and necrosis) in actively proliferating MG-63 osteosarcoma spheroids in response to two doses of ionizing radiation (5 and 30 Gy). Cell growth was examined by growth curves and by cell cycle analyses utilizing flow cytometry. Death was examined in both disaggregated and whole spheroids by the chromatin dye Hoechst and by Western blot analysis of the bcl-2 family of proteins known to be involved in the apoptotic process. The results indicate that after exposure to 5 Gy MG-63 spheroids die by apoptosis, while after exposure to 30 Gy they die by necrosis. The analysis of the bcl-2 family of proteins demonstrates that bcl-2, bax and bcl-XL are involved in triggering apoptosis in spheroids exposed to 5 Gy. The possibility of studying the mechanisms responsible for radiation-induced cell death in three-dimensional spheroids (which represent much more closely in vivo tumors) is extremely important if the foundations for more selective and controllable clinical radiotherapeutic protocols are to be laid.
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PMID:Induction of apoptosis or necrosis by ionizing radiation is dose-dependent in MG-63 osteosarcoma multicellular spheroids. 1289 34


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