Hyaluronic acid (HA), a ligand of CD44, accumulates in some types of tumors and is responsible for tumor progression. The nuclear factor erythroid 2-like 2 (NRF2) regulates cytoprotective genes and drug transporters, which promotes therapy resistance in tumors. Previously, we showed that high levels of CD44 are associated with NRF2 activation in cancer stem like-cells. Herein, we demonstrate that HA production was increased in doxorubicin-resistant breast cancer MCF7 cells (MCF7-DR) via the upregulation of HA synthase-2 (HAS2). HA incubation increased NRF2, aldo-keto reductase 1C1 (AKR1C1), and multidrug resistance gene 1 (MDR1) levels. Silencing of HAS2 or CD44 suppressed NRF2 signaling in MCF7-DR, which was accompanied by increased doxorubicin sensitivity. The treatment with a HAS2 inhibitor, 4-methylumbelliferone (4-MU), decreased NRF2, AKR1C1, and MDR1 levels in MCF7-DR. Subsequently, 4-MU treatment inhibited sphere formation and doxorubicin resistance in MCF7-DR. The Cancer Genome Atlas (TCGA) data analysis across 32 types of tumors indicates the amplification of HAS2 gene is a common genetic alteration and is negatively correlated with the overall survival rate. In addition, high HAS2 mRNA levels are associated with increased NRF2 signaling and poor clinical outcome in breast cancer patients. Collectively, these indicate that HAS2 elevation contributes to chemoresistance and sphere formation capacity of drug-resistant MCF7 cells by activating CD44/ NRF2 signaling, suggesting a potential benefit of HAS2 inhibition.

PURPOSE: The following study has been carried out to find the symptoms of hypoglycemia and the symptoms of transient focal neurologic deficit, which were complained by insulin dependent diabetes mellitus patients and their parents. METHODS: The subjects of this study were 16 insulin dependent diabetic patients who were admitted to the pediatric department of Samsung Medical Center. From the 28 possible symptoms of hypoglycemia, the patients and their parents were asked to choose the symptoms they were experiencing through questionnaires, and the mean score was obtained by dividing the frequency of each symptom manifestation by 4 levels. RESULTS: Of the 16 patients, there were 6 males and 10 females and their average age was 13 years. The complaints raised by insulin dependent diabetic patients and their parents regarding the symptoms of hypoglycemia were relatively similar. However the frequency of observed symptoms such as pounding heart, dizziness and trembling was higher in the complaints of patients, and the mean score of objective symptoms such as slurred speech, odd behaviors, aggressiveness was much higher in the complaints of parents. During symptoms of hypoglycemia, three cases were seen throwing fits of convulsions due to neurologic deficit. CONCLUSION: It is thought that parents can offer a reasonably accurate information on the symptoms of hypoglycemia in insulin dependent diabetic patients, and particularly, behavioral changes in young children with diabetes mellitus is considered as an important characteristic for testing hypoglycemia.
Child* ; Diabetes Mellitus ; Diabetes Mellitus, Type 1* ; Dizziness ; Female ; Heart ; Humans ; Hypoglycemia ; Insulin ; Male ; Neurologic Manifestations ; Parents* ; Surveys and Questionnaires ; Seizures

The infections by human papillomaviruses (HPVs) are clearly associated with the subsequent development of cervical cancer. In this study, HPV genotype distribution and prevalence were detected in Korean women from January to December 2008 using PCR-DNA sequencing. A total of 2,562 cervical samples from Korean women having routine Pap smear cytology screening were used. HPV DNA was extracted from cervical swab samples and amplified by PCR in L1 region of HPV. HPV DNA was detected in 23.2% and 65.5% from the groups of normal and abnormal Pap cytology, respectively. The prevalence of high-risk types of HPV had the highest frequency in the <30 year-olds' group (50.6%). The prevalence of HPV in normal, ASCUS, LSIL and HSIL groups was 23.2%, 58.1%, 96.3% and 97.0%, respectively. Moreover, the frequencies of the high-risk types of HPV were 16.2% in the normal Pap cytology, 44.7% in the ASCUS, 76.1% in the LSIL and 94.1% in the HSIL groups. The prevalence of the high-risk types of HPV increased in proportion to the severity of the cytological classification. In the HSIL group, HPV type 16 was the most frequently found at 32.4%, followed by types 58, 53 and 33 at 17.6%, 14.7% and 11.8%, respectively. HPV type 82 was found in 5.6% of the HSIL group and was not detected in the normal Pap cytology group. The frequency of high-risk type of HPV 82 is firstly reported in Korean women. This finding could be an informative basis for the development of future HPV vaccination strategies in Korean women.
DNA ; Female ; Genotype ; Humans ; Mass Screening ; Polymerase Chain Reaction ; Prevalence ; Uterine Cervical Neoplasms ; Vaccination

Erdheim-Chester disease (ECD) is non-Langerhans cell histiocytosis that leads to multi-organ involvement with unknown etiology. We report a 64-year-old woman with a dry cough and dyspnea. She had interlobular septal thickening and ground-glass opacity in both lungs, suggesting lymphangitic lung metastasis. However, she was diagnosed with ECD after a long bone and immunohistological evaluation.
Cough ; Dyspnea ; Erdheim-Chester Disease ; Female ; Histiocytosis ; Humans ; Lung ; Middle Aged ; Neoplasm Metastasis ; Retroperitoneal Fibrosis

BACKGROUND: Melasma is a common, acquired, symmetrical hypermelanosis that occurs on sun exposed areas of the skin. It is more prevalent among Asian women than among Caucasian women. Many different treatment modalities have been used with various efficacies, but none of them have been completely satisfactory. Arbutin is a naturally occurring gluconopyranoside that may reduce tyrosinase activity, which is a rate-limiting enzyme for melanin production. OBJECTIVE: The purpose of this study was to investigate the depigmenting effect and safety of a mask that contains 2% arbutin for the treatment of melasma. METHODS: A total of 54 female volunteers with melasma were enrolled in this randomized, double-blind, 8-week treatment study. The patients were instructed to apply an arbutin-containing mask or an arbutin-free mask once a day for 8 weeks. The assessment of outcomes included the Melasma Area and Severity Index (MASI) score, colorimetric value (L*), overall patient satisfaction and investigator assessment score (evaluated using photography). RESULTS: The arbutin-containing mask significantly increased the right and left colorimetric values (L*) after the 8-week treatment (p<0.05) compared to the arbutin-free mask. The MASI score was decreased more in the arbutin mask group (p>0.05). The arbutin mask scored better than the control in patient satisfaction and investigator assessment. No significant adverse reactions were observed. CONCLUSION: The arbutin mask appears to be effective and well-tolerated when used for the treatment of melasma.
Arbutin ; Asian Continental Ancestry Group ; Female ; Humans ; Hydrogel ; Hyperpigmentation ; Masks ; Melanins ; Melanosis ; Monophenol Monooxygenase ; Patient Satisfaction ; Research Personnel ; Skin ; Solar System

On December 3, 2014, a type O foot-and-mouth disease (FMD) outbreak began in Korea. Although vaccinations were administered, FMD cases increased steadily for five months, and reached 185 cases by April 2015. Most of the affected animals were pigs, which are vulnerable to vaccination. The FMD virus belonged to the South-East Asia (SEA) topotype that had been observed three times in Korea between April 2010 and July 2014. However, the FMD virus isolated in December 2014 had a unique feature; that is, partial deletion of the 5′ non-coding region, a deletion not seen in previous SEA topotype isolates identified in Korea. We conclude that this outbreak included the introduction of a new FMD strain to Korea, and that Korea was now affected by genetically similar FMD virus strains that are related to those from neighboring countries.
Animals ; Asia ; Foot-and-Mouth Disease ; Korea ; Swine ; Vaccination

BACKGROUND: Smoking cessation is the most powerful intervention to modify progress of chronic obstructive pulmonary disease (COPD), and nicotine dependence is one of the most important determinants of success or failure in smoking cessation. We evaluated nicotine dependence status and investigated factors associated with moderate to high nicotine dependence in patients with COPD. METHODS: We included 53 current smokers with COPD in the Korean Obstructive Lung Disease II cohort enrolled between January 2014 and March 2016. Nicotine dependence was measured by using Fagerstrom test for nicotine dependence (FTND). Cognitive function was assessed by Korean version of Montreal Cognitive Assessment. RESULTS: The median FTND score was 3, and 32 patients (60%) had moderate to high nicotine dependence. The median smoking amount was 44 pack-years, which was not related to nicotine dependence. Multiple logistic regression analysis revealed that high education status (odds ratio, 1.286; 95% confidence interval, 1.036–1.596; p=0.023), age <70 (odds ratio, 6.407; 95% confidence interval, 1.376–29.830; p=0.018), and mild to moderate airflow obstruction (odds ratio, 6.969; 95% confidence interval, 1.388–34.998; p=0.018) were related to moderate to high nicotine dependence. CONCLUSION: Nicotine dependence does not correlate with smoking amount, but with education level, age, and severity of airflow obstruction. Physicians should provide different strategies of smoking cessation intervention for current smokers with COPD according to their education levels, age, and severity of airflow obstruction.
Cognition ; Cohort Studies ; Education ; Humans ; Logistic Models ; Lung Diseases, Obstructive ; Nicotine* ; Pulmonary Disease, Chronic Obstructive* ; Smoke ; Smoking ; Smoking Cessation ; Tobacco Use Disorder*