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| 4. |
- Saevarsdottir, S., et al.
(författare)
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Multiomics analysis of rheumatoid arthritis yields sequence variants that have large effects on risk of the seropositive subset
- 2022
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 81:8
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To find causal genes for rheumatoid arthritis (RA) and its seropositive (RF and/or ACPA positive) and seronegative subsets. Methods We performed a genome-wide association study (GWAS) of 31 313 RA cases (68% seropositive) and similar to 1 million controls from Northwestern Europe. We searched for causal genes outside the HLA-locus through effect on coding, mRNA expression in several tissues and/or levels of plasma proteins (SomaScan) and did network analysis (Qiagen). Results We found 25 sequence variants for RA overall, 33 for seropositive and 2 for seronegative RA, altogether 37 sequence variants at 34 non-HLA loci, of which 15 are novel. Genomic, transcriptomic and proteomic analysis of these yielded 25 causal genes in seropositive RA and additional two overall. Most encode proteins in the network of interferon-alpha/beta and IL-12/23 that signal through the JAK/STAT-pathway. Highlighting those with largest effect on seropositive RA, a rare missense variant in STAT4 (rs140675301-A) that is independent of reported non-coding STAT4-variants, increases the risk of seropositive RA 2.27-fold (p=2.1x10(-9)), more than the rs2476601-A missense variant in PTPN22 (OR=1.59, p=1.3x10(-160)). STAT4 rs140675301-A replaces hydrophilic glutamic acid with hydrophobic valine (Glu128Val) in a conserved, surface-exposed loop. A stop-mutation (rs76428106-C) in FLT3 increases seropositive RA risk (OR=1.35, p=6.6x10(-11)). Independent missense variants in TYK2 (rs34536443-C, rs12720356-C, rs35018800-A, latter two novel) associate with decreased risk of seropositive RA (ORs=0.63-0.87, p=10(-9)-10(-27)) and decreased plasma levels of interferon-alpha/beta receptor 1 that signals through TYK2/JAK1/STAT4. Conclusion Sequence variants pointing to causal genes in the JAK/STAT pathway have largest effect on seropositive RA, while associations with seronegative RA remain scarce.
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| 5. |
- Oddsson, Asmundur, et al.
(författare)
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Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Genotypes causing pregnancy loss and perinatal mortality are depleted among living individuals and are therefore difficult to find. To explore genetic causes of recessive lethality, we searched for sequence variants with deficit of homozygosity among 1.52 million individuals from six European populations. In this study, we identified 25 genes harboring protein-altering sequence variants with a strong deficit of homozygosity (10% or less of predicted homozygotes). Sequence variants in 12 of the genes cause Mendelian disease under a recessive mode of inheritance, two under a dominant mode, but variants in the remaining 11 have not been reported to cause disease. Sequence variants with a strong deficit of homozygosity are over-represented among genes essential for growth of human cell lines and genes orthologous to mouse genes known to affect viability. The function of these genes gives insight into the genetics of intrauterine lethality. We also identified 1077 genes with homozygous predicted loss-of-function genotypes not previously described, bringing the total set of genes completely knocked out in humans to 4785.
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| 6. |
- Stacey, Simon N, et al.
(författare)
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A germline variant in the TP53 polyadenylation signal confers cancer susceptibility.
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:11, s. 1098-103
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Tidskriftsartikel (refereegranskat)abstract
- To identify new risk variants for cutaneous basal cell carcinoma, we performed a genome-wide association study of 16 million SNPs identified through whole-genome sequencing of 457 Icelanders. We imputed genotypes for 41,675 Illumina SNP chip-typed Icelanders and their relatives. In the discovery phase, the strongest signal came from rs78378222[C] (odds ratio (OR) = 2.36, P = 5.2 × 10(-17)), which has a frequency of 0.0192 in the Icelandic population. We then confirmed this association in non-Icelandic samples (OR = 1.75, P = 0.0060; overall OR = 2.16, P = 2.2 × 10(-20)). rs78378222 is in the 3' untranslated region of TP53 and changes the AATAAA polyadenylation signal to AATACA, resulting in impaired 3'-end processing of TP53 mRNA. Investigation of other tumor types identified associations of this SNP with prostate cancer (OR = 1.44, P = 2.4 × 10(-6)), glioma (OR = 2.35, P = 1.0 × 10(-5)) and colorectal adenoma (OR = 1.39, P = 1.6 × 10(-4)). However, we observed no effect for breast cancer, a common Li-Fraumeni syndrome tumor (OR = 1.06, P = 0.57, 95% confidence interval 0.88-1.27).
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| 7. |
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| 8. |
- Kiemeney, Lambertus A, et al.
(författare)
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A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer.
- 2010
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 415-9
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Tidskriftsartikel (refereegranskat)abstract
- Previously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 x 10(-12)). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC.
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| 15. |
- Thorleifsson, Gudmar, et al.
(författare)
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Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:10, s. 906-909
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a genome-wide association study for primary open-angle glaucoma (POAG) in 1,263 affected individuals (cases) and 34,877 controls from Iceland. We identified a common sequence variant at 7q31 (rs4236601[ A], odds ratio (OR) = 1.36, P = 5.0 x 10(-10)). We then replicated the association in sample sets of 2,175 POAG cases and 2,064 controls from Sweden, the UK and Australia (combined OR = 1.18, P = 0.0015) and in 299 POAG cases and 580 unaffected controls from Hong Kong and Shantou, China (combined OR = 5.42, P = 0.0021). The risk variant identified here is located close to CAV1 and CAV2, both of which are expressed in the trabecular meshwork and retinal ganglion cells that are involved in the pathogenesis of POAG.
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| 19. |
- Stacey, Simon N, et al.
(författare)
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Ancestry-shift refinement mapping of the C6orf97-ESR1 breast cancer susceptibility locus.
- 2010
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Ingår i: PLoS genetics. - : Public Library of Science. - 1553-7404. ; 6:7, s. e1001029-
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Tidskriftsartikel (refereegranskat)abstract
- We used an approach that we term ancestry-shift refinement mapping to investigate an association, originally discovered in a GWAS of a Chinese population, between rs2046210[T] and breast cancer susceptibility. The locus is on 6q25.1 in proximity to the C6orf97 and estrogen receptor alpha (ESR1) genes. We identified a panel of SNPs that are correlated with rs2046210 in Chinese, but not necessarily so in other ancestral populations, and genotyped them in breast cancer case:control samples of Asian, European, and African origin, a total of 10,176 cases and 13,286 controls. We found that rs2046210[T] does not confer substantial risk of breast cancer in Europeans and Africans (OR = 1.04, P = 0.099, and OR = 0.98, P = 0.77, respectively). Rather, in those ancestries, an association signal arises from a group of less common SNPs typified by rs9397435. The rs9397435[G] allele was found to confer risk of breast cancer in European (OR = 1.15, P = 1.2 x 10(-3)), African (OR = 1.35, P = 0.014), and Asian (OR = 1.23, P = 2.9 x 10(-4)) population samples. Combined over all ancestries, the OR was 1.19 (P = 3.9 x 10(-7)), was without significant heterogeneity between ancestries (P(het) = 0.36) and the SNP fully accounted for the association signal in each ancestry. Haplotypes bearing rs9397435[G] are well tagged by rs2046210[T] only in Asians. The rs9397435[G] allele showed associations with both estrogen receptor positive and estrogen receptor negative breast cancer. Using early-draft data from the 1,000 Genomes project, we found that the risk allele of a novel SNP (rs77275268), which is closely correlated with rs9397435, disrupts a partially methylated CpG sequence within a known CTCF binding site. These studies demonstrate that shifting the analysis among ancestral populations can provide valuable resolution in association mapping.
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| 20. |
- Dand, Nick, et al.
(författare)
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Exome-wide association study reveals novel psoriasis susceptibility locus at TNFSF15 and rare protective alleles in genes contributing to type I IFN signalling
- 2017
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Ingår i: Human Molecular Genetics. - : OXFORD UNIV PRESS. - 0964-6906 .- 1460-2083. ; 26:21, s. 4301-4313
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Tidskriftsartikel (refereegranskat)abstract
- Psoriasis is a common inflammatory skin disorder for which multiple genetic susceptibility loci have been identified, but few resolved to specific functional variants. In this study, we sought to identify common and rare psoriasis-associated gene-centric variation. Using exome arrays we genotyped four independent cohorts, totalling 11 861 psoriasis cases and 28 610 controls, aggregating the dataset through statistical meta-analysis. Single variant analysis detected a previously unreported risk locus at TNFSF15 (rs6478108; P = 1.50 x 10(-8), OR = 1.10), and association of common protein-altering variants at 11 loci previously implicated in psoriasis susceptibility. We validate previous reports of protective low-frequency protein-altering variants within IFIH1 (encoding an innate antiviral receptor) and TYK2 (encoding a Janus kinase), in each case establishing a further series of protective rare variants (minor allele frequency amp;lt; 0.01) via gene-wide aggregation testing (IFIH1: p(burden) = 2.53 x 10(-7), OR = 0.707; TYK2: p(burden) = 6.17 x 10(-4), OR = 0.744). Both genes play significant roles in type I interferon (IFN) production and signalling. Several of the protective rare and low-frequency variants in IFIH1 and TYK2 disrupt conserved protein domains, highlighting potential mechanisms through which their effect may be exerted.
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| 25. |
- Hartmann, R. W., et al.
(författare)
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The Wittig bioconjugation of maleimide derived, water soluble phosphonium ylides to aldehyde-tagged proteins
- 2021
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Ingår i: Organic and biomolecular chemistry. - : Royal Society of Chemistry (RSC). - 1477-0520 .- 1477-0539. ; 19:47, s. 10417-10423
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Tidskriftsartikel (refereegranskat)abstract
- Herein we disclose the transformation of maleimides into water-soluble tris(2-carboxyethyl)phosphonium ylides and their subsequent application in the bioconjugation of protein- and peptide-linked aldehydes. The new entry into Wittig bioconjugate chemistry proceeds under mild conditions and relies on highly water soluble reagents, which are likely already part of most biochemists' inventory.
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| 26. |
- Langstrom, B, et al.
(författare)
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PET i klinisk verksamhet.
- 1995
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Ingår i: Läkartidningen. ; 92, s. 3202-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 27. |
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| 28. |
- Liedberg, F., et al.
(författare)
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Robot-assisted nephroureterectomy for upper tract urothelial carcinoma—feasibility and complications : a single center experience
- 2022
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 56:4, s. 301-307
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Tidskriftsartikel (refereegranskat)abstract
- Background: Robot-assisted nephroureterectomy (RANU) is the primary treatment for upper tract urothelial carcinoma (UTUC) at our hospital for patients with clinical stage less than T2, and for patients with invasive tumours, but unfit for major surgery. Objective: To assess peri-operative conditions and outcomes of RANU at our unit, and to evaluate the safety of the procedure. Methods: The medical records of all 166 patients undergoing RANU for suspected UTUC and followed for more than three months in a large university hospital in Sweden were reviewed retrospectively. After the exclusion of twenty patients because of previous cystectomy, simultaneous surgical procedure, or other tumour types than UTUC in the pathological report, 146 patients remained for the analyses. The primary endpoint was complication rate according to Clavien-Dindo at 90 days. Secondary endpoints were perioperative bleeding, violation of oncological surgical principles, hospital stay, and re-admission within 90 days. Results: The median age was 75 [(Inter Quartile Range) IQR 70–80] years and 57% of the patients had an ASA score above 2. According to Clavien-Dindo, one patient had a grade 3 complication, and no patient had a grade 4–5 complication. The median blood loss was 50 (IQR 20–100) ml and the median hospital stay was 6 (IQR 5–7) days. Twelve patients were re-admitted to the hospital within 90 days (eight with urinary tract infection/haematuria, one with hematoma, and three with other diseases). Conclusion: Robot-assisted nephroureterectomy is a safe procedure for patients with upper tract urothelial carcinoma, with a low risk of major surgical complications.
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| 29. |
- Makitie, AA, et al.
(författare)
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Head and neck cancer management in the Nordic countries: an effort to harmonize treatment
- 2017
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Ingår i: European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. - : Springer Science and Business Media LLC. - 1434-4726. ; 274:5, s. 2363-2365
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 30. |
- Otero, Jaime, et al.
(författare)
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Basin-scale phenology and effects of climate variability on global timing of initial seaward migration of Atlantic salmon (Salmo salar)
- 2014
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 20:1, s. 61-75
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Tidskriftsartikel (refereegranskat)abstract
- Migrations between different habitats are key events in the lives of many organisms. Such movements involve annually recurring travel over long distances usually triggered by seasonal changes in the environment. Often, the migration is associated with travel to or from reproduction areas to regions of growth. Young anadromous Atlantic salmon (Salmo salar) emigrate from freshwater nursery areas during spring and early summer to feed and grow in the North Atlantic Ocean. The transition from the freshwater ('parr') stage to the migratory stage where they descend streams and enter salt water ('smolt') is characterized by morphological, physiological and behavioural changes where the timing of this parr-smolt transition is cued by photoperiod and water temperature. Environmental conditions in the freshwater habitat control the downstream migration and contribute to within- and among-river variation in migratory timing. Moreover, the timing of the freshwater emigration has likely evolved to meet environmental conditions in the ocean as these affect growth and survival of the post-smolts. Using generalized additive mixed-effects modelling, we analysed spatio-temporal variations in the dates of downstream smolt migration in 67 rivers throughout the North Atlantic during the last five decades and found that migrations were earlier in populations in the east than the west. After accounting for this spatial effect, the initiation of the downstream migration among rivers was positively associated with freshwater temperatures, up to about 10 °C and levelling off at higher values, and with sea-surface temperatures. Earlier migration occurred when river discharge levels were low but increasing. On average, the initiation of the smolt seaward migration has occurred 2.5 days earlier per decade throughout the basin of the North Atlantic. This shift in phenology matches changes in air, river, and ocean temperatures, suggesting that Atlantic salmon emigration is responding to the current global climate changes.
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| 31. |
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| 32. |
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| 33. |
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| 34. |
- Almet, Axel A., et al.
(författare)
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A Roadmap for a Consensus Human Skin Cell Atlas and Single-Cell Data Standardization
- 2023
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Ingår i: Journal of Investigative Dermatology. - : Elsevier. - 0022-202X .- 1523-1747. ; 143:9, s. 1667-1677
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Forskningsöversikt (refereegranskat)abstract
- Single-cell technologies have become essential to driving discovery in both basic and translational investigative dermatology. Despite the multitude of available datasets, a central reference atlas of normal human skin, which can serve as a reference resource for skin cell types, cell states, and their molecular signatures, is still lacking. For any such atlas to receive broad acceptance, participation by many investigators during atlas construction is an essential prerequisite. As part of the Human Cell Atlas project, we have assembled a Skin Biological Network to build a consensus Human Skin Cell Atlas and outline a roadmap toward that goal. We define the drivers of skin diversity to be considered when selecting sequencing datasets for the atlas and list practical hurdles during skin sampling that can result in data gaps and impede comprehensive representation and technical considerations for tissue processing and computational analysis, the accounting for which should minimize biases in cell type enrichments and exclusions and decrease batch effects. By outlining our goals for Atlas 1.0, we discuss how it will uncover new aspects of skin biology.
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| 35. |
- Almet, A, et al.
(författare)
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A roadmap for the human skin cell atlas
- 2023
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Ingår i: JOURNAL OF INVESTIGATIVE DERMATOLOGY. - 0022-202X. ; 143:9, s. B10-B10
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 36. |
- Bain, C. C., et al.
(författare)
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Resident and pro-inflammatory macrophages in the colon represent alternative context-dependent fates of the same Ly6C(hi) monocyte precursors
- 2013
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Ingår i: Mucosal Immunology. - : Elsevier BV. - 1933-0219. ; 6:3, s. 498-510
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Tidskriftsartikel (refereegranskat)abstract
- Macrophages (m phi) are essential for intestinal homeostasis and the pathology of inflammatory bowel disease (IBD), but it is unclear whether discrete m phi populations carry out these distinct functions or if resident m phi change during inflammation. We show here that most resident m phi in resting mouse colon express very high levels of CX3CR1, are avidly phagocytic and MHCII hi, but are resistant to Toll-like receptor (TLR) stimulation, produce interleukin 10 constitutively, and express CD163 and CD206. A smaller population of CX3CR1(int) cells is present in resting colon and it expands during experimental colitis. Ly6C(hi) CCR2(+) monocytes can give rise to all m phi subsets in both healthy and inflamed colon and we show that the CX3CR1int pool represents a continuum in which newly arrived, recently divided monocytes develop into resident CX3CR1 hi m phi. This process is arrested during experimental colitis, resulting in the accumulation of TLR-responsive pro-inflammatory m phi. Phenotypic analysis of human intestinal m phi indicates that analogous processes occur in the normal and Crohn's disease ileum. These studies show for the first time that resident and inflammatory m phi in the intestine represent alternative differentiation outcomes of the same precursor and targeting these events could offer routes for therapeutic intervention in IBD.
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| 37. |
- Burger, Maximilian, et al.
(författare)
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ICUD-EAU International Consultation on Bladder Cancer 2012: Non-Muscle-Invasive Urothelial Carcinoma of the Bladder
- 2013
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 63:1, s. 36-44
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Forskningsöversikt (refereegranskat)abstract
- Context: Our aim was to present a summary of the Second International Consultation on Bladder Cancer recommendations on the diagnosis and treatment options for non-muscle-invasive urothelial cancer of the bladder (NMIBC) using an evidence-based approach. Objective: To critically review the recent data on the management of NMIBC to arrive at a general consensus. Evidence acquisition: A detailed Medline analysis was performed for original articles addressing the treatment of NMIBC with regard to diagnosis, surgery, intravesical chemotherapy, and follow-up. Proceedings from the last 5 yr of major conferences were also searched. Evidence synthesis: The major findings are presented in an evidence-based fashion. We analyzed large retrospective and prospective studies. Conclusions: Urothelial cancer of the bladder staged Ta, T1, and carcinoma in situ (CIS), also indicated as NMIBC, poses greatly varying but uniformly demanding challenges to urologic care. On the one hand, the high recurrence rate and low progression rate with Ta low-grade demand risk-adapted treatment and surveillance to provide thorough care while minimizing treatment-related burden. On the other hand, the propensity of Ta high-grade, T1, and CIS to progress demands intense care and timely consideration of radical cystectomy. (C) 2012 European Association of Urology. Published by Elsevier B. V. All rights reserved.
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| 40. |
- Johannsson, Oskar T, et al.
(författare)
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Characterization of a novel breast carcinoma xenograft and cell line derived from a BRCA1 germ-line mutation carrier
- 2003
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Ingår i: Laboratory Investigation. - 1530-0307. ; 83:3, s. 96-387
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Tidskriftsartikel (refereegranskat)abstract
- A human tumor xenograft (L56Br-X1) was established from a breast cancer axillary lymph node metastasis of a 53-year-old woman with a BRCA1 germ-line nonsense mutation (1806C>T; Q563X), and a cell line (L56Br-C1) was subsequently derived from the xenograft. The xenograft carries only the mutant BRCA1 allele and expresses mutant BRCA1 mRNA but no BRCA1 protein as determined by immunoprecipitation or Western blotting. The primary tumor, lymph node metastasis, and xenograft were hypodiploid by DNA flow cytometry, whereas the cell line displayed an aneuploidy apparently developed via polyploidization. Cytogenetic analysis, spectral karyotyping, and comparative genomic hybridization of the cell line revealed a highly complex karyotype with numerous unbalanced translocations. The xenograft and cell line had retained a somatic TP53 missense mutation (S215I) originating from the primary tumors, as well as a lack of immunohistochemically detectable expression of steroid hormone receptors, epidermal growth factor receptor, human epidermal growth factor receptor 2 (HER-2), and keratin 8. Global gene expression analysis by cDNA microarrays supported a correlation between the expression profiles of the primary tumor, lymph node metastasis, xenograft, and cell line. We conclude that L56Br-X1 and L56Br-C1 are useful model systems for studies of the pathogenesis and new therapeutic modalities of BRCA1-induced human breast cancer.
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| 41. |
- Jonsson, Stefan, et al.
(författare)
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Identification of sequence variants influencing immunoglobulin levels
- 2017
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 49:8, s. 1182-1191
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Tidskriftsartikel (refereegranskat)abstract
- Immunoglobulins are the effector molecules of the adaptive humoral immune system. In a genome-wide association study of 19,219 individuals, we found 38 new variants and replicated 5 known variants associating with IgA, IgG or IgM levels or with composite immunoglobulin traits, accounted for by 32 loci. Variants at these loci also affect the risk of autoimmune diseases and blood malignancies and influence blood cell development. Notable associations include a rare variant at RUNX3 decreasing IgA levels by shifting isoform proportions (rs188468174[C>T]: P = 8.3 × 10(-55), β = -0.90 s.d.), a rare in-frame deletion in FCGR2B abolishing IgG binding to the encoded receptor (p.Asn106del: P = 4.2 × 10(-8), β = 1.03 s.d.), four IGH locus variants influencing class switching, and ten new associations with the HLA region. Our results provide new insight into the regulation of humoral immunity.
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| 42. |
- Juratli, Tareq A., et al.
(författare)
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Targeted treatment of papillary craniopharyngiomas harboring BRAF V600E mutations
- 2019
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Ingår i: Cancer. - : WILEY. - 0008-543X .- 1097-0142. ; 125:17, s. 2910-2914
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Papillary craniopharyngiomas (PCPs) are characterized by the presence of BRAF V600E mutations, which are emerging as a useful guide for diagnosis and treatment decision making. The ongoing multicenter phase 2 Alliance A071601 trial is evaluating the efficacy of BRAF and mitogen-activated protein kinase kinase (MEK) inhibitors for patients with PCPs. With continued successful responses, it is proposed that BRAF (and MEK) inhibitors be evaluated for the neoadjuvant treatment of patients with PCPs.
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| 43. |
- Magnusson, Maria K, 1972, et al.
(författare)
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Macrophage and dendritic cell subsets in IBD: ALDH cells are reduced in colon tissue of patients with ulcerative colitis regardless of inflammation
- 2016
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Ingår i: Mucosal Immunology. - : Elsevier BV. - 1935-3456 .- 1935-3456 .- 1933-0219. ; 9:1, s. 171-182
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Tidskriftsartikel (refereegranskat)abstract
- Disruption of the homeostatic balance of intestinal dendritic cells (DCs) and macrophages (MQs) may contribute to inflammatory bowel disease. We characterized DC and MQ populations, including their ability to produce retinoic acid, in clinical material encompassing Crohn's ileitis, Crohn's colitis and ulcerative colitis (UC) as well as mesenteric lymph nodes (MLNs) draining these sites. Increased CD14+DRint MQs characterized inflamed intestinal mucosa while total CD141+ or CD1c+ DCs numbers were unchanged. However, CD103+ DCs, including CD141+CD103+ and CD1c+CD103+ DCs, were reduced in inflamed intestine. In MLNs, two CD14- DC populations were identified: CD11cintHLADRhi and CD11chiHLADRint cells. A marked increase of CD11chiHLADRint DC, particularly DRintCD1c+ DCs, characterized MLNs draining inflamed intestine. The fraction of DC and MQ populations expressing aldehyde dehydrogenase (ALDH) activity, reflecting retinoic acid synthesis, in UC colon, both in active disease and remission, were reduced compared to controls and inflamed Crohn's colon. In contrast, no difference in the frequency of ALDH+ cells among blood precursors was detected between UC patients and non-inflamed controls. This suggests that ALDH activity in myeloid cells in the colon of UC patients, regardless of whether the disease is active or in remission, is influenced by the intestinal environment.
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| 46. |
- Norling, Rikke, et al.
(författare)
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Radiological imaging of the neck for initial decision-making in oral squamous cell carcinomas-A questionnaire survey in the Nordic countries
- 2012
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Ingår i: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 51:3, s. 355-361
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Tidskriftsartikel (refereegranskat)abstract
- Background. Fast and accurate work-up is crucial to ensure the best possible treatment and prognosis for patients with head and neck cancer. The presence or absence of neck lymph node metastases is important for the prognosis and the choice of treatment. Clinical lymph node (N)-staging is done by palpation and diagnostic imaging of the neck. We investigated the current practice of the initial radiological work-up of patients with oral squamous cell carcinomas (OSCC) in the Nordic countries. Methods. A questionnaire regarding the availability and use of guidelines and imaging modalities for radiological N-staging in OSCC was distributed to 21 Head and Neck centres in Denmark (n = 4), Finland (n = 5), Iceland (n = 1), Norway (n = 4) and Sweden (n = 7). We also asked for a description of the radiological criteria for determining the lymph nodes as clinical positive (cN+) or negative (cN0). Results. All 21 Head and Neck centres responded to the questionnaire. Denmark and Finland have national guidelines, while Norway and Sweden have local or regional guidelines. Seventeen of the 19 centres with available guidelines recommended computed tomography (CT) of the cN0 neck. The waiting time may influence the imaging modalities used. Lymph node size was the most commonly used criteria for radiological cN+, but the cut-off measures vary from 0.8 to 2.0 cm. Conclusion. Overall, CT is the most commonly recommended and used imaging modality for OSCC. Despite availability of national guidelines the type and number of radiological examinations vary between centres within a country, but the implementation of a fast-track programme may facilitate fast access to imaging. The absence of uniform criteria for determining the lymph nodes of the neck as cN+ complicates the comparison of the accuracy of the imaging modalities. Well-defined radiological strategies and criteria are needed to optimise the radiological work-up in OSCC.
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| 47. |
- Nyberg, Gunnar, et al.
(författare)
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Hjärnstamsimplantat kan återge hörsel. Behandling av dövhet vid dubbelsidiga akustikusneurinom : Brain stem implant can restore hearing. Treatment of deafness in bilateral acoustic neuroma
- 2007
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 104:47, s. 3553-3556
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Tidskriftsartikel (refereegranskat)abstract
- Auditory brain stem implant (ABI) is a method to restore some hearing in patients with bilateral acoustic neuroma (vestibular schwannoma) or neurofibromatosis type 2 (NF 2). The ABI device may re-establish some hearing improving patient lip reading, awareness of sound and facilitate speech production after onset of total deafness. Today ABI is an established technique for treatment of deafness in patients with NF 2, with a low complication rate. New indications are inner ear malformations with lacking auditory nerve and severe calcification of the cochlea in children. Additional improvements in technical design and more knowledge about the microanatomy and function of the central auditory pathways, including the cochlear nucleus, will most likely lead to still better results in the near future.
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| 48. |
- Sigurdsson, Valgardur, et al.
(författare)
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Endothelial Induced EMT in Breast Epithelial Cells with Stem Cell Properties
- 2011
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:9
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Tidskriftsartikel (refereegranskat)abstract
- Epithelial to mesenchymal transition (EMT) is a critical event in cancer progression and is closely linked to the breast epithelial cancer stem cell phenotype. Given the close interaction between the vascular endothelium and cancer cells, especially at the invasive front, we asked whether endothelial cells might play a role in EMT. Using a 3D culture model we demonstrate that endothelial cells are potent inducers of EMT in D492 an immortalized breast epithelial cell line with stem cell properties. Endothelial induced mesenchymal-like cells (D492M) derived from D492, show reduced expression of keratins, a switch from E-Cadherin (E-Cad) to N-Cadherin (N-Cad) and enhanced migration. Acquisition of cancer stem cell associated characteristics like increased CD44(high)/CD24(low) ratio, resistance to apoptosis and anchorage independent growth was also seen in D492M cells. Endothelial induced EMT in D492 was partially blocked by inhibition of HGF signaling. Basal-like breast cancer, a vascular rich cancer with stem cell properties and adverse prognosis has been linked with EMT. We immunostained several basal-like breast cancer samples for endothelial and EMT markers. Cancer cells close to the vascular rich areas show no or decreased expression of E-Cad and increased N-Cad expression suggesting EMT. Collectively, we have shown in a 3D culture model that endothelial cells are potent inducers of EMT in breast epithelial cells with stem cell properties. Furthermore, we demonstrate that basal-like breast cancer contains cells with an EMT phenotype, most prominently close to vascular rich areas of these tumors. We conclude that endothelial cells are potent inducers of EMT and may play a role in progression of basal-like breast cancer.
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| 49. |
- Styrkarsdottir, Unnur, et al.
(författare)
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Severe osteoarthritis of the hand associates with common variants within the ALDH1A2 gene and with rare variants at 1p31.
- 2014
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 46:5, s. 498-502
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Tidskriftsartikel (refereegranskat)abstract
- Osteoarthritis is the most common form of arthritis and is a major cause of pain and disability in the elderly. To search for sequence variants that confer risk of osteoarthritis of the hand, we carried out a genome-wide association study (GWAS) in subjects with severe hand osteoarthritis, using variants identified through the whole-genome sequencing of 2,230 Icelanders. We found two significantly associated loci in the Icelandic discovery set: at 15q22 (frequency of 50.7%, odds ratio (OR) = 1.51, P = 3.99 × 10(-10)) in the ALDH1A2 gene and at 1p31 (frequency of 0.02%, OR = 50.6, P = 9.8 × 10(-10)). Among the carriers of the variant at 1p31 is a family with several members in whom the risk allele segregates with osteoarthritis. The variants within the ALDH1A2 gene were confirmed in replication sets from The Netherlands and the UK, yielding an overall association of OR = 1.46 and P = 1.1 × 10(-11) (rs3204689).
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