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)

Previous in vitro studies have shown that the effect of fluoride to increase avian osteoblast-like cell proliferation was dependent on the phosphate concentration. In vitro studies have further revealed that fluoride could also have direct effects on osteoblast-like cells to increase phosphate uptake and transiently increase cytosolic calcium. The current studies were intended to determine whether fluoride could increase net 45Ca uptake by human osteosarcoma (SaOS-2) cells and, if so, whether those effects would also be phosphate dependent. The results of these studies indicate that fluoride increased net 45Ca uptake by SaOS-2 cells, with biphasic dose and time dependencies. After 30 minutes of exposure, net 45Ca uptake was increased to a greater extent by 50 microM fluoride (217 +/- 16% of control, P < 0.001) than by 200 microM fluoride; and the stimulatory effect of 100 microM fluoride on net 45Ca uptake was greater after 20 minutes (187 +/- 22% of control, P < 0.001) than after 60 minutes (122 +/- 7% of control, P < 0.05). These effects of fluoride to increase net 45Ca uptake were dependent on the phosphate concentration in the medium. Fluoride had no effect on net 45Ca uptake in medium containing 0.4 mM phosphate, but increased net 45Ca uptake in medium containing 1.2 or 2.0 mM phosphate (P < 0.005). As the phosphate concentration was increased, the biphasic fluoride dose-response curve was shifted to a lower range of fluoride concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fluoride increases net 45Ca uptake by SaOS-2 cells: The effect is phosphate dependent. 824 71

The in vitro osteogenic effects of fluoride have not always been consistently observed in human bone cells. The present study sought to test if dexamethasone (Dex) could potentiate the action of fluoride to increase the detectability of the stimulatory effects of fluoride on [3H]thymidine incorporation, alkaline phosphatase (ALP) specific activity, collagen synthesis, and osteocalcin secretion in human TE85 osteosarcoma cells. Neither Dex at 10(-10)-10(-6) M or fluoride at a mitogenic dose (100 microM) had any consistent stimulatory effects on thymidine incorporation. When the cells were treated with both agents simultaneously, significant and highly reproducible stimulations were observed. The mitogenic effects of the two agents were confirmed with cell number counting. Analysis of variance (ANOVA) revealed a significant interaction (P < 0.001) between fluoride and Dex on cell proliferation. The enhancing effect of Dex on [3H]thymidine incorporation was not due to a shift of the optimal dose response of fluoride. Though fluoride alone or Dex alone also had no consistent effect on ALP specific activity, the co-treatment with fluoride and Dex for 24 hours produced significant (P < 0.001, ANOVA) stimulation in ALP specific activity. Fluoride alone had no consistent effect on collagen synthesis and on 1, 25(OH)2D3-dependent osteocalcin secretion, whereas Dex treatment consistently inhibited these two osteoblastic parameters in a dose-dependent manner. However, both the collagen synthesis and osteocalcin secretion rates were significantly higher (P < 0.001 ANOVA for each) when the cells were co-treated with Dex and fluoride (100 microM) than when they were treated with Dex alone. Thus, these data indicate that the response in collagen synthesis and osteocalcin secretion to fluoride stimulation was more readily observed in the presence of Dex than in its absence. ANOVA analysis revealed that the interaction between fluoride and Dex on collagen synthesis, but not the 1,25(OH)2D3-dependent osteocalcin secretion, was significant (P < 0.02). In summary, we have demonstrated for the first time that in TE85 cells (1) Dex potentiated the effects of fluoride on cell proliferation, ALP specific activity, and collagen synthesis; (2) while Dex at 10(-7)-10(-6) M alone inhibited the collagen synthesis and at 10(-9)-10(-6) M reduced osteocalcin secretion, Dex at 10(-8)-10(-6) M significantly stimulated the proliferation of TE85 cells; and (3) Dex interacted with fluoride to increase the percentage of experiments showing an osteogenic action of fluoride. In conclusion, the in vitro osteogenic actions of fluoride in human TE85 cells are more consistently observed in the presence than in the absence of Dex.
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PMID:Dexamethasone enhances the osteogenic effects of fluoride in human TE85 osteosarcoma cells in vitro. 866 71

Fluoride, at micromolar concentrations, stimulates bone cell proliferation in vitro. In this study, we sought to test whether fluoride at mitogenic doses increases the tyrosyl phosphorylation level and specific activity of a mitogen-activated protein kinase (MAPK) in human TE85 osteosarcoma cells. Analysis by immunoprecipitation with antiphosphotyrosine antibody followed by Western analysis using an anti-pan extracellular signal-regulated kinase antibody revealed that fluoride at the optimal mitogenic dose (i.e. 100 mumol/L) induced a time-dependent increase in the steady state tyrosyl phosphorylation level of p44mapk, but not p42mapk, with the maximal increase (4- to 13-fold) after 1-3 h fluoride treatment. The effect was sustained in that a 9-fold increase was seen after 12 h of the fluoride treatment. The sustained nature of the effect is consistent with an inhibition of dephosphorylation rather than a direct stimulation of phosphorylation. The fluoride effect on the tyrosyl phosphorylation level of p44mapk was dose dependent, with the optimal dose being 100 mumol/L fluoride. The mitogenic dose of fluoride also increased the specific activity and the in-gel kinase activity of p44mapk, but not that of p42mapk, in a time-dependent manner similar to the effect on the p44mapk tyrosyl phosphorylation level. Fluoride at the same micromolar doses did not increase cell proliferation, tyrosyl phosphorylation, or specific activity of any MAPK in human skin foreskin fibroblasts, which are fluoride-nonresponsive cells. Consistent with the interpretation that the effect of fluoride on the steady state tyrosyl phosphorylation level of p44mapk is a consequence of an inhibition of a phosphotyrosyl phosphatase (PTP), mitogenic doses of orthovanadate, a bone cell mitogen and a PTP inhibitor, also increased the steady state tyrosyl phosphorylation level of p44mapk, but not p42mapk, in a time-dependent sustained manner similar to that observed with fluoride. Together, these findings support the concept that inhibition of a PTP activity in bone cells could lead to an activation of MAPK activity.
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PMID:Fluoride at mitogenic doses induces a sustained activation of p44mapk, but not p42mapk, in human TE85 osteosarcoma cells. 910 May 84

Immunoscintigraphy is a tumour imaging technique that can have specificity, but high background radioactivity makes it difficult to obtain tumour imaging soon after the injection of radioconjugate. The aim of this study is to see whether clear tumour images can be obtained soon after injection of a radiolabelled reagent using a new linker with antibody fragments (Fab), in conditions of induced hypertension in mice. Fab fragments of a murine monoclonal antibody against human osteosarcoma were labelled with radioiodinated 3'-iodohippuryl N-epsilon-maleoyl-L-lysine (HML) and were injected intravenously to tumour-bearing mice. Angiotensin II was administered for 4 h before and for 1 h after the injection of radiolabelled Fab. Kidney uptake of 125I-labelled-HML-Fab was much lower than that of 125I-labelled-Fab radioiodinated by the chloramine-T method, and the radioactivity of tumour was increased approximately two-fold by angiotensin II treatment at 3 h after injection, indicating high tumour-to-normal tissue ratios. A clear tumour image was obtained with 131I-labelled-HML-Fab at 3 h post-injection. The use of HML as a radiolabelling reagent, combined with angiotensin II treatment, efficiently improved tumour targeting and enabled the imaging of tumours. These results suggest the feasibility of PET scan using antibody fragment labelled with 18F-fluorine substitute for radioiodine.
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PMID:A novel immunoscintigraphy technique using metabolizable linker with angiotensin II treatment. 1020 95

Objective: Positron emission tomography (PET) using fluorine-18-fluoro-2-D-deoxyglucose (FDG) is increasingly being used to evaluate and manage oncology patients. Several reports have documented its utility in diagnosis, staging, response to treatment, and tumor viability assessment. There is, however, a paucity of literature on PET scanning in patients with osteosarcoma. We report results of serial F-18 FDG-PET scans in 16 untreated patients with osteosarcoma who underwent chemotherapy prior to surgical resection of the primary tumor site.Procedure: Changes in tumor fluoro-2-D-deoxyglucose (FDG) uptake were correlated with percent tumor necrosis on histopathology. PET studies were analyzed by visual assessment of tumor uptake of FDG by 3 independent observers, calculating a tumor to normal background activity ratio (TBR) by drawing regions of interest (ROIs) around the tumor and background activity in the contralateral normal limb, and percent change in TBR values between baseline and presurgical study.Results: All patients had positive baseline scans. Baseline TBRs ranged between 2.5-8.7 and visual assessment of intensity of FDG uptake was 2-3 on a scale of 0-3. At histopathologic examination, 8 patients were classified as good responses with more than 90% tumor necrosis and 8 patients as poor responses with less than 90% necrosis. Tumor necrosis was accurately predicted on PET scan in 15/16 patients by visual assessment, 14/15 patients by final TBR value on presurgery scans, and 7/15 patients using percent change of TBR on serial scans.Conclusions: The results of this small series suggest that FDG-PET scanning is fairly accurate in evaluating the response of osteosarcoma to chemotherapy. Visual assessment and TBR are more accurate in predicting tumor necrosis than percent change in TBR on serial scans.
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PMID:Response of Osteosarcoma to Chemotherapy. Evaluation with F-18 FDG-PET Scans. 1083 5

The effects of fluoride and insulin-like growth factor (IGF)-I on sodium-dependent (Na(d)) alanine and phosphate (Pi) transport were compared in a human osteosarcoma cell line, SAOS-2/B-10. Fluoride stimulated Na(d) alanine but not Pi uptake in a dose-dependent manner, whereas IGF-I stimulated both alanine and Na(d)Pi transport. IGF-I and low concentrations of fluoride stimulated Na(d) alanine transport rapidly. Genistein, an inhibitor of tyrosine kinase blocked IGF-I- but not fluoride-stimulated Na(d) alanine transport. The effects of fluoride and IGF-I were additive and not associated with corresponding changes in cell number or protein content. In conclusion, low concentrations of fluoride rapidly and selectively stimulate Na(d) alanine transport in SAOS-2 cells.
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PMID:Differential effects of fluoride and insulin-like growth factor I on sodium-dependent alanine and phosphate transport in a human osteoblast-like cell line. 1099 Apr 45

The purpose of this study was to compare positron emission tomography using fluorine-18 fluorodeoxyglucose (FDG-PET) and technetium-99m methylene diphosphonate (MDP) bone scintigraphy in the detection of osseous metastases from malignant primary osseous tumours. In 70 patients with histologically proven malignant primary bone tumours (32 osteosarcomas, 38 Ewing's sarcomas), 118 FDG-PET examinations were evaluated. FDG-PET scans were analysed with regard to osseous metastases in comparison with bone scintigraphy. The reference methods for both imaging modalities were histopathological analysis, morphological imaging [additional conventional radiography, computed tomography (CT) or magnetic resonance imaging (MRI)] and/or clinical follow-up over 6-64 months (median 20 months). In 21 examinations (18%) reference methods revealed 54 osseous metastases (49 from Ewing's sarcomas, five from osteosarcomas). FDG-PET had a sensitivity of 0.90, a specificity of 0.96 and an accuracy of 0.95 on an examination-based analysis. Comparable values for bone scintigraphy were 0.71, 0.92 and 0.88. On a lesion-based analysis the sensitivity of FDG-PET and bone scintigraphy was 0.80 and 0.72, respectively. Analysing only Ewing's sarcoma patients, the sensitivity, specificity and accuracy of FDG-PET and bone scan were 1.00, 0.96 and 0.97 and 0.68, 0.87 and 0.82, respectively (examination-based analysis). None of the five osseous metastases from osteosarcoma were detected by FDG-PET, but all of them were true-positive using bone scintigraphy. In conclusion, the sensitivity, specificity and accuracy of FDG-PET in the detection of osseous metastases from Ewing's sarcomas are superior to those of bone scintigraphy. However, in the detection of osseous metastases from osteosarcoma, FDG-PET seems to be less sensitive than bone scintigraphy.
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PMID:FDG-PET for detection of osseous metastases from malignant primary bone tumours: comparison with bone scintigraphy. 1100 11

Fluoride is used in dentistry as a prophylactic agent to reduce caries rates due to the demineralization/remineralization effect and its influence on the metabolism of cariogenic bacteria. The purpose of this study was to evaluate the cytotoxic effects of sodium fluoride (NaF) on three different cell lines and the antibacterial potency on Streptococcus sobrinus. Cell lines were treated with various concentrations of NaF ranging from 0.039 mM to 10 mM for 24 h. For microbial assays, concentrations of NaF between 0.03 mM and 10 mM were added to liquid cultures of bacteria. Our results showed that immortalized human keratinocytes (HaCaT) and human osteogenic sarcoma cells (SAOS-2) were similarly affected by concentrations up to 2.5 mM. However, cell growth of HaCaT was slightly more inhibited at 2.5 mM of NaF than SAOS-2. At concentrations between 0.62 mM and 10 mM, 3T3 mouse fibroblast cells reacted more sensitively than HaCaT and SAOS-2 to NaF. The 3T3 cells did not survive in the presence of 10 mM NaF. NaF caused no significant effect on all tested cells at concentrations of < or = 0.31 mM. NaF at 0.039 mM and 0.06 mM did not affect growth of S. sobrinus. At concentrations of 0.125 mM and 0.5 mM, growth was slightly reduced. The proliferation of S. sobrinus significantly decreased at 1 mM and 2 mM NaF. S. sobrinus survived at 4 mM, revealing a delayed log phase with a decreased proliferation. No viable S. sobrinus cells were detected at concentrations of > or = 8 mM NaF. Data analysis revealed that overall treatment effects were highly significant (P<0.05, analysis of variance, Tukey's difference test). This study indicates that cytotoxic effects due to NaF significantly vary in dependence upon the applied cell line. The toxicity of NaF approached 50% (TC50) at concentrations of 6 mM for HaCaT, 2.3 mM for 3T3 cells, and 7.5 mM for SAOS-2. Additionally, NaF revealed antimicrobial effects only at concentrations that are significantly higher than oral fluoride concentrations.
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PMID:Chemical-biological interactions of NaF with three different cell lines and the caries pathogen Streptococcus sobrinus. 1216 20

Concentrations of the naturally occurring alpha-emitting radioelements, radium-226, radium-228, and lead-210, and of stable lead and fluorine were determined in bone specimens from 32 individuals having a verified osteogenic sarcoma. Comparison of these results with those for the average person showed no significant differences in either the absorbed dose (rad) from the accumulated radioisotopes or in the concentrations of the elements studied.
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PMID:RADIUM-226, RADIUM-228, LEAD-210, AND FLUORINE IN PERSONS WITH OSTEOGENIC SARCOMA. 1416 42

A series of fluorine containing tricyclic analogues of acyclovir (ACV, 1) and ganciclovir (GCV, 2) were synthesized and evaluated for their activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) and cytostatic activity against HSV-1 thymidine kinase (TK) gene-transduced human osteosarcoma tumour cells. It was found that fluorine substitution reduced the antiviral activity, but most of the new compounds were pronounced cytostatic agents with potency and selectivity similar to those of parental ACV and GCV. Compounds 12, 13 and 16 seem to be promising as labeled substrates for (19)F NMR studies of the HSV TK-ligand interaction and/or monitoring of their metabolites in cells expressing HSV TK.
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PMID:Fluorosubstitution and 7-alkylation as prospective modifications of biologically active 6-aryl derivatives of tricyclic acyclovir and ganciclovir analogues. 1572 62

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