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1.  Gentamicin-Loaded Wound Dressing With Polyvinyl Alcohol/Dextran Hydrogel: Gel Characterization and In Vivo Healing Evaluation 
AAPS PharmSciTech  2010;11(3):1092-1103.
To develop a gentamicin-loaded wound dressing, cross-linked hydrogel films were prepared with polyvinyl alcohol (PVA) and dextran using the freezing–thawing method. Their gel properties such as gel fraction, swelling, water vapor transmission test, morphology, tensile strength, and thermal property were investigated. In vitro protein adsorption test, in vivo wound healing test, and histopathology were performed. Dextran decreased the gel fraction, maximum strength, and thermal stability of hydrogels. However, it increased the swelling ability, water vapor transmission rate, elasticity, porosity, and protein adsorption. The drug gave a little positive effect on the gel properties of hydrogels. The gentamicin-loaded wound dressing composed of 2.5% PVA, 1.13% dextran, and 0.1% drug was more swellable, flexible, and elastic than that with only PVA because of its cross-linking interaction with PVA. In particular, it could provide an adequate level of moisture and build up the exudates on the wound area. From the in vivo wound healing and histological results, this gentamicin-loaded wound dressing enhanced the healing effect more compared to conventional product because of the potential healing effect of gentamicin. Thus, this gentamicin-loaded wound dressing would be used as a potential wound dressing with excellent forming and improved healing effect in wound care.
doi:10.1208/s12249-010-9474-0
PMCID: PMC2974132  PMID: 20607628
dextran; gentamicin; histological examination; wound dressing; wound healing effect
2.  ZNF282 (Zinc finger protein 282), a novel E2F1 co-activator, promotes esophageal squamous cell carcinoma 
Oncotarget  2014;5(23):12260-12272.
Zincfinger protein 282 (ZNF282) is a newly identified transcription factor and little is known about its expression and function. Originally, ZNF282 is known to bind U5RE (U5 repressive element) of HLTV-1 (human T cell leukemia virus type 1) with a repressive effect. Recently we reported that ZNF282 functions as an estrogen receptor co-activator and plays an essential role in breast tumorigenesis. Although these results suggest the possible role of ZNF282 in cancers, clinical significance and function of ZNF282 are completely unknown in most of cancers. Here we found that ZNF282 was frequently overexpressed in esophageal squamouscell carcinoma (ESCC) (n=165) compared with normal esophageal epithelium and its overexpression was correlated with adverse clinical outcome. Multivariate survival analysis indicated that ZNF282 expressionwas an independent prognostic predictor for poor survival in ESCC (HR: 2.56 (95% CI 1.54-4.26), p<0.001). In addition, depletion of ZNF282 inhibited the cell cycle progression, migration, and invasion of ESCC cells and reduced the tumorigenicity of ESCC xenograft in nude mouse. We further showed that ZNF282 is required for E2F1-mediated gene expression in ESCC cells. Thus, ZNF282 is E2F1 co-activator involved in ESCC and elevated expression of ZNF282 is an independent adverse prognostic factor in ESCC.
PMCID: PMC4323012  PMID: 25373738
ZNF282; E2F1; Cell cycle; Esophageal squamous cell carcinoma; Prognosis
3.  Treatment and Outcomes for Gangliogliomas: A Single-Center Review of 16 Patients 
Background
Ganglioglioma is a rare and slowly growing benign tumor. We investigated the outcomes of patients who underwent different combination treatments.
Methods
Between 1998 and 2012, 16 patients, including 11 men and 5 women, with a median age of 12.5 years (range, 2.5-65 years) were treated for intracranial gangliogliomas at our institution. The median follow-up period was 5.7 years (range, 48 days-15.6 years). Fifteen cases were included in the outcome assessment because one patient was lost to follow-up. Complete resection was achieved in 8 (53%) patients. Six (40%) patients underwent incomplete resection with or without adjuvant radiotherapy, and one patient with a brainstem tumor underwent only stereotactic biopsy.
Results
Gangliogliomas predominantly affected young (87.5%), male patients and most frequently presented with seizures (64%). Of eight patients who underwent complete resection, seven did not show recurrence, whereas only three of six with incomplete resection showed no recurrence. Four patients with recurrence received salvage treatments (two repeat surgeries and two radiosurgeries). A tumor control rate of 93% (14/15) was achieved at the last follow-up. No recurrence or malignant changes were observed after a median follow-up of 12 and 4.5 years in four patients who received gamma knife (GK) radiosurgery as adjuvant and salvage treatment.
Conclusion
Complete resection produced the best outcomes and incomplete resection followed by adjuvant or salvage treatments showed favorable outcomes. In patients who are not eligible for complete resection because of tumor location or potential neurologic deficits following surgery, GK radiosurgery should be considered for the treatment of residual or recurrent tumors.
doi:10.14791/btrt.2014.2.2.49
PMCID: PMC4231627  PMID: 25408925
Ganglioglioma; Radiosurgery
4.  HAX1 regulates E3 ubiquitin ligase activity of cIAPs by promoting their dimerization 
Oncotarget  2014;5(20):10084-10099.
HS-1-associated protein X-1 (HAX1) is a multi-functional protein which was first identified as a Hematopoietic cell specific Lyn Substrate 1 (HS1)-binding protein. Although the roles of HAX1 in apoptosis have been unraveled and HAX1 has been proposed to be involved in several diseases, additional roles of HAX1 are still being identified. Here, we demonstrated that HAX1 directly interacted with cellular Inhibitor of Apoptosis Proteins (cIAPs), ubiquitin E3 ligases which regulate the abundance of cellular proteins, via ubiquitin-dependent proteasomal degradation. We showed that HAX1 promotes auto-ubiquitination and degradation of cIAPs by facilitating the intermolecular homodimerization of RING finger domain. Moreover, HAX1 regulates the non-canonical Nuclear Factor-κB (NF-κB) signaling pathway by modulating the stability of NF-κB-Inducing Kinase (NIK), which is one of the substrates of cIAPs. Taken together, these results unveil a novel role of HAX1 in the non-canonical NF-κB pathway, and provide an important clue that HAX1 is a potential therapeutic target for the treatment of cancer.
PMCID: PMC4259407  PMID: 25275296
5.  Thyroid Metastasis from Breast Carcinoma Accompanied by Papillary Thyroid Carcinoma 
Case Reports in Oncology  2014;7(2):528-533.
Abstract
Metastasis to the thyroid gland is very rare. Recently, we experienced a case of thyroid metastasis from breast cancer accompanying a papillary thyroid. A 51-year-old female patient presented with a palpated lymph node on her left lateral neck. The patient had undergone a left modified radical mastectomy followed by chemotherapy and hormonal therapy 12 years prior. Ultrasonography of the neck revealed a malignant looking nodule at the left thyroid lobe, measuring 0.9 × 0.9 cm, and several cystic nodules at the right thyroid lobe. Ultrasonography of the neck additionally revealed a malignant looking lymph node at the right level VI. Fine-needle aspiration of the left thyroid lobe resulted in a diagnosis of papillary thyroid carcinoma and that of the right level VI in Hurthle cell lesion. The patient had a total thyroidectomy with selective dissection of the left neck node. Pathologic assessment of the specimen revealed metastatic carcinoma from the breast carcinoma and papillary thyroid carcinoma. Although the thyroid gland is highly vascularized, metastasis of malignant tumors to the thyroid is relatively rare and detection of metastasis shows a low frequency. So a careful evaluation of thyroid tumor should be considered in a patient with a history of other malignancy.
doi:10.1159/000365748
PMCID: PMC4164070  PMID: 25232322
Metastatic thyroid carcinoma; Breast carcinoma; Papillary thyroid carcinoma
6.  Identification of the novel substrates for caspase-6 in apoptosis using proteomic approaches 
BMB Reports  2013;46(12):588-593.
Apoptosis, programmed cell death, is a process involved in the development and maintenance of cell homeostasis in multicellular organisms. It is typically accompanied by the activation of a class of cysteine proteases called caspases. Apoptotic caspases are classified into the initiator caspases and the executioner caspases, according to the stage of their action in apoptotic processes. Although caspase-3, a typical executioner caspase, has been studied for its mechanism and substrates, little is known of caspase-6, one of the executioner caspases. To understand the biological functions of caspase-6, we performed proteomics analyses, to seek for novel caspase-6 substrates, using recombinant caspase-6 and HepG2 extract. Consequently, 34 different candidate proteins were identified, through 2-dimensional electrophoresis/MALDI-TOF analyses. Of these identified proteins, 8 proteins were validated with in vitro and in vivo cleavage assay. Herein, we report that HAUSP, Kinesin5B, GEP100, SDCCAG3 and PARD3 are novel substrates for caspase-6 during apoptosis. [BMB Reports 2013; 46(12): 588-593]
doi:10.5483/BMBRep.2013.46.12.081
PMCID: PMC4133863  PMID: 24195789
Apoptosis; Caspase-6; Degradomics; Proteomic screening; Substrate
7.  Prognostic Factors and Therapeutic Outcomes in 22 Patients with Pleomorphic Xanthoastrocytoma 
Objective
Pleomorphic xanthoastrocytoma (PXA) is a rare primary low-grade astrocytic tumor classified as WHO II. It is generally benign, but disease progression and malignant transformation have been reported. Prognostic factors for PXA and optimal therapies are not well known.
Methods
The study period was January 2000 to March 2012. Data on MR findings, histology, surgical extents and adjuvant therapies were reviewed in twenty-two patients diagnosed with PXA.
Results
The frequent symptoms of PXA included seizures, headaches and neurologic deficits. Tumors were most common in the temporal lobe followed by frontal, parietal and occipital lobes. One patient who died from immediate post-operative complications was excluded from the statistical analysis. Of the remaining 21 patients, 3 (14%) died and 7 (33%) showed disease progression. Atypical tumor location (p<0.001), peritumoral edema (p=0.022) and large tumor size (p=0.048) were correlated with disease progression, however, Ki-67 index and necrosis were not statistically significant. Disease progression occurred in three (21%) of 14 patients who underwent GTR, compared with 4 (57%) of 7 patients who did not undergo GTR, however, it was not statistically significant. Ten patients received adjuvant radiotherapy and the tumors were controlled in 5 of these patients.
Conclusion
The prognosis for PXA is good; in our patients overall survival was 84%, and event-free survival was 59% at 3 years. Atypical tumor location, peritumoral edema and large tumor size are significantly correlated with disease progression. GTR may provide prolonged disease control, and adjuvant radiotherapy may be beneficial, but further study is needed.
doi:10.3340/jkns.2013.53.5.281
PMCID: PMC3730029  PMID: 23908701
Pleomorphic xanthoastrocytoma; Prognosis; outcome; Radiotherapy
8.  Intracranial Extraskeletal Myxoid Chondrosarcoma : Case Report and Literature Review 
Intracranial extraskeletal myxoid chondrosarcoma is extremely rare, with only seven patients previously reported. We present a case report of a 21-year-old woman admitted for weakness in her right extremities and symptoms of increased intracranial pressure. Magnetic resonance imaging (MRI) revealed hydrocephalus and a well-enhanced large mass around her left thalamus. A left parietal craniotomy and a cortisectomy at the superior parietal lobule were performed. Total surgical resection was also performed, and pathology results confirmed an extraskeletal myxoid chondrosarcoma. Postoperative MRI showed no residual tumor, and the patient underwent radiotherapy. After six months of radiotherapy, the patient's headache and weakness had improved to grade IV. This malignant tumor showed high rates of recurrence in previous reports. We here report another occurrence of this highly malignant and rare tumor in a patient treated using total surgical excision and adjuvant radiotherapy.
doi:10.3340/jkns.2012.52.3.246
PMCID: PMC3483328  PMID: 23115670
Brain neoplasms; Chondrosarcoma; Choroid plexus
9.  Blockade of ERK Phosphorylation in the Nucleus Accumbens Inhibits the Expression of Cocaine-induced Behavioral Sensitization in Rats 
Repeated administration of psychostimulants such as cocaine leads to the development of behavioral sensitization. Extracellular signal-Regulated Kinase (ERK), an enzyme important for long-term neuronal plasticity, has been implicated in such effects of these drugs. Although the nucleus accumbens (NAcc) is the site mediating the expression of behavioral sensitization by drugs of abuse, the precise role of ERK activation in this site has not been determined. In this study we demonstrate that blockade of ERK phosphorylation in the NAcc by a single bilateral microinjections of PD98059 (0.5 or 2.0µ g/side), or U0126 (0.1 or 1.0µg/side), into this site dose-dependently inhibited the expression of cocaine-induced behavioral sensitization when measured at day 7 following 6 consecutive daily cocaine injections (15 mg/kg, i.p.). Acute microinjection of either vehicle or PD98059 alone produced no different locomotor activity compared to saline control. Further, microinjection of PD98059 (2.0µ g/side) in the NAcc specifically lowered cocaine-induced increase of ERK phosphorylation levels in this site, while unaffecting p-38 protein levels. These results indicate that ERK activation in the NAcc is necessary for the expression of cocaine-induced behavioral sensitization, and further suggest that repeated cocaine evokes neuronal plasticity involving ERK pathway in this site leading to long-lasting behavioral changes.
doi:10.4196/kjpp.2011.15.6.389
PMCID: PMC3282227  PMID: 22359477
Cocaine; Behavioral sensitization; PD98059; U0126; Nucleus accumbens
10.  Experience and analysis of level VII cervical lymph node metastases in patients with papillary thyroid carcinoma 
Purpose
Papillary thyroid cancer with level VII (anterior superior mediastinal lymph nodes) lymph node metastasis belongs to Stage IV a according to the Americal Joint Committee on Cancer cancer staging. The aim of our study was to identify clinicopathologic factors that are related to level VII cervical lymph node metastasis and to suggest recommendations for level VII dissection.
Methods
We reviewed 195 patients with papillary thyroid carcinoma who had their initial operation containing level VII dissection from April 2006 to June 2007. Level VII dissection involved lymph nodes in the anterior superior mediastinum and tracheoesophageal grooves, extending from the suprasternal notch to the innominate artery. Clinicophathologic factors, such as gender, age and lateral neck metastasis, related to Level VII metastasis were analyzed by tumor size, multifocality of tumor, extrathyroidal extension and lymphovascular invasion.
Results
Nine (4.6%) of 195 patients with papillary thyroid carcinoma had level VII metastasis. Clinicopathologic factors that were related to level VII metastasis included lateral neck metastasis (P < 0.01), tumor size (P < 0.01) and lymphovascular invasion (P < 0.05).
Conclusion
If preoperatively, the tumor size is over 1.5 cm, or there is lateral neck metastasis, level VII dissection must be considered. If there is lymphovascular invasion pathologic findings postoperatively, special attention should be paid for detection of level VII recurrence.
doi:10.4174/jkss.2011.80.5.307
PMCID: PMC3204699  PMID: 22066053
Level VII dissection; Papillary thyroid carcinoma
11.  Case of an Ectopic Thyroid Gland at the Lateral Neck Masquerading as a Metastatic Papillary Thyroid Carcinoma 
Journal of Korean Medical Science  2008;23(3):548-550.
Ectopic thyroid glands generally occur in the midline as a result of abnormal median migration, and their presence lateral to the midline is rare. We present one case of an ectopic thyroid gland masquerading as a lateral neck metastasis of a papillary thyroid carcinoma (PTC). In this case of a 54-yr-old woman with left PTC, we suspected left lateral neck metastasis on preoperative neck computed tomography. The patient underwent total thyroidectomy, central compartment neck dissection, and left modified radical neck dissection (MRND). The patient was diagnosed as having an accessory thyroid gland on the lateral neck on the final pathologic report. Surgeons should be aware of the existence of an ectopic thyroid gland in unusual locations.
doi:10.3346/jkms.2008.23.3.548
PMCID: PMC2526509  PMID: 18583899
Ectopic Thyroid; Carcinoma, Papillary
12.  A Suggestion of Modified Classification of Trigeminal Schwannomas According to Location, Shape, and Extension 
Background
Comprehensive knowledge of the anatomical features of trigeminal schwannomas (TSs) is essential in planning surgery to achieve complete tumor resection. In the current report, we propose a modified classification of TSs according to their location of origin, shape, and extension into the adjacent compartment, and discuss appropriate surgical strategies with this classification.
Methods
We retrospectively analyzed 49 patients with TS who were treated surgically by a single neurosurgeon at the Asan Medical Center between 1993 and 2013.
Results
There were 22 males and 27 females, with the median age of 40 years (range, 21-75 years). Median tumor size was 4.0 cm in diameter (2.0-7.0 cm). Tumors were classified as follows: Type M (confined to the middle fossa; 8 cases, 19.0%), P (confined to the posterior fossa; 2 cases, 4.8%), MP (involving equally both middle and posterior fossae; 5 cases, 11.9%), Mp (predominantly middle fossa with posterior fossa extension; 6 cases, 14.3%), Pm (predominantly posterior fossa with middle fossa extension; 16 cases, 38.1%), Me (predominantly middle fossa with extracranial extension; 4 cases, 9.5%). Surgical approach was chosen depending on the tumor classification. More specifically, a frontotemporal craniotomy and extradural approach with or without zygomatic or orbitozygomatic osteotomy was applied to M- or Mp-type tumors; a lateral suboccipital craniotomy with or without suprameatal approach was applied to the majority of P- or Pm-type tumors; and a posterior transpetrosal approach was used in four tumors (three Pm and one MP). Gross total resection was achieved in 95.9% of patients, and the overall recurrence rate was 4.1% (2 patients). Postoperatively, trigeminal symptoms were improved or unchanged in 51.0% of cases (25 patients). Surgical complications included meningitis (5 patients) and cerebrospinal fluid leakage (3 patients). There was no mortality.
Conclusion
TSs are well to be classified with our modified classification and able to be removed effectively and safely by selecting appropriate surgical approaches.
doi:10.14791/btrt.2014.2.2.62
PMCID: PMC4231622  PMID: 25408927
Classification; Neurilemmoma; Surgical procedure; Trigeminal nerve
13.  Correlation between HER2 Overexpression and Clinicopathological Characteristics in Gastric Cancer Patients Who Have Undergone Curative Resection 
Journal of Gastric Cancer  2014;14(3):180-186.
Purpose
At present, a human epidermal growth factor receptor 2 (HER2)-based concept of tumor biology has been established, and trastuzumab (Herceptin®; Genentech/Roche, San Francisco, CA, USA), a monoclonal humanized antibody directed against HER2, is a pivotal agent for the management of HER2 positive (HER2+) metastatic breast cancer. It is also known that HER2 has a predictive value in gastric cancer; however, its association with the prognosis of this disease remains uncertain. The purpose of this study was to evaluate both the relationship between HER2 overexpression in the tumors of gastric cancer patients, and the prognosis of these patients who have had curative resection.
Materials and Methods
A total of 139 consecutive patients with gastric cancer who underwent surgery at the Kosin University Gospel Hospital between October 2011 and March 2012 were included in this retrospective study. All tumor samples were examined for HER2 expression by immunohistochemistry. A retrospective review of the medical records was conducted to determine the correlation between the presence of HER2 overexpression and clinicopathological factors.
Results
The HER2+ rate was 15.1%. HER2 overexpression was associated with histological grade (P=0.044) and Lauren classification (P=0.036). There was no significant difference in the 2-year overall survival between HER2+ and HER2- patients (P=0.396). Multivariate analysis showed that HER2 was not an independent prognostic factor.
Conclusions
HER2 overexpression in tumors was associated with histological grade and Lauren classification in gastric cancer patients with curative resection. However, HER2 was not an independent prognostic factor for gastric cancer in our study.
doi:10.5230/jgc.2014.14.3.180
PMCID: PMC4199885  PMID: 25328763
Stomach neoplasms; Human epidermal growth factor receptor 2; Prognosis
14.  A practical scoring system to determine whether to proceed with surgical resection in recurrent glioblastoma 
Neuro-Oncology  2013;15(8):1096-1101.
Background
To determine the benefit of surgical management in recurrent glioblastoma, we analyzed a series of patients with recurrent glioblastoma who had undergone surgery, and we devised a new scale to predict their survival.
Methods
Clinical data from 55 consecutive patients with recurrent glioblastoma were evaluated after surgical management. Kaplan–Meier survival analysis and Cox proportional hazards regression modeling were used to identify prognostic variables for the development of a predictive scale. After the multivariate analysis, performance status (P = .078) and ependymal involvement (P = .025) were selected for inclusion in the new prognostic scale. The devised scale was validated with a separate set of 96 patients from 3 different institutes.
Results
A 3-tier scale (scoring range, 0–2 points) composed of additive scores for the Karnofsky performance status (KPS) (0 for KPS ≥ 70 and 1 for KPS < 70) and ependymal involvement (0 for no enhancement and 1 for enhancement of the ventricle wall in the magnetic resonance imaging) significantly distinguished groups with good (0 points; median survival, 18.0 months), intermediate (1 point; median survival, 10.0 months), and poor prognoses (2 points; median survival, 4.0 months). The new scale was successfully applied to the validation cohort of patients showing distinct prognosis among the groups (median survivals of 11.0, 9.0, and 4.0 months for the 0-, 1-, and 2-point groups, respectively).
Conclusions
We developed a practical scale to facilitate deciding whether to proceed with surgical management in patients with recurrent glioblastoma. This scale was useful for the diagnosis of prognostic groups and can be used to develop guidelines for patient treatment.
doi:10.1093/neuonc/not069
PMCID: PMC3714158  PMID: 23800677
ependymal involvement; performance status; recurrent glioblastoma; scoring system; surgery
15.  Impact of Aerobic Exercise Training on Endothelial Function in Acute Coronary Syndrome 
Annals of Rehabilitation Medicine  2014;38(3):388-395.
Objective
To confirm the improvement in arterial endothelial function by aerobic exercise training, flow-mediated dilation (FMD) was tested by ultrasonography.
Methods
Patients who received percutaneous coronary intervention due to acute coronary syndrome were included. The patients who participated in cardiac rehabilitation (CR) program were categorized as the CR group, and others who did not participate as the control. Both groups underwent initial graded exercise test (GXT) and FMD testing. Subsequently, the CR group performed aerobic exercise training sessions. Patients in control only received advice regarding the exercise methods. After six weeks, both groups received follow-up GXT and FMD testing.
Results
There were 16 patients in each group. There were no significant differences in the general characteristics between the groups. The VO2peak was 28.6±4.7 mL/kg/min in the CR group and 31.5±7.4 mL/kg/min in the control at first GXT, and was 31.1±5.1 ml/kg/min in the CR group and 31.4±6.0 ml/kg/min in the control at the follow-up GXT in six weeks. There was a statistically significant improvement in VO2peak only for CR group patients. FMD value was 7.59%±1.26% in the CR group, 7.36%±1.48% in the control at first and 9.46%±1.82% in the CR group, and 8.31%±2.04% in the control after six weeks. There was a statistically significant improvement in FMD value in the CR group.
Conclusion
According to the results of GXT and FMD testing, six-week exercise-based CR program improved VO2peak and endothelial functions significantly. Thus, exercise-based CR program is necessary in patients with coronary artery disease.
doi:10.5535/arm.2014.38.3.388
PMCID: PMC4092181  PMID: 25024964
Acute coronary syndrome; Exercise; Rehabilitation; Endothelial cell; Flow-mediated dilation
16.  A Novel Adenovirus in Chinstrap Penguins (Pygoscelis antarctica) in Antarctica 
Viruses  2014;6(5):2052-2061.
Adenoviruses (family Adenoviridae) infect various organ systems and cause diseases in a wide range of host species. In this study, we examined multiple tissues from Chinstrap penguins (Pygoscelis antarctica), collected in Antarctica during 2009 and 2010, for the presence of novel adenoviruses by PCR. Analysis of a 855-bp region of the hexon gene of a newly identified adenovirus, designated Chinstrap penguin adenovirus 1 (CSPAdV-1), showed nucleotide (amino acid) sequence identity of 71.8% (65.5%) with South Polar skua 1 (SPSAdV-1), 71% (70%) with raptor adenovirus 1 (RAdV-1), 71.4% (67.6%) with turkey adenovirus 3 (TAdV-3) and 61% (61.6%) with frog adenovirus 1 (FrAdV-1). Based on the genetic and phylogenetic analyses, CSPAdV-1 was classified as a member of the genus, Siadenovirus. Virus isolation attempts from kidney homogenates in the MDTC-RP19 (ATCC® CRL-8135™) cell line were unsuccessful. In conclusion, this study provides the first evidence of new adenovirus species in Antarctic penguins.
doi:10.3390/v6052052
PMCID: PMC4036538  PMID: 24811321
adenovirus; Siadenovirus; Chinstrap penguin; Antarctica
17.  Frontal White Matter Alterations in Short-Term Medicated Panic Disorder Patients without Comorbid Conditions: A Diffusion Tensor Imaging Study 
PLoS ONE  2014;9(4):e95279.
The frontal cortex might play an important role in the fear network, and white matter (WM) integrity could be related to the pathophysiology of panic disorder (PD). A few studies have investigated alterations of WM integrity in PD. The aim of this study was to determine frontal WM integrity differences between patients with PD without comorbid conditions and healthy control (HC) subjects by using diffusion tensor imaging. Thirty-six patients with PD who had used medication within 1 week and 27 age- and sex-matched HC subjects participated in this study. Structural brain magnetic resonance imaging was performed on all participants. Panic Disorder Severity Scale and Beck Anxiety Inventory (BAI) scores were assessed. Tract-based spatial statistics (TBSS) was used for image analysis. TBSS analysis showed decreased fractional anisotropy (FA) in frontal WM and WM around the frontal lobe, including the corpus callosum of both hemispheres, in patients with PD compared to HC subjects. Moreover, voxel-wise correlation analysis revealed that the BAI scores for patients with PD were positively correlated with their FA values for regions showing group differences in the FA of frontal WM of both hemispheres. Altered integrity in frontal WM of patients with PD without comorbid conditions might represent the structural pathophysiology in these patients, and these changes could be related to clinical symptoms of PD.
doi:10.1371/journal.pone.0095279
PMCID: PMC4005735  PMID: 24788587
18.  Analysis on Bilateral Hindlimb Mapping in Motor Cortex of the Rat by an Intracortical Microstimulation Method 
Journal of Korean Medical Science  2014;29(4):587-592.
Intracortical microstimulation (ICMS) is a technique that was developed to derive movement representation of the motor cortex. Although rats are now commonly used in motor mapping studies, the precise characteristics of rat motor map, including symmetry and consistency across animals, and the possibility of repeated stimulation have not yet been established. We performed bilateral hindlimb mapping of motor cortex in six Sprague-Dawley rats using ICMS. ICMS was applied to the left and the right cerebral hemisphere at 0.3 mm intervals vertically and horizontally from the bregma, and any movement of the hindlimbs was noted. The majority (80%±11%) of responses were not restricted to a single joint, which occurred simultaneously at two or three hindlimb joints. The size and shape of hindlimb motor cortex was variable among rats, but existed on the convex side of the cerebral hemisphere in all rats. The results did not show symmetry according to specific joints in each rats. Conclusively, the hindlimb representation in the rat motor cortex was conveniently mapped using ICMS, but the characteristics and inter-individual variability suggest that precise individual mapping is needed to clarify motor distribution in rats.
Graphical Abstract
doi:10.3346/jkms.2014.29.4.587
PMCID: PMC3991805  PMID: 24753709
Hindlimb; Deep Brain Stimulation; Brain Mapping; Motor Cortex
19.  Perspectives on the therapeutic potential of short-chain fatty acid receptors 
BMB Reports  2014;47(3):173-178.
There is rapidly growing interest in the human microbiome because of its implication in metabolic disorders and inflammatory diseases. Consequently, understanding the biology of short chain fatty acids and their receptors has become very important for identifying novel therapeutic avenues. GPR41 and GPR43 have been recognized as the cognate receptors for SCFAs and their roles in metabolism and inflammation have drawn much attention in recent years. GPR43 is highly expressed on immune cells and has been suggested to play a role in inflammatory diseases such as inflammatory bowel disease. Both GPR41 and GPR43 have been implicated in diabetes and obesity via the regulation of adipose tissue and gastrointestinal hormones. So far, many studies have provided contradictory results, and therefore further research is required to validate these receptors as drug targets. We will also discuss the synthetic modulators of GPR41 and GPR43 that are critical to understanding the functions of these receptors. [BMB Reports 2014; 47(3): 173-178]
doi:10.5483/BMBRep.2014.47.3.272
PMCID: PMC4163876  PMID: 24499669
GPR41; GPR43; Inflammation; Obesity; SCFA
20.  Immunostimulatory Effect of Fermented Red Ginseng in the Mouse Model 
In this study, Woongjin fermented red ginseng extract (WFRG) was evaluated for its potential ability to act as an adjuvant for the immune response of mice. For the in vitro study, macrophages were treated with serial concentrations (1 μg/mL, 10 μg/mL, and 100 μg/mL) of WFRG. For in vivo studies, mice were administered different concentrations (10 mg/kg/day, 100 mg/kg/day, and 200 mg/kg/day) of WFRG orally for 21 days. In vitro, the production of nitric oxide and TNF-α by RAW 264.7 cells increased in a dose-dependent manner. In vivo, WFRG enhanced the proliferation of splenocytes induced by two mitogens (i.e., concanavalin A and lipopolysaccharide [LPS]) and increased LPS-induced production of TNF-α and IL-6, but not IL-1β. In conclusion, WFRG has the potential to modulate immune function and should be further investigated as an immunostimulatory agent.
doi:10.3746/pnf.2014.19.1.010
PMCID: PMC3999803  PMID: 24772404
fermented red ginseng; immune responses; saponin; cytokine; anti-cancer
21.  SUMOylation of ZFP282 potentiates its positive effect on estrogen signaling in breast tumorigenesis 
Oncogene  2012;32(35):10.1038/onc.2012.420.
Estrogen receptor α (ERα) plays critical roles in development and progression of breast cancer, and the coiled-coil co-activator (CoCoA) is an important ERα co-activator for estrogen-induced gene expression. The small ubiquitin-like modifier (SUMO) pathway is hyperactivated in breast cancer, but the mechanism by which SUMOylation regulates ERα-mediated transcription remains poorly understood. Here, we identified ZFP282 as a CoCoA binding protein. ZFP282 associates directly with ERα and cooperates synergistically with CoCoA to enhance ERα function. ZFP282 is required for estrogen-induced expression of ERα target genes and estrogen-dependent breast cancer cell growth and tumorigenesis. In addition, we found that ZFP282 is SUMOylated and that SUMOylation positively regulates the co-activator activity of ZFP282 by increasing its binding affinity to ERα and CoCoA and consequently increasing recruitment of ZFP282-CoCoA complex to the promoter of ERα target genes. These findings reveal essential roles for ZFP282 and its SUMOylation in estrogen signaling and breast tumorigenesis.
doi:10.1038/onc.2012.420
PMCID: PMC3874449  PMID: 22986521
breast cancer; co-activator; CoCoA; SUMOylation; ZFP282
22.  Temozolomide Salvage Chemotherapy for Recurrent Anaplastic Oligodendroglioma and Oligo-Astrocytoma 
Objective
To evaluate the efficacy of temozolomide (TMZ) chemotherapy for recurrent anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA).
Methods
A multi-center retrospective trial enrolled seventy-two patients with histologically proven AO/AOA who underwent TMZ chemotherapy for their recurrent tumors from 2006 to 2010. TMZ was administered orally (150 to 200 mg/m2/day) for 5 days per 28 days until unacceptable toxicity occurred or tumor progression was observed.
Results
TMZ chemotherapy cycles administered was median 5.3 (range, 1-41). The objective response rate was 24% including 8 cases (11%) of complete response and another 23 patients (32%) were remained as stable disease. Severe side effects (≥grade 3) occurred only in 9 patients (13%). Progression-free survival (PFS) of all patients was a median 8.0 months (95% confidence interval, 6.0-10.0). The time to recurrence of a year or after was a favorable prognostic factor for PFS (p<0.05). Overall survival (OS) was apparently differed by the patient's histology, as AOA patients survived a median OS of 18.0 months while AO patients did not reach median OS at median follow-up of 11.5 months (range 2.7-65 months). Good performance status of Eastern Cooperative Oncology Group 0 and 1 showed prolonged OS (p<0.01).
Conclusion
For recurrent AO/AOA after surgery followed by radiation therapy, TMZ could be recommended as a salvage therapy at the estimated efficacy equal to procarbazine, lomustine, and vincristine (PCV) chemotherapy at first relapse. For patients previously treated with PCV, TMZ is a favorable therapeutic option as 2nd line salvage chemotherapy with an acceptable toxicity rate.
doi:10.3340/jkns.2013.54.6.489
PMCID: PMC3921276  PMID: 24527191
Anaplastic oligodendroglioma; Anaplastic oligoastrocytoma; Chemotherapy; Recurrence; Temozolomide
23.  Validation of the Korean version of the European Organization for Research and Treatment of Cancer brain cancer module (EORTC QLQ-BN20) in patients with brain tumors 
Background
The European Organization for Research and Treatment of Cancer Quality of Life Brain Cancer Module has been translated into Korean, but to date, its reliability and validity have been evaluated in a pilot study alone. The European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire is, overall, a valid instrument to assess the health-related quality of life in Korean cancer patients, although its reliability and validity have not yet been evaluated in patients with brain tumors. This study aimed at evaluating the psychometric properties of these instruments in patients with brain tumors.
Findings
The 2 instruments were used for 307 Korean patients with brain tumors. Multi-trait scaling confirmed the scale structure of the instruments with good item convergent and discriminant validity. The reliability was acceptable for all scales except for cognitive functioning and nausea and vomiting. The instruments could be used to distinguish between clinically distinct groups of patients.
Conclusions
The study findings indicate that the instruments are valid and suitable for the assessment of the health-related quality of life in patients with brain tumors as well as in those with primary brain cancer.
doi:10.1186/1477-7525-11-145
PMCID: PMC3766694  PMID: 23981813
Brain tumor; Health-related quality of life; QLQ-BN20; QLQ-C30; Validation; Korea
24.  CCAR1 promotes chromatin loading of androgen receptor (AR) transcription complex by stabilizing the association between AR and GATA2 
Nucleic Acids Research  2013;41(18):8526-8536.
Androgen receptor (AR), a ligand-dependent transcription factor, plays a critical role in prostate cancer onset and progression, and its transcriptional function is mediated largely by distinct nuclear receptor co-regulators. Here, we show that cell cycle and apoptosis regulator 1 (CCAR1) functions as an AR co-activator. CCAR1 interacted with and enhanced the transcriptional activity of AR. Depletion of CCAR1 caused reduction in androgen-dependent expression of a subset of AR target genes. We further showed that CCAR1 is required for recruitment of AR, MED1 and RNA polymerase II to the enhancers of AR target genes and for androgen-induced long-range prostate specific antigen enhancer–promoter interaction. The molecular mechanism underlying CCAR1 function in AR-mediated transcription involves CCAR1-mediated enhanced recruitment of GATA2, a pioneer factor for AR, to AR-binding sites. CCAR1 stabilized the interaction between AR and GATA2 by interacting directly with both proteins, thereby facilitating AR and GATA2 occupancy on the enhancers. Furthermore, CCAR1 depletion inhibited the growth, migration, invasion of prostate cancer cells and reduced the tumorigenicity of prostate cancer cells in vivo. Our results firmly established CCAR1 as an AR co-activator that plays a key role in AR transcription complex assembly and has an important physiological role in androgen signaling and prostate tumorigenesis.
doi:10.1093/nar/gkt644
PMCID: PMC3794601  PMID: 23887938
25.  Vertebral Distraction during Anterior Cervical Discectomy and Fusion Causes Postoperative Neck Pain 
Objective
Vertebral distraction is routinely performed during anterior cervical discectomy and fusion (ACDF). Overdistraction can injure the facet joints and may cause postoperative neck pain consequently. The purpose of this study was to investigate the clinical relevance of distraction force during ACDF.
Methods
This study included 24 consecutive patients with single level cervical disc disease undergoing single level ACDF. We measure the maximum torque just before the the arm of the Caspar retractor was suspended by the rachet mechanism by turning the lever on the movable arm using a torque meter. In order to turn the lever using the torque driver, we made a linear groove on the top of the lever. We compared the neck disability index (NDI) and visual analogue scale (VAS) scores between the high torque group (distraction force>6 kgf·cm) and the low torque group (distraction force≤6 kgf·cm) at routine postoperative intervals of 1, 3, 5 days and 1, 3, 6 months.
Results
The VAS scores for posterior neck pain had a linear correlation with torque at postoperative 1st and 3rd days (y=0.99×-1.1, r2=0.82; y=0.77×-0.63, r2=0.73, respectively). VAS scores for posterior neck pain were lower in the low torque group than in the high torque group on both 1 and 3 days postoperatively (3.1±1.3, 2.6±1.0 compared with 6.0±0.6, 4.9±0.8, p<0.01). However, the difference in NDI scores was not statistically significant in all postoperative periods.
Conclusion
Vertebral distraction may cause posterior neck pain in the immediate postoperative days. We recommend not to distract the intervertebral disc space excessively with a force of more than 6.0 kgf·cm.
doi:10.3340/jkns.2013.53.5.288
PMCID: PMC3730030  PMID: 23908702
Postoperative pain; Zygapophyseal joint; Spinal fusion; Cervical spine

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