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)

Plasmin-mediated extracellular proteolysis has been implicated in the degradation of bone in normal and pathological conditions. Normal and malignant osteoblasts can produce both tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). We have used the osteosarcoma cell line MG63 to address the question of whether the enhanced bone turnover in osteosarcomas is mediated by t-PA or by u-PAA and to study the effect of the cytokine interleukin-1 alpha (IL-1 alpha), known to influence bone degradation, on the plasminogen activator production and extracellular matrix degradation in malignant osteoblastic cells. Furthermore, the effect of IL-1 alpha on the synthesis of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) was analyzed. u-PA production by MG63 was high (approximately 180 ng/10(6) cells/24 h). Also t-PA and PAI-1 production was observed. u-PA production was rapidly increased in MG63 by IL-1 alpha (10 ng/ml), whereas an effect on t-PA production was only found after a prolonged incubation and hardly any effect of IL-1 alpha on PAI-1 production was observed. mRNA analysis revealed similar effects. u-PA receptor (u-PAR) mRNA was detectable in MG63 cells and could be increased by IL-1 alpha after 24 h. In MG63, u-PA-mediated extracellular matrix degradation was detectable, and IL-1 alpha increased the u-PA-mediated matrix degradation (approximately 2-fold). Under control conditions in MG63, only MMP-2, TIMP-1, and TIMP-2 mRNA could be observed. After the addition of IL-1 alpha, a very rapid increase in MMP-1 and MMP-3 mRNA could be observed as well as a moderate increase in TIMP-1 mRNA. The presence of MMP-2 was demonstrated by gelatin zymography. These results show that IL-1 alpha can stimulate u-PA production and can regulate extracellular proteolytic activity mainly via u-PA induction in the MG63 osteosarcoma cell line. Furthermore, IL-1 alpha has a strong stimulating effect on the production of MMP-1 and MMP-3. These findings suggest that u-PA and possibly MMP-1 and MMP-3 play an important role in the process of bone turnover in osteosarcomas.
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PMID:Regulation of plasminogen activation, matrix metalloproteinases and urokinase-type plasminogen activator-mediated extracellular matrix degradation in human osteosarcoma cell line MG63 by interleukin-1 alpha. 750 10

The effects of devitrification of an ionomer glass with a molar composition 4.5SiO(2).3Al(2)O(3).1.5P(2)O(5).3CaO.2CaF(2) on cement formation and in vitro biocompatibility were investigated. Differential thermal analysis was used to study the phase evolution in the glass, and to determine the heat treatments for production of glass-ceramics. X-ray diffraction patterns from glass frit heat-treated at 750 degrees C for 2h contained peaks corresponding to apatite (JCPDS 15-876), whereas for samples heat-treated at 950 degrees C for 2h apatite and mullite (JCPDS 15-776) were the major phases detected. Transmission electron microscopy (TEM) confirmed that apatite and apatite-mullite phases were present after heat treatments at 750 degrees C and 950 degrees C respectively. Glass and glass-ceramics were ground to prepare <45microm powders and glass ionomer cements were produced using a ratio of 1g powder: 0.2g PAA: 0.3g 10% m/v tartaric acid solution in water. In vitro biocompatibility was evaluated using cultured rat osteosarcoma (ROS) cells. Scanning electron microscopy (SEM) showed that cells colonised the surfaces of cements prepared using untreated ionomer glass and glass crystallised to form apatite (750 degrees C/2h). However, quantitative evaluation using MTT and total protein assays indicated that more cell growth occurred in the presence of cements prepared using ionomer glasses crystallised to apatite than cements prepared using untreated glass. The least cell growth and respiratory activity was observed on cements made with crystallised glass containing both apatite and mullite. It was concluded that the controlled devitrification of ionomer glasses could be used to produce GIC bone cements with improved biocompatibility.
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PMID:Devitrification of ionomer glass and its effect on the in vitro biocompatibility of glass-ionomer cements. 1289 88

A novel degradable composite system has been prepared by integrating hydroxyapatite, Ca(10)(PO(4))(6)(OH)(2), (HAP) in a polyelectrolyte complex matrix of chitosan (CHI) and poly(acrylic acid) (PAA). The composite was formulated by integrating 80 wt.% HAP in the polyelectrolyte complex matrix of CHI and PAA in the ratio 40/60 (designated as CPH). The composite could be easily fabricated into clinically significant shapes by a simple moulding procedure intended for bone graft applications. The adhesion behaviour of human osteosarcoma (HOS) cells on this degradable composite system was studied by selecting the polyelectrolyte complex, CHI/PAA 40/60 (designated as CP) as control sample. Light microscopic observations show that cells around CPH retained the typical morphology of HOS cells while cells around the polyelectrolyte complex showed a cytotoxic effect. The adhesion behaviour as well as morphological responses of the seeded cells was further investigated by scanning electron microscopy. The scanning electron micrographs of the polyelectrolyte complex, CP, showed the presence of rounded cells with raised nuclear regions, indicating delayed spreading; cells adhered on CPH were flattened with filopodia and showed good attachment and spreading, indicating better adhesion onto the HAP integrated composite. Comparing the MTT assay for quantitative evaluation of cell viability, CPH showed a higher percentage of metabolically active cells compared to CP.
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PMID:Human osteosarcoma cell adhesion behaviour on hydroxyapatite integrated chitosan-poly(acrylic acid) polyelectrolyte complex. 1689 18

The retinoblastoma (RB) tumour suppressor gene is implicated in the development of several malignancies including osteosarcoma. Recent studies postulated its loss of heterozygosity (LOH) to be a poor prognostic factor at diagnosis of osteosarcoma (OS). It remains unclear whether LOH of the RB gene is suitable as a prognostic factor at diagnosis in patients with osteosarcoma. In this study we aimed to determine the early prognostic value of RB-LOH as well as the ability of denaturating high performance liquid chromatography (DHPLC) to detect LOH at this gene locus in comparison to classical PAGE. We therefore analysed 41 samples of OS on restriction fragment length polymorphisms in introns 1, 17 and 25, and variable numbers of tandem repeats (VNTRs) in intron 20. PCR fragments were separated on 1.5% agarose gel electrophoresis. VNTRs with length differentiation of only a few base pairs were analysed by 8% PAA/Spreadex gels and additionally by DHPLC. One-hundred percent concordance was observed between the results obtained by classical PAGE and DHPLC. The latter improved intron 20 analysis as a sensitive and high throughput method for detecting LOH. Overall we found 16 RB-LOH in 41 OS (39%). Three tumours exhibited additional microsatellite instability. There was no significant correlation of the event-free- and overall-survival rate or response to chemotherapy with RB-LOH found in our study. LOH positivity was associated with a significantly younger age at diagnosis. In conclusion RB-LOH could not be verified as a poor prognostic factor for osteosarcoma in the present study.
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PMID:Determination of the prognostic value of loss of heterozygosity at the retinoblastoma gene in osteosarcoma. 1739 23

The cytotoxicity of polyelectrolytes commonly employed for layer-by-layer deposition of polyelectrolyte multilayers (PEMUs) was assessed using rat smooth muscle A7r5 and human osteosarcoma U-2 OS cells. Cell growth, viability, and metabolic assays were used to compare the responses of both cell lines to poly(acrylic acid), PAA, and poly(allylamine hydrochloride), PAH, in solution at concentrations up to 10 mM and to varying thicknesses of (PAA/PAH) PEMUs. Cytotoxicity correlated with increasing concentration of solution polyelectrolytes for both cell types and was greater for the positively charged PAH than for the negatively charged PAA. While metabolism and proliferation of both cell types was slower on PEMUs than on tissue culture plastic, little evidence for direct toxicity on cells was observed. In fact, evidence for more extensive adhesion and cytoskeletal organization was observed with PAH-terminated PEMUs. Differences in cell activity and viability on different thickness PEMU surfaces resulted primarily from differences in attachment for these adhesion-dependent cell lines.
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PMID:Cytotoxicity of free versus multilayered polyelectrolytes. 2202 11

Behaviors of rat aortic smooth muscle (A7r5) and human osteosarcoma (U2OS) cells on photo-cross-linked polyelectrolyte multilayers (PEMUs) with uniform, or gradients of, moduli were investigated. The PEMUs were built layer-by-layer with the polycation poly(allylamine hydrochloride) (PAH) and a polyanion poly(acrylic acid) (PAA) that was modified with photoreactive 4-(2-hydroxyethoxy) benzophenone (PAABp). PEMUs with different uniform and gradients of modulus were generated by varying the time of uniform ultraviolet light exposure and by exposure through optical density gradient filters. Analysis of adhesion, morphology, cytoskeletal organization, and motility of the cells on the PEMUs revealed that A7r5 cells established a polarized orientation toward increasing modulus on shallow modulus gradients (approximately 4.7 MPa mm(-1)) and durotaxed toward stiffer regions on steeper gradients (approximately 55 MPa mm(-1)). In contrast, U2OS cells exhibited little orientation or durotaxis on modulus gradients. These results demonstrate the utility of photo-cross-linked PEMUs to direct vascular and osteoblast cell behavior, a potential application for PEMU coatings on biomedical implants.
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PMID:Cell durotaxis on polyelectrolyte multilayers with photogenerated gradients of modulus. 2350 66

Current treatment options for debilitating bone diseases such as osteosarcoma, osteoporosis, and bone metastatic cancer are suboptimal and have low efficacy. New treatment options for these pathologies require targeted therapy that maximizes exposure to the diseased tissue and minimizes off-target side effects. This work investigates an approach for generating functional and targeted drug carriers specifically for treating primary osteosarcoma, a disease in which recurrence is common and the cure rate has remained around 20%. This approach utilizes the modularity of Layer-by-Layer (LbL) assembly to generate tissue-specific drug carriers for systemic administration. This is accomplished via surface modification of drug-loaded nanoparticles with an aqueous polyelectrolyte, poly(acrylic acid) (PAA), side-chain functionalized with alendronate, a potent clinically used bisphosphonate. Nanoparticles coated with PAA-alendronate are observed to bind and internalize rapidly in human osteosarcoma 143B cells. Encapsulation of doxorubicin, a front-line chemotherapeutic, in an LbL-targeted liposome demonstrates potent toxicity in vitro. Active targeting of 143B xenografts in NCR nude mice with the LbL-targeted doxorubicin liposomes promotes enhanced, prolonged tumor accumulation and significantly improved efficacy. This report represents a tunable approach towards the synthesis of drug carriers, in which LbL enables surface modification of nanoparticles for tissue-specific targeting and treatment.
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PMID:Osteotropic therapy via targeted layer-by-layer nanoparticles. 2412 32