oalib

Publish in OALib Journal

ISSN: 2333-9721

APC: Only $99

Submit

Any time

2015 ( 13 )

2014 ( 16 )

2013 ( 20 )

2012 ( 28 )

Custom range...

Search Results: 1 - 10 of 205 matches for " Troels Schepeler "
All listed articles are free for downloading (OA Articles)
Page 1 /205
Display every page Item
Clusterin expression can be modulated by changes in TCF1-mediated Wnt signaling
Troels Schepeler, Francisco Mansilla, Lise L Christensen, Torben F ?rntoft, Claus L Andersen
Journal of Molecular Signaling , 2007, DOI: 10.1186/1750-2187-2-6
Abstract: Over-expression of the cytoplasmic domain of E-cadherin tagged with GFP was used to abrogate Wnt signaling activity in LS174T and HCT116 colon carcinoma cells. This fusion construct sequestered signaling competent β-catenin whereby Wnt signaling was abrogated, and consequently cytoplasmic CLU protein levels increased as demonstrated by immunofluorescence. To determine which branch of the Wnt pathway was mediating the CLU response, we over-expressed dominant negative (dn) TCF1 and TCF4 transcription factors in stably transfected LS174T cells. We observed both intra- and extracellular levels of CLU protein to be induced by dnTCF1 but not dnTCF4. Subsequent analysis of the expression levels of three CLU mRNA variants by real time RT-PCR revealed only one CLU mRNA variant to be responsive to dnTCF1 over-expression. 5'-end RACE indicated that this CLU mRNA variant was shorter at the 5'-end than previously reported, and accordingly the translated protein was predicted to be shorter at the N-terminus and destined to the secretory pathway which fit our observations. Examination of the immediate expression kinetics of CLU after dnTCF1 over-expression using real time RT-PCR indicated that CLU might be a secondary Wnt target.In conclusion, we have demonstrated that the Wnt signaling pathway specifically regulates one out of three CLU mRNA variants via TCF1. This CLU transcript is shorter at the 5' end than reported by the RefSeq database, and produces the intracellular 60 kDa CLU protein isoform which is secreted as a ~80 kDa protein after post-translational processing.The clusterin (CLU) protein was first discovered more than 25 years ago in rat testis fluid because of its ability to facilitate clustering of a variety of cell types in culture[1]. Since then, homologues of the broadly expressed CLU gene have been identified in several species and CLU proteins have been found in most mammalian body fluids[2]. CLU is an enigmatic molecule, implicated in diverse biological proces
Tumor-specific usage of alternative transcription start sites in colorectal cancer identified by genome-wide exon array analysis
Kasper Thorsen, Troels Schepeler, Bodil ?ster, Mads H Rasmussen, S?ren Vang, Kai Wang, Kristian Q Hansen, Philippe Lamy, Jakob Pedersen, Asger Eller, Francisco Mansilla, Kirsti Laurila, Carsten Wiuf, S?ren Laurberg, Lars Dyrskj?t, Torben F ?rntoft, Claus L Andersen
BMC Genomics , 2011, DOI: 10.1186/1471-2164-12-505
Abstract: By profiling 108 colorectal samples using exon arrays, we identified nine genes (TCF12, OSBPL1A, TRAK1, ANK3, CHEK1, UGP2, LMO7, ACSL5, and SCIN) showing tumor-specific alternative TSS usage in both adenoma and cancer samples relative to normal mucosa. Analysis of independent exon array data sets corroborated these findings. Additionally, we confirmed the observed patterns for selected mRNAs using quantitative real-time reverse-transcription PCR. Interestingly, for some of the genes, the tumor-specific TSS usage was not restricted to colorectal cancer. A comprehensive survey of the nine genes in lung, bladder, liver, prostate, gastric, and brain cancer revealed significantly altered mRNA isoform ratios for CHEK1, OSBPL1A, and TCF12 in a subset of these cancer types.To identify the mechanism responsible for the shift in alternative TSS usage, we antagonized the Wnt-signaling pathway in DLD1 and Ls174T colorectal cancer cell lines, which remarkably led to a shift in the preferred TSS for both OSBPL1A and TRAK1. This indicated a regulatory role of the Wnt pathway in selecting TSS, possibly also involving TP53 and SOX9, as their transcription binding sites were enriched in the promoters of the tumor preferred isoforms together with their mRNA levels being increased in tumor samples.Finally, to evaluate the prognostic impact of the altered TSS usage, immunohistochemistry was used to show deregulation of the total protein levels of both TCF12 and OSBPL1A, corresponding to the mRNA levels observed. Furthermore, the level of nuclear TCF12 had a significant correlation to progression free survival in a cohort of 248 stage II colorectal cancer samples.Alternative TSS usage in colorectal adenoma and cancer samples has been shown for nine genes, and OSBPL1A and TRAK1 were found to be regulated in vitro by Wnt signaling. TCF12 protein expression was upregulated in cancer samples and correlated with progression free survival.Colorectal cancer (CRC) is a leading cause of cancer mo
Functional Screening Identifies miRNAs Influencing Apoptosis and Proliferation in Colorectal Cancer
Lise Lotte Christensen, Anja Holm, Juha Rantala, Olli Kallioniemi, Mads H. Rasmussen, Marie S. Ostenfeld, Frederik Dagnaes-Hansen, Bodil ?ster, Troels Schepeler, Heidi Tobiasen, Kasper Thorsen, Oliver M. Sieber, Peter Gibbs, Philippe Lamy, Torben F. Hansen, Anders Jakobsen, Eva M. Riising, Kristian Helin, Jan Lubinski, Rikke Hagemann-Madsen, S?ren Laurberg, Torben F. ?rntoft, Claus L. Andersen
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0096767
Abstract: MicroRNAs (miRNAs) play a critical role in many biological processes and are aberrantly expressed in human cancers. Particular miRNAs function either as tumor suppressors or oncogenes and appear to have diagnostic and prognostic significance. Although numerous miRNAs are dys-regulated in colorectal cancer (CRC) only a small fraction has been characterized functionally. Using high-throughput functional screening and miRNA profiling of clinical samples the present study aims at identifying miRNAs important for the control of cellular growth and/or apoptosis in CRC. The high-throughput functional screening was carried out in six CRC cell lines transfected with a pre-miR library including 319 synthetic human pre-miRs. Phenotypic alterations were evaluated by immunostaining of cleaved cPARP (apoptosis) or MKI67 (proliferation). Additionally, TaqMan Human MicroRNA Array Set v2.0 was used to profile the expression of 667 miRNAs in 14 normal colon mucosa and 46 microsatellite stable stage II CRC patients. Among the miRNAs that induced growth arrest and apoptosis in the CRC cell lines, and at same time were dys-regulated in the clinical samples, miR-375 was selected for further analysis. Independent in vitro analysis of transient and stable transfected CRC cell lines confirmed that miR-375 reduces cell viability through the induction of apoptotic death. We identified YAP1 as a direct miR-375 target in CRC and show that HELLS and NOLC1 are down-stream targets. Knock-down of YAP1 mimicked the phenotype induced by miR-375 over-expression indicating that miR-375 most likely exerts its pro-apoptotic role through YAP1 and its anti-apoptotic down-stream targets BIRC5 and BCL2L1. Finally, in vivo analysis of mouse xenograft tumors showed that miR-375 expression significantly reduced tumor growth. We conclude that the high-throughput screening successfully identified miRNAs that induce apoptosis and/or inhibit proliferation in CRC cells. Finally, combining the functional screening with profiling of CRC tissue samples we identified clinically relevant miRNAs and miRNA targets in CRC.
Tocilizumab: The evidence for its place in the treatment of juvenile idiopathic arthritis
Troels Herlin
Core Evidence , 2009, DOI: http://dx.doi.org/10.2147/CE.S5992
Abstract: cilizumab: The evidence for its place in the treatment of juvenile idiopathic arthritis Review (4378) Total Article Views Authors: Troels Herlin Published Date August 2009 Volume 2009:4 Pages 181 - 189 DOI: http://dx.doi.org/10.2147/CE.S5992 Troels Herlin Department of Pediatrics, Aarhus University Hospital, Skejby, Aarhus, Denmark Introduction: Juvenile idiopathic arthritis (JIA) is one of the most common chronic diseases with childhood onset. It comprises different subtypes of which the systemic onset subtype is often resistant to treatment. With the advent of biological treatment with tumor necrosis factor-α (TNFα)-inhibitors, the clinical outcome of JIA has improved considerably, but only for subtypes other than systemic JIA. Substantial evidence shows that the proinflammatory cytokine interleukin-6 (IL-6) plays a pivotal role in systemic JIA. The blockage of IL-6 action by tocilizumab, a humanized anti-IL-6-receptor monoclonal antibody, could therefore be an effective treatment of systemic JIA. Aims: The purpose of this article was to review the clinical trials of tocilizumab and to discuss its place in the treatment of JIA with the focus on the systemic onset of disease. Evidence review: Two phase II studies and one phase III clinical trial of tocilizumab demonstrating the clinical efficacy and safety in systemic onset JIA have been published. Within those studies, sustained and high response rates of clinical improvement have been achieved with American College of Rheumatology Pediatric criteria (ACRPed) 30, 50, and 70 observed in 98%, 94%, and 90% of patients, respectively, after 48 weeks. One study regarding the clinical efficacy of tocilizumab for the treatment of oligo- and polyarticular JIA has been presented only as a conference abstract. Place in therapy: The very promising results seen so far in patients with severe systemic JIA and acceptable tolerability gives tocilizumab a central role in the future therapy in controlling this disease. No other biological therapy has achieved similar high response rates when treating with tocilizumab 8 mg/kg every two weeks to patients with systemic onset JIA, but direct comparison of the efficacy of different biological agents are not yet available.
Scientific results from the deepened Lopra-1 borehole, Faroe Islands: Hydrocarbon gases in Palaeogene volcanic rocks from the Lopra-1/1A well, Faroe Islands
Laier, Troels
Geological Survey of Denmark and Greenland Bulletin , 2006,
Abstract: Hydrocarbon gases were monitored in the drilling fluid during deepening of the Lopra-1 well from 2178–3565 m, in which thermogenic, methane-rich gases had been found previously. The mud gas concentration, up to 105 ppm of methane, was generally higher in the hyaloclastite sequence, 2470 m – terminal depth (TD), than in the overlying lavas of the lower basalt formation. The highest concentrations of mud gas in the lower basalt formation were associated with the more porous tuffaceous zones, whereas no simple relationship could be established between measured mud gas concentrations and porosity of the hyaloclastic rocks, which showed less marked porosity variations than the lavas.Chemical (C2+ < 1%) and isotopic (δ13C1: –34 to –39‰) compositions of seven samples of mud gas collected at peak gas concentrations between 2657 m and 3442 m compare well with those of the hydrocarbon gases which had been seeping more or less continuously into the existing well since 1983, suggesting a common origin of the gases. Headspace methane concentrations measured in 135 canned samples of cuttings were scattered between 10 ppm and 6 × 103 ppm, with the exception of six samples from a short interval, 2685–2745 m, which showed consistently high values > 104 ppm. No particularly gas-rich zones were indicated, however, by the mud gas, nor was any significant change in lithology noted for this interval. It is possible that the technique of turbo-drilling, that had been attempted over a short interval, 2657–2675 m prior to collection of the high-level methane samples, may have caused enhanced degassingdue to the very fine cuttings produced. Chemical and isotopic composition of headspace gas and mud gas indicated the same type of gas throughout the well, although headspace methane tended to bemore enriched with respect to the 13C isotope.The origin of the Lopra-1 gas is discussed in the light of recent information obtained from source rock studies of central East Greenland and the Faroe–Shetland Basin.
Tocilizumab: The evidence for its place in the treatment of juvenile idiopathic arthritis
Troels Herlin
Core Evidence , 2009,
Abstract: Troels HerlinDepartment of Pediatrics, Aarhus University Hospital, Skejby, Aarhus, DenmarkIntroduction: Juvenile idiopathic arthritis (JIA) is one of the most common chronic diseases with childhood onset. It comprises different subtypes of which the systemic onset subtype is often resistant to treatment. With the advent of biological treatment with tumor necrosis factor-α (TNFα)-inhibitors, the clinical outcome of JIA has improved considerably, but only for subtypes other than systemic JIA. Substantial evidence shows that the proinflammatory cytokine interleukin-6 (IL-6) plays a pivotal role in systemic JIA. The blockage of IL-6 action by tocilizumab, a humanized anti-IL-6-receptor monoclonal antibody, could therefore be an effective treatment of systemic JIA.Aims: The purpose of this article was to review the clinical trials of tocilizumab and to discuss its place in the treatment of JIA with the focus on the systemic onset of disease. Evidence review: Two phase II studies and one phase III clinical trial of tocilizumab demonstrating the clinical efficacy and safety in systemic onset JIA have been published. Within those studies, sustained and high response rates of clinical improvement have been achieved with American College of Rheumatology Pediatric criteria (ACRPed) 30, 50, and 70 observed in 98%, 94%, and 90% of patients, respectively, after 48 weeks. One study regarding the clinical efficacy of tocilizumab for the treatment of oligo- and polyarticular JIA has been presented only as a conference abstract.Place in therapy: The very promising results seen so far in patients with severe systemic JIA and acceptable tolerability gives tocilizumab a central role in the future therapy in controlling this disease. No other biological therapy has achieved similar high response rates when treating with tocilizumab 8 mg/kg every two weeks to patients with systemic onset JIA, but direct comparison of the efficacy of different biological agents are not yet available.Keywords: tocilizumab, anti-IL-6-receptor antibody, biologics, systemic, juvenile idiopathic arthritis
Domain Structure of Black Hole Space-Times
Troels Harmark
Physics , 2009, DOI: 10.1103/PhysRevD.80.024019
Abstract: We introduce the domain structure for stationary black hole space-times. Given a set of commuting Killing vector fields of the space-time the domain structure lives on the submanifold where at least one of the Killing vector fields have zero norm. Depending on which Killing vector field has zero norm the submanifold is naturally divided into domains. A domain corresponds either to a set of fixed points of a spatial symmetry or to a Killing horizon, depending on whether the characterizing Killing vector field is space-like or time-like near the domain. The domain structure provides invariants of the space-time, both topological and geometrical. It is defined for any space-time dimension and any number of commuting Killing vector fields. We examine the domain structure for asymptotically flat space-times and find a canonical form for the metric of such space-times. The domain structure generalizes the rod structure introduced for space-times with D-2 commuting Killing vector fields. We analyze in detail the domain structure for Minkowski space, the Schwarzschild-Tangherlini black hole and the Myers-Perry black hole in six and seven dimensions. Finally we consider the possible domain structures for asymptotically flat black holes in six and seven dimensions.
Supergravity and Space-Time Non-Commutative Open String Theory
Troels Harmark
Physics , 2000, DOI: 10.1088/1126-6708/2000/07/043
Abstract: We study the non-critical space-time non-commutative open string (NCOS) theory using a dual supergravity description in terms of a certain near-horizon limit of the F1-Dp bound state. We find the thermodynamics of NCOS theory from supergravity. The thermodynamics is equivalent to Yang-Mills theory on a commutative space-time. We argue that this fact does not have to be in contradiction with the expected Hagedorn behaviour of NCOS theory. To support this we consider string corrections to the thermodynamics. We also discuss the relation to Little String Theory in 6 dimensions.
Small Black Holes on Cylinders
Troels Harmark
Physics , 2003, DOI: 10.1103/PhysRevD.69.104015
Abstract: We find the metric of small black holes on cylinders, i.e. neutral and static black holes with a small mass in d-dimensional Minkowski-space times a circle. The metric is found using an ansatz for black holes on cylinders proposed in hep-th/0204047. We use the new metric to compute corrections to the thermodynamics which is seen to deviate from that of the (d+1)-dimensional Schwarzschild black hole. Moreover, we compute the leading correction to the relative binding energy which is found to be non-zero. We discuss the consequences of these results for the general understanding of black holes and we connect the results to the phase structure of black holes and strings on cylinders.
A Note on the Quantum Query Complexity of the Hidden Subgroup Problem
Troels Windfeldt
Physics , 2004,
Abstract: We are concerned with the Hidden Subgroup Problem for finite groups. We present a simplified analysis of a quantum algorithm proposed by Hallgren, Russell and Ta-Shma as well as a detailed proof of a lower bound on the probability of success of the algorithm.
Page 1 /205
Display every page Item


Home
Copyright © 2008-2017 Open Access Library. All rights reserved.