| 1. |
- Baldetorp, Bo, et al.
(författare)
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Analysis of protein expression in pure cell nuclei populations isolated from human breast cancer tissue by DNA flow cytometric sorting.
- 2010
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Ingår i: Journal of Proteomics. - : Elsevier BV. - 1874-3919. ; 73, s. 1111-1116
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Tidskriftsartikel (refereegranskat)abstract
- In this study, cell nuclei from aneuploid breast cancer samples were sorted with respect to DNA content into pure diploid and aneuploid fractions using flow cytometry. The nuclear proteins were then separated by one-dimensional gel electrophoresis (1D-PAGE) and differences in protein expression patterns, between diploid and aneuploid nuclei from the same tumours, were compared. Using a combination of peptide finger printing and peptide identification by MALDI-TOF mass spectrometry, we identified proteins and confirmed that the proteins were of nuclear origins. The results in this study add further information to the knowledge about the breast cancer disease complexity and heterogeneity at molecular level. For some of the tumours studied different nuclei protein patterns were obtained, in the diploid respective aneuploid nuclei populations, whilst other tumours did not show these differences.
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| 2. |
- Sugihara, Yutaka, et al.
(författare)
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A New Look at Drugs Targeting Malignant Melanoma – An Application for Mass Spectrometry Imaging
- 2014
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Ingår i: Proteomics. - : Wiley. - 1615-9861 .- 1615-9853. ; 14:17-18, s. 1963-1970
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Forskningsöversikt (refereegranskat)abstract
- Malignant melanoma (MM) patients are being treated with an increasing number of personalized medicine (PM) drugs, several of which are small molecule drugs developed to treat patients with specific disease genotypes and phenotypes. In particular, the clinical application of protein kinase inhibitors (PKI) has been highly effective for certain subsets of MM patients. Vemurafenib, a PKI targeting BRAF mutated protein, has shown significant efficacy in slowing disease progression. In this paper we provide an overview of this new generation of targeted drugs, and demonstrate the first data on localization of personalized medicine drugs within tumor compartments. In this study, we have introduced matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to provide new information on one of the drugs currently used in the PM treatment of MM, vemurafenib. In a proof-of-concept in vitro study, MALDI-MSI was used to identify vemurafenib applied to metastatic lymph nodes tumors of subjects attending the regional hospital network of Southern Sweden. The paper provides evidence of BRAF overexpression in tumors isolated from MM patients and localization of the specific drug targeting BRAF, vemurafenib, using mass spectrometry fragment ion signatures. Our ability to determine drug uptake at the target sites of directed therapy provides important opportunity for increasing our understanding about the mode of action of drug activity within the disease environment.
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| 3. |
- Welinder, Charlotte, et al.
(författare)
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Analysis of Alpha-Synuclein in Malignant Melanoma - Development of a SRM Quantification Assay.
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:10
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Tidskriftsartikel (refereegranskat)abstract
- Globally, malignant melanoma shows a steady increase in the incidence among cancer diseases. Malignant melanoma represents a cancer type where currently no biomarker or diagnostics is available to identify disease stage, progression of disease or personalized medicine treatment. The aim of this study was to assess the tissue expression of alpha-synuclein, a protein implicated in several disease processes, in metastatic tissues from malignant melanoma patients. A targeted Selected Reaction Monitoring (SRM) assay was developed and utilized together with stable isotope labeling for the relative quantification of two target peptides of alpha-synuclein. Analysis of alpha-synuclein protein was then performed in ten metastatic tissue samples from the Lund Melanoma Biobank. The calibration curve using peak area ratio (heavy/light) versus concentration ratios showed linear regression over three orders of magnitude, for both of the selected target peptide sequences. In support of the measurements of specific protein expression levels, we also observed significant correlation between the protein and mRNA levels of alpha-synuclein in these tissues. Investigating levels of tissue alpha-synuclein may add novel aspect to biomarker development in melanoma, help to understand disease mechanisms and ultimately contribute to discriminate melanoma patients with different prognosis.
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| 4. |
- Welinder, Charlotte, et al.
(författare)
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Establishing a Southern Swedish Malignant Melanoma OMICS and Biobank Clinical Capability
- 2013
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Ingår i: Clinical and Translational Medicine. - : Wiley. - 2001-1326. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Southern Swedish Malignant Melanoma (SSMM) research team is a truly cross functional group with members from oncology, clinical, surgery, bioinformatics, proteomics, and genomics initiatives. The SSMM’s objectives and goals are to develop, build and utilize cutting edge biobanks and OMICS platforms to better understand disease pathology and drug mechanisms. Within the research team there are members who daily diagnose patients with suspect melanomas, do follow-ups on malignant melanoma patients and remove primary or metastatic lesions by surgery. This inter-disciplinary clinical patient care ensures a competence build as well as a best practice procedure where the patient benefits. The science output in these resulting study outcomes further strengthens the build of healthcare benefit in the complex challenges of malignant melanoma pathophysiology that is addressed by the novel personalized medicines entering the market. These patient biobank archives will be fully automated with novel ultralow temperature biobank storage units and used as a clinical resource. Methods: Clinical materials from patients before, during and after treatments, with clinical end points are being collected. Tissue samples as well as bio-fluid samples such as blood fractions, plasma, serum and whole blood will be archived in 384-high density sample tube formats. We are developing standardized approaches for patient selections, patient sampling, sample-processing and analysis platforms with dedicated protein assays and genomics platforms that will hold value for the research community. Results: An IT-infrastructure using a laboratory information management system (LIMS) has been established, that will be the key interface for the research teams in order to share and explore data generated within the project. The cross-site data repository in Lund will form the basis for sample processing, together with biological samples in southern Sweden, including blood fractions and tumor tissues. Clinical registries are being associated with the biobank materials, including pathology reports on disease diagnosis on the MM patients. Conclusions: We provide data on the developments of protein profiling and targeted protein target assays on isolated melanoma tumors, as well as reference blood standards that is used by the team members in the respective laboratories. These pilot data show biobank access and feasibility of performing quantitative proteomics in MM biobank repositories collected in southern Sweden.
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| 5. |
- Welinder, Charlotte, et al.
(författare)
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Feasibility Study on Measuring Selected Proteins in Malignant Melanoma Tissue by SRM Quantification.
- 2014
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 13:3, s. 1315-1326
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Tidskriftsartikel (refereegranskat)abstract
- Currently there are no clinically recognized molecular biomarkers for malignant melanoma (MM) for either diagnosing disease stage or measuring response to therapy. The aim of this feasibility study was to develop targeted selected reaction monitoring (SRM) assays for identifying candidate protein biomarkers in metastatic melanoma tissue lysate. In a pilot study applying the SRM assay, the tissue expression of nine selected proteins [complement 3 (C3), T-cell surface glycoprotein CD3 epsilon chain E (CD3E), dermatopontin, minichromosome maintenance complex component (MCM4), premelanosome protein (PMEL), S100 calcium binding protein A8 (S100A8), S100 calcium binding protein A13 (S100A13), transgelin-2 and S100B] was quantified in a small cohort of metastatic malignant melanoma patients. The SRM assay was developed using a TSQ Vantage triple quadrupole mass spectrometer that generated highly accurate peptide quantification. Repeated injection of internal standards spiked into matrix showed relative standard deviation (RSD) from 6% to 15%. All nine target proteins were identified in tumor lysate digests spiked with heavy peptide standards. The multiplex SRM peptide assay panel was then measured and quantified on a set of frozen MM tissue samples obtained from the Malignant Melanoma Biobank collected in Lund, Sweden. All nine proteins could be accurately quantified using the new SRM assay format. This study provides preliminary data on the heterogeneity of biomarker expression within MM patients. The S100B protein, which is clinically used as the pathology identifier of MM, was identified in 9 out of 10 MM tissue lysates. The use of the targeted SRM assay provides potential advancements in the diagnosis of MM that can aid in future assessments of disease in melanoma patients.
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| 6. |
- Andersen, Mette K., et al.
(författare)
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Association of variants in HLA-DQA1-DQB1, PTPN22, INS, and CTLA4 with GAD autoantibodies and insulin secretion in nondiabetic adults of the Botnia Prospective Study
- 2012
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 167:1, s. 27-33
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Previously, we observed an association between family history of type 1 diabetes and development of non-insulin-dependent diabetes. The aims of this study were to assess whether type 1 diabetes susceptibility gene variants explain this association and investigate the effect of the variants on insulin secretion and presence of glutamic acid decarboxylase autoantibodies (GADA) in nondiabetic adults. Design and methods: Polymorphisms in INS (rs689), PTPN22 (rs2476601), CTLA4 (rs3087243), and the HLA-DQA1-DQB1 regions (rs2187668 and rs7454108 tagging HLA-DQ2.5 and HLA-DQ8 respectively) were genotyped in the Botnia Prospective Study (n=2764), in which initially nondiabetic participants were followed for a mean of 8.1 years. Results: The variants did not explain the association between family history of type 1 diabetes and development of non-insulin-dependent diabetes. In these nondiabetic adults, HLA-DQ and PTPN22 risk genotypes were associated with GADA (HLA-DQ2.5/HLA-DQ8 or HLA-DQ8: OR (95% CI): 1.7 (1.3-2.3), P=0.0004; PTPN22 CT/TT: OR: 1.6 (1.2-2.2), P=0.003; P values were adjusted for sex, age, BMI, and follow-up time). A higher genetic risk score was associated with lower insulin secretion (insulinogenic index: 13.27 (16.27) vs 12.69 (15.27) vs 10.98 (13.06), P=0.02) and better insulin sensitivity index (risk score of 0-1 vs 2-3 vs 4-6: 142 (111) vs 144 (118) vs 157 (127), P=0.01) at baseline and a poorer capacity to compensate for the increased insulin demand after follow-up. Conclusions: In nondiabetic adults, HLA-DQ2.5/HLA-DQ8 and PTPN22 CT/TT genotypes were associated with GADA.
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| 7. |
- Andersen, Mette K., et al.
(författare)
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Latent Autoimmune Diabetes in Adults Differs Genetically From Classical Type 1 Diabetes Diagnosed After the Age of 35 Years
- 2010
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 33:9, s. 2062-2064
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE- We studied differences between patients with latent autoimmune diabetes in adults (LADA), type 2 diabetes, and classical type 1 diabetes diagnosed after age 35 years. RESEARCH DESIGN AND METHODS- Polymorphisms in HLA-DQB1, INS, PTPN22, and CTLA4 were genotyped in patients with LADA (n = 213), type 1 diabetes diagnosed at >35 years of age (T1D(>35y); n = 257) or <20 years of age (T1D(<20y); n = 158), and type 2 diabetes. RESULTS- Although patients with LADA had an increased frequency of HLA-DQB1 and PTPN22 risk genotypes and alleles compared with type 2 diabetic subjects, the frequency was significantly lower compared with T1D(>35y) patients. Genotype frequencies, measures of insulin secretion, and metabolic traits within LADA differed according to GAD antibody (GADA) quartiles, but even the highest quartile differed from type 1 diabetes. Having two or more risk genotypes was associated with lower C-peptide concentrations in LADA. CONCLUSIONS- LADA patients differed genetically and phenotypically from both T1D(>35y) and type 2 diabetic patients in a manner dependent on GADA levels.
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| 8. |
- Ardesjö Lundgren, Brita, et al.
(författare)
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Identification of complement C3 as an autoantigen in inflammatory bowel disease.
- 2010
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Ingår i: European journal of gastroenterology & hepatology. - 1473-5687 .- 0954-691X. ; 22:4, s. 429-436
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Autoantibodies against goblet cells in the gastrointestinal mucosa have been described in patients with inflammatory bowel disease (IBD) but a corresponding autoantigen has not yet been identified. The aim of this study was to identify such an antigen. METHODS: First, 10 candidate autoantigens were discarded based on double stainings of appendiceal sections and a mucin-producing cell line (HT29-mtx). Second, an appendiceal cDNA library was immunoscreened with IBD sera. RESULTS: Three out of 48 positive clones were identified as complement C3. Using immunoprecipitation of in vitro transcribed and translated C3, seven of 17 primary sclerosing cholangitis patient sera, 15 of 65 IBD sera, and none out of 54 sera from healthy blood donors showed C3 immunoreactivity. The results were confirmed using western blot and an enzyme-linked immunosorbent assay with alternative sources of C3 protein. CONCLUSION: In conclusion, we have identified complement C3 as a potential autoantigen in IBD and primary sclerosing cholangitis.
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| 9. |
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| 10. |
- Eriksson, Olof, et al.
(författare)
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Distribution of adoptively transferred porcine T-lymphoblasts tracked by (18)F-2-fluoro-2-deoxy-D-glucose and position emission tomography
- 2011
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Ingår i: Nuclear Medicine and Biology. - : Elsevier BV. - 0969-8051 .- 1872-9614. ; 38:6, s. 827-833
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Autologous or allogeneic transfer of tumor-infiltrating T-Iymphocytes is a promising treatment for metastatic cancers, but a major concern is the difficulty in evaluating cell trafficking and distribution in adoptive cell therapy. This study presents a method of tracking transfusion of T-Iymphoblasts in a porcine model by (18)F-2-fluoro-2-deoxy-D-glucose ([(18)F]FDG) and positron emission tomography. Methods: T-Iymphoblasts were labeled with the positron-emitting tracer [(18)F]FDG through incubation. The T-Iymphoblasts were administered into the bloodstream, and the distribution was followed by positron emission tomography for 120 min. The cells were administered either intravenously into the internal jugular vein (n=5) or intraarterially into the ascending aorta (n=1). Two of the pigs given intravenous administration were pretreated with low-molecular-weight dextran sulphate. Results: The cellular kinetics and distribution were readily quantifiable for up to 120 min. High (78.6% of the administered cells) heterogeneous pulmonary uptake was found after completed intravenous transfusion. The pulmonary uptake was decreased either by preineubating and coadministrating the T-Iymphoblasts with low-molecular-weight dextran sulphate or by administrating them intraarterially. Conclusions: The present work shows the feasibility of quantitatively monitoring and evaluating cell trafficking and distribution following administration of [(18)F]FDG-labeled T-Iymphoblasts. The protocol can potentially be transferred to the clinical setting with few modifications.
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| 11. |
- Espmark, Kristina, 1975-
(författare)
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Utanför gränserna : En vetenskapshistorisk biografi om Astrid Cleve von Euler
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation is a scientific biography of Astrid Cleve von Euler. She was Sweden’s first female Ph.D. graduate in the natural sciences (1898) and pursued a scientific career in spite of formal and cultural limitations. Though she failed to secure a professional position as a scientist, she published numerous papers throughout her life. The dissertation studies her life in general and analyses her research in particular. How did her research change over time in relation to the rest of her life? How did established scientists receive her research? How did her status as a woman on the fringes of academia affect her research? Sociologist Thomas F. Gieryn’s concepts of boundary-work and credibility contests are important analytical tools in the interpretation of these questions, as Cleve’sresearch was regulated by various boundaries: between professionals and amateurs, between men and women and between different academic disciplines.The study is divided into seven chapters. The first chapter introduces the dissertation, its objective and theoretical framework. The remaining chapters follow Cleve’s life in a chronological and sometimes thematic order and the source material is continually analysed. Chapter two accounts for Cleve’s childhood and student years in Uppsala, ending with her Ph.D. graduation. Chapter tree focuses on her research as a chemist and her ten years of marriage to a fellow researcher, Hans von Euler-Chelpin, a marriage that was closely intertwined with their academic studies. The fourth chapter studies Cleve’s controversy with some of the leading quaternary geologists in Sweden at the time, regarding the level changes of the Scandinavian land mass following the latest Ice Age. The fifth chapter diverges slightly from Cleve’s research, and investigates her undertakings in popular science and her political standpoints. Chapter six analyses her archaeological studies as part of the scientific controversy she was involved in, but also as influenced by political and religious views. Finally, the seventh chapter begins with a closer look at Cleve’s diatom studies, already part of most of the study but thus far not focused on as such, and ends with the main conclusions of the entire dissertation project.The dissertation shows that while science was part of Cleve’s life from childhood to death, factors other than her personal desire to uncover scientific truths governed her research opportunities and the topics of her studies. While she was consistently highly regarded as a diatom expert and gained some success as a chemist, disciplines she was formally educated in, she was met with scepticism and eventually silence when she tried to make an impact in quaternary geology and archaeology, fields of research in which she had no formal training. This demonstrates a possibility to simultaneously be regarded as credible and non-credible as a scientist, as credibility is not necessarily attached to the individual, but to his or her formal expertise in a particular area.
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| 12. |
- Friberg, Andrew S., et al.
(författare)
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Transplanted functional islet mass : donor islet preparation, and recipitent factors influence early graft function in islet-after-kidney patients
- 2012
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Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 93:6, s. 632-638
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Tidskriftsartikel (refereegranskat)abstract
- Background.The ability to predict clinical function of a specific islet batch released for clinical transplantation using standardized variables remains an elusive goal.Methods. Analysis of 10 donor, 7 islet isolation, 3 quality control, and 6 recipient variables was undertaken in 110 islet-after-kidney transplants and correlated to the pre- to 28-day posttransplant change in C-peptide to glucose and creatinine ratio ([DELTA]CP/GCr).Results.Univariate analysis yielded islet volume transplanted (Spearman r=0.360, P<0.001) and increment of insulin secretion (r=0.377, P<0.001) as variables positively associated to [DELTA]CP/GCr. A negative association to [DELTA]CP/GCr was cold ischemia time (r=-0.330, P<0.001). A linear, backward-selection multiple regression was used to obtain a model for the transplanted functional islet mass (TFIM). The TFIM model, composed of islet volume transplanted, increment of insulin secretion, cold ischemia time, and exocrine tissue volume transplanted, accounted for 43% of the variance of the clinical outcome in the islet-after-kidney data set.Conclusion.The TFIM provides a straightforward and potent tool to guide the decision to use a specific islet preparation for clinical transplantation.
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| 13. |
- Gad, Helge, et al.
(författare)
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MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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| 14. |
- Johansson, Henrik J., et al.
(författare)
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Retinoic acid receptor alpha is associated with tamoxifen resistance in breast cancer
- 2013
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Ingår i: Nature Communications. - : Nature Publishing Group: Nature Communications. - 2041-1723. ; 4:3175
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Tidskriftsartikel (refereegranskat)abstract
- About one-third of oestrogen receptor alpha-positive breast cancer patients treated with tamoxifen relapse. Here we identify the nuclear receptor retinoic acid receptor alpha as a marker of tamoxifen resistance. Using quantitative mass spectrometry-based proteomics, we show that retinoic acid receptor alpha protein networks and levels differ in a tamoxifen-sensitive (MCF7) and a tamoxifen-resistant (LCC2) cell line. High intratumoural retinoic acid receptor alpha protein levels also correlate with reduced relapse-free survival in oestrogen receptor alpha-positive breast cancer patients treated with adjuvant tamoxifen solely. A similar retinoic acid receptor alpha expression pattern is seen in a comparable independent patient cohort. An oestrogen receptor alpha and retinoic acid receptor alpha ligand screening reveals that tamoxifen-resistant LCC2 cells have increased sensitivity to retinoic acid receptor alpha ligands and are less sensitive to oestrogen receptor alpha ligands compared with MCF7 cells. Our data indicate that retinoic acid receptor alpha may be a novel therapeutic target and a predictive factor for oestrogen receptor alpha-positive breast cancer patients treated with adjuvant tamoxifen.
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| 15. |
- Leimalm, Ulrika, et al.
(författare)
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Off-gas dust in an experimental blast furnace part 1: Characterization of flue dust, sludge and shaft fines
- 2010
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Ingår i: ISIJ International. - : Iron and Steel Institute of Japan. - 0915-1559 .- 1347-5460. ; 50:11, s. 1560-1569
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Tidskriftsartikel (refereegranskat)abstract
- In blast furnace (BF) ironmaking, efforts are made to decrease coke consumption, which can be done by increasing the pulverized coal injection rate (PCR). This will cause changes in ¡n-furnace reduction conditions, burden distribution, demands on raw material strength, etc. In order to maintain stable operation, but also to obtain low amounts of material losses through the off-gas, it is important to understand fines generation and behaviour in the BF Off-gas dust and shaft fines generated in the LKAB Experimental Blast Furnace (EBF) were sampled during operation with olivine pellets and mixtures of acid pellets and sinter as iron-bearing materials. Characterization using XRD, SEM and LOM was focused on fines from iron-bearing materials, coke and slag formers. The results showed that flue dust, mainly <0.5 mm, was mechanically formed and created in the same manner for all investigated samples. Carbon-containing particles dominated in the fractions >0.075 mm and consisted mainly of coke particles from the shaft. Fe-containing particles, as Fe2O 3 from the top of the shaft, formed the major part of flue dust fractions <0.063 mm. Particles from slag formers such as quartzite and limestone were observed in flue dust when slag formers were utilized in the feed. Sludge consisted mainly of chemically formed spherical particles <1 μm precipitated from the ascending gas as the temperature decreased. © 2010 ISIJ.
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| 16. |
- Lundgren, Anders, 1978, et al.
(författare)
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Gold-nanoparticle-assisted self-assembly of chemical gradients with tunable sub-50 nm molecular domains
- 2014
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Ingår i: Particle & particle systems characterization. - : Wiley. - 0934-0866 .- 1521-4117. ; 31:2, s. 209-218
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Tidskriftsartikel (refereegranskat)abstract
- A simple and efficient principle for nanopatterning with wide applicability in the sub-50 nanometer regime is chemisorption of nanoparticles; at homogeneous substrates, particles carrying surface charge may spontaneously self-organize due to the electrostatic repulsion between adjacent particles. Guided by this principle, a method is presented to design, self-assemble, and chemically functionalize gradient nanopatterns where the size of molecular domains can be tuned to match the level corresponding to single protein binding events. To modulate the binding of negatively charged gold nanoparticles both locally (<100 nm) and globally (>100 μm) onto a single modified gold substrate, ion diffusion is used to achieve spatial control of the particles' mutual electrostatic interactions. By subsequent tailoring of different molecules to surface-immobilized particles and the void areas surrounding them, nanopatterns are obtained with variable chemical domains along the gradient surface. Fimbriated Escherichia coli bacteria are bound to gradient nanopatterns with similar molecular composition and macroscopic contact angle, but different sizes of nanoscopic presentation of adhesive (hydrophobic) and repellent poly(ethylene) glycol (PEG) domains. It is shown that small hydrophobic domains, similar in size to the diameter of the bacterial fimbriae, supported firmly attached bacteria resembling catch-bond binding, whereas a high number of loosely adhered bacteria are observed on larger hydrophobic domains. Chemical gradients with the resolution needed to address complex biological binding events at the single protein level are prepared using surface-deposited gold nanoparticles as a versatile template for orthogonal chemical modifications. The effect of hydrophobic domain arrangement on the sub-50 nm scale is shown to influence binding of fimbriae carrying E. coli bacteria. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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| 17. |
- Lundgren, Anna Sofia, 1972-, et al.
(författare)
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Inledning
- 2012
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Ingår i: Mitt i metoden. - Umeå : Institutionen för kultur- och medievetenskaper, Umeå universitet. - 9789174595093 ; , s. 7-16
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 18. |
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| 19. |
- Lundgren, Maria
(författare)
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Blast furnace coke properties and the influence on off-gas dust
- 2010
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In blast furnace ironmaking, efforts are made to decrease the coke consumption mainly by increasing the pulverized coal injection rate. This will cause changes in in-furnace reduction conditions, burden distribution and demands on raw material strength, etc. In order to maintain stable operation and minimize material losses through the off-gas, it is important to understand fines generation and behaviour in the blast furnace. The strength and reactivity of coke at high temperature, measured by the Coke Strength after Reaction (CSR) and Coke Reactivity Index (CRI), have been studied. Mechanisms of disintegration were evaluated using basket samples charged into the LKAB Experimental Blast Furnace (EBF) prior to quenching and dissection. Coke charged into basket samples was analysed with CSR/CRI tests and compared with treated coke from the blast furnace. Results from tumbling tests, chemical analyses of coarse and fine material, as well as Light Optical Microscope (LOM) studies of original and treated coke have been combined and evaluated. The results indicate a correlation between the ash composition and CSR values. Differences in the texture of the coke were determined with LOM, and a change in the coke texture during the CSR/CRI test conditions was found. The results suggest that the main reaction between coke and CO2 during the solution loss reaction took place in isotropic areas, which was especially pronounced in coke with a low CSR. Signs of degradation were apparent throughout the coke pieces that have undergone CSR/CRI testing, but were less observable in coke reacted in the blast furnace. The results indicate that the solution loss reaction was generally limited by the chemical reaction rate in the CSR/CRI test, while in the blast furnace the reaction is limited by the diffusion rate. Coke degradation is therefore mostly restricted to the coke surface in the blast furnace. At a later EBF campaign, off-gas dust and shaft fines were sampled during operation with different iron-bearing materials. EBF process data were used to evaluate the relationship between off-gas dust amounts and furnace conditions. Characterization was focused on fines from coke, iron-bearing materials and slag formers. The graphitization degree (Lc value) of coke taken out of the EBF shaft and coke in flue dust was determined in order to trace the fines generation position. The results showed that flue dust, mainly <0.5 mm, was mechanically formed and created in the same manner for all investigated samples. Carbon-containing particles dominated in the fractions >0.075 mm and consisted mainly of coke particles originating from the shaft. Solution loss in the shaft had a negligible effect on coke degradation and the coke particles which ended up in the flue dust were mainly derived from abrasion at low temperatures. Sludge consisted mainly of chemically formed spherical particles <1μm formed in the blast furnace high-temperature area and then precipitated from the ascending gas as the temperature decreased. The amount of alkali and SiO2 in sludge increased with higher pulverized coal injection rates and flame temperatures, which confirmed that submicron spherical particles in sludge originated from the high-temperature area around the raceway. Theoretical critical particle diameters of materials, which could be blown out with the off-gas, were estimated. Flow conditions in the top of the shaft as well as the properties of fine particles in terms of size and density are important when outflow of mechanical dust, such as flue dust, is concerned. Low off-gas temperatures, and thus lower off-gas velocities, are desirable for blast furnace operation with low amounts of flue dust.
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| 20. |
- Lundgren, Maria, et al.
(författare)
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High temperature coke characteristics in the blast furnace : evaluation of coke properties in the raceway area
- 2012
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Ingår i: Scanmet IV. - Luleå : MEFOS. - 9789163708596 ; , s. 157-168
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Konferensbidrag (refereegranskat)abstract
- Core-drilling into the coke bed of raceway and hearth has been performed in the LKAB Experimental Blast Furnace (EBF®) during short stoppages aiming to characterize raceway conditions corresponding to different operational conditions. All coke operation, injection of pulverized coal and injection of a mixture of coal and blast furnace flue dust (BFD) were evaluated and compared. The samples have been studied regarding particle size and distribution, coke have been evaluated with chemical composition and thermal history, i.e. coke graphitization degree. In addition, the results have been compared to drilled raceway core samples from SSAB industrial blast furnace in Luleå. Coke in drill-cores consists of bosh, raceway and deadman coke. In comparison with charged coke this coke has changed characteristics depending on the exposed conditions which vary along the radius of each drilled core. Coke in raceway area has increased ash content due to gasification of C and the ash composition is altered due to both reduction and gasification of ash minerals as e.g. SiO2 and alkalis in raceway and oxidation/condensation of gaseous compounds and uptake of compounds from the melt. Coke exposed to highest temperatures in the raceway area have increased the most in graphitization degree, and subsequent bird’s nest and deadman cokes graphitization degrees decreases. K2O-content in coke correlates to the graphitization degree as well as the SiO2/Al2O3 quotient which decreases at higher temperatures. Presence of slag and coke aggregates indicates the formation of bird’s nests at the end of the raceway. The end of raceway and position of a significant bird's nest in the industrial samples are indicated by the increasing content of K2O and increasing ratio of SiO2/Al2O3 in coke. In the industrial BF the pronounced formation of a bird’s nest redirect the gas from moving towards the BF center. As a result the coke in deadman cannot be heated and the temperature indicated by the graphitization degree decreases.Injection of BFD influences the raceway conditions as the combustion peak is moved further into the raceway when BFD and PC mix are injected. Analyze of fines shows remaining unreacted BFD, which contains iron oxide with oxidation degree between FeO and metallic Fe. Increased FeO-content in raceway will decrease the melting point of tuyere slag and therefore improve the permeability at raceway end and the fact that the core when drilled could be pushed further into the EBF than for the other cores indicates higher permeability after injection of PC and BFD mixture.
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| 21. |
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| 22. |
- Lundgren, Maria, et al.
(författare)
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Off-gas dust in an experimental blast furnace part 2: Relation to furnace conditions
- 2010
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Ingår i: ISIJ International. - : Iron and Steel Institute of Japan. - 0915-1559 .- 1347-5460. ; 50:11, s. 1570-1580
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Tidskriftsartikel (refereegranskat)abstract
- In the blast furnace process, material losses are caused by particles that are blown out of the furnace by the off-gas. In order to reduce these losses, it is important to understand the correlations between furnace conditions and off-gas dust formation. Off-gas dust, as flue dust and sludge, were collected during shaft probe sampling in LKAB Experimental Blast Furnace (EBF). Process data was used to evaluate the relationship between off-gas dust amounts and furnace conditions. The graphitization degree (Lc value) of shaft coke and coke in flue dust was determined using XRD measurements. Solution loss in the shaft had a negligible effect on coke degradation and the coke particles which ended up in the flue dust were mainly derived from abrasion at low temperatures. The amount of alkali and SiO2 in sludge increased with higher PCR and flame temperature, which confirmed that submicron spherical particles in sludge originated from the high temperature area around the raceway. Theoretical critical particle diameters of materials, which could be blown out with the off-gas, were estimated. Flow conditions in the top of the shaft as well as and the properties of fine particles in terms of size and density are important when outflow of mechanical dust, such as flue dust, is concerned. Low off-gas temperatures, and thus lower off-gas velocities, are favourable for low flue dust amounts expelled from the blast furnace. © 2010 ISIJ.
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| 23. |
- Lundgren, Maria, et al.
(författare)
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The Evolution of Structural Order as a Measure of Thermal History of Coke in the Blast Furnace
- 2014
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Ingår i: Metallurgical and materials transactions. B, process metallurgy and materials processing science. - : Springer Science and Business Media LLC. - 1073-5615 .- 1543-1916. ; 45:2, s. 603-616
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Tidskriftsartikel (refereegranskat)abstract
- Investigations were carried out on cokes heat treated in the laboratory and on cokes extracted from the experimental blast furnace (EBF) raceway and hearth. X-ray diffraction (XRD) measurements were performed to investigate changes in structural order (Lc), chemical transformations in coke ash along with comparative thermodynamic equilibrium studies and the influence of melt. Three data processing approaches were used to compute Lc values as a function of temperature and time and linear correlations were established between Lc and heat treatment temperatures during laboratory investigations. These were used to estimate temperatures experienced by coke in various regions of EBF and estimated raceway temperatures were seen to follow the profile of combustion peak. The MgAl2O4 spinel was observed in coke submerged in slag during laboratory studies and in cokes found further into the raceway. Coke in contact with hot metal showed XRD peaks corresponding to presence of Fe3Si. The intensity of SiO2 peak in coke ash was seen to decrease with increasing temperature and disappeared at around 1770 K (1500 °C) due to the formation of SiC. This study has shown that the evolution of structural order and chemical transformations in coke could be used to estimate its thermal history in blast furnaces.
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| 24. |
- Lundgren, Virve M., et al.
(författare)
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GAD Antibody Positivity Predicts Type 2 Diabetes in an Adult Population
- 2010
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 59:2, s. 416-422
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE-To evaluate the significance of GAD antibodies (GADAs) and family history for type 1 diabetes (FHT1) or type 2 diabetes (FHT2) in nondiabetic subjects. RESEARCH DESIGN AND METHODS-GADAs were analyzed in 4,976 nondiabetic relatives of type 2 diabetic patients or control subjects from Finland. Altogether, 289 (5.9%) were GADA(+)-a total of 253 GADA(+) and 2,511 GADA(-) subjects participated in repeated oral glucose tolerance tests during a median time of 8.1 years. The risk of progression to diabetes was assessed using Cox regression analysis. RESULTS-Subjects within the highest quartile of GADA(+) (GADA(high)(+)) had more often first-degree FHT1 (29.2 vs. 7.9%, P < 0.00001) and GADA(+) type 2 diabetic (21.3 vs. 13.7%, P = 0.002) or nondiabetic (26.4 vs. 13.3%, P = 0.010) relatives than GADA(-) subjects. During the follow-up, the GADA(+) subjects developed diabetes significantly more often than the GADA(-) subjects (36/253 [14.2%] vs. 134/2,511 [5.3%], P < 0.00001). GADA(high)(+) conferred a 4.9-fold increased risk of diabetes (95% CI 2.8-8.5) compared with GADA(-)-seroconversion to positive during the follow-up was associated with 6.5-fold (2.8-15.2) and first-degree FHT1 with 2.2-fold (1.2-4.1) risk of diabetes. Only three subjects developed type 1 diabetes, and others had a non-insulin-dependent phenotype 1 year after diagnosis. GADA(+) and GADA(-) subjects did not clinically differ at baseline, but they were leaner and less insulin resistant after the diagnosis of diabetes. CONCLUSIONS-GADA positivity clusters in families with type 1 diabetes or latent autoimmune diabetes in adults. GADA positivity predicts diabetes independently of family history of diabetes, and this risk was further increased with high GADA concentrations.
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| 25. |
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| 26. |
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| 27. |
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| 28. |
- Schmidt, L., et al.
(författare)
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Comparative drug pair screening across multiple glioblastoma cell lines reveals novel drug-drug interactions
- 2013
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Ingår i: Neuro-Oncology. - : Oxford University Press (OUP). - 1522-8517 .- 1523-5866. ; 15:11, s. 1469-1478
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Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma multiforme (GBM) is the most aggressive brain tumor in adults, and despite state-of-the-art treatment, survival remains poor and novel therapeutics are sorely needed. The aim of the present study was to identify new synergistic drug pairs for GBM. In addition, we aimed to explore differences in drug-drug interactions across multiple GBM-derived cell cultures and predict such differences by use of transcriptional biomarkers. We performed a screen in which we quantified drug-drug interactions for 465 drug pairs in each of the 5 GBM cell lines U87MG, U343MG, U373MG, A172, and T98G. Selected interactions were further tested using isobole-based analysis and validated in 5 glioma-initiating cell cultures. Furthermore, drug interactions were predicted using microarray-based transcriptional profiling in combination with statistical modeling. Of the 5 465 drug pairs, we could define a subset of drug pairs with strong interaction in both standard cell lines and glioma-initiating cell cultures. In particular, a subset of pairs involving the pharmaceutical compounds rimcazole, sertraline, pterostilbene, and gefitinib showed a strong interaction in a majority of the cell cultures tested. Statistical modeling of microarray and interaction data using sparse canonical correlation analysis revealed several predictive biomarkers, which we propose could be of importance in regulating drug pair responses. We identify novel candidate drug pairs for GBM and suggest possibilities to prospectively use transcriptional biomarkers to predict drug interactions in individual cases.
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| 29. |
- Takahashi, Tohru, et al.
(författare)
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Multipotent mesenchymal stromal cells synergize with costimulation blockade in the inhibition of immune responses and the induction of foxp3+ regulatory T cells.
- 2014
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Ingår i: Stem cells translational medicine. - : Oxford University Press (OUP). - 2157-6564 .- 2157-6580. ; 3:12, s. 1484-94
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Tidskriftsartikel (refereegranskat)abstract
- Multipotent mesenchymal stromal cell (MSC) therapy and costimulation blockade are two immunomodulatory strategies being developed concomitantly for the treatment of immunological diseases. Both of these strategies have the capacity to inhibit immune responses and induce regulatory T cells; however, their ability to synergize remains largely unexplored. In order to study this, MSCs from C57BL/6 (H2(b)) mice were infused together with fully major histocompatibility complex-mismatched Balb/c (H2(d)) allogeneic islets into the portal vein of diabetic C57BL/6 (H2(b)) mice, which were subsequently treated with costimulation blockade for the first 10 days after transplantation. Mice receiving both recipient-type MSCs, CTLA4Ig, and anti-CD40L demonstrated indefinite graft acceptance, just as did most of the recipients receiving MSCs and CTLA4Ig. Recipients of MSCs only rejected their grafts, and fewer than one half of the recipients treated with costimulation blockade alone achieved permanent engraftment. The livers of the recipients treated with MSCs plus costimulation blockade contained large numbers of islets surrounded by Foxp3(+) regulatory T cells. These recipients showed reduced antidonor IgG levels and a glucose tolerance similar to that of naïve nondiabetic mice. Intrahepatic lymphocytes and splenocytes from these recipients displayed reduced proliferation and interferon-γ production when re-exposed to donor antigen. MSCs in the presence of costimulation blockade prevented dendritic cell maturation, inhibited T cell proliferation, increased Foxp3(+) regulatory T cell numbers, and increased indoleamine 2,3-dioxygenase activity. These results indicate that MSC infusion and costimulation blockade have complementary immune-modulating effects that can be used for a broad number of applications in transplantation, autoimmunity, and regenerative medicine.
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