• Clinical and Experimental Pediatrics
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• v.49 no.1
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• pp.76-81
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• 2006

Purpose : This study evaluated the clinical characteristics of brain tumors in children according to their location, the parental delay and the doctor's delay between the onset of symptoms and the diagnosis of a pediatric brain tumor. In addition, this study compared the relationship between the pre-diagnostic symptomatic interval and the tumor location. Methods : A retrospective study was undertaken of 45 children with primary brain tumors admitted to Inha Hospital from July, 1986 to June, 2004. A diagnosis of the tumor location was made using brain MRI. Results : The male to female ratio was 1 : 0.67. The median age at diagnosis was 6.0 years in supratentorial tumors, 7.0 years in infratentorial tumors. Twenty four cases(53.3 percent) were located in the supratentorial area, 21 cases(46.6 percent) were located in the infratentorial area. The distribution of supratentorial tumors were 14(58.3 percent) in the cerebral hemisphere and temporal lobe, seven (29.1 percent) in the suprasellar area, and three(12.5 percent) in the pineal gland and posterial lateral ventricle. The distributions of the infratentorial tumors were 12(57.1 percent) in the cerebellar vermis and fourth ventricle, four(19.1 percent) in the brain stem, and five(23.8 percent) in the cerebellar hemisphere. The most common initial symptom was seizure(37.5 percent) in the supratentorial tumor and headache(38.0 percent) in infratentorial tumors. The median pre-diagnostic symptomatic interval (PSI) was 21 days(range 0-240 days). The median PSI with a parental delay in supratentorial tumor was six days(range 1-240 days), and 30 days(range 1-40 days) in the infratentorial tumor. We immediately diagnosed most cases after visiting the hospital. There was no significant relationship between the tumor location and the pre-diagnostic symptomatic interval. Conclusion : The most common symptom of supratentorial tumors and infratentorial tumors was seizure and headache, respectively. Although, the median pre-diagnostic symptomatic interval was shorter than in previous studies, a detailed medical history and a correctly interpreted neurological examination should lead to an earlier diagnosis of pediatric brain tumors.

• The Journal of Korean Society for Radiation Therapy
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• v.28 no.2
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• pp.139-148
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• 2016

Purpose : Range Compensator used for proton therapy compensates the proton beam dose which delivers to the normal tissues according to the Target's Distal Margin dose. We are going to check the improvement of dose on the target part by comparing the dose of PTV and OAR according to applying in different method of Smooth Thickness of Range Compensator which is used in brain tumor therapy. Materials and Methods : For 10 brain tumor patients taking proton therapy in National Cancer Center, Apply Smooth Thickness applied in Range Compensator in order from one to five by using Compensator Editor of Eclipse Proton Planning System(Version 10.0, Varian, USA). The therapy plan algorithm used Proton Convolution Superposition(version 8.1.20 or 10.0.28), and we compared Dmax, Dmin, Homogeneity Index, Conformity Index and OAR dose around tumor by applying Smooth Thickness in phase. Results : When Smooth Thickness was applied from one to five, the Dmax of PTV was decreased max 4.3%, minimum at 0.8 and average of 1.81%. Dmin increased max 1.8%, min 1.8% and average. Difference between max dose and minimum dose decreased at max 5.9% min 1.4% and average 2.6%. Homogeneity Index decreased average of 0.018 and Conformity Index didn't had a meaningful change. OAR dose decreased in Brain Stem at max 1.6%, min 0.1% and average 0.6% and in Optic Chiasm max 1.3%, min 0.3%, and average 0.5%. However, patient C and patient E had an increase each 0.3% and 0.6%. Additionally, in Rt. Optic Nerve, there was a decrease at max 1.5%, min 0.3%, and average 0.8%, however, patient B had 0.1% increase. In Lt. Optic Nerve, there was a decrease at max 1.8%, min 0.3%, and average 0.7%, however, patient H had 0.4 increase. Conclusion : As Smooth Thickness of Range Compensator which is used as the proton treatment for brain tumor patients is applied in stages, the resolution of Compensator increased and as a result the most optimized amount of proton beam dose can be delivered. This is considered to be able to irradiate the equal amount at PTV and reduce the unnecessary dose applied at OAR to reduce the side effects.

• Progress in Medical Physics
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• v.27 no.1
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• pp.14-24
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• 2016

Since the head and neck region is densely located with organs at risk (OAR), OAR-sparing is an important issue in the treatment of head and neck cancers. This study-in which different treatment plans were performed varying the head tilt angle on brain tumor patients-investigates the optimal head elevation angle for sparing normal organs (e.g. the hippocampus) and further compares the dosimetric characteristics of different types of radiation equipment. we performed 3D conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), and tomotherapy on 10 patients with brain tumors in the frontal lobe while varying the head tilt angle of patients to analyze the dosimetric characteristics of different therapy methods. In each treatment plan, 95% of the tumor volume was irradiated with a dose of 40 Gy in 10 fractions. The step and shoot technique with nine beams was used for IMRT, and the same prescription dose was delivered to the tumor volume for the 3D-CRT and tomotherapy plans. The homogeneity index, conformity index, and normal tissue complication probability (NTCP) were calculated. At a head elevation angle of $30^{\circ}$, conformity of the isodose curve to the target increased on average by 53%, 8%, and 5.4%. In 3D-CRT, the maximum dose received by the brain stem decreased at $15^{\circ}$, $30^{\circ}$, and $40^{\circ}$, compared to that observed at $0^{\circ}$. The NTCP value of the hippocampus observed in each modality was the highest at a head and neck angle of $0^{\circ}$ and the lowest at $30^{\circ}$. This study demonstrates that the elevation of the patients' head tilt angle in radiation therapy improves the target region's homogeneity of dose distribution by increasing the tumor control rate and conformity of the isodose curve to the target. Moreover, the study shows that the elevation of the head tilt angle lowers the NTCP by separating the tumor volume from the normal tissues, which helps spare OARs and reduce the delivered dose to the hippocampus.

• Korean Journal of Materials Research
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• v.20 no.3
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• pp.132-136
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• 2010

This study examined the biostability and drug delivery efficiency of g-$Fe_2O_3$ magnetic nanoparticles (GMNs) by cytotoxicity tests using various tumor cell lines and normal cell lines. The GMNs, approximately 20 nm in diameter, were prepared using a chemical coprecipitation technique, and coated with two surfactants to obtain a water-based product. The particle size of the GMNs loaded on hangamdan drugs (HGMNs) measured 20-50 nm in diameter. The characteristics of the particles were examined by X-ray diffraction (XRD), field emission scanning electron microscopy (FE-TEM) and Raman spectrometer. The Raman spectrum of the GMNs showed three broad bands at 274, 612 and $771\;cm^1$. A 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay showed that the GMNs were non-toxic against human brain cancer cells (SH-SY5Y, T98), human cervical cancer cells (Hela, Siha), human liver cancer cells (HepG2), breast cancer cells (MCF-7), colon cancer cells (CaCO2), human neural stem cells (F3), adult mencenchymal stem cells (B10), human kidney stem cells (HEK293 cell), human prostate cancer (Du 145, PC3) and normal human fibroblasts (HS 68) tested. However, HGMNs were cytotoxic at 69.99% against the DU145 prostate cancer cell, and at 34.37% in the Hela cell. These results indicate that the GMNs were biostable and the HGMNs served as effective drug delivery vehicles.

• Clinical and Experimental Pediatrics
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• v.45 no.8
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• pp.1016-1023
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• 2002

Purpose : Brain tumors are the most common solid tumor in children. We retrospectively investigated the clinical characteristics of pediatric brain tumors, such as age, sex, tumor site and survival, as seen in a single institution over the last 15 years. We tried to evaluate the role of chemotherapy on the survival of some brain tumors. Methods : Three hundred fifty four children with primary brain tumor who were treated at Severance Hospital from Jan. 1985 to Sep. 2001 were enrolled. Results : Pediatric brain tumors were found most frequently in 10-15 years of age group(35.3%) and the ratio of male to female was 1.3 : 1. Supratentorial tumors(52%) were more frequent than infratentorial tumors(48%). Medulloblastoma/primitive neuroectodermal tumor(PNET) was the most common type(24.6%), followed by cerebellar astrocytoma(14.1%). Ten year survival rate of medulloblastoma, cerebellar astrocytoma and cerebral astrocytoma were 59.4%, 79.3% and 71%, respectively. The prognosis for brain stem glioma and glioblastoma multiforme were still grim with a 10 year survival rate of 12.7% and 13.3%, respectively. The addition of chemotherapy for high grade medulloblastoma led to an improved 10 year survival rate of 54.5%, compared with 40% without chemotherapy. Conclusion : The combined use of chemotherapy and radiation and surgery improved survival rate of pediatric brain tumors in our study. Chemotherapy for high grade medulloblastoma improved the 10 year survival rate. Further data analysis of the treatment modalities will lead to better comparisons.

• Journal of Microbiology and Biotechnology
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• v.28 no.1
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• pp.165-174
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• 2018

Glioblastoma multiforme is the most lethal malignant brain tumor. Despite many intensive studies, the prognosis of glioblastoma multiforme is currently very poor, with a median overall survival duration of 14 months and 2-year survival rates of less than 10%. Although viral infections have been emphasized as potential cofactors, their influences on pathways that support glioblastoma progression are not known. Some previous studies indicated that human Kaposi's sarcoma-associated herpesvirus (KSHV) was detected in healthy brains, and its microRNA was also detected in glioblastoma patients' plasma. However, a direct link between KSHV infection and glioblastoma is currently not known. In this study, we infected glioblastoma cells and glioma stem-like cells (GSCs) with KSHV to establish an in vitro cell model for KSHV-infected glioblastoma cells and glioma stem-like cells in order to identify virologic outcomes that overlap with markers of aggressive disease. Latently KSHV-infected glioblastoma cells and GSCs were successfully established. Additionally, using these cell models, we found that KSHV infection modulates the proliferation of glioma stem-like cells.

• Biomedical Science Letters
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• v.19 no.4
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• pp.295-302
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• 2013

Some of the pituitary adenomas are invasive and spread into neighboring tissues. In previous studies, the invasion of pituitary adenomas is thought to be associated with epithelial-mesenchymal transition (EMT). In addition to that, we thought that mesenchymal stem cells (MSCs) exist in relevant microenvironment in pituitary adenoma. However, it has been little known about the existence of MSCs from pituitary adenoma. So we investigated whether mesenchymal stem-like cells (MSLCs) can be isolated from the pituitary adenoma specimen. We isolated and cultured candidate MSLCs from the fresh pituitary adenoma specimen with the same protocols used in culturing bone marrow derived MSCs (BM-MSCs). The cultured candidate MSLCs were analyzed by fluorescence-activated cell sorting (FACS) for surface markers associated with MSCs. Candidate MSLCs were exposed to mesenchymal differentiation conditions to determine the mesenchymal differentiation potential of these cells. To evaluate the tumorigenesis of candidate MSLCs from pituitary adenoma, we implanted these cells into the brain of athymic nude mice. We isolated cells resembling BM-MSCs named pituitary adenoma stroma mesenchymal stem-like cells (PAS-MSLCs). PAS-MSLCs were spindle shaped and had adherent characteristics. FACS analysis identified that the PAS-MSLCs had a bit similar surface markers to BM-MSCs. Isolated cells expressed surface antigen, positive for CD105, CD75, and negative for CD45, NG2, and CD90. We found that these cells were capable of differentiation into adipocytes, osteocytes and chondrocytes. Tumor was not developed in the nude mice brains that were implanted with the PAS-MSLCs. In this study, we showed that MSLCs can be isolated from a pituitary adenoma specimen which is not tumorigenic.

• International Journal of Stem Cells
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• v.17 no.3
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• pp.319-329
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• 2024

Leucine-rich repeat kinase 2 (LRRK2), a large GTP-regulated serine/threonine kinase, is well-known for its mutations causing late-onset Parkinson's disease. However, the role of LRRK2 in glioblastoma (GBM) carcinogenesis has not yet been fully elucidated. Here, we discovered that LRRK2 was overexpressed in 40% of GBM patients, according to tissue microarray analysis, and high LRRK2 expression correlated with poor prognosis in GBM patients. LRRK2 and stemness factors were highly expressed in various patient-derived GBM stem cells, which are responsible for GBM initiation. Canonical serum-induced differentiation decreased the expression of both LRRK2 and stemness factors. Given that LRRK2 is a key regulator of glioma stem cell (GSC) stemness, we developed DNK72, a novel LRRK2 kinase inhibitor that penetrates the blood-brain barrier. DNK72 binds to the phosphorylation sites of active LRRK2 and dramatically reduced cell proliferation and stemness factors expression in in vitro studies. Orthotopic patient-derived xenograft mouse models demonstrated that LRRK2 inhibition with DNK72 effectively reduced tumor growth and increased survival time. We propose that LRRK2 plays a significant role in regulating the stemness of GSCs and that suppression of LRRK2 kinase activity leads to reduced GBM malignancy and proliferation. In the near future, targeting LRRK2 in patients with high LRRK2-expressing GBM could offer a superior therapeutic strategy and potentially replace current clinical treatment methods.

• Journal of Life Science
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• v.29 no.5
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• pp.530-536
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• 2019

Glioblastoma (GBM) is the most incurable brain cancer derived from the transformed glial cells. Standard anti-GBM treatment, including surgery and chemoradiotherapy, does not ensure good prognosis for the patients with GBM, because successful therapy is often impeded by presence of glioma stem cells (GSCs). GSCs, which is generally divided into proneural (PN) and mesenchymal (MES) subtype, are understood as subpopulation of cancer cells responsible for GBM initiation, progression and recurrence after standard treatments. In the present study, we demonstrate that PN subtype GSCs differentially transit to MES subtype GSCs by specific cytokines. The expression of CD44, a marker of MES subtype GSCs, was observed when GSC11 PN subtype GSCs were exposed to tumor necrosis factor alpha ($TNF-{\alpha}$) cytokine and GSC23 PN subtype GSCs were treated to transforming growth factor beta 1 ($TGF-{\beta}1$) cytokine. Ivy glioblastoma atlas project (Ivy GAP) bioinformatics database showed that $TNF-{\alpha}$ and $TGF-{\beta}1$ were highly expressed in necrotic region and perivascular region, respectively. In addition, $TNF-{\alpha}$ signaling was relatively upregulated in necrotic region, while $TGF-{\beta}$ signaling was increased in perivascular region. Taken together, our observations suggest that MES subtype GSCs can be derived from various PN subtype GSCs by multimodal cytokine stimuli provided by neighboring tumor microenvironment.

• Journal of Korean Neurosurgical Society
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• v.30 no.12
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• pp.1399-1405
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• 2001

Objectives : Gliomatosis cerebri is an uncommon primary brain tumor characterized by diffuse neoplastic proliferation of glial cells, with the preservation of the underlying cytoarchitecture. The aim of this study is to evaluate clinical features, outcome of surgical treatment and adjuvant therapy of gliomatosis cerebri. Methods : Between Jan. 1990 and Dec. 2000, 12 patients were diagnosed with gliomatosis cerebri based on characteristic radiological and histological findings. The patients' age ranged from 18 to 77(mean 44) years and the male to female ratio was 7 : 5. Nine patients underwent decompressive surgery and three, biopsy only. Postoperative radiation therapy was given in all cases except three. In addition to radiation therapy, four patients received chemotherapy. The mean duration of follow-up period was 18.8 months. Results : The most common presenting symptom were seizure and motor weakness. The mean duration of symptom was 5.9 months. There was 5 bilateral lesions and tumor involved corpus callosum in 5, basal ganglia-thalamus in 4, and brain stem in 2. There was no operative mortality but four patients died during the follow-up. The mean survival period for 11 patients was 20.5 months from the time of diagnosis. In univariate analysis, the lesion involving corpus callosum, basal ganglia-thalamus and brain stem correlated significantly with the short length of survival(p<0.05). Also, postoperative radiation as a adjuvant therapy prolonged the patient's survival(p<0.05). Conclusions : In the management of gliomatosis cerebri patients, early detection by MR imaging, active management of increased intracranial pressure, decompressive surgical removal and postoperative adjuvant therapy such as radiation is thought to be a good treatment modality.