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)

The anti-caries effects of water fluoridation are well-established. The non-dental tissue effects of fluoride in drinking water, either naturally occurring or as an additive, have been too poorly studied to permit definitive conclusions to be drawn. Claims have been made that fluoride results in an increased occurrence of malignancies, particularly osteogenic sarcoma. Experimental rat data have not resolved this issue, and epidemiologic studies are equally unclear. Initial claims that fluoride offers protection against atherosclerosis remain viable, but here too, much more directed research is needed. Early studies suggested that a water fluoride content greater than 1 ppm resulted in a lower prevalence of osteoporotic fractures. Recent epidemiologic data seriously question this conclusion and raise the possibility that even this relatively low level may increase the prevalence of osteoporotic hip fractures. Other elements, including calcium and magnesium, also vary in amount as water fluoride content varies, and it has proved difficult to distinguish the independent effects of the various nutrients in water from each other. Therapeutic use of fluoride has been largely restricted to studies of its effect on the osteoporotic study, this important issue remains unresolved. This review provides an overview of these issues, focusing on the uncertainties alluded to, and attempting to develop strategies for future research.
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PMID:Non-dental tissue effects of fluoride. 799 58

Circulating monocytes mediate inflammation in atherosclerosis and may serve as easily accessible reporters of disease. To search for markers of atherosclerosis, we compared the in vivo transcriptomes of monocytes purified from patients undergoing carotid endarterectomy and normal subjects by using the serial analysis of gene expression technique. We selected a subset of differentially expressed monocyte-specific genes and confirmed their expression levels. The Finkel-Biskis-Jinkins osteosarcoma (FOS) gene was significantly increased in patients, and the highest levels of FOS associated with patients who had previously undergone coronary revascularization. The correlation between coronary revascularization and FOS was higher than that compared with the cardiac risk marker high sensitivity C-reactive protein. In vitro inhibition of FOS using small interfering RNA and 3-hydroxy-3-methyl-glutaryl CoA reductase inhibitor simvastatin (statin) affected monocyte activation and suggested an important role in pathogenesis. Given the prominent role of FOS in inflammation and calcification, its association with atherosclerosis severity has clear pathophysiologic bases as well as clinical implications as a marker. Our results suggest that analysis of gene expression in circulating cells may provide biological and clinical insights into human atherosclerosis, and that this type of approach may be applicable for studying other types of diseases.
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PMID:Circulating transcriptome reveals markers of atherosclerosis. 1572 78

Translational studies using genomic techniques in cardiovascular diseases are still in their infancy. Access to disease-associated cardiovascular tissues from patients has been a major impediment to progress in contrast to the diagnostic advances made by oncologists using gene expression on readily available tumor samples. Nonetheless, progress is being made for atherosclerosis by carefully designed experiments utilizing diseased tissue or surrogate specimens. This review details the rationale and findings of a study utilizing freshly isolated blood mononuclear cells from patients undergoing carotid endarterectomy due to atherosclerotic stenosis and from matched healthy subjects. By querying this cardiovascular tissue surrogate, the messenger RNA levels of the Finkel-Biskis-Jenkins osteosarcoma gene in circulating monocytes were found to correlate with atherosclerosis severity in patients and with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy in healthy subjects. The major finding of this investigation is discussed in relation to observations from other human atherosclerosis gene expression studies. These distinct studies converge to demonstrate the unequivocal importance of inflammation in atherosclerosis. Although the clinical utility of the specific findings remains open, the identification of similar genes by different investigations serves to validate our report. They also provide us with insights into pathogenesis that may impact future translational applications.
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PMID:Genomic analysis of circulating cells: a window into atherosclerosis. 1678 50

The immunoregulatory cytokine IL-10 plays an essential role in down-modulating adaptive and innate immune responses leading to chronic inflammatory diseases. In contrast, cysteinyl leukotrienes (cysLTs), important proinflammatory mediators of cell trafficking and innate immune responses, are thought to enhance immune reactions in the pathogenesis of diseases, such as bronchial asthma, atherosclerosis, and pulmonary fibrosis. The aim of this study was to determine the IL-10 regulatory role in cysLT-induced activation of human monocytes and monocyte-derived dendritic cells. Herein we show that cysLT-induced activation and chemotaxis of human monocytes and monocyte-derived immature dendritic cells (iDC) are inhibited by IL-10 pretreatment. IL-10 down-regulated cysLT type 1 and 2 receptors' mRNA in a time- and concentration-dependent fashion. cysLT-induced activation of monocytes and iDCs measured by intracellular calcium flux and immediate-early gene expression (FBJ murine osteosarcoma viral oncogen homolog B and early growth response-2) was potently decreased by IL-10 and by the cysLT antagonist MK571. Chemotaxis of monocytes and iDCs to increasing concentrations of leukotriene D(4) (LTD(4)) was also inhibited by IL-10. LTD(4) enhanced iDC migration in response to CCL5. IL-10 selectively inhibited LTD(4)-induced chemotaxis without affecting migration to CCL5. These data indicate that cysLT-induced activation of human monocytes and dendritic cells may be specifically inhibited by IL-10, suggesting a direct link between the 5-lipoxygenase proinflammatory pathway and IL-10 regulatory mechanisms. Antileukotriene therapies may reproduce some regulatory mechanisms played by IL-10 in inflammatory processes.
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PMID:IL-10 inhibits cysteinyl leukotriene-induced activation of human monocytes and monocyte-derived dendritic cells. 1849 Jul 62

Clusterin/apolipoprotein J (CLU) is a secreted glycoprotein associated with many severe physiological disturbances that represent states of increased oxidative stress, such as aging, cancer, atherosclerosis, diabetes, and renal and neurodegenerative diseases. The aim of our work was to examine the effect of proteasome and lysosome inhibition on CLU expression and to determine whether those proteolytic pathways are implicated in CLU gene regulation and protein degradation. To this end we used two different model systems, namely the U-2 OS osteosarcoma cell line and the WI38 primary human embryonic lung fibroblasts. We report that proteasome inhibition promotes both heat-shock factor 1 (HSF-1)-dependent CLU gene expression induction and protein accumulation due to reduced degradation. In contrast, lysosome inhibition results in elevated levels of CLU protein but does not affect the CLU mRNA levels. We also provide direct evidence that both the intracellular precursor, psCLU, and the mature secreted, sCLU, isoforms constitute proteolytic substrates of the proteasome and the lysosome. Overall our findings indicate that CLU overexpression after proteasome inhibition relates to both positive gene transcriptional regulation by HSF-1 and posttranslational protein accumulation due to reduced proteasomal and lysosomal degradation.
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PMID:Transcriptional and posttranslational regulation of clusterin by the two main cellular proteolytic pathways. 1935 83

Cross-talk between sterol regulatory pathways and inflammatory pathways has been demonstrated to significantly impact the development of both atherosclerosis and infectious disease. The oxysterol 25-hydroxycholesterol (25HC) plays multiple roles in lipid biosynthesis and immunity. We recently used a systems biology approach to identify 25HC as an innate immune mediator that had a predicted role in atherosclerosis and we demonstrated a role for 25HC in foam cell formation. Here, we show that this mediator also has several complex roles in the antiviral response. The host response to viruses involves gene regulatory circuits with multiple feedback loops and we show here that 25HC acts as an amplifier of inflammatory signaling in macrophages. We determined that 25HC amplifies inflammatory signaling, at least in part, by mediating the recruitment of the AP-1 components FBJ osteosarcoma oncogene (FOS) and jun proto-oncogene (JUN) to the promoters of a subset of Toll-like receptor-responsive genes. Consistent with previous reports, we found that 25HC inhibits in vitro infection of airway epithelial cells by influenza. Surprisingly, we found that deletion of Ch25h, the gene encoding the enzyme responsible for 25HC production, is protective in a mouse model of influenza infection as a result of decreased inflammatory-induced pathology. Thus, our study demonstrates, for the first time to our knowledge, that in addition to its direct antiviral role, 25HC also regulates transcriptional responses and acts as an amplifier of inflammation via AP-1 and that the resulting alteration in inflammatory response leads to increased tissue damage in mice following infection with influenza.
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PMID:25-Hydroxycholesterol acts as an amplifier of inflammatory signaling. 2499 1

Quantitative phase imaging (QPI) technique is used to determine various biophysical parameters, such as refractive index, cell thickness, morphology, etc. On the other hand, fluorescence microscopy is used to acquire information regarding molecular specificity of the biological cells and tissues. Conventionally, a fully coherent light source such as laser is used in QPI technique to obtain the interference fringes with ease; however, its high coherence is also responsible for the generation of speckle and spurious fringes, which results in degraded image quality and affects the phase measurement results too. In this paper, we report a multi-modal system that can be effectively utilized to acquire time varied diverse information about the biological specimen with high spatial phase sensitivity. Herein, a single unit comprising of a fluorescence microscope and the Linnik based interferometer specially equipped with a partially spatially coherent light source illumination was developed. The integrated system is capable to procure molecular specificity and phase information of biological specimen, in a single shot, utilizing a single-chip color CCD camera. Here, we performed experiments on MG63 osteosarcoma cells, and the composite interferometric-fluorescence images were obtained and then digitally decomposed into red and green colors; and, the phase maps were reconstructed using the Fourier fringe analysis method. Furthermore, the cultured cells were monitored over a time-span to observe and investigate the time dependent morphological changes along with the quantification of cellular adhesion and spreading. Hence, the proposed system can be utilized to quantify time dependent changes in the cell's morphology and in cell adhesion which can be an indicator for the detection of various range of diseases such as arthritis, cancer, osteoporosis and atherosclerosis.
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PMID:Simultaneous fluorescence and quantitative phase imaging of MG63 osteosarcoma cells to monitor morphological changes with time using partially spatially coherent light source. 3232 33