| 1. |
- Staaf, Johan, et al.
(författare)
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Relation between smoking history and gene expression profiles in lung adenocarcinomas
- 2012
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Ingår i: BMC Medical Genomics. - : Springer Science and Business Media LLC. - 1755-8794. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lung cancer is the worldwide leading cause of death from cancer. Tobacco usage is the major pathogenic factor, but all lung cancers are not attributable to smoking. Specifically, lung cancer in never-smokers has been suggested to represent a distinct disease entity compared to lung cancer arising in smokers due to differences in etiology, natural history and response to specific treatment regimes. However, the genetic aberrations that differ between smokers and never-smokers' lung carcinomas remain to a large extent unclear. Methods: Unsupervised gene expression analysis of 39 primary lung adenocarcinomas was performed using Illumina HT-12 microarrays. Results from unsupervised analysis were validated in six external adenocarcinoma data sets (n=687), and six data sets comprising normal airway epithelial or normal lung tissue specimens (n=467). Supervised gene expression analysis between smokers and never-smokers were performed in seven adenocarcinoma data sets, and results validated in the six normal data sets. Results: Initial unsupervised analysis of 39 adenocarcinomas identified two subgroups of which one harbored all never-smokers. A generated gene expression signature could subsequently identify never-smokers with 79-100% sensitivity in external adenocarcinoma data sets and with 76-88% sensitivity in the normal materials. A notable fraction of current/former smokers were grouped with never-smokers. Intriguingly, supervised analysis of never-smokers versus smokers in seven adenocarcinoma data sets generated similar results. Overlap in classification between the two approaches was high, indicating that both approaches identify a common set of samples from current/former smokers as potential never-smokers. The gene signature from unsupervised analysis included several genes implicated in lung tumorigenesis, immune-response associated pathways, genes previously associated with smoking, as well as marker genes for alveolar type II pneumocytes, while the best classifier from supervised analysis comprised genes strongly associated with proliferation, but also genes previously associated with smoking. Conclusions: Based on gene expression profiling, we demonstrate that never-smokers can be identified with high sensitivity in both tumor material and normal airway epithelial specimens. Our results indicate that tumors arising in never-smokers, together with a subset of tumors from smokers, represent a distinct entity of lung adenocarcinomas. Taken together, these analyses provide further insight into the transcriptional patterns occurring in lung adenocarcinoma stratified by smoking history.
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| 2. |
- Aronsson, Per, et al.
(författare)
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An operational decision support tool for stump harvest
- 2011
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- A multi-criteria decision support tool was developed to optimise stump harvesting for energy in Sweden. The decision tool takes account of multiple, sometimes conflicting, criteria relating to stump harvest; energy and climate, economics, biodiversity, and soil and water. Data on harvested stems are used as primary input data in the tool. Such data are routinely collected in harvester computers. The tool effectively deals with mixed sets of data; quantitative harvest data are re-calculated to metric (e.g. stump biomass), and qualitative data (e.g. biodiversity implications) are incorporated. A digital terrain map derived from air-borne laser scanning provides basic data for estimating soil wetness, while digital maps of water courses, key habitats and protected areas, or other sensitive habitats, are used to identify potentially and practically harvestable stumps.In four sub-models, an index from 0 to 10 is calculated for each stump, with 0 representing ‘Not at all suitable’ and 10 ‘Highly suitable for extraction’. Through this, a stump of high value for wood-living species is assigned a low index in the biodiversity sub-model and a large, easily accessible stump is assigned a high index in the economic sub-model. When calculating the net index, the sub-indices can be weighted according to the preferences of the end-user.An energy and climate sub-model incorporates greenhouse gas (GHG) emissions from forest operations and the effect of advancing GHG emissions when stump biomass is incinerated instead of being left to decompose. In the economic sub-model the potential monetary return from each stump is calculated based on estimated revenue from harvested stump biomass and the costs of stump harvesting and forwarding operations (based on cost functions and GIS calculations of transport distances).The biodiversity sub-model considers four types of wood-dependent organisms (lichens, mosses, insects and fungi) in terms of their habitat requirements, vulnerability, sun exposure preferences, locality, etc. A panel of external experts has drawn up a grading scale of stump values for the different taxonomic groups. The proximity to key habitats and exposure to sunlight are derived from a spatial model.Soil and water issues are handled within a sub-model estimating the consequences for long-term soil fertility (nutrient cycling and soil compaction) and water (leaching of plant nutrients and mercury, and particle transport due to soil damage by heavy machinery).The tool offers the end-user possibilities to prioritise and plan for cost-effective stump harvesting, while minimising negative environmental impacts.
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| 3. |
- Blom, Kristin, et al.
(författare)
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Eosinophil associated genes in the inflammatory bowel disease 4 region : Correlation to inflammatory bowel disease revealed
- 2012
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Ingår i: World Journal of Gastroenterology. - : Baishideng Publishing Group Inc.. - 1007-9327 .- 2219-2840. ; 18:44, s. 6409-6419
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To study the association between inflammatory bowel disease (IBD) and genetic variations in eosinophil protein X (EPX) and eosinophil cationic protein (ECP). METHODS: DNA was extracted from ethylene diamine tetraacetic acid blood of 587 patients with Crohn's disease (CD), 592 with ulcerative colitis (UC) and 300 healthy subjects. The EPX405 (G > C, rs2013109), ECP434 (G > C, rs2073342) and ECP562 (G > C, rs2233860) gene polymorphisms were analysed, by the 5'-nuclease allelic discrimination assay. For determination of intracellular content of EPX and ECP in granulocytes, 39 blood samples was collected and extracted with a buffer containing cetyltrimethylammonium bromide. The intracellular content of EPX was analysed using an enzyme-linked immunosorbent assay. The intracellular content of ECP was analysed with the UniCAP (R) system as described by the manufacturer. Statistical tests for calculations of results were chi(2) test, Fisher's exact test, ANOVA, Student-Newman-Keuls test, and Kaplan-Meier survival curve with Log-rank test for trend, the probability values of P < 0.05 were considered statistically significant. RESULTS: The genotype frequency for males with UC and with an age of disease onset of >= 45 years (n = 57) was for ECP434 and ECP562, GG = 37%, GC = 60%, CC = 4% and GG = 51%, GC = 49%, CC = 0% respectively. This was significantly different from the healthy subject's genotype frequencies of ECP434 (GG = 57%, GC = 38%, CC = 5%; P = 0.010) and ECP562 (GG = 68%, GC = 29 /0,CC = 3%; P = 0.009). The genotype frequencies for females, with an age of disease onset of >= 45 years with CD (n = 62), was for the ECP434 and ECP562 genotypes GG = 37%, GC = 52%, CC = 11% and GG = 48%, GC = 47% and CC = 5% respectively. This was also statistically different from healthy controls for both ECP434 (P = 0.010) and ECP562 (P = 0.013). The intracellular protein concentration of EPX and ECP was calculated in mu g/10(6) eosinophils and then correlated to the EPX 405 genotypes. The protein content of EPX was highest in the patients with the CC genotype of EPX405 (GG = 4.65, GC = 5.93, and CC = 6.57) and for ECP in the patients with the GG genotype of EPX405 (GG = 2.70, GC = 2.47 and CC = 1.90). ANOVA test demonstrated a difference in intracellular protein content for EPX (P = 0.009) and ECP (P = 0.022). The age of disease onset was linked to haplotypes of the EPX405, ECP434 and ECP562 genotypes. Kaplan Maier curve showed a difference between haplotype distributions for the females with CD (P = 0.003). The highest age of disease onset was seen in females with the EPX405CC, ECP434GC, ECP562CC haplotype (34 years) and the lowest in females with the EPX405GC, ECP434GC, ECP562GG haplotype (21 years). For males with UC there was also a difference between the highest and lowest age of the disease onset (EPX405CC, ECP434CC, ECP562CC, mean 24 years vs EPX405GC, ECP434GC, ECP562GG, mean 34 years, P = 0.0009). The relative risk for UC patients with ECP434 or ECP562-GC/CC genotypes to develop dysplasia/cancer was 2.5 (95%CI: 1.2-5.4, P = 0.01) and 2.5 (95%CI: 1.1-5.4, P = 0.02) respectively, compared to patients carrying the GG-genotypes. CONCLUSION: Polymorphisms of EPX and ECP are associated to IBD in an age and gender dependent manner, suggesting an essential role of eosinophils in the pathophysiology of IBD.
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| 4. |
- Brunnström, Hans, et al.
(författare)
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Immunohistochemistry in the differential diagnostics of primary lung cancer: an investigation within the southern Swedish lung cancer study.
- 2013
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Ingår i: American Journal of Clinical Pathology. - 1943-7722. ; 140:1, s. 37-46
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To assess immunohistochemical (IHC) stains differentially expressed between different types of lung cancer. Methods: We evaluated 16 different IHC stains in 209 prospectively included, surgically treated primary lung cancers, including 121 adenocarcinomas, 65 squamous cell carcinomas, 15 large-cell carcinomas, 5 adenosquamous carcinomas, 2 sarcomatoid carcinomas, and 1 small-cell carcinoma, using the tissue microarray technique. Results: Cytokeratin 5 (CK5) and P63 were both positive in 10% or more of the cells in 97% of the squamous cell carcinomas, with the former being positive (<10% of the cells) in only 2 non-squamous cell carcinomas. Thyroid transcription factor 1 (TTF1) and napsin A were positive in 10% or more of the cells in 88% and 87% of the adenocarcinomas, respectively, with 94% of the adenocarcinomas being positive in at least 1 marker. Fifteen percent of the adenocarcinomas were positive for estrogen receptor. Conclusions: CK5, TTF1, and napsin A are sensitive markers for squamous cell carcinoma and adenocarcinoma of the lung.
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| 5. |
- Isaksson, Sofi, et al.
(författare)
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Detecting EGFR alterations in clinical specimens-pitfalls and necessities.
- 2013
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Ingår i: Virchows Archiv: an international journal of pathology. - : Springer Science and Business Media LLC. - 1432-2307. ; 463:6, s. 755-764
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the epidermal growth factor receptor (EGFR) status in early stage lung cancer in Southern Sweden, a population for which there are no previous reports on the EGFR mutation frequency. Three hundred fifty small cell lung cancers, adenocarcinomas (AC), squamous cell carcinomas (SqCC), and large cell carcinomas were analyzed using a combination of techniques for the analysis of protein expression, gene copy numbers, and mutations. Immunohistochemical (IHC) staining with antibodies for the EGFR mutations L858R and del E746-A750 revealed intratumoral heterogeneity and several discrepant cases when compared to mutation-specific polymerase chain reaction (PCR)-based analysis. The frequencies of these two mutations, when considering IHC staining with mutation-specific antibodies in a cohort of 298 cases and subsequent confirmation by PCR, were 10 % in AC and <2 % in SqCC. Furthermore, screening by sequencing of EGFR in a cohort of 52 lung AC and squamous carcinomas demonstrated a more diverse mutation spectrum, not covered by the mutation-specific antibodies. High expression of total EGFR protein was correlated to high gene copy numbers but did not reflect the mutational status of the tumors. We believe that the mutation spectra in a Southern Swedish population is too diverse to be covered by the mutation-specific antibodies, and we also raise some other issues regarding the use of the mutation-specific antibodies, for example concerning heterogeneous expression of the mutated protein, optimal antibody dilution, and discrepancies between staining results and PCR.
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| 6. |
- Jönsson, Anna Maria, et al.
(författare)
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Annual changes in MODIS vegetation indices of Swedish coniferous forests in relation to snow dynamics and tree phenology
- 2010
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Ingår i: Remote Sensing of Environment. - : Elsevier BV. - 0034-4257 .- 1879-0704. ; 114:11, s. 2719-2730
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Tidskriftsartikel (refereegranskat)abstract
- Remote sensing provides spatially and temporally continuous measures of forest reflectance, and vegetation indices calculated from satellite data can be useful for monitoring climate change impacts on forest tree phenology. Monitoring of evergreen coniferous forest is more difficult than monitoring of deciduous forest, as the new buds only account for a small proportion of the green biomass, and the shoot elongation process is relatively slow. In this study, we have analyzed data from 186 coniferous monitoring sites in Sweden covering boreal, southern-boreal, and boreo-nemoral conditions. Our objective was to examine the possibility to track seasonal changes in coniferous forests by time-series of MODIS eight-day vegetation indices, testing the coherence between satellite monitored vegetation indices (VI) and temperature dependent phenology. The relationships between two vegetation indices (NDVI and WDRVI) and four phenological indicators (length of snow season, modeled onset of vegetation period, tree cold hardiness level and timing of budburst) were analyzed. The annual curves produced by two curve fitting methods for smoothening of seasonal changes in NDVI and WDRVI were to a large extent characterized by the occurrence of snow, producing stable seasonal oscillations in the northern part and irregular curves with less pronounced annual amplitude in the southern part of the country. Measures based on threshold values of the VI-curves, commonly used for determining the timing of different phenological phases, were not applicable for Swedish coniferous forests. Evergreen vegetation does not have a sharp increase in greenness during spring, and the melting of snow can influence the vegetation indices at the timing of bud burst in boreal forests. However, the interannual variation in VI-values for specific eight-day periods was correlated with the phenological indicators. This relation can be used for satellite monitoring of potential climate change impacts on northern coniferous spring phenology. (C) 2010 Elsevier Inc. All rights reserved.
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| 7. |
- Mehanovic, Sanela
(författare)
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The Potential and Challenges of the Use of Dynamic Software in Upper Secondary Mathematics : Students’ and Teachers’ Work with Integrals in GeoGebra Based Environments
- 2011
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- An introduction of computer software into mathematics classrooms makes the didactical situation more complex compared with previous learning environments (Blomhøj, 2005). A technological tool becoming a mathematic work tool in the hands of the students is a process that has turned up unexpectedly complex (Artigue, 2002). In addition to this problem, the teachers as the users of the tool go through the same process, while, at the same time, trying to integrate the tool into their teaching activities in a meaningful way. For these reasons it seems important to contribute to the research focused on the learning and teaching conditions in environments, where computer software is newly introduced, in order to better understand impacts of the introduction of different software in mathematics classrooms.In this study the dynamic mathematical software GeoGebra was used. GeoGebra is freely available for a number of platforms and has drawn much attention during the last years with growing user communities (www.GeoGebra.org). However, being generally available just recently, there are, comparatively, few studies on the use of GeoGebra in classroom settings.In this thesis the introduction and integration of GeoGebra was investigated in two studies with different perspectives. In the first study students’ work with GeoGebra in their mathematical activities related to the integral concept has been researched. In the second study teachers’ utilization of the didactical potential has been investigated. The results of the two studies show that GeoGebra as a mathematical tool in the hands of the students and the teachers can have a significant role in supporting their mathematical work if exploited in a, from a didactical perspective, adequate way. A learning and teaching environment based on GeoGebra bring with it a possibility to work with mathematical concepts in a broader way compared with blackboard based classrooms. GeoGebra’s facilities makes it possible to communicate mathematics in different ways and expressing mathematical concepts in different representations in a more direct way than in non dynamical environments. Communicating mathematics in different ways and expressing mathematics knowledge through different representations is of significant importance for students, not least in relation to the new curriculum for mathematics in Sweden (The Swedish National Agency for Education, 2011), where these aspects are explicitly named as aims for students to work towards.On the other hand, the investigations also showed that the introduction and the integration of GeoGebrawas a complex process for both the students and the teachers in this research. The introduction and integration of the software in the students’ mathematical activities made the didactical situation more complex and a differentiation of students’ work with the software was observed. For some students the use of the software seemingly supported their mathematical work, and at the same time for some students the result was the opposite; the use of the software was seen as a disturbing factor in their mathematical activities. When it comes to the study of teachers’ work with GeoGebra the investigations revealed that they encountered different types of obstacles that prevented them from utilizing the full didactical potential of the software in their teaching of mathematics. Three different types of obstacles were identified:technical - a teacher is not able to operate the software in the intended way;epistemological - a teacher is not aware of the didactical potential of GeoGebra and howto exploit it in in a way that supports students’ learning of integrals;didactical - a teacher is not aware of the complexity of technology based environments or he/she is aware of this aspect, but not comfortable with his/her competence in carrying out the process of integration of the software into his/her teaching without external help and support.Even if it is difficult to see the software detached from the context in this research, it seems that many of the obstacles perceived by the teachers in the experimental group, as well as difficulties students perceived in their work with the software, were related to the fact that they were inexperienced with the software and, consequently, lacked in knowledge in how to exploit its features in their mathematical activities. As it seems, the teachers would encounter the same obstacles every time they try to integrate a new, to them unfamiliar, software into their teaching practice. Also many of the students would experience same difficulties if they are not adequately supported in this process. Based on this, there are reasons to believe that problems with integration of GeoGebra into mathematics classrooms identified in this research would be similar in relation to integration of other dynamic mathematic software into mathematics classrooms, or even broader, other types of software as e.g. Computer Algebra Systems (CAS), as long as the integration considers the use of an unfamiliar software.
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| 8. |
- Salomonsson, Annette, et al.
(författare)
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Histological specificity of alterations and expression of KIT and KITLG in non-small cell lung carcinoma.
- 2013
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257. ; 52:11, s. 1088-1096
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Tidskriftsartikel (refereegranskat)abstract
- Characterization of molecules within important oncogenetic pathways may have future implications for development of therapies and biomarkers in lung cancer. One such target is the tyrosine kinase receptor KIT (c-KIT). We evaluated alterations and expression of KIT and its ligand, KITLG (also known as SCF), in 72 clinical lung tumor specimens of different histologies. Gene copy number, mRNA expression levels, and protein expression were assayed using array-based comparative genomic hybridization, real-time quantitative reverse transcription PCR and immunohistochemistry, respectively. For validation, we investigated copy number alterations and mRNA expression in external microarray data sets of 1,600 and 555 primary lung tumors, respectively. Positivity for KIT staining was most common in large cell neuroendocrine carcinoma (LCNEC) which also showed the highest KIT mRNA expression levels whereas expression was lowest in squamous cell carcinoma (SqCC). KIT mRNA expression levels were higher in KIT immunopositive samples, but expression was not affected by KIT copy numbers. Copy number gains of KIT were significantly more frequent in SqCC compared with adenocarcinoma in our own series and in the 1,600-sample data set. Immunopositivity for both KIT and KITLG in the same tumor was rare except in LCNEC. Our results highlight an increased KIT mRNA expression and frequent KIT immunopositivity in LCNEC but point out a poor correlation between KIT copy numbers and expression in SqCC, perhaps reflecting the existence of a protective mechanism against KIT alterations in this subgroup. © 2013 Wiley Periodicals, Inc.
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| 9. |
- Staaf, Johan, et al.
(författare)
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Landscape of somatic allelic imbalances and copy number alterations in human lung carcinoma
- 2013
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 132:9, s. 2020-2031
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Tidskriftsartikel (refereegranskat)abstract
- Lung cancer is the worldwide leading cause of death from cancer and has been shown to be a heterogeneous disease at the genomic level. To delineate the genomic landscape of copy number alterations, amplifications, loss-of-heterozygosity (LOH), tumor ploidy and copy-neutral allelic imbalance in lung cancer, microarray-based genomic profiles from 2,141 tumors and cell lines including adenocarcinomas (AC, n = 1,206), squamous cell carcinomas (SqCC, n = 467), large cell carcinomas (n = 37) and small cell lung carcinomas (SCLC, n = 88) were assembled from different repositories. Copy number alteration differences between lung cancer histologies were confirmed in 285 unrelated tumors analyzed by BAC array comparative genomic hybridization. Tumor ploidy patterns were validated by DNA flow cytometry analysis of 129 unrelated cases. Eighty-nine recurrent copy number alterations (55 gains, 34 losses) were identified harboring genes with gene expression putatively driven by gene dosage through integration with gene expression data for 496 cases. Thirteen and 26 of identified regions discriminated AC/SqCC and AC/SqCC/SCLC, respectively, while 48 regions harbored recurrent (n > 15) high-level amplifications comprising established and putative oncogenes, differing in frequency and coamplification patterns between histologies. Lung cancer histologies displayed differences in patterns/frequency of copy number alterations, genomic architecture, LOH, copy-neutral allelic imbalance and tumor ploidy, with AC generally displaying less copy number alterations and allelic imbalance. Moreover, a strong association was demonstrated between different types of copy number alterations and allelic imbalances with tumor aneuploidy. In summary, these analyses provide a comprehensive overview of the landscape of genomic alterations in lung cancer, highlighting differences but also similarities between subgroups of the disease.
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| 10. |
- Örtorp, Anders, 1964, et al.
(författare)
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The fit of cobalt-chromium three-unit fixed dental prostheses fabricated with four different techniques: A comparative in vitro study.
- 2011
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Ingår i: Dental materials. - : Elsevier BV. - 1879-0097 .- 0109-5641. ; 27:4, s. 356-363
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: This study sought to evaluate and compare the marginal and internal fit in vitro of three-unit FDPs in Co-Cr made using four fabrication techniques, and to conclude in which area the largest misfit is present. METHODS: An epoxy resin master model was produced. The impression was first made with silicone, and master and working models were then produced. A total of 32 three-unit Co-Cr FDPs were fabricated with four different production techniques: conventional lost-wax method (LW), milled wax with lost-wax method (MW), milled Co-Cr (MC), and direct laser metal sintering (DLMS). Each of the four groups consisted of eight FDPs (test groups). The FDPs were cemented on their cast and standardised-sectioned. The cement film thickness of the marginal and internal gaps was measured in a stereomicroscope, digital photos were taken at 12× magnification and then analyzed using measurement software. Statistical analyses were performed with one-way ANOVA and Tukey's test. RESULTS: Best fit based on the means (SDs) in μm for all measurement points was in the DLMS group 84 (60) followed by MW 117 (89), LW 133 (89) and MC 166 (135). Significant differences were present between MC and DLMS (p<0.05). The regression analyses presented differences within the parameters: production technique, tooth size, position and measurement point (p<0.05). SIGNIFICANCE: Best fit was found in the DLMS group followed by MW, LW and MC. In all four groups, best fit in both abutments was along the axial walls and in the deepest part of the chamfer preparation. The greatest misfit was present occlusally in all specimens.
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