| 1. |
- Campbell, PJ, et al.
(författare)
-
Pan-cancer analysis of whole genomes
- 2020
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
-
Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Lehtomaki, K, et al.
(författare)
-
Lead Time and Prognostic Role of Serum CEA, CA19-9, IL-6, CRP, and YKL-40 after Adjuvant Chemotherapy in Colorectal Cancer
- 2021
-
Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:15
-
Tidskriftsartikel (refereegranskat)abstract
- In colorectal cancer (CRC), 20–50% of patients relapse after curative-intent surgery with or without adjuvant therapy. We investigated the lead times and prognostic value of post-adjuvant (8 months from randomisation to adjuvant treatment) serum CEA, CA19-9, IL-6, CRP, and YKL-40. We included 147 radically resected stage II–IV CRC treated with 24 weeks of adjuvant 5-fluorouracil-based chemotherapy in the phase III LIPSYT-study (ISRCTN98405441). All 147 were included in lead time analysis, but 12 relapsing during adjuvant therapy were excluded from post-adjuvant analysis. Elevated post-adjuvant CEA, IL-6, and CRP were associated with impaired disease-free survival (DFS) with hazard ratio (HR) 5.21 (95% confidence interval 2.32–11.69); 3.72 (1.99–6.95); 2.58 (1.18–5.61), respectively, and elevated IL-6 and CRP with impaired overall survival (OS) HR 3.06 (1.64–5.73); 3.41 (1.55–7.49), respectively. Elevated post-adjuvant IL-6 in CEA-normal patients identified a subgroup with impaired DFS. HR 3.12 (1.38–7.04) and OS, HR 3.20 (1.39–7.37). The lead times between the elevated biomarker and radiological relapse were 7.8 months for CEA and 10.0–53.1 months for CA19-9, IL-6, CRP, and YKL-40, and the lead time for the five combined was 27.3 months. Elevated post-adjuvant CEA, IL-6, and CRP were associated with impaired DFS. The lead time was shortest for CEA.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
- Andersson, Erik, et al.
(författare)
-
Ambio fit for the 2020s
- 2022
-
Ingår i: Ambio. - : Springer Nature. - 0044-7447 .- 1654-7209. ; 51:5, s. 1091-1093
-
Tidskriftsartikel (refereegranskat)
|
|
| 13. |
- Barnett, A.H., et al.
(författare)
-
Angiotensin-receptor blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy
- 2004
-
Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 351:19, s. 1952-1961
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Few studies have directly compared the renoprotective effects of angiotensin II-receptor blockers and angiotensin-converting-enzyme (ACE) inhibitors in persons with type 2 diabetes. METHODS: In this prospective, multicenter, double-blind, five-year study, we randomly assigned 250 subjects with type 2 diabetes and early nephropathy to receive either the angiotensin II-receptor blocker telmisartan (80 mg daily, in 120 subjects) or the ACE inhibitor enalapril (20 mg daily, in 130 subjects). The primary end point was the change in the glomerular filtration rate (determined by measuring the plasma clearance of iohexol) between the baseline value and the last available value during the five-year treatment period. Secondary end points included the annual changes in the glomerular filtration rate, serum creatinine level, urinary albumin excretion, and blood pressure, the rates of end-stage renal disease and cardiovascular events, and the rate of death from all causes. RESULTS: After five years, the change in the glomerular filtration rate was -17.9 ml per minute per 1.73 m2 of body-surface area, where the minus sign denotes a decrement, with telmisartan (in 103 subjects), as compared with -14.9 ml per minute per 1.73 m2 with enalapril (in 113 subjects), for a treatment difference of -3.0 ml per minute per 1.73 m2 (95 percent confidence interval, -7.6 to 1.6 ml per minute per 1.73 m2). The lower boundary of the confidence interval, in favor of enalapril, was greater than the pre-defined margin of -10.0 ml per minute per 1.73 m2, indicating that telmisartan was not inferior to enalapril. The effects of the two agents on the secondary end points were not significantly different after five years. CONCLUSIONS: Telmisartan is not inferior to enalapril in providing long-term renoprotection in persons with type 2 diabetes. These findings do not necessarily apply to persons with more advanced nephropathy, but they support the clinical equivalence of angiotensin II-receptor blockers and ACE inhibitors in persons with conditions that place them at high risk for cardiovascular events. Copyright © 2004 Massachusetts Medical Society.
|
|
| 14. |
|
|
| 15. |
- Caretta, Martina Angela, et al.
(författare)
-
Water
- 2022
-
Ingår i: Climate Change 2022: Impacts, Adaptation and Vulnerability : Contribution of Working Group II to the Sixth Assessment Report of the Intergovernmental Panel on Climate Change - Contribution of Working Group II to the Sixth Assessment Report of the Intergovernmental Panel on Climate Change.
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
|
|
| 16. |
|
|
| 17. |
- Gerstung, M, et al.
(författare)
-
The evolutionary history of 2,658 cancers
- 2020
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 122-
-
Tidskriftsartikel (refereegranskat)abstract
- Cancer develops through a process of somatic evolution1,2. Sequencing data from a single biopsy represent a snapshot of this process that can reveal the timing of specific genomic aberrations and the changing influence of mutational processes3. Here, by whole-genome sequencing analysis of 2,658 cancers as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)4, we reconstruct the life history and evolution of mutational processes and driver mutation sequences of 38 types of cancer. Early oncogenesis is characterized by mutations in a constrained set of driver genes, and specific copy number gains, such as trisomy 7 in glioblastoma and isochromosome 17q in medulloblastoma. The mutational spectrum changes significantly throughout tumour evolution in 40% of samples. A nearly fourfold diversification of driver genes and increased genomic instability are features of later stages. Copy number alterations often occur in mitotic crises, and lead to simultaneous gains of chromosomal segments. Timing analyses suggest that driver mutations often precede diagnosis by many years, if not decades. Together, these results determine the evolutionary trajectories of cancer, and highlight opportunities for early cancer detection.
|
|
| 18. |
- Heby, Margareta, et al.
(författare)
-
Additive clinical impact of epidermal growth factor receptor and podocalyxin-like protein expression in pancreatic and periampullary adenocarcinomas
- 2020
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- The outcome of periampullary adenocarcinomas remains poor with few treatment options. Podocalyxin-like protein (PODXL) is an anti-adhesive protein, the high expression of which has been shown to confer a poor prognosis in numerous malignancies. A correlation and adverse prognostic synergy between PODXL and the epidermal growth factor receptor (EGFR) has been observed in colorectal cancer. Here, we investigated whether this also applies to periampullary adenocarcinomas. We analyzed the immunohistochemical expression of PODXL and EGFR in tissue microarrays with tumors from two patient cohorts; (Cohort 1, n = 175) and (Cohort 2, n = 189). The effect of TGF-β-induced expression and siRNA-mediated knockdown of PODXL and EGFR, were investigated in pancreatic cancer cells (PANC-1) in vitro. We found a correlation between PODXL and EGFR in these cancers, and a synergistic adverse effect on survival. Furthermore, silencing PODXL in pancreatic cancer cells resulted in the down-regulation of EGFR, but not vice versa. Consequently, these findings suggest a functional link between PODXL and EGFR, and the potential combined utility as biomarkers possibly improving patient stratification. Further studies examining the mechanistic basis underlying these observations may open new avenues of targeted treatment options for subsets of patients affected by these particularly aggressive cancers.
|
|
| 19. |
- Hepojoki, J, et al.
(författare)
-
Acute hantavirus infection induces galectin-3-binding protein
- 2014
-
Ingår i: The Journal of general virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 95:Pt 11, s. 2356-2364
-
Tidskriftsartikel (refereegranskat)abstract
- Hantaviruses are zoonotic viruses that cause life-threatening diseases when transmitted to humans. Severe hantavirus infection is manifested by impairment of renal function, pulmonary oedema and capillary leakage. Both innate and adaptive immune responses contribute to the pathogenesis, but the underlying mechanisms are not fully understood. Here, we showed that galectin-3-binding protein (Gal-3BP) was upregulated as a result of hantavirus infection bothin vitroandin vivo. Gal-3BP is a secreted glycoprotein found in human serum, and increased Gal-3BP levels have been reported in chronic viral infections and in several types of cancer. Ourin vitroexperiments showed that, whilst Vero E6 cells (an African green monkey kidney cell line) constitutively expressed and secreted Gal-3BP, this protein was detected in primary human cells only as a result of hantavirus infection. Analysis of Gal-3BP levels in serum samples of cynomolgus macaques infected experimentally with hantavirus indicated that hantavirus infection induced Gal-3BP alsoin vivo. Finally, analysis of plasma samples collected from patients hospitalized because of acute hantavirus infection showed higher Gal-3BP levels during the acute than the convalescent phase. Furthermore, the Gal-3BP levels in patients with haemorrhagic fever with renal syndrome correlated with increased complement activation and with clinical variables reflecting the severity of acute hantavirus infection.
|
|
| 20. |
|
|
| 21. |
- Kordas, K., et al.
(författare)
-
Magnetic-field induced efficient alignment of carbon nanotubes in aqueous solutions
- 2007
-
Ingår i: Chemistry of Materials. - : American Chemical Society (ACS). - 0897-4756 .- 1520-5002. ; 19:4, s. 787-791
-
Tidskriftsartikel (refereegranskat)abstract
- Efficient alignment of aqueous carboxyl-functionalized multiwalled carbon nanotubes having remanent iron catalyst particles are carried out in relatively low external magnetic fields (B <= 1017 mT). The nanotubes were grown by catalytic chemical vapor deposition and then functionalized in a multistep oxidation process using nitric acid and potassium permanganate. In the field-induced ordering, the ferromagnetic property of iron nanoparticles entrapped in the inner-tubular cavity of nanotubes is exploited. Considerable dichroism of nanotube solutions (up to 3.02) is measured and deposition of aligned CNT networks from the solutions on silicon substrates is demonstrated.
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
- Mantzouki, Evanthia, et al.
(författare)
-
Temperature Effects Explain Continental Scale Distribution of Cyanobacterial Toxins
- 2018
-
Ingår i: Toxins. - : MDPI. - 2072-6651. ; 10:4
-
Tidskriftsartikel (refereegranskat)abstract
- Insight into how environmental change determines the production and distribution of cyanobacterial toxins is necessary for risk assessment. Management guidelines currently focus on hepatotoxins (microcystins). Increasing attention is given to other classes, such as neurotoxins (e.g., anatoxin-a) and cytotoxins (e.g., cylindrospermopsin) due to their potency. Most studies examine the relationship between individual toxin variants and environmental factors, such as nutrients, temperature and light. In summer 2015, we collected samples across Europe to investigate the effect of nutrient and temperature gradients on the variability of toxin production at a continental scale. Direct and indirect effects of temperature were the main drivers of the spatial distribution in the toxins produced by the cyanobacterial community, the toxin concentrations and toxin quota. Generalized linear models showed that a Toxin Diversity Index (TDI) increased with latitude, while it decreased with water stability. Increases in TDI were explained through a significant increase in toxin variants such as MC-YR, anatoxin and cylindrospermopsin, accompanied by a decreasing presence of MC-LR. While global warming continues, the direct and indirect effects of increased lake temperatures will drive changes in the distribution of cyanobacterial toxins in Europe, potentially promoting selection of a few highly toxic species or strains.
|
|
| 28. |
- Moilanen, A. M., et al.
(författare)
-
WDR12, a Member of Nucleolar PeBoW-Complex, Is Up-Regulated in Failing Hearts and Causes Deterioration of Cardiac Function
- 2015
-
Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 10:4
-
Tidskriftsartikel (refereegranskat)abstract
- Aims In a recent genome-wide association study, WD-repeat domain 12 (WDR12) was associated with early-onset myocardial infarction (MI). However, the function of WDR12 in the heart is unknown. We characterized cardiac expression of WDR12, used adenovirus-mediated WDR12 gene delivery to examine effects of WDR12 on left ventricular (LV) remodeling, and analyzed relationship between MI associated WDR12 allele and cardiac function in human subjects. LV WDR12 protein levels were increased in patients with dilated cardiomyopathy and rats post-infarction. In normal adult rat hearts, WDR12 gene delivery into the anterior wall of the LV decreased interventricular septum diastolic and systolic thickness and increased the diastolic and systolic diameters of the LV. Moreover, LV ejection fraction (9.1%, P<0.05) and fractional shortening (12.2%, P<0.05) were declined. The adverse effects of WDR12 gene delivery on cardiac function were associated with decreased cellular proliferation, activation of p38 mitogen-activated protein kinase (MAPK)/heat shock protein (HSP) 27 pathway, and increased protein levels of Block of proliferation 1 (BOP1), essential for ribosome biogenesis. Post-infarction WDR12 gene delivery decreased E/A ratio (32%, P<0.05) suggesting worsening of diastolic function. In human subjects, MI associated WDR12 allele was associated significantly with diastolic dysfunction and left atrial size. WDR12 triggers distinct deterioration of cardiac function in adult rat heart and the MI associated WDR12 variant is associated with diastolic dysfunction in human subjects.
|
|
| 29. |
- Plyusnin, A, et al.
(författare)
-
Puumala hantavirus genome in patients with nephropathia epidemica: correlation of PCR positivity with HLA haplotype and link to viral sequences in local rodents
- 1997
-
Ingår i: Journal of clinical microbiology. - : American Society for Microbiology. - 0095-1137 .- 1098-660X. ; 35:5, s. 1090-1096
-
Tidskriftsartikel (refereegranskat)abstract
- Reverse transcription-PCR was used to analyze specimens from 20 Finnish nephropathia epidemica (NE) patients hospitalized during the period from October 1994 to January 1995. Blood and/or urine sediment specimens from seven patients were found to be positive for the genome sequences of Puumala hantavirus (PUU). PCR positivity of the specimens from the patients correlated well with the HLA-DRB1*0301 and HLA B8 alleles, which previously were shown to associate with severe courses of NE. Genetic analysis of the partial M-and/or S-segment sequences obtained from three severely ill NE patients revealed three PUU strains related to but distinct from previously reported strains from Finland. The M-segment sequence of PUU from bank voles trapped near the probable site of infection for one of the patients showed 98.2% identity to that of the PUU strain obtained from the patient, suggesting a link between wild-type PUU from the natural focus and the NE case. The S-segment sequences from the patient and the bank voles, however, showed substantially lower identity (95.8%). As this difference in diversity for M and S genes (1.8 and 4.2%) is atypical for PUU genetic drift, one possibility is that the strain acquired at the putative place of infection is a reassortant one.
|
|
| 30. |
|
|
| 31. |
- Stenman, S, et al.
(författare)
-
The prognostic significance of tall cells in papillary thyroid carcinoma: A case-control study
- 2018
-
Ingår i: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. - : IOS Press. - 1423-0380. ; 40:7, s. 1010428318787720-
-
Tidskriftsartikel (refereegranskat)abstract
- The subtype of the papillary thyroid carcinoma tall-cell variant has a worse prognosis than does the conventional papillary type (papillary thyroid carcinoma). The new World Health Organization 2017 classification defines a tall-cell variant as a tumour consisting of over 30% of cells that are two or three times as tall as they are wide. However, thresholds have differed. Our aim was to study how tall cells affect the prognosis of papillary thyroid carcinoma patients and to determine, for such cells, a cut-off percentage. Our cohort included 65 papillary thyroid carcinoma patients who underwent surgery at Helsinki University Hospital between 1973 and 1996: originally, 36 otherwise-matched patient pairs, eventually comprising 34 patients with an adverse outcome plus 31 who had recovered. All samples were digitally scanned and scored by two investigators based on tall cell composition. The cohort was analysed with four tall cell thresholds: 10%, 30%, 50% and 70% with a median follow-up of 22 years. In survival analysis, only the 70% threshold showed a correlation with reduced overall survival, disease-specific survival and relapse-free survival. A correlation also emerged with death from papillary thyroid carcinoma. In multivariate analysis, a 70% cut-off and age at diagnosis significantly affected DSS. Increasing tall cell score correlated with increasing age and extrathyroidal extensions. A tall cell composition of 10%, 30% or 50% showed no correlation with adverse outcome and suggests that the choice of pathologists reporting tall-cell variant should be a 70% threshold.
|
|
| 32. |
- Söderberg, Charlotta, et al.
(författare)
-
Options for governance,institutional arrangements andprivate and public decision-making across scales and sectors
- 2018
-
Ingår i: Biodiversity and ecosystem services in Nordic coastal ecosystems. - Copenhagen : Nordisk Ministerråd. - 9789289356640 - 9789289356657 ; , s. 161-189
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- This report describes the status and trends of biodiversity and ecosystem services in the Nordic region, the drivers and pressures affecting them, interactions and effects on people and society, and options for governance. The main report consists of two volumes. Volume 1 The general overview (this report) and Volume 2 The geographical case studies. This study has been inspired by the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystems Services (IPBES). It departs from case studies (Volume 2, the geographical case studies) from ten geographical areas in the Nordic countries (Denmark, Finland, Iceland, Norway, Sweden) and the autonomous areas of Faroe Islands, Greenland, and Åland. The aim was to describe status and trends of biodiversity and ecosystem services in the Nordic region, including the drivers and pressures affecting these ecosystems, the effects on people and society and options for governance. The Nordic study is structured as closely as possible to the framework for the regional assessments currently being finalized within IPBES. The report highlights environmental differences and similarities in the Nordic coastal areas, like the inhabitants´ relation to nature and the environment as well as similarities in social and policy instruments between the Nordic countries. This study provides background material for decision-making and it is shown that Nordic cooperation is of great importance for sustainable coastal management and should be strengthened in future work.
|
|
| 33. |
|
|
| 34. |
|
|
| 35. |
- Vapalahti, O, et al.
(författare)
-
Hantavirus infections in Europe
- 2003
-
Ingår i: The Lancet. Infectious diseases. - 1473-3099. ; 3:10, s. 653-661
-
Tidskriftsartikel (refereegranskat)
|
|
| 36. |
- Vapalahti, O, et al.
(författare)
-
Hantavirus infections in Europe
- 2003
-
Ingår i: LANCET INFECTIOUS DISEASES. - 1473-3099. ; 3:12, s. 753-754
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
