| 1. |
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| 2. |
- Ansari, Daniel, et al.
(författare)
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Pancreatic cancer : Yesterday, today and tomorrow
- 2016
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Ingår i: Future Oncology. - : Future Medicine Ltd. - 1479-6694 .- 1744-8301. ; 12:16, s. 1929-1946
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic cancer is one of our most lethal malignancies. Despite substantial improvements in the survival rates for other major cancer forms, pancreatic cancer survival rates have remained relatively unchanged since the 1960s. Pancreatic cancer is usually detected at an advanced stage and most treatment regimens are ineffective, contributing to the poor overall prognosis. Herein, we review the current understanding of pancreatic cancer, focusing on central aspects of disease management from radiology, surgery and pathology to oncology.
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| 3. |
- Ansari, Daniel, et al.
(författare)
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Protein deep sequencing applied to biobank samples from patients with pancreatic cancer.
- 2015
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Ingår i: Journal of Cancer Research and Clinical Oncology. - : Springer Science and Business Media LLC. - 1432-1335 .- 0171-5216. ; 141:2, s. 369-380
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic cancer is commonly detected at advanced stages when the tumor is no longer amenable to surgical resection. Therefore, finding biomarkers for early stage disease is urgent. Here, we show that high-definition mass spectrometry (HDMS(E)) can be used to identify serum protein alterations associated with early stage pancreatic cancer.
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| 4. |
- Aronsson, Linus, et al.
(författare)
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High-density and targeted glycoproteomic profiling of serum proteins in pancreatic cancer and intraductal papillary mucinous neoplasm
- 2018
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 53:12, s. 1597-1603
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Glycoproteomics is an emerging subfield of proteomics. Tumor-specific variations in protein glycosylation might be potential targets for the development of new cancer diagnostics. Here, we performed high-throughput screening and targeted verification of glycome alterations in serum samples from patients with pancreatic cancer and the precancerous lesion intraductal papillary mucinous neoplasm (IPMN). Material and methods: The glycosylation profile of 1000 proteins was mapped in a discovery cohort comprising serum samples from 16 individuals, including 8 patients with pancreatic cancer and 8 healthy controls. The top 10 glycoprotein biomarker candidates with the highest signal intensity difference in glycosylation levels were evaluated in a cohort consisting of 109 serum samples, including 49 patients with resectable pancreatic cancer, 13 patients with resectable noninvasive IPMN and 47 healthy controls, using a targeted assay. Results: Multivariable analysis defined sets of panels comprising CA19-9 and distinctively glycosylated proteins for discrimination between pancreatic cancer, IPMN and healthy controls. A panel including CA 19-9, IL.17E, B7.1 and DR6 gave an AUC of 0.988 at 100% sensitivity at 90% specificity for the discrimination of stage 1 pancreatic cancer and healthy controls. B7.1 was found to be a valuable biomarker for differentiating between IPMN and healthy controls, with better performance alone than CA 19-9. Conclusions: Measurement of protein glycosylation profiles in serum may aid in the early detection of pancreatic cancer and precursor lesions.
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| 5. |
- Bauden, Monika, et al.
(författare)
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Circulating nucleosomes as epigenetic biomarkers in pancreatic cancer.
- 2015
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Ingår i: Clinical Epigenetics. - : Springer Science and Business Media LLC. - 1868-7075 .- 1868-7083. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- To improve the prognosis of patients with pancreatic cancer, new biomarkers are required for earlier, pre-symptomatic diagnosis. Epigenetic mutations take place at the earliest stages of tumorigenesis and therefore offer new approaches for detecting and diagnosing disease. Nucleosomes are the repeating subunits of DNA and histone proteins that constitute human chromatin. Because of their release into the circulation, intact nucleosome levels in serum or plasma can serve as diagnostic disease biomarkers, and elevated levels have been reported in various cancers. However, quantifying nucleosomes in the circulation for cancer detection has been challenging due to nonspecific elevation in sera of patients with benign diseases. Here, we report for the first time differential, disease-associated epigenetic profiles of intact cell-free nucleosomes (cfnucleosomes) containing specific DNA and histone modifications as well as histone variants circulating in the blood. The study comprised serum samples from 59 individuals, including 25 patients with resectable pancreatic cancer, 10 patients with benign pancreatic disease, and 24 healthy individuals using Nucleosomics(®), a novel ELISA method.
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| 6. |
- Bauden, Monika, et al.
(författare)
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Histone profiling reveals the H1.3 histone variant as a prognostic biomarker for pancreatic ductal adenocarcinoma
- 2017
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epigenetic alterations have been recognized as important contributors to the pathogenesis of PDAC. However, the role of histone variants in pancreatic tumor progression is still not completely understood. The aim of this study was to explore the expression and prognostic significance of histone protein variants in PDAC patients. Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed for qualitative analysis of histone variants and histone related post-translational modifications (PTMs) in PDAC and normal pancreatic tissues. Survival analysis was conducted using the Kaplan-Meier method and Cox proportional hazards regression. Results: Histone variant H1.3 was found to be differentially expressed (p = 0.005) and was selected as a PDAC specific histone variant candidate. The prognostic role of H1.3 was evaluated in an external cohort of patients with resected PDAC using immunohistochemistry. Intratumor expression of H1.3 was found to be an important risk factor for overall survival in PDAC, with an adjusted HR value of 2.6 (95% CI 1.1-6.1), p = 0.029. Conclusion: We suggest that the intratumor histone H1.3 expression as reported herein, may serve as a new epigenetic biomarker for PDAC.
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| 7. |
- Hagey, Daniel W., et al.
(författare)
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Distinct transcription factor complexes act on a permissive chromatin landscape to establish regionalized gene expression in CNS stem cells
- 2016
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 26:7, s. 908-917
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Tidskriftsartikel (refereegranskat)abstract
- Spatially distinct gene expression profiles in neural stem cells (NSCs) are a prerequisite to the formation of neuronal diversity, but how these arise from the regulatory interactions between chromatin accessibility and transcription factor activity has remained unclear. Here, we demonstrate that, despite their distinct gene expression profiles, NSCs of the mouse cortex and spinal cord share the majority of their DNase I hypersensitive sites (DHSs). Regardless of this similarity, domain-specific gene expression is highly correlated with the relative accessibility of associated DHSs, as determined by sequence read density. Notably, the binding pattern of the general NSC transcription factor SOX2 is also largely cell type specific and coincides with an enrichment of LHX2 motifs in the cortex and HOXA9 motifs in the spinal cord. Interestingly, in a zebrafish reporter gene system, these motifs were critical determinants of patterned gene expression along the rostral-caudal axis. Our findings establish a predictive model for patterned NSC gene expression, whereby domain-specific expression of LHX2 and HOX proteins act on their target motifs within commonly accessible cis-regulatory regions to specify SOX2 binding. In turn, this binding correlates strongly with these DHSs relative accessibility-a robust predictor of neighboring gene expression.
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| 8. |
- Pielberg, Gerli Rosengren, et al.
(författare)
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A cis-acting regulatory mutation causes premature hair graying and susceptibility to melanoma in the horse
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 40:8, s. 1004-1009
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Tidskriftsartikel (refereegranskat)abstract
- In horses, graying with age is an autosomal dominant trait associated with a high incidence of melanoma and vitiligo-like depigmentation. Here we show that the Gray phenotype is caused by a 4.6-kb duplication in intron 6 of STX17 (syntaxin-17) that constitutes a cis-acting regulatory mutation. Both STX17 and the neighboring NR4A3 gene are overexpressed in melanomas from Gray horses. Gray horses carrying a loss-of-function mutation in ASIP (agouti signaling protein) had a higher incidence of melanoma, implying that increased melanocortin-1 receptor signaling promotes melanoma development in Gray horses. The Gray horse provides a notable example of how humans have cherry-picked mutations with favorable phenotypic effects in domestic animals.
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| 9. |
- Seltenhammer, Monika H., et al.
(författare)
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Establishment and characterization of a primary and a metastatic melanoma cell line from Grey horses
- 2014
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Ingår i: In vitro Cellular & Developmental Biology-Animal. - : Springer Science and Business Media LLC. - 1071-2690 .- 1543-706X. ; 50:1, s. 56-65
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Tidskriftsartikel (refereegranskat)abstract
- The Grey horse phenotype, caused by a 4.6 kb duplication in Syntaxin 17, is strongly associated with high incidence of melanoma. In contrast to most human melanomas with an early onset of metastasis, the Grey horse melanomas have an extended period of benign growth, after which 50% or more eventually undergo progression and may metastasize. In efforts to define changes occurring during Grey horse melanoma progression, we established an in vitro model comprised of two cell lines, HoMel-L1 and HoMel-A1, representing a primary and a metastatic stage of the melanoma, respectively. The cell lines were examined for their growth and morphological characteristics, in vitro and in vivo oncogenic potential, chromosome numbers, and expression of melanocytic antigens and tumor suppressors. Both cell lines exhibited malignant characteristics; however, the metastatic HoMel-A1 showed a more aggressive phenotype characterized by higher proliferation rates, invasiveness, and a stronger tumorigenic potential both in vitro and in vivo. HoMel-A1 displayed a near-haploid karyotype, whereas HoMel-L1 was near-diploid. The cell lines expressed melanocytic lineage markers such as TYR, TRP1, MITF, PMEL, ASIP, MC1R, POMC, and KIT. The tumor suppressor p53 was strongly expressed in both cell lines, while the tumor suppressors p16 and PTEN were absent in HoMel-A1, potentially implicating significance of these pathways in the melanoma progression. This in vitro model system will not only aid in understanding of the Grey horse melanoma pathogenesis, but also in unraveling the steps during melanoma progression in general as well as being an invaluable tool for development of new therapeutic strategies.
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| 10. |
- Akbarshahi, Hamid, et al.
(författare)
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Enrichment of Murine CD68(+)CCR2(+) and CD68(+)CD206(+) Lung Macrophages in Acute Pancreatitis-Associated Acute Lung Injury.
- 2012
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:10
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Tidskriftsartikel (refereegranskat)abstract
- Acute lung injury (ALI) is an important cause of mortality in critically ill patients. Acute pancreatitis (AP) is one of the risk factors for developing this syndrome. Among the inflammatory cells, macrophages have a key role in determining the severity of the acute lung injury. In the lungs, macrophages constitute a heterogeneous cell population distributed in different compartments. Changes in not only the macrophage count, but also in their phenotype have been seen during the course of lung injury. A murine ductal ligation model of acute pancreatitis showed substantial morphological changes in the pancreas and lungs. Immunohistochemistry showed neutrophil recruitment into both organs after 9 hours and later on. F4/80(+) cells in the pancreas increased in the ligated animals, though there was not a significant difference in their number in the lungs as compared to sham operated animals. Flow cytometry analysis of lung macrophages demonstrated an enrichment of F4/80(-) CD68(+)CCR2(+) and F4/80(-) CD68(+)CD206(+) lung macrophages in ligated animals (AP) as compared to the sham operated group. The level of interleukin-6 in plasma increased 3 hours after ligation compared to the sham operated group, as a first indicator of a systemic inflammatory response.This study suggests a role for F4/80(-) CD68(+) macrophages in the pathogenesis of acute lung injury in acute pancreatitis. Studying lung macrophages for different phenotypic markers, their polarization, activation and recruitment, in the context of acute lung injury, is a novel area to potentially identify interventions which may improve the outcome of acute lung injury.
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| 11. |
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| 12. |
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| 13. |
- Andersson, Lars Gustaf, et al.
(författare)
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Efterord
- 2022
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Ingår i: Donaudikter. - 9789198706949 ; , s. 19-22
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Bokkapitel (populärvet., debatt m.m.)
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| 14. |
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| 15. |
- Andersson, Marie, 1977, et al.
(författare)
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Normalized Urinary Flow at Puberty after Tubularized Incised Plate Urethroplasty of Hypospadias in Childhood.
- 2015
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Ingår i: The Journal of urology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3792 .- 0022-5347. ; 194:5, s. 1407-1413
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Tidskriftsartikel (refereegranskat)abstract
- An obstructive urinary flow pattern is frequently seen after tubularized incised plate urethroplasty for hypospadias. However, the significance of this finding has not been determined and long-term results are few. We describe postoperative long-term uroflowmetry results after puberty in males who underwent tubularized incised plate urethroplasty in childhood.
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| 16. |
- Andersson, Monika
(författare)
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Thyroid hormones and their receptors in transcriptional regulation
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The thyroid hormone receptors (TRs) are encoded by two genes, alpha and ß, and belong to a family of hormone activated nuclear receptors. This family includes the receptors for retinoids and vitamin D3 as well as the receptors for steroid hormones. Transcriptional control by hormone is mediated through receptor binding to target gene DNA and subsequent control of gene regulation. Here we have studied several aspects of gene regulation controlled by TR and its oncogenic counterpart P75gag-v-erbA, to gain insights into the specificity in DNA-binding and into which domains of the receptor are important for intracellular localization and control of erythroid differentiation. The specificity of binding of TR to DNA regulatory response elements (TREs) was tested with band shift analysis in the absence and presence of thyroid hormones. TR interacts as a monomer or homodimer to form complexes with direct repeat, palindromic and with everted repeat AGGTCA core motifs. The thyroid hormones T3 and T4, but not T2, disrupt homodimer- and increase monomer complexes bound to TREs. A TR conformational change induced by T3 is detected in TR monomers and in TR which forms a heterodimer with RXR. TR is unique within the superfamily of receptors by the ability to bind response elements with core motifs positioned in several different configurations. TR binding to direct repeat and palindromic TREs containing O to 6 nucleotides between the core motifs (spacer) was assayed in band shift analyses. High affinity binding and low off rate was observed for complexes containing TR on TREs with direct repeats separated by a spacer of 4 nucleotides and on a palindromic TRE without a spacer. The oncoprotein P75gag-v-erbA blocks TR-induced erythroid differentiation. A number of TR / P75gag-v-erbA chimeric proteins were tested for their effects of differentiation and it was shown that the DNA binding domain (DBD) of P75gag-v-erbA is essential for self-renewal and to keep cells undifferentiated. TR is localized to the nucleus both in the presence and absence of thyroid hormones. To define the regions important for nuclear localization we determined the intracellular localization of TR, P75gag-v-erbA and various N-terminal variants of TR by immunocytochemistry following transfection. The data show that the N-terminal first 12 amino acids of TR are essential for exclusive nuclear localization. P75gag-v-erbA represses TR/T3 activated transcription. To pinpoint which regions in P75gag-v-erbA that are responsible for this, we expressed P75gag-v-erbA and various TR / P75gag-v-erbA chimeric receptors in cells expressing high levels of endogenous TR. A chimeric receptor, containing the DBD and the N-terminus from TR and the ligand binding domain from P75gag-v-erbA, was able to repress a TRE not regulated by P75gag-v-erbA.
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| 17. |
- Andersson Odén, Tomas, 1952, et al.
(författare)
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Kriskommunikation 2.0. Allmänhet, medier och myndigheter i det digitala medielandskapet
- 2016
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Hur uppfattar allmänheten nyhetsmediernas rapportering och myndigheternas kriskommunikation? Och hur kriskommunicerar allmänheten själv i de sociala mediernas tidevarv? Det är frågor som ställt i denna bok, där kriskommunikationen i samband med fem dramatiska svenska händelser jämförs och analyseras, med medborgarnas kommunikationsbehov som utgångspunkt. Boken vänder sig till kommunikatörer i offentlig tjänst, till mediemedarbetare, samt till forskare och andra med intresse av kriskommunikation. Boken utgör slutrapport från projektet Kriskommunikation 2.0, som finansierats av Myndighten för samhällsskydd och beredskap (MSB)
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| 18. |
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| 19. |
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| 20. |
- Andersson, Torbjörn
(författare)
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Aesthetic Flexibility : Modularity of Visual Form in Product Portfolios and Branded Products
- 2016
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The increase in competition amongst companies that produce complex or large product portfolios has created a need to utilise modularity strategies not only to flexibly manage technical complexity in a costeffective manner but also for visual appearance. This research aims to understand how the visual appearance of products is affected by modular product development strategies. Specifically, the aim is to understand how such strategies induce constraints and generate possibilities for management of visual appearance in the design process.Five studies have been conducted during the course of this licentiate thesis. Two were conducted with professionals and students in design, while the remaining three are theoretical studies based on findings in the literature, theory building, and experimental research. The goal has been to investigate how designers work when they are put to the task of changing and developing the designs of complex products that are part of a portfolio. The challenge has been to study what suitable strategies exist that manage complex products and product brands, then investigate how these influence designers’ practices.The first study examined how coherence towards a product category influences the design of new products. The outcome of the study was a method to explore visual coherence and diversity in the appearance of a product category.The remaining four studies investigated how modularity, brand management and the redesign of product portfolios influence a design process. The second study described a design phenomenon known as aesthetic flexibility, which was further explored in studies three and five. The outcome from these studies was a proposal for four aesthetic flexibility strategies.The fourth study investigated in what way portfolio extension strategies found in brand management and design research are related, and how such strategies influence aesthetic flexibility. The results from study four were illustrated as a model.The main contribution of this work is the phenomenon of ‘aesthetic flexibility’, which helps understand the factors that influence designers when working with branded modular products. Understanding visual flexibility serves as a starting point in further investigations of how different development strategies affect the possibilities for visual product design.The findings of this work serve to illustrate and explain a complex and multi-facetted design phenomenon which many designers manage more or less intuitively today, thus advancing academics’, teachers’ and professional designers’ understanding of the field.
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| 21. |
- Andersson, Thomas, et al.
(författare)
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Effects of chewing gum against postoperative ileus after pancreaticoduodenectomy - a randomized controlled trial.
- 2015
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Ingår i: BMC research notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Postoperative ileus is common after surgery. One non-pharmacological intervention that has shown promising results in reducing the duration of postoperative ileus is chewing gum after surgery. However, this has not been investigated in upper gastrointestinal surgery such as pancreatic surgery. Hence the aim of this study was to investigate the effects of chewing gum treatment on patients undergoing pancreaticoduodenectomy ad modum whipple due to pancreatic or periampullary cancer.
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| 22. |
- Andersson, Thomas K., et al.
(författare)
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PACADI: translation and adaptation of a Swedish-language version of the pancreatic cancer disease impact score
- 2022
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Ingår i: Bmc Research Notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective The Norwegian pancreatic cancer disease impact score (PACADI) is a digitalized analogue questionnaire that assesses different disease-specific symptoms. There is a need of translations of it into other languages. Therefore, the aim of this article is to describe the translation process of a Swedish version of PACADI and present its validity to EORCT QLQ PAN26. The self-administered questionnaire PACADI was translated according to guidelines and assessed by an expert panel of health care personnel. The test of its validity was performed with the disease-specific questionnaire for EORCT QLQ PAN26. Both questionnaires were completed by 66 subjects with pancreatic cancer, either before, at discharge or three months after surgery. Result The results between the groups indicate that patients suffer from different symptoms at different times. The correlations between the different symptoms of the two questionnaires were fair to good. In conclusion, PACADI and QLQ PAN 26 have a good correlation and PACADI can be used in clinical practise.
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| 23. |
- Andersson, Ulrika, et al.
(författare)
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Introductory Chapter: Rape Narratives in Motion
- 2019
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Ingår i: Rape Narratives in Motion. - Cham : Springer International Publishing. - 9783030138516 - 9783030138523 ; , s. 1-16
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 24. |
- Andersson, Ulrika, et al.
(författare)
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Vulnerability, agency and the ambivalence of place in narratives of rape in three high-profile Swedish cases
- 2018
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Ingår i: NORA - Nordic Journal of Feminist and Gender Research. - : Informa UK Limited. - 0803-8740 .- 1502-394X. ; 26:3, s. 197-209
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Tidskriftsartikel (refereegranskat)abstract
- For decades, the media have frequently been instrumental in framing rape cases by linking the deed with the place. This study demonstrates that law courts are not innocent of such social framing; on the contrary, they are significant agents. We argue that courts, by shaping the plot in rape cases, participate in an ongoing cultural production of meaning, although in a more subtle and ambivalent way than the media. In a narrative analysis of three contemporary rape cases in Sweden, we bring together feminist research on place with the concepts of vulnerability and agency. We argue that place is framed as ambivalent in relation to vulnerability and agency and dependent on the positioning of the plaintiff and the defendant. In court narratives geographical places are made relevant, including the locations where the alleged rapes took place. Court narratives of rape include highly ambivalent connotations to place in relation to vulnerability and agency, distinguished by different narratives and outcomes in the various instances. The legal and social implications of our work should include an awareness of the relevance of place in relation to rape.
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| 25. |
- Ansari, Daniel, et al.
(författare)
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Analysis of MUC4 Expression in Human Pancreatic Cancer Xenografts in Immunodeficient Mice.
- 2014
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Ingår i: Anticancer research. - 1791-7530. ; 34:8, s. 3905-3910
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Tidskriftsartikel (refereegranskat)abstract
- Mucin 4 (MUC4) is a cell surface glycoprotein that is overexpressed in most pancreatic tumors. The aim of the present study was to characterize MUC4 expression in experimental pancreatic cancer in order to clarify the correlation between MUC4 and pancreatic cancer histology in vivo.
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| 26. |
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| 27. |
- Ansari, Daniel, et al.
(författare)
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Centrosomal Abnormalities in Pancreatic Cancer : Molecular Mechanisms and Clinical Implications
- 2018
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Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 38:3, s. 1241-1245
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Forskningsöversikt (refereegranskat)abstract
- The centrosome is the main microtubule-organizing center in human cells. It regulates normal cell-cycle progression and cell division. Aberrations in the number, structure and function of centrosomes have been found to drive genomic instability and tumorigenesis. Pancreatic cancer frequently displays centrosomal aberrations. Supernumerary and abnormal centrosomes are observed in the earliest stages of pancreatic tumor development, and the p53 pathway acts as an initial barrier to the proliferation of cells with extra centrosomes. In this review, we summarize recent advances in the understanding of centrosomal aberrations in pancreatic cancer, focusing on regulatory mechanisms and prospects for future anticancer treatment.
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| 28. |
- Ansari, Daniel, et al.
(författare)
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Comparison of MUC4 expression in primary pancreatic cancer and paired lymph node metastases.
- 2013
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 48:10, s. 1183-1187
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Objective. Mucin 4 (MUC4) is a transmembrane glycoprotein that is expressed in pancreatic ductal adenocarcinoma (PDAC), but not in normal pancreatic tissue. MUC4 has a proposed role in pancreatic tumor progression and metastasis. The purpose of this pilot study was to investigate MUC4 expression during PDAC metastasis by comparing the expression in the primary tumor and paired lymph node metastases from the same patient. Material and methods. Surgical specimens from 17 cases of primary PDAC and paired lymph node metastases were immunohistochemically analyzed for MUC4 expression. The modified histochemical score (H-score) was used for staining assessment. Results. Positive staining for MUC4 was detected in most primary and metastatic PDAC tumors (15/17 vs. 14/17). The concordance for MUC4 expression in primary tumors and corresponding lymph node metastases was 82%. In two cases, the primary tumor was MUC4-positive and the lymph node metastases were negative, while in one patient with a MUC4-negative primary tumor, the lymph node metastasis was positive. The distribution of H-score for expression of MUC4 significantly correlated (r = 0.615; p = 0.009) between primary tumors and paired metastatic lesions. Conclusions: MUC4 was observed in both primary and matched metastatic tumors with a high level of concordance, suggesting that MUC4 expression is retained following PDAC metastasis.
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| 29. |
- Ansari, Daniel, et al.
(författare)
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Pancreatic cancer : Disease dynamics, tumor biology and the role of the microenvironment
- 2018
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 9:5, s. 6644-6651
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Forskningsöversikt (refereegranskat)abstract
- Pancreatic cancer is known for its propensity to metastasize. Recent studies have challenged the commonly held belief that pancreatic cancer is a stepwise process, where tumor cells disseminate late in primary tumor development. Instead it has been suggested that pancreatic tumor cells may disseminate early and develop independently and in parallel to the primary tumor. Circulating tumor cells can be found in most patients with pancreatic cancer, even in those with localized stage. Also, recent phylogenetic analyses have revealed evidence for a branched evolution where metastatic lineages can develop early in tumor development. In this Review, we discuss current models of pancreatic cancer progression and the importance of the tumor microenvironment, in order to better understand the recalcitrant nature of this disease.
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| 30. |
- Ansari, Daniel, et al.
(författare)
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Pancreatic cancer stroma : controversies and current insights
- 2017
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 52:6-7, s. 641-646
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Forskningsöversikt (refereegranskat)abstract
- Pancreatic cancer is characterized by a dense stromal response. The stroma includes a heterogeneous mass of cells, including pancreatic stellate cells, fibroblasts, immune cells and nerve cells, as well as extracellular matrix proteins, cytokines and growth factors, which interact with the tumor cells. Previous research has indicated that stromal elements contribute to tumor growth and aggressiveness. However, recent studies suggest that some elements of the stroma may actually restrain the tumor. This review focuses on the complex interactions between the stromal microenvironment and tumor cells, discussing molecular mechanisms and potential future diagnostic and therapeutic approaches by targeting the stroma.
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| 31. |
- Ansari, Daniel, et al.
(författare)
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The hippo signaling pathway in pancreatic cancer
- 2019
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Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 39:7, s. 3317-3321
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Forskningsöversikt (refereegranskat)abstract
- Hippo signaling is a key regulator of organ size, tissue hemostasis and regeneration. Dysregulation of the Hippo pathway has been recognized in a variety of human cancers, including pancreatic cancer. YES-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are the two major downstream effectors of the Hippo pathway. YAP and TAZ have been found to promote pancreatic tumor development and progression, even in the absence of mutant Kirsten RAS (KRAS). Pancreatic cancer is associated with an abundant stromal reaction leading to tumor growth and immune escape. It has been found that YAP and TAZ modulate behavior of pancreatic stellate cells and recruitment of tumor-associated macrophages and myeloid-derived suppressor cells. Moreover, YAP and TAZ are associated with chemoresistance and poor prognosis in pancreatic cancer. This review dissects the role of Hippo signaling in pancreatic cancer, focusing on molecular mechanisms and prospects for future intervention.
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| 32. |
- Ansari, Daniel, et al.
(författare)
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The role of PEDF in pancreatic cancer
- 2019
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Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 39:7, s. 3311-3315
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Forskningsöversikt (refereegranskat)abstract
- Pigment epithelium-derived factor (PEDF) is an important antiangiogenic and antitumorigenic factor in a variety of cancer forms, including pancreatic cancer. PEDF is mainly secreted as a soluble monomeric glycoprotein. In human pancreatic cancer PEDF levels are decreased, both in the tissue and serum. The decrease is associated with increased tumor angiogenesis, fibrosis, inflammation, autophagy, occurrence of liver metastasis and worse prognosis. In murine models, loss of PEDF is sufficient to induce invasive carcinoma and this phenotype is associated with large lesions characterized by poor differentiation. Lentiviral gene transfer of PEDF has resulted in decreased microvessel density and has inhibited tumor growth. Herein we review the multifunctional role of PEDF in pancreatic cancer and its therapeutic potential.
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| 33. |
- Asteberg, Inger, et al.
(författare)
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A food-borne streptococcal sore throat outbreak in a small community.
- 2006
-
Ingår i: Scandinavian journal of infectious diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 38:11-12, s. 988-94
-
Tidskriftsartikel (refereegranskat)abstract
- Beta-haemolytic group A streptococci (GAS) is a common cause of sore throat, usually spread person-to-person. Outbreaks related to infected food have more seldom been reported. The bacteria may originate from the throat or from wounds on the hands of persons handling the food. An outbreak in Sätila, Sweden, in April/May 2003 involving 153 individuals who fell ill after eating contaminated 'sandwich-layer cakes' was investigated in a descriptive, retrospective cohort study. Questionnaires were distributed, one immediately after the outbreak and one 3 months later. The average attack rate was 72%. 143 individuals sought medical care and 137 were treated with antibiotics. 76 individuals were ill for more than 4 days. GAS isolates of identical T-type were obtained from the throats of the patients, wounds on the caterer's fingers and also from the cakes. PFGE banding patterns of 14 representative isolates were identical, as well as the emm-sequence type, emm 89, of 3 chosen isolates. The study shows that GAS from a small wound on a finger can cause illness in a large number of individuals. To prevent further outbreaks, it is important to increase public awareness of this type of transmission.
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| 34. |
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| 35. |
- Bauden, Monika, et al.
(författare)
-
Characterization of histone-related chemical modifications in formalin-fixed paraffin-embedded and fresh-frozen human pancreatic cancer xenografts using LC-MS/MS
- 2017
-
Ingår i: Laboratory Investigation. - : Elsevier BV. - 0023-6837. ; 97:3, s. 279-288
-
Tidskriftsartikel (refereegranskat)abstract
- Post-translational modifications (PTMs) of histones including acetylation, methylation, and ubiquitination are known to be involved in the epigenetic regulation of gene expression and thus can have an important role in tumorigenesis. A number of PTMs have been linked to pancreatic cancer and are frequently studied as potential targets for cancer therapy or diagnosis. The availability of biobank-stored, formalin-fixed, paraffin-embedded (FFPE) materials and advanced proteomic analytical tools make it possible to detect histone-related PTMs using predicted mass shifts caused by specific modification. It is, however, important to take into account the fact that formaldehyde (FA) present in the FFPE material is chemically reactive and may undergo condensation reactions, for example, with terminal amino groups and active CH functionalities of the studied proteins. As supported by the results of this study, the possibility to misinterpret such protein condensation product as endogenous PTMs should be taken into consideration in all proteomic analytical work involving FFPE materials. In this study, we used liquid chromatography-tandem mass spectrometry to assess preassumed modification of the lysine residues of histone proteins in FFPE or fresh-frozen (FF) tumor xenografts, derived from the human pancreatic cancer cell line, Capan-1. Here we report modifications with a defined mass shift of +14.016, +28.031, +42.011, or +114.043 Da, corresponding to apparent methylation, dimethylation, acetylation, or ubiquitination that were differentially distributed between the groups. The identified modifications were significantly more frequent in FFPE samples as compared with FF samples. Our results indicate that FFPE tissue processing may result in persistent chemical modifications of histones, which correspond in mass shift of important PTMs. Herein, we highlight the importance to investigate and report FA-formed modifications in FFPE-treated tissues, as well as the necessity of careful manual examination of observed modifications to eliminate false-positive PTMs.
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| 36. |
- Bauden, Monika, et al.
(författare)
-
Novel anti-adhesive barrier Biobarrier reduces growth of colon cancer cells.
- 2014
-
Ingår i: Journal of Surgical Research. - : Elsevier BV. - 1095-8673 .- 0022-4804. ; 191:1, s. 196-202
-
Tidskriftsartikel (refereegranskat)abstract
- Postoperative peritoneal carcinomatosis together with adhesion formation are considered as two major clinical complications after resection of malignant abdominal tumors, jeopardizing the beneficial effect of the curative surgery. Biobarrier is a novel anti-adhesive barrier fulfilling the criteria for a good adhesion preventive agent, possessing biochemical properties that may enable it to function as a dual efficient device, reducing both adhesion and tumor development. This study aims to evaluate the effect of novel anti-adhesive device Biobarrier on intra-abdominal tumor progression.
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| 37. |
- Björklund, Patrik, et al.
(författare)
-
Västerås slott : Slott och borgar
- 2000
-
Rapport (populärvet., debatt m.m.)abstract
- En majoritet av dagens byggnadsuppgifter gäller att hantera det redan byggda. När vi står inför situationen att restaurera en befintlig byggnad är det viktigt att förstå olika tidsperioders stilideal liksom byggnadsteknik och material. Först då kan vi göra en väl avvägd analys, som tar tillvara och utvecklar de kvaliteter som byggnaderna själva besitter. Därför är utbildningen upplagd som ett växelspel mellan föreläsningar, seminarier, exkursioner och en för året vald studieuppgift.Slott och borgar har varit läsårets tema. Vi har valt att arbeta med Västerås och Örebro slott - två ganska bortglömda Vasaslott som är väl värda att lyfta fram. Särskilt har vi studerat de senaste 300 årens förändringar, som inte tidigare ägnats lika stora forskarmöda som medelitden och Vasatiden. I dessa två exempel finns en provkarta på estetiska, praktiska och tekniska ingrepp från Carl Hårlemans tid och fram till idag.Studierna har således omfattat både gestaltning, funktion och byggnadsteknik. Avsikten är att visa på kvaliteter i de omvandlingar och restaureringar som skett, men också att peka på problem och analysera olika möjligheter inför framtiden. Arbetet har skett i samarbete med Statens fastighetsverk och är tänkt att utgöra ett underlag till vårdprogram och framtida restaureringsinsatser.
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| 38. |
- Boström, Magnus, 1972-, et al.
(författare)
-
Conditions for Transformative Learning for Sustainable Development : A Theoretical Review and Approach
- 2018
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Ingår i: Sustainability. - : MDPI. - 2071-1050. ; 10:12
-
Tidskriftsartikel (refereegranskat)abstract
- Continued unsustainability and surpassed planetary boundaries require not only scientific and technological advances, but deep and enduring social and cultural changes. The purpose of this article is to contribute a theoretical approach to understand conditions and constraints for societal change towards sustainable development. In order to break with unsustainable norms, habits, practices, and structures, there is a need for learning for transformation, not only adaption. Based on a critical literature review within the field of learning for sustainable development, our approach is a development of the concept of transformative learning, by integrating three additional dimensions—Institutional Structures, Social Practices, and Conflict Perspectives. This approach acknowledges conflicts on macro, meso, and micro levels, as well as structural and cultural constraints. It contends that transformative learning is processual, interactional, long-term, and cumbersome. It takes place within existing institutions and social practices, while also transcending them. The article adopts an interdisciplinary social science perspective that acknowledges the importance of transformative learning in order for communities, organizations, and individuals to be able to deal with global sustainability problems, acknowledging the societal and personal conflicts involved in such transformation.
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| 39. |
- Brittebo, Eva, 1951-, et al.
(författare)
-
Bioactivation and effects of environmental pollutants in human and rodent blood vessel endothelial cells
- 2012
-
Ingår i: Organohalogen compound database (http://www.dioxin20xx.org/ohc_database_search.htm).
-
Konferensbidrag (refereegranskat)abstract
- IntroductionRecent epidemiological studies reveal associations between exposure to environmental pollutants and cardiovascular disorders in humans. Elevated serum concentrations of polychlorinated biphenyls (PCBs) have for instance been associated with cardiovascular risk factors such as hypertension (1-3). Exposure to the carbonate plastic monomer bisphenol A (BPA) has been associated with an increased incidence of cardiovascular disease and atherogenic changes in the vascular wall (4-6). The contention that the human cardiovascular system is a sensitive target for toxic chemicals gain support from our earlier and recent experimental studies in rodents, birds and fish, as well as in cultured human primary endothelial cells. It is also compatible with earlier observations that certain polycyclic aromatic hydrocarbons (PAHs) are environmental carcinogens that may also contribute to atherosclerosis in mice and birds (7,8).In this presentation we will briefly discuss effects of Ah receptor (AhR) agonists (e.g. the coplanar PCB126 or BNF, ß-naphthoflavone) on the expression of cytochrome P450 (CYP)1 enzymes in various endothelia in rodents in vivo or ex vivo, as well as in cultured human umbilical vein endothelial cells (HUVEC). The CYP1-dependent bioactivation and irreversible binding of prototype polyaromatic hydrocarbons (PAH) and heterocyclic amines such as benzo(a)pyrene (BaP), 7,12-dimethyl- benz(a)anthracene (DMBA) and 3-amino-1,4-dimethyl-5H-pyrido- [4,3-b]indole (Trp-P1) in these endothelia will be reviewed. We will also report how PCB126 affects vasoactive factors in HUVEC, and how these effects are modulated by physiological 17ß-oestradiol concentrations. Some effects of PCB126, 1-nitropyrene (1-NP) and bisphenol A (BPA) on biomarkers for endothelial dysfunction, cell stress and DNA damage in HUVEC will finally be presented.Material and methodsHuman umbilical vein endothelial cells (HUVEC) were purchased from Science Cell Research laboratories, Carlsbad, CA. C57Bl mice and Wistar or Sprague Dawley rats were purchased from various suppliers. All animal experiments were approved by the Local Ethical Committee for Research on Animals in Uppsala and the studies followed the guidelines laid down by the Swedish and European Union legislation on animal experimentation. Rodents, tissue-slices and cultured cells were treated with model chemicals as previously described. Tape section and light microscopy autoradiographic imaging using 3H-labelled BaP, DMBA and Trp-P-1 and immunohistochemistry was performed as previously described (9-19). Precision-cut tissue slices for in vitro autoradiography were prepared as described in (14) and the slices were incubated with various 3H-labelled chemicals. HUVEC were exposed to various compounds and the detection of biomarkers of endothelial dysfunction, DNA damage were performed as described (20-22). Finally, female Fischer rats were exposed to BPA (0.025, 0.25 and 2.5 mg/l) and fructose (50 g/l) in the drinking water from 5 to 15 weeks of age to mimic human exposure (unpublished data).Results and discussionCo-localization of CYP1A1 expression and BaP, DMBA and Trp-P-1 adduct formation in endothelial linings As demonstrated by immunohistochemistry, a high CYP1A immunoreactivity occurred in capillaries of the heart, skeletal muscle, uterus and in blood-brain interfaces such as the leptomeninges and plexus choroideus, whereas no expression was observed for instance in cerebral capillary endothelial cells of mice treated with AhR agonists (9-11). No, or very low constitutive immunoreactivities were observed in these endothelia in vehicle-treated animals. No basal or induced CYP1B1 expression was observed in endothelial cells, while a weak CYP1B1 immunostaining was detected in the muscle layer of small arteries. It should be noted that in subcellular preparations of whole organs, e.g. heart and brain, the CYP1A1 in endothelial cells is diluted due to cells that do not express high levels of CYP1A1, for examples myocytes or neurons, in excess. A cell-specific metabolism in endothelial cells may therefore remain undetected due to the presence of metabolically inactive cells. In order to detect minor sites of bioactivation such as endothelial linings we employed light microscopic autoradiographic imaging to examine the bioactivation and subsequent irreversible binding of the radiolabelled prototype toxicants in tissues of animals pretreated with AhR-agonists. As determined by light microscopic autoradiography of AhR-agonist-treated mice exposed to 3H-labelled BaP, DMBA or Trp-P-1 and birds exposed to 3H-Trp-P-1 a significant accumulation of non-extractable radioactivity occurred in endothelial linings (9-18). The bound radioactivity occurred in the nuclei and the perinuclear cytoplasm, suggesting that the autoradiograms depict both DNA- and protein-bound adducts. Since the binding sites of 3H-labelled BaP, DMBA or Trp-P-1 corresponded with the sites of CYP1A1 induction, we concluded that rodents express a constitutively low but highly inducible and functional CYP1A1 in endothelial cells. The binding of reactive metabolites in endothelial cells exceeded the binding in all other cell types in AhR-agonist treated mice and was abolished by pretreatment with the CYP1A1 inhibitor ellipticine, supporting a CYP1A1-catalysed metabolic activation in situ to a reactive species (9, 10,12). These findings imply that there is a preferential CYP1A1-catalysed formation of reactive metabolites from all three carcinogens in endothelial cells expressing high CYP1A1 levels. Interestingly, however, carcinogenesis in endothelial cells is a relative rare finding, suggesting that degenerative lesions and cell death may be more prevalent responses to metabolism-activated carcinogens/mutagens in these cells. Experiments with 3H-DMBA and 3H-Trp-P-1 in HUVEC confirmed that AhR-agonists induced an increased bioactivation, suggesting that also human endothelial cells should be targets for toxicity of reactive intermediates formed from CYP1A1- activated carcinogens/mutagens (17-18). This conclusion is supported by immunohistochemical studies on the heavily vascularized human endometrium demonstrating an expression of CYP1A1 and CYP1B1 protein in and around human endometrial blood vessels, although a large interindividualvariation was observed (19). None of the endometrial biopsy samples displayed vascular expression of CYP2A6, CYP2B6, CYP2C8/2C9/2C19, CYP2D6, or CYP3A4/5 protein.Effects of PCB 126, 1-NP, and BPA on biomarkers of endothelial dysfunction and cell stress in endothelial cells In vitro studies demonstrated that PCB126 increased the levels of vasoconstriction factors and decreased the levels of vasodilating factors in cultured HUVEC in a fashion that is characteristic for endothelial dysfunction related to human hypertension. The study showed that the co-planar PCB126 induced expression of the endothelium-derived vasoconstriction factor COX-2 and stimulated formation of the vasoconstrictor prostaglandin PGF2 via the AhR in HUVEC (20). COX-2 is known to play a role in hypertension by catalysing the formation of vasoconstriction prostaglandins and by stimulating reactive oxygen species (ROS) production. Further studies demonstrated that PCB126 increased the production of the vasoconstriction prostaglandin PGF2 and ROS in HUVEC. The relationship between increased ROS production and human hypertension is well established, ROS promotes vasoconstriction by stimulating the production of vasoconstriction prostaglandins and by reducing bioavailability of the vasorelaxing factor NO. Indeed, exposure to PCB126 slightly reduced the production of NO in HUVEC. Furthermore, the PCB126-induced mRNA expressions of CYP1A1, CYP1B1 and COX-2 in HUVEC were enhanced in the presence of physiological levels of 17- estradiol. This suggests that increased levels of oestrogen stimulate AhR-dependent transcription of genes previously associated with endothelial dysfunction and hypertension.In another study we have examined the effects of a nitrated PAH, 1-nitropyrene, that is abundant in diesel exhausts (21). The results revealed that 1-NP induced DNA damage, increased levels of ROS and increased protein expression of the endoplasmic reticulum stress chaperone GRP78 in cultured HUVEC. Induction of CYP1A1 by PCB126 as well as inhibition of nitroreductive metabolism by dicoumarol attenuated the induction of DNA damage, intracellular ROS levels and GRP78 expression. This suggests that the effects of 1-NP on HUVEC were mediated by metabolites mainly formed at nitroreduction and not by CYP1-dependent bioactivation to reactive intermediates.Recent in vitro studies demonstrated that bisphenol A increased the mRNA expression of genes that regulate vasoconstriction and angiogenesis in HUVEC (eNOS, VEGF, VEGFR2, connexin 43 and ACE1) and in human cardiomyocytes (eNOS and ACE1) (22). The results also showed that BPA increased the expression of P-eNOS(ser1177) and the production of NO in HUVEC. NO is the main effector molecule in angiogenesis downstream of VEGF. Based on the findings that BPA increase the expression of proangiogenic factors we investigated whether BPA could stimulate in vitro angiogenesis in HUVEC using the endothelial tube formation assay. The results demonstrated that BPA increased HUVEC tube formation suggesting that BPA can act directly on the endothelium and stimulate angiogenesis. Long-term exposure in rats revealed that environmentally relevant levels of BPA, increased the cardiac mRNA expression of genes that regulate vasoconstriction and angiogenesis. Ten weeks exposure of rats from preadolescence to adulthood to BPA in the drinking water increased theexpression of eNOS, VEGF, VEGFR2 and ACE1 in the heart. Taken together, the genes that were upregulated in rat cardiac tissues in vivo were also upregulated in human endothelial cells and cardiomyocytes in vitro. The heart is a heavily vascularized t
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| 40. |
- Bruhn-Olszewska, Bozena, et al.
(författare)
-
Loss of Y in leukocytes as a risk factor for critical COVID-19 in men.
- 2022
-
Ingår i: Genome medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemic, which has a prominent social and economic impact worldwide, shows a largely unexplained male bias for the severity and mortality of the disease. Loss of chromosome Y (LOY) is a risk factor candidate in COVID-19 due to its prior association with many chronic age-related diseases, and its impact on immune gene transcription.Publicly available scRNA-seq data of PBMC samples derived from male patients critically ill with COVID-19 were reanalyzed, and LOY status was added to the annotated cells. We further studied LOY in whole blood for 211 COVID-19 patients treated at intensive care units (ICU) from the first and second waves of the pandemic. Of these, 139 patients were subject to cell sorting for LOY analysis in granulocytes, low-density neutrophils (LDNs), monocytes, and PBMCs.Reanalysis of available scRNA-seq data revealed LDNs and monocytes as the cell types most affected by LOY. Subsequently, DNA analysis indicated that 46%, 32%, and 29% of critically ill patients showed LOY above 5% cut-off in LDNs, granulocytes, and monocytes, respectively. Hence, the myeloid lineage that is crucial for the development of severe COVID-19 phenotype is affected by LOY. Moreover, LOY correlated with increasing WHO score (median difference 1.59%, 95% HDI 0.46% to 2.71%, p=0.025), death during ICU treatment (median difference 1.46%, 95% HDI 0.47% to 2.43%, p=0.0036), and history of vessel disease (median difference 2.16%, 95% HDI 0.74% to 3.7%, p=0.004), among other variables. In 16 recovered patients, sampled during ICU stay and 93-143 days later, LOY decreased significantly in whole blood and PBMCs. Furthermore, the number of LDNs at the recovery stage decreased dramatically (median difference 76.4 per 10,000 cell sorting events, 95% HDI 55.5 to 104, p=6e-11).We present a link between LOY and an acute, life-threatening infectious disease. Furthermore, this study highlights LOY as the most prominent clonal mutation affecting the myeloid cell lineage during emergency myelopoiesis. The correlation between LOY level and COVID-19 severity might suggest that this mutation affects the functions of monocytes and neutrophils, which could have consequences for male innate immunity.
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| 41. |
- Byrskog, Ulrika, 1970-, et al.
(författare)
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Rationale, development and feasibility of group antenatal care for immigrant women in Sweden : a study protocol for the Hooyo Project
- 2019
-
Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 9:7
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Somali-born women comprise a large group of immigrant women of childbearing age in Sweden, with increased risks for perinatal morbidity and mortality and poor experiences of care, despite the goal of providing equitable healthcare for the entire population. Rethinking how care is provided may help to improve outcomes.OVERALL AIM: To develop and test the acceptability, feasibility and immediate impacts of group antenatal care for Somali-born immigrant women, in an effort to improve experiences of antenatal care, knowledge about childbearing and the Swedish healthcare system, emotional well-being and ultimately, pregnancy outcomes. This protocol describes the rationale, planning and development of the study.METHODS AND ANALYSIS: An intervention development and feasibility study. Phase I includes needs assessment and development of contextual understanding using focus group discussions. In phase II, the intervention and evaluation tools, based on core values for quality care and person-centred care, are developed. Phase III includes the historically controlled evaluation in which relevant outcome measures are compared for women receiving individual care (2016-2018) and women receiving group antenatal care (2018-2019): care satisfaction (Migrant Friendly Maternity Care Questionnaire), emotional well-being (Edinburgh Postnatal Depression Scale), social support, childbirth fear, knowledge of Swedish maternity care, delivery outcomes. Phase IV includes the process evaluation, investigate process, feasibility and mechanisms of impact using field notes, observations, interviews and questionnaires. All phases are conducted in collaboration with a stakeholder reference group.ETHICS AND DISSEMINATION: The study is approved by the Regional Ethical Review Board, Stockholm, Sweden. Participants receive information about the study and their right to decline/withdraw without consequences. Consent is given prior to enrolment. Findings will be disseminated at antenatal care units, national/international conferences, through publications in peer-reviewed journals, seminars involving stakeholders, practitioners, community and via the project website. Participating women will receive a summary of results in their language.
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| 42. |
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| 43. |
- Cebrián, María José García, et al.
(författare)
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Paradoxical role of hmgb1 in pancreatic cancer : Tumor suppressor or tumor promoter?
- 2016
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Ingår i: Anticancer research. - : Anticancer Research USA Inc.. - 0250-7005. ; 36:9, s. 4381-4390
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Forskningsöversikt (refereegranskat)abstract
- Pancreatic cancer has a dismal prognosis and there is an increasing and unmet need to identify better diagnostic and therapeutic targets in order to ameliorate the course of the disease. HMGB1, a nuclear DNA-binding protein that acts as a transcription factor, is currently in the limelight. HMGB1 exhibits a dual role in pancreatic cancer; when intracellular, it acts as an anti-tumor protein stabilizing the genome, whereas extracellular HMGB1 behaves as a protumor protein with cytokine, chemokine and growth factor functions. Although the exact mechanisms of HMGB1 in pancreatic cancer are still to be elucidated, the significance of this protein for processes, such as autophagy, immunogenic cell death, tumor growth, metastasis and resistance to chemotherapy, have become increasingly clear. In this review, we provide a systematic summary and review of the biological and clinical relevance of HMGB1 in pancreatic cancer.
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| 44. |
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| 45. |
- Curik, Ino, et al.
(författare)
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Complex Inheritance of Melanoma and Pigmentation of Coat and Skin in Grey Horses
- 2013
-
Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 9:2, s. e1003248-
-
Tidskriftsartikel (refereegranskat)abstract
- The dominant phenotype of greying with age in horses, caused by a 4.6-kb duplication in intron 6 of STX17, is associated with a high incidence of melanoma and vitiligo-like skin depigmentation. However, the progressive greying and the incidence of melanoma, vitiligo-like depigmentation, and amount of speckling in these horses do not follow a simple inheritance pattern. To understand their inheritance, we analysed the melanoma grade, grey level, vitiligo grade, and speckling grade of 1,119 Grey horses (7,146 measurements) measured in six countries over a 9-year period. We estimated narrow sense heritability (h(2)), and we decomposed this parameter into polygenic heritability (h(POLY)(2)), heritability due to the Grey (STX17) mutation (h(STX17)(2)), and heritability due to agouti (ASIP) locus (h(ASIP)(2)). A high heritability was found for greying (h(2) = 0.79), vitiligo (h(2) = 0.63), and speckling (h(2) = 0.66), while a moderate heritability was estimated for melanoma (h(2) = 0.37). The additive component of ASIP was significantly different from zero only for melanoma (h(ASIP)(2) = 0.02). STX17 controlled large proportions of phenotypic variance (h(STX17)(2) = 0.18-0.55) and overall heritability (h(STX17)(2)/h(2) = 0.28-0.83) for all traits. Genetic correlations among traits were estimated as moderate to high, primarily due to the effects of the STX17 locus. Nevertheless, the correlation between progressive greying and vitiligo-like depigmentation remained large even after taking into account the effects of STX17. We presented a model where four traits with complex inheritance patterns are strongly influenced by a single mutation. This is in line with evidence of recent studies in domestic animals indicating that some complex traits are, in addition to the large number of genes with small additive effects, influenced by genes of moderate-to-large effect. Furthermore, we demonstrated that the STX17 mutation explains to a large extent the moderate to high genetic correlations among traits, providing an example of strong pleiotropic effects caused by a single gene.
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| 46. |
- Deicher, Anton, et al.
(författare)
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Targeting dendritic cells in pancreatic ductal adenocarcinoma
- 2018
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Ingår i: Cancer Cell International. - : Springer Science and Business Media LLC. - 1475-2867. ; 18:1
-
Forskningsöversikt (refereegranskat)abstract
- Dendritic cells (DC) are an integral part of the tumor microenvironment. Pancreatic cancer is characterized by reduced number and function of DCs, which impacts antigen presentation and contributes to immune tolerance. Recent data suggest that exosomes can mediate communication between pancreatic cancer cells and DCs. Furthermore, levels of DCs may serve as prognostic factors. There is also growing evidence for the effectiveness of vaccination with DCs pulsed with tumor antigens to initiate adaptive cytolytic immune responses via T cells. Most experience with DC-based vaccination has been gathered for MUC1 and WT1 antigens, where clinical studies in advanced pancreatic cancer have provided encouraging results. In this review, we highlight the role of DC in the course, prognosis and treatment of pancreatic cancer.
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| 47. |
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| 48. |
- Ekström, Elin
(författare)
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From a place without speech : negotiations of othering among unaccompanied female minors in Sweden
- 2019
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The study presented in this thesis focuses on unaccompanied female minors and their experiences as newly arrived migrants in Sweden. As a group, unaccompanied female minors have until recently been rather invisible in both academic research and media. However, according to previous research on migration and integration, they risk being constructed as ‘others’ both due to their status as unaccompanied minors, being female and in relation to general perceptions of what it means to be Swedish.This study is based on qualitative interviews with 11 girls, 13 to 18 years old, who arrived in Sweden as unaccompanied minors in the period between 2014 and 2017. The interviews were conducted in two phases, with nine months to one year between the first and second phases. Whereas the focus in the first phase was on getting to know the participants, the second phase provided an opportunity to delve deeper into discussions on recurring themes from the first phase. The interviews were transcribed using a denaturalised approach and thematically analysed through an abductive process.The thesis explores the girls’ narratives of everyday experiences and interprets them through a theoretical framework of othering. Without losing sight of the social structures that situates the girls’ experiences, othering is approached as a reciprocal, three-dimensional relationship, focusing on knowledge, values and conduct towards the other.The findings indicate that the girls participating in this study were often seen through the normative perception of an already othered context, and as a consequence, their own voices and agency were disregarded. They were, metaphorically, put in places without speech. However, by engaging a critical perspective on their everyday interactions, the girls were also able to recognise and resist othering by keeping true to their own experiences. The thesis concludes that by exploring the margins between their comfort zones and new contexts the girls engage in an epistemic merging of different horizons, which can be understood as a slow but insistent process of moving out from the place without speech.
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| 49. |
- Fagevik Olsén, Monika, 1964, et al.
(författare)
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Development of and adherence to an ERAS® and prehabilitation protocol for patients undergoing pancreatic surgery: An observational study
- 2023
-
Ingår i: Scandinavian Journal of Surgery. - 1457-4969 .- 1799-7267. ; 112:4, s. 235-245
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective: There are still gaps in knowledge concerning the adherence to different multimodal pathways in pancreatic surgery. The aim of this trial was to explore and evaluate an Enhanced Recovery After Surgery (ERAS®) and prehabilitation protocol in patients undergoing open pancreatic surgery. Methods: Three groups of patients were included: two prospective series of 75 patients undergoing open pancreatic surgery following an ERAS® protocol with or without prehabilitation, and one group of 55 historical controls. Variables regarding adherence to, and effects of the protocols, were collected from the local database and the patients’ hospital records. Patients’ adherence to advice given pre-operatively was followed up using a study-specific questionnaire. Results: The patients reported high adherence to remembered advice given. The health care professionals’ adherence to the various parts of the concepts varied. ERAS® implementation resulted in more frequent gut motility stimulation (p < 0.001) and shorter duration of epidural anesthesia, site drains, and urinary catheter (p = 0.001). With prehabilitation, more patients were screened concerning nutritional status and prescribed preoperative training (p < 001). There was a significant change in weight before surgery, a shorter time to first flatus and a shorter length of stay after implementation of the concepts (p < 0.05). Complications were rare in all three groups and there were no significant differences between the groups. Conclusion: The implementation of an ERAS® and a prehabilitation protocol increased adherence to the protocols by both patients and healthcare professionals. An implementation of an ERAS® protocol with and without prehabilitation decreases length of stay and may decrease preoperative weight loss and time to bowel movement.
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| 50. |
- Ferreira, Alexandra Gabriela, et al.
(författare)
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Restoring tumor immunogenicity with dendritic cell reprogramming
- 2022
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Ingår i: Cancer immunology research. - 2326-6074. ; 10:12 suppl
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Konferensbidrag (refereegranskat)abstract
- Immunotherapy is revolutionizing cancer treatment, but success is limited to a fraction of patients. Tumor immunosurveillance and immunotherapy relies on presentation of tumor-associated antigens by conventional dendritic cells type 1 (cDC1). However, tumors develop mechanisms to avoid immune recognition such as downregulation of antigen presentation and exclusion of cDC1. We have previously demonstrated that enforced expression of the transcription factors PU.1, IRF8 and BATF3 (PIB) imposes the lineage conversion of fibroblasts to cDC1 by direct cell reprogramming. Here, we hypothesize that PIB reprograms cancer cells directly into functional tumor-antigen presenting cells (tumor-APCs) with enhanced immunogenicity. First, we show that enforced expression of PIB in a wide range of murine and human cancer cells from different origins is sufficient to induce surface expression of hematopoietic and DC-lineage specific markers (CD45 and Clec9a). Moreover, reprogramming restored the expression of antigen presentation complexes (MHC-I and MHC-II) and activated the expression of the co-stimulatory molecules CD40, CD80 and CD86, required for productive T cell activation. Transcriptomic analysis using mRNA-sequencing showed that PIB imposes a global cDC1 gene signature and an antigen presentation program in tumor cells as early as day 3 of reprogramming, overriding the original cancer cell program. Furthermore, Assay for Transposase-Accessible Chromatin (ATAC) sequencing analysis revealed that PIB-mediated cDC1 reprogramming elicited rapid epigenetic remodeling followed by gradual rewiring of transcriptional program and stabilization of cDC1 identity. Functionally, tumor-APCs present endogenous antigens on MHC-I, prime naïve CD8+ T and become prone to CD8+ T cell mediated killing. Tumor-APCs secrete pro-inflammatory cytokines (IL-12) and chemoattractants (CXCL10), uptake and process exogenous antigens, phagocyte dead cells, and cross-present exogenous antigens to activate naïve T-cells. In addition, reprogrammed tumor cells harboring TP53, KRAS and PTEN mutations downregulated proliferation and showed impaired tumorigenicity in vitro and in vivo. Importantly, we show that intra-tumoral injection of reprogrammed tumor-APCs elicited tumour growth control in vivo alongside increasing infiltration of CD8+ T and NK cells in B16-OVA tumors. Finally, we showed that our approach can be employed to convert primary cancer cells derived from melanoma, lung, breast, pancreatic, urothelial, and head and neck carcinomas as well as cancer associated fibroblasts. In summary, we provide evidence for the direct reprogramming of tumor cells into immunogenic cDC1-like cells, with restored antigen presentation capacity and the ability to reinstate anti-tumor immunity. Our approach elicits the immune system against cancer and counteract major tumor evasion mechanisms including tumor heterogeneity and impaired antigen presentation, laying the foundation for developing immunotherapeutic strategies based on the cellular reprogramming of human cancer cells.
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