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PeerJ 2023It is of great importance to recognize bio-markers for cancer prognosis. However, the association between solute carrier family 7 member 11 (SLC7A11) and prognosis is... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
It is of great importance to recognize bio-markers for cancer prognosis. However, the association between solute carrier family 7 member 11 (SLC7A11) and prognosis is still controversial. Therefore, we conducted this systematic review and meta-analysis to identify the prognostic and clinicopathological significance of SLC7A11 in human cancers.
METHODS
PubMed, Web of Science, Scopus, the Cochrane Library and Embase database were searched from database inceptions to March 19th 2022. Hand searches were also conducted in references. Prognosis and clinicopathological data were extracted and analyzed.
RESULTS
A total of 12 eligible studies with 1,955 patients were included. The results indicated that SLC7A11 expression is associated with unfavorable overall survival (OS), unfavorable recurrence-free survival (RFS) and unfavorable progression free survival (PFS). And SLC7A11 expression is also associated with more advanced tumor stage.
CONCLUSIONS
SLC7A11 expression is associated with more unfavorable prognosis and more advanced tumor stage. Therefore, SLC7A11 could be a potential biomarker for human cancer prognosis.
Topics: Humans; Prognosis; Neoplasms; Databases, Factual; Gene Library; Hand; Amino Acid Transport System y+
PubMed: 36874967
DOI: 10.7717/peerj.14931 -
Inflammation Research : Official... Aug 2017Ankylosing spondylitis (AS) is a chronic inflammatory joint disease. The transporter associated with antigen processing (TAP) has been identified to play an important... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Ankylosing spondylitis (AS) is a chronic inflammatory joint disease. The transporter associated with antigen processing (TAP) has been identified to play an important role in immune response as well as the HLA-associated diseases. The aim of our meta-analysis was to investigate the contribution of TAP (TAP1 and TAP2) polymorphisms to the risk of AS.
METHODS
Meta-analyses were performed between 2 polymorphisms in TAP1 (TAP1-333, -637) and 3 polymorphisms in TAP2 (TAP2-379, -565, and -665) and AS.
RESULTS
The meta-analyses were involved with 6 studies with 415 cases and 659 controls. Significant association was found between TAP1-333Val, TAP1-637Gly, and TAP2-565Thr and AS compared with combined control group (TAP1-333Val: p = 0.009, OR = 1.40, 95% CI 1.09-1.80; TAP1-637Gly: p = 0.002, OR = 1.48, 95% CI 1.15-1.91; p = 0.03, OR = 1.38, 95% CI 1.04-1.84). Subgroup analysis shown that significant association was only found in AS when compared with HLA-B27-negative controls (TAP1-333Val: p = 0.004, OR = 1.53, 95% CI 1.14-2.06; TAP1-637Gly: p = 0.004, OR = 1.52, 95% CI 1.15-2.02; p = 0.02, OR = 1.56, 95% CI 1.09-2.24), but not in AS when compared with HLA-B27-positive controls (p > 0.05). Moreover, no significant associations were found between haplotypes in TAP1 and TAP2 in both the combined and the subgroup analyses (p > 0.05).
CONCLUSIONS
TAP1-333Val, TAP1-637Gly, and TAP2-565Thr were likely to be associated with AS.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 2; ATP Binding Cassette Transporter, Subfamily B, Member 3; Genetic Predisposition to Disease; Humans; Spondylitis, Ankylosing
PubMed: 28405734
DOI: 10.1007/s00011-017-1047-1 -
The Journal of Pediatrics Mar 2019To evaluate the clinical features of erythromelalgia in childhood associated with gain-of-function SCN9A mutations that increase activity of the Na1.7 voltage-gated...
OBJECTIVES
To evaluate the clinical features of erythromelalgia in childhood associated with gain-of-function SCN9A mutations that increase activity of the Na1.7 voltage-gated sodium channel, we conducted a systematic review of pediatric presentations of erythromelalgia related to SCN9A mutations, and compared pediatric clinical presentations of symptomatic erythromelalgia, with or without SCN9A mutations.
STUDY DESIGN
PubMed, Embase, and PsycINFO Databases were searched for reports of inherited erythromelalgia in childhood. Clinical features, management, and genotype were extracted. Case notes of pediatric patients with erythromelalgia from the Great Ormond Street Hospital Pain Service were reviewed for clinical features, patient-reported outcomes, and treatments. Children aged over 10 years were recruited for quantitative sensory testing.
RESULTS
Twenty-eight publications described erythromelalgia associated with 15 different SCN9A gene variants in 25 children. Pain was severe and often refractory to multiple treatments, including nonspecific sodium channel blockers. Skin damage or other complications of cold immersion for symptomatic relief were common (60%). SCN9A mutations resulting in greater hyperpolarizing shifts in Na1.7 sodium channels correlated with symptom onset at younger ages (P = .016). Variability in reporting, and potential publication bias toward severe cases, limit any estimations of overall prevalence. In our case series, symptoms were similar but comorbidities were more common in children with SCN9A mutations. Quantitative sensory testing revealed marked dynamic warm allodynia.
CONCLUSIONS
Inherited erythromelalgia in children is associated with difficult-to-manage pain and significant morbidity. Standardized reporting of outcome and management in larger series will strengthen identification of genotype-phenotype relationships. More effective long-term therapies are a significant unmet clinical need.
Topics: Adolescent; Child; Erythromelalgia; Female; Humans; Male; Mutation; NAV1.7 Voltage-Gated Sodium Channel; Pain; Retrospective Studies; Symptom Assessment
PubMed: 30416015
DOI: 10.1016/j.jpeds.2018.10.024 -
Pathology, Research and Practice Oct 2018Transporter associated with antigen processing protein (TAP) is a heterodimer protein consist of TAP1 and TAP2, act a pivotal part in the immune surveillance. In recent... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Transporter associated with antigen processing protein (TAP) is a heterodimer protein consist of TAP1 and TAP2, act a pivotal part in the immune surveillance. In recent days, controversial relationships were reported between TAP polymorphisms and cancer risk, thus, a systematic meta-analysis was performed to resolve this discrepancy.
METHODS
We searched the PubMed, EMbase, Web of Science, CNKI and Wanfang databases, the cited references were also manually searched again, covering all the papers published until March 25, 2018. Quality assessment was conducted using the Newcastle-Ottawa Scale. All the meta-analysis was conducted with Stata version 12.0 software to assess the strength of the association.
RESULTS
4719 cases and 4215 controls from 24 case-control studies related to TAP polymorphisms were enrolled. There was no significant association between TAP1-rs1135216, TAP1-rs4148873, TAP2-rs2228396, TAP2-rs241447 and TAP2-rs4148873 and cancer sensibility. Interestingly, a significant positive association was observed between TAP2 rs4148876 C/T polymorphism and increase cancer risk in homozygote and recessive models. Further in-silico results indicated the expression of TAP2 in cancer tissue is higher than that in normal tissue (cervical cancer, TPM = 70.2 vs. 24.0 respectively, P < 0.01; acute myeloid leukemia, TPM = 52.5 vs. 8.8 respectively, P < 0.01), and influence the survival time of acute myeloid leukemia patients (Log-rank P < 0.05).
CONCLUSIONS
Our finding suggested that TAP1-rs1135216, TAP1-rs4148873, TAP2-rs2228396, TAP2-rs241447 and TAP2-rs4148873 might not be involved in cancer risk, but the T allele of TAP2-rs4148876 might be a potential biomarker for judging cancer risk, and larger-scale studies are required to confirm our findings.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 2; ATP Binding Cassette Transporter, Subfamily B, Member 3; Biomarkers, Tumor; Genetic Predisposition to Disease; Humans; Neoplasms; Polymorphism, Single Nucleotide
PubMed: 30082158
DOI: 10.1016/j.prp.2018.07.018 -
Epilepsia May 2013Increasing evidence suggests that genetic variants from ABCC2 transporter may be associated with an altered response to antiepileptic drugs (AEDs). However, the... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Increasing evidence suggests that genetic variants from ABCC2 transporter may be associated with an altered response to antiepileptic drugs (AEDs). However, the variability in the selective inclusion of genetic variants in different studies makes delineation of the causal variant/s difficult. Furthermore, the differences in the frequency distribution and linkage disequilibrium (LD) pattern among genetic variants in different populations add to the heterogeneity in the reported results. The aim of this study is to carry out a systematic assessment of the published studies by performing meta-analysis of the commonly reported genetic variants from ABCC2 with drug response in patients with epilepsy (PWE).
METHODS
A literature search of the electronic databases namely Embase, Medline, Web of Science, and Cochrane database of systematic reviews available to the September 8, 2012 was performed. Pooled crude odds ratios (ORs) and 95% confidence intervals (CI) were calculated using both fixed-effect and random-effect models.
KEY FINDINGS
A total of eight reports were identified as eligible studies, which included 1,294 good responders and 1,529 poor responders. Of all the commonly reported variants that included c.-24C>T or rs717620, c.1249G>A or rs2273697 (V417I) and c.3972C>T or rs3740066 (I1324I), we observed an overall significant association of high activity promoter variant c.-24C>T with drug response (TT + CT vs. CC: OR(dom) = 1.38 (1.11-1.71), p(dom) = 0.004, I(2) = 3%; CT vs. CC: OR(co-dom) = 1.28 (1.02-1.61), p(co-dom) = 0.03, I(2) = 0%; T vs. C: OR(all) = 1.34 (1.11-1.61), p(all) = 0.002, I(2) = 35%). However, all the associations were lost after testing for multiple corrections. Tests for publication bias did not reveal any significant influence on the observed results.
SIGNIFICANCE
In summary, the results of our meta-analysis indirectly suggests possible role of the ABCC2 transporter at the blood brain barrier in altered drug response in PWE. Further studies are warranted in different ethnic groups to investigate the effects of the ABCC2 haplotypic variants and perform stratified analysis on the basis of different phenotypic covariates.
Topics: ATP-Binding Cassette Transporters; Anticonvulsants; Epilepsy; Female; Genetic Variation; Humans; Male; Multidrug Resistance-Associated Protein 2; Mutation
PubMed: 23506516
DOI: 10.1111/epi.12132 -
International Journal of Biological... 2021The transient receptor potential cation channel subfamily V member 1 (TRPV1) is a transmembrane protein that can be activated by various physical and chemical stimuli...
The transient receptor potential cation channel subfamily V member 1 (TRPV1) is a transmembrane protein that can be activated by various physical and chemical stimuli and is associated with pain transduction. In recent years, TRPV1 was discovered to play essential roles in cancer tumorigenesis and development, as TRPV1 expression levels are altered in numerous cancer cell types. Several investigations have discovered direct associations between TRPV1 and cancer cell proliferation, cell death, and metastasis. Furthermore, about two dozen TRPV1 agonists/antagonists are under clinical trial, as TRPV1 is a potential drug target for treating various diseases. Hence, more researchers are focusing on the effects of TRPV1 agonists or antagonists on cancer tumorigenesis and development. However, both agonists and antagonists may reveal anti-cancer effects, and the effect may function via or be independent of TRPV1. In this review, we provide an overview of the impact of TRPV1 on cancer cell proliferation, cell death, and metastasis, as well as on cancer therapy and the tumor microenvironment, and consider the implications of using TRPV1 agonists and antagonists for future research and potential therapeutic approaches.
Topics: Antineoplastic Agents; Carcinogenesis; Drug Development; Humans; Neoplasms; TRPV Cation Channels
PubMed: 34131404
DOI: 10.7150/ijbs.59918 -
The Australian and New Zealand Journal... Sep 2016The neurotransmitter serotonin is understood to control mood and drug response. Carrying a genetic variant in the serotonin transporter gene (5HTT) may increase the risk... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The neurotransmitter serotonin is understood to control mood and drug response. Carrying a genetic variant in the serotonin transporter gene (5HTT) may increase the risk of major depressive disorder and alcohol dependence. Previous estimates of the association of the S allele of 5HTTLPR polymorphism with major depressive disorder and alcohol dependence have been inconsistent.
METHODS
For the systematic review, we used PubMed MEDLINE and Discovery of The University of Melbourne to search for all relevant case-control studies investigating the associations of 5HTTLPR polymorphism with major depressive disorder and alcohol dependence. Summary odds ratios (OR) and their 95% confidence intervals (CI) were estimated. To investigate whether year of publication, study population or diagnostic criteria used were potential sources of heterogeneity, we performed meta-regression analyses. Publication bias was assessed using Funnel plots and Egger's statistical tests.
RESULTS
We included 23 studies of major depressive disorder without alcohol dependence containing 3392 cases and 5093 controls, and 11 studies of alcohol dependence without major depressive disorder containing 2079 cases and 2273 controls. The summary OR for homozygote carriers of the S allele of 5HTTLPR polymorphism compared with heterozygote and non-carriers combined (SS vs SL+LL genotype) was 1.33 (95% CI = [1.19, 1.48]) for major depressive disorder and 1.18 (95% CI = [1.01, 1.38]) for alcohol dependence. The summary OR per S allele of 5HTTLPR polymorphism was 1.16 (95% CI = [1.08, 1.23]) for major depressive disorder and 1.12 (95% CI = [1.01, 1.23]) for alcohol dependence. Meta-regression models showed that the associations did not substantially change after adjusting for year of publication, study population and diagnostic criteria used. There was no evidence for publication bias of the studies included in our meta-analysis.
CONCLUSIONS
Our meta-analysis confirms that individuals with the homozygous S allele of 5HTTLPR polymorphism are at increased risks of major depressive disorder as well as alcohol dependence. Further studies are required to investigate the association between 5HTTLPR polymorphism and the comorbidity of major depressive disorder and alcohol dependence as well as gene × environmental interactions.
Topics: Alcohol-Related Disorders; Depressive Disorder, Major; Humans; Serotonin Plasma Membrane Transport Proteins
PubMed: 26979101
DOI: 10.1177/0004867416637920 -
Journal of Neurology Nov 2021Glymphatic fluid circulation may be considered the lymphatic system of the brain and the main role of such system seems to be played by aquaporins (AQPs), a family of... (Review)
Review
INTRODUCTION
Glymphatic fluid circulation may be considered the lymphatic system of the brain and the main role of such system seems to be played by aquaporins (AQPs), a family of proteins which regulates water exchange, in particular AQP4 and 1. Alterations of glymphatic fluid circulation through AQPs variations are now emerging as central elements in the pathophysiology of different brain conditions, like hydrocephalus. This systematic review provides an insight about the role of AQPs in hydrocephalus establishment and compensation, investigating their possible role as diagnostic tools or therapeutic targets.
METHODS
PubMed database was screened searching for the relevant existing literature in English language published until February 29th 2020, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement.
RESULTS
A total of 40 articles met the inclusion criteria for our systematic analysis. AQP4 resulted the most studied water channel, followed by AQP1. The changes in cerebrospinal fluid (CSF), brain parenchyma and choroid plexus (CP) in different hydrocephalus type were analyzed. Moreover, important pharmacological interactions regarding AQP and molecules or conditions were discussed. A very interesting result is the general consensus on increase of AQP4 in hydrocephalic patients, unless in patients suffering from idiopathic normal pressure hydrocephalus, where AQP4 shows a tendency in reduction.
CONCLUSION
AQP seem to play a central role in the pathophysiology of hydrocephalus and in its compensation mechanisms. Further studies are required to definitively establish their precise roles and their quantitative changes to allow their utilization as diagnostic tools or therapeutic targets.
Topics: Aquaporin 4; Aquaporins; Brain; Humans; Hydrocephalus
PubMed: 32747978
DOI: 10.1007/s00415-020-10122-z -
Genetics in Medicine : Official Journal... Nov 2014Statins, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors, have proven efficacy in both lowering low-density-lipoprotein levels and preventing major coronary... (Review)
Review
Statins, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors, have proven efficacy in both lowering low-density-lipoprotein levels and preventing major coronary events, making them one of the most commonly prescribed drugs in the United States. Statins exhibit a class-wide side effect of muscle toxicity and weakness, which has led regulators to impose both dosage limitations and a recall. This review focuses on the best-characterized genetic factors associated with increased statin muscle concentrations, including the genes encoding cytochrome P450 enzymes (CYP2D6, CYP3A4, and CYP3A5), a mitochondrial enzyme (GATM), an influx transporter (SLCO1B1), and efflux transporters (ABCB1 and ABCG2). A systematic literature review was conducted to identify relevant research evaluating the significance of genetic variants predictive of altered statin concentrations and subsequent statin-related myopathy. Studies eligible for inclusion must have incorporated genotype information and must have associated it with some measure of myopathy, either creatine kinase levels or self-reported muscle aches and pains. After an initial review, focus was placed on seven genes that were adequately characterized to provide a substantive review: CYP2D6, CYP3A4, CYP3A5, GATM, SLCO1B1, ABCB1, and ABCG2. All statins were included in this review. Among the genetic factors evaluated, statin-related myopathy appears to be most strongly associated with variants in SLCO1B1.
Topics: ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily G, Member 2; ATP-Binding Cassette Transporters; Amidinotransferases; Cytochrome P-450 Enzyme System; Dose-Response Relationship, Drug; Genetic Variation; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Liver-Specific Organic Anion Transporter 1; Muscular Diseases; Neoplasm Proteins; Organic Anion Transporters; Simvastatin
PubMed: 24810685
DOI: 10.1038/gim.2014.41 -
Molecular Psychiatry Jan 2022Brain imaging techniques enable the visualization of serotonin transporter (SERT) occupancy as a measure of the proportion of SERT blocked by an antidepressant at a... (Review)
Review
Brain imaging techniques enable the visualization of serotonin transporter (SERT) occupancy as a measure of the proportion of SERT blocked by an antidepressant at a given dose. We aimed to systematically review the evidence on the relationship between antidepressant dose and SERT occupancy. We searched PubMed and Embase (last search 20 May 2021) for human in vivo, within-subject PET, or SPECT studies measuring SERT occupancy at any dose of any antidepressant with highly selective radioligands ([C]-DASB, [I]-ADAM, and [C]-MADAM). We summarized and visualized the dose-occupancy relationship for antidepressants across studies, overlaying the plots with a curve based on predicted values of a standard 2-parameter Michaelis-Menten model fitted using the observed data. We included seventeen studies of 10 different SSRIs, SNRIs, and serotonin modulators comprising a total of 294 participants, involving 309 unique occupancy measures. Overall, following the Michaelis-Menten equation, SERT occupancy increased with a higher dose in a hyperbolic relationship, with occupancy increasing rapidly at lower doses and reaching a plateau at approximately 80% at the usual minimum recommended dose. All the studies were small, only a few investigated the same antidepressant, dose, and brain region, and few reported information on factors that may influence SERT occupancy. The hyperbolic dose-occupancy relationship may provide mechanistic insight of relevance to the limited clinical benefit of dose-escalation in antidepressant treatment and the potential emergence of withdrawal symptoms. The evidence is limited by non-transparent reporting, lack of standardized methods, small sample sizes, and short treatment duration. Future studies should standardize the imaging and reporting procedures, measure occupancy at lower antidepressant doses, and investigate the moderators of the dose-occupancy relationship.
Topics: Antidepressive Agents; Brain; Citalopram; Humans; Serotonin Plasma Membrane Transport Proteins; Selective Serotonin Reuptake Inhibitors
PubMed: 34548628
DOI: 10.1038/s41380-021-01285-w