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Increasing Expression (increasing + expression)
Selected AbstractsIncreasing Expression of the Retinoic X Receptor-B During Malignant Melanoma ProgressionJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2005S.J. McAlhany Retinoic X receptor-b (RXR-b) is a heterodimerization partner for vitamin D receptor (VDR). 1,25-dihydroxyvitamin D3 activation of VDR leads to growth inhibition in numerous cell lines, including some melanoma lines. Evaluation of VDR and RXR-b expression in vivo in melanocytic neoplasms will increase our understanding of this pathways potential role in growth control. Previous studies in our laboratory showed decreased VDR expression in superficially invasive melanoma, and progressive loss of expression in deeply invasive melanomas and metastatic melanomas (MET). We next sought to evaluate RXR-b expression. Twenty-eight melanocytic neoplasms including 8 melanomas in situ (MIS), 9 primary invasive melanomas (PIM), and 11 MET were evaluated for RXR-b expression by immunohistochemistry. Nuclear labeling was assessed as 0 (0%), 1+(<5%), 2+(>5% but <50%), or 3+(>=50%). A significant increase in RXR-b expression from low (0,1+) to high (>1+) was found when comparing MIS to PIM and MET (chi2 p < 0.05). These data suggest: 1) potential loss of 1,25-dihydroxyvitamin D3 induced growth inhibition during melanoma progression may be due to decreased VDR expression without concomitant loss of RXR-b; and 2) increased RXR-b expression during melanoma progression may offer selective advantage through alternative signaling pathways. [source] Advanced glycation endproducts: what is their relevance to diabetic complications?DIABETES OBESITY & METABOLISM, Issue 3 2007N. Ahmed Glycation is a major cause of spontaneous damage to proteins in physiological systems. This is exacerbated in diabetes as a consequence of the increase in glucose and other saccharides derivatives in plasma and at the sites of vascular complications. Protein damage by the formation of early glycation adducts is limited to lysine side chain and N-terminal amino groups whereas later stage adducts, advanced glycation endproducts (AGEs), modify these and also arginine and cysteine residues. Metabolic dysfunction in vascular cells leads to the increased formation of methylglyoxal which adds disproportionately to the glycation damage in hyperglycaemia. AGE-modified proteins undergo cellular proteolysis leading to the formation and urinary excretion of glycation free adducts. AGEs may potentiate the development of diabetic complications by activation of cell responses by AGE-modified proteins interacting with specific cell surface receptors, activation of cell responses by AGE free adducts, impairment of protein,protein and enzyme,substrate interactions by AGE residue formation, and increasing resistance to proteolysis of extracellular matrix proteins. The formation of AGEs is suppressed by intensive glycaemic control, and may in future be suppressed by thiamine and pyridoxamine supplementation, and several other pharmacological agents. Increasing expression of enzymes of the enzymatic defence against glycation provides a novel and potentially effective future therapeutic strategy to suppress protein glycation. [source] Thrombopoietin activates the growth of megakaryoblasts in patients withchronic myeloproliferative disorders and myelodysplastic syndromeEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2000Shigeo Hashimoto Abstract: The effects of thrombopoietin (TPO) on cell proliferation and differentiation, and the relation between these effects and the expression of c-mpl on leukemia cells were studied in seven acute myelogeneous leukemia cell lines and seven myelogeneous blast cell preparations from patients with chronic myeloproliferative disorders (CMPDs) and myelodysplastic syndrome (MDS). Among the leukemia cells, five preparations of megakaryoblastic leukemia cells from patients and one megakaryoblastic cell line, CMK 11.5, proliferated in response to TPO in vitro. CMK 11.5 and the blastic cells from one patient diagnosed with MDS with myelofibrosis differentiated with increasing expression of CD41a in response to TPO. However, TPO had no effect on the cells lacking megakaryocytic characteristics. Some patients with CMPD and MDS develop acute transformation with blasts demonstrating megakaryocytic features, and some of these cells show growth in response to TPO. Therefore, in vivo administration of TPO should be considered carefully for patients with CMPD or MDS, since TPO may induce leukemic cell proliferation. [source] AKT and MAPK signaling in KGF-treated and UVB-exposed human epidermal cellsJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2007Lavinia Vittoria Lotti Regulation of proliferation and differentiation in keratinocyte is a complex and dynamic process that involves activation of multiple signaling pathways triggered by different growth factors. Keratinocyte growth factor (KGF) is not only a potent mitogen, but differently from other growth factors, is a potent inducer of differentiation. The MAP kinase and AKT pathways are involved in proliferation and differentiation of many cell types including keratinocytes. We investigated here the role of KGF in modulating AKT and MAPK activity during differentiation of human keratinocytes. Our results show that the mechanisms of action of KGF are dose-dependent and that a sustained activation of the MAPK signaling cascade causes a negative regulation of AKT. We also demostrated increasing expression of KGFR substrates, such as PAK4 during keratinocyte differentiation parallel to the receptor upregulation. J. Cell. Physiol. 212:633,642, 2007. © 2007 Wiley-Liss, Inc. [source] Autocrine TGF, signaling mediates vitamin D3 analog-induced growth inhibition in breast cellsJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2001Limin Yang In this study, we address whether TGF, signaling mediates vitamin D3 analog-induced growth inhibition in nonmalignant and malignant breast cells. Normal mammary epithelial cells (184), immortalized nonmalignant mammary epithelial cells (184A1 and MCF10A), and breast cancer cells (early passage MCF7: MCF7E) were sensitive to the inhibitory effects of vitamin D3 analogs (EB1089 and MC1288) while late passage MCF7 breast cancer (MCF7L) cells were relatively resistant. A similar pattern of sensitivity to TGF, was observed with these cells. Thus, the sensitivity to the vitamin D3 analogs correlated with the sensitivity to TGF,. MCF7L TGF,RII-transfected cells, which have autocrine TGF, activity, were more sensitive to EB1089 than MCF7L cells. TGF, neutralizing antibody was found to block the inhibitory effects of these analogs. These results are consistent with the idea that autocrine TGF, signaling mediates the anti-proliferative effects of the vitamin D3 analogs in these cells. The expression of TGF, isoforms and/or TGF, receptors was induced by the analogs in the vitamin D3 and TGF, sensitive cells. Vitamin D3 analogs did not induce TGF, or TGF, receptor expression in the resistant MCF7L cells. Therefore, EB1089 induces autocrine TGF, activity through increasing expression of TGF, isoforms and/or TGF, receptors. In addition, EB1089 induced nuclear VDR protein levels in the sensitive 184A1 cells but not in the resistant MCF7L cells. 184A1 cells were more sensitive to EB1089-induced VDR-dependent transactivation than MCF7L cells as measured by a luciferase reporter construct containing the VDRE, indicating a defect of VDR signaling in MCF7L cells. Smad3, a TGF, signaling mediator, coactivated VDR-dependent transactivation in 184A1 cells but not in MCF7L cells. These results indicate that Smad3 coactivates VDR to further enhance TGF, signaling and vitamin D3 signaling in the sensitive 184A1 cells. The results also indicate that Smad3 is not of itself sufficient to coactivate VDR in TGF,/vitamin D3 resistant MCF7L cells and other factors are required. We found that the PI 3-kinase pathway inhibitor LY29004 inhibited the synergy of TGF, and EB1089 on VDR-dependent transactivation activity. This indicates that the crosstalk between TGF, and vitamin D signaling is also PI 3-kinase pathway dependent. © 2001 Wiley-Liss, Inc. [source] The allergen Bet v 1 in fractions of ambient air deviates from birch pollen countsALLERGY, Issue 7 2010J. T. M. Buters To cite this article: Buters JTM, Weichenmeier I, Ochs S, Pusch G, Kreyling W, Boere AJF, Schober W, Behrendt H. The allergen Bet v 1 in fractions of ambient air deviates from birch pollen counts. Allergy 2010; 65: 850,858. Abstract Background:, Proof is lacking that pollen count is representative for allergen exposure, also because allergens were found in nonpollen-bearing fractions of ambient air. Objective:, We monitored simultaneously birch pollen and the major birch pollen allergen Bet v 1 in different size fractions of ambient air from 2004 till 2007 in Munich, Germany. Methods:, Air was sampled with a ChemVol® high-volume cascade impactor equipped with stages for particulate matter (PM)>10 ,m, 10 ,m>PM>2.5 ,m, and 2.5 ,m>PM>0.12 ,m. Allergen was determined with a Bet v 1-specific ELISA. Pollen count was assessed with a Burkard pollen trap. We also measured the development of allergen in pollen during ripening. Results:, About 93 ± 3% of Bet v 1 was found in the PM,>,10 ,m fraction, the fraction containing birch pollen. We did not measure any Bet v 1 in 2.5 ,m,>,PM,>,0.12 ,m. Either in Munich no allergen was in this fraction or the allergen was absorbed to diesel soot particles that also deposit in this fraction. Pollen released 115% more Bet v 1 in 2007 than in 2004. Also within 1 year, the release of allergen from the same amount of pollen varied more than 10-fold between different days. This difference was explained by a rapidly increasing expression of Bet v 1 in pollen in the week just before pollination. Depending on the day the pollen is released during ripening, its potency varies. Conclusion:, In general, pollen count and allergen in ambient air follow the same temporal trends. However, because a 10-fold difference can exist in allergen potency of birch pollen, symptoms might be difficult to correlate with pollen counts, but perhaps better with allergen exposure. [source] Co-regulation of Xanthomonas campestris virulence by quorum sensing and a novel two-component regulatory system RavS/RavRMOLECULAR MICROBIOLOGY, Issue 6 2009Ya-Wen He Summary Xanthomonas campestris pv. campestris (Xcc) is known to regulate virulence through a quorum-sensing mechanism. Detection of the quorum-sensing signal DSF by sensor RpfC leads to activation of the response regulator RpfG, which influences virulence by degrading cyclic-di-GMP and by subsequent increasing expression of the global regulator Clp. In this study, we show that mutation of a response regulator RavR containing the GGDEF,EAL domains decreases Xcc virulence factor production. The functionality of RavR is dependent on its EAL domain-associated cyclic-di-GMP phosphodiesterase activity. Deletion of a multidomain sensor gene ravS, which shares the same operon with ravR, results in similar phenotype changes as the ravR mutant. In addition, the sensor mutant phenotypes can be rescued by in trans expression of the response regulator, supporting the notion that RavS and RavR constitute a two-component regulatory system. Significantly, mutation of either the PAS domain or key residues of RavS implicated in sensing low-oxygen tension abrogates the sensor activity in virulence regulation. Moreover, similar to the DSF signalling system, RavS/RavR regulates virulence gene expression through the global regulator Clp. These results outline a co-regulation mechanism that allows Xcc to integrate population density and environmental cues to modulate virulence factor production and adaptation. [source] | |||||||||||||