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.Impacts of Atherosclerotic Coronary Risk Factors on Atherosclerotic Surrogates in Patients with Coronary Artery Disease.
Won Min HWANG ; Jang Ho BAE ; Ki Young KIM ; Yi Chul SYNN
Korean Circulation Journal 2005;35(2):131-139
BACKGROUND AND OBJECTIVES: The carotid intima-media thickness, endothelial function and arterial stiffness have been shown to be parameters of atherosclerosis. We have performed this study to evaluate the impact of atherosclerotic coronary risk factors on several atherosclerotic parameters in patients with coronary artery disease. SUBJECTS AND METHODS: The study subjects consisted of one hundred and forty (140) consecutive patients (mean age: 61 years, and 85 males), who demonstrated via coronary angiogram more than 50% stenosis in at least 1 major coronary artery. In an overnight fasting state, the carotid intima-media thickness (IMT), and endothelial function (flow-mediated brachial artery dilatation, FMD) were measured by high-resolution ultrasound, and arterial stiffness (pulse wave velocity, PWV) was measured by using a non-invasive pulse wave analyser. RESULTS: The hypertensive group showed more evidence of greater arterial stiffness (aorta; 8.5+/-1.0 m/s vs. 7.9+/-1.2 m/s, p=0.004, and greater stiffness of the artery of the lower extremity; 9.2+/-1.2 m/s vs. 8.7+/-1.3 m/s, p=0.010), which was measured by the pulse wave velocity, than that of the normotensive group. The carotid IMT and the endothelial function showed no significant differences between the two groups. Furthermore, these parameters did not show significant differences with other parameters such as diabetes mellitus, smoking, and hyperlipidemia. Multivariate analysis revealed that hypertension and systolic blood pressure were still the independent factors of arterial stiffness, but carotid IMT and endothelial function were not independent factors. CONCLUSION: Hypertension and systolic blood pressure are the independent factors of arterial stiffness in patients with coronary artery disease (CAD), but this study did not show that carotid IMT and endothelial function made a significant difference in arterial stiffness. However, in this study, other risk factors were not associated with the differences of these parameters.
Arteries
;
Atherosclerosis
;
Blood Pressure
;
Brachial Artery
;
Carotid Intima-Media Thickness
;
Constriction, Pathologic
;
Coronary Artery Disease*
;
Coronary Vessels*
;
Diabetes Mellitus
;
Dilatation
;
Endothelium
;
Fasting
;
Humans
;
Hyperlipidemias
;
Hypertension
;
Lower Extremity
;
Multivariate Analysis
;
Pulse Wave Analysis
;
Risk Factors*
;
Smoke
;
Smoking
;
Tunica Intima
;
Ultrasonography
;
Vascular Stiffness
3.A Case of a Successful Percutaneous Coronary Intervention Using Percusurge(r) System in a Massive Intracoronary Thrombi Patient.
Yi Chul SYNN ; Jang Ho BAE ; Ki Rack PARK ; Ki Young KIM ; Hyun Ju YOON
Korean Circulation Journal 2004;34(4):405-409
A massive intracoronary thrombus, during percutaneous coronary intervention (PCI), implies a high risk of major adverse cardiac events. We experienced a case of successful PCI, using Percusurge(r), in an acute myocardial infarc-tion patient, with massive intracoronary thrombi. The TIMI 3 coronary flow could not be restored during a primary PCI of the right coronary artery, despite repeated ballooning, intracoronary urokinase injection, parenteral abciximab and heparin. However, successful PCI, with stenting, was performed by aspiration of the large intracoronary thrombi, with the Percusurge(r) system, 5 days after the primacy PCI.
Angioplasty, Balloon, Coronary
;
Coronary Vessels
;
Heparin
;
Humans
;
Percutaneous Coronary Intervention*
;
Stents
;
Thrombosis
;
Urokinase-Type Plasminogen Activator
4.A Case of a Successful Percutaneous Coronary Intervention Using Percusurge(r) System in a Massive Intracoronary Thrombi Patient.
Yi Chul SYNN ; Jang Ho BAE ; Ki Rack PARK ; Ki Young KIM ; Hyun Ju YOON
Korean Circulation Journal 2004;34(4):405-409
A massive intracoronary thrombus, during percutaneous coronary intervention (PCI), implies a high risk of major adverse cardiac events. We experienced a case of successful PCI, using Percusurge(r), in an acute myocardial infarc-tion patient, with massive intracoronary thrombi. The TIMI 3 coronary flow could not be restored during a primary PCI of the right coronary artery, despite repeated ballooning, intracoronary urokinase injection, parenteral abciximab and heparin. However, successful PCI, with stenting, was performed by aspiration of the large intracoronary thrombi, with the Percusurge(r) system, 5 days after the primacy PCI.
Angioplasty, Balloon, Coronary
;
Coronary Vessels
;
Heparin
;
Humans
;
Percutaneous Coronary Intervention*
;
Stents
;
Thrombosis
;
Urokinase-Type Plasminogen Activator
5.Is Arterial Stiffness Useful in Differentiating Patients with Coronary Artery Disease from Risk Factor Only Patients?.
Yi Chul SYNN ; Jang Ho BAE ; Ki Young KIM ; Hyun Ju YOON ; Hoon Sup KOO ; Jung Kyu KIM ; Won Min HWANG ; Dong Mi LIM ; In Beom JEONG
Korean Circulation Journal 2004;34(9):845-855
BACKGROUND AND OBJECTIVE: The endothelial function, carotid intima-media thickness (CIMT) and arterial stiffness are known as surrogates of atherosclerosis, but it is not clear whether these surrogates can discriminate patients with coronary artery disease (CAD) from those with risk factor. The intention was to compare these 3 surrogates in patients with CAD and those with risk factor only. SUCJECTS AND METHODS: Forty-three patients with CAD (mean age:58, 32 men), 18 age and sex matched healthy people (mean age:52, 9 men) and 16 patients (mean age:53, 12 men) with atherosclerosis risk factor only were enrolled. The endothelial function (flow-mediated brachial artery dilation, FMD) and CIMT were measured by high-resolution ultrasound and the arterial stiffness by an oscillometric method. RESULTS: There was a significant difference between the CAD and risk factor groups (3.46+/-1.3% vs. 5.77+/-2.54%, p<0.05), but there was no significant difference between the risk factor and healthy groups (5.29+/-2.0% vs. 5.77+/-2.54%, p>0.05) in the measured FMD. The CIMT showed a significant difference between the CAD and healthy groups (0.89+/-0.14 mm vs. 0.78+/-0.07 mm, p<0.05), but there was no significant difference between the CAD and risk factor groups(0.89+/-0.14 mm vs. 0.83+/-0.12 mm, p>0.05). There were significant differences among all groups in relation to the arterial stiffness (CAD group:1524+/-289 cm/sec, risk group:1342+/-202 cm/sec, healthy group:1195+/-119 cm/sec, p<0.05). The arterial stiffness showed significant correlation with the FMD (r=-0.322, p=0.005) and CIMT (r=0.310, p=0.007). CONCLUSION: Of the 3 surrogates, the arterial stiffness measurement showed the best reliability in differentiating the CAD from the risk factor only groups as well as from healthy subjects. This study suggests the arterial stiffness can be used as a novel noninvasive test for early diagnosis of CAD in patients at high risk of atherosclerosis.
Arteries
;
Atherosclerosis
;
Brachial Artery
;
Carotid Intima-Media Thickness
;
Coronary Artery Disease*
;
Coronary Vessels*
;
Early Diagnosis
;
Endothelium
;
Humans
;
Intention
;
Risk Factors*
;
Ultrasonography
;
Vascular Stiffness*
6.Correlation between Endothelial Function and the Extent of Coronary Atherosclerosis.
Yi Chul SYNN ; Jang Ho BAE ; Ki Young KIM
Korean Circulation Journal 2004;34(8):752-760
BACKGROUND AND OBJECTIVES: The purposes of this study were to provide evidence of any correlation between the endothelial dysfunction and the extent of coronary atherosclerosis, and the relationship between the endothelial function and individual atherosclerosis risk factors in patients with significant coronary artery stenosis. SUBJECTS AND METHODS: The endothelial function was measured by hyperemia induced brachial artery dilation, using high resolution ultrasound, in 284 consecutive patients (mean age 59 years, men: 176) having undergone coronary angiography. The subjects were divided into four groups according to the number of coronary arteries narrowed by more than 50%; 0 (n=88), 1 (n=98), 2 (n=54) and 3 (n=44). The endothelial functions were compared to see if significant coronary artery disease was present, according to the groups and the presence of individual atherosclerosis risk factors. RESULTS: There were no significant differences in the endothelial dysfunction between the narrowed and normal coronary artery groups (4.66+/-2.45% vs. 4.43+/-1.53% p>0.05) or between the four groups. The endothelial function in patients with significant coronary artery stenosis (n=196) was significantly lower when coupled with hypertension (n=84, 2.99+/-2.4% vs. 4.20+/-2.4%, p<0.05), diabetes (n=44, 4.07+/-2.7% vs. 4.84+/-2.5%, p<0.05) and hypercholesterolemia (n=82, 4.26+/-1.9% vs. 4.95+/-2.7%, p<0.05), but not with smoking. CONCLUSION: The endothelial function showed no difference according to the extent of coronary atherosclerosis. Risk factors of atherosclerosis, such as hypertension, diabetes mellitus and hypercholesterolemia, can deteriorate the endothelial function further, even in the patients with significant coronary artery stenosis.
Atherosclerosis
;
Brachial Artery
;
Coronary Angiography
;
Coronary Artery Disease*
;
Coronary Stenosis
;
Coronary Vessels
;
Diabetes Mellitus
;
Endothelium, Vascular
;
Humans
;
Hypercholesterolemia
;
Hyperemia
;
Hyperlipidemias
;
Hypertension
;
Male
;
Risk Factors
;
Smoke
;
Smoking
;
Ultrasonography
7.Safety and efficacy of arbutamine stress echocardiography.
Yi Chul SYNN ; Kee Sik KIM ; Jang Ho BAE ; Seong Wook HAN ; So Young PARK ; Chang Wook NAM ; Ki Young KIM ; Yoon Nyun KIM ; Kwon Bae KIM ; You Hee KIM
Korean Journal of Medicine 2000;58(1):39-47
BACKGROUND: Exercise and pharmacologic stress echocardiography are widely used for detecting coronary artery disease. Arbutamine is a new synthetic mild alpha1-receptor and - receptor agonist developed specifically for stress echocardiography. Arbutamine is superior to dobutamine owing to its enforced chronotropic action than that of dobutamine. We intended to know safety and efficacy of arbutamine stress echocardiography in inducing myocardial ischemia and detecting coronary artery disease. METHODS: We underwent arbutamine stress echocardiography on 52 patients, dobutamine stress echocardiography in 35 patients. Alteration of blood pressure, heart rate, regional wall motion on echocardiography were evaluated. Sensitivity and specificity were determined by coronary angiography for 61 patients(Arbutamine: 31, Dobutamine : 30) RESULTS: 1) Hemodynamic alterations respect to stress agents Baseline Maximal Baseline Maximal Interval for Blood pressure Blood pressure Heartrate Heart rate maximal heartrate Arbutamine 122/70mmHg 138/72mmHg 69BPM 137BPM 8.2 min* Dobutamine 126/73mmHg 136/77mmHg 74BPM 102BPM 11.4 min* (* p < 0.05) 2) Comparison of Arbutamine and Dobutamine in sensitivity Sensitivity(Specificity) Side effects Atropine Arbutamine 80.1% (90%) 33(63.5%) 8(15.4%) Dobutamine 78.2% (71.4%) 21(60%) 7(20%) 3) Side effects of stress agents Hypotension Palpitation, tremor Arrhythmia Chest pain Arbutamine 15(28.8%)* 4(7.7%)* 21(40.4%) 8(9.2%) Dobutamine 3(8.6%)* 9(25.7%)* 12(34.3%) 5(5.7%) (* p < 0.05) 4) Premature ventricular contraction was most common arrhythmia in both group. There was no fatal or significant complication, and most complications were subsided after discontinuation of stress agents. CONCLUSION: Arbutamine is an effective and safe pharmacologic stress agent in detecting myocardial ischemia and superior to dobutamine in increasing heart rate. Sensitivity and specificity of arbutamine were higher than that of dobutamine.
Arrhythmias, Cardiac
;
Atropine
;
Blood Pressure
;
Chest Pain
;
Coronary Angiography
;
Coronary Artery Disease
;
Dobutamine
;
Echocardiography
;
Echocardiography, Stress*
;
Heart Rate
;
Hemodynamics
;
Humans
;
Hypotension
;
Myocardial Ischemia
;
Sensitivity and Specificity
;
Tremor
;
Ventricular Premature Complexes
8.Secondary T Wave Changes in Patients with Wolff-Parkinson-White(WPW) Syndrome.
Jang Ho BAE ; Yoon Nyun KIM ; Yi Chul SYNN ; So Young PARK ; Ki Young KIM ; Chang Wook NAM ; Kee Sik KIM ; Kwon Bae KIM ; Shee Juhn CHUNG
Korean Circulation Journal 1999;29(7):705-711
OBJECTIVES: The purpose of this study is to evaluate the incidence of secondary T wave changes in WPW syndrome and the relation between the incidence of the secondary T wave changes and sex, age (duration of preexcitation), mean and maximal QRS duration (from the onset of delta wave to the end of S wave) of standard 12 lead electrocardiogram (ECG) and the site of accessory pathway (AP). The secondary purpose of this study is to evaluate the relation between the site of secondary T wave changes and the location of the AP. METHODS: Of the total 128 patients (pts) with WPW syndrome, standard 12 lead ECGs of 125 pts (mean age 35, male 71 pts) who were free from bundle branch block (n=2) and myocardial ischemia (n=1) were analyzed. The locations of Aps were divided into 4 categories (anterior, left lateral, posterior and right lateral) by intracardiac mapping. RESULTS: 82 (66%) pts of 125 pts showed secondary T wave changes. The incidence of secondary T wave changes was not related to sex or duration of preexcitation, but mean QRS duration (<0.12: 46%, 0.12: 88%, p<0.001), maximal QRS duration (<0.12: 32%, 0.12: 73%, p<0.001) and the site of AP (right: 80%, left: 54%, p=0.003). The most frequent lead showing secondary T wave changes in ECG was lateral (lead I, aVL) in pts with anterior (43%, 9 out of 21), posterior (50%, 25 out of 50) and right lateral (86%, 6 out of 7) AP. But, no secondary T wave change was found in most pts with left lateral (n=47) AP. CONCLUSION: The incidence of the secondary T wave changes in pts with WPW syndrome is high (66%). These changes are not related to sex and duration of preexcitation, but to the mean and maximal QRS duration during preexcitation and the location of the AP. The ECG lead showing secondary T wave changes in pts with WPW syndrome appears to be related to the location of the AP and the most frequent lead is I and aVL.
Bundle-Branch Block
;
Electrocardiography
;
Humans
;
Incidence
;
Male
;
Myocardial Ischemia
;
Wolff-Parkinson-White Syndrome
9.Clinical Characteristics of Acute Myocardial Infarction Died during Hospitalization.
Dae Woo HYUN ; Kee Sik KIM ; Yi Chul SYNN ; So Young PARK ; Jang Ho BAE ; Chang Yeob HAN ; Yoon Nyun KIM ; Kwon Bae KIM
Korean Circulation Journal 1998;28(9):1518-1526
BACKGROUND: Recently, the incidence of acute myocardial infarction (AMI) rapidly increased with prolongation of life spans, improvements of food and life styles in Korea. The mortality rate of AMI is higher than other disease. The purpose of this study is to evaluate which factors can affect the early outcome of AMI in Korean. METHODS: A retrospective clinical study was done on 555 consecutive patients{Male:Female=387 (69.7%):168 (30.3%), mean age 61.3 years} with AMI who had been admitted to Dong-San Medical Center from January 1990 to May 1997 . The subjects were devided into two groups. Group I was dead patients during the in-hospital period (85 patients, 15.3%), and Group II was living patients (470 patients, 84.7%) wen they discharged from hospital. We compared clinical and laboratory results in both groups and analysed the cause of death according to the time of death during hospitalization. RESULTS: The results were as folows; 1) The mean age and female percentage of Group I (65.4 years, 43%) were higher than Group II (60.5 years, 28%). The mean of systolic/diastolic blood pressure and percentage of smoker of Group I (108/65mmHg, 48%) were lower than Group II (125/76mmHg, 65%), significantly. 2) The degree of Killip classification was higher in Group I (class 1:29.4%, II:18.8%, III:21.2%, IV:30.6%) than in Group II patients (class 1:73.4%, II:13.6%, III:8.7%, IV:4.3%), significantly. 3) 47 patients were died first day of hospitalization and the most common cause of death was cardiogenic shock (27 patients, 31%). The most common cause of death within 1 week was cardiogenic shock, afterthen congestive heart failure. 4) The most common cause of death in Killip class I patients was ventricular tachycardia or ventricular fibrillation and in Killip class II-IV patients was cardiogenic shock. CONCLUSION: The risk of in-hospital death was higher in elderly, female sex, and patients with higher killip classification. Cardiogenic shock was most common cause of death within 1 week, and was congestive heart failure after 1 week.
Aged
;
Blood Pressure
;
Cause of Death
;
Classification
;
Female
;
Heart Failure
;
Hospitalization*
;
Humans
;
Incidence
;
Korea
;
Life Style
;
Life Support Care
;
Mortality
;
Myocardial Infarction*
;
Retrospective Studies
;
Shock, Cardiogenic
;
Tachycardia, Ventricular
;
Ventricular Fibrillation
10.A Case of Congenital Cystic Adenomatoid Malformation of the Lung.
Young Joo BAEK ; Jeong Aa LEE ; Eui Sook KIM ; Won Seok LEE ; Kang Ryang LEE ; Gwang Seob LEE ; Synn Eung KIM ; In Cheol SUNWOO ; Dae Ha KIM ; Jie Jeong JANG ; Young Sook HAN ; Mi Kyeng JEE
Korean Journal of Medicine 1997;52(1):143-147
Congenital cystic adenomatoid malformation(C.C. A.M.) is a rare variant of congenital pulmonary cystic diseases. C.C.A.M. was first distinguished from other pulmonary cystic lesions by Ch`in and Tang in 1949. It is characterized by cessation of bronchiolar maturation with an overgrowth of mesenchymal elements and proliferation of polypoid glandular tissue in the absence of normal alveolar differentiation. In 80% to 95% of cases, C.C.A.M. of the lung is confinded to a single lobe and there is no lobe predilection and right and left predominance. The clinical presentation may be widely variable, ranging from intrauterine fetal death secondary to nonimmune hydrops fetalis to discovery in childhood after recurrent pulmonary infections. Definitive treatment is removal of affected lobe. In rare instances, there is cases of myxosarcoma, embryonal rhabdomyosarcoma. Bronchoalveolar carcinoma arising in C.C.A.M.. So, resection is recommended even if they are asymtomatic. We have experienced a case of congenital cystic adenomatoid malformation (type II) of the lung in 15 year old man with pneumonia. After the improvement of pneumonia, surgical operation was performed. A brief review of the related literature is presented.
Adolescent
;
Cystic Adenomatoid Malformation of Lung, Congenital*
;
Fetal Death
;
Humans
;
Hydrops Fetalis
;
Lung*
;
Myxosarcoma
;
Pneumonia
;
Rhabdomyosarcoma, Embryonal

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