| 1. |
- Augsten, Martin, et al.
(författare)
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CXCL14 is an autocrine growth factor for fibroblasts and acts as a multi-modal stimulator of prostate tumor growth
- 2009
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 106:9, s. 3414-3419
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Tidskriftsartikel (refereegranskat)abstract
- This study explored the role of secreted fibroblast-derived factors in prostate cancer growth. Analyses of matched normal and tumor tissue revealed up-regulation of CXCL14 in cancer-associated fibroblasts of a majority of prostate cancer. Fibroblasts over-expressing CXCL14 promoted the growth of prostate cancer xenografts, and increased tumor angiogenesis and macrophage infiltration. Mechanistic studies demonstrated that autocrine CXCL14-stimulation of fibroblasts stimulate migration and ERK-dependent proliferation of fibroblasts. CXCL14-stimulation of monocyte migration was also demonstrated. Furthermore, CXCL14-producing fibroblasts, but not recombinant CXCL14, enhanced in vitro proliferation and migration of prostate cancer cells and in vivo angiogenesis. These studies thus identify CXCL14 as a novel autocrine stimulator of fibroblast growth and migration, with multi-modal tumor-stimulatory activities. In more general terms, our findings suggest autocrine stimulation of fibroblasts as a previously unrecognized mechanism for chemokine-mediated stimulation of tumor growth, and suggest a novel mechanism whereby cancer-associated fibroblasts achieve their pro-tumorigenic phenotype.
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| 2. |
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| 3. |
- Hedefalk, Maria
(författare)
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Förskola för hållbar utveckling : Förutsättningar för barns utveckling av handlingskompetens för hållbar utveckling
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of the thesis is to contribute with knowledge about the conditions for preschool children’s meaning making with regard to sustainable development. With a focus on critical actions, the thesis explores how education is executed and how a critical action may be conducted in a preschool practice.Different teaching situations in preschool have been analysed in order to determine how and which actions are privileged in the various situations, what the consequences of these actions are, and what kind of conditions that enable children to develop critical action competence.The results show that teachers affect children’s meaning making by directing actions toward a specific learning content. The conditions in which children learn action competences for sustainable development may be affected by which actions are privileged or excluded in the situation. The analyses of conditions for children to act critically in this thesis are when:the teacher aims the attention towards a pluralistic teaching content, where the content consists of value judgments.variations of views are highlighted – by the help of other children or from example different viewpoints in a book.children have the courage or/and feel safe expressing contradicting views.Although the situations in which children act critically are few and far between in the empirical material, they do exist and are important to highlight, especially as few other studies explore what meaning making processes look like when critical actions are privileged. The thesis therefore contributes to the research by providing analyses of situations in which children act critically in preschool.
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| 4. |
- Hesson, Jenny Christina, et al.
(författare)
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Temporal Variation in Sindbis Virus Antibody Prevalence in Bird Hosts in an Endemic Area in Sweden
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- Sindbis virus (SINV) is a mosquito-borne bird virus that occasionally causes human disease in Fennoscandia, suggested to have cyclic 7-year intervals between outbreaks. Reliable data on human infections in Sweden is however lacking. Here we investigated the SINV antibody prevalence among birds in a Swedish area endemic to SINV to scrutinize if a cyclic variation in antibody prevalence is present in the natural host of SINV. Serum from birds were sampled in the summers of 2002-2004 and 2009 in the floodplains of the River Dalalven in central Sweden, with 2002 and 2009 representing hypothesized years of SINV outbreaks. A total of 963 birds from 52 species (mainly passerines) were tested for the presence of SINV antibodies using a plaque reduction neutralization test. The highest SINV antibody prevalence was found in Turdidae species, specifically Fieldfare, Redwing and Song thrush in which more than 70% of sampled individuals had antibodies to SINV in 2009. The SINV antibody prevalence significantly varied between years with 2% in 2002, 8% in 2003, 14% in 2004 and 37% in 2009. Antibodies were found equally often in hatchlings and in adults and increased from early to late in the season. Clearly, the SINV antibody prevalence was not elevated in the bird hosts in the predicted outbreak year 2002, thus solid evidence of a cyclic occurrence of SINV in Sweden is still lacking.
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| 5. |
- Häggarth, Lars, et al.
(författare)
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Diagnostic biomarkers of prostate cancer
- 2011
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 45:1, s. 60-67
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Diagnostic tissue biomarkers for prostate cancer (PC) include basal cell markers and alpha-methylacyl-coenzyme A-racemase (AMACR), often used in combination. Their sensitivity and specificity are not perfect and there is a need for additional diagnostic biomarkers for PC in cases that are difficult to diagnose on routine stained sections. Material and methods. This study investigated the diagnostic accuracy of three novel tissue biomarkers for PC found through a search in the Human Protein Atlas database (www.proteinatlas.com): somatic cytochrome c (CYCS), intestinal cell kinase (ICK) and inhibitor of nuclear factor-kappa B kinase subunit beta (IKBKB), and compared the results with AMACR. A tissue microarray was constructed from 40 consecutive radical prostatectomy (RP) specimens including benign prostatic tissue, atrophy, high-grade prostatic intraepithelial neoplasia (HGPIN) and PC. Immunoreactivity was scored based on staining intensity and extent. Real-time polymerase chain reaction (PCR) was performed on malignant and benign frozen tissue samples from 32 RP specimens. Results. All four biomarkers showed a stronger expression in PC and HGPIN than in benign tissue (p < 0.001). The highest diagnostic accuracy for PC was achieved with ICK and AMACR at 97%. The area under the curve for CYCS, ICK, IKBKB and AMACR was 0.859, 0.997, 0.865 and 0.983, respectively. The presence of mRNA transcripts of the genes was confirmed by real-time PCR in benign and malignant prostatic tissue. Conclusions. AMACR is an accurate diagnostic tissue marker for PC. However, in some PCs AMACR is false negative and a panel of CYCS, ICK and IKBKB may serve as ancillary diagnostic tool.
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| 6. |
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| 7. |
- Micke, Patrick, et al.
(författare)
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In situ identification of genes regulated specifically in fibroblasts of human basal cell carcinoma.
- 2007
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Ingår i: The Journal of investigative dermatology. - : Elsevier BV. - 1523-1747 .- 0022-202X. ; 127:6, s. 1516-23
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Tidskriftsartikel (refereegranskat)abstract
- Basal cell carcinoma (BCC) is characterized by slow growth, virtual absence of metastases, and strong stroma-dependency. Cancer-associated fibroblasts (CAFs) in the tumor stroma influence tumor growth, invasion, and metastasis. To comprehensively characterize CAFs of BCC in their in situ cancer environment, laser capture microdissection, linear gene amplification, microarray analysis, and quantitative real-time PCR (qRT-PCR) were combined. Pair-wise comparison of gene expression of microdissected CAFs and corresponding normal perifollicular fibroblasts identified 65 genes that were significantly upregulated in at least two of three different patients. Among the annotated genes, as many as 13 genes encoded secreted proteins, of which six were previously implicated as CAF-associated proteins in various tumor types. Four of the seven novel CAF genes--matrix Gla-protein, secreted frizzled-related protein 2, angiopoietin-related protein-2, and platelet-derived growth factor receptor-like protein--were selected for further analyses by qRT-PCR and were found to be frequently upregulated in CAFs of three independent BCC tissues. Analyses of CAFs from squamous cell cancer, prostate cancer, and colon cancer did not indicate that these genes were upregulated in these cancers. This study thus validates a novel approach for comprehensive characterization CAFs in their in situ environment of BCC. The results suggest a specific expression profile of CAFs in BCC possibly accounting for disease-specific pathological roles.
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| 8. |
- Moro, Carlos Fernandez, et al.
(författare)
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An idiosyncratic zonated stroma encapsulates desmoplastic liver metastases and originates from injured liver
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- A perimetastatic capsule is a strong positive prognostic factor in liver metastases, but its origin remains unclear. Here, we systematically quantify the capsule's extent and cellular composition in 263 patients with colorectal cancer liver metastases to investigate its clinical significance and origin. We show that survival improves proportionally with increasing encapsulation and decreasing tumor-hepatocyte contact. Immunostaining reveals the gradual zonation of the capsule, transitioning from benign-like NGFR(high) stroma at the liver edge to FAP(high) stroma towards the tumor. Encapsulation correlates with decreased tumor viability and preoperative chemotherapy. In mice, chemotherapy and tumor cell ablation induce capsule formation. Our results suggest that encapsulation develops where tumor invasion into the liver plates stalls, representing a reparative process rather than tumor-induced desmoplasia. We propose a model of metastases growth, where the efficient tumor colonization of the liver parenchyma and a reparative liver injury reaction are opposing determinants of metastasis aggressiveness.
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| 9. |
- Wahlström, Jens, et al.
(författare)
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The effect of flooring on musculoskeletal symptoms in the lower extremities and low back among female nursing assistants
- 2012
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Ingår i: Ergonomics. - London : Taylor & Francis. - 0014-0139 .- 1366-5847. ; 55:2, s. 248-255
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Tidskriftsartikel (refereegranskat)abstract
- This study examines the effect of changing the floor from a 2-mm homogenous vinyl floor to a 4-mm heterogeneous vinyl floor (1.5-mm wear layer and 2.5-mm foam layer) on musculoskeletal symptoms in the lower extremities and low back among nursing assistants in a geriatric care centre. A pre-post design with a reference group consisting of nursing assistants from a similar geriatric care centre was used. Follow-up measurements were carried out 12 and 24 months after the intervention by means of questionnaires. At the 1-year follow-up, the pain intensity score in the feet of the intervention group had decreased compared with the baseline value and remained statistically significant at the 2-year follow-up. The decrease in pain intensity score of the feet in the intervention group was statistically significantly different from the reference group, both after 1 and 2 years. Statement of Relevance: The results show the importance of flooring in the workplace with regard to reducing musculoskeletal symptoms. Appropriate flooring is especially important in the female-dominated health care sector, where workers must stand or walk for long periods.
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| 10. |
- Österlund, Barbro, et al.
(författare)
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Impaired myocardial t-PA release in patients with coronary artery disease
- 2008
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Ingår i: Acta Anaesthesiol Scand. - : Wiley. - 1399-6576. ; 52:10, s. 1375-84
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Myocardial ischemia remains a significant perioperative complication in coronary artery disease (CAD) patients. We hypothesized that noxious stimuli during major surgery are associated with an acute release of tissue-type plasminogen activator (t-PA) into the coronary circulation, and that this response is reduced by CAD. METHODS AND RESULTS: Two patient groups, with (n=14) and without (n=8) CAD, were studied during the initial phase of heart surgery. After retrograde great cardiac vein catheterizations during closed-chest conditions, coronary arterial-venous concentration gradients of t-PA and plasminogen activator inhibitor type-1 (PAI-1) were measured together with coronary blood flow measurements, allowing derivation of coronary net release rates. Pre-surgery atrial pacing, performed to evaluate the influence of increases in heart rate (+ 40 beats/min) and coronary blood flow (+ 80 ml/min), did not significantly alter coronary net release of t-PA or PAI-1 in either patient group. Sternotomy induced a prominent increase in coronary net release of both total and active t-PA in the non-CAD group. This response was considerably reduced in the CAD group. CONCLUSIONS: This study provides the first analysis of coronary t-PA release during major surgery and demonstrates a deficient local endothelial t-PA release in patients with CAD. This suggests a reduced local fibrinolytic capacity in CAD patients, which may explain the increased risk for coronary thrombosis in this patient group.
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