Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multilayered coatings composed of mixtures of HA and P2O5-based bioactive glasses are of potential clinical benefit in orthopaedic and dental surgery. Pre-immersion of these materials has been reported to further enhance their efficacy in vivo, although the precise biological effects of this treatment are not yet known. In this study we have therefore prepared double-layer plasma-sprayed coatings and evaluated the effects of pre-immersion on the growth and function of human osteosarcoma cells in vitro, using the MTT assay and flow cytometry analysis, respectively. The results showed that the increase in numbers of viable cells was the same or elevated following incubation on the pre-immersed HA and glass-reinforced HA coatings compared with the non-immersed materials. In addition, the expression of bone sialoprotein and fibronectin, two key connective tissue antigens, was up-regulated in cultures grown on the pre-immersed surfaces compared with the non-treated materials. Moreover, cell numbers and antigen expression both improved as the proportion of glass increased, particularly in the pre-immersed samples. Our findings thus suggest that the immersion treatment of these materials appeared to improve the response of these bone-like cells.
 ...
PMID:Flow cytometry analysis of the effects of pre-immersion on the biocompatibility of glass-reinforced hydroxyapatite plasma-sprayed coatings. 1072 50

The effects of recombinant human bone morphogenetic protein-2 (rhBMP-2) on cell growth were studied in three human osteosarcoma cell lines, NOS-1, HuO9, and HuO-3N1; one human prostate cancer cell line, PC-3; and one human breast cancer cell line, OCUB-1M. The growth of these cell lines was not promoted by rhBMP-2 at concentrations of 50, 100, 250, and 500 ng/ml, as evaluated by colorimetric 3 (4,5-dimethyl-thiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) assay. Furthermore, the protein induced osteogenic differentiation, characterized by increased alkaline phosphatase activity, and increased production of type I collagen and gamma-carboxylated osteocalcin in NOS-1 cells. The results of this study may suggest the feasibility of using rhBMP-2 for the reconstruction of bone defects caused by malignant tumors, although the data are still preliminary and require further investigation.
 ...
PMID:Effects of bone morphogenetic protein-2 on human tumor cell growth and differentiation: a preliminary report. 1118 Sep 25

Multidrug resistance (MDR) is one of the major problems in osteosarcoma chemotherapy. Therefore, methods of overcoming MDR are urgently needed. In this study, we investigated the effects of pulsing electromagnetic field stimulation (PEMFs) on a MDR murine osteosarcoma cell line which strongly expresses P-glycoprotein (P-gp). To assess the reversal effects of PEMFs on doxorubicin (DOX) resistance, MTT assay was applied. Viable cells were assessed by the trypan blue exclusion test. Fluorescence intensity of DOX binding to nuclear DNA of each cell was measured using a cytofluorometer. Changes in P-gp expression in each cell were detected by the indirect immunofluorescence method using an antibody to Pgp. PEMFs increased DOX binding ability to nuclear DNA and inhibited cell growth, although it had no significant effect on P-gp expression. These findings indicated that PEMFs reversed the DOX resistance of the MOS/ADR1 cells by inhibiting P-gp function. The results suggested that PEMFs may be useful as a local treatment for MDR osteosarcoma.
 ...
PMID:Drug resistance modification using pulsing electromagnetic field stimulation for multidrug resistant mouse osteosarcoma cell line. 1129 55

We have investigated the effect of changes in the gravity vector on osteoblast behaviour, using the clinostat set at 8 rpm. Two sources of osteoblasts were used: secondary cultures of fetal rat bone cells, and the rat osteosarcoma line 17/2.8 (ROS). Cell number was determined by incubation with 3-(4,dimethyl-2yl)-2,3 diphenyl) tetrazolium bromide (MTT) and measurement of optical density at 570 nm (OD). Alkaline phosphatase activity was detected by standard cytochemical methods. Dividing cells were localised by labelling dividing nuclei with Bromodeoxyuridine (BrdU), detected by immunofluorescence. Cell culture was initiated at densities between 1-4x10(4) cells ml-1. Growth rates in all cultures during the first 48 hours exposure to clinostat rotation were less than in stationary controls. After 3 days, ROS cell numbers were 35% lower, and calvarial cells 39% lower than their respective controls. Alkaline phosphatase activity in calvarial control cultures was uniformly present in characteristically polygonal cells, but after culture in the clinostat the enzyme was present sporadically, and the cells were cuboid. There was also no BrdU uptake in nuclei, but it was present in cell cytoplasms. We conclude that the clinostat decreases cell numbers and cell division. Both cell shape and the distribution of alkaline phosphatase activity in calvarial cell cultures were also affected. This implies that changes in the gravity vector can affect osteoblasts directly, without interaction with other cell types.
 ...
PMID:Effect of clinostat rotation on differentiation of embryonic bone in vitro. 1153 15

We mixed various amounts of methotrexate with bone cement and measured the absorbance daily for 4 weeks. The cytotoxic effects on SaOS2 and MG63 osteosarcoma cells were examined by the MTT assay, and analysed according to the methotrexate concentration and the elapsed time. The amount of eluted methotrexate was greatest during the first day, and then decreased rapidly reaching a plateau in the third week. The number of viable tumour cells decreased significantly after 72 h, and they were hardly seen after 1 week.
 ...
PMID:The cytotoxic effect of methotrexate loaded bone cement on osteosarcoma cell lines. 1182 Apr 38

We sought to determine whether gemcitabine, a new pyrimidine antimetabolite, could inhibit the growth of human osteosarcoma cells (OS) in vitro and in vivo. Four human OS cell lines (MG-63, TE-85, SAOS-2 and SAOS-LM7) were used to assess the activity of the drug in vitro. Gemcitabine caused growth inhibition and cell death in all four cell lines as measured using the MTT and colony-forming assays (IC(50) = 6.5 nM-9 microM and 7-14 nM, respectively). Using our newly developed human SAOS-LM7 OS lung metastasis mouse model, we assessed the in vivo activity of gemcitabine given i.p. and intranasally (i.n.). Mice were treated twice weekly for 3 weeks and then once weekly for 3 weeks using either i.p. or i.n. gemcitabine starting 4 weeks after tumor cell injection. The i.p. injection, at 120 mg/kg, resulted in a decrease in lung weights and the size of the nodules. However, no significant reduction in the number of metastatic nodules was seen (control median: >200 versus gemcitabine median: 150, p = 0.084). In contrast, the number of lung metastases was significantly decreased in mice that received i.n. gemcitabine at 15 (median: 1; range: 0-115, p<0.005) and 12 mg/kg (median: 41; range: 7-163, p = 0.005) when compared with control mice (median: >200). Intranasal therapy is a non-invasive method of drug delivery and has the advantage of targeting the lung, resulting in a higher drug concentration in the tumor area. In our study, i.n. instillation of gemcitabine inhibited the growth of lung metastases at an 8- to 10-fold lower dose than that used i.p. and appeared to be more effective in eradicating OS lung nodules. Because the lung is the most common site of OS metastasis, our data suggest that i.n. gemcitabine may be a novel therapeutic approach in the treatment of OS lung metastases.
 ...
PMID:Eradication of osteosarcoma lung metastasis using intranasal gemcitabine. 1190 8

Activation of PPAR gamma, a transcription factor member of the family of peroxisome proliferator-activated receptors, induces apoptosis in several normal and tumor cell lines. In our study, we investigated whether treatment with troglitazone (TRO), a known PPAR gamma agonist, induced apoptosis in the human osteosarcoma (OS) cell lines G292, MG63, SAOS and U2OS that express PPAR gamma. In our experiments, TRO never induced apoptosis of OS cells; on the contrary, TRO increased cell number, based on MTT proliferation assay. Remarkably, the TRO-induced cell number increase depended on a decrease of apoptosis that naturally occurred in the culture and was not due to an increased cell proliferation rate. TRO also prevented staurosporin-induced apoptosis. The TRO-mediated survival effect correlated with the activation of Akt, a well-known mediator of survival stimuli. Our work describes a new function for TRO and indicates that the Akt survival pathway may be a mediator of TRO-induced increase of survival.
 ...
PMID:Troglitazione affects survival of human osteosarcoma cells. 1192 May 84

The cytokines IL-6, initially recognized as a regulator of immune and inflammatory response and IL-8, a potential regulator of angiogenesis, also regulate the growth of many tumor cells. Human cancer cells selected for multidrug resistance to common chemotherapeutic agents demonstrate increased expression of IL-6 and IL-8. To determine whether IL-6 or IL-8 overexpression contributes directly to the drug resistant phenotype, IL-6 or IL-8 cDNA were introduced into the paclitaxel sensitive human osteosarcoma cell line U-2OS using the pIRESneo bicistronic expression vector. Interleukin-6 and IL-8 transfectants were selected for either high IL-6 or IL-8 secretion and evaluated in drug resistance assays. Two IL-6 and two IL-8 secreting clones express IL-6 or IL-8 levels of 10 ng/ml and 1 ng/ml in culture, while parental U-2OS and pIRESneo vector transfected control cells express IL-6 and IL-8 levels of 0.005 ng/ml and 0.1 ng/ml, respectively. MTT cytotoxicity with IL-6 transfected cells demonstrates a five-fold increase in resistance to paclitaxel and a four-fold increase in resistance to doxorubicin as compared to U-2OS. There are no changes in mitoxantrone or topotecan resistance in the IL-6 transfectants as compared to parental U-2OS. Northern analysis of IL-6 transfectants demonstrates that the resistant phenotype is not related to increased levels of MDR-1, MRP-1, or LRP. Western analysis also confirms that P-glycoprotein levels are not altered in IL-6 transfectants. Further supporting an MDR-1 independent mechanism of drug resistance, verapamil cannot reverse paclitaxel resistance in transfected cells, findings further supported by rhodamine 123 exclusion data. Treatment of IL-6 transfected cells with paclitaxel, compared with drug-sensitive parental U-2OS, shows U-2OS(IL-6) are significantly more resistant to apoptosis induced by paclitaxel and exhibit decreased proteolytic activation of caspase-3. In contrast U-2OS(IL-8) transfectants demonstrate no appreciable increase in paclitaxel resistance when compared with parental cells. In summary, while both IL-6 and IL-8 are overexpressed in paclitaxel resistant cell lines, only IL-6 has the potential to contribute directly to paclitaxel and doxorubicin resistance in U-2OS. This resistance is through a non-MDR-1 pathway.
 ...
PMID:Overexpression of IL-6 but not IL-8 increases paclitaxel resistance of U-2OS human osteosarcoma cells. 1202 4

Thymoquinone (TQ) is likely responsible for the chemotherapeutic effects of N. sativa extract; however, the cellular mechanisms remain ill-defined. TQ-induced cytotoxicity was investigated using canine osteosarcoma (COS31), its cisplatin-resistant variant (COS31/rCDDP), human breast adenocarcinoma (MCF7), human ovarian adenocarcinoma (BG-1) and Madin-Darby canine (MDCK) cell lines. TQ-induced cytotoxicity was determined using a proliferation assay (MTT assay) and apoptosis assays. Effects of TQ on the cell cycle were determined using flow cytometry. COS31/rCDDP resistant cells were the most sensitive cell line to TQ and MDCK cells were the least sensitive. TQ (25 micro M) induced apoptosis of COS31 cells 6 h after treatment and decreased the number of COS31 cells in S-phase and increased cells in G1-phase, indicating cell cycle arrest at G1. These results suggest that TQ kills cancer cells by a process that involves apoptosis and cell cycle arrest. Non-cancerous cells are relatively resistant to TQ.
 ...
PMID:In vitro inhibition of growth and induction of apoptosis in cancer cell lines by thymoquinone. 1246 92

Chitosan-DNA nanoparticles were synthesized from the complexation of the cationic polymer with a ss-gal DNA plasmid, in order to study the efficacy of chitosan to develop a non-viral gene delivery system that can be optimized for efficient gene therapy. The optimal binding conditions were determined with the fluorescamine and PicoGreen assays. DNA distribution within the nanoparticle was visualized by electron transmission microscopy, while the size and morphology were assessed by atomic force microscopy. The transfection potential was evaluated for the first time on human mesenchymal stem cells (MSCs), on human osteosarcoma cells (MG63) and on human embryonic kidney cells (HEK293). The LipofectAMINE(TM) 2000 (LF) reagent was used in comparison. The effect of chitosan-DNA nanoparticles on cell viability was illustrated with the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. The nanoparticles formed are of a diameter inferior to 100nm with a homogenous distribution of DNA. The transfection of HEK293 cells is superior to that seen with MG63 cells and MSCs, however not surpassing that seen with LF. Minimal cytotoxicity is seen with the polyplexes compared to greater than 50% toxicity with LF. These results suggest that chitosan-DNA nanoparticles have favorable characteristics for non-viral gene delivery, are cell type dependent and not cytotoxic.
 ...
PMID:Mesenchymal stem cells, MG63 and HEK293 transfection using chitosan-DNA nanoparticles. 1252 66


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>