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- Salomonsson, Annette, et al.
(författare)
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Comprehensive analysis of RNA binding motif protein 3 (RBM3) in non-small cell lung cancer
- 2020
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Ingår i: Cancer Medicine. - : Blackwell Publishing Ltd. - 2045-7634. ; 9:15, s. 5609-5619
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Tidskriftsartikel (refereegranskat)abstract
- Aims High expression of the RNA-binding motif protein 3 (RBM3) correlates with improved prognosis in several major types of cancer. The aim of the present study was to examine the prognostic value of RBM3 protein and mRNA expression in non-small cell lung cancer (NSCLC).Methods and results Immunohistochemical expression of RBM3 was evaluated in surgically treated NSCLC from two independent patient populations (n = 213 and n = 306). Staining patterns were correlated with clinicopathological parameters, overall survival (OS), and recurrence-free interval (RFI). Cases with high nuclear RBM3 protein expression had a prolonged 5-year OS in both cohorts when analyzing adenocarcinomas separately (P = .02 and P = .01). RBM3 remained an independent prognostic factor for OS in multivariable analysis of cohort I (HR 0.44, 95% CI 0.21-0.90) and for RFI in cohort II (HR 0.38, 95% CI 0.22-0.74). In squamous cell carcinoma, there was instead an insignificant association to poor prognosis. Also, the expression levels of RBM3 mRNA were investigated in 2087 lung adenocarcinomas and 899 squamous cell carcinomas assembled from 13 and 8 public gene expression microarray datasets, respectively. The RBM3 mRNA levels were not clearly associated with patient outcome in either adenocarcinomas or squamous cell carcinomas.Conclusions The results from this study support that high protein expression of RBM3 is linked to improved outcome in lung adenocarcinoma.
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| 5. |
- Eriksson, Göran, et al.
(författare)
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A new maximal bicycle test using a prediction algorithm developed from four large COPD studies
- 2020
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Ingår i: European clinical respiratory journal. - : Informa UK Limited. - 2001-8525. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Maximum exercise workload (WMAX) is today assessed as the first part of Cardiopulmonary Exercise testing. The WMAX test exposes patients with COPD, often having cardiovascular comorbidity, to risks. Our research project was initiated with the final aim to eliminate the WMAX test and replace this test with a predicted value of WMAX, based on a prediction algorithm of WMAX derived from multicentre studies. Methods: Baseline data (WMAX, demography, lung function parameters) from 850 COPD patients from four multicentre studies were collected and standardized. A prediction algorithm was prepared using Random Forest modelling. Predicted values of WMAX were used in a new WMAX test, which used a linear increase in order to reach the predicted WMAX within 8 min. The new WMAX test was compared with the standard stepwise WMAX test in a pilot study including 15 patients with mild/moderate COPD. Results: The best prediction algorithm of WMAX included age, sex, height, weight, and six lung function parameters. FEV1 and DLCO were the most important predictors. The new WMAX test had a better correlation (R2 = 0.84) between predicted and measured WMAX than the standard WMAX test (R2 = 0.66), with slopes of 0.50 and 0.46, respectively. The results from the new WMAX test and the standard WMAX test correlated well. Conclusion: A prediction algorithm based on data from four large multicentre studies was used in a new WMAX test. The prediction algorithm provided reliable values of predicted WMAX. In comparison with the standard WMAX test, the new WMAX test provided similar overall results.
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| 6. |
- Franzén, Sara, et al.
(författare)
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Compositional tuning of gas-phase synthesized Pd–Cu nanoparticles
- 2023
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Ingår i: Nanoscale Advances. - 2516-0230. ; 5:22, s. 6069-6077
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Tidskriftsartikel (refereegranskat)abstract
- Bimetallic nanoparticles have gained significant attention in catalysis as potential alternatives to expensive catalysts based on noble metals. In this study, we investigate the compositional tuning of Pd–Cu bimetallic nanoparticles using a physical synthesis method called spark ablation. By utilizing pure and alloyed electrodes in different configurations, we demonstrate the ability to tailor the chemical composition of nanoparticles within the range of approximately 80 : 20 at% to 40 : 60 at% (Pd : Cu), measured using X-ray fluorescence (XRF) and transmission electron microscopy energy dispersive X-ray spectroscopy (TEM-EDXS). Time-resolved XRF measurements revealed a shift in composition throughout the ablation process, potentially influenced by material transfer between electrodes. Powder X-ray diffraction confirmed the predominantly fcc phase of the nanoparticles while high-resolution TEM and scanning TEM-EDXS confirmed the mixing of Pd and Cu within individual nanoparticles. X-ray photoelectron and absorption spectroscopy were used to analyze the outermost atomic layers of the nanoparticles, which is highly important for catalytic applications. Such comprehensive analyses offer insights into the formation and structure of bimetallic nanoparticles and pave the way for the development of efficient and affordable catalysts for various applications.
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| 9. |
- Jönsson, Linnéa, et al.
(författare)
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The effect of electrode composition on bimetallic AgAu nanoparticles produced by spark ablation
- 2024
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Ingår i: Journal of Aerosol Science. - 0021-8502. ; 177
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Tidskriftsartikel (refereegranskat)abstract
- A flexible way to generate bimetallic nanoparticles with high control of their composition is to use spark ablation of alloyed electrodes. It has been generally accepted and stated that particles produced using spark ablation of alloyed electrodes obtain the same chemical composition as the electrodes. However, we identify a lack of studies fully supporting the connection between electrode and particle composition, presented in a small literature survey. The aim of the study is, hence, to explore the validity of the statement by analysing the relation between alloyed electrodes and their resulting particle composition using three sets of AgAu electrodes containing Au and 25, 50, and 75 atomic % Ag, respectively. The resulting composition is thoroughly investigated using both single particle (scanning- and transmission electron microscopy) and ensemble particle techniques (inductive coupled plasma-mass spectroscopy, x-ray photoelectron spectroscopy, x-ray fluorescence, and optical measurements of surface plasmon resonance. We also investigate how sample size (e.g., the number of particles analysed) affects the reliability of the resulting sample mean. For single-particle measurements of a sample with a compositional standard deviation of a few atomic percentage points, a sample size of 20 particles is a good benchmark for obtaining reliable results of the sample mean. Furthermore, this article aims to challenge the practice in which the composition of nanoparticles is measured, presented, and interpreted, to improve and facilitate future research related to this topic. From the results of this study, it could be concluded that for the investigated Ag–Au material system, the particles obtained a composition very similar to the alloyed AgAu electrodes.
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| 10. |
- Karlsson, Anna, et al.
(författare)
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Gene Expression Profiling of Large Cell Lung Cancer Links Transcriptional Phenotypes to the New Histological WHO 2015 Classification
- 2017
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Ingår i: Journal of Thoracic Oncology. - : ELSEVIER SCIENCE INC. - 1556-0864 .- 1556-1380. ; 12:8, s. 1257-1267
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Large cell lung cancer (LCLC) and large cell neuroendocrine carcinoma (LCNEC) constitute a small proportion of NSCLC. The WHO 2015 classification guidelines changed the definition of the debated histological subtype LCLC to be based on immunomarkers for adenocarcinoma and squamous cancer. We sought to determine whether these new guidelines also translate into the transcriptional landscape of lung cancer, and LCLC specifically.Methods: Gene expression profiling was performed by using Illumina V4 HT12 microarrays (Illumina, San Diego, CA) on samples from 159 cases (comprising all histological subtypes, including 10 classified as LCLC WHO 2015 and 14 classified as LCNEC according to the WHO 2015 guidelines), with complimentary mutational and immunohistochemical data. Derived transcriptional phenotypes were validated in 199 independent tumors, including six WHO 2015 LCLCs and five LCNECs.Results: Unsupervised analysis of gene expression data identified a phenotype comprising 90% of WHO 2015 LCLC tumors, with characteristics of poorly differentiated proliferatiVe cancer, a 90% tumor protein p53 gene (TP53) mutation rate, and lack of well-known NSCLC oncogene driver alterations. Validation in independent data confirmed aggregation of WHO 2015 LCLCs in the specific phenotype. For LCNEC tumors, the unsupervised gene expression analysis suggested two different transcriptional patterns corresponding to a proposed genetic division of LCNEC tumors into SCLC-like and NSCLC-like cancer on the basis of TP53 and retinoblastoma 1 gene (RB1) alteration patterns.Conclusions: Refined classification of LCLC has implications for diagnosis, prognostics, and therapy decisions. Our molecular analyses support the WHO 2015 classification of LCLC and LCNEC tumors, which herein follow different tumorigenic paths and can accordingly be stratified into different transcriptional subgroups, thus linking diagnostic immunohistochemical staining driven classification with the transcriptional landscape of lung cancer.
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| 11. |
- Nordahl, Linnea, et al.
(författare)
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Direct Observation of Na,K‐ATPase Oligomers in The Plasma Membrane of Living Cells by FRET‐FCS
- 2022
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Ingår i: The FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 36:S1
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Tidskriftsartikel (refereegranskat)abstract
- The sodium pump, Na,K-ATPase, is an integral plasma membrane protein, expressed in all eukaryotic cells. Na,K-ATPase transforms chemical energy from ATP into a gradient of Na+ and K+ over the plasma membrane by actively exporting three Na+ ions and importing two K+ ions for each hydrolyzed ATP. It is responsible for maintenance of the transmembrane Na+ gradient and is the major determinant of the membrane potential. It provides the driving force for all Na+-coupled transport processes, thereby controlling essential functions in the cell. Na,K-ATPase is formed by three subunits alpha/beta/FXYD, where alpha is the catalytic ion-transporting subunit, beta is a regulatory subunit and FXYD is accessory.Self-interaction and oligomerization of the Na,K-ATPase alpha/beta heterodimer in cell membranes has been proposed and discussed for a long time but is still an open question.Here we have used a combination of FRET and Fluorescence Correlation Spectroscopy, FRET-FCS, in order to detect oligomers of Na,K-ATPase. Compared to conventional cross-correlation FCCS, FRET-FCS is one to two orders of magnitude more sensitive when detecting oligomers. Moreover, FRET-FCS is inherently insensitive to unbalanced labeling, which is a great advantage during live cell measurements.We hypothesized that Na,K-ATPase can exist in a higher order oligomeric state and demonstrate the use of FRET-FCS to test this hypothesisWe have introduced fluorescent labels by using expression of non-canonical amino acid modified beta subunits. The FRET pair Alexa488 and Alexa647 was directly conjugated to the beta subunits using selective click chemistry. Conventional FCS measurements of labeled cells revealed the absolute density of labeled and unlabeled Na,K-ATPase. With FRET-FCS we could observe FRET signals and FCS curves demonstrating the existence of oligomers. Positive controls for the FRET-FCS measurements were constructed by labeling alpha subunits with Alexa488 and beta subunits with Alexa647.Furthermore, we performed Monte Carlo simulations of Na,K-ATPase, as monomer and as oligomer of increasing order, together with its ligands in a picket and fence diffusion model of the plasma membrane. The simulations suggest that oligomerization can have an impact on the net efficiency of the Na,K-ATPase measured as ATP turnover.In conclusion we find that Na,K-ATPase can be found in the plasma membrane as oligomers. Further we discuss the consequences of oligomerization and propose that it can have a regulatory effect for the Na,K-ATPase net efficiency.
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| 12. |
- Tufvesson, Ellen, et al.
(författare)
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A new protocol for exercise testing in COPD; improved prediction algorithm for WMAX and validation of the endurance test in a placebo-controlled double bronchodilator study
- 2021
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Ingår i: Therapeutic Advances in Respiratory Disease. - : SAGE Publications. - 1753-4658 .- 1753-4666. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Two new protocols have been developed for bicycle exercise testing in chronic obstructive pulmonary disease (COPD) with an individualized cardiopulmonary exercise test (ICPET) and subsequent customized endurance test (CET), which generate less interindividual spread in endurance time compared with the standard endurance test. Main objectives of this study were to improve the prediction algorithm for WMAX for the ICPET and validate the CET by examining treatment effects on exercise performance of indacaterol/glycopyrronium (IND/GLY) compared with placebo. Methods: COPD patients, with forced expiratory volume in 1 s (FEV1) 40–80% predicted, were recruited. Pooled baseline data from two previous studies (n = 38) were used for the development of an improved WMAX prediction algorithm. Additional COPD patients (n = 14) were recruited and performed the ICPET, using the new prediction formula at visit 1. Prior to the CET at visits 2 and 3, they were randomized to a single dose of IND/GLY (110/50 µg) or placebo. Results: The improved multiple regression algorithm for WMAX includes diffusing capacity for carbon monoxide (DLCO), FEV1, sex, age and height and correlated to measured WMAX (R2 = 0.89 and slope = 0.89). Treatment with IND/GLY showed improvement in endurance time versus placebo, mean 113 s [95% confidence interval (CI): 6–220], p = 0.037, with more prominent effect in patients with FEV1 < 70% predicted. Conclusion: The two new protocols for ICPET (including the new improved algorithm) and CET were retested with consistent results. In addition, the CET showed a significant and clinically relevant prolongation of endurance time for IND/GLY versus placebo in a small number of patients.
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| 13. |
- Tufvesson, Ellen, et al.
(författare)
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Reduced variability of endurance time in new protocols for exercise tests in COPD
- 2020
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Ingår i: International Journal of COPD. - 1176-9106. ; 15, s. 3003-3012
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: For exercise testing of COPD patients, a standard endurance test (ET) with constant workload is recommended. The test suffers from large inter-individual variability and need for large sample sizes in order to evaluate treatment effects. Methods: A new protocol for ET in COPD was designed. In contrast to the standard ET, the new ET involved an increasing workload in order to reduce the standard deviation of endurance time. Two new ETs were compared with the standard ET. In Study A, the new ET started at 75% of the patient’s maximum workload (WMAX) and increased stepwise with 3%/2 min until exhaustion. Study B started at 70% of WMAX and increased linearly with 1%/ min. Results: In Study A, that included 15 patients, the standard deviation and range for endurance time and work capacity were narrower for the new versus the standard ET. However, the higher mean workload at end and the low mean work capacity relative to the standard ET indicated that the stepwise increase was too aggressive. In Study B, that included 18 patients, with a modified protocol, the averages for endurance time, workload at end and work capacity were similar for new and standard ET, while the standard deviations and ranges for endurance time and work capacity were kept more narrow in the new ET. The variances for endurance time were not equal between the standard ET and the two new ETs (p<0.05 for both according to Levene’s test). Conclusion: The new ET reduced the number of patients with extreme endurance times (short and long) compared to the standard test. The new test showed a significant lower variance for endurance time, which potentially can lead to fewer patients needed in com-parative studies. The overall best results were observed with a low linear increase during endurance.
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