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| 2. |
- Jonasson, Emma, 1987, et al.
(författare)
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Identification of breast cancer stem cell related genes using functional cellular assays combined with single-cell RNA sequencing in MDA-MB-231 cells
- 2019
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Ingår i: Frontiers in Genetics. - : Frontiers Media SA. - 1664-8021. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer tumors display different cellular phenotypes. A growing body of evidence points toward a population of cancer stem cells (CSCs) that is important for metastasis and treatment resistance, although the characteristics of these cells are incomplete. We used mammosphere formation assay and label-retention assay as functional cellular approaches to enrich for cells with different degree of CSC properties in the breast cancer cell line MDA-MB-231 and performed single-cell RNA sequencing. We clustered the cells based on their gene expression profiles and identified three subpopulations, including a CSC-like population. The cell clustering into these subpopulations overlapped with the cellular enrichment approach applied. To molecularly define these groups, we identified genes differentially expressed between the three subpopulations which could be matched to enriched gene sets. We also investigated the transition process from CSC-like cells into more differentiated cell states. In the CSC population we found 14 significantly upregulated genes. Some of these potential breast CSC markers are associated to reported stem cell properties and clinical survival data, but further experimental validation is needed to confirm their cellular functions. Detailed characterization of CSCs improve our understanding of mechanisms for tumor progression and contribute to the identification of new treatment targets. © 2019 Jonasson, Ghannoum, Persson, Karlsson, Kroneis, Larsson, Landberg and Ståhlberg. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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| 3. |
- Landberg, Göran, 1963, et al.
(författare)
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Characterization of cell-free breast cancer patient-derived scaffolds using liquid chromatography-mass spectrometry/mass spectrometry data and RNA sequencing data
- 2020
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Ingår i: Data in Brief. - : Elsevier BV. - 2352-3409. ; 31
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Tidskriftsartikel (refereegranskat)abstract
- Patient-derived scaffolds (PDSs) generated from primary breast cancer tumors can be used to model the tumor microenvironment in vitro . Patient-derived scaffolds are generated by repeated detergent washing, removing all cells. Here, we analyzed the protein composition of 15 decellularized PDSs using liquid chromatography-mass spectrometry/mass spectrometry. One hundred forty-three proteins were detected and their relative abundance was calculated using a reference sample generated from all PDSs. We performed heatmap analysis of all the detected proteins to display their expression patterns across different PDSs together with pathway enrichment analysis to reveal which processes that were connected to PDS protein composition. This protein dataset together with clinical information is useful to investigators studying the microenvironment of breast cancers. Further, after repopulating PDSs with either MCF7 or MDA-MB-231 cells, we quantified their gene expression profiles using RNA sequencing. These data were also compared to cells cultured in conventional 2D conditions, as well as to cells cultured as xenografts in immune-deficient mice. We investigated the overlap of genes regulated between these different culture conditions and performed pathway enrichment analysis of genes regulated by both PDS and xenograft cultures compared to 2D in both cell lines to describe common processes associated with both culture conditions. Apart from our described analyses of these systems, these data are useful when comparing different experimental model systems. Downstream data analyses and interpretations can be found in the research article "Patient-derived scaffolds uncover breast cancer promoting properties of the microenvironment" [1] . (C) 2020 The Authors. Published by Elsevier Inc.
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| 4. |
- Landberg, Göran, et al.
(författare)
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Patient-derived scaffolds uncover breast cancer promoting properties of the microenvironment
- 2020
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Ingår i: Biomaterials. - : Elsevier Ltd. - 0142-9612 .- 1878-5905. ; 235
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Tidskriftsartikel (refereegranskat)abstract
- Tumor cells interact with the microenvironment that specifically supports and promotes tumor development. Key components in the tumor environment have been linked to various aggressive cancer features and can further influence the presence of subpopulations of cancer cells with specific functions, including cancer stem cells and migratory cells. To model and further understand the influence of specific microenvironments we have developed an experimental platform using cell-free patient-derived scaffolds (PDSs) from primary breast cancers infiltrated with standardized breast cancer cell lines. This PDS culture system induced a series of orchestrated changes in differentiation, epithelial-mesenchymal transition, stemness and proliferation of the cancer cell population, where an increased cancer stem cell pool was confirmed using functional assays. Furthermore, global gene expression profiling showed that PDS cultures were similar to xenograft cultures. Mass spectrometry analyses of cell-free PDSs identified subgroups based on their protein composition that were linked to clinical properties, including tumor grade. Finally, we observed that an induction of epithelial-mesenchymal transition-related genes in cancer cells growing on the PDSs were significantly associated with clinical disease recurrences in breast cancer patients. Patient-derived scaffolds thus mimics in vivo-like growth conditions and uncovers unique information about the malignancy-inducing properties of tumor microenvironment. © 2019 The Authors
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| 5. |
- Larsson, Linda, et al.
(författare)
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Pathogen reduced red blood cells as an alternative to irradiated and washed components with potential for up to 42 days storage
- 2024
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Ingår i: Blood Transfusion. - : SIMTIPRO Srl. - 1723-2007. ; 22:2, s. 130-139
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Tidskriftsartikel (refereegranskat)abstract
- Background - The urgency of maintaining a safe and adequate blood supply is increasing. One approach to ensure a sufficient supply is to limit the outdating frequency of blood components. Pathogen inactivation technology was developed primarily to increase safety by preventing transmission of infectious diseases. The Intercept Blood System for pathogen reduction of red blood cells (RBC) has additional benefits such as inactivation of leucocytes and removal of plasma and storage debris through centrifugation. Irradiation and automated washing are detrimental to the RBC membrane and often implicate shortened shelf-life. We aimed to assess whether pathogen inactivation can replace RBC irradiation and washing to avoid shelf-life reduction. Materials and methods - RBC concentrates (No.=48) were pooled-and-split into four study arms, which underwent pathogen inactivation treatment, irradiation, automated washing or no treatment (reference). RBC quality was evaluated during 42 days by assessment of storage lesion. Washing efficacy was defined by IgA and albumin reduction. Results - Pathogen reduced RBCs had similar membrane preservation to reference RBCs (hemolysis, microvesicles and extracellular potassium ions), whereas the RBCs were negatively impacted by irradiation or automated washing. ATP increased substantially post-pathogen inactivation, while 2,3-DPG decreased. Pathogen inactivation considerably reduced albumin and IgA, though slightly less efficiently than automated washing. Discussion - RBCs exhibit superior membrane preservation after pathogen inactivation treatment, compared to both irradiation and automated washing. This suggests that replacement is possible, even though the plasma reduction protocol could be further optimised. Replacement of irradiated and washed RBC concentrates with pathogen reduced RBC concentrates storable up to 42 days would be advantageous for both the blood supply and patient safety.
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| 6. |
- Larsson, Mikael, 1982, et al.
(författare)
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Evaluation of Carboxymethyl-Hexanoyl Chitosan as a Protein Nanocarrier
- 2013
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Ingår i: Nanomaterials and Nanotechnology. - : SAGE Publications. - 1847-9804. ; 3:1, s. Art. no. 7-
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Tidskriftsartikel (refereegranskat)abstract
- Carboxymethyl‐hexanoyl chitosan (CHC) has the ability to self‐assemble into nanocapsules in anaqueous solution and it has recently shown potentialin numerous biomedical applications. Here weinvestigate the protein loading efficiency and release,as well as the structural properties of CHC proteinnanocarriers. Bovine serum albumin (BSA) or itschromophore labelled version, fluorescein‐BSA, wasused as a model protein and the loading wasperformed with a simple mixing of pre‐formednanocapsules and protein. Dynamic light scatteringand zeta potential analysis revealed that proteinloaded nanocarriers with high positive zeta potentialwere formed. The protein loaded nanocarriersdisplayed a loading efficiency of 75% and a very slowprotein release. In summary, our results highlight thepotential of CHC as a protein nanocarrier, but alsoindicate that protein‐CHC interactions need to beconsidered in protein containing CHC formulationswhere protein release is not the main function.
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| 7. |
- Moberg, Christina, et al.
(författare)
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De unga gör helt rätt när de stämmer staten
- 2022
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Ingår i: Aftonbladet. - 1103-9000.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
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| 9. |
- Sawcer, Stephen, et al.
(författare)
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Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
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| 10. |
- Wulf Hanson, Sarah, et al.
(författare)
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A global systematic analysis of the occurrence, severity, and recovery pattern of long COVID in 2020 and 2021
- 2022
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Importance: While much of the attention on the COVID-19 pandemic was directed at the daily counts of cases and those with serious disease overwhelming health services, increasingly, reports have appeared of people who experience debilitating symptoms after the initial infection. This is popularly known as long COVID.Objective: To estimate by country and territory of the number of patients affected by long COVID in 2020 and 2021, the severity of their symptoms and expected pattern of recovery.Design: We jointly analyzed ten ongoing cohort studies in ten countries for the occurrence of three major symptom clusters of long COVID among representative COVID cases. The defining symptoms of the three clusters (fatigue, cognitive problems, and shortness of breath) are explicitly mentioned in the WHO clinical case definition. For incidence of long COVID, we adopted the minimum duration after infection of three months from the WHO case definition. We pooled data from the contributing studies, two large medical record databases in the United States, and findings from 44 published studies using a Bayesian meta-regression tool. We separately estimated occurrence and pattern of recovery in patients with milder acute infections and those hospitalized. We estimated the incidence and prevalence of long COVID globally and by country in 2020 and 2021 as well as the severity-weighted prevalence using disability weights from the Global Burden of Disease study.Results: Analyses are based on detailed information for 1906 community infections and 10526 hospitalized patients from the ten collaborating cohorts, three of which included children. We added published data on 37262 community infections and 9540 hospitalized patients as well as ICD-coded medical record data concerning 1.3 million infections. Globally, in 2020 and 2021, 144.7 million (95% uncertainty interval [UI] 54.8-312.9) people suffered from any of the three symptom clusters of long COVID. This corresponds to 3.69% (1.38-7.96) of all infections. The fatigue, respiratory, and cognitive clusters occurred in 51.0% (16.9-92.4), 60.4% (18.9-89.1), and 35.4% (9.4-75.1) of long COVID cases, respectively. Those with milder acute COVID-19 cases had a quicker estimated recovery (median duration 3.99 months [IQR 3.84-4.20]) than those admitted for the acute infection (median duration 8.84 months [IQR 8.10-9.78]). At twelve months, 15.1% (10.3-21.1) continued to experience long COVID symptoms.Conclusions and relevance: The occurrence of debilitating ongoing symptoms of COVID-19 is common. Knowing how many people are affected, and for how long, is important to plan for rehabilitative services and support to return to social activities, places of learning, and the workplace when symptoms start to wane.Key Points: Question: What are the extent and nature of the most common long COVID symptoms by country in 2020 and 2021?Findings: Globally, 144.7 million people experienced one or more of three symptom clusters (fatigue; cognitive problems; and ongoing respiratory problems) of long COVID three months after infection, in 2020 and 2021. Most cases arose from milder infections. At 12 months after infection, 15.1% of these cases had not yet recovered.Meaning: The substantial number of people with long COVID are in need of rehabilitative care and support to transition back into the workplace or education when symptoms start to wane.
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