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- Andersson, Mattias K, 1979, et al.
(author)
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IGF2/IGF1R Signaling as a Therapeutic Target in MYB-Positive Adenoid Cystic Carcinomas and Other Fusion Gene-Driven Tumors
- 2019
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In: Cells. - : MDPI AG. - 2073-4409. ; 8:8
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Journal article (peer-reviewed)abstract
- Chromosome rearrangements resulting in pathogenetically important gene fusions are a common feature of many cancers. They are often potent oncogenic drivers and have key functions in central cellular processes and pathways and encode transcription factors, transcriptional co-regulators, growth factor receptors, tyrosine kinases, and chromatin modifiers. In addition to being useful diagnostic biomarkers, they are also targets for development of new molecularly targeted therapies. Studies in recent decades have shown that several oncogenic gene fusions interact with the insulin-like growth factor (IGF) signaling pathway. For example, the MYB-NFIB fusion in adenoid cystic carcinoma is regulated by IGF1R through an autocrine loop, and IGF1R is a downstream target of the EWSR1-WT1 and PAX3-FKHR fusions in desmoplastic small round cell tumors and alveolar rhabdomyosarcoma, respectively. Here, we will discuss the mechanisms behind the interactions between oncogenic gene fusions and the IGF signaling pathway. We will also discuss the role of therapeutic inhibition of IGF1R in fusion gene driven malignancies.
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- Andersson, Mattias K, 1979, et al.
(author)
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The multifunctional FUS, EWS and TAF15 proto-oncoproteins show cell type-specific expression patterns and involvement in cell spreading and stress response
- 2008
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In: BMC Cell Biology. - : Springer Science and Business Media LLC. - 1471-2121. ; 9
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Journal article (peer-reviewed)abstract
- BACKGROUND: FUS, EWS and TAF15 are structurally similar multifunctional proteins that were first discovered upon characterization of fusion oncogenes in human sarcomas and leukemias. The proteins belong to the FET (previously TET) family of RNA-binding proteins and are implicated in central cellular processes such as regulation of gene expression, maintenance of genomic integrity and mRNA/microRNA processing. In the present study, we investigated the expression and cellular localization of FET proteins in multiple human tissues and cell types. RESULTS: FUS, EWS and TAF15 were expressed in both distinct and overlapping patterns in human tissues. The three proteins showed almost ubiquitous nuclear expression and FUS and TAF15 were in addition present in the cytoplasm of most cell types. Cytoplasmic EWS was more rarely detected and seen mainly in secretory cell types. Furthermore, FET expression was downregulated in differentiating human embryonic stem cells, during induced differentiation of neuroblastoma cells and absent in terminally differentiated melanocytes and cardiac muscle cells. The FET proteins were targeted to stress granules induced by heat shock and oxidative stress and FUS required its RNA-binding domain for this translocation. Furthermore, FUS and TAF15 were detected in spreading initiation centers of adhering cells. CONCLUSION: Our results point to cell-specific expression patterns and functions of the FET proteins rather than the housekeeping roles inferred from earlier studies. The localization of FET proteins to stress granules suggests activities in translational regulation during stress conditions. Roles in central processes such as stress response, translational control and adhesion may explain the FET proteins frequent involvement in human cancer.
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- Nilsson, Petra, 1980-, et al.
(author)
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How to make a workplace health promotion questionnaire process applicable, meaningful, and sustainable
- 2011
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In: Journal of Nursing Management. - : Wiley-Blackwell. - 0966-0429 .- 1365-2834. ; 19:7, s. 906-914
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Journal article (peer-reviewed)abstract
- Background In workplace health promotion, a questionnaire could be of great use. Unfortunately, fatigue regarding answering questionnaires has recently become greater than before. An action research approach could be a possible way of increasing employee participation.Aim This study reports an attempt to explore key aspects for participation in, and commitment to, a workplace health promotion questionnaire process.Method The study was conducted at two wards in a Swedish hospital. Data was collected during an action research process. Data were analysed with regard to a framework of questions.Findings The three key aspects for participation in, and commitment to, a workplace health promotion questionnaire process were: an applicable questionnaire, a meaningful questionnaire process and a continuous and sustainable questionnaire process. A structure is presented as practical advice to managers, describing how such a process could be established to be applicable, meaningful and sustainable.Conclusion This study has identified key aspects and prerequisites for questionnaire processes. The prerequisites – share decision-making, involve a core group and follow a structure – are discussed and proposed for managers and workgroups to consider in further workplace health promotion questionnaire processes.Implications for nursing management The key aspects and prerequisites presented could provide a stimulating standpoint or advice, useful for planning and accomplishing workplace questionnaire processes.
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| 6. |
- Adman, Per, et al.
(author)
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171 forskare: ”Vi vuxna bör också klimatprotestera”
- 2019
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In: Dagens nyheter (DN debatt). - Stockholm. - 1101-2447.
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Journal article (pop. science, debate, etc.)abstract
- DN DEBATT 26/9. Vuxna bör följa uppmaningen från ungdomarna i Fridays for future-rörelsen och protestera eftersom det politiska ledarskapet är otillräckligt. Omfattande och långvariga påtryckningar från hela samhället behövs för att få de politiskt ansvariga att utöva det ledarskap som klimatkrisen kräver, skriver 171 forskare i samhällsvetenskap och humaniora.
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| 7. |
- Afshari, Maryam K., et al.
(author)
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Activation of PLAG1 and HMGA2 by gene fusions involving the transcriptional regulator gene NFIB
- 2020
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In: Genes Chromosomes & Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 59:11, s. 652-660
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Journal article (peer-reviewed)abstract
- The pleomorphic adenoma (PA), which is the most common salivary gland neoplasm, is a benign tumor characterized by recurrent chromosome rearrangements involving 8q12 and 12q14-15. We have previously shown that thePLAG1andHMGA2oncogenes are the targets of these rearrangements. Here, we have identified previously unrecognized subsets of PAs with ins(9;8)/t(8;9) (n = 5) and ins(9;12)/t(9;12) (n = 8) and breakpoints located in the vicinity of thePLAG1andHMGA2loci. RNA-sequencing and reverse transcriptase (RT)-PCR analyses of a case with an ins(9;8) revealed a novelNFIB-PLAG1fusion in whichNFIBexon 4 is linked toPLAG1exon 3. In contrast to the developmentally regulatedPLAG1gene,NFIBwas highly expressed in normal salivary gland, indicating thatPLAG1in this case, as in other variant fusions, is activated by promoter swapping. RT-PCR analysis of three PAs with t(9;12) revealed two tumors with chimeric transcripts consisting ofHMGA2exon 4 linked toNFIBexons 9 or 3 and one case with a fusion linkingHMGA2exon 3 toNFIBexon 9. TheNFIBfusion events resulted in potent activation ofPLAG1andHMGA2. Analysis of the chromatin landscape surroundingNFIBrevealed several super-enhancers in the 5 '- and 3 '-parts of theNFIBlocus and its flanking sequences. These findings indicate thatPLAG1andHMGA2, similar toMYBin adenoid cystic carcinoma, may be activated by enhancer-hijacking events, in which super-enhancers inNFIBare translocated upstream ofPLAG1or downstream ofHMGA2. Our results further emphasize the role ofNFIBas a fusion partner to multiple oncogenes in histopathologically different types of salivary gland tumors.
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- Alm, Anita, 1953, et al.
(author)
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BMI status in Swedish children and young adults in relation to caries prevalence.
- 2011
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In: Swedish dental journal. - : Swedish Dental Association. - 0347-9994. ; 35:1, s. 1-8
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Journal article (peer-reviewed)abstract
- Overweight and obesity are increasing as health problems at global level. Dental caries and obesity are both multifactorial diseases and are associated with dietary habits. The aim of the present study was to investigate the relationship between body weight status and caries prevalence in an unselected population followed from pre-school years to young adulthood. The present investigation was designed as a longitudinal analysis of the association between overweight/obesity and dental caries in one population at 3, 6, 15 and 20 years of age. The result shows that adolescents (15 years) and young adults (20 years) who are overweight/obese had a statistically significantly higher caries prevalence than normal-weight young people. At 6 years of age, the odds (OR) of having caries among obese children are 2.5 times higher than the odds for caries among six-year-old children of normal weight (p = 0.04). At 3 years of age, no association between overweight/obesity and caries was found. To conclude, overweight and obese adolescents and young adults had more caries than normal-weight individuals. The present study emphasises the need for multidisciplinary approaches to change the lifestyle factors causing both overweight/obesity and dental caries.
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| 10. |
- Andersson, Ellinor, et al.
(author)
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High-resolution genomic profiling reveals gain of chromosome 14 as a predictor of poor outcome in ileal carcinoids.
- 2009
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In: Endocrine-related cancer. - 1479-6821. ; 16:3, s. 953-66
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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.
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