• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.7
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• pp.948-957
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• 2016

We previously developed an herbal composition (HemoHIM) based on the water extracts of Angelica gigas radix, Cnidium officinale rhizoma, and Paeonia japonica radix to protect and recover hematopoietic and intestinal tissues against radiation injuries. In this study, to develop a composition with improved activities based on enhanced fat-soluble polyphenol contents, we prepared a new herbal composition, MH-30, from the above three herbs by 30% ethanol extraction and hot water extraction. HPLC analysis of the ethanol fractions of MH-30 and HemoHIM revealed that MH-30 had higher contents of many fat-soluble polyphenol compounds than HemoHIM (8.7-fold increase for decursin), whereas contents of water-soluble polyphenol compounds showed little differences between the two compositions. Then, we evaluated MH-30 and HemoHIM for their in vitro antioxidant and immune cell-stimulating activities as well as in vivo protective effects against radiation injuries in hematopoietic and self-renewal tissues. In antioxidant activity assays, MH-30 showed higher hydroxyl radical scavenging activity than HemoHIM (1.4- to 1.9-fold for compositions and 2.3- to 4.5-fold for ethanol fractions). On the other hand, MH-30 and HemoHIM exhibited similar immune cell-stimulating activities as measured by in vitro lymphocyte proliferation. MH-30 increased endogenous spleen colony formation, decreased bone marrow cell apoptosis, and enhanced survival of intestinal crypts in irradiated mice, demonstrating effective protection of MH-30 against radiation-induced injuries in hematopoietic and self-renewal tissues. The 30-day survival rate of lethally irradiated mice, a comprehensive index for radioprotective efficacy, was also elevated by MH-30. Noticeably, MH-30 showed higher protective effects than HemoHIM in all mouse experiments. These results demonstrate that MH-30 can protect hematopoietic and self-renewal tissues against radiation injuries more effectively than HemoHIM. Therefore, MH-30 can be a good candidate to reduce radiation injuries in hematopoietic and self-renewal tissues incurred by radiation accidents or cancer radiation therapy.

• Clinical and Experimental Reproductive Medicine
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• v.36 no.4
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• pp.283-292
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• 2009

Objective: Human embryonic stem cells (hESCs) can proliferate indefinitely and differentiate into all kinds of cell types in vitro. Therefore, hESCs can be used as a cell source for cell-based therapy. Transduction of foreign genes to hESCs could be useful for tracing differentiation processes of hESCs and elucidation of gene function. Thus, we tried to introduce enhanced green fluorescent protein (eGFP) gene to hESCs, XX and XY cell lines in this study. Methods: Lentivirus containing eGFP was packaged in 293T cells and applied to hESCs to transduce eGFP. Expression of transduced eGFP was evaluated under the fluorescence microscope and eGFP positive population was analyzed by FACS. Expression of undifferentiation state markers such as Oct4, Nanog, SSEA4 and Tra-1-81 was examined by RT-PCR and/or immunofluorescence in eGFP-hESCs after transduction. In addition, the ability of eGFP-hESCs to form embryoid bodies (EBs) was tested. Results: eGFP was successfully transduced to hESCs by lentivirus. eGFP expression was stably maintained up to more than 40 passages. eGFP-hESCs retained expression patterns of undifferentiation state markers after transduction. Interestingly, disappearance of transduced eGFP was notably observed during spontaneous differentiation of eGFP-hESCs. Conclusion: We established eGFP expressing hESC lines using lentivirus and showed the maintenance of undifferentiation characteristics of these eGFP-hESCs. This reporter-containing hESCs could be useful for tracing the processes of differentiation of hESCs and other studies.

• Tuberculosis and Respiratory Diseases
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• v.46 no.5
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• pp.636-644
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• 1999

Background : Tumor necrosis factor(TNF) has been considered as an important candidate for cancer gene therapy based on its potent anti-tumor activity. The mechanisms of TNF cytotoxicity are not clearly understood and some has reported that reactive oxygen species(ROS) might be associated with them, but there is controversy about antioxidant effect on TNF cytotoxicity. This study was designed to compare the TNF cytotoxicity after antioxidant pretreatment with that of control to evaluate the role of ROS in the mechanism of TNF cytotoxicity. Method : We compared the TNF cytotoxicies to WEHI164(murine fibrosarcoma cell line) and ME180(human cervix cancer cell line) after antioxidant pretreatment with those of control by MIT(dimethylthiazolyl-diphenyltetrazolium bromide) assay. Results : In the control group, the TNF cytotoxicities were $92.2{\pm}2.8%$(WEHI164) and $59.9{\pm}7.0%$(MEl80). In the TMTU(tetramethyl thiourea) pretreatment group, those were $91.4{\pm}3.7%$ and $74.6{\pm}7.0%$. In the PMZ(promethazine) pretreatment group, those were $90.2{\pm}2.5%$ and $62.5{\pm}5.7%$. In the BHT(butylated hydroxytoluene) pretreatment group, those were $93.2{\pm}1.3%$ and $66.3{\pm}6.1%$. So there was no reduction in TNF cytotoxicity after antioxidants pretreatment. Conclusion : The ROS may not have major role in the mechanisms of TNF cytotoxicity.

• Journal of Mushroom
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• v.14 no.4
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• pp.155-161
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• 2016

A recent study reported that Pleurotus ostreatus has the potential to be used as a ${\beta}-glucan-based$ cream for supportive complementary therapy of atopic dermatitis. KH054 is a new herbal prescription consisting of P. ostreatus and Panax ginseng. The effects of atopic dermatitis-induced materials on the expression of cytokine genes in human monocytes (THP-1, EoL- 1) have been examined. Some reports demonstrated that P. ginseng augments the activity of natural killer cells, which plays an important role in innate immunity against infection and tumor development. Monocyte chemotactic protein 1 (MCP-1), interleukin (IL)-6, and IL-8 have important roles in mediating the infiltration of various cells into the skin of atopic dermatitis and psoriasis. The present study investigated whether KH054 on induced IL-6, IL-8, and MCP-1 secretion by house dust mite (Dermatophagoides pteronissinus) in THP-1 (human acute monocytic leukemia) and EoL-1(Human eosinophilic leukemia) cell. D. pteronissinus functions in the pathogenesis of allergic diseases, including atopic dermatitis and asthma. The inhibitory effect of KH054 on the induction of IL-6, IL-8, and MCP-1 secretion by D. pteronissinus extract in THP-1 and EoL-1 cells was examined. KH054 potently suppressed the elevated production of IL-6 and IL-8 induced by D. pteronissinus treatment in THP-1 and EoL-1 cells. Based on the present results, KH054 may be useful for developing functional foods to treat atopic dermatitis.

• Radiation Oncology Journal
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• v.21 no.4
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• pp.269-275
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• 2003

Purpose: To evaluate the results of radiation management on recurrence, survival and prognostic factors of patients with nasopharyngeal cancer Materials and Methods: Forty-nine patients, treated for nasopharyngeal cancer by radiotherapy between January 1984 and June 2000, were retrospectively studied. All patients were followed up for at least 2.5 years. Their median age was 52 years (range 17$\~$78). The histological types were 21 squamous cell carcinoma, 25 undifferentiated carcinoma, and 3 adenoid cystic carcinoma. The tumor stages were as follows: T1 in 14 patients, T2 in 24, T3 in 3, and T4 in 8, and N0 in 17 patients, Nl in 15, N2 in 4 and N3 in 13. Stages I, IIa, IIb ,III, IV and IVb were 4, 7, 12, 5, 8, and 13 patients respectively. Radiation doses of 58$\~$70 Gy (median 68.7 Gy) were given to the nasopahryngeal and involved lymphatic areas and of 46 $\~$ 50 Gy to the uninvolved neck areas. Results: The overall 5 and 10-year actuarial and disease free survival rates were 54.53$\%$ and 47$\%$ and 55.7$\%$ and 45.3$\%$, respectively The overall five-year survival rates were 100$\%$ in stage I , 80$\%$ in stage IIa, 59.5$\%$ in stage IIIb, 40$\%$ in stage III, and 42.2$\%$ in stage IV tumors. Twenty-three patients fatted either loco-regionally or distantly. Incidences of local failure, regional failure and distant metastasis for the first failure were 20.4$\%$, 8.2$\%$ and 20.4$\%$, respectively. Local recurrences were 4.3$\%$ in T1, 12.5$\%$ in T2, 0$\%$ in T3, and 62.5$\%$ in T4 lesions. Distant metastasis was seen in 41.2$\%$ of N2-3 lesions. Fifty percent of local recurrence appeared within 2 years of treatment at the primary lesion, whereas 70$\%$ of distant metastasis appeared within 2 years following treatment. Young age, female, early T stage, N0 stage; and poorly differentiated carcinoma were all related with good survival. However only stage showed statistically significance. Conclusionn: Based on the results of this study, radiation therapy to nasopharyngeal cancer showed high local recurrence in T4 and increased metastasis in N2-3 lesions. To improve local failure, further radiation doses, such as stereotactic radiation or IMRT radiation, are necessary especially in T4 lesions. The high incidence of distant metastasis in positive lymph node patients, indicates that combined radiation and effective chemotherapeutic agents with appropriated schedule are necessary.

• Radiation Oncology Journal
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• v.14 no.4
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• pp.299-306
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• 1996

Purpose : Respiratory symptoms related with malignant airway disease have been the main causes of lowered qualify of life and also sometimes may be life-threatening if not properly managed. The authors report the short-term experiences of endobronchial brachytherapy for symptomatic malignant airway obstruction using high dose rate after-loading brachytherapy unit. Materials and Methdos : Twenty-five Patients with symptomatic malignant airway obstruction were treated with endobronchial brachytherapy between the period of December 1994 and March 1996 at Department of Radiation Oncology of Samsung Medical Center Twenty-one ($84\%$) were patients with non-small cell lung cancer, three with tracheal malignancies, and one with recurrence of esophageal cancer. Twenty Patients were given elective external beam radiation therapy, while six were given endobronchial laser evaporation therapy on emergency bases in addition to endobronchial brachytherapy. Three procedures for each patient were planned and total of 70 procedures were completed. Results : Improvement rates of major respiratory symptoms after endobronchial brachytherapy procedures were $88\%$(22/25). $96\%$(22/23), $100\%$ (15/15), and $100\%$(9/9) for cough, dyspnea, hemoptysis and obstructive pneumonia, respectively. ECOG performance scores were improved in $56\%$ of total patients group, while there was no case with worsened ECOG score. Fifteen patients died and the median interval from the start of treatment to death was 4 months (range: $1\~17$ months), while that of ten survivors was 9 months (range $5\~19$ months). There were five patients with controlled intrathoracic disease, who have survived over one rear. All deaths were associated with uncontrolled local and/or distant disease. Four Patients died of massive fatal hemoptysis, three of who received emergency endobronchial laser evaporation therapy before the start of endobronchial brachytherapy. Conclusion : Endobronchial brachytherapy has been confirmed as an excellent palliative treatment modality improving respiratory symptoms as well as patients' general performance status. Based on the current observations, use of endobronchial brachytherapy in curative setting as a boost technique may be warranted.

• Tuberculosis and Respiratory Diseases
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• v.59 no.5
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• pp.510-516
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• 2005

Backgroud : Lung cancer is the leading cause of cancer deaths in Korea and the number of lung cancer deaths is increasing. The higher response rates, decreased toxicity and improved performance status of the first-line treatments have resulted in an increased number of patients becoming candidates for second-line therapy. Several new antineoplastic agents, including gemcitabine, docetaxel and paclitaxel, have recently demonstrated second-line activity. This phase II study evaluated the efficacy and toxicity of gemcitabine and vinorelbine as combination chemotherapy for Korean patients with NSCLC as a second-line treatment. Methods : Sixty response-evaluable patients were enrolled from December 2000 to July 2003. We conducted a phase II study of a combination gemcitabine and vinorelbine chemotherapy for patients with histologically confirmed NSCLC that was stage IIIB and IV disease at the time of diagnosis, and the disease had progressed onward or the patients had relapsed after first-line platinum-based chemotherapy. They were treated with intravenous gemcitabine $1000mg/m^2$ and intravenous vinorelbine $25mg/m^2$ on days 1 and 8. This chemotherapy regimen was repeated every 3 weeks. Results : A total of 215 cycles of treatment were given and the mean number of cycles was 3.6 cycles. All the patients were evaluable for the toxicity profile. The response rate was 10% according to the WHO criteria. The median progression free survival was 3.8 months and the median survival time was 10.1 months. The 1-year survival rate was 32.9%. Grade III and IV neutropenia were seen in 20 (33.3%) and 7 (11.7%) patients, respectively. Conclusion : The combination of gemcitabine and vinorelbine is active and well tolerated as a second-line therapy for patients with advanced nonsmall cell lung carcinoma.

• 한국유가공학회:학술대회논문집
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• 2007.09a
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• pp.49-58
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• 2007

Inflammatory process leads to the well-known mucosal damage and therefore a further disturbance of the epithelial barrier function, resulting abnormal intestinal wall function, even further accelerating the inflammatory process[1]. Despite of the records, etiology and pathogenesis of IBD remain rather unclear. There are many studies over the past couple of years have led to great advanced in understanding the inflammatory bowel disease(IBD) and their underlying pathophysiologic mechanisms. From the current understanding, it is likely that chronic inflammation in IBD is due to aggressive cellular immune responses including increased serum concentrations of different cytokines. Therefore, targeted molecules can be specifically eliminated in their expression directly on the transcriptional level. Interesting therapeutic trials are expected against adhesion molecules and pro-inflammatory cytokines such as TNF-${\alpha}$. The future development of immune therapies in IBD therefore holds great promises for better treatment modalities of IBD but will also open important new insights into a further understanding of inflammation pathophysiology. Treatment of cytokine inhibitors such as Immunex(Enbrel) and J&J/Centocor(Remicade) which are mouse-derived monoclonal antibodies have been shown in several studies to modulate the symptoms of patients, however, theses TNF inhibitors also have an adverse effect immune-related problems and also are costly and must be administered by injection. Because of the eventual development of unwanted side effects, these two products are used in only a select patient population. The present study was performed to elucidate the ability of TNF-${\alpha}$ antibodies produced in sheep colostrums to neutralize TNF-${\alpha}$ action in a cell-based bioassay and in a small animal model of intestinal inflammation. In vitro study, inhibitory effect of anti-TNF-${\alpha}$ antibody from the sheep was determined by cell bioassay. The antibody from the sheep at 1 in 10,000 dilution was able to completely inhibit TNF-${\alpha}$ activity in the cell bioassay. The antibodies from the same sheep, but different milkings, exhibited some variability in inhibition of TNF-${\alpha}$ activity, but were all greater than the control sample. In vivo study, the degree of inflammation was severe to experiment, despite of the initial pilot trial, main trial 1 was unable to figure out of any effect of antibody to reduce the impact of PAF and LPS. Main rat trial 2 resulted no significant symptoms like characteristic acute diarrhea and weight loss of colitis. This study suggested that colostrums from sheep immunized against TNF-${\alpha}$ significantly inhibited TNF-${\alpha}$ bioactivity in the cell based assay. And the higher than anticipated variability in the two animal models precluded assessment of the ability of antibody to prevent TNF-${\alpha}$ induced intestinal damage in the intact animal. Further study will require to find out an alternative animal model, which is more acceptable to test anti-TNF-${\alpha}$ IgA therapy for reducing the impact of inflammation on gut dysfunction. And subsequent pre-clinical and clinical testing also need generation of more antibody as current supplies are low.

• Tuberculosis and Respiratory Diseases
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• v.57 no.3
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• pp.257-264
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• 2004

Background : There are many combinations of treatment for locally advanced non-small cell lung cancer (NSCLC). Recent studies have showed the efficacy of concurrent chemoradiotherapy (CCRT) in NSCLC. At present, however, there is no consensus about the optimal dosages and timing of radiation and chemotherapeutic agents. The aims of study were to determine the feasibility, toxicity, response rate, and survival rate in locally advanced NSCLC patients treated with doxetaxel and cisplatin based CCRT. Method : Sixteen patients with unresectable stage III NSCLC were evaluated from May 2000 until September 2001. Induction chemoradiotherapy consisted of 3 cycles of docetaxel (75 $mg/m^2/IV$ on day 1) and cisplatin (60 $mg/m^2/IV$ on day 1) chemotherapy every 3 weeks and concomitant hyperfractionated chest irradiation (1.15 Gy/BID, total dose of 69 Gy) in 6 weeks. Patient who had complete or partial response, and stable disease were applied consolidation chemotherapy of docetaxel and cisplatin. Results : All patients showed response to CCRT. Four patients achieved complete response (25%), partial responses in 12 patients (75%). The major common toxicities were grade III or more of neutropenia (87.3%), grade III esophagitis (68.8%), pneumonia (18.8%) and grade III radiation pneumonitis (12.5%). Thirteen patients were ceased during follow-up period. Median survival time was 19.9 months (95% CI; 4.3-39.7 months). The survival rates in one, two, and three years are 68.7%, 43.7%, and 29.1%, respectively. Local recurrence was found in 11 patients (66.8%), bone metastasis in 2, and brain metastasis in 1 patient. Conclusion : The response rate and survival time of CCRT with docetaxel/cisplatin in locally advanced NSCLC were encouraging, but treatment related toxicities were high. Further modification of therapy seems to be warranted.

• Clinical and Experimental Pediatrics
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• v.48 no.2
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• pp.186-190
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• 2005

Purpose : The purpose of this study was to evaluate the responses and toxicities of risk-adapted chemotherapy in pediatric intracranial germ cell tumors(IC-GCT). Methods : Fourteen patients who were diagnosed as IC-GCT from October 2002 to December 2003 received chemotherapy as an initial treatment modality. The low risk(LR) group was defined as follows : Pure germinoma and normal AFP level. Beta-hCG level 50 mIU/mL or less. The others belonged to the high risk(HR) group. Chemotherapy was composed of cisplatin, cyclophosphamide, etoposide and vincristine. Double doses of cisplatin and cyclophosphamide was used in HR patients. Results : Pathologic confirmation was done in all but one. Median age at diagnosis was 11.6 yr (1.2-18.7 yr), and nine patients belonged to the HR group. Tumor markers were normalized after chemotherapy in all patients whose tumor markers had been elevated. Four LR patients(80 percent) and seven HR patients(77.8 percent) showed complete response(CR) at the end of chemotherapy. An additional two of the three patients with partial response(PR) achieved CR after radiation therapy (RT), and the remaining one relapsed before RT. Four LR and all HR patients experienced infectious episodes that required hospitalization. Four of the nine HR patients(44.4 percent) suffered from tinnitus, three of whom developed sensorineural hearing loss. All but one are surviving, event-free, with a median follow-up of 13.9 mo(8.1-22.3 mo). Conclusion : Risk-adapted cisplatin-based chemotherapy was effective even in HR patients, but regimen modification seems to be necessary to avoid an unacceptably high toxicity rate.