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1.  Late Infection from Anterior Cervical Discectomy and Fusion after Twenty Years 
Korean Journal of Spine  2014;11(1):22-24.
Anterior cervical discectomy and fusion (ACDF) has been performed for degenerative and traumatic cervical diseases to improve pain and neurologic symptoms including sensory change and motor weakness. Infection, however, is a rare complication of ACDF, and late infection is even much rarer. We present a case of late Infection from ACDF C4-5 using Biocompatible Osteoconductive Polymer (BOP) after twenty years in the absence of an esophageal perforation, Zenker's diverticulum, or recent surgery or bacteremia. Late infection from ACDF after 20 years is extremely rare in the literature. However, possibility of such a late complication should be appreciated during the follow-up period and surgical resection will be required for proper treatment.
PMCID: PMC4040633  PMID: 24891869
Infection; Late complication; Late infection
2.  Triple Primary Origin Tumor: A Case Report 
Korean Journal of Spine  2013;10(2):91-93.
Generally, among the extradural spinal tumors, metastatic spinal tumor is much more common than primary spinal tumors. Thus, in the case of a spinal tumor patient with cancer history (such as lung cancer, breast cancer, etc.), we used to infer that the spinal lesion is the metastasis from, primary malignancy. We introduce an experience of a case of triple primary origin tumor in a 57-year-old man. When the spinal lesion was found on the abdominal computed tomography scan, he already had a history of colon cancer and liver cancer. Initially, it was thought that the lesion would probably be a metastatic tumor from the liver or colon cancers, and the operation was performed accordingly. In the pathologic final report, however, the mass was proven to plasmacytoma - the third primary lesion. The patient underwent chemotherapy after surgery. Globally, the triple primary origin tumor has been reported very rarely. With this report, we wish to emphasize the necessity of pathologic confirmation and adequate treatment even in a patient with known malignancies.
PMCID: PMC3941720  PMID: 24757467
Triple primary origin tumor; Spinal metastasis; Primary spinal tumor; Pathologic diagnosis
3.  New Classification of Focal Cortical Dysplasia: Application to Practical Diagnosis 
Journal of Epilepsy Research  2012;2(2):38-42.
Background and Purpose:
Malformation of cortical development (MCD) is a well-known cause of drug-resistant epilepsy and focal cortical dysplasia (FCD) is the most common neuropathological finding in surgical specimens from drug-resistant epilepsy patients. Palmini’s classification proposed in 2004 is now widely used to categorize FCD. Recently, however, Blumcke et al. recommended a new system for classifying FCD in 2011.
We applied the new classification system in practical diagnosis of a sample of 117 patients who underwent neurosurgical operations due to drug-resistant epilepsy at Severance Hospital in Seoul, Korea.
Among 117 cases, a total of 16 cases were shifted to other FCD subtypes under the new classification system. Five cases were reclassified to type IIIa and five cases were categorized as dual pathology. The other six cases were changed within the type I category.
The most remarkable changes in the new classification system are the advent of dual pathology and FCD type III. Thus, it will be very important for pathologists and clinicians to discriminate between these new categories. More large-scale research needs to be conducted to elucidate the clinical influence of the alterations within the classification of type I disease. Although the new FCD classification system has several advantages compared to the former, the correlation with clinical characteristics is not yet clear.
PMCID: PMC3952321  PMID: 24649461
Epilepsy; Focal cortical dysplasia; Malformations of cortical development
4.  Cytologic Features of Giant Cell Ependymoma: A Case Report and Review of the Literature 
Korean Journal of Pathology  2012;46(5):507-513.
Here, we present a case of anaplastic giant cell ependymoma (GCE) occurring in a 15-year-old woman. Squash smear slides for intraoperative frozen section diagnosis revealed oval to round cell clusters with a papillary structure in a fibrillary background. This was occasionally accompanied by the presence of bizarre pleomorphic giant cells with hyperchromatic nuclei and prominent intranuclear inclusions. These intranuclear inclusions were a key clue to diagnosis of ependymoma. Histologic analysis revealed features of a high-grade tumor with perivascular pseudorosettes and bizarre pleomorphic giant cells, which established the diagnosis of GCE. We performed a review of literatures about the cytologic features of GCE, including our case, thus proposing that intraoperative frozen diagnosis of GCE would be established by squash smear preparations featuring the mitosis and necrosis, as well as the high cellularity, and the presence of giant cells showing hyperchromatic nuclei with eosinophilic cytoplasm and intranuclear inclusions/pseudoinclusions.
PMCID: PMC3490116  PMID: 23136581
Ependymoma; Intranuclear inclusion bodies; Giant cells
5.  Identification of prognostic gene signatures of glioblastoma: a study based on TCGA data analysis 
Neuro-Oncology  2013;15(7):829-839.
The Cancer Genome Atlas (TCGA) project is a large-scale effort with the goal of identifying novel molecular aberrations in glioblastoma (GBM).
Here, we describe an in-depth analysis of gene expression data and copy number aberration (CNA) data to classify GBMs into prognostic groups to determine correlates of subtypes that may be biologically significant.
To identify predictive survival models, we searched TCGA in 173 patients and identified 42 probe sets (P = .0005) that could be used to divide the tumor samples into 3 groups and showed a significantly (P = .0006) improved overall survival. Kaplan-Meier plots showed that the median survival of group 3 was markedly longer (127 weeks) than that of groups 1 and 2 (47 and 52 weeks, respectively). We then validated the 42 probe sets to stratify the patients according to survival in other public GBM gene expression datasets (eg, GSE4290 dataset). An overall analysis of the gene expression and copy number aberration using a multivariate Cox regression model showed that the 42 probe sets had a significant (P < .018) prognostic value independent of other variables.
By integrating multidimensional genomic data from TCGA, we identified a specific survival model in a new prognostic group of GBM and suggest that molecular stratification of patients with GBM into homogeneous subgroups may provide opportunities for the development of new treatment modalities.
PMCID: PMC3688008  PMID: 23502430
comparative genomic hybridization; EMT; gene expression; glioblastoma; prognostic marker; TCGA
6.  Alteration of Ryanodine-receptors in Cultured Rat Aortic Smooth Muscle Cells 
Vascular smooth muscle cells can obtain a proliferative function in environments such as atherosclerosis in vivo or primary culture in vitro. Proliferation of vascular smooth muscle cells is accompanied by changes in ryanodine receptors (RyRs). In several studies, the cytosolic Ca2+ response to caffeine is decreased during smooth muscle cell culture. Although caffeine is commonly used to investigate RyR function because it is difficult to measure Ca2+ release from the sarcoplasmic reticulum (SR) directly, caffeine has additional off-target effects, including blocking inositol trisphosphate receptors and store-operated Ca2+ entry. Using freshly dissociated rat aortic smooth muscle cells (RASMCs) and cultured RASMCs, we sought to provide direct evidence for the operation of RyRs through the Ca2+- induced Ca2+-release pathway by directly measuring Ca2+ release from SR in permeabilized cells. An additional goal was to elucidate alterations of RyRs that occurred during culture. Perfusion of permeabilized, freshly dissociated RASMCs with Ca2+ stimulated Ca2+ release from the SR. Caffeine and ryanodine also induced Ca2+ release from the SR in dissociated RASMCs. In contrast, ryanodine, caffeine and Ca2+ failed to trigger Ca2+ release in cultured RASMCs. These results are consistent with results obtained by immunocytochemistry, which showed that RyRs were expressed in dissociated RASMCs, but not in cultured RASMCs. This study is the first to demonstrate Ca2+ release from the SR by cytosolic Ca2+ elevation in vascular smooth muscle cells, and also supports previous studies on the alterations of RyRs in vascular smooth muscle cells associated with culture.
PMCID: PMC3282232  PMID: 22359482
Cell culture; Ca2+-induced Ca2+ release; Ryanodine receptor; Rat aortic smooth muscle
7.  Indoleamine 2,3-dioxygenase (IDO) is frequently expressed in stromal cells of Hodgkin lymphoma and is associated with adverse clinical features: a retrospective cohort study 
BMC Cancer  2014;14:335.
Regulation of tumor microenvironment is closely involved in the prognosis of Hodgkin lymphoma (HL). Indoleamine 2,3-dioxygenase (IDO) is an enzyme acting as immune modulator through suppression of T-cell immunity. This study aims to investigate role of IDO in the microenvironment of HL.
A total of 121 cases of HL were enrolled to do immunohistochemistry for IDO, CD163, CD68, CD4, CD8, and FoxP3. Positivity was evaluated from area fractions or numbers of positive cells using automated image analyzer. Correlations between IDO expression and various cellular infiltrates and clinicopathologic parameters were examined and survival analyses were performed.
IDO was expressed in histiocytes, dendritic cells and some endothelial cells with variable degrees, but not in tumor cells. IDO positive cells were more frequently found in mixed cellularity type than other histologic types, and in cases with EBV+, high Ann Arbor stages, B symptoms, and high IPS (all p < 0.05). High IDO expression was associated with inferior survival (p < 0.001) and reflects an independent prognostic factor in nodular sclerosis HL.
This is the first study suggesting that IDO is the principle immunomodulator and is involved to adverse clinical outcomes of HL.
PMCID: PMC4026588  PMID: 24886161
Hodgkin disease; Indoleamine-pyrrole 2,3-dioxygenase; Macrophages; Stromal cells; Tumor microenvironment; Epstein-barr virus infections; Pathology
8.  Asymptomatic thoracic Pantopaque cyst mimicking an intradural extramedullary lipoma on MR images 
European Spine Journal  2012;22(Suppl 3):321-328.
Oil-based contrast media such as Pantopaque have not used for imaging for several decades, but because these contrast media have an extremely low clearance rate, the remnant contrast media or residual sequelae of these materials may be encountered in the clinical field.
Clinical presentation
A 63-year-old woman presented to our hospital complaining of increasing lower back pain and lower extremity paresthesia with incontinence for 2 years. A plain X-ray film revealed single droplet-like mass at the lower thoracic T9–T10. A magnetic resonance image (MRI) study revealed a dorsally placed extramedullary intradural lesion, compressing the thoracic cord and minimally displacing it anteriorly. Spinal stenosis was also noted at the L4–5 level.
The patient was performed for two consecutive surgeries. Total laminectomy was performed at T9–T10 to remove mass. A 0.5 × 0.5 × 4 cm yellowish intradural extramedullary cystic mass was removed without any leakage of cystic contents. Partial hemi-laminectomy and foraminotomy was then done at L4–5 levels for radiculopathy symptom relief. The fluid from the cyst was composed mainly of iodide.
Intraspinal masses showing metal-like density in X-ray or computed tomography but in MRI showing only lipoma or cystic lesions, not metallic characteristics, the differential diagnosis should include iophendylate (Pantopaque) cyst. Oil-based contrast medium is believed to have the potential to make a syrinx formation via arachnoiditis, which can lead to severe neurologic deteriorations, so even if the patients do not represent with an acute neurologic deficit, surgical total removal of remnant material without leaking should be considered.
PMCID: PMC3641277  PMID: 22610440
Arachnoiditis; Arachnoid cysts; Contrast media; Iophendylate; Pantopaque
9.  Glioma is formed by active Akt1 alone and promoted by active Rac1 in transgenic zebrafish 
Neuro-Oncology  2013;15(3):290-304.
Ongoing characterization of glioma has revealed that Akt signaling plays a crucial role in gliomagenesis. In mouse models, however, Akt alone was not sufficient to induce glioma.
We established transgenic zebrafish that overexpressed dominant-active (DA) human Akt1 or Rac1G12V (DARac1) at ptf1a domain and investigated transgenic phenotypes and mechanisms leading to gliomagenesis.
Transgene expressions were spatiotemporally restricted without any developmental abnormality of embryos and persisted at cerebellum and medulla in adult zebrafish. DAAkt1 alone induced glioma (with visible bumps at the head), with incidences of 36.6% and 49% at 6 and 9 months, respectively. Histologically, gliomas showed various histologic grades, increased proliferation, and frequent invasion into the fourth ventricle. Preferential location of small tumors at periventricular area and coexpression of Her4 suggested that tumors originated from Ptf1a- and Her4-positive progenitor cells at ventricular zone. Gliomagenesis was principally mediated by activation of survival pathway through upregulation of survivin genes. Although DARac1 alone was incapable of gliomagenesis, when coexpressed with DAAkt1, gliomagenesis was accelerated, showing higher tumor incidences (62.0% and 73.3% at 6 and 9 months, respectively), advanced histologic grade, invasiveness, and shortened survival. DARac1 upregulated survivin2, cyclin D1, β-catenin, and snail1a but downregulated E-cadherin, indicating that DARac1 promotes gliomagenesis by enhancing proliferation, survival, and epithelial-to-mesenchymal transition. On pharmacologic tests, only Akt1/2 inhibitor effectively suppressed gliomagenesis, inhibited cellular proliferation, and induced apoptosis in established gliomas.
The zebrafish model reinforces the pivotal role of Akt signaling in gliomagenesis and suggests Rac1 as an important protein involved in progression.
PMCID: PMC3578497  PMID: 23325864
Akt1; epithelial-mesenchymal transition; glioma; Rac1; transgenic zebrafish
10.  Feasibility and Outcomes of Hypofractionated Simultaneous Integrated Boost-Intensity Modulated Radiotherapy for Malignant Gliomas: A Preliminary Report 
Yonsei Medical Journal  2013;55(1):70-77.
The aim of this study was to assess the feasibility and efficacy of hypofractionated simultaneous integrated boost-intensity modulated radiotherapy (SIB-IMRT) using three-layered planning target volumes (PTV) for malignant gliomas.
Materials and Methods
We conducted a retrospective analysis of 12 patients (WHO grade IV-10; III-2) postoperatively treated with SIB-IMRT with concurrent temozolomide. Three-layered PTVs were contoured based on gadolinium-enhanced magnetic resonance imaging as follows; high risk PTV (H-PTV) as the area of surgical bed including residual gross tumor with a 0.5 cm margin; low risk PTV (L-PTV) as the area surrounding the high risk PTV with 1.5 cm margin; moderate risk PTV (M-PTV) as a line at one-third the distance from high risk PTV to low risk PTV. Total dose to high risk PTV was 70 Gy in 8 and 62.5 Gy in 4 patients.
The median follow-up time was 52 months in surviving patients. The 2- and 5-year overall survival (OS) rates were 66.6% and 47.6%, respectively. The 2- and 5-year progression-free survival (PFS) rates were 57.1% and 45.7%, respectively. The median OS and PFS were 48 and 31 months, respectively. Six patients (50%) progressed: in-field only in one, out-field or disseminated in 4, and both in one patient. All patients completed planned treatments without a toxicity-related gap. Asymptomatic radiation necrosis was observed in 4 patients at post-radiotherapy 9-31 months.
An escalated dose of hypofractionated SIB-IMRT using three-layered PTVs can be safely performed in patients with malignant glioma, and might contribute to better tumor control and survival.
PMCID: PMC3874925  PMID: 24339289
Radiotherapy; intensity-modulated; malignant glioma; hypofractionation; simultaneous integrated boost
11.  Development of Inspection Robots for Bridge Cables 
The Scientific World Journal  2013;2013:967508.
This paper presents the bridge cable inspection robot developed in Korea. Two types of the cable inspection robots were developed for cable-suspension bridges and cable-stayed bridge. The design of the robot system and performance of the NDT techniques associated with the cable inspection robot are discussed. A review on recent advances in emerging robot-based inspection technologies for bridge cables and current bridge cable inspection methods is also presented.
PMCID: PMC3888749  PMID: 24459453
12.  Diagnostic Accuracy of Cerebrospinal Fluid (CSF) Cytology in Metastatic Tumors: An Analysis of Consecutive CSF Samples 
Korean Journal of Pathology  2013;47(6):563-568.
Cerebrospinal fluid (CSF) examination can be used to verify the presence of primary malignancies as well as cases of central nervous system (CNS) metastasis. Because of its importance, there have been several studies concerning the sensitivity of CSF cytology. To determine the practical use and reproducibility of diagnoses based on CSF cytology, we evaluated this test by analyzing cytology results from consecutive CSF samples.
Between July 2010 and June 2013, 385 CSF cytology samples from 42 patients were collected. The samples were gathered using a ventricular catheter and reservoir. CSF cytology of all patients was examined more than two times with immunocytochemistry for cytokeratin.
Primary neoplastic sites and histologic types of patients' metastatic cancer were diverse. The overall sensitivity for detecting malignancy was 41.3%. Even within short-term intervals, diagnoses frequently changed.
Our results were inconsistent, with low sensitivity, when compared to the results of previous studies. However, CSF evaluation can still provide valuable diagnostic and prognostic information because adjuvant treatments are now routinely performed in patients with CNS metastasis. Negative CSF cytology results should not be ignored, and continuous CSF follow-up is essential for following the clinical course of patients with metastatic cancer involving the CNS.
PMCID: PMC3887159  PMID: 24421850
Central nervous system; Neoplasm metastasis; Cerebrospinal fluid
13.  IgG4-Related Sclerosing Disease Involving the Superior Vena Cava and the Atrial Septum of the Heart 
Yonsei Medical Journal  2013;54(5):1285-1288.
A 55-year-old woman presented with frequent episodes of syncope due to sinus pauses. During ambulatory Holter monitoring, atrial fibrillation and first-degree atrioventricular nodal block were observed. Magnetic resonance imaging and CT scans showed a tumor-like mass from the superior vena cava to the right atrial septum. Open chest cardiac biopsy was performed. The tumor was composed of proliferating IgG4-positive plasma cells and lymphocytes with surrounding sclerosis. The patient was diagnosed with IgG4-related sclerosing disease. Because of frequent sinus pauses and syncope, a permanent pacemaker was implanted. The cardiac mass was inoperable, but it did not progress during the one-year follow-up.
PMCID: PMC3743176  PMID: 23918583
IgG4-related sclerosing disease; sinoatrial node dysfunction; pacemaker
14.  Preoperative N Staging of Gastric Cancer by Stomach Protocol Computed Tomography 
Journal of Gastric Cancer  2013;13(3):149-156.
Clinical stage of gastric cancer is currently assessed by computed tomography. Accurate clinical staging is important for the tailoring of therapy. This study evaluated the accuracy of clinical N staging using stomach protocol computed tomography.
Materials and Methods
Between March 2004 and November 2012, 171 patients with gastric cancer underwent preoperative stomach protocol computed tomography (Jeju National University Hospital; Jeju, Korea). Their demographic and clinical characteristics were reviewed retrospectively. Two radiologists evaluated cN staging using axial and coronal computed tomography images, and cN stage was matched with pathologic results. The diagnostic accuracy of stomach protocol computed tomography for clinical N staging and clinical characteristics associated with diagnostic accuracy were evaluated.
The overall accuracy of stomach protocol computed tomography for cN staging was 63.2%. Computed tomography images of slice thickness 3.0 mm had a sensitivity of 60.0%; a specificity of 89.6%; an accuracy of 78.4%; and a positive predictive value of 78.0% in detecting lymph node metastases. Underestimation of cN stage was associated with larger tumor size (P<0.001), undifferentiated type (P=0.003), diffuse type (P=0.020), more advanced pathologic stage (P<0.001), and larger numbers of harvested and metastatic lymph nodes (P<0.001 each). Tumor differentiation was an independent factor affecting underestimation by computed tomography (P=0.045).
Computed tomography with a size criterion of 8 mm is highly specific but relatively insensitive in detecting nodal metastases. Physicians should keep in mind that computed tomography may not be an appropriate tool to detect nodal metastases for choosing appropriate treatment.
PMCID: PMC3804673  PMID: 24156034
Stomach neoplasms; Neoplasm staging; Technology, radiologic
15.  The Role of Adiponectin in Secondary Inflammatory Reaction in Cerebral Ischemia 
In this study, we investigate the role of adiponectin in the interaction between leukocytes and endothelium in the secondary inflammatory reaction of cerebral ischemia.
Adiponectin knock-out mice group (APN-KO) (n = 8) and wild-type mice group (WT) (n = 8) were prepared. Each group was sub-divided into 2 groups by reperfusion time. One-hour middle cerebral artery occlusion and reperfusion were induced using the intraluminal filament technique. At 6 and 12 hours after the occlusion, the mice were placed on a stereotactic frame to perform craniotomy in the left parietal area. After craniotomy, a straight pial venule was selected as a target vessel. With the fluorescence intravital microscope, the number of rolling leukocytes and leukocytes that adhered to endothelium were counted and documented at 6 and 12 hours after the reperfusion.
At 6 and 12 hours after the reperfusion, more rolling leukocyte and leukocyte adhesion were observed in the APN-KO mice than in the WT mice. The difference in leukocyte numbers between the APN-KO and WT mice was found to be statistically significant (p = 0.029) by Mann-Whitney U-test.
We found that adiponectin inhibits the interaction between the endothelium and leukocytes in cerebral ischemia-reperfusion. Therefore adiponectin might prevent the secondary insult caused by the inflammation reaction.
PMCID: PMC3804654  PMID: 24167796
Adiponectin; Cerebral ischemia; Secondary inflammatory reaction; MCAO-R
16.  Primary Cardiac Angiofibroma 
Korean Circulation Journal  2013;43(9):636-639.
Cardiac Angiofibroma is an uncommon intracardiac tumor. Thus far, only 4 cases of the rare intracardiac tumor have been reported. The present case-report describes an intracardiac angiofibroma in a 57-year-old healthy female. The patient was incidentally diagnosed with a left ventricle mass during echocardiography. We performed cardiac imaging, surgical excision and histological evaluation of the mass. The angiofibroma demonstrated features different from the relatively common cardiac tumors such as fibroma, myxoma and angiosarcoma. The cardiac MRI showed slightly high signal intensity on both T1 and T2, with the central core of lower signal intensity. The resected tumor was a whitish and rubbery mass. Histologically, the tumor showed the benign vascular proliferations associated with the surrounding collagen deposition.
PMCID: PMC3808861  PMID: 24174966
Cardiac tumor; Magnetic resonance imaging
17.  Rupture of De Novo Anterior Communicating Artery Aneurysm 8 Days after the Clipping of Ruptured Middle Cerebral Artery Aneurysm 
Rapidly developed de novo aneurysm is very rare. We present a rapidly developed and ruptured de novo anterior communicating aneurysm 8 days after the rupture of another aneurysm. This de novo aneurysm was not apparent in the initial 3-dimensional computed tomography and digital subtraction angiography. We reviewed the literature and discussed possible mechanisms for the development of this de novo aneurysm.
PMCID: PMC3836932  PMID: 24278654
De novo aneurysm; Subarachnoid hemorrhage; Aneurysm formation; Computed tomography angiography; Digital subtraction angiography
18.  Clinical necessity of the immunohistochemical reassessment of para-aortic lymph nodes in resected pancreatic ductal adenocarcinoma 
Oncology Letters  2013;6(5):1189-1194.
Para-aortic lymph node (PALN) metastasis is widely regarded as a systemic disease in cancer. Undetected PALN micrometastases during routine hematoxylin and eosin (HE) staining may be a cause of poor prognosis following a potentially curative pancreatectomy for pancreatic cancer. In the present study, paraffin-embedded PALN tissue blocks from 99 patients who underwent a pancreatectomy were re-evaluated by immunohistochemical staining using cytokeratin (CK)-19. Patients with PALN metastasis were summarized according to the clinicopathological data. A total of 484 PALNs (median, 4.9 nodes per patient; range, 1–19) were evaluated. PALN metastases were revealed in eight patients (8.1%) by routine HE staining of frozen section biopsies and in one patient (1.0%) by HE staining of a permanent section. Only one patient (1.0%) demonstrated micrometastasis by IHC; this patient did not display any adverse pathological characteristics and had a relatively favorable survival period of 41 months. The present study concluded that an additional reassessment for micrometastasis in PALNs using CK-19 immunohistochemistry (IHC) is not a viable method for determining the survival outcome. A careful examination of a frozen section biopsy is sufficient for attempting curative surgery.
PMCID: PMC3813805  PMID: 24179493
pancreatic cancer; paraaortic lymph node; micrometastasis; immunohistochemistry
19.  Evidence for the Primo Vascular System above the Epicardia of Rat Hearts 
We for the first time reported evidence for the existence of a novel network, a PVS, abovethe epicardium of the rat heart. (1) We were consecutively able to visualize the PVs and the PNs above the epicardial spaces of five rats' hearts by using Cr-Hx spraying or injection. (2) Hematoxylin and eosin (H&E) and toluidine blue staining of the PVs and the PNs showed that they consisted of a basophilic matrix; specifically the PNs contained several mast cells, some of which were degranulating into pericardial space. Also, 4′, 6-diamidino-2 phenylindole (DAPI) images of the PVs and the PNs showed that they contained various kinds of cells. (3) Transmission electron microscopic (TEM) longitudinal image of the PVs showed that the sinuses contained many granules with high-electron-density cores in parallel with putative endothelial cells. (4) TEM images of the PNs demonstrated that they consisted of lumen-containing cells surrounded by fibers and that they had mast cells that were degranulating toward the epicardium of the rat heart. The above data suggest that mast-cells-containing novel network exists above the epicardium of the rat heart.
PMCID: PMC3762136  PMID: 24023576
20.  Relapsed Herpes Simplex Virus Encephalitis after Epilepsy Surgery 
Journal of Epilepsy Research  2013;3(1):28-31.
Relapsed herpes simplex virus (HSV) encephalitis after neurosurgery is a very rare condition. An 11-year-old boy suffered from relapsed HSV encephalitis five days after neurosurgery to remove the epileptogenic focus six years after prior HSV encephalitis. He was diagnosed with HSV encephalitis reactivation after positive HSV polymerase chain reaction results following a lumbar puncture, and this diagnosis was supported by consistent radiologic and histopathologic findings. Moreover, focal cortical dysplasia coexisted with inflammatory changes resulting from a viral infection based upon the removed brain tissue. This case may support the hypothesis that neurosurgery may be a triggering factor of HSV reactivation.
PMCID: PMC3957312  PMID: 24649468
Herpes simplex virus; Encephalitis; Neurosurgery
21.  Solitary Primary Leptomeningeal Glioma: Case Report 
We report a case of solitary primary leptomeningeal glioma. The mass was totally removed under awake surgery. Intraoperatively, no parenchymal involvement was noted. Histopathological study revealed a predominant anaplastic oligodendroglioma component and a focal anaplastic astrocytoma component, which was consistent with an anaplastic oligoastrocytoma. Adjuvant tomotherapy was followed and the tumor has not recurred until 12 months after surgery. A focal type of primary leptomeningeal glioma is extremely rare. We report a rare case of solitary primary leptomeningeal anaplastic oligoastrocytoma.
PMCID: PMC4027116  PMID: 24904888
Glioma; Leptomeningeal; Oligoastrocytoma; Solitary
22.  Development of a porcine skin injury model and characterization of the dose-dependent response to high-dose radiation 
Journal of Radiation Research  2013;54(5):823-831.
A porcine skin model was developed to characterize the dose-dependent response to high-dose radiation. The dorsal skin of a mini pig was divided into four paraspinal sections, with 11 small irradiation fields (2 cm × 2 cm) in each section, and a single fraction of 15, 30, 50 or 75 Gy was delivered to each section using a 6 MeV electron beam. A spectrophotometer measured gross skin changes, and a biopsy for each radiation dose was performed in the 1st, 2nd, 4th, 6th and 9th weeks for histology, immunostaining with anti-CD31, and western blotting with IL-6 and TGF-β1 to determine the degree of skin damage. After a 4-week latency period, erythema and dry desquamation, moist desquamation, and ulceration appeared at 4, 6 and 9 weeks, respectively. Gross skin toxicity was more pronounced, occurred early and continued to progress with irradiation >50 Gy, whereas complete healing was observed 12 weeks after 15 Gy. Spectrophotometry showed erythema indices rapidly increased during the first 4 weeks after irradiation. The number of eosinophils began rising sharply at 4 weeks and normalized after reaching peaks at 7–8 weeks. Microvessel density showed a biphasic pattern with a transient peak at 1 week, a nadir at 4–6 weeks, and maximum recovery at 9 weeks. Increase in the levels of IL-6 and TGF-β1 was detected soon after irradiation. Most of these parameters indicated complete healing of the skin 12 weeks after 15 Gy. Our porcine skin model provides an effective platform for studying high-dose radiation-induced skin injury, in particular histologic and molecular changes, during the early latency period.
PMCID: PMC3766288  PMID: 23449639
radiation skin injury; porcine skin model; high-dose radiation
23.  Induction of cytokines and growth factors by rapamycin in the microenvironment of brain metastases of lung cancer 
Oncology Letters  2013;5(3):953-958.
The association between rapamycin and astrocytes in a tumor-bearing mouse model with brain metastases of non-small cell lung cancer (NSCLC) was investigated. For in vitro experiments, NCI-H358, a human lung adenocarcinoma cell line, was co-cultured with immortalized astrocytes, and treated with rapamycin, an mTOR inhibitor. We evaluated the expression of interleukin-1 (IL-1), interleukin-3 (IL-3), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), insulin-like growth factor-1 (IGF-1), platelet-derived growth factor (PDGF), chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1 (MIP-1) in tumor cells in vivo. Rapamycin is cytotoxic in vitro; however, co-culturing tumor cells and astrocytes induced tumor cell survival. IL-1, IL-3, IL-6, TNF-α, TGF-β, PDGF, MCP-1 and MIP-1 expression were higher in rapamycin-treated mice compared to the control group, however, IGF-1 expression was lower. Notably, treatment with rapamycin before inoculating tumor cells affected cytokine expression in the tumor microenvironment. We suggest that growth factors and cytokines in the tumor microenvironment play a role in the survival of cancer cells in brain metastases.
PMCID: PMC3576186  PMID: 23426399
brain metastasis; non-small cell lung cancer; rapamycin; astrocytes; microenvironment
24.  Correlations of Dynamic Contrast-Enhanced Magnetic Resonance Imaging with Morphologic, Angiogenic, and Molecular Prognostic Factors in Rectal Cancer 
Yonsei Medical Journal  2012;54(1):123-130.
To investigate the correlations between parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and prognostic factors in rectal cancer.
Materials and Methods
We studied 29 patients with rectal cancer who underwent gadolinium contrast-enhanced, T1-weighted DCE-MRI with a three Tesla scanner prior to surgery. Signal intensity on DCE-MRI was independently measured by two observers to examine reproducibility. A time-signal intensity curve was generated, from which four semiquantitative parameters were calculated: steepest slope (SLP), time to peak (Tp), relative enhancement during a rapid rise (Erise), and maximal enhancement (Emax). Morphologic prognostic factors including T stage, N stage, and histologic grade were identified. Tumor angiogenesis was evaluated in terms of microvessel count (MVC) and microvessel area (MVA) by morphometric study. As molecular factors, the mutation status of the K-ras oncogene and microsatellite instability were assessed. DCE-MRI parameters were correlated with each prognostic factor using bivariate correlation analysis. A p-value of <0.05 was considered significant.
Erise was significantly correlated with N stage (r=-0.387 and -0.393, respectively, for two independent data), and Tp was significantly correlated with histologic grade (r=0.466 and 0.489, respectively). MVA was significantly correlated with SLP (r=-0.532 and -0.535, respectively) and Erise (r=-0.511 and -0.446, respectively). MVC was significantly correlated with Emax (r=-0.435 and -0.386, respectively). No significant correlations were found between DCE-MRI parameters and T stage, K-ras mutation, or microsatellite instability.
DCE-MRI may provide useful prognostic information in terms of histologic differentiation and angiogenesis in rectal cancer.
PMCID: PMC3521250  PMID: 23225808
Colorectal neoplasms; prognosis; diagnostic imaging; magnetic resonance imaging
25.  Immediately transcripted genes in various hepatic ischemia models 
To elucidate the characteristic gene transcription profiles among various hepatic ischemia conditions, immediately transcribed genes and the degree of ischemic injury were compared among total ischemia (TI), intermittent clamping (IC), and ischemic preconditioning (IPC).
Sprague-Dawley rats were equally divided into control (C, sham-operated), TI (ischemia for 90 minutes), IC (ischemia for 15 minutes and reperfusion for 5 minutes, repeated six times), and IPC (ischemia for 15 minutes, reperfusion for 5 minutes, and ischemia again for 90 minutes) groups. A cDNA microarray analysis was performed using hepatic tissues obtained by partial hepatectomy after occluding hepatic inflow.
The cDNA microarray revealed the following: interleukin (IL)-1β expression was 2-fold greater in the TI group than in the C group. In the IC group, IL-1α/β expression increased by 2.5-fold, and Na+/K+ ATPase β1 expression decreased by 2.4-fold. In the IPC group, interferon regulatory factor-1, osteoprotegerin, and retinoblastoma-1 expression increased by approximately 2-fold compared to that in the C group, but the expression of Na+/K+ ATPase β1 decreased 3-fold.
The current findings revealed characteristic gene expression profiles under various ischemic conditions. However, additional studies are needed to clarify the mechanism of protection against IPC.
PMCID: PMC3491232  PMID: 23166889
Reperfusion injury; Ischemic preconditioning; Necrosis; Apoptosis; Microarray analysis

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