1.Antiproliferative Activity of Gibbosic Acid H throughInduction of G0/G1 Cell Cycle Arrest and Apoptosis inHuman Lung Cancer Cells
Jaeho HAN ; Donghwa KIM ; Hyen Joo PARK ; Hee-Juhn PARK ; Sang Kook LEE
Journal of Cancer Prevention 2023;28(4):201-211
Lung cancer is one of the most common causative cancers worldwide. Particularly, non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases. NSCLC is a serious form of lung cancer that requires prompt diagnosis, and the 5-year survival rate for patients with this disease is only 24%. Gibbosic acid H (GaH), a natural lanostanoid obtained from the Ganoderma species (Ganodermataceae), has antiproliferative activities against colon and lung cancer cells. The aim of the present study was to evaluate the antiproliferative activity of GaH in NSCLC cells and to elucidate the underlying molecular mechanisms.GaH was found to induce G0/G1 cell cycle arrest and autophagy by activating adenosine monophosphate-activated protein kinase in A549 and H1299 cells. The induction of this cell cycle arrest was associated with the downregulation of cyclin E1 and CDK2.Additionally, the induction of autophagy by GaH was correlated with the upregulation of LC3B, beclin-1, and p53 expression. GaH also induced apoptosis by upregulating cleaved caspase-3 and Bax in the lung cancer cells. These findings suggest that GaH has a potential in the growth inhibition of human lung cancer cells.
2.Anti-Proliferative Activity of Nodosin, a Diterpenoid from Isodon serra, via Regulation of Wnt/β-Catenin Signaling Pathways in Human Colon Cancer Cells
Eun Seo BAE ; Young-Mi KIM ; Dong-Hwa KIM ; Woong Sub BYUN ; Hyen Joo PARK ; Young-Won CHIN ; Sang Kook LEE
Biomolecules & Therapeutics 2020;28(5):465-472
Colorectal cancer (CRC) is one of the most malignant type of cancers and its incidence is steadily increasing, due to life style factors that include western diet. Abnormal activation of canonical Wnt/β-catenin signaling pathway plays an important role in colorectal carcinogenesis. Therefore, targeting Wnt/β-catenin signaling has been considered a crucial strategy in the discovery of small molecules for CRC. In the present study, we found that Nodosin, an ent-kaurene diterpenoid isolated from Isodon serra, effectively inhibits the proliferation of human colon cancer HCT116 cells. Mechanistically, Nodosin effectively inhibited the overactivated transcriptional activity of β-catenin/T-cell factor (TCF) determined by Wnt/β-catenin reporter gene assay in HEK293 and HCT116 cells. The expression of Wnt/β-catenin target genes such as Axin2, cyclin D1, and survivin were also suppressed by Nodosin in HCT116 cells. Further study revealed that a longer exposure of Nodosin induced the G 2/M phase cell cycle arrest and subsequently apoptosis in HCT116 cells. These findings suggest that the anti-proliferative activity of Nodosin in colorectal cancer cells might in part be associated with the regulation of Wnt/β-catenin signaling pathway.
3.Phenotypes of Severe Cutaneous Adverse Reactions Caused by Nonsteroidal Anti-inflammatory Drugs
Suh Young LEE ; Young Hee NAM ; Young Il KOH ; Sae Hoon KIM ; Sujeong KIM ; Hye Ryun KANG ; Min Hye KIM ; Jun Gyu LEE ; Jung Won PARK ; Hye Kyung PARK ; Hyen O LA ; Mi Yeong KIM ; Seong Ju PARK ; Yong Eun KWON ; Jae Woo JUNG ; Sang Hyon KIM ; Cheol Woo KIM ; Min Seok YANG ; Min Gyu KANG ; Jin Yong LEE ; Joo Hee KIM ; Sang Heon KIM ; Gyu Young HUR ; Young Koo JEE ; Hyun Jung JIN ; Chan Sun PARK ; Yi Yeong JEONG ; Young Min YE
Allergy, Asthma & Immunology Research 2019;11(2):212-221
PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are common cause of severe cutaneous adverse reactions (SCARs). The present study aimed to investigate the characteristics of SCARs induced by NSAIDs in the Korean SCAR registry. METHODS: A retrospective survey of NSAID-induced SCARs recorded between 2010 and 2015 at 27 university hospitals in Korea was conducted. Clinical phenotypes of SCARs were classified into Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), SJS-TEN overlap syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS). Causative NSAIDs were classified into 7 groups according to their chemical properties: acetaminophen, and propionic, acetic, salicylic, fenamic and enolic acids. RESULTS: A total of 170 SCARs, consisting of 85 SJS, 32 TEN, 17 SJS-TEN overlap syndrome and 36 DRESS reactions, were induced by NSAIDs: propionic acids (n=68), acetaminophen (n=38), acetic acids (n=23), salicylic acids (n=16), coxibs (n=8), fenamic acids (n=7), enolic acids (n=5) and unclassified (n=5). Acetic acids (22%) and coxibs (14%) accounted for higher portions of DRESS than other SCARs. The phenotypes of SCARs induced by both propionic and salicylic acids were similar (SJS, TEN and DRESS, in order). Acetaminophen was primarily associated with SJS (27%) and was less involved in TEN (10%). DRESS occurred more readily among subjects experiencing coxib-induced SCARs than other NSAID-induced SCARs (62.5% vs. 19.7%, P = 0.013). The mean time to symptom onset was longer in DRESS than in SJS or TEN (19.1 ± 4.1 vs. 6.8 ±1.5 vs. 12.1 ± 3.8 days). SCARs caused by propionic salicylic acids showed longer latency, whereas acetaminophen- and acetic acid-induced SCARs appeared within shorter intervals. CONCLUSIONS: The present study indicates that the phenotypes of SCARs may differ according to the chemical classifications of NSAIDs. To establish the mechanisms and incidences of NSAID-induced SCARs, further prospective studies are needed.
Acetaminophen
;
Acetates
;
Acetic Acid
;
Anti-Inflammatory Agents, Non-Steroidal
;
Cicatrix
;
Classification
;
Cyclooxygenase 2 Inhibitors
;
Diethylpropion
;
Drug Hypersensitivity
;
Drug Hypersensitivity Syndrome
;
Hospitals, University
;
Incidence
;
Korea
;
Phenotype
;
Propionates
;
Prospective Studies
;
Retrospective Studies
;
Salicylates
;
Salicylic Acid
;
Stevens-Johnson Syndrome
4.Severe Cutaneous Adverse Reactions to Antiepileptic Drugs: A Nationwide Registry-Based Study in Korea
Chan Sun PARK ; Dong Yoon KANG ; Min Gyu KANG ; Sujeong KIM ; Young Min YE ; Sae Hoon KIM ; Hye Kyung PARK ; Jung Won PARK ; Young Hee NAM ; Min Suk YANG ; Young Koo JEE ; Jae Woo JUNG ; Sang Hyon KIM ; Cheol Woo KIM ; Mi Yeong KIM ; Joo Hee KIM ; Jaechun LEE ; Jun Gyu LEE ; Sang Hyun KIM ; Hyen O LA ; Min Hye KIM ; Seoung Ju PARK ; Young Il KOH ; Sang Min LEE ; Yong Eun KWON ; Hyun Jung JIN ; Hee Kyoo KIM ; Hye Ryun KANG ; Jeong Hee CHOI ;
Allergy, Asthma & Immunology Research 2019;11(5):709-722
PURPOSE: Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) to antiepileptic drug (AED), are rare, but result in significant morbidity and mortality. We investigated the major culprit drugs, clinical characteristics, and clinical course and outcomes of AED-induced SCARs using a nationwide registry in Korea. METHODS: A total of 161 patients with AED-induced SCARs from 28 referral hospitals were analyzed. The causative AEDs, clinical characteristics, organ involvements, details of treatment, and outcomes were evaluated. We compared the clinical and laboratory parameters between SJS/TEN and DRESS according to the leading causative drugs. We further determined risk factors for prolonged hospitalization in AED-induced SCARs. RESULTS: Carbamazepine and lamotrigine were the most common culprit drugs causing SCARs. Valproic acid and levetiracetam also emerged as the major causative agents. The disease duration and hospital stay in carbamazepine-induced SJS/TEN were shorter than those in other AEDs (P< 0.05, respectively). In younger patients, lamotrigine caused higher incidences of DRESS than other drugs (P= 0.045). Carbamazepine, the most common culprit drug for SCARs, was associated with a favorable outcome related with prolonged hospitalization in SJS (odds ratio, 0.12; 95% confidence interval, 0.02-0.63, P= 0.12), and thrombocytopenia was found to be a risk factor for prolonged hospitalization in DRESS. CONCLUSION: This was the first large-scale epidemiological study of AED-induced SCARs in Korea. Valproic acid and levetiracetam were the significant emerging AEDs causing SCARs in addition to the well-known offending AEDs such as carbamazepine and lamotrigine. Carbamazepine was associated with reduced hospitalization, but thrombocytopenia was a risk factor for prolonged hospitalization. Our results suggest that the clinical characteristics and clinical courses of AED-induced SCARs might vary according to the individual AEDs.
Anticonvulsants
;
Carbamazepine
;
Cicatrix
;
Drug Hypersensitivity Syndrome
;
Epidemiologic Studies
;
Hospitalization
;
Humans
;
Incidence
;
Korea
;
Length of Stay
;
Mortality
;
Referral and Consultation
;
Risk Factors
;
Stevens-Johnson Syndrome
;
Thrombocytopenia
;
Valproic Acid
5.Found at Old Age and Continuously Growing WHO Grade II Fourth Ventricle Ependymoma: A Case Report
Moowan PARK ; Eun Kyeong HONG ; Sang Hyen LEE ; Ho Shin GWAK
Brain Tumor Research and Treatment 2019;7(2):141-146
A 74-year-old woman presented with a month-long nausea and vomiting, then she could not take a meal. She had found an asymptomatic 4th ventricular mass 6 year ago as a preoperative work-up for ovarian cancer. And during the yearly follow-up, the mass had grown continuously over 6 years, and caused symptoms in the seventh year. MRI revealed a large ovoid extra-axial mass in the fourth ventricle compressing adjacent medulla and cerebellum. Surgery achieved near total resection since the tumor tightly adhered to the brain stem of 4th ventricle floor. The histological diagnosis was ependymoma (WHO grade II). She transferred rehabilitation facility for mild gait disturbance, hoarseness and swallowing difficulty. Fourth ventricle ependymoma in the elderly is extremely rare and the growth rate has not been reported. Here, we present a rare care of 4th ventricle ependymoma found asymptomatic at elderly but continuously grow to cause local pressure symptoms.
Aged
;
Brain Stem
;
Cerebellum
;
Deglutition
;
Diagnosis
;
Ependymoma
;
Female
;
Follow-Up Studies
;
Fourth Ventricle
;
Gait
;
Hoarseness
;
Humans
;
Magnetic Resonance Imaging
;
Meals
;
Nausea
;
Ovarian Neoplasms
;
Rehabilitation
;
Vomiting
6.Anti-proliferative Effect of 15,16-Dihydrotanshinone I Through Cell Cycle Arrest and the Regulation of AMP-activated Protein Kinase/Akt/mTOR and Mitogen-activated Protein Kinase Signaling Pathway in Human Hepatocellular Carcinoma Cells
Ji Young HONG ; So Hyun PARK ; Hyen Joo PARK ; Sang Kook LEE
Journal of Cancer Prevention 2018;23(2):63-69
BACKGROUND: 15,16-dihydrotanshinone I (DHTS) is a natural abietane diterpenoid that is mainly found in the roots of Salvia miltiorrhiza Bunge (Labiatae). DHTS exhibits a potential anti-proliferative effect in various human cancer cells. However, the mechanisms of action of DHTS as an anti-cancer agent have not been fully elucidated. Therefore, the present study investigated the anti-cancer effect of DHTS in terms of cell cycle regulation and the regulation of the AMP-activated protein kinase (AMPK)/Akt/mTOR signaling pathway in SK-HEP-1 human hepatocellular carcinoma cells. METHODS: The anti-proliferative effects of DHTS were evaluated by the sulforhodamine B assay in SK-HEP-1 cells. Cell cycle distribution was analyzed by flow cytometry. The elucidation of mechanisms of action such as the AMPK/AKT/mTOR and mitogen-activated protein kinase (MAPK) pathway was assessed by Western blot analysis. RESULTS: DHTS showed a significant anti-proliferative activity against SK-HEP-1 cells. DHTS induced cell cycle arrest in the G0/G1 phase, which was mediated by downregulation of cyclin D1, cyclin A, cyclin E, CDK4, CDK2, c-Myc and p-Rb expression and with increased expression of the CDK inhibitor p21. DHTS also activated the AMPK signaling. In addition, DHTS downregulated the Akt/mTOR and MAPK signaling pathways. CONCLUSIONS: Our results suggest that the anti-proliferative activity of DHTS might be associated with the induction of G0/G1 phase cell cycle arrest and regulation of AMPK/Akt/mTOR and MAPK signaling pathways in SK-HEP-1 cells.
AMP-Activated Protein Kinases
;
Blotting, Western
;
Carcinoma, Hepatocellular
;
Cell Cycle Checkpoints
;
Cell Cycle
;
Cyclin A
;
Cyclin D1
;
Cyclin E
;
Cyclins
;
Down-Regulation
;
Flow Cytometry
;
Humans
;
Protein Kinases
;
Salvia miltiorrhiza
7.Serum cardiac troponin I concentrations in clinically normal and Dirofilaria immitis infected Korean Jindo dogs.
Soo Hyen HWANG ; Hyung Jin PARK ; Kyoung Won SEO ; Sang Eun LEE ; Kun Ho SONG
Korean Journal of Veterinary Research 2014;54(1):53-54
This study was conducted to determine the serum cardiac troponin I (cTnI) concentrations in clinically normal (uninfected) Korean Jindo dogs and those infected with Dirofilaria (D.) immitis. Forty Korean Jindo dogs (22 females, 18 males) were obtained from two kennels in the Boryeong area of Chungnam Province and the Daejeon area, Korea. Significantly higher cTnI concentrations were observed in D. immitis-infected dogs than clinically normal dogs. cTnI testing in addition to thoracic radiography, echocardiography, and electrocardiography shows promise as an additional method for diagnosis of heartworm infection.
Animals
;
Chungcheongnam-do
;
Diagnosis
;
Dirofilaria immitis*
;
Dirofilaria*
;
Dogs*
;
Echocardiography
;
Electrocardiography
;
Female
;
Humans
;
Korea
;
Radiography, Thoracic
;
Troponin I*
;
Troponin*
8.Seasonal Specificity of Seasonal Allergens and Validation of the ARIA Classification in Korea.
Young Jun CHUNG ; Il Kwon CHO ; Ki Il LEE ; Sung Hyen BAE ; Jae Wook LEE ; Phil Sang CHUNG ; Ji Hun MO
Allergy, Asthma & Immunology Research 2013;5(2):75-80
PURPOSE: In Korea, tree pollens are known to be prevalent in spring, grass pollens in summer and weed pollens in autumn. However, few studies have revealed their seasonal specificity for allergic rhinitis symptoms. An ARIA (Allergic Rhinitis and its Impact on Asthma) classification of allergic rhinitis was recently introduced and its clinical validation has not been well proved. The aim of this study was to evaluate the seasonal specificity of seasonal allergens and to validate the ARIA classification with the conventional seasonal and perennial allergic rhinitis (SAR/PAR) classification. METHODS: Two hundred twenty six patients with allergic rhinitis were included in this study. The patients were classified according to the sensitized allergens and the ARIA classifications. A questionnaire survey was performed and the data on the seasonal symptom score, the severity of symptoms and the SNOT (sinonasal outcome test)-20 score was obtained and the data was analyzed and compared between the conventional SAR/PAR classification and the ARIA classification. RESULTS: Seasonal pollens (tree, grass, weed) were not specific to the pollen peak season and the patients' symptoms were severe during spring and autumn regardless of the offending pollens. More than 60% of the patients with SAR showed persistent symptoms and 33% of the patients with perennial allergic rhinitis (PAR) had intermittent symptoms, showing the lack of association between the SAR/PAR/PAR+SAR classification and the ARIA classification. The ARIA classification showed better association not only with the symptomatic score, but also with the SNOT-20 score, which showed better validity than the conventional SAR/PAR classifications. CONCLUSIONS: Seasonal pollens were not specific to their season of prevalence in terms of the severity of symptoms, and the ARIA classification showed better representation of allergic symptoms and quality of life (SNOT-20 score) than did the SAR/PAR classification.
Allergens
;
Humans
;
Korea
;
Poaceae
;
Pollen
;
Prevalence
;
Quality of Life
;
Rhinitis
;
Rhinitis, Allergic, Perennial
;
Rhinitis, Allergic, Seasonal
;
Seasons
;
Sensitivity and Specificity*
;
Surveys and Questionnaires
9.Efficacy and Safety of Albis(R) in Acute and Chronic Patients with Gastritis: A Double-blind, Placebo-controlled, Randomized Multi-center Study.
Hae Won HAN ; Myung Gyu CHOI ; Sang Young SEOL ; Dong Ho LEE ; Hwoon Yong JUNG ; Tae Nyeun KIM ; Suck Chei CHOI ; Hyen Soo KIM
Korean Journal of Gastrointestinal Endoscopy 2011;42(4):215-221
BACKGROUND/AIMS: Albis(R) is a newly developed drug comprised of ranitidine, bismuth and sucralfate. The aim of the study was to demonstrate the efficacy and safety superiority of Albis(R) compared to Stillen(R) for treating erosive gastritis. METHODS: This study was a randomized, double-blind, multi-center trial. The primary endpoint was 2 weeks of treatment. RESULTS: Of the 229 patients in the intention-to-treat (ITT) population, 87 from the Albis(R), and 96 from the Stillen(R) group were included in the per protocol (PP) analysis. The endoscopic improvement rate was not different between the Albis(R)(R) group and the control in both the PP (42.5%, 39.6%) and ITT (35.3%, 34.5%) populations. The endoscopic cure of erosion was also not different in the Albis(R) group than that in the control group in both the PP (32.3%, 31.3%) and ITT (27.6%, 27.4%) populations. The endoscopic improvement rate for hemorrhage, edema, and erythema were also not different between the two groups in both the PP and ITT populations. No statistically significant differences were observed for adverse events between the two groups. CONCLUSIONS: Half of the approved dose of Albis(R) for peptic ulcers was superior to Stillen(R). A low dosage of Albis(R) is more cost efficient and safe than that of Stillen(R).
Bismuth
;
Edema
;
Erythema
;
Hemorrhage
;
Humans
;
Peptic Ulcer
;
Ranitidine
;
Sucralfate
10.A Case of Functionary Cystic Parathyroid Adenoma with Papillary Thyroid Carcinoma.
Woo Jin CHANG ; Hyun Hee JUNG ; Sang Hyen PARK ; Se Hoon SOHN ; Ji Sung YOON ; Hyoung Woo LEE ; Kyu Chang WON ; In Ho CHO
Yeungnam University Journal of Medicine 2010;27(2):139-145
Cystic parathyroid adenoma is one of rare causes of hyperparathyroidism, and tends to cause increased serum level of parathyroid hormone, alkaline phosphate and serum calcium level similar to when compared to those of solid adenoma.
Adenoma
;
Calcium
;
Carcinoma
;
Hyperparathyroidism
;
Parathyroid Hormone
;
Parathyroid Neoplasms
;
Thyroid Gland
;
Thyroid Neoplasms

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