• Journal of Life Science
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• v.26 no.12
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• pp.1383-1391
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• 2016

Anti-estrogen drugs such as tamoxifen have been used for treating patients with ER-positive, early breast cancer. However, resistance to anti-estrogen treatment is inevitable in most patients. Breast cancer anti-estrogen resistance-3 (BCAR3) has been identified as the protein responsible for the induction of tamoxifen resistance in estrogen-dependent human breast cancer. We have previously reported that BCAR3 regulates the cell cycle progression and the signaling pathway of EGF and insulin leading to DNA synthesis. In this study, we investigated the functional role of BCAR3 in regulating c-Jun transcription in non-tumorigenic human breast epithelial MCF-12A cells. A transient transfection of BCAR3 increased both the mRNA and protein of c-Jun expression, and stable expression of BCAR3 increased c-Jun protein expression. The overexpression of BCAR3 directly activated the promoter of c-jun, AP-1, and SRE but not that of $NF-{\kappa}B$. Furthermore, single-cell microinjection of BCAR3 expression plasmid in the cell cycle-arrested MCF-12A cells induced c-Jun protein expression, and co-injection of dominant negative mutants of Ras, Rac, and Rho suppressed the transcriptional activity of c-Jun in the presence of BCAR3. Furthermore, stable expression of BCAR3 increased the proliferation of MCF-12A cells. The microinjection of inhibitory materials such as anti-BCAR3 antibody and siRNA BCAR3 inhibited EGF-induced c-Jun expression but did not affect IGF-1 induced upregulation of c-Jun. Taken together, we propose that BCAR3 plays a crucial role in c-Jun protein expression and cell proliferation and that small GTPases (e.g., Ras, Rac, and Rho) are required for the BCAR3-mediated activation of c-Jun expression.

• Radiation Oncology Journal
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• v.25 no.3
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• pp.170-176
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• 2007

Purpose: To determine the role of radiotherapy for the treatment of portal vein thrombosis (PVT) from hepatocellular carcinoma (HCC). Material and Methods: A retrospective analysis was performed on 70 patients that had been diagnosed with HCC and were treated with three-dimensional conformal radiotherapy (3D-CRT) for the PVT. The radiation dose ranged from 40 Gy to 60 Gy (median dose: 48 Gy) and the biological effective dose (BED) ranged from 31.3 Gy to 78.0 $Gy_{10}$ (median dose: 61.6 $Gy_{10}$). Response was determined by measuring the extent of the PVT on a CT image at 0, 1 and 3 months after completion of the radiotherapy. The median follow-up period was 9 months. Results: The response rate was 47.1% (33 patients), with two patients (2.9%) showing a complete response, 31 patients (44.3%) showing a partial response, and 35 patients (50%) showing stable disease or no response. The 1-year progression-free survival rate was 60%, and the median progression-free survival time was 17 months. The median overall survival time was 11 months, the median survival time in the responders was 15 months and in the nonresponders was 8 months (p=0.032). Four patients (5.7%) had transient liver function impairment during treatment. Radiation induced liver disease (RILD) was observed in only one patient (1.4%). Conclusion: Three-dimensional conformal radiotherapy for the treatment of PVT from advanced HCC was a relatively effective and safe method.

• Journal of Chest Surgery
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• v.31 no.9
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• pp.877-883
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• 1998

Background: Cardiopulmonary bypass(CPB), a standard adjunct for open heart surgery, can also play an important role in treating patients with noncardiac diseases. Material and Method: We report a collective analysis of noncardiac applications of cardiopulmonary bypass experienced at Seoul National University Hospital from 1969 to 1996. Out of a total of 20 patients, 8 were treated for membranous obstruction of inferior vena cava(MOVC), 5 for malignant melanoma, 3 for pulmonary embolism, 1 for double lung transplantation, 1 for intracranial giant aneurysm(GA), 1 for renal cell carcinoma(RC), and 1 for liposarcoma. CPB was used to induce profound hypothermia with circulatory arrest in 6 patients(MOVC 4, GA 1, RC 1). Result: CPB time was 113 mins on average for MOVC, 161 mins for GA, and 156 mins for RC, while the lowest rectal temperature was 26$^{\circ}C$ on average in MOVC, and 19$^{\circ}C$ in GA and RC. Postoperative recovery was good in all MOVC patients. The patient with GA, who underwent reoperation for the removal of hematoma, died 14 days postoperatively. The patient with RC recovered from the operation in a good condition but died from metastatic spread 6 months later. CPB was instituted for pulmonary embolectomy in 3 patients, in whom postoperative courses were uneventful, except in 1 patient who showed transient neurologic symptoms. CPB was used in a patient with double-lung transplantation for hemodynamic and ventilatory support. The patient was weaned successfully from CPB but died from low output and septicemia 19 days postoperatively. CPB without circulatory arrest was used to treat in 4 patients with MOVC. These patients showed good postoperative courses. CPB was used to administer high concentrations of chemotherapeutic agents to the extremities in 6 patients(malignant melanoma 5, recurrent liposarcoma 1). CPB time was 153 mins on average. No complications such as edema and neurologic disability were found. Conclusion: Although CPB has a limited indication in noncardiac diseases, if properly applied, it can be a very useful adjunct in a variety of surgical cases.

• Radiation Oncology Journal
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• v.23 no.2
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• pp.92-97
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• 2005

Purpose : Reports on the outcome of curative radiotherapy for the primary hepatocellular carcinoma (HCC) are rarely encountered in the literature. in this study, we report our experience of a clinical trial where fractionated stereotactic radiotherapy (SRT) was used in treating a primary HCC. Materials and Methods : A retrospective analysis was peformed on 20 patients who had been histologically diagnosed as HCC and treated by fractionated SRT. The long diameter of tumor measured by CT was $2\~6.5$ cm (average: 3.8 cm). A single dose of radiation used in fractionated SRT was S or 10 Gy: each dose was prescribed based on the planning target volume and normalized to $85\~99\%$ isocenter dose. Patients were treated $3\~5$ times per week for 2 weeks, with each receiving a total dose of 50 Gy (the median dose: 50 Gy). The follow up period was $\~55$ months (the median follow up period: 23 months). Results : The response rate was $50\%$ (12 patients), with 4 patients showing complete response ($20%$), 8 patients showing partial response ($40\%$), and 8 patients showing stable disease ($40\%$). The 1-year and 2-year survival rates were $70.0\%$ and $43.1\%$, respectively, and the median survival time was 20 months. The 1-year and 2-year disease free survival rates were $65\%$ and $32.5\%$, respectively, and the median disease-free survival rate was 19 months. Some acute complications of the treatment were noted as follows: dyspepsia in 12 patients ($60\%$), nausea/emesis in 8 patients ($40\%$), and transient liver function impairment in 6 patients ($30\%$). However, there was no treatment related death. Conclusion : The study indicates that fractionated SRT is a relatively safe and effective method for treating primary HCC. Thus, fractionated SRT may be suggested as a local treatment for HCC of small lesion and containing a single lesion, when the patients are inoperable or operation is refused by the patients. We thought that fractionated SRT is a challenging treatment modality for the HCC.

• Journal of the Korean Institute of Traditional Landscape Architecture
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• v.28 no.2
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• pp.23-36
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• 2010

The purpose of this study is to infer the aspects and significance of Musa basjoo of latter part of Chosun Dynasty by analyzing the planting tendency and planting location of Musa basjoos drawn in total 77 old paintings and the characteristics of the paintings where Musa basjoos appeared, while trying to understand symbolic meanings of floral languages as well as the images and significance of Musa basjoos which appeared in the prose and poetry of Chosun Dynasty, and the results are as follows; With its floral languages of 'waiting', 'parting' and 'beauty', Musa basjoo represented the wealth and resuscitation and it aroused the elegance of hermits in its Taoistic sense. And it also represented 'the unworldliness to get out of transient human affairs' in its Buddhistic sense. Musa basjoos which appeared in 'Garden Custom Painting(庭園雅集圖)', 'Gosa Figure Painting(故事人物圖)' and 'Gyehoe Painting(契會圖)' is considered a device to increase the unworldly atmosphere of gardens and to dignify the elegant meetings of scholars, reflected by the high appearance frequencies of cranes and deer. And it seems that the meaning of Musa basjoo in certain paintings like 'Life-time Paintings(平生圖)', 'Castle City Painting(盛市圖), and 'Cultivating and Weaving Painting(耕織圖)' is an aspiration for wealth and prosperity, and the Musa basjoos planted in temples are considered to have symbolic meanings of aspiration for 'Salvation through Belief' as well as a unworldly meaning which reminds the transiency of human affairs. In addition, the expected effect of experiencing 'the sound of rain falling on the leaves of Musa basjoo' has been pursued, which can be confirmed by the fact that Firmiana simlex with wide leaves similar to Musa basjoo can be frequently spotted near the houses. Meanwhile, Musa basjoos seem to have been planted mainly in front garden or side garden around detached house and Musa basjoos inside the houses seem to have been planted mainly in right side when viewed from the entrance, in relation with the location of bedrooms where it is easier to hear the sounds from the right side of the environment. And the paintings where Musa basjoos appear with strange rocks and bizarre stones among other things have greater part of all the paintings, which is considered a kind of intentional landscaping and a product of mixed materials for elegant appreciation. And the major characters of the painting were involved in the activities of scholars such as arts, and the activities of minor characters were greatly related to their everyday lives. Musa basjoo of Chosun Dynasty in $17^{th}$ and $18^{th}$ century was one of the symbols necessary for description of gardens. And it provided the images of rainy scenes together with scholar culture which had a meaning of self-discipline, and it is assumed that the planting of Musa basjoo with the spirit of cease lessen deavor of a new leaf pushing up the tree and the spirit of resuscitation had the same trace of wheels in the city space of our country as the decline of scholar culture of Chosun Dynasty.

• Journal of Life Science
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• v.31 no.11
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• pp.1028-1036
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• 2021

Firefly luciferase (FLuc) can function as an efficient marker in the gene and viral therapies. Nonetheless, its clinical translation has been unaccomplished with the concerns on its exogenous nature and the similarity with human fatty acyl-CoA synthetase. In this study, we aimed to show safety of FLuc by conducting a set of preclinical experiments and a human use. Initially, FLuc permeability across the plasma membrane was investigated by delivering the FLuc-carrying viral vector, OTS-412, or the FLuc recombinant protein. After in vitro infection of OTS-412 into different cancer cell lines, FLuc activity was detected only in the cell lysates, but not in culture media. In addition, recombinant FLuc protein further showed the impermeability against the plasma membrane. Similar result was also observed in the in vivo experiment. After being injected into the VX2 tumor-bearing rabbit, the FLuc exclusively resided within the tumor tissue without being detected in the blood plasma or other organs. Human cancer cell lines originated from various organs were lysed and treated to the FLuc, and none of the human substrates was reactive against the FLuc. As a final step, FLuc recombinant protein was intravenously injected into a human. The luciferase was degraded with the half-life of 20 to 30 minutes in blood, and was untraceable from 1.5 hr after the injection. In addition, the blood plasma was nonresponsive against the fatty acids. Hematological analysis was also comparable between the pre- and post-injection. Altogether, our study collectively demonstrates the safety of the firefly luciferase.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.3
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• pp.192-200
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• 2008

To evaluate the hemodynamic changes and the predictive factors of the clinical outcome in pediatric patients with moyamoya disease, we analyzed pre/post basal/acetazolamide stress brain perfusion SPECT with automated volume of interest (VOIs) method. Methods: Total fifty six (M:F = 33:24, age $6.7{\pm}3.2$ years) pediatric patients with moyamoya disease, who underwent basal/acetazolamide stress brain perfusion SPECT within 6 before and after revascularization surgery (encephalo-duro-arterio-synangiosis (EDAS) with frontal encephalo-galeo-synangiosis (EGS) and EDAS only followed on contralateral hemisphere), and followed-up more than 6 months after post-operative SPECT, were included. A mean follow-up period after post-operative SPECT was $33{\pm}21$ months. Each patient's SPECT image was spatially normalized to Korean template with the SPM2. For the regional count normalization, the count of pons was used as a reference region. The basal/acetazolamide-stressed cerebral blood flow (CBF), the cerebral vascular reserve index (CVRI), and the extent of area with significantly decreased basal/acetazolamide- stressed rCBF than age-matched normal control were evaluated on both medial frontal, frontal, parietal, occipital lobes, and whole brain in each patient's images. The post-operative clinical outcome was assigned as good, poor according to the presence of transient ischemic attacks and/or fixed neurological deficits by pediatric neurosurgeon. Results: In a paired t-test, basal/acetazolamide-stressed rCBF and the CVRI were significantly improved after revascularization (p<0.05). The significant difference in the pre-operative basal/acetazolamide-stressed rCBF and the CVRI between the hemispheres where EDAS with frontal EGS was performed and their contralateral counterparts where EDAS only was done disappeared after operation (p<0.05). In an independent student t-test, the pre-operative basal rCBF in the medial frontal gyrus, the post-operative CVRI in the frontal lobe and the parietal lobe of the hemispheres with EDAS and frontal EGS, the post-operative CVRI, and ${\Delta}CVRI$ showed a significant difference between patients with a good and poor clinical outcome (p<0.05). In a multivariate logistic regression analysis, the ${\Delta}CVRI$ and the post-operative CVRI of medial frontal gyrus on the hemispheres where EDAS with frontal EGS was performed were the significant predictive factors for the clinical outcome (p =0.002, p =0.015), Conclusion: With probabilistic map, we could objectively evaluate pre/post-operative hemodynamic changes of pediatric patients with moyamoya disease. Specifically the post-operative CVRI and the post-operative CVRI of medial frontal gyrus where EDAS with frontal EGS was done were the significant predictive factors for further clinical outcomes.

• Journal of Chest Surgery
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• v.32 no.7
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• pp.603-612
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• 1999

Background : It has been documented that brief repetitive periods of ischemia and reperfusion (ischemic preconditioning, IP) enhances the recovery of post-ischemic contractile function and reduces infarct size after a longer period of ischemia. Many mechanisms have been proposed to explain this process. Recent studies have suggested that transient increase in the intracellular calcium may have triggered the activation of protein kinase C(PKC); however, there are still many controversies. Accordingly, the author performed the present study to test the hypothesis that preconditioning with high concentration of calcium before sustained subsequent ischemia(calcium preconditioning) mimics IP by PKC activation. Material and Method : The isolated hearts from the New Zealand White rabbits(1.5∼2.0 kg body weight) Method: The isolated hearts from the New Zealand White rabbits(1.5∼2.0 kg body weight) were perfused with Tyrode solution by Langendorff technique. After stabilization of baseline hemodynamics, the hearts were subjected to 45-minute global ischemia followed by a 120-minute reperfusion with IP(IP group, n=13) or without IP(ischemic control, n=10). IP was induced by single episode of 5-minute global ischemia and 10-minute reperfusion. In the Ca2+ preconditioned group, perfusate containing 10(n=10) or 20 mM(n=11) CaCl2 was perfused for 10 minutes after 5-minute ischemia followed by a 45-minute global ischemia and a 120-minute reperfusion. Baseline PKC was measured after 50-minute perfusion without any treatment(n=5). Left ventricular function including developed pressure(LVDP), dP/dt, heart rate, left ventricular end-diastolic pressure(LVEDP) and coronary flow(CF) was measured. Myo car ial cytosolic and membrane PKC activities were measured by 32P-${\gamma}$-ATP incorporation into PKC-specific pepetide. The infarct size was determined using the TTC (tetrazolium salt) staining and planimetry. Data were analyzed using one-way analysis of variance(ANOVA) variance(ANOVA) and Tukey's post-hoc test. Result: IP increased the functional recovery including LVDP, dP/dt and CF(p<0.05) and lowered the ascending range of LVEDP(p<0.05); it also reduced the infarct size from 38% to 20%(p<0.05). In both of the Ca2+ preconditioned group, functional recovery was not significantly different in comparison with the ischemic control, however, the infarct size was reduced to 19∼23%(p<0.05). In comparison with the baseline(7.31 0.31 nmol/g tissue), the activities of the cytosolic PKC tended to decrease in both the IP and Ca2+ preconditioned groups, particularly in the 10 mM Ca2+ preconditioned group(4.19 0.39 nmol/g tissue, p<0.01); the activity of membrane PKC was significantly increased in both IP and 10 mM Ca2+ preconditioned group (p<0.05; 1.84 0.21, 4.00 0.14, and 4.02 0.70 nmol/g tissue in the baseline, IP, and 10 mM Ca2+ preconditioned group, respectively). However, the activity of both PKC fractions were not significantly different between the baseline and the ischemic control. Conclusion: These results indicate that in isolated Langendorff-perfused rabbit heart model, calcium preconditioning with high concentration of calcium does not improve post-ischemic functional recovery. However, it does have an effect of limiting(reducing) the infart size by ischemic preconditioning, and this cardioprotective effect, at least in part, may have resulted from the activation of PKC by calcium which acts as a messenger(or trigger) to activate membrane PKC.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.1
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• pp.10-18
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• 2009

Purpose: We investigated quantification of dopaminergic transporter (DAT) and serotonergic transporter (SERT) on $^{123}I$-FP-CIT SPECT for differentiating between multiple systemic atrophy (MSA) and idiopathic Parkinson's disease (IPD). Materials and Methods: N-fluoropropyl-$2{\beta}$-carbomethoxy-$3{\beta}$-4-[$^{123}I$]-iodophenylnortropane SPECT ($^{123}I$-FP-CIT SPECT) was performed in 8 patients with MSA (mean age: $64.0{\pm}4.5yrs$, m:f=6:2), 13 with early IPD (mean age: $65.5{\pm}5.3yrs$, m:f=9:4), and 12 healthy controls (mean age: $63.3{\pm}5.7yrs$, m:f=8:4). Standard regions of interests (ROls) of striatum to evaluate DAT, and hypothalamus and midbrain for SERT were drawn on standard template images and applied to each image taken 4 hours after radiotracer injection. Striatal specific binding for DAT and hypothalamic and midbrain specific binding for SERT were calculated using region/reference ratio based on the transient equilibrium method. Group differences were tested using ANOVA with the postHoc analysis. Results: DAT in the whole striatum and striatal subregions were significantly decreased in both patient groups with MSA and early IPD, compared with healthy control (p<0.05 in all). In early IPD, a significant increase in the uptake ratio in anterior and posterior putamen and a trend of increase in caudate to putamen ratio was observed. In MSA, the decrease of DAT was accompanied with no difference in the striatal uptake pattern compared with healthy controls. Regarding the brain regions where $^{123}I$-FP-CIT binding was predominant by SERT, MSA patients showed a decrease in the binding of $^{123}I$-FP-CIT in the pons compared with controls as well as early IPD patients (MSA: $0.22{\pm}0.1$ healthy controls: $0.33{\pm}0.19$, IPD: $0.29{\pm}0.19$), however, it did not reach the statistical significance. Conclusion: In this study, the differential patterns in the reduction of DAT in the striatum and the reduction of pontine $^{123}I$-FP-CIT binding predominant by SERT could be observed in MSA patients on $^{123}I$-FP-CIT SPECT. We suggest that the quantification of SERT as well as DAT using $^{123}I$-FP-CIT SPECT is helpful to differentiate parkinsonian disorders in early stage.

• Pediatric Infection and Vaccine
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• v.5 no.2
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• pp.230-238
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• 1998

Purpose : Worldwidely, the incidence of the hepatitis A has been markedly decreased in the past years. Also in Korea, there has been only a few sporadic cases without evidence of epidemics since the mid 1980s. However, the incidence of the hepatitis A in young adults and childen has been in trends of increasing since 1996. So, we retrospectively performed the study on the epidemiolgical changes and the clinical feature of hepatitis A in childen, living in Kyung-gi province, since 1988 to 1998. Methods : The four affiliated hospitals of the Catholic University of Korea, Our lady of Mercy's hospital, Holy family hospital, Eui-Jung-bu St. Mary's hospital, and St. Vincent hospital, were enrolled in this study. We conducted statistical analysis on the incidence of hepatitis A since 1988 to 1998, concerning with the period (monthly, annually), age, sex and related epidemiological property, by reviewing the hospital records of the patients with hepatitis A. We simultaneously performed the study concerning with the clinical characteristics of hepatitis A. Results : 1) During the study period, 46 children was diagnosed as hepatitis A, and among them 28 children (60.1%) developed sporadically in the 1998. And sex ratio was 1.2(male):1(female). 2) Most of the patients developed between March and July, and hepatitits A were mainly developed in the patients above the 10 year old ages(37 patients; 80.4%). 3) The socioeconomic and educational status of the patient's parents was almostly below the middle and low class. Although, we could not find the etiological factors in most cases, but we found the evidence of interfamilial transmission in one family. 4) The patients complained the symptoms of nausea and vomiting, jaundice, poor appetite, mild fever, fatigueness, abdominal pain, URI symptom, dyspepsia, dark urine, headache and diarrhea in order, and findings of jaundice, hepatomegaly, RUQ tenderness, splenomegaly and LLQ tenderness in order were seen. 5) All patients showed abnormal findings of the liver function tests, and the pattern of cholestatic hepatitis were seen in most cases, but these findings were normalized within the 2~4 weeks. The findings of the gall bladder wall thickening, hepatomegaly, splenomegaly and ascites were seen on abodominal sonogram. 6) The prognosis of all patients were good without complications, except in one case who had the episode of transient recuurence. And the mean hospitalization dates were 11.1 days. Conclusion : We found that the incidence of hepatitis A showed the increasing trend, and peaked in the 1998 in Kyung-gi province children. And hepatitis A mainly developed in children above the 10 year old ages. The scioeconomic and educational status of patient's family was almostly below the middle class. All of them showed abnormal liver function, and clinically cholestatic hepatitis features were seen in most cases. But, the prognosis was excellent without complication in all cases.