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1.  Use of transient elastography to predict de novo recurrence after radiofrequency ablation for hepatocellular carcinoma 
OncoTargets and therapy  2015;8:347-356.
Background/purpose
Liver stiffness (LS) measurement using transient elastography can accurately assess the degree of liver fibrosis, which is associated with the risk of the development of hepatocellular carcinoma (HCC). We investigated whether LS values could predict HCC de novo recurrence after radiofrequency ablation (RFA).
Methods
This retrospective, multicenter study analyzed 111 patients with HCC who underwent RFA and LS measurement using transient elastography between May 2005 and April 2011. All patients were followed until March 2013 to monitor for HCC recurrence.
Results
This study included 76 men and 35 women with a mean age of 62.4 years, and the mean LS value was 21.2 kPa. During the follow-up period (median 22.4 months), 47 (42.3%) patients experienced HCC de novo recurrence, and 18 (16.2%) died. Patients with recurrence had significantly more frequent liver cirrhosis, more frequent history of previous treatment for HCC, higher total bilirubin, larger spleen size, larger total tumor size, higher tumor number, higher LS values, and lower platelet counts than those without recurrence (all P<0.05). On multivariate analysis, together with previous anti-HCC treatment history, patients with LS values >13.0 kPa were at significantly greater risk for recurrence after RFA, with a hazard ratio (HR) of 3.115 (95% confidence interval [CI], 1.238–7.842, P<0.05). Moreover, LS values independently predicted the mortality after RFA, with a HR of 9.834 (95% CI, 1.148–84.211, P<0.05), together with total bilirubin.
Conclusions
Our data suggest that LS measurement is a useful predictor of HCC de novo recurrence and overall survival after RFA.
doi:10.2147/OTT.S75077
PMCID: PMC4322870  PMID: 25678801
hepatocellular carcinoma; radiofrequency ablation; recurrence; liver stiffness; fibroscan
2.  Factors Affecting the Accuracy of Controlled Attenuation Parameter (CAP) in Assessing Hepatic Steatosis in Patients with Chronic Liver Disease 
PLoS ONE  2014;9(6):e98689.
Background & Aims
Controlled attenuation parameter (CAP) can measure hepatic steatosis. However, factors affecting its accuracy have not been described yet. This study investigated predictors of discordance between liver biopsy (LB) and CAP.
Methods
A total of 161 consecutive patients with chronic liver disease who underwent LB and CAP were enrolled prospectively. Histological steatosis was graded as S0 (<5%), S1 (5–33%), S2 (34–66%), and S3 (>66% of hepatocytes). Cutoff CAP values were calculated from our cohort (250, 301, and 325 dB/m for ≥S1, ≥S2, and S3). Discordance was defined as a discrepancy of at least two steatosis stages between LB and CAP.
Results
The median age (102 males and 59 females) was 49 years. Repartition of histological steatosis was as follows; S0 26.1% (n = 42), S1 49.7% (n = 80), S2 20.5% (n = 33), and S3 3.7% (n = 6). In multivariate linear regression analysis, CAP value was independently associated with steatosis grade along with body mass index (BMI) and interquartile range/median of CAP value (IQR/MCAP) (all P<0.05). Discordance was identified in 13 (8.1%) patients. In multivariate analysis, histological S3 (odd ratio [OR], 9.573; 95% confidence interval [CI], 1.207–75.931; P = 0.033) and CAP value (OR, 1.020; 95% CI, 1.006–1.034; P = 0.006) were significantly associated with discordance, when adjusting for BMI, IQR/MCAP, and necroinflammation, reflected by histological activity or ALT level.
Conclusions
Patients with high grade steatosis or high CAP values have a higher risk of discordance between LB and CAP. Further studies are needed to improve the accuracy of CAP interpretation, especially in patients with higher CAP values.
doi:10.1371/journal.pone.0098689
PMCID: PMC4046989  PMID: 24901649
3.  Concise Review: Stem Cell Microenvironment on a Chip: Current Technologies for Tissue Engineering and Stem Cell Biology 
Stem Cells Translational Medicine  2015;4(11):1352-1368.
Stem cells are highly sensitive to a variety of physicochemical cues, and their fate can be easily altered by a slight change of environment. This review introduces diverse microplatforms to provide in vitro stem cell niches. Microplatforms could control microenvironments around cells and have recently attracted much attention in biology including stem cell research. These microplatforms and the future directions of stem cell microenvironment are described.
Stem cells have huge potential in many therapeutic areas. With conventional cell culture methods, however, it is difficult to achieve in vivo-like microenvironments in which a number of well-controlled stimuli are provided for growing highly sensitive stem cells. In contrast, microtechnology-based platforms offer advantages of high precision, controllability, scalability, and reproducibility, enabling imitation of the complex physiological context of in vivo. This capability may fill the gap between the present knowledge about stem cells and that required for clinical stem cell-based therapies. We reviewed the various types of microplatforms on which stem cell microenvironments are mimicked. We have assigned the various microplatforms to four categories based on their practical uses to assist stem cell biologists in using them for research. In particular, many examples are given of microplatforms used for the production of embryoid bodies and aggregates of stem cells in vitro. We also categorized microplatforms based on the types of factors controlling the behaviors of stem cells. Finally, we outline possible future directions for microplatform-based stem cell research, such as research leading to the production of well-defined environments for stem cells to be used in scaled-up systems or organs-on-a-chip, the regulation of induced pluripotent stem cells, and the study of the genetic states of stem cells on microplatforms.
Significance
Stem cells are highly sensitive to a variety of physicochemical cues, and their fate can be easily altered by a slight change of environment; therefore, systematic analysis and discrimination of the extracellular signals and intracellular pathways controlling the fate of cells and experimental realization of sensitive and controllable niche environments are critical. This review introduces diverse microplatforms to provide in vitro stem cell niches. Microplatforms could control microenvironments around cells and have recently attracted much attention in biology including stem cell research. These microplatforms and the future directions of stem cell microenvironment are described.
doi:10.5966/sctm.2015-0095
PMCID: PMC4622410  PMID: 26450425
Stem cell microenvironment; Microplatform; Embryoid body; Stem cell behaviors; Stem cell fate; Organ regeneration
4.  Anticancer activity of TTAC-0001, a fully human anti-vascular endothelial growth factor receptor 2 (VEGFR-2/KDR) monoclonal antibody, is associated with inhibition of tumor angiogenesis 
mAbs  2015;7(6):1195-1204.
Vascular endothelial growth factor (VEGF) and its receptors are considered the primary cause of tumor-induced angiogenesis. Specifically, VEGFR-2/kinase insert domain receptor (KDR) is part of the major signaling pathway that plays a significant role in tumor angiogenesis, which is associated with the development of various types of tumor and metastasis. In particular, KDR is involved in tumor angiogenesis as well as cancer cell growth and survival. In this study, we evaluated the therapeutic potential of TTAC-0001, a fully human antibody against VEGFR-2/KDR. To assess the efficacy of the antibody and pharmacokinetic (PK) relationship in vivo, we tested the potency of TTAC-0001 in glioblastoma and colorectal cancer xenograft models. Antitumor activity of TTAC-0001 in preclinical models correlated with tumor growth arrest, induction of tumor cell apoptosis, and inhibition of angiogenesis. We also evaluated the combination effect of TTAC-0001 with a chemotherapeutic agent in xenograft models. We were able to determine the relationship between PK and the efficacy of TTAC-0001 through in vivo single-dose PK study. Taken together, our data suggest that targeting VEGFR-2 with TTAC-0001 could be a promising approach for cancer treatment.
doi:10.1080/19420862.2015.1086854
PMCID: PMC4966428  PMID: 26325365
TTAC-0001; VEGF signaling; fully human neutralizing antibody, angiogenesis inhibitor; tumor growth inhibition; pharmacokinetics; glioblastoma; colorectal cancer
5.  Prognostic Implications of Serum Lipid Metabolism over Time during Sepsis 
BioMed Research International  2015;2015:789298.
Background. Despite extensive research and an improved standard of care, sepsis remains a disorder with a high mortality rate. Sepsis is accompanied by severe metabolic alterations. Methods. We evaluated 117 patients with sepsis (severe sepsis [n = 19] and septic shock [n = 98]) who were admitted to the intensive care unit. Serum cholesterol, triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), free fatty acid (FFA), and apolipoprotein (Apo) A-I levels were measured on days 0, 1, 3, and 7. Results. Nonsurvivors had low levels of cholesterol, TG, HDL, LDL, and Apo A-I on days 0, 1, 3, and 7. In a linear mixed model analysis, the variations in TG, LDL, FFA, and Apo A-I levels over time differed significantly between the groups (p = 0.043, p = 0.020, p = 0.005, and p = 0.015, resp.). According to multivariate analysis, TG levels and SOFA scores were associated with mortality on days 0 and 1 (p = 0.018 and p = 0.008, resp.). Conclusions. Our study illustrated that TG levels are associated with mortality in patients with sepsis. This may be attributable to alterations in serum lipid metabolism during sepsis, thus modulating the host response to inflammation in critically ill patients.
doi:10.1155/2015/789298
PMCID: PMC4553311  PMID: 26351639
6.  Box-Shape Cervical Expansive Laminoplasty: Clinical and Radiological Outcomes 
Korean Journal of Spine  2014;11(3):152-156.
Objective
Box-shape cervical expansive laminoplasty is a procedure that utilizes a Miniplate® or Maxpacer® to achieve maximal canal expansion. This method is expected to show much larger canal expansion and good clinical outcome. So we investigated the clinical and radiological outcome of Box-shape cervical expansive laminoplasty.
Methods
Between June 2008 and July 2013, we performed cervical expansive laminoplasty in 87 and 48 patients using the Box-shape cervical expansive laminoplasty, respectively. We analyzed the clinical results of these operations using the Japanese Orthopedic Association (JOA) scoring system and by assessing the position of intralaminar screws with postoperative computed tomography (CT) at POD-6 months.
Results
A total of 48 patients with ossification of the posterior longitudinal ligament (OPLL) (36 pts), cervical spondylotic myelopathy (CSM) (12 pts) were enrolled. Overall JOA scores improved from 11.49 to 14.22 at POD-6 months (OPLL: 11.32 -->14.3; CSM: 12-->14). Postoperative CT scans were performed in 39 patients at 177 levels for a total of 354 screws. The malpositioning rate of intralaminar screws was 3.4% and hardware-related neurologic complications did not occur.
Conclusion
Box-shape cervical expansive laminoplasty creates maximal spinal canal expansion and leads to improved cervical myelopathy. The use of intralaminar screws to fix the remodeled lamina-facet does not represent a significant difficulty.
doi:10.14245/kjs.2014.11.3.152
PMCID: PMC4206966  PMID: 25346761
Open door laminoplasty; Double door laminoplasty; Intralaminar screw; Spinal canal area; Box-shape laminoplasty
7.  New Empirical Equation for the Atomic Form Factor Function in the Momentum Transfer Range, q = 0–50 Å−1 for the Elements in the Range 1≤ Z ≤30 
PLoS ONE  2013;8(8):e69608.
The importance of Atomic Form Factors (f) is well-known to the scientific community. Tabulated values for f are mostly used in calculating cross-sections and Monte Carlo sampling for the coherent scattering of photons. The uses of these values are subjected to different approximations and interpolation techniques because the available data points for f in the literature for specified momentum-transfer-grids are very limited. In order to make it easier to accurately use the tabulated data, a mathematical expression for f functions would be a great achievement. Therefore, the current study was designed to suggest an empirical expression for the f functions. In the results, an empirical equation for Hubbell's tabulated data for f is created in the momentum transfer range, q = 0–50 Å−1 for the elements in the range 1≤ Z ≤30. The number of applied parameters was seven. The fitting to f showed that the maximum deviation was within 3%, 4% and 5% for the element having, Z = 1–11, Z = 12–22 and Z = 23–30, respectively, while the average deviations were within 0.3–2.25% for all elements (i.e., Z = 1–30). The values generated by the analytical equation were used in the Monte Carlo code instead of Hubbell’s tabulated values. The statistical noise in the Probability Distribution Functions of coherently scattered photons was efficiently removed. Furthermore, it also reduced the dependence on different interpolation techniques and approximations, and on the use of large tabulated data for f with the specified elements.
doi:10.1371/journal.pone.0069608
PMCID: PMC3731328  PMID: 23936339
8.  Therapeutic Effects of Acupuncture through Enhancement of Functional Angiogenesis and Granulogenesis in Rat Wound Healing 
Acupuncture regulates inflammation process and growth factors by increasing blood circulation in affected areas. In this study, we examined whether acupuncture has an effect on wound healing in injured rat. Rats were assigned randomly into two groups: control group and acupuncture group. Acupuncture treatment was carried out at 8 sites around the wounded area. We analyzed the wound area, inflammatory cytokines, proliferation of resident cells, and angiogenesis and induction of extracelluar matrix remodeling. At 7 days after-wounding the wound size in acupuncture-treat group was decreased more significantly compared to control group. In addition, the protein levels of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were significantly decreased compared to the control at 2 and 7 days post-wounding. Also, we analyzed newly generated cells by performing immunostaining for PCNA and using several phenotype markers such as CD-31, α-SMA, and collagen type I. In acupuncture-treated group, PCNA-positive cell was increased and PCNA labeled CD-31-positive vessels, α-SMA- and collagen type I-positive fibroblastic cells, were increased compared to the control group at 7 days post-wounding. These results suggest that acupuncture may improve wound healing through decreasing pro-inflammatory response, increasing cell proliferation and angiogenesis, and inducing extracellular matrix remodeling.
doi:10.1155/2012/464586
PMCID: PMC3529882  PMID: 23304201
9.  Assessment of Collagen-Induced Arthritis Using Cyanine 5.5 Conjugated with Hydrophobically Modified Glycol Chitosan Nanoparticles: Correlation with 18F-Fluorodeoxyglucose Positron Emission Tomography Data 
Korean Journal of Radiology  2012;13(4):450-457.
Objective
To evaluate the potential and correlation between near-infrared fluorescence (NIRF) imaging using cyanine 5.5 conjugated with hydrophobically modified glycol chitosan nanoparticles (HGC-Cy5.5) and 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) imaging of collagen-induced arthritis (CIA).
Materials and Methods
We used 10 CIA and 3 normal mice. Nine days after the injecting collagen twice, microPET imaging was performed 40 minutes after the intravenous injection of 9.3 MBq 18F-FDG in 200 µL PBS. One day later, NIRF imaging was performed two hours after the intravenous injection of HGC-cy5.5 (5 mg/kg). We assessed the correlation between these two modalities in the knees and ankles of CIA mice.
Results
The mean standardized uptake values of 18F-FDG for knees and ankles were 1.68 ± 0.76 and 0.79 ± 0.71, respectively, for CIA mice; and 0.57 ± 0.17 and 0.54 ± 0.20 respectively for control mice. From the NIRF images, the total photon counts per 30 mm2 for knees and ankles were 2.32 ± 1.54 × 105 and 2.75 ± 1.51 × 105, respectively, for CIA mice, and 1.22 ± 0.27 × 105 and 0.88 ± 0.24 × 105, respectively, for control mice. These two modalities showed a moderate correlation for knees (r = 0.604, p = 0.005) and ankles (r = 0.464, p = 0.039). Moreover, both HGC-Cy5.5 (p = 0.002) and 18F-FDG-PET (p = 0.005) imaging also showed statistically significant differences between CIA and normal mice.
Conclusion
NIRF imaging using HGC-Cy5.5 was moderately correlated with 18F-FDG-PET imaging in the CIA model. As such, HGC-Cy5.5 imaging can be used for the early detection of rheumatoid arthritis.
doi:10.3348/kjr.2012.13.4.450
PMCID: PMC3384827  PMID: 22778567
HGC-Cy5.5; 18F-FDG PET; Near-infrared fluorescence imaging; Rheumatoid arthritis
10.  Effects of Morphological Characteristics of Muscle Fibers on Porcine Growth Performance and Pork Quality 
The aim of this study was to investigate the effects of morphological characteristics of porcine muscle fibers on growth performance, muscle fiber characteristics, and pork quality taken from the longissimus dorsi muscle. A total of 239 crossbred pigs (164 castrated males and 75 females) were used in this study. Experimental pigs were categorized by the total number of muscle fiber (TNF: High and Low) and cross sectional area of muscle fiber (CSAF: Large, Middle, and Small). Their combinations were classified into six groups (High-Large, HL; High-Middle, HM; High-Small, HS; Low-Large, LL; Low-Middle, LM; Low-Small, LS). The TNF and CSAF were significantly (p<0.05) correlated with growth rate and carcass productivity, while the only of the type I number had no meaningful relationships excluding the correlation with loin area (p<0.001). The proportion of type I area was positively correlated with pH45 min while the proportion of type IIB area was negatively correlated with pH45 min and pH24 h (p<0.05). Drip loss and protein denaturation had strong relationships with the proportion of type IIB number or area. The HL group exhibited the greatest growth performance. In addition, the HL group had significantly greater values in protein solubility than the other groups. In conclusion, this study suggest that high TNF combined to large CSAF improve the ultimate lean meat productivity and assure normal meat quality simultaneously with increased both proportion of number and area of type I, type IIA muscle fibers and lowered proportion of number and area of type IIB.
doi:10.5851/kosfa.2016.36.5.583
PMCID: PMC5112420  PMID: 27857533
muscle fiber morphology; total number of muscle fiber; cross sectional area of muscle fiber; growth performance; pork quality
11.  Evaluation of the Chondromalacia Patella Using a Microscopy Coil: Comparison of the Two-Dimensional Fast Spin Echo Techniques and the Three-Dimensional Fast Field Echo Techniques 
Korean Journal of Radiology  2011;12(1):78-88.
Objective
We wanted to compare the two-dimensional (2D) fast spin echo (FSE) techniques and the three-dimensional (3D) fast field echo techniques for the evaluation of the chondromalacia patella using a microscopy coil.
Materials and Methods
Twenty five patients who underwent total knee arthroplasty were included in this study. Preoperative MRI evaluation of the patella was performed using a microscopy coil (47 mm). The proton density-weighted fast spin echo images (PD), the fat-suppressed PD images (FS-PD), the intermediate weighted-fat suppressed fast spin echo images (iw-FS-FSE), the 3D balanced-fast field echo images (B-FFE), the 3D water selective cartilage scan (WATS-c) and the 3D water selective fluid scan (WATS-f) were obtained on a 1.5T MRI scanner. The patellar cartilage was evaluated in nine areas: the superior, middle and the inferior portions that were subdivided into the medial, central and lateral facets in a total of 215 areas. Employing the Noyes grading system, the MRI grade 0-I, II and III lesions were compared using the gross and microscopic findings. The sensitivity, specificity and accuracy were evaluated for each sequence. The significance of the differences for the individual sequences was calculated using the McNemar test.
Results
The gross and microscopic findings demonstrated 167 grade 0-I lesions, 40 grade II lesions and eight grade III lesions. Iw-FS-FSE had the highest accuracy (sensitivity/specificity/accuracy = 88%/98%/96%), followed by FS-PD (78%/98%/93%, respectively), PD (76%/98%/93%, respectively), B-FFE (71%/100%/93%, respectively), WATS-c (67%/100%/92%, respectively) and WATS-f (58%/99%/89%, respectively). There were statistically significant differences for the iw-FS-FSE and WATS-f and for the PD-FS and WATS-f (p < 0.01).
Conclusion
The iw-FS-FSE images obtained with a microscopy coil show best diagnostic performance among the 2D and 3D GRE images for evaluating the chondromalacia patella.
doi:10.3348/kjr.2011.12.1.78
PMCID: PMC3017887  PMID: 21228943
Cartilage; Magnetic resonance (MR); Knee; Histopathologic correlation
12.  Interoperation of an UHF RFID Reader and a TCP/IP Device via Wired and Wireless Links 
Sensors (Basel, Switzerland)  2011;11(11):10664-10674.
A main application in radio frequency identification (RFID) sensor networks is the function that processes real-time tag information after gathering the required data from multiple RFID tags. The component technologies that contain an RFID reader, called the interrogator, which has a tag chip, processors, coupling antenna, and a power management system have advanced significantly over the last decade. This paper presents a system implementation for interoperation between an UHF RFID reader and a TCP/IP device that is used as a gateway. The proposed system consists of an UHF RFID tag, an UHF RFID reader, an RF end-device, an RF coordinator, and a TCP/IP I/F. The UHF RFID reader, operating at 915 MHz, is compatible with EPC Class-0/Gen1, Class-1/Gen1 and 2, and ISO18000-6B. In particular, the UHF RFID reader can be combined with the RF end-device/coordinator for a ZigBee (IEEE 802.15.4) interface, which is a low-power wireless standard. The TCP/IP device communicates with the RFID reader via wired links. On the other hand, it is connected to the ZigBee end-device via wireless links. The web based test results show that the developed system can remotely recognize information of multiple tags through the interoperation between the RFID reader and the TCP/IP device.
doi:10.3390/s111110664
PMCID: PMC3274307  PMID: 22346665
UHF RFID; RFID reader; RFID tag; RF coordinator; ZigBee; interrogator; TCP/IP; UHF antenna
13.  Carcinoma of the middle bile duct: Is bile duct segmental resection appropriate? 
AIM: To compare survival between bile duct segmental resection (BDSR) and pancreaticoduodenectomy (PD) for treating distal bile duct cancers.
METHODS: Retrospective analysis was conducted for 45 patients in a BDSR group and for 149 patients in a PD group.
RESULTS: The T-stage (P < 0.001), lymph node invasion (P = 0.010) and tumor differentiation (P = 0.005) were significant prognostic factors in the BDSR group. The 3- and 5-year overall survival rates for the BDSR group and PD group were 51.7% and 36.6%, respectively and 46.0% and 38.1%, respectively (P = 0.099). The BDSR group and PD group did not show any significant difference in survival when this was adjusted for the TNM stage. The 3- and 5-year survival rates were: stage Ia [BDSR (100.0% and 100.0%) vs PD (76.9% and 68.4%) (P = 0.226)]; stage Ib [BDSR (55.8% and 32.6%) vs PD (59.3% and 59.3%) (P = 0.942)]; stage IIb [BDSR (19.2% and 19.2%) vs PD (31.9% and 14.2%) (P = 0.669)].
CONCLUSION: BDSR can be justified as an alternative radical operation for patients with middle bile duct in selected patients with no adjacent organ invasion and resection margin is negative.
doi:10.3748/wjg.15.5966
PMCID: PMC2795184  PMID: 20014461
Bile duct cancer; Segmental resection; Pancreaticoduodenectomy
14.  Predicting survival of patients with idiopathic pulmonary fibrosis using GAP score: a nationwide cohort study 
Respiratory Research  2016;17:131.
Background
The clinical course of idiopathic pulmonary fibrosis (IPF) varies widely. Although the GAP model is useful for predicting mortality, survivals have not yet been validated for each GAP score. We aimed to elucidate how prognosis is related to GAP score and GAP stage in IPF patients.
Methods
The Korean Interstitial Lung Disease Study Group conducted a national survey to evaluate various characteristics in IPF patients from 2003 to 2007. Patients were diagnosed according to the 2002 criteria of the ATS/ERS. We enrolled 1,685 patients with IPF; 1,262 had undergone DLCO measurement. Patients were stratified based on GAP score (0–7): GAP score Group 0 (n = 26), Group 1 (n = 150), Group 2 (n = 208), Group 3 (n = 376), Group 4 (n = 317), Group 5 (n = 138), Group 6 (n = 39), and Group 7 (n = 8).
Results
Higher GAP score and GAP stage were associated with a poorer prognosis (p < 0.001, respectively). Survival time in Group 3 was lower than those in Groups 1 and 2 (p = 0.043 and p = 0.039, respectively), and higher than those in groups 4, 5, and 6 (p = 0.043, p = 0.032, and p = 0.003, respectively). Gender, age, and DLCO (%) differed significantly between Groups 2 and 3. All four variables in the GAP model differed significantly between Groups 3 and 4.
Conclusion
The GAP system showed significant predictive ability for mortality in IPF patients. However, prognosis in IPF patients with a GAP score of 3 were significantly different from those in the other stage I groups and stage II groups of Asian patients.
Electronic supplementary material
The online version of this article (doi:10.1186/s12931-016-0454-0) contains supplementary material, which is available to authorized users.
doi:10.1186/s12931-016-0454-0
PMCID: PMC5069824  PMID: 27756398
Idiopathic pulmonary fibrosis; GAP stage; Prognosis
15.  Evaluation of Tumor Angiogenesis with a Second-Generation US Contrast Medium in a Rat Breast Tumor Model 
Korean Journal of Radiology  2008;9(3):243-249.
Objective
Tumor angiogenesis is an important factor for tumor growth, treatment response and prognosis. Noninvasive imaging methods for the evaluation of tumor angiogenesis have been studied, but a method for the quantification of tumor angiogenesis has not been established. This study was designed to evaluate tumor angiogenesis in a rat breast tumor model by the use of a contrast-enhanced ultrasound (US) examination with a second-generation US contrast agent.
Materials and Methods
The alkylating agent 19N-ethyl-N-nitrosourea (ENU) was injected into the intraperitoneal cavity of 30-day-old female Sprague-Dawley rats. Three to four months later, breast tumors were detected along the mammary lines of the rats. A total of 17 breast tumors larger than 1 cm in nine rats were evaluated by gray-scale US, color Doppler US and contrast-enhanced US using SonoVue. The results were recorded as digital video images; time-intensity curves and hemodynamic parameters were analyzed. Pathological breast tumor specimens were obtained just after the US examinations. The tumor specimens were stained with hematoxylin and eosin (H & E) and the expression of CD31, an endothelial cell marker, was determined by immunohistochemical staining. We also evaluated the pathological diagnosis of the tumors and the microvessel density (MVD). Spearman's correlation and the Kruskal-Wallis test were used for the analysis.
Results
The pathological diagnoses were 11 invasive ductal carcinomas and six benign intraductal epithelial proliferations. The MVD did not correlate with the pathological diagnosis. However, blood volume (BV) showed a statistically significant correlation with MVD (Spearman's correlation, p < 0.05).
Conclusion
Contrast-enhanced US using a second-generation US contrast material was useful for the evaluation of tumor angiogenesis of breast tumors in the rat.
doi:10.3348/kjr.2008.9.3.243
PMCID: PMC2627259  PMID: 18525227
Breast neoplasms; Breast, US; Contrast media; Experimental study
16.  Spinal Epidural Abscess with Pyogenic Arthritis of Facet Joint Treated with Antibiotic-Bone Cement Beads - A Case Report - 
Asian Spine Journal  2007;1(1):61-64.
Most epidural abscesses are a secondary lesion of pyogenic spondylodiscitis. An epidural abscess associated with pyogenic arthritis of the facet joint is quite rare. To the best of our knowledge, there is no report of the use of antibiotic-cement beads in the surgical treatment of an epidural abscess. This paper reports a 63-year-old male who sustained a 1-week history of radiating pain to both lower extremities combined with lower back pain. MRI revealed space-occupying lesions, which were located in both sides of the anterior epidural space of L4, and CT scans showed irregular widening and bony erosion of the facet joints of L4-5. A staphylococcal infection was identified after a posterior decompression and an open drainage. Antibiotic- bone cement beads were used as a local controller of the infection and as a spacer or an indicator for the second operation. An intravenous injection of anti-staphylococcal antibiotics resolved the back pain and radicular pain and normalized the laboratory findings. We point out not only the association of an epidural abscess with facet joint infection, but also the possible indication of antibiotic-bone cement beads in the treatment of epidural abscesses.
doi:10.4184/asj.2007.1.1.61
PMCID: PMC2857502  PMID: 20411156
Epidural abscess; Facet joint infection; Lumbar spine; Antibiotic-bone cement bead
17.  DAMGO modulates two-pore domain K+ channels in the substantia gelatinosa neurons of rat spinal cord 
The analgesic mechanism of opioids is known to decrease the excitability of substantia gelatinosa (SG) neurons receiving the synaptic inputs from primary nociceptive afferent fiber by increasing inwardly rectifying K+ current. In this study, we examined whether a µ-opioid agonist, [D-Ala2,N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO), affects the two-pore domain K+ channel (K2P) current in rat SG neurons using a slice whole-cell patch clamp technique. Also we confirmed which subtypes of K2P channels were associated with DAMGO-induced currents, measuring the expression of K2P channel in whole spinal cord and SG region. DAMGO caused a robust hyperpolarization and outward current in the SG neurons, which developed almost instantaneously and did not show any time-dependent inactivation. Half of the SG neurons exhibited a linear I~V relationship of the DAMGO-induced current, whereas rest of the neurons displayed inward rectification. In SG neurons with a linear I~V relationship of DAMGO-induced current, the reversal potential was close to the K+ equilibrium potentials. The mRNA expression of TWIK (tandem of pore domains in a weak inwardly rectifying K+ channel) related acid-sensitive K+ channel (TASK) 1 and 3 was found in the SG region and a low pH (6.4) significantly blocked the DAMGO-induced K+ current. Taken together, the DAMGO-induced hyperpolarization at resting membrane potential and subsequent decrease in excitability of SG neurons can be carried by the two-pore domain K+ channel (TASK1 and 3) in addition to inwardly rectifying K+ channel.
doi:10.4196/kjpp.2016.20.5.525
PMCID: PMC5014999  PMID: 27610039
DAMGO; K+ current; Opioid; SG neuron; TASK
18.  Relationship between pulmonary function and bone mineral density in the Korean National Health and Nutrition Examination Survey 
Background/Aims:
Osteoporosis is common in chronic obstructive pulmonary disease (COPD) patients. The relationship between osteoporosis and COPD has been primarily reported in patients with moderate to severe COPD, but there is no report in the general population. The aim of this study is to investigate the relationship between bone mineral density (BMD) and lung function in the general Korean population.
Methods:
This study was based on data acquired from the Fourth and Fifth Korea National Health and Nutrition Examination Surveys (KNHANES IV and V), conducted from 2008 to 2010. The study population included 4,501 subjects (aged ≥ 50 years) who underwent both spirometry and BMD. The study populations were divided into two groups by sex to correct for the effects of gender on BMD. All female participants were postmenopausal women.
Results:
The BMD values of the femur neck, total femur, and L-spine tended to decrease with degree of airflow limitation in both genders. To correct confounding factors, data were analyzed and adjusted for age, body mass index, fat free mass index, body fat percentage, smoking amount, parathyroid hormone levels, daily calcium and phosphorus intake, and alkaline phosphatase (ALP) levels. While the BMD of the femur neck, total femur, and L-spine was reduced significantly as age and ALP increased, the correlation between airway obstruction and BMD of all regions disappeared in both genders.
Conclusions:
In the general population aged 50 years and older, diminution of BMD is not associated with airway obstruction. Further investigation along other factors is needed to determine the possible role of pulmonary function and BMD.
doi:10.3904/kjim.2015.127
PMCID: PMC5016283  PMID: 27604798
Respiratory function tests; Bone density; Osteoporosis
19.  D-Dimer Levels Predict Myocardial Injury in ST-Segment Elevation Myocardial Infarction: A Cardiac Magnetic Resonance Imaging Study 
PLoS ONE  2016;11(8):e0160955.
Objectives
Elevated D-dimer levels on admission predict prognosis in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI), but the association of D-dimer levels with structural markers of myocardial injury in these patients is unknown.
Methods
We performed cardiac magnetic resonance (CMR) imaging in 208 patients treated with primary PCI for STEMI. CMR was performed a median of 3 days after the index procedure. Of the 208 patients studied, 75 patients had D-dimer levels above the normal range on admission (>0.5 μg/mL; high D-dimer group) while 133 had normal levels (≤0.5 μg/mL; low D-dimer group). The primary outcome was myocardial infarct size assessed by CMR. Secondary outcomes included area at risk (AAR), microvascular obstruction (MVO) area, and myocardial salvage index (MSI).
Results
In CMR analysis, myocardial infarct size was larger in the high D-dimer group than in the low D-dimer group (22.3% [16.2–30.5] versus 18.8% [10.7–26.7]; p = 0.02). Compared to the low D-dimer group, the high D-dimer group also had a larger AAR (38.1% [31.7–46.9] versus 35.8% [24.2–45.3]; p = 0.04) and a smaller MSI (37.7 [28.2–46.9] versus 47.1 [33.2–57.0]; p = 0.01). In multivariate analysis, high D-dimer levels were significantly associated with larger myocardial infarct (OR 2.59; 95% CI 1.37–4.87; p<0.01) and lower MSI (OR 2.62; 95% CI 1.44–4.78; p<0.01).
Conclusions
In STEMI patients undergoing primary PCI, high D-dimer levels on admission were associated with a larger myocardial infarct size, a greater extent of AAR, and lower MSI, as assessed by CMR data. Elevated initial D-dimer level may be a marker of advanced myocardial injury in patients treated with primary PCI for STEMI.
doi:10.1371/journal.pone.0160955
PMCID: PMC4981325  PMID: 27513758
20.  Gene expression profile comparison in the penile tissue of diabetes and cavernous nerve injury-induced erectile dysfunction rat model 
Purpose
To investigate the effects of cavernous nerve injury (CNI) on gene expression profiles in the cavernosal tissue of a CNI-induced erectile dysfunction (ED) model and to provide a basis for future investigations to discover potential target genes for ED treatment.
Materials and Methods
Young adult rats were divided randomly into 2 groups: sham operation and bilateral CN resection. At 12 weeks after CNI we measured erectile responses and performed microarray experiments and gene set enrichment analysis to reveal gene signatures that were enriched in the CNI-induced ED model. Alterations in gene signatures were compared with those in the diabetes-induced ED model. The diabetic-induced ED data is taken from GSE2457.
Results
The mean ratio of intracavernosal pressure/blood pressure for the CNI group (0.54±0.4 cmH2O) was significantly lower than that in the sham operation group (0.73±0.8 cmH2O, p<0.05). Supervised and unsupervised clustering analysis showed that the diabetes- and CNI-induced ED cavernous tissues had different gene expression profiles from normal cavernous tissues. We identified 46 genes that were upregulated and 77 genes that were downregulated in both the CNI- and diabetes-induced ED models.
Conclusions
Our genome-wide and computational studies provide the groundwork for understanding complex mechanisms and molecular signature changes in ED.
doi:10.4111/icu.2016.57.4.286
PMCID: PMC4949699  PMID: 27437539
Erectile dysfunction; Gene expression; Microarray analysis; Peripheral nerve injuries
21.  First-Generation Versus Second-Generation Drug-Eluting Stents in Coronary Chronic Total Occlusions: Two-Year Results of a Multicenter Registry 
PLoS ONE  2016;11(6):e0157549.
Background
Limited data are available regarding the long-term clinical outcomes of second-generation drug-eluting stents (DES) versus first-generation DES in patients with coronary chronic total occlusion (CTO) who undergo percutaneous coronary intervention (PCI). The aim of this study was to compare the clinical outcomes of second-generation DES with those of first-generation DES for the treatment of CTO.
Methods and Results
Between March 2003 and February 2012, 1,006 consecutive patients with CTO who underwent successful PCI using either first-generation DES (n = 557) or second-generation DES (n = 449) were enrolled in a multicenter, observational registry. Propensity-score matching was also performed. The primary outcome was cardiac death over a 2-year follow-up period. No significant differences were observed between the two groups regarding the incidence of cardiac death (first-generation DES versus second-generation DES; 2.5% vs 2.0%; hazard ratio [HR]: 0.86; 95% confidence interval [CI]: 0.37 to 1.98; p = 0.72) or major adverse cardiac events (MACE, 11.8% vs 11.4%; HR: 1.00; 95% CI: 0.67 to 1.50; p = 0.99). After propensity score matching, the incidences of cardiac death (HR: 0.86; 95% CI: 0.35 to 2.06; p = 0.86) and MACE (HR: 0.93; 95% CI: 0.63 to 1.37; p = 0.71) were still similar in both groups. Furthermore, no significant differences were observed between sirolimus-eluting, paclitaxel-eluting, zotarolimus-eluting, and everolimus-eluting stents regarding the incidence of cardiac death or MACE.
Conclusion
This study shows that the efficacy of second-generation DES is comparable to that of first-generation DES for treatment of CTO over 2 years of follow-up.
doi:10.1371/journal.pone.0157549
PMCID: PMC4912116  PMID: 27314589
22.  Antioxidant Contents and Antioxidant Activities of White and Colored Potatoes (Solanum tuberosum L.) 
This study was performed to evaluate and compare the antioxidant substance content and antioxidant activities of white (Superior) and colored (Hongyoung, Jayoung, Jasim, Seohong, and Jaseo) potatoes. The potatoes were extracted with 80% ethanol and were evaluated for the total polyphenol, flavonoid, and anthocyanin contents and for 1,1-diphenyl- 2-picrylhydrazyl (DPPH)/2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical scavenging activity, reducing power, and ferrous metal ion chelating effect. The total polyphenol, flavonoid, and anthocyanin contents of Hongyoung and Jayoung were higher than white and other colored potatoes. All colored potato extracts, except for Jaseo and Seohong, showed higher ABTS radical scavenging activities than the general white potato extract. Hongyoung and Jayoung had the highest ABTS and DPPH radical scavenging activities. Optical density values for the reducing power of Jayoung and Jaseo at concentration of 2 mg/mL were 0.148 and 0.090, respectively. All colored potato extracts had lower ferrous metal ion chelating effect than the white potato. A significant (P<0.05) positive correlation was observed between total polyphenol content and total flavonoid content (r=0.919), anthocyanin content (r=0.992), and ABTS radical scavenging activity (r=0.897). Based on these results, this research may be useful in developing the Hongyoung and Jayoung cultivars with high antioxidant activities.
doi:10.3746/pnf.2016.21.2.110
PMCID: PMC4935237  PMID: 27390727
colored potato; polyphenol; flavonoid; anthocyanin; antioxidant activities
23.  Statin Use and Its Impact on Survival in Pancreatic Cancer Patients 
Medicine  2016;95(19):e3607.
Supplemental Digital Content is available in the text
Abstract
Statins are cholesterol-lowering medications that are associated with a number of signaling pathways involved in carcinogenesis. Recent observational studies raised the possibility that the use of statins may reduce overall mortality in various types of cancer. We investigated whether statins used after pancreatic cancer diagnosis are associated with longer survival in pancreatic cancer patients.
We retrospectively analyzed data from 1761 patients newly diagnosed with pancreatic adenocarcinoma between January 1, 2006, and December 31, 2014. We used the time-dependent Cox proportional hazards regression model to estimate mortality among pancreatic cancer patients according to statin use.
Among the 1761 pancreatic cancer patients, 118 patients had used statins. During the study period, 1176 patients (66.7%) died. After adjusting for age, sex, location of cancer, cancer stage, diabetes mellitus, hypertension, dyslipidemia, smoking, alcohol use, body mass index, and CA 19-9, statin use was associated with a lower risk of cancer death (hazard ratio [HR], 0.780; 95% confidence interval [CI], 0.617–0.986), especially among simvastatin users (HR, 0.554; 95% CI, 0.312–0.982) and atorvastatin users (HR, 0.636; 95% CI, 0.437–0.927). Subgroup analysis showed that overall survival was statistically significantly longer in patients with nonmetastatic pancreatic cancer (log-rank P = 0.024).
We found that the use of simvastatin and atorvastatin after cancer diagnosis is associated with longer survival in patients with nonmetastatic pancreatic adenocarcinoma.
doi:10.1097/MD.0000000000003607
PMCID: PMC4902509  PMID: 27175667
24.  Viscoelastic lithography for fabricating self-organizing soft micro-honeycomb structures with ultra-high aspect ratios 
Nature Communications  2016;7:11269.
High-aspect ratio micro- and nano-structures have been used for the production of a variety of applications. In this paper, we describe a simple and cost-effective approach to fabricate an arrayed microarchitecture with an ultra-high aspect ratio using soft materials. The shapes and sizes of the honeycomb structure can be easily modulated by changing the dimensions and position of the base mould pattern and the pressure. The honeycomb structure is used to prepare a drug delivery patch and a microwell array to form cell spheroids without cell loss. The honeycomb structures prepared using natural ECM (collagen–Matrigel) materials are successfully fabricated. The hepatocytes and endothelial cells are seeded and co-cultured in the ECM-based micro-honeycomb to prepare a 3D liver model successfully mimicking an ultrastructure of liver and providing enhanced liver function.
Tissue engineering applications call for controllable micro-structural units as a platform, but their fabrication remains challenging. Here, Jeong et al. show a method that enables soft materials to self-organize into highly packed micro-honeycomb structures with aspect ratios up to 500, and tunable shapes.
doi:10.1038/ncomms11269
PMCID: PMC4865738  PMID: 27157977
25.  TTAC-0001, a human monoclonal antibody targeting VEGFR-2/KDR, blocks tumor angiogenesis 
mAbs  2015;7(5):957-968.
Angiogenesis is one of the most important processes for cancer cell survival, tumor growth and metastasis. Vascular endothelial growth factor (VEGF) and its receptor, particularly VEGF receptor-2 (VEGFR-2, or kinase insert domain-containing receptor, KDR), play critical roles in tumor-associated angiogenesis. We developed TTAC-0001, a human monoclonal antibody against VEGFR-2/KDR from a fully human naïve single-chain variable fragment phage library. TTAC-0001 was selected as a lead candidate based on its affinity, ligand binding inhibition and inhibition of VEGFR-2 signal in human umbilical vein endothelial cells (HUVEC). TTAC-0001 inhibited binding of VEGF-C and VEGF-D to VEGFR-2 in addition to VEGF-A. It binds on the N-terminal regions of domain 2 and domain 3 of VEGFR-2. It could inhibit the phosphorylation of VEGFR-2/KDR and ERK induced by VEGF in HUVEC. TTAC-0001 also inhibited VEGF-mediated endothelial cell proliferation, migration and tube formation in vitro, as well as ex vivo vessel sprouting from rat aortic rings and neovascularization in mouse matrigel model in vivo. Our data indicates that TTAC-0001 blocks the binding of VEGFs to VEGFR-2/KDR and inhibits VEGFR-induced signaling pathways and angiogenesis. Therefore, these data strongly support the further development of TTAC-0001 as an anti-cancer agent in the clinic.
doi:10.1080/19420862.2015.1045168
PMCID: PMC4622656  PMID: 25942475
angiogenesis; cross species reactivity; anti-VEGFR2 monoclonal antibody; TTAC-0001; VEGF; VEGFR-2(KDR)

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