| 1081. |
- Larsson, Anna H, et al.
(författare)
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Podocalyxin-like protein expression in primary colorectal cancer and synchronous lymph node metastases
- 2013
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Ingår i: Diagnostic Pathology. - : Springer Science and Business Media LLC. - 1746-1596. ; 8:1, s. 109-
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Previous studies have shown that membranous expression of podocalyxin-like protein (PODXL) is associated with poor prognosis in colorectal cancer (CRC). In this study, we compared PODXL expression in primary CRC and synchronous lymph node metastases. We further analyzed whether its expression changed in rectal tumours after neoadjuvant radiation therapy. Methods and results: The studied cohort consists of 73 consecutive patients from the South-Swedish Colorectal Cancer Biobank. Immunohistochemical PODXL expression was examined on full-face sections from all primary tumours and all 140 available lymph node metastases from 31 cases. Membranous PODXL expression was denoted in 18/73 (24,7%) primary tumours, with a high concordance between primary and metastatic lesions. While all negative primary tumours had negative metastases, some PODXL positive primaries had a varying proportion of positive and negative metastatic lymph nodes. PODXL expression was also found to be mainly unaltered in pre- and post-irradiation surgically resected tumour specimens in rectal cancer patients (n=16). Conclusions: The findings in this study suggest that analysis of PODXL expression in the primary tumour is sufficient for its use as a prognostic and treatment predictive biomarker in CRC, also in patients with metastatic disease.
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| 1082. |
- Larsson, Anna H., et al.
(författare)
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Significant association and synergistic adverse prognostic effect of podocalyxin-like protein and epidermal growth factor receptor expression in colorectal cancer
- 2016
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Ingår i: Journal of Translational Medicine. - : BioMed Central. - 1479-5876. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Podocalyxin-like 1 (PODXL) is an anti-adhesive transmembrane protein that has been demonstrated to be an independent factor of poor prognosis in colorectal cancer (CRC). The gene encoding PODXL is located to chromosome 7, which also harbours the gene for the epidermal growth factor receptor (EGFR). The aim of this study was to examine the associations between PODXL and EGFR expression in CRC in vitro and in vivo. Methods: EGFR expression was analysed in tumours from three independent patient cohorts; cohort 1 (n = 533), cohort 2 (n = 259) and cohort 3 (n = 310), previously analysed for immunohistochemical PODXL expression and KRAS and BRAF mutations (cohort 1 and 3). Levels of EGFR and PODXL were determined by western blot in six different CRC cell lines. Results: High expression of PODXL was significantly associated with high EGFR expression (p < 0.001) in all three cohorts, and with BRAF mutation (p < 0.001) in cohort 1 and 3. High EGFR expression correlated with BRAF mutation (p < 0.001) in cohort 1. High EGFR expression was associated with adverse clinicopathological factors and independently predicted a reduced 5-year overall survival (OS) in cohort 1 (HR 1.77; 95 % CI 1.27-2.46), cohort 2 (HR 1.58; 95 % CI 1.05-2.38) and cohort 3 (HR 1.83; 95 % CI 1.19-2.81). The highest risk of death within 5 years was observed in patients with tumours displaying high expression of both EGFR and PODXL in cohort 1 and 3 (HR 1.97; 95 % CI 1.18-3.28 and HR 3.56; 95 % CI 1.75-7.22, respectively). Western blot analysis showed a uniform expression of PODXL and EGFR in all six examined CRC cell lines. Conclusions: The results from this study demonstrate that high expression of EGFR is an independent factor of poor prognosis in CRC. Moreover, strong links have been uncovered between expression of the recently proposed biomarker candidate PODXL with EGFR expression in CRC in vivo and in vitro, and with BRAF mutation in vivo. High expression of both PODXL and EGFR may also have a synergistic adverse effect on survival. These findings suggest a potential functional link in CRC between PODXL, EGFR and BRAF, all originating from chromosome 7, which may be highly relevant in the clinical setting and therefore merit future in-depth study.
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| 1083. |
- Larsson, Anna H, et al.
(författare)
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Validation of podocalyxin-like protein as a biomarker of poor prognosis in colorectal cancer
- 2012
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 12, s. 282-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Podocalyxin-like 1 (PODXL) is a cell-adhesion glycoprotein and stem cell marker that has been associated with an aggressive tumour phenotype and adverse outcome in several cancer types. We recently demonstrated that overexpression of PODXL is an independent factor of poor prognosis in colorectal cancer (CRC). The aim of this study was to validate these results in two additional independent patient cohorts and to examine the correlation between PODXL mRNA and protein levels in a subset of tumours. Method: PODXL protein expression was analyzed by immunohistochemistry in tissue microarrays with tumour samples from a consecutive, retrospective cohort of 270 CRC patients (cohort 1) and a prospective cohort of 337 CRC patients (cohort 2). The expression of PODXL mRNA was measured by real-time quantitative PCR in a subgroup of 62 patients from cohort 2. Spearman's Rho and Chi-Square tests were used for analysis of correlations between PODXL expression and clinicopathological parameters. Kaplan Meier analysis and Cox proportional hazards modelling were applied to assess the relationship between PODXL expression and time to recurrence (TTR), disease free survival (DFS) and overall survival (OS). Results: High PODXL protein expression was significantly associated with unfavourable clinicopathological characteristics in both cohorts. In cohort 1, high PODXL expression was associated with a significantly shorter 5-year OS in both univariable (HR = 2.28; 95% CI 1.43-3.63, p = 0.001) and multivariable analysis (HR = 2.07; 95% CI 1.25-3.43, p = 0.005). In cohort 2, high PODXL expression was associated with a shorter TTR (HR = 2.93; 95% CI 1.26-6.82, p = 0.013) and DFS (HR = 2.44; 95% CI 1.32-4.54, p = 0.005), remaining significant in multivariable analysis, HR = 2.50; 95% CI 1.05-5.96, p = 0.038 for TTR and HR = 2.11; 95% CI 1.13-3.94, p = 0.019 for DFS. No significant correlation could be found between mRNA levels and protein expression of PODXL and there was no association between mRNA levels and clinicopathological parameters or survival. Conclusions: Here, we have validated the previously demonstrated association between immunohistochemical expression of PODXL and poor prognosis in CRC in two additional independent patient cohorts. The results further underline the potential utility of PODXL as a biomarker for more precise prognostication and treatment stratification of CRC patients.
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| 1084. |
- Larsson, Alfred, et al.
(författare)
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In situ quantitative analysis of electrochemical oxide film development on metal surfaces using ambient pressure X-ray photoelectron spectroscopy : Industrial alloys
- 2023
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Ingår i: Applied Surface Science. - : Elsevier BV. - 0169-4332 .- 1873-5584. ; 611
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Tidskriftsartikel (refereegranskat)abstract
- Ambient Pressure X-ray Photoelectron Spectroscopy combined with an electrochemical setup is used to study, in situ, the electrochemical oxide growth on an in-dustrial Ni-Cr-Mo alloy. The native oxide film was characterized in vacuum and in water vapor at 17 mbar, and was found to be 11.4 & ANGS; thick and rich in Cr3+. In 0.1 M NaCl electrolyte, anodic growth of the oxide film at potentials up to 700 mV vs Ag/AgCl nearly doubled the thickness of the oxide film. Moreover, a transformation of the oxide composition occurred, as the oxide became enriched in Mo6+ with a chemical fingerprint more like that of pure MoO3. Both thermodynamics and kinetics of the oxidation of the alloying elements dictate the oxide film growth and composition. Furthermore, we develop the quantitative analysis of oxide composition and thickness to take into account the attenuation through the liquid water and the water vapor atmosphere. Finally, we discuss the differences between ex situ, UHV, in situ, and operando measurements. Our approach is robust, fast, simple, and suitable for systematically probing metal surfaces after aqueous exposure and electro-chemical polarization, which promises wide applications for studies of solid-liquid interfaces in corrosion, batteries, fuel cells, and electrocatalysis.
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| 1085. |
- Larsson, Alfred, et al.
(författare)
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Operando Surface Optical Reflectance Microscopy Study of Corrosion Film Growth on a Ni-Cr-Mo Alloy During Anodic Polarization
- 2023
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Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 127:44, s. 21871-21877
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Tidskriftsartikel (refereegranskat)abstract
- The solid-liquid interface, where corrosion reactions occur, is notoriously difficult to study in operando conditions. Few experimental techniques can provide surface sensitivity and spatial and temporal resolution and are compatible with liquid environments. 2-Dimensional surface optical reflectance (2D-SOR) is an emerging optical technique providing microscopic information with high temporal resolution. It complements methods such as ambient pressure X-ray photoelectron spectroscopy or inductively coupled plasma-mass spectrometry, which provides valuable chemical information from the surface and the dissolving species but lacks spatial resolution. Here, we show how 2D-SOR can be used to measure the formation and growth of corrosion products in operando through oscillations in the reflected signal caused by constructive and destructive interference of the light in the film of growing corrosion products. The total thickness of the corrosion product film obtained with 2D-SOR agrees well with that measured using scanning electron microscopy ex situ. 2D-SOR has proved to be an excellent and valuable tool for monitoring the corrosion process with spatial resolution in operating conditions.
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| 1086. |
- Larsson, Alfred, et al.
(författare)
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The Oxygen Evolution Reaction Drives Passivity Breakdown for Ni–Cr–Mo Alloys
- 2023
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Ingår i: Advanced Materials. - : Wiley. - 0935-9648 .- 1521-4095. ; 35:39
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Tidskriftsartikel (refereegranskat)abstract
- Corrosion is the main factor limiting the lifetime of metallic materials, and a fundamental understanding of the governing mechanism and surface processes is difficult to achieve since the thin oxide films at the metal–liquid interface governing passivity are notoriously challenging to study. In this work, a combination of synchrotron-based techniques and electrochemical methods is used to investigate the passive film breakdown of a Ni–Cr–Mo alloy, which is used in many industrial applications. This alloy is found to be active toward oxygen evolution reaction (OER), and the OER onset coincides with the loss of passivity and severe metal dissolution. The OER mechanism involves the oxidation of Mo4+ sites in the oxide film to Mo6+ that can be dissolved, which results in passivity breakdown. This is fundamentally different from typical transpassive breakdown of Cr-containing alloys where Cr6+ is postulated to be dissolved at high anodic potentials, which is not observed here. At high current densities, OER also leads to acidification of the solution near the surface, further triggering metal dissolution. The OER plays an important role in the mechanism of passivity breakdown of Ni–Cr–Mo alloys due to their catalytic activity, and this effect needs to be considered when studying the corrosion of catalytically active alloys.
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| 1087. |
- Larsson, Alfred, et al.
(författare)
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Thickness and composition of native oxides and near-surface regions of Ni superalloys
- 2022
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Ingår i: Journal of Alloys and Compounds. - : Elsevier BV. - 0925-8388 .- 1873-4669. ; 895
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Tidskriftsartikel (refereegranskat)abstract
- The surface chemistry and thickness of the native oxide, hydroxide, and modified sub-surface layer of three Ni superalloys (alloy 59, 625, and 718) were determined by synchrotron X-ray Photoelectron Spectroscopy (XPS) and X-ray Reflectivity (XRR). Taking advantage of the synchrotron radiation techniques, a procedure for normalizing the photoelectron intensity was employed, which allowed for accurate quantitative analysis revealing a total oxide thickness for all samples of 12-13 A, a hydroxide layer of 2-3 A, and a thickness of the sub-surface alloy layer of 20-35 A. The thickness results were compared to structural atomic models suggesting that the oxide thickness corresponds to four planes of metal cations in the oxide matrix. The XPS data revealed that the native oxides were enriched in Cr3+, Mo-(4,Mo-5,Mo-6)+, and Nb5+, while no Ni oxide was detected. The hydroxide layer mainly contained Ni2+ and Cr3+ hydroxide. The sub-surface layer was enriched in Ni and depleted in Cr, Fe, Mo, and Nb. The obtained oxide composition can be explained using thermodynamics, and it was found that the oxide composition correlates with the enthalpy of oxide formation for the metal elements in the alloys. Finally, the advantages of synchrotron radiation for composition and thickness determination are discussed.
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| 1088. |
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| 1089. |
- Larsson, Gustaf, et al.
(författare)
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Duration of load behaviour of a glued shear plate dowel joint
- 2020
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Ingår i: European Journal of Wood and Wood Products. - : Springer. - 0018-3768 .- 1436-736X. ; 78:1, s. 5-15
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Tidskriftsartikel (refereegranskat)abstract
- An experimental study on the duration of load effects in a glued shear plate dowel joint was conducted. The joint design features a single large diameter dowel for load transfers between members, via external steel plates, which are bonded to the timber with a low stiffness bond line. Due to the low bond line stiffness, the timber element is subjected to a close to uniform shear stress distribution over the bond area. The study comprises a total of 80 test specimens loaded in shear, both parallel and perpendicular to the grain, at three load levels in the range of 50–80% of the short-term failure load. All specimens failed within approximately 110 days in outdoor sheltered conditions during which time deformations were recorded for one specimen of each type and load level. The study found a significantly larger influence of duration of load for this dominant shear action than what is reported in the literature for bending tests. The method of ranked stress was used to determine a suggested reduction factor kmod for the shear plate dowel joint to 0.10 and 0.30 for parallel and perpendicular loading, respectively. This is a rough estimate based upon a 50-year extrapolation of 4-month data. Thus, it must be concluded that the studied shear plate dowel joint is not efficient in terms of long-duration loads in outdoor sheltered climate, and that further studies are needed in order to verify the use in other climates. It is also evident in this study that there is a lack of knowledge and empirical evidence on the duration of load effects in timber for shear loading.
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| 1090. |
- Larsson Ivanov, Oskar, et al.
(författare)
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The practical value of structural health information for time dependence in bridge maintenance
- 2021
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Ingår i: Structure and Infrastructure Engineering. - : Informa UK Limited. - 1573-2479 .- 1744-8980. ; , s. 1-16
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Tidskriftsartikel (refereegranskat)abstract
- For practical decisions on common recurring maintenance actions, the information from routine inspections form a decision basis for the bridge manager. It is often difficult to assess whether this information is sufficient for deciding on a repair action, or if more information is needed. For many bridges the information for supporting decisions may be limited, although those bridges cause large yearly maintenance costs for the society. The purpose of the study presented in this paper is to show how two different models for decision making based on Bayesian decision theory, a point-in-time decision model and a sequential updating decision model, can be used to improve the decision-making process for common maintenance decisions. The models use information from routine inspections and incorporates time dependent aspects such as material degradation and time value of money to improve the decision-making process. The focus is on presenting the methodology with a case study of a concrete bridge in Sweden where the edge beams may have to be replaced. Three assessment approaches are considered: (i) no assessment, (ii) desktop evaluation and (iii) measurements. The main finding is that sequential updating decision making will provide a higher benefit than a point-in-time decision, and thus give higher Value of Information. This value becomes even higher when the measurements are selected for the assessment. The results also show that the edge beams should be replaced. The general approach presented can be applicable to many decision scenarios related to maintenance of deteriorating structures.
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