| 1. |
- Anderberg, Charlotte
(författare)
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Small talk in the tumor microenvironment : the contribution of fibroblasts and endothelial cells to the malignant phenotype
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cancer is the result of aberrant cells developing into tumor cells that act in concert with the micro- and macroenvironment like any other organ in our bodies. The cells and molecules of the tumor microenvironment are important contributors to the tumorigenic process. However, we are still far from understanding the full complexity and intricate molecular interactions that affect the process. We show that platelet-derived growth factor (PDGF)-CC, expressed by tumor cells, recruit cancer-associated fibroblasts (CAFs) to the tumor microenvironment resulting in an accelerated tumor growth rate. Among the CAFs, we identify three different subclasses by their variable expression of fibroblast specific protein (FSP)-1 and PDGF receptor (PDGFR)-α. Two of these subclasses express osteopontin (OPN), which is responsible for the increased tumor growth rate. In subsequent studies, we reveal that PDGF-CC expression is high in breast cancer and that PDGF-CC presence in epithelial cells is an independent prognostic marker for patient survival in a large cohort of patients. We also developed a monoclonal antibody for PDGF-CC, which as a monotherapy reduces tumor growth rate proving the in vivo efficacy of targeting PDGF-CC. Transforming growth factor (TGF)-β family members have been attributed complex and contradictory effects on angiogenesis. We have studied the effect of ablation of endoglin or activin receptor-like kinase 1 (ALK1) in tumor models. Targeting endoglin results in adaptation and no effect on tumor growth or vessel density. We do however detect increased metastatic seeding as a consequence of endothelial to mesenchymal transition (EndMT). Endoglin deficiency prolongs the tumor sensitivity to antiangiogenic therapy that otherwise induce resistance. However, pharmacological and genetic targeting of ALK1 results in reduction of tumor formation and burden due to decrease in the vessel density. Molecular characterization reveals that the combination of TGF-β and bone morphogenic protein (BMP)-9 is responsible for inducing activation of endothelial cells and angiogenesis.
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| 2. |
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| 3. |
- Billgren, Charlotte, 1979-
(författare)
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Making Sense of Environmental Values : Wetlands in Kenya
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- En av de viktigaste frågorna i världen idag är naturresurshantering. Med en väx-ande befolkning och hoten från klimatförändringar kommer förvaltningen av jordens naturresurser bli än viktigare, såväl för dagens generation som kommande generationer. En viktig aspekt när det gäller naturresurshantering är hur människor uppfattar och värderar naturen. För att komma närmare dessa miljövärden har ett flertal olika vetenskapliga tillvägagångssätt föreslagits. Den här avhandlingen undersöker hur det är möjligt att närma sig miljövärden under olika omständighe-ter och utifrån olika behov. Detta görs genom att undersöka hur olika teorier har använts, och kan användas, avseende olika våtmarker i Kenya. I utvecklingslän-der har naturresurser, teoretiskt sett, ett högre värde eftersom fattiga människor till en högre grad är direkt beroende av naturresurser och ekosystemtjänster. Ut-gångspunkten i denna avhandling är sex våtmarksområden i Kenya under olika förvaltning och med ett flertal, både aktuella och potentiella, användare. I av-handlingen undersöks hur lokalsamhället, myndigheter, industrier och turister uppfattar och värderar våtmarkerna. Genom att applicera ett arenaperspektiv, som betonar vikten av tvärvetenskap, diskuteras i avhandlingen det ekonomiska värdet av miljön för att sedan applicera andra metoder såsom emergy analys, stakeholder analys, kulturteori och riskanalys för att bredda och berika värderingen av miljön.
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| 4. |
- Chivukula, Indira V, et al.
(författare)
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Decoding breast cancer tissue-stroma interactions using species-specific sequencing.
- 2015
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Decoding transcriptional effects of experimental tissue-tissue or cell-cell interactions is important; for example, to better understand tumor-stroma interactions after transplantation of human cells into mouse (xenografting). Transcriptome analysis of intermixed human and mouse cells has, however, frequently relied on the need to separate the two cell populations prior to transcriptome analysis, which introduces confounding effects on gene expression.
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| 5. |
- Cunha, Sara I, et al.
(författare)
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Genetic and pharmacological targeting of activin receptor-like kinase 1 impairs tumor growth and angiogenesis
- 2010
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Ingår i: Journal of Experimental Medicine. - : The Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 207:1, s. 85-100
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Tidskriftsartikel (refereegranskat)abstract
- Members of the transforming growth factor beta (TGF-beta) family have been genetically linked to vascular formation during embryogenesis. However, contradictory studies about the role of TGF-beta and other family members with reported vascular functions, such as bone morphogenetic protein (BMP) 9, in physiological and pathological angiogenesis make the need for mechanistic studies apparent. We demonstrate, by genetic and pharmacological means, that the TGF-beta and BMP9 receptor activin receptor-like kinase (ALK) 1 represents a new therapeutic target for tumor angiogenesis. Diminution of ALK1 gene dosage or systemic treatment with the ALK1-F(c) fusion protein RAP-041 retarded tumor growth and progression by inhibition of angiogenesis in a transgenic mouse model of multistep tumorigenesis. Furthermore, RAP-041 significantly impaired the in vitro and in vivo angiogenic response toward vascular endothelial growth factor A and basic fibroblast growth factor. In seeking the mechanism for the observed effects, we uncovered an unexpected signaling synergy between TGF-beta and BMP9, through which the combined action of the two factors augmented the endothelial cell response to angiogenic stimuli. We delineate a decisive role for signaling by TGF-beta family members in tumor angiogenesis and offer mechanistic insight for the forthcoming clinical development of drugs blocking ALK1 in oncology.
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| 6. |
- Jönsson, Bodil, et al.
(författare)
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Situated research and design for everyday life
- 2004
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This paper elaborates theoretical and methodological aspects of design processes in a disability context and aims to relate them to other sciences. It particularly emphasizes situated aspects of research: the need for being there, with the users in their
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| 7. |
- Jönsson, Bodil, et al.
(författare)
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Situated research and design for everyday life
- 2005
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Ingår i: Proceedings of Nordes, Nordic Design Research.
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Konferensbidrag (refereegranskat)abstract
- This paper presents examples of different aspects of design in a disability context with the aim of revealing some of its fundamentals. It particularly emphasizes situated aspects of research: the need for being there, with the users in their daily lives – where the action is.
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| 8. |
- Romare, Charlotte, et al.
(författare)
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Burden of care related to monitoring patient vital signs during intensive care; a descriptive retrospective database study
- 2022
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Ingår i: Intensive & Critical Care Nursing. - : Elsevier. - 0964-3397 .- 1532-4036. ; 71
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to describe burden of care related to monitoring patient vital signs of intensive care unit patients in a Swedish hospital. Setting: Data collected by “The Swedish Intensive Care Registry” from one general category II intensive care unit in a Swedish hospital was included in this study. Data from year 2014 to 2020 was analysed comprising a total of 3617 intensive care episodes and 29,165 work shifts. Research methodology: This is a retrospective database study. Descriptive statistics gave an overview of the dataset. To test for differences between variables related to burden of care for “Documentation of monitoring” Mann Whitney U test and Kruskal Wallis test was performed using STATA. Results: “Documentation of monitoring” was reported to generate a prominent burden of care during intensive care. Nearly all patients had continuous monitoring. Comparison for burden of care related to “Documentation of monitoring” for sexes generated no statistically significant difference. Comparison for burden of care related to “Documentation of monitoring” among age groups, diagnose groups and time of day generated statistically significant differences. Conclusion: Monitoring patient vital signs was clearly present during intensive care, hence impacting intensive care nurses’ clinical practice. Further research is endorsed to improve and facilitate monitoring to keep improving patient safety.
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| 9. |
- Romare, Charlotte, 1979-, et al.
(författare)
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Nurse anesthetists’ experiences using smart glasses to monitor patients’ vital signs during anesthesia care : A qualitative study
- 2021
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 16:4 April
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To describe nurse anesthetists’ experiences using smart glasses to monitor patients’ vital signs during anesthesia care. Methods Data was collected through individual semi-structured interviews with seven nurse anesthetists who had used smart glasses, with a customized application for monitoring vital signs, during clinical anesthesia care. Data was analyzed using thematic content analysis. Results An overarching theme became evident during analysis; Facing and embracing responsibility. Being a nurse anesthetist entails a great responsibility, and the participants demonstrated that they shouldered this responsibility with pride. The theme was divided in two sub-themes. The first of these, A new way of working, comprised the categories Adoption and Utility. This involved incorporating smart glasses into existing routines in order to provide safe anesthesia care. The second sub-theme, Encountering side effects, consisted of the categories Obstacles and Personal affect. This sub-theme concerned the possibility to use smart glasses as intended, as well as the affect on nurse anesthetists as users. Conclusion Smart glasses improved access to vital signs and enabled continuous monitoring regardless of location. Continued development and improvement, both in terms of the application software and the hardware, are necessary for smart glasses to meet nurse anesthetists’ needs in clinical practice. Copyright:
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| 10. |
- Roswall, Pernilla, et al.
(författare)
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Microenvironmental control of breast cancer subtype elicited through paracrine platelet-derived growth factor-CC signaling
- 2018
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 24, s. 463-473
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Tidskriftsartikel (refereegranskat)abstract
- Breast tumors of the basal-like, hormone receptor-negative subtype remain an unmet clinical challenge, as there is high rate of recurrence and poor survival in patients following treatment. Coevolution of the malignant mammary epithelium and its underlying stroma instigates cancer-associated fibroblasts (CAFs) to support most, if not all, hallmarks of cancer progression. Here we delineate a previously unappreciated role for CAFs as determinants of the molecular subtype of breast cancer. We identified paracrine crosstalk between cancer cells expressing platelet-derived growth factor (PDGF)-CC and CAFs expressing the cognate receptors in human basal-like mammary carcinomas. Genetic or pharmacological intervention of PDGF-CC activity in mouse models of cancer resulted in conversion of basal-like breast cancers into a hormone receptor-positive state that enhanced sensitivity to endocrine therapy in previously resistant tumors. We conclude that specification of breast cancer to the basal-like subtype is under microenvironmental control and is therapeutically actionable.
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