1.Primary Tumor Suppression and Systemic Immune Activation of Macrophages through the Sting Pathway in Metastatic Skin Tumor
Chun-Bong SYNN ; Dong Kwon KIM ; Jae Hwan KIM ; Youngseon BYEON ; Young Seob KIM ; Mi Ran YUN ; Ji Min LEE ; Wongeun LEE ; Eun Ji LEE ; Seul LEE ; You-Won LEE ; Doo Jae LEE ; Hyun-Woo KIM ; Chang Gon KIM ; Min Hee HONG ; June Dong PARK ; Sun Min LIM ; Kyoung-Ho PYO
Yonsei Medical Journal 2022;63(1):42-55
Purpose:
Agonists of the stimulator of interferon genes (STING) play a key role in activating the STING pathway by promoting the production of cytokines. In this study, we investigated the antitumor effects and activation of the systemic immune response of treatment with DMXAA (5,6-dimethylxanthenone-4-acetic acid), a STING agonist, in EML4-ALK lung cancer and CT26 colon cancer.
Materials and Methods:
The abscopal effects of DMXAA in the treatment of metastatic skin nodules were assessed. EML4-ALK lung cancer and CT26 colon cancer models were used to evaluate these effects after DMXAA treatment. To evaluate the expression of macrophages and T cells, we sacrificed the tumor-bearing mice after DMXAA treatment and obtained the formalin-fixed paraffin-embedded (FFPE) tissue and tumor cells. Immunohistochemistry and flow cytometry were performed to analyze the expression of each FFPE and tumor cell.
Results:
We observed that highly infiltrating immune cells downstream of the STING pathway had increased levels of chemokines after DMXAA treatment. In addition, the levels of CD80 and CD86 in antigen-presenting cells were significantly increased after STING activation. Furthermore, innate immune activation altered the systemic T cell-mediated immune responses, induced proliferation of macrophages, inhibited tumor growth, and increased numbers of cytotoxic memory T cells. Tumor-specific lymphocytes also increased in number after treatment with DMXAA.
Conclusion
The abscopal effect of DMXAA treatment on the skin strongly reduced the spread of EML4-ALK lung cancer and CT26 colon cancer through the STING pathway and induced the presentation of antigens.
2.Monitoring Radiation Doses during Diagnostic and Therapeutic Neurointerventional Procedures: Multicenter Study for Establishment of Reference Levels
Yon-Kwon IHN ; Bum-soo KIM ; Hae Woong JEONG ; Sang Hyun SUH ; Yoo Dong WON ; Young-Jun LEE ; Dong Joon KIM ; Pyong JEON ; Chang-Woo RYU ; Sang-il SUH ; Dae Seob CHOI ; See Sung CHOI ; Sang Heum KIM ; Jun Soo BYUN ; Jieun RHO ; Yunsun SONG ; Woo Sang JEONG ; Noah HONG ; Sung Hyun BAIK ; Jeong Jin PARK ; Soo Mee LIM ; Jung-Jae KIM ; Woong YOON
Neurointervention 2021;16(3):240-251
Purpose:
To assess patient radiation doses during diagnostic and therapeutic neurointerventional procedures from multiple centers and propose dose reference level (RL).
Materials and Methods:
Consecutive neurointerventional procedures, performed in 22 hospitals from December 2020 to June 2021, were retrospectively studied. We collected data from a sample of 429 diagnostic and 731 therapeutic procedures. Parameters including dose-area product (DAP), cumulative air kerma (CAK), fluoroscopic time (FT), and total number of image frames (NI) were obtained. RL were calculated as the 3rd quartiles of the distribution.
Results:
Analysis of 1160 procedures from 22 hospitals confirmed the large variability in patient dose for similar procedures. RLs in terms of DAP, CAK, FT, and NI were 101.6 Gy·cm2, 711.3 mGy, 13.3 minutes, and 637 frames for cerebral angiography, 199.9 Gy·cm2, 3,458.7 mGy, 57.3 minutes, and 1,000 frames for aneurysm coiling, 225.1 Gy·cm2, 1,590 mGy, 44.7 minutes, and 800 frames for stroke thrombolysis, 412.3 Gy·cm2, 4,447.8 mGy, 99.3 minutes, and 1,621.3 frames for arteriovenous malformation (AVM) embolization, respectively. For all procedures, the results were comparable to most of those already published. Statistical analysis showed male and presence of procedural complications were significant factors in aneurysmal coiling. Male, number of passages, and procedural combined technique were significant factors in stroke thrombolysis. In AVM embolization, a significantly higher radiation dose was found in the definitive endovascular cure group.
Conclusion
Various RLs introduced in this study promote the optimization of patient doses in diagnostic and therapeutic interventional neuroradiology procedures. Proposed 3rd quartile DAP (Gy·cm2) values were 101.6 for diagnostic cerebral angiography, 199.9 for aneurysm coiling, 225.1 for stroke thrombolysis, and 412.3 for AVM embolization. Continual evolution of practices and technologies requires regular updates of RLs.
3.Development and Validation of a Symptom-Focused Quality of Life Questionnaire (KOQUSS-40) for Gastric Cancer Patients after Gastrectomy
Bang Wool EOM ; Joongyub LEE ; In Seob LEE ; Young-Gil SON ; Keun Won RYU ; Sung Geun KIM ; Hyoung-Il KIM ; Young-Woo KIM ; Seong-Ho KONG ; Oh Kyoung KWON ; Ji-Ho PARK ; Ji Yeong AN ; Chang Hyun KIM ; Byoung-Jo SUH ; Hong Man YOON ; Myoung Won SON ; Ji Yeon PARK ; Jong-Min PARK ; Sang-Ho JEONG ; Moon-Won YOO ; Geum Jong SONG ; Han-Kwang YANG ; Yun-Suhk SUH ; Ki Bum PARK ; Sang-Hoon AHN ; Dong Woo SHIN ; Ye Seob JEE ; Hye-Seong AHN ; Sol LEE ; Jae Seok MIN ; Haejin IN ; Ahyoung KIM ; Hoon HUR ; Hyuk-Joon LEE ;
Cancer Research and Treatment 2021;53(3):763-772
Purpose:
Patients who have undergone gastrectomy have unique symptoms that are not appropriately assessed using currently available tools. This study developed and validated a symptom-focused quality of life (QoL) questionnaire for patients who have received gastrectomy for gastric cancer. Materials and Methods Based on a literature review, patient interviews, and expert consultation by the KOrean QUality of life in Stomach cancer patients Study group (KOQUSS), the initial item pool was developed. Two large-scale developmental studies were then sequentially conducted for exploratory factor analyses for content validity and item reduction. The final item pool was validated in a separate cohort of patients and assessed for internal consistency, test-retest reliability, construct validity, and clinical validity.
Results
The initial questionnaire consisted of 46-items in 12 domains. Data from 465 patients at 11 institutions, followed by 499 patients at 13 institutions, were used to conduct item reduction and exploratory factor analyses. The final questionnaire (KOQUSS-40) comprised 40 items within 11 domains. Validation of KOQUSS-40 was conducted on 413 patients from 12 hospitals. KOQUSS-40 was found to have good model fit. The mean summary score of the KOQUSS-40 was correlated with the EORTC QLQ-C30 and STO22 (correlation coefficients, 0.821 and 0.778, respectively). The KOQUSS-40 score was also correlated with clinical factors, and had acceptable internal consistency (> 0.7). Test-retest reliability was greater than 0.8. Conclusion The KOQUSS-40 can be used to assess QoL of gastric cancer patients after gastrectomy and allows for a robust comparison of surgical techniques in clinical trials.
4.Development and Validation of a Symptom-Focused Quality of Life Questionnaire (KOQUSS-40) for Gastric Cancer Patients after Gastrectomy
Bang Wool EOM ; Joongyub LEE ; In Seob LEE ; Young-Gil SON ; Keun Won RYU ; Sung Geun KIM ; Hyoung-Il KIM ; Young-Woo KIM ; Seong-Ho KONG ; Oh Kyoung KWON ; Ji-Ho PARK ; Ji Yeong AN ; Chang Hyun KIM ; Byoung-Jo SUH ; Hong Man YOON ; Myoung Won SON ; Ji Yeon PARK ; Jong-Min PARK ; Sang-Ho JEONG ; Moon-Won YOO ; Geum Jong SONG ; Han-Kwang YANG ; Yun-Suhk SUH ; Ki Bum PARK ; Sang-Hoon AHN ; Dong Woo SHIN ; Ye Seob JEE ; Hye-Seong AHN ; Sol LEE ; Jae Seok MIN ; Haejin IN ; Ahyoung KIM ; Hoon HUR ; Hyuk-Joon LEE ;
Cancer Research and Treatment 2021;53(3):763-772
Purpose:
Patients who have undergone gastrectomy have unique symptoms that are not appropriately assessed using currently available tools. This study developed and validated a symptom-focused quality of life (QoL) questionnaire for patients who have received gastrectomy for gastric cancer. Materials and Methods Based on a literature review, patient interviews, and expert consultation by the KOrean QUality of life in Stomach cancer patients Study group (KOQUSS), the initial item pool was developed. Two large-scale developmental studies were then sequentially conducted for exploratory factor analyses for content validity and item reduction. The final item pool was validated in a separate cohort of patients and assessed for internal consistency, test-retest reliability, construct validity, and clinical validity.
Results
The initial questionnaire consisted of 46-items in 12 domains. Data from 465 patients at 11 institutions, followed by 499 patients at 13 institutions, were used to conduct item reduction and exploratory factor analyses. The final questionnaire (KOQUSS-40) comprised 40 items within 11 domains. Validation of KOQUSS-40 was conducted on 413 patients from 12 hospitals. KOQUSS-40 was found to have good model fit. The mean summary score of the KOQUSS-40 was correlated with the EORTC QLQ-C30 and STO22 (correlation coefficients, 0.821 and 0.778, respectively). The KOQUSS-40 score was also correlated with clinical factors, and had acceptable internal consistency (> 0.7). Test-retest reliability was greater than 0.8. Conclusion The KOQUSS-40 can be used to assess QoL of gastric cancer patients after gastrectomy and allows for a robust comparison of surgical techniques in clinical trials.
5.Early efficacy and safety of statin therapy in Korean patients with hypercholesterolemia: Daegu and Gyeongbuk Statin Registry
Han Joon BAE ; Yun-Kyeong CHO ; Hyoung-Seob PARK ; Hyuck-Jun YOON ; Hyungseop KIM ; Seongwook HAN ; Seung-Ho HUR ; Yoon-Nyun KIM ; Kwon-Bae KIM ; Jae-Kean RYU ; Deug Young NAH ; Chang-Wook NAM
The Korean Journal of Internal Medicine 2020;35(2):342-350
Background/Aims:
To date, prospective data are limited on efficacy and safety profiles of statin therapy in Korean hypercholesterolemic patients. Hence, the aim of this study was to evaluate the practice patterns of statin therapy and its efficacy and safety through the prospective Daegu and Gyeongbuk statin registry.
Methods:
Statin naïve patients who were prescribed statins according to the criteria of Korean Guidelines for Management of Dyslipidemia were enrolled. Clinical and laboratory evaluations were performed at baseline and at week 8, where the efficacy was assessed with the same guidelines.
Results:
Of 908 patients, atorvastatin and rosuvastatin were most frequently prescribed statins (63.1% and 29.3%, respectively). High intensity statins (atorvastatin 40 mg or rosuvastatin 20 mg) were prescribed in 24.7% of all patients and in 79.5% of high and very high risk groups. The total and low density lipoprotein (LDL) cholesterol levels decreased from 203.7 ± 43.0 to 140.6 ± 28.6 mg/dL and 134.4 ± 35.7 to 79.5 ± 21.3 mg/dL, respectively. The achievement rate of the LDL target goal was 98.6% in low risk, 95.0% in moderate risk, 88.1% in high risk, and 42.1% in very high risk patients (59.7% in overall). There was no significant difference in the efficacy between atorvastatin and rosuvastatin. Adverse events were observed in 12.0% of patients and led to 1.4% of treatment cessation.
Conclusions
The efficacy of the usual starting dose of statins in daily practice was relatively insufficient for Korean hypercholesterolemic patients with high or very high risks. Short-term adverse events of statin therapy were not common in Korean patients with a low discontinuation rate.
6.Anti-microbial and anti-inflammatory effects of Cheonwangbosim-dan against Helicobacter pylori-induced gastritis
Hee-Seon PARK ; Hye-Yun JEONG ; Young-Suk KIM ; Chang-Seob SEO ; Hyekyung HA ; Hyo-Jung KWON
Journal of Veterinary Science 2020;21(3):e39-
Background:
There are various Helicobacter species colonizing the stomachs of animals. Although Helicobacter species usually cause asymptomatic infection in the hosts, clinical signs can occur due to gastritis associated with Helicobacter in animals. Among them, Helicobacter pylori is strongly associated with chronic gastritis, gastric ulcers, and gastric cancers. As the standard therapies used to treat H. pylori have proven insufficient, alternative options are needed to prevent and eradicate the diseases associated with this bacterium. Cheonwangbosim-dan (CBD), a traditional herbal formula that is popular in East Asia, has been commonly used for arterial or auricular flutter, neurosis, insomnia, and cardiac malfunction-induced disease.
Objectives:
The present study investigated the antimicrobial effect of CBD on H. pylori-infected human gastric carcinoma AGS cells and model mice.
Methods:
AGS cells were infected with H. pylori and treated with a variety of concentrations of CBD or antibiotics. Mice were given 3 oral inoculations with H. pylori and then dosed with CBD (100 or 500 mg/kg) for 4 weeks or with standard antibiotics for 1 week. One week after the last treatment, gastric samples were collected and examined by histopathological analysis, real-time quantitative polymerase chain reaction, and immunoblotting.
Results:
Our results showed that CBD treatment of AGS cells significantly reduced the H. pylori-induced elevations of interleukin-8, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). In the animal model, CBD treatment inhibited the colonization of H. pylori and the levels of malondialdehyde, inflammation, proinflammatory cytokines, iNOS, and COX-2 in gastric tissues. CBD also decreased the phosphorylation levels of p38 mitogen-activated protein kinase family.
Conclusions
This study suggests that CBD might be a prospective candidate for treatingH. pylori-induced gastric injury.
7.The Implication of Cardiac Injury Score on In-hospital Mortality of Coronavirus Disease 2019
In-Cheol KIM ; Jin Eun SONG ; Hee Jung LEE ; Jeong-Ho PARK ; Miri HYUN ; Ji Yeon LEE ; Hyun Ah KIM ; Yong Shik KWON ; Jae Seok PARK ; Jong-Chan YOUN ; Jongmin HWANG ; Cheol Hyun LEE ; Yun-Kyeong CHO ; Hyoung-Seob PARK ; Hyuck-Jun YOON ; Chang-Wook NAM ; Seongwook HAN ; Seung-Ho HUR ; Howard J. EISEN ; Hyungseop KIM
Journal of Korean Medical Science 2020;35(39):e349-
Background:
s: The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has spread worldwide. Cardiac injury after SARS-CoV-2 infection is a major concern. The present study investigated impact of the biomarkers indicating cardiac injury in coronavirus disease 2019 (COVID-19) on patients' outcomes.
Methods:
This study enrolled patients who were confirmed to have COVID-19 and admitted at a tertiary university referral hospital between February 19, 2020 and March 15, 2020. Cardiac injury was defined as an abnormality in one of the following result markers: 1) myocardial damage marker (creatine kinase-MB or troponin-I), 2) heart failure marker (N-terminal-pro B-type natriuretic peptide), and 3) electrical abnormality marker (electrocardiography). The relationship between each cardiac injury marker and mortality was evaluated. Survival analysis of mortality according to the scoring by numbers of cardiac injury markers was also performed.
Results:
A total of 38 patients with COVID-19 were enrolled. Twenty-two patients (57.9%) had at least one of cardiac injury markers. The patients with cardiac injuries were older (69.6 ± 14.9 vs. 58.6 ± 13.9 years old, P = 0.026), and were more male (59.1% vs. 18.8%, P = 0.013).They showed lower initial oxygen saturation (92.8 vs. 97.1%, P = 0.002) and a trend toward higher mortality (27.3 vs. 6.3%, P = 0.099). The increased number of cardiac injury markers was significantly related to a higher incidence of in-hospital mortality which was also evidenced by Kaplan-Meier survival analysis (P = 0.008).
Conclusion
The increased number of cardiac injury markers is related to in-hospital mortality in patients with COVID-19.
8.Serotype Distribution and Antimicrobial Resistance of Invasive and Noninvasive Streptococcus pneumoniae Isolates in Korea between 2014 and 2016
Dong Chul PARK ; Si Hyun KIM ; Dongeun YONG ; In Bum SUH ; Young Ree KIM ; Jongyoun YI ; Wonkeun SONG ; Sae Am SONG ; Hee Won MOON ; Hae Kyung LEE ; Kyoung Un PARK ; Sunjoo KIM ; Seok Hoon JEONG ; Jaehyeon LEE ; Joseph JEONG ; Yu Kyung KIM ; Miae LEE ; Jihyun CHO ; Jong Wan KIM ; Kyeong Seob SHIN ; Sang Hyun HWANG ; Jae Woo CHUNG ; Hye In WOO ; Chae Hoon LEE ; Namhee RYOO ; Chulhun L CHANG ; Hyun Soo KIM ; Jayoung KIM ; Jong Hee SHIN ; Soo Hyun KIM ; Mi Kyung LEE ; Seong Gyu LEE ; Sook Jin JANG ; Kyutaeg LEE ; HunSuk SUH ; Yong Hak SOHN ; Min Jung KWON ; Hee Joo LEE ; Ki Ho HONG ; Kwang Sook WOO ; Chul Min PARK ; Jeong Hwan SHIN
Annals of Laboratory Medicine 2019;39(6):537-544
BACKGROUND: Several factors contribute to differences in Streptococcus pneumoniae serotype distribution. We investigated the serotype distribution and antimicrobial resistance of S. pneumoniae isolated between 2014 and 2016 in Korea. METHODS: We collected a total of 1,855 S. pneumoniae isolates from 44 hospitals between May 2014 and May 2016, and analyzed the serotypes by sequential multiplex PCR. We investigated the distribution of each serotype by patient age, source of the clinical specimen, and antimicrobial resistance pattern. RESULTS: The most common serotypes were 11A (10.1%), followed by 19A (8.8%), 3 (8.5%), 34 (8.1%), 23A (7.3%), and 35B (6.2%). The major invasive serotypes were 3 (12.6%), 19A (7.8%), 34 (7.8%), 10A (6.8%), and 11A (6.8%). Serotypes 10A, 15B, 19A, and 12F were more common in patients ≤5 years old, while serotype 3 was more common in patients ≥65 years old compared with the other age groups. The coverage rates of pneumococcal conjugate vaccine (PCV)7, PCV10, PCV13, and pneumococcal polysaccharide vaccine 23 were 11.8%, 12.12%, 33.3%, and 53.6%, respectively. Of the 1,855 isolates, 857 (46.2%) were multi-drug resistant (MDR), with serotypes 11A and 19A predominant among the MDR strains. The resistance rates against penicillin, cefotaxime, and levofloxacin were 22.8%, 12.5%, and 9.4%, respectively. CONCLUSIONS: There were significant changes in the major S. pneumoniae serotypes in the community. Non-PCV13 serotypes increased in patients ≤5 years old following the introduction of national immunization programs with the 10- and 13-polyvalent vaccines.
Cefotaxime
;
Humans
;
Immunization Programs
;
Korea
;
Levofloxacin
;
Multiplex Polymerase Chain Reaction
;
Penicillins
;
Pneumococcal Vaccines
;
Pneumonia
;
Serogroup
;
Streptococcus pneumoniae
;
Streptococcus
;
Vaccines
9.Influence of Local Myocardial Infarction on Endothelial Function, Neointimal Progression, and Inflammation in Target and Non-Target Vascular Territories in a Porcine Model of Acute Myocardial Infarction
Hyun Kuk KIM ; Han Byul KIM ; Joo Myung LEE ; Sung Soo KIM ; In Ho BAE ; Dae Sung PARK ; Jun Kyu PARK ; Jae Won SHIM ; Joo Young NA ; Min Young LEE ; Joong Sun KIM ; Doo Sun SIM ; Young Joon HONG ; Chang Wook NAM ; Joon Hyung DOH ; Jonghanne PARK ; Bon Kwon KOO ; Sun Uk KIM ; Kyung Seob LIM ; Myung Ho JEONG
Journal of Korean Medical Science 2019;34(19):e145-
BACKGROUND: Patients with acute myocardial infarction (AMI) have worse clinical outcomes than those with stable coronary artery disease despite revascularization. Non-culprit lesions of AMI also involve more adverse cardiovascular events. This study aimed to investigate the influence of AMI on endothelial function, neointimal progression, and inflammation in target and non-target vessels. METHODS: In castrated male pigs, AMI was induced by balloon occlusion and reperfusion into the left anterior descending artery (LAD). Everolimus-eluting stents (EES) were implanted in the LAD and left circumflex (LCX) artery 2 days after AMI induction. In the control group, EES were implanted in the LAD and LCX in a similar fashion without AMI induction. Endothelial function was assessed using acetylcholine infusion before enrollment, after the AMI or sham operation, and at 1 month follow-up. A histological examination was conducted 1 month after stenting. RESULTS: A total of 10 pigs implanted with 20 EES in the LAD and LCX were included. Significant paradoxical vasoconstriction was assessed after acetylcholine challenge in the AMI group compared with the control group. In the histologic analysis, the AMI group showed a larger neointimal area and larger area of stenosis than the control group after EES implantation. Peri-strut inflammation and fibrin formation were significant in the AMI group without differences in injury score. The non-target vessel of the AMI also showed similar findings to the target vessel compared with the control group. CONCLUSION: In the pig model, AMI events induced endothelial dysfunction, inflammation, and neointimal progression in the target and non-target vessels.
Acetylcholine
;
Arteries
;
Balloon Occlusion
;
Constriction, Pathologic
;
Coronary Artery Disease
;
Drug-Eluting Stents
;
Endothelium
;
Fibrin
;
Follow-Up Studies
;
Humans
;
Inflammation
;
Male
;
Myocardial Infarction
;
Reperfusion
;
Stents
;
Swine
;
Vasoconstriction
10.Arterial Spin Labeling Perfusion MRI of Crossed Cerebellar Diaschisis in a Patient with Simple Partial Status Epilepticus.
Hye hoon KANG ; Young Soo KIM ; Da Hye JEONG ; Do Hyung KIM ; Dae Seob CHOI ; Jeong Jin YI ; Min Won PARK ; Kee Hong PARK ; Chang Hun KIM ; Soo Kyoung KIM ; Heeyoung KANG ; Nack Cheon CHOI ; Oh Young KWON ; ByeongHoon LIM
Journal of the Korean Neurological Association 2017;35(3):142-147
Crossed cerebellar diaschisis (CCD) is known to be due to a contralateral supratentorial lesion decreasing blood flow and the metabolism in a cerebellar hemisphere. Arterial spin labeling (ASL) is an imaging technique that utilizes arterial blood water as a tracer for quantifying the regional cerebral blood flow in magnetic resonance imaging (MRI). This case was a patient with simple partial status epilepticus (SPSE) and CCD confirmed by ASL-perfusion MRI. Controlling the SPSE resulted in improvement of CCD being observed in the follow-up ASL-perfusion MRI.
Cerebrovascular Circulation
;
Follow-Up Studies
;
Humans
;
Magnetic Resonance Imaging*
;
Metabolism
;
Perfusion*
;
Status Epilepticus*
;
Water

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