Purpose: Previous report from the ASCEND-8 trial showed consistent efficacy with less gastrointestinal (GI) toxicity in patients with anaplastic lymphoma kinase-rearranged (ALK+) advanced/metastatic non–small cell lung cancer (NSCLC) treated with ceritinib 450-mg with food compared with 750-mg fasted. In this subgroup analysis, we report outcomes in Asian patients of the ASCEND-8 trial. Materials and Methods: Key efficacy endpoints were blinded independent review committee (BIRC)–assessed overall response rate (ORR) and duration of response (DOR) evaluated per Response Evaluation Criteria in Solid Tumors v1.1. Other efficacy endpoints were investigator-assessed ORR and DOR; BIRC- and investigator-assessed progression-free survival (PFS) and disease control rate; overall survival (OS). Safety was evaluated by frequency and severity of adverse events. Results: At final data cutoff (6 March 2020), 198 treatment-naïve patients were included in efficacy analysis, of which 74 (37%) comprised the Asian subset; 450-mg fed (n=29), 600-mg fed (n=19), and 750-mg fasted (n=26). Baseline characteristics were mostly comparable across study arms. At baseline, more patients in 450-mg fed arm (44.8%) had brain metastases than in 750-mg fasted arm (26.9%). Per BIRC, patients in the 450-mg fed arm had a numerically higher ORR, 24-month DOR rate and 24-month PFS rate than the 750-mg fasted arm. The 36-month OS rate was 93.1% in 450-mg fed arm and 70.9% in 750-mg fasted arm. Any-grade GI toxicity occurred in 82.8% and 96.2% of patients in the 450-mg fed and 750-mg fasted arms, respectively. Conclusion Asian patients with ALK+ advanced/metastatic NSCLC treated with ceritinib 450-mg fed showed numerically higher efficacy and lower GI toxicity than 750-mg fasted patients.

Purpose: Osimertinib is a third-generation, irreversible, oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that potently and selectively inhibits both EGFR sensitizing mutation and EGFR T790M and has demonstrated efficacy in non-small cell lung cancer (NSCLC) central nervous system (CNS) metastases. We present results of a subgroup analysis of Korean patients from the pooled data of two global phase II trials: AURA extension (NCT01802632) and AURA2 (NCT02094261). Materials and Methods: Enrolled patients had EGFR T790M-positive NSCLC and disease progression during or after EGFR-TKI therapy. Patients received osimertinib 80 mg orally once daily until disease progression. The primary endpoint was objective response rate (ORR). Results: In total, 66 Korean patients received osimertinib treatment with a median treatment duration of 19 months. In the evaluable-for-response population (n=62), ORR was 74% (95% confidence interval [CI], 61.5 to 84.5) and median duration of response was 9.8 months (95% CI, 7.1 to 16.8). In the full analysis set (n=66), median progression-free survival was 10.9 months (95% CI, 8.3 to 15.0; data cutoff November 1, 2016), and median overall survival was 29.2 months (95% CI, 24.8 to 35.7; data cutoff May 1, 2018). Eight patients with CNS metastases were evaluable for response, none of whom showed CNS progression. The most common adverse events were rash (53%), cough (33%), paronychia, diarrhea, and decreased appetite (each 32%). Conclusion Efficacy and safety profiles of osimertinib in this subgroup are consistent with the global phase II pooled population, which supports osimertinib as a recommended treatment for Korean patients with T790M positive NSCLC.

BACKGROUND AND OBJECTIVES: The conventional transseptal transsphenoidal approach can inhibit visualization of the surgical field and may change the shape of external nose. We used the transseptal transsphenoidal technique to remove septal cartilage except the L strut via a modified Killian's incision and preserved the ‘key-stone area.’ The aim of this study was to verify the usefulness of this technique. SUBJECTS AND METHOD: Retrospective analysis was carried out on 42 pituitary tumor patients who received this technique by a single otolaryngologist from March 2005 to March 2012 at Kangbuk Samsung Hospital. RESULTS: The mean patient age at time of surgery was 52 years, and 41 cases were pituitary adenoma and 1 was Rathke's cleft cyst. Three patients had undergone prior surgery; of which 2 used a pterional approach and 1 a transsphenoidal approach. With regard to complication, there were 2 cases of CSF leakage and 5 cases of septal laceration. There were no cases of meningitis, deformity of external nose, septal perforation, anosmia, or sinusitis. In post operation follow up, 25 cases (59.5%) had no residual tumor, while 17 cases (40.5%) had residual tumor. CONCLUSION: This study reveals that transseptal transsphenoidal surgery with septal cartilage removal and a replacement technique for a pituitary tumor are effective, allow easy exposure, and result in a low complication rate.
Cartilage ; Congenital Abnormalities ; Follow-Up Studies ; Humans ; Lacerations ; Meningitis ; Methods ; Neoplasm, Residual ; Nose ; Olfaction Disorders ; Pituitary Neoplasms ; Retrospective Studies ; Sinusitis

We have examined isolation and identification protocols for three virus simulant candidates to biological warfare agents. MS2 phage, a simulant for yellow fever virus and Hantaan virus, was propagated using as a host an E. coli strain with F pilus. MS2 phage genome was examined by reverse transcription and polymerase chain reaction (RT-PCR). Coat protein of the phage preparation was examined by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and mass spectrometric analysis. Cydia pomonella granulosis virus (CpGV) is a virus simulant candidate to smallpox virus. CpGV was isolated from a commercialized CpGV pellet. In this study, we developed new isolation and identification protocols for CpGV. One disadvantage of using CpGV is that it is not easy to determine viability of the virus. Here, we have included T4 phage as an alternative. We established a high titer production protocol and developed an easy genome identification protocol that does not require purified phage DNA. Stability of these virus preparations was also examined under various storage conditions. When the virus preparations were not subjected to freeze drying, MS2 phage was most stable when it was stored in liquid nitrogen but unstable at 4℃. In contrast, T4 phage was most stable when it was stored at 4℃. CpGV was stable at −20℃ but not at 4℃. Stability during or after freeze drying was also investigated. The result showed that 70~80% MS2 survived the freeze drying process. In contrast, only about 15% of T4 phage survived during the freeze drying. CpGV was found to be degraded during freeze drying.
Bacteriophage T4 ; Bacteriophages ; Biological Warfare Agents ; DNA ; Electrophoresis ; Freeze Drying ; Genome ; Granulovirus ; Hantaan virus ; Levivirus ; Nitrogen ; Polymerase Chain Reaction ; Reverse Transcription ; Variola virus ; Yellow fever virus

OBJECTIVE: The noradrenaline system is involved in the reward effects of various kinds of abused drugs. Betaxolol (BTX) is a highly selective β1-antagonist. In the present study, we evaluated the effect of BTX on methamphetamine (MAP)-induced conditioned place preference (CPP) and hyperactivity in mice. METHODS: The mice (n=72) were treated with MAP or saline every other day for a total of 6 days (from day 3 to day 8; 3-times MAP and 3-times saline). Each mouse was given saline (1 mL/kg) or MAP (1 mg/kg, s.c.) or BTX (5 mg/kg, i.p.) or MAP with BTX (5 mg/kg, i.p.) 30 min prior to the administration of MAP (1 mg/kg, s.c.) every other day and paired with for 1 h (three-drug and three-saline sessions). We then compared the CPP score between the two groups. After the extinction of CPP, the mice were given BTX (5 mg/kg, i.p.) or saline (1 mL/kg) 24 h prior to a priming injection of MAP, and were then immediately tested to see whether the place preference was reinstated. RESULTS: The repeated administration of BTX 30 min prior to the exposure to MAP significantly reduced the development of MAP-induced CPP. When BTX was administered 24 h prior to the CPP-testing session on day 9, it also significantly attenuated the CPP, but did not result in any change of locomotor activity. In the drug-priming reinstatement study, the extinguished CPP was reinstated by a MAP (0.125 mg/kg, s.c.) injection and this was significantly attenuated by BTX. CONCLUSION: These findings suggest that BTX has a therapeutic and preventive effect on the development, expression, and drug-priming reinstatement of MAP-induced CPP.
Animals ; Betaxolol* ; Methamphetamine* ; Mice* ; Motor Activity ; Norepinephrine ; Reward

PURPOSE: We aimed to translate the Test for Respiratory and Asthma Control in Kids (TRACK) instrument into Korean, with subsequent linguistic validation. METHODS: The multistep process of forward translation, reconciliation, back-translation, cognitive debriefing, and proofreading of the Korean version of the TRACK was completed. RESULTS: Two bilingual medical personnel independently translated the original English version of the TRACK into Korean one. After moderating the translation into a single reconciled one, 4 other bilingual persons were invited to translate the Korean draft back into an English one. Discrepancies between the original English version and the back-translated one were reviewed, and the need to modify the reconciled Korean draft was discussed. Twenty caregivers of asthmatic children took part in interviews that examine the appropriateness of the Korean version of the TRACK. The feedback from caregivers were then reviewed by a panel of pediatric allergists and reflected in the final Korean version. The document was finally proofread to check the spelling, grammar, layout and formatting. CONCLUSION: Translation and linguistic validation of the Korean version of the TRACK instrument were completed.
Asthma* ; Caregivers ; Child ; Humans ; Linguistics* ; Translations

The objective of the present study was to investigate the effects of three different culture media on the development of canine somatic cell nuclear transfer (SCNT) embryos. Canine cloned embryos were cultured in modified synthetic oviductal fluid (mSOF), porcine zygote medium-3 (PZM-3), or G1/G2 sequential media. Our results showed that the G1/G2 media yielded significantly higher morula and blastocyst development in canine SCNT embryos (26.1% and 7.8%, respectively) compared to PZM-3 (8.5% and 0%) or mSOF (2.3% and 0%) media. In conclusion, this study suggests that blastocysts can be produced more efficiently using G1/G2 media to culture canine SCNT embryos.
Animals ; Blastocyst/cytology ; Cloning, Organism/*veterinary ; Culture Media/metabolism ; Dogs/*embryology ; Embryo Culture Techniques/*veterinary ; *Embryonic Development ; Nuclear Transfer Techniques/*veterinary

PURPOSE: Pulmonary function tests are useful and important methods for evaluating patients with respiratory diseases. To assess lung function, we need to establish normal values of lung function, which vary according to population, age, gender and growth, particularly in children. This study was undertaken to establish normal predicted values of pulmonary function tests and to predict renewed reference values by spirometry in Korean school children. METHODS: Spirometric forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), forced expiratory flow at 25% to 75% of FVC (FEF25%-75%), and peak expiratory flow rate (PEFR) were measured in 406 healthy elementary school children (age, 6-12 years old) in May, 2012. Multiple linear regression analysis was performed for each spirometric parameter against age, height, weight and body surface area (BSA) separately for boys and girls, and derived reference equations and coefficients for all the spirometric parameters. RESULTS: All the measured spirometric parameters were significantly correlated with age, height, weight, and BSA. FVC was higher in boys aged 6-10 years than girls at ages matched. Height showed the highest correlation coefficient for all the spirometric parameters followed by BSA, weight and age in both genders. The normal predicted values of FVC and FEV1 at 130 cm in this study using renewed reference equations were approximately in the middle compared to previous studies. CONCLUSION: We reported here the renewed reference equations for normal predicted values of pulmonary function tests with high coefficients of determination based on updated data in healthy Korean children.
Body Surface Area ; Child* ; Female ; Forced Expiratory Volume ; Humans ; Linear Models ; Lung ; Peak Expiratory Flow Rate ; Reference Values* ; Respiratory Function Tests* ; Spirometry ; Vital Capacity

We observed and measured the structures showing the golden ratio in human body. Southeast Asian tribes, Aka and Lahu who live in Thailand, Miyanmar and China mountain areas and Koreans were examined by means of facial photography. The pictures of lateral facial view were taken by the fixed method. Then the length and width of auricles were measured by Phi-matrix software (version 1.1) on the scanned images. Helix ratio were also obtained by the same method. As a results, the ratio of the ear of Southeast Asian tribes showed the golden ratio and the racial and the individual differences were noticed a little.
Asian Continental Ancestry Group ; Beauty ; China ; Ear ; Human Body ; Humans ; Individuality ; Photography ; Population Groups ; Thailand

Anterior gradient-2 (AGR2) promotes tumor growth, cell migration, and cellular transformation, and is one of the specific mRNA markers for circulating tumor cells in patients with gastrointestinal cancer. We investigated the feasibility of AGR2 as a potent antigen for tumor immunotherapy against colorectal cancer (CRC) cells using dendritic cells (DCs) transduced with a recombinant adenovirus harboring the AGR2 gene (AdAGR2). DCs transduced with a recombinant adenovirus encoding the AGR2 gene (AdAGR2/DCs) were characterized. These genetically-modified DCs expressed AGR2 mRNA as well as AGR2 protein at a multiplicity of infection of 1,000 without any significant alterations in DC viability and cytokine secretion (IL-10 and IL-12p70) compared with unmodified DCs as a control. In addition, AdAGR2 transduction did not impair DC maturation, but enhanced expression of HLA-DR, CD80, and CD86. AdAGR2/DCs augmented the number of IFN-gamma-secreting T-cells and elicited potent AGR2-specific cytotoxic T lymphocytes capable of lysing AGR2-expressing CRC cell lines. These results suggest that AGR2 act as a potentially important antigen for immunotherapy against CRC in clinical applications.
Adenoviridae ; Antigen Presentation/genetics ; Antigens, Neoplasm/immunology ; Carcinoma/*therapy ; Cell Line, Tumor ; Colorectal Neoplasms/*therapy ; Cytotoxicity, Immunologic/genetics ; Dendritic Cells/immunology ; Humans ; *Immunotherapy, Adoptive ; Interferon-gamma/secretion ; Lymphocyte Activation/genetics ; Proteins/genetics/*metabolism ; T-Lymphocytes, Cytotoxic/*immunology ; Transduction, Genetic ; Transgenes/genetics ; Tumor Markers, Biological/immunology