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Herlev, Denmark

Wang J.,Nordic Bioscience A S | Willumsen N.,Biomarkers and Research | Zheng Q.,Nordic Bioscience A S | Xue Y.,Nordic Bioscience A S | And 2 more authors.
Future Oncology | Year: 2013

Cancer is a heterogeneous disease and consequently an exact diagnosis is as important as the actual therapy. Therefore, identification of novel diagnostic biomarker targets is urgently needed. Physiological and pathological changes are reflected by post-translational modifications of proteins. Each post-translational modification (e.g., proteolytic cleavage) is the result of a specific local process and may produce disease-specific neoepitopes. Neoepitopes have been successfully used as biomarkers in many diseases, and may also serve as promising tools in the development of future diagnostic assays within oncology. By specifically targeting neoepitopes, more information regarding disease-type and -state may be obtained and future research into neoepitopes will provide important and novel means for the diagnosis, prognosis and treatment efficacy in cancer. In this paper, we focus on protein ectodomain shedding and the generation of neoepitopes as future noninvasive (serological) cancer biomarkers. We use the protein ectodomain shedding of the human epidermal growth factor receptor 2, which is associated with breast cancer, as an example. We assess the current status of measuring human epidermal growth factor receptor 2 and discuss how this potentially could be improved. Furthermore, we expand the discussion to include examples of other cancer associated proteins. © 2013 Future Medicine Ltd. Source

Siebuhr A.S.,Biomarkers and Research | Bay-Jensen A.C.,Biomarkers and Research | Karsdal M.A.,Biomarkers and Research | Lories R.J.,Catholic University of Leuven | De Vlam K.,Catholic University of Leuven
Biomarkers in Medicine | Year: 2016

To investigate if tissue turnover biomarkers were efficacy biomarkers in ankylosing spondylitis and if the biomarkers at baseline predicted a good outcome (BASDAI50). Patients and methods: Twenty-two etanercept treated ankylosing spondylitis patients were investigated for inflammation (CRP, ESR, CRPM) and tissue turnover (C1M, C2M, C3M) during the first year of treatment. Biomarkers profiles and treatment response were investigated. Results: ESR, CRP, BASDAI and C1M were decreased with treatment (p ≤ 0.04). C1M and CRP segregated patients into two populations predicting treatment efficacy. Conclusion: C1M and CRP were efficacy biomarkers and baseline biomarkers could select who benefited (by biomarkers) from treatment. C1M was not superior to CRP, but the biomarkers evaluate different pathologic events, indicating that C1M and CRP identify different events. © 2016 Future Medicine Ltd. Source

Inekci D.,Biomarkers and Research | Inekci D.,Technical University of Denmark | Jonesco D.S.,Biomarkers and Research | Kennard S.,Biomarkers and Research | And 2 more authors.
Frontiers in Neurology | Year: 2015

The diagnosis of dementia is challenging and early stages are rarely detected limiting the possibilities for early intervention. Another challenge is the overlap in the clinical features across the different dementia types leading to difficulties in the differential diagnosis. Identifying biomarkers that can detect the pre-dementia stage and allow differential diagnosis could provide an opportunity for timely and optimal intervention strategies. Also, such biomarkers could help in selection and inclusion of the right patients in clinical trials of both Alzheimer's disease and other dementia treatment candidates. The cerebrospinal fluid (CSF) has been the most investigated source of biomarkers and several candidate proteins have been identified. However, looking solely at protein levels is too simplistic to provide enough detailed information to differentiate between dementias, as there is a significant crossover between the proteins involved in the different types of dementia. Additionally, CSF sampling makes these biomarkers challenging for presymptomatic identification. We need to focus on disease-specific protein fragmentation to find a fragment pattern unique for each separate dementia type - a form of protein fragmentology. Targeting protein fragments generated by disease-specific combinations of proteins and proteases opposed to detecting the intact protein could reduce the overlap between diagnostic groups as the extent of processing as well as which proteins and proteases constitute the major hallmark of each dementia type differ. In addition, the fragments could be detectable in blood as they may be able to cross the blood-brain barrier due to their smaller size. In this review, the potential of the fragment-based biomarker discovery for dementia diagnosis and prognosis is discussed, especially highlighting how the knowledge from CSF protein biomarkers can be used to guide blood-based biomarker development. © 2015 Inekci, Jonesco, Kennard, Karsdal and Henriksen. Source

Kjelgaard-Petersen C.,Biomarkers and Research | Siebuhr A.S.,Biomarkers and Research | Christiansen T.,Gentofte University Hospital | Ladel C.,Biomarkers and Research | And 2 more authors.
Biomarkers | Year: 2016

Objective: Characterize biomarkers measuring extracellular matrix turnover of inflamed osteoarthritis synovium. Methods: Human primary fibroblast-like synoviocytes and synovial membrane explants (SMEs) treated with various cytokines and growth factors were assessed by C1M, C3M, and acMMP3 in the conditioned medium. Results: TNFα significantly increased C1M up to seven-fold (p = 0.0002), C3M up to 24-fold (p = 0.0011), and acMMP3 up to 14-fold (p < 0.0001) in SMEs. IL-1β also significantly increased C1M up to five-fold (p = 0.00094), C3M four-fold (p = 0.007), and acMMP3 18-fold (p < 0.0001) in SMEs. Conclusion: The biomarkers C1M, C3M, and acMMP-3 were synovitis biomarkers ex vivo and provide a translational tool together with the SME model. © 2016 The Author(s). Published by Taylor & Francis. Source

Sand J.M.B.,Copenhagen University | Knox A.J.,University of Nottingham | Lange P.,Copenhagen University | Sun S.,Biomarkers and Research | And 5 more authors.
Respiratory Research | Year: 2015

Background: Exacerbations of chronic obstructive pulmonary disease (COPD) contribute significantly to disease progression. However, the effect on tissue structure and turnover is not well described. There is an urgent clinical need for biomarkers of disease activity associated with disease progression. Extracellular matrix (ECM) turnover reflects activity in tissues and consequently assessment of ECM turnover may serve as biomarkers of disease activity. We hypothesized that the turnover of lung ECM proteins were altered during exacerbations of COPD. Methods: 69 patients with COPD hospitalised for an exacerbation were recruited at admission and returned for a 4 weeks follow-up. Competitive ELISAs measuring circulating protein fragments in serum or plasma assessed the formation and degradation of collagen types III (Pro-C3 and C3M, respectively), IV (P4NP 7S and C4M, respectively), and VI (Pro-C6 and C6M, respectively), and degradation of elastin (ELM7 and EL-NE) and versican (VCANM). Results: Circulating levels of C3M, C4M, C6M, ELM7, and EL-NE were elevated during an exacerbation of COPD as compared to follow-up (all P <0.0001), while VCANM levels were decreased (P <0.0001). Pro-C6 levels were decreased and P4NP 7S levels were elevated during exacerbation (P <0.0001). Pro-C3 levels were unchanged. At time of exacerbation, degradation/formation ratios were increased for collagen types III and VI and decreased for collagen type IV. Conclusions: Exacerbations of COPD resulted in elevated levels of circulating fragments of structural proteins, which may serve as markers of disease activity. This suggests that patients with COPD have accelerated ECM turnover during exacerbations which may be related to disease progression. © 2015 Sand et al. Source

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