1.Revolutionizing Non–Small Cell Lung Cancer Diagnosis: Ultra-High-Sensitive ctDNA Analysis for Detecting Hotspot Mutations with Long-term Stored Plasma
Ji-Young LEE ; Seyeon JEON ; Ha Ra JUN ; Chang Ohk SUNG ; Se Jin JANG ; Chang-Min CHOI ; Sung-Min CHUN
Cancer Research and Treatment 2024;56(2):484-501
Purpose:
Circulating cell-free DNA (cfDNA) has great potential in clinical oncology. The prognostic and predictive values of cfDNA in non–small cell lung cancer (NSCLC) have been reported, with epidermal growth factor receptor (EGFR), KRAS, and BRAF mutations in tumor-derived cfDNAs acting as biomarkers during the early stages of tumor progression and recurrence. However, extremely low tumor-derived DNA rates hinder cfDNA application. We developed an ultra-high-sensitivity lung version 1 (ULV1) panel targeting BRAF, KRAS, and EGFR hotspot mutations using small amounts of cfDNA, allowing for semi-quantitative analysis with excellent limit-of-detection (0.05%).
Materials and Methods:
Mutation analysis was performed on cfDNAs extracted from the plasma of 104 patients with NSCLC by using the ULV1 panel and targeted next-generation sequencing (CT-ULTRA), followed by comparison analysis of mutation patterns previously screened using matched tumor tissue DNA.
Results:
The ULV1 panel demonstrated robust selective amplification of mutant alleles, enabling the detection of mutations with a high degree of analytical sensitivity (limit-of-detection, 0.025%-0.1%) and specificity (87.9%-100%). Applying ULV1 to NSCLC cfDNA revealed 51.1% (23/45) samples with EGFR mutations, increasing with tumor stage: 8.33% (stage I) to 78.26% (stage IV). Semi-quantitative analysis proved effective for low-mutation-fraction clinical samples. Comparative analysis with PANAMutyper EGFR exhibited substantial concordance (κ=0.84).
Conclusion
Good detection sensitivity (~80%) was observed despite the limited volume (1 mL) and long-term storage (12-50 months) of plasma used and is expected to increase with high cfDNA inputs. Thus, the ULV1 panel is a fast and cost-effective method for early diagnosis, treatment selection, and clinical follow-up of patients with NSCLC.
2.Establishing Patient-Derived Cancer Cell Cultures and Xenografts in Biliary Tract Cancer
Jihoon KANG ; Ji-Young LEE ; Sunmin LEE ; Danbee KIM ; Jinyeong LIM ; Ha Ra JUN ; Seyeon JEON ; Young-Ae KIM ; Hye Seon PARK ; Kyu-pyo KIM ; Sung-Min CHUN ; Hee Jin LEE ; Changhoon YOO
Cancer Research and Treatment 2023;55(1):219-230
Purpose:
Biliary tract cancers (BTCs) are rare and show a dismal prognosis with limited treatment options. To improve our understanding of these heterogeneous tumors and develop effective therapeutic agents, suitable preclinical models reflecting diverse tumor characteristics are needed. We established and characterized new patient-derived cancer cell cultures and patient-derived xenograft (PDX) models using malignant ascites from five patients with BTC.
Materials and Methods:
Five patient-derived cancer cell cultures and three PDX models derived from malignant ascites of five patients with BTC, AMCBTC-01, -02, -03, -04, and -05, were established. To characterize the models histogenetically and confirm whether characteristics of the primary tumor were maintained, targeted sequencing and histopathological comparison between primary tissue and xenograft tumors were performed.
Results:
From malignant ascites of five BTC patients, five patient-derived cancer cell cultures (100% success rate), and three PDXs (60% success rate) were established. The morphological characteristics of three primary xenograft tumors were compared with those of matched primary tumors, and they displayed a similar morphology. The mutated genes in samples (models, primary tumor tissue, or both) from more than one patient were TP53 (n=2), KRAS (n=2), and STK11 (n=2). Overall, the pattern of commonly mutated genes in BTC cell cultures was different from that in commercially available BTC cell lines.
Conclusion
We successfully established the patient-derived cancer cell cultures and xenograft models derived from malignant ascites in BTC patients. These models accompanied by different genetic characteristics from commercially available models will help better understand BTC biology.
3.Eosinophil-mediated lung inflammation associated with elevated natural killer T cell response in COVID-19 patients
Dong-Min KIM ; Jun-Won SEO ; Yuri KIM ; Uni PARK ; Na-Young HA ; Hyoree PARK ; Na Ra YUN ; Da Young KIM ; Sung Ho YOON ; Yong Sub NA ; Do Sik MOON ; Sung-Chul LIM ; Choon-Mee KIM ; Yeon-Sook KIM ; Nam-Hyuk CHO
The Korean Journal of Internal Medicine 2022;37(1):201-209
Background/Aims:
Coronavirus disease 2019 (COVID-19) is associated with acute respiratory syndrome. The mechanisms underlying the different degrees of pneumonia severity in patients with COVID-19 remain elusive. This study provides evidence that COVID-19 is associated with eosinophil-mediated inflammation.
Methods:
We performed a retrospective case series of three patients with laboratory and radiologically confirmed COVID-19 pneumonia admitted to Chosun University Hospital. Demographic and clinical data on inflammatory cell lung infiltration and cytokine levels in patients with COVID-19 were collected.
Results:
Cytological analysis of sputum, tracheal aspirates, and bronchoalveolar lavage fluid (BALF) samples from all three patients revealed massive infiltration of polymorphonuclear cells (PMNs), such as eosinophils and neutrophils. All sputum and BALF specimens contained high levels of eosinophil cationic proteins. The infiltration of PMNs into the lungs, together with elevated levels of natural killer T (NKT) cells in BALF and peripheral blood samples from patients with severe pneumonia in the acute phase was confirmed by flow cytometry.
Conclusions
These results suggest that the lungs of COVID-19 patients can exhibit eosinophil-mediated inflammation, together with an elevated NKT cell response, which is associated with COVID-19 pneumonia.
4.Developing a Diagnostic Bundle for Bronchiectasis in South Korea: A Modified Delphi Consensus Study
Hayoung CHOI ; Hyun LEE ; Seung Won RA ; Jong Geol JANG ; Ji-Ho LEE ; Byung Woo JHUN ; Hye Yun PARK ; Ji Ye JUNG ; Seung Jun LEE ; Kyung-Wook JO ; Chin Kook RHEE ; Changwhan KIM ; Sei Won LEE ; Kyung Hoon MIN ; Yong-Soo KWON ; Deog Kyeom KIM ; Jin Hwa LEE ; Yong Bum PARK ; Eun Hee CHUNG ; Yae-Jean KIM ; Kwang Ha YOO ; Yeon-Mok OH
Tuberculosis and Respiratory Diseases 2022;85(1):56-66
Background:
Because the etiologies of bronchiectasis and related diseases vary significantly among different regions and ethnicities, this study aimed to develop a diagnostic bundle for bronchiectasis in South Korea.
Methods:
A modified Delphi method was used to develop expert consensus statements on a diagnostic bundle for bronchiectasis in South Korea. Initial statements proposed by a core panel, based on international bronchiectasis guidelines, were discussed in an online meeting and two email surveys by a panel of experts (≥70% agreement).
Results:
The study involved 21 expert participants, and 30 statements regarding a diagnostic bundle for bronchiectasis were classified as recommended, conditional, or not recommended. The consensus statements of the expert panel were as follows: A standardized diagnostic bundle is useful in clinical practice; diagnostic tests for specific diseases, including immunodeficiency and allergic bronchopulmonary aspergillosis, are necessary when clinically suspected; initial diagnostic tests, including sputum microbiology and spirometry, are essential in all patients with bronchiectasis, and patients suspected with rare causes such as primary ciliary dyskinesia should be referred to specialized centers.
Conclusion
Based on this Delphi survey, expert consensus statements were generated including specific diagnostic, laboratory, microbiological, and pulmonary function tests required to manage patients with bronchiectasis in South Korea.
5.Assessment of Objective Audiometry to Predict Subjective Satisfaction in Patients With Hearing Aids
Min Young KWAK ; Woo Ri CHOI ; Jun Woo PARK ; Eun Jeong HWANG ; Yeo Ra HA ; Jong Woo CHUNG ; Woo Seok KANG
Clinical and Experimental Otorhinolaryngology 2020;13(2):141-147
Objectives:
. To investigate the correlation of objective audiometry with user satisfaction as measured with the questionnaire scores.
Methods:
. Twenty patients with hearing loss, who agreed to wear a hearing aid and were referred for hearing aid fitting, were included in this prospective clinical study. All patients used the in-the-canal type of Wide7 hearing aid provided by BSL Co., Ltd. We performed the Korean version of the Hearing Handicap Inventory for the Elderly (K-HHIE) and the International Outcome Inventory for Hearing Aids (K-IOI-HA) before and 1, 3, and 6 months after wearing the hearing aid. We also performed pure tone audiometry (PTA), speech audiometry (SA), functional gain (FG), hearing in noise test (HINT), and central auditory processing disorder tests, such as frequency pattern test (CA-f), duration pattern test (CA-d), and dichotic test (CA-Di). Patients were divided into two groups (group A-HHIE, improved; group B-HHIE, same or worse) by comparing the score of K-HHIE before and 6 months after wearing the hearing aid. In the 6-month K-IOI-HA questionnaire, 21 points were considered as the average score. Based on this, we further divided patients into two groups (group A-IOI, >21 points; group B-IOI, ≤21 points).
Results:
. Group A-HHIE included six patients and group B-HHIE included 14 patients. In PTA, SA, HINT, CA-d, and CA-Di, group A-HHIE showed higher improvements than group B-HHIE, which were not statistically significant. Group A-IOI included 12 patients and group B-IOI included eight patients. No statistically significant difference was noted in the improvement of audiometric results over a period of 6 months after wearing the hearing aid between groups A-IOI and B-IOI.
Conclusion
. There were no significant and consistent audiometric results to reflect patient’s satisfaction with the hearing aid. Therefore, when analyzing the hearing aid-fitting outcome, both the objective audiometric tests and subjective questionnaire should be performed together for validating hearing aid performance.
6.The Effectiveness of Dexmedetomidine in Vacuum-Assisted Breast Biopsy Under Monitored Anesthesia Care
Kyung Woo KIM ; Jun Ha PARK ; Seunghwan KIM ; Eun Jin AHN ; Hyo Jin KIM ; Hey Ran CHOI ; Yeo Goo CHANG ; Si Ra BANG
Kosin Medical Journal 2019;34(1):24-29
OBJECTIVES: Vacuum-assisted breast biopsy (VABB) is a widely used technique for the diagnosis of breast lesions. It is carried out with local anesthesia, but procedural pain and stress are still problematic. Dexmedetomidine is a α-2 receptor agonist that can sedate without significant respiratory depression. The study aimed to report the effectiveness of sedation with monitored anesthesia care (MAC) using dexmedetomidine in VABB. METHODS: This was a retrospective chart review of patients who received VABB under MAC with dexmedetomidine. Forty-seven patients during the period of February 2015 to July 2016 were included. We collected data on patient characteristics, infusion drug and dose, induction to incision time, anesthetic, operation, and recovery time and other complications and vital signs. RESULTS: The mean operating time was 50.1 ± 24.9 minutes, and the anesthetic time was 71.2 ± 28.3 minutes. The mean time from induction to incision was 17.0 ± 5.2 minutes, and the recovery time was 20.1 ± 10.3 minutes. None of the patients needed an advanced airway management. Further, none of them showed hemodynamic instability. CONCLUSIONS: VABB was successfully performed with MAC using dexmedetomidine, and there was no respiratory depression or hemodynamic instability.
Airway Management
;
Anesthesia
;
Anesthesia, Local
;
Biopsy
;
Breast
;
Dexmedetomidine
;
Diagnosis
;
Hemodynamics
;
Humans
;
Respiratory Insufficiency
;
Retrospective Studies
;
Vital Signs
7.Induction of Melanoma Cell-Selective Apoptosis Using Anti-HER2 Antibody-Conjugated Gold Nanoparticles
Hyeon Jun JEON ; Byul Bo Ra CHOI ; Kwang Ha PARK ; Dae Seok HWANG ; Uk Kyu KIM ; Gyoo Cheon KIM
Yonsei Medical Journal 2019;60(6):509-516
PURPOSE: This study was conducted to verify the induction and mechanism of selective apoptosis in G361 melanoma cells using anti-HER2 antibody-conjugated gold nanoparticles (GNP-HER2). MATERIALS AND METHODS: Following GNP-HER2 treatment of G361 cells, cell cycle arrest and apoptosis were measured by WST-1 assay, Hemacolor staining, Hoechst staining, immunofluorescence staining, fluorescence-activated cell sorting analysis, and Western blotting.
Actins
;
Apoptosis Inducing Factor
;
Apoptosis
;
Blotting, Western
;
Caspase 3
;
Caspases
;
Cell Adhesion
;
Cell Cycle
;
Cell Cycle Checkpoints
;
Cell Death
;
Cyclin A
;
Cyclin D1
;
Cyclin E
;
Cyclins
;
Cytochromes c
;
Cytoplasm
;
DNA Fragmentation
;
Down-Regulation
;
Flow Cytometry
;
Fluorescent Antibody Technique
;
Focal Adhesions
;
Melanoma
;
Mitochondria
;
Nanoparticles
;
Phosphotransferases
;
Receptor, Epidermal Growth Factor
;
Up-Regulation
8.A case of intra-abdominal abscess caused by unconsciously ingestion of fish bone in elderly patient
Bo Ra KIM ; Hong Jun KIM ; Jong Ryeal HAHM ; Chang Yoon HA ; Woon Tae JUNG ; Ok Jae LEE
Kosin Medical Journal 2018;33(3):415-421
Cases showing complications such as esophageal injury, deep neck infection, and mediastinitis caused by accidental ingestion of fish bone are common. But ingestion of fish bone rarely causes perforation of the gastrointestinal tract or an intra-abdominal abscess. We report herein a case of a 78-year-old man with a periumbilical mesenteric abscess caused by fish bone which was ingested unconsciously. The fish bone was found in the terminal ileum and it was removed by colonoscopy. The patient improved and he was discharged after systemic antibiotic therapy. Occasionally, when patients swallow fish bone without a foreign body sensation, clinicians should suspect perforation caused by fish bone in case of an intra-abdominal abscess of unknown cause.
Abdominal Abscess
;
Abscess
;
Aged
;
Colonoscopy
;
Eating
;
Foreign Bodies
;
Gastrointestinal Tract
;
Humans
;
Ileum
;
Mediastinitis
;
Neck
;
Sensation
9.Current Situation of Assistive Devices and Appliances Provision for Persons with Cerebral Palsy in Korea
Seong Woo KIM ; Ha Ra JEON ; Ji Cheol SHIN ; Jun Min CHA ; Taemi YOUK ; Jiyong KIM
Health Policy and Management 2018;28(2):145-150
BACKGROUND: The aim of this study was to investigate the current state of the assistive devices and appliances provision system for cerebral palsy patients registered with brain disability. METHODS: From 2003 to 2013, we analyzed the records of cerebral palsy patients who had assistive devices and appliances provisioned at least once in their lives based on National Health Information Database. Patients with cerebral palsy were divided into three groups: infants and toddlers, school age and adolescence, and adults. RESULTS: Data on short leg plastic orthoses, ankle joint orthoses, and wheelchair were mainly analyzed. The types of ankle joint orthoses divided into three categories: limited, 90° limited, and Klenzac. Limited ankle joint orthoses was most frequently supported of the three in all age groups. Powered wheelchair and scooter were most supported to adult patients. When the re-supply duration was evaluated, the duration was suitable to the duration on guideline of regulation of re-supplement according to the related laws in adult patients but not in infants/toddlers and school age/adolescence as the actual re-supplement duration was much shorter than the reference value. CONCLUSION: This study confirmed the pattern of assistive devices and appliances supply differed depending on the age of cerebral palsy patients.
Adolescent
;
Adult
;
Ankle Joint
;
Brain
;
Cerebral Palsy
;
Foot Orthoses
;
Humans
;
Infant
;
Jurisprudence
;
Korea
;
Leg
;
Orthotic Devices
;
Plastics
;
Reference Values
;
Self-Help Devices
;
Wheelchairs
10.Predictive Factors of Subepithelial Tumor and Gastrointestinal Stromal Tumor in the Patients with Upper Gastrointestinal Subepithelial Lesions.
Ra Ri CHA ; Hye Won OH ; Hyun Seon YOO ; Jeong Woo HONG ; Sang Soo LEE ; Hong Jun KIM ; Chang Yoon HA ; Hyun Jin KIM ; Tae Hyo KIM ; Ok Jae LEE
The Korean Journal of Gastroenterology 2014;64(4):189-197
BACKGROUND/AIMS: Differentiating subepithelial tumor (SET) from non-neoplastic gastrointestinal subepithelial lesion (SEL) and gastrointestinal stromal tumor (GIST) from leiomyoma are very important for proper management. This study was conducted to analyze factors that could predict the presence of SET and GIST in patients with upper gastrointestinal (UGI) SELs. METHODS: A total of 527 patients were diagnosed with UGI SELs endosonographically at Gyeongsang National University Hospital from January 2008 to June 2013. Among these patients, histologic diagnosis was made in 84 patients. Data were collected by retrospectively reviewing the medical records. Variables that could differentiate neoplastic from non-neoplastic SELs and GIST from leiomyoma were analyzed. RESULTS: Among 84 patients with SELs, 64 (76.2%) had SETs including GIST (42.9%) and leiomyoma (19.0%). The patients' mean age (p=0.047), peak age distribution (p=0.047), proportions of patient > or =50 years (p=0.015), and number of proper muscle-originated lesions (p=0.001) were higher in neoplastic than non-neoplastic group. There were no significant differences in gender (p=0.195), size (p=0.266) and echogenicity (p=0.051) of the lesions. Older age (57.7 vs. 47.0 years, p=0.049), age > or =50 years (p=0.016), location in gastric body (p<0.001), and proper muscle origin (p=0.003) were significantly related to the presence of GIST compared to leiomyoma. Multiple regression analysis showed that the patients' age > or =50 years, size > or =30 mm, and proper muscle-origin of lesion were independent predictors of SET; however, there were no predictive factors that could differentiate GIST from leiomyoma. CONCLUSIONS: In patients with SEL, the possibility of having SET should be considered for patients > or =50 years with UGI SELs > or =30 mm that arise from the proper muscle. Thorough monitoring and aggressive management is warranted for those with gastric muscular SET since factors predictive of GIST are lacking.
Age Distribution
;
Diagnosis
;
Gastrointestinal Stromal Tumors*
;
Humans
;
Leiomyoma
;
Medical Records
;
Retrospective Studies

Result Analysis
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