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)

Efficient gene delivery of a baculovirus-derived vector (BV-p53-lacZ) to a human osteogenic sarcoma cell line, Saos-2, was serendipitously found while evaluating the vector for gene delivery to human p53-null tumour cells in a previous study. Therefore, we investigated other human, rat and mouse osteogenic sarcoma and other types of tumour cell lines for transduction efficiency via baculovirus vectors containing a lacZ reporter gene under the control of either a cytomegalovirus or Rous sarcoma virus promoter. The expression of beta-galactosidase protein, assessed by X-Gal staining and beta-galactosidase ELISA, demonstrated an extremely high level of transduction efficiency in some osteogenic sarcoma cell lines, such as U-2OS, Saos-2 and Saos-LM2. These human osteogenic sarcoma cell lines showed levels of beta-galactosidase expression 5-40 times greater than HepG2 cells, which were previously thought to be the mammalian cells most susceptible to baculovirus-mediated gene delivery. The level of acetylated histone proteins in these tumour lines did not correlate well with the high level of reporter gene expression. These results strongly suggest that some osteogenic sarcoma cells are highly susceptible to baculovirus-mediated gene delivery and that a baculovirus-derived vector is an efficient gene delivery vehicle into human osteogenic sarcoma cells.
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PMID:Effective transduction of osteogenic sarcoma cells by a baculovirus vector. 1260 22

The transfection efficiency of cationic liposomes varies according to cell type, but the specific cellular characteristics that affect transfection efficiency have not yet been defined. We investigated whether the transfection efficiency of cationic liposomes correlates with cell proliferation activity or cell membrane potential in oral malignant melanoma (HMG) and oral osteosarcoma cell lines (HOSM-1 and HOSM-2). The cell membrane potential was assessed by uptake of a cationic probe. Three oral tumor cell lines were exposed to a cationic liposome complexed with a beta-galactosidase expression plasmid, and beta-galactosidase expression was compared. Cell proliferation was about 2-fold higher in HOSM-1 cells than in HMG cells. The cell membrane potential in HMG and HOSM-1 cells was comparable, while the membrane potential in HOSM-2 cells was 1.6-fold higher. beta-galactosidase expression was measured by X-Gal staining in 7.0% of HMG, 17.0% of HOSM-1 and 11.5% of HOSM-2 cells. The present study demonstrates that gene therapy with cationic liposomes may be a promising new strategy for treatment of oral malignant melanoma and osteosarcoma. In addition, the transfection efficiency of cationic liposomes appears to be influenced by cell proliferation activity, but not cell membrane potential.
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PMID:The influence of oral tumor cell proliferation activity and membrane potential on the transfection efficiency of a cationic liposome. 1627 43

The Forkhead box m1 (Foxm1) gene is critical for G(1)/S transition and essential for mitotic progression. However, the transcriptional mechanisms downstream of FoxM1 that control these cell cycle events remain to be determined. Here, we show that both early-passage Foxm1(-)(/)(-) mouse embryonic fibroblasts (MEFs) and human osteosarcoma U2OS cells depleted of FoxM1 protein by small interfering RNA fail to grow in culture due to a mitotic block and accumulate nuclear levels of cyclin-dependent kinase inhibitor (CDKI) proteins p21(Cip1) and p27(Kip1). Using quantitative chromatin immunoprecipitation and expression assays, we show that FoxM1 is essential for transcription of the mitotic regulatory genes Cdc25B, Aurora B kinase, survivin, centromere protein A (CENPA), and CENPB. We also identify the mechanism by which FoxM1 deficiency causes elevated nuclear levels of the CDKI proteins p21(Cip1) and p27(Kip1). We provide evidence that FoxM1 is essential for transcription of Skp2 and Cks1, which are specificity subunits of the Skp1-Cullin 1-F-box (SCF) ubiquitin ligase complex that targets these CDKI proteins for degradation during the G(1)/S transition. Moreover, early-passage Foxm1(-)(/)(-) MEFs display premature senescence as evidenced by high expression of the senescence-associated beta-galactosidase, p19(ARF), and p16(INK4A) proteins. Taken together, these results demonstrate that FoxM1 regulates transcription of cell cycle genes critical for progression into S-phase and mitosis.
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PMID:Forkhead box M1 regulates the transcriptional network of genes essential for mitotic progression and genes encoding the SCF (Skp2-Cks1) ubiquitin ligase. 1631 12

A radio-labeled plasmid pTracer/Bsd/LacZ containing LacZ reporter gene was complexed with different molecular weights of chitosans (CS). Mouse myoblast cell line C2C12 was transfected by these chitosan-plasmid DNA complexes, and lipofectamine 2000 was used as control. Forty-eight hours after transfection, the activity of beta-galactosidase and radioactive count of cell lysis were determined. It was found that chitosan, especially low molecular weight species, had a surprising ability to deliver DNA into cells, since the radioactive count of cells transfected by chitosan-DNA complexes was even two times that of cells transfected by lipofectamine 2000. But the beta-galactosidase activity of chitosan/DNA complexes was much lower compared to that of lipofectamine 2000. Chitosanase which could degrade chitosan in specific mode was transported into C2C12 cells by osmotic lysis prior to gene delivery. Then these chitosanase-modified cells were transfected by CS-DNA complexes. The results indicated that beta-galactosidase activity in these cells increased markedly to 425.4 +/- 45.1 U/mg protein, nearly two-fold as that of cells transfected by liposome. This transfection protocol was also applied to 3T3 mouse fibroblast, 2T3 mouse osteoblast and MG63 human osteosarcoma cell lines, and an increased gene expression level was observed without exception. It is thought that the incorporated chitosanase could aid in chitosan degradation, which would promote gene unpacking, consequently increasing gene expression.
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PMID:Pre-deliver chitosanase to cells: a novel strategy to improve gene expression by endocellular degradation-induced vector unpacking. 1656 55

IFI16 is a member of the interferon-inducible p200-protein family, capable of modulating cell proliferation, and cellular senescence. In this study, these effects of IFI16 were studied in tumor cells derived from bone and cartilage. The level of IFI16 was markedly lower in human osteosarcomas as compared with its level in normal bone. Overexpression of functional IFI16 in human osteosarcoma and chondrosarcoma cell lines markedly inhibited colony formation, and significantly inhibited cell growth, an effect that could be reversed by introduction of gene specific siRNA into tumor cells. These inhibitory effects of IFI16 were associated with upregulation of p21 and inhibition of cyclin E, cyclin D1, c-Myc and Ras. In addition, ectopic expression of IFI16 in tumor cells increased senescence-associated beta-galactosidase and induced a senescence-like phenotype. In view of such effects, IFI16 might be a suitable target for therapeutic intervention in osteosarcoma and chondrosarcoma.
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PMID:IFI16 inhibits tumorigenicity and cell proliferation of bone and cartilage tumor cells. 1756 15


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