Significance of EGFR investigation in odontogenic keratocyst: a narrative review.

BACKGROUND: The recent classification of odontogenic keratocysts (OKSs) recognized them as benign neoplasms, although previous findings have revealed their aggressive nature. Immunohistochemical and molecular analyses have investigated OKSs, but the role of epidermal growth factor receptor (EGFR) has not been fully investigated, despite the importance of this oncogene in the process of carcinogenesis in tumors of epithelial origin. The EGFR protein is usually overexpressed, and the EGFR gene is mutated or amplified. AIMS OF STUDY: This brief review aims to emphasize the importance of EGFR detection in these types of cysts. METHODS AND RESULTS: It was revealed that the majority of the studies examined EGFR protein expression using immunohistochemical methods; however, considering EGFR gene variants, mutations were less explored in the previous period from 1992 to 2023. Although EGFR gene polymorphisms are clinically important, they were not identified in the present study. CONCLUSIONS: In light of the current significance of EGFR variants, it would be beneficial to examine them in odontogenic lesions. This would enable resolving of discrepancies about their nature, and potentially enhance classifications OKCs in the future.

Analyses of P16INK4a gene promoter methylation relative to molecular, demographic and clinical parameters characteristics in non-small cell lung cancer patients: A pilot study.

BACKGROUND: The aim of this study was to examine the methylation status of p16INK4a promoter region in non small cell lung cancer (NSCLC) patients and their associations with single nucleotide polymorphisms (SNPs) of the epidermal growth factor receptor (EGFR) gene, as well as with demographic or clinical characteristics. METHODS: Formalin-fixed and paraffin-embedded (FFPE) DNA samples extracted from 22 NSCLC patients were analyzed with methylation-specific polymerase chain reaction (PCR) method to obtain promoter methylation profile. The same cohort was genotyped for - 216G > T, -191 C > A, and 181,946 C > T EGFR SNPs. RESULTS: There was a significant association between methylated p16INK4a in patients prior therapy (p = 0.017) since a significantly higher frequency of methylated p16INK4a was detected in these patients (40.9%) in comparison to frequency in patients after therapy (31.8%). Also, a higher frequency of methylated p16INK4a was detected among patients with leucopenia (p = 0.056). No associations were observed between the methylation status of the p16INK4a promoter region and EGFR SNPs or other clinical and demographic data in this cohort. CONCLUSION: High frequency of methylation of the p16INK4a gene promoter was observed in NSCLC patients prior therapy and with leucopenia that can indicate their significance related to advanced clinical stage.

Application of the conventional and novel methods in testing EGFR variants for NSCLC patients in the last 10 years through different regions: a systematic review.

Variants in the epidermal growth factor receptor (EGFR) gene are recognized as predictors of therapy response and are correlated with progression-free and overall survival in non-small cell lung cancer (NSCLC) patients. Molecularly guided therapy needs precise and cost-effective molecular tests. This review focused primarily on screening or target methods for the EGFR variants detection with diagnostic and prognostic potential in the clinical research published papers. Concerning the inclusion and exclusion criteria, the search interval comprised available articles published from 2010 until 2020 in three electronic databases, ISI Web of Science, Pub Med, and Scopus. The analysis of eligible studies started with 5647 and obtained the final 987 full-text articles analyzed as clinical research. The regions comprised were Africa, America, Australia, Asia, Euro-Asia, Europe, or a consortium of different countries. All of the tested methods were applied prevalently in Asia. In clinical research, the polymerase chain reaction (PCR), followed by sequencing methods have been involved mostly over the years. The identified high-through output approaches evolved to improve the survival and quality of the NSCLC patient's life becoming more sensitive, specific, and cost-effective.

Incorporation of cellulose fiber in glass ionomer cement.

This study investigated the effect of discontinuous cellulose microfibers with various loading fractions on selected physical properties of glass polyalkenoate (glass ionomer) cement (GIC). Fiber-reinforced GIC (Exp-GIC) was prepared by adding discontinuous cellulose microfiber (with an average length of 500 µm) at various mass ratios (1, 2, 3, 4, and 5 mass%) to the powder of conventional GIC (GC Fuji IX) using a high-speed mixing device. Fracture toughness, work of fracture, and compressive strength were determined for each experimental and control material. The specimens (n = 6) were wet stored (37°C for 1 d) before testing. A scanning electron microscope equipped with an energy dispersive spectroscope was used to examine the surface of fibers after treatment with cement liquid. Data were analyzed using ANOVA. The Exp-GIC (5 mass%) specimen had statistically significantly higher fracture toughness (0.9 MPa.m1/2 ) than unreinforced material (0.4 MPa.m1/2 ). On the other hand, Exp-GIC with 1 mass% displayed the highest compressive strength (116 MPa) among all tested groups. The use of discontinuous cellulose microfibers with conventional GIC matrix considerably increased the toughening performance compared with the particulate GICs used.

Distribution of EGFR SNPs -191C/A and 181946G/A in patients with lung cancer depending on smoking status in the Republic of Srpska, Bosnia and Herzegovina.

PURPOSE: To analyze the frequencies of two single nucleotide polymorphisms (SNPs) of EGFR gene, -191C/A and 181946G/A, among lung cancer patients from the Republic of Srpska, Bosnia and Hercegovina, as well as to assess the association of SNP genotypes with the cancer type and other demographic characteristics of patients, particularly with the smoking status. METHODS: This study enrolled 41 lung cancer patients from the territory of Republic Srpska, Bosnia and Herzegovina. Detection EGFR SNPs was performed using PCR-RFLP methodology. PCR was performed on 2720 Thermal Cycler (Applied Biosystems, United States). PCR, as well as RFLP products, were detected by gel electrophoresis. SPSS-17 software (SPSS, Inc.) was used for statistical analyses. RESULTS: There was significantly more male than female smokers in our cohort (p=0.006). In addition, the proportion of smokers was higher among patients with adenocarcinoma in comparison to patients with other lung cancer types (p=0.044). Adenocarcinoma was less common in patients older than 64 years (p=0.035). The wild type homozygous genotype of both SNPs was the most frequent genotype in all the tested demographic groups. Using dominant genetic model for -191C/A SNP, we observed statistically significant association of -191CC genotype and adenocarcinoma (p=0.043) in the subgroup of patients younger than 64 years. Namely, patients younger than 64 years and carriers of -191CC genotype had higher risk (odds ratio/OR=9.6; 95% confidence interval/CI= 0.8477 to 108.7214) for adenocarcinoma than the ones carrying -191CA or -191AA genotype. CONCLUSIONS: Patients younger than 64 years and carriers of -191CC genotype have significantly higher risk for adenocarcinoma than carriers of -191CA or -191AA genotype. Further studies on larger cohorts are necessary to evaluate -191C/A SNP as a potential biomarker.

Frequencies of EGFR single nucleotide polymorphisms in non-small cell lung cancer patients and healthy individuals in the Republic of Serbia: a preliminary study.

The purpose of this study was to determine the frequencies of EGFR -216G>T, -191C>A, and 181946C>T in Serbian non-small cell lung cancer (NSCLC) patients, as well as to compare it with healthy individuals, in order to assess their potential importance for lung cancer in Serbia. The study involved 56 NSCLC patients and 53 unrelated healthy volunteers, and genotyping was performed on DNA samples obtained from formalin-fixed paraffin-embedded lung tumor tissue and blood, respectively. This was the first time to show genotype frequencies of those single nucleotide polymorphisms for this study group from the territory of the Republic of Serbia. There was very strong evidence of association between age and death due to lung cancer (Pearson chi-square = 43.439, df = 2, p < 0,001), as well as between ever smoking and death due to lung cancer (Pearson chi-square = 31.727, df = 1, p < 0.001). When dominant genetic model (GG vs. GT+TT) was used for -216G>T, we have found significant association (p = 0.012) between -216GG genotype and NSCLC patients within smokers' subgroup. So, carriers of -216GG genotype had higher risk (OR = 4.33, 95 % CI = 1.324-14.179) than noncarriers (GT and TT) for developing non-small cell lung cancer in our patients.

Optimization of PCR conditions for amplification of GC-Rich EGFR promoter sequence.

BACKGROUND: Polymerase chain reaction (PCR) is an extremely sensitive method that often demands optimization, especially when difficult templates need to be amplified. The aim of the present study was to optimize the PCR conditions for amplification of the epidermal growth factor receptor (EGFR) promoter sequence featuring an extremely high guanine-cytosine (GC) content in order to detect single nucleotide polymorphisms -216G>T and -191C>A. METHODS: Genomic DNA used for amplification was extracted from formalin-fixed paraffin-embedded lung tumor tissue and PCR products were detected by agarose gel electrophoresis. RESULTS: Results showed that addition of 5% dimethyl sulfoxide (DMSO), as well as DNA concentration in PCR reaction of at least 2 µg/ml, were necessary for successful amplification. Due to high GC content, optimal annealing temperature was 7°C higher than calculated, while adequate MgCl2 concentration ranged from 1.5 to 2.0 mM. CONCLUSION: In conclusion, EGFR promoter region is a difficult PCR target, but it could be amplified after optimization of MgCl2 concentration and annealing temperature in the presence of DMSO and the DNA template of acceptable concentration.

Side effects of tyrosine kinase inhibitors therapy in patients with non-small cell lung cancer and associations with EGFR polymorphisms: A systematic review and meta-analysis.

Rash and diarrhea are common side effects of tyrosine kinase inhibitor (TKI) therapy administered to patients with non-small cell lung cancer (NSCLC). The polymorphisms of the epidermal growth factor receptor (EGFR) gene may be a potential predictor of these side effects. The aim of the present meta-analysis was to examine the association of EGFR polymorphisms and TKI-associated toxicities. Electronic databases (PubMed, Scopus and ISI Web of Science) were searched for relevant studies. According to the inclusion and exclusion criteria, a search of the databases identified 4,918 results, among which 6 clinical trials were obtained with 1,318 patients with NSCLC. A total of 9 EGFR single nucleotide polymorphisms (SNPs) associated with TKI toxicity were identified including, rs11568315, rs712829, rs712830, rs2227983, rs2075102, rs2293347, rs11977388, rs4947492 and rs884225. The data associated with skin toxicity from rs11568315, rs712829 and rs712830 were analyzed in the present meta-analysis. Data from rs11568315 were also analyzed in relation to diarrhea. Among all the examined SNPs, statistically significant results were obtained under the dominant genetic model for CA repeats in rs11568315 (SS vs. SL+LL) with skin toxicity. The long CA repeat (SL+LL) carriers were more likely to experience skin toxicity associated with TKIs (P=0.005). By contrast, there was no significant result for diarrhea (P=0.661) under dominant genetic model for CA repeats.

Lipid peroxidative damage on Cisplatin exposure and alterations in antioxidant defense system in rat kidneys: a possible protective effect of selenium.

Cisplatin (Cis-diamminedichloroplatinum II, CP) is an important chemotherapeutic agent, useful in the treatment of several cancers, but with several side effects such as nephrotoxicity. The present study investigated the possible protective effect of selenium (Se) against CP-induced oxidative stress in the rat kidneys. Male Wistar albino rats were injected with a single dose of cisplatin (7 mg CP/kg b.m., i.p.) and selenium (6 mg Se/kg b.m, as Na(2)SeO(3), i.p.), alone or in combination. The obtained results showed that CP increased lipid peroxidation (LPO) and decreased reduced glutathione (GSH) concentrations, suggesting the CP-induced oxidative stress, while Se treatment reversed this change to control values. Acute intoxication of rats with CP was followed by statistically significant decreased activity of antioxidant defense enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR) and glutathione-S-transferase (GST). Treatment with Se reversed CP-induced alterations of antioxidant defense enzyme activities and significantly prevented the CP-induced kidney damage.

EGFR Polymorphism and Survival of NSCLC Patients Treated with TKIs: A Systematic Review and Meta-Analysis.

Tyrosine kinase inhibitor- (TKI-) based therapy revolutionized the overall survival and the quality of life in non-small-cell lung cancer (NSCLC) patients that have epidermal growth factor receptor (EGFR) mutations. However, EGFR is a highly polymorphic and mutation-prone gene, with over 1200 single nucleotide polymorphisms (SNPs). Since the role of EFGR polymorphism on the treatment outcome is still a matter of debate, this research analyzed the available literature data, according to the PRISMA guidelines for meta-analyses. Research includes PubMed, Scopus, ISI Web of Science, and 14 of genome-wide association studies (GWAS) electronic databases in order to provide quantitative assessment of the association between ten investigated EGFR SNPs and the survival of NSCLC patients. The pooled HR and their 95% CI for OS and PFS for different EGFR polymorphisms using a random or fixed effect model based on the calculated heterogeneity between the studies was applied. The longest and the shortest median OSs were reported for the homozygous wild genotype and a variant allele carriers for rs712829 (-216G>T), respectively. Quantitative synthesis in our study shows that out of ten investigated EGFR SNPs (rs11543848, rs11568315, rs11977388, rs2075102, rs2227983, rs2293347, rs4947492, rs712829, rs712830, and rs7809028), only four, namely, rs712829 (-216G>T), rs11568315 (CA repeat), rs2293347 (D994D), and rs4947492, have been reported to affect the outcome of TKI-based NSCLC treatment. Of these, only -216G>T and variable CA repeat polymorphisms have been confirmed by meta-analysis of available data to significantly affect OS and PFS in gefitinib- or erlotinib-treated NSCLC patients.

Epidermal Growth Factor Receptor Gene in Non-Small-Cell Lung Cancer: The Importance of Promoter Polymorphism Investigation.

Recently, epidermal growth factor receptor (EGFR) was a key molecule in investigation of lung cancer, and it was a target for a new therapeutic strategy, based on molecular analyses. In this review, we have summarized some issues considering the role of EGFR in lung cancer, its coding gene, and its promoter gene polymorphisms (SNPs) -216G/T and -191C/A in non-small-cell lung cancer (NSCLC). The position of the SNPs indicates their significant role in EGFR regulation. The accumulation of knowledge regarding SNPs lately suggests their significant and important role in the onset of carcinogenesis, the prediction of the onset of metastases, the response to therapy with TKI inhibitors, and the onset of toxic effects of the applied therapy. Based on this, we suggest further studies of the relationship of clinical significance to SNPs in patients with lung tumors.

Cellulose Fibre-Reinforced Biofoam for Structural Applications.

Traditionally, polymers and macromolecular components used in the foam industry are mostly derived from petroleum. The current transition to a bio-economy creates demand for the use of more renewable feedstocks. Soybean oil is a vegetable oil, composed mainly of triglycerides, that is suitable material for foam production. In this study, acrylated epoxidized soybean oil and variable amounts of cellulose fibres were used in the production of bio-based foam. The developed macroporous bio-based architectures were characterised by several techniques, including porosity measurements, nanoindentation testing, scanning electron microscopy, and thermogravimetric analysis. It was found that the introduction of cellulose fibres during the foaming process was necessary to create the three-dimensional polymer foams. Using cellulose fibres has potential as a foam stabiliser because it obstructs the drainage of liquid from the film region in these gas-oil interfaces while simultaneously acting as a reinforcing agent in the polymer foam. The resulting foams possessed a porosity of approximately 56%, and the incorporation of cellulose fibres did not affect thermal behaviour. Scanning electron micrographs showed randomly oriented pores with irregular shapes and non-uniform pore size throughout the samples.

Effects of DMSO, glycerol, betaine and their combinations in detecting single nucleotide polymorphisms of epidermal growth factor receptor (EGFR) gene promoter sequence in non-small-cell lung cancer (NSCLC) patients.

The aim of the study was to examine the effects of frequently used polymerase chain reaction (PCR) additives DMSO, glycerol and betaine on amplification of GC-rich epidermal growth factor receptor (EGFR) gene promoter region, in order to detect the presence of -216G>T and -191C>A gene variations in non-small-cell lung cancer (NSCLC) patients. PCR products and restriction fragments were detected by electrophoresis on 8% polyacrylamide gel and 3% agarose gel. Our analysis shows that single used additives including DMSO in concentration of 7% and 10%, glycerol in concentration of 10%, 15% and 20%, as well as betaine in concentration of 1M, 1.5M and 2M significantly enhanced the yield and specificity of PCR reaction. In addition, the combination of 10% DMSO with 15% glycerol has shown positive effects, whereas other analyzed combinations of additives failed to amplify the EGFR promoter region.

Evaluation of current methods to detect the mutations of epidermal growth factor receptor in non-small cell lung cancer patients.

Many different methods were developed to detect commonly known mutations and to screen new mutations of the epidermal growth factor receptor in non-small cell lung cancer patients. Some of these methods are so sensitive as to be able to detect even one epidermal growth factor receptor mutant tumor cell among up to 1000-2000 normal cells. We have considered current methods chronologically reported to detect mutations in epidermal growth factor receptor in patients with non-small cell lung cancer. We also gave a short preview of their significance for routine clinical works. A Pub Med literature search was performed in order to demonstrate what methods are mostly used in mutation detection and to show their distribution through the last 10 years.

Cholecystokinin-producing (I) cells of intestinal mucosa in dexamethasone-treated rats.

The aim of this study was to investigate the morphological, immunohistochemical and ultrastructural changes of cholecystokinin-producing (I) cells of gastrointestinal mucosa in dexamethasone-treated rats (D). After 12-daily intraperitoneal administration of 2mg/kg dexamethasone, rats developed diabetes similar to human diabetes mellitus type 2. The mean diameter of the duodenum was significantly decreased due to significant reduction of volume fraction and profile area of lamina propria. There was a decrease in volume fraction and number of cholecystokinin (CCK)-producing cells per mm(2) of mucosa, as well as their numerical density, but without statistical significance. Also, dexamethasone induced appearance of hyperactive duodenal I-cells with small number of granules and dilated endoplasmic reticulum. In conclusion, the present study showed that morphological changes in duodenum cholecystokinin-producing (I) cells occurred in diabetic rats, in a manner which, suggests compensatory effort of CCK cells in diabetic condition.