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PeerJ 2024To elucidate the relationship between cancer-associated fibroblast (CAFs) biomarkers and the prognosis of breast cancer patients for individualized CAFs-targeting... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To elucidate the relationship between cancer-associated fibroblast (CAFs) biomarkers and the prognosis of breast cancer patients for individualized CAFs-targeting treatment.
METHODOLOGY
PubMed, Web of Science, Cochrane, and Embase databases were searched for CAFs-related studies of breast cancer patients from their inception to September, 2023. Meta-analysis was performed using R 4.2.2 software. Sensitivity analyses were performed to explore the sources of heterogeneity. Funnel plot and Egger's test were used to assess the publication bias.
RESULTS
Twenty-seven studies including 6,830 patients were selected. Univariate analysis showed that high expression of platelet-derived growth factor receptor- (PDGFR-) ( = 0.0055), tissue inhibitor of metalloproteinase-2 (TIMP-2) ( < 0.0001), matrix metalloproteinase (MMP) 9 ( < 0.0001), MMP 11 ( < 0.0001) and MMP 13 ( = 0.0009) in CAFs were correlated with reduced recurrence-free survival (RFS)/disease-free survival (DFS)/metastasis-free survival (MFS)/event-free survival (EFS) respectively. Multivariate analysis showed that high expression of -smooth muscle actin (-SMA) ( = 0.0002), podoplanin (PDPN) ( = 0.0008), and PDGFR- ( = 0.0470) in CAFs was associated with reduced RFS/DFS/MFS/EFS respectively. Furthermore, PDPN and PDGFR- expression in CAFs of poorly differentiated breast cancer patients were higher than that of patients with relatively better differentiated breast cancer. In addition, there is a positive correlation between the expression of PDPN and human epidermal growth factor receptor-2 (HER-2).
CONCLUSIONS
The high expression of -SMA, PDPN, PDGFR- in CAFs leads to worse clinical outcomes in breast cancer, indicating their roles as prognostic biomarkers and potential therapeutic targets.
Topics: Humans; Female; Breast Neoplasms; Cancer-Associated Fibroblasts; Tissue Inhibitor of Metalloproteinase-2; Biomarkers, Tumor; Breast; Receptor, Platelet-Derived Growth Factor beta
PubMed: 38410801
DOI: 10.7717/peerj.16958 -
American Journal of Obstetrics &... Mar 2024In recent years, the ratio of soluble fms-like tyrosine kinase 1 to placental growth factor for use in predicting preeclampsia has been explored extensively. Despite... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
In recent years, the ratio of soluble fms-like tyrosine kinase 1 to placental growth factor for use in predicting preeclampsia has been explored extensively. Despite extensive research, available data on its effectiveness in predicting preeclampsia in twin pregnancies are limited and conflicting. This meta-analysis aimed to assess the diagnostic accuracy of the soluble fms-like tyrosine kinase 1 to placental growth factor ratio in distinguishing cases with preeclampsia in twin pregnancies from healthy controls.
DATA SOURCES
Studies that evaluated the use of the soluble fms-like tyrosine kinase 1 to placental growth factor ratio in predicting preeclampsia were searched in PubMed, Embase, and Cochrane databases from inception to August 6, 2023, without language restriction.
STUDY ELIGIBILITY CRITERIA
The following population, exposure, comparators, outcomes, and study designs were included: women with twin pregnancies; an increased soluble fms-like tyrosine kinase 1 to placental growth factor ratio with preeclampsia as the outcome; women without preeclampsia; a 2 × 2 diagnostic table, diagnostic accuracy data, and the incidence of preeclampsia; and prospective cohort studies and observational comparative studies, respectively.
STUDY APPRAISAL AND SYNTHESIS METHODS
The quality of the included studies was evaluated. Key parameters, including the specificity, sensitivity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio, were calculated using the random- and fixed-effects models. In addition, the area under the receiver operating characteristic curve and the summary receiver operating characteristic curve were evaluated.
RESULTS
A total of 7 studies were included, including 442 women with twin pregnancies (115 patients with preeclampsia and 327 controls without preeclampsia). The results highlighted the promising effectiveness of the soluble fms-like tyrosine kinase 1 to placental growth factor ratio in predicting preeclampsia in twin pregnancies with a pooled specificity of 0.89 (95% confidence interval, 0.80-0.95), a sensitivity of 0.84 (95% confidence interval, 0.73-0.93), a positive likelihood ratio of 32.76 (95% confidence interval, 12.82-83.74), and a negative likelihood ratio of 0.03 (95% confidence interval, 0.01-0.08). The combined diagnostic odds ratio was 35.72 (95% confidence interval, 12.92-98.76), and the area under the receiver operating characteristic curve was 0.92.
CONCLUSION
These collective findings underscore the potential of the soluble fms-like tyrosine kinase 1 to placental growth factor ratio as an accurate marker for identifying preeclampsia among women with twin pregnancies.
Topics: Female; Humans; Pregnancy; Placenta Growth Factor; Pre-Eclampsia; Pregnancy, Twin; Prospective Studies; Vascular Endothelial Growth Factor Receptor-1
PubMed: 38401234
DOI: 10.1016/j.ajogmf.2024.101290 -
BMC Cancer Feb 2024To compare the efficacy, safety and effects on quality of life of different ALK-inhibitors for global and Asian patients with advanced ALK-positive non-small-cell lung... (Meta-Analysis)
Meta-Analysis
Identifying optimal ALK inhibitors in first- and second-line treatment of patients with advanced ALK-positive non-small-cell lung cancer: a systematic review and network meta-analysis.
OBJECTIVES
To compare the efficacy, safety and effects on quality of life of different ALK-inhibitors for global and Asian patients with advanced ALK-positive non-small-cell lung cancer (NSCLC).
METHODS
The included RCTs were identified through a systematic search of PubMed, EMBASE, Cochrane Library, Clinical Trials.gov, and major cancer conferences. The assessment of progression-free survival (PFS), intracranial PFS, overall survival (OS), and patient-reported outcomes (PROs) was carried out using restricted mean survival time (RMST) model, fractional polynomial model and Royston-Parmar model. Time-invariant hazard ratio (HR) models were also used to validate and supplement the primary analysis. Objective response rate (ORR) and adverse events with any grade, grade 3-5 were assessed through a Bayesian network meta-analysis. The primary measures for OS, PFS, and PROs were HR and RMST. The odds ratio was the metric for evaluating safety, ORR, 12-month PFS rate, 24-month OS rate, and the 12-month non-deterioration rate of PROs. Subgroup analyses based on patient characteristics were performed.
RESULTS
A total of fourteen studies (ten for first-line, four for second-line) consisting of nine treatments (chemotherapy, crizotinib, alectinib [600mg BID], low-dose alectinib [300mg BID], brigatinib, ceritinib, ensartinib, envonalkib, and lorlatinib) were included. In the first-line setting, alectinib showed a significant advantage over crizotinib and had the longest OS among all ALK-inhibitors. Compared to crizotinib, lorlatinib had the best efficacy regarding PFS for global patients, followed closely by alectinib and brigatinib. For Asian patients, alectinib significantly improved PFS compared to other treatments. In second-line, alectinib had the highest PFS for patients pretreated with crizotinib, followed by brigatinib, ceritinib and chemotherapy. Alectinib, irrespective of the dose, was the safest first-line option, whereas lorlatinib, brigatinib, and ceritinib showed poorer safety profiles. Alectinib was also the safest ALK-inhibitor for crizotinib-resistant patients. Brigatinib had the best performance in terms of PROs.
CONCLUSIONS
Considering both efficacy and safety, alectinib appears to be the preferable treatment in first-line and second-line, particularly for Asian patients.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Crizotinib; Lung Neoplasms; Network Meta-Analysis; Bayes Theorem; Quality of Life; Anaplastic Lymphoma Kinase; Protein Kinase Inhibitors; Carbazoles; Sulfones; Aminopyridines; Lactams; Pyrimidines; Pyrazoles; Organophosphorus Compounds
PubMed: 38331773
DOI: 10.1186/s12885-024-11916-4 -
Scientific Reports Feb 2024Individual trials of abemaciclib, palbociclib, and ribociclib show a similar impact on progression-free survival yet differing statistical significance for overall... (Meta-Analysis)
Meta-Analysis
Individual trials of abemaciclib, palbociclib, and ribociclib show a similar impact on progression-free survival yet differing statistical significance for overall survival (OS). A robust comparative evaluation of OS, safety, and tolerability of the three drugs is warranted. A systematic literature search identified phase 3 randomized clinical trials reporting OS of CDK4/6 inhibitors (CDK4/6i) in combination with endocrine therapy in ER-positive/HER2-negative advanced breast cancer. Trial-level data on OS and common and serious adverse events (AE) were extracted for each drug. In the absence of direct comparisons, a network meta-analysis was performed to evaluate pairwise comparative efficacy, safety, and tolerability of each of the CDK4/6i. Seven studies comprising of 4415 patients met the inclusion criteria. Median follow-up was 73.3 months (range: 48.7-97.2 months). There were no statistically significant differences in OS between any of the CDK4/6i. Compared to palbociclib, ribociclib and abemaciclib both showed significantly higher GI toxicity (grade 1-2 vomiting OR 1.87 [95% CI 1.37-2.56] and OR 2.27 [95% CI 1.59-3.23] respectively). Compared to palbociclib, abemaciclib was associated with more grade 3-4 diarrhea OR 118.06 [95% CI 7.28-1915.32]. In contrast, palbociclib was associated with significantly more neutropenia than ribociclib and abemaciclib but significantly lower risk of grade 3-4 infections. Abemaciclib had significantly less grade 3-4 transaminitis and grade 3-4 neutropenia than ribociclib. Treatment discontinuation and death due to AE were significantly higher with abemaciclib than palbociclib and ribociclib. There is no statistically significant difference in OS between CDK4/6i despite differing statistical significance levels of individual trials. Real-world data analyses may help to identify if there is a meaningful inter-drug difference in efficacy. Significant differences between CDK4/6i are observed for safety and tolerability outcomes.
Topics: Female; Humans; Aminopyridines; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Breast Neoplasms; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Cyclin-Dependent Kinase Inhibitor Proteins; Neutropenia; Purines; Clinical Trials, Phase III as Topic; Randomized Controlled Trials as Topic
PubMed: 38326452
DOI: 10.1038/s41598-024-53151-8 -
Frontiers in Oncology 2023The EGFR gene encodes a protein that stimulates molecular pathways that allow the growth and development of the tumor microenvironment. The current preferred tyrosine...
Effectiveness and safety of the bevacizumab and erlotinib combination erlotinib alone in EGFR mutant metastatic non-small-cell lung cancer: systematic review and meta-analysis.
BACKGROUND
The EGFR gene encodes a protein that stimulates molecular pathways that allow the growth and development of the tumor microenvironment. The current preferred tyrosine kinase inhibitor (TKI) for the first-line treatment of EGFRm metastatic non-small cell lung cancer (NSCLC) is osimertinib. However, the combination of angiogenesis inhibitors and TKI has produced discordant results. We aimed to assess the effects of the bevacizumab and erlotinib combination in EGFRm metastatic NSCLC.
METHODS
Using eligibility criteria focused on patients with EGFRm metastatic NSCLC treated with bevacizumab and erlotinib, we searched databases including clinical trial randomized studies and reviews published until April 15, 2023 in Medline (PubMed), Scopus, and Embase. Eight clinical trials (1,052 patients) were selected from 1,343 articles for quantitative and qualitative assessment. The risk of bias was assessed using the Cochrane Risk of Bias tool. Data were synthesized through random-effects meta-analysis.
RESULTS
The bevacizumab and erlotinib combination significantly improved the progression-free survival (PFS) (log(HR) = 0.63; 95% CI: 0.54-0.73, < 0.001) and overall response ratio (ORR) (RR = 0.79; 95% CI, 0.64-0.97, = 0.03). However, it did not improve the overall survival (log(HR) = 0.93; 95% CI, 0.78-1.10, = 0.38) and was associated with higher serious adverse events (SAEs) (OR = 3.48; 95% CI, 1.76-6.88, = 0.005). A subgroup analysis suggested similar benefits in different mutation subtypes and brain metastasis condition. The evidence is limited by a moderate risk of bias across studies and heterogeneity in the reporting of SAEs.
CONCLUSIONS
The bevacizumab and erlotinib combination significantly improved PFS and ORR in EGFRm metastatic NSCLC but were also associated with higher-grade (≥3) adverse events. These results suggest that while the combination therapy may enhance progression-free survival and overall response, it does not improve the overall survival and is associated with higher toxicity. Thus, the treatment should be personalized based on individual patient comorbidities. Further prospective trials are needed to validate these results.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/#searchadvanced, identifier CDR 42022364692.
PubMed: 38322283
DOI: 10.3389/fonc.2023.1335373 -
ESMO Open Feb 2024Trastuzumab deruxtecan (T-DXd) has shown promising results in patients with breast cancer brain metastases (BCBMs). We conducted a systematic review and meta-analysis to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Trastuzumab deruxtecan (T-DXd) has shown promising results in patients with breast cancer brain metastases (BCBMs). We conducted a systematic review and meta-analysis to evaluate the effectiveness and safety of T-DXd in the human epidermal growth factor receptor 2 (HER2)-positive BCBM population.
PATIENTS AND METHODS
We searched PubMed, Embase, and Cochrane Library databases as well as American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), and San Antonio Breast Cancer Symposium (SABCS) websites for clinical trials (CTs) and observational studies evaluating T-DXd in patients with HER2-positive BCBM. Heterogeneity was assessed with I statistics. Random effects models were used for all statistical analyses, which were carried out using R software (version 4.2.2).
RESULTS
Ten studies were included, six CTs (n = 189) and four observational studies (n = 130), with a total of 319 patients. The median progression-free survival was 15 months [95% confidence interval (CI) 13.9-16.1 months]. The objective response rate (ORR) was 61% (95% CI 52% to 70%), and the intracranial (IC)-ORR was 61% (95% CI 54% to 69%). No significant differences in ORR and IC-ORR were observed between CTs and observational studies (P = 0.31 and 0.58, respectively). The clinical benefit rate (CBR) was 80% (95% CI 52% to 94%), and the IC-CBR was 70% (95% CI 54% to 82%). The ORR was 68% (95% CI 57% to 77%) in the subgroup of patients with stable BMs and 60% (95% CI 48%-72%) in patients with active BM, with no significant difference between groups (P = 0.35).
CONCLUSIONS
Our systematic review and meta-analysis supports the IC activity of T-DXd in patients with stable BM and active BM.
TRIAL REGISTRATION
International Prospective Register of Systematic Reviews (PROSPERO) under the protocol number CRD42023422589.
Topics: Humans; Female; Breast Neoplasms; Trastuzumab; Brain Neoplasms; Camptothecin; Receptor, ErbB-2; Immunoconjugates
PubMed: 38320430
DOI: 10.1016/j.esmoop.2024.102233 -
Biology of Sex Differences Jan 2024The incidence of Alzheimer's disease (AD)-the most frequent cause of dementia-is expected to increase as life expectancies rise across the globe. While sex-based... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The incidence of Alzheimer's disease (AD)-the most frequent cause of dementia-is expected to increase as life expectancies rise across the globe. While sex-based differences in AD have previously been described, there remain uncertainties regarding any association between sex and disease-associated molecular mechanisms. Studying sex-specific expression profiles of regulatory factors such as microRNAs (miRNAs) could contribute to more accurate disease diagnosis and treatment.
METHODS
A systematic review identified six studies of microRNA expression in AD patients that incorporated information regarding the biological sex of samples in the Gene Expression Omnibus repository. A differential microRNA expression analysis was performed, considering disease status and patient sex. Subsequently, results were integrated within a meta-analysis methodology, with a functional enrichment of meta-analysis results establishing an association between altered miRNA expression and relevant Gene Ontology terms.
RESULTS
Meta-analyses of miRNA expression profiles in blood samples revealed the alteration of sixteen miRNAs in female and 22 miRNAs in male AD patients. We discovered nine miRNAs commonly overexpressed in both sexes, suggesting a shared miRNA dysregulation profile. Functional enrichment results based on miRNA profiles revealed sex-based differences in biological processes; most affected processes related to ubiquitination, regulation of different kinase activities, and apoptotic processes in males, but RNA splicing and translation in females. Meta-analyses of miRNA expression profiles in brain samples revealed the alteration of six miRNAs in female and four miRNAs in male AD patients. We observed a single underexpressed miRNA in female and male AD patients (hsa-miR-767-5p); however, the functional enrichment analysis for brain samples did not reveal any specifically affected biological process.
CONCLUSIONS
Sex-specific meta-analyses supported the detection of differentially expressed miRNAs in female and male AD patients, highlighting the relevance of sex-based information in biomedical data. Further studies on miRNA regulation in AD patients should meet the criteria for comparability and standardization of information.
Topics: Humans; Male; Female; Alzheimer Disease; MicroRNAs; Brain
PubMed: 38297404
DOI: 10.1186/s13293-024-00588-1 -
Nutrients Jan 2024Epicatechin is a polyphenol compound that promotes skeletal muscle differentiation and counteracts the pathways that participate in the degradation of proteins. Several... (Review)
Review
Epicatechin is a polyphenol compound that promotes skeletal muscle differentiation and counteracts the pathways that participate in the degradation of proteins. Several studies present contradictory results of treatment protocols and therapeutic effects. Therefore, the objective of this systematic review was to investigate the current literature showing the molecular mechanism and clinical protocol of epicatechin in muscle atrophy in humans, animals, and myoblast cell-line. The search was conducted in Embase, PubMed/MEDLINE, Cochrane Library, and Web of Science. The qualitative analysis demonstrated that there is a commonness of epicatechin inhibitory action in myostatin expression and atrogenes MAFbx, FOXO, and MuRF1. Epicatechin showed positive effects on follistatin and on the stimulation of factors related to the myogenic actions (MyoD, Myf5, and myogenin). Furthermore, the literature also showed that epicatechin can interfere with mitochondrias' biosynthesis in muscle fibers, stimulation of the signaling pathways of AKT/mTOR protein production, and amelioration of skeletal musculature performance, particularly when combined with physical exercise. Epicatechin can, for these reasons, exhibit clinical applicability due to the beneficial results under conditions that negatively affect the skeletal musculature. However, there is no protocol standardization or enough clinical evidence to draw more specific conclusions on its therapeutic implementation.
Topics: Animals; Humans; Catechin; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Atrophy; MyoD Protein; TOR Serine-Threonine Kinases
PubMed: 38276564
DOI: 10.3390/nu16020326 -
International Journal of Molecular... Jan 2024High-grade glial tumors (HGGs) exhibit aggressive growth patterns and high recurrence rates. The prevailing treatment approach comprises radiation therapy (RT),... (Review)
Review
High-grade glial tumors (HGGs) exhibit aggressive growth patterns and high recurrence rates. The prevailing treatment approach comprises radiation therapy (RT), chemotherapy (CMT), and surgical resection. Despite the progress made in traditional treatments, the outlook for patients with HGGs remains bleak. Tumor metabolism is emerging as a potential target for glioma therapies, a promising approach that harnesses the metabolism to target tumor cells. However, the efficacy of therapies targeting the metabolism of HGGs remains unclear, compelling a comprehensive review. This study aimed to assess the outcome of present trials on HGG therapies targeting metabolism. A comprehensive search of PubMed, Ovid MEDLINE, and Ovid EMBASE was conducted until November 2023. The search method used pertinent Medical Subject Heading (MeSH) terminologies and keywords referring to "high-grade gliomas", "metabolism", "target therapies", "monoclonal antibodies", "overall survival", and "progression-free survival". The review analyzed studies that focused on therapies targeting the metabolism of HGGs in human subjects. These studies included both randomized controlled trials (RCTs) and non-randomized controlled trials (NRCTs). Out of 284 articles identified, 23 trials met the inclusion criteria and were thoroughly analyzed. Phase II trials were the most numerous (62%). Targeted metabolic therapies were predominantly used for recurrent HGGs (67%). The most common targeted pathways were the vascular endothelial growth factor (VEGF, 43%), the human epidermal growth factor receptor (HER, 22%), the platelet-derived growth factor (PDGF, 17%), and the mammalian target of rapamycin (mTOR, 17%). In 39% of studies, the subject treatment was combined with CMT (22%), RT (4%), or both (13%). The median OS widely ranged from 4 to 26.3 months, while the median PFS ranged from 1.5 to 13 months. This systematic literature review offers a thorough exploration of the present state of metabolic therapies for HGGs. The multitude of targeted pathways underscores the intricate nature of addressing the metabolic aspects of these tumors. Despite existing challenges, these findings provide valuable insights, guiding future research endeavors. The results serve as a foundation for refining treatment strategies and enhancing patient outcomes within the complex landscape of HGGs.
Topics: Humans; Glioma; Neuroglia; Aggression; Antibodies, Monoclonal; ErbB Receptors; Platelet-Derived Growth Factor
PubMed: 38255798
DOI: 10.3390/ijms25020724 -
Journal of Cancer Research and Clinical... Jan 2024The numerous first-line treatment regimens for human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC) necessitate a comprehensive... (Meta-Analysis)
Meta-Analysis
PURPOSE
The numerous first-line treatment regimens for human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC) necessitate a comprehensive evaluation to inform clinical decision-making. We conducted a Bayesian network meta-analysis (NMA) to compare the efficacy and safety of different interventions.
METHODS
We systematically searched for relevant randomized controlled trials (RCTs) in Pubmed, Embase, Cochrane Library and online abstracts from inception to June 1, 2023. NMA was performed to calculate and analyze progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and adverse events of grade 3 or higher (≥ 3 AEs).
RESULTS
Out of the 10,313 manuscripts retrieved, we included 28 RCTs involving 11,680 patients. Regarding PFS and ORR, the combination of trastuzumab with tyrosine kinase inhibitors (TKIs) was more favorable than dual-targeted therapy. If only using trastuzumab, combination chemotherapy is superior to monochemotherapy in terms of PFS. It is important to note that the addition of anthracycline did not result in improved PFS. For patients with hormone receptor-positive HER2-positive diseases, dual-targeted combined with endocrine therapy showed better benefit in terms of PFS compared to dual-targeted alone, but it did not reach statistical significance. The comprehensive analysis of PFS and ≥ 3 AEs indicates that monochemotherapy combined with dual-targeted therapy still has the optimal balance between efficacy and safety.
CONCLUSION
Monochemotherapy (Docetaxel) plus dual-target (Trastuzumab and Pertuzumab) therapy remains the optimal choice among all first-line treatment options for ABC. The combination of trastuzumab with TKIs (Pyrotinib) demonstrated a significant improvement in PFS and ORR, but further data are warranted to confirm the survival benefit.
Topics: Humans; Female; Network Meta-Analysis; Randomized Controlled Trials as Topic; Breast Neoplasms; Trastuzumab; Receptor, ErbB-2; Docetaxel; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38244085
DOI: 10.1007/s00432-023-05530-3