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Find video protocols related to scientific articles indexed in Pubmed.
Serum YKL-40 for monitoring myocardial ischemia after revascularization in patients with stable coronary artery disease.
Biomark Med
PUBLISHED: 10-25-2014
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The aim was to investigate the inflammatory biomarker YKL-40 as a monitor of myocardial ischemia in patients with coronary artery disease (CAD).
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Plasma YKL-40 in Inuit and Danes.
Alcohol Alcohol.
PUBLISHED: 10-22-2014
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The aim of the present study was to investigate whether there are differences in plasma levels of YKL-40 between Inuit in Greenland and in Denmark and in Danes, as well as to study the relationship between alcohol intake, plasma YKL-40 and other factors in Inuit.
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YKL-40 and Alcoholic Liver and Pancreas Damage and Disease in 86258 Individuals from the General Population: Cohort and Mendelian Randomization Studies.
Clin. Chem.
PUBLISHED: 09-15-2014
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We tested the hypothesis that observationally and genetically increased YKL-40 concentrations are associated with alcoholic liver and pancreas damage and disease.
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Serum YKL-40 and uterine artery Doppler -- a prospective cohort study, with focus on preeclampsia and small-for-gestational-age.
Acta Obstet Gynecol Scand
PUBLISHED: 05-16-2014
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To test if serum YKL-40 is increased in women developing preeclampsia or small-for-gestational age fetuses. We also assessed the association between uterine artery pulsatility index, notching and serum YKL-40 levels.
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CRP genotype and haplotype associations with serum C-reactive protein level and DAS28 in untreated early rheumatoid arthritis patients.
Arthritis Res. Ther.
PUBLISHED: 03-21-2014
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IntroductionSingle nucleotide polymorphisms (SNPs) in the CRP gene are implicated in the regulation of the constitutional C-reactive protein (CRP) expression and its response to pro-inflammatory stimuli. Previous reports suggest these effects may have an impact on clinical decision-making based on CRP, for example DAS28. We aimed to investigate the possible association between 7 CRP SNPs, their haplotypes, and the serum level of CRP as well as the DAS28 score in two cohorts of untreated active early rheumatoid arthritis (RA) patients followed during their initial treatment.MethodsOverall, 315 disease-modifying anti-rheumatic drugs and steroid naïve RA patients with disease duration <6 months were included from two randomized controlled trials (the CIMESTRA and OPERA trials). Seven CRP SNPs were investigated: rs11265257, rs1130864, rs1205, rs1800947, rs2808632, rs3093077 and rs876538. The genotype and haplotype associations to CRP and DAS28 levels were evaluated using linear regression analysis adjusted for age, sex and treatment.ResultsThe minor allele of rs1205 C¿>¿T was associated with decreased CRP levels at baseline (P =0.03), with the TT genotype having a 50% reduction in CRP from 16.7 to 8.4 mg/L (P =0.005) compared to homozygosity of the major allele, but no association was observed at year one (P =0.38). The common H2 haplotype, characterized by the T allele of rs1205, was associated with a 26% reduction in CRP at baseline (P =0.043), although no effect was observed at year one (P =0.466). No other SNP or haplotype was associated with CRP at baseline or year one (P ¿0.09). We observed no associations between SNPs or haplotypes and DAS28 scores at baseline or year one (P ¿0.10).Conclusion CRP genotype and haplotype were only marginally associated with serum CRP levels and without any association to the DAS28 score. This study shows that DAS28, the core parameter for inflammatory activity in RA, can be used for clinical decision-making without adjustment for CRP gene variants.Trial registrationThe OPERA study is registered at clinicaltrials.gov (NCT00660647). The Cimestra study is not listed in a clinical trials registry due to inclusion of patients between October 1999 and October 2002.
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Brain barriers and a subpopulation of astroglial progenitors of developing human forebrain are immunostained for the glycoprotein YKL-40.
J. Histochem. Cytochem.
PUBLISHED: 03-04-2014
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YKL-40, a glycoprotein involved in cell differentiation, has been associated with neurodevelopmental disorders, angiogenesis, neuroinflammation and glioblastomas. We evaluated YKL-40 protein distribution in the early human forebrain using double-labeling immunofluorescence and immunohistochemistry. Immunoreactivity was detected in neuroepithelial cells, radial glial end feet, leptomeningeal cells and choroid plexus epithelial cells. The subpial marginal zone was YKL-40-positive, particularly in the hippocampus, from an early beginning stage in its development. Blood vessels in the intermediate and subventricular zones showed specific YKL-40 reactivity confined to pericytes. Furthermore, a population of YKL-40-positive, small, rounded cells was identified in the ventricular and subventricular zones. Real-time quantitative RT-PCR analysis showed strong YKL-40 mRNA expression in the leptomeninges and the choroid plexuses, and weaker expression in the telencephalic wall. Immunohistochemistry revealed a differential distribution of YKL-40 across the zones of the developing telencephalic wall. We show that YKL-40 is associated with sites of the brain barrier systems and propose that it is involved in controlling local angiogenesis and access of peripheral cells to the forebrain via secretion from leptomeningeal cells, choroid plexus epithelium and pericytes. Furthermore, we suggest that the small, rounded, YKL-40-positive cells represent a subpopulation of astroglial progenitors, and that YKL-40 could be involved in the differentiation of a particular astrocytic lineage.
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Tissue MicroRNAs as Predictors of Outcome in Patients with Metastatic Colorectal Cancer Treated with First Line Capecitabine and Oxaliplatin with or without Bevacizumab.
PLoS ONE
PUBLISHED: 01-01-2014
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We tested the hypothesis that expression of microRNAs (miRNAs) in cancer tissue can predict effectiveness of bevacizumab added to capecitabine and oxaliplatin (CAPEOX) in patients with metastatic colorectal cancer (mCRC).
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miR-345 in metastatic colorectal cancer: a non-invasive biomarker for clinical outcome in non-KRAS mutant patients treated with 3rd line cetuximab and irinotecan.
PLoS ONE
PUBLISHED: 01-01-2014
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MicroRNAs (miRNAs) have important regulatory functions in cellular processes and have shown promising potential as prognostic markers for disease outcome in patients with cancer. The aim of the present study was to find miRNA expression profiles in whole blood that were prognostic for overall survival (OS) in patients with metastatic colorectal cancer (mCRC) treated with cetuximab and irinotecan.
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Antibody directed against human YKL-40 increases tumor volume in a human melanoma xenograft model in scid mice.
PLoS ONE
PUBLISHED: 01-01-2014
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Induced overexpression of the secretory protein YKL-40 promotes tumor growth in xenograft experiments. We investigated if targeting YKL-40 with a monoclonal antibody could inhibit tumor growth. YKL-40 expressing human melanoma cells (LOX) were injected subcutenously in Balb/c scid mice. Animals were treated with intraperitoneal injections of anti-YKL-40, isoptype control or PBS. Non-YKL-40 expressing human pancreatic carcinoma cell line PaCa 5061 served as additional control. MR imaging was used for evaluation of tumor growth. Two days after the first injections of anti-YKL-40, tumor volume had increased significantly compared with controls, whereas no effects were observed for control tumors from PaCa 5061 cells lacking YKL-40 expression. After 18 days, mean tumor size of the mice receiving repeated anti-YKL-40 injections was 1.82 g, >4 times higher than mean tumor size of the controls (0.42 g). The effect of anti-YKL-40 on the increase of tumor volume started within hours after injection and was dose dependent. Intratumoral hemorrhage was observed in the treated animals. The strong effect on tumor size indicates important roles for YKL-40 in melanoma growth and argues for a careful evaluation of antibody therapy directed against YKL-40.
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Plasma YKL-40 in patients with metastatic colorectal cancer treated with first line oxaliplatin-based regimen with or without cetuximab: RESULTS from the NORDIC VII Study.
PLoS ONE
PUBLISHED: 01-01-2014
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We aim to test the hypothesis that high plasma YKL-40 is associated with short progression-free survival (PFS) and overall survival (OS) in patients with metastatic colorectal cancer (mCRC) treated with first-line oxaliplatin and 5-flourouracil with or without cetuximab.
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Genetic variants in CHI3L1 influencing YKL-40 levels: resequencing 900 individuals and genotyping 9000 individuals from the general population.
J. Med. Genet.
PUBLISHED: 09-23-2013
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Despite its important role in many serious diseases, the genetic background for plasma YKL-40 has still not been systematically catalogued. Therefore, we aimed at identifying genetic variants in CHI3L1 influencing plasma YKL-40 levels in the general population.
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Plasma YKL-40 and all-cause mortality in patients with chronic obstructive pulmonary disease.
BMC Pulm Med
PUBLISHED: 04-21-2013
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Chronic obstructive pulmonary disease (COPD) is hallmarked by inflammatory processes and a progressive decline of lung function. YKL-40 is a potential biomarker of inflammation and mortality in patients suffering from inflammatory lung disease, but its prognostic value in patients with COPD remains unknown. We investigated whether high plasma YKL-40 was associated with increased mortality in patients with moderate to very severe COPD.
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Plasma YKL-40 and CHI3L1 in systemic inflammation and sepsis-experience from two prospective cohorts.
Immunobiology
PUBLISHED: 04-16-2013
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YKL-40, derived from the CHI3L1 gene, has been associated with outcome of infectious and inflammatory diseases. We hypothesized that plasma YKL-40 concentrations and CHI3L1 genotype could be used as prognostic biomarkers in the assessment of systemic inflammatory response syndrome (SIRS) and sepsis. The objective of the study was to assess the prognostic value of plasma YKL-40 and CHI3L1 genotype in patients with SIRS and sepsis. Plasma YKL-40 and CHI3L1 genotype (rs4950928) were analyzed at time of admission to intensive care units (ICU), in two prospective cohorts of consecutive SIRS patients (cohort 1, n=272; cohort 2, n=502). The plasma YKL-40 cut-off for predicting survival was determined in cohort 1 by receiver operator characteristic analyses and validated in cohort 2. In cohort 1 patients with plasma YKL-40 ?505ng/ml (area under the curve 0.64 (95% confidence interval (CI) 0.57-0.70), p<0.001, sensitivity 53%, specificity 76%) had superior day 90 survival (81% vs. 55%, p<0.001, hazard ratio (HR) 2.29 (95% CI 1.29-4.07)). In the second cohort plasma YKL-40 ?505ng/ml was also associated with superior survival (61% vs. 38%, p<0.001, HR 1.43 (1.03-1.99)). CHI3L1 minor allele homozygosity was associated with low plasma YKL-40 at time of admission (p=0.002) and no variation (p=0.462) in concentrations throughout the first 14 days in the ICU, but this was not associated with better survival. In conclusion patients with SIRS and sepsis, plasma YKL-40 ?505ng/ml at time of ICU admission was associated with better survival. However, this association was not observed for patients homozygous for the low expressing YKL-40 CHI3L1 allele.
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The frequency of anti-infliximab antibodies in patients with rheumatoid arthritis treated in routine care and the associations with adverse drug reactions and treatment failure.
Rheumatology (Oxford)
PUBLISHED: 03-04-2013
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To investigate the frequency of anti-infliximab antibodies in patients with RA and the associations with adverse drug reactions and treatment failure.
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Adalimumab added to a treat-to-target strategy with methotrexate and intra-articular triamcinolone in early rheumatoid arthritis increased remission rates, function and quality of life. The OPERA Study: an investigator-initiated, randomised, double-blind,
Ann. Rheum. Dis.
PUBLISHED: 02-23-2013
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OBJECTIVES: An investigator-initiated, double-blinded, placebo-controlled, treat-to-target protocol (Clinical Trials:NCT00660647) studied whether adalimumab added to methotrexate and intra-articular triamcinolone as first-line treatment in early rheumatoid arthritis (ERA) increased the frequency of low disease activity (DAS28CRP<3.2) at 12 months. METHODS: In 14 Danish hospital-based clinics, 180 disease-modifying anti-rheumatic drugs (DMARD)-naïve ERA patients (<6 months duration) received methotrexate 7.5 mg/week (increased to 20 mg/week within 2 months) plus adalimumab 40 mg every other week (adalimumab-group, n=89) or methotrexate+placebo-adalimumab (placebo-group, n=91). At all visits, triamcinolone was injected into swollen joints (max. four joints/visit). If low disease activity was not achieved, sulfasalazine 2 g/day and hydroxychloroquine 200 mg/day were added after 3 months, and open-label biologics after 6-9 months. Efficacy was assessed primarily on the proportion of patients who reached treatment target (DAS28CRP<3.2). Secondary endpoints included DAS28CRP, remission, Health Assessment Questionnaire (HAQ), EQ-5D and SF-12. Analysis was by intention-to-treat with last observation carried forward. RESULTS: Baseline characteristics were similar between groups. In the adalimumab group/placebo group the 12-month cumulative triamcinolone doses were 5.4/7.0 ml (p=0.08). Triple therapy was applied in 18/27 patients (p=0.17). At 12 months, DAS28CRP<3.2 was reached in 80%/76% (p=0.65) and DAS28CRP was 2.0 (1.7-5.2) (medians (5th/95th percentile ranges)), versus 2.6 (1.7-4.7) (p=0.009). Remission rates were: DAS28CRP<2.6: 74%/49%, Clinical Disease Activity Index?2.8: 61%/41%, Simplified Disease Activity Index<3.3: 57%/37%, European League Against Rheumatism/American College of Rheumatology Boolean: 48%/30% (0.0008
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YKL-40 is differentially expressed in human embryonic stem cells and in cell progeny of the three germ layers.
J. Histochem. Cytochem.
PUBLISHED: 12-01-2011
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The secreted glycoprotein YKL-40 participates in cell differentiation, inflammation, and cancer progression. High YKL-40 expression is reported during early human development, but its functions are unknown. Six human embryonic stem cell (hESC) lines were cultured in an atmosphere of low or high oxygen tension, in culture medium with or without basic fibroblast growth factor, and on feeder layers comprising mouse embryonic fibroblasts or human foreskin fibroblasts to evaluate whether hESCs and their progeny produced YKL-40 and to characterize YKL-40 expression during differentiation. Secreted YKL-40 protein and YKL-40 mRNA expression were measured by enzyme-linked immunosorbent assay (ELISA) and quantitative RT-PCR. Serial-sectioned colonies were stained for YKL-40 protein and for pluripotent hESC (OCT4, NANOG) and germ layer (HNF-3?, PDX1, CD34, p63, nestin, PAX6) markers. Double-labeling showed YKL-40 expression in OCT4-positive hESCs, PAX6-positive neuroectodermal cells, and HNF-3?-positive endodermal cells. The differentiating progeny showed strong YKL-40 expression. Abrupt transition between YKL-40 and OCT4-positive hESCs and YKL-40-positive ecto- and neuroectodermal lineages was observed within the same epithelial-like layer. YKL-40-positive cells within deeper layers lacked contact with OCT4-positive cells. YKL-40 may be important in initial cell differentiation from hESCs toward ectoderm and neuroectoderm, with retained epithelial morphology, whereas later differentiation into endoderm and mesoderm involves a transition into the deeper layers of the colony.
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Radiographic progression is associated with resolution of systemic inflammation in patients with axial spondylarthritis treated with tumor necrosis factor ? inhibitors: a study of radiographic progression, inflammation on magnetic resonance imaging, and c
Arthritis Rheum.
PUBLISHED: 12-01-2011
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To investigate the relationship of circulating biomarkers of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6], and YKL-40), angiogenesis (vascular endothelial growth factor), cartilage turnover (C-terminal crosslinking telopeptide of type II collagen [CTX-II], total aggrecan, matrix metalloproteinase 3 [MMP-3], and cartilage oligomeric matrix protein [COMP]), and bone turnover (CTX-I and osteocalcin) to inflammation on magnetic resonance imaging (MRI) and radiographic progression in patients with axial spondylarthritis (SpA) beginning tumor necrosis factor ? (TNF?) inhibitor therapy.
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Metabolomic NMR fingerprinting to identify and predict survival of patients with metastatic colorectal cancer.
Cancer Res.
PUBLISHED: 11-11-2011
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Earlier detection of patients with metastatic colorectal cancer (mCRC) might improve their treatment and survival outcomes. In this study, we used proton nuclear magnetic resonance ((1)H-NMR) to profile the serum metabolome in patients with mCRC and determine whether a disease signature may exist that is strong enough to predict overall survival (OS). In 153 patients with mCRC and 139 healthy subjects from three Danish hospitals, we profiled two independent sets of serum samples in a prospective phase II study. In the training set, (1)H-NMR metabolomic profiling could discriminate patients with mCRC from healthy subjects with a cross-validated accuracy of 100%. In the validation set, 96.7% of subjects were correctly classified. Patients from the training set with maximally divergent OS were chosen to construct an OS predictor. After validation, patients predicted to have short OS had significantly reduced survival (HR, 3.4; 95% confidence interval, 2.06-5.50; P = 1.33 × 10(-6)). A number of metabolites concurred with the (1)H-NMR fingerprint of mCRC, offering insights into mCRC metabolic pathways. Our findings establish that (1)H-NMR profiling of patient serum can provide a strong metabolomic signature of mCRC and that analysis of this signature may offer an independent tool to predict OS.
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The inflammatory biomarker YKL-40 as a new prognostic marker for all-cause mortality in patients with heart failure.
Immunobiology
PUBLISHED: 09-21-2011
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Despite progress in management of patients with heart failure (HF) these patients still have a poor prognosis. We tested the hypothesis whether the inflammatory biomarker YKL-40 alone or in combination with high-sensitivity C-reactive protein (hs-CRP) and/or N-terminal-pro-B natriuretic peptide (NT-proBNP) could be a new prognostic biomarker for all-cause mortality in patients with HF.
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Plasma YKL-40 in relation to the degree of coronary artery disease in patients with stable ischemic heart disease.
Scand. J. Clin. Lab. Invest.
PUBLISHED: 08-11-2011
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YKL-40 is a glycoprotein secreted by macrophages and neutrophils in tissues with inflammation. Plasma YKL-40 is increased in patients with coronary artery disease (CAD) and associated with cardiovascular and all-cause mortality. Furthermore, plasma YKL-40 seems related to the number of diseased main vessels in patients with stable CAD. The aim was to further study the relation between YKL-40 and stenosis degree, stenosis type and actual ischemia in stable CAD patients.
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ASDAS, BASDAI and different treatment responses and their relation to biomarkers of inflammation, cartilage and bone turnover in patients with axial spondyloarthritis treated with TNF? inhibitors.
Ann. Rheum. Dis.
PUBLISHED: 05-08-2011
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To investigate the relation between ankylosing spondylitis disease activity score (ASDAS), Bath ankylosing spondylitis disease activity index (BASDAI) and treatment response and biomarkers of inflammation (C-reactive protein (CRP), interleukin-6 (IL-6), YKL-40), angiogenesis (vascular endothelial growth factor (VEGF)), cartilage (C-terminal crosslinking telopeptide of type II collagen (CTX-II), matrix metalloproteinase-3 (MMP-3), total aggrecan, cartilage oligomeric matrix protein) and bone (C-terminal crosslinking telopeptide of type I collagen, osteocalcin) turnover in 60 patients with axial spondyloarthritis initiating tumour necrosis factor alpha (TNF?) inhibitor therapy.
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IL-6, but not TNF-?, increases plasma YKL-40 in human subjects.
Cytokine
PUBLISHED: 02-27-2011
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Plasma levels of YKL-40 are elevated in patients with systemic infection, inflammatory disorders and cancer. Both monocytes/macrophages, neutrophils, and cancer cells have the capacity to produce YKL-40, but the regulation during the inflammatory response is unknown. To study the possible role of interleukin-6 (IL-6) and tumor necrosis factor (TNF)-? in the regulation of YKL-40 plasma levels, we included healthy men, who received either recombinant human (rh)IL-6 (n=6), rhTNF-? (n=8) or vehicle (n=7) for 3h. The plasma levels of IL-6 and TNF-? reached ? 150 and ? 18 pg/ml, respectively, during the infusions. Following the IL-6 infusion, the plasma level of YKL-40 increased from ? 30 to ? 57 ng/ml (p<0.05) at 24h, and returned to normal values after 48 h. The plasma level of YKL-40 did not change during TNF-? infusion or infusion of vehicle. These data demonstrate that IL-6, but not TNF-?, has a key-role in the regulation of plasma YKL-40 levels during inflammation.
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Promoter polymorphisms in the chitinase 3-like 1 gene influence the serum concentration of YKL-40 in Danish patients with rheumatoid arthritis and in healthy subjects.
Arthritis Res. Ther.
PUBLISHED: 01-30-2011
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The present study investigates the association between single nucleotide polymorphisms (SNPs) in the chitinase 3-like 1 (CHI3L1) gene and serum concentrations of YKL-40 in Danish patients with rheumatoid arthritis (RA) and healthy controls as well as the association with RA in the Danish population. The CHI3L1 gene is located on chromosome 1q32.1 and encodes the YKL-40 glycoprotein. YKL-40 concentrations are elevated in the serum of patients with RA compared to healthy subjects, and YKL-40 has been suggested to be an auto-antigen and may play a role in development of RA and in inflammation.
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Plasma YKL-40 levels in healthy subjects from the general population.
Clin. Chim. Acta
PUBLISHED: 01-07-2011
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Plasma YKL-40 is a new biomarker in patients with cancer and inflammatory diseases. High plasma YKL-40 is associated with poor prognosis. Our aim was to determine reference levels in healthy subjects.
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The prognostic value of YKL-40 concentrations in nonmyeloablative conditioning allogeneic hematopoietic cell transplantation.
Biol. Blood Marrow Transplant.
PUBLISHED: 01-04-2011
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Increased plasma concentrations of YKL-40, also called chitinase-3-like-1 protein (CHI3L1), have been correlated with disease severity in a variety of malignant and inflammatory diseases. The objective of the current study was to assess pretransplant recipient and donor CHI3L1 polymorphisms and plasma YKL-40 concentrations as prognostic biomarkers in a cohort of 149 patients treated with hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning for hematologic malignancies. Recipients with pretransplant YKL-40 concentrations above the age-adjusted 95th percentile (high) had higher relapse-related mortality (33% versus 18%, P = .04; hazard ratio (HR) = 4.41, P = .01), lower progression-free survival (38% versus 64%, P < .01; HR = 2.84, P = .01), and overall survival (42% versus 69%, P = .01; HR = 3.09, P = .01). Recipients transplanted with donors with high YKL-40 concentrations had an increased probability and risk of grade 2-4 acute graft-versus-host disease (aGVHD) (93% versus 62%, P < .01; HR = 2.25, P = .02). CHI3L1 polymorphisms were associated with plasma YKL-40 concentrations, but not with clinical outcomes. In conclusion, our study suggests that plasma YKL-40 could function as a biomarker for relapse risk and treatment-related toxicity, and possibly as a tool complementing clinical risk scores such as the HCT comorbidity index.
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Elevated plasma YKL-40 levels and ischemic stroke in the general population.
Ann. Neurol.
PUBLISHED: 10-30-2010
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We hypothesized that elevated plasma YKL-40 levels are associated with increased risk of ischemic cardiovascular disease in the general population. In contrast to C-reactive protein (CRP) produced in the liver in response to inflammation, YKL-40 is produced by lipid-laden macrophages inside the vessel wall.
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YKL-40 and mast cells are associated with detrusor fibrosis in patients diagnosed with bladder pain syndrome/interstitial cystitis according to the 2008 criteria of the European Society for the Study of Interstitial Cystitis.
Histopathology
PUBLISHED: 09-16-2010
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Bladder pain syndrome/interstitial cystitis (BPS/IC), diagnosed according to the new 2008 criteria of the European Society for the Study of Interstitial Cystitis (ESSIC), may lead to detrusor fibrosis. In some inflammatory diseases, fibrosis is related to YKL-40. The aims were to examine YKL-40 antigenic expression in bladder tissue and levels in serum and urine in BPS/IC and to evaluate whether YKL-40 could be a non-invasive, prognostic biomarker for bladder fibrogenesis and treatment intensity.
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Plasma YKL-40 and total and disease-specific mortality in the general population.
Clin. Chem.
PUBLISHED: 08-26-2010
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Increased plasma YKL-40 is associated with short-term survival in patients with cardiovascular disease and cancer. We tested the hypothesis that increased plasma YKL-40 is associated with total and disease-specific mortality in the general population.
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Elevated pretreatment serum concentration of YKL-40-An independent prognostic biomarker for poor survival in patients with metastatic nonsmall cell lung cancer.
Cancer
PUBLISHED: 06-22-2010
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The glycoprotein YKL-40 is synthesized both by cancer cells and by tumor-associated macrophages and plays a functional role in tumor progression. Consequently, high serum YKL-40 levels have been associated with a poor prognosis in patients with several cancer types. However, the role of YKL-40 has not been established in nonsmall cell lung cancer (NSCLC).
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The influence of statin treatment on the inflammatory biomarkers YKL-40 and HsCRP in patients with stable coronary artery disease.
Inflamm. Res.
PUBLISHED: 06-13-2010
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The inflammatory biomarker YKL-40 is elevated and associated with mortality in patients with stable coronary artery disease (CAD). The aim was to investigate the influence of statin treatment and lipid status on serum YKL-40 and Hs-CRP in patients with stable CAD.
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Investigation of potential non-HLA rheumatoid arthritis susceptibility loci in a European cohort increases the evidence for nine markers.
Ann. Rheum. Dis.
PUBLISHED: 05-24-2010
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Genetic factors have a substantial role in determining development of rheumatoid arthritis (RA), and are likely to account for 50-60% of disease susceptibility. Genome-wide association studies have identified non-human leucocyte antigen RA susceptibility loci which associate with RA with low-to-moderate risk.
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Vaccination with autologous dendritic cells pulsed with multiple tumor antigens for treatment of patients with malignant melanoma: results from a phase I/II trial.
Cytotherapy
PUBLISHED: 05-01-2010
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Dendritic cells are regarded as the most effective antigen presenting cells and coordinators of the immune response and therefore suitable as vaccine basis. Here we present results from a clinical study in which patients with malignant melanoma (MM) with verified progressive disease received vaccination with autologous monocyte-derived mature dendritic cells (DC) pulsed with p53, survivin and telomerase-derived peptides (HLA-A2+ patients) or with autologous/allogeneic tumor lysate (HLA-A2(?) patients) in combination with low-dose interleukin (IL)-2 and interferon (IFN)-alpha2b.
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Plasma YKL-40 and recovery of left ventricular function after acute myocardial infarction.
Scand. J. Clin. Lab. Invest.
PUBLISHED: 01-28-2010
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Plasma YKL-40 is increased early in patients with ST-elevation myocardial infarction (STEMI). It is not known whether plasma YKL-40 is related to infarct size and recovery of ventricular function after primary percutaneous coronary intervention (PCI) of STEMI and whether granulocyte colony-stimulating factor (G-CSF) therapy influence plasma YKL-40 concentration.
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Circulating levels of interleukin-6, vascular endothelial growth factor, YKL-40, matrix metalloproteinase-3, and total aggrecan in spondyloarthritis patients during 3 years of treatment with TNF? inhibitors.
Clin. Rheumatol.
PUBLISHED: 01-14-2010
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The objectives of the study were to investigate short and long-term changes and relations to treatment response of plasma interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), YKL-40, matrix metalloproteinase-3 (MMP-3), and total aggrecan in patients with spondyloarthritis (SpA) treated with tumor necrosis factor-alpha (TNF?) inhibitors and to compare with levels in healthy subjects. Biomarkers were measured in an observational cohort of 49 SpA patients (ankylosing spondylitis, n=32, and psoriatic arthritis, n=17) initiating TNF? inhibitor therapy (infliximab, n=38; etanercept, n=8; and adalimumab, n=3) and compared with levels in healthy subjects. Clinical parameters and biomarkers were measured at baseline, weeks 2, 6, and every 6-12 weeks for up to 3 years. Patients with co-morbidities (n=4), missing baseline samples (n=3), and adverse events (n=5) were excluded. Patients with SpA had compared with healthy subjects elevated IL-6 (median 8.5 ng/l (range, 0.98-64) vs. 1.3 (0.33-26)), VEGF (105 ng/l (22-752) vs. 45 (12-351)), YKL-40 (74 ?g/l (14-572) vs. 43 (20-184)), and MMP-3 (43 ?g/l (9.1-401) vs. 16 (2.5-47), p?0.001), whereas total aggrecan was lower (662 ?g/l (223-2,219) vs. 816 (399-2,190), p?0.001). Two weeks after first treatment, all biomarker levels changed towards normal levels (p?0.03) in clinical responders (n=24), and persistent reductions over 3 years were found in IL-6, VEGF, YKL-40, and MMP-3. Only MMP-3 decreased (p?0.02) in non-responders (n=13). The study demonstrated changes of plasma IL-6, VEGF, YKL-40, MMP-3, and total aggrecan and a potential value for monitoring disease activity and treatment response in SpA patients. Larger prospective studies are required to clarify clinical utility of these biomarkers.
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Plasma YKL-40: a potential new cancer biomarker?
Future Oncol
PUBLISHED: 10-02-2009
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YKL-40, a 40-kDa secreted glycoprotein, with its gene located on chromosome 1q32.1, is produced by cancer cells and inflammatory cells and has a role in inflammation, cell proliferation, differentiation, protection against apoptosis, stimulation of angiogenesis and regulation of extracellular tissue remodeling. Plasma levels of YKL-40 are elevated in a subgroup of patients with primary or advanced cancer compared with age-matched healthy subjects, but also in patients with many different diseases characterized by inflammation. Elevated plasma YKL-40 levels are an independent prognostic biomarker of short survival. There is still insufficient evidence to support its value outside of clinical trials as a screening tool, prognosticator of survival, predictor of treatment response and as a monitoring tool in the routine management of individual patients with cancer or diseases characterized by inflammation. Large prospective, longitudinal clinical cancer studies are needed to determine if plasma YKL-40 is a new cancer biomarker, or is mainly a biomarker of inflammation.
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Changes in plasma IL-6, plasma VEGF and serum YKL-40 during Treatment with Etanercept and Methotrexate or Etanercept alone in Patients with Active Rheumatoid Arthritis Despite Methotrexate Therapy.
Biomark Insights
PUBLISHED: 09-23-2009
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Changes in plasma IL-6, plasma VEGF and serum YKL-40 were determined in rheumatoid arthritis (RA) patients during treatment with etanercept alone or in combination with methotrexate. Twenty-five patients with active RA (DAS28 >/= 3.2) were randomized to receive etanercept (25 mg sc. biweekly) plus methotrexate (n = 12) or etanercept alone (n = 13). Plasma IL-6, plasma VEGF and serum YKL-40 were determined by ELISA. The 3 biomarkers and DAS28 scores were evaluated at baseline and after 4, 8, 12 and 16 weeks of treatment. At inclusion all patients had significantly (p < 0.001) elevated plasma IL-6, plasma VEGF and serum YKL-40 compared to healthy subjects. Eighteen patients responded to treatment (pooled data from both treatment groups), and they had significant (p < 0.05 to p < 0.001) decreases in plasma IL-6, plasma VEGF, serum YKL-40, ESR and DAS28 after 4 weeks of treatment and throughout the study (except serum YKL-40 at week 16). Plasma IL-6 showed the largest reductions. Non-responders had unchanged biomarkers. At week 16 the patients with DAS28 < 3.2 had lower levels compared to baseline values in plasma IL-6 (p = 0.005), plasma VEGF (p = 0.014), and ESR (p = 0.024).Plasma IL-6, plasma VEGF and serum YKL-40, which reflect different aspects of the inflammatory process, may provide useful information regarding early differentiation of responders from non-responders.
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Plasma YKL-40 is elevated in patients with recurrent atrial fibrillation after catheter ablation.
Inflamm. Res.
PUBLISHED: 08-25-2009
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To study plasma YKL-40 in patients with atrial fibrillation (AF) treated with radiofrequency (RF) catheter ablation and to assess the predictive role of plasma YKL-40 and its changes after restoration of sinus rhythm (SR).
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Plasma YKL-40, a new biomarker for atrial fibrillation?
Europace
PUBLISHED: 05-02-2009
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The aim of this study was to determine changes in a new potential biomarker plasma YKL-40 in patients with atrial fibrillation (AF) before and after electrical cardioversion (CV).
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YKL-40: a novel marker shared by chronic inflammation and oncogenic transformation.
Methods Mol. Biol.
PUBLISHED: 04-07-2009
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YKL-40, a member of mammalian chitinase-like proteins, is secreted by macrophages, neutrophils, chondrocytes, endothelial-, vascular smooth muscle-, and cancer cells. High serum YKL-40 is a biomarker of poor prognosis in patients with cancer, inflammation and increased tissue remodelling. High YKL-40 protein expression assessed by immunohistochemistry is found in breast carcinomas associated with short disease-free survival and in glioblastomas with increased resistance to radiotherapy and decreased overall survival. In this chapter we describe the methods for the detection of (1) YKL-40 protein expression in human tissues (using immunohistochemistry) and cell cultures (using immunocytochemistry); (2) YKL-40 mRNA expression in human tissues (using in situ hybridization and Polymerase Chain Reaction); and (3) YKL-40 protein concentrations in serum or plasma (using Enzyme-Linked ImmunoSorbent Assay).
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High serum YKL-40 concentration is associated with cardiovascular and all-cause mortality in patients with stable coronary artery disease.
Eur. Heart J.
PUBLISHED: 03-06-2009
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Macrophages in atherosclerotic plaques secrete YKL-40. We tested the hypothesis if high serum YKL-40 concentration predicts coronary events and death of patients with stable coronary artery disease (CAD).
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Elevated plasma YKL-40 predicts increased risk of gastrointestinal cancer and decreased survival after any cancer diagnosis in the general population.
J. Clin. Oncol.
PUBLISHED: 02-20-2009
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Elevated plasma YKL-40 is a biomarker of poor prognosis in cancer patients. We tested the hypotheses that elevated plasma YKL-40 predicts risk of cancer as well as survival after a cancer diagnosis in the general population.
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YKL-40 tissue expression and plasma levels in patients with ovarian cancer.
BMC Cancer
PUBLISHED: 01-09-2009
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YKL-40 (chitinase-3-like-1) is a member of "mammalian chitinase-like proteins". The protein is expressed in many types of cancer cells and the highest plasma YKL-40 levels have been found in patients with metastatic disease, short recurrence/progression-free intervals, and short overall survival. The aim of the study was to determine the expression of YKL-40 in tumor tissue and plasma in patients with borderline ovarian tumor or epithelial ovarian cancer (OC), and investigate prognostic value of this marker.
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Serum YKL-40 predicts long-term mortality in patients with stable coronary disease: a prognostic study within the CLARICOR trial.
Immunobiology
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We investigated whether the inflammatory biomarker YKL-40 could improve the long-term prediction of death made by common risk factors plus high-sensitivity C-reactive protein (hs-CRP) and N-terminal-pro-B natriuretic peptide (NT-proBNP) in patients with stable coronary artery disease (CAD).
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MicroRNA expression profiles associated with pancreatic adenocarcinoma and ampullary adenocarcinoma.
Mod. Pathol.
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MicroRNAs have potential as diagnostic cancer biomarkers. The aim of this study was (1) to define microRNA expression patterns in formalin-fixed parafin-embedded tissue from pancreatic ductal adenocarcinoma, ampullary adenocarcinoma, normal pancreas and chronic pancreatitis without using micro-dissection and (2) to discover new diagnostic microRNAs and combinations of microRNAs in cancer tissue. The expression of 664 microRNAs in tissue from 170 pancreatic adenocarcinomas and 107 ampullary adenocarcinomas were analyzed using a commercial microRNA assay. Results were compared with chronic pancreatitis, normal pancreas and duodenal adenocarcinoma. In all, 43 microRNAs had higher and 41 microRNAs reduced expression in pancreatic cancer compared with normal pancreas. In all, 32 microRNAs were differently expressed in pancreatic adenocarcinoma compared with chronic pancreatitis (17 higher; 15 reduced). Several of these microRNAs have not before been related to diagnosis of pancreatic cancer (eg, miR-492, miR-614, miR-622). MiR-614, miR-492, miR-622, miR-135b and miR-196 were most differently expressed. MicroRNA profiles of pancreatic and ampullary adenocarcinomas were correlated (0.990). MicroRNA expression profiles for pancreatic cancer described in the literature were consistent with our findings, and the microRNA profile for pancreatic adenocarcinoma (miR-196b-miR-217) was validated. We identified a more significant expression profile, the difference between miR-411 and miR-198 (P=2.06 × 10(-54)) and a diagnostic LASSO classifier using 19 microRNAs (sensitivity 98.5%; positive predictive value 97.8%; accuracy 97.0%). We also identified microRNA profiles to subclassify ampullary adenocarcinomas into pancreatobiliary or intestinal type. In conclusion, we found that combinations of two microRNAs could roughly separate neoplastic from non-neoplastic samples. A diagnostic 19 microRNA classifier was constructed which without micro-dissection could discriminate pancreatic and ampullary adenocarcinomas from chronic pancreatitis and normal pancreas with high sensitivity and accuracy. Ongoing prospective studies will evaluate if these microRNA profiles are useful on fine-needle biopsies for early diagnosis of pancreatic cancer.
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Prognostic microRNAs in cancer tissue from patients operated for pancreatic cancer--five microRNAs in a prognostic index.
World J Surg
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The aim of the present study was to identify a panel of microRNAs (miRNAs) that can predict overall survival (OS) in non micro-dissected cancer tissues from patients operated for pancreatic cancer (PC).
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Frequencies and prognostic role of KRAS and BRAF mutations in patients with localized pancreatic and ampullary adenocarcinomas.
Pancreas
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The frequencies and prognostic role of KRAS and BRAF mutations in patients operated on for pancreatic ductal adenocarcinomas (PDACs) and ampullary adenocarcinomas (A-ACs) are scantily studied.
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CD6 and syntaxin binding protein 6 variants and response to tumor necrosis factor alpha inhibitors in Danish patients with rheumatoid arthritis.
PLoS ONE
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TNF? inhibitor therapy has greatly improved the treatment of patients with rheumatoid arthritis, however at least 30% do not respond. We aimed to investigate insertions and deletions (INDELS) associated with response to TNF? inhibitors in patients with rheumatoid arthritis (RA).
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Serum interleukin-6 as a prognostic biomarker in patients with metastatic melanoma.
Melanoma Res.
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Interleukin-6 (IL-6) is an immunomodulatory cytokine produced by both normal cells and tumor cells, including melanoma cells. The specific biological function of IL-6 in melanoma is unknown. The present study examined whether the serum concentration of IL-6 can predict prognosis in patients with metastatic melanoma. IL-6 was measured by ELISA in serum samples from 103 patients with metastatic melanoma obtained before IL-2-based immunotherapy. Patients with metastatic melanoma had higher serum IL-6 than healthy individuals (median 3.4 ng/l, range 0.3-93 ng/l vs. median 1.4 ng/l, range 0.25-22.5 ng/l, P<0.0001). Pretreatment serum IL-6 was elevated in 43% of the patients. Patients with elevated pretreatment serum IL-6 had shorter overall survival (OS) compared with patients with normal serum IL-6 (P<0.0002). The median OS was 10.8 months [95% confidence interval (CI): 8.86-13.46] in patients with normal serum IL-6 compared with 4.5 months (95% CI: 3.04-7.39) in patients with elevated serum IL-6. Multivariate Cox analysis showed that serum IL-6 [hazard ratio (HR)=1.82, 95% CI: 1.19-2.78, P=0.006] and serum lactate dehydrogenase (HR=2.02, 95% CI: 1.31-3.11, P=0.001) were independent prognostic biomarkers of OS. A combination variable of elevated serum IL-6 and elevated serum lactate dehydrogenase almost quadrupled the risk of early death (HR=3.67, 95% CI: 2.17-6.20, P<0.0001) compared with patients with normal serum levels of these two biomarkers. Elevated serum IL-6 is an independent prognostic biomarker of short OS in patients with metastatic melanoma. A larger retrospective study is ongoing to confirm the findings. To validate serum IL-6 further as a prognostic biomarker, a prospective study is required.
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Investigation of single nucleotide polymorphisms and biological pathways associated with response to TNF? inhibitors in patients with rheumatoid arthritis.
Pharmacogenet. Genomics
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Recently, two genome-wide association studies identified single nucleotide polymorphisms (SNPs) significantly associated with the treatment response to tumor necrosis factor ? (TNF?) inhibitors in patients with rheumatoid arthritis (RA). We aimed to replicate these results and identify SNPs and the possible biological pathways associated with the treatment response to TNF? inhibitors.
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YKL-40 levels and atrial fibrillation in the general population.
Int. J. Cardiol.
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Atrial fibrillation is associated with inflammation. In contrast to inflammatory markers like C-reactive protein (CRP) and fibrinogen produced in the liver, YKL-40 is produced at the site of inflammation including in the myocardium. We hypothesized that elevated plasma YKL-40 levels associate with increased risk of atrial fibrillation.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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