scholarly journals Baseline serum angiopoietin-2 and VEGF levels predict the deterioration of the liver functional reserve during lenvatinib treatment for hepatocellular carcinoma

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247728
Author(s):  
Taku Shigesawa ◽  
Goki Suda ◽  
Megumi Kimura ◽  
Osamu Maehara ◽  
Yoshimasa Tokuchi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Growth Factor ◽  
Clinical Data ◽  
Characteristic Curve ◽  
Laboratory Data ◽  
Complete Response ◽  
Serum Samples ◽  
Functional Reserve ◽  
Baseline Serum ◽  
Liver Functional Reserve

A deteriorated liver functional reserve during systemic therapy for unresectable hepatocellular carcinoma (HCC) causes poor patient outcomes. We aimed to identify predictive factors associated with the deterioration of Child-Pugh score at 8 weeks after lenvatinib initiation. Patients with adequate clinical data and baseline preserved serum samples available were included. Baseline fibroblast growth factor (FGF)19 and 21, angiopoietin (ANG)2, and vascular endothelial growth factor (VEGF) levels were evaluated. Thirty-seven patients were included, and 6, 15, 14, and 2 experienced complete response, partial response, stable disease, and progressive disease, respectively. Twenty-four (65%) and 13 (35%) patients showed a maintained/improved and deteriorated Child-Pugh-score, respectively. While baseline clinical data, treatment response, and laboratory data were similar between these two patient groups, baseline ANG2 and VEGF levels were significantly higher (P = 0.0017) and lower (P = 0.0231), respectively, in patients with deteriorated Child-Pugh score than in those without. Based on receiver operating characteristic curve analysis, cut-off values for ANG2 and VEGF were found to be 3,108 pg/mL and 514.9 pg/mL, respectively. Among patients with low VEGF and high ANG2, 89% (8/9) exhibited a deteriorated Child-Pugh score, whereas none of the patients (0/9) with high VEGF and low ANG2 did. The deterioration of the Child-Pugh score in patients with unresectable HCC who are treated with lenvatinib may be predictable based on combined baseline serum ANG2 and VEGF levels.

A dysregulated interleukin-18–interferon-γ–CXCL9 axis impacts treatment response to canakinumab in systemic juvenile idiopathic arthritis

Rheumatology ◽  
2021 ◽  
Author(s):  
Tanja Hinze ◽  
Christoph Kessel ◽  
Claas H Hinze ◽  
Julia Seibert ◽  
Hermann Gram ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Complete Response ◽  
Interferon Γ ◽  
Response To Therapy ◽  
Inactive Disease ◽  
Serum Samples ◽  
Open Label ◽  
Baseline Serum ◽  
Ifn Γ

Abstract Objectives The monoclonal IL-1β antibody canakinumab is approved for the treatment of systemic juvenile idiopathic arthritis (SJIA). Its efficacy has been proven in several trials, but not all patients show a complete and sustained response to therapy. We aimed to analyse the association of baseline serum biomarkers with treatment outcome in patients with SJIA treated with canakinumab. Methods Serum samples from 54 patients with active SJIA without recent macrophage activation syndrome (MAS) treated with canakinumab in an open-label response characterization study were subjected to a multiplexed bead array assay. Interesting targets from these analyses were validated by ELISA. Clinical treatment outcomes included modified paediatric ACR (pACR) 30 and 90 responses, clinically inactive disease (CID) within 15 days of treatment and sustained complete response, defined as pACR100 or CID within 15 days of treatment plus no future flare or MAS. Results In canakinumab-naïve patients most biomarkers were elevated when compared with healthy controls at baseline and some rapidly decreased by day 15 [IL-1 receptor antagonist (IL-1RA), IL-6, IL-18 and S100A12]. Responders had higher IL-18 and IFN-γ levels and lower chemokine (C-X-C motif) ligand 9 (CXCL9) levels at baseline, emphasized by the IL-18: CXCL9 and IFN-γ: CXCL9 ratios. These ratios had significant accuracy in predicting treatment responses. Conclusion Differential regulation of the IL-18–IFN-γ–CXCL9 axis is observed in patients with SJIA. Higher IL-18: CXCL9 and IFN-γ: CXCL9 ratios at baseline are associated with a better clinical response to canakinumab treatment in SJIA. Future studies are needed to validate these findings and determine their generalizability to patients with recent MAS.

Angiogenic Cytokines Are Increased in the Serum of Patients with Waldenastrom’s Macroglobulinemia (WM): Correlations with Clinical Data.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5006-5006
Author(s):  
Athanasios Anagnostopoulos ◽  
Evangelos Terpos ◽  
Konstantinos Zervas ◽  
Efstathios Kastritis ◽  
Vangelis Eleftherakis-Papaiakovou ◽  
...  
Keyword(s):  
Growth Factor ◽  
Clinical Data ◽  
Serum Levels ◽  
Hematologic Malignancies ◽  
Sample Collection ◽  
Serum Samples ◽  
Symptomatic Disease ◽  
Endothelial Growth Factor ◽  
Angiogenic Cytokines ◽  
Angiopoietin 1

Abstract Angiogenesis is essential step of disease progression in several hematologic malignancies including multiple myeloma (MM). Bone marrow (BM) angiogenesis, assessed by microvessel density (MVD), is increased in 30% of patients with WM and showed only weak correlation with BM infiltration. Two major classes of angiogenic factors, namely the vascular endothelial growth factor (VEGF and mainly its A component (VEGF-A)) and angiopoietins 1 and 2 (Ang-1, Ang-2), has been shown to play pivotal role in tumor angiogenesis. Angiogenin is member of the ribonuclease family, which participates in angiogenesis by influencing the migration and proliferation of endothelial cells. Basic fibroblast growth factor (bFGF) is another cytokine, which is produced by stromal cells and plays significant role in MM pathogenesis. Aim of the study was the evaluation of angiogenesis, as assessed by the measurement of the above angiogenic cytokines, in pts with WM and its correlation with clinical data of the pts. We studied serum samples of 67 pts with serum monoclonal IgM (SMIgM) (44M/23F; median age: 71 years, range: 39–85 years) in various phases of their disease. Fifty-three pts had overt WM (21 untreated, 20 in relapse and 12 in remission). Furthermore, 14 pts with IgM MGUS (N=11) or asymptomatic WM (N=3) were also included. VEGF, VEGF-A, angiogenin, angiopoietin-1 and 2 and bFGF were measured using ELISA methodology (Diaclone, France for VEGF-A and R&D Systems, MN, USA for other cytokines). In all pts, we also evaluated hemoglobin, PLT count, β2-microglobulin (β2m) and albumin levels as well as the presence of splenomegaly, hepatomegaly and lymphadenopathy at the time of sample collection. The same cytokines were also measured in 30 gender- and age-matched controls. All pts with SMIgM had increased serum levels of all cytokines except angiopoietin-1 compared to controls: mean ±SD for VEGF was 299±228 vs. 106±76 pg/ml in pts and controls, respectively (p<0.0001); for VEGF-A 105±102 vs. 6.7±13.6 pg/ml (p<0.0001), for angiogenin 442.9±216.5 ng/ml vs. 239.5±58.5 ng/ml (p<0.0001); for Ang-1 25.1±22 vs. 21±13.5 ng/ml (p=0,4), for Ang-2 3,212±2,110 vs. 1,746±1,023 pg/ml (p=0.0004) and for bFGF 10.2±17.1 vs. 1.3±3.15 pg/ml (p=0.005). However, pts with IgM MGUS or asymptomatic WM (N=14) had elevated values of Ang-1 (40.16±21.66 ng/ml) compared with controls (p=0.002) and pts with symptomatic WM (p=0.003). Pts with active WM (untreated and relapsed) had increased levels of angiogenin compared with asymptomatic WM-MGUS pts and with pts in remission. At the time of sample collection, 16 pts had anemia (Hb<10 g/dl), while 14 pts had increased levels of β2m (>3.5 mg/l), and 11 pts had reduced albumin levels (<3.5 g/dl). Pts with high VEGF-A had higher β2m (r=0.28, p=0.03), high angiogenin was correlated with low albumin (r=−0.39, p=0.001), while high Ang-1 was correlated with low β2m (r=−0.47, p=0.0009) and high Hb levels (r=0.27, p=0.04). Our study suggests that angiogenic cytokines increase in pts with SMIgM supporting a possible paracrine role of these molecules. Ang-1 is the only cytokine which is increased in pts with IgM-MGUS and asymptomatic WM but returns to normal in pts with symptomatic disease. Our results, if confirmed, may provide the basis for clinical trials in WM, which involve anti-angiogenic agents.

scholarly journals Development and application of a fluorescence protein microarray for detecting serum alpha-fetoprotein in patients with hepatocellular carcinoma

2016 ◽  
Vol 44 (6) ◽  
pp. 1414-1423 ◽  
Author(s):  
Aiying Zhang ◽  
Chengzeng Yin ◽  
Zhenshun Wang ◽  
Yonghong Zhang ◽  
Yuanshun Zhao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Protein Microarray ◽  
Characteristic Curve ◽  
Alpha Fetoprotein ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
Control Subjects ◽  
Serum Alpha Fetoprotein ◽  
Healthy Control ◽  
Fluorescence Protein

Objective To develop a simple, effective, time-saving and low-cost fluorescence protein microarray method for detecting serum alpha-fetoprotein (AFP) in patients with hepatocellular carcinoma (HCC). Method Non-contact piezoelectric print techniques were applied to fluorescence protein microarray to reduce the cost of prey antibody. Serum samples from patients with HCC and healthy control subjects were collected and evaluated for the presence of AFP using a novel fluorescence protein microarray. To validate the fluorescence protein microarray, serum samples were tested for AFP using an enzyme-linked immunosorbent assay (ELISA). Results A total of 110 serum samples from patients with HCC ( n = 65) and healthy control subjects ( n = 45) were analysed. When the AFP cut-off value was set at 20 ng/ml, the fluorescence protein microarray had a sensitivity of 91.67% and a specificity of 93.24% for detecting serum AFP. Serum AFP quantified via fluorescence protein microarray had a similar diagnostic performance compared with ELISA in distinguishing patients with HCC from healthy control subjects (area under receiver operating characteristic curve: 0.906 for fluorescence protein microarray; 0.880 for ELISA). Conclusion A fluorescence protein microarray method was developed for detecting serum AFP in patients with HCC.

scholarly journals Redefining Tumor Burden in Patients with Intermediate-Stage Hepatocellular Carcinoma: The Seven-Eleven Criteria

Liver Cancer ◽  
2021 ◽  
pp. 1-12
Author(s):  
Ya-Wen Hung ◽  
I-Cheng Lee ◽  
Chen-Ta Chi ◽  
Rheun-Chuan Lee ◽  
Chien-An Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Odds Ratio ◽  
Characteristic Curve ◽  
Intermediate Stage ◽  
Complete Response ◽  
Tumor Burden ◽  
Hazard Ratio ◽  
Information Criteria ◽  
High Burden ◽  
High Tumor Burden

<b><i>Background and Aims:</i></b> For patients with intermediate-stage hepatocellular carcinoma (HCC), the definition of high tumor burden remains controversial. This study aimed to compare the prognostic value of different criteria of tumor burden in patients with intermediate-stage HCC undergoing transarterial chemoembolization (TACE). <b><i>Methods:</i></b> From 2007 to 2019, 632 treatment-naive patients with intermediate-stage HCC undergoing TACE were retrospectively enrolled. We compared different criteria of tumor burden in discriminating radiologic response and survival, including up-to-7, up-to-11, 5–7, 7 lesions criteria, and newly proposed 7–11 criteria. <b><i>Results:</i></b> The proportions of patients classified as high tumor burden were varied by different criteria. Among the 5 criteria, 7–11 criteria have the best performance to discriminate complete response (CR) and overall survival (OS) after TACE. In patients with low, intermediate, and high tumor burden classified by 7–11 criteria, the CR rate was 21, 12, and 2.5%, respectively (<i>p</i> &#x3c; 0.001), and the median OS was 33.1, 22.3, and 11.9 months, respectively (<i>p</i> &#x3c; 0.001). By multivariate analysis, 7–11 criteria were significantly associated with CR (intermediate vs. high burden, odds ratio = 4.617, <i>p</i> = 0.002; low vs. high burden, odds ratio = 8.675, <i>p</i> &#x3c; 0.001) and OS (intermediate vs. high burden, hazard ratio = 0.650, <i>p</i> &#x3c; 0.001; low vs. high burden, hazard ratio = 0.520, <i>p</i> &#x3c; 0.001). Seven to 11 criteria also had the lowest corrected Akaike information criteria, highest homogeneity value, and highest area under the receiver operating characteristic curve in predicting 1-, 2-, and 3-year mortality among all criteria. <b><i>Conclusion:</i></b> Conventional definitions of tumor burden were not optimal for patients with intermediate HCC. The new 7–11 criteria had the best discriminative power in predicting radiologic response and survival in patients with intermediate-stage HCC undergoing TACE.

scholarly journals Evaluation of Endothelial Biomarkers on the Prognosis of Patients on Extracorporeal Membrane Oxygenation

2019 ◽  
Author(s):  
Tsung-Yu Tsai ◽  
Kun-Hua Tu ◽  
Feng-Chun Tsai ◽  
Yu-Yun Nan ◽  
Pei-Chun Fan ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Extracorporeal Membrane Oxygenation ◽  
Characteristic Curve ◽  
Tertiary Care ◽  
Laboratory Data ◽  
Endothelial Activation ◽  
Organ Damage ◽  
Care Hospital ◽  
Serum Samples ◽  
Membrane Oxygenation

Abstract Background Extracorporeal membrane oxygenation (ECMO) is often used in critical patients with severe myocardial failure. However, patients on ECMO often have high mortality rate and poor prognosis. Recent studies suggest that endothelial activation with subsequent vascular barrier breakdown is a critical pathogenic mechanism in organ damage and related to the outcome in critical illness. This study aimed to determine whether the endothelial biomarkers could serve as prognostic factors for the outcome of patients on ECMO. Methods This prospective study enrolled total 23 critically ill patients on veno-arterial ECMO in the intensive care units of a tertiary care hospital between March 2014 and February 2015. Serum samples were tested for thrombomodulin, angiopoietin (Ang)-1, Ang-2, and vascular endothelial growth factor (VEGF). Demographic, clinical, and laboratory data were also collected. Results The overall mortality rate was 56.5%. The combination of Ang-2 at the time of ECMO support (day 0) and VEGF at day 2 had modest prognostic ability of discriminating mortality (area under receiver operating characteristic curve [AUROC], 0.854; 95% confidence interval: 0.645-0.965). Conclusions In this study, we found that the combination of Ang-2 at day 0 and VEGF at day 2 was a modest model for mortality discrimination in this group of patients.

scholarly journals Proteomic Approaches to Defining Remission and the Risk of Relapse in Rheumatoid Arthritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Liam J. O’Neil ◽  
Pingzhao Hu ◽  
Qian Liu ◽  
Md. Mohaiminul Islam ◽  
Victor Spicer ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Machine Learning ◽  
Serum Proteins ◽  
Learning Algorithm ◽  
Characteristic Curve ◽  
Serum Samples ◽  
Das28 Score ◽  
Baseline Serum ◽  
Disease Flare ◽  
Serum Proteomics

ObjectivesPatients with Rheumatoid Arthritis (RA) are increasingly achieving stable disease remission, yet the mechanisms that govern ongoing clinical disease and subsequent risk of future flare are not well understood. We sought to identify serum proteomic alterations that dictate clinically important features of stable RA, and couple broad-based proteomics with machine learning to predict future flare.MethodsWe studied baseline serum samples from a cohort of stable RA patients (RETRO, n = 130) in clinical remission (DAS28&lt;2.6) and quantified 1307 serum proteins using the SOMAscan platform. Unsupervised hierarchical clustering and supervised classification were applied to identify proteomic-driven clusters and model biomarkers that were associated with future disease flare after 12 months of follow-up and RA medication withdrawal. Network analysis was used to define pathways that were enriched in proteomic datasets.ResultsWe defined 4 proteomic clusters, with one cluster (Cluster 4) displaying a lower mean DAS28 score (p = 0.03), with DAS28 associating with humoral immune responses and complement activation. Clustering did not clearly predict future risk of flare, however an XGboost machine learning algorithm classified patients who relapsed with an AUC (area under the receiver operating characteristic curve) of 0.80 using only baseline serum proteomics.ConclusionsThe serum proteome provides a rich dataset to understand stable RA and its clinical heterogeneity. Combining proteomics and machine learning may enable prediction of future RA disease flare in patients with RA who aim to withdrawal therapy.

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