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.

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.

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

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

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

Sotos syndrome is a rare sporadic genetic disorder characterized by pathognomonic facial features, motor developmental delay induced by hypotonia, learning difficulties, and cardiac and renal anomalies. This report describes the case of a 4-year-old child with Sotos syndrome who underwent a right hydrocelectomy under general anesthesia. We report our experience with airway management, choice of anesthetic drugs, and other anesthetic implications in Sotos syndrome.
Airway Management ; Anesthesia, General ; Anesthetics ; Child* ; Child, Preschool ; Humans ; Learning ; Muscle Hypotonia ; Neuromuscular Blockade ; Sotos Syndrome*

BACKGROUND: This study examined moderating effects of optimism and family support on the depression of family caregivers of cancer patients aged 55 and over by adopting stress process model. METHODS: 359 family caregivers who accompanied with cancer patients to out-patient clinics were recruited and completed questionnaire at three university hospitals located in Seoul and Gyeonggi province. Exploratory factor analysis was applied to test validity of the construction of the scale. Hierarchical multiple regression analysis was used to determine moderating effects of optimism and family support on depression after making mean centering of each variable. RESULTS: Results showed that spouse caregivers have more depression than do adult children as the nursing period gets longer. Education and income status were significant variables affecting depression of family caregivers. Optimism and family support for family caregivers have moderating effects on the association between stressors (emotional functioning of cancer patients and role overload of family caregivers) and depression of family caregivers. CONCLUSIONS: The findings suggest that more attentions are needed to the depression of spouse caregivers. Interventions are strongly recommended for health professionals to provide cancer patients and their family caregivers with "holding environments" caring for emotions and facilitating adjustment.
Adult Children ; Attention ; Caregivers* ; Depression* ; Education ; Gyeonggi-do ; Health Occupations ; Hospitals, University ; Humans ; Nursing ; Optimism* ; Outpatients ; Seoul

INTRODUCTION: To evaluate the 3-dimensional changes in the pharyngeal airway of skeletal class III patients after bimaxillary surgery. MATERIALS AND METHODS: The study sample consisted of 18 Korean patients that had undergone maxillary setback or posterosuperior movement and mandibular bilateral sagittal split osteotomy setback surgery due to skeletal class III malocclusion (8 males, 10 females; mean age of 28.7). Cone beam computed tomography was taken 1 month before and 6 months after orthognathic surgery. Preoperative and postoperative volumes of the nasopharyngeal, oropharyngeal, and laryngopharyngeal airways and minimum axial areas of the oropharyngeal and laryngopharyngeal spaces were measured. Moreover, the pharyngeal airway volume of the patient group that had received genioplasty advancement was compared with the other group that had not. RESULTS: The nasopharyngeal and laryngopharyngeal spaces did not show significant differences before or after surgery. However, the oropharyngeal space volume and total volume of pharyngeal airway decreased significantly (P<0.05). The minimum axial area of the oropharynx also decreased significantly. CONCLUSION: The results indicate that bimaxillary surgery decreased the volume and the minimum axial area of the oropharyngeal space. Advanced genioplasty did not seem to have a significant effect on the volumes of the oropharyngeal and laryngopharyngeal spaces.
Cone-Beam Computed Tomography ; Genioplasty ; Humans ; Male ; Malocclusion ; Oropharynx ; Orthognathic Surgery ; Osteotomy ; Pharynx

Cone-Beam Computed Tomography ; Humans ; Incisor ; Lip ; Mandible ; Maxilla ; Orthognathic Surgery ; Osteotomy ; Osteotomy, Sagittal Split Ramus ; Spine

BACKGROUND/AIMS: Dominant genotype of hepatitis A virus (HAV) in Korea had been known to be genotype 1A in 1990s. Recently, the epidemiologic change of HAV genotype was reported with an upsurge of acute hepatitis A in Korea. The aim of this study was to investigate the change of HAV genotypes and clinical characteristics in Gwangju and Jeonnam province. METHODS: From November 2008 to October 2009, a total of 82 patients with acute hepatitis A were enrolled prospectively. HAV genotype was determined using reverse transcriptase polymerase chain reaction and sequencing of the PCR products of VP1/2A region of HAV. RESULTS: HAV RNA was detected in 82% (67/82). The genotype IIIA (88%, 59 cases) was significantly more frequent than genotype IA (12%, 8 cases) (p< or =0.01). The subtypes of genotype IIIA were AJ299467 Norway (49%), HA-JNG04-09 Japan (27%), HS-14-12-00 Spain (22%) and H-122 Sweden (2%). The subtypes of IA were FH1 Japan (50%) and HA J04-3 Japan (50%). The substitutions of amino acid were more frequent in genotype IIIA than IA (p< or =0.01). There was no difference in the clinical characteristics between the patients with genotype IIIA and IA. CONCLUSIONS: Genotype IIIA was a dominant genotype of recent HAV infection in Gwangju and Jeonnam province. This study provides valuable epidemiologic information of genetic distributions of HAV in Korea.