Purpose: Recently, we developed allele-discriminating priming system (ADPS) technology. This method increases the sensitivity of conventional quantitative polymerase chain reaction up to 100 folds, with limit of detection, 0.01%, with reinforced specificity. This prospective study aimed to develop and validate the accuracy of ADPS epidermal growth factor receptor (EGFR) Mutation Test Kit using clinical specimens. Materials and Methods: In total 189 formalin-fixed paraffin-embedded tumor tissues resected from patients with non–small cell lung cancer were used to perform a comparative evaluation of the ADPS EGFR Mutation Test Kit versus the cobas EGFR Mutation Test v2, which is the current gold standard. When the two methods had inconsistent results, next-generation sequencing–based CancerSCAN was utilized as a referee. Results: The overall agreement of the two methods was 97.4% (93.9%-99.1%); the positive percent agreement, 95.0% (88.7%-98.4%); and the negative percent agreement, 100.0% (95.9%-100.0%). EGFR mutations were detected at a frequency of 50.3% using the ADPS EGFR Mutation Test Kit and 52.9% using the cobas EGFR Mutation Test v2. There were 10 discrepant mutation calls between the two methods. CancerSCAN reproduced eight ADPS results. In two cases, mutant allele fraction was ultra-low at 0.02% and 0.06%, which are significantly below the limit of detection of the cobas assay and CancerSCAN. Based on the EGFR genotyping by ADPS, the treatment options could be switched in five patients. Conclusion The highly sensitive and specific ADPS EGFR Mutation Test Kit would be useful in detecting the patients who have lung cancer with EGFR mutation, and can benefit from the EGFR targeted therapy.

Background: and Purpose Focal cortical dysplasia (FCD) is one of the most common causes of drug-resistant epilepsy, and necessitates a multimodal evaluation to ensure optimal surgical treatment. This study aimed to determine the supportive value of the morphometric analysis program (MAP) in detecting FCD using data from a single institution in Korea. Methods: To develop a standard reference for the MAP, normal-looking MRIs by two scanners that are frequently used in this center were chosen. Patients with drug-resistant epilepsy and FCD after surgery were candidates for the analysis. The three-dimensional T1-weighted MRI scans of the patients were analyzed as test cases using the MAP. Results: The MRI scans of 87 patients were included in the analysis. The radiologist detected abnormal findings correlated with FCD (RAD positive [RAD(+)]) in 34 cases (39.1%), while the MAP could detect FCD in 25.3% of cases. A combination of the MAP (MAP[+] cases) with interpretations by the radiologist increased the detection to 42.5% (37 cases). The lesion detection rate was not different according to the type of reference scanners except in one case. MAP(+)/RAD(-) presented in three cases, all of which had FCD type IIa. The detection rate was slightly higher using the same kind of scanner as a reference, but not significantly (35.0% vs. 22.4% p=0.26). Conclusions The results of postprocessing in the MAP for detecting FCD did not depend on the type of reference scanner, and the MAP was the strongest in detecting FCD IIa. We suggested that the MAP could be widely utilized without developing institutional standards and could become an effective tool for detecting FCD lesions.

The therapeutic effects of mesenchymal stem cells (MSCs) in musculoskeletal diseases (MSDs) have been verified in many human and animal studies. Although some tissues contain MSCs, the number of cells harvested from those tissues and rate of proliferation in vitro are not enough for continuous transplantation. In order to produce and maintain stable MSCs, many attempts are made to induce differentiation from pluripotent stem cells (iPSCs) into MSCs. In particular, it is also known that the paracrine action of stem cell-secreted factors could promote the regeneration and differentiation of target cells in damaged tissue. MicroRNAs (miRNAs), one of the secreted factors, are small non-coding RNAs that regulate the translation of a gene. It is known that miRNAs help communication between stem cells and their surrounding niches through exosomes to regulate the proliferation and differentiation of stem cells. While studies have so far been underway targeting therapeutic miRNAs of MSDs, studies on specific miRNAs secreted from MSCs are still minimal. Hence, our ultimate goal is to obtain sufficient amounts of exosomes from iPSC-MSCs and develop them into therapeutic agents, furthermore to select specific miRNAs and provide safe cell-free clinical setting as a cell-free status with purpose of delivering them to target cells. This review article focuses on stem cell therapy on MSDs, specific microRNAs regulating MSDs and updates on novel approaches.

The therapeutic effects of mesenchymal stem cells (MSCs) in musculoskeletal diseases (MSDs) have been verified in many human and animal studies. Although some tissues contain MSCs, the number of cells harvested from those tissues and rate of proliferation in vitro are not enough for continuous transplantation. In order to produce and maintain stable MSCs, many attempts are made to induce differentiation from pluripotent stem cells (iPSCs) into MSCs. In particular, it is also known that the paracrine action of stem cell-secreted factors could promote the regeneration and differentiation of target cells in damaged tissue. MicroRNAs (miRNAs), one of the secreted factors, are small non-coding RNAs that regulate the translation of a gene. It is known that miRNAs help communication between stem cells and their surrounding niches through exosomes to regulate the proliferation and differentiation of stem cells. While studies have so far been underway targeting therapeutic miRNAs of MSDs, studies on specific miRNAs secreted from MSCs are still minimal. Hence, our ultimate goal is to obtain sufficient amounts of exosomes from iPSC-MSCs and develop them into therapeutic agents, furthermore to select specific miRNAs and provide safe cell-free clinical setting as a cell-free status with purpose of delivering them to target cells. This review article focuses on stem cell therapy on MSDs, specific microRNAs regulating MSDs and updates on novel approaches.

Eosinophilic esophagitis (EoE) is an immune or antigen-mediated chronic inflammatory esophageal disorder that is relatively rarein Asian countries. The main symptoms of EoE are dysphagia and food impaction. Although chest pain is a symptom of EoE, it isalso a symptom of coronary heart disease. This paper reports a case of EoE with angina pectoris in a 45-year-old male who wasreferred to the authors’ hospital for chest pain. He was diagnosed with angina pectoris because of mild stenosis in the left coronaryartery on coronary angiography. On the other hand, the symptoms did not improve with angina medication therapy.Therefore, he underwent a chest CT scan, which revealed esophageal thickening. Esophagogastroduodenoscopy was performed.His endoscopic findings showed linear furrows with edema, and >90 eosinophils existed per high-power field on the histologyfindings. He was diagnosed with EoE. Through additional examinations, he was also diagnosed with asthma. The patient wastreated with a proton pump inhibitor and a fluticasone inhaler. His symptoms and abnormal endoscopic findings disappeared aftereight weeks of treatment. This case shows that physicians should consider the possibility of the symptoms for EoE when unexplainedchest pain persists.

Activities of Daily Living ; Adult ; Cohort Studies ; Follow-Up Studies ; Gait ; Geriatric Assessment ; Humans ; Insurance, Long-Term Care ; Long-Term Care ; Mass Screening ; National Health Programs

BACKGROUND: This study aimed to evaluate the association between baseline results of the Timed Up and Go (TUG) test and subsequent functional dependency occurrence. METHODS: From the National Health Insurance Service-Senior Cohort database, we identified 39,519 people who participated in the National Screening Program for Transitional Ages at the age of 66 during 2007–2008. Impaired mobility was defined as taking 10 seconds or longer to perform the TUG test. Functional dependency occurrence was defined as the initiation of receiving national Long-Term Care Insurance services—home care or admission to long-term care facilities. Cox proportional hazard regression models were used to assess the hazard ratios (HRs) for dependency occurrence according to baseline TUG test results. RESULTS: The mean follow-up period was 5.7 years. Occurrence rates of dependency were 2.0 and 3.4 cases per 1,000 person-years in the normal and impaired TUG groups, respectively. Impaired mobility was associated with a higher risk of functional dependency occurrence (adjusted HR [aHR], 1.65; 95% confidence interval [CI], 1.40–1.95; P < 0.001). Additionally, in the subgroup analysis for the participants with intact baseline activities of daily living, impaired mobility was associated with a higher risk of dependency occurrence (aHR, 1.65; 95% CI, 1.33–2.04; P < 0.001). CONCLUSION The TUG test might be a useful predictive marker of subsequent functional dependency occurrence. Intervention to prevent functional dependency may be helpful for older adults with impairment on the TUG test.

Purpose: Targeted next-generation sequencing (NGS) panels for solid tumors have been useful in clinical framework for accurate tumor diagnosis and identifying essential molecular aberrations. However, most cancer panels have been designed to address a wide spectrum of pan-cancer models, lacking integral prognostic markers that are highly specific to gliomas. Materials and Methods: To address such challenges, we have developed a glioma-specific NGS panel, termed “GliomaSCAN,” that is capable of capturing single nucleotide variations and insertion/deletion, copy number variation, and selected promoter mutations and structural variations that cover a subset of intron regions in 232 essential glioma-associated genes. We confirmed clinical concordance rate using pairwise comparison of the identified variants from whole exome sequencing (WES), immunohistochemical analysis, and fluorescence in situ hybridization. Results: Our panel demonstrated high sensitivity in detecting potential genomic variants that were present in the standard materials. To ensure the accuracy of our targeted sequencing panel, we compared our targeted panel to WES. The comparison results demonstrated a high correlation. Furthermore, we evaluated clinical utility of our panel in 46 glioma patients to assess the detection capacity of potential actionable mutations. Thirty-two patients harbored at least one recurrent somatic mutation in clinically actionable gene. Conclusion We have established a glioma-specific cancer panel. GliomaSCAN highly excelled in capturing somatic variations in terms of both sensitivity and specificity and provided potential clinical implication in facilitating genome-based clinical trials. Our results could provide conceptual advance towards improving the response of genomically guided molecularly targeted therapy in glioma patients.

PURPOSE: Identification of biomarkers to predict recurrence risk is essential to improve adjuvant treatment strategies in stage II/III gastric cancer patients. This study evaluated biomarkers for predicting survival after surgical resection. MATERIALS AND METHODS: This post-hoc analysis evaluated patients from the CLASSIC trial who underwent D2 gastrectomywith orwithout adjuvant chemotherapy (capecitabine plus oxaliplatin) at the Yonsei Cancer Center. Tumor expressions of thymidylate synthase (TS), excision repair cross-complementation group 1 (ERCC1), and programmed death-ligand 1 (PD-L1) were evaluated by immunohistochemical (IHC) staining to determine their predictive values. RESULTS: Among 139 patients, IHC analysis revealed high tumor expression of TS (n=22, 15.8%), ERCC1 (n=23, 16.5%), and PD-L1 (n=42, 30.2%) in the subset of patients. Among all patients, high TS expression tended to predict poor disease-free survival (DFS; hazard ratio [HR], 1.80; p=0.053), whereas PD-L1 positivity was associated with favorable DFS (HR, 0.33; p=0.001) and overall survival (OS; HR, 0.38; p=0.009) in multivariate Cox analysis. In the subgroup analysis, poor DFS was independently predicted by high TS expression (HR, 2.51; p=0.022) in the adjuvant chemotherapy subgroup (n=66). High PD-L1 expression was associated with favorable DFS (HR, 0.25; p=0.011) and OS (HR, 0.22; p=0.015) only in the surgery-alone subgroup (n=73). The prognostic impact of high ERCC1 expression was not significant in the multivariate Cox analysis. CONCLUSION: This study shows that high TS expression is a predictive factor for worse outcomes on capecitabine plus oxaliplatin adjuvant chemotherapy, whereas PD-L1 expression is a favorable prognostic factor in locally advanced gastric cancer patients.
Biomarkers ; Capecitabine ; Chemotherapy, Adjuvant ; Disease-Free Survival ; DNA Repair ; Humans ; Immunohistochemistry ; Prognosis ; Prospective Studies ; Recurrence ; Stomach Neoplasms ; Thymidylate Synthase

BACKGROUND: Women with family history of breast cancer are more likely to be worried about having cancer and participate in breast cancer screening. However, few studies have examined relationship between family history, cancer worries, and participating in breast cancer screening in Korea. This study is to identify relationship between family history, cancer worries, and participating in breast cancer screening among women with and without family history of cancer. METHODS: Respondents were 2,364 women who based on the 2013 Korean National Cancer Screening Survey which is done by National Cancer Center in Korea. Chi-square tests were performed to determine differences of cancer worries, undergoing of breast cancer screening and methods such as mammogram and ultrasonogram with and without cancer family history. Univariate and multiple logistic regression were performed to identify if family history and cancer worries are related factors on participating in breast cancer screening and methods. Stratified analysis was performed to confirm the effect of ultrasonogram on the dense breast by age. RESULTS: Women with cancer family history frequently checked condition for conscious of having cancer (p=0.0299) and had highly perception of risk about having cancer in the future (p≤0.0001). Women aged 30–49 did not perform significantly more ultrasonogram than women aged over 50 years old. Checking condition (moderate odds ratio [OR], 1.38; 95% confidence interval [CI], 1.20–2.08; frequently OR, 1.58; 95% CI, 1.08–1.76) and perception of risk (moderate OR, 3.12; 95% CI, 1.06–7.06; high OR, 2.74; 95% CI, 1.20–8.08) were related to participate in mammogram and ultrasonogram. A positive family history was related to 1.35 higher odds of performing only breast ultrasonogram (95% CI, 1.04–1.75). CONCLUSION: This study requires national education and publicity to reduce the unnecessary cost of screening, to be possible cost effective screening and to encourage women to receive more mammogram, especially women aged over 50 years old and with socioeconomic factors related to opportunistic screening.
Breast Neoplasms* ; Breast* ; Early Detection of Cancer ; Education ; Female ; Humans ; Korea ; Logistic Models ; Mass Screening* ; Odds Ratio ; Socioeconomic Factors ; Surveys and Questionnaires ; Ultrasonography