• Radiation Oncology Journal
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• v.16 no.3
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• pp.291-301
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• 1998

Purpose : A retrospective study was conducted comparing single daily fraction (SDF) thoracic radiotherapy (TRT) with twice daily (BID) TRT to determine the potential benefit of BID TRT in limited-stage small cell lung cancer (SCLC). Endpoints of the study were response. survival, pattern of failure, and acute toxicity. Materials and Methods : Between November 1989 to December 1996, 78 patients with histologically proven limited-stage SCLC were treated at the Department of Therapeutic Radiology, Chungnam National University Hospital. Of these, 9 were irradiated for palliative intent, and 1 had recurrent disease. Remaining 68 patients were enrolled in this study. There were 26 patients with a median age of 58 years, and 22 (85$\%$) ECOG performance score of less than 1 in SDF TRT. There were 42 patients with a median age of 57 years, and 36 (86$\%$) ECOG performance score of less than 1 in BID TRT By radiation fractionation regimen, there were 26 in SDF TRT and 42 in BID TRT. SDF TRT consisted of 180 cGy, 5 days a week. BID TRT consisted of 150 cGy BID, 5 days a week in 13 of 42 and 120 cGy BID, in 29 of 42. And the twice daily fractions were separated by at least 4 hours. Total radiotherapy doses were between 5040 and 6940 cGy (median, 5040 cGy) in SDF TRT and was between 4320 and 5100 cGy (median, 4560 cGy) in BID TRT. Prophylactic cranial irradiation (PCI) was recommended for patients who achieved a CR. The recommended PCI dose was 2500 cGy/10 fractions. Chemotherapy consisted of CAV (cytoxan 1000 mg/$m^2$, adriamycin 40 mg/$m^2$, vincristine 1 mg/$m^2$) alternating with VPP (cisplatin 60 mg/$m^2$, etoposide 100 mg/$m^2$) every 3 weeks in 25 (96$\%$) of SDF TRT and in 40 (95$\%$) of BID TRT. Median cycle of chemotherapy was six in both group. Timing for chemotherapy was sequential in 23 of SDF TRT and in 3 BID TRT, and concurrent in 3 of SDF TRT and in 39 of BID TRT Follow-up ranged from 2 to 99 months (median, 14 months) in both groups. Results : Of the 26 SDF TRT, 9 (35$\%$) achieved a complete response (CR) and 14 (54$\%$) experienced a partial response (PR). Of the 42 BID TRT, 18 (43$\%$) achieved a CR and 23 (55$\%$) experienced a PR. There was no significant response difference between the two arms (p=0.119). Overall median and 2-year survival were 15 months and 26.8$\%$, respectively. The 2-year survivals were 26.9$\%$ and 28$\%$ in both arm, respectively (p=0.51). The 2-rear survivals were 35$\%$ in CR and 24.2$\%$ in PR, respectively. The grade 2 to 3 esophageal toxicities and grade 2 to 4 neutropenias were more common in BID TRT (p=0.028 0.003). There was no difference in locoregional and distant metastasis between the two arms (p=0 125 and 0.335, respectively). The most common site of distant metastasis was the brain. Conclusion : The median survival and 2-year survival were 17 months and 20.9$\%$ in SDF TRT with sequential chemotherapy, and 15 months and 28$\%$ in BID TRT with concurrent chemotherapy, respectively. We did not observe a substantial improvement of long-term survival in the BID TRT with concurrent chemotherapy compared with standard schedules of SDF TRT with sequential chemotherapy. The grade 2 to 3 esophageal toxicities and glade 2 to 4 neutropenias were more common in BID TRT with concurrent chemotherapy. Although the acute toxicities were more common in BID TRT with concurrent chemotherapy than SDF TRT with sequential chemotherapy, a concurrent chemotherapy and twice daily TRT was feasible. However further patient accrual and long-term follow up are needed to determine the potential benefits of BID TRT in limited-stage SCLC.

• Radiation Oncology Journal
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• v.19 no.2
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• pp.163-170
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• 2001

Purpose : The measurement of radiation survival using a clonogenic assay, the established standard, can be difficult and time consuming. In this study, We have used the MTT assay, based on the reduction of a tetrazolium salt to a purple formazan precipitate by living cells, as a substitution for clonogenic assay and have examined the optimal condition for performing this assay in determination of radiation sensitivity. Materials and Methods : Four human cancer cell lines - PCI-1, SNU-1066, NCI-H630 and RKO cells have been used. For each cell line, a clonogenic assay and a MTT assay using Premix WST-1 solution, which is one of the tetrazolium salts and does not require washing or solubilization of the precipitate were carried out after irradiation of 0, 2, 4, 6, 8, 10 Gy. For clonogenic assay, cells in $25\;cm^2$ flasks were irradiated after overnight incubation and the resultant colonies containing more than 50 cells were scored after culturing the cells for $10\~14$ days. For MTT assay, the relationship between absorbance and cell number, optimal seeding cell number, and optimal timing of assay was determined. Then, MTT assay was performed when the irradiated cells had regained exponential growth or when the non-irradiated cells had undergone four or more doubling times. Results : There was minimal variation in the values gained from these two methods with the standard deviation generally less than $5\%$, and there were no statistically significant differences between two methods according to t-test in low radiation dose (below 6 Gy). The regression analyses showed high linear correlation with the $R^2$ value of $0.975\~0.992$ between data from the two different methods. The optimal cell numbers for MTT assay were found to be dependent on plating efficiency of used cell line. Less than 300 cells/well were appropriate for cells with high plating efficiency (more than $30\%$). For cells with low plating efficiency (less than $30\%$), 500 cells/well or more were appropriate for assay. The optimal time for MTT assay was after 6 doubling times for the results compatible with those of clonogenic assay, at least after 4 doubling times was required for valid results. In consideration of practical limits of assay (12 days, in this study) cells with doubling time more than 3 days were inappropriate for application. Conclusion : In conclusion, it is found that MTT assay can successfully replace clonogenic assay of tested cancer cell lines after irradiation only if MTT assay was undertaken with optimal assay conditions that included plating efficiency of each cell line and doubling time at least.

• Radiation Oncology Journal
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• v.21 no.3
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• pp.227-237
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• 2003

Purpose: The human chronic myelogenous leukemia cell line, K562, expresses the chimeric bcr-abl oncoprotein, whose deregulated protein tyrosine kinase activity antagonizes via DNA damaging agents. Previous experiments have shown that nanomolar concentrations of herbimycin A (HWA) coupled with X-irradiation have a synergistic effect in inducing apoptosis in the Ph-positive K562 leukemia cell line, but genistein, a PTK inhibitor, is non selective for the radiation-induced apoptosils on $p210^{bcr/abl}$ protected K562 cells. In these experiments, the cytoplasmic signal transduction pathways, the Induction on a number of transcription factors and the differential gene expression in this model were investigated. Materials and Methids: K562 cells in the exponential growth phase were used in this study. The cells were irradiated with 0.5-12 Gy, using a 6 Mev Linac (Clinac 1800, Varian, USA). Immediately after irradiation, the cells were treated with $0.25/muM$ of HMA and $25/muM$ of genistein, and the expressions and the activities of abl kinase, MAPK family, NF- kB, c-fos, c-myc, and thymidine kinase1 (TK1) were examined. The differential gene expressions induced by PTK inhibitors were also investigated. Results: The modulating effects of herbimycin A and genistein on the radiosensitivity of K562 cells were not related to the bcr-abl kinase activity. The signaling responses through the MAPK family of proteins, were not involved either in association with the radiation-induced apoptosis, which is accelerated by HMA, the expression of c-myc was increased. The combined treatment of genistein, with irradiation, enhanced NF- kB activity and the TK1 expression and activity. Conclusion: The effects of HMA and genistein on the radiosensitivity on the K562 cells were not related to the bcr-abl kinase activity in this study, another signaling pathway, besides the WAPK family responses to radiation to K562 cells, was found. Further evaluation using this model will provide valuable information for the optional radiosensitization or radioprotection.

• The Korean Journal of Nuclear Medicine
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• v.35 no.3
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• pp.131-141
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• 2001

Purpose: We evaluated the sensitivity of the F-18 FDG PET by visual assessment and statistical parametric mapping (SPM) analysis for the localization of the epileptogenic zones in frontal lobe epilepsy. Materials and Methods: Twenty-four patients with frontal lobe epilepsy were examined. All patients exhibited improvements after surgical resection (Engel class I or II). Upon pathological examination, 18 patients revealed cortical dysplasia, 4 patients revealed tumor, and 2 patients revealed cortical scar. The hypometabolic lesions were found in F-18 FDG PET by visual assessment and SPM analysis. On SPM analysis, cutoff threshold was changed. Results: MRI showed structural lesions in 12 patients and normal results in the remaining 12. F-18 FDG PET correctly localized epileptogenic zones in 13 patients (54%) by visual assessment. Sensitivity of F-18 FDG PET in MR-negative patients (50%) was similar to that in MR-positive patients (67%). On SPM analysis, sensitivity decreased according to the decrease of p value. Using uncorrected p value of 0.05 as threshold, sensitivity of SPM analysis was 53%, which was not statistically different from that of visual assessment. Conclusion: F-18 FDG PET was sensitive in finding epileptogenic zones by revealing hypometabolic areas even in MR-negative patients with frontal lobe epilepsy as well as in MR-positive patients. SPM analysis showed comparable sensitivity to visual assessment and could be used as an aid in the diagnosis of epileptogenic zones in frontal lobe epilepsy.

• 한국지구물리탐사학회:학술대회논문집
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• 2005.09a
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• pp.125-153
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• 2005

It has been widely known that the seismic piezo-cone penetration test (SCPTU) is one of the most useful techniques for investigating the geotechnical characteristics including dynamic soil properties. As the practical applications in Korea, SCPTU was carried out at two sites in Busan and four sites in Incheon, which are mainly composed of alluvial or marine soil deposits. From the SCPTU waveform data obtained from the testing sites, the first arrival times of shear waves were and the corresponding time differences with depth were determined using the cross-over method, and the shear wave velocity profiles (VS) were derived based on the refracted ray path method based on Snell's law and similar to the trend of cone tip resistance (qt) profiles. In Incheon area, the testing depths of SCPTU were deeper than those of conventional down-hole seismic tests. Moreover, for the application of the conventional CPTU to earthquake engineering practices, the correlations between VS and CPTU data were deduced based on the SCPTU results. For the empirical evaluation of VS for all soils together with clays and sands which are classified unambiguously in this study by the soil behavior type classification Index (IC), the authors suggested the VS-CPTU data correlations expressed as a function of four parameters, qt, fs, $\sigma$, v0 and Bq, determined by multiple statistical regression modeling. Despite the incompatible strain levels of the down-hole seismic test during SCPTU and the conventional CPTU, it is shown that the VS-CPTU data correlations for all soils clays and sands suggested in this study is applicable to the preliminary estimation of VS for the Korean deposits and is more reliable than the previous correlations proposed by other researchers.

• Radiation Oncology Journal
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• v.21 no.4
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• pp.306-314
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• 2003

Purpose : In our Previous study, we have shown the main cel1 death pattern Induced by irradiation or protein tyrosine kinase (PTK) inhibitors in K562 human myeiogenous leukemic cell line. Death of the cells treated with irradiation alone was characterized by mitotic catastrophe and typical radiation-induced apoptosis was accelerated by herblmycin A (HMA). Both types of cell death were inhibited by genistein. In this study, we investigated the effects of HMA and genistein on cell cycle regulation and its correlation with the alterations of radiation-induced cell death. Materials and Methods: K562 cells In exponential growth phase were used for this study. The cells were Irradiated with 10 Gy using 6 MeV Linac (200-300 cGy/min). Immediately after irradiation, cells were treated with 250 nM of HMA or 25 $\mu$N of genistein. The distributions of cell cycle, the expressions of cell cycle-related protein, the activities of cyclin-dependent kinase, and the yield of senescence and differentiation were analyzed. Results: X-irradiated cells were arrested In the G2 phase of the cell cycle but unlike the p53-positive cells, they were not able to sustain the cell cycle arrest. An accumulation of cells in G2 phase of first ceil-cycle post-treatment and an increase of cyclin Bl were correlated with spontaneous, premature, chromosome condensation and mitotic catastrophe. HMA induced rapid G2 checkpoint abrogation and concomitant p53-independent Gl accumulation. HMA-induced cell cycle modifications correlated with the increase of CDK2 kinase activity, the decrease of the expressions of cyclins I and A and of CDK2 kinase activity, and the enhancement of radiation-induced apoptosis. Genistein maintained cells that were arrested in the G2-phase, decreased the expressions of cyclin Bl and cdc25c and cdc25C kinase activity, increased the expression of pl6, and sustained senescence and megakaryocytic differentiation. Conclusion: The effects of HMA and genistein on the radiation-induced cell death of KS62 cells were closely related to the cell cycle regulatory activities. In this study, we present a unique and reproducible model in which for investigating the mechanisms of various, radiation-induced, cancer cell death patterns. Further evaluation by using this model will provide a potent target for a new strategy of radiotherapy.

• Journal of the Korean Society of Radiology
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• v.14 no.5
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• pp.553-561
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• 2020

In this study aims to investigate the radiation protection effect of avocado peel extracts on the Sprague-Dawely rats. 52 male rats were randomly classified into 4 groups. NC Group was a normal control group, PA Group was a group injected avocado peel extracts, IR Group was irradiated group, and lastly PA+IR Group was set as an irradiated group after injected of avocado peel extracts. Avocado peel extract was administered orally at 200 mg/kg once a day for 14 days before irradiation, and the radiation dose was systemically irradiated with 6 MV X-ray of 7 Gy. On the 4 and 21 days after irradiation, the experimental animals were sacrificed to evaluate the change in blood cell composition, spleen index, and histopathological evaluation of the liver and small intestine. As a result, the PA+IR Group showed a significantly greater recovery of lymphocytes(p<0.01), red blood cells(p<0.01), and platelets(p<0.05) than the IR Group. It was also confirmed that the activation of Superoxide Dismutase(SOD) was further increased. Histopathologically, observed that nuclei aggregation and cytoplasmic expansion were slightly reduced in the PA+IR Group in the liver. and the damage was significantly reduce(p<0.01) in the change of villi length due to damage to the small intestine cells. Based on the above results, avocado peel extract can be expected to act as a radiation protection agent that can reduce damage to blood cells and major organs caused by irradiation.

• Radiation Oncology Journal
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• v.25 no.4
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• pp.206-212
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• 2007

Purpose: Heterotopic ossification is a well-known postoperative and post-traumatic complication of the elbow. We reviewed the treatment outcome for the use of low-dose radiation after surgical intervention of the elbow to prevent recurrence of heterotopic ossification (HO). Materials and Methods: Forty-five patients with HO underwent surgical intervention and postoperative radiotherapy of the elbow. The median age of the patients was 29 years ($16{\sim}75$ years), and 27 of the patients were men and 18 were women. The occurrence of HO was mainly due to surgery after fracture (24/45) and traumatic injury (21/45). Limitation of the range of motion (ROM) was the most common symptom of the patients. Thirty-four patients received postoperative radiotherapy with a dose of 8 Gy in 2 fractions; 5 patients received a dose of 10 Gy in 5 fractions and 6 patients received a dose of 7 Gy in 1 fraction. Postoperative radiotherapy was given on the first two postoperative days for most of the patients. Sixteen patients were not given anti-inflammatory medication and 29 patients were given NSAIDs for $1{\sim}8$ months. Results: After a median follow-up period of 18 months (range $6{\sim}72$ months), 41 patients showed clinical improvement and two patients did not show improvement. Assessment of the ROM showed a mean improvement from $0{\sim}135^{\circ}$ to $60{\sim}145^{\circ}$ (p=0.028), and assessment of the functional outcome according to MEPI was from ($15{\sim}95$) to ($80{\sim}100$) (p<0.0001). Two of the 34 patients that were followed-up with radiography had mild radiological recurrence of heterotopic ossification. No complications were observed after the radiotherapy. Conclusion: These results suggested that low-dose radiation administered after surgical intervention is safe and effective to prevent the recurrence of HO in the elbow.

• Journal of the Korean Society of Food Science and Nutrition
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• v.22 no.5
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• pp.517-523
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• 1993

This study was designed to observe the efforts of the feeding Platycodon grandiflorum, Codonopsis ianceolata, perilla oil and safflower oil on the improvement of the lipids in the serum and liver of dietary hypercholes-terolemic rats. Experimental groups mixed with 5% cellulose+10% lard (group 1, control group), 2% cholestyramine＋10% lard (group 2), 5% C. Ianceolata+10％ perilla oil (group3). 5％ P. grandiflorum＋10% perilla oil(group 4), 5% C. ianceolata+10% safflower oil(group 5) and 5% P. grandiflorum＋10% safflower oil (group 6) were administered to the male rats of the Sprague Dawley for 3 weeks. Concentrations of total cholesterol in serum were significantly lower in the all experimental groups (2~6 groups) than in the control group, and particularly, the lowest in the group 2 and 6. Concentrations of HDL-cholesterol in serum were remarkably higher in the groups 2 and 4. The ratio of HDL-cholesterol to total cholesterol was the highest in the group 2. Atherosclerotic index was lower in the groups 2, 4 and 6. Concentrations of LDL, phospholipid and triglyceride in serum were remarkably lower in the all experimental groups than in the control group, and particularly, lower in the groups 2, 4 and 6. Concentrations of free cholesterol and cholesteryl ester in serum were significantly lower in the all experimental groups than in the control group, and particularly, the lowest in the group 2. Concentrations of glucose in blood were the lowest in the group 2. And groups 3 and 5 were slgnificantly lower. Contents of total cholesterol and triglyceride in liver were significantly lower in the all experimental groups than in the control group, and particularlyr the lowest in the groups 2 and 3. Phospholipid content was showed little differenre among groups but the lowest in the group 2. From the above research, the feeding 5% Platycodon grandiflorum＋10% perilla oil and 5% Platycodon grandiflorum＋10% safflower oil were effective on the improvement of the lipid compositions in serum and liver.