Real-world experience of first-line afatinib in patients with EGFR-mutant advanced NSCLC: a multicenter observational study

Background: This study aimed to evaluate the efficacy, side-effects and resistance mechanisms of first-line afatinib in a real-world setting. Methods: This is a multicenter observational study of first-line afatinib in Malaysian patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small cell lung cancer (NSCLC). Patients’ demographic, clinical and treatment data, as well as resistance mechanisms to afatinib were retrospectively captured. The statistical methods included Chi-squared test and independent t-test for variables, Kaplan-Meier curve and log-rank test for survival, and Cox regression model for multivariate analysis. Results: Eighty-five patients on first-line afatinib from 1st October 2014 to 30th April 2018 were eligible for the study. EGFR mutations detected in tumors included exon 19 deletion in 80.0%, exon 21 L858R point mutation in 12.9%, and rare or complex EGFR mutations in 7.1% of patients. Among these patients, 18.8% had Eastern Cooperative Oncology Group performance status of 2–4, 29.4% had symptomatic brain metastases and 17.6% had abnormal organ function. Afatinib 40 mg or 30 mg once daily were the most common starting and maintenance doses. Only one-tenth of patients experienced severe side-effects with none having grade 4 toxicities. The objective response rate was 76.5% while the disease control rate was 95.3%. At the time of analysis, 56 (65.9%) patients had progression of disease (PD) with a median progression-free survival (mPFS) of 14.2 months (95% CI, 11.85–16.55 months). Only 12.5% of the progressed patients developed new symptomatic brain metastases. The overall survival (OS) data was not mature. Thirty-three (38.8%) patients had died with a median OS of 28.9 months (95% CI, 19.82–37.99 months). The median follow-up period for the survivors was 20.0 months (95% CI, 17.49–22.51 months). Of patients with PD while on afatinib, 55.3% were investigated for resistance mechanisms with exon 20 T790M mutation detected in 42.0% of them. Conclusions: Afatinib is an effective first-line treatment for patients with EGFR-mutant advanced NSCLC with a good response rate and long survival, even in patients with unfavorable clinical characteristics. The side-effects of afatinib were manageable and T790 M mutation was the most common resistance mechanism causing treatment failure

STUDY OF ELECTROCHEMICAL POLYMERIZATION OF THIOPENE AND THIOPHENE-3-ACETIC ACID AND THEIR APPLICATIONS AS CHEMICAL PROBES FOR ANALYSIS

Master'sMASTER OF SCIENC

Alcohol Dehydrogenase Biosensor based on Poly (Aniline)-Poly (Vinylsulfonate) modified electrode and enhancement effect of CA2+ ions on the Electrocatalytic oxidation of NADH at Poly(Aniline)-Poly (Vinylsulfonate) and Poly (Aniline)-Poly (Styrenesulfonate) modified Electrodes

A membrane enzyme electrode sensitive towards ethanol was fabricated based on poly(aniline)-poly(vinylsulfonate) modified electrodes. Using the membrane electrode design and by varying the physical parameters, we established that the membrane enzyme electrode current response was consistent with a reversible enzyme kinetic model. Under conditions in which the product concentration was negligible within the enzyme layer of the enzyme electrode, the substrate-dependent current response could be described using a coupled reaction-diffusion model based on irreversible enzyme kinetics. This is the first report on the use of poly(aniline) modified electrodes as amperoraetric biosensors for the detection of ethanol. In the second part of this work, we investigated the enhancement of steady-state current towards NADH at poly(aniline)-poly(vinylsulfonate) and poly(aniline)- poly(styrenesulfonate) modified electrodes in the presence of calcium ions, using electrochemical methods, ^'P NMR and kinetic modelling. We observed reversible binding between Ca^^ and poly(aniline)-poly(vinylsulfonate) from cyclic voltammetry and steady- state experiments. The enhancement of electrocatalytic current towards NADH in the presence of between 20 and 40 mM Ca^^ were about 12 and 27 times for thin films of poly(aniline)-poly(vinylsulfonate) and poly(aniline)-poly(styrenesulfonate), respectively. This enhancement effect of Ca^^ ions on the electrocatalytic oxidation of NADH at poly(aniline) modified electrodes was much greater than those observed by workers using other mediators. From kinetic modelling of the experimental data, we found that the enhancement effect of Ca^^ ions was due to a large change in the polymer binding affinity for NADH or partitioning of NADH into the polymer film. The binding energy gain was estimated to be about 14 kJ m o f' in the presence of 25 mM Ca^^. This was confirmed by measurements using solid state ^'P NMR which indicated that NADH accumulated in the polymer film only in the presence of Ca^^.</p

Impedimetric DNA biosensor based on a nanoporous alumina membrane for the detection of the specific oligonucleotide sequence of dengue virus

A novel and integrated membrane sensing platform for DNA detection is developed based on an anodic aluminum oxide (AAO) membrane. Platinum electrodes (~50–100 nm thick) are coated directly on both sides of the alumina membrane to eliminate the solution resistance outside the nanopores. The electrochemical impedance technique is employed to monitor the impedance changes within the nanopores upon DNA binding. Pore resistance (Rp) linearly increases in response towards the increasing concentration of the target DNA in the range of 1 × 10−12 to 1 × 10−6 M. Moreover, the biosensor selectively differentiates the complementary sequence from single base mismatched (MM-1) strands and non-complementary strands. This study reveals a simple, selective and sensitive method to fabricate a label-free DNA biosensor.Published versio

Electrochemical amplification strategies in DNA nanosensors

Electrochemical DNA nanosensors exploit the intrinsic property of ssDNA to hybridize to its complementary sequence and this selective hybridization event can be translated into detectable electrochemical signals following electrochemical amplification. This review describes some of the advanced electrochemical signal amplification strategies in DNA detection relying on specific sequence hybridization with focus on electro-active intercalating reagents, primary and secondary reporter DNA probes and 'de-amplification' of signals derived from nanopores and nanochannels. These amplification strategies elegantly achieve extremely low detection limits of pico- to femtomolarity concentration and zeptomolar amount of DNAs and high specificity responses without the use of multi-step polymerase chain reaction (PCR) procedures or high sensitivity instrumentation

Novel biosensing methodologies for ultrasensitive detection of viruses

Various infectious diseases caused by the spread of viruses create adverse implications on global biosecurity. Increasing demands for virus surveillance and effective control of the spread of diseases reveal the need for rapid and sensitive virus diagnostic devices. Due to the remarkable sensitivity and specificity of biosensors, they appear as a potential and promising tool for accurate and quantitative detection of viruses. Furthermore, recent advancements in transduction systems, nanotechnology and genetic engineering offer various strategies to improve the detection performance of biosensors. This review presents an overview of the current states of novel biosensing methodologies for the ultrasensitive detection of viruses with highly promising applications for future disease diagnosis. Additionally, a brief summary of the recent state-of-the-art virus diagnostic molecular technologies is included.ASTAR (Agency for Sci., Tech. and Research, S’pore

Electrochemical nanoporous alumina membrane-based label-free DNA biosensor for the detection of Legionella sp

An electrochemical nanoporous alumina membrane-based label free DNA biosensor is developed using 5′-aminated DNA probes immobilized into the nanochannels of alumina. Alumina nanoporous membrane-like structure is carved over platinum wire electrode of 76 μm diameter dimension by electrochemical anodization. The hybridization of complementary target DNA with probe DNA molecules attached inside the nanochannels influences the pore size and ionic conductivity. Electrochemical biosensing signal is derived from only redox species Fe(CN)64− across single wire Pt electrode. The biosensors sensing mechanism relies on the monitoring of electrode's Faradaic current response toward redox species, Fe(CN)64−, which is sensitive toward the hybridization of complementary target with probe DNA immobilized into the alumina nanochannels. The biosensor demonstrates wide linear range over 7 orders of magnitude with ultrasensitive detection limit 3.1×10−13 M for the quantification of ss 21mer DNA sequence and selectively differentiates the complementary sequence from target sequences with single base mismatch (MM1) and triple bases mismatch (MM3) of different strain of Legionella sp. Its applicability is also challenged against real time Legionella pneumophila genomic DNA sample derived from the asymmetric PCR method

Self-powering amperometric sensor and biosensor

A unique Prussian blue nanotubes sensor using a two-compartment cell derives the current signal from the chemical energy of the hydrogen peroxide analyte, without input of electrical potentials, is described. The Prussian blue reduces hydrogen peroxide and is itself reduced by electron flow from the counter reaction at the auxiliary electrode. The concentrations of the Prussian blue (PB) and Everitt’s salt (ES) forms of the Prussian blue are maintained at steady-state values, by the hydrogen peroxide reduction and the galvanic cell reaction. This strategy gives low detection limit of 0.1 μM H2O2 with linear range up to 80 μM and is further demonstrated in a model glucose biosensor. The simple design to reduce energy usage opens up the study of amperometricsensor development by selecting anodic and cathodic reactions with suitable thermodynamic potentials with consideration of reactions at the sensing and auxiliary electrodes modified with appropriate mediators or enzymes

Evaluation of the fuzzy ARTMAP neural network using off-line and on-line learning strategies

This paper describes an experimental study of the Fuzzy ARTMAP (FAM) neural network as an autonomous learning system for pattern classification tasks. A benchmark database of radar signals from ionosphere has been employed for the system to classify arbitrary sequences of pattern into distinct categories. A number of simulations have been conducted systematically to evaluate the applicability and usefulness of FAM in this context. First, we identify the \u27optimum\u27 parameter settings of FAM for the problem at hand, and investigate the effects of different training schemes and learning rules on classification results, using an off-line learning methodology. We then examine a voting strategy to improve classification accuracy by combining results from multiple FAM classifiers. In addition to off-line learning, we evaluate the prospect of using FAM as an autonomously learning pattern classification system for on-line, non-stationary environments. The performance of FAM is comparable with other reported results, but with the added advantage of on-line and incremental learning

A dual K+-Na+ selective prussian blue nanotubes sensor

A strategy for dual sensing of Na+ and K+ ions using Prussian blue nanotubes via selective inter/deintercalation of K+ ion and competitive inhibition by Na+ ion, is reported. The analytical signal is derived from the cyclic voltammetry cathodic peak position Epc of Prussian blue nanotubes. Na+ and K+ levels in a sample solution can be determined conveniently using one Prussian blue nanotubes sensor. In addition, this versatile method can be applied for the analysis of single type of either Na+ or K+ ions. The dual-ion sensor response towards Na+ and K+ can be described using a model based on the competitive inhibition effects of Na+ on K+ inter/deintercalation in Prussian blue nanotubes. Successful application of the Prussian blue nanotubes sensor for Na+ and K+ determination is demonstrated in artificial saliva.Accepted versio