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Iksung Cho,
Jaemin Shim,
Hyuk-Jae Chang, Ji Min Sung,
Youngtaek Hong,
Hackjoon Shim,
Young Jin Kim,
Byoung Wook Choi,
James K Min,
Ji-Ye Kim,
Chi-Young Shim,
Geu-Ru Hong,
Namsik Chung
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ABSTRACT: OBJECTIVES: This study was designed to determine the prognostic value of multidetector coronary computed tomography angiography (CTA) in relation to exercise electrocardiography (XECG) findings. BACKGROUND: The prognostic usefulness of coronary CTA findings of coronary artery disease in relation to XECG findings has not been explored systematically. METHODS: Patients with suspected coronary artery disease who had undergone both coronary CTA and XECG (<90 days between tests) from 2003 through 2009 were enrolled retrospectively. Coronary CTA results were classified according to the severity of maximal stenosis (normal, mild: <40% of luminal stenosis, moderate: 40% to 69%, severe: ≥70%), XECG results were categorized as positive and negative, and Duke XECG score was calculated. Clinical follow-up data were collected for major adverse cardiac events (MACE): cardiac death, nonfatal myocardial infarction, unstable angina requiring hospitalization, and revascularization after 90 days from index coronary CTA. C-statistics were calculated to compare discriminatory values of each test. RESULTS: Among the 2,977 (58 ± 10 years) study patients, 12% demonstrated positive XECG results. By coronary CTA, patients were categorized as normal (56%) or having mild (26%), moderate (13%), or severe (5%) disease. During a median follow-up of 3.3 years (interquartile range: 2.3 to 4.6), 97 MACE were observed and the 5-year cumulative event rate was 3.6% (95% confidence interval: 3.0 to 4.3). Although both XECG (C-statistic: 0.790) and coronary CTA (C-statistic: 0.908) improved risk stratification beyond clinical risk factors (C-statistic: 0.746, p < 0.05 for all), XECG in addition to coronary CTA (C-statistic: 0.907) did not provide better discrimination than coronary CTA alone (p = 0.389). In subgroup analyses, coronary CTA stratified risk of MACE in groups with both positive and negative XECG results (all p < 0.001 for trend). However, positive XECG results predicted risk of MACE on coronary CTA only in the moderate stenosis group (hazard ratio: 2.58, 95% confidence interval: 1.29 to 5.19, p = 0.008) and severe stenosis group (hazard ratio: 2.28, 95% confidence interval: 1.19 to 4.38, p = 0.013). CONCLUSIONS: In patients with suspected coronary artery disease, coronary CTA discriminates future risk of MACE in patients independent of XECG results. Compared with coronary CTA, XECG has an additive prognostic value only in patients with moderate to severe stenosis on coronary CTA.
Journal of the American College of Cardiology 10/2012; · 14.16 Impact Factor
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ABSTRACT: Cardiac resynchronization therapy (CRT) has been known to improve the outcome of advanced heart failure (HF) but is still underutilized in clinical practice. We investigated the prognosis of patients with advanced HF who were suitable for CRT but were treated with conventional strategies. We also developed a risk model to predict mortality to improve the facilitation of CRT.
Patients with symptomatic HF with left ventricular ejection fraction ≤35% and QRS interval >120 ms were consecutively enrolled at cardiovascular hospital. After excluding those patients who had received device therapy, 239 patients (160 males, mean 67±11 years) were eventually recruited.
During a follow-up of 308±236 days, 56 (23%) patients died. Prior stroke, heart rate >90 bpm, serum Na ≤135 mEq/L, and serum creatinine ≥1.5 mg/dL were identified as independent factors using Cox proportional hazards regression. Based on the risk model, points were assigned to each of the risk factors proportional to the regression coefficient, and patients were stratified into three risk groups: low- (0), intermediate-(1-5), and high-risk (>5 points). The 2-year mortality rates of each risk group were 5, 31, and 64 percent, respectively. The C statistic of the risk model was 0.78, and the model was validated in a cohort from a different institution where the C statistic was 0.80.
The mortality of patients with advanced HF who were managed conventionally was effectively stratified using a risk model. It may be useful for clinicians to be more proactive about adopting CRT to improve patient prognosis.
Korean Circulation Journal 10/2012; 42(10):659-67.
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ABSTRACT: Although radiation resistance is a primary issue in radiation therapy, attempts to find predictors of radiation resistance have met with little success. The authors therefore aimed to determine predictors for radiation resistance to improve the prognosis of head and neck squamous cell carcinoma (HNSCC).
HNSCC cell lines, SCC15, SCC25, and QLL1, irradiated with an acute dose of 4 grays (Gy) (RR-4), a cumulative dose of 60 Gy (RR-60), and a booster dose of 4 Gy over 60 Gy (RR-60 + 4), were used with nonirradiated cell lines. Those were used in cDNA microarray, proteomics, Western blotting, and immunofluorescence, respectively. One hundred five HNSCC tissue samples with radiation resistance were analyzed by immunohistochemistry.
Western blot analysis of RR-60 cell lines was identical to the data of Nm23-H1 overexpression by cDNA array and proteomic screening. Immunofluorescence demonstrated significant nuclear translocation of Nm23-H1 in RR-4 and RR-60 cell lines, and less but still intense nuclear shuttling in RR-60 + 4. Similarly, Nm23-H1 nuclear localization was observed in 20% (21 of 105) of tissue samples. Univariate analysis demonstrated that Nm23-H1 nuclear localization was strongly associated with overall and recurrence-free survival. Multivariate stepwise Cox regression analysis showed that Nm23-H1 nuclear localization (odds ratio [OR], 7.48) and N stage (OR, 2.13) were associated with overall survival, and Nm23-H1 nuclear localization (OR, 3.02), T stage (OR, 1.43), and insufficient tumor margin (OR, 3.27) were associated with recurrence-free survival.
Overexpression of Nm23-H1, specifically its nuclear translocation, may be a powerful predictor of radiation resistance in HNSCC.
Cancer 05/2011; 117(9):1864-73. · 4.77 Impact Factor
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ABSTRACT: To evaluate the prognostic outcome of cardiac computed tomography (CT) for prediction of major adverse cardiac events (MACEs) in low-risk patients suspected of having coronary artery disease (CAD) and to explore the differential prognostic values of coronary artery calcium (CAC) scoring and coronary CT angiography.
Institutional review committee approval and informed consent were obtained. In 4338 patients who underwent 64-section CT for evaluation of suspected CAD, both CAC scoring and CT angiography were concurrently performed by using standard scanning protocols. Follow-up clinical outcome data regarding composite MACEs were procured. Multivariable Cox proportional hazards models were developed to predict MACEs. Risk-adjusted models incorporated traditional risk factors for CAC scoring and coronary CT angiography.
During the mean follow-up of 828 days ± 380, there were 105 MACEs, for an event rate of 3%. The presence of obstructive CAD at coronary CT angiography had independent prognostic value, which escalated according to the number of stenosed vessels (P < .001). In the receiver operating characteristic curve (ROC) analysis, the superiority of coronary CT angiography to CAC scoring was demonstrated by a significantly greater area under the ROC curve (AUC) (0.892 vs 0.810, P < .001), whereas no significant incremental value for the addition of CAC scoring to coronary CT angiography was established (AUC = 0.892 for coronary CT angiography alone vs 0.902 with addition of CAC scoring, P = .198).
Coronary CT angiography is better than CAC scoring in predicting MACEs in low-risk patients suspected of having CAD. Furthermore, the current standard multisection CT protocol (coronary CT angiography combined with CAC scoring) has no incremental prognostic value compared with coronary CT angiography alone. Therefore, in terms of determining prognosis, CAC scoring may no longer need to be incorporated in the cardiac CT protocol in this population.
Radiology 01/2011; 259(1):92-9. · 5.73 Impact Factor
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ABSTRACT: Changes in the HPV genotype detected in patients over time could alter cervical disease progression. Identification of patterns in the alteration of HPV genotype should also be related to cytological and histological findings. Thus, we assessed the risk for low-grade squamous intraepithelial lesion (LSIL) or high-grade SIL (HSIL)/squamous cell carcinoma (SCC) associated with alterations in the HPV genotype detected, presence of multiple HPV genotypes, and individual genotyping or HPV clade grouping.
The 1052 participants were monitored by HPV chip and Pap smear. We calculated odds ratios and applied sequential association analysis (SAA) and decision tree analysis (DTA).
We classified HPV alteration as persistence, regression (spontaneous vs. therapeutic), or metatyping (progressive vs. regressive). Spontaneous regression occurred in 71.9% of patients. Metatyping was strongly associated with progression (RR: 3.9, p=0.0242), with progressive metatyping showing a higher risk of progression (RR: 31.49, p=0.00448). Few patients with multiple infections were identified in the initial screen but 30.8% of patients had multiple infections in the final analysis. HPV-16, -35, -52, and -58 were commonly associated with HPV persistence. Univariate analysis determined that final diagnosis significantly associated with HPV type at the endpoint (p<0.0001), persistence (p=0.0001), and progressive metatyping (p=0.0022). SAA determined that HPV-66, -68, and -69 were significantly associated with HSIL, and HPV-16 and -18 persistence significantly association with SCC. DTA indicated an age less than 28 years had a peak in LSIL, and an age between 32 and 48 years had a peak in HSIL. A bimodal peak in SCC for HR-2 at the endpoint was observed in participants less than 32 and greater than 48 years of age.
The alteration patterns of HPV infection detected included persistence, regression, and metatyping. HPV persistence and progressive metatyping are significant signatures of disease progression.
Gynecologic Oncology 11/2010; 120(2):284-90. · 3.89 Impact Factor
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ABSTRACT: The objective of this study is to compare the skill retention of two groups of lay persons, six months after their last CPR training. The intervention group was provided with animation-assisted CPRII (AA-CPRII) instruction on their cellular phones, and the control group had nothing but what they learned from their previous training.
This study was a single blind randomized controlled trial. The participants' last CPR trainings were held at least six months ago. We revised our CPR animation for on-site CPR instruction content emphasizing importance of chest compression. Participants were randomized into two groups, the AA-CPRII group (n=42) and the control group (n=38). Both groups performed three cycles of CPR and their performances were video recorded. These video clips were assessed by three evaluators using a checklist. The psychomotor skills were evaluated using the ResusciAnne SkillReporter.
Using the 30-point scoring checklist, the AA-CPRII group had a significantly better score compared to the control group (p<0.001). Psychomotor skills evaluated with the AA-CPRII group demonstrated better performance in hand positioning (p=0.025), compression depth (p=0.035) and compression rate (p<0.001) than the control group.
The AA-CPRII group resulted in better checklist scores, including chest compression rate, depth and hand positioning. Animation-assisted CPR could be used as a reminder tool in achieving effective one-person-CPR performance. By installing the CPR instruction on cellular phones and having taught them CPR with it during the training enabled participants to perform better CPR.
Resuscitation 07/2009; 80(6):680-4. · 3.60 Impact Factor
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Ji-Min Sung,
Hee-Jung Cho,
Hee Yi,
Chi-Ho Lee,
Hye-Sun Kim,
Dong-Ku Kim,
A M Abd El-Aty,
Jin-Suk Kim,
Christopher P Landowski,
Matthias A Hediger,
Ho-Chul Shin
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ABSTRACT: We isolated a stem cell subpopulation from human lung cancer A549 cells using FACS/Hoechst 33342. This side population (SP), which comprised 24% of the total cell population, totally disappeared after treatment with the selective ABCG 2 inhibitor fumitremorgin C. In a repopulation study, isolated SP and non-SP cells were each able to generate a heterogeneous population of SP and non-SP cells, but this repopulation occurred more rapidly in SP cells than non-SP. An MTT assay and cell cycle distribution analysis reveal a similar profile between SP and non-SP groups. However, in the presence of doxorubicin (DOX) and methotrexate (MTX), SP cells showed significantly lower Annexin V staining when compared to non-SP cells. Taken together, these results demonstrate that SP cells have an active regeneration capacity and high anti-apoptotic activity compared with non-SP cells. Furthermore, our GeneChip data revealed a heightened mRNA expression of ABCG2 and ABCC2 in SP cells. Overall these data explain why the SP of A549 has a unique ability to resist DOX and MTX treatments. Therefore, we suggest that the expression of the ABCG2 transporter plays an important role in the multidrug resistance phenotype of A549 SP cells.
Biochemical and Biophysical Research Communications 07/2008; 371(1):163-7. · 2.48 Impact Factor
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Hye-Ryoung Kim,
Sung-Won Park,
Hee-Jung Cho,
Kyung-Ae Chae, Ji-Min Sung,
Jin-Suk Kim,
Christopher P Landowski,
Duxin Sun,
A M Abd El-Aty,
Gordon L Amidon,
Ho-Chul Shin
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ABSTRACT: We have studied gene expression profiles of intestinal transporters in model animals and humans. Total RNA was isolated from duodenum and the mRNA expression was measured using Affymetrix GeneChip oligonucleotide arrays. Detected genes from the intestine of mice, rats, and humans were about 60% of 22,690 sequences, 40% of 8739, and 47% of 12,559, respectively. A total of 86 genes involving transporters expressed in mice, 50 genes in rats, and 61 genes in humans were detected. Mice exhibited abundant mRNA expressions for peptide transporter HPT1, amino acid transporters CSNU3, CT1 and ASC1, nucleoside transporter CNT2, organic cation transporter SFXN1, organic anion transporter NBC3, glucose transporter SGLT1, and fatty acid transporters FABP1 and FABP2. Rats showed high expression profiles of peptide transporter PEPT1, amino acid transporters CSNU1 and 4F2HC, nucleoside transporter CNT2, organic cation transporter OCT5, organic anion transporter SDCT1, glucose transporter GLUT2 and GLUT5, and folate carrier FOLT. In humans, the highly expressed genes were peptide transporter HPT1, amino acid transporters LAT3, 4F2HC and PROT, nucleoside transporter CNT2, organic cation transporter OCTN2, organic anion transporters NADC1, NBC1 and SBC2, glucose transporters SGLT1 and GLUT5, multidrug resistance-associated protein RHO12, fatty acid transporters FABP1 and FABP2, and phosphate carrier PHC. Overall these data reveal diverse transcriptomic profiles for intestinal transporters among these species. Therefore, this transcriptional data may lead to more effective use of the laboratory animals as a model for oral drug development.
Pharmacological Research 10/2007; 56(3):224-36. · 4.44 Impact Factor
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ABSTRACT: The primary objective of this study was to compare the pharmacokinetics of a new anti-human immunodeficiency virus agent 1-(2-amino-pyridin-4-ylmethyl)-6-(3,5-dimethylbenzoyl)-5-isopropyl-1H-pyrimidine-2,4-dione (VP-0502) with its amino acid prodrug alanine amide of VP-0502 (VP-0502AL), following intravenous and oral administrations to rats. The plasma concentrations of both analytes were analyzed via high-performance liquid chromatography coupled with photodiode-array detection (HPLC-DAD). When VP-0502 was intravenously administered at 20 mg/kg, the analyte appeared in low levels with an AUC of 0.3 microg . h/ml, and C(0) of 0.2 microg/ml in plasma. However, both the prodrug VP-0502AL and its metabolite VP-0502 appeared at comparatively higher levels following intravenous injection of VP-0502AL at the same dose. VP-0502AL's pharmacokinetic parameters were V(d): 4.6 l/kg; AUC: 3 microg . h/ml; t(1/2): 0.5 h; C(0): 6 microg/ml; CL(tot): 7 l/h/kg; and MRT: 0.6 h. Following oral administration of VP-0502 (100 mg/kg), it was not detectable in plasma (<50 ng/ml), while after the oral administration of VP-0502AL, VP-0502 was quantitatively detected as an active metabolite for the first 7 h, with a maximum plasma concentration (C(max)) of 0.8 microg/ml, and an area under the concentrationtime curve (AUC) of 2 microg . h/ml. The oral pharmacokinetic parameters of VP-0502AL were calculated to be: maximum concentration time (t(max)) 2.7 h; C(max) 0.2 microg/ml; elimination half-life (t(1/2)): 0.8 h; and AUC 0.5 microg . h/ml. Overall the findings indicate that VP-0502AL has a favorable pharmacokinetic profile as a prodrug with rapid transformation into the active metabolite, and that the attachment of the amino acid alanine to VP-0502 is an effective approach to improve its oral bioavailability. VP-0502AL is predicted to become a new highly bioavailable anti-AIDS drug candidate and/or lead compound.
Journal of Veterinary Science 09/2007; 8(3):263-7. · 1.16 Impact Factor
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ABSTRACT: The studies on cancer-stem-cells (CSCs) have attracted so much attention in recent years as possible therapeutic implications. This study was carried out to investigate the gene expression profile of CSCs in human lung adenocarcinoma A549 cells.
We isolated CSCs from A549 cell line of which side population (SP) phenotype revealed several stem cell properties. After staining the cell line with Hoechst 33342 dye, the SP and non-side population (non-SP) cells were sorted using flow cytometric analysis. The mRNA expression profiles were measured using an Affymetrix GeneChip(R) oligonucleotide array. Among the sixty one differentially expressed genes, the twelve genes inclusive three poor prognostic genes; Aldo-keto reductase family 1, member C1/C2 (AKR1C1/C2), Transmembrane 4 L six family member 1 nuclear receptor (TM4SF1), and Nuclear receptor subfamily 0, group B, member 1 (NR0B1) were significantly up-regulated in SP compared to non-SP cells.
This is the first report indicating the differences of gene expression pattern between SP and non-SP cells in A549 cells. We suggest that the up-regulations of the genes AKR1C1/C2, TM4SF1 and NR0B1 in SP of human adenocarcinoma A549 cells could be a target of poor prognosis in anti-cancer therapy.
Molecular Cancer 02/2007; 6:75. · 3.99 Impact Factor
