| 1. |
- Antonson, Hans, et al.
(författare)
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Kulturhistoriska värden i ett förändrat klimat. Hot, risker och hanteringkopplat till vägar och banor
- 2021
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Rapport (refereegranskat)abstract
- Klimatförändringar utgör en bred palett av risker för kulturmiljö och landskap,inklusive de kulturhistoriska lämningar som har en nära eller direkt kopplingtill transportinfrastruktur. I detta projekt tittade vi på ett antal av dessa riskeri syfte att hjälpa Trafikverket att utveckla tjänster för bättre förutsägelse ochhantering av riskerna i anslutning till vägar och banor. Forskningen inleddesgenom en översikt av befintliga offentliga publikationer om klimatförändringenshot, risker, metoder, anpassningsåtgärder och kulturmiljö. Detta följdesav en undersökning av upplevelsen av dessa frågor bland offentligt anställdaexperter som medverkar i planeringen. Geografiska informationssystem (GIS)användes för att identifiera kulturhistoriska lämningar som är klimatologisktriskutsatta sig i riskzonen för tre undersökningsområden, följt av fältbesökför att bedöma tillförlitligheten i GIS-resultaten. Analysen visade att en enkelGIS-analys kan vara till hjälp för att identifiera riskutsatta platser, men ocksåatt fältarbete kan medverka till att identifiera ytterligare risker men också problemmed noggrannheten i underliggande datamaterial. Projektet tillhandahållerockså grundläggande statistik om i vilken utsträckning olika typer avkulturhistoriska lämningar på nationell nivå riskerar att hotas enligt nuvarandeklimatförändringsmodeller. Projektet genomförde också fallstudier av 1) vägsaltetsrisker för milstolpar och andra arkeologiska företeelser i anslutning tillvägar, och 2) de historiska kartornas potential att användas för att identifierariskutsatta områden vid framtida klimatförändringar. Slutligen diskuteras konsekvensernaav dessa resultat för prioriteringar av klimatanpassningsaktivitetersamt presenterar förslag på metoder och modeller för att identifiera transportinfrastrukturenskulturmiljöer som är hotas av klimatförändringar.
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| 2. |
- Fletcher, John S., et al.
(författare)
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Correlated fluorescence microscopy and multi-ion beam secondary ion mass spectrometry imaging reveals phosphatidylethanolamine increases in the membrane of cancer cells over-expressing the molecular chaperone subunit CCT delta
- 2021
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 413, s. 445-453
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Tidskriftsartikel (refereegranskat)abstract
- Changes in the membrane composition of sub-populations of cells can influence different properties with importance to tumour growth, metastasis and treatment efficacy. In this study, we use correlated fluorescence microscopy and ToF-SIMS with C-60(+) and (CO2)(6k)(+) ion beams to identify and characterise sub-populations of cells based on successful transfection leading to over-expression of CCT delta, a component of the multi-subunit molecular chaperone named chaperonin-containing tailless complex polypeptide 1 (CCT). CCT has been linked to increased cell growth and proliferation and is known to affect cell morphology but corresponding changes in lipid composition of the membrane have not been measured until now. Multivariate analysis of the surface mass spectra from single cells, focused on the intact lipid ions, indicates an enrichment of phosphatidylethanolamine species in the transfected cells. While the lipid changes in this case are driven by the structural changes in the protein cytoskeleton, the consequence of phosphatidylethanolamine enrichment may have additional implications in cancer such as increased membrane fluidity, increased motility and an ability to adapt to a depletion of unsaturated lipids during cancer cell proliferation. This study demonstrates a successful fluorescence microscopy-guided cell by cell membrane lipid analysis with broad application to biological investigation. [GRAPHICS] .
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| 3. |
- Leiva, Maria Carmen, et al.
(författare)
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Breast cancer patient-derived scaffolds as a tool to monitor chemotherapy responses in human tumor microenvironments
- 2021
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Ingår i: Journal of Cellular Physiology. - : Wiley. - 0021-9541 .- 1097-4652. ; 236:6, s. 4709-4724
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is a heterogeneous disease where the tumor microenvironment, including extracellular components, plays a crucial role in tumor progression, potentially modulating treatment response. Different approaches have been used to develop three-dimensional models able to recapitulate the complexity of the extracellular matrix. Here, we use cell-free patient-derived scaffolds (PDSs) generated from breast cancer samples that were recellularized with cancer cell lines as an in vivo-like culture system for drug testing. We show that PDS cultured MCF7 cancer cells increased their resistance against the front-line chemotherapy drugs 5-fluorouracil, doxorubicin and paclitaxel in comparison to traditional two-dimensional cell cultures. The gene expression of the environmentally adapted cancer cells was modulated in different ways depending on the drug and the concentration used. High doses of doxorubicin reduced cancer stem cell features, whereas 5-fluorouracil increased stemness and decreased the proliferative phenotype. By using PDSs repopulated with other breast cancer cell lines, T-47D and MDA-MB-231, we observed both general and cell line specific drug responses. In summary, PDSs can be used to examine the extracellular matrix influence on cancer drug responses and for testing novel compounds in in vivo-like microenvironments.
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| 4. |
- Rosendahl, Jennifer, et al.
(författare)
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3D printed nanocellulose scaffolds as a cancer cell culture model system
- 2021
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Ingår i: Bioengineering. - : MDPI AG. - 2306-5354. ; 8:7
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Tidskriftsartikel (refereegranskat)abstract
- Current conventional cancer drug screening models based on two-dimensional (2D) cell culture have several flaws and there is a large need of more in vivo mimicking preclinical drug screening platforms. The microenvironment is crucial for the cells to adapt relevant in vivo characteristics and here we introduce a new cell culture system based on three-dimensional (3D) printed scaffolds using cellulose nanofibrils (CNF) pre-treated with 2,2,6,6-tetramethylpyperidine-1-oxyl (TEMPO) as the structural material component. Breast cancer cell lines, MCF7 and MDA-MB-231, were cultured in 3D TEMPO-CNF scaffolds and were shown by scanning electron microscopy (SEM) and histochemistry to grow in multiple layers as a heterogenous cell population with different morphologies, contrasting 2D cultured mono-layered cells with a morphologically homogenous cell population. Gene expression analysis demonstrated that 3D TEMPO-CNF scaffolds induced elevation of the stemness marker CD44 and the migration markers VIM and SNAI1 in MCF7 cells relative to 2D control. T47D cells confirmed the increased level of the stemness marker CD44 and migration marker VIM which was further supported by increased capacity of holoclone formation for 3D cultured cells. Therefore, TEMPO-CNF was shown to represent a promising material for 3D cell culture model systems for cancer cell applications such as drug screening. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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| 5. |
- Svanström, Andreas, et al.
(författare)
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Optimized alginate-based 3D printed scaffolds as a model of patient derived breast cancer microenvironments in drug discovery
- 2021
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Ingår i: Biomedical Materials (Bristol). - : IOP Publishing Ltd. - 1748-6041 .- 1748-605X. ; 16:4
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Tidskriftsartikel (refereegranskat)abstract
- The cancer microenvironment influences tumor progression and metastasis and is pivotal to consider when designing in vivo-like cancer models. Current preclinical testing platforms for cancer drug development are mainly limited to 2D cell culture systems that poorly mimic physiological environments and traditional, low throughput animal models. The aim of this work was to produce a tunable testing platform based on 3D printed scaffolds (3DPS) with a simple geometry that, by extracellular components and response of breast cancer reporter cells, mimics patient-derived scaffolds (PDS) of breast cancer. Here, the biocompatible polysaccharide alginate was used as base material to generate scaffolds consisting of a 3D grid containing periostin and hydroxyapatite. Breast cancer cell lines (MCF7 and MDA-MB-231) produced similar phenotypes and gene expression levels of cancer stem cell, epithelial-mesenchymal transition, differentiation and proliferation markers when cultured on 3DPS and PDS, contrasting conventional 2D cultures. Importantly, cells cultured on 3DPS and PDS showed scaffold-specific responses to cytotoxic drugs (doxorubicin and 5-fluorouracil) that were different from 2D cultured cells. In conclusion, the data presented support the use of a tunable alginate-based 3DPS as a tumor model in breast cancer drug discovery. © 2021 The Author(s). Published by IOP Publishing Ltd.
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| 6. |
- Svanström, Andreas, et al.
(författare)
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The Effect of Hypoxic and Normoxic Culturing Conditions in Different Breast Cancer 3D Model Systems
- 2021
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Ingår i: Frontiers in Bioengineering and Biotechnology. - : Frontiers Media S.A.. - 2296-4185. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The field of 3D cell cultures is currently emerging, and material development is essential in striving toward mimicking the microenvironment of a native tissue. By using the response of reporter cells to a 3D environment, a comparison between materials can be assessed, allowing optimization of material composition and microenvironment. Of particular interest, the response can be different in a normoxic and hypoxic culturing conditions, which in turn may alter the conclusion regarding a successful recreation of the microenvironment. This study aimed at determining the role of such environments to the conclusion of a better resembling cell culture model to native tissue. Here, the breast cancer cell line MCF7 was cultured in normoxic and hypoxic conditions on patient-derived scaffolds and compared at mRNA and protein levels to cells cultured on 3D printed scaffolds, Matrigel, and conventional 2D plastics. Specifically, a wide range of mRNA targets (40), identified as being regulated upon hypoxia and traditional markers for cell traits (cancer stem cells, epithelial–mesenchymal transition, pluripotency, proliferation, and differentiation), were used together with a selection of corresponding protein targets. 3D cultured cells were vastly different to 2D cultured cells in gene expression and protein levels on the majority of the selected targets in both normoxic and hypoxic culturing conditions. By comparing Matrigel and 3DPS-cultured cells to cells cultured on patient-derived scffolds, differences were also noted along all categories of mRNA targets while specifically for the GLUT3 protein. Overall, cells cultured on patient-derived scaffolds closely resembled cells cultured on 3D printed scaffolds, contrasting 2D and Matrigel-cultured cells, regardless of a normoxic or hypoxic culturing condition. Thus, these data support the use of either a normoxic or hypoxic culturing condition in assays using native tissues as a blueprint to optimize material composition. Copyright © 2021 Svanström, Rosendahl, Salerno, Jonasson, Håkansson, Ståhlberg and Landberg.
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