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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 -
PloS One 2017The association between circulating betatrophin levels and gestational diabetes mellitus (GDM) is controversial. The aim of our study was to systematically review... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The association between circulating betatrophin levels and gestational diabetes mellitus (GDM) is controversial. The aim of our study was to systematically review available literature linking betatrophin to GDM for a comprehensive understanding of the relationship between circulating betatrophin levels and GDM in human.
METHODS
PubMed, The Cochrane Library, Medline and CNKI were searched for studies published up to August 2016. Manual searches of references of the relevant original studies were conducted. Pooled estimates were measured using the fixed or random effect model. Overall effect was reported in a standard mean difference (SMD). All data were analyzed with Review Manager 5.3 and Stata 12.0.
RESULTS
Of 25 references reviewed, 8 studies met our inclusion criteria and contributed to meta-analysis. All the studies were used to evaluate the relationship between betatrophin levels in blood and GDM. Betatrophin levels were significantly elevated in women with GDM compared with those without GDM (SMD = 1.05; 95% CI: 0.41-1.68, P = 0.001). This evidence was more consistent among women with betatrophin blood draw during the third trimester (SMD = 1.3, 95% CI: 1-1.61, P < 0.001) and for women BMI ≥ 28 kg/m2 (SMD = 1.53, 95% CI: 1.30-1.75, P < 0.001).
CONCLUSIONS
The evidences from this meta-analysis indicated that the levels of circulating betatrophin were significantly elevated among women with GDM compared with women with normal glucose tolerance, especially with BMI ≥ 28 kg/m2 and in the third trimester.
Topics: Angiopoietin-Like Protein 8; Angiopoietin-like Proteins; Body Mass Index; Databases, Factual; Diabetes, Gestational; Female; Humans; Peptide Hormones; Pregnancy; Pregnancy Trimester, Third; Risk Factors
PubMed: 28081192
DOI: 10.1371/journal.pone.0169941 -
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 -
Disease Markers 2016In order to clarify previous ambiguous research conclusions, a meta-analysis was made to investigate the relationship between betatrophin levels in blood and type 2... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In order to clarify previous ambiguous research conclusions, a meta-analysis was made to investigate the relationship between betatrophin levels in blood and type 2 diabetes mellitus (T2DM).
METHODS
We have searched all the English and Chinese references regarding the relationship between betatrophin and diabetes in database both manually and online. Strict criteria have been established to include and exclude articles, with Mean and Standard Deviation as statistics to evaluate strength of association. We have chosen either fixed- or random effect model according to heterogeneity inspection results and used Begg's test and Egger's test to analyze publication bias.
RESULTS
A total of 11 studies were included in this meta-analysis. Meta-analysis indicated a significant association between betatrophin and T2DM (Mean: 329.46; 95% confidence interval: 182.51 to 476.42, P < 0.0001). However, in the subgroup analysis, there was no significant statistic between betatrophin concentration and T2DM within Caucasian population (Mean: 98.40; 95% confidence interval: -1585.08 to 1781.88, P = 0.91).
CONCLUSIONS
Such relationship may suggest preference for association between betatrophin and T2DM in different population.
Topics: Angiopoietin-Like Protein 8; Angiopoietin-like Proteins; Case-Control Studies; Diabetes Mellitus, Type 2; Humans; Peptide Hormones; White People
PubMed: 27242389
DOI: 10.1155/2016/9391837 -
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 -
Malaria Journal Dec 2016Levels of both angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) correlate with malaria disease severity and are proposed as biomarkers and possible therapeutic targets.... (Review)
Review
BACKGROUND
Levels of both angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) correlate with malaria disease severity and are proposed as biomarkers and possible therapeutic targets. To establish their role in malaria, a systematic review was performed of the literature on Ang-1 and Ang-2 with regard to their potential as biomarkers in malaria and discuss their possible place in adjuvant treatment regimens.
METHODS
Ten electronic databases were systematically searched to identify studies investigating Ang-1 and Ang-2 in human and murine malaria in both clinical and experimental settings. Information about the predictive value of Ang-1 and Ang-2 for disease severity and their regulatory changes in interventional studies were extracted.
RESULTS
Some 579 studies were screened; 26 were included for analysis. In all five studies that determined Ang-1 levels and in all 11 studies that determined Ang-2 in different disease severity states in falciparum malaria, a decline in Ang-1 and an increase of Ang-2 levels was associated with increasing disease severity. All nine studies that determined angiopoietin levels in Plasmodium falciparum patients to study their ability as biomarkers could distinguish between multiple disease severity states; the more the disease severity states differed, the better they could be distinguished. Five studies differentiating malaria survivors from non-survivors with Ang-2 as marker found an AUROC in a range of 0.71-0.83, which performed as well or better than lactate. Prophylactic administration of FTY720, rosiglitazone or inhalation of nitric oxide (NO) during malaria disease in mice resulted in an increase in Ang-1, a decrease in Ang-2 and an increased survival. For rosiglitazone, a decrease in Ang-2/Ang-1 ratio was observed after post-infection treatment in mice and humans with malaria, but for inhalation of NO, an effect on Ang-1 and survival was only observed in mice.
CONCLUSION
Both Ang-1 and Ang-2 levels correlate with and can distinguish between malaria disease severity states within the group of malaria-infected patients. However, distinct comparisons of disease severity states were made in distinct studies and not all distinctions made had clinical relevance. Changes in levels of Ang-1 and Ang-2 might also reflect treatment effectiveness and are promising therapeutic targets as part of multi-targeted therapy.
Topics: Angiopoietin-1; Angiopoietin-2; Animals; Biomarkers; Disease Models, Animal; Fingolimod Hydrochloride; Humans; Immunosuppressive Agents; Malaria, Falciparum; Mice; Predictive Value of Tests; ROC Curve; Survival Analysis; Treatment Outcome
PubMed: 27905921
DOI: 10.1186/s12936-016-1624-8 -
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 -
Medicine Sep 2017Angiogenesis is an essential process in the development and progression of malignant tumors including lung cancer, in which angiopoietin-2 (Ang-2) plays an important... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Angiogenesis is an essential process in the development and progression of malignant tumors including lung cancer, in which angiopoietin-2 (Ang-2) plays an important role. The objective of this study was to assess the prognostic value of serum Ang-2 levels in patients with lung cancer.
METHODS
A comprehensive systematic electronic search was performed in the Pubmed, Embase, Web of Science, china national knowledge infrastructure, and VIP databases update to October, 2016 (qikan.cqvip.com). Literatures examining the relevance of serum Ang-2 levels to progression and prognosis of lung cancer were eligible for our study. Standardized mean differences (SMD) with 95% confidence interval (95% CI) and a P value were applied to compare continuous variables, and hazard ratio (HR) with 95% CI as well as P value were applied for prognostic role.
RESULTS
Twenty studies with 1911 patients met the eligibility criteria. Among them, 7 studies with 575 patients with lung cancer assessed the association between expression of serum Ang-2 and prognosis. According to our results, higher levels of serum Ang-2 were associated with the later stage of tumor. Serum Ang-2 levels were significantly lower in stage I than in stage II (SMD: -0.51; 95% CI: -0.75 to -0.27; P < .001), in stage II than in stage III (SMD: -0.52; 95% CI: -0.80 to -0.24; P < .001), in stage III than in stage IV (SMD: -0.58; 95% CI: -0.93 to -0.23; P = .001). In addition, serum Ang-2 levels were higher in patients with lymph node metastasis (SMD: 1.06; 95% CI, 0.57-1.56; P < .001). Meanwhile, patients with lung cancer with higher levels of serum Ang-2 were associated with a significant poorer prognosis when compared to those with lower serum Ang-2 levels (HR: 1.64; 95% CI: 1.20-2.25; P = .002), and this role was further detected when stratified by ethnicity and histological type.
CONCLUSIONS
This systematic review and meta-analysis suggested that serum Ang-2 levels might be a potential predictor for staging, and were associated with prognosis of lung cancer.
Topics: Angiopoietin-2; Biomarkers, Tumor; Disease Progression; Humans; Lung Neoplasms; Prognosis
PubMed: 28906403
DOI: 10.1097/MD.0000000000008063 -
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