| 1. |
- Ericsson, Stina, et al.
(författare)
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Bland prinsessor och häxor : turtagning i barns interaktion med en smartplatta
- 2012
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Ingår i: OFTI 30 Stockholms universitet, 20–21 september 2012. ; , s. 8-
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Konferensbidrag (refereegranskat)abstract
- Som del av ett större projekt om svenskundervisning och IKT (Informations- och Kommunikations- Teknologi), undersöker vi här hur barn i skolans tidiga åldrar samspelar med varandra i det första mötet med en läsplatta. Materialet består av en videoinspelning av tre barn som tillsammans skapar en saga på en läsplatta. Sagan görs i programmet "Puppet pals", där barnen väljer figurer och bilder, och lägger på rörelser och tal. I skapandet av sagan kommunicerar barnen både verbalt och icke- verbalt. Det icke-verbala består inte minst av handrörelser på läsplattan, och icke-verbal turtagning görs bland annat särskilt konkret genom att barnen puttar bort varandras händer från pekskärmen. Vi är i början av arbetet och diskuterar gärna möjliga vägar vidare för såväl analys som teori och metod, särskilt med fokus på timing av verbala och icke-verbala aspekter av turtagningen.
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| 2. |
- Fristedt Duvefelt, Charlotte, et al.
(författare)
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Increased resistance to proteaome inhibitors in multiple myeloma mediated by cIAP2 : implications for a combinatorial treatment
- 2015
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Ingår i: Oncotarget. - 1949-2553. ; 6:24, s. 20621-20635
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Tidskriftsartikel (refereegranskat)abstract
- Despite the introduction of new treatment options for multiple myeloma (MM), a majority of patients relapse due to the development of resistance. Unraveling new mechanisms underlying resistance could lead to identification of possible targets for combinatorial treatment. Using TRAF3 deleted/mutated MM cell lines, we evaluated the role of the cellular inhibitor of apoptosis 2 (cIAP2) in drug resistance and uncovered the plausible mechanisms underlying this resistance and possible strategies to overcome this by combinatorial treatment. In MM, cIAP2 is part of the gene signature of aberrant NF-kappa B signaling and is heterogeneously expressed amongst MM patients. In cIAP2 overexpressing cells a decreased sensitivity to the proteasome inhibitors bortezomib, MG132 and carfilzomib was observed. Gene expression analysis revealed that 440 genes were differentially expressed due to cIAP2 overexpression. Importantly, the data imply that cIAPs are rational targets for combinatorial treatment in the population of MM with deleted/mutated TRAF3. Indeed, we found that treatment with the IAP inhibitor AT-406 enhanced the anti-MM effect of bortezomib in the investigated cell lines. Taken together, our results show that cIAP2 is an important factor mediating bortezomib resistance in MM cells harboring TRAF3 deletion/mutation and therefore should be considered as a target for combinatorial treatment.
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| 3. |
- Fristedt Duvefelt, Charlotte
(författare)
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Tumour Survival Signals and Epigenetic Gene Silencing in Multiple Myeloma : Implications for Biology and Therapy
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is focused on multiple myeloma (MM), a haematological malignancy that still remains incurable. The pathogenesis of MM is not fully understood and there is a large intra-tumour and interclonal genetic variation in MM patients. One of the most challenging areas in MM research is to find mechanisms for initiation and progression of MM, but also to overcome the arising resistance to therapy.In paper I, a signature of under-expressed genes in MM was found to significantly correlate with already defined Polycomb target genes. In selected genes from the profile we found an enrichment of H3K27me3, a repressive mark catalysed by Polycomb repressive complex 2 (PRC2), in MM patients and MM cell lines. Treatment with LBH589 (HDAC inhibitor) and DZNep (methyltransferase inhibitor) reactivated the H3K27me3 target genes and induced apoptosis in MM cell lines. LBH589 reduced tumour load and increased overall survival in the 5T33MM mice. These results suggest an important role for Polycomb complex in MM development and highlight PRC2 as a drug target in MM.In paper II, the insulin-like growth factor type 1 receptor tyrosine kinase (IGF-1RTK) inhibitor picropodophyllin (PPP) in combination with LBH589 synergistically inhibited cell proliferation and enhanced the apoptotic effect in MM. Since the bone marrow microenvironment has an important role in MM disease and also contributes to drug-resistance, we therefore evaluated the drug combination in the immunocompetent 5T33MM murine model. The drug combination significantly prolonged the survival of the 5T33MM mice compared to single drug treatment. We conclude that the combination of PPP and LBH589 has a therapeutic potential in MM.In paper III, the role of the cellular inhibitor of apoptosis protein 2 (cIAP2) was evaluated in MM cells harbouring TRAF3 deletion/mutation. By overexpressing cIAP2 in these cells we found an increased resistance to proteasome inhibitors. cIAP2 over-expression by lentiviral constructs led to decreased caspase activation, activation of the canonical NF-κB pathway, and down-regulation of tumour suppressor genes and genes that contribute to apoptosis. Supporting the role of cIAP2 mediated drug-resistance, we here demonstrate that inhibiting cIAP2 using an IAP antagonist, increased the sensitivity to the proteasome inhibitor, bortezomib.
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| 4. |
- Fristedt, Sofi, 1969-, et al.
(författare)
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"Am I representative (of my age)? No, I'm not"-Attitudes to technologies and technology development differ but unite individuals across rather than within generations
- 2021
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Ingår i: PLOS ONE. - : Public Library of Science (PLOS). - 1932-6203. ; 16:4
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Tidskriftsartikel (refereegranskat)abstract
- While a broad spectrum of technologies is integrated in everyday life and routines, most research on ageing, health and technology has focused on attitudes toward and adoption of digital technologies including e-health, or home based monitoring systems. The aim of this study was to explore differences and similarities in attitudes and experiences with different types of technologies and development within and between three generations. We applied a qualitative, descriptive design and recruited a purposeful sample of participants from three generations (30-39, 50-59, 70-79 year old). The 25 participants took part in 3 x 2 focus groups. Forming four categories, the findings show that technologies enable as well as complicate everyday life. Participants expressed trust as well as uncertainty about risks when using technology and stated that use of digital services is required while support is limited. They identified that technology development is inevitable but not always in the service of users. In conclusion, experiences of and attitudes towards technologies and technology development are not limited to generation; perspectives sometimes unite individuals across rather than within generations. Thus future technologies and technology development, as well as services and policies aiming to support the use of said technologies should consider individual user perspectives including needs, desires, beliefs or goals neglected in the existing technology models, and involve users beyond generations defined by chronological age. Such strategies are likely to be more successful in supporting development of technologies usable for all.
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| 5. |
- Kalushkova, Antonia, et al.
(författare)
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Polycomb target genes are silenced in multiple myeloma
- 2010
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:7, s. e11483-
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Tidskriftsartikel (refereegranskat)abstract
- Multiple myeloma (MM) is a genetically heterogeneous disease, which to date remains fatal. Finding a common mechanism for initiation and progression of MM continues to be challenging. By means of integrative genomics, we identified an underexpressed gene signature in MM patient cells compared to normal counterpart plasma cells. This profile was enriched for previously defined H3K27-tri-methylated genes, targets of the Polycomb group (PcG) proteins in human embryonic fibroblasts. Additionally, the silenced gene signature was more pronounced in ISS stage III MM compared to stage I and II. Using chromatin immunoprecipitation (ChIP) assay on purified CD138+ cells from four MM patients and on two MM cell lines, we found enrichment of H3K27me3 at genes selected from the profile. As the data implied that the Polycomb-targeted gene profile would be highly relevant for pharmacological treatment of MM, we used two compounds to chemically revert the H3K27-tri-methylation mediated gene silencing. The S-adenosylhomocysteine hydrolase inhibitor 3-Deazaneplanocin (DZNep) and the histone deacetylase inhibitor LBH589 (Panobinostat), reactivated the expression of genes repressed by H3K27me3, depleted cells from the PRC2 component EZH2 and induced apoptosis in human MM cell lines. In the immunocompetent 5T33MM in vivo model for MM, treatment with LBH589 resulted in gene upregulation, reduced tumor load and increased overall survival. Taken together, our results reveal a common gene signature in MM, mediated by gene silencing via the Polycomb repressor complex. The importance of the underexpressed gene profile in MM tumor initiation and progression should be subjected to further studies.
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| 6. |
- Kharaziha, Pedram, et al.
(författare)
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Sorafenib Has Potent Antitumor Activity against Multiple Myeloma In Vitro, Ex Vivo, and In Vivo in the 5T33MM Mouse Model
- 2012
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 72:20, s. 5348-5362
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Tidskriftsartikel (refereegranskat)abstract
- Multiple myeloma (MM) is a B-cell malignancy characterized by the expansion of clonal plasma blasts/plasma cells within the bone marrow that relies on multiple signaling cascades, including tyrosine kinase activated pathways, to proliferate and evade cell death. Despite emerging new treatment strategies, multiple myeloma remains at present incurable. Thus, novel approaches targeting several signaling cascades by using the multi-tyrosine kinase inhibitor (TKI), sorafenib, seem a promising treatment approach for multiple myeloma. Here, we show that sorafenib induces cell death in multiple myeloma cell lines and in CD138(+)-enriched primary multiple myeloma patient samples in a caspase-dependent and -independent manner. Furthermore, sorafenib has a strong antitumoral and -angiogenic activity in the 5T33MM mouse model leading to increased overall survival. Multiple myeloma cells undergo autophagy in response to sorafenib, and inhibition of this cytoprotective pathway potentiated the efficacy of this TKI. Mcl-1, a survival factor in multiple myeloma, is downregulated at the protein level by sorafenib allowing for the execution of cell death, as ectopic overexpression of this protein protects multiple myeloma cells. Concomitant targeting of Mcl-1 by sorafenib and of Bcl-2/Bcl-xL by the antagonist ABT737 improves the efficacy of sorafenib in multiple myeloma cell lines and CD138(+)-enriched primary cells in the presence of bone marrow stromal cells. Altogether, our data support the use of sorafenib as a novel therapeutic modality against human multiple myeloma, and its efficacy may be potentiated in combination with ABT737.
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| 7. |
- Lemaire, Miguel, et al.
(författare)
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The HDAC Inhibitor LBH589 Enhances the Antimyeloma Effects of the IGF-1RTK Inhibitor Picropodophyllin
- 2012
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 18:8, s. 2230-2239
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: We have previously shown the use of the insulin-like growth factor type 1 receptor tyrosine kinase (IGF-1RTK) inhibitor picropodophyllin (PPP) as an attractive strategy to combat multiple myeloma (MM) in vitro and in vivo. After a combinatorial drug screening, the histone deacetylase inhibitor LBH589 was shown to act in synergy with PPP reducing survival of MM cells. In this study, we tried to elucidate the molecular mechanisms underlying this combinatorial effect. Experimental Design: The in vitro anti-MM effects of PPP and LBH589 alone and in combination were evaluated by studying apoptosis, cell cycle distribution, and downstream transcriptome using both human MM cell lines and cells from the murine 5T3MM model. In vivo the effect on survival of 5T33MM-inoculated mice was evaluated. Results: In the human MM cell line RPMI8226, treatment with PPP and LBH589 in combination resulted in a five-fold increase of apoptosis, and an additive effect on the cleavage of the active forms of caspase-8 was observed as compared with the single drug treatments. Cell cycle analysis revealed an accumulation of cells in the G2-M phase and subsequent downregulation of cell cycle regulating proteins. These data were also confirmed in the 5T33MM cells in vitro. Also, the transcriptome was analyzed by Affymetrix arrays showing gene expression alterations mainly in categories of genes regulating apoptosis and cell adhesion. Combined treatment in vivo resulted in a significantly prolonged survival of 5T33MM-inoculated mice. Conclusions: The results indicate an improved MM treatment opportunity in using a combination of PPP and LBH589.
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| 8. |
- Schmidt, Steven M., et al.
(författare)
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User attitudes toward research and development of technologies : Perspectives from three generations
- 2020
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Konferensbidrag (refereegranskat)abstract
- New technologies are being touted as solutions to many societal challenges not least of which are ageing and health. However, the rapid development of new technologies is proceeding with little input from older adults. This presentation highlights the perceptions and attitudes of three age cohorts related to the continuous technological advancement of products intended to support active and healthy aging. Participants were 30-39 (n= 639), 50-59 (n=703), 70-79 (n=779) years-old randomly sampled from the Swedish population registry. Results showed both similarities and difference across generations. For example, 24%-35% of older adults would like to use home monitoring devices (e.g. fall sensors, smart home devices) to support active and healthy aging, compared to 35%-56% of younger groups. More than 82% of all groups highlighted the importance of involving intended users in the development process. Results can be used to support the needs and desires of current older adults and future generations.
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| 9. |
- Svärdh, Samantha, et al.
(författare)
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Attitudes, acceptance and use of everyday technologies – a generational perspective
- 2019
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Konferensbidrag (refereegranskat)abstract
- Technology is a fixed feature in today’s world, from smart phones to the everyday technology in our homes. Research is limited regarding perceptions of and attitudes to technology among people of different generations as related to the technological developments they have experienced during their lifetime, as well as their health. It is imperative that researchers focus on this topic in order to better meet the needs of older persons in their utilization of technology. This study is the first step in an ongoing research project concerning healthy ageing and technology from a broader sense, which takes a unique generational perspective. The study aims to develop new knowledge regarding perceptions, acceptance and usage amongst people of different generations as related to the technological developments they have experienced during their lifetimes. Data was collected through several focus group interviews with participants from three age groups (30-39, 50-59 and 70-79 year olds). This exploratory method was used to capture attitudes regarding technology through group discussions and dynamics. Interviews were analysed according to qualitative content analysis and then compared using NVivo software. Preliminary findings indicate that participants do not view non-digitalized items like kitchen appliances as technology. They problematize digital technology and its development, particularly concerning issues with privacy and integrity, as well as its effect on human relationships. However, most continue to use digital technology and even name their smartphone or computer as the most in their everyday life. Explicit desires for parallel pathways and individualized solutions nonetheless pervade. The 70-79ers had less trust in digital technology while the 30-39ers voiced issues regarding social pressures and inclusions; the 50-59ers had to consciously work to keep abreast of new technology. Digital technology engages and has a high usage among different generations; however, the human perspective needs to be further involved to fill basic needs of coming generations.
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| 10. |
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