| 1. |
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| 2. |
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| 3. |
- Ek, Hanna, et al.
(författare)
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Transitioning from conventional photon therapy to proton therapy for primary brain tumors
- 2023
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Ingår i: Acta oncologica (Stockholm, Sweden). - 1651-226X. ; 62:4, s. 391-399
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Proton radiation therapy (PT) has become a treatment option alongside photon therapy (XRT) for lower-grade gliomas (LGG). In this single-institution retrospective study, we investigate the patient characteristics and treatment outcomes, including pseudo-progression (PsP), for LGG patients selected for PT. Method: Adult patients with grade 2–3 glioma consecutively treated with radiotherapy (RT) from May 2012 to December 2019 were retrospectively included in this cohort study. Tumor characteristics and treatment data were collected. The groups treated with PT and XRT were compared regarding treatment characteristics, side effects, occurrence of PsP, and survival outcomes. PsP was defined as new or growing lesions followed by either decrease or stabilization during a 12 month-period with no treatment. Results: Out of 143 patients meeting the inclusion criteria, 44 were treated with PT, 98 with XRT and one with mixed PT + XRT. The patients receiving PT were younger, had a lower tumor grade, more oligodendrogliomas and received a lower mean brain and brainstem dose. PsP was observed in 21 out of 126 patients, with no difference between XRT and PT (p =.38). The rate of fatigue in immediate connection to RT (zero to three months after) was higher for XRT than for PT (p =.016). The PT patients had a significantly better PFS and OS than the XRT patients (p =.025 and.035), but in multivariate analysis radiation modality was non-significant. Higher average dose to both brain and brainstem was associated with inferior PFS and OS (p <.001). Median follow-up time were 69 months and 26 months for XRT and PT patients, respectively. Conclusion: Contrary to previous studies, there was no difference in risk of PsP for XRT and PT. PT was associated with lower rates of fatigue <3 months after RT. The superior survival outcomes for PT indicates that the patients with the best prognosis were referred to PT.
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| 4. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 5. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 6. |
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| 7. |
- Amer-Wåhlin, Isis, et al.
(författare)
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Slutrapport för EVIDIGVO
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Den här texten presenterar resultat från tre aktiviteter för kunskapsinsamling om implementering av digitala verktyg inom vård- och omsorg: en litteratursammanställning, en workshopserie i två delar och en enkätundersökning. Den primära målgruppen har varit verksamhetsutvecklare och projektledare i regioner och kommuner. Antalet svarande i enkätstudien var för lågt för att kunna dra några statistiska slutsatser, men resultatet kan, tillsammans med workshopserien, ändå användas för att identifiera områden där det verkar finnas utmaningar. Både litteratursammanställningen och enkätundersökningen pekar på ett behov av att utveckla strukturerade utvärderingsmodeller för implementering. Även under workshoppen diskuterades den bristande förmågan att ”samla in evidens under projektens gång”, och det fanns en önskan om att ett sådant arbetssätt skulle utvecklas. Enkäten och workshoppen pekar även på flera återkommande problem under implementeringsprojekts olika faser. I den inledande fasen efterfrågas bättre analyser och förankringsarbete. Analyser med användarfokus missas speciellt ofta, så som användarresa, hållbarhetsanalys och intressent- och behovsanalys. Även i andra ändan av processen, då system och arbetssätt ska avvecklas, finns utmaningar och förbättringsförslag, t.ex. saknas ofta beslut om utfasning av gamla lösningar, och ett förslag är att man redan när man skriver kontakt med en leverantör ska säkerställa att leverantören hjälper till med migrering vid utfasning. En annan genomgående problematik är osäkerhet, och ibland avsaknad, av roller, ansvar och kommunikation. Detta handlar om att man inte riktigt vet varför man ska göra saker, eller att verksamheten och personerna som ska göra förändringen inte är tillräckligt inblandade. Det kan också handla om att support och förvaltning inte är tillräckligt väl utvecklat, och om att man inte vet hur man kan samarbeta med leverantörer. Här identifieras även förändringsledning som ett viktigt verktyg för att underlätta en god implementering.
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| 8. |
- Belfrage, Emma, et al.
(författare)
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Predictive and Prognostic Biomarkers in Patients With Mycosis Fungoides and Sézary Syndrome (BIO-MUSE) : Protocol for a Translational Study
- 2024
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Ingår i: JMIR Research Protocols. - 1929-0748. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cutaneous T-cell lymphoma (CTCL) is a rare group of lymphomas that primarily affects the skin. Mycosis fungoides (MF) is the most common form of CTCL and Sézary syndrome (SS) is more infrequent. Early stages (IA-IIA) have a favorable prognosis, while advanced stages (IIB-IVB) have a worse prognosis. Around 25% of patients with early stages of the disease will progress to advanced stages. Malignant skin-infiltrating T-cells in CTCL are accompanied by infiltrates of nonmalignant T-cells and other immune cells that produce cytokines that modulate the inflammation. Skin infection, often with Staphylococcus aureus, is frequent in advanced stages and can lead to sepsis and death. S. aureus has also been reported to contribute to the progression of the disease. Previous reports indicate a shift from Th1 to Th2 cytokine production and dysfunction of the skin barrier in CTCL. Treatment response is highly variable and often unpredictable, and there is a need for new predictive and prognostic biomarkers.OBJECTIVE: This prospective translational study aims to identify prognostic biomarkers in the blood and skin of patients with MF and SS.METHODS: The Predictive and Prognostic Biomarkers in Patients With MF and SS (BIO-MUSE) study aims to recruit 120 adult patients with MF or SS and a control group of 20 healthy volunteers. The treatments will be given according to clinical routine. The sampling of each patient will be performed every 3 months for 3 years. The blood samples will be analyzed for lactate dehydrogenase, immunoglobulin E, interleukins, thymus and activation-regulated chemokine, and lymphocyte subpopulations. The lymphoma microenvironment will be investigated through digital spatial profiling and single-cell RNA sequencing. Microbiological sampling and analysis of skin barrier function will be performed. The life quality parameters will be evaluated. The results will be evaluated by the stage of the disease.RESULTS: Patient inclusion started in 2021 and is still ongoing in 2023, with 18 patients and 20 healthy controls enrolled. The publication of selected translational findings before the publication of the main results of the trial is accepted.CONCLUSIONS: This study aims to investigate blood and skin with a focus on immune cells and the microbiological environment to identify potential new prognostic biomarkers in MF and SS.TRIAL REGISTRATION: ClinicalTrials.gov NCT04904146; https://www.clinicaltrials.gov/study/NCT04904146.INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55723.
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| 9. |
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| 10. |
- Ek, Caroline, et al.
(författare)
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Increase in stable isotope ratios driven by metabolic alterations in amphipods exposed to the beta-blocker propranolol
- 2019
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:5
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Tidskriftsartikel (refereegranskat)abstract
- Anthropogenic pressures, such as contaminant exposure, may affect stable isotope ratios in biota. These changes are driven by alterations in the nutrient allocation and metabolic pathways induced by specific stressors. In a controlled microcosm study with the amphipod Gammarus spp., we studied effects of the beta-blocker propranolol on stable isotope signatures (delta N-15 and delta C-13), elemental composition (%C and %N), and growth (protein content and body size) as well as biomarkers of oxidative status (antioxidant capacity, ORAC; lipid peroxidation, TBARS) and neurological activity (acetylcholinesterase, AChE). Based on the known effects of propranolol exposure on cellular functions, i.e., its mode of action (MOA), we expected to observe a lower scope for growth, accompanied by a decrease in protein deposition, oxidative processes and AChE inhibition, with a resulting increase in the isotopic signatures. The observed responses in growth, biochemical and elemental variables supported most of these predictions. In particular, an increase in %N was observed in the propranolol exposures, whereas both protein allocation and body size declined. Moreover, both ORAC and TBARS levels decreased with increasing propranolol concentration, with the decrease being more pronounced for TBARS, which indicates the prevalence of the antioxidative processes. These changes resulted in a significant increase of the delta N-15 and delta C-13 values in the propranolol-exposed animals compared to the control. These findings suggest that MOA of beta-blockers may be used to predict sublethal effects in non-target species, including inhibited AChE activity, improved oxidative balance, and elevated stable isotope ratios. The latter also indicates that metabolism-driven responses to environmental contaminants can alter stable isotope signatures, which should be taken into account when interpreting trophic interactions in the food webs.
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| 11. |
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| 12. |
- Ek Fälth, Hanna, 1992
(författare)
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Insights from modeling renewable electricity systems and developing hydropower models
- 2023
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- One strategy for reaching a carbon-neutral electricity system is a large-scale deployment of wind and solar power. However, electricity systems with high shares of wind and solar power rely on other technologies, e.g., transmission and hydropower, to ensure that demand can be met at all times despite weather-dependent wind and solar power production. Moreover, the deployment of some technologies may be limited by public concern and land availability, which could increase the cost of decarbonizing electricity systems. To analyze designs and costs for future electricity systems with high shares of renewables, energy system models are crucial. In such models, the representation of hydropower is often significantly simplified, overestimating how flexibly hydropower can operate and, thereby, the hydropower’s ability to complement wind and solar power production. This thesis has two overarching aims addressed separately in the two appended papers. First, to explore how deployment limits on wind and solar power, transmission, and nuclear power each affect the cost of future carbon-neutral electricity and how it differs between the Middle East and North Africa region (MENA) and Europe (Paper A). Second, to investigate the accuracy of the hydropower representations used in energy system models and to develop a method for a more accurate hydropower representation (Paper B). In Paper A, we use an energy system model to show that the cost of a carbon-neutral electricity system is considerably lower in MENA than in Europe, which we link to MENA’s better wind and solar resource potential. Also, limiting the deployment of wind and solar power, transmission, or nuclear power can significantly affect system costs. However, the effect is markedly different in the two regions. Paper B examines how realistic different hydropower representations are by developing hydropower optimization models with different levels of detail and comparing them. We find that simple hydropower representations, such as those often used in energy system models, result in unrealistic production profiles and exaggerate the flexibility that hydropower can provide. In addition, we contribute a novel computationally efficient hydropower model that entails a more realistic hydropower production.
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| 13. |
- Ek Fälth, Hanna, 1992, et al.
(författare)
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MENA compared to Europe: The influence of land use, nuclear power, and transmission expansion on renewable electricity system costs
- 2021
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Ingår i: Energy Strategy Reviews. - : Elsevier BV. - 2211-467X. ; 33
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Tidskriftsartikel (refereegranskat)abstract
- Most studies that examine CO2-neutral, or near CO2-neutral, power systems by using energy system models investigate Europe or the United States, while similar studies for other regions are rare. In this paper, we focus on the Middle East and North Africa (MENA), where weather conditions, especially for solar, differ substantially from those in Europe. We use a green-field linear capacity expansion model with over-night investment to assess the effect on the system cost of (i) limiting/expanding the amount of land available for wind and solar farms, (ii) allowing for nuclear power and (iii) disallowing for international transmission. The assessment is done under three different cost regimes for solar PV and battery storage. First, we find that the amount of available land for wind and solar farms can have a significant impact on the system cost, with a cost increase of 0–50% as a result of reduced available land. In MENA, the impact on system cost from land availability is contingent on the PV and battery cost regime, while in Europe it is not. Second, allowing for nuclear power has a minor effect in MENA, while it may decrease the system cost in Europe by up to 20%. In Europe, the effect on system cost from allowing for nuclear power is highly dependent on the PV and battery cost regime. Third, disallowing for international transmission increases the system cost by up to 25% in both Europe and MENA, and the cost increase depends on the cost regime for PV and batteries. The impacts on system cost from these three controversial and policy-relevant factors in a decarbonized power system thus play out differently, depending on (i) the region and (ii) uncertain future investment costs for solar PV and storage. We conclude that a renewable power system in MENA is likely to be less costly than one in Europe, irrespective of future uncertainties regarding investment cost for PV and batteries, and policies surrounding nuclear power, transmission, and land available for wind- and solar farms. In MENA, the system cost varies between 42 and 96 $/MWh. In Europe, the system cost varies between 51 and 102 $/MWh.
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| 14. |
- Ek Fälth, Hanna, 1992, et al.
(författare)
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Trade-offs between aggregated and turbine-level representations of hydropower in optimization models
- 2023
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Ingår i: Renewable and Sustainable Energy Reviews. - 1879-0690 .- 1364-0321. ; 183
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Tidskriftsartikel (refereegranskat)abstract
- To model a future power system with high shares of variable renewables, it is essential to capture the flexibility of dispatchable technologies such as hydropower. However, the representation of hydropower is often oversimplified in energy system investment models, such that the flexibility of hydropower is significantly exaggerated. This suggests the need for improved representations of hydropower that capture physical river dynamics but are computationally efficient to maintain the tractability of large models. Here, we develop a series of hydropower optimization models for a single river with various levels of techno-physical detail to evaluate options for hydropower representations in energy system investment models. All models operate hourly over a full year with perfect foresight. We explore trade-offs between accuracy and computational time involved in including features such as the river network, head-dependent power production, and discharge-dependent turbine efficiencies. We find that the level of detail significantly affects the optimal production and confirm that a simplistic hydropower representation similar to those often used in investment models significantly overestimates the flexibility of hydropower. The most detailed nonconvex model includes a full river network, head-dependency, and turbine efficiencies and is solved in just one hour on a modern desktop computer. Furthermore, we linearize this detailed model, thereby reducing computation time to one minute while featuring production dynamics substantially more similar to the full nonconvex model than a naive linear network model. These contributions pave the way for improving hydropower representations in investment models to avoid overestimating the flexibility that hydropower may provide.
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| 15. |
- Ek, Moira, et al.
(författare)
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An anti-sortilin affibody-peptide fusion inhibits sortilin-mediated progranulin degradation
- 2024
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Heterozygous loss-of-function mutations in the GRN gene are a common cause of frontotemporal dementia. Such mutations lead to decreased plasma and cerebrospinal fluid levels of progranulin (PGRN), a neurotrophic factor with lysosomal functions. Sortilin is a negative regulator of extracellular PGRN levels and has shown promise as a therapeutic target for frontotemporal dementia, enabling increased extracellular PGRN levels through inhibition of sortilin-mediated PGRN degradation. Here we report the development of a high-affinity sortilin-binding affibody-peptide fusion construct capable of increasing extracellular PGRN levels in vitro. By genetic fusion of a sortilin-binding affibody generated through phage display and a peptide derived from the progranulin C-terminus, an affinity protein (A3-PGRNC15*) with 185-pM affinity for sortilin was obtained. Treating PGRN-secreting and sortilin-expressing human glioblastoma U-251 cells with the fusion protein increased extracellular PGRN levels up to 2.5-fold, with an EC50 value of 1.3 nM. Our results introduce A3-PGRNC15* as a promising new agent with therapeutic potential for the treatment of frontotemporal dementia. Furthermore, the work highlights means to increase binding affinity through synergistic contribution from two orthogonal polypeptide units.
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| 16. |
- Ek Österberg, Emma, et al.
(författare)
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Goda exempel som redskap i styrning
- 2022
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Ingår i: Förvaltningen i samhället. - Lund : Studentlitteratur AB. - 9789144165431 ; , s. 239-250
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- I kapitlet närmar vi oss den framväxande texttypen "goda exempel" som en styrande genre (genre of governance). Vi fokuserar på berättande texter om integration och hämtar våra analystexter från två organisationer, Falu kommun och Landsbygdsnätverket. Vår analys visar på både likheter och skillnader mellan texerna. En likhet är att alla texter framställer individer som hjältar - vare sig det handlar om driftiga och anpassningsbara personer som invandrat till Sverige och lyckats väl med sin individuella integration eller personer som levt hela sina liv i Sverige och som visat sig nytänkande och handlingskraftiga i arbetet med att förbättra integrationen. Texterna säger också en hel del om vilka egenskaper som ses som eftersträvansvärda och positiva i dagens svenska samhälle, exempelvis individuell handlingsförmåga, driv och engagemang, flexibilitet samt mod att se bortom det invanda och att utmana det etablerade - men också anpassningsvilja och tacksamhet. En skillnad är att berättelserna från Falun utöver att lyfta fram lyckade exempel på integration fyller funktionen att marknadsföra kommunen.
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| 17. |
- Ek Österberg, Emma, 1977, et al.
(författare)
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Goda exempel som redskap i styrning
- 2022
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Ingår i: Förvaltningen i samhället. - Lund : Studentlitteratur. - 9789144165431
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 18. |
- Eskilsson, Therese, 1970-, et al.
(författare)
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Hopeful struggling for health : Experiences of participating in computerized cognitive training and aerobic training for persons with stress-related exhaustion disorder
- 2020
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Ingår i: Scandinavian Journal of Psychology. - : Wiley-Blackwell. - 0036-5564 .- 1467-9450. ; 61:3, s. 361-68
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Tidskriftsartikel (refereegranskat)abstract
- It is important to understand how people with exhaustion disorder (ED) perceive interventions aiming to facilitate cognitive functioning. Therefore, the overall aim of this study was to explore experiences from persons with ED after participating in a 12-week intervention of either computerized cognitive training or aerobic training. Both interventions were performed in addition to a multimodal rehabilitation programme. Thirteen participants, 11 women and 2 men, were interviewed about pros and cons with participating in the training. The interviews were analysed with Qualitative Content Analysis. The analyses resulted in the theme hopeful struggling for health and the categories support, motivation and sensations. It was hard work recovering from ED. Support from others who are in the same situation, family members, and technology and routines for the training were strongly emphasized as beneficial for recovery. Timing, i.e., matching activities to the rehabilitation programme, getting feedback and perceiving joy in the training were important for motivation. Participants in both interventions experienced positive sensations with improved memory performance, everyday life functioning and increased faith in the prospect of recovery. However, it is important to consider various aspects of support and motivation in both computerized cognitive training and aerobic training to enable participants to pursue their participation.
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| 19. |
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| 20. |
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| 21. |
- Hassanzadeh Moghimi, Farzad, 1994-, et al.
(författare)
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Climate Policy and Strategic Operations in a Hydro-Thermal Power System
- 2023
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Ingår i: Energy Journal. - : International Association for Energy Economics (IAEE). - 0195-6574 .- 1944-9089. ; 44:5, s. 67-94
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Tidskriftsartikel (refereegranskat)abstract
- Decarbonisation of the Nordic power sector entails substantial variable renewable energy (VRE) adoption. While Nordic hydropower reservoirs can mitigate VRE output's intermittency, strategic hydro producers may leverage increased flexibility requirements to exert market power. Using a Nash-Cournot model, we find that even the current Nordic power system could yield modest gains from strategic reservoir operations regardless of a prohibition on "spilling" water to increase prices. Instead, strategic hydro producers could shift generation from peak to off-peak seasons. Such temporal arbitrage becomes more attractive under a climate package with a €100/t CO2 price and doubled VRE capacity. Since the package increases generation variability, lowers average prices, and makes fossil-fuelled plants unprofitable, strategic hydro producers face lower opportunity costs in shifting output from peak to off-peak seasons and encounter muted responses from price-taking fossil-fuelled plants. Hence, a climate package that curtails CO2 emissions may also bolster strategic hydro producers' leverage.
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| 22. |
- Henriksson, Pontus, 1982-, et al.
(författare)
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Physical fitness in relation to later body composition in pre-school children
- 2019
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Ingår i: Journal of Science and Medicine in Sport. - : Elsevier. - 1440-2440 .- 1878-1861. ; 22:5, s. 574-579
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesAlthough physical fitness is considered a marker of health in youth, little is known whether physical fitness in pre-school age is related to later body composition. Thus, this study investigated (i) associations of physical fitness at 4.5 years of age with body composition 12 months later and (ii) whether improvements in physical fitness during the 12-month follow-up were associated with changes in body composition.DesignThis study included 142 children, measured at 4.5 and 5.5 years, from the control group of the MINISTOP trial.MethodsPhysical fitness (cardiorespiratory fitness, lower- and upper-body muscular strength and motor fitness) was measured using the PREFIT test battery. Body composition was assessed using air-displacement plethysmography.ResultsIn adjusted regression analyses, greater cardiorespiratory fitness, lower-body muscular strength and motor fitness at 4.5 years were associated with a lower fat mass index at 5.5 years (standardized β= −0.182 to −0.229, p ≤ 0.028). Conversely, greater cardiorespiratory fitness, lower- and upper-body muscular strength as well as motor fitness at 4.5 years of age were associated with a higher fat-free mass index (standardized β = 0.255–0.447, p ≤ 0.001). Furthermore, improvements in cardiorespiratory fitness, lower-body muscular strength and motor fitness during the 12-month follow-up period were associated with decreases in fat mass index and/or % fat mass.ConclusionsIn conclusion, the results of this study provide evidence of the importance of physical fitness early in life. Nevertheless, further studies are needed in order to clarify the influence of physical fitness in the pre-school age with later health outcomes.
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| 23. |
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| 24. |
- Rosenquist, Richard, et al.
(författare)
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Genome-Wide DNA Methylation Profiling of Chronic Lymphocytic Leukemia Subsets Carrying Stereotyped B Cell Receptors
- 2017
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Ingår i: Blood. - 0006-4971. ; 130:Suppl 1, s. 57-57
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- In recent years, subsets of chronic lymphocytic leukemia (CLL) patients carrying quasi-identical or stereotyped B cell receptors (BcRs) have been identified that share clinicobiological features and disease outcome. While these stereotyped subsets show distinct gene expression and genomic profiles, the DNA methylation landscape remains largely unexplored. By applying high-resolution 450K methylation arrays, we investigated 176 CLL subset cases belonging to: (i) the clinically aggressive, IGHV-unmutated (U-CLL) subsets $$1 (clan I genes/IGKV(D)1-39, n=37) and $$8 (IGHV4-39/IGKV1(D)-39, n=21); (ii) the IGHV1-69-expressing U-CLL subsets $$3 (n=12), $$5 (n=9), $$6 (n=22), and $$7 (n=12); and, (iii) the indolent, IGHV-mutated (M-CLL) subset $$4 (IGHV4-34/IGKV2-30, n=28). In addition, we included subset $$2 cases (IGHV3-21/IGLV3-21, mixed mutation status, n=35) that have a poor outcome independent of IGHV mutation status. For comparative purposes, we included a cohort of CLL cases that do not express stereotyped BcRs ('non-subset', n=325). These patients were subgrouped according to the recently proposed epigenetic classification of CLL, i.e. poor-prognostic, naive-like CLL (n-CLL, n=102), favorable-prognostic, memory-like CLL (m-CLL; n=176), broadly corresponding to U-CLL and M-CLL, respectively, and a third intermediate CLL subgroup (i-CLL; n=47), which express borderline mutated IGHV genes and have an intermediate prognosis. Finally, a series of sorted normal subpopulations spanning different stages of B-cell differentiation [precursors (n=22), naive B cells (n=19) and germinal center/memory B-cells (n=33)] were also included in the analysis. Overall, unsupervised analysis of subset vs. non-subset CLL revealed that all U-CLL subsets clustered with n-CLL, subset $$4 clustered with m-CLL, while subset $$2 clustered separately with i-CLL (Figure 1). Supervised analysis revealed a limited number of CpG sites that were differentially methylated when comparing each U-CLL or M-CLL subset with non-subset cases. In contrast, almost all subset $$2 cases clustered separately from i-CLL in supervised analysis, indicating that this subset might represent a distinct subgroup of i-CLL. We recently demonstrated that the number of epigenetic changes that a tumor acquires, compared to its cellular origin (i.e. 'epigenetic burden'), may be a powerful predictor of clinical aggressiveness (Queiros et al, Cancer Cell 2016). When adopting this approach in CLL, comparison of specific subsets vs. their non-subset cases matched by epigenetic subgroup, revealed significant differences in the epigenetic burden amongst the various groupings; for instance, in subset $$1 vs. n-CLL (72K vs. 67K, plt;0.05) and in subset $$2 vs. i-CLL (76K vs. 68K, p=0.001), while no difference was observed between subset $$4 vs. m-CLL (83K vs. 82K, p=not significant). Subset $$2 cases frequently carry del(11q) and harbor SF3B1 mutations, however, neither the IGHV mutation status nor the presence of del(11q) or SF3B1 mutations had any impact on the epigenetic burden within subset $$2. In conclusion, U-CLL and M-CLL subsets generally clustered with n-CLL and m-CLL categories, respectively, implying common cellular origins. In contrast, subset $$2 emerged as the first defined member of the i-CLL group, which in turn alludes to a distinct cellular origin and/or pathogenetic process for subset $$2 and i-CLL patients.Disclosures Papakonstantinou: Janssen Pharmaceuticals: Research Funding; Gilead: Research Funding. Smedby: Janssen: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees. Gaidano: Roche: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Ghia: AbbVie: Consultancy; Adaptive: Consultancy; Gilead: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy; Roche: Consultancy; Novartis: Research Funding. Stamatopoulos: Novartis SA: Research Funding; Gilead: Consultancy, Honoraria, Research Funding; Janssen Pharmaceuticals: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding.↵* Asterisk with author names denotes non-ASH members.
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| 25. |
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| 26. |
- Turkington, RC, et al.
(författare)
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Immune activation by DNA damage predicts response to chemotherapy and survival in oesophageal adenocarcinoma
- 2019
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 68:11, s. 1918-1927
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Tidskriftsartikel (refereegranskat)abstract
- Current strategies to guide selection of neoadjuvant therapy in oesophageal adenocarcinoma (OAC) are inadequate. We assessed the ability of a DNA damage immune response (DDIR) assay to predict response following neoadjuvant chemotherapy in OAC.DesignTranscriptional profiling of 273 formalin-fixed paraffin-embedded prechemotherapy endoscopic OAC biopsies was performed. All patients were treated with platinum-based neoadjuvant chemotherapy and resection between 2003 and 2014 at four centres in the Oesophageal Cancer Clinical and Molecular Stratification consortium. CD8 and programmed death ligand 1 (PD-L1) immunohistochemical staining was assessed in matched resection specimens from 126 cases. Kaplan-Meier and Cox proportional hazards regression analysis were applied according to DDIR status for recurrence-free survival (RFS) and overall survival (OS).ResultsA total of 66 OAC samples (24%) were DDIR positive with the remaining 207 samples (76%) being DDIR negative. DDIR assay positivity was associated with improved RFS (HR: 0.61; 95% CI 0.38 to 0.98; p=0.042) and OS (HR: 0.52; 95% CI 0.31 to 0.88; p=0.015) following multivariate analysis. DDIR-positive patients had a higher pathological response rate (p=0.033), lower nodal burden (p=0.026) and reduced circumferential margin involvement (p=0.007). No difference in OS was observed according to DDIR status in an independent surgery-alone dataset.DDIR-positive OAC tumours were also associated with the presence of CD8+ lymphocytes (intratumoural: p<0.001; stromal: p=0.026) as well as PD-L1 expression (intratumoural: p=0.047; stromal: p=0.025).ConclusionThe DDIR assay is strongly predictive of benefit from DNA-damaging neoadjuvant chemotherapy followed by surgical resection and is associated with a proinflammatory microenvironment in OAC.
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| 27. |
- Glasbey, JC, et al.
(författare)
-
- 2021
-
swepub:Mat__t
|
|
| 28. |
|
|
