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European Journal of Clinical... Apr 2024The role of neoadjuvant epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) targeted therapy for EGFR-mutated non-small cell lung cancer (NSCLC) is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The role of neoadjuvant epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) targeted therapy for EGFR-mutated non-small cell lung cancer (NSCLC) is unclear. Previous studies have shown that EGFR-TKIs have excellent anti-tumor activity. However, almost all studies on neoadjuvant EGFR-TKI treatment for EGFR-mutated NSCLC have been non-randomized controlled trials with small sample sizes and different methods of statistical analysis, which may lead to a lack of valid metrics to assess the feasibility and safety of neoadjuvant EGFR-TKI treatment. This meta-analysis aimed to assess the efficacy and safety of neoadjuvant EGFR-TKI treatment for NSCLC patients with EGFR mutations.
METHODS
Relevant studies were systematically searched in PubMed, Embase, and Web of Science databases. Results including objective response rate (ORR), complete resection rate (R0), downstaging rate, pathological complete response (PCR), major pathological response (MPR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were used for further analysis.
RESULTS
This meta-analysis ultimately included 11 studies involving 344 patients with EGFR-positive mutations in NSCLC. In terms of tumor response, the pooled ORR was 57% (95% CI: 42%-73%), and in the Osimertinib subgroup, the pooled ORR was 80% (95% CI: 63%-98%). Analysis of studies that reported a downstaging rate showed the pooled downstaging rate of 41% (95% CI: 9%-74%) and the pooled downstaging rate of 74% (95% CI: 22%-100%) in the Osimertinib subgroup. In terms of surgical outcomes, the pooled pCR rate was 3% (95% CI: 0%-7%), the pooled MPR rate was 11% (95% CI: 6%-17%), and the pooled R0 resection rate was 91% (95% CI: 85%-95%). The most common adverse events associated with neoadjuvant therapy were rash and diarrhea. The pooled incidence of any grade of rash was 47.1% (95% CI: 25.4%-69.3%), and the pooled incidence of grade ≥ 3 rash was 0.6% (95% CI: 0.0%-2.5%). The pooled incidence of diarrhea of any grade was 28.8% (95% CI: 14.4%-45.4%), with the pooled incidence of grade ≥ 3 diarrhea of 0.2% (95% CI: 0.0%-1.6%). The pooled incidence of ≥ grade 3 adverse events was significantly lower.
CONCLUSIONS
Our meta-analysis confirmed the efficacy and safety of neoadjuvant EGFR-TKIs for the treatment of NSCLC patients with EGFR-positive mutations and that third-generation EGFR-TKIs were superior to first- and second-generation EGFR-TKIs in terms of shrinking tumor volume and lowering tumor stage; however, future large-scale and multicenter randomized controlled trials are needed to confirm this conclusion.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42023466731.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Neoadjuvant Therapy; Feasibility Studies; Antineoplastic Agents; Protein Kinase Inhibitors; ErbB Receptors; Diarrhea; Exanthema; Mutation; Multicenter Studies as Topic; Acrylamides; Aniline Compounds; Indoles; Pyrimidines
PubMed: 38300281
DOI: 10.1007/s00228-024-03620-w -
Environmental Science and Pollution... Aug 2023Acrylamide is widely found in a variety of fried foods and cigarettes and is not only neurotoxic and carcinogenic, but also has many potential toxic effects. The current... (Review)
Review
Acrylamide is widely found in a variety of fried foods and cigarettes and is not only neurotoxic and carcinogenic, but also has many potential toxic effects. The current assessment of acrylamide intake through dietary questionnaires is confounded by a variety of factors, which poses limitations to safety assessment. In this review, we focus on the levels of AAMA, the urinary metabolite of acrylamide in humans, and its association with other diseases, and discuss the current research gaps in AAMA and the future needs. We reviewed a total of 25 studies from eight countries. In the general population, urinary AAMA levels were higher in smokers than in non-smokers, and higher in children than in adults; the highest levels of AAMA were found in the population from Spain, compared with the general population from other countries. In addition, AAMA is associated with several diseases, especially cardiovascular system diseases. Therefore, AAMA, as a biomarker of internal human exposure, can reflect acrylamide intake in the short term, which is of great significance for tracing acrylamide-containing foods and setting the allowable intake of acrylamide in foods.
Topics: Adult; Child; Humans; Acetylcysteine; Acrylamide; Biomarkers; Surveys and Questionnaires
PubMed: 37458885
DOI: 10.1007/s11356-023-28714-3 -
Biomedicines Dec 2022This study aimed to assess whether degradation-resistant monomers included in experimental dental adhesives can improve long-term bond strength compared to conventional... (Review)
Review
This study aimed to assess whether degradation-resistant monomers included in experimental dental adhesives can improve long-term bond strength compared to conventional monomers. This study followed the latest PRISMA guidance (2020). The search for the systematic review was carried out in four electronic databases: PubMed/Medline, Scopus, SciELO and EMBASE, without restrictions on the year of publication and language. The last screening was conducted in July 2022. Interventions included were in vitro studies on experimental dental adhesives that tested short-term and long-term bond strength, but also water sorption and solubility data when available, in extracted human molars. Meta-analyses were performed using Rstudio v1.4.1106. A summary table analyzing the individual risk of bias was generated using the recent RoBDEMAT tool. Of the 177 potentially eligible studies, a total of 7 studies were included. Experimental monomers with acrylamides or methacrylamide−acrylamide hybrids in their composition showed better results of aged bond strength when compared to methacrylate controls (p < 0.05). The experimental monomers found better sorption and solubility compared to controls and were significantly different (p < 0.001). It is possible to achieve hydrolytically resistant formulations by adding novel experimental monomers, with chemical structures that bring benefit to degradation mechanisms.
PubMed: 36551861
DOI: 10.3390/biomedicines10123104 -
Critical Reviews in Food Science and... 2024Acrylamide (AA) is a toxic substance formed in many carbohydrate-rich food products, whose formation can be reduced by adding some additives. Furthermore, the type of...
Acrylamide (AA) is a toxic substance formed in many carbohydrate-rich food products, whose formation can be reduced by adding some additives. Furthermore, the type of food consumed determines the AA intake. According to the compiled information, the first route causing AA formation is the Maillard reaction. Some interventions, such as reducing AA precursors in raw materials, (i.e., asparagine), reducing sugars, or decreasing temperature and processing time can be applied to limit AA formation in food products. The L-asparaginase is more widely used in potato products. Also, coatings loaded with proteins, enzymes, and phenolic compounds are new techniques for reducing AA content. Enzymes have a reducing effect on AA formation by acting on asparagine; proteins by competing with amino acids to participate in Maillard, and phenolic compounds through their radical scavenging activity. On the other hand, some synthetic and natural additives increase the formation of AA. Due to the high exposure to AA and its toxic effects, it is essential to recognize suitable food additives to reduce the health risks for consumers. In this sense, this study focuses on different additives that are proven to be effective in the reduction or formation of AA in food products.
Topics: Asparagine; Acrylamide; Hot Temperature; Carbohydrates; Asparaginase; Maillard Reaction
PubMed: 36194060
DOI: 10.1080/10408398.2022.2126428 -
Metabolomics : Official Journal of the... Sep 2022Work-related exposures to harmful agents or factors are associated with an increase in incidence of occupational diseases. These exposures often represent a complex... (Review)
Review
INTRODUCTION
Work-related exposures to harmful agents or factors are associated with an increase in incidence of occupational diseases. These exposures often represent a complex mixture of different stressors, challenging the ability to delineate the mechanisms and risk factors underlying exposure-disease relationships. The use of omics measurement approaches that enable characterization of biological marker patterns provide internal indicators of molecular alterations, which could be used to identify bioeffects following exposure to a toxicant. Metabolomics is the comprehensive analysis of small molecule present in biological samples, and allows identification of potential modes of action and altered pathways by systematic measurement of metabolites.
OBJECTIVES
The aim of this study is to review the application of metabolomics studies for use in occupational health, with a focus on applying metabolomics for exposure monitoring and its relationship to occupational diseases.
METHODS
PubMed, Web of Science, Embase and Scopus electronic databases were systematically searched for relevant studies published up to 2021.
RESULTS
Most of reviewed studies included worker populations exposed to heavy metals such as As, Cd, Pb, Cr, Ni, Mn and organic compounds such as tetrachlorodibenzo-p-dioxin, trichloroethylene, polyfluoroalkyl, acrylamide, polyvinyl chloride. Occupational exposures were associated with changes in metabolites and pathways, and provided novel insight into the relationship between exposure and disease outcomes. The reviewed studies demonstrate that metabolomics provides a powerful ability to identify metabolic phenotypes and bioeffect of occupational exposures.
CONCLUSION
Continued application to worker populations has the potential to enable characterization of thousands of chemical signals in biological samples, which could lead to discovery of new biomarkers of exposure for chemicals, identify possible toxicological mechanisms, and improved understanding of biological effects increasing disease risk associated with occupational exposure.
Topics: Biomarkers; Environmental Pollutants; Humans; Metabolomics; Occupational Diseases; Occupational Exposure
PubMed: 36083566
DOI: 10.1007/s11306-022-01930-7 -
Reviews on Environmental Health Dec 2023Acrylamide is a known neurotoxic compound for humans. Foods that have high concentrations of acrylamide need to be identified. One of the food products containing... (Meta-Analysis)
Meta-Analysis Review
Acrylamide is a known neurotoxic compound for humans. Foods that have high concentrations of acrylamide need to be identified. One of the food products containing acrylamide is popcorn. Popcorn is an important source of snacks for children, especially students. The presented study is a systematic review and meta-analysis of the level of acrylamide in popcorn. The search was done in different databases with the keywords; acrylamide, popcorn, popped corn. 27 articles were found by searching various databases. After initial screening and full text evaluation, 8 articles were selected for systematic review and 6 articles for meta-analysis. The amount of acrylamide in this product was in the range of 1,017.7-106 μg/kg. Microwaved corn contains lower amounts of acrylamide than other methods of preparation. The type of popcorn also had an effect on the amount of acrylamide with Meta-regression. It was found that sweet popcorn contains higher amounts of acrylamide. The overall value of acrylamide concentration in popcorns was calculated to be 459.6 ± 220.3 μg/kg. This amount is high and requires measures to reduce the amount of acrylamide.
Topics: Child; Humans; Food Contamination; Neurotoxins; Acrylamide; Food; Zea mays
PubMed: 35960600
DOI: 10.1515/reveh-2022-0085 -
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 -
Molecular Biology Reports Dec 2022L-asparaginases are mostly obtained from bacterial sources for their application in the therapy and food industry. Bacterial L-asparaginases are employed in the...
L-asparaginases are mostly obtained from bacterial sources for their application in the therapy and food industry. Bacterial L-asparaginases are employed in the treatment of Acute Lymphoblastic Leukemia (ALL) and its subtypes, a type of blood and bone marrow cancer that results in the overproduction of immature blood cells. It also plays a role in the food industry in reducing the acrylamide formed during baking, roasting, and frying starchy foods. This importance of the enzyme makes it to be of constant interest to the researchers to isolate novel sources. Presently L-asparaginases from E. coli native and PEGylated form, Dickeya chrysanthemi (Erwinia chrysanthemi) are in the treatment regime. In therapy, the intrinsic glutaminase activity of the enzyme is a major drawback as the patients in treatment experience side effects like fever, skin rashes, anaphylaxis, pancreatitis, steatosis in the liver, and many complications. Its significance in the food industry in mitigating acrylamide is also a major reason. Acrylamide, a potent carcinogen was formed when treating starchy foods at higher temperatures. Acrylamide content in food was analyzed and pre-treatment was considered a valuable option. Immobilization of the enzyme is an advancing and promising technique in the effective delivery of the enzyme than in free form. The concept of machine learning by employing the Artificial Network and Genetic Algorithm has paved the way to optimize the production of L-asparaginase from its sources. Gene-editing tools are gaining momentum in the study of several diseases and this review focuses on the CRISPR-Cas9 gene-editing tool in ALL.
Topics: Humans; Acrylamide; Asparaginase; Dickeya chrysanthemi; Escherichia coli; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 35816224
DOI: 10.1007/s11033-022-07688-4 -
Molecular Biology Reports Nov 2022The current global scenario has instigated a steady upsurge of synthetic chemicals usage thereby creating a toxic environment unsuitable for animals and humans.... (Review)
Review
The current global scenario has instigated a steady upsurge of synthetic chemicals usage thereby creating a toxic environment unsuitable for animals and humans. Acrylamide and bisphenol A are some of the most common toxins found in the atmosphere due to their extensive involvement in numerous industrial processes. Acrylamide, an occupational hazard toxin has been known to cause severe nerve damage and peripheral neuronal damage in both animals and humans. General sources of acrylamide exposure are effluents from textile and paper industries, cosmetics, and thermally processed foods rich in starch. Bisphenol A (BPA) is generally found in food packaging materials, dental sealants, and plastic bottles. It is highly temperature-sensitive that can easily leach into the food products or humans on contact. The genotoxic and neurotoxic effects of acrylamide and bisphenol A have been widely researched; however, more attention should be dedicated to understanding the developmental toxicity of these chemicals. The developmental impacts of toxin exposure can be easily understood using Drosophila melanogaster as a model given considering its short life span and genetic homology to humans. In this review, we have discussed the toxic effects of acrylamide and BPA on the developmental process of Drosophila melanogaster.
Topics: Animals; Humans; Drosophila melanogaster; Acrylamide; Benzhydryl Compounds; Phenols
PubMed: 35753027
DOI: 10.1007/s11033-022-07642-4 -
Environmental Research Oct 2022Acrylamide is a food contaminant linked to developmental toxicity in animals and possibly in humans. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acrylamide is a food contaminant linked to developmental toxicity in animals and possibly in humans.
OBJECTIVES
We performed a systematic review and dose-response meta-analysis of epidemiological studies evaluating the relationship between maternal acrylamide exposure during pregnancy and the risk of being small for gestational age (SGA) and birth weight, birth head circumference and birth length.
METHODS
We performed the literature search in PubMed, Scopus, and Web of Science, until June 6th, 2022. Studies carried out in mother-newborn pairs, assessing maternal acrylamide exposure during pregnancy, either via dietary assessments or biomarkers i.e., hemoglobin adducts of acrylamide (AA-Hb) and glycidamide (GA-Hb), and evaluating birth outcomes were included. We employed a random-effects model to assess the pooled effect estimates and their 95% confidence intervals (CI) for the association between acrylamide exposure and birth outcomes. Risk of Bias for Nutrition Observational Studies tool was used for bias assessment.
RESULTS
Out of 169 records identified, five original studies were eligible, including 53,870 mother-newborn pairs in total. Means were 21.9 μg/day for estimated dietary acrylamide exposure (3 studies), and 18.4 and 14.9 pmol/g for AA-Hb and GA-Hb, respectively (2 studies). Higher risk of SGA and lower birth weight and head circumference were observed in the highest quartile of AA-Hb [odds ratio (OR): 1.20 (95% CI: 1.08; 1.33); mean difference (MD): -131 g (95% CI: -204; -58) and -0.31 cm (95% CI: -0.58; -0.04), respectively], and GA-Hb [OR: 1.36 (95% CI: 1.13; 1.64), MD: -161 g (95% CI: -271; -52); and MD: -0.38 cm (95% CI: -0.66; -0.10), respectively], whereas a lower birth length was observed only in the highest quartile of GA-Hb (MD: -0.85 cm (95% CI: -1.38; -0.33). Results from the dose-response meta-analysis between increasing maternal acrylamide exposure during pregnancy and birth weight showed no clear evidence of a deviation from linearity.
CONCLUSIONS
Overall, our findings strengthen the evidence of an adverse effect of maternal acrylamide exposure during pregnancy on fetal growth. These results encourage to increase preventive actions towards lowering acrylamide exposure in the population.
Topics: Acrylamide; Animals; Birth Weight; Epidemiologic Studies; Female; Fetal Development; Hemoglobins; Humans; Infant, Newborn; Maternal Exposure; Pregnancy; Pregnancy Outcome
PubMed: 35724727
DOI: 10.1016/j.envres.2022.113705