• Radiation Oncology Journal
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• v.7 no.2
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• pp.247-257
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• 1989

Thirty patients with nonresectable hepatocellular carcinoma (HCC) due to either locally advanced lesion or association with liver cirrhosis, treated with combined radiotherapy and hyperthermia between April 1988 and July 1988, at Dept. of Radiation Oncology, Yonsei university College of medicine, were analysed. External radiotherapy of a total dose of 3060cGy/3.5 wks was given. Hyperthermia was given twice a week with a total of 6 treatment sessions using 8MHz radiofrequency capacitive type heating device, i.e., Thermotron RF-8 and Cancermia. In all cases hyperthermia was given within 30 minutes after radiotherapy for 30~60min. Temperature was measured by inserting thermocouple into the tumor mass under the ultrasonographic guidance only for those who had not bleeding tendency. As a result, partial response (PR) was achieved in 12 patients (40%), and symptomatic improvement was observed in 22 patients (78.6%) among 28 patients who had suffered from abdominal pain. The most significant factor affecting the tumor response rate was the type of tumor (single massive: 10/14, 71.4%; diffuse infiltrative: 2/10, 20%; multinodular:0/6, 0%; p<0.005). There were not any significant side effects relating to combined treatment. The overall 1 year survival rate was 34%, with 50% in the PR group and 22% in the no response group (NR), respectively. Median survival was 6.5 months and longer for those of PR than of NR (11 mos. vs 5, p<0.05). In conclusion, combined radiotherapy and hyperthermia appeared to be effective in local control and symptomatic palliation of HCC. Further study including a larger number of the patients to confirm its effect in survival and detrimental side effect should be urged.

• Radiation Oncology Journal
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• v.23 no.2
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• pp.71-77
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• 2005

Purpose: This retrospective study was conduced to analyze the treatment results and to evaluate the prognostic factors affecting the survival of nasopharyngeal carcinoma patients. Materials and Methods: From 1987 to 2002, we analyzed 43 patients who had nasopharyngeal carcinomas that were histologically confirmed and who had also completed the planned radiation therapy course at Keimyung University Dongsan Medical Center According to the 6th edition of American Joint Committee on Cancer staging system, 12 patients ($27.9\%$) were at Stage 11, 13 ($30.2\%$) were at Stage III and 18 ($41.9\%$) were at Stage IV Histopathologically, there were 15 ($34.9\%$) squamous cell carcinomas, 8 ($18.5\%$) nonkeratinizing carcinomas, 17 ($39.5\%$) undifferentiated carcinomas, and 3 ($7.0\%$) lymphoepitheliomas. Among the total 43 patients, 31 patients ($72.1\%$) were treated with only radiation therapy. Neoadjuvant chemotherapy was peformed on 7 patients ($16.3\%$) and concurrent chemoradiotherapy was performed on S patients ($11.6\%$). Cisplatin and 5-Fluorouracil were administered to 11 patients for 4 cycles, and Cisplatin and Taxotere were administered to 1 patient for 6 cycles. The range of the total radiation dose delivered to the primary tumor was from 61.2 to 84 Gy (median 70.4 Gy), The follow-up period ranged from 2 to 197 months with median follow-up of 84 months. Results: The local control rate at 6 months after radiation therapy was $90.7\%$. The five year overall survival and disease free survival rates were $50.7\%$ and $48.9\%$, respectively. On the multivariate analysis, the age, T-stage ($T_{1-3}\;vs\;T_4$), N-stage and AJCC stage were the statistically significant prognostic factors affecting survival (p<0.05). The patterns of failure were as follows: local failure only in 3 patients ($7.0\%$), local and systemic failure in 1 patient ($2.3\%$), and distant metastasis only in 11 patients ($25.6\%$). Conclusion: The prognostic factors affecting the outcome of nasopharyngeal carcinoma were age, T-stage (7$T_{1-3}\;vs\;T_4$), N-stage and stage. Because systemic metastasis was the main failure pattern noted for nasopharyngeal carcinoma, systemic chemotherapy is needed to decrease the rate of distant metastasis for nasopharyngeal carcinoma. In audition, research for more effective chemotherapeutical regimens and schedules is also needed.

• Radiation Oncology Journal
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• v.19 no.3
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• pp.252-258
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• 2001

Purpose : The objectives of this study are to investigate the significance of apoptotic death compared to total cell death after $\gamma-ray$ irradiation in human H&N cancer cell lines and to find out correlation between apoptosis and radiation sensitivity. Materials and method : Head and neck cancer cell lines (PCI-1, PCI-13, and SNU-1066), leukemia cell line (CCRF-CEM), and fibroblast cell line (LM217) as a normal control were used for this study. Cells were irradiated using Cs-137 animal experiment irradiator. Total cell death was measured by clonogenic assay. Annexin-V staining was used to detect the fraction of apoptotic death. Results : Surviving fraction at 2 Gy (SF2) were 0.741, 0.544, 0.313, 0.302, and 0.100 for PCI-1, PCI-13, SNU-1066, CCRF-CEM, and LM217 cell lines, respectively. Apoptosis was detected in all cell lines. Apoptotic index reached peak value at 72 hours after irradiation in head and neck cancer cell lines, and that was at 24 hours in CCRF-CEM and LM217. Total cell death increased exponentially with increasing radiation dose from 0 Gy to 8 Gy, but the change was minimal in apoptotic index. Apoptotic fractions at 2 Gy were $46\%,\;48\%,\;46\%,\;24\%,\;and\;19\%$ and at 6 Gy were $20\%,\;33\%,\;35\%,\;17\%,\;and\;20\%$ for PCI-1, PCI-13, SNU-1066, CCRF-CEM, and LM217, respectively. The radioresistant cell lines showed more higher apoptotic fraction at 2 Gy, but there was not such correlation at 6 Gy. Conclusion : All cell lines used in this study showed apoptosis after irradiation, but time course of apoptosis was different from that of leukemia cell line and normal fibroblast cell line. Reproductive cell death was more important mode of cell death than apoptotic death in all cell lines used in this study. But there was correlation between apoptotic fraction and radiation sensitivity at 2 Gy.

• Radiation Oncology Journal
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• v.29 no.1
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• pp.44-52
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• 2011

Purpose: To evaluate the outcomes and prognostic factors of postoperative radiotherapy (PORT) for patients with pathological stage III non-small-cell lung cancer (NSCLC) at a single institution. Materials and Methods: From 2000 to 2007, 88 patients diagnosed as having pathologic stage III NSCLC after curative resection were treated with PORT. There were 80 patients with pathologic stage IIIA and eight patients with pathologic stage IIIB in the AJCC 6th staging system. The majority of patients (n=83) had pathologic N2 disease, and 56 patients had single station mediastinal LN metastasis. PORT was administered using conventional technique (n=76) or three-dimensional conformal technique (n=12). The median radiation dose was 54 Gy (range, 30.6 to 63 Gy). Thirty-six patients received chemotherapy. Radiation pneumonitis was graded by the Radiation Therapy Oncology Group system, and other treatment-related toxicities were assessed by CTCAE v 3.0. Results: Median survival was 54 months (range, 26 to 77 months). The 5-year overall survival (OS) and disease free survival (DFS) rates were 45% and 38%, respectively. The number of metastatic lymph nodes was associated with overall survival (hazard ratio, 1.037; p-value=0.040). The 5-year locoregional recurrence free survival (LRFS) and distant metastasis free survival (DMFS) rates were 88% and 48%, respectively. Multiple stations of mediastinal lymph node metastasis was associated with decreased DFS and DMFS rates (p-value=0.0014 and 0.0044, respectively). Fifty-one relapses occurred at the following sites: 10 loco-regional, 41 distant metastasis. Grade 2 radiation pneumonitis was seen in three patients, and symptoms were well tolerated with anti-tussive medication. Grade 2 radiation esophagitis was seen in 11 patients. There were no grade 3 or more severe complications associated with PORT. Conclusion: Our retrospective data show that PORT for pathological stage III NSCLC is a safe and feasible treatment and could improve loco-regional control. The number of metastatic lymph nodes and stations of mediastinal lymph node metastasis were analyzed as prognostic factors. Furthermore, efforts are needed to reduce distant metastasis, which is a major failure pattern of advanced stage NSCLC.

• Journal of Life Science
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• v.23 no.2
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• pp.197-206
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• 2013

The present study investigated whether leukemia-maintaining cells reside in a differentiation-resistant fraction using a megakaryocytic differentiation model of K562 cells. Treatment with phorbol-12-myristate-13-acetate (PMA) significantly inhibited the colony-forming efficiency of the K562 cells. At a PMA concentration of 1 nM or higher, colony was not formed, but approximately 40% of K562 cells still survived in soft agar. Approximately 70% of colony-forming cells that were isolated following the removal of PMA after exposure to the agent were differentiated after treatment with 10 nM PMA for 3 days. The differentiation rate of the colony-forming cells was gradually increased and reached about 90% 6 weeks after colony isolation, which was comparable to the level of a PMA-treated K562 control. Meanwhile, imatinib-resistant variants from the K562 cells, including K562/R1, K562/R2, and K562/R3 cells, did not show any colony-forming activity, and most imatinib-resistant variants were CD44 positive. After 4 months of culture in drug-free medium, the surface level of CD44 was decreased in comparison with primary imatinib-resistant variants, and a few colonies were formed from K562/R3 cells. In these cells, Bcr-Abl, which was lost in the imatinib-resistant variants, was re-expressed, and the original phenotypes of the K562 cells were partially recovered. These results suggest that leukemia-maintaining cells might reside in a differentiation-resistant population. Differentiation therapy to eliminate leukemia-maintaining cells could be a successful treatment for leukemia if the leukemia-maintaining cells were exposed to a differentiation inducer for a long time and at a high dose.

• The Korean Journal of Nuclear Medicine
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• v.39 no.1
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• pp.26-33
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• 2005

Purpose: The purpose of this study is to evaluate migration of technetium-99m hexamethylpropylene amine oxime ($^{99m}Tc$-HMPAO) labeled immature and mature dendritic cells (DC) in the mouse. Methods: DC were collected from bone marrow (BM) of tibiae and femurs of mice. Immature and mature DC from BM cells were radiolabeled with $^{99m}Tc$-HMPAO. To evaluate the functional and phenotypic changes of DC from radiolabeling, the allogeneic mixed lymphocyte reaction (MLR) and fluorescence-activated cell sorting (FACS) analysis were performed before and after labeling with $^{99m}Tc$-HMPAO. Migration of intravenously injected DC (iv-DC) was assessed by serial gamma camera images of mice with or without subcutaneous tumor. Percent injected dose per gram (%ID/g) was calculated in lungs, liver, spleen, kidneys, and tumor through dissection of each mice after 24 hours of injection. Results: Labeling efficiency of immature and mature DC were $60.4{\pm}5.4%\;and\;61.8{\pm}6.7%$, respectively. Iv-DC initially appeared in the lungs, then redistributed mainly to liver and spleen. Migration of mature DC to spleen was significantly higher than that of immature DC ($38.3{\pm}4.0%\;vs.\;32.2{\pm}4.1%$ in control group, $40.4{\pm}4.1%\;vs.\;35.9{\pm}3.8%$ in tumor group; p<0.05). Migration to tumor was also significantly higher in mature DC than in immature DC ($2.4{\pm}0.3%\;vs\;1.7{\pm}0.2%$; p=0.034). Conclusion: Assessment of migration pattern of DC in mice was possible using $^{99m}Tc$-HMPAO labeled immature and mature DC. Migration of mature DC to spleen and tumor was higher than that of immature DC when they were i.v. injected.

• Korean Journal of Food Science and Technology
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• v.45 no.1
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• pp.97-103
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• 2013

Pine bark extract is made from the bark of Pinus densiflora which naturally contains occurring phytochemicals such as phenolic compounds. PineXol$^{(R)}$ from products of pine bark extract is sold under the brand name. The aim of this study was to evaluate the total phenol, total flavonoids contents and antioxidant activity of the PineXol$^{(R)}$ as well as to assess the lipid accumulation during adipogenesis of 3T3-L1 cells. Our results demonstrate that the total phenolic and flavonoids contents of the PineXol$^{(R)}$ were $717.40{\pm}6.86$ GAE mg/mL and $54.44{\pm}0.01$ RE mg/mL, respectively. The antioxidative activities of the PineXol$^{(R)}$ were significantly increased in a dose dependent manner on DPPH (1,1-Diphenyl-2-picryl hydrazyl) radical scavenging, ABTS (2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt) radical scavenging, FRAP (ferric reducing antioxidant power) activity, reducing power, nitrite radical scavenging activity and ORAC (Oxygen radical absorbance capacity) value. In addition, the PineXol$^{(R)}$ inhibited the adipocyte differentiation of 3T3-L1 preadipocytes. Exposure to 200 ${\mu}g/mL$, PineXol$^{(R)}$ significantly reduced lipid accumulation (~80%) in 3T3-L1 cells compared to control cells.

• Journal of fish pathology
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• v.23 no.2
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• pp.245-254
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• 2010

Effects of heavy metal ions on the gene expression of cytochrome P4501A (CYP1A) were examined in cultured eel hepatocytes. When the expression of CYP1A mRNA was measured by RT-PCR after incubation of eel hepatocytes with benzo[$\alpha$]pyrene (B[$\alpha$]P) at concentrations of 10-8~10-5 M, the CYP1A expression increased with B[$\alpha$]P treatment in a dose dependent manner, showing significant increase at concentrations more than 10-7 M. When the eel hepatocyte was treated with cadmium (10-6 and 10-5 M), the expression of CYP1A was inhibited and especially at higher concentration (10-5 M). The inhibition of CYP1A expression by cadmium was also observed in cells treated with B[$\alpha$]P. In another study, effects of heavy metal ions on the expression of CYP1A were examined in cultured hepatocytes isolated from eel which was treated previously with B[$\alpha$]P in vivo. Hepatocytes isolated from the liver of eel taken at 48 hours after injection of B[$\alpha$]P (10 mg/kg) were cultured for 2 days with cadmium, copper, lead or zinc (10-6 and 10-5 M). The expression of CYP1A was found to be suppressed by the metal ions compared with the control in which CYP1A was induced with previous treatment of B[$\alpha$]P in vivo. The present results may provide an important basic information for studying the effects of heavy metal ions on CYP1A expression in other species of fish and studying toxicological mechanisms of heavy metal ions in aquatic livings.

• The Journal of Korean Obstetrics and Gynecology
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• v.29 no.1
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• pp.14-34
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• 2016

Objectives: The objective of this study was to evaluate the effects of cytotoxicity, skin regeneration, anti-wrinkle, whitening and skin moisturizing of Oncheongeum (OCE).Methods: The cytotoxicity of OCE lyophilized aqueous extracts (yield=13.82%) was observed against human normal fibroblast cells and B16/F10 murine melanoma cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium Bromide (MTT) assay, and skin regeneration and anti-wrinkle effects were also evaluated through the assay of collagen type I synthesis compared to the transformation of the growth factor (TGF)-β1, hyaluronidase, collagenase and matrix metalloproteinase (MMP)-1 inhibitory assays compared to oleanolic acid (OA), and elastase inhibitory effects compared to phosphoramidon disodium salt (PP). In addition, OCE’s whitening effects were measured by a tyrosinase inhibitory assay and melanin formation test in B16/F10 murine melanoma cells compared to arbutin, and skin moisturizing effects were observed through a mouse skin water content test, respectively. Results: No OCE treatment-related cytotoxic effects appeared on human normal fibroblasts and B16/F10 murine melanoma cells. OCE concentration-dependently increased the collagen Type I synthesis on human normal fibroblast cells, and also effectively inhibited hyaluronidase, elastase, collagenase and MMP-1 activities. In addition, OCE inhibited melanin production of B16/F10 murine melanoma cells and activity of tyrosinase. And significant and dose-dependent increases of skin water content were detected in OCE-treated mouse skin compared to vehicle control skins. Conclusions: OCE showed favorable and sufficient effects in skin regeneration, anti-wrinkle, whitening and skin moisturizing in this experiment. But more detail mechanisms and studies on the skin protective efficiency of in vivo are needed with the screening of active biological compounds in individual OCE herbs.

• Food Science and Preservation
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• v.11 no.1
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• pp.79-87
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• 2004

To investigate antioxidative effects of phenolic compounds separated from persimmon leaves(PL)(Diospyros kaki Thunb.) on the ethanol-induced hepatotoxicity in rat, Sprague-Dawley rats weighing 100-150 g were divided into 5 groups; control group(CON), PL(70 mg/kg) administered group(PEl), ethanol(5 mL/kg, 25％) administered group(ETH), PL(70 mg/kg) and ethanol administered group (PE2), and PL(140 mg/kg) and ethanol administered group(PE3), respectively. The antioxidative activity of persimmon leaves decreased in order of ethylacetate>interphase materials>n-butanol>chloroform>n-hexane>water fraction. The growth rate and feed efficiency ratio decreased by ethanol were gradually increased to the adjacent level of CON by administering PL. The serum activities of ALT, alkaline phosphatase and lactic acid dehydrogenase elevated by ethanol were decreased significantly. It was also observed that the activities of SOD, catalase, and GSH-Px of rat liver increased by ethanol were markedly decreased in PL administered group as compared to ETH. The GSH content of liver was decreased by ethanol, but that was increased in PE1 and PE2 compared with ETH as a dose-dependant manner. These results suggested that phenolic compounds separated from persimmon leaves have a possible protective and relievable effect on the ethanol-induced hepatotoxicity in rats.