| 1. |
|
|
| 2. |
|
|
| 3. |
- Ali, Mina, et al.
(author)
-
The multiple myeloma risk allele at 5q15 lowers ELL2 expression and increases ribosomal gene expression
- 2018
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 1649-
-
Journal article (peer-reviewed)abstract
- Recently, we identified ELL2 as a susceptibility gene for multiple myeloma (MM). To understand its mechanism of action, we performed expression quantitative trait locus analysis in CD138+ plasma cells from 1630 MM patients from four populations. We show that the MM risk allele lowers ELL2 expression in these cells (Pcombined = 2.5 × 10−27; βcombined = −0.24 SD), but not in peripheral blood or other tissues. Consistent with this, several variants representing the MM risk allele map to regulatory genomic regions, and three yield reduced transcriptional activity in plasmocytoma cell lines. One of these (rs3777189-C) co-locates with the best-supported lead variants for ELL2 expression and MM risk, and reduces binding of MAFF/G/K family transcription factors. Moreover, further analysis reveals that the MM risk allele associates with upregulation of gene sets related to ribosome biogenesis, and knockout/knockdown and rescue experiments in plasmocytoma cell lines support a cause–effect relationship. Our results provide mechanistic insight into MM predisposition.
|
|
| 4. |
- Andersson, Ellinor, et al.
(author)
-
Expression profiling of small intestinal neuroendocrine tumors identifies subgroups with clinical relevance, prognostic markers and therapeutic targets.
- 2016
-
In: Modern Pathology. - : Elsevier BV. - 0893-3952 .- 1530-0285. ; 29:6, s. 616-629
-
Journal article (peer-reviewed)abstract
- We wanted to define the transcriptome of small intestinal neuroendocrine tumors in order to identify clinically relevant subgroups of tumors, prognostic markers and novel targets for treatment. Genome-wide expression profiling was conducted on tumor biopsies from 33 patients with well-differentiated neuroendocrine tumors of the distal ileum and metastatic disease at the time of diagnosis. Unsupervised hierarchical clustering analysis identified three groups of tumors. The largest group, comprising half of the tumors, was characterized by longer patient survival and higher expression of neuroendocrine markers, including SSTR2. Tumors with higher grade (G2/3) or gain of chromosome 14 were associated with shorter patient survival and increased expression of cell cycle-promoting genes. Pathway analysis predicted the prostaglandin E receptor 2 (PTGER2) as the most significantly activated regulator in tumors of higher grade, whereas Forkhead box M1 (FOXM1) was the most significantly activated regulator in tumors with gain of chromosome 14. Druggable genes identified from expression profiles included clinically proven SSTR2 and also novel targets, for example, receptor tyrosine kinases (RET, FGFR1/3, PDGFRB and FLT1), epigenetic regulators, molecular chaperones and signal transduction molecules. Evaluation of candidate drug targets on neuroendocrine tumors cells (GOT1) showed significant inhibition of tumor cell growth after treatment with tyrosine kinase inhibitors or inhibitors of HDAC, HSP90 and AKT. In conclusion, we have defined the transcriptome of small intestinal neuroendocrine tumors and identified novel subgroups with clinical relevance. We found specific gene expression patterns associated with tumor grade and chromosomal alterations. Our data also suggest novel prognostic biomarkers and therapies for these patients.
|
|
| 5. |
- Andersson, Ellinor, et al.
(author)
-
High-resolution genomic profiling reveals gain of chromosome 14 as a predictor of poor outcome in ileal carcinoids.
- 2009
-
In: Endocrine-related cancer. - 1479-6821. ; 16:3, s. 953-66
-
Journal article (peer-reviewed)abstract
- Ileal carcinoids are malignant neuroendocrine tumours of the small intestine. The aim of this study was to obtain a high-resolution genomic profile of ileal carcinoids in order to define genetic changes important for tumour initiation, progression and survival. Forty-three patients with ileal carcinoids were investigated by high-resolution array-based comparative genomic hybridization. The average number of copy number alterations (CNAs) per tumour was 7.1 (range 1-22), with losses being more common than gains (ratio 1.4). The most frequent CNA was loss of chromosome 18 (74%). Other frequent CNAs were gain of chromosome 4, 5, 14 and 20, and loss of 11q22.1-q22.2, 11q22.3-q23.1 and 11q23.3, and loss of 16q12.2-q22.1 and 16q23.2-qter. Two distinct patterns of CNAs were found; the majority of tumours was characterized by loss of chromosome 18 while a subgroup of tumours had intact chromosome 18, but gain of chromosome 14. Survival analysis, using a series of Poisson regressions including recurrent CNAs, demonstrated that gain of chromosome 14 was a strong predictor of poor survival. In conclusion, high-resolution profiling demonstrated two separate patterns of CNAs in ileal carcinoids. The majority of tumours showed loss of chromosome 18, which most likely represents a primary event in the development and pathogenesis of tumours. A different genetic pathway is operative in a subgroup of tumours; this is characterized by gain of chromosome 14 and is strongly associated with poor prognosis. Predictive fluorescence in situ hybridization analysis of chromosome 14 status in patients with ileal carcinoids is suggested.
|
|
| 6. |
- Arvidsson, Yvonne, 1960, et al.
(author)
-
Amyloid precursor-like protein 1 is differentially upregulated in neuroendocrine tumours of the gastrointestinal tract.
- 2008
-
In: Endocrine-related cancer. - 1351-0088. ; 15:2, s. 569-81
-
Journal article (peer-reviewed)abstract
- We have examined the global gene expression profile of small intestinal carcinoids by microarray analysis. High expression of a number of genes was found including amyloid precursor-like protein 1 (APLP1). Quantitative real-time PCR and western blot analysis demonstrated higher expression of APLP1 in carcinoid metastases relative to primary tumours indicating a role of APLP1 in tumour dissemination. Tissue microarray analysis of gastroentero-pancreatic tumours demonstrated a high frequency of APLP1 expression and a low frequency of APLP2 expression in neuroendocrine (NE) tumours when compared with non-NE tumours at the same sites. Meta-analysis of gene expression data from a large number of tumours outside the gastrointestinal tract confirmed a correlation between APLP1 expression and NE phenotype where high expression of APLP1 was accompanied by downregulation of APLP2 in NE tumours. Cellular localization of APLP1, APLP2 and amyloid precursor protein (APP) in carcinoid cells (GOT1) by confocal microscopy demonstrated partial co-localization with synaptophysin. This suggests that the APP family of proteins is transported to the cell membrane by synaptic microvesicles and that they may influence tumour cell adhesion and invasiveness. We conclude that APLP1 is differentially upregulated in gastrointestinal NE tumours and that APLP1 may be important for the dissemination of small intestinal carcinoids. Identification of APLP1 in NE tumours offers a novel target for treatment and may also serve as a tumour-specific marker.
|
|
| 7. |
- Arvidsson, Yvonne, 1960, et al.
(author)
-
miRNA profiling of small intestinal neuroendocrine tumors defines novel molecular subtypes and identifies miR-375 as a biomarker of patient survival
- 2018
-
In: Modern Pathology. - : Elsevier BV. - 0893-3952 .- 1530-0285. ; 31, s. 1302-1317
-
Journal article (peer-reviewed)abstract
- © 2018, United States & Canadian Academy of Pathology. The aim of this study was to define the miRNA profile of small intestinal neuroendocrine tumors and to search for novel molecular subgroups and prognostic biomarkers. miRNA profiling was conducted on 42 tumors from 37 patients who underwent surgery for small intestinal neuroendocrine tumors. Unsupervised hierarchical clustering analysis of miRNA profiles identified two groups of tumor metastases, denoted cluster M1 and M2. The smaller cluster M1 was associated with shorter overall survival and contained tumors with higher grade (WHO grade G2/3) and multiple chromosomal gains including gain of chromosome 14. Tumors of cluster M1 had elevated expression of miR-1246 and miR-663a, and reduced levels of miR-488-3p. Pathway analysis predicted Wnt signaling to be the most significantly altered signaling pathway between clusters M1 and M2. Analysis of miRNA expression in relation to tumor proliferation rate showed significant alterations including downregulation of miR-137 and miR-204-5p in tumors with Ki67 index above 3%. Similarly, tumor progression was associated with significant alterations in miRNA expression, e.g. higher expression of miR-95 and miR-210, and lower expression of miR-378a-3p in metastases. Pathway analysis predicted Wnt signaling to be altered during tumor progression, which was supported by decreased nuclear translocation of β-catenin in metastases. Survival analysis revealed that downregulation of miR-375 was associated with shorter overall survival. We performed in situ hybridization on biopsies from an independent cohort of small intestinal neuroendocrine tumors using tissue microarrays. Expression of miR-375 was found in 578/635 (91%) biopsies and survival analysis confirmed that there was a correlation between downregulation of miR-375 in tumor metastases and shorter patient survival. We conclude that miRNA profiling defines novel molecular subgroups of metastatic small intestinal neuroendocrine tumors and identifies miRNAs associated with tumor proliferation rate and progression. miR-375 is highly expressed in small intestinal neuroendocrine tumors and may be used as a prognostic biomarker.
|
|
| 8. |
- Delisle Nystrom, Christine, et al.
(author)
-
International Study of Movement Behaviors in the Early Years (SUNRISE): Results from SUNRISE Swedens Pilot and COVID-19 Study
- 2020
-
In: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 17:22
-
Journal article (peer-reviewed)abstract
- The International Study of Movement Behaviors in the Early Years (SUNRISE) was initiated in response to the 2019 WHO guidelines for physical activity, sedentary behavior, and sleep in children aged 0-5 years. This Swedish pilot study aimed to: (i) assess the proportion of preschoolers meeting the guidelines, (ii) evaluate the feasibility of the methods for the SUNRISE study, and (iii) assess how movement behaviors have been affected in preschoolers during the COVID-19 pandemic. Physical activity and sleep (waist-worn ActiGraph); screen time and movement behaviors (parental questionnaire); motor skills (Ages and Stages Questionnaire); and executive functions (3 iPad games) were assessed in 100 Swedish preschoolers (n = 58 boys). There were 19.4% of preschoolers (n = 14) who met the WHO guidelines. The motor skill and executive function assessments were feasible; however, 20% refused to wear the ActiGraph overnight. Additionally, during the pandemic Swedish childrens physical activity, time spent outside on weekdays and weekend days, and screen time significantly increased (+53; +124; +68; +30min/day, respectively, all p-values <= 0.001). Methods for the SUNRISE study were feasible in a Swedish context; however, considerations to switch to a wrist-worn accelerometer should be made. Furthermore, childrens physical activity increased during the pandemic, which is likely due to how the rules/restrictions were implemented in Sweden.
|
|
| 9. |
- Edfors, Ellinor, et al.
(author)
-
Att vara nyanställd inom en allmänpsykiatrisk kliniks slutenvård : en kartläggning utifrån sjuksköterskors erfarenheter
- 2016
-
Reports (pop. science, debate, etc.)abstract
- Syftet med studien var att kartlägga sjuksköterskornas erfarenheter av att vara nyanställd inom en allmänpsykiatrisk kliniks slutenvård. Målet med kartläggningen var att den skulle kunna ligga till grund för utvecklingen av en handlingsplan som kan underlätta introduktionen för nyanställd personal. Studien genomfördes genom en modifierad form av Group Concept Mapping utifrån prompten ”Exempel på betydelsefulla erfarenheter av att vara nyanställd sjuksköterska på psykiatriska klinikens slutenvård är…”. I resultatet framkom följande betydelsefulla områden; introduktion, bemötande och arbetsklimat, ledning och organisation, information vid anställningsintervju, kunskaper specifika för psykiatri, rutiner och struktur, roller krav och förväntningar samt reflektion. Innehållet i samtliga områden ansågs vara lika betydelsefulla dock bör introduktionen utformas utifrån varje sjuksköterskas erfarenheter, kunskaper och individuella behov. Framträdande i resultatet var även betydelsen av en gynnsam miljö, som präglas av ett gott arbetsklimat, relevant stöd från kollegor och chefer, möjlighet till reflektion och att få vara ny på arbetsplatsen.
|
|
| 10. |
- Edfors, Ellinor, et al.
(author)
-
Att vara nyanställd inom en allmänpsykiatrisk kliniks slutenvård : en kartläggning utifrån sjuksköterskors erfarenheter
- 2016
-
Book (other academic/artistic)abstract
- Syftet med studien var att kartlägga sjuksköterskornas erfarenheter av att vara nyanställd inom en allmänpsykiatrisk kliniks slutenvård. Målet med kartläggningen var att den skulle kunna ligga till grund för utvecklingen av en handlingsplan som kan underlätta introduktionen för nyanställd personal. Studien genomfördes genom en modifierad form av Group Concept Mapping utifrån prompten ”Exempel på betydelsefulla erfarenheter av att vara nyanställd sjuksköterska på psykiatriska klinikens slutenvård är…”. I resultatet framkom följande betydelsefulla områden; introduktion, bemötande och arbetsklimat, ledning och organisation, information vid anställningsintervju, kunskaper specifika för psykiatri, rutiner och struktur, roller krav och förväntningar samt reflektion. Innehållet i samtliga områden ansågs vara lika betydelsefulla dock bör introduktionen utformas utifrån varje sjuksköterskas erfarenheter, kunskaper och individuella behov. Framträdande i resultatet var även betydelsen av en gynnsam miljö, som präglas avett gott arbetsklimat, relevant stöd från kollegor och chefer, möjlighet till reflektion och att få vara ny på arbetsplatsen.
|
|
