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British Journal of Clinical Pharmacology Aug 2015Currently, treatment for Alzheimer's disease (AD) focuses on the cholinergic hypothesis and provides limited symptomatic effects. Research currently focuses on other... (Review)
Review
AIMS
Currently, treatment for Alzheimer's disease (AD) focuses on the cholinergic hypothesis and provides limited symptomatic effects. Research currently focuses on other factors that are thought to contribute to AD development such as tau proteins and Aβ deposits, and how modification of the associated pathology affects outcomes in patients. This systematic review summarizes and appraises the evidence for the emerging drugs affecting Aβ and tau pathology in AD.
METHODS
A comprehensive, systematic online database search was conducted using the databases ScienceDirect and PubMed to include original research articles. A systematic review was conducted following a minimum set of standards, as outlined by The PRISMA Group . Specific inclusion and exclusion criteria were followed and studies fitting the criteria were selected. No human trials were included in this review. In vitro and in vivo AD models were used to assess efficacy to ensure studied agents were emerging targets without large bodies of evidence.
RESULTS
The majority of studies showed statistically significant improvement (P < 0.05) of Aβ and/or tau pathology, or cognitive effects. Many studies conducted in AD animal models have shown a reduction in Aβ peptide burden and a reduction in tau phosphorylation post-intervention. This has the potential to reduce plaque formation and neuronal degeneration.
CONCLUSIONS
There are many emerging targets showing promising results in the effort to modify the pathological effects associated with AD. Many of the trials also provided evidence of the clinical effects of such drugs reducing pathological outcomes, which was often demonstrated as an improvement of cognition.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Clinical Trials as Topic; Cognition; Drug Discovery; Drug Evaluation, Preclinical; Humans; Neuroprotective Agents; tau Proteins
PubMed: 25753046
DOI: 10.1111/bcp.12621 -
Journal of Ovarian Research Nov 2021STAT3 and p-STAT3 are often overexpressed in various human tumours and participate in cancer development and progression. However, whether STAT3/p-STAT3 expression is... (Meta-Analysis)
Meta-Analysis
PURPOSE
STAT3 and p-STAT3 are often overexpressed in various human tumours and participate in cancer development and progression. However, whether STAT3/p-STAT3 expression is associated with clinicopathologic characteristics and has prognostic significance for people suffering from ovarian cancer remains controversial. We conducted a systematic review and meta-analyses to clarify the associations between STAT3/p-STAT3 expression and clinicopathologic characteristics and prognostic factors of ovarian cancer.
METHODS
A systematic electronic search in the PubMed, Embase, CNKI, and Wanfang databases was conducted to identify relevant articles published before 3 April 2021. All statistical analyses were performed using Stata 15.1.
RESULTS
We included 16 eligible studies incorporating 1747 ovarian cancer patients. The expression of STAT3/p-STAT3 was upregulated in ovarian cancer samples versus normal ovarian tissue, benign tumours and borderline tumours (OR = 10.14, p < 0.00001; OR = 9.08, P < 0.00001; OR = 4.01, p < 0.00001, respectively). STAT3/p-STAT3 overexpression was significantly correlated with FIGO stage (I-II vs. III-IV) (OR = 0.36, p < 0.00001), tumour grade (G1 + G2 vs. G3) (OR = 0.55; p = 0.001) and lymph node metastasis (yes vs. no) (OR = 3.39; p < 0.00001). High STAT3/p-STAT3 expression was correlated with poorer prognosis of ovarian cancer patients for both overall survival (OS) (HR = 1.67, p < 0.00001) and progression-free survival (PFS) (HR = 1.40, p = 0.007).
CONCLUSION
The present meta-analysis indicated that high STAT3/p-STAT3 expression is likely predictive of an unfavourable prognosis in ovarian cancer patients. Nonetheless, prospective trials are required to confirm these associations.
Topics: Biomarkers, Tumor; Female; Humans; Lymphatic Metastasis; Neoplasm Grading; Neoplasm Staging; Ovarian Neoplasms; Phosphorylation; Prognosis; Progression-Free Survival; STAT3 Transcription Factor; Survival Rate
PubMed: 34789292
DOI: 10.1186/s13048-021-00918-6 -
Fluids and Barriers of the CNS May 2017The purpose of this systematic review and meta-analysis was to evaluate the performance of cerebrospinal fluid (CSF) beta amyloid 42 (Aβ42), total tau (t-tau), and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The purpose of this systematic review and meta-analysis was to evaluate the performance of cerebrospinal fluid (CSF) beta amyloid 42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) as potential diagnostic biomarkers for idiopathic normal-pressure hydrocephalus (iNPH) and to assess their utility indistinguishing patients with iNPH from those with Alzheimer disease (AD) and healthy normal controls.
METHODS
Studies were identified by searching PubMed, Embase, the Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Wanfang Chinese Periodical Database, VIP Chinese database, and Chinese Bio-medicine Database (CBM) before August 2016. The standardized mean difference (SMD) and 95% confidence interval (CI), comparing CSF Aβ42, t-tau, and p-tau levels between iNPH, AD and healthy controls, were calculated using random-effects models. Subgroup analyses were created according to ethnicity (Caucasian or Asian) and CSF type (lumbar or ventricular), and the publication bias was estimated using Egger's test and the Begg's test.
RESULTS
A total of 10 studies including 413 patients with iNPH, 186 patients with AD and 147 healthy controls were included in this systematic review and meta-analysis. The concentrations of CSF t-tau, and p-tau were significantly lower in iNPH patients compared to AD (SMD = -1.26, 95% CI -1.95 to -0.57, P = 0.0004; SMD = -1.54, 95% CI -2.34 to -0.74, P = 0.0002, respectively) and lower than healthy controls (SMD = -0.80, 95% CI -1.50 to -0.09, P = 0.03; SMD = -1.12, 95% CI -1.38 to -0.86, P < 0.00001, respectively). Patients with iNPH had significantly lower Aβ42 levels compared with controls (SMD = -1.14, 95% CI -1.74 to -0.55, P = 0.0002), and slightly higher Aβ42 levels compared with AD patients (SMD = 0.32, 95% CI 0.00-0.63, P = 0.05). Subgroup analyses showed that the outcomes may have been influenced by ethnicity and CSF source. Compared to AD, overall sensitivity in differentiating iNPH was 0.813 (95% CI 0.636-0.928) for Aβ42, 0.828 (95% CI 0.732-0.900) for t-tau, 0.943 (95% CI 0.871-0.981) for p-tau. Relative to AD, overall specificity in differentiating iNPH was 0.506 (95% CI 0.393-0.619) for Aβ42, 0.842 (95% CI 0.756-0.907) for t-tau, 0.851 (95% CI 0.767-0.914) for p-tau.
CONCLUSION
The results of our meta-analysis suggest that iNPH may be associated with significantly reduced levels of CSF Aβ42, t-tau and p-tau compared to the healthy normal state. Compared to AD, both t-tau and p-tau were significantly decreased in iNPH, but CSF Aβ42 was slightly increased. Prospective studies are needed to further assess the clinical utility of these and other CSF biomarkers in assisting in the diagnosis of iNPH and differentiating it from AD and other neurodegenerative disorders.
Topics: Amyloid beta-Peptides; Databases, Bibliographic; Diagnosis, Differential; Humans; Hydrocephalus, Normal Pressure; Peptide Fragments; Phosphorylation; tau Proteins
PubMed: 28486988
DOI: 10.1186/s12987-017-0062-5 -
JID Innovations : Skin Science From... Jul 2022As solid organ transplantation becomes more prevalent, more individuals are living as members of the immunosuppressed population with an elevated risk for cutaneous... (Review)
Review
As solid organ transplantation becomes more prevalent, more individuals are living as members of the immunosuppressed population with an elevated risk for cutaneous squamous cell carcinoma (cSCC). Although great progress has been made in understanding the pathogenesis of cSCC in general, little is known about the drivers of tumorigenesis in immunosuppressed patients and organ-transplant recipients, specifically. This systematic review sought to synthesize information regarding the genetic and epigenetic alterations as well as changes in protein and mRNA expression that place this growing population at risk for cSCC, influence treatment response, and promote tumor aggressiveness. This review will provide investigators with a framework to identify future areas of investigation and clinicians with additional insight into how to best manage these patients.
PubMed: 35620703
DOI: 10.1016/j.xjidi.2022.100126 -
Neurology. Clinical Practice Aug 2021There is an unmet need for reliable biomarkers to predict disease severity, prognosis, and treatment effect in patients with spinal muscular atrophy (SMA). The purpose... (Review)
Review
BACKGROUND
There is an unmet need for reliable biomarkers to predict disease severity, prognosis, and treatment effect in patients with spinal muscular atrophy (SMA). The purpose of this review is to evaluate the clinical utility of blood-based biomarkers in patients with SMA.
METHODS
A systematic review of MEDLINE, DARE, PEDro, PsycINFO, Cochrane Database, LILACS, OTSeeker, SpeechBITE, CINAHL, Scopus, Science Direct, clinicaltrial.gov, OpenGrey, and Google Scholar was performed with the last search data of June 30, 2019.
RESULTS
Survival motor neuron (SMN)-related biomarkers showed an important interpatient and cell variability with a wide overlap between SMA phenotypes and healthy controls. Several plasma protein analytes correlated with motor scores; however, validation studies are needed to rule out false positives. DNA methylation analysis distinguished between patients with mild/moderate SMA and healthy controls. Plasma phosphorylated neurofilament heavy chain (pNF-H) levels increased with disease severity and declined considerably after nusinersen treatment.
CONCLUSION
There is no sufficient evidence to support the clinical utility of SMN-related biomarkers to predict disease severity in SMA. pNF-H appears to be a promising biomarker of disease activity and treatment effect in SMA. Further studies should include longitudinal assessments of patients with SMA across functional groups and comparisons with age-matched healthy controls to evaluate the stability of putative biomarkers over time and in response to SMA therapeutics. PROSPERO registration: CRD42019139050.
PubMed: 34484951
DOI: 10.1212/CPJ.0000000000000872 -
Medicine Feb 2016The overexpression of phosphorylated signal transducer and activator of transcription 3 (p-stat3) was detected in a variety of human tumors. The published studies on... (Meta-Analysis)
Meta-Analysis Review
The overexpression of phosphorylated signal transducer and activator of transcription 3 (p-stat3) was detected in a variety of human tumors. The published studies on p-stat3 expression among gastric carcinoma patients remain controversial.In order to clarify the prognosis value of p-stat3 with overall survival and its association with clinicopathological characteristics in gastric carcinoma, we performed a systematic review and meta-analysis.Eligible studies were retrieved by searching PubMed, Embase, Cochrane library, and Chinese biomedical literature service system databases.Studies described the association between p-stat3 expression and clinicopathological characteristics and overall survival in gastric carcinoma patients; p-stat3 expression was detected by immunohistochemistry (IHC).Odds ratio (OR) and hazard ratio (HR) were considered as a measure of evaluating the association in meta-analysis; I was used to assess the heterogeneity across studies; publication bias was assessed with funnel plot, Egger test, and Begg test.Twenty-three studies including 2872 patients which evaluated the p-stat3 expression by IHC in gastric carcinoma were included. The pooled HR (HR = 2.02, 95% CI: 1.49-2.73, P < 0.00001) indicated that the increased p-stat3 expression was significantly associated with poor overall survival. In addition, when we investigated the association between p-stat3 overexpression and clinicopathological characteristics of gastric carcinoma, we found that the increased p-stat3 expression was significantly associated with tumor differentiation (poorly vs well-moderately: OR = 3.70, 95% CI: 1.98-6.93, P < 0.0001) and lymph node metastasis (present vs absent: OR = 2.40, 95% CI: 1.28-4.50, P = 0.007).The different type of primary antibody was used; the assessment methods of p-stat3 positive expression were defined differently; the locations of p-stat3 expression were different; the method of extrapolating HR from Kaplan-Meier survival curves did seem to be less reliable than when HR was extracted directly from literatures; sample sizes, the age of patients, and the follow-up durations are different.In conclusion, our meta-analysis indicates that the increased p-stat3 expression may be not only predict poor prognosis, but also be associated with worse tumor differentiation and lymph node metastasis in patients with gastric carcinoma.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma; Female; Humans; Kaplan-Meier Estimate; Lymphatic Metastasis; Male; Middle Aged; Odds Ratio; Phosphorylation; Predictive Value of Tests; Prognosis; STAT3 Transcription Factor; Stomach Neoplasms; Young Adult
PubMed: 26844481
DOI: 10.1097/MD.0000000000002641 -
Molecular Medicine Reports Mar 2018Arsenic is a toxic metal, which ultimately leads to cell apoptosis. ERK is considered a key transcriptional regulator of arsenic‑induced apoptosis. Due to a few... (Meta-Analysis)
Meta-Analysis Review
Arsenic is a toxic metal, which ultimately leads to cell apoptosis. ERK is considered a key transcriptional regulator of arsenic‑induced apoptosis. Due to a few controversial issues about arsenic‑mediated extracellular signal‑regulated MAP kinases (ERK) signaling, a meta‑analysis was performed. Subgroup analyses demonstrated that high doses (≥2 µmol/l) of arsenic increased the expression of Ras, ERK, ERK1, ERK2, phosphorylated (p)‑ERK, p‑ERK1, and p‑ERK2, while low doses (<2 µmol/l) decreased the expression of Ras, ERK1, p‑ERK, and p‑ERK2 when compared to control groups. Long term exposure (>24 h) to arsenic led to inhibition of expression of ERK1, p‑ERK1, and p‑ERK2, whereas short‑term exposure (≤24 h) triggered the expression of ERK1, ERK2, p‑ERK, p‑ERK1, and p‑ERK2. Furthermore, normal cells exposed to arsenic exhibited higher production levels of Ras and p‑ERK. Conversely, exposure of cancer cells to arsenic showed a lower level of production of Ras and p‑ERK as well as higher level of p‑ERK1 and p‑ERK2 as compared to control group. Short‑term exposure of normal cells to high doses of arsenic may promote ERK signaling pathway. In contrast, long‑term exposure of cancer cells to low doses of arsenic may inhibit ERK signaling pathway. This study may be helpful in providing a theoretical basis for the diverging result of arsenic adverse effects on one hand and therapeutic mechanisms on the other concerning arsenic‑induced apoptosis.
Topics: Arsenic; Databases, Factual; Extracellular Signal-Regulated MAP Kinases; Humans; Phosphorylation; Signal Transduction
PubMed: 29328451
DOI: 10.3892/mmr.2018.8383 -
American Journal of Obstetrics and... Jan 2016To assess the accuracy of the cervical phosphorylated insulin-like growth factor binding protein-1 (phIGFBP-1) test to predict preterm birth in women with and without... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess the accuracy of the cervical phosphorylated insulin-like growth factor binding protein-1 (phIGFBP-1) test to predict preterm birth in women with and without symptoms of preterm labor through the use of formal methods for systematic reviews and metaanalytic techniques.
DATA SOURCES
PubMed, Embase, Cinahl, Lilacs, and Medion (all from inception to June 30, 2015), reference lists, conference proceedings, and Google scholar.
STUDY ELIGIBILITY CRITERIA
Cohort or cross-sectional studies that reported on the predictive accuracy of the cervical phIGFBP-1 test for preterm birth.
STUDY APPRAISAL AND SYNTHESIS METHODS
Two reviewers independently selected studies, assessed the risk of bias, and extracted the data. Summary receiver-operating characteristic curves, pooled sensitivities and specificities, and summary likelihood ratios were generated.
RESULTS
Forty-three studies met the inclusion criteria, of which 15 provided data on asymptomatic women (n = 6583) and 34 on women with an episode of preterm labor (n = 3620). Among asymptomatic women, the predictive accuracy of the cervical phIGFBP-1 test for preterm birth at <37, <34, and <32 weeks of gestation was minimal, with pooled sensitivities and specificities and summary positive and negative likelihood ratios ranging from 14% to 47%, 76% to 93%, 1.5 to 4.4, and 0.6 to 1.0, respectively. Among women with an episode of preterm labor, the test had a low predictive performance for delivery within 7 and 14 days of testing, and preterm birth at <34 and <37 weeks of gestation with pooled sensitivities and specificities and summary positive and negative likelihood ratios that varied between 60% and 68%, 77% and 81%, 2.7 and 3.5, and 0.4 and 0.5, respectively. A negative test result in women with an episode of preterm labor had a low to moderate accuracy to identify women who are not at risk for delivering within the next 48 hours (summary negative likelihood ratio of 0.28 in all women and 0.23 in women with singleton gestations).
CONCLUSION
Cervical phIGFBP-1 has the potential utility to identify patients with an episode of preterm labor who will not deliver within 48 hours. However, its overall predictive ability for the identification of symptomatic and asymptomatic women at risk for preterm birth is limited.
Topics: Biomarkers; Cervix Uteri; Female; Humans; Insulin-Like Growth Factor Binding Protein 1; Obstetric Labor, Premature; Phosphorylation; Predictive Value of Tests; Pregnancy; Premature Birth
PubMed: 26149828
DOI: 10.1016/j.ajog.2015.06.060 -
Scientific Reports Jan 2015The prognostic value of phosphorylated Akt (pAkt) overexpression in breast cancer has been investigated by many studies with inconsistent results. This systematic review... (Meta-Analysis)
Meta-Analysis Review
The prognostic value of phosphorylated Akt (pAkt) overexpression in breast cancer has been investigated by many studies with inconsistent results. This systematic review was conducted to evaluate the association of pAkt overexpression with breast cancer prognosis in terms of overall survival and disease-free survival. Three electronic databases (PubMed, EMBASE and Chinese Biomedical Literature Database) were comprehensively searched. Hazard ratios (HRs) with 95% confidence intervals (CIs) from different studies were combined using the random-effects model. In total, 33 studies with 9,836 patients were included for final analysis. The summary HR for overall survival and disease-free survival was 1.52 (95% CI: 1.29-1.78) and 1.28 (95% CI: 1.13-1.45), respectively, indicating higher risk of death and disease recurrence associated with pAkt overexpression. The results were robust in sensitivity analyses by omitting one study each time and by using the fixed-effects model instead. Subgroup and meta-regression analyses did not show that the prognostic effect of pAkt overexpression would change materially with such factors as population, status of hormone receptors, hormonal or trastuzumab treatment given, analyzing method (univariate versus multivariate) and methodological quality of the original studies. In conclusion, the available evidence suggests that pAkt overexpression is an adverse prognostic factor for breast cancer.
Topics: Breast Neoplasms; Disease-Free Survival; Female; Humans; Phosphorylation; Proto-Oncogene Proteins c-akt; Publication Bias; Regression Analysis
PubMed: 25582346
DOI: 10.1038/srep07758 -
Oncotarget Apr 2016Accumulated studies have provided controversial evidences of the association between signal transducer and activator of transcription proteins 3 (STAT3) expression and... (Meta-Analysis)
Meta-Analysis Review
Accumulated studies have provided controversial evidences of the association between signal transducer and activator of transcription proteins 3 (STAT3) expression and survival of human solid tumors. To address this inconsistency, we performed a meta-analysis with 63 studies identified from PubMed, Medline and EBSCO. We found STAT3 overexpression was significantly associated with worse 3-year overall survival (OS) (OR = 2.06, 95% CI = 1.57 to 2.71, P < 0.00001) and 5-year OS (OR = 2.00, 95% CI = 1.53 to 2.63, P < 0.00001) of human solid tumors. Similar results were observed when disease free survival (DFS) were analyzed. Subgroup analysis showed that elevated STAT3 expression was associated with poor prognosis of gastric cancer, lung cancer, gliomas, hepatic cancer, osteosarcoma, prostate cancer, pancreatic cancer but better prognosis of breast cancer. The correlation between STAT3 and survival of solid tumors was related to its phosphorylated state. High expression level of STAT3 was also associated with advanced tumor stage. In conclusion, elevated STAT3 expression is associated with poor survival in most solid tumors. STAT3 is a valuable biomarker for prognosis prediction and a promising therapeutic target in human solid tumors.
Topics: Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Humans; Neoplasms; Prognosis; STAT3 Transcription Factor; Sensitivity and Specificity; Survival Analysis
PubMed: 26959884
DOI: 10.18632/oncotarget.7887