-
Frontiers in Endocrinology 2023Second-generation androgen receptor inhibitors (ARIs) have been developed and approved for treating castration-resistant prostate cancer (CRPC). There is a lack of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Second-generation androgen receptor inhibitors (ARIs) have been developed and approved for treating castration-resistant prostate cancer (CRPC). There is a lack of direct comparison of the therapeutic effects and adverse events between the conventional ARI (bicalutamide) and three second-generation ARIs (enzalutamide, apalutamide and darolutamide).
METHODS
Our network meta-analysis evaluated therapeutic effects and adverse events of the conventional ARI (bicalutamide) and the second-generation ARIs in treating CRPC. We systematically searched the Pubmed, Cochrane library and Embase databases for studies published until October 2022 and only randomized clinical trials (RCTs) were included. The progression-free survival, prostate-specific antigen (PSA) progression-free survival, overall survival (PFS/PSA-PFS/OS), PSA response rate and relative adverse events (AEs) of CRPC patients were collected and synthesized. We then performed subgroup analysis. The non-metastatic and metastatic CRPC (nm/mCRPC) observations were analyzed separately. Data analyses were performed using R software (4.2.1) based on Bayesian framework.
RESULTS
6,993 subjects from seven eligible RCTs were analyzed. Enzalutamide, apalutamide and darolutamide were more effective than bicalutamide in treating CRPC, and the performance of darolutamide was slightly worse than the other two second-generation ARIs. Similar adverse events rate were observed among the second-generation ARIs and bicalutamide. Apalutamide showed a slightly higher rate of Grade 3+ AEs, percentages of AE-related drug withdrawals and AE-related mortality. Patients receiving enzalutamide had significantly higher rate of hypertension and fatigue. In subgroup analysis, enzalutamide showed better therapeutic effects compared with bicalutamide in both nmCRPC and mCRPC groups. In nmCRPC group, enzalutamide and apalutamide had more benefits on PFS and PSA-PFS compared with darolutamide. We displayed the probability ranking map of PFS, PSA-PFS, OS, time to cytotoxic chemotherapy, PSA response rate and relative AE outcomes.
CONCLUSION
The current network meta-analysis indicated that the second-generation ARIs were superior to the conventional ARI, bicalutamide. The three second-generation ARIs showed incomplete equivalence on CRPC treatment. The darolutamide was slightly less effective compared with enzalutamide and apalutamide. The adverse events of apalutamide were worse than the others, but no statistical significance was observed among these vital AEs. All ARIs were generally well-tolerated. These results may provide reference to clinical decision and further direct comparison trials.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO, identifier CRD42022370842.
Topics: Male; Humans; Prostatic Neoplasms, Castration-Resistant; Receptors, Androgen; Prostate-Specific Antigen; Network Meta-Analysis; Treatment Outcome; Androgen Receptor Antagonists
PubMed: 36843606
DOI: 10.3389/fendo.2023.1131033 -
International Journal of Environmental... Apr 2017Few studies have assessed the association between leptin receptor (LEPR) gene polymorphism and the risk of cardiovascular disease (CVD). Of the few epidemiological... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Few studies have assessed the association between leptin receptor (LEPR) gene polymorphism and the risk of cardiovascular disease (CVD). Of the few epidemiological studies on this topic, the results are still controversial.
METHODS
PubMed and Embase were screened for studies from their inception to 9 October 2016. The pooled odds ratio (OR) with the corresponding confidence intervals (CI) were used to measure the effect size for studies that reported the association under allelic, homozygous, and dominant models. Pre-specified characteristics were conducted in the subgroup analysis. Heterogeneity between subgroups was evaluated by meta-regression analysis.
RESULTS
Seven eligible studies involving 44,133 participants were included in our meta-analysis. Borderline significant association was observed between the LEPR gene polymorphism (rs1137101, rs1137100, rs6700896, and rs8179183) and the increased risk of CVD with considerable heterogeneity under the allelic model, and the overall pooled OR (95% CI) was 1.10 (0.99, 1.22). The LEPR gene variant rs6700896, 109G allele, and 109GG genotype were significantly associated with the increased risk of CVD. Furthermore, stratified group analysis revealed that the association was more pronounced for stroke. Race-differences might also cause the considerable heterogeneity and non-significant association.
CONCLUSIONS
This is the first systematic review and meta-analysis to investigate the association between LEPR gene variants and CVD risk. Some LEPR gene variants were significantly associated with the increased risk of CVD. However, the present study is limited in its small number of included studies, considerable heterogeneity, and observational study design. Further research is still warranted to confirm the magnitude of the association.
Topics: Cardiovascular Diseases; Humans; Polymorphism, Genetic; Receptors, Leptin; Risk
PubMed: 28368354
DOI: 10.3390/ijerph14040375 -
The Yale Journal of Biology and Medicine Dec 2021Williams Syndrome (WS) is a rare genetic multisystem disorder that occurs because of a deletion of approximately 25 genes in the 7q11.23 chromosome region. This causes... (Review)
Review
Williams Syndrome (WS) is a rare genetic multisystem disorder that occurs because of a deletion of approximately 25 genes in the 7q11.23 chromosome region. This causes dysmorphic facial appearances, multiple congenital cardiovascular defects, delayed motor skills, and abnormalities in connective tissues and the endocrine system. The patients are mostly diagnosed with mild to moderate mental retardation, however, they have a hyper sociable, socially dis-inhibited, and outgoing personality, empathetic behavior, and are highly talkative. Oxytocin (OT), a neuropeptide synthesized at the hypothalamus, plays an important role in cognition and behavior, and is thought to be affecting WS patients' attitudes at its different amounts. Oxytocin receptor gene (), on chromosome 3p25.3, is considered regulating oxytocin receptors, via which OT exerts its effect. WS is a crucial disorder to understand gene, hormone, brain, and behavior associations in terms of sociality and neuropsychiatric conditions. Alterations to the WS gene region offer an opportunity to deepen our understandings of autism spectrum disorder, schizophrenia, anxiety, or depression. We aim to systematically present the data available of OT/ regulation and expression, and the evidence for whether these mechanisms are dysregulated in WS. These results are important, as they predict strong epigenetic control over social behavior by methylation, single nucleotide polymorphisms, and other alterations. The comparison and collaboration of these studies may help to establish a better treatment or management approach for patients with WS if backed up with future research.
Topics: Autism Spectrum Disorder; Humans; Oxytocin; Receptors, Oxytocin; Social Behavior; Williams Syndrome
PubMed: 34970101
DOI: No ID Found -
PloS One 2022This systematic review of the literature aims to evaluate possible associations between moral judgment and hormones. The electronic databases PsycINFO, PubMed, Scielo,...
This systematic review of the literature aims to evaluate possible associations between moral judgment and hormones. The electronic databases PsycINFO, PubMed, Scielo, Web of Science, Scopus, and LILACS were used. Twenty studies with different methodological designs were reviewed, covering the hormones cortisol, oxytocin, and testosterone, assessing aspects related to polymorphisms in receptor genes, endogenous levels, and exogenous administration. Taken together, the reviewed studies showed a trend towards an association between hormones and moral judgment, with important specificities involving biological, environmental, and individual aspects. Endogenous levels of cortisol, released under stress, showed negative associations with altruistic and utilitarian decisions only in highly emotionally charged dilemmas. Oxytocin receptor gene polymorphisms (rs2268498, rs237889, and rs2254298) and acute administration of this hormone were associated with variability in moral judgment, with sex as an important moderating variable. Testosterone studies have tended to show a positive association with utilitarian moral judgments, particularly in female and in individuals with low prenatal exposure to this hormone. Knowing how hormones influence moral judgment may help expand our understanding of the plurality of human behavior. However, this area of research is new and still little explored, which does not allow for conclusions with a high level of evidence. Subsequent research will benefit from methodological improvements to extend current findings.
Topics: Female; Humans; Hydrocortisone; Judgment; Morals; Receptors, Oxytocin; Testosterone
PubMed: 35385511
DOI: 10.1371/journal.pone.0265693 -
Cellular & Molecular Immunology Mar 2015Vitamin D receptor (VDR) polymorphisms have been studied as potential contributors to multiple sclerosis (MS). However, published studies differ with respect to study... (Meta-Analysis)
Meta-Analysis Review
Vitamin D receptor (VDR) polymorphisms have been studied as potential contributors to multiple sclerosis (MS). However, published studies differ with respect to study design and the significance of the effects detected. The aim of this study was to quantify the magnitude of the risk associated with the TaqI, BsmI, ApaI and FokI VDR polymorphisms in MS using a meta-analysis approach. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a systematic search and meta-analysis of the literature. Subgroup analyses were performed to detect potential sources of heterogeneity from the selected study characteristics. The stability of the summary risk was evaluated using sensitivity analyses. The meta-analysis included a total of 3300 cases and 3194 controls from 13 case-control studies. There were no significant associations found between TaqI and BsmI polymorphisms and MS risk. The association between the ApaI polymorphism and MS risk was significant in the homozygous and codominant models (P=0.013 and P=0.031, respectively), suggesting that the AA ApaI genotype might be a significant MS risk factor. Publication year and age significantly affected the association between TaqI polymorphisms and MS (P=0.014 and P=0.010, respectively), which indicates a protective effect of the major T allele. The AA ApaI and FF FokI genotypes are significant risk factors for MS. The association between the TaqI polymorphism and MS risk is significantly affected by study characteristics.
Topics: Case-Control Studies; Genetic Predisposition to Disease; Humans; Multiple Sclerosis; Polymorphism, Genetic; Receptors, Calcitriol; Risk Factors
PubMed: 24998351
DOI: 10.1038/cmi.2014.47 -
Annals of Oncology : Official Journal... Oct 2015The increased use of the androgen receptor axis-targeted (ARAT) agents abiraterone and enzalutamide in first- and second-line treatment of metastatic... (Review)
Review
BACKGROUND
The increased use of the androgen receptor axis-targeted (ARAT) agents abiraterone and enzalutamide in first- and second-line treatment of metastatic castration-resistant prostate cancer (mCRPC) has improved patient outcomes, but resistance to these agents is inevitable. Early identification of patients with primary or secondary resistance to ARAT therapy is of increasing clinical concern.
DESIGN
PubMed and conference proceedings were searched for studies of agents used after progression on abiraterone or enzalutamide. The key search terms (or aliases) used a combination of mCRPC and abiraterone or enzalutamide, and results were limited to clinical trials and comparative or validation studies.
RESULTS AND CONCLUSION
This systematic review assembles current evidence and provides an approach to treatment using available clinical factors. Issues of patient selection, use of laboratory and clinical biomarkers to identify patients at risk of poor outcomes, and the timing and sequencing of available treatment options are addressed. Our findings reveal a lack of high-level evidence regarding predictive factors and treatment of patients with resistance to ARAT therapy, and a need for further research in this area. In the meantime, we suggest practical strategies to guide management of ARAT treatment-resistant patients based on available data.
Topics: Antineoplastic Agents; Drug Resistance, Neoplasm; Humans; Male; Molecular Targeted Therapy; Prognosis; Prostatic Neoplasms, Castration-Resistant; Receptors, Androgen
PubMed: 26101426
DOI: 10.1093/annonc/mdv267 -
Steroids Sep 2022Genetic susceptibility to dyslipidaemia remains incompletely understood. The liver X receptors (LXRs), members of the nuclear receptor superfamily of ligand dependent... (Meta-Analysis)
Meta-Analysis
Genetic susceptibility to dyslipidaemia remains incompletely understood. The liver X receptors (LXRs), members of the nuclear receptor superfamily of ligand dependent transcription factors, are homeostatic regulators of lipid metabolism. Multiple single nucleotide polymorphisms (SNPs)have been identified previously in the coding and regulatory regions of the LXRs. The aim of this systematic review and meta-analysis was to summarise associations between SNPs of LXRs (α and β isoforms) with blood lipid and lipoprotein traits. Five databases (PubMed, Ovid Embase, Scopus, Web of Science, and the Cochrane Library) were systematically searched for population-based studies that assessed associations between one or more blood lipid/lipoprotein traits and LXR SNPs. Of seventeen articles included in the qualitative synthesis, ten were eligible for meta-analysis. Nine LXRα SNPs and five LXRβ SNPs were identified, and the three most studied LXRα SNPs were quantitatively summarised. Carriers of the minor allele A of LXRα rs12221497 (-115G>A) had higher triglyceride levels than GG homozygotes (0.13 mmol/L; 95%CI: [0.03, 0.23], P = 0.01). Heterozygote carriers of LXRα rs2279238 (297C/T) had higher total cholesterol levels (0.12 mmol/L; (95%CI: [0.01, 0.23], P = 0.04) than either CC or TT homozygotes. For LXRα rs11039155 (-6G>A), no significant differences in blood levels of either triglyceride (P = 0.39) or HDL-C (P = 0.98) were detected between genotypes in meta-analyses. In addition, there were no strong associations for other SNPs of LXRα and LXRβ. This study provides the evidence of an association between LXRα, but not LXRβ, SNPs and blood-lipid traits. Systematic review registration: PROSPERO No. CRD42021246158.
Topics: Lipids; Lipoproteins; Liver X Receptors; Orphan Nuclear Receptors; Polymorphism, Single Nucleotide; Triglycerides
PubMed: 35679909
DOI: 10.1016/j.steroids.2022.109057 -
International Journal of Molecular... Mar 2023Iron deficiency (ID) in conjunction with heart failure (HF) poses a challenge for clinicians and is associated with worse HF outcomes. Treatment of ID with IV iron... (Review)
Review
Iron deficiency (ID) in conjunction with heart failure (HF) poses a challenge for clinicians and is associated with worse HF outcomes. Treatment of ID with IV iron supplementation for patients with HF has demonstrated benefits in quality of life (QoL) and HF-related hospitalizations. The aim of this systematic review was to summarize the evidence linking iron metabolism biomarkers with outcomes in patients with HF to assist in the optimal use of these biomarkers for patient selection. A systematic review of observational studies in English from 2010 to 2022 was conducted using PubMed, with keywords of "Heart Failure" and respective iron metabolism biomarkers ("Ferritin", "Hepcidin", "TSAT", "Serum Iron", and "Soluble Transferrin Receptor"). Studies pertaining to HF patients, with available quantitative data on serum iron metabolism biomarkers, and report of specific outcomes (mortality, hospitalization rates, functional capacity, QoL, and cardiovascular events) were included, irrespective of left ventricular ejection fraction (LVEF) or other HF characteristics. Clinical trials of iron supplementation and anemia treatment were removed. This systematic review was conducive to formal assessment of risk of bias via Newcastle-Ottawa Scale. Results were synthesized based on their respective adverse outcomes and iron metabolism biomarker(s). Initial and updated searches identified 508 unique titles once duplicates were removed. The final analysis included 26 studies: 58% focused on reduced LVEF; age range was 53-79 years; males composed 41-100% of the reported population. Statistically significant associations of ID were observed with all-cause mortality, HF hospitalization rates, functional capacity, and QoL. Increased risk for cerebrovascular events and acute renal injury have also been reported, but these findings were not consistent. Varying definitions of ID were utilized among the studies; however, most studies employed the current European Society of Cardiology criteria: serum ferritin < 100 ng/mL or the combination of ferritin between 100-299 ng/mL and transferrin saturation (TSAT) < 20%. Despite several iron metabolism biomarkers demonstrating strong association with several outcomes, TSAT better predicted all-cause mortality, as well as long-term risk for HF hospitalizations. Low ferritin was associated with short-term risk for HF hospitalizations, worsening functional capacity, poor QoL, and development of acute renal injury in acute HF. Elevated soluble transferrin receptor (sTfR) levels were associated with worse functional capacity and QoL. Finally, low serum iron was significantly associated with increased risk for cardiovascular events. Considering the lack of consistency among the iron metabolism biomarkers for association with adverse outcomes, it is important to incorporate additional biomarker data, beyond ferritin and TSAT, when assessing for ID in HF patients. These inconsistent associations question how best to define ID to ensure proper treatment. Further research, potentially tailored to specific HF phenotypes, is required to optimize patient selection for iron supplementation therapy and appropriate targets for iron stores replenishment.
Topics: Humans; Male; Anemia, Iron-Deficiency; Quality of Life; Stroke Volume; Ventricular Function, Left; Iron; Iron Deficiencies; Ferritins; Heart Failure; Biomarkers; Receptors, Transferrin
PubMed: 36982717
DOI: 10.3390/ijms24065645 -
British Journal of Cancer Jul 2021We conducted a systematic review and meta-analysis of prospective studies to clarify the relation of fruit and vegetable consumption with incident breast cancer. (Meta-Analysis)
Meta-Analysis
BACKGROUND
We conducted a systematic review and meta-analysis of prospective studies to clarify the relation of fruit and vegetable consumption with incident breast cancer.
METHODS
We searched systematically PubMed and EMBASE databases up to November 2020 to include prospective studies that reported the association of fruit and vegetable consumption with incident breast cancer. The pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated for the highest versus the lowest category of total fruit and vegetable, total fruit and total vegetable consumption, as well as fruit juice and subgroups of vegetables in relation to breast cancer incidence, using a random-effect model.
RESULTS
Total fruit and vegetable consumption was associated with lower overall (RR = 0.91, 95% CI = 0.87-0.95) and postmenopausal breast cancer risk (RR = 0.88, 95% CI = 0.79-0.99). Total fruit consumption was associated with lower overall (RR = 0.93, 95% CI = 0.88-0.99) and postmenopausal breast cancer risk (RR = 0.93, 95% CI = 0.87-0.99). Total fruit and vegetable intake were associated with 11% and 26% lower risk of oestrogen- and progesterone-receptor-positive (ER+/PR+) and -negative (ER-/PR-) breast cancer, respectively. Total vegetable consumption was associated with 27% lower risk of ER-/PR- breast cancer. Fruit juice consumption was associated with increased overall breast cancer risk (RR = 1.04, 95% CI = 1.01-1.07). We did not find significant associations for subgroups of vegetable intake and breast cancer risk.
CONCLUSIONS
These findings suggest that high total fruit and vegetable consumption are associated with reduced risk of overall, postmenopausal, ER+/PR+ and ER-/PR- breast cancer.
Topics: Breast Neoplasms; Diet; Female; Fruit; Humans; Postmenopause; Receptors, Estrogen; Receptors, Progesterone; Vegetables
PubMed: 34006925
DOI: 10.1038/s41416-021-01373-2 -
International Journal of Molecular... Jul 2023The aim of this systematic review and meta-analysis was to evaluate the current evidence in relation to the clinicopathological and prognostic significance of epidermal... (Meta-Analysis)
Meta-Analysis
Prognostic and Clinicopathological Significance of Epidermal Growth Factor Receptor (EGFR) Expression in Oral Squamous Cell Carcinoma: Systematic Review and Meta-Analysis.
The aim of this systematic review and meta-analysis was to evaluate the current evidence in relation to the clinicopathological and prognostic significance of epidermal growth factor receptor (EGFR) overexpression in patients with oral squamous cell carcinoma (OSCC). We searched MEDLINE/PubMed, Embase, Web of Science, and Scopus for studies published before November 2022. We evaluated the quality of primary-level studies using the QUIPS tool, conducted meta-analyses, examined inter-study heterogeneity via subgroup analyses and meta-regressions, and performed small-study effects analyses. Fifty primary-level studies (4631 patients) met the inclusion criteria. EGFR overexpression was significantly associated with poor overall survival (hazard ratio [HR] = 1.38, 95% confidence intervals [CI] = 1.06-1.79, = 0.02), N+ status (odds ratio [OR] = 1.37, 95%CI = 1.01-1.86, = 0.04), and moderately-poorly differentiated OSCC (OR = 1.43, 95% CI = 1.05-1.94, = 0.02). In addition, better results were obtained by the application of a cutoff point ≥10% tumor cells with EGFR overexpression ( < 0.001). In conclusion, our systematic review and meta-analysis supports that the immunohistochemical assessment of EGFR overexpression may be useful as a prognostic biomarker for OSCC.
Topics: Humans; Carcinoma, Squamous Cell; Mouth Neoplasms; Squamous Cell Carcinoma of Head and Neck; Prognosis; ErbB Receptors; Head and Neck Neoplasms; Biomarkers, Tumor
PubMed: 37569265
DOI: 10.3390/ijms241511888