| 1. |
- Tobin, N. P., et al.
(författare)
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Molecular subtype and tumor characteristics of breast cancer metastases as assessed by gene expression significantly influence patient post-relapse survival
- 2015
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Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 26:1, s. 81-88
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Tidskriftsartikel (refereegranskat)abstract
- We and others have recently shown that tumor characteristics are altered throughout tumor progression. These findings emphasize the need for re-examination of tumor characteristics at relapse and have led to recommendations from ESMO and the Swedish Breast Cancer group. Here, we aim to determine whether tumor characteristics and molecular subtypes in breast cancer metastases confer clinically relevant prognostic information for patients. The translational aspect of the Swedish multicenter randomized trial called TEX included 111 patients with at least one biopsy from a morphologically confirmed locoregional or distant breast cancer metastasis diagnosed from December 2002 until June 2007. All patients had detailed clinical information, complete follow-up, and metastasis gene expression information (Affymetrix array GPL10379). We assessed the previously published gene expression modules describing biological processes [proliferation, apoptosis, human epidermal receptor 2 (HER2) and estrogen (ER) signaling, tumor invasion, immune response, and angiogenesis] and pathways (Ras, MAPK, PTEN, AKT-MTOR, PI3KCA, IGF1, Src, Myc, E2F3, and beta-catenin) and the intrinsic subtypes (PAM50). Furthermore, by contrasting genes expressed in the metastases in relation to survival, we derived a poor metastasis survival signature. A significant reduction in post-relapse breast cancer-specific survival was associated with low-ER receptor signaling and apoptosis gene module scores, and high AKT-MTOR, Ras, and beta-catenin module scores. Similarly, intrinsic subtyping of the metastases provided statistically significant post-relapse survival information with the worst survival outcome in the basal-like [hazard ratio (HR) 3.7; 95% confidence interval (CI) 1.3-10.9] and HER2-enriched (HR 4.4; 95% CI 1.5-12.8) subtypes compared with the luminal A subtype. Overall, 25% of the metastases were basal-like, 32% HER2-enriched, 10% luminal A, 28% luminal B, and 5% normal-like. We show that tumor characteristics and molecular subtypes of breast cancer metastases significantly influence post-relapse patient survival, emphasizing that molecular investigations at relapse provide prognostic and clinically relevant information.
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| 2. |
- Azimi, A, et al.
(författare)
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Silencing FLI or targeting CD13/ANPEP lead to dephosphorylation of EPHA2, a mediator of BRAF inhibitor resistance, and induce growth arrest or apoptosis in melanoma cells
- 2017
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Ingår i: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 8:8, s. e3029-
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Tidskriftsartikel (refereegranskat)abstract
- A majority of patients with BRAF-mutated metastatic melanoma respond to therapy with BRAF inhibitors (BRAFi), but relapses are common owing to acquired resistance. To unravel BRAFi resistance mechanisms we have performed gene expression and mass spectrometry based proteome profiling of the sensitive parental A375 BRAF V600E-mutated human melanoma cell line and of daughter cell lines with induced BRAFi resistance. Increased expression of two novel resistance candidates, aminopeptidase-N (CD13/ANPEP) and ETS transcription factor FLI1 was observed in the BRAFi-resistant daughter cell lines. In addition, increased levels of the previously reported resistance mediators, receptor tyrosine kinase ephrine receptor A2 (EPHA2) and the hepatocyte growth factor receptor MET were also identified. The expression of these proteins was assessed in matched tumor samples from melanoma patients obtained before BRAFi and after disease progression. MET was overexpressed in all progression samples while the expression of the other candidates varied between the individual patients. Targeting CD13/ANPEP by a blocking antibody induced apoptosis in both parental A375- and BRAFi-resistant daughter cells as well as in melanoma cells with intrinsic BRAFi resistance and led to dephosphorylation of EPHA2 on S897, previously demonstrated to cause inhibition of the migratory capacity. AKT and RSK, both reported to induce EPHA2 S897 phosphorylation, were also dephosphorylated after inhibition of CD13/ANPEP. FLI1 silencing also caused decreases in EPHA2 S897 phosphorylation and in total MET protein expression. In addition, silencing of FLI1 sensitized the resistant cells to BRAFi. Furthermore, we show that BRAFi in combination with the multi kinase inhibitor dasatinib can abrogate BRAFi resistance and decrease both EPHA2 S897 phosphorylation and total FLI1 protein expression. This is the first report presenting CD13/ANPEP and FLI1 as important mediators of resistance to BRAF inhibition with potential as drug targets in BRAFi refractory melanoma.
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| 3. |
- Buker, O., et al.
(författare)
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Metrological support for LNG custody transfer and transport
- 2016
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Ingår i: Proceedings of the 17th International Flow Measurement Conference (FLOMEKO 2016).
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Konferensbidrag (refereegranskat)abstract
- In the framework of the ongoing EMRP Joint Research Project (JRP) ENG 60 “Metrology for LNG” (2014-2017), co-funded by the European Union, a number of metrological challenges associated with custody transfer and transport of LNG will be faced. The project consists of four technical work packages (WP), whereby the main objective is to reduce the measurement uncertainty of LNG custody transfer by a factor two. The focus in WP1 is the design and development of a traceable mid-scale calibration standard for LNG mass and volume flow. The goal is to provide traceable mass and volume flow calibrations up to 400 m3/h (180000 kg/h). In WP2, the emphasis is on the development and validation of a LNG sampling and composition measurement reference standard, consisting of sampler, vaporizer, gas standards, and gas chromatography (GC), which will be used to test and calibrate commercially available LNG sampling and composition measurement systems. The priority in WP3 is given to the development and validation of a method for the determination of the methane number, including correlations based on the LNG composition and corrections for traces of nitrogen and higher hydrocarbons. Since physical properties and quantities play an important role in LNG custody transfer, WP4 comprises reference quality density measurements of LNG to validate and improve models for LNG density predictions, the uncertainty evaluation of enthalpy and calorific value calculations and the development of a novel cryogenic sensor for the simultaneous measurement of speed-of-sound and density. The present paper gives an overview of recently achieved objectives within the project and provides an outlook to future activities.
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| 4. |
- Stolt-Bergner, Peggy, et al.
(författare)
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Baculovirus-driven protein expression in insect cells : A benchmarking study
- 2018
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Ingår i: Journal of Structural Biology. - : Elsevier BV. - 1047-8477. ; 203:2, s. 71-80
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Tidskriftsartikel (refereegranskat)abstract
- Baculovirus-insect cell expression system has become one of the most widely used eukaryotic expression systems for heterologous protein production in many laboratories. The availability of robust insect cell lines, serum-free media, a range of vectors and commercially-packaged kits have supported the demand for maximizing the exploitation of the baculovirus-insect cell expression system. Naturally, this resulted in varied strategies adopted by different laboratories to optimize protein production. Most laboratories have preference in using either the E. coli transposition-based recombination bacmid technology (e.g. Bac-to-Bac®) or homologous recombination transfection within insect cells (e.g. flashBAC™). Limited data is presented in the literature to benchmark the protocols used for these baculovirus vectors to facilitate the selection of a system for optimal production of target proteins. Taking advantage of the Protein Production and Purification Partnership in Europe (P4EU) scientific network, a benchmarking initiative was designed to compare the diverse protocols established in thirteen individual laboratories. This benchmarking initiative compared the expression of four selected intracellular proteins (mouse Dicer-2, 204 kDa; human ABL1 wildtype, 126 kDa; human FMRP, 68 kDa; viral vNS1-H1, 76 kDa). Here, we present the expression and purification results on these proteins and highlight the significant differences in expression yields obtained using different commercially-packaged baculovirus vectors. The highest expression level for difficult-to-express intracellular protein candidates were observed with the EmBacY baculovirus vector system.
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| 5. |
- Suhonen, Riitta, et al.
(författare)
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Hospitalised cancer patients' perceptions of individualised nursing care in four European countries
- 2018
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Ingår i: European Journal of Cancer Care. - : Hindawi Limited. - 0961-5423 .- 1365-2354. ; 27:1
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to describe hospitalised cancer patients' perceptions of individualised care in four European countries and compare these perceptions using the patients' socio-demographic characteristics and the Individualized Care Scale. The patients' socio-demographic characteristics used were: education, age, gender, type of hospital admission, previous hospitalisation and hospital length of stay. The Individualized Care Scale has two parts (1) nurses' support of individuality and (2) patients' receipt of individuality. Data (n = 599) were collected in Cyprus (n = 150), Finland (n = 158), Greece (n = 150) and Sweden (n = 141). Multivariate analysis of variance models were constructed and differences in perceptions of individualised care were analysed using the patients' socio-demographic characteristics as covariates. The level of support for individuality and receipt of individualised care was reported as moderate and good respectively. Generally, the highest assessments were made by the Swedish respondents and the lowest by those in Greece. This study revealed some between-country differences in patients' perceptions of care individualisation. These differences, for example, conceptual, educational, based in clinical practice or in the health organisation, require further research. Enquiry into the individualised care perceptions of health care providers and the families of cancer patients would also be useful.
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| 6. |
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