• Journal of Chest Surgery
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• v.50 no.3
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• pp.153-162
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• 2017

Background: The mesenchymal-epithelial transition factor (MET) receptor can be overexpressed in solid tumors, including small cell lung cancer (SCLC). However, the molecular mechanism regulating MET stability and turnover in SCLC remains undefined. One potential mechanism of MET regulation involves the C-terminus of Hsp70-interacting protein (CHIP), which targets heat shock protein 90-interacting proteins for ubiquitination and proteasomal degradation. In the present study, we investigated the functional effects of CHIP expression on MET regulation and the control of SCLC cell apoptosis and invasion. Methods: To evaluate the expression of CHIP and c-Met, which is a protein that in humans is encoded by the MET gene (the MET proto-oncogene), we examined the expression pattern of c-Met and CHIP in SCLC cell lines by western blotting. To investigate whether CHIP overexpression reduced cell proliferation and invasive activity in SCLC cell lines, we transfected cells with CHIP and performed a cell viability assay and cellular apoptosis assays. Results: We found an inverse relationship between the expression of CHIP and MET in SCLC cell lines (n=5). CHIP destabilized the endogenous MET receptor in SCLC cell lines, indicating an essential role for CHIP in the regulation of MET degradation. In addition, CHIP inhibited MET-dependent pathways, and invasion, cell growth, and apoptosis were reduced by CHIP overexpression in SCLC cell lines. Conclusion: C HIP is capable of regulating SCLC cell apoptosis and invasion by inhibiting MET-mediated cytoskeletal and cell survival pathways in NCI-H69 cells. CHIP suppresses MET-dependent signaling, and regulates MET-mediated SCLC motility.

• Journal of Sensor Science and Technology
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• v.22 no.2
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• pp.144-149
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• 2013

In this research, we developed a biosensor to detect lung cancer-specific biomarker using Anodic Aluminum Oxide (AAO) chip based on interference and nano surface plasmon resonance (nanoSPR). The nano-porous AAO chip was fabricated $2{\mu}m$ of pore-depth by two-step anodizing method for surface uniformity. NanoSPR has sensitivity to the refractive index (RI) of the surrounding medium and also provides simple and label-free detection when specific antibodies are immobilized to the Au-deposited surface of nano-porous AAO chip. To detect the lung cancer-specific biomarker, antibodies were immobilized on the surface of the chip by Self Assembled Monolayer (SAM) method. Since then lung cancer-specific biomarker was applied atop the antibodies immobilized layer. The specific reaction of the antigen-antibody contributed to the change in the refractive index that cause shift of resonance spectrum in the interference pattern. The Limit of Detection (LOD) was 1 fg/ml by using our nano-porous AAO biosensor chip.

• Toxicological Research
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• v.20 no.2
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• pp.109-116
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• 2004

For the safety evaluation of adenovirus-mediated gene transfer, we investigated differential gene expressions after transfecting adenoviral vector containing p16 tumor suppressor gene (Ad5CMV-p16) into human non-small cell lung cancer cells. In the previous study, we showed adenovirus-mediated $p16^{INK4a}$ gene transfer resulted in significant inhibition of cancer cell growth. We investigated gene expression changes after transfecting Ad5CMV-p16, Ad5CMV (null type, a mock vector) into A549 cells by using cDNA chip and oligonucleotide microarray chip (1200 genes) which carries genes related with signal transduction pathways, cell cycle regulations, oncogenes and tumor suppressor genes. We found that $p16^{INK4a}$ gene transfer down regulated 5 genes (cdc2, cyclin D3, cyclin B, cyclin E, cdk2) among 26 genes involved in cell cycle regulations. Compared with serum-free medium treated cells, Ad5CMV-p16 changed 27 gene expressions, two fold or more on oligonucleotide chip. In addition, Ad5CMV-p16 did not seem to increase the tumorigenicity-related gene expression in A549 cells. Further studies will be needed to investigate the effect of Ad5CMV-p16 on normal human cells and tissues for safety evaluation.

• Journal of Biomedical Engineering Research
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• v.10 no.2
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• pp.151-156
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• 1989

Lung sound analyer which can provide an objective diagnosis of patients with pulmonary and bronchial disorders is designed. For the purpose of power spectrum analysis, adaptive digital filtering technique and TM - S320C25 DSP chip is used. As a results, adaptive lattice Wiener filter could eliminate heart sounds with a few of 10th order and on the distribution of power spectrum each patterns has shown in normal vescicular breathy from 100 Hz to 200 Hz, in crackle sound from 100 Hz to 400 Hz, in wheeze sound from 150 Hz to 600 Hz.

• Applied Chemistry for Engineering
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• v.29 no.6
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• pp.645-651
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• 2018

Lung cancer has the highest death rate of any cancer diseases in Koreans. However, patients often feel difficult to recognize their disease before facing the terminal diagnosis due to the absence of any significant symptoms. Furthermore, the clear detection of an early cancer stage is usually obscure with existing diagnostic methods. For this reason, extensive research efforts have been made on introducing a wide range of biochemical diagnostic tools for the molecular level analysis of biological fluids for lung cancer diagnoses. A chip-based biosensor, one type of the analytical devices, can be a great potential for the diagnosis, which can be used without any further expensive analytical equipments nor skilled analysts. In this mini review, we highlight recent research trends on searching biomarker candidates and bio-chip sensors for lung cancer diagnosis in addition to discussing their future aspects.

• Molecular & Cellular Toxicology
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• v.3 no.4
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• pp.306-313
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• 2007

The welding fume has been implicated as a causal agent in respiratory disease such as pneumoconiosis. The molecular mechanism by which welding fume induces toxicity in the lung is still unknown, but studies have focused on histological structure and indirect approach measuring the pulmonary damage markers. In the present study, gene expression profiles were analyzed in the lung of rats exposed by manual metal-arc stainless-steel (MMA-SS) welding fume for 30 days using Affymetrix GeneChip$^{(R)}$. Totally, 379 genes were identified as being either up- or down-regulated over 2-fold changes (P<0.01) in the lung of low- or high-dose group and were analyzed by using hierarchical clustering. We focused on genes involved in immune/inflammation responses were differentially regulated during lung injury induced by welding fume exposure. The information of these deregulated genes may contribute in elucidation of the inflammation mechanism during lung injury such as lung fibrosis.

• Journal of Life Science
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• v.34 no.5
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• pp.339-355
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• 2024

The pulmonary system is a highly complex system that can only be understood by integrating its functional and structural aspects. Hence, in vivo animal models are generally used for pathological studies of pulmonary diseases and the evaluation of inhalation toxicity. However, to reduce the number of animals used in experimentation and with the consideration of animal welfare, alternative methods have been extensively developed. Notably, the Organization for Economic Co-operation and Development (OECD) and the United States Environmental Protection Agency (USEPA) have agreed to prohibit animal testing after 2030. Therefore, the latest advances in biotechnology are revolutionizing the approach to developing in vitro inhalation models. For example, lung organ-on-a-chip (OoC) and organoid models have been intensively studied alongside advancements in three-dimensional (3D) bioprinting and microfluidic systems. These modeling systems can more precisely imitate the complex biological environment compared to traditional in vivo animal experiments. This review paper addresses multiple aspects of the recent in vitro modeling systems of lung OoC and organoids. It includes discussions on the use of endothelial cells, epithelial cells, and fibroblasts composed of lung alveoli generated from pluripotent stem cells or cancer cells. Moreover, it covers lung air-liquid interface (ALI) systems, transwell membrane materials, and in silico models using artificial intelligence (AI) for the establishment and evaluation of in vitro pulmonary systems.

• Toxicological Research
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• v.26 no.2
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• pp.137-147
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• 2010

Pulmonary fibrosis is a common consequence of many lung diseases and a leading cause of morbidity and mortality. The molecular mechanisms underlying the development of pulmonary fibrosis remain poorly understood. One model used successfully to study pulmonary fibrosis over the past few decades is the bleomycin-induced pulmonary fibrosis model. We aimed to identify the genes associated with fibrogenesis using an Affymetrix GeneChip system in a bleomycin-induced rat model for pulmonary fibrosis. To confirm fibrosis development, several analyses were performed, including cellular evaluations using bronchoalveolar lavage fluid, measurement of lactate dehydrogenase activity, and histopathological examinations. Common aspects of pulmonary fibrosis such as prolonged inflammation, immune cell infiltration, emergence of fibroblasts, and deposition of extracellular matrix and connective tissue elements were observed. Global gene expression analysis revealed significantly altered expression of genes ($\geq$ 1.5-fold, p < 0.05.) in a time-dependent manner during the development of pulmonary fibrosis. Our results are consistent with previous results of well-documented gene expression. Interestingly, the expression of triggering receptor expressed on myeloid cells 2 (Trem2), secreted phosphoprotein 1 (Spp1), and several proteases such as Tpsab1, Mcpt1, and Cma1 was considerably induced in the lung after bleomycin treatment, despite little evidence that they are involved in pulmonary fibrogenesis. These data will aid in our understanding of fibrogenic mechanisms and contribute to the identification of candidate biomarkers of fibrotic disease development.

• Applied Chemistry for Engineering
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• v.32 no.4
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• pp.461-466
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• 2021

In this article, a portable and cost-effective voltammetric biosensor with nanoparticles was developed for the measurements of heterogeneous nuclear ribonucleoprotein A1 protein (hnRNP A1) biomarker which can potentially be used for lung cancer diagnosis. Gold nanoparticles were first electrodeposited onto screen printed carbon electrode (SPCE) followed by immobilizing a single stranded DNA aptamer specific to hnRNP A1 onto the electrode surface. Ethanolamine was also used when immobilizing DNA aptamer on the surface to prevent signals from non-specific adsorption events. Sequential injection of hnRNP A1 biomarker and anti-hnRNP A1 conjugated with alkaline phosphatase (ALP) onto the aptamer chip surface allows to form the sandwich complex of DNA aptamer/hnRNP A1/ALP-anti-hnRNP A1 on the electrode surface which further reacted with 4-aminophenyl phosphate (APP). The electrocatalytic reaction of the enzyme, ALP, and the substrate, APP, resulting in the oxidative current response changes at -0.05 and -0.17 V (vs. Ag/AgCl) against the hnRNP A1 concentration was measured using cyclic and differential pulse voltammetry, respectively. The Au nanoparticles-integrated voltammetric biosensor was applied to analyze human normal serum solutions possibly suggesting potential applicability for lung cancer diagnosis.

• Asian-Australasian Journal of Animal Sciences
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• v.28 no.2
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• pp.166-170
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• 2015

Foot-and-mouth disease (FMD) is a highly contagious disease affecting cloven-hoofed animals and causes severe economic loss and devastating effect on international trade of animal or animal products. Since FMD outbreaks have recently occurred in some Asian countries, it is important to understand the relationship between diverse immunogenomic structures of host animals and the immunity to foot-and-mouth disease virus (FMDV). We performed genome wide association study based on high-density bovine single nucleotide polymorphism (SNP) chip for identifying FMD resistant loci in Holstein cattle. Among 624532 SNP after quality control, we found that 11 SNPs on 3 chromosomes (chr17, 22, and 15) were significantly associated with the trait at the p.adjust <0.05 after PERMORY test. Most significantly associated SNPs were located on chromosome 17, around the genes Myosin XVIIIB and Seizure related 6 homolog (mouse)-like, which were associated with lung cancer. Based on the known function of the genes nearby the significant SNPs, the FMD resistant animals might have ability to improve their innate immune response to FMDV infection.