• BMB Reports
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• v.51 no.10
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• pp.481-483
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• 2018

Glioblastoma (GBM) is the most common and aggressive form of human adult brain malignancy. The identification of the cell of origin harboring cancer-driver mutations is the fundamental issue for understanding the nature of GBM and developing the effective therapeutic target. It has been a long-term hypothesis that neural stem cells in the subventricular zone (SVZ) might be the origin-of-cells in human glioblastoma since they are known to have life-long proliferative activity and acquire somatic mutations. However, the cell of origin for GBM remains controversial due to lack of direct evidence thereof in human GBM. Our recent study using various sequencing techniques in triple matched samples such as tumor-free SVZ, tumor, and normal tissues from human patients identified the clonal relationship of driver mutations between GBM and tumor-free SVZ harboring neural stem cells (NSCs). Tumor-free SVZ tissue away from the tumor contained low-level GBM driver mutations (as low as 1% allelic frequency) that were found in the dominant clones in its matching tumors. Moreover, via single-cell sequencing and microdissection, it was discovered that astrocyte-like NSCs accumulating driver mutations evolved into GBM with clonal expansion. Furthermore, mutagenesis of cancer-driving genes of NSCs in mice leads to migration of mutant cells from SVZ to distant brain and development of high-grade glioma through the aberrant growth of oligodendrocyte precursor lineage. Altogether, the present study provides the first direct evidence that NSCs in human SVZ is the cell of origin that develops the driver mutations of GBM.

• Molecules and Cells
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• v.37 no.7
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• pp.562-567
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• 2014

Human Hertwig's epithelial root sheath/epithelial rests of Malassez (HERS/ERM) cells are epithelial remnants of teeth residing in the periodontium. Although the functional roles of HERS/ERM cells have yet to be elucidated, they are a unique epithelial cell population in adult teeth and are reported to have stem cell characteristics. Therefore, HERS/ERM cells might play a role as an epithelial component for the repair or regeneration of dental hard tissues; however, they are very rare population in periodontium and the primary isolation of them is considered to be difficult. To overcome these problems, we immortalized primary HERS/ERM cells isolated from human periodontium using SV40 large T antigen (SV40 LT) and performed a characterization of the immortalized cell line. Primary HERS/ERM cells could not be maintained for more than 6 passages; however, immortalized HERS/ERM cells were maintained for more than 20 passages. There were no differences in the morphological and immunophenotypic characteristics of HERS/ERM cells and immortalized HERS/ERM cells. The expression of epithelial stem cell and embryonic stem cell markers was maintained in immortalized HERS/ERM cells. Moreover, immortalized HERS/ERM cells could acquire mesenchymal phenotypes through the epithelial-mesenchymal transition via TGF-${\beta}1$. In conclusion, we established an immortalized human HERS/ERM cell line with SV40 LT and expect this cell line to contribute to the understanding of the functional roles of HERS/ERM cells and the tissue engineering of teeth.

• Journal of the Korean Society of Radiology
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• v.7 no.6
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• pp.433-439
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• 2013

In this study, human head-mimicking phantom was developed for brain disease treatment study using focused ultrasound. Acoustic parameters of skin, skull and brain were investigated through literature investigation and adequate substitutes according to each tissue were suggested. In the case of skin phantom, construction ratio of glycerol-based TMM phantom was controlled to mimic real skin. The suitability of skull substitutes was evaluated through measurement of acoustic parameters. In the case of brain phantom, transparent egg white phantom was used to observe thermal properties of focused ultrasound. Combined human-head-mimicking phantom using each substitutes was fabricated for development of brain disease treatment protocol. Denaturation of brain phantom according to ultrasonic condition was observed for validation.

• Proceedings of the Korean Society of Medical Physics Conference
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• 2002.09a
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• pp.90-93
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• 2002

In particle radiotherapy, a shape of the beam to conform the irradiation field is statically defined by the compensator, collimator and potal devices at the outside of the patient body. However the target such as lung or liver cancer moves along with respiration. This increases the irradiated volume of normal tissue. Prior discussions about organ motions along with respiration have been mainly focused on inferior-superior movement that was usually perpendicular to beam axis. On the other hand, the change of the target depth along the beam axis is very important especially in particle radiotherapy, because the range end of beam (Bragg peak) is so sharp as to be matched to distal edge of the target. In treatment planning, the range of the particle beam inside the body is calculated using a calibration curve relating CT number and water equivalent path length (WEL) to correct the inhomogeneities of tissues. The variation in CT number along the beam path would cause the uncertainties of range calculation at treatment planning for particle radiotherapy. To estimate the uncertainties of the range calculation associated with patient breathing, we proposed the method using sequential CT images with respiration waveform, and analyzed organ motions and WELs at patients that had lung or liver cancer. The variation of the depth along the beam path was presented in WEL rather than geometrical length. In analyzed cases, WELs around the diaphragm were remarkably changed depending on the respiration, and the magnitude of these WEL variations was almost comparable to inferior-superior movement of diaphragm. The variation of WEL around the lung was influenced by heartbeat.

• Biomolecules & Therapeutics
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• v.22 no.5
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• pp.431-437
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• 2014

Synthetic compounds that are used in the clinic to regulate skin hyperpigmentation, such as arbutin, hydroquinone, and kojic acid, are only moderately effective. But, their use is limited by side effects. As part of an effort to overcome the limitations, we developed resveratrol-enriched rice (RR) using genetic engineering technique. Each of resveratrol and rice has been reported to produce anti-melanogenic effects. Therefore, we hypothesized that RR would show more anti-melanogenic effects than those of resveratrol or rice alone. Anti-melanogenic effect of RR was done by using melan-a mouse melanocytes. The depigmenting efficacy was then observed following topical application of the RR to UVB-stimulated hyperpigmented dorsal skin of guinea pigs. Treatment with RR extract resulted a $21.4{\pm}0.7%$ decrease in tyrosinase expression at melan-a cells. Colorimetric analysis showed a significantly lower depigmenting value by day 9 following treatment with RR in UVB-irradiated guinea pigs the dorsal skin (p<0.01), indicating that RR produced a depigmentation effect. By staining with Fontana-Masson stain, we found that the RR-treated group had more effect histopathologically in epidermal melanin production than resveratrol or rice alone-treated group. RR was associated with reduction in the levels of microphthalmia-associated transcription factor (MITF), and downregulation of tyrosinase and tyrosinase-related protein (TRP-2) expression, leading to inhibit epidermal melanin production by western blot analysis. This study suggests that the resveratrol-enriched rice may be a promising candidate in regulating skin pigmentation with UVB exposure.

• Journal of the Institute of Electronics Engineers of Korea TC
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• v.46 no.12
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• pp.102-107
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• 2009

As technology gets developed, medical equipments are also modernized and leading-edge systems, such as PACS become popular. Many scientists noticed importance of medical image processing technology. Technique of region segmentation is the first step of digital medical image processing. Segmentation technique helps doctors to find out abnormal symptoms early, such as tumors, edema, and necrotic tissue, and helps to diagnoses correctly. Segmentation of white matter, gray matter and CSF of a brain image is very crucial part. However, the segmentation is not easy due to ambiguous boundaries and inhomogeneous physical characteristics. The rate of incorrect segmentation is high because of these difficulties. Fuzzy-based segmentation algorithms are robust to even ambiguous boundaries. In this paper a modified Fuzzy-based segmentation algorithm is proposed to handle the noise of MR scanners. A proposed algorithm requires minimal computations of mean and variance of neighbor pixels to adjust a new neighbor list. With the addition of minimal compuation, the modified FCM(mFCM) lowers the rate of incorrect clustering below 30% approximately compared the traditional FCM.

• KSBB Journal
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• v.7 no.3
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• pp.191-200
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• 1992

Several strains of Agrobacterium tumefaciens were isolated from soil in the Taegu area and characterized to develop some useful vector systems for higher plant genetic engineering. The selected colonies had a unique form, and strains from the colonies were capable of tumor formation on the sunflower leaf surface. They had a large plasmid. The restriction analysis showed that they were another kinds of Ti plasmic compared with C58 and Ach5. The isolated strains were identified as the nopaline type and also as biovar 1 A. tumefaciens, according to their tumor morphology, blophyslcal and biochemical characteristics. One of the isolated strains, AK204 was transformed with binary vector (pGA642), having selectable marker (Kmr, Tcr). Furthermore, maize tissue cells were transformed by cocultivation with AK204/pGA642, and the transformants were selected on the selective medium and identified using PAGE patterns of their soluble proteins.

• Biomedical Science Letters
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• v.21 no.1
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• pp.40-49
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• 2015

Mesenchymal stem cells (MSCs) have the ability to self-renew and differentiate into multi-lineage cells, thus highlighting the feasibility of using umbilical cord blood-derived MSCs (UCB-MSCs) for cell-therapy and tissueengineering. However, the low numbers of UCB-MSC derived from clinical samples requires that an ex vivo expansion step be implemented. As most stem cells reside in low oxygen tension environments (i.e., hypoxia), we cultured the UCBMSCs under 3% $O_2$ or 21% $O_2$ and the following parameters were examined: proliferation, senescence, differentiation and stem cell specific gene expression. UCB-MSCs cultured under hypoxic conditions expanded to significantly higher levels and showed less senescence compared to UCB-MSCs cultured under normoxic conditions. In regards to differentiation potential, UCB-MSCs cultured under hypoxic and normoxic conditions both underwent similar levels of osteogenesis as determined by ALP and von Kossa assay. Furthermore, UCB-MSCs cultured under hypoxic conditions exhibited higher expression of OCT4, NANOG and SOX2 genes. Moreover, cells expanded under hypoxia maintained a stem cell immnunophenotype as determined by flow cytometry. These results demonstrate that the expansion of human UCB-MSCs under a low oxygen tension microenvironment significantly improved cell proliferation and differentiation. These results demonstrate that hypoxic culture can be rapidly and easily implemented into the clinical-scale expansion process in order to maximize UCB-MSCs yield for application in clinical settings and at the same time reduce culture time while maintaining cell product quality.

• The Korean Journal of Nuclear Medicine
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• v.19 no.1
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• pp.137-143
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• 1985

Using chelating agents such as Nitrilotriaceticacid(NTA), ticacid(DTPA) and Ethylenediaminenitrilotetraceticacid(EDTA), with TC-99m were determined in vitro and in vivo. Methods.of separation and determination of TC-99m-liposomes added chelating agents were practiced by thin layer chromatogram scan and gel filtration. Biodistributions of Tc-99m-liposomes in normal and sarcoma 180 cells bearing mice were observed. The results were as follows: 1) Maximum amount of $Sn^{+2}$ to reduction from pertechnetium$(10\sim20{\mu}ci)$ by adding 0, 1, 10 and $100{\mu}g$ of $SnCl_2$ in 0.2 ml of oxygen free water was $10{\mu}g$. 2) The large amounts of $SnCl_2$ were not changed but the small amounts of $SnCl_2$ were much changed by labeling with TC-99m to add chelating agents. EDTA in small amounts of $SnCl_2$ were reduced more strongly than DTPA or NTA. Using a hydrophilic chelate, DTPA, the uptake of liposomes could not accumulated in liver and spleen by a lipophilic chelate NTA were significant in vivo. 3) Uptake by tumor was achived 1.14% of injected dose per gram tissue and tumor to organ ratios were measured in low with TC-99m-NTA-liposomes(+).

• CELLMED
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• v.2 no.1
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• pp.10.1-10.6
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• 2012

Acupuncture works by stimulating peripheral sensory nerves and their endings causing an increase in cutaneous blood flow and microcirculation, as well as release of neurotransmitters, neuropeptides, and hormones. SP6 Patch is a nanoscale nontransdermal device that mildly stimulates Stomach 36 (zusanli) and other acupuncture points. As stimulation of these points has been indicated to have an effect on hypothalamic function, it is of great research interest to investigate the effect of SP6 Patch on the physiology of organs that are affected by hypothalamic regulation. Bioelectrical tissue impedance data indicative of cellular physiologic organ function, using an Electro Interstitial Scan (EIS) system, were acquired from hypothalamus, pancreas, liver, intestines, kidneys, thyroid and adrenal glands in 10 (1 male, 9 females) volunteers while wearing the SP6 Patch daily for 1 week. EIS testing was performed at baseline with no patch, 30 min after wearing the patch, and after wearing the patch 12 h/day for 1 week. Subjects were instructed to keep well hydrated during the study period. All subjects served as their own control. The hypothesis was: The SP6 Patch worn 12 h/day on the Stomach 36 acupuncture point for 1 week, may significantly improve cellular physiologic functional status of different organs measured by EIS. All tested organs achieved significant improvement in their functional physiologic status after wearing the SP6 Pach 12 h/day for 1 week compared to baseline with an overall average statistical power > 89%. Based upon these results the hypothesis was accepted as true.