| 1. |
- Hill, Rebecca M., et al.
(författare)
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Combined MYC and P53 Defects Emerge at Medulloblastoma Relapse and Define Rapidly Progressive, Therapeutically Targetable Disease
- 2015
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Ingår i: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 27:1, s. 72-84
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Tidskriftsartikel (refereegranskat)abstract
- We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC family amplifications and P53 pathway defects commonly emerged at relapse, and all patients in this group died of rapidly progressive disease postrelapse. To study this interaction, we investigated a transgenic model of MYCN-driven medulloblastoma and found spontaneous development of Trp53 inactivating mutations. Abrogation of p53 function in this model produced aggressive tumors that mimicked characteristics of relapsed human tumors with combined P53-MYC dysfunction. Restoration of p53 activity and genetic and therapeutic suppression of MYCN all reduced tumor growth and prolonged survival. Our findings identify P53-MYC interactions at medulloblastoma relapse as biomarkers of clinically aggressive disease that may be targeted therapeutically.
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| 2. |
- Barwick, Vicki, et al.
(författare)
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Method validation in analytical sciences: discussions on current practice and future challenges
- 2017
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Ingår i: Accreditation and Quality Assurance. - : Springer Science and Business Media LLC. - 0949-1775 .- 1432-0517. ; 22:5, s. 253-263
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Tidskriftsartikel (refereegranskat)abstract
- Eurachem held a workshop on method validation in analytical sciences in Gent, Belgium, on 9–10 May 2016. A summary of the working group discussions is provided here. The discussions covered a range of issues concerned with current practice and future challenges in method validation, i.e. setting requirements for a method to be validated; planning validation studies; validation of qualitative and semi-quantitative methods; validation of multi-parameter methods; determination of trueness/bias; assessment of working range; validation in microbiology; and method validation under flexible scope of accreditation. Delegates (129) from 24 different countries and from different backgrounds, e.g. from both public and private laboratories, laboratory associations, accreditation bodies and universities, attended the working groups, thus providing opportunities to collect a variety of views and experiences as well as to identify potential gaps in current guidance and regulations. While the practicalities of assessing method performance characteristics are generally well understood, the issue of setting requirements for those characteristics beforehand is less straightforward. Although a number of documents addressing the principles of method validation are available, guidance on dealing with more complex and ‘non-ideal’ situations, as well as examples of good practice, would be welcomed and greater harmonisation of approaches was deemed necessary. There remains a need for guidance on both the concepts that apply to ‘qualitative’ or ‘nominal’ test methods and on the practical implementation of validation studies in such cases.
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| 3. |
- Cozza, Michela, 1978-, et al.
(författare)
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Hacking age
- 2022
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Ingår i: Sociology Compass. - : Wiley. - 1751-9020.
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Tidskriftsartikel (refereegranskat)abstract
- This article is a critical interdisciplinary study of biohacking as a specific case of transhumanism and its goals of enhancement and age intervention. It focuses on the organising principles underlying the biohacking movement's relationship to ageing and technoscience. The argument traces how the historical and scientific body technologies of molecularisation, functional age, optimisation, and quantification made possible the biohacking vision of the ageing body as amenable to modification, enhancement and improvement beyond its natural limits. Conclusions consider the wider implications of biohacking by pointing out four important issues that frame our cultural ambivalence about ageing: the tension between biohacking's supposedly liberating enhancement technologies and their obeisance to a tyranny of self-disciplinary practices and the authority of bio-data; the social meaning of biohacking hierarchies of human value, based on modifiable fitness and enhanceable performance; the implications of the biohacking program for gendered ageism; and the ethical limits of biohacking, not only in terms of potential harms to a person but what it can mean to exceed the natural limits of life.
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| 4. |
- Ellison, Stephen, et al.
(författare)
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Attenuation of Experimental Atherosclerosis by Interleukin-19.
- 2013
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1524-4636. ; 33:10, s. 2316-2324
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin-19 (IL-19) is a putative Th2, anti-inflammatory interleukin. Its expression and potential role in atherogenesis are unknown. IL-19 is not detected in normal artery and is expressed to a greater degree in plaque from symptomatic versus asymptomatic patients, suggesting a compensatory counter-regulatory function. We tested whether IL-19 could reduce atherosclerosis in susceptible mice and identified plausible mechanisms.
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| 5. |
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| 6. |
- Holmfeldt, Linda, et al.
(författare)
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The genomic landscape of hypodiploid acute lymphoblastic leukemia
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:3, s. 242-252
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Tidskriftsartikel (refereegranskat)abstract
- The genetic basis of hypodiploid acute lymphoblastic leukemia (ALL), a subtype of ALL characterized by aneuploidy and poor outcome, is unknown. Genomic profiling of 124 hypodiploid ALL cases, including whole-genome and exome sequencing of 40 cases, identified two subtypes that differ in the severity of aneuploidy, transcriptional profiles and submicroscopic genetic alterations. Near-haploid ALL with 24-31 chromosomes harbor alterations targeting receptor tyrosine kinase signaling and Ras signaling (71%) and the lymphoid transcription factor gene IKZF3 (encoding AIOLOS; 13%). In contrast, low-hypodiploid ALL with 32-39 chromosomes are characterized by alterations in TP53 (91.2%) that are commonly present in nontumor cells, IKZF2 (encoding HELIOS; 53%) and RB1 (41%). Both near-haploid and low-hypodiploid leukemic cells show activation of Ras-signaling and phosphoinositide 3-kinase (PI3K)-signaling pathways and are sensitive to PI3K inhibitors, indicating that these drugs should be explored as a new therapeutic strategy for this aggressive form of leukemia.
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| 7. |
- Hu, Xuchen, et al.
(författare)
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GPIHBP1 expression in gliomas promotes utilization of lipoprotein-derived nutrients
- 2019
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Ingår i: eLIFE. - : ELIFE SCIENCES PUBLICATIONS LTD. - 2050-084X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- GPIHBP1, a GPI-anchored protein of capillary endothelial cells, binds lipoprotein lipase (LPL) within the subendothelial spaces and shuttles it to the capillary lumen. GPIHBP1-bound LPL is essential for the margination of triglyceride-rich lipoproteins (TRLs) along capillaries, allowing the lipolytic processing of TRLs to proceed. In peripheral tissues, the intravascular processing of TRLs by the GPIHBP1-LPL complex is crucial for the generation of lipid nutrients for adjacent parenchymal cells. GPIHBP1 is absent from the capillaries of the brain, which uses glucose for fuel; however, GPIHBP1 is expressed in the capillaries of mouse and human gliomas. Importantly, the GPIHBP1 in glioma capillaries captures locally produced LPL. We use NanoSIMS imaging to show that TRLs marginate along glioma capillaries and that there is uptake of TRL-derived lipid nutrients by surrounding glioma cells. Thus, GPIHBP1 expression in gliomas facilitates TRL processing and provides a source of lipid nutrients for glioma cells.
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| 8. |
- Thomas, HS, et al.
(författare)
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- 2019
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