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Future Oncology (London, England) Jun 2023A meta-analysis was conducted to systematically review the risks of all-grade as well as high-grade rash in chronic myelogenous leukemia (CML) patients using... (Meta-Analysis)
Meta-Analysis Review
A meta-analysis was conducted to systematically review the risks of all-grade as well as high-grade rash in chronic myelogenous leukemia (CML) patients using different types of BCR-ABL inhibitors. Literature published between 2000 and April 2022 were searched using PubMed, Cochrane Library, Embase and ClinicalTrials.gov. A total of 12 studies were included for meta-analysis. The results showed that the incidence of all-grade or high-grade rash associated with new-generation BCR-ABL inhibitors had no significant difference compared with a standard dose of imatinib. Subgroup analysis suggested that, compared with imatinib, the incidence of all grades of rash was higher in the nilotinib, bosutinib and ponatinib groups. For CML patients treated with nilotinib, bosutinib and ponatinib, the occurrence of skin toxicity should not be ignored.
Topics: Humans; Imatinib Mesylate; Fusion Proteins, bcr-abl; Protein Kinase Inhibitors; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Exanthema; Antineoplastic Agents; Drug Resistance, Neoplasm
PubMed: 37368411
DOI: 10.2217/fon-2022-1008 -
PloS One 2017Phosphorylated mammalian target of rapamycin (p-mTOR) is a promising prognostic marker in many types of cancer. However, its survival benefit in patients with breast... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Phosphorylated mammalian target of rapamycin (p-mTOR) is a promising prognostic marker in many types of cancer. However, its survival benefit in patients with breast carcinoma remains unknown. The aim of the present study was to assess the relationship between p-mTOR expression and prognosis in breast carcinoma based on a systematic review and meta-analysis.
MATERIALS AND METHODS
Electronic databases (including Pubmed, Embase, ISI web of science, and Cochrane Library) were searched up to November 24, 2015. The outcome measures were hazard ratios (HRs) with 95% confidence interval (CI) for the association between the prognosis of breast carcinoma patients and p-mTOR expression. Primary end points were disease-free survival (DFS), overall survival (OS), and recurrence-free survival (RFS). Statistical analysis was performed with STATA 12.0.
RESULTS
Nine cohort studies including 3051 patients met full eligibility criteria. The pooled HRs (95% CI) for OS, DFS, and RFS were 0.84 (0.27-2.63), 0.71 (0.40-1.23), and 0.48 (0.20-1.18), respectively.
CONCLUSIONS
Our findings suggested that p-mTOR overexpression was not significantly related to prognosis in breast carcinoma regarding OS and disease recurrence. Prospective studies are warranted to examine the association between p-mTOR expression and survival outcomes in breast carcinoma.
Topics: Breast Neoplasms; Female; Humans; Survival Analysis; TOR Serine-Threonine Kinases
PubMed: 28114374
DOI: 10.1371/journal.pone.0170302 -
Biomolecules Sep 2023Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6is) have transformed the treatment of hormone receptor-positive (HR+) and human epidermal growth factor receptor... (Review)
Review
Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6is) have transformed the treatment of hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer over the last decade. These inhibitors are currently established as first- and second-line systemic treatment choices for both endocrine-sensitive and -resistant breast cancer populations alongside endocrine therapy (ET) or monotherapy. Data on targeted therapy continue to mature, and the number of publications has been constantly rising. Although these drugs have been demonstrated to prolong overall survival (as well as progression-free survival (PFS) in breast cancer patients), changing the paradigm of all current knowledge, they also cause important adverse events (AEs). This review provides the latest summary and update on the safety profile of the three CDK4/6 inhibitors, as it appears from all major phase II and III randomized clinical trials regarding palbociclib, ribociclib, and abemaciclib, including the most relevant 15 clinical trials.
Topics: Humans; Female; Breast Neoplasms; Progression-Free Survival; Cyclin-Dependent Kinase 4; Clinical Trials, Phase II as Topic
PubMed: 37759823
DOI: 10.3390/biom13091422 -
BMC Cancer Nov 2023RAS mutations affect prognosis in patients with metastatic colorectal cancer (mCRC) and have been identified as strong negative predictive markers for anti-epidermal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
RAS mutations affect prognosis in patients with metastatic colorectal cancer (mCRC) and have been identified as strong negative predictive markers for anti-epidermal growth factor receptor monoclonal antibody (anti-EGFR mAb) therapy, but many tumors containing wild-type RAS genes still do not respond to these therapies. Some additional biomarkers may have prognostic or predictive roles, but conclusions remain controversial.
METHODS
We performed a meta-analysis and systematic review of randomized controlled trials comparing anti-EGFR mAb therapy with alternative therapy that investigated the prognostic and predictive impact of additional biomarkers in RAS wild-type (wt) mCRC patients. Hazard ratios (HRs) and 95% confidence intervals (CIs) for progression-free survival (PFS) and overall survival (OS) and odds ratios (ORs) for objective response rate (ORR) were calculated. The prognostic value of biomarkers was investigated by separately pooling HR and OR for different treatment groups in an individual study. The predictive value was assessed by pooling study interactions between treatment effects and biomarker subgroups.
RESULTS
Thirty publications reporting on eighteen trials were selected, including a total of 13,507 patients. In prognostic analysis, BRAF mutations were associated with poorer PFS [HRs = 3.76 (2.47-5.73) and 2.69 (1.82-3.98)] and OS [HRs = 2.66 (1.95-3.65) and 2.45 (1.55-3.88)] in both the experimental and control arms; low miR-31-3p expression appeared to have longer PFS and OS. In terms of predictive effect, a lack of response to anti-EGFR therapy was observed in patients with BRAF mutant tumors (P < 0.01 for PFS). Patients with tumors with any mutation in the KRAS/NRAS/BRAF/PIK3CA gene also showed similar results compared with all wild-type tumors (P for PFS, OS, and ORR were < 0.01, < 0.01 and 0.01, respectively). While low miR-31-3p expression could predict PFS (P = 0.01) and OS (P = 0.04) benefit. The prognostic and predictive value regarding PIK3CA mutations, PTEN mutations or deletions, EGFR, EREG/AREG, HER2, HER3, and HER4 expression remains uncertain.
CONCLUSIONS
In RAS wt mCRC patients receiving EGFR-targeted therapy, BRAF mutation is a powerful prognostic and therapy-predictive biomarker, with no effect found for PIK3CA mutation, PTEN mutation or deletion, but the combined biomarker KRAS/NRAS/BRAF/PIK3CA mutations predict resistance to anti-EGFR therapy. Low miR-31-3p expression may have positive prognostic and therapy predictive effects. Evidence on the prognostic and predictive roles of EGFR and its ligands, and HER2/3/4 is insufficient.
Topics: Humans; Prognosis; Proto-Oncogene Proteins B-raf; Colorectal Neoplasms; Proto-Oncogene Proteins p21(ras); ErbB Receptors; Antibodies, Monoclonal; Colonic Neoplasms; Rectal Neoplasms; Biomarkers; Class I Phosphatidylinositol 3-Kinases; Mutation; MicroRNAs; Biomarkers, Tumor
PubMed: 37974093
DOI: 10.1186/s12885-023-11600-z -
International Journal of Molecular... Aug 2023The early identification of women with an increased risk of preeclampsia (PE) is desirable, but apart from soluble fms-like tyrosine kinase-1 (sFlt-1), few biomarkers... (Meta-Analysis)
Meta-Analysis Review
The early identification of women with an increased risk of preeclampsia (PE) is desirable, but apart from soluble fms-like tyrosine kinase-1 (sFlt-1), few biomarkers have previously been identified as relevant for predicting preeclampsia. Since kinases and phosphatases regulate critical biological processes and previous evidence suggests a potential role of these molecules in preeclampsia, we performed this systematic review and metanalysis. The objective was to determine if there are kinases and phosphatases whose serum levels are different between women with and without PE, being relevant biomarkers of PE. We followed the recommendations of Cochrane and the Preferred Reported Items for Systematic Reviews and Metanalysis (PRISMA) to perform this study. The MESH terms preeclampsia, kinases, phosphatases, angiopoietins, soluble tyrosine protein kinase receptor (sTIE2), and cellular-mesenchymal-epithelial transition factor (c-MET) were combined to find relevant articles in the PubMed, PROSPERO, and Cochrane databases. Then, a qualitative and quantitative analysis was performed in R Studio software. From 580 abstracts identified, 37 were included in the final analysis, which comprised 24,211 pregnant women (2879 with PE and 21,332 women without PE [HP]. The pooled analysis showed that serum creatine kinase (CK) (SMD: 2.43, CI 95% 0.25-4.62) was significantly higher in PE, whereas sTIE2 and anti-angiogenic factor soluble c-Met (sMet)were significantly lower in PE than in HP (SMD: -0.23, CI95% -0.37 to -0.09; and SMD:0.24, CI95% 0.01-0.47, respectively). Adenosine monophosphate-activated protein kinase (AMPK), angiopoietin-1 (ANG-1), angiopoietin-2 (ANG-2), the ratio angiopoietin-1/angiopoietin-2, acid phosphatase, and alkaline phosphatase were not different between women with PE and HP. In summary CK, sTIE2, and c-MET are relevant biomarkers of PE. It is desirable to incorporate them into current models for PE prediction to evaluate their utility as biomarkers.
Topics: Pregnancy; Female; Humans; Phosphoric Monoester Hydrolases; Angiopoietin-1; Angiopoietin-2; Pre-Eclampsia; Antibodies; Receptor, trkA
PubMed: 37629025
DOI: 10.3390/ijms241612842 -
Journal of Strength and Conditioning... Mar 2023Lee, CJ and Nicoll, JX. Time course evaluation of mitogen-activated protein kinase phosphorylation to resistance exercise: a systematic review. J Strength Cond Res...
Lee, CJ and Nicoll, JX. Time course evaluation of mitogen-activated protein kinase phosphorylation to resistance exercise: a systematic review. J Strength Cond Res 37(3): 710-725, 2023-Resistance exercise (RE) can increase the signaling activities of mitogen-activated protein kinases (MAPKs), specifically extracellular signal-regulated kinases 1/2 (ERK1/2), p90 ribosomal S6 kinases (p90RSK), c-Jun NH2-terminal kinases (JNK), and p38-MAPK. These RE-induced responses contribute to various intracellular processes modulating growth and development in skeletal muscles, playing an essential role in resistance training adaptations. The time course of MAPK phosphorylation to different RE conditions, such as training experience and varying loads, remains ambiguous. A systematic review was conducted to determine the effects of different post-RE recovery time points on the MAPK signaling cascade. In addition, the effects of loading and training statuses on MAPK responses were also investigated. The review was performed according to the preferred reporting items for systematic reviews and meta-analyses guidelines with a literature search incorporating 3 electronic databases. A modified version of the Downs and Black checklist was used to evaluate the methodological quality of the studies. The signaling responses were measured within a time range between immediately post-RE and >6 hours post-RE. Forty-four studies met the inclusion criteria, and all were classified as good-to-moderate methodological quality. Mitogen-activated protein kinase phosphorylation increased to different levels after RE, with the highest near the cessation of exercise. Although overall signaling was attenuated among trained individuals likely because of training adaptations, greater MAPK responses can be attributed to moderate loads of 65-85% 1RM regardless of the training experience. However, specific training-induced responses remain equivocal, and further investigations are required to determine the ideal training parameters to optimize anabolic intramuscular signaling, which may likely optimize resistance training adaptations.
Topics: Humans; Mitogen-Activated Protein Kinases; Phosphorylation; Resistance Training; Mitogen-Activated Protein Kinase 1; MAP Kinase Signaling System
PubMed: 36727997
DOI: 10.1519/JSC.0000000000004409 -
Cancer Metastasis Reviews Mar 2022Neuroblastoma is a devastating disease accounting for 15% of all childhood cancer deaths. Yet, our understanding of key molecular drivers such as receptor tyrosine... (Review)
Review
BACKGROUND
Neuroblastoma is a devastating disease accounting for 15% of all childhood cancer deaths. Yet, our understanding of key molecular drivers such as receptor tyrosine kinases (RTKs) in this pathology remains poorly clarified. Here, we provide a systematic analysis of the RTK superfamily in the context of neuroblastoma pathogenesis.
METHODS
Statistical correlations for all RTK family members' expression to neuroblastoma patient survival across 10 independent patient cohorts were annotated, synthesized, and ranked using the R2: Genomics Analysis and Visualization Platform. Gene expression of selected members across different cancer cell lines was further analyzed in the Cancer Cell Line Encyclopedia, part of the Cancer Dependency Map portal (depmap portal ( http://depmap.org )). Finally, we provide a detailed literature review for highly ranked candidates.
RESULTS
Our analysis defined two subsets of RTKs showing robust associations with either better or worse survival, constituting potential novel players in neuroblastoma pathophysiology, diagnosis, and therapy. We review the available literature regarding the oncogenic functions of these RTKs, their roles in neuroblastoma pathophysiology, and potential utility as therapeutic targets.
CONCLUSIONS
Our systematic analysis and review of the RTK superfamily in neuroblastoma pathogenesis provides a new resource to guide the research community towards focused efforts investigating signaling pathways that contribute to neuroblastoma tumor establishment, growth, and/or aggressiveness and targeting these druggable molecules in novel therapeutic strategies.
Topics: Carcinogenesis; Cell Line, Tumor; Child; Humans; Neuroblastoma; Receptor Protein-Tyrosine Kinases; Signal Transduction
PubMed: 34716856
DOI: 10.1007/s10555-021-10001-7 -
Critical Reviews in Oncology/hematology Sep 2022A growing number of regimens have been approved as first-line treatments for patients with advanced epidermal growth factor receptor (EGFR) mutated non-small cell lung... (Meta-Analysis)
Meta-Analysis Review
Comparison of the efficacy and safety of first-line treatments based on clinicopathological characteristics for patients with advanced epidermal growth factor receptor mutated non-small-cell lung cancer: A systematic review and network meta-analysis.
BACKGROUND
A growing number of regimens have been approved as first-line treatments for patients with advanced epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer. However, the optimal regimen has not been determined, especially for patients with different clinicopathological characteristics. Therefore, we performed this meta-analysis to compare the efficacy and safety of first-line treatments for patients with EGFR-mutated NSCLC based on clinicopathological characteristics, thereby providing evidence for individual patient clinical decision-making.
METHODS
The PubMed, Embase, Cochrane Library databases, and abstracts of ASCO, ESMO, and WCLC were searched from inception to 3 June 2021 to identify eligible randomized controlled trials (RCTs). The outcomes of progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and grade 3 or higher adverse events (≥3AEs) were compared and ranked based on various clinicopathological characteristics among 14 regimens by network meta-analysis (NMA) and the surface under the cumulative ranking curve (SUCRA), respectively.
RESULTS
25 RCTs were included, with a total of 6965 patients and 14 treatment regimens. The primary endpoint of all RCTs was PFS, and OS, ORR, and ≥3AEs were secondary endpoints. Regarding overall patients, the most distinct PFS benefit was observed in osimertinib (OSI), with the fewest ≥3AEs, whereas gefitinib plus pemetrexed-based chemotherapy (GEF+PB) provided the greatest benefit for OS. When considering EGFR mutation type, aumolertinib (AUM) and GEF+PB could be the optimal regimens in terms of PFS for patients with EGFR 19DEL and EGFR 21L858R, respectively. Notably, the efficacy of the 14 regimens for PFS varied across clinicopathological characteristics, with GEP+PB ranking first in Eastern Cooperative Oncology Group performance status (ECOG PS)= 1, Asian, age<65 and smoking subgroups, with AUM ranking first in ECOG PS= 0 and female subgroups, with ICO+PB ranking first in age ≥65 and no smoking subgroups, and with AFA+CET ranking first in the male subgroup. In terms of brain metastases, third-generation EGFR-TKI showed obvious superiority, with AUM and OSI optimally prolonging PFS in patients with and without brain metastases, respectively. In addition, GEF+PB is a superior alternative, ranking second in terms of PFS regardless of the presence of brain metastases.
CONCLUSIONS
OSI and GEF+PB were the most two effective first-line regimens for overall patients, ranking first in PFS and OS, respectively. GEF+PB ranked first in terms of PFS in subgroups of EGFR 21L858R, ECOG PS= 1, Asian, age <65, and smoking. Meanwhile, AUM in subgroups of EGFR 19DEL, ECOG PS= 0, female, brain metastasis, OSI in the subgroup of without brain metastasis, ICO+PB in no smoking subgroup, and AFA+CET in male subgroup were the best options as for their evident superiority in PFS.
Topics: Acrylamides; Aged; Antineoplastic Agents; Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Female; Humans; Indoles; Lung Neoplasms; Male; Middle Aged; Mutation; Network Meta-Analysis; Protein Kinase Inhibitors; Pyrimidines
PubMed: 35870763
DOI: 10.1016/j.critrevonc.2022.103760 -
International Journal of Sport... May 2018Coffee is one of the most consumed beverages in the world, and it can improve insulin sensitivity, stimulating glucose uptake in skeletal muscle when adequate... (Review)
Review
Coffee is one of the most consumed beverages in the world, and it can improve insulin sensitivity, stimulating glucose uptake in skeletal muscle when adequate carbohydrate intake is observed. The aim of this review is to analyze the effects of coffee and coffee components on muscle glycogen metabolism. A literature search was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis, and seven studies were included, that explored the effects of coffee components on various substances and signaling proteins. In one of the studies with humans, caffeine was shown to increase glucose levels, Ca/calmodulin-dependent protein kinase phosphorylation, glycogen resynthesis rates, and glycogen accumulation after exercise. After intravenous injection of caffeine in rats, caffeine increased adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation, and glucose transport. In in vitro studies, caffeine raised AMPK and ACC phosphorylation, increasing glucose transport activity and reducing energy status in rat muscle cells. Cafestol and caffeic acid increased insulin secretion in rat beta cells and glucose uptake into human muscle cells. Caffeic acid also increased AMPK and ACC phosphorylation, reducing the energy status and increasing glucose uptake in rat muscle cells. Chlorogenic acid did not show any positive or negative effect. The findings from this review must be taken with caution due to the limited number of studies on the subject. In conclusion, various coffee components had a neutral or positive role in the metabolism of glucose and muscle glycogen, whereas no detrimental effect was described. Coffee beverages should be tested as an option for athletes' glycogen recovery.
Topics: AMP-Activated Protein Kinases; Acetyl-CoA Carboxylase; Animals; Coffee; Exercise; Glycogen; Humans; Insulin Resistance; Insulin-Secreting Cells; Muscle Cells; Muscle, Skeletal; Phosphorylation; Rats
PubMed: 29345166
DOI: 10.1123/ijsnem.2017-0342 -
Translational Neurodegeneration Apr 2022A growing amount of evidence has indicated contributions of variants in causative genes of Parkinson's disease (PD) to the development of sleep disturbance in PD and... (Meta-Analysis)
Meta-Analysis Review
A growing amount of evidence has indicated contributions of variants in causative genes of Parkinson's disease (PD) to the development of sleep disturbance in PD and prodromal PD stages. In this article, we aimed to investigate the role of genetics in sleep disorders in PD patients and asymptomatic carriers at prodromal stage of PD. A systematic review and meta-analysis of observational studies was conducted based on the MEDLINE, EMBASE and PsychINFO databases. A pooled effect size was calculated by odds ratio (OR) and standard mean difference (SMD). Forty studies were selected for quantitative analysis, including 17 studies on glucocerebrosidase (GBA), 25 studies on Leucine-rich repeat kinase 2 (LRRK2) and 7 on parkin (PRKN) genes, and 3 studies on alpha-synuclein gene (SNCA) were used for qualitative analysis. Patients with PD carrying GBA variants had a significantly higher risk for rapid-eye-movement behavior disorders (RBD) (OR, 1.82) and higher RBD Screening Questionnaire scores (SMD, 0.33). Asymptomatic carriers of GBA variants had higher severity of RBD during follow-up. Patients with PD carrying the LRRK2 G2019S variant had lower risk and severity of RBD compared with those without LRRK2 G2019S. Variants of GBA, LRRK2 and PRKN did not increase or decrease the risk and severity of excessive daytime sleepiness and restless legs syndrome in PD. Our findings suggest that the genetic heterogeneity plays a role in the development of sleep disorders, mainly RBD, in PD and the prodromal stage of PD.
Topics: Genetic Heterogeneity; Glucosylceramidase; Humans; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; Mutation; Parkinson Disease; Prodromal Symptoms; Sleep Wake Disorders; alpha-Synuclein
PubMed: 35395825
DOI: 10.1186/s40035-022-00294-1