[Show abstract][Hide abstract] ABSTRACT: Aurivillius phase Bi7Fe3(Ti3 − xWx)O21 + δ (x = 0 and 0.06) thin films were deposited on Pt(1 1 1)/Ti/SiO2/Si(1 0 0) substrates by using a chemical solution deposition method. The W6+-ion doped Bi7Fe3Ti3O21 thin film exhibited tremendous improvements in the electrical and multiferroic properties, namely a low leakage current density, good stability against electrical breakdown, large ferroelectric polarization and large magnetization as compared to the un-doped thin film. The Bi7Fe3(Ti2.94W0.06)O21 + δ thin film was stable against electrical break down at applied electric fields up to 1275 kV/cm, at which the measured remnant polarization (2Pr) and the coercive field (2Ec) values were 33.5 μC/cm2 and 825 kV/cm, respectively whereas, the measured 2Pr value of the un-doped Bi7Fe3Ti3O21 thin film was 3.5 μC/cm2 at an applied electric field of 318 kV/cm. Furthermore, the Bi7Fe3(Ti2.94W0.06)O21 + δ thin film showed a well-saturated ferromagnetic hysteresis loop with large magnetization at room temperature.
[Show abstract][Hide abstract] ABSTRACT: Despite the remarkable advances in cardiovascular imaging over the last decade, it is still challenging to identify high-risk atherosclerotic plaques prior to onset of major cardiovascular complications. Accumulating knowledge regarding the pathophysiological properties of vulnerable plaque (VP) has driven the development of molecular imaging technologies that target biologic process to characterize vulnerable plaques. Given the importance of VP detection in vivo, molecular imaging has emerged as an attractive diagnostic tool to more accurately estimate the risk of plaque rupture.
Current Cardiovascular Imaging Reports 06/2015; 8(6). DOI:10.1007/s12410-015-9338-9
[Show abstract][Hide abstract] ABSTRACT: Structural remodeling of the left atrium is a risk factor for recurrent arrhythmia after catheter ablation for atrial fibrillation; however, data are sparse regarding the role of functional left atrial remodeling in predicting procedural outcomes. We evaluated whether left atrial transport function could be used to predict recurrent atrial fibrillation. From July 2008 through August 2010, we enrolled 202 consecutive patients who underwent catheter ablation for atrial fibrillation (paroxysmal=120, persistent=82). Left atrial volumes (LAVs) were measured by means of multislice computed tomography at every 10% of the R-R interval, and measurements were adjusted for body surface area to yield the LAV index (LAVI) at baseline. The left atrial emptying fraction (LAEF) was calculated according to LAV differences. During the mean follow-up period of 10 ± 4 months after a single ablation procedure, atrial fibrillation recurred in 59 patients (paroxysmal=19, persistent=40). Multivariate analysis revealed that persistent atrial fibrillation, early mitral inflow velocity, LAVImax, LAVImin, LAEF, LAVImax/LAEF, and LAVImin/LAEF were all independent predictors of atrial fibrillation, but the best predictor was LAVImin/LAEF (β=1.329, P=0.001). The cutoff value was 1.61 (mL/m(2))/%, and the sensitivity and specificity were 74.6% and 62.2%, respectively (area under the curve=0.761). Our study shows that adjusted left atrial emptying fraction with use of multislice computed tomography might be a useful, noninvasive method to select patients for ablation.
Texas Heart Institute journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital 06/2015; 42(3):216-225. DOI:10.14503/THIJ-14-4524 · 0.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cisplatin is a potent chemotherapeutic agent, but its nephrotoxicity, which results in acute kidney injury (AKI), often limits its clinical application. Although many studies have attempted to target the mechanism responsible for its nephrotoxicity, no such method has been demonstrated to be effective in clinical trials. Recently, a dipeptidyl peptidase-4 (DPP4) inhibitor has been reported to have a renoprotective effect in a mouse model of cisplatin-induced AKI. Therefore, we will evaluate whether a DPP4 inhibitor protects the kidney from cisplatin-induced injury in humans.
This is a single-center, prospective, randomized, double-blind, placebo-controlled trial. A total of 182 participants who are scheduled for cisplatin treatment will be enrolled and randomly assigned to receive either a DPP4 inhibitor (gemigliptin) or a placebo. Participants will take the study drugs for 8 days starting 1 day before cisplatin treatment. The primary outcome of interest is the incidence of AKI at 7 days after finishing treatment with cisplatin. The secondary outcomes include changes in serum creatinine levels and estimated glomerular filtration rates from baseline to 7 days after cisplatin treatment.
This is the first clinical trial to investigate the effect of a DPP4 inhibitor on cisplatin-induced AKI.
ClinicalTrials.gov number NCT02250872, December 26, 2014.
[Show abstract][Hide abstract] ABSTRACT: High purity sodium hydroxide (NaOH) solution is extremely important in the large-scale manufacturing of impurity-free silicon (Si) wafers for solar cells. In this paper, we demonstrate the purification of highly concentrated NaOH via electrowinning. By optimizing temperature, current density, and the type of electrode for both anodes and cathodes, we maximized the selectivity toward cathodic deposition of Fe and Ni. Our results suggest that removal of metal impurities in the concentrated 50 wt.% NaOH is highly dependent on the reactor temperature (>90 °C) due to enhanced reaction kinetics and decreased solution viscosity. Meanwhile, current density has limited effect on the metal removal efficiency. We further demonstrate that the cathodic deposition of Fe and Ni strongly relies on the type of electrode pair used, with platinum (Pt) and nickel (Ni) as the anode and cathode, respectively, exhibiting the best removal performance. The good electrochemical performance arises from the high catalytic activity of Pt anode and good stability of Ni cathode from the highly corrosive concentrated alkaline conditions. Following these results, we recommend future scientific and technical studies on the use of electrowinning as a possible alternative to the costly membrane-based purification techniques.
[Show abstract][Hide abstract] ABSTRACT: This is a phase I/II study of second-line chemotherapy with paclitaxel and irinotecan in fluoropyrimidine- and platinum-pretreated patients with metastatic or recurrent gastric cancer.
Phase I part with a standard 3 + 3 dose-escalation design was conducted to define the recommended phase II dose (RP2D) using four predefined dose levels of paclitaxel and irinotecan. The efficacy of RP2D was evaluated in a phase II part.
In phase I part, 12 patients were enrolled. Dose-limiting toxicity was not observed. The RP2D was established as level 4 (paclitaxel-135 mg/m(2) and irinotecan-160 mg/m(2), every 3 weeks). In phase II part, 27 patients were enrolled. Thirty patients, including three patients at dose level 4 in the phase I part, were analyzed for efficacy. There was no complete response. Partial response and stable disease were reported in four and 16 patients, respectively (response rate 13.3 %, 95 % CI 0.0-25.5 %; disease control rate 66.6 %, 95 % CI 49.0-83.0 %). The median time to progression and overall survival was 3.0 months (95 % CI 1.8-4.2) and 10.1 months (95 % CI 6.6-13.6), respectively. Grade 3/4 toxicities included neutropenia (2 patients, 7.4 %), thrombocytopenia (1, 3.7 %), neutropenic fever (1, 3.7 %), and diarrhea (1, 3.7 %). There were no treatment-related deaths.
The RP2D of the paclitaxel and irinotecan combination is paclitaxel (135 mg/m(2)) and irinotecan (160 mg/m(2)), every 3 weeks. This combination as a second-line treatment for advanced gastric cancer shows tolerable toxicity and modest efficacy.
Cancer Chemotherapy and Pharmacology 04/2015; 75(6). DOI:10.1007/s00280-015-2732-9 · 2.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Lipoprotein(a) [Lp(a)] is known to be associated with cardiovascular complications and atherothrombotic properties in general populations. However, it has not been examined whether Lp(a) levels are able to predict adverse cardiovascular outcomes in patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DESs). A total of 595 consecutive patients with angina pectoris who underwent elective PCI with DESs were enrolled from 2004 to 2010. The patients were divided into two groups according to the levels of Lp(a): Lp(a) <50 mg/dl (n=485 patients), and Lp(a) ≥ 50 mg/dL (n=111 patients). Six-to-9 months angiographic outcomes and 3-year cumulative major clinical outcomes were compared between the two groups. Binary restenosis occurred in 26 of 133 lesions (19.8%) in high Lp(a) group and 43 of 550 lesions (7.9%) in low Lp(a) group (p=0.001). In multivariate analysis, the reference vessel diameter, low dense lipoprotein cholesterol, total lesion length, and Lp(a) ≥ 50 mg/dL were predictors of binary restenosis. In Cox proportional hazards regression analysis, Lp(a)>50 mg/dL was significantly associated with the 3-year adverse clinical outcomes including any myocardial infarction, revascularization [target lesion revascularization (TLR) and target vessel revascularization (TVR)], TLR-major adverse cardiac events (MACEs), TVR-MACE, and All-MACEs. In our study, high Lp(a) level ≥ 50 mg/dL in angina pectoris patients undergoing elective PCI with DESs was significantly associated with binary restenosis and 3-year adverse clinical outcomes in Asian population. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Clinical and Experimental Pharmacology and Physiology 04/2015; 42(6). DOI:10.1111/1440-1681.12396 · 2.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Critical limb ischemia (CLI) is associated with a high risk of cardiovascular ischemic events. We assessed the strategy of routine coronary angiography and subsequent coronary revascularization, if clinically indicated, in patients with CLI who underwent percutaneous transluminal angioplasty (PTA).
Of a total 286 consecutive CLI patients treated by PTA, 252 patients who underwent coronary angiography before or after PTA were enrolled. Coronary artery disease (CAD) was defined as angiographic stenosis ≥50% and significant CAD as ≥70% stenosis.
Of the 252 patients with CLI who underwent coronary angiography, a total of 167 patients (66.3%) had CAD and 85 patients (33.7%) did not have CAD. Patients in the CAD group were older, had a higher prevalence of diabetes and cerebrovascular disease, and had a lower mean ejection fraction. In the CAD group, of the 145 patients with significant CAD, percutaneous coronary intervention (PCI) was performed in 114 patients (78.6%). At 1 year, the CAD and non-CAD groups had no statistically significant differences in mortality (7.1% vs 4.7%; P=.45), myocardial infarction (1.1% vs 0%; P=.31), and PCI (4.7% vs 1.1%; P=.31). These outcomes were similar after the adjustment of baseline confounders. At 1 year, the CAD and non-CAD groups had similar rates of repeat PTA (16.7% vs 17.6%; P=.86), target lesion revascularization (13.7% vs 14.1%; P=.94), and amputation (19.1% vs 16.4%; P=.60).
A strategy of routine coronary angiography and coronary revascularization may be a reasonable treatment option for these patients who have high risk for severe CAD. A randomized trial is needed to determine if this is the preferred strategy for CLI patients.
The Journal of invasive cardiology 04/2015; 27(4):213-7. · 0.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We analyzed the expression levels of fluoropyrimidine-metabolizing enzymes (thymidylate synthase [TS], dihydropyrimidine dehydrogenase [DPD], thymidine phosphorylase [TP] and orotate phosphoribosyltransferase [OPRT]) to identify potential biomarkers related to treatment outcomes in gastric cancer (GC) patients receiving adjuvant S-1 chemotherapy. In this study, 184 patients who received curative gastrectomy (D2 lymph node dissection) and adjuvant S-1 were included. Immunohistochemistry and quantitative reverse transcription polymerase chain reaction were performed to measure the protein and mRNA levels of TS, DPD, TP, and OPRT in tumor tissue. In univariate analysis, low intratumoral DPD protein expression was related to poorer 5-year disease-free survival (DFS; 78% vs. 88%; P = 0.068). Low intratumoral DPD mRNA expression (1st [lowest] quartile) was also related to poorer DFS (69% vs. 90%; P < 0.001) compared to high intratumoral DPD expression (2nd to 4th quartiles). In multivariate analyses, low intratumoral DPD protein or mRNA expression was related to worse DFS (P < 0.05), irrespective of other clinical variables. TS, TP, and OPRT expression levels were not related to treatment outcomes. Severe non-hematologic toxicities (grade ≥ 3) had a trend towards more frequent development in patients with low intratumoral DPD mRNA expression (29% vs. 16%; P = 0.068). In conclusion, GC patients with high intratumoral DPD expression did not have inferior outcome following adjuvant S-1 therapy compared with those with low DPD expression. Instead, low intratumoral DPD expression was related to poor DFS.
PLoS ONE 03/2015; 10(3):e0120324. DOI:10.1371/journal.pone.0120324 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: HM781-36B is a novel and irreversible pan-human epidermal growth factor receptor (HER) inhibitor with TEC cytoplasmic kinase inhibition. The aim of this study is to evaluate the antitumor activity and mechanism of action for HM781-36B in CRC cell lines.
The CRC cell lines were exposed to HM781-36B and/or oxaliplatin (L-OHP), 5-fluorouracil (5-FU), SN-38. The cell viability was examined by Cell Titer-Glo luminescent cell viability assay kit. Change in the cell cycle and protein expression was determined by flow cytometry and immunoblot analysis, respectively. Synergism between 2 drugs was evaluated by the combination index.
The addition of HM781-36B induced potent growth inhibition in both DiFi cells with EGFR overexpression and SNU-175 cells (IC50 = 0.003 and 0.005 M, respectively). Furthermore, HM781-36B induced G1 arrest of the cell cycle and apoptosis, and reduced the levels of HER family and downstream signaling molecules, pERK and pAKT, as well as nonreceptor/cytoplasmic tyrosine kinase, BMX. The combination of HM781-36B with 5-FU, L-OHP, or SN-38 showed an additive or synergistic effect in most CRC cells.
These findings suggest the potential roles of HM781-36B as the treatment for EGFR-overexpressing colon cancer, singly or in combination with chemotherapeutic agents. The role of BMX expression as a marker of response to HM781-36B should be further explored.
Cancer Research and Treatment 03/2015; DOI:10.4143/crt.2014.260 · 2.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Peripheral arterial disease (PAD) is associated with poor outcomes. We assessed the clinical outcomes of diabetic versus non-diabetic patients with PAD who underwent peripheral transluminal angioplasty (PTA).
The outcomes of 239 consecutive patients with symptomatic PAD who underwent PTA were analyzed. Restenosis and clinical outcomes were assessed at a follow-up of 2 years.
Diabetic patients had a higher percentage of wound as the initial diagnosis for PTA (72.7% vs 14.2%; P<.001), chronic kidney disease (26.7% vs 6.3%; P<.01), need for dialysis (19.3% vs 3.1%; P<.01), and coronary artery disease (67.6% vs 50.7%; P=.02). Infrapopliteal PTA was more commonly performed in the diabetic group (70.4% vs 25.3%; P<.001). Diabetic patients had lower rates of angiographic follow-up at 8 months (38.6% vs 60.3%; P<.01). Diabetic patients had higher binary restenosis (54.4% vs 31.5%; P=.02) and had a trend toward a higher incidence of total occlusion (34.0% vs 19.5%; P=.08). At 2-year follow-up, the amputation rate was higher in the diabetic group (24.4% vs 1.5%; P<.001) despite PTA.
Diabetic patients more frequently presented with critical limb ischemia compared with non-diabetic patients and had higher rates of restenosis and amputation at 2 years following standard PTA. Improved therapies are needed for this high-risk group of patients.
The Journal of invasive cardiology 03/2015; 27(3):167-71. · 0.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this study, the structural, electrical and multiferroic properties of Bi6Fe2Ti3O18 and Bi6Fe1.5Co0.5Ti3O18−δ thin films were investigated. A chemical solution deposition method was used to prepare the thin films on Pt(111)/Ti/SiO2/Si(100) substrates. Both of the thin films crystallized with single phase Aurivillius orthorhombic structures were confirmed by means of X-ray diffraction and Raman spectroscopy studies. X-ray diffraction study further revealed Co2+-ion doping to have a significant influence on the orientation of the Bi6Fe2Ti3O18 thin film. Electrical studies revealed that the leakage current density of the Bi6Fe1.5Co0.5Ti3O18−δ thin film was about two orders of magnitude lower than that of the Bi6Fe2Ti3O18 thin film. An enhanced remnant polarization (2Pr) of 7.4 μC/cm2 and a remnant magnetization (2Mr) of 0.97 emu/cm3 was obtained for the Bi6Fe1.5Co0.5Ti3O18−δ thin film by measuring the ferroelectric and ferromagnetic hysteresis loops at room temperature.