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1.  Stealth nanotubes: strategies of shielding carbon nanotubes to evade opsonization and improve biodistribution 
International Journal of Nanomedicine  2014;9(Suppl 1):85-105.
Carbon nanotubes (CNTs) have recently been in the limelight for their potential role in disease diagnostics and therapeutics, as well as in tissue engineering. Before these medical applications can be realized, there is a need to address issues like opsonization, phagocytosis by macrophages, and sequestration to the liver and spleen for eventual elimination from the body; along with equally important issues such as aqueous solubility, dispersion, biocompatibility, and biofunctionalization. CNTs have not been shown to be able to evade such biological obstacles, which include their nonspecific attachments to cells and other biological components in the bloodstream, before reaching target tissues and cells in vivo. This will eventually determine their longevity in circulation and clearance rate from the body. This review article discusses the current status, challenges, practical strategies, and implementations of coating CNTs with biocompatible and opsonin-resistant moieties, rendering CNTs transparent to opsonins and deceiving the innate immune response to make believe that the CNTs are not foreign. A holistic approach to the development of such “stealth” CNTs is presented, which encompasses not only several biophysicochemical factors that are not limited to surface treatment of CNTs, but also extraneous biological factors such as the protein corona formation that inevitably controls the in vivo fate of the particles. This review also discusses the present and potential applications, along with the future directions, of CNTs and their hybrid-based nanotheranostic agents for multiplex, multimodal molecular imaging and therapy, as well as in other applications, such as drug delivery and tissue engineering.
PMCID: PMC4024978  PMID: 24872705
opsonins; macrophage; in vivo biocompatibility; near-infrared contrast nanoagents; nanotheranostics; nanomedicine
2.  A comparison of dimensional standard of several nickel-titanium rotary files 
The aim of this study was to compare the dimensional standard of several nickel-titanium (Ni-Ti) rotary files and verify the size conformity.
Materials and Methods
ProFile (Dentsply Maillefer), RaCe (FKG Dentaire), and TF file (SybronEndo) #25 with a 0.04 and 0.06 taper were investigated, with 10 in each group for a total of 60 files. Digital images of Ni-Ti files were captured under light microscope (SZX16, Olympus) at 32×. Taper and diameter at D1 to D16 of each files were calculated digitally with AnalySIS TS Materials (OLYMPUS Soft Imaging Solutions). Differences in taper, the diameter of each level (D1 to D16) at 1 mm interval from (ANSI/ADA) specification No. 101 were statistically analyzed using one-way ANOVA and Scheffe's post-hoc test at 95% confidence level.
TF was the only group not conform to the nominal taper in both tapers (p < 0.05). All groups except 0.06 taper ProFile showed significant difference from the nominal diameter (p < 0.05).
Actual size of Ni-Ti file, especially TF, was different from the manufacturer's statements.
PMCID: PMC3916510  PMID: 24516823
Diameter; Ni-Ti rotary files; Size verification; Taper; TF
3.  Accuracy of Root ZX in teeth with simulated root perforation in the presence of gel or liquid type endodontic irrigant 
To evaluate the accuracy of the Root ZX in teeth with simulated root perforation in the presence of gel or liquid type endodontic irrigants, such as saline, 5.25% sodium hypochlorite (NaOCl), 2% chlorhexidine liquid, 2% chlorhexidine gel, and RC-Prep, and also to determine the electrical conductivities of these endodontic irrigants.
Materials and Methods
A root perforation was simulated on twenty freshly extracted teeth by means of a small perforation made on the proximal surface of the root at 4 mm from the anatomic apex. Root ZX was used to locate root perforation and measure the electronic working lengths. The results obtained were compared with the actual working length (AWL) and the actual location of perforations (AP), allowing tolerances of 0.5 or 1.0 mm. Measurements within these limits were considered as acceptable. Chi-square test or the Fisher's exact test was used to evaluate significance. Electrical conductivities of each irrigant were also measured with an electrical conductivity tester.
The accuracies of the Root ZX in perforated teeth were significantly different between liquid types (saline, NaOCl) and gel types (chlorhexidine gel, RC-Prep). The accuracies of electronic working lengths in perforated teeth were higher in gel types than in liquid types. The accuracy in locating root perforation was higher in liquid types than gel types. 5.25% NaOCl had the highest electrical conductivity, whereas 2% chlorhexidine gel and RC-Prep gel had the lowest electrical conductivities among the five irrigants.
Different canal irrigants with different electrical conductivities may affect the accuracy of the Root ZX in perforated teeth.
PMCID: PMC3569399  PMID: 23431125
Electrical conductivity; Root canal irrigants; Root perforation; Root ZX
4.  Development and Application of Quantitative Detection Method for Viral Hemorrhagic Septicemia Virus (VHSV) Genogroup IVa 
Viruses  2014;6(5):2204-2213.
Viral hemorrhagic septicemia virus (VHSV) is a problematic pathogen in olive flounder (Paralichthys olivaceus) aquaculture farms in Korea. Thus, it is necessary to develop a rapid and accurate diagnostic method to detect this virus. We developed a quantitative RT-PCR (qRT-PCR) method based on the nucleocapsid (N) gene sequence of Korean VHSV isolate (Genogroup IVa). The slope and R2 values of the primer set developed in this study were −0.2928 (96% efficiency) and 0.9979, respectively. Its comparison with viral infectivity calculated by traditional quantifying method (TCID50) showed a similar pattern of kinetic changes in vitro and in vivo. The qRT-PCR method reduced detection time compared to that of TCID50, making it a very useful tool for VHSV diagnosis.
PMCID: PMC4036551  PMID: 24859343
viral hemorrhagic septicemia virus (VHSV); quantitative detection; real-time PCR; diagnostic; olive flounder
5.  Conditional Deletion of Pten Leads to Defects in Nerve Innervation and Neuronal Survival in Inner Ear Development 
PLoS ONE  2013;8(2):e55609.
All cellular phenomena and developmental events, including inner ear development, are modulated through harmonized signaling networks. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a tumor suppressor, is a major signaling component involved in cross talk with key regulators of development; i.e., Wnt, Notch, and bone morphogenetic proteins. Although Pten function has been studied in various systems, its role in inner ear development is poorly understood. Here, we used inner ear-specific Pten conditional knockout mice and examined the characteristics of the inner ear. In a detailed analysis of the phenotype, reduced cochlear turning and widened epithelia were observed. Phalloidin staining of sensory epithelium revealed that hair cell patterns were disturbed; i.e., additional rows of hair cells were discovered. The neural abnormality revealed a reduction in and disorganization of nerve fibers, including apoptosis at the neural precursor stage. Pten deficiency induced increased phosphorylation of Akt at Ser473. The elevation of inhibitory glycogen synthase kinase 3β Ser9 phosphorylation (pGSK3β) was sustained until the neuronal differentiation stage at embryonic day 14.5, instead of pGSK3β downregulation. This is the first report on the influence of Pten/Akt/GSK3β signaling on the development of spiral ganglia. These results suggest that Pten is required for the maintenance of neuroblast number, neural precursors, and differentiation in the inner ear.
PMCID: PMC3564925  PMID: 23393595
6.  Nanotheranostics of Circulating Tumor Cells, Infections and Other Pathological Features In Vivo 
Molecular pharmaceutics  2013;10(3):813-830.
Many life-threatening diseases are disseminated through biological fluids, such as blood, lymph and cerebrospinal fluid. The migration of tumor cells through the vascular circulation is a mandatory step in metastasis, which is responsible for ∼90% of cancer-associated mortality. Circulating pathogenic bacteria, viruses, or blood clots lead to other serious conditions including bacteremia, sepsis, viremia and infarction. Therefore, technologies capable of detecting circulating tumor cells (CTCs), circulating bacterial cells (CBCs), circulating endothelial cells (CECs), cancer biomarkers such as microparticles and exosomes, which contain important microRNA signatures, and other abnormal features in biological fluids may facilitate early diagnosis and treatment of metastatic cancers, infections and adverse cardiovascular events. Unfortunately, even in a disease setting, circulating abnormal cells are rare events that are easily obscured by the overwhelming background material in whole blood. Existing detection methods mostly rely on ex vivo analyses of limited volumes (a few mL) of whole blood. These small volumes limit the probability of detecting CTCs, CECs, CBCs and other rare phenomena. In vivo detection platforms capable of continuously monitoring the entire circulation may substantially increase the probability of detecting circulating abnormal cells and, in particular, increase the opportunity to identify exceedingly rare and potentially dangerous subsets of these cells, such as circulating cancer stem cells (CCSCs). In addition, in vivo detection technologies capable of destroying and/or capturing circulating abnormal cells may inhibit disease progression. This article reviews novel therapeutic and diagnostic (theranostic) platforms integrating in vivo realtime early diagnosis of CTCs, CECs, CBCs and other abnormal objects in circulation. This critical review particularly focuses on nanotechnology-based theranostic (nanotheranostic) approaches, especially in vivo photoacoustic (PA) and photothermal (PT) nanotheranostic platforms. We emphasize an urgent need for in vivo platforms comprised of multifunctional contrast nanoagents, which utilize diverse modalities to realize a breakthrough for early detection and treatment of harmful diseases disseminated through the circulation.
PMCID: PMC3752784  PMID: 23379366
Metastasis; circulating tumor cells (CTCs); circulating endothelial cells (CECs); circulating cancer stem cells (CCSCs); circulating microparticles and exosomes; circulating pathogens and viruses; blood clots; blood and lymph flow; contrast nanoagents; positive and negative photoacoustic contrasts; microbubbles; multimodal; multicolor; nanotechnology; multifunctional real-time nanotheranostics; nanomedicine
7.  Chronic maxillary sinusitis caused by root canal overfilling of Calcipex II 
This is a case report of chronic maxillary sinusitis caused by root canal overfilling of Calcipex II (Techno-Dent). A 60 year-old male complained of dull pain in the right maxillary molar area after complicated endodontic treatment using Calcipex II paste and was finally diagnosed with a chronic maxillary sinusitis through a clinical and radiological observation. In the biopsy examination, the periapical granuloma contained a lot of dark and translucent Calcipex II granules which were not stained with hematoxylin and eosin. They were usually engulfed by macrophages but rarely resorbed, resulting in scattering and migrating into antral mucosa. Most of the Calcipex II granules were also accumulated in the cytoplasms of secretory columnar epithelial cells, and small amount of Calcipex II granules were gradually secreted into sinus lumen by exocytosis. However, chronic granulomatous inflammation occurred without the additional recruitment of polymorphonuclear leukocytes (PMNs) and lymphocytes, and many macrophages which engulfed the Calcipex II granules were finally destroyed in the processes of cellular apoptosis. It is presumed that Calcipex II granules are likely to have a causative role to induce the granulomatous foreign body inflammation in the periapical region, and subsequently to exacerbate the chronic maxillary sinusitis in this study.
PMCID: PMC3916508  PMID: 24516832
Calcipex II; Foreign body granuloma; Maxillary sinusitis
8.  A Cathepsin B Inhibitor, E-64, Improves the Preimplantation Development of Bovine Somatic Cell Nuclear Transfer Embryos 
Bovine somatic cell nuclear transfer (SCNT) is an important and powerful tool for basic research and biomedical and agricultural applications, however, the efficiency of SCNT has remained extremely low. In this study, we investigated the effects of cathepsin B inhibitor (E-64) supplementation of culture medium on in vitro development of bovine SCNT embryos. We initially used three concentrations of E-64 (0.1, 0.5, 1.0 μm), among which 0.5 μm resulted in the highest rate of blastocysts production after in vitro fertilization (IVF), and was therefore used for further experiments. Blastocyst development of SCNT embryos in the E-64 treatment group also increased relative to the control. Moreover, the cryosurvival rates of IVF and SCNT blastocysts were increased in E-64 treatment groups when compared with the control. On the other hand, we found that IVF and SCNT blastocysts derived from E-64-treated groups had increased total cell numbers and decreased apoptotic nuclei. Furthermore, assessment of the expression of apoptosis-related genes (Bax and Bcl-xL) in bovine IVF and SCNT blastocysts treated with E-64 by real-time RT-PCR analysis revealed suppressed expression of the pro-apoptotic gene Bax and stimulated expression of the anti-apoptotic gene Bcl-xL. Taken together, these finding indicate that addition of E-64 to embryo culture medium may have important implications for improving developmental competence and preimplantation quality in bovine IVF and SCNT embryos.
PMCID: PMC3963301  PMID: 24240170
Apoptosis; Blastocysts; Bovine; Cathepsin B inhibitor (E-64); Somatic cell nuclear transfer (SCNT)
9.  Effect of Korean red ginseng on cold hypersensitivity in the hands and feet: study protocol for a randomized controlled trial 
Trials  2013;14:438.
Cold hypersensitivity in the hands and feet (CHHF) is one of the most common complaints among Asians, especially in women. Korean red ginseng (KRG), which is a steamed form of Panax ginseng, has vasodilating action in the peripheral vessels and increases blood flow under cold stress. However, few studies have evaluated the effect of KRG on cold hypersensitivity.
This trial is a randomized, double-blind, placebo-controlled trial in 80 CHHF patients. The trial will be implemented at Kyung Hee University Hospital at Gangdong in Seoul, Korea. The participants will take KRG or a placebo for eight weeks, after which they will be followed-up for four weeks. During the administration period, six capsules of 500 mg KRG or placebo will be provided twice a day. The primary outcome is change of skin temperature in the hands between baseline and after treatment. The secondary outcomes include the visual analogue scale scores of cold hypersensitivity in the hands, change of skin temperature and the VAS scores of cold hypersensitivity in the feet, the recovery rate of the skin temperature by the cold stress test of the hands, the distal-dorsal difference of the hands, power variables of heart rate variability, and the 36-item short form health survey.
This study is the first trial to evaluate the efficacy of KRG on CHHF by using infrared thermography. Our study will provide basic evidence regarding CHHF.
Trial registration NCT01664156
PMCID: PMC3878242  PMID: 24354675
Cold hypersensitivity in the hands and feet; Korean red ginseng; Infrared thermography; Cold stress test; Distal-dorsal difference
10.  Pleural Fluid Pentraxin-3 for the Differential Diagnosis of Pleural Effusions 
Conventional biomarkers cannot always establish the cause of pleural effusions; thus, alternative tests permitting rapid and accurate diagnosis are required. The primary aim of this study is to assess the ability of pentraxin-3 (PTX3) in order to diagnose the cause of pleural effusion and compare its efficacy to that of other previously identified biomarkers.
We studied 118 patients with pleural effusion, classified as transudates and exudates including malignant, tuberculous, and parapneumonic effusions (MPE, TPE, and PPE). The levels of PTX3, C-reactive protein (CRP), procalcitonin (PCT) and lactate in the pleural fluid were assessed.
The levels of pleural fluid PTX3 were significantly higher in patients with PPE than in those with MPE or TPE. PTX3 yielded the most favorable discriminating ability to predict PPE from MPE or TPE by providing the following: area under the curve, 0.74 (95% confidence interval, 0.63-0.84), sensitivity, 62.07%; and specificity, 81.08% with a cut-off point of 25.00 ng/mL.
Our data suggests that PTX3 may allow improved differentiation of PPE from MPE or TPE compared to the previously identified biomarkers CRP and PCT.
PMCID: PMC3884112  PMID: 24416055
PTX3 Protein; Pleural Effusion
11.  Assessing the Detection Capacity of Microarrays as Bio/Nanosensing Platforms 
BioMed Research International  2013;2013:310461.
Microarray is one of the most powerful detection systems with multiplexing and high throughput capability. It has significant potential as a versatile biosensing platform for environmental monitoring, pathogen detection, medical therapeutics, and drug screening to name a few. To date, however, microarray applications are still limited to preliminary screening of genome-scale transcription profiling or gene ontology analysis. Expanding the utility of microarrays as a detection tool for various biological and biomedical applications requires information about performance such as the limits of detection and quantification, which are considered as an essential information to decide the detection sensitivity of sensing devices. Here we present a calibration design that integrates detection limit theory and linear dynamic range to obtain a performance index of microarray detection platform using oligonucleotide arrays as a model system. Two different types of limits of detection and quantification are proposed by the prediction or tolerance interval for two common cyanine fluorescence dyes, Cy3 and Cy5. Besides oligonucleotide, the proposed method can be generalized to other microarray formats with various biomolecules such as complementary DNA, protein, peptide, carbohydrate, tissue, or other small biomolecules. Also, it can be easily applied to other fluorescence dyes for further dye chemistry improvement.
PMCID: PMC3845509  PMID: 24324959
12.  Placental Transmogrification of the Lung 
Korean Journal of Radiology  2013;14(6):977-980.
Placental transmogrification is a very rare lung disease, where the alveoli resemble the chorionic villi of placenta, and this change is a characteristic finding. A 31-year-old female patient presented with cough and dyspnea that had begun 2 weeks prior to admission. Along with giant bulla found in the left upper lung field, subsegmental consolidation was also identified in the lingular segment on plain chest radiograph and CT scan. Wedge resection was performed to remove the bulla. Pathologic examination of the resected bulla revealed destruction of the normal structures and characteristic villous and papillary changes. These changes led to a diagnosis of placental transmogrification. We made an encounter of an unusual placental transmogrification which had different image findings from other reported transmogrification cases. Thus, we report an atypical placental transmogrification case where both consolidation and giant bulla coexist.
PMCID: PMC3835648  PMID: 24265576
Lung; Placenta; Chorionic villi; Emphysema
13.  Effects of Vibratory Stimulations on Maximal Voluntary Isometric Contraction from Delayed Onset Muscle Soreness 
Journal of Physical Therapy Science  2013;25(9):1093-1095.
[Purpose] The aim of this study was to investigate the effect of vibratory stimulation on maximal voluntary isometric contraction (MVIC) from delayed onset muscle soreness (DOMS). [Subjects] Sixty healthy adults participated in this study. The exclusion criteria were orthopedic or neurologic disease. [Methods] The researchers induced DOMS in the musculus extensor carpi radialis longus of each participant. Subjects in the control group received no treatment. The ultrasound group received ultrasound treatment (intensity, 1.0 W/cm2; frequency 1 MHz; time, 10 minutes). The vibration group received vibration stimulation (frequency, 20 MHz; time, 10 minutes). Maximal voluntary isometric contraction (MVIC) was recorded at baseline, immediately after exercise, and 24, 48, and 72 hours after exercise. [Results] MVIC measurements showed statistically significant differences in the vibration group compared with the control group. [Conclusion] Vibratory stimulation had a positive effect on recovery of muscle function from DOMS.
PMCID: PMC3818754  PMID: 24259922
Vibratory stimulation; Ultrasound; Isometric contraction
14.  A Study of Effect of the Compound Physical Activity Therapy on Muscular Strength in Obese Women 
Journal of Physical Therapy Science  2013;25(8):1039-1041.
[Purpose] The aim of this study was to determine how compound physical activity affects muscular strength of middle-aged obese women. [Subjects] The research subjects were 40–50 year-old middle-aged women with excess body fat (30%). [Methods] The subjects were randomly assigned to two group, the experimental group and the control group. The experimental group performed two types of exercise programs for 16 weeks. Aerobic physical activity was performed 5 times per week, and anaerobic physical activity was performed every two days, and the exercise program each day was composed of a warm-up, the main exercise, and cooldown. The type of exercise focused on walking at a quick pace, and the intensity of the exercise focused on long periods of exercise at low intensity with the level of HRmax being 40–60%. The weight training, which was useful for beginners, as a type of kinetic load exercise, was applied with a composition recommended by the ACSM for muscle fitness (intensity of 40–60% of 1 RM and 10–15 repetitions). SPSS version 16.0 was used to analyze the data by ANCOVA and the t-test. [Results] The chest, leg, and abdominal strengths were significantly increased in the experimental group, and this indicates that compound physical activity is effective for improvement of muscular strength. [Conclusion] In conclusion, there were significant differences between groups in terms of muscular strength.
PMCID: PMC3820232  PMID: 24259911
Therapy; Muscular; Strength
15.  The Utility of a Three-Dimensional Approach with T-Shaped Osteotomy in Osseous Genioplasty 
Archives of Plastic Surgery  2013;40(4):433-439.
Facial beauty depends on the form, proportion, and position of various units of the face. In terms of the frontal view and facial profile, the chin is the most prominent aesthetic element of the lower third of the face. Many methods have been implemented to obtain good proportions of the lower face. In this study, we applied the T-shaped genioplasty method to correcting chin deformities.
All of the procedures in 9 cases were performed under general anesthesia. For genioplasty, a horizontal cutting line and 1 or 2 vertical cutting lines were drawn 5 mm below the mental foramen. Osteotomed bone segments of the chin were used for horizontal widening using bone grafts or for horizontal shortening. Likewise, they were used as bone grafts for vertical lengthening or vertical shortening. The bone segments were approximated in the midline and held in place using miniplates.
The postoperative appearance of the 9 cases showed that the lower third of the face had been naturally changed. At the same time, vertical lengthening or shortening, and horizontal widening or shortening could be implemented during the operation. Satisfactory results were obtained based on reviews of the patients' preoperative and postoperative photographs. The patients were also satisfied with the outcomes.
Using T-shaped genioplasty, we efficiently adjusted the shape and position of the chin to obtain good proportions of the lower face and change its contour to obtain an aesthetically appealing oval face in accordance with East Asians' aesthetic preferences.
PMCID: PMC3724007  PMID: 23898443
Chin; Genioplasty; Mandibular osteotomy
16.  Suppression of Tak1 Promotes Prostate Tumorigenesis 
Cancer research  2012;72(11):2833-2843.
Over 30% of primary prostate cancers contain a consensus deletion of an approximately 800 kb locus on chromosome 6q15.1. The MAP3K7 gene, which encodes TGF-β Activated Kinase-1 (Tak1), is a putative prostate tumor suppressor gene within this region whose precise function remains obscure. In this study, we investigated the role of Tak1 in human and murine prostate cancers. In 50 well-characterized human cancer specimens, we found that Tak1 expression was progressively lost with increasing Gleason grade, both within each cancer and across all cancers. In murine prostate stem cells and Tak1-deficient prostatic epithelial cells, Tak1 loss increased proliferation, migration, and invasion. When prostate stem cells attenuated for Tak1 were engrafted with fetal urogenital mesenchyme, the histopathology of the grafts reflected the natural history of prostate cancer leading from prostatic intraepithelial neoplasia to invasive carcinoma. In the grafts containing Tak1-suppressed prostate stem cells, p38 and JNK activity was attenuated and proliferation was increased. Together, our findings functionally validate the proposed tumor suppressor role of Tak1 in prostate cancer.
PMCID: PMC3654674  PMID: 22467172
Tak1; Prostate cancer; Tumor suppressor; Tissue recombination; TGF-β
17.  Is the Expression of Androgen Receptor Protein Associated With the Length of AC Repeats in the Type III 5-α Reductase Gene in Prostate Cancer Patients? 
Korean Journal of Urology  2013;54(6):404-408.
Type III 5-α reductase (SRD5A3; steroid 5-α reductase 3) may be associated with the progression of prostate cancer (PCa). The aim of our study was to determine whether the length of AC repeats in the SRD5A3 gene is associated with the risk of PCa and the expression of androgen receptor (AR) protein in Korean men.
Materials and Methods
We compared the length of AC repeats in the short tandem repeat (STR) region of the SRD5A3 gene in 68 PCa patients and 81 control subjects by genotyping. A total of 55 patients in the PCa group underwent radical prostatectomy. We evaluated the expression of AR protein by using Western blotting and tested the association between the type of AC repeats in the SRD5A3 gene and AR protein expression and clinical and pathologic parameters.
The short type of STR had less than 21 copies of AC repeats in the SRD5A3 gene. The SS type (short and short type) of STR of the SRD5A3 gene was 2.2 times as likely to occur in PCa patients as in controls (odds ratio, 2.21; 95% confidence interval, 1.14 to 4.31; p=0.019). However, AC repeats of the SRD5A3 gene were not associated with AR protein expression or clinical or pathologic parameters in PCa samples.
These results suggest that the short AC repeats of SRD5A3 polymorphism are associated with an increased risk of PCa. SRD5A3 polymorphism may contribute to a genetic predisposition for PCa.
PMCID: PMC3685642  PMID: 23789051
3-Oxo-5-alpha-Steroid 4-Dehydrogenase; Androgen receptors; Genetic polymorphism; Prostatic neoplasms
18.  Genetic and epigenetic inactivation of LPL gene in human prostate cancer 
Lipoprotein lipase (LPL) is in chromosome 8p22, site of one of the most common somatic deletions in prostate tumors. Additionally, a CpG island (CGI) was identified in the LPL promoter region. To test the hypothesis that LPL is a tumor suppressor gene, which is inactivated by somatic deletion and hypermethylation in prostate cancer, we evaluated somatic DNA deletion and methylation status at LPL in 56 pairs of DNA samples isolated from prostate cancer tissues and matching normal controls and 11 prostate cell lines. We found that the DNA in 21 of 56 primary cancers (38%) was methylated in the LPL promoter CGI, whereas no methylation was detected in any normal samples. In addition, we found a hemizygous deletion at LPL in 38 of the 56 tumors (68%). When the results of deletion and methylation were considered together, we found LPL promoter CGI methylation occurred in 45% of LPL deleted tumors and in 22% of LPL retained tumors. Within several clinical characteristics tested, the preoperative PSA levels were found to be significantly higher in subjects with LPL promoter CGI methylation compared with subjects without LPL promoter methylation (p = 0.0012). Additionally, demethylation of the LPL promoter CGI was accompanied by transcriptional reactivation of LPL in the prostate cancer cell lines DU145 and PC3. In summary, we report a novel finding that the LPL gene is commonly methylated in prostate tumors, and our results suggest that biallelic inactivation of LPL by chromosomal deletion and promoter hypermethylation may play a role in human prostate cancer.
PMCID: PMC3667349  PMID: 19004026
LPL; promoter methylation; prostate cancer; somatic deletion; biallelic inactivation
19.  In vivo magnetic enrichment and multiplex photoacoustic detection of circulating tumour cells 
Nature nanotechnology  2009;4(12):855-860.
The spread of cancer cells between organs, a process known as metastasis, is the cause of most cancer deaths1,2. Detecting circulating tumour cells—a common marker for the development of metastasis3,4—is difficult because ex vivo methods are not sensitive enough owing to limited blood sample volume and in vivo diagnosis is time-consuming as large volumes of blood must be analysed5–7. Here, we show a way to magnetically capture circulating tumour cells in the bloodstream of mice followed by rapid photoacoustic detection. Magnetic nanoparticles, which were functionalized to target a receptor commonly found in breast cancer cells, bound and captured circulating tumour cells under a magnet. To improve detection sensitivity and specificity, gold-plated carbon nanotubes conjugated with folic acid were used as a second contrast agent for photoacoustic imaging. By integrating in vivo multiplex targeting, magnetic enrichment, signal amplification and multicolour recognition, our approach allows circulating tumour cells to be concentrated from a large volume of blood in the vessels of tumour-bearing mice, and this could have potential for the early diagnosis of cancer and the prevention of metastasis in humans.
PMCID: PMC3663137  PMID: 19915570
20.  Golden carbon nanotubes as multimodal photoacoustic and photothermal high-contrast molecular agents 
Nature nanotechnology  2009;4(10):688-694.
Carbon nanotubes have shown promise as contrast agents for photoacoustic and photothermal imaging of tumours and infections because they offer high resolution and allow deep tissue imaging. However, in vivo applications have been limited by the relatively low absorption displayed by nanotubes at near-infrared wavelengths and concerns over toxicity. Here, we show that gold-plated carbon nanotubes—termed golden carbon nanotubes—can be used as photoacoustic and photothermal contrast agents with enhanced near-infrared contrast (~102-fold) for targeting lymphatic vessels in mice using extremely low laser fluence levels of a few mJ cm−2. Antibody-conjugated golden carbon nanotubes were used to map the lymphatic endothelial receptor, and preliminary in vitro viability tests show golden carbon nanotubes have minimal toxicity. This new nanomaterial could be an effective alternative to existing nanoparticles and fluorescent labels for non-invasive targeted imaging of molecular structures in vivo.
PMCID: PMC3663138  PMID: 19809462
21.  In vivo fiber-based multicolor photoacoustic detection and photothermal purging of metastasis in sentinel lymph nodes targeted by nanoparticles 
Journal of biophotonics  2009;2(0):528-539.
This report introduces a novel diagnostic and therapeutic platform for in vivo noninvasive detection and treatment of metastases in sentinel lymph nodes (SLNs) at single cell level using an integrated system of multicolor photoacoustic (PA) lymph flow cytometry, PA lymphography, absorption image cytometry, and photothermal (PT) therapy. A melanoma-bearing mouse model was used to demonstrate the capability of this platform for real-time lymphatic mapping, counting of disseminated tumor cells (DTCs) in prenodal lymphatics, and detection of metastasis in SLNs and its purging. The detection and ablation of non-pigmented breast cancer cells in SLNs was achieved by labeling them with nanoparticles. The association between DTC count and SLN metastasis progression supports lymphatic DTCs as a novel prognostic marker of metastasis. The fiber-based portable PA device may replace the conventional SLN(s) excision and histology-based staging. The earliest detection of DTCs in the lymphatic vessels before the establishment of nodal metastasis may prevent metastasis by well-timed ablation of DTCs.
Photoacoustic mapping of melanoma metastasis in sentinel lymph node (1.6 × 3 mm) at single cancer cell level using tumor-bearing mouse model at week one (left) and two (right) of tumor development. Red pseudo-color peaks indicate the photoacoustic signals with maximum amplitudes.
PMCID: PMC3663141  PMID: 19743443
metastasis; sentinel lymph nodes; photoacoustic imaging; photothermal therapy; nanoparticles
22.  Compartmentalization of Vertebrate Optic Neuroephithelium: External Cues and Transcription Factors 
Molecules and Cells  2012;33(4):317-324.
The vertebrate eye is a laterally extended structure of the forebrain. It develops through a series of events, including specification and regionalization of the anterior neural plate, evagination of the optic vesicle (OV), and development of three distinct optic structures: the neural retina (NR), optic stalk (OS), and retinal pigment epithelium (RPE). Various external signals that act on the optic neuroepithelium in a spatial- and temporal-specific manner control the fates of OV subdomains by inducing localized expression of key transcription factors. Investigating the mechanisms underlying compartmentalization of these distinct optic neuroepithelium-derived tissues is therefore not only important from the standpoint of accounting for vertebrate eye morphogenesis, it is also helpful for understanding the fundamental basis of fate determination of other neuroectoderm-derived tissues. This review focuses on the molecular signatures of OV subdomains and the external factors that direct the development of tissues originating from the OV.
PMCID: PMC3887801  PMID: 22450691
eye morphogenesis; optic stalk; retina; retinal pigment epithelium (RPE)
23.  Klinefelter Syndrome Diagnosed by Prenatal Screening Tests in High-Risk Groups 
Korean Journal of Urology  2013;54(4):263-265.
Klinefelter syndrome is a chromosomal disorder present in 1 out of 400 to 1,000 male newborns in Western populations. Two-thirds of affected newborns show a karyotype of 47,XXY. Few studies have examined the incidence of Klinefelter syndrome in Korea. The aim of this study was to investigate the incidence of Klinefelter syndrome by use of prenatal screening tests.
Materials and Methods
From January 2001 to December 2010, 18,049 pregnant women who had undergone a chromosomal study for fetal anomalies were included. For fetuses that were diagnosed as having Klinefelter syndrome, the patients' medical records were retrospectively reviewed. Both parents' ages, the reason for the chromosomal studies, and karyotypes were investigated.
We found that 22 of 18,049 (0.12%) fetuses were diagnosed with Klinefelter syndrome. The incidence of this disorder in male fetuses was 22 of 9,387 (0.23%). Also, 19 of the newborns (86.4%) showed a karyotype of 47,XXY; the other newborns showed karyotypes of 48,XXY,+21; 48,XXY,+12[12]/46,XY[54]; and 47,XXY[6]/45,X[1]/46,XY[95]. The mean age of the mothers was 36.1 years, and 2 women had a past history of a Down syndrome pregnancy. Nine mothers had a normal spontaneous delivery, 9 mothers underwent artificial abortion, and 2 fetuses were spontaneously aborted.
The incidence of Klinefelter syndrome as reported in this study is higher than in previous studies. Further studies with a broader population should be considered to confirm these results.
PMCID: PMC3630347  PMID: 23614065
Karyotype; Klinefelter syndrome; Male infertility
24.  Association of prostate cancer risk with SNPs in regions containing androgen receptor binding sites captured by ChIP-on-chip analyses 
The Prostate  2011;72(4):376-385.
Genome-wide association studies (GWAS) have identified approximately three dozen single nucleotide polymorphisms (SNPs) consistently associated with prostate cancer (PCa) risk. Despite the reproducibility of these associations, the molecular mechanism for most of these SNPs has not been well elaborated as most lie within non-coding regions of the genome. Androgens play a key role in prostate carcinogenesis. Recently, using ChIP-on-chip technology, 22,447 androgen receptor (AR) binding sites have been mapped throughout the genome, greatly expanding the genomic regions potentially involved in androgen-mediated activity.
Methodology/Principal findings
To test the hypothesis that sequence variants in AR binding sites are associated with PCa risk, we performed a systematic evaluation among two existing PCa GWAS cohorts; the Johns Hopkins Hospital and the Cancer Genetic Markers of Susceptibility (CGEMS) study population. We demonstrate that regions containing AR binding sites are significantly enriched for PCa risk-associated SNPs, i.e. more than expected by chance alone. In addition, compared with the entire genome, these newly observed risk-associated SNPs in these regions are significantly more likely to overlap with established PCa risk-associated SNPs from previous GWAS. These results are consistent with our previous finding from a bioinformatics analysis that one-third of the 33 known PCa risk-associated SNPs discovered by GWAS are located in regions of the genome containing AR binding sites.
The results to date provide novel statistical evidence suggesting an androgen-mediated mechanism by which some PCa associated SNPs act to influence PCa risk. However, these results are hypothesis generating and ultimately warrant testing through in-depth molecular analyses.
PMCID: PMC3366362  PMID: 21671247
AR; prostate cancer; GWAS; pathway association study
25.  Survey of Attitudes on Professionalism in Plastic and Reconstructive Surgery 
Archives of Plastic Surgery  2013;40(2):134-140.
The purpose of this study is to analyze the current attitudes toward professionalism, the core values, and the type of professionalism among plastic surgeons in Korea to establish a code of ethics regarding the role of professionalism for plastic and reconstructive surgeons.
From March 9, to July 1, 2012, face-to-face and mail surveys were conducted targeting the 325 participants (256 specialists and 69 residents) who are registered members of the Korean Society of Plastic and Reconstructive Surgeons. The proportion of each response given to an item was obtained through statistical processing through frequency analysis. The Mann-Whitney U test was used to compare the differences in the responses between the resident group and the specialist group.
The survey results on the perception of professionalism in plastic surgery showed that a high proportion (90.5%) of the respondents viewed the future of plastic surgeons as bright. Through evaluation of the importance of the value items,"professional dominance" (4.58 pts), "autonomy" (4.45 pts), "lifestyle" (4.34 pts), and "commercialism" (4.31 pts) were assessed as critical values. "Altruism" (3.84 pts), "interpersonal competence" (3.79 pts), and "social justice" (3.61 pts) were viewed as lesser values. This difference showed the characteristics of an entrepreneurial outlook.
Plastic surgeons should pursue excellence, humanism, accountability, and altruism in order to overcome the crisis of professionalism in plastic surgery. In order to develop the necessary competencies of professionals, vocational education should be arranged by the Korean Society of Plastic Surgeons, and an appropriate code of ethics should be established.
PMCID: PMC3605558  PMID: 23533062
Code of ethics; Plastic surgery; Professional role

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