Objective: Dysregulation of type I collagen metabolism has a great impact on human health. We have previously seen that matrix metalloproteinase-degraded type I collagen (C1M) is associated with early death and age-related pathologies. To dissect the biological impact of type I collagen dysregulatio...
September 20, 2020
Journal:
Neurol Genet
Author:
Tang ME, Blair JPM, Bager CL, Bay-Jensen AC, Henriksen K, Christiansen C, Karsdal MA.
There is an unmet need for high-quality liquid biomarkers that can safely and reproducibly predict the stage of fibrosis and the outcomes of chronic liver disease (CLD). The requirement for such markers has intensified because of the high global prevalence of diseases such as non-alcoholic fatty liv...
April 9, 2020
Journal:
Liver Int
Author:
Karsdal MA, Daniels SJ, Nielsen SH, Bager CL, Rasmussen DGK, Loomba R, Surabattula R, Villesen IF, Luo Y, Shevell D, Gudmann NS, Nielsen MJ, George J, Christian R, Leeming DJ, Schuppan D
This study investigated the association between body composition and risk of atrial fibrillation (AF) in postmenopausal women. In a retrospective analysis we assessed data from 5704 postmenopausal women (age 70.7 ± 6.5 yrs.) who in 1999-2001 participated in The Prospective Epidemiological Risk Facto...
January 17, 2020
Journal:
Sci Rep
Author:
Worm MS, Bager CL, Blair JPM, Secher NH, Riis BJ, Christiansen C, Nielsen HB
There is an increasing demand for accurate endotyping of patients according to their pathogenesis to allow more targeted treatment. We explore a combination of blood-based joint tissue metabolites (neoepitopes) to enable patient clustering through distinct disease profiles. We analysed data from two...
BACKGROUND: Osteoarthritis (OA) leads to joint failure and total joint replacement (TJR, either hip (H) or knee (K)). Worsening of pain and joint space narrowing are believed to be surrogates for joint failure; however, we hypothesize that TJR, as a reflection of joint failure, can be used as an end...
June 26, 2019
Journal:
BMC Musculoskelet Disord
Author:
Bager CL, Karsdal MA, Bihlet A, Thudium CS, Byrjalsen I, Bay-Jensen AC
BACKGROUND: Several epidemiological studies have shown an association between bone mineral density (BMD) and risk of breast cancer in postmenopausal women, but it remains unknown whether bone turnover is associated with increased risk of cancer. The aim of this study was to investigate if markers of...
Studies with direct measures of body fat distribution are required to explore the association between central and general obesity to cancer risk in postmenopausal women. This study investigates the association between central obesity and general obesity to overall/site-specific cancer risk in postme...
March 29, 2019
Journal:
Sci Rep
Author:
Stanstrup LM, Nielsen HB, Pedersen BK, Karsdal MA, Blair JPM, Christensen JF, Bager CL
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. DESIGN ...
November 30, 2018
Journal:
Biochem Biophys Rep
Author:
Leeming DJ, Willumsen N, Sand JM, Holm Nielsen S, Dasgupta B, Brodmerkel C, Bager CL, Karsdal MA
BACKGROUND: The relationship between levels of extracellular matrix (ECM) turnover and mortality is currently unknown. The study aimed to determine if levels of ECM turnover are predictors of all-cause mortality in a large cohort of post-menopausal women. METHODS: 5,855 postmenopausal Danish women ...
July 14, 2018
Journal:
J Gerontol A Biol Sci Med Sci
Author:
Bager CL, Willumsen N, Bay-Jensen AC, Nielsen HB, Karsdal MA
Chronic fibro-proliferative diseases are associated with nearly 45% of all deaths in the developed world. Matrix metalloproteinase (MMP) mediated remodeling of the extracellular matrix (ECM) plays an important role in disease development. Degradation of type I collagen is considered having a major r...
March 29, 2018
Journal:
Sci Rep
Author:
Bertelsen DM, Neergaard JS, Bager CL, Nielsen SH, Secher NH, Svendsen JH, Bihlet AR, Andersen JR, Karsdal MA, Christiansen C, Nielsen HB
Immuno-therapy has begun to revolutionize cancer treatment. However, despite the significant progress achieved in regard to the duration of clinical benefits, a substantial number of patients do not respond to these therapies. To improve the outcome of patients receiving immuno-therapy, there is a n...
November 8, 2017
Journal:
Cancer Immunol Immunother
Author:
Willumsen N, Thomsen LB, Bager CL, Jensen C, Karsdal MA
Background: Decorin is one of the most abundant proteoglycans of the extracellular matrix and is mainly secreted and deposited in the interstitial matrix by fibroblasts where it plays an important role in collagen turnover and tissue homeostasis. Degradation of decorin might disturb normal tissue ho...
August 9, 2017
Journal:
BMC Pulm Med.
Author:
Karsdal MA, Leeming DJ, Brix S, Curran M, Brodmerkel C, Dasgupta B, Willumsen N, Bager CL, Kehlet SN
Matrix metalloprotease (MMP)-mediated tissue remodeling is one of the malignant changes driving colorectal cancer. Measurement of altered MMP expression/activity is not sufficient to fully understand the effect of MMP-mediated tissue remodeling. Biomarkers are required that specifically reflect the ...
May 13, 2017
Journal:
Oncol Lett
Author:
Willumsen N, Bager CL, Bay-Jensen AC, Kehlet SN, Harling H, Leeming DJ, Karsdal MA, Jorgensen LN
Loss of basement membrane (BM) integrity is typically associated with cancer. Nidogen-1 is an essential component of the BM. Nidogen-1 is a substrate for cathepsin-S (CatS) which is released into the tumor microenvironment. Measuring nidogen-1 degraded by CatS may therefore have biomarker potential ...
Extensive tissue remodeling mediated by matrix metalloproteases (MMPs) is an important part of cancer. The aim of this study was to investigate whether serum biomarkers reflecting MMP-mediated degradation of type I collagen (C1M), type IV collagen (C4M) and citrullinated vimentin (VICM) were predict...
February 11, 2017
Journal:
Oncotarget
Author:
Willumsen N, Bager CL, Kehlet SN, Dragsbaek K, Neergaard JS, Hansen HB, Bay-Jensen AC, Leeming DJ, Lipton A, Christiansen C, Karsdal MA
Altered architecture, composition and quality of the extracellular matrix (ECM) are pathological hallmarks of several inflammatory and fibro-proliferative pathological processes such as osteoarthritis (OA), rheumatoid arthritis (RA), fibrosis and cancer. One of the most important components of the E...
July 27, 2016
Journal:
Biochem Biophys Res Commun
Author:
Bager CL, Gudmann NS, Willumsen N, Leeming DJ, Karsdal MA, Bay-Jensen AC, Høgdall E, Balslev I, He Y
BACKGROUND: An altered tumor microenvironment is one of the earliest signs of cancer and an important driver of the disease. We have seen previously that biomarkers reflecting tumor microenvironment modifications, such as matrix metalloproteinase (MMP)-degraded type 1 collagen (C1M), MMP-degraded ty...
July 13, 2016
Journal:
Cancer Epidemiol Biomarkers Prev.
Author:
Bager CL, Willumsen N, Kehlet SN, Hansen HB, Bay-Jensen AC, Leeming DJ, Dragsbæk K, Neergaard JS, Christiansen C, Høgdall E, Karsdal MA
Background: During cancer the otherwise tightly controlled homeostasis of the extracellular matrix (ECM) is disturbed. The protein composition changes, the ECM stiffens and increased levels of proteases are secreted. The combination of these processes result in release of specific protein fragments ...
August 3, 2015
Journal:
Cancer Biomarkers
Author:
Bager CL, Willumsen N, Leeming DJ, Smith V, Karsdal MA, Dornan D, Bay-Jensen AC
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...
May 15, 2015
Journal:
Am J Physiol Gastrointest Liver Physiol
Author:
Karsdal MA, Manon-Jensen T, Genovese F, Kristensen JH, Nielsen MJ, Sand JM, Brandt-Hansen NU, Bay-Jensen AC, Bager CL, Krag A, Blanchard A, Krarup H, Leeming DJ, Schuppan D
Extracellular matrix (ECM) proteins, such as collagen type I and elastin, and intermediate filament (IMF) proteins, such as vimentin are modified and dysregulated as part of the malignant changes leading to disruption of tissue homeostasis. Noninvasive biomarkers that reflect such changes may have a...
October 3, 2014
Journal:
Cancer Med
Author:
Willumsen N, Bager CL, Leeming DJ, Smith V, Christiansen C, Karsdal MA, Dornan D, Bay-Jensen AC
Background: Pancreatic cancer (PC) is an aggressive disease with an urgent need for biomarkers. Hallmarks of PC include increased collagen deposition (desmoplasia) and increased matrix metalloproteinase (MMP) activity. The aim of this study was to investigate whether protein fingerprints of specific...
November 21, 2013
Journal:
BMC Cancer
Author:
Willumsen N, Bager CL, Leeming DJ, Smith V, Karsdal MA, Dornan D, Bay-Jensen AC
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