PURPOSE: Pim kinases are highly conserved serine/threonine kinases, and different expression patterns of each isoform (Pim-1, Pim-2, and Pim-3) have been observed in various types of human cancers, including gastric cancer. AZD1208 is a potent and selective inhibitor that affects all three isoforms of Pim. We investigated the effects of AZD1208 as a single agent and in combination with an Akt inhibitor in gastric cancer cells. MATERIALS AND METHODS: The antitumor activity of AZD1208 with/without an Akt inhibitor was evaluated in a large panel of gastric cancer cell lines through growth inhibition assays. The underlying mechanism was also examined by western blotting, immunofluorescence assay, and cell cycle analysis. RESULTS: AZD1208 treatment decreased gastric cancer cell proliferation rates and induced autophagy only in long-term culture systems. Light chain 3B (LC3B), a marker of autophagy, was increased in sensitive cells in a dose-dependent manner with AZD1208 treatment, which suggested that the growth inhibition effect of AZD1208 was achieved through autophagy, not apoptosis. Moreover, we found that cells damaged by Pim inhibition were repaired by activation of the DNA damage repair pathway, which promoted cell survival and led the cells to become resistant to AZD1208. We also confirmed that the combination of an Akt inhibitor with AZD1208 produced a highly synergistic effect in gastric cancer cell lines. CONCLUSION: Treatment with AZD1208 alone induced considerable cell death through autophagy in gastric cancer cells. Moreover, the combination of AZD1208 with an Akt inhibitor showed synergistic antitumor effects through regulation of the DNA damage repair pathway.
Apoptosis ; Autophagy ; Blotting, Western ; Cell Cycle ; Cell Death ; Cell Line ; Cell Proliferation ; Cell Survival ; DNA Damage ; Fluorescent Antibody Technique ; Humans ; Phosphotransferases ; Protein Isoforms ; Stomach Neoplasms

PURPOSE: To investigate the correlation between Glutathione-S-transferase (GST) genes and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (DM). METHODS: In this case-control study, 131 patients who were diagnosed with DR, 105 diabetic patients who did not have DR, and 45 nondiabetic controls were examined from January 2013 to November 2015. To analyze deletion of the GSTT1 and GSTM1 genes, polymerase chain reactions of DNA in a buffy coat from peripheral blood were performed via electrophoresis. RESULTS: There were no statistically significant differences in age, sex, or spherical equivalent between the 236 type 2 diabetic patients and the 45 normal controls (p > 0.05). In both univariate and multivariate analyses, the duration of type 2 DR was longer (p = 0.004, p = 0.013), and HbA1c was higher (p = 0.004, p = 0.007) in the DR group than in the non-DR group. Presence of a GSTM1 deletion is associated with a lower frequency of DR (p = 0.017, p = 0.012). CONCLUSIONS: Deletion of the GSTT1 gene is not associated with an increased risk of DR, whereas GSTM1 deletion is associated with a lower risk of DR in patients with type 2 DM in the Korean population. Additional studies with larger sample sizes and different types of GST genes are needed to confirm this study.
Case-Control Studies ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Diabetic Retinopathy* ; DNA ; Electrophoresis ; Humans ; Multivariate Analysis ; Polymerase Chain Reaction ; Sample Size

In 2010, the Asian Society of Cardiovascular Imaging (ASCI) provided recommendations for cardiac CT and MRI, and this document reflects an update of the 2010 ASCI appropriate use criteria (AUC). In 2016, the ASCI formed a new working group for revision of AUC for noninvasive cardiac imaging. A major change that we made in this document is the rating of various noninvasive tests (exercise electrocardiogram, echocardiography, positron emission tomography, single-photon emission computed tomography, radionuclide imaging, cardiac magnetic resonance, and cardiac computed tomography/angiography), compared side by side for their applications in various clinical scenarios. Ninety-five clinical scenarios were developed from eight selected pre-existing guidelines and classified into four sections as follows: 1) detection of coronary artery disease, symptomatic or asymptomatic; 2) cardiac evaluation in various clinical scenarios; 3) use of imaging modality according to prior testing; and 4) evaluation of cardiac structure and function. The clinical scenarios were scored by a separate rating committee on a scale of 1–9 to designate appropriate use, uncertain use, or inappropriate use according to a modified Delphi method. Overall, the AUC ratings for CT were higher than those of previous guidelines. These new AUC provide guidance for clinicians choosing among available testing modalities for various cardiac diseases and are also unique, given that most previous AUC for noninvasive imaging include only one imaging technique. As cardiac imaging is multimodal in nature, we believe that these AUC will be more useful for clinical decision making.
Area Under Curve ; Asian Continental Ancestry Group* ; Clinical Decision-Making ; Consensus* ; Coronary Artery Disease ; Echocardiography ; Electrocardiography ; Heart Diseases ; Humans ; Magnetic Resonance Imaging ; Methods ; Positron-Emission Tomography ; Radionuclide Imaging ; Tomography, Emission-Computed

PURPOSE: To report a case of unilateral trochlear nerve schwannoma in a patient without neurofibromatosis. CASE SUMMARY: A 58-year-old male presented with acute onset of diplopia which developed 10 days prior. Alternate prism cover test, ductions and versions and Bielschowsky three-step test were compatible with left superior oblique muscle palsy. High-resolution magnetic resonance imaging showed a 6-mm-sized lobulated mass in the cisternal segment of the left trochlear nerve passing lateral to the brainstem. An additional thin-section gadolinium-enhanced orbit magnetic resonance imaging showed definite enhancement in the entire portion of the lobulated mass, compatible with a trochlear nerve schwannoma. Diplopia was managed conservatively with prism glasses and regular follow-up examinations were recommended without further treatment. CONCLUSIONS: A trochlear nerve tumor should be considered in adults who develop diplopia associated with acquired superior oblique muscle palsy.
Adult ; Brain Stem ; Diplopia* ; Eyeglasses ; Follow-Up Studies ; Glass ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neurilemmoma* ; Neurofibromatoses ; Orbit ; Paralysis ; Telescopes* ; Trochlear Nerve*

PURPOSE: The effective management of atopic dermatitis (AD) adjusted to individual clinical courses and demands can be challenging to both patients and physicians. Understanding of actual situations, experienced and perceived by patients with AD and their caregivers, is essential to improve clinical outcomes and satisfaction in real practice. METHODS: This multicenter survey was conducted in patients with AD or their caregivers from 9 centers with questionnaires on diagnosis and management of AD. RESULTS: A total of 324 patients and caregivers participated in the study. Most of the AD cases were initially diagnosed by physicians (80.6%), followed by self-diagnosis. Patients and caregivers thought that allergic substances, such as house dust mites, food, and pollutants, are responsible for AD development; moisturization, environmental control, and improvement of the body constitution are important for AD management. Allergy tests were performed in 194 patients (59.9%), but allergen avoidance strategy was instructed in only 81 subjects (41.8%). Major topical medications were steroids (81.8%) and topical immunomodulators (34.3%), while systemic medications were steroids (42.6%), antihistamines (36.4%), and cyclosporins (2.8%). One hundred eighty-one subjects (55.9%) had received complementary alternative medicine, including Oriental medicine. Many subjects desired to receive individualized management, use of specialized institutions for AD as well as evidence-based, effective, sustainable treatment. CONCLUSION: Our findings suggest that there may still be an unmet need for patients with AD in real practice. Personalized, evidencebased, and multidisciplinary approaches, including patient education, should be implemented for good outcomes.
Body Constitution ; Caregivers ; Complementary Therapies ; Cyclosporine ; Cyclosporins ; Dermatitis, Atopic* ; Diagnosis ; Histamine Antagonists ; Humans ; Hypersensitivity ; Immunologic Factors ; Korea* ; Medicine, East Asian Traditional ; Patient Education as Topic ; Pyroglyphidae ; Steroids

beta-lapachone is a naturally occurring quinone that selectively induces apoptotic cell death in a variety of human cancer cells in vitro and in vivo; however, its mechanism of action needs to be further elaborated. In this study, we investigated the effects of beta-lapachone on the induction of apoptosis in human gastric carcinoma AGS cells. beta-lapachone significantly inhibited cellular proliferation, and some typical apoptotic characteristics such as chromatin condensation and an increase in the population of sub-G1 hypodiploid cells were observed in beta-lapachone-treated AGS cells. Treatment with beta-lapachone caused mitochondrial transmembrane potential dissipation, stimulated the mitochondria-mediated intrinsic apoptotic pathway, as indicated by caspase-9 activation, cytochrome c release, Bcl-2 downregulation and Bax upregulation, as well as death receptor-mediated extrinsic apoptotic pathway, as indicated by activation of caspase-8 and truncation of Bid. This process was accompanied by activation of caspase-3 and concomitant with cleavage of poly(ADP-ribose) polymerase. The general caspase inhibitor, z-VAD-fmk, significantly abolished beta-lapachone-induced cell death and inhibited growth. Further analysis demonstrated that the induction of apoptosis by beta-lapachone was accompanied by inactivation of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. The PI3K inhibitor LY29004 significantly increased beta-lapachone-induced apoptosis and growth inhibition. Taken together, these findings indicate that the apoptotic activity of beta-lapachone is probably regulated by a caspase-dependent cascade through activation of both intrinsic and extrinsic signaling pathways, and that inhibition of the PI3K/Akt signaling may contribute to beta-lapachone-mediated AGS cell growth inhibition and apoptosis induction.
Apoptosis* ; Caspase 3 ; Caspase 8 ; Caspase 9 ; Cell Death ; Cell Proliferation ; Chromatin ; Cytochromes c ; Down-Regulation ; Humans ; Membrane Potentials ; Phosphatidylinositol 3-Kinase ; Poly(ADP-ribose) Polymerases ; Up-Regulation

PURPOSE: In this study, we aimed to investigate the perinatal clinical conditions of very low birth weight (VLBW) infants born to mothers with pregnancy-induced hypertension (PIH) focusing on the effects of early postnatal neutropenia. METHODS: We reviewed the medical records of 191 VLBW infants who were born at Konyang University Hospital, between March 2003 and May 2011. We retrospectively analyzed the clinical characteristics of the infants and their mothers and compared the incidence of perinatal diseases and mortality of the infants according to the presence or absence of maternal PIH and neutropenia on the first postnatal day. RESULTS: Infants born to mothers with PIH showed an increased incidence of neutropenia on the first postnatal day (47.4%), cesarean delivery, and intrauterine growth restriction. When the infants born to mothers with PIH showed neutropenia on the first postnatal day, their incidence of respiratory distress syndrome (RDS) was increased (P=0.031); however, the difference was not found to be significant through logistic regression analysis. In all the VLBW infants, neutropenia on the first postnatal day was correlated with the development of RDS. The incidence of the other perinatal diseases involving sepsis and mortality did not significantly differ according to the presence or absence of neutropenia in infants born to mothers with PIH. CONCLUSION: In VLBW infants born to mothers with PIH, the incidence of neutropenia on the first postnatal day was increased and it was not significantly correlated with the development of perinatal diseases involving RDS, sepsis, and mortality.
Female ; Humans ; Hypertension, Pregnancy-Induced ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Logistic Models ; Medical Records ; Mothers ; Neutropenia ; Pregnancy ; Retrospective Studies ; Sepsis

The funding acknowledgment in this article was omitted as published.

PURPOSE: The prevalence of allergic rhinitis is rapidly increasing and results in relatively high socio-economic burden on their family and community. However, studies on the economic burden of pediatric allergic rhinitis in Korea are limited. Therefore, we conducted this study to investigate the impact of pediatric allergic rhinitis on economic burden. METHODS: Two hundred sixty two children with allergic rhinitis were enrolled in 6 secondary or tertiary medical centers in Seoul from July to September, 2008. We collected data of the economic burden of allergic rhinitis (direct medical costs, direct nonmedical costs, and indirect costs) by face to face questionnaire survey. We compared the economic burden according to the severity and the duration of allergic rhinitis. RESULTS: The mean age of subjects was 6.54 years, and male were 174 (66.4%). Direct medical costs (10,000 Korean Won/yr) were 177.75, and direct nonmedical costs were 57.92. Although, there was no statistical significance, direct medical costs showed increasing trends in severe allergic rhinitis.(P=0.053) In addition, direct medical costs were positively correlated with duration of allergic rhinitis.(R=0.195, P=0.002). About 17% of the parents who care the allergic rhinitis children experienced the work absence due to their child's illness. CONCLUSION: The economic burdens of allergic rhinitis were positively correlated with the severity and duration of illness. Particularly costs for alternative medicine including oriental medicine were related with severity and duration allergic rhinitis. Therefore, special efforts for education with evidence based treatment strategy are necessary to decrease the economic burden of allergic rhinitis.
Child ; Complementary Therapies ; Humans ; Korea ; Male ; Medicine, East Asian Traditional ; Parents ; Prevalence ; Surveys and Questionnaires ; Rhinitis ; Rhinitis, Allergic, Perennial

Since laparoscopic liver resection was first introduced in 2001, Korean surgeons have chosen a laparoscopic procedure as one of the treatment options for benign or malignant liver disease. We distributed and analyzed a nationwide questionnaire to members of the Korean Laparoscopic Liver Surgery Study Group (KLLSG) in order to evaluate the current status of laparoscopic liver resection in Korea. Questionnaires were sent to 24 centers of KLLSG. The questionnaire consisted of operative procedure, histological diagnosis of liver lesions, indications for resection, causes of conversion to open surgery, and postoperative outcomes. A laparoscopic liver resection was performed in 416 patients from 2001 to 2008. Of 416 patients, 59.6% had malignant tumors, and 40.4% had benign diseases. A total laparoscopic approach was performed in 88.7%. Anatomical laparoscopic liver resection was more commonly performed than non-anatomical resection (59.9% vs 40.1%). The anatomical laparoscopic liver resection procedures consisted of a left lateral sectionectomy (29.3%), left hemihepatectomy (19.2%), right hemihepatectomy (6%), right posterior sectionectomy (4.3%), central bisectionectomy (0.5%), and caudate lobectomy (0.5%). Laparoscopy-related serious complications occurred in 12 (2.8%) patients. The present study findings provide data in terms of indication, type and method of liver resection, and current status of laparoscopic liver resection in Korea.
*Hepatectomy/statistics & numerical data ; Humans ; *Laparoscopy/statistics & numerical data ; Liver/*surgery ; Liver Diseases/pathology/surgery ; Liver Neoplasms/pathology/surgery ; Postoperative Complications/epidemiology ; Questionnaires ; Republic of Korea