| 1. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 2. |
- Lauc, Gordan, et al.
(författare)
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Loci Associated with N-Glycosylation of Human Immunoglobulin G Show Pleiotropy with Autoimmune Diseases and Haematological Cancers
- 2013
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 9:1, s. e1003225-
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Tidskriftsartikel (refereegranskat)abstract
- Glycosylation of immunoglobulin G (IgG) influences IgG effector function by modulating binding to Fc receptors. To identify genetic loci associated with IgG glycosylation, we quantitated N-linked IgG glycans using two approaches. After isolating IgG from human plasma, we performed 77 quantitative measurements of N-glycosylation using ultra-performance liquid chromatography (UPLC) in 2,247 individuals from four European discovery populations. In parallel, we measured IgG N-glycans using MALDI-TOF mass spectrometry (MS) in a replication cohort of 1,848 Europeans. Meta-analysis of genome-wide association study (GWAS) results identified 9 genome-wide significant loci (P<2.27x10(-9)) in the discovery analysis and two of the same loci (B4GALT1 and MGAT3) in the replication cohort. Four loci contained genes encoding glycosyltransferases (ST6GAL1, B4GALT1, FUT8, and MGAT3), while the remaining 5 contained genes that have not been previously implicated in protein glycosylation (IKZF1, IL6ST-ANKRD55, ABCF2-SMARCD3, SUV420H1, and SMARCB1-DERL3). However, most of them have been strongly associated with autoimmune and inflammatory conditions (e. g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). Follow-up functional experiments in haplodeficient Ikzf1 knock-out mice showed the same general pattern of changes in IgG glycosylation as identified in the meta-analysis. As IKZF1 was associated with multiple IgG N-glycan traits, we explored biomarker potential of affected N-glycans in 101 cases with SLE and 183 matched controls and demonstrated substantial discriminative power in a ROC-curve analysis (area under the curve=0.842). Our study shows that it is possible to identify new loci that control glycosylation of a single plasma protein using GWAS. The results may also provide an explanation for the reported pleiotropy and antagonistic effects of loci involved in autoimmune diseases and haematological cancer.
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| 3. |
- Lukic, Ana
(författare)
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Eicosanoids and exosomes : a link between macrophages and lung cancer
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chronic inflammation increases the risk of lung cancer. Macrophages (MO) are important players in inflammation, with regulatory and executive functions. Eicosanoids and exosomes can be both triggers and mediators of these functions. Cysteinyl leukotrienes (CysLTs) are the most potent mediators of broncho-constriction in the lungs, a function exerted via CysLT1 receptor. Their function in asthma is well described, but little is known about CysLTs and lung cancer. In the first study we investigated how the interaction between pulmonary epithelium and leukocytes affects CysLTs formation. Monocytic cells and eosinophils formed LTC4, which was exported and promptly converted to LTD4 by pulmonary epithelial cells in a transcellular manner. The lung cancer cell line A549 expressing γ-glutamyl transpeptidase 1 (GGT-1) showed a high activity. Exosomes released by A549 cells also contained GGT-1 and efficiently converted LTC4 to LTD4. On the other hand, healthy bronchial epithelial cells (PBEC) expressing GGT-5 formed LTD4 12 times more slowly. The results highlight an active role for epithelial cells and their exosomes in biosynthesis of LTD4, which may be of particular relevance in the lung, given that LTD4 is the most potent agonist of CysLT1. MOs can be differentiated from blood monocytes with GM-CSF and M-CSF, resulting in cells primed toward the inflammatory M1- and resolving M2-states. A comprehensive analysis of eicosanoid formation in these two in vitro models is missing and our second study focused on this gap. By LC-MS analysis, we observed that both MO phenotypes released pro-resolving lipid mediators (PGE metabolite, LXA4) in resting conditions. When the same cells were incubated (30 min) with bacterial stimuli, there was a shift to pro-inflammatory eicosanoids: M-CSF MOs produced high amounts of LTC4, relevant for M2 functions in asthma. GM-CSF cells expressed the highest levels of cPLA2, 5-LO and FLAP; and in ionophore incubations these cells also produced the highest levels of 5-HETE. However, MCSF MO formed more products apparently due to a better response to bacterial stimuli, demonstrated by enhanced mobilization and activation of cPLA2 and 5-LO. In conclusion, GM-CSF and M-CSF can regulate specific pathways in MOs, and it appears that eicosanoid biosynthesis primarily reflect the cellular response and activation mechanisms, rather than the protein expression profile. In colon cancer a pro-tumorigenic effect of LTD4 but not LTC4 has been demonstrated. A pro-tumorigenic effect has been shown also for exosomes. To extend the findings of our first study, we used pleura exudates from lung cancer patients to isolate primary cancer cells and exosomes. Both cells and exosomes metabolized LTC4 to LTD4, and we also found that exosomes stimulated CysLTs formation in the cancer cells. Cancer cells from all patients expressed CysLT1, and exosomes promoted their migration and survival in a CysLT1 dependent manner, as demonstrated by the inhibition by montelukast (MK) treatment, a CysLT1 antagonist used to treat asthma. In cancer, interactions between the transformed cancer cells and other recruited cell types in the tumor are important. Tumor associated macrophages (TAMs) provide cancer cells with a suitable low-grade inflammation milieu including growth promoting factors. Taken together, the results in this thesis suggest a novel pro-tumorigenic mechanism based on this theme, driven by the exosomes/CysLT1 cascade: TAMs provide LTC4 that lung cancer cells and their exosomes convert to LTD4. Via CysLT1 receptor this promotes survival and migration of the cancer cells. A protective effect in lung cancer has been previously described for MK and our results suggest a possible mechanism for this, driven by the exosomes/ CysLT1 cascade, further encouraging the use of this drug in lung cancer treatment.
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| 4. |
- Magalhaes, Isabelle, et al.
(författare)
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Facing the future : challenges and opportunities in adoptive T cell therapy in cancer
- 2019
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Ingår i: Expert Opinion on Biological Therapy. - : Taylor & Francis Group. - 1471-2598 .- 1744-7682. ; 19:8, s. 811-827
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: In recent years, immunotherapy for the treatment of solid cancer has emerged as a promising therapeutic alternative. Adoptive cell therapy (ACT), especially T cell-based, has been found to cause tumor regression and even cure in a percentage of treated patients. Checkpoint inhibitors further underscore the potential of the T cell compartment in the treatment of cancer. Not all patients respond to these treatments; however, many challenges remain.AREAS COVERED: This review covers the challenges and progress in tumor antigen target identification and selection, and cell product manufacturing for T cell ACT. Tumor immune escape mechanisms and strategies to overcome those in the context of T cell ACT are also discussed.EXPERT OPINION: The immunotherapy toolbox is rapidly expanding and improving, and the future promises further breakthroughs in the T cell ACT field. The heterogeneity of the tumor microenvironment and the multiplicity of tumor immune escape mechanisms pose formidable challenges to successful T cell immunotherapy in solid tumors, however. Individualized approaches and strategies combining treatments targeting different immunotherapeutic aspects will be needed in order to expand the applicability and improve the response rates in future.
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| 5. |
- Mayén, Ana Lucia, et al.
(författare)
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A longitudinal evaluation of alcohol intake throughout adulthood and colorectal cancer risk
- 2022
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 37:9, s. 915-929
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alcohol intake is an established risk factor for colorectal cancer (CRC); however, there is limited knowledge on whether changing alcohol drinking habits during adulthood modifies CRC risk. Objective: Leveraging longitudinal exposure assessments on alcohol intake at different ages, we examined the relationship between change in alcohol intake and subsequent CRC risk. Methods: Within the European Prospective Investigation into Cancer and Nutrition, changes in alcohol intake comparing follow-up with baseline assessments were investigated in relation to CRC risk. The analysis included 191,180, participants and 1530 incident CRC cases, with exclusion of the first three years of follow-up to minimize reverse causation. Trajectory profiles of alcohol intake, assessed at ages 20, 30, 40, 50 years, at baseline and during follow-up, were estimated using latent class mixed models and related to CRC risk, including 407,605 participants and 5,008 incident CRC cases. Results: Mean age at baseline was 50.2 years and the follow-up assessment occurred on average 7.1 years later. Compared to stable intake, a 12 g/day increase in alcohol intake during follow-up was positively associated with CRC risk (HR = 1.15, 95%CI 1.04, 1.25), while a 12 g/day reduction was inversely associated with CRC risk (HR = 0.86, 95%CI 0.78, 0.95). Trajectory analysis showed that compared to low alcohol intake, men who increased their alcohol intake from early- to mid- and late-adulthood by up to 30 g/day on average had significantly increased CRC risk (HR = 1.24; 95%CI 1.08, 1.42), while no associations were observed in women. Results were consistent by anatomical subsite. Conclusions: Increasing alcohol intake during mid-to-late adulthood raised CRC risk, while reduction lowered risk.
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| 6. |
- Morales-Berstein, Fernanda, et al.
(författare)
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Ultra-processed foods, adiposity and risk of head and neck cancer and oesophageal adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition study : a mediation analysis
- 2024
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Ingår i: European Journal of Nutrition. - 1436-6215. ; 63:2, s. 377-396
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To investigate the role of adiposity in the associations between ultra-processed food (UPF) consumption and head and neck cancer (HNC) and oesophageal adenocarcinoma (OAC) in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.METHODS: Our study included 450,111 EPIC participants. We used Cox regressions to investigate the associations between the consumption of UPFs and HNC and OAC risk. A mediation analysis was performed to assess the role of body mass index (BMI) and waist-to-hip ratio (WHR) in these associations. In sensitivity analyses, we investigated accidental death as a negative control outcome.RESULTS: During a mean follow-up of 14.13 ± 3.98 years, 910 and 215 participants developed HNC and OAC, respectively. A 10% g/d higher consumption of UPFs was associated with an increased risk of HNC (hazard ratio [HR] = 1.23, 95% confidence interval [CI] 1.14-1.34) and OAC (HR = 1.24, 95% CI 1.05-1.47). WHR mediated 5% (95% CI 3-10%) of the association between the consumption of UPFs and HNC risk, while BMI and WHR, respectively, mediated 13% (95% CI 6-53%) and 15% (95% CI 8-72%) of the association between the consumption of UPFs and OAC risk. UPF consumption was positively associated with accidental death in the negative control analysis.CONCLUSIONS: We reaffirmed that higher UPF consumption is associated with greater risk of HNC and OAC in EPIC. The proportion mediated via adiposity was small. Further research is required to investigate other mechanisms that may be at play (if there is indeed any causal effect of UPF consumption on these cancers).
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| 7. |
- Rudovica, Vita, et al.
(författare)
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Valorization of Marine Waste : Use of Industrial By-Products and Beach Wrack Towards the Production of High Added-Value Products
- 2021
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Ingår i: Frontiers in Marine Science. - : Frontiers Media S.A.. - 2296-7745. ; 8
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Forskningsöversikt (refereegranskat)abstract
- Biomass is defined as organic matter from living organisms represented in all kingdoms. It is recognized to be an excellent source of proteins, polysaccharides and lipids and, as such, embodies a tailored feedstock for new products and processes to apply in green industries. The industrial processes focused on the valorization of terrestrial biomass are well established, but marine sources still represent an untapped resource. Oceans and seas occupy over 70% of the Earth's surface and are used intensively in worldwide economies through the fishery industry, as logistical routes, for mining ores and exploitation of fossil fuels, among others. All these activities produce waste. The other source of unused biomass derives from the beach wrack or washed-ashore organic material, especially in highly eutrophicated marine ecosystems. The development of high-added-value products from these side streams has been given priority in recent years due to the detection of a broad range of biopolymers, multiple nutrients and functional compounds that could find applications for human consumption or use in livestock/pet food, pharmaceutical and other industries. This review comprises a broad thematic approach in marine waste valorization, addressing the main achievements in marine biotechnology for advancing the circular economy, ranging from bioremediation applications for pollution treatment to energy and valorization for biomedical applications. It also includes a broad overview of the valorization of side streams in three selected case study areas: Norway, Scotland, and the Baltic Sea.
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