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Current Issues in Molecular Biology Sep 2022Neuroendocrine neoplasms are a heterogeneous group of tumors that raise challenges in terms of diagnosis, treatment and monitoring. Despite continuous efforts, no... (Review)
Review
BACKGROUND
Neuroendocrine neoplasms are a heterogeneous group of tumors that raise challenges in terms of diagnosis, treatment and monitoring. Despite continuous efforts, no biomarker has showed satisfying accuracy in predicting outcome or response to treatment.
METHODS
We conducted a systematic review to determine relevant circulating biomarkers for angiogenesis in neuroendocrine tumors. We searched three databases (Pubmed, Embase, Web of Science) using the keywords "neuroendocrine" and "biomarkers", plus specific biomarkers were searched by full and abbreviated name. From a total of 2448 publications, 11 articles met the eligibility criteria.
RESULTS
VEGF is the most potent and the most studied angiogenic molecule, but results were highly controversial. Placental growth factor, Angiopoietin 2 and IL-8 were the most consistent markers in predicting poor outcome and aggressive disease behavior.
CONCLUSIONS
There is no robust evidence so far to sustain the use of angiogenic biomarkers in routine practice, although the results show promising leads.
PubMed: 36135186
DOI: 10.3390/cimb44090274 -
International Journal of Molecular... Aug 2023The early identification of women with an increased risk of preeclampsia (PE) is desirable, but apart from soluble fms-like tyrosine kinase-1 (sFlt-1), few biomarkers... (Meta-Analysis)
Meta-Analysis Review
The early identification of women with an increased risk of preeclampsia (PE) is desirable, but apart from soluble fms-like tyrosine kinase-1 (sFlt-1), few biomarkers have previously been identified as relevant for predicting preeclampsia. Since kinases and phosphatases regulate critical biological processes and previous evidence suggests a potential role of these molecules in preeclampsia, we performed this systematic review and metanalysis. The objective was to determine if there are kinases and phosphatases whose serum levels are different between women with and without PE, being relevant biomarkers of PE. We followed the recommendations of Cochrane and the Preferred Reported Items for Systematic Reviews and Metanalysis (PRISMA) to perform this study. The MESH terms preeclampsia, kinases, phosphatases, angiopoietins, soluble tyrosine protein kinase receptor (sTIE2), and cellular-mesenchymal-epithelial transition factor (c-MET) were combined to find relevant articles in the PubMed, PROSPERO, and Cochrane databases. Then, a qualitative and quantitative analysis was performed in R Studio software. From 580 abstracts identified, 37 were included in the final analysis, which comprised 24,211 pregnant women (2879 with PE and 21,332 women without PE [HP]. The pooled analysis showed that serum creatine kinase (CK) (SMD: 2.43, CI 95% 0.25-4.62) was significantly higher in PE, whereas sTIE2 and anti-angiogenic factor soluble c-Met (sMet)were significantly lower in PE than in HP (SMD: -0.23, CI95% -0.37 to -0.09; and SMD:0.24, CI95% 0.01-0.47, respectively). Adenosine monophosphate-activated protein kinase (AMPK), angiopoietin-1 (ANG-1), angiopoietin-2 (ANG-2), the ratio angiopoietin-1/angiopoietin-2, acid phosphatase, and alkaline phosphatase were not different between women with PE and HP. In summary CK, sTIE2, and c-MET are relevant biomarkers of PE. It is desirable to incorporate them into current models for PE prediction to evaluate their utility as biomarkers.
Topics: Pregnancy; Female; Humans; Phosphoric Monoester Hydrolases; Angiopoietin-1; Angiopoietin-2; Pre-Eclampsia; Antibodies; Receptor, trkA
PubMed: 37629025
DOI: 10.3390/ijms241612842 -
Scientific Reports Jan 2024We conducted a systematic review and meta-analysis to evaluate the visual, anatomical, and safety outcomes of the intravitreal faricimab, a novel vascular endothelial... (Meta-Analysis)
Meta-Analysis
We conducted a systematic review and meta-analysis to evaluate the visual, anatomical, and safety outcomes of the intravitreal faricimab, a novel vascular endothelial growth factor (VEGF)/angiopoietin-2 (Ang-2) bispecific agent, in neovascular age-related macular degeneration (nAMD) patients. The follow-up times in the included studies ranged from a minimum of 36 weeks to a maximum of 52 weeks. EMBASE, Ovid-Medline, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Scopus, the WHO ICTRP, ClinicalTrial.gov, the EU Clinical Trials Register, and Chinese Clinical Trial Registry (ChiCTR) were searched (The last literature search was performed on August 17, 2023) for randomized controlled trials (RCTs) comparing faricimab with control groups for neovascular age-related macular degeneration (nAMD). The risk of bias for eligible RCTs was independently assessed using the Cochrane Risk of Bias Tool by two authors (W.-T.Y. and C.-S.W.). The meta-analysis was conducted using Review Manager 5.4 software. The mean best corrected visual acuity (BCVA), central subfield thickness (CST), total choroidal neovascularization (CNV) area, and total lesion leakage were analyzed as continuous variables and the outcome measurements were reported as the weighted mean difference (WMD) with a 95% confidence interval (CI). The ocular adverse events and ocular serious adverse events were analyzed as dichotomous variables and the outcome measurements were analyzed as the odds ratios (ORs) with a 95% CI. Random-effects model was used in our study for all outcome synthesizing due to different clinical characteristics. Four RCTs with 1,486 patients were eligible for quantitative analysis. There was no statistically significant difference between intravitreal faricimab and anti-VEGF in BCVA [weighted mean difference (WMD) = 0.47; 95% CI: (- 0.17, 1.11)]. The intravitreal faricimab group showed numerically lower CST [WMD = - 5.96; 95% CI = (- 7.11, - 4.82)], total CNV area [WMD = - 0.49; 95% CI = (- 0.68, - 0.30)], and total lesion leakage [WMD = - 0.88; 95% CI = (- 1.08, - 0.69)] after intravitreal therapy compared with the intravitreal anti-VEGF group. There were no statistically significant differences between intravitreal faricimab and anti-VEGF in ocular adverse events (AEs) [pooled odds ratio (OR) = 1.10; 95% CI = (0.81, 1.49)] and serious adverse events (SAEs) [pooled OR = 0.84; 95% CI = (0.37, 1.90)]. The intravitreal bispecific anti-VEGF/angiopoietin 2 (Ang2) antibody faricimab with a extended injection interval was non-inferior to first-line anti-VEGF agents in BCVA. It was safe and had better anatomical recovery. Large, well-designed RCTs are needed to explore the potential benefit of extended faricimab for nAMD. This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42022327450).
Topics: Humans; Angiogenesis Inhibitors; Antibodies, Bispecific; Intravitreal Injections; Macular Degeneration
PubMed: 38291069
DOI: 10.1038/s41598-024-52942-3 -
Diagnostics (Basel, Switzerland) Mar 2023(1) Background: Among new anti-angiogenesis agents being developed and ever-changing guidelines indications, the question of the benefits/safety ratio remains unclear.... (Review)
Review
(1) Background: Among new anti-angiogenesis agents being developed and ever-changing guidelines indications, the question of the benefits/safety ratio remains unclear. (2) Methods: We performed a systematic review combined with a meta-analysis of 23 randomized controlled trials (12,081 patients), evaluating overall survival (OS), progression free survival (PFS) and toxicity (grade ≥ 3 toxic effects, type, and number of all adverse effects. (3) Results: The analysis showed improvement of pooled-PFS (HR, 0.71; 95% CI, 0.64-0.78; I = 77%; < 0.00001) in first-line (HR, 0.85; 95% CI, 0.78-0.93; = 0.0003) or recurrent cancer (HR, 0.62; 95% CI, 0.56-0.70; < 0.00001) and regardless of the type of anti-angiogenesis drug used (Vascular endothelial growth factor (VEGF) inhibitors, VEGF-receptors (VEGF-R) inhibitors or angiopoietin inhibitors). Improved OS was also observed (HR, 0.95; 95% CI, 0.90-0.99; = 0.03). OS benefits were only observed in recurrent neoplasms, both platinum-sensitive and platinum-resistant neoplasms. Grade ≥ 3 adverse effects were increased across all trials. Anti-angiogenetic therapy increased the risk of hypertension, infection, thromboembolic/hemorrhagic events, and gastro-intestinal perforations but not the risk of wound-related issues, anemia or posterior leukoencephalopathy syndrome. (4) Conclusions: Although angiogenesis inhibitors improve PFS, there are little-to-no OS benefits. Given the high risk of severe adverse reactions, a careful selection of patients is required for obtaining the best results possible.
PubMed: 36980348
DOI: 10.3390/diagnostics13061040 -
Journal of Vitreoretinal Diseases 2020Evidence suggests that inflammatory cytokines not only play a role in the pathogenesis of retinal vein occlusion (RVO) but also may be useful as biomarkers to predict... (Review)
Review
PURPOSE
Evidence suggests that inflammatory cytokines not only play a role in the pathogenesis of retinal vein occlusion (RVO) but also may be useful as biomarkers to predict disease severity and response to treatment. We aimed to quantitatively summarize data on inflammatory cytokines associated with RVO.
METHODS
A systematic search of peer-reviewed English-language articles was performed without year limitation up to August 19, 2019. Studies were included if they provided data on aqueous or vitreous cytokine concentrations in patients with RVO. Data were extracted from 116 studies that encompassed 3242 study eyes with RVO and 1402 control eyes. Effect sizes were generated as standardized mean differences (SMDs) of cytokine concentrations between patients with RVO vs controls.
RESULTS
Among the 4644 eyes in 116 studies, aqueous and vitreous concentrations (SMD, 95% CI, and value) of interleukin (IL)-6 (aqueous: 1.23, 0.65 to 1.81, .001 vitreous: 0.70, 0.49 to 0.90, .001), IL-8 (aqueous: 1.11, 0.73 to 1.49, .001; vitreous: 1.19, 0.73 to 1.65, .001), monocyte chemoattractant protein 1(aqueous: 1.22, 0.72 to 1.72, .001; vitreous 1.42, 0.92 to 1.91, .001), vascular endothelial growth factor (VEGF) (aqueous: 1.52, 1.09 to 1.94, .001; vitreous: 0.99, 0.78 to 1.21, .001) were significantly higher in patients with RVO than in healthy controls. Only aqueous concentrations of IL-10 (0.81, 0.45 to 1.18, .001), angiopoietin 4 (1.96, 0.92 to 3.00, .001), and platelet-derived growth factor (PDGF)-AA (0.82, 0.35 to 1.30, .001) were significantly higher in patients with RVO than in healthy controls. Only the vitreous concentration of soluble intercellular adhesion molecule-1 (sICAM-1) (1.23, 0.83 to 1.63, .001) was significantly higher in patients with RVO. No differences, failed sensitivity analyses, or insufficient data were found between patients with RVO and healthy controls for the concentrations of the remaining cytokines.
CONCLUSIONS
Several cytokines in addition to VEGF have the potential to be useful biomarkers and therapeutic targets in RVO.
PubMed: 37009560
DOI: 10.1177/2474126419880391 -
Journal of Extracellular Vesicles Aug 2020Severe COVID-19 infection results in bilateral interstitial pneumonia, often leading to acute respiratory distress syndrome (ARDS) and pulmonary fibrosis in survivors.... (Review)
Review
Severe COVID-19 infection results in bilateral interstitial pneumonia, often leading to acute respiratory distress syndrome (ARDS) and pulmonary fibrosis in survivors. Most patients with severe COVID-19 infections who died had developed ARDS. Currently, ARDS is treated with supportive measures, but regenerative medicine approaches including extracellular vesicle (EV)-based therapies have shown promise. Herein, we aimed to analyse whether EV-based therapies could be effective in treating severe pulmonary conditions that affect COVID-19 patients and to understand their relevance for an eventual therapeutic application to human patients. Using a defined search strategy, we conducted a systematic review of the literature and found 39 articles (2014-2020) that reported effects of EVs, mainly derived from stem cells, in lung injury models (one large animal study, none in human). EV treatment resulted in: (1) attenuation of inflammation (reduction of pro-inflammatory cytokines and neutrophil infiltration, M2 macrophage polarization); (2) regeneration of alveolar epithelium (decreased apoptosis and stimulation of surfactant production); (3) repair of microvascular permeability (increased endothelial cell junction proteins); (4) prevention of fibrosis (reduced fibrin production). These effects were mediated by the release of EV cargo and identified factors including miRs-126, -30b-3p, -145, -27a-3p, syndecan-1, hepatocyte growth factor and angiopoietin-1. This review indicates that EV-based therapies hold great potential for COVID-19 related lung injuries as they target multiple pathways and enhance tissue regeneration. However, before translating EV therapies into human clinical trials, efforts should be directed at developing good manufacturing practice solutions for EVs and testing optimal dosage and administration route in large animal models.
PubMed: 32944185
DOI: 10.1080/20013078.2020.1795365 -
Lipids in Health and Disease May 2021Angiopoietin-like proteins (ANGPTLs) are closely related to insulin resistance and lipid metabolism, and may be a key in metabolic syndrome. Non-alcoholic fatty liver... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Angiopoietin-like proteins (ANGPTLs) are closely related to insulin resistance and lipid metabolism, and may be a key in metabolic syndrome. Non-alcoholic fatty liver disease (NAFLD) (newly named metabolic-associated fatty liver disease (MAFLD)) is based on metabolic dysfunction. There may be some correlation between ANGPTLs and MAFLD, but the specific correlation is unclear. This study aims to explore the predictive role of ANGPTLs in MAFLD and its progression.
METHODS
Seven databases (PubMed, EMBASE, Cochrane Library, CNKI, WANFANG, CBM and Clinicaltrials.gov ) were searched with free terms and MeSH terms. The random-effects model was used to pool the data, and Standardized Mean Difference (SMD) and 95% confidence intervals (CI) were taken as the overall outcome. No language restrictions existed in the article selection. RevMan 5.3, Stata 16 and MetaXL software were applied to analyse the data and the GRADE system was utilized to assess the certainty of evidence.
RESULTS
After reviewing 823 related articles, 13 studies (854 cases and 610 controls) met the inclusion criteria, and contributed to this meta-analysis. The results showed that circulating ANGPTL8 level was significantly elevated in the MAFLD group than in the healthy control group (SMD = 0.97 pg/mL, 95%CI: 0.77, 1.18). Conversely, there was no significant difference in the ANGPTL4 (SMD = 0.11 ng/mL, 95%CI: - 0.32, 0.54) and ANGPTL3 (SMD = - 0.95 ng/mL, 95%CI: - 4.38, 2.48) between the two groups. Subgroup analysis showed that: 1) the MAFLD group had significantly higher ANGPTL8 levels than the healthy control group in Asian and other races; 2) the ANGPTL8 levels in Body Mass Index (BMI) > 25 kg/m patients with MAFLD were higher than those in the healthy control group; 3) the higher ANGPTL8 levels were observed in moderate to severe MAFLD group than the healthy control group. Meta-regression demonstrated that BMI might effectively explain the high heterogeneity. No significant publication bias existed (P > 0.05). The certainty of evidence was assessed as very low by the GRADE system.
CONCLUSIONS
The ANGPTLs may be related to MAFLD. The increased ANGPTL8 level may be positively correlated with different situations of MAFLD, which may act as a potential indicator to monitor the development trends.
Topics: Adult; Aged; Angiopoietin-Like Protein 3; Angiopoietin-Like Protein 4; Angiopoietin-Like Protein 8; Biomarkers; Body Mass Index; Case-Control Studies; Female; Gene Expression; Humans; Lipid Metabolism; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Peptide Hormones
PubMed: 34034750
DOI: 10.1186/s12944-021-01481-1 -
Wiener Klinische Wochenschrift Jan 2022The relationship between acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) and levels of certain inflammatory factors remains controversial. The purpose... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The relationship between acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) and levels of certain inflammatory factors remains controversial. The purpose of this meta-analysis was to summarize the available studies evaluating the association between levels of inflammatory factors and ARDS/ALI incidence.
METHODS
We searched the PubMed, EmBase, and Cochrane databases for studies published up to July 2017. For each inflammatory factor, a random effects model was employed to pool results from different studies.
RESULTS
We identified 63 studies that included 6243 patients in our meta-analysis. Overall, the results indicated that the levels of angiopoietin (ANG)-2 (standard mean difference, SMD: 1.34; P < 0.001), interleukin (IL)-1β (SMD: 0.92; P = 0.012), IL‑6 (SMD: 0.66; P = 0.005), and tumor necrosis factor (TNF)-α (SMD: 0.98; P = 0.001) were significantly higher in patients with ARDS/ALI than in unaffected individuals. No significant differences were observed between patients with ARDS/ALI and unaffected individuals in terms of the levels of IL‑8 (SMD: 0.61; P = 0.159), IL-10 (SMD: 1.10; P = 0.231), and plasminogen activator inhibitor (PAI)-1 (SMD: 0.70; P = 0.060).
CONCLUSIONS
ARDS/ALI is associated with a significantly elevated levels of ANG‑2, IL-1β, IL‑6, and TNF‑α, but not with IL‑8, IL-10, and PAI‑1 levels.
Topics: Acute Lung Injury; Biomarkers; Humans; Respiratory Distress Syndrome; Tumor Necrosis Factor-alpha
PubMed: 34860273
DOI: 10.1007/s00508-021-01971-3 -
Annals of Intensive Care Nov 2019Angiopoietin-1 (Ang-1) and 2 (Ang-2), high mobility group box 1 (HMGB1), soluble receptor for advanced glycation endproducts (sRAGE), soluble triggering receptor...
BACKGROUND
Angiopoietin-1 (Ang-1) and 2 (Ang-2), high mobility group box 1 (HMGB1), soluble receptor for advanced glycation endproducts (sRAGE), soluble triggering receptor expressed on myeloid cells 1 (sTREM1), and soluble urokinase-type plasminogen activator receptor (suPAR) have shown promising results for predicting all-cause mortality in critical care patients. The aim of our systematic review and meta-analysis was to assess the prognostic value of these biomarkers for mortality in adult patients with sepsis.
METHODS
A systematic literature search of the MEDLINE, PubMed, EMBASE, and Cochrane Library databases, for articles in English published from 01.01.1990 onwards, was conducted. The systematic review focused exclusively on observational studies of adult patients with sepsis, any randomized trials were excluded. For the meta-analysis, only studies which provide biomarker concentrations within 24 h of admission in sepsis survivors and nonsurvivors were included. Results are presented as pooled mean differences (MD) between nonsurvivors and survivors with 95% confidence interval for each of the six biomarkers. Studies not included in the quantitative analysis were narratively summarized. The risk of bias was assessed in all included studies using the Quality in Prognosis Studies (QUIPS) tool.
RESULTS
The systematic literature search retrieved 2285 articles. In total, we included 44 studies in the qualitative analysis, of which 28 were included in the meta-analysis. The pooled mean differences in biomarker concentration (nonsurvivors - survivors), measured at onset of sepsis, are listed as follows: (1) Ang-1: - 2.9 ng/ml (95% CI - 4.1 to - 1.7, p < 0.01); (2) Ang-2: 4.9 ng/ml (95% CI 2.6 to 7.1, p < 0.01); (3) HMGB1: 1.2 ng/ml (95% CI 0.0 to 2.4, p = 0.05); (4) sRAGE: 1003 pg/ml (95% CI 628 to 1377, p < 0.01); (5) sTREM-1: 87 pg/ml (95% CI 2 to 171, p = 0.04); (6) suPAR: 5.2 ng/ml (95% CI 4.5 to 6.0, p < 0.01).
CONCLUSIONS
Ang-1, Ang-2, and suPAR provide beneficial prognostic information about mortality in adult patients with sepsis. The further development of standardized assays and the assessment of their performance when included in panels with other biomarkers may be recommended. Trial registration This study was recorded on PROSPERO, prospective register of systematic reviews, under the registration ID: CRD42018081226.
PubMed: 31705327
DOI: 10.1186/s13613-019-0600-1 -
Therapeutic Advances in Respiratory... 2020Angiopoietin-2 (Ang-2), as one of the ligands of endothelial receptor Tie2, is known to be significant for vessel maturation and stabilization after birth. Previous... (Meta-Analysis)
Meta-Analysis
Circulating angiopoietin-2 and the risk of mortality in patients with acute respiratory distress syndrome: a systematic review and meta-analysis of 10 prospective cohort studies.
BACKGROUND
Angiopoietin-2 (Ang-2), as one of the ligands of endothelial receptor Tie2, is known to be significant for vessel maturation and stabilization after birth. Previous studies showed the relationship between Ang-2 level and the risk of mortality in patients with acute respiratory distress syndrome (ARDS). However, the link between circulating Ang-2 and the risk of mortality in patients with ARDS varied in different investigations.
RESULTS
We performed a systematic review and meta-analysis of all available cohort studies regarding the association between baseline circulating Ang-2 and mortality in patients with ARDS. Among the 10 eligible studies, pooled odds ratio (OR) showed that high Ang-2 level contributed to ARDS mortality [OR = 1.56, 95% confidence interval (CI): 1.30-1.89, = 76.2%]. Stratified analysis revealed that higher circulating Ang-2 was related to a 30% higher risk in the high-quality scores group (OR = 1.68, 95% CI: 1.33-2.68, = 62.4%). The of the bad compliance group decreased from 76.2% to 8.5%, which suggested that compliance is a significant source of heterogeneity. This association may be blunted by potential bias, although the results was not meaningfully changed by omitting only one study at a time. Further subgroup analysis and meta-regression support that compliance of patients also affects the results significantly, compared with the publication year, follow-up duration, the samples, or population characteristics.
CONCLUSION
Participants with higher baseline Ang-2 were at a higher risk for future risk of mortality in patients with ARDS. Higher circulating Ang-2 levels could independently predict the risk of mortality in patients with ARDS. However, further large scale prospective cohorts or even interventional studies are warranted to evaluate the diagnostic power of Ang-2 and its causative role on ARDS outcome.
Topics: Adolescent; Adult; Angiopoietin-2; Biomarkers; Child; Child, Preschool; Female; Humans; Infant; Male; Middle Aged; Predictive Value of Tests; Prognosis; Respiratory Distress Syndrome; Risk Assessment; Risk Factors; Up-Regulation; Young Adult
PubMed: 32043429
DOI: 10.1177/1753466620905274