GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    Revisiting Circulating Extracellular Matrix Fragments as Disease Markers in Myelofibrosis and Related Neoplasms
    MDPI AG ; 2023
    In:  Cancers Vol. 15, No. 17 ( 2023-08-29), p. 4323-
    Details
    In: Cancers, MDPI AG, Vol. 15, No. 17 ( 2023-08-29), p. 4323-
    Abstract: Philadelphia chromosome-negative chronic myeloproliferative neoplasms (MPNs) arise due to acquired somatic driver mutations in stem cells and develop over 10–30 years from the earliest cancer stages (essential thrombocythemia, polycythemia vera) towards the advanced myelofibrosis stage with bone marrow failure. The JAK2V617F mutation is the most prevalent driver mutation. Chronic inflammation is considered to be a major pathogenetic player, both as a trigger of MPN development and as a driver of disease progression. Chronic inflammation in MPNs is characterized by persistent connective tissue remodeling, which leads to organ dysfunction and ultimately, organ failure, due to excessive accumulation of extracellular matrix (ECM). Considering that MPNs are acquired clonal stem cell diseases developing in an inflammatory microenvironment in which the hematopoietic cell populations are progressively replaced by stromal proliferation—“a wound that never heals”—we herein aim to provide a comprehensive review of previous promising research in the field of circulating ECM fragments in the diagnosis, treatment and monitoring of MPNs. We address the rationales and highlight new perspectives for the use of circulating ECM protein fragments as biologically plausible, noninvasive disease markers in the management of MPNs.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers15174323
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527080-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Association between Markers of Synovial Inflammation, Matrix Turnover and Symptoms in Knee Osteoarthritis: A Cross-Sectional Study
    MDPI AG ; 2021
    In:  Cells Vol. 10, No. 7 ( 2021-07-20), p. 1826-
    Details
    In: Cells, MDPI AG, Vol. 10, No. 7 ( 2021-07-20), p. 1826-
    Abstract: To investigate the association between markers of synovial inflammation and matrix turnover (MRI-based and serum biomarkers) and knee symptoms in established knee osteoarthritis (KOA). This cross-sectional study utilised data from a randomised, multicentre placebo-controlled trial (UK-VIDEO) of vitamin D therapy in symptomatic KOA. Data on serum biomarkers, type III collagen degradation (C3M), metabolite of C-reactive protein (CRPM) and cartilage oligomeric matrix protein (COMP), were available at baseline whilst contrast-enhanced (CE) MRI data were acquired in a subsample at baseline and annually. Knee symptoms were assessed using WOMAC at all visits. We examined the cross-sectional association between knee symptoms and three MRI-based and three serum markers of synovitis and matrix turnover, respectively. A total of 447 participants were included in the serum and 136 participants in the MRI analyses. MRI-defined medial perimeniscal synovitis was positively associated with knee pain and, suprapatellar and medial perimeniscal synovitis with knee function in multivariate analysis. We observed a statistically significant, negative association between a higher concentration of serum C3M and CRPM and knee pain, respectively. Furthermore, the highest CRPM quartile was negatively associated with knee function. Our findings suggest that, in established painful radiographic KOA, MRI-defined medial perimeniscal and suprapatellar synovitis were positively associated with knee symptoms. Serum-based C3M and CRPM markers were negatively associated with knee symptoms. Pain fluctuations are common in KOA and a better understanding of the relationship between markers of synovitis and matrix turnover and knee symptoms would facilitate a more accurate assessment of temporal changes in disease progression.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells10071826
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2661518-6
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Serological Biomarkers of Extracellular Matrix Turnover and Neutrophil Activity Are Associated with Long-Term Use of Vedolizumab in Patients with Crohn’s Disease
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 15 ( 2022-07-23), p. 8137-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 15 ( 2022-07-23), p. 8137-
    Abstract: Crohn’s disease (CD) is a relapsing-remitting inflammatory disease of the gastrointestinal (GI) tract characterized by increased extracellular matrix (ECM) remodeling. The introduction of the α4β7-integrin inhibitor vedolizumab (VEDO) has improved disease management, although there is a high rate of primary non-response in patients with CD. We studied whether ECM biomarkers of neutrophil activity and mucosal damage could predict long-term response to VEDO in patients with CD. Serum levels of human neutrophil elastase (HNE)-derived fragments of calprotectin (CPa9-HNE), and matrix metalloproteinase (MMP)-derived fragments of type I (C1M), III (C3M), IV (C4M), and VI (C6Ma3) collagen, type III collagen formation (PRO-C3), basement membrane turnover (PRO-C4) and T-cell activity (C4G), were measured using protein fingerprint assays in patients with CD (n = 32) before VEDO therapy. Long-term response was defined as VEDO treatment of at least 12 months. CPa9-HNE was significantly increased at baseline in non-responders compared with responders (p 〈 0.05). C1M, C3M, C4M, C6Ma3, and PRO-C4 were also significantly increased at baseline in non-responders compared with responders (all p 〈 0.05). All biomarkers were associated with response to VEDO (all p 〈 0.05). To conclude, baseline levels of serum biomarkers for neutrophil activity and mucosal damage are linked to the pathology of CD, and are associated with long-term use of VEDO in patients with CD. Therefore, these biomarkers warrant further validation and could aid in therapeutic decision-making concerning vedolizumab therapy.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23158137
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Type IX Collagen Turnover Is Altered in Patients with Solid Tumors
    MDPI AG ; 2024
    In:  Cancers Vol. 16, No. 11 ( 2024-05-27), p. 2035-
    Details
    In: Cancers, MDPI AG, Vol. 16, No. 11 ( 2024-05-27), p. 2035-
    Abstract: The fibrotic tumor microenvironment, characterized by its intricate extracellular matrix (ECM), consists of many collagens with diverse functions and unexplored biomarker potential. Type IX collagen is a member of the low-abundance collagen family known as the fibril-associated collagen with interrupted triple helices (FACITs) and is found mostly in cartilage. Its role in the tumor microenvironment remains unexplored. To investigate the biomarker potential of a type IX collagen in cancer, an immuno-assay was developed (PRO-C9) and technical assay performance was evaluated for the assessment of serum. PRO-C9 levels were measured in serum samples from 259 patients with various solid tumor types compared to serum levels from 73 healthy controls. PRO-C9 levels were significantly elevated in patients with solid tumors including bladder, breast, colorectal, gastric, head and neck, lung, melanoma, ovarian, pancreatic, and renal compared to levels in healthy controls (p 〈 0.05–p 〈 0.0001). PRO-C9 could discriminate between patients with cancer and healthy controls, with the area under the receiver operating characteristic values ranging from 0.58 to 0.86 (p 〈 0.3–p 〈 0.0001), indicating potential diagnostic utility. This study suggests that type IX collagen turnover is altered in patients with solid tumors and demonstrates the feasibility of using PRO-C9 as a non-invasive serum-based biomarker with relevance in multiple cancer types. Furthermore, these results underscore the potential utility of PRO-C9 to better elucidate the biology of FACITs in cancers.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers16112035
    Language: English
    Publisher: MDPI AG
    Publication Date: 2024
    detail.hit.zdb_id: 2527080-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Type XX Collagen Is Elevated in Circulation of Patients with Solid Tumors
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 8 ( 2022-04-08), p. 4144-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 8 ( 2022-04-08), p. 4144-
    Abstract: In the tumor microenvironment, the extracellular matrix (ECM) has been recognized as an important part of cancer development. The dominant ECM proteins are the 28 types of collagens, each with a unique function in tissue architecture. Type XX collagen, however, is poorly characterized, and little is known about its involvement in cancer. We developed an ELISA quantifying type XX collagen, named PRO-C20, using a monoclonal antibody raised against the C-terminus. PRO-C20 and PRO-C1, an ELISA targeting the N-terminal pro-peptide of type I collagen, was measured in sera of 219 patients with various solid cancer types and compared to sera levels of 33 healthy controls. PRO-C20 was subsequently measured in a separate cohort comprising 36 patients with pancreatic ductal adenocarcinoma (PDAC) and compared to 20 healthy controls and 11 patients with chronic pancreatitis. PRO-C20 was significantly elevated in all cancers tested: bladder, breast, colorectal, head and neck, kidney, lung, melanoma, ovarian, pancreatic, prostate, and stomach cancer (p 〈 0.01–p 〈 0.0001). PRO-C1 was only elevated in patients with ovarian cancer. PRO-C20 could discriminate between patients and healthy controls with AUROC values ranging from 0.76 to 0.92. Elevated levels were confirmed in a separate cohort of patients with PDAC (p 〈 0.0001). High PRO-C20 levels (above 2.57 nM) were predictive of poor survival after adjusting for the presence of metastasis, age, and sex (HR: 4.25, 95% CI: 1.52–11.9, p-value: 0.006). Circulating type XX collagen is elevated in sera of patients with various types of cancer and has prognostic value in PDAC. If validated, PRO-C20 may be a novel biomarker for patients with solid tumors and can help understand the ECM biology of cancer.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23084144
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Nitisinone Treatment Affects Biomarkers of Bone and Cartilage Remodelling in Alkaptonuria Patients
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 13 ( 2023-07-01), p. 10996-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 13 ( 2023-07-01), p. 10996-
    Abstract: Nitisinone has been approved for treatment of alkaptonuria (AKU). Non-invasive biomarkers of joint tissue remodelling could aid in understanding the molecular changes in AKU pathogenesis and how these can be affected by treatment. Serological and urinary biomarkers of type I collagen and II collagen in AKU were investigated in patients enrolled in the randomized SONIA 2 (NCT01916382) clinical study at baseline and yearly until the end of the study (Year 4). The trajectories of the biomarkers over time were observed. After treatment with nitisinone, the biomarkers of type I collagen remodelling increased at Year 1 (19% and 40% increase in CTX-I and PRO-C1, respectively), which was potentially reflected in the higher degree of mobility seen following treatment. The biomarkers of type II collagen remodelling decreased over time in the nitisinone group: C2M showed a 9.7% decline at Year 1, and levels then remained stable over the following visits; CTX-II showed a 26% decline at Year 3 and 4 in the nitisinone-treated patients. Nitisinone treatment induced changes in biomarkers of bone and cartilage remodelling. These biomarkers can aid patient management and deepen our knowledge of the molecular mechanisms of this rare disease.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms241310996
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Type XXII Collagen Complements Fibrillar Collagens in the Serological Assessment of Tumor Fibrosis and the Outcome in Pancreatic Cancer
    MDPI AG ; 2022
    In:  Cells Vol. 11, No. 23 ( 2022-11-24), p. 3763-
    Details
    In: Cells, MDPI AG, Vol. 11, No. 23 ( 2022-11-24), p. 3763-
    Abstract: Circulating fragments of type III collagen, measured by PRO-C3, has shown promising results as a tumor fibrosis biomarker. However, the fibrotic tumor microenvironment consists of many other collagens with diverse functions and unexplored biomarker potential. One example hereof is type XXII collagen (COL22). In this study, we investigated the biomarker potential of COL22 by measuring this in serum. An ELISA, named PRO-C22, was developed and measured in two serum cohorts consisting of patients with various solid tumors (n = 220) and healthy subjects (n = 33) (Cohort 1), and patients with pancreatic ductal adenocarcinoma (PDAC) (n = 34), and healthy subjects (n = 20) (Cohort 2). In Cohort 1, PRO-C22 was elevated in the serum from patients with solid tumors, compared to healthy subjects (p 〈 0.01 to p 〈 0.0001), and the diagnostic accuracy (AUROC) ranged from 0.87 to 0.98, p 〈 0.0001. In Cohort 2, the high levels of PRO-C22, in patients with PDAC, were predictive of a worse overall survival (HR = 4.52, 95% CI 1.90–10.7, p = 0.0006) and this remained significant after adjusting for PRO-C3 (HR = 4.27, 95% CI 1.24–10.4, p = 0.0013). In conclusion, PRO-C22 has diagnostic biomarker potential in various solid tumor types and prognostic biomarker potential in PDAC. Furthermore, PRO-C22 complemented PRO-C3 in predicting mortality, suggesting an additive prognostic value when quantifying different collagens.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells11233763
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2661518-6
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    A Highly Sensitive Biomarker of Type II Collagen C-Terminal Pro-Peptide Associated with Cartilage Formation
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 24, No. 1 ( 2022-12-27), p. 454-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 1 ( 2022-12-27), p. 454-
    Abstract: The type II collagen C-terminal pro-peptide is one of the most abundant polypeptides in cartilage. The purpose of this study was to develop a competitive chemiluminescence enzyme-linked immunosorbent assay, CALC2, targeting this pro-peptide as a marker of cartilage formation. Technical assay parameters were evaluated. CALC2 level was measured after in vitro cleavage of recombinant type II collagen with bone morphogenetic protein-1 (BMP-1) and treatment of ex vivo human osteoarthritis (OA) cartilage explant model (HEX) with insulin-like growth factor-1 (IGF-1). Serum CALC2 levels were assessed in 18 patients with rheumatoid arthritis (RA), 19 patients with ankylosing spondylitis (AS), and 18 age- and sex-matched controls in cohort 1 and 8 patients with OA and 14 age- and sex-matched controls in cohort 2. Type II collagen cleavage with BMP-1 increased the CALC2 level. IGF-1 treatment increased the CALC2 levels in HEX compared with the untreated explants (p 〈 0.05). Results were confirmed using Western blot analysis. CALC2 levels were decreased in the patients with RA and AS compared with the healthy controls (p = 0.01 and p = 0.02, respectively). These findings indicate that CALC2 may be a novel biomarker of type II collagen formation. However, further preclinical and clinical studies are required to validate these findings.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms24010454
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 9
    Online Resource
    Online Resource
    In Contrast to Anti-CCP, MMP-Degraded and Citrullinated Vimentin (VICM) Is Both a Diagnostic and a Treatment Response Biomarker
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 24, No. 1 ( 2022-12-24), p. 321-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 1 ( 2022-12-24), p. 321-
    Abstract: Protein citrullination and degradation by matrix metalloproteinases (MMP) plays a central role in the pathology of rheumatoid arthritis (RA). Autoantibodies are known to target citrullinated vimentin. The aim of this study was to investigate the relationship between the blood levels of MMP-degraded and citrullinated vimentin (VICM), as compared with the levels of MMP-degraded and non-citrullinated vimentin (VIM), and the standard anti-CCP biomarker in RA patients undergoing treatment. Thus, VIM, VICM and anti-CCP were quantified by ELISA in serum samples from baseline and week 8 of patients (n = 257) with RA, treated with either tocilizumab (8 mg/kg), methotrexate (7.5–15 mg/kg) or a placebo and compared with a reference cohort (n = 64). The three biomarkers were elevated in RA serum compared with the reference cohort: medians were 1.7 vs. 0.8 ng/mL (p 〈 0.05) for VIM; 7.5 vs. 0.7 ng/mL (p 〈 0.0001) for VICM; 57 vs. 4 RU/mL (p 〈 0.001) for anti-CCP. VICM was decreased in response to tocilizumab (2.9-fold, p 〈 0.0001) and to methotrexate (1.5-fold, p 〈 0.05) compared with the placebo, while anti-CCP was not. Serum VIM was also modulated by both drugs, although to a lesser degree. A high baseline level of VICM was predictive of a low disease activity response at week 8. In conclusion, VICM can differentiate between RA and healthy donors in a similar manner to anti-CCP; furthermore, VICM is also a pharmacodynamic marker.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms24010321
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 10
    Online Resource
    Online Resource
    Biomarkers of Type IV Collagen Turnover Reflect Disease Activity in Patients with Early-Stage Non-Alcoholic Fatty Liver (NAFL)
    MDPI AG ; 2023
    In:  Biology Vol. 12, No. 8 ( 2023-08-04), p. 1087-
    Details
    In: Biology, MDPI AG, Vol. 12, No. 8 ( 2023-08-04), p. 1087-
    Abstract: Background: Identification of progressive liver disease necessitates the finding of novel non-invasive methods to identify and monitor patients in need of early intervention. Investigating patients with early-liver injury may help identify unique biomarkers. Early-liver injury is characterized by remodeling of the hepatocyte basement membrane (BM) of the extracellular matrix. Thus, we quantified biomarkers targeting two distinct neo-epitopes of the major BM collagen, type IV collagen (PRO-C4 and C4M), in patients spanning the non-alcoholic fatty liver disease (NAFLD) spectrum. Methods: We evaluated PRO-C4 and C4M in a cross-sectional study with 97 patients with NAFLD confirmed on histology. Serological levels of PRO-C4 and C4M were quantified using validated competitive enzyme-linked immunosorbent assays (ELISA). Using the fatty liver inhibition of progression (FLIP) algorithm, we stratified patients into two groups: non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). Biomarker levels were investigated in the two groups in patients stratified by the NAFLD activity score (NAS). In both groups, biomarker measurements were analyzed in relation to histological scorings of steatosis, inflammation, ballooning, and fibrosis. Results: Patients had a body mass index (BMI) of 30.9 ± 5.6 kg/m2, age of 53 ± 13 years and a NAS range of 1–8. Upon stratification by FLIP, the NASH patients had higher platelets, ALT, and AST levels than the NAFL group. Both PRO-C4 (p = 0.0125) and C4M (p = 0.003) increased with increasing NAS solely within the NAFL group; however, a large variability was present in the NASH group. Furthermore, both markers were significantly associated with lobular inflammation (p = 0.020 and p = 0.048) and steatosis (p = 0.004 and p = 0.015) in patients with NAFL. Conclusions: This study found that type IV collagen turnover increased with the increase in NAS in patients with NAFL; however, this was not the case in patients with NASH. These findings support the assessments of the BM turnover using biomarkers in patients with early-disease development. These biomarkers may be used to track specific processes involved in the early pathobiology of NAFL.
    Type of Medium: Online Resource
    ISSN: 2079-7737
    URL: Article
    DOI: 10.3390/biology12081087
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2661517-4
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...