• Journal of Radiopharmaceuticals and Molecular Probes
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• v.9 no.1
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• pp.3-8
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• 2023

Parkinson's disease is a neurodegenerative disease caused by damage to brain neurons related to dopamine. Non-clinical animal models mainly used in Parkinson's disease research include drug-induced models of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine, and genetically modified transgenic animal models. Parkinson's diagnosis can be made using brain imaging of the substantia nigra-striatal dopamine system and using a radiotracer that specifically binds to the dopamine transporter. In this study, ¹⁸F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane was used to confirm the image evaluation cutoff between normal and parkinson's disease models, and to confirm model persistence over time. In addition, the efficacy of single or combined administration of clinically used therapeutic drugs in parkinson's animal models was evaluated. Image analysis was performed using the PMOD software. Converted to standardized uptake value, and analyzed by standardized uptake value ratio by dividing the average value of left striatum by the average value of right striatum obtained by applying positron emission tomography images to the atlas magnetic resonance template. The image cutoff of the normal and the parkinson's disease model was calculated as SUVR=0.829, and it was confirmed that it was maintained during the test period. In the three-drug combination administration group, the right and left striatum showed a high symmetry of more than 0.942 on average and recovered significantly. Images using ¹⁸F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane are thought to be able to diagnose and evaluate treatment efficacy of non-clinical Parkinson's disease.

• Genomics & Informatics
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• v.13 no.4
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• pp.132-136
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• 2015

Studies of cancer heterogeneity have received considerable attention recently, because the presence or absence of resistant sub-clones may determine whether or not certain therapeutic treatments are effective. Previously, we have reported G64, a co-regulated gene module composed of 64 different genes, can differentiate tumor intra- or inter-subpopulations in lung adenocarcinomas (LADCs). Here, we investigated whether the G64 module genes were also expressed distinctively in different subpopulations of other cancers. RNA sequencing-based transcriptome data derived from 22 cancers, except LADC, were downloaded from The Cancer Genome Atlas (TCGA). Interestingly, the 22 cancers also expressed the G64 genes in a correlated manner, as observed previously in an LADC study. Considering that gene expression levels were continuous among different tumor samples, tumor subpopulations were investigated using extreme expressional ranges of G64-i.e., tumor subpopulation with the lowest 15% of G64 expression, tumor subpopulation with the highest 15% of G64 expression, and tumor subpopulation with intermediate expression. In each of the 22 cancers, we examined whether patient survival was different among the three different subgroups and found that G64 could differentiate tumor subpopulations in six other cancers, including sarcoma, kidney, brain, liver, and esophageal cancers.

• The Korean Journal of Nuclear Medicine
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• v.36 no.6
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• pp.317-324
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• 2002

Purpose: The use of statistical parametric mapping (SPM) program has increased for the analysis of brain PET and SPECT images. Montreal Neurological Institute (MNI) coordinate is used in SPM program as a standard anatomical framework. While the most researchers look up Talairach atlas to report the localization of the activations detected in SPM program, there is significant disparity between MNI templates and Talairach atlas. That disparity between Talairach and MNI coordinates makes the interpretation of SPM result time consuming, subjective and inaccurate. The purpose of this study was to develop a program to provide objective anatomical information of each x-y-z position in ICBM coordinate. Materials and Methods: Program was designed to provide the anatomical information for the given x-y-z position in MNI coordinate based on the Statistical Probabilistic Anatomical Map (SPAM) images of ICBM. When x-y-z position was given to the program, names of the anatomical structures with non-zero probability and the probabilities that the given position belongs to the structures were tabulated. The program was coded using IDL and JAVA language for 4he easy transplantation to any operating system or platform. Utility of this program was shown by comparing the results of this program to those of SPM program. Preliminary validation study was peformed by applying this program to the analysis of PET brain activation study of human memory in which the anatomical information on the activated areas are previously known. Results: Real time retrieval of probabilistic information with 1 mm spatial resolution was archived using the programs. Validation study showed the relevance of this program: probability that the activated area for memory belonged to hippocampal formation was more than 80%. Conclusion: These programs will be useful for the result interpretation of the image analysis peformed on MNI coordinate, as done in SPM program.

• Korean Journal of Biological Psychiatry
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• v.21 no.3
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• pp.81-86
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• 2014

Objectives Total intracranial volume (TIV) is a major nuisance of neuroimaging research for interindividual differences of brain structure and function. Authors intended to prove the reliability of the atlas scaling factor (ASF) method for TIV estimation in FreeSurfer by comparing it with the results of manual tracing as reference method. Methods The TIVs of 26 normal children and 26 children with attention-deficit hyperactivity disorder (ADHD) were obtained by using FreeSurfer reconstruction and manual tracing with T1-weighted images. Manual tracing performed in every 10th slice of MRI dataset from midline of sagittal plane by one researcher who was blinded from clinical data. Another reseacher performed manual tracing independently for randomly selected 20 dataset to verify interrater reliability. Results The interrater reliability was excellent (intraclass coefficient = 0.91, p < 7.1e-07). There were no significant differences of age and gender distribution between normal and ADHD groups. No significant differences were found between TIVs from ASF method and manual tracing. Strong correlation between TIVs from 2 different methods were shown (r = 0.90, p < 2.2e-16). Conclusions The ASF method for TIV estimation by using FreeSurfer showed good agreement with the reference method. We can use the TIV from ASF method for correction in analysis of structural and functional neuroimaging studies with not only elderly subjects but also children, even with ADHD.

• 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.

• Applied Microscopy
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• v.18 no.2
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• pp.177-186
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• 1988

Degeneration of the axon terminals of mamillo-thalamic tract following the electrical coagulation of mamillary body is well known. In this study, the author investigated the ultrastructural alterations of neuropil components, initiated by terminal degenerations. Rats weighing approximately 250 gm were fixed on the stereotaxic instrument(David Kopf Inc., Heavy duty model), and NE 300 active electrode(Rhodes Med. Instr. Inc.) was introduced to the mamillary position of anterior 3.8 mm, lateral 0.5 mm, height 3.8 mm and lateral angle of $23^{\circ}$ according to De Groot's Atlas. Electric current of 20 mA was applied during 1 minute between active and inactive electrodes with Radio Frequency Lesion Generator(RFG 4, Radionics Inc.). Two hours, 2 days, 1 week and 2 weeks following the electrical coagulation of mamillary body, ipsilateral anterior thalamic nucleus was fixed in 1% glutaraldehyde-l% paraformaldehyde and 2% osmium tetroxide, embedded in Araldite mixture, cutted with LKB ultra tome V, stained with uranyl acetate-lead citrate and observed with JEOL 100 CX electron microscope. Observed results were as follows; 1. Degenerated mamillo-thalamic synapses were observed to form asymmetric axospinous or axo-dendritic types. 2. Terminal degeneration was not easily discernible at 2 hours interval after mamillary lesion, but following 2 days the terminal degeneration was apparent. 3. Postsynaptic spines, dendrites and even their cell bodies show edematic changes caused by the degeneration of postsynaptic counterpart. 4. Astrocytic territories, including perivascular processes forming glial limitans of blood-brain barrier, exhibit remarkable expansion. 5. Oligoglia and astroglia are actively engaged in the removal of degenerated elements. 6. Active forms of microglia were increased. 7. The observed results may represent typical ultrastructural alteration pattern within neuropil following the degeneration of certain input axon terminals.

• Journal of Korean Neurosurgical Society
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• v.45 no.4
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• pp.219-223
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• 2009

Objective : Functional magnetic resonance imaging (fMRI) is frequently used to localize language areas in a non-invasive manner. Various paradigms for presurgical localization of language areas have been developed, but a systematic quantitative evaluation of the efficiency of those paradigms has not been performed. In the present study, the authors analyzed different language paradigms to see which paradigm is most efficient in localizing frontal language areas. Methods : Five men and five women with no neurological deficits participated (mean age, 24 years) in this study. All volunteers were right-handed. Each subject performed 4 tasks, including fixation (Fix), sentence reading (SRI. pseudoword reading (PR), and word generation (WG). Fixation and pseudoword reading were used as contrasts. The functional area was defined as the area(s) with a t-value of more than 3.92 in fMRI with different tasks. To apply an anatomical constraint, we used a brain atlas mapping system, which is available in AFNI, to define the anatomical frontal language area. The numbers of voxels in overlapped area between anatomical and functional area were individually counted in the frontal expressive language area. Results : Of the various combinations, the word generation task was most effective in delineating the frontal expressive language area when fixation was used as a contrast (p<0.05). The sensitivity of this test for localizing Broca's area was 81 % and specificity was 70%. Conclusion : Word generation versus fixation could effectively and reliably delineate the frontal language area. A customized effective paradigm should be analyzed in order to evaluate various language functions.

• Asian Spine Journal
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• v.12 no.6
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• pp.1117-1122
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• 2018

Study Design: Prospective study. Purpose: To assess the prevalence of periodontoid calcification and its associations with acute cervical pain. Overview of Literature: Calcium pyrophosphate dihydrate (CPPD) deposition disease is a common rheumatological disorder that occurs especially in elderly patients. Although CPPD crystals induce acute arthritis, these crystals are not usually symptomatic. Calcification surrounding the odontoid process (periodontoid calcification) has been reported to induce inflammation, resulting in acute neck pain. This disease is called crowned dens syndrome. Whether calcification induces inflammation or whether the crystals are symptomatic remains unclear. Methods: The prevalence of periodontoid calcification at the atlas transverse ligament was examined by computed tomography of the upper cervical spine in patients suspected of brain disease but no cervical pain (control group, n=296), patients with pseudogout of the peripheral joints but no cervical pain (arthritis group, n=41), and patients with acute neck pain (neck pain group, n=22). Next, the correlation between the prevalence of periodontoid calcification and symptoms was analyzed. Results: In the control group, 40 patients (13.5%) showed periodontoid calcification with no significant difference in the prevalence with gender. The prevalence of calcification increased significantly with age (p=0.002). In the arthritis group, 26 patients (63.4%) reported periodontoid calcification. In the neck pain group, 14 patients (63.6%) reported periodontoid calcification. Multiple logistic regression analysis by age and group revealed that higher age, inclusion in the arthritis group, and inclusion in the neck pain group significantly affected the prevalence of calcification. Conclusions: Our results cumulatively suggest that periodontoid calcification is an aging-related reaction and that calcification per se does not always cause neck pain. Periodontoid calcification was observed more frequently in patients with pseudogout of the peripheral joints and in those with acute neck pain than in asymptomatic control patients.

• International Journal of Stem Cells
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• v.16 no.3
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• pp.315-325
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• 2023

Background and Objectives: Glioblastoma (GBM) is an aggressive primary brain tumor characterized by its heterogeneity and high recurrence and lethality rates. Glioblastoma stem cells (GSCs) play a crucial role in therapy resistance and tumor recurrence. Therefore, targeting GSCs is a key objective in developing effective treatments for GBM. The role of Parathyroid hormone-related peptide (PTHrP) in GBM and its impact on GSCs remains unclear. This study aimed to investigate the effect of PTHrP on GSCs and its potential as a therapeutic target for GBM. Methods and Results: Using the Cancer Genome Atlas (TCGA) database, we found higher expression of PTHrP in GBM, which correlated inversely with survival. GSCs were established from three human GBM samples obtained after surgical resection. Exposure to recombinant human PTHrP protein (rPTHrP) at different concentrations significantly enhanced GSCs viability. Knockdown of PTHrP using target-specific siRNA (siPTHrP) inhibited tumorsphere formation and reduced the number of BrdU-positive cells. In an orthotopic xenograft mouse model, suppression of PTHrP expression led to significant inhibition of tumor growth. The addition of rPTHrP in the growth medium counteracted the antiproliferative effect of siPTHrP. Further investigation revealed that PTHrP increased cAMP concentration and activated the PKA signaling pathway. Treatment with forskolin, an adenylyl cyclase activator, nullified the antiproliferative effect of siPTHrP. Conclusions: Our findings demonstrate that PTHrP promotes the proliferation of patient-derived GSCs by activating the cAMP/PKA signaling pathway. These results uncover a novel role for PTHrP and suggest its potential as a therapeutic target for GBM treatment.

• Oncology Letters
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• v.18 no.6
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• pp.5731-5738
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• 2019

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer. Novel biomarkers of ccRCC may provide crucial information on tumor features and prognosis. The present study aimed to determine whether the expression of γ-aminobutyric acid (GABA) A receptor subunit θ (GABRQ) could serve as a novel prognostic marker of ccRCC. GABA is the main inhibitory neurotransmitter in the brain that activates the receptor GABAA, which is comprised of three subunit isoforms: GABRA3, GABRB3 and GABRQ. A recent study reported that GABRQ is involved in the initiation and progression of hepatocellular carcinoma; however, the role of GABRQ in ccRCC remains unknown. In the present study, clinical and transcriptomic data were obtained from cohorts of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). Differential GABRQ expression levels among early (TI and II), late (TIII and IV), nonmetastatic (M0) and metastatic (M1, primary tumor) stages of ccRCC samples were then identified. Furthermore, the use of GABRQ as a prognostic gene was analyzed using Uno's C-index based on the time-dependent area under the curve (AUC), the AUC of the receiver operating characteristic curve at 5 years, the Kaplan-Meier survival curve and multivariate analysis. The survival curve analysis revealed that low GABRQ mRNA expression was significantly associated with a poor prognosis of ccRCC (P<0.001 and P=0.0012 for TCGA and ICGC data, respectively). In addition, analyses of the C-index and AUC values further supported this discriminatory power. Furthermore, the prognostic value of GABRQ mRNA expression was confirmed by multivariate Cox regression analysis. Taken together, these results suggested that GABRQ mRNA expression may be considered as a novel prognostic biomarker of ccRCC.