Respiratory System, Idiopathic Pulmonary Fibrosis, Oncology, Lung
30. Nov 2018
A serological marker of the N-terminal neoepitope generated during LOXL2 maturation is elevated in patients with cancer or idiopathic pulmonary fibrosis
OBJECTIVES:
Lysyl oxidase like 2 (LOXL2) is associated with poor prognosis in idiopathic pulmonary disease (IPF) and cancer. We developed an Enzyme-linked immunosorbent assay (ELISA) targeting the LOXL2 neo-epitope generated through the release of the signal peptide during LOXL2 maturation.
DESI…
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Journal:
Authors:
- Leeming DJ,
- Willumsen N,
- Sand JM,
- Holm Nielsen S,
- Dasgupta B,
- Brodmerkel C,
- Bager CL,
- Karsdal MA,
Respiratory System, Chronic Obstructive Pulmonary Disease
1. Oct 2018
Collagen Degradation and Formation Are Elevated in Exacerbated COPD Compared With Stable Disease.
BACKGROUND:
The role of the extracellular matrix (ECM) structure and remodeling thereof in lung diseases is gaining importance. Pathology-related changes in ECM turnover may result in deleterious changes in lung architecture, leading to disease in the small airways. Here, degradation fragments of t…
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Journal:
Authors:
- Schuppan D,
- Leeming DJ,
- papakonstantinou E,
- Kostikas K,
- Boersma W,
- Louis R,
- Milenkovik B,
- Aerts J,
- Sand JM,
- Wouters EFM,
- Rohde G,
- Prat C,
- Torres A,
- Welte T,
- Tamm M,
- Karsdal M,
- Stolz D,
Respiratory System, Chronic Obstructive Pulmonary Disease
10. Sep 2018
Lung tissue destruction by proteinase 3 and cathepsin G mediated elastin degradation is elevated in chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease (COPD) is characterized by high levels of protease activity leading to degradation of elastin followed by loss of elasticity of the lung and the development of emphysema. Elastin is an essential structural component of the lung parenchyma to support the expansio…
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Journal:
Authors:
- Gudmann NS,
- Manon-Jensen T,
- Sand JM,
- Diefenbach C,
- Sun S,
- Danielsen A,
- Karsdal MA,
- Leeming DJ,
Extracellular Matrix Research
21. Jul 2017
The good and the bad collagens of fibrosis - Their role in signaling and organ function
Usually the dense extracellular structure in fibrotic tissues is described as extracellular matrix (ECM) or simply as collagen. However, fibrosis is not just fibrosis, which is already exemplified by the variant morphological characteristics of fibrosis due to viral versus cholestatic, autoimmune or…
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Journal:
Authors:
- Karsdal MA,
- Nielsen SH,
- Leeming DJ,
- Langholm LL,
- Nielsen MJ,
- Manon-Jensen T,
- Siebuhr AS,
- Gudmann NS,
- Rønnow S,
- Sand JM,
- Daniels SJ,
- Mortensen JH,
- Schuppan D,
Extracellular Matrix Research
19. Jan 2017
Biomarkers of extracellular matrix turnover are associated with emphysema and eosinophilic-bronchitis in COPD
BACKGROUND:
Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction and loss of lung tissue mainly consisting of extracellular matrix (ECM). Three of the main ECM components are type I collagen, the main constituent in the interstitial matrix, type VI collagen, and elas…
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Journal:
Authors:
- Bihlet AR,
- Karsdal MA,
- Sand JM,
- Leeming DJ,
- Roberts M,
- Bowler R,
- White W,
Chronic Obstructive Pulmonary Disease
11. Jan 2017
Development of a Novel Enzyme-Linked Immunosorbent Assay Targeting a Neo-Epitope Generated by Cathepsin-Mediated Turnover of Type III Collagen and Its Application in Chronic Obstructive Pulmonary Disease
A high level of extracellular matrix (ECM) turnover characterizes several lung diseases with fibrotic features. Type III collagen is one of the most abundant collagens in lung parenchyma, and cathepsins play a role in lung pathology, being responsible for tissue remodeling. In this study, we explore…
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Authors:
Extracellular Matrix Research, Respiratory System
4. Oct 2016
High levels of biomarkers of collagen remodeling are associated with increased mortality in COPD - results from the ECLIPSE study
BACKGROUND:
There is a need to identify individuals with COPD at risk for disease progression and mortality. Lung tissue remodeling is associated with the release of extracellular matrix (ECM) fragments into the peripheral circulation. We hypothesized that ECM remodeling was associated with mortali…
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Journal:
Authors:
- Sand JM,
- Leeming DJ,
- Byrjalsen I,
- Bihlet AR,
- Lange P,
- Tal-Singer R,
- Miller BE,
- Karsdal MA,
- Vestbo J,
Respiratory System, Chronic Obstructive Pulmonary Disease
7. Sep 2016
Characterization of serological neo-epitope biomarkers reflecting collagen remodeling in clinically stable chronic obstructive pulmonary disease
OBJECTIVES:
Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation that leads to excessive remodeling of the lung extracellular matrix (ECM), resulting in release of protein fragments (neo-epitopes) to the blood. Serological markers assessing this have previously been…
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Journal:
Authors:
- Lange P,
- Leeming DJ,
- Karsdal MA,
- Midjord AK,
- Martinez G,
- Sand JM,
Chronic Obstructive Pulmonary Disease
26. Aug 2016
Systemic Biomarkers of Collagen and Elastin Turnover Are Associated With Clinically Relevant Outcomes in COPD
BACKGROUND:
Extracellular matrix (ECM) remodeling of the lung tissue releases protein fragments into the blood, where they may be detected as serologic surrogate markers of disease activity in COPD. Our goal was to assess the association of ECM turnover with severity and outcome of COPD.
METHODS…
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Journal:
Authors:
- Leeming DJ,
- Kristensen JH,
- Karsdal MA,
- Sand JM,
Extracellular Matrix Research
1. Aug 2016
Type VIII collagen is elevated in diseases associated with angiogenesis and vascular remodeling
OBJECTIVES:
Type VIII collagen is involved in angiogenesis and remodeling of arteries. We hypothesized that type VIII collagen was upregulated in diseases associated with vascular remodeling, e.g. pulmonary fibrosis and cancer. In this paper we present the development and validation of a competiti…
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Journal:
Authors:
- Hansen NU,
- Willumsen N,
- Sand JM,
- Larsen L,
- Karsdal MA,
- Leeming DJ,
Respiratory System, Idiopathic Pulmonary Fibrosis
9. Jul 2015
Levels of circulating MMP-7 degraded elastin are elevated in pulmonary disorders
OBJECTIVES:
Elastin is a signature protein of the lungs. Matrix metalloproteinase-7 (MMP-7) is important in lung defence mechanisms and degrades elastin. However, MMP-7 activity in regard to elastin degradation has never been quantified serologically in patients with lung diseases. An assay for the…
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Journal:
Authors:
- Kristensen JH,
- Larsen L,
- Dasgupta B,
- Brodmerkel C,
- Curran M,
- Karsdal MA,
- Sand JM,
- Willumsen N,
- Knox AJ,
- Bolton CE,
- Johnson SR,
- Hägglund P,
- Svensson B,
- Leeming DJ,
Respiratory System, Chronic Obstructive Pulmonary Disease
1. Jul 2015
Clinical Drug Development Using Dynamic Biomarkers to Enable Personalized Health Care in COPD
Despite massive investments in the development of novel treatments for heterogeneous diseases such as COPD, the resources spent have only benefited a fraction of the population treated. Personalized health care to guide selection of a suitable patient population already in the clinical development o…
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Journal:
Authors:
- Bihlet A,
- Karsdal MA,
- Bay-Jensen AC,
- Read S,
- Kristensen JH,
- Sand JM,
- Leeming DJ,
- Andersen JR,
- Lange P,
- Vestbo J,
Chronic Obstructive Pulmonary Disease, Respiratory System
11. Jun 2015
Accelerated extracellular matrix turnover during exacerbations of COPD
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 progress…
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Journal:
Authors:
- Sand JM,
- Knox AJ,
- Lange P,
- Sun S,
- Kristensen JH,
- Leeming DJ,
- Karsdal MA,
- Bolton CE,
- Johnson SR,
Hepatic System, Non-Alcoholic Fatty Liver Disease
15. May 2015
Novel insights into the function and dynamics of extracellular matrix in liver fibrosis
Emerging evidence suggests that altered components and posttranslational modifications of proteins in the extracellular matrix (ECM) may both initiate and drive disease progression. The ECM is a complex grid consisting of multiple proteins, most of which play a vital role in containing the essential…
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Authors:
- Karsdal MA,
- Manon-Jensen T,
- Genovese F,
- Kristensen JH,
- Nielsen MJ,
- Sand JM,
- Hansen NU,
- Bay-Jensen AC,
- Bager CL,
- Krag A,
- Blanchard A,
- Krarup H,
- Leeming DJ,
- Schuppan D,
Respiratory System, Chronic Obstructive Pulmonary Disease
3. May 2015
Serological assessment of neutrophil elastase activity on elastin during lung ECM remodeling
BACKGROUND:
During the pathological destruction of lung tissue, neutrophil elastase (NE) degrades elastin, one of the major constituents of lung parenchyma. However there are no non-invasive methods to quantify NE degradation of elastin. We selected specific elastin fragments generated by NE for an…
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Journal:
Authors:
- Kristensen JH,
- Karsdal MA,
- Sand JM,
- Willumsen N,
- Diefenbach C,
- Svensson B,
- Hägglund P,
- Oersnes-Leeming DJ,
Extracellular Matrix Research, Hepatic System
5. Aug 2014
Review article: the efficacy of biomarkers in chronic fibroproliferative diseases - early diagnosis and prognosis, with liver fibrosis as an exemplar
BACKGROUND:
Nearly 45% of all deaths are associated with chronic fibroproliferative diseases, of which the primary characteristic is altered remodelling of the extracellular matrix. A major difficulty in developing anti-fibrotic therapies is the lack of accurate and established techniques to estima…
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Journal:
Authors:
- Karsdal MA,
- Krarup H,,
- Sand JM,
- Christensen PB,
- Gerstoft J,
- Leeming DJ,
- Weis N,
- Schaffalitzky de Muckadell OB,
- Krag A,
Respiratory System, Chronic Obstructive Pulmonary Disease
13. Dec 2013
MMP mediated degradation of type IV collagen alpha 1 and alpha 3 chains reflects basement membrane remodeling in experimental and clinical fibrosis--validation of two novel biomarker assays
OBJECTIVES:
Fibrosis is characterized by excessive tissue remodeling resulting from altered expression of various growth factors, cytokines and proteases. We hypothesized that matrix metalloproteinase (MMP) mediated degradation of type IV collagen, a main component of the basement membrane, will re…
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Journal:
Authors:
- Sand JM,
- Larsen L,
- Hogaboam C,
- Martinez F,
- Han M,
- Røssel Larsen M,
- Nawrocki A,
- Zheng Q,
- Karsdal MA,
- Leeming DJ,
Extracellular Matrix Research
11. Mar 2013
Extracellular matrix remodeling: the common denominator in connective tissue diseases. Possibilities for evaluation and current understanding of the matrix as more than a passive architecture, but a key player in tissue failure
Increased attention is paid to the structural components of tissues. These components are mostly collagens and various proteoglycans. Emerging evidence suggests that altered components and noncoded modifications of the matrix may be both initiators and drivers of disease, exemplified by excessive ti…
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Journal:
Authors:
- Karsdal MA,
- Nielsen MJ,
- Sand JM,
- Henriksen K,
- Genovese F,
- Bay-Jensen AC,
- Adamkewicz JI,
- Christiansen C,
- Leeming DJ,
Respiratory System, Chronic Obstructive Pulmonary Disease, Idiopathic Pulmonary Fibrosis
11. Jul 2012
Serological investigation of the collagen degradation profile of patients with chronic obstructive pulmonary disease or idiopathic pulmonary fibrosis
In both chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), abnormally high collagen remodeling occurs within the lung tissue. Matrix metalloproteinase (MMP)-degraded type I, III, IV, V and VI collagen and a disintegrin and metalloproteinase with thrombospondin moti…
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Journal:
Authors:
- Leeming DJ,
- Sand JM,
- Nielsen MJ,
- Genovese F,
- Martinez FJ,
- Hogaboam CM,
- Han MK,
- Klickstein LB,
- Karsdal MA,