• Radiation Oncology Journal
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• v.22 no.1
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• pp.55-63
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• 2004

Purpose : To evaluate the reflection of tumor motion according to the planning CT scan time. Material and Methods : A model of N-shape, which moved aiong the longitudinal axis during the ventilation caused by a mechanical ventilator, was produced. The model was scanned by planning CT, while setting the relative CT scan time (T: CT scan time/ventilatory period) to 0.33, 0.50, 0.67, 0.75, 1.00, 1.337, and 1.537. In addition, three patients with non-small cell lung cancer who received stereotactic radiosurgery In the Department of Radiation Oncology, Asan Medical Center from 03/19/2002 to 05/21/2002 were scanned. Slow (10 Premier, Picker, scan time 2.0 seconds per slice) and fast CT scans (Lightspeed, GE Medical Systems, with a scan time of 0.8 second per slice) were peformed for each patient. The magnitude of reflected movement of the N-shaped model was evaluated by measuring the transverse length, which reflected the movement of the declined bar of the model at each slice. For patients' scans, all CT data sets were registered using a stereotactic body frame scale with the gross tumor volumes delineated in one CT image set. The volume and three-dimensional diameter of the gross tumor volume were measured and analyzed between the slow and fast CT scans. Results : The reflection degree of longitudinal movement of the model increased in proportion to the relative CT scan times below 1.00 7, but remained constant above 1.00 T Assuming the mean value of scanned transverse lengths with CT scan time 1.00 T to be $100\%$, CT scans with scan times of 0.33, 0.50, 0.57, and 0.75 T missed the tumor motion by 30, 27, 20, and $7.0\%$ respectively, Slow (scan time 2.0 sec) and Fast (scan time 0.8 sec) CT scans of three patients with longitudinal movement of 3, 5, and 10 mm measured by fluoroscopy revealed the increases in the diameter along the longitudinal axis Increased by 6.3, 17, and $23\%$ in the slow CT scans. Conculsion : As the relative CT scan time increased, the reflection of the respiratory tumor movement on planning CT also Increased, but remained constant with relative CT scan times above 1.00 T When setting the planning CT scan time above one respiration period (>1.00 T), only the set-up margin is needed to delineate the planning target volume. Therefore, therapeutic ratio can be increased by reducing the radiation dose delivered to normal lung tissue.

• Radiation Oncology Journal
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• v.24 no.1
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• pp.67-76
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• 2006

Purpose: Oral mucositis is a common toxicity of radiation or chemotherapy, which is used a treatment for head and neck cancer. We investigated effects of recombinant human epidermal growth factor (rhEGF) on radiation-induced oral mucositis in rat model. Materials and Methods: Spraque-Dawley rats (7 per group) exposed to a single dose of 25 Gy (day 0) on their head, except for one group, were randomly divided into un-treated, vehicle-treated, and two rhEGF-treated groups. Rats were topically applied with rhEGF (15 or $30{\mu}g/oral$ cavity/day) or vehicle to their oral mucosa. Survival rate of rats, weight changes, and food intakes were examined from day 0 to 18 after radiation. Histology study was performed from oral mucosa of rats at day 7 and 18 after radiation. Results: rhEGF-treated groups (15 or $30{\mu}g/oral$) showed all survival rate 33%, whereas un-treated and vehicle-treated groups showed all survival rate 0% at the end of experiment. rhEGF-treated groups statistically had less weight loss compared to vehicle-treated group from day 2 to 7 after radiation. Food intake of rats with rhEGF treatment turned to increase at day 14 after radiation. At 7 day after radiation, un-treated and vehicle-treated groups showed severe pseudomembraneous or ulcerative oral mucositis. On the other hand, rhEGF-treated groups had no more than cellular swelling and degeneration of epidermal cells in oral mucosa of rats. Conclusion: These results suggest that rhEGF has significantly positive effects on radiation-induced oral mucositis in rats. rhEGF display a therapeutic potential on a clinical level.

• Radiation Oncology Journal
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• v.11 no.1
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• pp.29-34
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• 1993

Experiments have been carried out with C3H mouse fibrosarcoma (FSa II) to determine the effect of different sequence and time intervals between irradiation and administration of cis-diammihedichloroplatinum (cis-DDP) with gross tumors (6 mm in diameter), microscopic tumors (3 days after transplantation of $10^3$ cells) and cells in culture. The drug was administered either 24, 12, 8, 4, 2, 1, 0.5 hour before irradiation, immediately before irradiation, or 0.5, 1, 2, 4, 8, 12, 24 hours after irradiation. In case of in vivo studies, tumor growth delay was used as an end point. Clonogenic cell surviving fraction was used for in vitro studies. Tumor growth delay for gross tumor after 10 Gy radiation plus 10 mg/kg cis-DDP ranged from 6.3 to 10.66 days and the enhancement ratio ranged from 1.37 to 2.23. The most effective combination was when cis-DDP was given 4 hours before irradiation. Tumor growth delay for microscopic tumor after 5 Gy of radiation and 5 mg/kg of cis-DDP ranged from 3.55 to 11.98 days with enhancement ratio from 2.05 to 6.92. Microscopic tumors showed response significantly greater than additive in every time interval and the most effective treatments were when cis-DDP was given 2 and 1 hour before irradiation. In in vitro experiment, the surviving fraction after 6 Gy of radiation and 1 hour exposure to 4 ${\mu}M$ cis-DDP fluctuated as a function of time between treatments, but the difference between maximum and minimum surviving fractions was very small. According to the above results the sequence and time interval between irradiation and chemotherapy is very critical especially for the management of microscopic tumors as in the case of postoperative adjuvant treatment.

• KSBB Journal
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• v.24 no.6
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• pp.541-548
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• 2009

For investigation of anti-angiogenesis mechanism of Anthrisci radix, Psoraleae semen, Siegesbeckiae herba and Corni fructus, anti-cell adhesion experiment was performed. The adhesion of U937 cells to IL-$1\beta$-stimulated HUVECs was completely suppressed by 276% at 0.2 mg/L of Anthrisci radix, 220% at 5 mg/L of Psoraleae semen, 158% at 10 mg/L of Siegesbeckiae herba and 132% at 20 mg/L of Corni fructus, respectively. And the adhesion of PMA-chemical stimulated U937 cells to HUVECs, it was inhibited 139% at 0.2 mg/L of Anthrisci radix, 442% at 5 mg/L of Psoraleae semen, 720% at 10 mg/L of Siegesbeckiae herba and 664% at 20 mg/L of Corni fructus. Also, the adhesion of chemical stimulated U937 cells to IL-$1\beta$/chemical stimullated HUVECs, it was inhibited by 286% at 0.2 mg/L of Anthrisci radix, 146% at 5 mg/L of Psoraleae semen, 436% at 10 mg/L of Siegesbeckiae herba and 297% at 20 mg/L of Corni fructus, respectively. It would be a useful substance for anti-cell adhesion based on anti-angiogenesis for anti-obesity and anti-cancer.

• Journal of Life Science
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• v.30 no.4
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• pp.331-342
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• 2020

The suppression of neuroinflammatory responses in microglial cells can be considered a key target for improving the progression of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Asparagus cochinchinensis has traditionally been used as a medicine to treat fever, cough, kidney disease, breast cancer, inflammatory diseases, and brain diseases. In this study, we investigated the neuroprotective mechanism of an aqueous extract from A. cochinchinensis root (AEAC), particularly its anti-inflammatory effects on lipopolysaccharide (LPS)-activated BV-2 microglial cells. BV-2 cells were treated with four different concentrations of AEAC. No significant toxicity was detected in BV-2 cells treated with AEAC. Nitric oxide (NO), cyclooxygenase-2 (COX-2) mRNA, and inducible nitric oxide synthase (iNOS) mRNA levels were 21% lower in the AEAC+LPS group than in the Vehicle+LPS group. Lower proinflammatory (TNF-α and IL-1β) and anti-inflammatory cytokine (IL-6 and IL-10) levels were also detected in the AEAC+LPS group than in the Vehicle+LPS group, albeit at varying rates. Moreover, the phosphorylation of mitogen-activated protein kinase (MAPK) members after LPS treatment was significantly recovered in the AEAC-pretreated group compared to the Vehicle+LPS group, enhancement of the phosphorylation of mitogen-activated protein kinase (MAPK) members after LPS treatment was significantly recovered in the AEAC-pretreated group, while cell cycle arrest at the G2/M phase caused by LPS treatment was less severe in the AEAC+LPS group. The increase in reactive oxygen species (ROS) generation induced by LPS treatment was also lower in the AEAC-pretreated group than in the Vehicle+LPS group. This is the first study to show that AEAC exerts anti-neuroinflammatory activity against LPS stimulation by regulating the MAPK signaling pathway, the cell cycle, and ROS production.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.9 no.1
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• pp.9-16
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• 2023

Liposomes as drug delivery system have proved useful carrier for various disease, including cancer. In addition, perfluorocarbon cored microbubbles are utilized in conjunction with high-intensity focused-ultrasound (HIFU) to enable simultaneous diagnosis and treatment. However, microbubbles generally exhibit lower drug loading efficiency, so the need for the development of a novel liposome-based drug delivery material that can efficiently load and deliver drugs to targeted areas via HIFU. This study aims to develop a liposome-based drug delivery material by introducing a substance that can burst liposomes using ultrasound energy and confirm the ability to target tumors using PET imaging. Liposomes (Lipo-DOX, Lipo-DOX-Au, Lipo-DOX-Au-RGD) were synthesized with gold nanoparticles using an avidin-biotin bond, and doxorubicin was mounted inside by pH gradient method. The size distribution was measured by DLS, and encapsulation efficiency of doxorubicin was analyzed by UV-vis spectrometer. The target specificity and cytotoxicity of liposomes were assessed in vitro by glioblastoma U87mg cells to HIFU treatment and analyzed using CCK-8 assay, and fluorescence microscopy at 6-hour intervals for up to 24 hours. For the in vivo study, U87mg model mouse were injected intravenously with 1.48 MBq of ⁶⁴Cu-labeled Lipo-DOX-Au and Lipo-DOX-Au-RGD, and PET images were taken at 0, 2, 4, 8, and 24 hours. As a result, the size of liposomes was 108.3 ± 5.0 nm at Lipo-DOX-Au and 94.1 ± 12.2 nm at Lipo-DOX-Au-RGD, and it was observed that doxorubicin was mounted inside the liposome up to 52%. After 6 hours of HIFU treatment, the viability of U87mg cells treated with Lipo-DOX-Au decreased by around 20% compared to Lipo-DOX, and Lipo-DOX-Au-RGD had a higher uptake rate than Lipo-DOX. In vivo study using PET images, it was confirmed that ⁶⁴Cu-Lipo-DOX-Au-RGD was taken up into the tumor immediately after injection and maintained for up to 4 hours. In this study, drugs released from liposomes-gold nanoparticles via ultrasound and RGD targeting were confirmed by non-invasive imaging. In cell-level experiments, HIFU treatment of gold nanoparticle-coupled liposomes significantly decreased tumor survival, while RGD-liposomes exhibited high tumor targeting and rapid release in vivo imaging. It is expected that the combination of these models with ultrasound is served as an effective drug delivery material with therapeutic outcomes.

• Pediatric Infection and Vaccine
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• v.12 no.2
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• pp.140-148
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• 2005

Purpose : To characterize the epidemiology and clinical features of invasive pneumococcal infections in Korean children. Methods : One hundred ninety four cases of invasive pneumococcal infections diagnosed at the Seoul National University Children's Hospital from October 1985 to December 2003 were analysed retrospectively. All isolates were screened for resistance to penicillin by oxacillin disc diffusion test. Serotypes were determined for 125 isolates. Results : The types of infection were bacteremia without focus 84/194(43%), meningitis 36/194(19%), pneumonia with bacteremia 36/194(19%), peritonitis 24/194(12%), other focal infections 3/194(2%). Fifty seven percent(110/194) of the episodes developed in the immunocompromised and 20%(37/194) were nosocomially acquired. The patients younger than 2 years of age was 60% in the immunocompetent patients and 25% in the immunocompromised patients. The overall case fatality rate was 7%. All the isolates by 1988 were susceptible to penicillin screened by oxacillin disk. Penicillin resistance was first detected in 1989(20%), and then increased rapidly; 89% in 1995, 69% in 1996, and 80~100% thereafter. The seven most frequently isolated serotypes were 23F, 19F, 14, 6B, 6A, 9V and 19A, which accounted for 70% of total isolates. Conclusion : S. pneumoniaeis an important cause of morbidity and mortality in children. Invasive infections caused by S. pneumoniae most often occurred in infants and young children, while they are frequent in older immunocompromised children as well. This is the largest case series on invasive pneumococcal infections in Korean children.

• Clinical and Experimental Pediatrics
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• v.48 no.11
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• pp.1193-1200
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• 2005

Purpose : Invasive bacterial infection is a major cause of morbidity and mortality in children. Previously, we reported etiology of invasive infections in healthy children in 1985-1995. This study was performed to update etiology of invasive bacterial infections in the previously healthy children. Methods : We reviewed medical records of 98 episodes of invasive bacterial infections in immunocompetent children at the Seoul National University Children's Hospital in 1996-2004. Results : The frequent pathogens identified over all age groups were Streptococcus pneumoniae (33%) and Staphylococcus aureus(33%). The proportion of Salmonella species and Haemophilus influenzae has been declined to 4% each from 23% and 14%, respectively, compared to previous study. S. agalactiae was the most common isolate in the infants ${\leq}3$ months. Among the infants and children aged 3 months to 2 years and children of 2-5 years, S. pneumoniae(57%, 52%, respectively, in each group) was the most common isolates followed by S. aureus(17% and 24%, respectively). S. aureus was the most common isolates(73%) in children >5 years. Primary bacteremia was the most common clinical diagnosis(27%). S. pneumoniae was responsible for 42% of primary bacteremia, 50% of meningitis, and 69% of bacteremic pneumonia and empyema. S. aureus accounted for 80% of bone and joint infections. The case fatality rate was 8.1% for all invasive infections. Conclusion : We reviewed frequency of bacterial agents of invasive infections in children. The data may be useful for pediatricians to select adequate empirical antibiotics in the management of invasive bacterial infections.

• Radiation Oncology Journal
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• v.26 no.1
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• pp.1-9
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• 2008

Purpose: To evaluate the impact of postoperative radiotherapy on loco-regional failure in patients with vulvar carcinoma and to determine the treatment strategy for inguinal lymph nodes. Materials and Methods: Sixty-six patients who received treatment for primary vulvar carcinoma at Seoul National University Hospital, from October 1979 through June 2004, were retrospectively analyzed. Sixteen patients were excluded from the analysis due to the following reasons: distant metastases in two patients; palliative intent for six patients; previous radiotherapy given to the pelvis in three patients; follow-up loss after surgery for four patient; insufficient medical records for one patient. Of 50 eligible patients, 35 were treated with surgery alone(S), ten were treated with surgery followed by radiotherapy(S+RT), and five were treated with radiotherapy alone. Results: The 5-year overall survival(OS) and disease-free survival(DFS) rates of all patients were 91% and 78%, respectively. Twelve patients(26%) experienced treatment failures and the sites of initial failure were as follows: a primary site in eight patients; regional lymph nodes in three patients; the lung in one patient. Although risk factors for failure were more common in the S+RT group than the S group of patients(p<0.05), the DFS rates were similar for the two groups(5-year DFS rates, 78% vs. 83%, p=0.66). The incidences of occult lymph node metastases was 10%. Ten of 31 patients with clinically negative lymph nodes did not received inguinal lymph node dissection, but no patient experienced regional failure. Conclusion: Postoperative radiotherapy may have a potential benefit for patients with risk factors for failure. The omission of inguinal dissection or elective radiotherapy to the inguinal lymph nodes may be considered in low-risk patients with clinically negative lymph nodes.

• Neonatal Medicine
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• v.18 no.1
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• pp.42-48
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• 2011

Purpose: Several factors including prolonged inflammatory response are thought to contribute to the pathogenesis of bronchopulmonary dysplasia (BPD). The clinical findings can be explained by an increased production of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-$\alpha$ ). We investigated the relationship between susceptibility to BPD and TNF-$\alpha$ promoter polymorphisms to identify genetic factors of the disease. Methods: Thirty-eight preterm infants who had developed BPD and 55 controlled infants with a birth weight <1,500 g were analyzed for TNF-$\alpha$ genotypes. The alleles of five promoter sites (-1031/-863/-857/-308/-238) of TNF-$\alpha$ gene were determined using $Taqman^{(R)}$-based allelic discrimination assays. Results: Gestational age ($27^{+5}{\pm}2^{+0}$ wk vs. $29^{+2}{\pm}1^{+4}$ wk, P<0.0001) and birth weight (990${\pm}$270 g vs. 1,220${\pm}$230 g, P<0.0001) were lower in the BPD group compared to the control group. The incidence of respiratory distress syndrome (71.1% vs. 49.1%, P=0.035) and patent ductus arteriosus (71.1% vs. 50.9%, P=0.052) was higher in the BPD group compared to the control group. The frequencies of the alleles and genotypes of five promoter sites (-1031/-863/-857/-308/-238) of TNF-$\alpha$ gene did not show differences between the BPD group and the control group. Conclusion: TNF-$\alpha$ promoter polymorphisms are not associated with susceptibility to BPD in Korean preterm infants.