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Search Results: 1 - 10 of 462979 matches for " Marianne A Merok "
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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
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
DNA Sequence Profiles of the Colorectal Cancer Critical Gene Set KRAS-BRAF-PIK3CA-PTEN-TP53 Related to Age at Disease Onset
Marianne Berg,Stine A. Danielsen,Terje Ahlquist,Marianne A. Merok,Trude H. ?gesen,Morten H. Vatn,Tom Mala,Ole H. Sjo,Arne Bakka,Ingvild Moberg,Torunn Fetveit,?ystein Mathisen,Anders Husby,Oddvar Sandvik,Arild Nesbakken,Espen Thiis-Evensen,Ragnhild A. Lothe
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0013978
Abstract: The incidence of colorectal cancer (CRC) increases with age and early onset indicates an increased likelihood for genetic predisposition for this disease. The somatic genetics of tumor development in relation to patient age remains mostly unknown. We have examined the mutation status of five known cancer critical genes in relation to age at diagnosis, and compared the genomic complexity of tumors from young patients without known CRC syndromes with those from elderly patients. Among 181 CRC patients, stratified by microsatellite instability status, DNA sequence changes were identified in KRAS (32%), BRAF (16%), PIK3CA (4%), PTEN (14%) and TP53 (51%). In patients younger than 50 years (n = 45), PIK3CA mutations were not observed and TP53 mutations were more frequent than in the older age groups. The total gene mutation index was lowest in tumors from the youngest patients. In contrast, the genome complexity, assessed as copy number aberrations, was highest in tumors from the youngest patients. A comparable number of tumors from young (<50 years) and old patients (>70 years) was quadruple negative for the four predictive gene markers (KRAS-BRAF-PIK3CA-PTEN); however, 16% of young versus only 1% of the old patients had tumor mutations in PTEN/PIK3CA exclusively. This implies that mutation testing for prediction of EGFR treatment response may be restricted to KRAS and BRAF in elderly (>70 years) patients. Distinct genetic differences found in tumors from young and elderly patients, whom are comparable for known clinical and pathological variables, indicate that young patients have a different genetic risk profile for CRC development than older patients.
Diversity dynamics in Nymphalidae butterflies: Effect of phylogenetic uncertainty on diversification rate shift estimates
Carlos Pe?a,Marianne Espeland
Quantitative Biology , 2013,
Abstract: The family Nymphalidae is the largest family within the true butterflies and has been used to develop hypotheses explaining evolutionary interactions between plants and insects. Theories of insect and hostplant dynamics predict accelerated diversification in some scenarios. We investigated whether phylogenetic uncertainty affects a commonly used method (MEDUSA, modelling evolutionary diversity using stepwise AIC) for estimating shifts in diversification rates in lineages of the family Nymphalidae, by extending the method to run across a random sample of phylogenetic trees from the posterior distribution of a Bayesian run. We found that phylogenetic uncertainty greatly affects diversification rate estimates. Different trees from the posterior distribution can give diversification rates ranging from high values to almost zero for the same clade, and for some clades both significant rate increase and decrease were estimated. Only three out of 13 significant shifts found on the maximum credibility tree were consistent across more than 95% of the trees from the posterior: (i) accelerated diversification for Solanaceae feeders in the tribe Ithomiini; (ii) accelerated diversification in the genus Charaxes, and (iii) deceleration in the Danaina. By using the binary speciation and extinction model (BISSE), we found that a hostplant shift to Solanaceae or a codistributed character is responsible for the increase in diversification rate in Ithomiini, and the result is congruent with the diffuse cospeciation hypothesis. A shift to Apocynaceae is not responsible for the slowdown of diversification in Danaina. Our results show that taking phylogenetic uncertainty into account when estimating diversification rate shifts is of great importance, and relying on the maximum credibility tree alone potentially can give erroneous results.
Leadership Ideas—A Study with Prospective Nursing Leaders  [PDF]
Marianne Frilund
Open Journal of Nursing (OJN) , 2015, DOI: 10.4236/ojn.2015.55054
Abstract: Introduction: The study is based on P. Kostenbaums theory about leadership as greatness. His theory distinguishes four interdependent leadership “orientations”: ethics, vision, courage and reality. People with qualities have developed greatness and wisdom in their mind, as well as competence to act ethically. The leadership research has shaped a leadership figure that can be described as a picture of a hero. Aim: The aim of this paper is to find out the idea of leadership based on earlier research and analyse their relevancy for nursing-management. Method: The study is a qualitative study based on earlier studies with focus on the basic idea of leadership with relevancy for nursing management and leadership. Sex students, from a master degree program in Finland, collected data based on earlier research. Findings and Interpretation: The ideas of leadership consist of three basic ideas: leadership as greatness, leadership as interactions and relations, and leadership based on the idea of shared leadership. Discussion: The prospects for leading others are to master the balance between the degree of freedom and control, to build trust, and to provide directives and control until confidence. To lead without “meeting” makes that the employers never give desired results. The purposes of the ideas of leadership are to create trust, confidence and understanding of where the other person is located. Being seen and being confirmed is fundamental to pace an individual and create opportunities to lead within nursing care.
Mapping Trajectories of Attention to Drug Related Issues in Estonian Main Dailies  [PDF]
Marianne Paimre
Advances in Journalism and Communication (AJC) , 2015, DOI: 10.4236/ajc.2015.32005
Abstract: Illicit drugs have been a burning social issue in Estonia over the last fifteen years. Estonia has taken the lead in Europe with regard to drug-related deaths and prevalence of HIV among injecting drug users. Experimental drug use among Estonian students is more widespread than the European average. It is important to study press coverage, because according to agenda setting theory, the media plays an important role in influencing the salience of social issues on the public agenda. The aim of this article is to map fluctuations in attention received from Estonian two major dailies to different drug related issues during the last 25 years. The author focuses on issues highlighted in national and international drug reports such as drug addiction, drug related crime, spread of HIV among addicts, drug-induced deaths, drug problem in schools etc. Content analysis of almost 1000 press articles reflecting drug problems in Estonia was carried out from 1990 to 2014. The study revealed that since 1995, attention received from the major newspapers to drug related crime has been high and quite stable compared to other drug issues. Press interest with regard to problem drug use and HIV was notice a bleat the turn of the millennium and in the beginning of the new century, but almost lost by 2014. More intense periods of coverage were triggered by specific events. Only a few articles have reflected drug induced death despite the fact that Estonia is the undisputed leader in the EU regarding this indicator. This reflects that the coverage was not been in line with the drug situation in Estonia. It seems that the attention of the press depends rather on newsworthiness of the issue and the agenda setting processes.
Multicultural Working Teams and Safety Awareness: How Effective Leadership Can Motivate Safety Behaviour  [PDF]
Marianne Starren
Psychology (PSYCH) , 2016, DOI: 10.4236/psych.2016.77102
Abstract: This empirical study focuses on the diversity of cultural values and leadership preferences in multicultural working teams and how this interaction makes it difficult to guarantee and motivate safety at the workfloor. It is often hypothesized that when employees from different national identities have to work together in one team, their different cultural backgrounds make a common mental state of safety awareness very complex. In managing this diversity of cultural values, the role of leadership style could be crucial. The results show that a cultural value as uncertainty avoidance clearly has its influence on safety awareness and that this outcome is mediated by the motivating leadership style.
Breaching the Kinetic Barrier to in Vitro Somatic Stem Cell Propagation
Joshua R. Merok,James L. Sherley
Journal of Biomedicine and Biotechnology , 2001, DOI: 10.1155/s1110724301000067
Abstract: Here we have reviewed the conventional definitions and fundamental characteristics of the two basic types of stem cells, embryonic stem cells (ESCs) and somatic stem cells (SSCs). By taking into account the often-overlooked asymmetric cell kinetics of SSCs, we consider the evidence that should SSCs retain these growth kinetics in vitro, a natural kinetic barrier to SSC propagation exists. Recent discoveries showing that the tumor suppressor gene p53 can act as a regulator of asymmetric cell kinetics provide a target pathway for in vitro SSC propagation strategies.
Breaching the kinetic barrier to in vitro somatic stem cell propagation
Merok Joshua R.,Sherley James L.
Journal of Biomedicine and Biotechnology , 2001,
Abstract: Here we have reviewed the conventional definitions and fundamental characteristics of the two basic types of stem cells, embryonic stem cells (ESCs) and somatic stem cells (SSCs). By taking into account the often-overlooked asymmetric cell kinetics of SSCs, we consider the evidence that should SSCs retain these growth kinetics in vitro, a natural kinetic barrier to SSC propagation exists. Recent discoveries showing that the tumor suppressor gene p53 can act as a regulator of asymmetric cell kinetics provide a target pathway for in vitro SSC propagation strategies.
18FDG-PET/CT Is a Useful Tool in Staging Procedure before Chemo-Radiotherapy in Patients with Limited Disease Small-Cell Lung Cancer. Pattern of Failure and Survival Is Analyzed  [PDF]
Anne Winther Larsen, Azza A. Khalil, Peter Meldgaard, Marianne M. Knap
Journal of Cancer Therapy (JCT) , 2012, DOI: 10.4236/jct.2012.324049
Abstract: Background: The purpose of this study was to evaluate the use of 18FDG-PET/CT in staging procedure, the pattern of failure and survival in patients with small-cell lung cancer limited disease (LD-SCLC) undergoing chemo-radiotherapy. Methods: A total of 79 LD-SCLC patients were treated with a combination of chemotherapy and chest radiotherapy. Radiotherapy of the tumour and the pathological lymph nodes was performed either as 45 Gy twice-daily or 46 - 50 Gy once-daily. 18Fluro-2-deoxy-D-glucose (18FDG)-PET/CT was performed in 35 patients as part of the staging procedure. Results: With a median follow-up time of 17 months 6% developed isolated loco-regional failures while 57% developed distant metastases. No isolated regional failures were seen. Median overall survival was 22 months. Patients staged with a 18FDG-PET/CT had a significantly lower incidence of distant failures and a significantly improved overall survival compared with patients only staged with a CT scan (p = 0.03) (median overall survival of 34 versus 17 months, respectively). Conclusion: The pattern of failure showed a high risk of distant metastases but a low incidence of isolated loco-regional failures. Patients staged with an 18FDG-PET/CT had a significantly lower incidence of distant failures and better overall survival, indicating that 18FDG-PET could be beneficial in patients with LD-SCLC before deciding on treatment regimen.
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