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| 8. |
- Abe, O, et al.
(författare)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Tidskriftsartikel (refereegranskat)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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| 13. |
- Tobias, Deirdre K, et al.
(författare)
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Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
- 2023
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Ingår i: Nature Medicine. - 1546-170X. ; 29:10, s. 2438-2457
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Forskningsöversikt (refereegranskat)abstract
- Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
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| 14. |
- Goubet, AG, et al.
(författare)
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Prolonged SARS-CoV-2 RNA virus shedding and lymphopenia are hallmarks of COVID-19 in cancer patients with poor prognosis
- 2021
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Ingår i: Cell death and differentiation. - : Springer Science and Business Media LLC. - 1476-5403 .- 1350-9047. ; 28:12, s. 3297-3315
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Tidskriftsartikel (refereegranskat)abstract
- Patients with cancer are at higher risk of severe coronavirus infectious disease 2019 (COVID-19), but the mechanisms underlying virus–host interactions during cancer therapies remain elusive. When comparing nasopharyngeal swabs from cancer and noncancer patients for RT-qPCR cycle thresholds measuring acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in 1063 patients (58% with cancer), we found that malignant disease favors the magnitude and duration of viral RNA shedding concomitant with prolonged serum elevations of type 1 IFN that anticorrelated with anti-RBD IgG antibodies. Cancer patients with a prolonged SARS-CoV-2 RNA detection exhibited the typical immunopathology of severe COVID-19 at the early phase of infection including circulation of immature neutrophils, depletion of nonconventional monocytes, and a general lymphopenia that, however, was accompanied by a rise in plasmablasts, activated follicular T-helper cells, and non-naive Granzyme B+FasL+, EomeshighTCF-1high, PD-1+CD8+ Tc1 cells. Virus-induced lymphopenia worsened cancer-associated lymphocyte loss, and low lymphocyte counts correlated with chronic SARS-CoV-2 RNA shedding, COVID-19 severity, and a higher risk of cancer-related death in the first and second surge of the pandemic. Lymphocyte loss correlated with significant changes in metabolites from the polyamine and biliary salt pathways as well as increased blood DNA from Enterobacteriaceae and Micrococcaceae gut family members in long-term viral carriers. We surmise that cancer therapies may exacerbate the paradoxical association between lymphopenia and COVID-19-related immunopathology, and that the prevention of COVID-19-induced lymphocyte loss may reduce cancer-associated death.
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| 15. |
- Shin, J. H., et al.
(författare)
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IA-2 autoantibodies in incident type I diabetes patients are associated with a polyadenylation signal polymorphism in GIMAP5
- 2007
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Ingår i: Genes Immun. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:6, s. 503-12
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Tidskriftsartikel (refereegranskat)abstract
- In a large case-control study of Swedish incident type I diabetes patients and controls, 0-34 years of age, we tested the hypothesis that the GIMAP5 gene, a key genetic factor for lymphopenia in spontaneous BioBreeding rat diabetes, is associated with type I diabetes; with islet autoantibodies in incident type I diabetes patients or with age at clinical onset in incident type I diabetes patients. Initial scans of allelic association were followed by more detailed logistic regression modeling that adjusted for known type I diabetes risk factors and potential confounding variables. The single nucleotide polymorphism (SNP) rs6598, located in a polyadenylation signal of GIMAP5, was associated with the presence of significant levels of IA-2 autoantibodies in the type I diabetes patients. Patients with the minor allele A of rs6598 had an increased prevalence of IA-2 autoantibody levels compared to patients without the minor allele (OR=2.2; Bonferroni-corrected P=0.003), after adjusting for age at clinical onset (P=8.0 x 10(-13)) and the numbers of HLA-DQ A1*0501-B1*0201 haplotypes (P=2.4 x 10(-5)) and DQ A1*0301-B1*0302 haplotypes (P=0.002). GIMAP5 polymorphism was not associated with type I diabetes or with GAD65 or insulin autoantibodies, ICA, or age at clinical onset in patients. These data suggest that the GIMAP5 gene is associated with islet autoimmunity in type I diabetes and add to recent findings implicating the same SNP in another autoimmune disease.
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| 17. |
- Zaborowski, AM, et al.
(författare)
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Microsatellite instability in young patients with rectal cancer: molecular findings and treatment response
- 2022
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Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 109:3, s. 251-255
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Tidskriftsartikel (refereegranskat)abstract
- In this study of 400 patients with early-onset rectal cancer, 12.5 per cent demonstrated microsatellite instability (MSI). MSI was associated with a reduced likelihood of nodal positivity, an increased rate of pathological complete response, and improved disease-specific survival.
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| 21. |
- Ashwood, C., et al.
(författare)
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Proceedings of the EuBIC-MS 2020 Developers’ Meeting
- 2020
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Ingår i: EuPA Open Proteomics. - : Elsevier B.V.. - 2212-9685. ; 24, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- The 2020 European Bioinformatics Community for Mass Spectrometry (EuBIC-MS) Developers’ meeting was held from January 13th to January 17th 2020 in Nyborg, Denmark. Among the participants were scientists as well as developers working in the field of computational mass spectrometry (MS) and proteomics. The 4-day program was split between introductory keynote lectures and parallel hackathon sessions. During the latter, the participants developed bioinformatics tools and resources addressing outstanding needs in the community. The hackathons allowed less experienced participants to learn from more advanced computational MS experts, and to actively contribute to highly relevant research projects. We successfully produced several new tools that will be useful to the proteomics community by improving data analysis as well as facilitating future research. All keynote recordings are available on https://doi.org/10.5281/zenodo.3890181.
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| 22. |
- Bailey-Wilson, Joan E, et al.
(författare)
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Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG) families
- 2012
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Ingår i: BMC Medical Genetics. - London : BioMed Central. - 1471-2350. ; 13, s. 46-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive.Methods: Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG). Meta-analyses of the resultant family-specific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed.Results: Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD) of 1.28, and an allele-sharing lod score (LOD) of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM) versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2-3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM). For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM) when families used in the original published report of linkage to Xq27-28 were excluded.Conclusions: Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2-3 affected individuals and with some evidence of male to male disease transmission showed stronger linkage signals. Our results suggest that the genetic basis for prostate cancer in our families is much more complex than a single susceptibility locus on the X chromosome, and that future explorations of the Xq27-28 region should focus on the subset of families identified here with the strongest evidence of linkage to this region.
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| 23. |
- Christensen, G Bryce, et al.
(författare)
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Genome-wide linkage analysis of 1,233 prostate cancer pedigrees from the International Consortium for prostate cancer Genetics using novel sumLINK and sumLOD analyses.
- 2010
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Ingår i: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 70, s. 735-744
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prostate cancer (PC) is generally believed to have a strong inherited component, but the search for susceptibility genes has been hindered by the effects of genetic heterogeneity. The recently developed sumLINK and sumLOD statistics are powerful tools for linkage analysis in the presence of heterogeneity. METHODS: We performed a secondary analysis of 1,233 PC pedigrees from the International Consortium for Prostate Cancer Genetics (ICPCG) using two novel statistics, the sumLINK and sumLOD. For both statistics, dominant and recessive genetic models were considered. False discovery rate (FDR) analysis was conducted to assess the effects of multiple testing. RESULTS: Our analysis identified significant linkage evidence at chromosome 22q12, confirming previous findings by the initial conventional analyses of the same ICPCG data. Twelve other regions were identified with genome-wide suggestive evidence for linkage. Seven regions (1q23, 5q11, 5q35, 6p21, 8q12, 11q13, 20p11-q11) are near loci previously identified in the initial ICPCG pooled data analysis or the subset of aggressive PC pedigrees. Three other regions (1p12, 8p23, 19q13) confirm loci reported by others, and two (2p24, 6q27) are novel susceptibility loci. FDR testing indicates that over 70% of these results are likely true positive findings. Statistical recombinant mapping narrowed regions to an average of 9 cM. CONCLUSIONS: Our results represent genomic regions with the greatest consistency of positive linkage evidence across a very large collection of high-risk PC pedigrees using new statistical tests that deal powerfully with heterogeneity. These regions are excellent candidates for further study to identify PC predisposition genes. Prostate (c) 2010 Wiley-Liss, Inc.
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| 24. |
- Galluzzi, L, et al.
(författare)
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Consensus guidelines for the definition, detection and interpretation of immunogenic cell death
- 2020
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Ingår i: Journal for immunotherapy of cancer. - : BMJ. - 2051-1426. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular and microenvironmental features determine the propensity of RCD to drive adaptive immunity. Here, we provide an updated operational definition of immunogenic cell death (ICD), discuss the key factors that dictate the ability of dying cells to drive an adaptive immune response, summarize experimental assays that are currently available for the assessment of ICD in vitro and in vivo, and formulate guidelines for their interpretation.
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| 25. |
- Ignjatovic, Vera, et al.
(författare)
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Mass Spectrometry-Based Plasma Proteomics : Considerations from Sample Collection to Achieving Translational Data
- 2019
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 18:12, s. 4085-4097
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Forskningsöversikt (refereegranskat)abstract
- The proteomic analysis of human blood and blood-derived products (e.g., plasma) offers an attractive avenue to translate research progress from the laboratory into the clinic. However, due to its unique protein composition, performing proteomics assays with plasma is challenging. Plasma proteomics has regained interest due to recent technological advances, but challenges imposed by both complications inherent to studying human biology (e.g., interindividual variability) and analysis of biospecimens (e.g., sample variability), as well as technological limitations remain. As part of the Human Proteome Project (HPP), the Human Plasma Proteome Project (HPPP) brings together key aspects of the plasma proteomics pipeline. Here, we provide considerations and recommendations concerning study design, plasma collection, quality metrics, plasma processing workflows, mass spectrometry (MS) data acquisition, data processing, and bioinformatic analysis. With exciting opportunities in studying human health and disease though this plasma proteomics pipeline, a more informed analysis of human plasma will accelerate interest while enhancing possibilities for the incorporation of proteomics-scaled assays into clinical practice.
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| 26. |
- Lejaeghere, Kurt, et al.
(författare)
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Reproducibility in density functional theory calculations of solids.
- 2016
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 351:6280, s. 1415-1422
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Tidskriftsartikel (refereegranskat)abstract
- The widespread popularity of density functional theory has given rise to an extensive range of dedicated codes for predicting molecular and crystalline properties. However, each code implements the formalism in a different way, raising questions about the reproducibility of such predictions. We report the results of a community-wide effort that compared 15 solid-state codes, using 40 different potentials or basis set types, to assess the quality of the Perdew-Burke-Ernzerhof equations of state for 71 elemental crystals. We conclude that predictions from recent codes and pseudopotentials agree very well, with pairwise differences that are comparable to those between different high-precision experiments. Older methods, however, have less precise agreement. Our benchmark provides a framework for users and developers to document the precision of new applications and methodological improvements.
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| 27. |
- Lenz, Tobias L., et al.
(författare)
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Widespread non-additive and interaction effects within HLA loci modulate the risk of autoimmune diseases
- 2015
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Ingår i: Nature Genetics. - : Macmillan Publishers Ltd.. - 1061-4036 .- 1546-1718. ; 47:9, s. 1085-1090
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Tidskriftsartikel (refereegranskat)abstract
- Human leukocyte antigen (HLA) genes confer substantial risk for autoimmune diseases on a log-additive scale. Here we speculated that differences in autoantigen-binding repertoires between a heterozygote's two expressed HLA variants might result in additional non-additive risk effects. We tested the non-additive disease contributions of classical HLA alleles in patients and matched controls for five common autoimmune diseases: rheumatoid arthritis (n(cases) = 5,337), type 1 diabetes (T1D; n(cases) = 5,567), psoriasis vulgaris (n(cases) = 3,089), idiopathic achalasia (n(cases) = 727) and celiac disease (ncases = 11,115). In four of the five diseases, we observed highly significant, non-additive dominance effects (rheumatoid arthritis, P = 2.5 x 10(-12); T1D, P = 2.4 x 10(-10); psoriasis, P = 5.9 x 10(-6); celiac disease, P = 1.2 x 10(-87)). In three of these diseases, the non-additive dominance effects were explained by interactions between specific classical HLA alleles (rheumatoid arthritis, P = 1.8 x 10(-3); T1D, P = 8.6 x 10(-27); celiac disease, P = 6.0 x 10(-100)). These interactions generally increased disease risk and explained moderate but significant fractions of phenotypic variance (rheumatoid arthritis, 1.4%; T1D, 4.0%; celiac disease, 4.1%) beyond a simple additive model.
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| 29. |
- Lu, Lingyi, et al.
(författare)
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Chromosomes 4 and 8 implicated in a genome wide SNP linkage scan of 762 prostate cancer families collected by the ICPCG
- 2012
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Ingår i: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 72:4, s. 410-426
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND In spite of intensive efforts, understanding of the genetic aspects of familial prostate cancer (PC) remains largely incomplete. In a previous microsatellite-based linkage scan of 1,233 PC families, we identified suggestive evidence for linkage (i.e., LOD?=?1.86) at 5q12, 15q11, 17q21, 22q12, and two loci on 8p, with additional regions implicated in subsets of families defined by age at diagnosis, disease aggressiveness, or number of affected members. METHODS. In an attempt to replicate these findings and increase linkage resolution, we used the Illumina 6000 SNP linkage panel to perform a genome-wide linkage scan of an independent set of 762 multiplex PC families, collected by 11 International Consortium for Prostate Cancer Genetics (ICPCG) groups. RESULTS. Of the regions identified previously, modest evidence of replication was observed only on the short arm of chromosome 8, where HLOD scores of 1.63 and 3.60 were observed in the complete set of families and families with young average age at diagnosis, respectively. The most significant linkage signals found in the complete set of families were observed across a broad, 37cM interval on 4q13-25, with LOD scores ranging from 2.02 to 2.62, increasing to 4.50 in families with older average age at diagnosis. In families with multiple cases presenting with more aggressive disease, LOD cores over 3.0 were observed at 8q24 in the vicinity of previously identified common PC risk variants, as well as MYC, an important gene in PC biology. CONCLUSIONS. These results will be useful in prioritizing future susceptibility gene discovery efforts in thiscommon cancer. Prostate 72: 410-426, 2012. (C) 2011 Wiley Periodicals, Inc.
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| 30. |
- Martins, I, et al.
(författare)
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Anticancer chemotherapy and radiotherapy trigger both non-cell-autonomous and cell-autonomous death
- 2018
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Ingår i: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 9:7, s. 716-
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Tidskriftsartikel (refereegranskat)abstract
- Even though cell death modalities elicited by anticancer chemotherapy and radiotherapy have been extensively studied, the ability of anticancer treatments to induce non-cell-autonomous death has never been investigated. By means of multispectral imaging flow-cytometry-based technology, we analyzed the lethal fate of cancer cells that were treated with conventional anticancer agents and co-cultured with untreated cells, observing that anticancer agents can simultaneously trigger cell-autonomous and non-cell-autonomous death in treated and untreated cells. After ionizing radiation, oxaliplatin, or cisplatin treatment, fractions of treated cancer cell populations were eliminated through cell-autonomous death mechanisms, while other fractions of the treated cancer cells engulfed and killed neighboring cells through non-cell-autonomous processes, including cellular cannibalism. Under conditions of treatment with paclitaxel, non-cell-autonomous and cell-autonomous death were both detected in the treated cell population, while untreated neighboring cells exhibited features of apoptotic demise. The transcriptional activity of p53 tumor-suppressor protein contributed to the execution of cell-autonomous death, yet failed to affect the non-cell-autonomous death by cannibalism for the majority of tested anticancer agents, indicating that the induction of non-cell-autonomous death can occur under conditions in which cell-autonomous death was impaired. Altogether, these results reveal that chemotherapy and radiotherapy can induce both non-cell-autonomous and cell-autonomous death of cancer cells, highlighting the heterogeneity of cell death responses to anticancer treatments and the unsuspected potential contribution of non-cell-autonomous death to the global effects of anticancer treatment.
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| 32. |
- Omenn, G. S., et al.
(författare)
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Progress on Identifying and Characterizing the Human Proteome : 2019 Metrics from the HUPO Human Proteome Project
- 2019
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Ingår i: Journal of Proteome Research. - : American Chemical Society. - 1535-3893 .- 1535-3907. ; 18:12, s. 4098-4107
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Tidskriftsartikel (refereegranskat)abstract
- The Human Proteome Project (HPP) annually reports on progress made throughout the field in credibly identifying and characterizing the complete human protein parts list and making proteomics an integral part of multiomics studies in medicine and the life sciences. NeXtProt release 2019-01-11 contains 17 694 proteins with strong protein-level evidence (PE1), compliant with HPP Guidelines for Interpretation of MS Data v2.1; these represent 89% of all 19 823 neXtProt predicted coding genes (all PE1,2,3,4 proteins), up from 17 470 one year earlier. Conversely, the number of neXtProt PE2,3,4 proteins, termed the "missing proteins" (MPs), has been reduced from 2949 to 2129 since 2016 through efforts throughout the community, including the chromosome-centric HPP. PeptideAtlas is the source of uniformly reanalyzed raw mass spectrometry data for neXtProt; PeptideAtlas added 495 canonical proteins between 2018 and 2019, especially from studies designed to detect hard-to-identify proteins. Meanwhile, the Human Protein Atlas has released version 18.1 with immunohistochemical evidence of expression of 17 000 proteins and survival plots as part of the Pathology Atlas. Many investigators apply multiplexed SRM-targeted proteomics for quantitation of organ-specific popular proteins in studies of various human diseases. The 19 teams of the Biology and Disease-driven B/D-HPP published a total of 160 publications in 2018, bringing proteomics to a broad array of biomedical research.
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| 33. |
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| 34. |
- Shao, WG, et al.
(författare)
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The SysteMHC Atlas project
- 2018
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Ingår i: Nucleic acids research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 46:D1, s. D1237-D1247
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Tidskriftsartikel (refereegranskat)
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| 35. |
- Wang, Yingdi, et al.
(författare)
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Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 465:7297
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Tidskriftsartikel (refereegranskat)abstract
- In development, tissue regeneration or certain diseases, angiogenic growth leads to the expansion of blood vessels and the lymphatic vasculature. This involves endothelial cell proliferation as well as angiogenic sprouting, in which a subset of cells, termed tip cells, acquires motile, invasive behaviour and extends filopodial protrusions. Although it is already appreciated that angiogenesis is triggered by tissue-derived signals, such as vascular endothelial growth factor (VEGF) family growth factors, the resulting signalling processes in endothelial cells are only partly understood. Here we show with genetic experiments in mouse and zebrafish that ephrin-B2, a transmembrane ligand for Eph receptor tyrosine kinases, promotes sprouting behaviour and motility in the angiogenic endothelium. We link this pro-angiogenic function to a crucial role of ephrin-B2 in the VEGF signalling pathway, which we have studied in detail for VEGFR3, the receptor for VEGF-C. In the absence of ephrin-B2, the internalization of VEGFR3 in cultured cells and mutant mice is defective, which compromises downstream signal transduction by the small GTPase Rac1, Akt and the mitogen-activated protein kinase Erk. Our results show that full VEGFR3 signalling is coupled to receptor internalization. Ephrin-B2 is a key regulator of this process and thereby controls angiogenic and lymphangiogenic growth.
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| 36. |
- Adhikari, Subash, et al.
(författare)
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A high-stringency blueprint of the human proteome
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Forskningsöversikt (refereegranskat)abstract
- The Human Proteome Organization (HUPO) launched the Human Proteome Project (HPP) in 2010, creating an international framework for global collaboration, data sharing, quality assurance and enhancing accurate annotation of the genome-encoded proteome. During the subsequent decade, the HPP established collaborations, developed guidelines and metrics, and undertook reanalysis of previously deposited community data, continuously increasing the coverage of the human proteome. On the occasion of the HPP’s tenth anniversary, we here report a 90.4% complete high-stringency human proteome blueprint. This knowledge is essential for discerning molecular processes in health and disease, as we demonstrate by highlighting potential roles the human proteome plays in our understanding, diagnosis and treatment of cancers, cardiovascular and infectious diseases.
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| 37. |
- Bret, Antoine, et al.
(författare)
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Magnetic field effects on instabilities driven by a field-aligned relativistic warm electron beam and warm bulk electrons
- 2007
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Ingår i: 34th European Physical Society Conference on Plasma Physics,2007. - Warsaw : European Physical Society. ; , s. P2.079-
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Konferensbidrag (refereegranskat)abstract
- Instabilities driven by relativistic electron beams are being investigated due to their importance for plasma heating and electromagnetic field generation in astrophysical and laboratory plasmas. Particle-in-cell (PIC) simulations of initially unmagnetized colliding plasmas have demonstrated the generation of strong magnetic fields and a moderate electron acceleration. The inclusion of a flow-aligned magnetic field suppresses the electromagnetic filamentation instability and PIC simulations have shown that the plasma dynamics turns quasi-electrostatic. To quantify the impact of the magnetic field, we have analyzed numerically a magnetized multi-fluid model that includes a kinetic pressure term. This fluid model allows us to examine the beam-driven instability at all angles between the wavevector and the magnetic field vector. More accurate kinetic models typically focus only on the filamentation instability, due to the increased analytical complexity. We present here the fluid model and a growth rate map of the entire k-space for a beam Lorentz factor 4. We verify that the two-stream, mixed mode and filamentation instability belong to the same wave branch and that the magnetic field selects the fastest-growing mode. We estimate the magnetic fields required to suppress the filamentation and the mixed mode instabilities.
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| 38. |
- Bret, Antoine, et al.
(författare)
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Oblique electromagnetic instabilities for a hot relativistic beam interacting with a hot and magnetized plasma
- 2006
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Ingår i: Physics of Plasmas. - : AIP Publishing. - 1070-664X .- 1089-7674. ; 13:8, s. 082109-1-082109-8
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Tidskriftsartikel (refereegranskat)abstract
- The temperature-dependent fluid model from Phys. Plasmas 13, 042106 (2006) is expanded in order to explore the oblique electromagnetic instabilities, which are driven by a hot relativistic electron beam that is interpenetrating a hot and magnetized plasma. The beam velocity vector is parallel to the magnetic-field direction. The results are restricted to nonrelativistic temperatures. The growth rates of all instabilities but the two-stream instability can be reduced by a strong magnetic field so that the distribution of unstable waves becomes almost one dimensional. For high beam densities, highly unstable oblique modes dominate the spectrum of unstable waves as long as omega(c)/omega(p)less than or similar to 2 gamma(3/2)(b), where omega(c) is the electron gyrofrequency, omega(p) is the electron plasma frequency, and gamma(b) is the relativistic factor of the beam. A uniform stabilization over the entire k space cannot be achieved.
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| 39. |
- Deutsch, Eric W., et al.
(författare)
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p Advances and Utility of the Human Plasma Proteome
- 2021
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 20:12, s. 5241-5263
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Forskningsöversikt (refereegranskat)abstract
- The study of proteins circulating in blood offers tremendous opportunities to diagnose, stratify, or possibly prevent diseases. With recent technological advances and the urgent need to understand the effects of COVID19, the proteomic analysis of blood-derived serum and plasma has become even more important for studying human biology and pathophysiology. Here we provide views and perspectives about technological developments and possible clinical applications that use mass-spectrometry(MS)- or affinity-based methods. We discuss examples where plasma proteomics contributed valuable insights into SARS-CoV-2 infections, aging, and hemostasis and the opportunities offered by combining proteomics with genetic data. As a contribution to the Human Proteome Organization (HUPO) Human Plasma Proteome Project (HPPP), we present the Human Plasma PeptideAtlas build 2021-07 that comprises 4395 canonical and 1482 additional nonredundant human proteins detected in 240 MS-based experiments. In addition, we report the new Human Extracellular Vesicle PeptideAtlas 2021-06, which comprises five studies and 2757 canonical proteins detected in extracellular vesicles circulating in blood, of which 74% (2047) are in common with the plasma PeptideAtlas. Our overview summarizes the recent advances, impactful applications, and ongoing challenges for translating plasma proteomics into utility for precision medicine.
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| 40. |
- Eifert, S, et al.
(författare)
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Applying the Gender Lens to Risk Factors and Outcome after Adult Cardiac Surgery
- 2014
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Ingår i: Viszeralmedizin. - : S. Karger AG. - 1662-6664. ; 30:2, s. 99-106
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background: </i></b>Applying the gender lens to risk factors and outcome after adult cardiac surgery is of major clinical interest, as the inclusion of sex and gender in research design and analysis may guarantee more comprehensive cardiovascular science and may consecutively result in a more effective surgical treatment as well as cost savings in cardiac surgery. <b><i>Methods: </i></b>We have reviewed classical cardiovascular risk factors (diabetes, arterial hypertension, hyperlipidemia, smoking) according to a gender-based approach. Furthermore, we have examined comorbidities such as depression, renal insufficiency, and hormonal influences in regard to gender. Gender-sensitive economic aspects have been evaluated, surgical outcome has been analyzed, and cardiovascular research has been considered from a gender perspective. <b><i>Results: </i></b>The influence of typical risk factors and outcome after cardiac surgery has been evaluated from a gender perspective, and the gender-specific distribution of these risk factors is reported on. The named comorbidities are listed. Economic aspects demonstrated a gender gap. Outcome after coronary and valvular surgeries as well as after heart transplantation are displayed in this regard. Results after postoperative use of intra-aortic balloon pump are shown. Gender-related aspects of clinical and biomedical cardiosurgical research are reported. <b><i>Conclusions: </i></b>Female gender has become an independent risk factor of survival after the majority of cardiosurgical procedures. Severely impaired left ventricular ejection fraction independently predicts survival in men, whereas age does in females.
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| 41. |
- Fransner, Filippa, et al.
(författare)
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Tracing terrestrial DOC in the Baltic Sea - a 3-D model study
- 2016
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Ingår i: Global Biogeochemical Cycles. - 0886-6236 .- 1944-9224. ; 30:2, s. 134-148
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Tidskriftsartikel (refereegranskat)abstract
- The fate of terrestrial organic matter brought to the coastal seas by rivers, and its role in the global carbon cycle, are still not very well known. Here the degradation rate of terrestrial dissolved organic carbon (DOCter) is studied in the Baltic Sea, a subarctic semi-enclosed sea, by releasing it as a tracer in a 3-D circulation model and applying linear decay constants. A good agreement with available observational data is obtained by parameterizing the degradation in two rather different ways; one by applying a decay time on the order of 10 years to the whole pool of DOCter, and one by dividing the DOCter into one refractory pool and one pool subject to a decay time on the order of 1 year. The choice of parameterization has a significant effect on where in the Baltic Sea the removal takes place, which can be of importance when modeling the full carbon cycle and the CO2 exchange with the atmosphere. In both cases the biogeochemical decay operates on time scales less than the water residence time. Therefore only a minor fraction of the DOCter reaches the North Sea, whereas approximately 80% is removed by internal sinks within the Baltic Sea. This further implies that DOCter mineralization is an important link in land-sea-atmosphere cycling of carbon in coastal- and shelf seas that are heavily influenced by riverine DOC.
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| 42. |
- Harrison, Dick, et al.
(författare)
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Sverige i andra världskriget
- 2010
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Ingår i: Om Tyskland segrat - 53 alternativa scenarier. - 9789185183999 ; , s. 291-314
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 43. |
- Joseph, A, et al.
(författare)
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Metabolic features of cancer cells impact immunosurveillance
- 2021
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Ingår i: Journal for immunotherapy of cancer. - : BMJ. - 2051-1426. ; 9:6
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Tidskriftsartikel (refereegranskat)abstract
- Tumors rewire their metabolism to achieve robust anabolism and resistance against therapeutic interventions like cisplatin treatment. For example, a prolonged exposure to cisplatin causes downregulation of pyridoxal kinase (PDXK), the enzyme that generates the active vitamin B6, and upregulation of poly ADP-ribose (PAR) polymerase-1 (PARP1) activity that requires a supply of nicotinamide (vitamin B3) adenine dinucleotide. We investigated the impact of the levels of PDXK and PAR on the local immunosurveillance (ie, density of the antigen presenting cells and adaptive immune response by CD8 T lymphocytes) in two different tumor types.MethodsTumors from patients with locally advanced cervical carcinoma (LACC) and non-small cell lung cancer (NSCLC) were stained for PAR, PDXK, dendritic cell lysosomal associated membrane glycoprotein (DC-LAMP) and CD8 T cell infiltration. Their correlations and prognostic impact were assessed. Cisplatin-resistant NSCLC cell clones isolated from Lewis-lung cancer (LLC) cells were evaluated for PAR levels by immunoblot. Parental (PARlow) and cisplatin-resistant (PARhigh) clones were subcutaneously injected into the flank of C57BL/6 mice. Tumors were harvested to evaluate their immune infiltration by flow cytometry.ResultsThe infiltration of tumors by CD8 T and DC-LAMP+ cells was associated with a favorable overall survival in patients with LACC (p=0.006 and p=0.008, respectively) and NSCLC (p<0.001 for both CD8 T and DC-LAMP cells). We observed a positive correlation between PDXK expression and the infiltration by DC-LAMP (R=0.44, p=0.02 in LACC, R=0.14, p=0.057 in NSCLC), and a negative correlation between PAR levels and CD8 T lymphocytes (R=−0.39, p=0.034 in LACC, R=−0.18, p=0.017 in NSCLC). PARP1 is constitutively hyperactivated in cisplatin-resistant LLC cells manifesting elevated intracellular levels of poly(ADP-ribosyl)ated proteins (PARhigh). Tumors formed by such cancer cells injected into immunocompetent mice were scarcely infiltrated by CD8 T (p=0.028) and antigen presenting cells (p=0.086).ConclusionsOncometabolic features can impact local immunosurveillance, providing new functional links between cisplatin resistance and therapeutic failure.
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| 44. |
- Legrain, Pierre, et al.
(författare)
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The Human Proteome Project : Current State and Future Direction
- 2011
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- After the successful completion of the Human Genome Project, the Human Proteome Organization has recently officially launched a global Human Proteome Project (HPP), which is designed to map the entire human protein set. Given the lack of protein-level evidence for about 30% of the estimated 20,300 protein-coding genes, a systematic global effort will be necessary to achieve this goal with respect to protein abundance, distribution, subcellular localization, interaction with other biomolecules, and functions at specific time points. As a general experimental strategy, HPP research groups will use the three working pillars for HPP: mass spectrometry, antibody capture, and bioinformatics tools and knowledge bases. The HPP participants will take advantage of the output and cross-analyses from the ongoing Human Proteome Organization initiatives and a chromosome-centric protein mapping strategy, termed C-HPP, with which many national teams are currently engaged. In addition, numerous biologically driven and disease-oriented projects will be stimulated and facilitated by the HPP. Timely planning with proper governance of HPP will deliver a protein parts list, reagents, and tools for protein studies and analyses, and a stronger basis for personalized medicine. The Human Proteome Organization urges each national research funding agency and the scientific community at large to identify their preferred pathways to participate in aspects of this highly promising project in a HPP consortium of funders and investigators.
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| 45. |
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| 46. |
- Mayer, Gerhard, et al.
(författare)
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The HUPO proteomics standards initiative-mass spectrometry controlled vocabulary
- 2013
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Ingår i: Database: the journal of biological databases and curation. - : Oxford University Press (OUP). - 1758-0463. ; , s. 009-009
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Tidskriftsartikel (refereegranskat)abstract
- Controlled vocabularies (CVs), i.e. a collection of predefined terms describing a modeling domain, used for the semantic annotation of data, and ontologies are used in structured data formats and databases to avoid inconsistencies in annotation, to have a unique (and preferably short) accession number and to give researchers and computer algorithms the possibility for more expressive semantic annotation of data. The Human Proteome Organization (HUPO)-Proteomics Standards Initiative (PSI) makes extensive use of ontologies/CVs in their data formats. The PSI-Mass Spectrometry (MS) CV contains all the terms used in the PSI MS-related data standards. The CV contains a logical hierarchical structure to ensure ease of maintenance and the development of software that makes use of complex semantics. The CV contains terms required for a complete description of an MS analysis pipeline used in proteomics, including sample labeling, digestion enzymes, instrumentation parts and parameters, software used for identification and quantification of peptides/proteins and the parameters and scores used to determine their significance. Owing to the range of topics covered by the CV, collaborative development across several PSI working groups, including proteomics research groups, instrument manufacturers and software vendors, was necessary. In this article, we describe the overall structure of the CV, the process by which it has been developed and is maintained and the dependencies on other ontologies.
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| 47. |
- Omenn, Gilbert S., et al.
(författare)
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Progress on Identifying and Characterizing the Human Proteome : 2018 Metrics from the HUPO Human Proteome Project
- 2018
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 17:12, s. 4031-4041
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Tidskriftsartikel (refereegranskat)abstract
- The Human Proteome Project (HPP) annually reports on progress throughout the field in credibly identifying and characterizing the human protein parts list and making proteomics an integral part of multiomics studies in medicine and the life sciences. NeXtProt release 2018-01-17, the baseline for this sixth annual HPP special issue of the Journal of Proteome Research, contains 17 470 PE1 proteins, 89% of all neXtProt predicted PE1-4 proteins, up from 17 008 in release 2017-01-23 and 13 975 in release 2012-02-24. Conversely, the number of neXtProt PE2,3,4 missing proteins has been reduced from 2949 to 2579 to 2186 over the past two years. Of the PEI proteins, 16 092 are based on mass spectrometry results, and 1378 on other kinds of protein studies, notably protein protein interaction findings. PeptideAtlas has 15 798 canonical proteins, up 625 over the past year, including 269 from SUMOylation studies. The largest reason for missing proteins is low abundance. Meanwhile, the Human Protein Atlas has released its Cell Atlas, Pathology Atlas, and updated Tissue Atlas, and is applying recommendations from the International Working Group on Antibody Validation. Finally, there is progress using the quantitative multiplex organ-specific popular proteins targeted proteomics approach in various disease categories.
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| 48. |
- Omenn, Gilbert S., et al.
(författare)
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Research on the Human Proteome Reaches a Major Milestone : > 90% of Predicted Human Proteins Now Credibly Detected, According to the HUPO Human Proteome Project
- 2020
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 19:12, s. 4735-4746
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Tidskriftsartikel (refereegranskat)abstract
- According to the 2020 Metrics of the HUPO Human Proteome Project (HPP), expression has now been detected at the protein level for >90% of the 19 773 predicted proteins coded in the human genome. The HPP annually reports on progress made throughout the world toward credibly identifying and characterizing the complete human protein parts list and promoting proteomics as an integral part of multiomics studies in medicine and the life sciences. NeXtProt release 2020-01 classified 17 874 proteins as PE1, having strong protein-level evidence, up 180 from 17 694 one year earlier. These represent 90.4% of the 19 773 predicted coding genes (all PE1,2,3,4 proteins in neXtProt). Conversely, the number of neXtProt PE2,3,4 proteins, termed the "missing proteins" (MPs), was reduced by 230 from 2129 to 1899 since the neXtProt 2019-01 release. PeptideAtlas is the primary source of uniform reanalysis of raw mass spectrometry data for neXtProt, supplemented this year with extensive data from MassIVE. PeptideAtlas 2020-01 added 362 canonical proteins between 2019 and 2020 and MassIVE contributed 84 more, many of which converted PE1 entries based on non-MS evidence to the MS-based subgroup. The 19 Biology and Disease-driven B/D-HPP teams continue to pursue the identification of driver proteins that underlie disease states, the characterization of regulatory mechanisms controlling the functions of these proteins, their proteoforms, and their interactions, and the progression of transitions from correlation to coexpression to causal networks after system perturbations. And the Human Protein Atlas published Blood, Brain, and Metabolic Atlases.
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| 49. |
- Omenn, Gilbert S., et al.
(författare)
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The 2023 Report on the Proteome from the HUPO Human Proteome Project
- 2024
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 23:2, s. 532-549
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Forskningsöversikt (refereegranskat)abstract
- Since 2010, the Human Proteome Project (HPP), the flagship initiative of the Human Proteome Organization (HUPO), has pursued two goals: (1) to credibly identify the protein parts list and (2) to make proteomics an integral part of multiomics studies of human health and disease. The HPP relies on international collaboration, data sharing, standardized reanalysis of MS data sets by PeptideAtlas and MassIVE-KB using HPP Guidelines for quality assurance, integration and curation of MS and non-MS protein data by neXtProt, plus extensive use of antibody profiling carried out by the Human Protein Atlas. According to the neXtProt release 2023-04-18, protein expression has now been credibly detected (PE1) for 18,397 of the 19,778 neXtProt predicted proteins coded in the human genome (93%). Of these PE1 proteins, 17,453 were detected with mass spectrometry (MS) in accordance with HPP Guidelines and 944 by a variety of non-MS methods. The number of neXtProt PE2, PE3, and PE4 missing proteins now stands at 1381. Achieving the unambiguous identification of 93% of predicted proteins encoded from across all chromosomes represents remarkable experimental progress on the Human Proteome parts list. Meanwhile, there are several categories of predicted proteins that have proved resistant to detection regardless of protein-based methods used. Additionally there are some PE1–4 proteins that probably should be reclassified to PE5, specifically 21 LINC entries and ∼30 HERV entries; these are being addressed in the present year. Applying proteomics in a wide array of biological and clinical studies ensures integration with other omics platforms as reported by the Biology and Disease-driven HPP teams and the antibody and pathology resource pillars. Current progress has positioned the HPP to transition to its Grand Challenge Project focused on determining the primary function(s) of every protein itself and in networks and pathways within the context of human health and disease.
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| 50. |
- Schwenk, Jochen M., et al.
(författare)
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The Human Plasma Proteome Draft of 2017 : Building on the Human Plasma PeptideAtlas from Mass Spectrometry and Complementary Assays
- 2017
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 16:12, s. 4299-4310
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Forskningsöversikt (refereegranskat)abstract
- Human blood plasma provides a highly accessible window to the proteome of any individual in health and disease. Since its inception in 2002, the Human Proteome Organization's Human Plasma Proteome Project (HPPP) has been promoting advances in the study and understanding of the full protein complement of human plasma and on determining the abundance and modifications of its components. In 2017, we review the history of the HPPP and the advances of human plasma proteomics in general, including several recent achievements. We then present the latest 2017-04 build of Human Plasma PeptideAtlas, which yields ∼43 million peptide-spectrum matches and 122,730 distinct peptide sequences from 178 individual experiments at a 1% protein-level FDR globally across all experiments. Applying the latest Human Proteome Project Data Interpretation Guidelines, we catalog 3509 proteins that have at least two non-nested uniquely mapping peptides of nine amino acids or more and >1300 additional proteins with ambiguous evidence. We apply the same two-peptide guideline to historical PeptideAtlas builds going back to 2006 and examine the progress made in the past ten years in plasma proteome coverage. We also compare the distribution of proteins in historical PeptideAtlas builds in various RNA abundance and cellular localization categories. We then discuss advances in plasma proteomics based on targeted mass spectrometry as well as affinity assays, which during early 2017 target ∼2000 proteins. Finally, we describe considerations about sample handling and study design, concluding with an outlook for future advances in deciphering the human plasma proteome.
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