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)

Although the radiopharmaceuticals used for bone scintigraphy are of very high quality, the search for an "ideal" agent continues. To optimise the detectability of bone lesions, we analysed 244 different 99mTc-labeled phosphonates in animal experiments. In osteosarcoma-carrying rats 99mTc-labeled 1-Hydroxy-3-methyl-phosphinic-1, 1-propanediphosphonic acid (HMPD) was shown to produce the best lesion/normal bone ratio. 99mTc-MDP was used as reference. The ratio was found to be 1.28 for 99mTc-HMPD. The transferability of our results in animals to the situation in man was studied in 10 patients with bone metastases. There was for 99mTc-HMPD an improvement of the lesion/normal bone ratio by more than 60% but also an additional reduction of the soft tissue contrast by about 40%. 15% of the metastases were detected by scintigraphy using 99mTc-HMPD only and not with 99mTc-MDP. The new agent should make possible a better and earlier discrimination of bone lesions in the scintigram.
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PMID:[A phosphine-substituted diphosphonic acid (HMPD) for improved scintigraphic detection of bone lesions]. 146 53

7-Hydroxy-MTX production after consecutive high-dose MTX therapy (12 g/m2) was measured in 7 patients with osteosarcoma by HPLC. 7-Hydroxy-MTX serum values in the last cycle were found to be significantly lower compared with the first high-dose MTX treatment of the adjuvant chemotherapy protocol (COSS 80). Moreover, in another patient highly reduced 7-hydroxy-MTX production was correlated with severe clinical toxicity. As 7-hydroxy-MTX is a 200 fold less potent dihydrofolic acid reductase inhibitor compared with MTX decreased production of the metabolite may lead to enhanced clinical toxicity which may not be predictable monitoring MTX serum levels alone.
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PMID:7-Hydroxy-methotrexate and clinical toxicity following high-dose methotrexate therapy. 385 53

Folic acid derivatives such as folinic acid and methotrexate (MTX) have been successfully hybridized with layered double hydroxide (LDH) by ion-exchange reaction. The X-ray diffraction patterns and spectroscopic analyses indicate that these molecules intercalated into the hydroxide interlayer space are stabilized in the tilted longitudinal monolayer mode by electrostatic interaction. No significant changes in their structural and functional properties are found in the hybrids. The cellular uptake test of MTX-LDH hybrid is carried out in the fibroblast (human tendon) and SaOS-2 cell line (Osteosarcoma, human) by in vitro MTT (3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyl tetrazolium bromide) assay. The initial proliferation of SaOS-2 cell is more strongly suppressed by treatment with MTX-LDH hybrid than with MTX alone. This study clearly shows that LDH not only plays a role as a biocompatible-delivery matrix for drugs but also facilitates a significant increase in the delivery efficiency.
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PMID:Layered double hydroxide as an efficient drug reservoir for folate derivatives. 1496 39

Ideal root end filling materials should have good physical and chemical properties, and the most important is that the material should be biocompatible with periradicular tissue. The biocompatibility of three root end filling materials, mineral trioxide aggregate, calcium hydroxide-based cement, and eugenol-based cement, were investigated in vitro by culturing extracts of these materials with human osteogenic sarcoma cells (U2OS). Extracts of each of the materials were made after incubation of the materials for 1 day and 1 week with complete McCoy's medium. The extracts were serially diluted and then incubated with U2OS cells for 24 and 48 h. Cell survival rates were assessed by means of a viability assay for mitochondrial dehydrogenase activity. Differences in mean cell survival rates were statistically assessed using one-way ANOVA. Results showed that the survival rates of U2OS cells were largest with mineral trioxide aggregate, followed by calcium hydroxide-based cement and eugenol-based cement at 24- and 48-h exposures using the 1-day and 1-week extracts. The duration of root end filling material extraction time and treatment time showed variable influence on the survival rates. The results suggest that mineral trioxide aggregate is more biocompatible than the other root end filling materials and is suitable for use in the clinical setting.
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PMID:Biocompatibility of human osteosarcoma cells to root end filling materials. 1538 32

The aim of this study was to compare the effects of different materials used in primary root canal fillings on the cell viability of human osteosarcoma cell lines. The experimental group contained six different types of root canal filling materials, including zinc oxide (ZnO) + eugenol + formocresol (FC), Ca(OH)(2) + FC, Ca(OH)(2) + Iodoform, Ca(OH)(2) + Iodoform + camphorated parachlorophenol (CPC), Ca(OH)(2) + CPC, and Vitapex. Cell viability tests were performed using tetrazolium bromide colorimetric (MTT) assay on human osteosacorma cell lines (U2OS). The results were analyzed using one-way analysis of variance (ANOVA) and Student-Newman-Keul's test with p < 0.05 showed statistical differences. The ZnO + eugenol + FC group and Ca(OH)(2) + FC group showed the lowest survival rates (p < 0.05). The Ca(OH)(2) + Iodoform + CPC group and Ca(OH)(2) + CPC group showed significantly lower survival rates at concentrations above 6 microL/mL (p < 0.05). The Ca(OH)(2) + Iodoform group and Vitapex group showed the highest survival rates (p < 0.05). We concluded that the use of calcium hydroxide with iodoform as a root filling base material is a better option than other medications.
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PMID:Biocompatibility of various formula root filling materials for primary teeth. 1686 58

The use of root-end filling materials designed to stimulate hard and soft tissue repair in periradicular tissues is highly recommended. The materials should demonstrate good cell and tissue compatibility. The aim of the present study was to compare in vitro biocompatibility and in vivo tissue reaction with calcium hydroxide-based, eugenol-based and mineral trioxide aggregate root-end filling materials. The human osteosarcoma cell line was treated with immersed root end filling materials. The test materials were implanted in rats and the results observed at 6 and 8 weeks. In vitro, the highest survival rate was demonstrated for the mineral trioxide aggregate (p<0.05). In vivo, a radiopaque ring was evident in the calcium hydroxide implants on the eight-week radiograph. Histopathology revealed eugenol-based material with the inflammatory cells around the implant, with fibrous connective tissue forming around the calcium hydroxide-based analog. The mineral trioxide aggregate appears to be well tolerated by the tissue.
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PMID:Tissue and cell reactions to implanted root-end filling materials. 1693 67

The purpose of this study was to monitor the expression of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) produced by an osteoblastic cell line MG63 stimulated with Prevotella nigrescens lipopolysaccharides (LPS), and to compare the level of secretion before and after the P. nigrescens LPS was treated with calcium hydroxide [Ca(OH)2]. The underlying hypothesis is that the balance between MMP and TIMP secretion is the key to an understanding of the host degradative pathways involved in the pathogenesis of bacterial derived pulpal and periapical diseases. Confluent monolayers of MG63 human osteosarcoma cells were exposed to varying concentrations of P. nigrescens or Escherichia coli LPS. Alternately, confluent cultures were exposed to 10 microg/ml of bacterial LPS pretreated with Ca(OH)2 (12.5 mg/ml) for 72 hours. At the end of the experimental period, total RNA was extracted and real-time quantitative polymerase chain reaction (PCR) was performed for MMP-1, TIMP-1, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The results showed that the expression of MMP-1 mRNA was low and invariant for the experimental period in the negative controls. However, exposure to P. nigrescens LPS increased expression after 48 hours. Expression of TIMP-1 mRNA was highly increased at 24 and 48 hours with lower concentrations of LPS in contrast to a suppression with a concentration of 10 microg/ml. Treatment of P. nigrescens LPS with Ca(OH)2 resulted in a down-regulation of MMP-1, whereas pretreated E. coli LPS demonstrated no stimulatory activity for MMP-1 gene expression. Both types of LPS when pretreated with Ca(OH)2 induced slightly up-regulated expression of TIMP-1.
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PMID:Effect of calcium hydroxide-treated Prevotella nigrescens on the gene expression of matrix metalloproteinase and its inhibitor in MG63 cells. 1717 69

Many researches have shown that anionic clays can be used as delivery carriers for drug or gene molecules due to their efficient cellular uptake in vitro, and enhanced permeability and retention effect in vivo. It is, therefore, highly required to establish a guideline on their potential toxicity for practical applications. The toxicity of anionic clay, layered metal hydroxide nanoparticle, was evaluated in two human lung epithelial cells, carcinoma A549 cells and normal L-132 cells, and compared with that in other human cancer cell lines such as cervical adenocarcinoma cells (HeLa) and osteosarcoma cells (HOS). The present nanoparticles showed little cytotoxic effects on the proliferation and viability of four cell lines tested at the concentrations used (<250 microg/ml) within 48 h. However, exposing cancer cells to high concentrations (250-500 microg/ml) for 72 h resulted in an inflammatory response with oxidative stress and membrane damage, which varied with the cell type (A549>HOS>HeLa). On the other hand, the toxicity mechanism seems to be different from that of other inorganic nanoparticles frequently studied for biological and medicinal applications such as iron oxide, silica, and single walled carbon nanotubes. Iron oxide caused cell death associated with membrane damage, while single walled carbon nanotube induced oxidative stress followed by apoptosis. Silica triggered an inflammation response without causing considerable cell death for both cancer cells and normal cells, whereas layered metal hydroxide nanoparticle did not show any cytotoxic effects on normal L-132 cells in terms of inflammation response, oxidative stress, and membrane damage at the concentration of less than 250 microg/ml. It is , therefore, highly expected that the present nanoparticle can be used as a efficient vehicle for drug delivery and cancer cell targeting as well.
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PMID:Toxicological effects of inorganic nanoparticles on human lung cancer A549 cells. 1918 88

Intracellular drug delivery of layered double hydroxide (LDH) nanocarriers have been examined in human osteosarcoma Saos-2 cell culture line by both electron and confocal microscopies. For transmission electron microsopic (TEM) study, LDHs and anticancer drug, methotrexate (MTX) loaded LDHs were synthesized and the particle size was controlled. From the scanning electron microscopic (SEM) studies, morphologies of LDH nanoparticle and its MTX intercalated form were proven to be platelike hexagonal with an average size of approximately 150 nm. In order to understand the cellular penetration behavior, both nanoparticles were treated to human osteosarcoma Saos-2 cell culture lines and the cellular uptake pattern with respect to incubation time was observed by TEM and SEM. We observed that the nanoparticles are attached at the cellular membrane at first and then internalized into the cells via endocytosis within 1 h. Then are located in the intracellular vacuole (endosome). In order to examine the intracellular drug delivery mechanism of LDH nanoparticles, fluorescein 5-isothiocyanate (FITC) labeled MTX was intercalated into LDH and treated on Saos-2 cells. Laser scanning confocal microscopic studies revealed that the FITC-MTX molecules were first internalized with LDH nanocarriers via endocytosis, and located in endosome to deliver loaded drug to target cellular organ. It was, therefore, concluded that LDH could play a role as drug delivery nanocarriers.
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PMID:Intracellular drug delivery of layered double hydroxide nanoparticles. 2145 54

A methotrexate (MTX)-loaded layered double hydroxide (LDH) nanoparticle system was synthesized by intercalating MTX into the interlayer spaces of LDH. In vivo pharmacokinetic study demonstrated that the MTX-LDH hybrid had similar kinetic behaviors as free MTX, showing a rapid decline in the plasma MTX level, with characteristics of a biexponential function. However, the hybrid system remarkably suppressed tumor growth in human osteosarcoma-bearing mice compared to an equivalent amount of free MTX. Using MTX-LDH nanoparticles, a significantly high amount of MTX was delivered to target tumor tissue, whereas a low level was found in normal tissues. Moreover, LDH nanocarriers did not accumulate in any specific tissue nor cause acute toxicity up to the applied dose for the hybrid system. These results suggest that the MTX-LDH nanohybrid system has great potential as an anti-cancer drug with enhanced in vivo anti-tumor activity and bioavailability in target tumor tissue along with reduced side effects.
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PMID:In vivo anticancer activity of methotrexate-loaded layered double hydroxide nanoparticles. 2348 99


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