BACKGROUND: Development of chemotherapeutics for the treatment of advanced hepatocellular carcinoma (HCC) has been lagging. Screening of candidate therapeutic agents by using patient-derived preclinical models may facilitate drug discovery for HCC patients. METHODS: Four primary cultured HCC cells from surgically resected tumor tissues and six HCC cell lines were used for high-throughput screening of 252 drugs from the Prestwick Chemical Library. The efficacy and mechanisms of action of the candidate anti-cancer drug were analyzed via cell viability, cell cycle assays, and western blotting. RESULTS: Guanabenz acetate, which has been used as an antihypertensive drug, was screened as a candidate anti-cancer agent for HCC through a drug sensitivity assay by using the primary cultured HCC cells and HCC cell lines. Guanabenz acetate reduced HCC cell viability through apoptosis and autophagy. This occurred via inhibition of growth arrest and DNA damage-inducible protein 34, increased phosphorylation of eukaryotic initiation factor 2α, increased activating transcription factor 4, and cell cycle arrest. CONCLUSIONS: Guanabenz acetate induces endoplasmic reticulum stress–related cell death in HCC and may be repositioned as an anti-cancer therapeutic agent for HCC patients.
Activating Transcription Factor 4 ; Apoptosis ; Autophagy ; Blotting, Western ; Carcinoma, Hepatocellular ; Cell Cycle ; Cell Cycle Checkpoints ; Cell Death ; Cell Line ; Cell Survival ; DNA ; Drug Discovery ; Drug Repositioning ; Endoplasmic Reticulum ; Guanabenz ; Humans ; Mass Screening ; Peptide Initiation Factors ; Phosphorylation ; Primary Cell Culture

CHARGE syndrome (coloboma, heart defects, atresia choanae, retarded growth and development, genital hypoplasia, and ear abnormalities) is characterized by multiple malformations and is diagnosed using distinct consensus criteria. Mutations in the gene encoding chromodomain helicase DNA-binding protein 7 (CHD7) are the major cause of CHARGE syndrome. Clinical features of CHARGE syndrome considerably overlap those of 22q11.2 deletion syndrome. Of these features, immunodeficiency and hypocalcemia are frequently reported in patients with 22q11.2 deletion syndrome but are rarely reported in patients with CHARGE syndrome. In this report, we have described the case of a patient with typical phenotypes of 22q11.2 deletion syndrome but without the proven chromosome microdeletion. Mutation analysis of CHD7 identified a pathogenic mutation (c.2238+1G>A) in this patient. To our knowledge, this is the first case of CHARGE syndrome with immunodeficiency and hypocalcemia in Korea. Our observations suggest that mutation analysis of CHD7 should be performed for patients showing the typical phenotypes of 22q11.2 deletion syndrome but lacking the proven chromosome microdeletion.
CHARGE Syndrome* ; Consensus ; DiGeorge Syndrome ; Ear ; Growth and Development ; Heart ; Humans ; Hypocalcemia* ; Korea ; Nasopharynx ; Phenotype

Callosal anomalies are frequently associated with other central nervous system (CNS) and/or somatic anomalies. We retrospectively analyzed the clinical features of corpus callosal agenesis/hypoplasia accompanying other CNS and/or somatic anomalies. We reviewed the imaging and clinical information of patients who underwent brain magnetic resonance imaging in our hospital, between 2005 and 2012. Callosal anomalies were isolated in 13 patients, accompanied by other CNS anomalies in 10 patients, associated with only non-CNS somatic anomalies in four patients, and with both CNS and non-CNS abnormalities in four patients. Out of 31 patients, four developed normally, without impairments in motor or cognitive functions. Five of nine patients with cerebral palsy were accompanied by other CNS and/or somatic anomalies, and showed worse Gross Motor Function Classification System scores, compared with the other four patients with isolated callosal anomaly. In addition, patients with other CNS anomalies also had a higher seizure risk.
Adolescent* ; Brain ; Central Nervous System ; Cerebral Palsy ; Child* ; Classification ; Humans ; Magnetic Resonance Imaging ; Retrospective Studies ; Seizures

The pneumonia severity index (PSI) and CURB-65 are widely used tools for the prediction of community-acquired pneumonia (CAP). This study was conducted to evaluate validation of severity scoring system including the PSI and CURB-65 scores of Korean CAP patients. In the prospective CAP cohort (participated in by 14 hospitals in Korea from January 2009 to September 2011), 883 patients aged over 18 yr were studied. The 30-day mortalities of all patients were calculated with their PSI index classes and CURB scores. The overall mortality rate was 4.5% (40/883). The mortality rates per CURB-65 score were as follows: score 0, 2.3% (6/260); score 1, 4.0% (12/300); score 2, 6.0% (13/216); score 3, 5.7% (5/88); score 4, 23.5% (4/17); and score 5, 0% (0/2). Mortality rate with PSI risk class were as follows: I, 2.3% (4/174); II, 2.7% (5/182); III, 2.3% (5/213); IV, 4.5% (11/245); and V, 21.7% (15/69). The subgroup mortality rate of Korean CAP patients varies based on the severity scores and CURB-65 is more valid for the lower scores, and PSI, for the higher scores. Thus, these variations must be considered when using PSI and CURB-65 for CAP in Korean patients.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; Cohort Studies ; Community-Acquired Infections/*mortality ; Female ; Humans ; Intensive Care Units ; Male ; Middle Aged ; Pneumonia/*mortality ; Prospective Studies ; Republic of Korea ; *Severity of Illness Index ; Young Adult

BACKGROUND: This study evaluates the effectiveness of immunochemotherapy and radiation therapy in the treatment of patients with primary bone lymphoma (PBL). METHODS: We retrospectively reviewed the medical records of 33 patients with PBL who were treated at 6 medical centers in Korea from 1992 to 2010. Clinicopathological features and treatment outcomes were analyzed. RESULTS: The median age of the patients participating in our study was 40 years. The most common sites of involvement were the pelvis (12.36%) and femur (11.33%). CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) or CHOP-like regimens were administered to 20 patients (61%), and R-CHOP (rituximab plus CHOP) was administered to the remaining 13 patients (39%). The overall response rate was 89% (complete response, 76%; partial response, 12%). The overall survival (OS) of patients with solitary bone lesions was longer than that of patients with multiple bone lesions (median OS: not reached vs. 166 months, respectively; P=0.089). Addition of rituximab to CHOP did not significantly affect either OS or progression-free survival (P=0.53 and P=0.23, respectively). Combining radiation therapy with chemotherapy also did not improve the OS or progression-free survival of patients with solitary bone lesions. CONCLUSION: Conventional cytotoxic chemotherapy remains an effective treatment option for patients with PBL. Additional benefits of supplementing chemotherapy with either rituximab or radiation therapy were not observed in this study. Further investigation is needed to characterize the role of immunochemotherapy in treating patients with PBL.
Antibodies, Monoclonal, Murine-Derived ; Disease-Free Survival ; Doxorubicin ; Femur ; Humans ; Korea ; Lymphoma ; Medical Records ; Pelvis ; Retrospective Studies ; Vincristine ; Rituximab

This study aimed to characterize and MRI track the mesenchymal stem cells labeled with chitosan-coated superparamagnetic iron oxide (Chitosan-SPIO). Chitosan-SPIO was synthesized from a mixture of FeCl2 and FeCl3. The human bone marrow derived mesenchymal stem cells (hBM-MSC) were labeled with 50 microg Fe/mL chitosan-SPIO and Resovist. The labeling efficiency was assessed by iron content, Prussian blue staining, electron microscopy and in vitro MR imaging. The labeled cells were also analyzed for cytotoxicity, phenotype and differentiation potential. Electron microscopic observations and Prussian blue staining revealed 100% of cells were labeled with iron particles. MR imaging was able to detect the labeled MSC successfully. Chitosan-SPIO did not show any cytotoxicity up to 200 microgram Fe/mL concentration. The labeled stem cells did not exhibit any significant alterations in the surface markers expression or adipo/osteo/chondrogenic differentiation potential when compared to unlabeled control cells. After contralateral injection into rabbit ischemic brain, the iron labeled stem cells were tracked by periodical in vivo MR images. The migration of cells was also confirmed by histological studies. The novel chitosan-SPIO enables to label and track MSC for in vivo MRI without cellular alteration.
Animals ; Brain Ischemia/chemically induced/pathology/therapy ; Cell Differentiation ; Chitosan/*chemistry ; Coordination Complexes/*chemistry/toxicity ; Ferric Compounds/*chemistry ; Humans ; Magnetic Resonance Imaging ; Magnetics ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells/*chemistry/cytology ; Metal Nanoparticles/*chemistry ; Phenotype ; Rabbits

OBJECTIVE: The purpose of this study was to establish reference ranges for the fetal orbital diameters (OD) and outer orbital diameters at 16 to 38 weeks' gestation. METHODS: This prospective longitudinal study enrolled 41 consecutive women with uncomplicated singleton gestations during their first trimester of pregnancy. Serial measurements of the fetal orbits by ultrasound examination were performed at intervals of 4 weeks until 28 weeks, and then every 2 weeks until 36 weeks, and weekly thereafter. Linear regression was used for statistical analysis. RESULTS: A total of 331 fetal orbital diameters and 298 outer orbital diameters were measured. The reference ranges for orbital diameters and outer orbital diameters were presented as mean, 95% confidence interval of the mean and percentiles. A linear growth function was observed between gestational age (GA), orbital diameter (Y=0.654 x GA - 0.856; r2=0.948; p<0.0001) and outer orbital diameter (Y=1.679 x GA+0.510; r2=0.942; p<0.0001). Significant correlation was also found between orbital diameter and outer orbital diameter (Y=2.451 x OD+4.840; r2=0.906; p<0.0001). CONCLUSION: We have presented percentile tables and regression formulas for fetal orbital diameters and outer orbital diameters. These results provide normative data of the growth of the fetal orbit and may be useful in assessing fetal orbital architecture in patients at risk of ocular abnormalities.
Female ; Gestational Age ; Humans ; Linear Models ; Longitudinal Studies* ; Orbit* ; Pregnancy ; Pregnancy Trimester, First ; Prospective Studies* ; Reference Values* ; Ultrasonography

PURPOSE: The matrix metalloproteinases (MMPs) are a family of proteolytic enzymes. MMPs are known to be involved in tumor invasion, and several have been implicated in tumor prognosis. The aim of this study was to evaluate the prognostic significances of the expressions of MMP-7 and -9 in rectal cancer. MATERIALS AND METHODS: The tumor tissues of 87 patients with stage II or III rectal carcinoma that underwent potentially curative resection followed by postoperative adjuvant chemoradiation and 5-fluorouracil based chemotherapy, were investigated immunohistochemically using monoclonal antibodies against MMP-7 and MMP-9. Clinical information, including tumor grades, carcinoembryonic antigen (CEA) levels, and disease-free survival and overall survival were evaluated with respect to the expressions of MMP-7 and -9. RESULTS: Median follow-up duration was 53.2 months, and median patient age was 55+/-11 years (range 32~75). MMP-7 expression in tumor tissue was found to be significantly correlated with the presence of nodal metastasis (p=0.029), whilst MMP-9 expression correlated with depth of tumor invasion (p=0.019). No relatio- nships were found between the expressions of MMP-7 or -9 and age, sex, tumor size, tumor grade, or CEA level. Univariate analysis showed that MMP-7 expression was associated with poor 5-year overall survival (12.8 months vs. 65.3 months, p=0.0405). Multivariate analysis confirmed that MMP-7 was independently associated with an adverse outcome (Relative risk: 1.415, p=0.027). However, MMP-9 expression was not found to be related to clinical outcome. CONCLUSION: MMP-7 expression in tumor tissue is associated with lymph node metastasis and a poor 5-year overall survival in rectal cancer patients.
Antibodies, Monoclonal ; Carcinoembryonic Antigen ; Disease-Free Survival ; Drug Therapy ; Fluorouracil ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Lymph Nodes ; Matrix Metalloproteinase 7* ; Matrix Metalloproteinases ; Multivariate Analysis ; Neoplasm Metastasis ; Peptide Hydrolases ; Prognosis ; Rectal Neoplasms*

OBJECTIVE: To investigate the clinical efficacy of assisted hatching (AH) with partial zona dissection (PZD) in intrauterine embryo transfer in the patients who failed more than 2 times with standard IVF-ET protocol (Group R), were more than 37 years old (Group A), or had high basal serum FSH levels more than 15 mIU/ml (Group F). METHODS: From January, 1998 to June, 2002, 156 cycles of AH with partial zona dissection were performed in 117 infertile patients in Department of Obstetrics and Gynecology, Seoul National University Hospital. The outcomes of AH were analyzed according to pregnancy rate. RESULTS: The number of oocytes retrieved after controlled ovarian hyperstimulation (COH) was 8.3 +/- 5.2 in 104 cycles of 75 patients who failed more than 2 times with standard IVF-ET protocol (Group I: Groups R, R+A, R+F, and R+A+F), 7.7 +/- 5.0 in 82 cycles of 67 patients who were more than 37 years old (Group II: Groups A, R+A, A+F, and R+A+F), and 7.2 +/- 4.9 in 38 cycles of 30 patients who had high basal serum FSH levels more than 15 mIU/ml (Group III: Groups F, R+F, A+F, and R+A+F). The number of embryos transferred after AH was 4.1 +/- 1.5 in Group I, 3.7 +/- 1.3 in Group II, and 4.0 +/- 1.7 in Group III. The mean cumulative embryo score (CES) was 81.9 +/- 46.5 in Group I, 75.9 +/- 43.0 in Group II, and 75.7 +/- 40.2 in Group III. There were no significant differences in the numbers of oocytes retrieved, embryos transferred and CES among 3 groups. The overall clinical pregnancy rate was 22.4% (35/156) per cycle and 29.9% (35/117) per patient. The clinical pregnancy rate per cycle and per patient was 18.3% (19/104) and 25.3% (19/75) in Group I, 15.9% (13/82) and 19.4% (13/67) in Group II, and 31.6% (12/38) and 40.0% (12/30) in Group III, and there was a significant difference between Group II and Group III. CONCLUSION: AH of human embryos with PZD might be promising for the improvement of pregnancy rates, especially in the patients with the past history of repeated failure, old age, or high basal serum FSH level.
Adult ; Embryo Transfer* ; Embryonic Structures* ; Gynecology ; Herpes Zoster* ; Humans ; Obstetrics ; Oocytes ; Pregnancy Rate ; Seoul

Two cases of ABO discrepancy were observed in thirty-year old woman with gall bladder abscess and fifty-five-year old woman with hepatocellular carcinoma. Their red cells were typed as group O and their serum had only anti-A antibody. Absence of A and B antigens on their RBCs were confirmed by adsorption elution test and saliva test. The B transferase activities were not demonstrated in their serum. Their ABO genotypes were O/O by sequence specific polymerase chain reaction. Their serum protein electrophoresis showed hypogammaglobulinemia pattern, and immunoglobulin levels (IgG, IgA, IgM) were decreased (39 mg/dL, 46 mg/dL, <5 mg/dL and 63 mg/dL, 65 mg/dL, 12 mg/dL, respectively).
Abscess ; Adsorption ; Agammaglobulinemia* ; Carcinoma, Hepatocellular ; Electrophoresis ; Female ; Genotype ; Humans ; Immunoglobulin A ; Immunoglobulins ; Polymerase Chain Reaction ; Saliva ; Transferases ; Urinary Bladder