52 Publication(s) found
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Hepatic System, Extracellular Matrix Research, Biomarker position
28. Dec 2019

Cirrhotic Human Liver Extracellular Matrix 3D Scaffolds Promote Smad-Dependent TGF-β1 Epithelial Mesenchymal Transition.

An altered liver microenvironment characterized by a dysregulated extracellular matrix (ECM) supports the development and progression of hepatocellular carcinoma (HCC). The development of experimental platforms able to reproduce these physio-pathological conditions is essential in order to identify …

Extracellular Matrix Research, Pancreas
24. Dec 2019

Collagen fragments quantified in serum as measures of desmoplasia associate with survival outcome in patients with advanced pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) patients have poor prognosis and poor response to treatment. This is largely due to PDAC being associated with a dense and active stroma and tumor fibrosis (desmoplasia). Desmoplasia is characterized by excessive degradation and formation of the extracellular …

Hepatic System, Extracellular Matrix Research
18. Dec 2019

Is the Total Amount as Important as Localization and Type of Collagen in Liver Fibrosis Attributable to Steatohepatitis?

Is liver fibrosis just liver fibrosis? Or do the subtype of collagen, its spatial localization in the liver, its cell of origin, and the time point at which it is synthesized also matter? It is important, since the various collagen subtypes hold different informative values regarding reparative proc…

Respiratory System, Chronic Obstructive Pulmonary Disease, Extracellular Matrix Research
2. Dec 2019

End-product of fibrinogen is elevated in emphysematous chronic obstructive pulmonary disease and is predictive of mortality in the ECLIPSE cohort.

BACKGROUND:
Chronic obstructive pulmonary disease (COPD) is characterized by abnormal epithelial repair process that may result in intra-airway accumulation of fibrin. Given that plasma fibrinogen is the only FDA approved biomarker that predicts mortality and COPD exacerbations, we hypothesized tha…

Respiratory System, Lung, Chronic Obstructive Pulmonary Disease, Extracellular Matrix Research, Biomarker position
26. Nov 2019

Post-translational modifications of vimentin reflect different pathological processes associated with non-small cell lung cancer and chronic obstructive pulmonary disease.

Vimentin has shown to be highly implicated in cancer initiation and progression. Vimentin is often a target of post-translational modifications (PTMs) which can be disease specific, thus targeting these specific modifications can be of high biomarker potential. In this study we set out to evaluate t…

Rheumatology, Osteoarthritis, Extracellular Matrix Research
14. Nov 2019

Inflammation and joint destruction may be linked to the generation of cartilage metabolites of ADAMTS-5 through activation of toll-like receptors.

OBJECTIVE:
Links between pain and joint degradation are poorly understood. We investigated the role of activation of Toll-like receptors (TLR) by cartilage metabolites in initiating and maintaining the inflammatory loop in OA causing joint destruction.

METHODS:
Synovial membrane explants (SMEs)…

Cardiovascular System, Central Nervous System
6. Nov 2019

A caspase-6-cleaved fragment of Glial Fibrillary Acidic Protein as a potential serological biomarker of CNS injury after cardiac arrest.

Blood levels of Glial Fibrillary Acidic protein (GFAP) reflect processes associated with different types of CNS injury. Evidence suggests that GFAP is cleaved by caspases during CNS injury, hence positioning GFAP fragments as potential biomarkers of injury-associated processes. We set out to develop…

Renal System, Chronic Renal Disease, Extracellular Matrix Research, Biomarker position
5. Nov 2019

Collagen turnover profiles in chronic kidney disease.

Renal fibrosis is a hallmark of chronic kidney disease (CKD) caused by an imbalance between formation and degradation of extracellular matrix proteins. We investigated the collagen turnover profile of 81 non-dialysis CKD stage 2-5 patients by measuring peptides reflecting formation and degradation o…

Rheumatology, Extracellular Matrix Research
3. Nov 2019

An Ex Vivo Tissue Culture Model of Cartilage Remodeling in Bovine Knee Explants.

Ex vivo culture systems cover a broad range of experiments dedicated to studying tissue and cellular function in a native setting. Cartilage is a unique tissue important for proper function of the synovial joint and is constituted by a dense extracellular matrix (ECM), rich in proteoglycan and type …

Hematology, Hemophilia
1. Nov 2019

Mechanisms of vascular permeability and remodeling associated with hemarthrosis in factor VIII-deficient mice.

Vascular remodeling associated with hemophilic arthropathy (HA) may contribute to bleed propagation, but the mechanisms remain poorly understood.

OBJECTIVES:
To explore molecular mechanisms of HA and the effects of hemostasis correction on synovial vascular remodeling after joint injury in hypoc…

Hepatic System
25. Oct 2019

A Phase 1 Trial of Autologous Macrophage Therapy for Liver Cirrhosis

Therapies to reduce liver fibrosis and stimulate organ regeneration are urgently needed. We conducted a first-in-human, phase 1 dose-escalation trial of autologous macrophage therapy in nine adults with cirrhosis and a Model for End-Stage Liver Disease (MELD) score of 10-16 (ISRCTN 10368050). Groups…

Pancreas, Extracellular Matrix Research, Biomarker position
23. Oct 2019

Clinical value of serum hyaluronan and propeptide of type III collagen in patients with pancreatic cancer.

Hyaluronan (HA) and collagen are highly expressed in pancreatic cancer (PC) stroma. HA and collagen accumulation increase tumor interstitial fluid pressure, compromising blood flow and drug penetration. The aim of this biomarker study was to determine the clinical utility of serum HA and the propept…

Gastrointestinal, Inflammatory Bowel Disease, Extracellular Matrix Research
22. Oct 2019

The intestinal tissue homeostasis - the role of extracellular matrix remodeling in inflammatory bowel disease

Introduction: Extracellular matrix (ECM) remodeling of the intestinal tissue is important in inflammatory bowel disease (IBD) due to the extensive mucosal remodeling. There are still gaps in our knowledge as to how ECM remodeling is related to intestinal epithelium homeostasis and healing of the int…

Hepatic System, Non-Alcoholic Fatty Liver Disease
16. Oct 2019

Improvement of non-invasive markers of NAFLD from an individualised, web-based exercise program.

BACKGROUND:
Lifestyle modifications remain the cornerstone of treatment in non-alcoholic fatty liver disease (NAFLD). However, they requently fail related to the inability of patients to implement lasting changes.

AIMS:
To evaluate the effects of a short, web-based, individualised exercise prog…

Hepatic System, Biomarker position
16. Oct 2019

Serum markers of type III and IV procollagen processing predict recurrence of fibrosis in liver transplanted patients.

Following liver transplantation (LT), 10-30% of patients develop recurrent cirrhosis (RC). There is an urgent need for predictive non-invasive markers for improved monitoring of these patients. Here we studied extracellular matrix biomarkers as predictors of RC after LT. Forty-seven LT patients were…

Rheumatology, Clinical Data Quality, Osteoarthritis
8. Oct 2019

Effect of Intra-Articular Sprifermin vs Placebo on Femorotibial Joint Cartilage Thickness in Patients With Osteoarthritis: The FORWARD Randomized Clinical Trial.

IMPORTANCE:
Sprifermin is under investigation as a disease-modifying osteoarthritis drug.

OBJECTIVE:
To evaluate the effects of sprifermin on changes in total femorotibial joint cartilage thickness in the more symptomatic knee of patients with osteoarthritis.

DESIGN, SETTING, AND PARTICIPANT…

Rheumatology, Bone, Osteoporosis, Osteoarthritis, Biomarker position
30. Sep 2019

Biochemical markers in osteoarthritis with lessons learned from osteoporosis.

Osteoarthritis (OA) is a disease of the whole joint, including synovium, bone and cartilage. OA is a slow degenerative and very heterogeneous disease, with both varying levels of disease activity and progression. Biomarkers are urgently needed to assist drug developers in selecting and developing th…

Endocrinology, Type 1-Diabetes, Renal System, Cardiovascular System
13. Sep 2019

Markers of Collagen Formation and Degradation Reflect Renal Function and Predict Adverse Outcomes in Patients With Type 1 Diabetes.

OBJECTIVE:
Patients with type 1 diabetes (T1D) have a higher risk of developing chronic kidney disease, cardiovascular events (CVEs), and mortality than the general population. We hypothesized that two previously published biomarkers, namely PRO-C6, a biomarker of collagen type VI formation, and C3…

Rheumatology, Osteoarthritis, Biomarker position, Bone
3. Sep 2019

Associations between biomarkers of bone and cartilage turnover, gender, pain categories and radiographic severity in knee osteoarthritis.

BACKGROUND:
Excessive cartilage degradation is a known characteristic of osteoarthritis (OA). Biochemical markers, such as uCTX-II, have been shown to be associated with disease severity, yet the tissue origin of CTX-II has been disputed. This analysis investigates the association between OA knee j…

Extracellular Matrix Research, Biomarker position, Breast
15. Aug 2019

Clinical Relevance of Collagen Protein Degradation Markers C3M and C4M in the Serum of Breast Cancer Patients Treated with Neoadjuvant Therapy in the GeparQuinto Trial.

Background: Remodeling of extracellular matrix through collagen degradation is a crucial step in the metastatic cascade. The aim of this study was to evaluate the potential clinical relevance of the serum collagen degradation markers (CDM) C3M and C4M during neoadjuvant chemotherapy for breast cance…

Rheumatology, Spondyloarthropathies, Biomarker position
2. Aug 2019

Metabolites of type I, II, III, and IV collagen may serve as markers of disease activity in axial spondyloarthritis.

Local inflammation in axial spondyloarthritis (axSpA) leads to the release of collagen metabolites from the disease-affected tissue. We investigated whether collagen metabolites were associated with disease activity and could distinguish non-radiographic(nr)-axSpA from ankylosing spondylitis (AS). A…

Rheumatology, Osteoarthritis, Rheumatoid Arthritis
24. Jul 2019

Identification of pathological RA endotypes using blood-based biomarkers reflecting tissue metabolism. A retrospective and explorative analysis of two phase III RA studies.

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…

Respiratory System, Biomarker position, Extracellular Matrix Research, Idiopathic Pulmonary Fibrosis
12. Jul 2019

Biomarkers of collagen synthesis predict progression in the PROFILE idiopathic pulmonary fibrosis cohort.

Idiopathic pulmonary fibrosis (IPF) is characterised by excessive extracellular matrix (ECM) deposition and remodelling. Measuring this activity provides an opportunity to develop tools capable of identifying individuals at-risk of progression. Longitudinal change in markers of ECM synthesis was ass…

Hepatic System, Extracellular Matrix Research
11. Jul 2019

Circulating levels of PRO-C3 reflect liver fibrosis and liver function in HIV positive patients receiving modern cART

Abstract
Background and aims
Although combined antiretroviral treatment (cART) has improved overall survival of HIV infected patients, liver fibrosis and liver related-mortality still constitute major challenges in HIV positive patients. Collagen accumulates in the liver during fibrogenesis. Recen…

Extracellular Matrix Research, Hepatic System, Non-Alcoholic Fatty Liver Disease
4. Jul 2019

Performance of the PRO-C3 collagen neo-epitope biomarker in non-alcoholic fatty liver disease.

There is an unmet need for non-invasive biomarkers in non-alcoholic fatty liver disease (NAFLD) that can diagnose advanced disease and identify patients suitable for clinical trials. The PRO-C3 collagen neo-epitope is a putative direct marker of fibrogenesis. We assessed the performance of PRO-C3 in…

Obesity, Endocrinology
1. Jul 2019

The Dual Amylin and Calcitonin Receptor Agonist KBP-088 Induces Weight Loss and Improves Insulin Sensitivity Superior to Chronic Amylin Therapy

KBP-088 (KeyBiosciencePeptide 088) is a potent dual amylin and calcitonin receptor agonist (DACRA). DACRAs are known to elicit potent activity in terms of typical amylin-induced responses, such as reducing food intake and body weight. However, to what extent amylin infusion can mimic the effects of …

Hepatic System, Endocrinology, Type 2-Diabetes
1. Jul 2019

Use of Plasma Fragments of Propeptides of Type III, V, and VI Procollagen for the Detection of Liver Fibrosis in Type 2 Diabetes

OBJECTIVE:
This study assessed the utility of plasma fragments of propeptides of type III (PRO-C3), V (PRO-C5), and VI (PRO-C6) procollagen for the detection of liver fibrosis in patients with type 2 diabetes mellitus (T2DM).

RESEARCH DESIGN AND METHODS:
Patients with T2DM (n = 191) underwent a…

Rheumatology, Osteoarthritis
26. Jun 2019

Incidence of total hip and total knee replacements from the prospective epidemiologic risk factor study: considerations for event driven clinical trial design

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 en…

Osteoporosis, Bone
10. Jun 2019

Hematopoietic stem cell-targeted neonatal gene therapy with a clinically applicable lentiviral vector corrects osteopetrosis in oc/oc mice.

Infantile malignant osteopetrosis (IMO) is an autosomal recessive disorder characterized by nonfunctional osteoclasts. Approximately 50% of the patients have mutations in the TCIRG1 gene, encoding for a subunit of the osteoclast proton pump. Gene therapy represents a potential alternative treatment …

Bone, Rheumatology, Osteoarthritis
5. Jun 2019

A dual amylin and calcitonin receptor agonist inhibits pain behavior and reduces cartilage pathology in an osteoarthritis rat model

OBJECTIVES:
Pain and disability are the main clinical manifestations of osteoarthritis, for which only symptomatic therapies are available. Hence, there is a need for therapies that can simultaneously alter disease progression and provide pain relief. KBP is a dual amylin- and calcitonin-receptor a…

1. Jun 2019

Serological Assessment of the Quality of Wound Healing Processes in Crohn's Disease.

BACKGROUND AND AIMS:
Crohn's disease (CD) is a chronic inflammatory condition characterized by continuous mucosal damage and ongoing wound healing of the intestines. The fibrinolytic system is involved in early parts of the wound healing process. Fibrin is a key mediator of primary blood clot forma…

31. May 2019

Serum tau fragments as predictors of death or poor neurological outcome after out-of-hospital cardiac arrest

Background: Anoxic brain injury is the primary cause of death after resuscitation from out-of-hospital cardiac arrest (OHCA) and prognostication is challenging. The aim of this study was to evaluate the potential of two fragments of tau as serum biomarkers for neurological outcome.

Methods: Sing…

Endocrinology
23. May 2019

Circulating Biomarkers of Testosterone's Anabolic Effects on Fat-Free Mass

BACKGROUND:
Biomarkers that predict response to anabolic therapies could expedite the development of function promoting anabolic drugs. This study aimed to identify serum biomarkers that are responsive to testosterone administration and associated with increases in fat-free mass (FFM).

METHODS: …

Cardiovascular System, Respiratory System
17. May 2019

Pressure overload induced right ventricular remodeling is not attenuated by the anti-fibrotic agent pirfenidone

Cardiac fibrosis contributes to the development of heart failure in pulmonary hypertension. We aimed to assess the development of fibrosis and the effects of treatment with the anti-fibrotic agent pirfenidone in pressure overload induced right ventricular (RV) failure. Wistar rat weanlings were rand…

12. May 2019

Matrix Metalloprotease Generated Fragments of Type VI Collagen Have Serum Biomarker Potential in Cancer - A Proof of Concept Study

BACKGROUND:
Type VI collagen (COL6) is associated with several pro-tumorigenic events. COL6 is primarily composed of three alpha-chains (a1-a3) forming a specialized microfibrillar network to support tissue architecture. COL6 homeostasis is lost in the tumor due to increased COL6 synthesis by activ…

29. Mar 2019

Cancer risk in relation to body fat distribution, evaluated by DXA-scans, in postmenopausal women - the Prospective Epidemiological Risk Factor (PERF) study

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…

Respiratory System, Chronic Obstructive Pulmonary Disease
9. Mar 2019

Specific elastin degradation products are associated with poor outcome in the ECLIPSE COPD cohort

Chronic obstructive pulmonary disease (COPD) is characterized by a slow heterogeneous progression. Therefore, improved biomarkers that can accurately identify patients with the highest likelihood of progression and therefore the ability to benefit from a given treatment, are needed. Elastin is an es…

Oncology
6. Mar 2019

Collagens and Cancer associated fibroblasts in the reactive stroma and its relation to Cancer biology

The extracellular matrix (ECM) plays an important role in cancer progression. It can be divided into the basement membrane (BM) that supports epithelial/endothelial cell behavior and the interstitial matrix (IM) that supports the underlying stromal compartment. The major components of the ECM are th…

Hepatic System, Non-Alcoholic Steatohepatitis
1. Mar 2019

Biochemical and histological characterisation of an experimental rodent model of non-alcoholic steatohepatitis - Effects of a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist and a glucagon-like peptide-1 analogue

BACKGROUND:
Non-alcoholic steatohepatitis (NASH) is a prevalent disease that is highly associated with the metabolic syndrome and type II diabetes. The development of in vivo models that reflect all nuances of the human NASH pathology is essential for drug discovery and development. We aimed to fur…

Rheumatology, Systemic Sclerosis
1. Mar 2019

Association of metabolites reflecting type III and VI collagen formation with modified Rodnan skin score in systemic sclerosis - a cross-sectional study

OBJECTIVE:
The objective was to investigate blood-based biomarkers of type I (PRO-C1), III (PRO-C3) and VI (PRO-C6) collagen formation in systemic sclerosis (SSc) patients and examine their correlation to modified Rodnan skin score (mRSS).

METHODS:
Limited (lSSc, n = 76) and diffuse SSc (dSSc, …

Rheumatology, Bone
28. Feb 2019

GPDPLQ1237-A Type II Collagen Neo-Epitope Biomarker of Osteoclast- and Inflammation-Derived Cartilage Degradation in vitro

C-telopeptide of type II collagen (CTX-II) has been shown to be a highly relevant biomarker of cartilage degradation in human rheumatic diseases, if measured in synovial fluid or urine. However, serum or plasma CTX-II have not been demonstrated to have any clinical utility to date. Here, we describe…

Rheumatology, Rheumatoid Arthritis, Bone
22. Feb 2019

Combining Naproxen and a Dual Amylin and Calcitonin Receptor Agonist improves pain and structural outcomes in the Collagen-Induced Arthritis rat model

BACKGROUND:
Pain is a debilitating symptom of rheumatoid arthritis (RA), caused by joint inflammation and cartilage and bone destruction. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat pain and inflammation in RA, but are not disease-modifying and do not prevent joint destruction w…

Hepatic System, Gastrointestinal
12. Feb 2019

Enhanced processing of von Willebrand factor reflects disease severity and discriminates severe portal hypertension in cirrhosis

OBJECTIVES:
Portal hypertension in cirrhosis is associated with endothelial dysfunction, impaired wound healing, and decreased platelet count. Increased von Willebrand factor (VWF) formation has been suggested as a compensatory mechanism, but the role of VWF processing has not been directly assesse…

Extracellular Matrix Research, Respiratory System, Idiopathic Pulmonary Fibrosis, Lung, Chronic Obstructive Pulmonary Disease
12. Feb 2019

Serological Assessment of Activated Fibroblasts by alpha-Smooth Muscle Actin (α-SMA): A Noninvasive Biomarker of Activated Fibroblasts in Lung Disorders

OBJECTIVES:
Remodeling of the extracellular matrix (ECM) is a key event in different lung disorders, such as fibrosis and cancer. The most common cell type in the connective tissue is fibroblasts, which transdifferentiate into myofibroblasts upon activation. All myofibroblasts express α-SMA, which …

Rheumatology, Spondyloarthropathies
11. Feb 2019

Metabolites of C-reactive protein and vimentin are associated with disease activity of axial spondyloarthritis.

OBJECTIVES:
Non-radiographic (nr-axSpA) and radiographic (AS) forms of axial spondyloarthritis (axSpA) share clinical features, but have different radiographic patterns. Radiographic progression is not associated with the current disease activity biomarkers. We investigated a matrix metalloproteina…

Hepatic System, Extracellular Matrix Research, Renal System
9. Feb 2019

Collagen type IV remodelling gender-specifically predicts mortality in decompensated cirrhosis

BACKGROUND & AIMS:
Remodelling of extracellular matrix is crucial in progressive liver fibrosis. Collagen type III desposition has been shown in acute decompensation. Extratracellular matrix is compiled of deposition of various components. The role of basement membrane collagen type IV in advanced …

Rheumatology, Osteoarthritis
31. Jan 2019

Molecular taxonomy of osteoarthritis for patient stratification, disease management and drug development

PURPOSE OF REVIEW:
This review focuses on the molecular taxonomy of osteoarthritis from the perspective of molecular biomarkers. We discuss how wet biochemical markers may be used to understand disease pathogenesis and progression and define molecular endotypes of osteoarthritis and how these corre…

Gastrointestinal, Inflammatory Bowel Disease
31. Jan 2019

Initiation of the Wound Healing Cascade in Inflammatory Bowel Disease: Assessment of Von Willebrand Factor ADAMTS-13 Processing and Formation in Crohn’s Disease

Background: Crohn’s disease (CD) is a chronic inflammatory condition of the intestinal tract resulting in severe intestinal tissue
damage. The concept of mucosal healing has therefore gained significant interest as a therapeutic end point in the treatment of
inflammatory bowel disease (IBD). Given…

Rheumatology, Osteoarthritis, Rheumatoid Arthritis
14. Jan 2019

Potential diagnostic value of a type X collagen neo-epitope biomarker for knee osteoarthritis.

OBJECTIVE:
Phenotypic changes of chondrocytes toward hypertrophy might be fundamental in the pathogenesis of OA, of which type X collagen (Col10) is a well-known marker. The purpose was to develop a specific immunoassay for blood quantification of a newly identified neo-epitope of type X collagen t…

Oncology, Colorectal
9. Jan 2019

Vastatin (the NC1 domain of human type VIII collagen a1 chain) is linked to stromal reactivity and elevated in serum from patients with colorectal cancer.

Vastatin, a fragment derived from type VIII collagen, is one of the least studied collagen-derived matrikines. Vastatin can be detected in serum but little is known regarding the relevance of serum vastatin in colorectal cancer (CRC). In this study, serum vastatin was measured (ELISA) in 67 healthy …

Idiopathic Pulmonary Fibrosis, Respiratory System, Oncology, Lung, Extracellular Matrix Research
2. Jan 2019

The mTORC1/4E-BP1 axis represents a critical signaling node during fibrogenesis.

Myofibroblasts are the key effector cells responsible for excessive extracellular matrix deposition in multiple fibrotic conditions, including idiopathic pulmonary fibrosis (IPF). The PI3K/Akt/mTOR axis has been implicated in fibrosis, with pan-PI3K/mTOR inhibition currently under clinical evaluatio…