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Search Results: 1 - 10 of 88 matches for " Arild Nesbakken "
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Transcriptome instability in colorectal cancer identified by exon microarray analyses: Associations with splicing factor expression levels and patient survival
Anita Sveen, Trude H ?gesen, Arild Nesbakken, Torleiv O Rognum, Ragnhild A Lothe, Rolf I Skotheim
Genome Medicine , 2011, DOI: 10.1186/gm248
Abstract: Exon microarray profiles from two independent series including a total of 160 CRCs were investigated for their relative amounts of exon usage differences. Each exon in each sample was assigned an alternative splicing score calculated by the FIRMA algorithm. Amounts of deviating exon usage per sample were derived from exons with extreme splicing scores.There was great heterogeneity within both series in terms of sample-wise amounts of deviating exon usage. This was strongly associated with the expression levels of approximately half of 280 splicing factors (54% and 48% of splicing factors were significantly correlated to deviating exon usage amounts in the two series). Samples with high or low amounts of deviating exon usage, associated with overall transcriptome instability, were almost completely separated into their respective groups by hierarchical clustering analysis of splicing factor expression levels in both sample series. Samples showing a preferential tendency towards deviating exon skipping or inclusion were associated with skewed transcriptome instability. There were significant associations between transcriptome instability and reduced patient survival in both sample series. In the test series, patients with skewed transcriptome instability showed the strongest prognostic association (P = 0.001), while a combination of the two characteristics showed the strongest association with poor survival in the validation series (P = 0.03).We have described transcriptome instability as a characteristic of CRC. This transcriptome instability has associations with splicing factor expression levels and poor patient survival.Colorectal cancer (CRC) is a prevalent disease with a world-wide incidence of more than one million new cases each year, making it the third most commonly diagnosed cancer among men and women [1]. Colorectal tumors are heterogeneous and evolve through multiple pathways. Malignant transformation is dependent on the accumulation of numerous genetic c
High Frequency of Fusion Transcripts Involving TCF7L2 in Colorectal Cancer: Novel Fusion Partner and Splice Variants
Torfinn Nome, Andreas M. Hoff, Anne Cathrine Bakken, Torleiv O. Rognum, Arild Nesbakken, Rolf I. Skotheim
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0091264
Abstract: VTI1A-TCF7L2 was reported as a recurrent fusion gene in colorectal cancer (CRC), found to be expressed in three out of 97 primary cancers, and one cell line, NCI-H508, where a genomic deletion joins the two genes [1]. To investigate this fusion further, we analyzed high-throughput DNA and RNA sequencing data from seven CRC cell lines, and identified the gene RP11-57H14.3 (ENSG00000225292) as a novel fusion partner for TCF7L2. The fusion was discovered from both genome and transcriptome data in the HCT116 cell line. By triplicate nested RT-PCR, we tested both the novel fusion transcript and VTI1A-TCF7L2 for expression in a series of 106 CRC tissues, 21 CRC cell lines, 14 normal colonic mucosa, and 20 normal tissues from miscellaneous anatomical sites. Altogether, 42% and 45% of the CRC samples expressed VTI1A-TCF7L2 and TCF7L2-RP11-57H14.3 fusion transcripts, respectively. The fusion transcripts were both seen in 29% of the normal colonic mucosa samples, and in 25% and 75% of the tested normal tissues from other organs, revealing that the TCF7L2 fusion transcripts are neither specific to cancer nor to the colon and rectum. Seven different splice variants were detected for the VTI1A-TCF7L2 fusion, of which three are novel. Four different splice variants were detected for the TCF7L2-RP11-57H14.3 fusion. In conclusion, we have identified novel variants of VTI1A-TCF7L2 fusion transcripts, including a novel fusion partner gene, RP11-57H14.3, and demonstrated detectable levels in a large fraction of CRC samples, as well as in normal colonic mucosa and other tissue types. We suggest that the fusion transcripts observed in a high frequency of samples are transcription induced chimeras that are expressed at low levels in most samples. The similar fusion transcripts induced by genomic rearrangements observed in individual cancer cell lines may yet have oncogenic potential as suggested in the original study by Bass et al.
Phospholipase C Isozymes Are Deregulated in Colorectal Cancer – Insights Gained from Gene Set Enrichment Analysis of the Transcriptome
Stine A. Danielsen, Lina Cekaite, Trude H. ?gesen, Anita Sveen, Arild Nesbakken, Espen Thiis-Evensen, Rolf I. Skotheim, Guro E. Lind, Ragnhild A. Lothe
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0024419
Abstract: Colorectal cancer (CRC) is one of the most common cancer types in developed countries. To identify molecular networks and biological processes that are deregulated in CRC compared to normal colonic mucosa, we applied Gene Set Enrichment Analysis to two independent transcriptome datasets, including a total of 137 CRC and ten normal colonic mucosa samples. Eighty-two gene sets as described by the Kyoto Encyclopedia of Genes and Genomes database had significantly altered gene expression in both datasets. These included networks associated with cell division, DNA maintenance, and metabolism. Among signaling pathways with known changes in key genes, the “Phosphatidylinositol signaling network”, comprising part of the PI3K pathway, was found deregulated. The downregulated genes in this pathway included several members of the Phospholipase C protein family, and the reduced expression of two of these, PLCD1 and PLCE1, were successfully validated in CRC biopsies (n = 70) and cell lines (n = 19) by quantitative analyses. The repression of both genes was found associated with KRAS mutations (P = 0.005 and 0.006, respectively), and we observed that microsatellite stable carcinomas with reduced PLCD1 expression more frequently had TP53 mutations (P = 0.002). Promoter methylation analyses of PLCD1 and PLCE1 performed in cell lines and tumor biopsies revealed that methylation of PLCD1 can contribute to reduced expression in 40% of the microsatellite instable carcinomas. In conclusion, we have identified significantly deregulated pathways in CRC, and validated repression of PLCD1 and PLCE1 expression. This illustrates that the GSEA approach may guide discovery of novel biomarkers in cancer.
Identification of an epigenetic biomarker panel with high sensitivity and specificity for colorectal cancer and adenomas
Guro E Lind, Stine A Danielsen, Terje Ahlquist, Marianne A Merok, Kim Andresen, Rolf I Skotheim, Merete Hektoen, Torleiv O Rognum, Gunn I Meling, Geir Hoff, Michael Bretthauer, Espen Thiis-Evensen, Arild Nesbakken, Ragnhild A Lothe
Molecular Cancer , 2011, DOI: 10.1186/1476-4598-10-85
Abstract: Candidate biomarkers were subjected to quantitative methylation analysis in test sets of tissue samples from colorectal cancers, adenomas, and normal colonic mucosa. All findings were verified in independent clinical validation series. A total of 523 human samples were included in the study. Receiver operating characteristic (ROC) curve analysis was used to evaluate the performance of the biomarker panel.Promoter hypermethylation of the genes CNRIP1, FBN1, INA, MAL, SNCA, and SPG20 was frequent in both colorectal cancers (65-94%) and adenomas (35-91%), whereas normal mucosa samples were rarely (0-5%) methylated. The combined sensitivity of at least two positives among the six markers was 94% for colorectal cancers and 93% for adenoma samples, with a specificity of 98%. The resulting areas under the ROC curve were 0.984 for cancers and 0.968 for adenomas versus normal mucosa.The novel epigenetic marker panel shows very high sensitivity and specificity for both colorectal cancers and adenomas. Our findings suggest this biomarker panel to be highly suitable for early tumor detection.Colorectal cancer is the third most common cancer type in the US and is a major contributor to cancer-death [1]. Most cases of colorectal cancer develop from benign precursors (adenomas) during a long time interval. This provides a good opportunity for detection of colorectal cancer at an early curable stage and to screen for potentially pre-malignant adenomas [2]. Both flexible sigmoidoscopy and the Fecal Occult Blood Test (FOBT) have been tested in randomized trials and shown to reduce mortality from colorectal cancer [3]. By sigmoidoscopy adenomas may be detected and removed and thus the incidence of cancer will be reduced [4], however, this screening is invasive and cumbersome for the patient. FOBT on the other hand is non-invasive and currently the most commonly used screening test for colorectal cancer in Europe. Although the sensitivity and specificity measurements of FOBT have been
Distinct high resolution genome profiles of early onset and late onset colorectal cancer integrated with gene expression data identify candidate susceptibility loci
Marianne Berg, Trude H ?gesen, Espen Thiis-Evensen, [the INFAC-study group], Marianne A Merok, Manuel R Teixeira, Morten H Vatn, Arild Nesbakken, Rolf I Skotheim, Ragnhild A Lothe
Molecular Cancer , 2010, DOI: 10.1186/1476-4598-9-100
Abstract: The total fraction of the genome with aberrant copy number, the overall genomic profile and the TP53 mutation spectrum were similar between the two age groups. However, both the number of chromosomal aberrations and the number of breakpoints differed significantly between the groups. Gains of 2q35, 10q21.3-22.1, 10q22.3 and 19q13.2-13.31 and losses from 1p31.3, 1q21.1, 2q21.2, 4p16.1-q28.3, 10p11.1 and 19p12, positions that in total contain more than 500 genes, were found significantly more often in the early onset group as compared to the late onset group. Integration analysis revealed a covariation of DNA copy number at these sites and mRNA expression for 107 of the genes. Seven of these genes, CLC, EIF4E, LTBP4, PLA2G12A, PPAT, RG9MTD2, and ZNF574, had significantly different mRNA expression comparing median expression levels across the transcriptome between the two groups.Ten genomic loci, containing more than 500 protein coding genes, are identified as more often altered in tumors from early onset versus late onset CRC. Integration of genome and transcriptome data identifies seven novel candidate genes with the potential to identify an increased risk for CRC.Less than five percent of all patients diagnosed with colorectal cancers (CRC) carry known genetic germline alterations that predispose to the disease [1]. However, it has been estimated that up to 30% of all CRC patients may carry a genetic risk as suggested by young age at onset, multiple tumors in the same patient, and an excess of individuals with CRC within a family [2,3]. Many studies have tried to identify some of these genetic risk factors, and several recent genome-wide association studies (GWAS) have pinpointed SNP loci on chromosome arms 8q, 10p, 11q, 14q, 15q, 16q, 18q, 19q, and 20p to be associated with CRC [4-10]. Furthermore, a study by Mourra et al. [11] showed that microsatellite loci within chromosome arm 14q, known to be deleted in about 30% of all colorectal cancers, were more frequently
The Service University
Arild Tjeldvoll
Managing Global Transitions , 2010,
Abstract: The traditional western research university’s academic freedom is increasingly challenged by external economical interests. This has consequences for what has been regarded as a key quality dimension of a university. The balance between institutional autonomy, academic freedom and accountability to external stakeholders is claimed to be changing in disfavour of the academic freedom kept up by the professoriate. From its stakeholders the institution is expected to serve politicians, state bureaucracy and market in a qualitatively different way from before, primarily from economic motives. Is academic freedom at all possible in an institution predominantly financed by producing services to meet economic criteria? A likely answer would be no, and another tentative, answer could be that yes, it is possible, due to the strong academic legacy imbedded in western academics’ identity – and to the global communicative room of free actions made possible by the new information technology.
School Management: Norwegian Legacies Bowing to New Public Management
Arild Tjeldvoll
Managing Global Transitions , 2008,
Abstract: The purpose of the study was to investigate the relevance of school management training programmes to current Norwegian education policies and strategies. A specific question was asked: How relevant is the teaching professors’ understanding of school management competence? The findings indicate a split understanding of policy relevant understanding of school management. A majority of respondents had an understanding of school management coherent with the national policies and strategies. A minority did not. They saw the headmaster primarily as a communicative facilitator for teachers’ work, and an ‘administrative caretaker’. In an international perspective the findings represent a Norwegian particularity. There is a collision between Norwegian anti-management legacies of running schools and the Government’s need for effective and accountable management. This may imply a slower speed of implementing educational reforms in Norway.
Anti-essentialisme og receptionsforskning. Et forsvar for teksten
Arild Fetveit
MedieKultur : Journal of Media and Communication Research , 1996,
Abstract: Hvad var rsagen til, at receptionsforskningen i 1980′erne kunne opn en s omfattende popularitet inden for medieforskningen? Arild Fetveit argumenterer i artiklen for, at receptionsforskningens succes bunder i, at den var i stand til at indkorporere tidens st rke anti-essentialistiske str mninger inden for human- og samfundsvidenskaberne. Han argu- menterer endvidere for, at et opg r med de relativistiske tendenser p feltet kr ver en n rmere dr ftelse af de teoretiske problemer som anti-essentialismen har bragt med sig. Han p begynder hermed et teore- tisk opg r med hvad han ser som overvurderingen af l serens frihed og undermineringen af tekstbegrebet. Artiklen tr kker p teoretikere som Kant, Heidegger, Gadamer, Rorty, Eco og Fosh, og diskuterer de positi- oner inden for medieforskningen, som er belvet fremf rt af Morley, Fiske, Bruhn Jensen og Schr der. Ved at g Fish og Rorty p klingen n r Arild Fetveit frem til den overraskende pointe, at de anti-essentialistiske, kon- struktivistiske positioner i virkeligheden er facade for en mere metafysisk tekstopfattelse.
Det kannibalske je: virkelighedsshow, eksperimentfjernsyn og den nye kreativitet i fjernsynsunderholdningen
Arild Fetveit
MedieKultur : Journal of Media and Communication Research , 2002,
Abstract: Artiklen diskuterer to nye tendenser i 1990’ernes tv: virkeligheds- showene i form af programmer om politi- og redningsarbejde, som vandt frem i f rste halvden af rtiet, og eksperimentformater, som med Big Brother fik stor popularitet sidst i rtiet. I virkeligheds- showene foretages en rekontekstualisering af faktamaterialet, som sv kker dets referentialitet, og dokumentarismen ndrer karakter fra information til underholdning. Eksperimentfjernsynet g r endnu videre, idet kategorierne fakta og fiktion opl ses til fordel for et socialt eksperiment i et iscenesat laboratorium. Afslutningsvist argumenterer artiklen for, at de to reality-formater er f lles om at indbyde til en ny m de at se tv p – det kannibalistiske je. Dette blik afl ser en empa- tisk betragtning og er dermed symptomatisk for det test- og overv g- ningssamfund, som forfatteren ved hj lp af kulturkritisk teori (Benja- min, Debord) skitserer omridsene af.
Do students profit from feedback?
Arild Raaheim
Seminar.net , 2006,
Abstract: Undergraduate students in psychology were given the opportunity to exchange the traditional exam with portfolio assessment. The students received written feedback, by way of a standard feedback form, on two of the three essays of the portfolio. To investigate whether students attend to and act on the feedback, a comparison was made between unofficial marks on the first draft of the first essay and the official marks on the full portfolio at the end of the semester. With approximately 20% of the first drafts being unacceptable in the end only 1.6% of the portfolios failed to reach the level of acceptance. The result is taken to indicate that the students did indeed attend to and profit from the written feedback.
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