| 1. |
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| 2. |
- Björner, Sofie, et al.
(författare)
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Body mass index influences the prognostic impact of combined nuclear insulin receptor and estrogen receptor expression in primary breast cancer
- 2017
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 8:NOV
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Tidskriftsartikel (refereegranskat)abstract
- The prognostic importance of tumor-specific nuclear insulin receptor (InsR) expression in breast cancer is unclear, while membrane and cytoplasmic localization of InsR is better characterized. The insulin signaling network is influenced by obesity and may interact with the estrogen receptor a (ERα) signaling. The purpose was to investigate the interplay between nuclear InsR, ER, body mass index (BMI), and prognosis. Tumor-specific expression of nuclear InsR was evaluated by immunohistochemistry in tissue microarrays from 900 patients with primary invasive breast cancer without preoperative treatment, included in a population-based cohort in Sweden (2002-2012) in relation to prognosis. Patients were followed for up to 11 years during which 107 recurrences were observed. Nuclear InsR+ expression was present in 214 patients (23.8%) and increased with longer time between surgery and staining (P < 0.001). There were significant effect modifications by ER status and BMI in relation to clinical outcomes. Nuclear InsR+ conferred higher recurrence-risk in patients with ER+ tumors, but lower risk in patients with ER- tumors (Pinteraction = 0.003). Normal-weight patients with nuclear InsR+ tumors had higher recurrence-risk, while overweight or obese patients had half the recurrence-risk compared to patients with nuclear InsR- tumors (Pinteraction = 0.007). Normal-weight patients with a nuclear InsR-/ER+ tumor had the lowest risk for recurrence compared to all other nuclear InsR/ER combinations [HRadj 0.50, 95% confidence interval (CI): 0.25-0.97], while overweight or obese patients with nuclear InsR-/ER- tumors had the worst prognosis (HRadj 7.75, 95% CI: 2.04-29.48). Nuclear InsR was more prognostic than ER among chemotherapy-treated patients. In summary, nuclear InsR may have prognostic impact among normal-weight patients with ER+ tumors and in overweight or obese patients with ER- tumors. Normal-weight patients with nuclear InsR-/ER+ tumors may benefit from less treatment than normal-weight patients with other nuclear InsR/ER combinations. Overweight or obese patients with nuclear InsR-/ER- tumors may benefit from more tailored treatment or weight management.
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| 3. |
- Björner, Sofie, et al.
(författare)
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Coffee is associated with lower breast tumor insulin-like growth factor receptor 1 levels in normal-weight patients and improved prognosis following tamoxifen or radiotherapy treatment
- 2018
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 9:JUN
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Tidskriftsartikel (refereegranskat)abstract
- Coffee is associated with decreased breast cancer risk, but the impact of body mass index (BMI) in combination with coffee consumption on prognosis is unclear. The suppressive effect of coffee constituents on the insulin-like growth factor receptor 1 (IGF1R) levels in breast cancer cells may play a role. The aim was to investigate the prognostic impact of coffee consumption and possible associations with tumor-specific IGF1R protein expression and BMI in a population-based cohort in Sweden, comprising 1,014 primary breast cancer patients without pretreatment enrolled 2002-2012 and followed for up to 13 years. Patients with higher coffee consumption had lower tumor IGF1R levels (P = 0.025), but only among the normal-weight patients (P = 0.005). Coffee did not impact the recurrence-risk overall. However, tamoxifen-treated patients with ER+ tumors drinking ≥ 2 cups of coffee/day had lower recurrence-risk [adjusted HR (HRadj) 0.57, 95% CI, 0.34-0.97] compared with patients with lower intake, although only among normal-weight patients (HRadj 0.37, 95% CI: 0.17-0.78; Pinteraction = 0.039). Similarly, coffee consumption ≥ 2 cups/day was associated with significantly lower recurrence-risk among the 640 radiotherapy-treated patients irrespective of BMI (HRadj 0.59, 95% CI 0.36-0.98) and in the 296 normal-weight patients (HRadj 0.36, 95% CI 0.17-0.76) but not in the 329 overweight or obese patients (HRadj 0.88, 95% CI 0.42-1.82) although the interaction was not significant (Pinteraction = 0.093). In conclusion, coffee consumption was negatively associated with tumor-specific IGF1R levels only among normal-weight patients. Though, IGF1R did not explain the association between coffee intake and improved prognosis among normal-weight tamoxifen- or radiotherapy-treated patients. Studies of IGF1R-targeting therapies may benefit from taking BMI and coffee consumption into account.
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| 4. |
- Björner, Sofie, et al.
(författare)
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Combined and individual tumor-specific expression of insulinlike growth factor-I receptor, insulin receptor and phosphoinsulin- like growth factor-I receptor/insulin receptor in primary breast cancer : Implications for prognosis in different treatment groups
- 2017
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:6, s. 9093-9107
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Tidskriftsartikel (refereegranskat)abstract
- Clinical trials examining insulin-like growth factor-I receptor (IGF1R)-targeting strategies have emphasized that better predictive biomarkers are required to improve patient selection. Immunohistochemical tumor-specific protein expression of IGF1R, insulin receptor (InsR), and phosphorylated IGF1R/InsR (pIGF1R/InsR) individually and combined in relation to breast cancer prognosis was evaluated in a populationbased cohort of 1,026 primary invasive breast cancer patients without preoperative treatment diagnosed in Sweden. IGF1R (n = 923), InsR (n = 900), and pIGF1R/InsR (n = 904) combined cytoplasmic and membrane staining was dichotomized. IGF1Rstrong/InsRmod/strong/pIGF1R/InsRpos tumors were borderline associated with 2-fold risk for events, HRadj (2.00; 95%CI 0.96-4.18). Combined IGF1R and pIGF1R/InsR status only impacted prognosis in patients with InsRmod/strong expressing tumors (Pinteraction = 0.041). IGF1Rstrong expression impacted endocrine treatment response differently depending on patients' age and type of endocrine therapy. Phospho-IGF1R/InsRpos was associated with lower risk for events among non-endocrine-treated patients irrespective of ER status, HRadj (0.32; 95%CI 0.16-0.63), but not among endocrinetreated patients (Pinteraction = 0.024). In non-endocrine-treated patients, pIGF1R/InsRpos was associated with lower risk for events after radiotherapy, HRadj (0.31; 95%CI 0.12-0.80), and chemotherapy, HRadj (0.29; 95%CI 0.09-0.99). This study highlights the complexity of IGF hetero-and homodimer signaling network and its interplay with endocrine treatment, suggesting that combinations of involved factors may improve patient selection for IGF1R-targeted therapy.
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| 5. |
- Busse, Christian, et al.
(författare)
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A FINITE ELEMENT STUDY OF THE EFFECT OF CRYSTAL ORIENTATION AND MISALIGNMENT ON THE CRACK DRIVING FORCE IN A SINGLE-CRYSTAL SUPERALLOY
- 2016
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Ingår i: PROCEEDINGS OF THE ASME TURBO EXPO: TURBINE TECHNICAL CONFERENCE AND EXPOSITION, 2016, VOL 7A. - : AMER SOC MECHANICAL ENGINEERS. - 9780791849835
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Konferensbidrag (refereegranskat)abstract
- The elastic and plastic anisotropy of the single-crystal materials bring many difficulties in terms of modeling, evaluation and prediction of fatigue crack growth. In this paper a single-crystal material model has been adopted to a finite element-environment, which is paired with a crack growth tool. All simulations are performed in a three-dimensional context. This methodology makes it possible to analyze complex finite element-models, which are more application-near than traditional two-dimensional models. The influence of the crystal orientation, as well as the influence of misalignments of the crystal orientation due to the casting process are investigated. It is shown that both the crystal orientation and the misalignment from the ideal crystal orientation are important for the crack driving force. The realistic maximum limit of 10 degrees misalignment is considered. It can be seen that crack growth behavior is highly influenced by the misalignment. This knowledge is of great interest for the industry in order to evaluate the crack growth in single-crystal components more accurately.
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| 6. |
- Busse, Christian, 1989-
(författare)
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Aspects of Crack Growth in Single-Crystal Nickel-Base Superalloys
- 2017
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This Licentiate of Engineering thesis is a product of the results generated in the research project KME-702, which comprises modelling, microstructure investigations and material testing of cast nickel-base superalloys.The main objective of this work is to model the fatigue crack propagation behaviour in single-crystal nickel-base superalloys. To achieve this, the influence of the crystal orientations on the cracking behaviour is assessed. The results show that the crystal orientation is strongly affecting the material response and must be accounted for. Furthermore, a linear elastic crack driving force parameter suitable for describing crystallographic cracking has been developed. This parameter is based on resolved anisotropic stress intensity factors and is able to predict the correct crystallographic cracking plane after a transition from a Mode I crack. Finally, a method to account for inelastic deformations in a linear elastic fracture mechanics context was investigated. A residual stress field is extracted from an uncracked finite-element model with a perfectly plastic material model and superimposed on the stress field from the cracked model with a linear elastic material model to account for the inelastic deformations during the determination of the crack driving force. The modelling work is validated by material testing on two different specimen geometries at different temperatures.This Licentiate of Engineering thesis consists of two parts, where Part I gives an introduction and background to the research area, while Part II consists of three papers.
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| 7. |
- Busse, Christian, et al.
(författare)
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Criteria evaluation for the transition of cracking modes in a single-crystal nickel-base superalloy
- 2020
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Ingår i: Theoretical and applied fracture mechanics (Print). - : ELSEVIER. - 0167-8442 .- 1872-7638. ; 106
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Tidskriftsartikel (refereegranskat)abstract
- Single-crystal nickel-base superalloys frequently experience two distinct fatigue crack growth modes. It has been observed that, under certain conditions, cracks transition from a path perpendicular to the loading direction to a crystallographic slip plane. As crystallographic cracking is associated with an increased fatigue crack growth rate, it is important to be able to predict when this transition occurs. In this work three different criteria for crystallographic cracking based on resolved anisotropic stress intensity factors are evaluated in a three-dimensional finite element context. The criteria were calibrated and evaluated using isothermal fatigue experiments on two different specimen geometries. It is suggested by the results, that a threshold value of a resolved shear stress intensity factor can act as a conservative criterion indicating cracking mode transition. Further, a trend hinting towards a loading frequency dependency could be observed.
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| 8. |
- Busse, Christian, et al.
(författare)
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Evaluation of the crystallographic fatigue crack growth rate in a single-crystal nickel-base superalloy
- 2019
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Ingår i: International Journal of Fatigue. - : ELSEVIER SCI LTD. - 0142-1123 .- 1879-3452. ; 127, s. 259-267
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Tidskriftsartikel (refereegranskat)abstract
- Cracks in single-crystal nickel-base superalloys have been observed to switch cracking mode from Mode I to crystallographic cracking. The crack propagation rate is usually higher on the crystallographic planes compared to Mode I, which is important to account for in crack growth life predictions. In this paper, a method to evaluate the crystallographic fatigue crack growth rate, based on a previously developed crystallographic crack driving force parameter, is presented. The crystallographic crack growth rate was determined by evaluating heat tints on the fracture surfaces of the test specimens from the experiments. Complicated crack geometries including multiple crystallographic crack fronts were modelled in a three dimensional finite element context, The data points of the crystallographic fatigue crack growth rate collapse on a narrow scatter band for the crystallographic cracks indicating a correlation with the previously developed crystallographic crack driving force.
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| 9. |
- Busse, Christian, 1989-
(författare)
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Modelling of Crack Growth in Single-Crystal Nickel-Base Superalloys
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation was produced at the Division of Solid Mechanics at Linköping University and is part of a research project, which comprises modelling, microstructure investigations and material testing of cast nickel-base superalloys. The main objective of this work was to deepen the understanding of the fracture behaviour of single-crystal nickel-base superalloys and to develop a model to predict the fatigue crack growth behaviour. Frequently, crack growth in these materials has been observed to follow one of two distinct cracking modes; Mode I like cracking perpendicular to the loading direction or crystallographic crack growth on the octahedral {111}-planes, where the latter is associated with an increased fatigue crack growth rate. Thus, it is of major importance to account for this behaviour in component life prediction. Consequently, a model for the prediction of the transition of cracking modes and the correct active crystallographic plane, i.e. the crack path, and the crystallographic crack growth rate has been developed. This model is based on the evaluation of appropriate crack driving forces using three-dimensional finite-element simulations. A special focus was given towards the influence of the crystallographic orientation on the fracture behaviour. Further, a model to incorporate residual stresses in the crack growth modelling is presented. All modelling work is calibrated and validated by experiments on different specimen geometries with different crystallographic orientations. This dissertation consists of two parts, where Part I gives an introduction and background to the field of research, while Part II consists of six appended papers.
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| 10. |
- Busse, Christian, 1989-, et al.
(författare)
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Prediction of crystallographic cracking planes in single-crystal nickel-base superalloys
- 2018
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Ingår i: Engineering Fracture Mechanics. - : Elsevier. - 0013-7944 .- 1873-7315. ; 196, s. 206-223
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Tidskriftsartikel (refereegranskat)abstract
- The inherent anisotropy of single-crystal nickel-base superalloys brings many difficulties in terms of modelling, evaluation and prediction of fatigue crack growth. Two models to predict on which crystallographic plane cracking will occur is presented. The models are based on anisotropic stress intensity factors resolved on crystallographic slip planes calculated in a three-dimensional finite-element context. The developed models have been compared to experiments on two different test specimen geometries. The results show that a correct prediction of the crystallographic cracking plane can be achieved. This knowledge is of great interest for the industry and academia to better understand and predict crack growth in single-crystal materials.
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