PURPOSE: With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data. MATERIALS AND METHODS: To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory. Samples were either fresh frozen or formalin-fixed, paraffin embedded (FFPE) and the quality and yield of extracted genomic DNA was assessed. In order to estimate the effect of sample condition on the quality of sequencing results, tissue preparation method, specimen type (resected or biopsied) and tissue storage time were compared. RESULTS: We detected 7,360 non-synonymous point mutations, 1,164 small insertions and deletions, 3,173 copy number alterations, and 462 structural variants. Fifty-four percent of tumors had one or more clinically relevant genetic mutation. The distribution of actionable variants was variable among different genes. Fresh frozen tissues, surgically resected specimens, and recently obtained specimens generated superior sequencing results over FFPE tissues, biopsied specimens, and tissues with long storage duration. CONCLUSION: In order to overcome, challenges involved in bringing NGS testing into routine clinical use, a centralized laboratory model was designed that could improve the NGS workflows, provide appropriate turnaround times and control costs with goal of enabling precision medicine.
Academies and Institutes ; Asian Continental Ancestry Group ; DNA ; Humans ; Korea ; Methods ; Paraffin ; Point Mutation ; Precision Medicine ; Prevalence

PURPOSE: This study evaluated the effect of surgery-radiotherapy interval (SRI) on outcomes in patients treated with adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) and adjuvant four cycles of doxorubicin/cyclophosphamide (AC) followed by four cycles of taxane. MATERIALS AND METHODS: From 1999 to 2007, 397 eligible patients were diagnosed. The effect of SRI on outcomes was analyzed using a Cox proportional hazards model, and a maximal chi-square method was used to identify optimal cut-off value of SRI for each outcome. RESULTS: The median SRI was 6.7 months (range, 5.6 to 10.3 months). A SRI of 7 months was the significant cut-off value for distant metastasis-free survival (DMFS) and disease-free survival (DFS) using a maximal chi-square method. For overall survival, a significant cut-off value was not found. The patients with SRI > 7 months had worse 6-year DMFS and DFS than those with SRI ≤ 7 months on univariate analysis (DMFS, 81% vs. 91%, p=0.003; DFS, 78% vs. 89%, p=0.002). On multivariate analysis, SRI > 7 months did not affect DMFS and DFS. CONCLUSION: RT delayed for more than 7 months after BCS and adjuvant four cycles of AC followed by four cycles of taxane did not compromise clinical outcomes.
Breast Neoplasms* ; Breast* ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Humans ; Mastectomy, Segmental* ; Multivariate Analysis ; Proportional Hazards Models ; Radiotherapy ; Radiotherapy, Adjuvant ; Time-to-Treatment

OBJECTIVE: Although guideline recommends beta blockers (BBs) as first line antianginal agent and calcium channel blockers (CCBs) as alternatives after percutaneous coronary intervention (PCI), the prescription patterns in real practice are not in accordance with the guideline. We aimed to investigate the prescribing patterns of primary antianginal drug and relating factors in patients who underwent PCI. METHODS: Patients who have undergone PCI without myocardial infarction (MI) from November 2012 to June 2014 and followed up at least one year in a tertiary teaching hospital were included. Prescribing patterns of primary antianginal drug before, at the time of, and one year after PCI were described. Factors affecting drug selection, and their relationship with incidence of clinical outcomes defined as MI and repeated PCI, unscheduled admission or visit related with heart problem were analyzed with multivariate logistic regression. RESULTS: A total of 506 patients were included and as primary antianginal drugs, BB, CCB, and both were prescribed in 32.2%, 24.5%, and 17.8% of patients, respectively. Also, neither BB nor CCB was prescribed at the time of PCI in 25.5% of patients. Compared with BB, CCBs were more likely prescribed in patients who had hypertension (Odds Ratio, OR 2.18, 95% confidence interval, CI 1.16-4.07), use of same class before PCI (OR 7.18, 3.37-15.2) and concomitant angiotensin receptor blocker (ARB) use (OR, 1.92, 95% CI 1.10-3.33). Incidence of clinical outcomes were not significantly greater in patients who prescribed CCB compared with BB at the time of PCI (aOR 1.32, CI 0.65-2.68). CONCLUSION: This study demonstrated that half of the patients who underwent PCI were prescribed BB. CCB were favored in patients with hypertension, use of same class before PCI, and concomitant ARB use. Significant difference in clinical outcome was not observed between BB and CCB selection as primary antianginal drug.
Angiotensins ; Calcium Channel Blockers* ; Calcium Channels* ; Calcium* ; Heart ; Hospitals, Teaching ; Humans ; Hypertension ; Incidence ; Logistic Models ; Myocardial Infarction ; Percutaneous Coronary Intervention* ; Prescriptions*

OBJECTIVES: The purpose of this study was to estimate the prevalence and correlated factors of high myopia in 19 year-old men in Southeast Korea. METHODS: This retrospective study was based on the medical checkup data of conscription during 2005. The study subjects were 19 years old men in Busan, Ulsan and Gyeongsangnam-do. The health checkup data of the conscripts consisted of noncycloplegic autorefraction test, the biometric data and social factors. To analyze the social and biometric effects, we classified the biometric factors into 4 or 5 groups and the social factors into 3 groups. High myopia was defined as a spherical equivalent of under -6.0 diopter. Data analysis was performed using the chi square test for trends and multiple logistic regression analysis. The SAS(version 9.1) program was used for all the analyses. RESULTS: The prevalence of high myopia was 12.39% (6256 / 50 508). The factors correlated with high myopia were the residence area (OR, 2.07; 95% CI, 1.77 to 2.4 for small city; OR, 2.01; 95% CI, 1.72 to 2.34 for metropolis; the reference group was rural area), academic achievement (OR, 1.43; 95% CI, 1.34 to 1.53 for students of 4-and 6-year-course university; the reference group was high school graduates & under) and blood pressure (OR, 1.54; 95% CI, 1.10 to 2.16 for hypertension; OR, 1.09; 95% CI, 1.02 to 1.17 for prehypertension; OR, 1.10; 95% CI, 1.01 to 1.20 for hypotension; the reference group was normal blood pressure). CONCLUSIONS: More than one tenth of the young men were high myopia as one of the risk factor for visual loss. Further studies on high myopia and its complications are needed to improve eye health in Southeast Korea.
Body Mass Index ; Cluster Analysis ; Comorbidity ; Humans ; Hypertension/*epidemiology ; Hypotension/*epidemiology ; Male ; Military Personnel/statistics & numerical data ; Myopia/classification/*epidemiology ; Prevalence ; Republic of Korea/epidemiology ; *Residence Characteristics ; Retrospective Studies ; Rural Population ; Severity of Illness Index ; Urban Population ; Young Adult

PURPOSE: Metabolic syndrome (MS), characterized by obesity and insulin resistance, elicits risk factors such as hyperlipidemia, hypertension, and glucose intolerance with additive effects on atherosclerosis, leading to cardiovascular diseases. The purposes of this study were to evaluate the prevalence of MS among overweight and obese adolescents and to investigate the impact of obesity on the cardiovascular system. METHODS: tal cholesterol, triglyceride, low-density-lipoprotein (LDL)-cholesterol, high-density-lipoprotein (HDL)-cholesterol, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and high-sensitive C-reactive protein (hs-CRP) were measured in the patients with a BMI of >85 percentile. Brachial-ankle pulse wave velocity (BaPWV) and ankle brachial index were measured using Vascular Profiler (VP)-1000. RESULTS: MS was confirmed in 19.5% of the overweight and obese adolescents and 50.8% of the obese adolescents. The systolic and diastolic blood pressure, height, weight, fat mass, %fat, BMI, obesity index, and waist circumference were higher in the overweight and obese adolescents with MS. Moreover, the triglyceride, AST, ALT, and hs-CRP levels were higher, whereas HDL-cholesterol level was significantly lower in this group. The overweight and obese adolescents with MS showed shorter diastolic and systolic times, higher heart rate and BaPWV, and longer E-wave deceleration time by echocardiography. CONCLUSION: Overweight and obese adolescents showed characteristic MS features such as hypertension and hyperlipidemia. Thus, obese adolescents predisposed to MS should be provided early treatment for obesity.
Adolescent ; Alanine Transaminase ; Ankle Brachial Index ; Aspartate Aminotransferases ; Atherosclerosis ; Blood Pressure ; C-Reactive Protein ; Cardiovascular Diseases ; Cardiovascular System ; Cholesterol ; Deceleration ; Glucose Intolerance ; Heart Diseases ; Heart Rate ; Humans ; Hyperlipidemias ; Hypertension ; Insulin Resistance ; Obesity ; Overweight ; Prevalence ; Pulse Wave Analysis ; Risk Factors ; Waist Circumference

The ketogenic diet (KD) has been used to treat intractable childhood epilepsy. However, its mechanism of action remains unknown. In the present study, we examined the effects of KD on the expression of multiple constituents of the GABAergic system in the hippocampus through immunohistochemistry and northern blot analysis. From the results, we have shown that KD increased expression of GABA and decreased GABA transporter1 (GABATp) and GABA transaminase (GABA-T) mRNA levels in the hippocampus. These results suggest that the neuroinhibitory effect of KD may be mediated, at least in part, by the increment of GABAergic activity in the hippocampus. KD may increase the GABA levels in the synaptic space by limiting GABA reuptake and in the presynaptic nerve terminal by inhibiting GABA degradation.
4-Aminobutyrate Transaminase ; Animals ; Blotting, Northern ; Epilepsy ; gamma-Aminobutyric Acid* ; Glutamate Dehydrogenase ; Hippocampus* ; Immunohistochemistry ; Ketogenic Diet* ; Mice* ; RNA, Messenger

Renal artery stenosis is a rare cause of acute pulmonary edema. So-called flash pulmonary edema is associated with bilateral renal artery stenosis or stenosis in a single functioning kidney. Flash pulmonary edema has been recognized as an absolute indication for vascular intervention. A 33-year old man was admitted with acute shortness of breath. Renal angiography showed occlusion of the right renal artery. He underwent a right renal artery bypass graft. However, after the renal artery bypass graft, episodes of pulmonary edema recurred. A renal angiography showed complete obstruction of the right renal artery and bypass graft. The left renal angiography showed an intact renal artery and decreased kidney size.
Adult ; Angiography ; Constriction, Pathologic ; Dyspnea ; Humans ; Kidney ; Pulmonary Edema* ; Renal Artery Obstruction* ; Renal Artery* ; Transplants*

Renal involvement is common in systemic lupus erythematosus (SLE). The typical lupus nephropathy demonstrates polyclonal immunoglobulin immune deposits with predominance of IgG, usually heavy polytypic complement factors C1q, C3 and C4. In SLE patients, the superimposition and occurrence of non- lupus nephropathy have rarely been reported. We describe a 28-year-old, 15 weeks pregnant women affected by SLE and IgA nephropathy. She was admitted to our hospital due to generalized edema and arthralgia. The ANA titer was 1: 640, anti-ds DNA levels were 354.2 U/mL and other blood tests included thrombocytopenia and hypoclomplementemia. These clinical and laboratory data allowed the diagnosis of SLE. Renal biopsy showed modest segmental mesangial hypercellularity. Immunofluorescence microscopy revealed distinct mesangial IgA and C3 with absence of IgG, IgM, C1q, and C4. Electron microscopy confirmed the presence of electron-dense deposits throughout the mesangium. These features were consistent with the coexistence of IgA nephropathy. A course of prednisolone (50 mg/day) was given for six months and she responded well with resolution of proteinuria. At the present follow- up time point (48 months), she continues to be treated with prednisolone (5 mg/day); proteinuria and ANA are undetectable.
Adult ; Arthralgia ; Biopsy ; Complement System Proteins ; Diagnosis ; DNA ; Edema ; Female ; Glomerulonephritis, IGA* ; Hematologic Tests ; Humans ; Immunoglobulin A* ; Immunoglobulin G ; Immunoglobulin M ; Immunoglobulins ; Lupus Erythematosus, Systemic ; Lupus Nephritis* ; Microscopy, Electron ; Microscopy, Fluorescence ; Nephrotic Syndrome ; Prednisolone ; Pregnant Women ; Proteinuria ; Thrombocytopenia

Pituitary adenylate cyclase activating polypeptide (PACAP) was first isolated from ovine hypothalamus and was known to stimulate the release of growth factor in various cells. Recently, we reported the cellular localization of PACAP and its type I (PAC1 ) receptor in rat placenta during pregnancy. Placenta is a critical organ that synthesizes several growth factors and angiogenic factors for the fetal development and its own growth. However, there is little information regarding the cellular localization of PACAP and its receptor in human placenta at various gestations. The aim of the present study was to define the expression and distribution of PACAP and PAC1 receptor mRNAs in the human placenta during the pregnancy period. PACAP and PAC1 receptor mRNAs were expressed in stroma cells of stem villi and terminal villi. At the early stage, on 7 and 14 weeks, PACAP and PAC1 receptor genes were moderately expressed in stroma cells surrounding the blood vessels within stem villi. These genes were strongly expressed in stroma cells of stem villi and terminal villi on 24 and 38 weeks. The expression of these genes was increased as gestation advanced, and localized in the same areas. Localization of PACAP and PAC1 receptor demonstrate the evidence that PACAP may play an important role, as an autoregulator or pararegulator via its PAC1 receptor. In conclusion, our findings strongly suggest that PACAP may have a critical role in physiological function of the placenta for gestational maintenance and fetal growth.
Chorionic Villi/metabolism ; Female ; Gene Expression ; Humans ; Nerve Growth Factors/*biosynthesis ; Neuropeptides/*biosynthesis ; Neurotransmitter Agents/*biosynthesis ; Pituitary Adenylate Cyclase-Activating Polypeptide ; Placenta/*metabolism ; Pregnancy ; Pregnancy Trimester, First ; Pregnancy Trimester, Second ; RNA, Messenger ; Receptors, Cell Surface/*biosynthesis ; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide ; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I

The hippocampus is a central area of the memory-related neural system. Combined immunohistochemistry against choline acetyl transferase and retrograde transneuronal labelling of the pseudorabies virus were used to identify cholinergic neurons in the central nervous system projecting to the hippocampal formation of the rat. Five to ten microL of Bartha strain of pseudorabies virus were injected into the dentate gyrus, CA1 and CA3 of the hippocampus of 20 Sprague Dawley rats using stereotaxic instrument. Forty eight to 96 hr after the injection, the brains were removed and the tissue sections were processed for double immunofluorescence procedure using polyclonal antibodies against pseudorabies virus or choline acetyl transferase. The double labelled neurons were distributed at several different nuclei and the labelling patterns of three different areas of the hippocampus were similar. These data suggests that the cholinergic innervation to the hippocampus were distributed in a transsynaptic manner throughout the whole brain area.
Animal ; Antibodies ; Choline O-Acetyltransferase/*analysis/immunology ; Cholinergic Fibers/*enzymology ; Herpesvirus 1, Suid/immunology ; Hippocampus/*cytology ; Immunohistochemistry ; Microinjections ; Neural Pathways ; Rats ; Rats, Sprague-Dawley