• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.1241-1245
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• 2015

Background: Thyroid carcinoma is the most common malignancy of the endocrine organs. Although the majority of thyroid cancer patients experience positive outcomes, anaplastic thyroid carcinoma is considered one of the most aggressive malignancies. Current therapeutic regimens do not confer a significant survival benefit, and new therapies are urgently needed. Oncolytic herpes simplex virus (oHSV) may represent a promising therapy for cancer. In the present study, we investigated the therapeutic effects of a third-generation HSV vector, $G47{\Delta}$, on various human thyroid carcinoma cell lines in vitro. Two subcutaneous (s.c.) models of anaplastic thyroid carcinoma were also established to evaluate the in vivo anti-tumor efficacy of $G47{\Delta}$. Materials and Methods: The human thyroid carcinoma cell line ARO, FRO, WRO, and KAT-5, were infected with $G47{\Delta}$ at different multiplicities of infection (MOIs) in vitro. The survival rates of infected cells were calculated each day. Two s.c. tumor models were established using ARO and FRO cells in Balb/c nude mice, which were intratumorally (i.t.) treated with either $G47{\Delta}$ or mock. Tumor volumes and mouse survival times were documented. Results: $G47{\Delta}$ was highly cytotoxic to different types of thyroid carcinomas. For ARO, FRO, and KAT-5, greater than 30% and 80% of cells were killed at MOI=0.01 and MOI=0.1, respectively on day 5. WRO cells displayed modest sensitivity to $G47{\Delta}$, with only 21% and 38% of cells killed. In the s.c. tumor model, both of the anaplastic thyroid carcinoma cell lines (ARO and FRO) were highly sensitive to $G47{\Delta}$; $G47{\Delta}$ significantly inhibited tumor growth and prolonged the survival of mice bearing s.c. ARO and FRO tumors. Conclusions: The oHSV $G47{\Delta}$ can effectively kill different types of human thyroid carcinomas in vitro. $G47{\Delta}$ significantly inhibited growth of anaplastic thyroid carcinoma in vivo and prolonged animal survival. Therefore, $G47{\Delta}$ may hold great promise for thyroid cancer patients.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.36 no.2
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• pp.87-93
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• 2010

Introduction: In our previous studies, we isolated porcine skin-derived mesenchymal stem cells (pSDMSCs) from the ears of adult miniature pigs and evaluated the pluripotency of these pSDMSCs based on expressions of transcription factors, such as Oct-4, Sox-2, and Nanog. Moreover, the characteristic of mesenchymal stem cells was revealed by the expression of various mesenchymal stem cell markers, including CD29, CD44, CD90, and vimentin. The aim of this study was to evaluate in vivo osteogenesis after maxillary sinus lift procedures with autogenous pSDMSCs and scaffold. Materials and Methods: The autogenous pSDMSCs were isolated from the 4 miniature pigs, and cultured to 3rd passage with same methods of our previous studies. After cell membranes were labeled using a PKH26, $1{\times}10^{7}$ cells/$100{\mu}L$ of autogenous pSDMSCs were grafted into the maxillary sinus with a demineralized bone matrix (DBM) and fibrin glue scaffold. In the contralateral control side, only a scaffold was grafted, without SDMSCs. After two animals each were euthanized at 2 and 4 weeks after grafting, the in vivo osteogenesis was evaluated with histolomorphometric and osteocalcin immunohistochemical studies. Results: In vivo PKH26 expression was detected in all specimens at 2 and 4 weeks after grafting. Trabecular bone formation and osteocalcin expression were more pronounced around the grafted materials in the autogenous pSDMSCs-grafted group compared to the control group. Newly generated bone was observed growing from the periphery to the center of the grafted material. Conclusion: The results of the present study suggest that autogenous skin-derived mesenchymal stem cells grafting with a DBM and fibrin glue scaffold can be a predictable method in the maxillary sinus floor elevation technique for implant surgery.

• Journal of Veterinary Science
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• v.23 no.5
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• pp.74.1-74.16
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• 2022

Background: Previous studies have presented evidence to support the significant association between red meat intake and colon cancer, suggesting that heme iron plays a key role in colon carcinogenesis. Epigallocatechin-3-gallate (EGCG), the major constituent of green tea, exhibits anti-oxidative and anti-cancer effects. However, the effect of EGCG on red meat-associated colon carcinogenesis is not well understood. Objectives: We aimed to investigate the regulatory effects of hemin and EGCG on colon carcinogenesis and the underlying mechanism of action. Methods: Hemin and EGCG were treated in Caco2 cells to perform the water-soluble tetrazolium salt-1 assay, lactate dehydrogenase release assay, reactive oxygen species (ROS) detection assay, real-time quantitative polymerase chain reaction and western blot. We investigated the regulatory effects of hemin and EGCG on an azoxymethane (AOM) and dextran sodium sulfate (DSS)-induced colon carcinogenesis mouse model. Results: In Caco2 cells, hemin increased cell proliferation and the expression of cell cycle regulatory proteins, and ROS levels. EGCG suppressed hemin-induced cell proliferation and cell cycle regulatory protein expression as well as mitochondrial ROS accumulation. Hemin increased nuclear factor erythroid-2-related factor 2 (Nrf2) expression, but decreased Keap1 expression. EGCG enhanced hemin-induced Nrf2 and antioxidant gene expression. Nrf2 inhibitor reversed EGCG reduced cell proliferation and cell cycle regulatory protein expression. In AOM/DSS mice, hemin treatment induced hyperplastic changes in colon tissues, inhibited by EGCG supplementation. EGCG reduced the hemin-induced numbers of total aberrant crypts and malondialdehyde concentration in the AOM/DSS model. Conclusions: We demonstrated that EGCG reduced hemin-induced proliferation and colon carcinogenesis through Nrf2-inhibited mitochondrial ROS accumulation.

• Journal of Korean Neurosurgical Society
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• v.60 no.5
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• pp.511-517
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• 2017

Objective : Spontaneous intracerebral hemorrhage (ICH) and ischemic stroke share common vascular risk factors such as aging and hypertension. Previous studies suggested that the rate of recurrent ICH and ischemic stroke might be similar after ICH. Presence of cerebral arterial stenosis is a potential risk factor for future ischemic stroke. This study investigated the prevalence and factors associated with cerebral arterial stenosis in Korean patients with spontaneous ICH. Methods : A total of 167 patients with spontaneous ICH were enrolled. Intracranial arterial stenosis (ICAS) and extracranial arterial stenosis (ECAS) were assessed by computed tomography angiography. Presence of ICAS was defined if patients had arterial stenosis in at least one intracranial artery. ECAS was assessed in the extracranial carotid artery. More than 50% luminal stenosis was defined as presence of stenosis. Prevalence and factors associated with presence of ICAS and cerebral arterial stenosis (presence of ICAS and/or ECAS) were investigated by multivariable logistic regression analysis. Results : Thirty-two (19.2%) patients had ICAS, 7.2% had ECAS, and 39 (23.4%) patients had any cerebral arterial stenosis. Frequency of ICAS and ECAS did not differ among ganglionic ICH, lobar ICH, and brainstem ICH. Age was higher in patients with ICAS ($67.6{\pm}11.8$ vs. $58.9{\pm}13.6years$ p=0.004) and cerebral arterial stenosis ($67.9{\pm}11.6$ vs. $59.3{\pm}13.5years$, p<0.001) compared to those without stenosis. Patients with ICAS were older, more frequently had diabetes, had a higher serum glucose level, and had a lower hemoglobin level than those without ICAS. Patients with cerebral arterial stenosis were older, had diabetes and lower hemoglobin level, which was consistent with findings in patients with ICAS. However, patients with cerebral arterial stenosis showed higher prevalence of hypertension and decreased kidney function compared to those without cerebral arterial stenosis. Multivariable logistic regression analyses showed that aging and presence of diabetes independently predicted the presence of ICAS, and aging, diabetes, and hypertension were independently associated with presence of cerebral arterial stenosis. Conclusion : 19.2% of patients with spontaneous ICH had ICAS, but the prevalence of ECAS was relatively lower (7.2%) compared with ICAS. Aging and diabetes were independent factors for the presence of ICAS, whereas aging, hypertension, and diabetes were factors for the cerebral arterial stenosis.

• Clinical and Experimental Reproductive Medicine
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• v.31 no.1
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• pp.19-27
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• 2004

Objective: This study was to examine the in vitro neural cell differentiation patterns of human embryonic stem (hES) cells following treatment of various neurotrophic factors [basic fibroblast growth factor (bFGF), retinoic acid (RA), brain derived neurotrophic factor (BDNF) and transforming growth factor (TGF)-$\alpha$], particulary in dopaminergic neuron formation. Methods: The hES cells were induced to differentiate by bFGF and RA. Group I) In bFGF induction method, embryoid bodies (EBs, for 4 days) derived from hES were plated onto gelatin dish, selected for 8 days in ITSFn medium and expanded at the presence of bFGF (10 ng/ml) for another 6 days followed by a final differentiation in N2 medium for 7, 14 and 21 days. Group II) For RA induction, EBs were exposed of RA ($10^{-6}M$) for 4 days and allowed to differentiate in N2 medium for 7, 14 and 21 days. Group III) To examine the effects of additional neurotrophic factors, bFGF or RA induced cells were exposed to either BDNF (10 ng/ml) or TGF-$\alpha$ (10 ng/ml) during the 21 days of final differentiation. Neuron differentiation and dopamine secretion were examined by indirect immunocytochemistry and HPLC, respectively. Results: The bFGF or RA treated hES cells were resulted in similar neural cell differentiation patterns at the terminal differentiation stage, specifically, 75% neurons and 11% glial cells. Additionally, treatment of hES cells with BDNF or TGF-$\alpha$ during the terminal differentiation stage led to significantly increased tyrosine hydroxylase (TH) expression of a dopaminergic neuron marker, compared to control (p<0.05). In contrast, no effect was observed on the rate of mature neuron (NF-200) or glutamic acid decarboxylase-positive neurons. Immunocytochemistry and HPLC analyses revealed the higher levels of TH expression (20.3%) and dopamine secretion (265.5 $\pm$ 62.8 pmol/mg) in bFGF and TGF-sequentially treated hES cells than those in $\alpha$ RA or BDNF treated hES cells. Conclusion: These results indicate that the generation of dopamine secretory neurons from in vitro differentiated hES cells can be improved by TGF-$\alpha$ addition in the bFGF induction protocol.

• Journal of Korean Neurosurgical Society
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• v.59 no.6
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• pp.570-576
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• 2016

Objective : Elevated cell counts and protein levels in cerebrospinal fluid (CSF) result from disease activity in patients with leptomeningeal carcinomatosis (LMC). Previous studies evaluated the use of CSF profiles to monitor a treatment response or predict prognosis. CSF profiles vary, however, according to the sampling site and the patient's systemic condition. We compared lumbar and ventricular CSF profiles collected before intraventricular chemotherapy for LMC and evaluated the association of these profiles with patients' systemic factors and LMC disease activity. Methods : CSF profiles were retrospectively collected from 228 patients who underwent Ommaya reservoir insertion for intraventricular chemotherapy after a diagnosis of LMC. Lumbar samples taken via lumbar puncture were used for the diagnosis, and ventricular samples were obtained later at the time of Ommaya reservoir insertion. LMC disease activity was defined as the presence of LMC-related symptoms such as increased intracranial pressure, hydrocephalus, cranial neuropathy, and cauda equina syndrome. Results : Cell counts (median : 8 vs. 1 cells/mL) and protein levels (median : 68 vs. 17 mg/dL) significantly higher in lumbar CSF than in ventricular CSF (p<0.001). Among the evaluated systemic factors, concomitant brain metastasis and previous radiation were significantly correlated with higher protein levels in the lumbar CSF (p=0.01 and <0.001, respectively). Among the LMC disease activity, patients presenting with hydrocephalus or cauda equina syndrome showed higher lumbar CSF protein level compared with that in patients without those symptoms (p=0.049 and p<0.001, respectively). The lumbar CSF cell count was significantly lower in patients with cranial neuropathy (p=0.046). The ventricular CSF cell counts and protein levels showed no correlation with LMC symptoms. Carcinoembryonic antigen (CEA), which was measured from ventricular CSF after the diagnosis in 109 patients, showed a significant association with the presence of hydrocephalus (p=0.01). Conclusion : The protein level in lumbar CSF indicated the localized disease activity of hydrocephalus and cauda equina syndrome. In the ventricular CSF, only the CEA level reflected the presence of hydrocephalus. We suggest using more specific biomarkers for the evaluation of ventricular CSF to monitor disease activity and treatment response.

• Progress in Medical Physics
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• v.16 no.3
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• pp.116-124
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• 2005

Absorbed dose dosimetry protocols of high energy photon and electron beams, which are widely used and based on an air kerma calibration factors, have somewhat complex formalism and limitations for improving dosimetric accuracy due to uncertainty of the physical parameters used. Recently the IAEA and the AAPM published the absorbed dose to water-based dosimetry protocol. In this work web-based dose calibration program for IAEA TRS-398 and AAPM TG-51 protocols were developed. This program developed using the Visual C$\#$ language can be used in the internet. User selectable dosimetry protocol on the web allows the absorbed dose to water data of the two protocols at a reference point to be easily compared, and enables to conveniently manage and understand the current status of the dosimetry calibration performed at participating institutions in korea. This program and the resultant database from the web-based calibration can be useful in developing new dosimetry protocols in Korea.

• Journal of Biomedical Engineering Research
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• v.20 no.1
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• pp.81-90
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• 1999

This paper describes an EEG(electroencephalogram) software for two-channel cerebral function monitoring system to detect the cerebral ischemia. In the software, two-channel bipolar analog EEG signals are digitized and from the signals various EEG parameters are extracted and displayed on a monitor in real-time. Digitized EEG signal is transformed by FFT(Fast Fourier transform) and represented as CSA(compressed spectral array) and DSA(density spectral array). Additional 5 parameters, such as alpha ratio, percent delta, spectral edge frequency, total power, and difference in total power, are estimated using the FFT spectra. All of these are effectively merged in a monitor and displayed in real-time. Through animal experiments and clinical trials on men, the software is modified and enhanced. Since the software provides raw EEG, CSA, DSA, simultaneously with additional 5 parameters in a monitor, it is possible to observe patients multilaterally. For easy comparison of patient's status, reference patterns of CSA, DSA can be captured and displayed on top of the monitor. And user can mark events of surgical operation and patient's conditions on the software, this allow him jump to the points of events directly, when reviewing the recorded EEG file afterwards. Other functions, such as forward/backward jump, gain control, file management are equipped and these are operated by simple mouse click. Clinical tests in a university hospital show that the software responds accurately according to the conditions of patients and medical doctors can use the software easily.

• The Korean Journal of Pharmacology
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• v.13 no.2
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• pp.19-34
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• 1977

1) The relationship of arterial blood pressure and heart rate with raised intracranial pressure induced by the epidural balloon method was investigated in anesthetized rabbits and cats. 2) In both animals marked increase of the blood pressure was observed when the intracranial pressure became close to the blood pressure. 3) In both animals marked decrease in the blood pressure and transitory marked decrease in the heart rate were observed, when the level of the intracranial pressure exceeded that of the blood pressure. 4) In reserpinized animals raised intracranial pressure produced decrease in the blood pressure and heart rate. 5) During raised intracranial pressure, the 6-hydroxydopamine-treated (by intracerebral administration) animals showed increase of the blood pressure less than control animals. 6) The depressor response to raised intracranial pressure in the reserpinized animals was reversed to the marked pressor one by the administration of norepinephrine into the lateral ventricle. 7) These results suggest that the pressor response to raised intracranial pressure is due to the increase of norepinephrine release resulted from local stimulation of the central sympathetic neurons by the raised intracranial pressure.

• Journal of Korean Neurosurgical Society
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• v.63 no.2
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• pp.188-201
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• 2020

Objective : The purpose of this study was to suggest that computed tomography angiography (CTA) is valuable as the only preliminary examination for mechanical thrombectomy (MT). MT after single examination of CTA including noncontrast computed tomography (NCCT) and maximum intensity projection (MIP) improves door-to-puncture time as well as results in favorable outcomes. Methods : A total of 157 patients who underwent MT at Dong Kang Medical Center from April 2015 to March 2019 were divided into two groups based on the examination performed prior to MT : CTA group who underwent CTA with NCCT and MIP, and NCCT+magnetic resonance image (MRi) group who underwent MRI including perfusion images after NCCT. In the two groups, time to CTA imaging or NCCT+MRi imaging after symptom onset, and time to arterial puncture and reperfusion were characterized as time-related outcomes. The evaluation of vascular recanalization after MT was defined as a modified thrombolysis in cerebral infarction (mTICI) scale. National Institutes of Health Stroke Scale (NIHSS) was assessed at the time of the visit to the emergency room and modified Rankin Scale (mRS) was assessed after 90 days. Results : Typically, there were 34 patients in the CTA group and 33 patients in the NCCT+MRi group. A significantly shorter delay for door-to-puncture time was observed (mean, 86±22.1 vs. 176±47.5 minutes; <0.01). Also, a significantly shorter door-to-imege time in the CTA group was observed (mean, 13±6.8 vs. 93±30.8 minutes; p<0.01). Moreover, a significantly shorter onset-to-puncture time was observed (mean, 195±128.0 vs. 314±157.6 minutes; p<0.01). Reperfusion result of mTICI ≥2b was 100% (34/34) in the CTA group and 94% (31/33) in the NCCT+MRi group, and mTICI 3 in 74% (25/34) in the CTA group and 73% (24/33) in the NCCT+MRi group. Favorable functional outcomes (mRS score ≤2 at 90 days) were 68% (23/34) in the CTA group and 60% (20/33) in the NCCT+MRi group. Conclusion : A single-phase CTA including NCCT and MIP images was performed as a single preliminary examination, which led to a reduction in the time of the procedure and resulted in good results of prognosis. Consequently, it is concluded that this method is of sufficient value as the only preliminary examination for decision making.