scholarly journals Aluminosilicate Nanocomposite on Genosensor: A Prospective Voltammetry Platform for Epidermal Growth Factor Receptor Mutant Analysis in Non-small Cell Lung Cancer

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Santheraleka Ramanathan ◽  
Subash C. B. Gopinath ◽  
M. K. Md Arshad ◽  
Prabakaran Poopalan ◽  
Periasamy Anbu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Egfr Mutation ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Single Base ◽  
Base Pair Mismatch ◽  
Epidermal Growth ◽  
Single Base Pair

AbstractLung cancer is one of the most serious threats to human where 85% of lethal death caused by non-small cell lung cancer (NSCLC) induced by epidermal growth factor receptor (EGFR) mutation. The present research focuses in the development of efficient and effortless EGFR mutant detection strategy through high-performance and sensitive genosensor. The current amplified through 250 µm sized fingers between 100 µm aluminium electrodes indicates the voltammetry signal generated by means of the mutant DNA sequence hybridization. To enhance the DNA immobilization and hybridization, ∼25 nm sized aluminosilicate nanocomposite synthesized from the disposed joss fly ash was deposited on the gaps between aluminium electrodes. The probe, mutant (complementary), and wild (single-base pair mismatch) targets were designed precisely from the genomic sequences denote the detection of EGFR mutation. Fourier-transform Infrared Spectroscopy analysis was performed at every step of surface functionalization evidences the relevant chemical bonding of biomolecules on the genosensor as duplex DNA with peak response at 1150 cm−1 to 1650 cm−1. Genosensor depicts a sensitive EGFR mutation as it is able to detect apparently at 100 aM mutant against 1 µM DNA probe. The insignificant voltammetry signal generated with wild type strand emphasizes the specificity of genosensor in the detection of single base pair mismatch. The inefficiency of genosensor in detecting EGFR mutation in the absence of aluminosilicate nanocomposite implies the insensitivity of genosensing DNA hybridization and accentuates the significance of aluminosilicate. Based on the slope of the calibration curve, the attained sensitivity of aluminosilicate modified genosensor was 3.02E-4 A M−1. The detection limit of genosensor computed based on 3σ calculation, relative to the change of current proportional to the logarithm of mutant concentration is at 100 aM.

A multicenter, open label, randomized phase II study of osimertinib plus ramucirumab versus osimertinib alone as initial chemotherapy for EGFR mutation-positive non-squamous non-small cell lung cancer: TORG1833.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS9120-TPS9120 ◽  
Author(s):  
Yoshiro Nakahara ◽  
Terufumi Kato ◽  
Reiko Isomura ◽  
Nobuhiko Seki ◽  
Naoki Furuya ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Egfr Mutation ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Epidermal Growth ◽  
Nsclc Patients

TPS9120 Background: Vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) pathways are shown to be interrelated in several preclinical studies. Furthermore, recent clinical studies have shown the adding effect of an anti VEGF monoclonal antibody with an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for the non-small-cell lung cancer (NSCLC) patients with EGFR mutation. Thus, osimertinib plus ramucirumab would be the promising candidate for the new standard treatment in EGFR mutation positive NSCLC. Methods: This study is an investigator initiated trial. Previously untreated EGFR mutation positive advanced non squamous NSCLC patients aged 20 years or older with a performance status of 0 or 1 are randomized at a 1:1 ratio to receive osimertinib (80mg) every day either without or with ramucirumab (10mg/kg) every 2 weeks until evidence of disease progression or development of unacceptable toxicity. The primary endpoint of the study is progression free survival (PFS) assessed by the central image reviewer. Secondly endpoints include PFS (assessed by an attending physician), objective response rate (ORR), disease control rate (DCR), duration of response (DOR), overall survival (OS), safety and toxicity profile. Stratification factors are gender and the type of EGFR mutation (exon 19 deletion, Leu858Arg point mutation in exon 21). We determined that, with a sample size of 120 patients (60 in each arm), the trial will have 80% power to show a hazard ratio for disease progression or death of 0.667 at a one-sided alpha level of 0.2 (as calculated on the basis of 80 such events) for comparison between the two arms with 1.5-year accrual and 2-year follow-up periods. Study enrollment began in November 2018 and is continued for 3.5 years among 20 sites of Thoracic Oncology Research Group (TORG). Seven patients were enrolled at time of submission. Clinical trial information: 184146.

scholarly journals The Role of Mutation Status of the Epidermal Growth Factor Receptor Gene In Advanced Non–Small Cell Lung Cancer

Medicina ◽  
2012 ◽  
Vol 48 (4) ◽  
pp. 25 ◽  
Author(s):  
Neringa Vagulienė ◽  
Marius Žemaitis ◽  
Valdas Šarauskas ◽  
Astra Vitkauskienė ◽  
Skaidrius Miliauskas
Keyword(s):  
Lung Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Egfr Mutation ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Positive Group ◽  
Epidermal Growth ◽  
Never Smokers

Objective. The aim of this study was to examine the prevalence of epidermal growth factor receptor (EGFR) gene mutations among patients with advanced nonsquamous non–small cell lung cancer (NSCLC) treated in our institution and to evaluate the associations between EGFR mutations and clinicopathological characteristics. Materials and Methods. A total of 103 patients with NSCLC were examined from April 2010 to September 2011. The patients were screened for EGFR mutations in exons 19 and 21 using sequence analysis. Results. EGFR mutations were detected in 10 patients (9.71%): 23.1% of women and 5.2% of men (P<0.05), 31.8% of never-smokers and 4.7% of smokers (P<0.05), and 12.3% of patients with adenocarcinomas and 6.25% of patients with large cell carcinomas (P>0.05). Eight mutations (80.0%) were found in exon 21: 7 patients had the L858R mutation and 1 patient had the L861G mutation. Two mutations (20.0%) were found in exon 19: 1 patient had the L747-A748 deletion and 1 patient had the L747-A750insE deletion. The overall response rate was significantly greater in the EGFR mutation-positive group than in the EGFR mutation-negative or control groups (P<0.05). The median progression-free survival in the EGFR mutation-negative group and the control group that received systemic standard chemotherapy was 5.6 months (95% CI, 4.3 to 7.0) and 5.3 months (95% CI, 4.9 to 5.7), respectively, but it was not achieved in the EGFR mutation-positive group that received EGFR tyrosine kinase inhibitors (P<0.05). Conclusions. The frequency of EGFR mutations in our patients with nonsquamous NSCLC was found to be similar to that reported in Europe. EGFR mutations were more frequent in women and never-smokers

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