Discrimination of Lung Cancer and Benign Lung Diseases Using BALF Exosome DNA Methylation Profile.

Benign lung diseases are common and often do not require specific treatment, but they pose challenges in the distinguishing of them from lung cancer during low-dose computed tomography (LDCT). This study presents a comprehensive methylation analysis using real-time PCR for minimally invasive diagnoses of lung cancer via employing BALF exosome DNA. A panel of seven epigenetic biomarkers was identified, exhibiting specific methylation patterns in lung cancer BALF exosome DNA.

A prospective phase 2 study of expeditious genotyping and immediate therapeutic initiation through extracellular vesicles (EV)-based bronchoalveolar lavage fluid (BALF) liquid biopsy in advanced NSCLC patients.

Background: In our previous study, epidermal growth factor receptor () genotyping using extracellular vesicles (EV)-derived DNA isolated from bronchoalveolar lavage fluid (BALF) was proven to be highly concordant with conventional tissue-based genotyping and its turn-around-time (TAT) was only 1-2 days. On this background, we prospectively validated the performance of EV-based BALF liquid biopsy for genotyping in the real practice of advanced non-small cell lung cancer (NSCLC) patients.

Methods: After screening 120 newly diagnosed stage III-IV NSCLC patients, 51 cases were detected as -mutated by EV-based BALF genotyping and 40 patients were enrolled for gefitinib treatment.

Extracellular Vesicle-Based Bronchoalveolar Lavage Fluid Liquid Biopsy for EGFR Mutation Testing in Advanced Non-Squamous NSCLC.

To overcome the limitations of the tissue biopsy and plasma cfDNA liquid biopsy, we performed the EV-based BALF liquid biopsy of 224 newly diagnosed stage III-IV NSCLC patients and compared it with tissue genotyping and 110 plasma liquid biopsies. Isolation of EVs from BALF was performed by ultracentrifugation. EGFR genotyping was performed through peptide nucleic acid clamping-assisted fluorescence melting curve analysis.

Efficacy of newly discovered DNA aptamers targeting AXL in a lung cancer cell with acquired resistance to Erlotinib.

Background: Accumulating evidences indicate that AXL overexpression or activation is associated with cancer progression and acquired resistance to targeted anti-cancer drugs such as epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). Despite recent development of several drugs that target multiple receptor tyrosine kinases (RTKs), drugs that selectively target AXL signaling are extremely rare. Short nucleic acid aptamers are non-immunogenic molecules with high binding affinity and specificity to their target molecules that could potentially be used as a novel cancer treatment.

Characteristics and Clinical Application of Extracellular Vesicle-Derived DNA.

Extracellular vesicles (EVs) carry RNA, proteins, lipids, and diverse biomolecules for intercellular communication. Recent studies have reported that EVs contain double-stranded DNA (dsDNA) and oncogenic mutant DNA. The advantage of EV-derived DNA (EV DNA) over cell-free DNA (cfDNA) is the stability achieved through the encapsulation in the lipid bilayer of EVs, which protects EV DNA from degradation by external factors.

Liquid biopsy using extracellular vesicle-derived DNA in lung adenocarcinoma.

Blood liquid biopsy has emerged as a way of overcoming the clinical limitations of repeat biopsy by testing for the presence of acquired resistance mutations to therapeutic agents. Despite its merits of repeatability and non-invasiveness, this method is currently only used as a supplemental test due to a relatively low sensitivity rate of 50%-60%, and cannot replace tissue biopsy. The circulating tumor DNAs used in blood liquid biopsies are passive products of fragmented DNA with a short half-life released following tumor cell death; the low sensitivity seen with liquid blood biopsy results from this instability, which makes increasing the sensitivity of this test fundamentally difficult.

Current status and future perspectives of liquid biopsy in non-small cell lung cancer.

With advances in target therapy, molecular analysis of tumors is routinely required for treatment decisions in patients with advanced non-small cell lung cancer (NSCLC). Liquid biopsy refers to the sampling and analysis of circulating cell-free tumor DNA (ctDNA) in various body fluids, primarily blood. Because the technique is minimally invasive, liquid biopsies are the future in cancer management.

Risk factors for primary lung cancer among never-smoking women in South Korea: a retrospective nationwide population-based cohort study.

Background/aims: We performed a large-scale, retrospective, nationwide, cohort study to investigate the risk factors for lung cancer among never-smoking Korean females.

Methods: The study data were collected from a general health examination and questionnaire survey of eligible populations conducted between January 1, 2003 and December 31, 2004; the data were acquired from the tailored big data distribution service of the National Health Insurance Service. After a 1-year clearance period, 5,860,922 of 6,318,878 never-smoking female participants with no previous history of lung cancer were investigated.

Extracellular vesicle-based EGFR genotyping in bronchoalveolar lavage fluid from treatment-naive non-small cell lung cancer patients.

Background: Extracellular vesicles (EV) have been proven to contain double-stranded DNA reflecting the mutational status of the parental tumor cells in non-small cell lung cancer (NSCLC), which can be translated into clinically useful EV-based liquid biopsy for Epidermal growth factor receptor (EGFR) genotyping using bronchoalveolar lavage fluid (BALF) obtained from tumor site.

Methods: Patients subjected for an initial lung cancer work-up underwent bronchoscopy and BALF was obtained from tumor site. After isolating EVs from BALF by ultracentrifugation, EV-derived DNA (EV DNA) was extracted for subsequent EGFR genotyping performed through peptide nucleic acid (PNA)-mediated Real-Time PCR.

CDK7 inhibition as a promising therapeutic strategy for lung squamous cell carcinomas with a SOX2 amplification.

Purpose: Despite the development of molecular targeted therapies, few advances have been made in the treatment of lung squamous cell carcinoma (SCC). SOX2 amplification is one of the most common genetic alterations in SCC. Here, we investigated the effects of THZ1, a potent cyclin-dependent kinase 7 (CDK7) inhibitor that plays a key role in gene transcription, in SCC.

Liquid biopsy using the supernatant of a pleural effusion for EGFR genotyping in pulmonary adenocarcinoma patients: a comparison between cell-free DNA and extracellular vesicle-derived DNA.

Background: EGFR genotyping in pulmonary adenocarcinoma patients who develop pleural effusions is mostly performed using cytology or cell block slides with low sensitivity. Liquid biopsy using the supernatant of pleural effusions may be more effective because they contain many components released by cancer cells. Extracellular vesicles (EVs) are known to carry oncogenic double-stranded DNA that is considered a notable biomarker.

Clinical Activity of Pan-HER Inhibitors Against HER2-Mutant Lung Adenocarcinoma.

Introduction: HER2 mutations are found in 2% to 4% of non-small-cell lung cancer cases and are usually mutually exclusive with other genetic alterations. We screened a large cohort of patients from multiple institutions in Korea, described the characteristics of HER2-mutant cases, and reported on several patients who were treated with pan-HER inhibitors.

Patients And Methods: The study population consisted of 360 patients diagnosed with adenocarcinoma from 4 institutions in Korea from June 2015 to September 2016.

Extracellular vesicle-derived DNA for performing EGFR genotyping of NSCLC patients.

Tumor cells shed an abundance of extracellular vesicles (EVs) to body fluids containing bioactive molecules including DNA, RNA, and protein. Investigations in the field of tumor-derived EVs open a new horizon in understanding cancer biology and its potential as cancer biomarkers as well as platforms for personalized medicine. This study demonstrates that successfully isolated EVs from plasma and bronchoalveolar lavage fluid (BALF) of non-small cell lung cancer (NSCLC) patients contain DNA that can be used for EGFR genotyping through liquid biopsy.

Efficacy of Afatinib in a Previously-Treated Patient with Non-Small Cell Lung Cancer Harboring HER2 Mutation: Case Report.

Human epidermal growth factor receptor 2 (HER2) mutation in non-small cell lung cancer (NSCLC) is an oncogenic driver that possibly becomes a druggable target to HER2-targeted therapy. The benefit of HER2-targeted therapy is much less defined especially in eastern populations. We provide evidence of clinical benefit of afatinib in a 50-year-old Asian woman with HER2-mutant NSCLC who previously failed cytotoxic chemotherapy and gefitinib treatment.

Assessment of EGFR mutation status using cell-free DNA from bronchoalveolar lavage fluid.

Background: Much attention has been focused on epidermal growth factor receptor (EGFR) mutation testing since the introduction of EGFR-tyrosine kinase inhibitors have improved survival in EGFR-positive lung cancer patients. Liquid biopsy using circulating tumor cells or cell-free DNA (cfDNA) has enabled less invasive testing, but requires a highly sensitive method. To date, liquid biopsy using bronchoalveolar lavage (BAL) fluid has rarely been used.

Superior Efficacy and Selectivity of Novel Small-Molecule Kinase Inhibitors of T790M-Mutant EGFR in Preclinical Models of Lung Cancer.

The clinical utility of approved EGFR small-molecule kinase inhibitors is plagued both by toxicity against wild-type EGFR and by metastatic progression in the central nervous system, a disease sanctuary site. Here, we report the discovery and preclinical efficacy of GNS-1486 and GNS-1481, two novel small-molecule EGFR kinase inhibitors that are selective for T790M-mutant isoforms of EGFR. Both agents were effective in multiple mouse xenograft models of human lung adenocarcinoma (T790M-positive or -negative), exhibiting less activity against wild-type EGFR than existing approved EGFR kinase inhibitors (including osimertinib).

Right Ventricular Myocardial Infarction due to Right Coronary Artery Total Occlusion Originating From the Distal Left Circumflex Artery.

An isolated single coronary artery is rare but often associated with other congenital cardiac malformations and myocardial ischemia. We report a rare case of right ventricular myocardial infarction due to total occlusion of the right coronary artery originating from the distal left circumflex artery.

Structure-function studies of a plant tyrosyl-DNA phosphodiesterase provide novel insights into DNA repair mechanisms of Arabidopsis thaliana.

TDP1 (tyrosyl-DNA phosphodiesterase 1), a member of the PLD (phospholipase D) superfamily, catalyses the hydrolysis of a phosphodiester bond between a tyrosine residue and the 3'-phosphate of DNA. We have previously identified and characterized the AtTDP gene in Arabidopsis thaliana, an orthologue of yeast and human TDP1 genes. Sequence alignment of TDP1 orthologues revealed that AtTDP has both a conserved C-terminal TDP domain and, uniquely, an N-terminal SMAD/FHA (forkhead-associated) domain.

Synchronization of cell cycle of Saccharomyces cerevisiae by using a cell chip platform.

Cell synchrony is a critical requirement for the study of eukaryotic cells. Although several chemical and genetic methods of cell cycle synchronization are currently available, they have certain limitations, such as unnecessary perturbations to cells. We developed a novel cell cycle synchronization method that is based on a cell chip platform.

High-throughput single-cell quantification using simple microwell-based cell docking and programmable time-course live-cell imaging.

Extracting single-cell information during cellular responses to external signals in a high-throughput manner is an essential step for quantitative single-cell analyses. Here, we have developed a simple yet robust microfluidic platform for measuring time-course single-cell response on a large scale. Our method combines a simple microwell-based cell docking process inside a patterned microfluidic channel, with programmable time-course live-cell imaging and software-aided fluorescent image processing.

Quantitative profiling of dual phosphorylation of Fus3 MAP kinase in Saccharomyces cerevisiae.

Mitogen-activated protein kinase (MAPK) signaling is a crucial component of eukaryotic cells; it plays an important role in responses to extracellular stimuli and in the regulation of various cellular activities. The signaling cascade is evolutionarily conserved in the eukaryotic kingdom from yeast to human. In response to a variety of extracellular signals, MAPK activity is known to be regulated via phosphorylation of a conserved TxY motif at the activation loop in which both threonine and tyrosine residues are phosphorylated by the upstream kinase.