1. |
- Andersson, Bengt-Åke, et al.
(författare)
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Cigarette smoking affects microRNAs and inflammatory biomarkers in healthy individuals and an association to single nucleotide polymorphisms is indicated
- 2019
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Ingår i: Biomarkers. - : Taylor & Francis. - 1354-750X .- 1366-5804. ; 24:2, s. 180-185
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cigarette smoke induces inflammation and remodels immune response. Genetic and epigenetic alterations might be involved in the pathogenesis of smoking related diseases. In this study, we investigated the effect of smoking on systemic inflammation biomarkers and epigenetic changes at microRNA (miRNA) expression level. We also examined if the levels of inflammatory biomarkers were associated with selected single nucleotide polymorphisms (SNPs).METHOD: From 39 smokers and 101 non-smokers, levels of total white blood cells (WBCs) and its subpopulations, plasma cytokines/chemokines/proteins and miRNAs were analysed. For three biomarkers, C-reactive protein (CRP), MCP-1 and IFN-γ that were affected by smoking, the influence of SNPs was analyzed.RESULT: Elevated levels of total WBCs, neutrophils, monocytes, lymphocytes, CRP, MCP-1, IFN-γ and lower levels of miR-21 were detected in smokers. The elevated levels of IFN-γ in smokers was only statistically significantly associated with rs2069705 AG/GG SNP-genotype.CONCLUSIONS: A lower level of oncomir miRNA-21 and a higher level of immune modelling cytokine IFN-γ detected in smokers could be a protective immune response to cigarette smoke. The higher level of IFN-γ in smokers with a specific SNP genotype also suggests that a genetic interaction with smoking might predict the pathobiology of smoking related disease.
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2. |
- Andersson, Bengt-Åke
(författare)
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Circulating Biomarkers in Patients with Head and Neck Cancer and the Influence of Cigarette Smoking
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Head and neck cancer (HNC) is a collective name for heterogeneous tumors located in the head and neck regions for which smoking, alcohol and human papillomavirus (HPV) are documented risk factors. The survival of HNC patients has only improved marginally during the last decade. The most important prognostic factors are tumor size, local spread and distant metastases, tumor node metastasis (TNM) staging. Prognostic biomarkers are needed as a complement to TNM staging.The aim for this thesis was to investigate rapid and low cost blood based biomarkers which could indicate the risk of HNC, recurrence of the disease or the survival of HNC patients. Furthermore, the aim was to examine how cigarette smoking influences the levels of biomarkers.In paper I, a possible role of plasma cytokines or proteins associated with immune response or inflammation, as biomarkers for the survival of HNC patients was investigated. Higher levels of C-reactive protein (CRP) and tumor necrosis factor alpha (TNF-α) were detected in plasma of the patients compared with the levels in the controls. The elevated levels of these two biomarkers detected in patients were associated with decreased survival.In paper II, the influence of 45 single nucleotide polymorphisms (SNPs) located in 41 genes associated with cell cycle progression, cell death, DNA repair or immune response on cancer risk, tumor recurrence and survival in HNC patients were investigated. SNPs in immune response genes were associated with risk for HNC, an elevated risk for recurrence and a decreased survival in HNC patients.In paper III, the influence of cigarette smoking on levels of inflammatory cells, proteins or cytokines/chemokines, microRNAs (miRNAs) and SNPs was analysed in healthy smokers and non-smokers. Higher levels of total white blood cells (WBCs), neutrophils, monocytes, lymphocytes, neutrophil to lymphocyte ratio (NLR), CRP, monocyte chemoattractant protein- 1 (MCP-1) and interferon gamma (IFN-γ) were detected in smokers compared to non-smokers and indicate an inflammatory response. Also, a lower level of oncomiRNA miR-21was detected in smokers. This alteration, in combination with the elevated levels of IFN-γ in smokers could be a protective response to cigarette smoke. The higher levels of IFN-γ in smokers compared to non-smokers were however only detected in individuals with SNP rs2069705 genotype AG/GG. This indicates a genetic association of the levels of IFN-γ.In paper IV, the separate effects of cigarette smoking and HNC on inflammatory or immune biomarkers and the impact of high risk human papillomavirus, age and gender were investigated. Comparisons of circulating levels of WBCs and its subpopulations, plasma proteins or cytokines/chemokines between smoking and non-smoking patients, smoking and non-smoking controls and between the patient and control groups were analysed. Smoking had highest impact on elevated levels of WBCs, IFN-γ and MCP-1, and HNC had highest impact on elevated levels of neutrophils, monocytes, NLR, CRP, macrophage inflammatory protein 1 beta and TNF-α.In conclusion, host immune response associated parameters could be suitable as biomarkers for the risk of HNC, risk of recurrence or in predicting survival of HNC patients. This thesis show that HNC are associated with systemic inflammatory response and upregulated CRP and TNF-α is related to shorter survival in HNC patients. Additionally, SNPs in immune response genes such as rs1800629 in the TNF-α gene indicates a risk for HNC or an elevated risk for recurrence and a decreased survival in HNC patients. These rapid and low cost blood based biomarkers could be used in combination or as a supplement to established biomarkers in the clinic for a more personalized treatment modality.
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3. |
- Eboh, Francis Chinweuba, et al.
(författare)
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Economic evaluation of improvements in a waste-to-energy combined heat and power plant
- 2019
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Ingår i: Waste Management. - : Elsevier. - 0956-053X .- 1879-2456.
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Tidskriftsartikel (refereegranskat)abstract
- Improving the efficiency of waste-to-energy combined heat and power plants increases their production of both electricity and heat. Economic evaluation of such improvements enables adequate decisions to be made between the various alternatives with respect to economic viability of the plant. In this study, the cost and profitability of different modifications to improve efficiency in a waste-to-energy plant are considered: these include the re-arrangement of air heaters, the introduction of a reheater, flue gas condensation (FGC) and an integrated gasification-combustion process. The base case and the modifications are evaluated and compared when operating either as a combined heat and power plant or as a power plant. Modelling, simulation and cost estimations were performed with the Aspen Plus software. Although the integrated gasification-combustion technology with FGC has the highest exergy efficiency, its higher capital cost is greater than all of the other alternatives. Modification 6, which involves both re-arrangement and changing the air heating medium has the lowest capital cost with respect to enhancing exergy efficiency. Modifications 1 and 7, involving FGC, are the best alternatives for the capital cost per total unit of revenue generated. These modifications not only provides the highest heat production but also the highest net present value (NPV). The base case and the modifications investigated all have positive NPV, indicating that a waste-to-energy combined heat and power plant is an attractive investment. However, an increase of about 122% in the gate fees would be required for a system with only electricity production to be profitable.
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4. |
- Lewin, Nongnit, et al.
(författare)
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Single Nucleotide Polymorphism and Cancer Risk, Tumour Recurrence, or Survival of Head and Neck Cancer Patients
- 2017
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Ingår i: Oncology. - : S. Karger AG. - 0030-2414 .- 1423-0232. ; 92, s. 161-169
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This paper aims at studying the influence of single-nucleotide polymorphisms (SNPs) on cancer risk, tumor recurrence, and survival in head and neck (H&N) cancer patients. Methods: A total of 45 SNPs in 41 genes were investigated. A total of 174 Caucasian H&N cancer patients and 245 healthy blood donors were enrolled in the study. Results: Ten SNPs were associated with H&N cancer risk, but the identified SNPs differed among males and females. Some of the SNPs were related to immune response genes. The immune response gene SNPs were also related to survival. In particular, we noted that the tumor necrosis factor alpha (TNFα) rs1800629 could have an influence on cancer risk, tumor recurrence as well as survival. Conclusion: Genetic variation of the TNFα rs1800629 might be useful as a biomarker in clinical decision-making since it was found to be related to cancer risk, tumor recurrence, and survival of H&N cancer patients.
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5. |
- Lewin, Nongnit, et al.
(författare)
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The Influence of Adjuvant Radiotherapy and Single Nucleotide Polymorphisms on Circulating Immune Response Cell Numbers and Phenotypes of Patients With Breast Cancer
- 2019
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Ingår i: Anticancer Research. - : INT INST ANTICANCER RESEARCH. - 0250-7005 .- 1791-7530. ; 39:9, s. 4957-4963
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: Adjuvant radiotherapy (RT) damages multiple layers of skin, muscle, blood vessels and blood cells that are included within the RT area. Indirect, bystander systemic effects could also develop in cells not directly hit by radiation. Materials and Methods: Ninety-three female patients recovering from breast cancer surgery and 82 female healthy blood donors were analyzed. For identification of systemic adaptive and innate immune response, rapid and low-cost blood-based biomarkers were assayed. Results: Post-operated breast cancer patients had a decreased number of circulating adaptive immune response cells but increased number of circulating immunosuppressive myeloid subpopulations. RT decreased the number of T-cells and platelets without influencing the number of immunosuppressive myeloid subpopulations. Alterations in the number and phenotypes of T-cell subpopulations were associated with SNPs. Conclusion: The combination of RT and immunotherapy might provide optimal treatment for cancer patients.
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6. |
- Lewin, Nongnit, et al.
(författare)
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The Influence of Single Nucleotide Polymorphisms and Adjuvant Radiotherapy on Systemic Inflammatory Proteins, Chemokines and Cytokines of Patients With Breast Cancer
- 2019
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Ingår i: Anticancer Research. - : INT INST ANTICANCER RESEARCH. - 0250-7005 .- 1791-7530. ; 39:3, s. 1287-1292
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Tidskriftsartikel (refereegranskat)abstract
- Independently of tumour and treatment modulation, the host immune response status plays an important role in the clinical outcome of patients with cancer. The influence of single nucleotide polymorphisms (SNPs) and adjuvant radiotherapy (RT) on the systemic immune response status of patients with breast cancer was investigated. Materials and Methods: Eighty-six female patients recovering from breast cancer surgery were investigated. As a control cohort, 82 healthy female blood donors were used. Blood-based SNPs, plasma C-reactive protein (CRP), cytokines and chemokines were analyzed for this purpose. Results: Independently of tumour stage and hormone receptor status, dysregulation of plasma CRP, chemokine (C-C motif) ligand 4 (CCL4) and interleukin 2 (IL2), but not CCL5, CCL2, platelet-derived growth factor, IL6, IL10, IL12, interferon-gamma or tumour necrosis factor alpha were detected in the patients when compared to controls. The extent of alteration in plasma levels of CRP and IL2 patients was significantly associated with SNPs in CRP rs1800947 and IL2 rs6822844, respectively. These SNPs had no influence on the levels of corresponding plasma biomarkers in the healthy controls. Adjuvant RT reduced plasma CRP and CCL5 levels in patients with regards to CRP rs1800947CC, CCL5 rs2107538GG and CCL5 rs2280789AA sequences. Conclusion: Dysregulation of immune responses, as indicated by plasma levels of CRP, CCL4 and IL2 were found in patients with breast cancer despite the removal of the tumour mass. The benefit of adjuvant RT, as indicated by reduced plasma amounts of inflammatory protein CRP and chemokine CCL5 were based on the SNPs of the patients. Analyses of blood-based SNPs, plasma CRP, IL2 and CCL5 are low cost, rapid and can be carried out using general laboratory facilities while requiring only a peripheral blood sample. The possibility of using these blood-based biomarkers as an indicator of patient immune status for selection of individual patient treatment warrants further investigation.
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7. |
- Lewin, Nongnit, et al.
(författare)
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The use of rapid and cost-effective blood-based biomarkers in combination with tumour TNM stage for individual head and neck cancer patient treatment selection
- 2017
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Ingår i: Medical Oncology. - : HUMANA PRESS INC. - 1357-0560 .- 1559-131X. ; 34:4
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Forskningsöversikt (refereegranskat)abstract
- Head and neck (Hamp;N) cancer is an aggressive disease and the incidence has increased in younger population worldwide. Tumour TNM staging is the main basis for treatment decision despite significant variation in clinical outcome. Survival time of these patients has marginally improved during the last 30 years. Various biomarkers with cumbersome analysis, high cost, time consumption and requirement of special laboratory facilities have been investigated. However, none of these biomarkers have been shown to be suitable to use for individual Hamp;N cancer patient treatment selection in the clinic. For practical use in clinical settings, the given biomarkers must be simple to analyse, rapid, cost effective and available in routine laboratories. With this intension, we suggested the combination of standard TNM staging and biomarkers associated with inflammation such as neutrophils, neutrophil to lymphocyte ratio, plasma C-reactive protein or plasma tumour necrosis factor alpha (TNFa) and single-nucleotide polymorphism in TNFa rs1800629 using blood-based analysis. The optimal treatment outcome of Hamp;N cancer by using combination of TNM stage and these blood-based biomarkers for individual patient selection need further investigation.
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8. |
- Lind, Fredrik, 1978, et al.
(författare)
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12,000 Hours of Operation with Oxygen-Carriers in Industrially Relevant Scale (75,000 kWth).
- 2017
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Ingår i: VGB PowerTech.
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Tidskriftsartikel (refereegranskat)abstract
- Oxygen carrier aided combustion (OCAC) is a novel combustion method and a spin-off from chemical-looping combustion (CLC). The core of the technique lies in the utilization of an oxygen carrier (OC) as bed material, and the purpose to enhance the distribution of oxygen in fluidized bed (FB) boilers. The concept combines the robustness of the well-established technology FB boilers with the novel features of oxygen active properties introduced by the OC. Due to several similarities, the OCAC concept can also contribute with knowledge in a transitional path for the scale-up of other chemical-looping techniques, such as CLC, from lab to industrial scale. In this work, the first experiences are presented where a 75,000 kWth CFB-boiler has been operated with ilmenite (FeTiO3) as bed material during 12,000 hours with municipal solid waste as fuel. The investigation shows that ilmenite can replace the commonly used bed material silica-sand without any retrofitting of boiler equipment, and that ilmenite enhances the mass transfer of oxygen inside the furnace. The results show that ilmenite can drastically reduce the amount of carbon monoxide in the flue gas, even when the furnace is operated with an oxygen concentration that is lower compared to ordinary silica-sand operation. Even though still being in the early stages, this concept can contribute to overcome the threshold of understanding the mass transfer and mixing conditions in industrial conditions to enable scale-up of CLC.
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9. |
- Luetragoon, Thitiya, et al.
(författare)
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Interaction among smoking status, single nucleotide polymorphisms and markers of systemic inflammation in healthy individuals
- 2018
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Ingår i: Immunology. - : John Wiley & Sons. - 0019-2805 .- 1365-2567. ; 154:1, s. 98-103
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Tidskriftsartikel (refereegranskat)abstract
- Cigarette smoke contains toxic and carcinogenic substances that contribute to the development of cancer and various diseases. Genetic variation might be important, because not all smokers develop smoking-related disease. The current study addressed the possible interactions among selected single nucleotide polymorphisms (SNPs) in genes related to systemic inflammation, smoking status, the levels of circulating immune response cells and plasma biomarkers of systemic inflammation. Sixty-four healthy blood donors were recruited, 31 of whom were current smokers and 33 were never-users of tobacco products, references. Compared to references, the smokers showed significantly increased levels of circulating total white blood cells, lymphocytes, monocytes, neutrophils, basophils and C-reactive protein (CRP). Smokers also more frequently exhibited circulating cell phenotypes that are associated with an immunocompromised state: CD8dim cells in the lymphocyte group, CD13+CD11+, CD13+CD14+, CD13+CD56+ cells in the monocyte group and CD13+CD11+, CD13+CD56+ cells in the neutrophil group. We observed an interaction among SNPs, smoking status and some of the studied biomarkers. The average plasma CRP level was significantly higher among the smokers, with the highest level found among those with the CRP rs1800947 CC genotype. Additionally, an increased CD8+GZB+ cells in the CD8dim group were found among smokers with the GZB rs8192917 AA genotype. Thus, smoking appears to be associated with systemic inflammation and increased levels of circulating immunosuppressive cells. The extent of these effects was associated with SNPs among the smokers. This observation may contribute to a better understanding of the genetic susceptibility of smoking-related disease and the variations observed in clinical outcomes.
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10. |
- Oliva, Delmy, 1967-, et al.
(författare)
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Individual genetic variation might predict acute skin reactions in women undergoing adjuvant breast cancer radiotherapy
- 2018
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 38:12, s. 6763-6770
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Tidskriftsartikel (refereegranskat)abstract
- Adverse skin reactions during radiotherapy (RT) are common. The aim of this study was to explore whether genetic variation might be linked to acute radiation skin reactions (ARSR). Materials and Methods: One hundred and nineteen women undergoing adjuvant RT for breast cancer were included. The symptoms of itching, burning and irritation were self-reported twice using the visual analogue scale. Assessments used the Radiation Therapy Oncology Group scoring system for acute RT skin reaction (RTOG scale). Blood-based single nucleotide polymorphism (SNP) analysis was performed. Thirty SNPs of well-defined functional genes were investigated. Results: All women were assessed with ARSR. After RT, the women self-reported itching (n=97), burning (n=64) and irritation (n=96). Two SNPs in X-Ray Repair Cross Complementing 2 gene (XRCC2) rs2040639 and interferon gamma (IFNG) rs2069705 genes were found to be associated with ARSR. Conclusion: An association between two SNPs and ARSR was found. The possibility of using these SNPs as prognostic biomarkers for ARSR as tools to improve the care of patients needs further investigation.
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