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International Journal of Oncology Jan 2018Annexin A2 is a 36-kDa protein interfering with multiple cellular processes especially in cancer progression. The present review aimed to show the relations between... (Review)
Review
Annexin A2 is a 36-kDa protein interfering with multiple cellular processes especially in cancer progression. The present review aimed to show the relations between Annexin A2 and cancer. A systematic search for studies investigating cancer and Annexin A2 expression was conducted using PubMed. Acute lymphoblastic leukaemia, acute promyelocytic leukaemia, clear cell renal cell carcinoma, breast, cervical, colorectal, endometrial, gastric cancer, glioblastoma, hepatocellular carcinoma, lung, multiple myeloma, oesophageal squamous cell carcinoma, ovarian cancer, pancreatic duct adenocarcinoma, prostate cancer and urothelial carcinoma were evaluated. Annexin A2 expression correlates with resistance to treatment, binding to the bone marrow, histological grade and type, TNM-stage and shortened overall survival. The regulation of Annexin A2 is of interest due to its potential as target for a more individualized cancer management.
Topics: Animals; Annexin A2; Biomarkers, Tumor; Humans; Neoplasms
PubMed: 29115416
DOI: 10.3892/ijo.2017.4197 -
Molecules (Basel, Switzerland) Aug 2020Annexin A1 has been extensively investigated as an anti-inflammatory protein, but its role in different types of cancer has not been consolidated in a single systematic...
Annexin A1 has been extensively investigated as an anti-inflammatory protein, but its role in different types of cancer has not been consolidated in a single systematic review to date. Thus, the aim of this paper is to systematically review and critically analyse 18 studies (in-vivo and in-vitro) to consolidate, in a concerted manner, all the information on differential expression of Annexin A1 in different types of cancer and the role this protein plays in tumorigenesis. Pubmed, Scopus, Web of Science, and ScienceDirect were used for the literature search and the keywords used are "annexin A1," "lipocortin 1," "cancer," "malignancy," "neoplasm," "neoplasia," and "tumor." A total of 1128 articles were retrieved by implementing a standard search strategy subjected to meticulous screening processes and 442 articles were selected for full article screening. A total of 18 articles that adhered to the inclusion criteria were included in the systematic review and these articles possessed low to moderate bias. These studies showed a strong correlation between Annexin A1 expression and cancer progression via modulation of various cancer-associated pathways. Differential expression of Annexin A1 is shown to play a role in cellular proliferation, metastasis, lymphatic invasion, and development of resistance to anti-cancer treatment. Meta-analysis in the future may provide a statistically driven association between Annexin A1 expression and malignancy progression.
Topics: Animals; Annexin A1; Apoptosis; Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Humans; Neoplasms; Signal Transduction
PubMed: 32823805
DOI: 10.3390/molecules25163700 -
European Journal of Nuclear Medicine... Dec 2015(99m)Tc-Annexin A5 has been used as a molecular imaging probe for the visualization, characterization and measurement of apoptosis. In an effort to define the... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
(99m)Tc-Annexin A5 has been used as a molecular imaging probe for the visualization, characterization and measurement of apoptosis. In an effort to define the quantitative (99m)Tc-annexin A5 uptake criteria that best predict tumor response to treatment, we performed a systematic review and meta-analysis of the results of all clinical imaging trials found in the literature or publicly available databases.
METHODS
Included in this review were 17 clinical trials investigating quantitative (99m)Tc-annexin A5 (qAnx5) imaging using different parameters in cancer patients before and after the first course of chemotherapy and/or radiation therapy. Qualitative assessment of the clinical studies for diagnostic accuracy was performed using the QUADAS-2 criteria. Of these studies, five prospective single-center clinical trials (92 patients in total) were included in the meta-analysis after exclusion of one multicenter clinical trial due to heterogeneity. Pooled positive predictive values (PPV) and pooled negative predictive values (NPV) (with 95% CI) were calculated using Meta-Disc software version 1.4.
RESULTS
Absolute quantification and/or relative quantification of (99m)Tc-annexin A5 uptake were performed at baseline and after the start of treatment. Various quantitative parameters have been used for the calculation of (99m)Tc-annexin A5 tumor uptake and delta (Δ) tumor changes post-treatment compared to baseline including: tumor-to-background ratio (TBR), ΔTBR, tumor-to-noise ratio, relative tumor ratio (TR), ΔTR, standardized tumor uptake ratio (STU), ΔSTU, maximum count per pixel within the tumor volume (Cmax), Cmax%, absolute ΔU and percentage (ΔU%), maximum ΔU counts, semiquantitative visual scoring, percent injected dose (%ID) and %ID/cm(3). Clinical trials investigating qAnx5 imaging have included patients with lung cancer, lymphoma, breast cancer, head and neck cancer and other less common tumor types. In two phase I/II single-center clinical trials, an increase of ≥25% in uptake following treatment was considered a significant threshold for an apoptotic tumor response (partial response, complete response). In three other phase I/II clinical trials, increases of ≥28%, ≥42% and ≥47% in uptake following treatment were found to be the mean cut-off levels in responders. In a phase II/III multicenter clinical trial, an increase of ≥23% in uptake following treatment was found to be the minimum cut-off level for a tumor response. In one clinical trial, no significant difference in (99m)Tc-annexin A5 uptake in terms of %ID was found in healthy tissues after chemotherapy compared to baseline. In two other clinical trials, intraobserver and interobserver measurements of (99m)Tc-annexin A5 tumor uptake were found to be reproducible (mean difference <5%, kappa = 0.90 and 0.82, respectively) and to be highly correlated with treatment outcome (Spearman r = 0.99, p < 0.0001). The meta-analysis demonstrated a pooled positive PPV of 100% (95% CI 92 - 100%) and a pooled NPV of 70% (95% CI 55 - 82%) for prediction of a tumor response after the first course of chemotherapy and/or radiotherapy in terms of ΔU%. In a symmetric sROC analysis, the AUC was 0.919 and the Q* index was 85.21 %.
CONCLUSION
Quantitative (99m)Tc-annexin A5 imaging has been investigated in clinical trials for the assessment of apoptotic tumor responses. This meta-analysis showed a high pooled PPV and a moderate pooled NPV with ΔU cut-off values ranging between 20% and 30%. Standardization of quantification and harmonization of results are required for high-quality clinical research. A standardized uptake value score (SUV, ΔSUV) using quantitative SPECT/CT imaging may be a promising approach to the simple, reproducible and semiquantitative assessment of apoptotic tumor changes.
Topics: Annexin A5; Apoptosis; Clinical Trials as Topic; Humans; Multimodal Imaging; Neoplasms; Organotechnetium Compounds; Positron-Emission Tomography; Radiopharmaceuticals; Tomography, X-Ray Computed
PubMed: 26275392
DOI: 10.1007/s00259-015-3152-0 -
International Journal of Molecular... Jul 2022Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that is often associated with a poorer prognosis and does not respond to hormonal therapy.... (Review)
Review
Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that is often associated with a poorer prognosis and does not respond to hormonal therapy. Increasing evidence highlights the exploitability of Annexin A1 (AnxA1), a calcium dependent protein, as a precision medicine for TNBC. To systematically summarize the role of AnxA1 and its associated mechanisms in TNBC, we performed data mining using three main databases: PubMed, Scopus, and Ovid/Medline. The papers retrieved were based on two different sets of key words such as "Annexin A1" or "Lipocortin 1" and "Breast cancer" or "TNBC". A total of 388 articles were identified, with 210 chosen for comprehensive screening and 13 papers that met inclusion criteria were included. Current evidence from cell culture studies showed that AnxA1 expression is correlated with NF-κB, which promotes migration by activating ERK phosphorylation. AnxaA1 also activates TGF-β signaling which upregulates MMP-9 and miR196a expression to enhance epithelial-mesenchymal transition and migratory capacity of TNBC cells. AnxA1 can steer the macrophage polarization toward the M2 phenotype to create a pro-tumor immune environment. Existing research suggests a potential role of AnxA1 in the metastasis and immune landscape of TNBC tumors. Preclinical and clinical experiments are warranted to investigate the feasibility and effectiveness of targeting AnxA1 in TNBC.
Topics: Annexin A1; Cell Line, Tumor; Cell Movement; Cell Proliferation; Epithelial-Mesenchymal Transition; Humans; NF-kappa B; Triple Negative Breast Neoplasms
PubMed: 35897832
DOI: 10.3390/ijms23158256 -
Human Reproduction (Oxford, England) Jan 2015Do any proteomic biomarkers previously identified for pre-eclampsia (PE) overlap with those identified in women with polycystic ovary syndrome (PCOS). (Comparative Study)
Comparative Study Review
STUDY QUESTION
Do any proteomic biomarkers previously identified for pre-eclampsia (PE) overlap with those identified in women with polycystic ovary syndrome (PCOS).
SUMMARY ANSWER
Five previously identified proteomic biomarkers were found to be common in women with PE and PCOS when compared with controls.
WHAT IS KNOWN ALREADY
Various studies have indicated an association between PCOS and PE; however, the pathophysiological mechanisms supporting this association are not known.
STUDY DESIGN, SIZE, DURATION
A systematic review and update of our PCOS proteomic biomarker database was performed, along with a parallel review of PE biomarkers. The study included papers from 1980 to December 2013.
PARTICIPANTS/MATERIALS, SETTING, METHODS
In all the studies analysed, there were a total of 1423 patients and controls. The number of proteomic biomarkers that were catalogued for PE was 192.
MAIN RESULTS AND THE ROLE OF CHANCE
Five proteomic biomarkers were shown to be differentially expressed in women with PE and PCOS when compared with controls: transferrin, fibrinogen α, β and γ chain variants, kininogen-1, annexin 2 and peroxiredoxin 2. In PE, the biomarkers were identified in serum, plasma and placenta and in PCOS, the biomarkers were identified in serum, follicular fluid, and ovarian and omental biopsies.
LIMITATIONS, REASONS FOR CAUTION
The techniques employed to detect proteomics have limited ability in identifying proteins that are of low abundance, some of which may have a diagnostic potential. The sample sizes and number of biomarkers identified from these studies do not exclude the risk of false positives, a limitation of all biomarker studies. The biomarkers common to PE and PCOS were identified from proteomic analyses of different tissues.
WIDER IMPLICATIONS OF THE FINDINGS
This data amalgamation of the proteomic studies in PE and in PCOS, for the first time, discovered a panel of five biomarkers for PE which are common to women with PCOS, including transferrin, fibrinogen α, β and γ chain variants, kininogen-1, annexin 2 and peroxiredoxin 2. If validated, these biomarkers could provide a useful framework for the knowledge infrastructure in this area. To accomplish this goal, a well co-ordinated multidisciplinary collaboration of clinicians, basic scientists and mathematicians is vital.
STUDY FUNDING/COMPETING INTERESTS
No financial support was obtained for this project. There are no conflicts of interest.
Topics: Biomarkers; Female; Humans; Polycystic Ovary Syndrome; Pre-Eclampsia; Pregnancy; Proteins; Proteomics; Retrospective Studies
PubMed: 25351721
DOI: 10.1093/humrep/deu268 -
Eye (London, England) Jul 2023Corneal and ocular surface diseases (OSDs) carry significant psychosocial and economic burden worldwide. We set out to review the literature on the application of... (Review)
Review
Corneal and ocular surface diseases (OSDs) carry significant psychosocial and economic burden worldwide. We set out to review the literature on the application of artificial intelligence (AI) and bioinformatics for analysis of biofluid biomarkers in corneal and OSDs and evaluate their utility in clinical decision making. MEDLINE, EMBASE, Cochrane and Web of Science were systematically queried for articles using AI or bioinformatics methodology in corneal and OSDs and examining biofluids from inception to August 2021. In total, 10,264 articles were screened, and 23 articles consisting of 1058 individuals were included. Using various AI/bioinformatics tools, changes in certain tear film cytokines that are proinflammatory such as increased expression of apolipoprotein, haptoglobin, annexin 1, S100A8, S100A9, Glutathione S-transferase, and decreased expression of supportive tear film components such as lipocalin-1, prolactin inducible protein, lysozyme C, lactotransferrin, cystatin S, and mammaglobin-b, proline rich protein, were found to be correlated with pathogenesis and/or treatment outcomes of dry eye, keratoconus, meibomian gland dysfunction, and Sjögren's. Overall, most AI/bioinformatics tools were used to classify biofluids into diseases subgroups, distinguish between OSD, identify risk factors, or make predictions about treatment response, and/or prognosis. To conclude, AI models such as artificial neural networks, hierarchical clustering, random forest, etc., in conjunction with proteomic or metabolomic profiling using bioinformatics tools such as Gene Ontology or Kyoto Encylopedia of Genes and Genomes pathway analysis, were found to inform biomarker discovery, distinguish between OSDs, help define subgroups with OSDs and make predictions about treatment response in a clinical setting.
Topics: Humans; Artificial Intelligence; Proteomics; Dry Eye Syndromes; Cornea; Tears
PubMed: 36380089
DOI: 10.1038/s41433-022-02307-9 -
Systematic Reviews Jun 2022Cancer morbidity and mortality rates remain high, and thus, at present, considerable efforts are focused on finding drugs with higher sensitivity against tumor cells and...
BACKGROUND AND OBJECTIVES
Cancer morbidity and mortality rates remain high, and thus, at present, considerable efforts are focused on finding drugs with higher sensitivity against tumor cells and fewer side effects. Disulfiram (DSF), as an anti-alcoholic drug, kills the cancer cells by inducing apoptosis. Several preclinical and clinical studies have examined the potential of repurposing DSF as an anticancer treatment. This systematic review aimed to assess evidence regarding the antineoplastic activity of DSF in in vitro and in vivo models, as well as in humans.
METHODS
Two authors independently conducted this systematic review of English and Chinese articles from the PubMed, Embase, and the Cochrane Library databases up to July 2019. Eligible in vitro studies needed to include assessments of the apoptosis rate by flow cytometry using annexin V/propidium iodide, and studies in animal models and clinical trials needed to examine tumor inhibition rates, and progression-free survival (PFS) and overall survival (OS), respectively. Data were analyzed using descriptive statistics.
RESULTS
Overall, 35 studies, i.e., 21 performed in vitro, 11 based on animal models, and three clinical trials, were finally included. In vitro and animal studies indicated that DSF was associated with enhanced apoptosis and tumor inhibition rates, separately. Human studies showed that DSF prolongs PFS and OS. The greatest anti-tumor activity was observed when DSF was used as combination therapy or as a nanoparticle-encapsulated molecule. There was no noticeable body weight loss after DSF treatment, which indicated that there was no major toxicity of DSF.
CONCLUSIONS
This systematic review provides evidence regarding the anti-tumor activity of DSF in vitro, in animals, and in humans and indicates the optimal forms of treatment to be evaluated in future research.
Topics: Animals; Antineoplastic Agents; Disulfiram; Humans; Neoplasms
PubMed: 35655266
DOI: 10.1186/s13643-021-01858-4 -
PloS One 2017We performed a comprehensive review and meta-analysis to evaluate the diagnostic values of serum single and multiplex tumor-associated autoantibodies (TAAbs) in patients... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
We performed a comprehensive review and meta-analysis to evaluate the diagnostic values of serum single and multiplex tumor-associated autoantibodies (TAAbs) in patients with lung cancer (LC).
METHODS
We searched the MEDLINE and EMBASE databases for relevant studies investigating serum TAAbs for the diagnosis of LC. The primary outcomes included sensitivity, specificity and accuracy of the test.
RESULTS
The systematic review and meta-analysis included 31 articles with single autoantibody and 39 with multiplex autoantibodies. Enzyme-linked immunosorbent assay (ELISA) was the most common detection method. For the diagnosis of patients with all stages and early-stage LC, different single or combinations of TAAbs demonstrated different diagnostic values. Although individual TAAbs showed low diagnostic sensitivity, the combination of multiplex autoantibodies offered relatively high sensitivity. For the meta-analysis of a same panel of autoantibodies in patients at all stages of LC, the pooled results of the panel of 6 TAAbs (p53, NY-ESO-1, CAGE, GBU4-5, Annexin 1 and SOX2) were: sensitivity 38% (95% CI 0.35-0.40), specificity 89% (95% CI 0.86-0.91), diagnostic accuracy 65.9% (range 62.5-81.8%), AUC 0.52 (0.48-0.57), while the summary estimates of 7 TAAbs (p53, CAGE, NY-ESO-1, GBU4-5, SOX2, MAGE A4 and Hu-D) were: sensitivity 47% (95% CI 0.34-0.60), specificity 90% (95% CI 0.89-0.92), diagnostic accuracy 78.4% (range 67.5-88.8%), AUC 0.90 (0.87-0.93). For the meta-analysis of the same panel of autoantibodies in patients at early-stage of LC, the sensitivities of both panels of 7 TAAbs and 6 TAAbs were 40% and 29.7%, while their specificities were 91% and 87%, respectively.
CONCLUSIONS
Serum single or combinations of multiplex autoantibodies can be used as a tool for the diagnosis of LC patients at all stages or early-stage, but the combination of multiplex autoantibodies shows a higher detection capacity; the diagnostic value of the panel of 7 TAAbs is higher than the panel of 6 TAAbs, which may be used as potential biomarkers for the early detection of LC.
Topics: Autoantibodies; Biomarkers, Tumor; Humans; Lung Neoplasms; Neoplasm Staging; Publication Bias; ROC Curve; Sensitivity and Specificity
PubMed: 28750095
DOI: 10.1371/journal.pone.0182117 -
International Journal of Molecular... Apr 2023The extracellular matrix (ECM) of the brain is a dynamic structure made up of a vast network of bioactive macromolecules that modulate cellular events. Structural,... (Review)
Review
The extracellular matrix (ECM) of the brain is a dynamic structure made up of a vast network of bioactive macromolecules that modulate cellular events. Structural, organizational, and functional changes in these macromolecules due to genetic variation or environmental stressors are thought to affect cellular functions and may result in disease. However, most mechanistic studies to date usually focus on the cellular aspects of diseases and pay less attention to the relevance of the processes governing the dynamic nature of the extracellular matrix in disease pathogenesis. Thus, due to the ECM's diversified biological roles, increasing interest in its involvement in disease, and the lack of sufficient compiled evidence regarding its relationship with Parkinson's disease (PD) pathology, we aimed to compile the existing evidence to boost the current knowledge on the area and provide refined guidance for the future research. Here, in this review, we gathered postmortem brain tissue and induced pluripotent stem cell (iPSC)-related studies from PubMed and Google Scholar to identify, summarize and describe common macromolecular alterations in the expression of brain ECM components in Parkinson's disease (PD). A literature search was conducted up until 10 February 2023. The overall hits from the database and manual search for proteomic and transcriptome studies were 1243 and 1041 articles, respectively. Following a full-text review, 10 articles from proteomic and 24 from transcriptomic studies were found to be eligible for inclusion. According to proteomic studies, proteins such as collagens, fibronectin, annexins, and tenascins were recognized to be differentially expressed in Parkinson's disease. Transcriptomic studies displayed dysregulated pathways including ECM-receptor interaction, focal adhesion, and cell adhesion molecules in Parkinson's disease. A limited number of relevant studies were accessed from our search, indicating that much work remains to be carried out to better understand the roles of the ECM in neurodegeneration and Parkinson's disease. However, we believe that our review will elicit focused primary studies and thus support the ongoing efforts of the discovery and development of diagnostic biomarkers as well as therapeutic agents for Parkinson's disease.
Topics: Humans; Parkinson Disease; Proteomics; Brain; Extracellular Matrix; Tenascin
PubMed: 37108598
DOI: 10.3390/ijms24087435 -
Sarcoidosis, Vasculitis, and Diffuse... Aug 2016The associations of ANXA11 gene polymorphisms and susceptibility to sarcoidosis have been evaluated in recent years. However, the results remain controversial,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
The associations of ANXA11 gene polymorphisms and susceptibility to sarcoidosis have been evaluated in recent years. However, the results remain controversial, especially in different ethnicity. To assess the associations between ANXA11 and sarcoidosis, we conducted this meta-analysis.
METHOD
Articles were searched in MEDLINE, EMBASE and PubMed from their establishment date to August of 2014, and 4,567 sarcoidosis patients and 4,278 controls from 6 studies were included. The strength of associations was determined by ORs with 95% CIs. The associations between ANXA11 SNP rs1049550, rs2573346, rs2789679 polymorphisms and sarcoidosis risk were assessed using additive, recessive and dominant models.
RESULTS
ANXA11 SNP rs2573346 and rs2789679 T allele conferred protection against sarcoidosis (OR: 0.664, 95% CI: 0.607-0.726 for rs2573346, and OR: 0.698, 95% CI: 0.640-0.762 for rs2789679). For SNP rs1049550, individuals carrying the ''T'' allele (TT+CT) had a nearly 46% increased risk for the development of sarcoidosis, when compared with CC homozygotes (OR: 1.461, 95% CI: 1.183-1.803) in overall population. A significant association was also found in additive model (OR: 1.477, 95% CI: 1.328-1.642 for CC vs. CT; OR: 0.610, 95% CI: 0.412-0.905 for TT vs. CC). In addition, ethnicity factors may contribute to the disease risk.
CONCLUSION
The meta-analysis revealed that ''T'' allele of ANXA11 SNP rs2573346 and rs2789679 conferred protection against sarcoidosis. ''C'' allele of SNP rs1049550 may be a risk factor for sarcoidosis in overall population. Our study shows that ANXA11 closely associated with the development of sarcoidosis but further studies in different ethnicity were needed.
Topics: Animals; Annexins; Case-Control Studies; Chi-Square Distribution; Genetic Association Studies; Genetic Predisposition to Disease; Heterozygote; Homozygote; Humans; Odds Ratio; Phenotype; Polymorphism, Single Nucleotide; Protective Factors; Risk Factors; Sarcoidosis
PubMed: 27537711
DOI: No ID Found