1.Effector Function Characteristics of Exhausted CD8+ T-Cell in Microsatellite Stable and Unstable Gastric Cancer
Dong-Seok HAN ; Yoonjin KWAK ; Seungho LEE ; Soo Kyung NAM ; Seong-Ho KONG ; Do Joong PARK ; Hyuk-Joon LEE ; Nak-Jung KWON ; Hye Seung LEE ; Han-Kwang YANG
Cancer Research and Treatment 2024;56(4):1146-1163
Purpose:
Gastric cancer exhibits molecular heterogeneity, with the microsatellite instability–high (MSI-H) subtype drawing attention for its distinct features. Despite a higher survival rate, MSI-H gastric cancer lack significant benefits from conventional chemotherapy. The immune checkpoint inhibitors, presents a potential avenue, but a deeper understanding of the tumor immune microenvironment of MSI-H gastric cancer is essential.
Materials and Methods:
We explored the molecular characteristics of CD8+ T-cell subtypes in three MSI-H and three microsatellite stable (MSS) gastric cancer samples using single-cell RNA sequencing and spatial transcriptome analysis.
Results:
In MSI-H gastric cancer, significantly higher proportions of effector memory T cell (Tem), exhausted T cell (Tex), proliferative exhausted T cell (pTex), and proliferative T cell were observed, while MSS gastric cancer exhibited significantly higher proportions of mucosal-associated invariant T cell and natural killer T cell. In MSI-H gastric cancer, Tex and pTex exhibited a significant upregulation of the exhaustion marker LAG3, as well as elevated expression of effector function markers such as IFNG, GZMB, GZMH, and GZMK, compared to those in MSS gastric cancer. The interferon γ (IFN-γ) signaling pathway of Tex and pTex was retained compared to those of MSS gastric cancer. The spatial transcriptome analysis demonstrates the IFN-γ signaling pathway between neighboring Tex and malignant cell, showcasing a significantly elevated interaction in MSI-H gastric cancer.
Conclusion
Our study reveals novel finding indicating that IFN-γ signaling pathway is retained in Tex and pTex of MSI-H gastric cancer, offering a comprehensive perspective for future investigations into immunotherapy for gastric cancer.
2.Longitudinal Comparative Analysis of Circulating Tumor DNA and Matched Tumor Tissue DNA in Patients with Metastatic Colorectal Cancer Receiving Palliative First-Line Systemic Anti-Cancer Therapy
Seung-been LEE ; Ji-Won KIM ; Hong-Geun KIM ; Sung-Hyun HWANG ; Kui-Jin KIM ; Ju Hyun LEE ; Jeongmin SEO ; Minsu KANG ; Eun Hee JUNG ; Koung Jin SUH ; Se Hyun KIM ; Jin Won KIM ; Yu Jung KIM ; Jee Hyun KIM ; Nak-Jung KWON ; Keun-Wook LEE
Cancer Research and Treatment 2024;56(4):1171-1182
Purpose:
This study aimed to compare tumor tissue DNA (ttDNA) and circulating tumor DNA (ctDNA) to explore the clinical applicability of ctDNA and to better understand clonal evolution in patients with metastatic colorectal cancer undergoing palliative first-line systemic therapy.
Materials and Methods:
We performed targeted sequencing analysis of 88 cancer-associated genes using germline DNA, ctDNA at baseline (baseline-ctDNA), and ctDNA at progressive disease (PD-ctDNA). The results were compared with ttDNA data.
Results:
Among 208 consecutively enrolled patients, we selected 84 (41 males; median age, 59 years; range, 35 to 90 years) with all four sample types available. A total of 202 driver mutations were found in 34 genes. ttDNA exhibited the highest mutation frequency (n=232), followed by baseline-ctDNA (n=155) and PD-ctDNA (n=117). Sequencing ctDNA alongside ttDNA revealed additional mutations in 40 patients (47.6%). PD-ctDNA detected 13 novel mutations in 10 patients (11.9%) compared to ttDNA and baseline-ctDNA. Notably, seven mutations in five patients (6.0%) were missense or nonsense mutations in APC, TP53, SMAD4, and CDH1 genes. In baseline-ctDNA, higher maximal variant allele frequency (VAF) values (p=0.010) and higher VAF values of APC (p=0.012), TP53 (p=0.012), and KRAS (p=0.005) mutations were significantly associated with worse overall survival.
Conclusion
While ttDNA remains more sensitive than ctDNA, our ctDNA platform demonstrated validity and potential value when ttDNA was unavailable. Post-treatment analysis of PD-ctDNA unveiled new pathogenic mutations, signifying cancer’s clonal evolution. Additionally, baseline-ctDNA’s VAF values were prognostic after treatment.
3.Real-world Prescription Patterns and Patient Satisfaction Regarding Maintenance Therapy of Gastroesophageal Reflux Disease: An Observational, Cross-sectional, Multicenter Study
Cheal Wung HUH ; Nak Hoon SON ; Young Hoon YOUN ; Da Hyun JUNG ; Min Kyung KIM ; Eun Jeong GONG ; Kyu Chan HUH ; Seung Young KIM ; Moo In PARK ; Ju Yup LEE ; Joong Goo KWON ; Jae Hak KIM ; Cheol Min SHIN ; Kee Wook JUNG ; Su Jin HONG ; Hee Man KIM ; Suck Chei CHOI ; Hye-Kyung JUNG ; Hyun Jin KIM ; Kwang Jae LEE
Journal of Neurogastroenterology and Motility 2023;29(4):470-477
Background/Aims:
Gastroesophageal reflux disease (GERD) is a common chronic gastrointestinal disorder that typically requires long-term maintenance therapy. However, little is known about patient preferences and satisfaction and real-world prescription patterns regarding maintenance therapy for GERD.
Methods:
This observational, cross-sectional, multicenter study involved patients from 18 referral hospitals in Korea. We surveyed patients who had been prescribed proton pump inhibitors (PPIs) for GERD for at least 90 days with a minimum follow-up duration of 1 year. The main outcome was overall patient satisfaction with different maintenance therapy modalities.
Results:
A total of 197 patients were enrolled. Overall patient satisfaction, patient preferences, and GERD health-related quality of life scores did not significantly differ among the maintenance therapy modality groups. However, the on-demand therapy group experienced a significantly longer disease duration than the continuous therapy group. The continuous therapy group demonstrated a lower level of awareness of potential adverse effects associated with PPIs than the on-demand therapy group but received higher doses of PPIs than the on-demand therapy group. The prescribed doses of PPIs also varied based on the phenotype of GERD, with higher doses prescribed for non-erosive reflux disease than erosive reflux disease.
Conclusion
Although overall patient satisfaction did not significantly differ among the different PPI maintenance therapy modality groups, awareness of potential adverse effects was significantly different between the on-demand and continuous therapy groups.
4.Virus Isolation from the First Patient with SARS-CoV-2 in Korea
Wan Beom PARK ; Nak Jung KWON ; Su Jin CHOI ; Chang Kyung KANG ; Pyoeng Gyun CHOE ; Jin Yong KIM ; Jiyoung YUN ; Gir Won LEE ; Moon Woo SEONG ; Nam Joong KIM ; Jeong Sun SEO ; Myoung don OH
Journal of Korean Medical Science 2020;35(7):84-
Novel coronavirus (SARS-CoV-2) is found to cause a large outbreak started from Wuhan since December 2019 in China and SARS-CoV-2 infections have been reported with epidemiological linkage to China in 25 countries until now. We isolated SARS-CoV-2 from the oropharyngeal sample obtained from the patient with the first laboratory-confirmed SARS-CoV-2 infection in Korea. Cytopathic effects of SARS-CoV-2 in the Vero cell cultures were confluent 3 days after the first blind passage of the sample. Coronavirus was confirmed with spherical particle having a fringe reminiscent of crown on transmission electron microscopy. Phylogenetic analyses of whole genome sequences showed that it clustered with other SARS-CoV-2 reported from Wuhan.
China
;
Coronavirus
;
Crowns
;
Genome
;
Humans
;
Korea
;
Microscopy, Electron
;
Microscopy, Electron, Transmission
;
Phylogeny
;
Vero Cells
5.Virus Isolation from the First Patient with SARS-CoV-2 in Korea
Wan Beom PARK ; Nak Jung KWON ; Su Jin CHOI ; Chang Kyung KANG ; Pyoeng Gyun CHOE ; Jin Yong KIM ; Jiyoung YUN ; Gir Won LEE ; Moon Woo SEONG ; Nam Joong KIM ; Jeong Sun SEO ; Myoung don OH
Journal of Korean Medical Science 2020;35(7):e84-
Novel coronavirus (SARS-CoV-2) is found to cause a large outbreak started from Wuhan since December 2019 in China and SARS-CoV-2 infections have been reported with epidemiological linkage to China in 25 countries until now. We isolated SARS-CoV-2 from the oropharyngeal sample obtained from the patient with the first laboratory-confirmed SARS-CoV-2 infection in Korea. Cytopathic effects of SARS-CoV-2 in the Vero cell cultures were confluent 3 days after the first blind passage of the sample. Coronavirus was confirmed with spherical particle having a fringe reminiscent of crown on transmission electron microscopy. Phylogenetic analyses of whole genome sequences showed that it clustered with other SARS-CoV-2 reported from Wuhan.
6.Single Incision Laparoscopic Appendectomy for Management of Complicated Appendicitis: Comparison between Single-Incision and Conventional.
Yoon Jung OH ; Nak Song SUNG ; Won Jun CHOI ; Dae Sung YOON ; In Seok CHOI ; Sang Eok LEE ; Ju Ik MOON ; Seong Uk KWON ; Si Min PARK ; In Eui BAE
Journal of Minimally Invasive Surgery 2018;21(4):148-153
PURPOSE: Single incision laparoscopic appendectomy (SILA) is a widely used surgical procedure for treatment of appendicitis with better cosmesis. However, many surgeons generally tend to choose conventional multiport laparoscopic appendectomy regarding with complicated appendicitis. The aim of this study is to demonstrate the safety and feasibility of SILA for treatment of complicated appendicitis by comparison with 3-ports conventional laparoscopic appendectomy (CLA). METHODS: Retrospective chart review of patients diagnosed appendicitis at single hospital during January 2015 to May 2017 collected 500 patients. Among 134 patients with complicated appendicitis, we compared outcomes for 29 patients who got SILA and 105 patients who got CLA. RESULTS: 179 and 321 patients were treated by SILA and CLA, respectively. 134 (26.8%) patients were treated for complicated appendicitis, 29 patients by SILA and 105 patients by CLA, respectively. There was no case converted to open or added additional trocar in both groups. There were no differences in demographics with regard to age, sex, body mass index (BMI), and American society of anesthesiologists (ASA) scores. There was no difference in mean operating time (58.97±18.53 (SILA) vs. 57.57±21.48 (CLA), p=0.751). The drain insertion rate (6.9% vs 37.1%, p=0.001) and the length of hospital stay (2.76±1.41 vs. 3.97±2.97, p=0.035) were lower in SILA group with significance. There was no significant difference in the rate of surgical site infection (6.9% vs. 6.7%, p=1.000). CONCLUSION: This study demonstrates that SILA is a feasible and safe procedure for treatment of complicated appendicitis.
Appendectomy*
;
Appendicitis*
;
Body Mass Index
;
Demography
;
Humans
;
Length of Stay
;
Retrospective Studies
;
Surgeons
;
Surgical Instruments
;
Surgical Wound Infection
7.Analysis of Fifty Hotspot Mutations of Lung Squamous Cell Carcinoma in Never-smokers.
Ha Youn LEE ; Se Hoon LEE ; Jae Kyung WON ; Dong Soo LEE ; Nak Jung KWON ; Sun Mi CHOI ; Jinwoo LEE ; Chang Hoon LEE ; Sang Min LEE ; Jae Joon YIM ; Chul Gyu YOO ; Young Whan KIM ; Sung Koo HAN ; Young Sik PARK
Journal of Korean Medical Science 2017;32(3):415-420
Smoking is the major risk factor for lung squamous cell carcinoma (SCC), although a small number of lung SCCs occurs in never-smokers. The purpose of this study was to compare 50 hotspot mutations of lung SCCs between never-smokers and smokers. We retrospectively reviewed the medical records of patients newly diagnosed with lung SCC between January 1, 2011 and December 31, 2013 in the Seoul National University Hospital. Formalin-fixed, paraffin-embedded tumor samples were used for analysis of hotspot mutations. Fifty cancer-related genes in never-smokers were compared to those in ever-smokers. Of 379 lung SCC patients, 19 (5.0%) were never-smokers. The median age of these 19 patients was 67 years (interquartile range 57–73 years), and 10 of these patients were women (52.5%). The incidence rates of stage I, II, III, and IV disease in this group were 26.4%, 5.3%, 31.6%, and 36.8%, respectively, and sequencing was performed successfully in 14 cases. In the 26 lung SCC tumor samples (12 from never-smokers and 14 from ever-smokers) sequenced using personal genome machine, the most common mutations were in TP53 (75.0%), RAS (66.7%), and STK11 (33.3%), but mutations were also found in EGFR, KIT, and PTEN. The distribution of hotspot mutations in never-smokers was similar to that in ever-smokers. There was no significant difference in overall survival between the 2 groups. The 50 hotspot mutations of lung SCC in never-smokers were similar to those of ever-smokers.
Carcinoma, Squamous Cell*
;
Epithelial Cells*
;
Female
;
Genome
;
Humans
;
Incidence
;
Lung Neoplasms
;
Lung*
;
Medical Records
;
Retrospective Studies
;
Risk Factors
;
Seoul
;
Smoke
;
Smoking
8.Isolation of Middle East Respiratory Syndrome Coronavirus from a Patient of the 2015 Korean Outbreak.
Wan Beom PARK ; Nak Jung KWON ; Pyoeng Gyun CHOE ; Su Jin CHOI ; Hong Sang OH ; Sang Min LEE ; Hyonyong CHONG ; Jong Il KIM ; Kyoung Ho SONG ; Ji Hwan BANG ; Eu Suk KIM ; Hong Bin KIM ; Sang Won PARK ; Nam Joong KIM ; Myoung Don OH
Journal of Korean Medical Science 2016;31(2):315-320
During the 2015 outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) in Korea, 186 persons were infected, resulting in 38 fatalities. We isolated MERS-CoV from the oropharyngeal sample obtained from a patient of the outbreak. Cytopathic effects showing detachment and rounding of cells were observed in Vero cell cultures 3 days after inoculation of the sample. Spherical virus particles were observed by transmission electron microscopy. Full-length genome sequence of the virus isolate was obtained and phylogenetic analyses showed that it clustered with clade B of MERS-CoV.
Animals
;
Cercopithecus aethiops
;
Coronavirus Infections/*diagnosis/epidemiology/*virology
;
Disease Outbreaks
;
Humans
;
Microscopy, Electron
;
Middle East Respiratory Syndrome Coronavirus/classification/genetics/*isolation & purification/ultrastructure
;
Phylogeny
;
Polymerase Chain Reaction
;
RNA, Viral/analysis/chemistry/metabolism
;
Republic of Korea/epidemiology
;
Sequence Analysis, RNA
;
Vero Cells
9.A Concealed Brugada Electrocardiogram Pattern Revealed after Administering Propafenone to a Patient with Atrial Fibrillation.
Hyoung Hun SIM ; Nak Hyun KWON ; Joo Yeong BAEG ; Chang Yong YUN ; Soo Min AHN ; Yu Mi OH ; Young Jung KIM
Korean Journal of Medicine 2014;86(1):70-73
Brugada syndrome is characterized by sudden cardiac death associated with ventricular tachyarrhythmia in patients without structural heart disease. We recently observed a case of concealed Brugada ECG pattern, which appeared after oral propafenone administration for atrial fibrillation. A 34-year-old male patient who experienced syncope was admitted to the emergency department with acute atrial fibrillation (AF). Three hundred milligrams of propafenone that were administered to convert AF to sinus rhythm unmasked the Brugada ECG pattern that had remained concealed. The patient showed a type 1 Brugada ECG pattern after taking propafenone.
Adult
;
Atrial Fibrillation*
;
Brugada Syndrome
;
Death, Sudden, Cardiac
;
Electrocardiography*
;
Emergency Service, Hospital
;
Heart Diseases
;
Humans
;
Male
;
Propafenone*
;
Syncope
;
Tachycardia
10.Prevalence of Congenital Coronary Artery Anomalies of Korean Men Detected by Coronary Computed Tomography.
Jae Hyun PARK ; Nak Hyun KWON ; Jun Hwan KIM ; Yu Jin KO ; Seo Hee RYU ; Seok Jin AHN ; Young Jung KIM ; Joo Yeong BAEG ; Jung Im KIM
Korean Circulation Journal 2013;43(1):7-12
BACKGROUND AND OBJECTIVES: It has been demonstrated that the anomalous origin of coronary arteries (AOCA) are generally asymptomatic and rare diseases. However, some cases can cause severe life threatening events. To detect these anomalies, coronary angiographies and autopsies were used to detect coronary artery anomalies, but these procedures have limitations because of their invasiveness. The new device, Multidetector Computed Tomography (MDCT), now replaces the method of choice for detecting coronary anomalies. The prevalence of these anomalies in Korea has not been studied yet. This present analysis attempted to determine the prevalence of AOCA in Korean men by MDCT. SUBJECTS AND METHODS: 1582 Korean male police officers underwent coronary MDCT for their health screening voluntarily. After reconstruction of CT images, we could confirm coronary artery anomalies. RESULTS: The prevalence of AOCA in Korean men was 1.14% (18 out of 1582 cases). The most common abnormality (11 cases, 0.70%) was the origin of the coronary artery. Anomalies of the coronary artery end point were observed in 5 cases (0.32%). The anomalous location of coronary ostium on the aortic root was observed in 1 case (0.06%). An anomalous collateral vessel was observed in 1 case (0.06%). CONCLUSION: The prevalence of coronary artery anomalies in Korean men was 1.14%. Coronary CT is a safe and noninvasive modality for detecting coronary anomalies.
Autopsy
;
Coronary Angiography
;
Coronary Vessel Anomalies
;
Coronary Vessels
;
Humans
;
Korea
;
Male
;
Mass Screening
;
Multidetector Computed Tomography
;
Police
;
Prevalence
;
Rare Diseases

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