• Journal of Life Science
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• v.19 no.11
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• pp.1581-1590
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• 2009

Hizikia fusiforme is a kind of brown edible seaweed that mainly grows in the temperate seaside areas of the northwest pacific, including Korea, Japan and China, and has been widely used as a health food for hundreds of years. Recently, H. fusiforme has been known to exert pharmacological activities including antioxidant, antimutagenic and anticoagulant activities. However, the molecular mechanisms of H. fusiforme in malignant cells have not been clearly elucidated yet. In this study, the effects of ethyl alcohol extract of H. fusiforme (EAHF) on the anti-proliferative effects of MDA-MB-231 and MCF-7 human breast cancer cells were investigated. EAHF treatment resulted in a concentration-dependent growth inhibition by including apoptosis in MDA-MB-231 cells and G1 phase arrest in MCF-7 cells, which could be proved by MTT assay, DAPI staining, agarose gel electrophoresis and flow cytometry analysis. In MDA-MB-231 cells, the increase in apoptosis induced by EAHF treatment correlated with up-regulation of pro-apoptotic Bax expression. EAHF treatment induced the proteolytic activation of caspase-3 and caspase-9, and a concomitant inhibition of poly (ADP-ribose) polymerase, $\beta$-catenin, phospholipase-${\gamma}1$ protein and DNA fragmentation factor 45/inhibitor of caspase-activated DNase. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of H. fusiforme.

• Journal of Life Science
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• v.19 no.11
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• pp.1637-1643
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• 2009

Shikonin, a component of Lithospermum erythrorhizon Sieb. et Zucc, exerts various characteristics such as anti-inflammatory, anti-cancer and anti-obesity functions. To elucidate the molecular mechanism of shikonin-induced inhibition of adipogenesis, we analyzed the mRNA expression level of various adipogenesis-related factors including C/EBPs (CCAAT/enhancerbinding proteins) and $PPAR{\gamma}$ (peroxisome proliferator-activated receptor $\gamma$). The data showed that mRNA expressions of C/$EBP{\beta}$ and C/$EPB{\delta}$ were only slightly changed by shikonin treatment, but mRNA expressions of $PPAR{\gamma}$ and C/$EPB{\alpha}$ were significantly down-regulated. Then, we tested whether upstream regulators of C/$EBP{\beta}$ and $PPAR{\gamma}$ were involved in anti-adipogenesis of shikonin. C/$EBP{\gamma}$ and CHOP (C/EBP homologous protein), which are upstream regulators of C/$EBP{\beta}$, were not affected by shikonin treatment. On the contrary, the mRNA level of KROX20 was markedly down-regulated by shikonin treatment. These results suggest that KROX20 might regulate downstream factors of adipogenesis through C/$EBP{\beta}$-independent pathway. The expression of KLF15 (Kruppel-like factor15), which is a member of KLF family and is a upstream regulator of $PPAR{\gamma}$, was dramatically decreased by shikonin treatment, but KLF2 was not changed. Shikonin had no impact on the expression of KLF5 in the early stage of adipogenesis, but shikonin increased expression of KLF5 in the late stage of adipogenesis. Even though mRNA expression of KLF5 was moderately changed by shikonin treatment, its effect may be small compared with the effect of KLF15, which was markedly inhibited. Taken together, these results suggest that shikonin inhibits adipogenesis through the down-regulation of $PPAR{\gamma}$ and C/$EPB{\alpha}$, which is mediated by the down-regulation of two pro-adipogenic factors, KROX20 and KLF15.

• Journal of Life Science
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• v.23 no.5
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• pp.710-720
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• 2013

Radiotherapy is commonly used in treating many kinds of cancers which cannot be cured by other therapeutic strategies. However, radiotherapy also induces the damages on the normal tissues. Radiation-induced fibrosis is frequently observed in the patients undergoing radiotherapy, and becomes a major obstacle in the treatment of intrahepatic cancer. Hedgehog (Hh) that is an essential in the liver formation during embryogenesis is not detected in the healthy liver, but activated and modulates the repair process in damaged livers in adult. The expression of Hh increases with the degree of liver damage, regulating the proliferation of hepatic progenitors and hepatic stellate cells (HSC). In addition, Hh induces epithelial-to-mesencymal transition (EMT) and activation of myofibroblasts. In the irradiated livers, up-regulated expression of Hh signaling was associated with proliferation of progenitors, EMT induction, and increased fibrosis. Female-specific expression of Hh leaded to the expansion of progenitors and the accumulation of collagen in the irradiated livers of female mice, indicating that gender disparity in Hh expression may be related with radiation-susceptibility in female. Hence, Hh signaling becomes a novel object of studies for fibrogenesis induced by radiation. However, the absence of the established experimental animal models showing the similar physiopathology with human liver diseases and fibrosis-favorable microenvironment hamper the studies for the radiation-induced fibrosis, providing a few descriptive results. Therefore, further research on the association of Hh with radiation-induced fibrosis can identify the cell and tissue-specific effects of Hh and provides the basic knowledge for underlying mechanisms, contributing to developing therapies for preventing the radiation-induced fibrosis.

• Journal of Life Science
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• v.23 no.3
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• pp.389-398
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• 2013

Platycodin D is a major constituent of triterpene saponins, which is found in the root of Platycodon grandiflorum, Platycodi Radix, which is widely used in traditional Oriental medicine for the treatment of many chronic inflammatory diseases. Several pharmacological effects of this compound have been reported recently, such as anti-inflammation, immunogenicity, anti-adipogenesis, lowered cholesterol, and anti-cancer activity. However, the mechanism by which this action occurs is poorly understood. In this study, we found that platycodin D greatly increased the potential of the anti-proliferative effect in various cancer cell lines. Our data revealed that platycodin D treatment resulted in a time- and concentration-response growth inhibition of U937 cells by inducing apoptosis, as evidenced by the formation of apoptotic bodies, chromatin condensation, and the accumulation of cells in the sub-G1 phase. Apoptosis induction of U937 cells by platycodin D correlated with an increase in the Bax/Bcl-2 ratio and caused the down-regulation of IAP family members. In addition, platycodin D treatment resulted in proteolytic activation of caspase-3, the concomitant degradation of poly(ADP-ribose) polymerases, and the collapse of the mitochondria membrane potential (${\Delta}{\Psi}_m$). However, the cytotoxic effects induced by platycodin D treatment were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, which demonstrated the important role that caspase-3 played in the observed cytotoxic effect. These findings suggest that platycodin D may be a potential chemotherapeutic agent for use in the control of human leukemia U937 cells. These findings also provided important new insights into possible molecular mechanisms of the anti-cancer activity of platycodin D.

• Journal of Life Science
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• v.27 no.4
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• pp.383-389
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• 2017

This study intends to analyze the contents of rutin, procyanidin B3, quercetin, kaempferol, known to have antioxidant, anti-inflammatory and anti-carcinogenic effects, among the polyphenol type contained in the grape pruning stem extracts (GPSE), utilizing grape stems being discarded after harvest, measure the effects on the skin moisture, inhibition of skin cell proliferation, anti-inflammatory on the damaged skin of a HR-1 mice induced with UVB, and verify the applicability as a material for functional food and functional cosmetics. The results of verifying the photoprotection effects through the skin proliferation control through of GPSE showed similar result to suncream was achieved at the GPSE concentration of 2,000 mg/kg on the epidermis (p<0.05). The results showed anti-inflammatory effects on all groups applied with GPSE as compared to the control group irradiated with UVB, but at the GPSE concentration of 1,000 mg/kg, a lower COX-2 protein expression at 8%, lower than the 22% of suncream, was observed to achieve an excellent anti-inflammatory effect (p<0.05). The results of this study confirmed the existence of active polyphenol type, such as rutin, kaempferol, querocetin and procyanidin B3, within the GPSE, and GPSE has improvement effects on moisturizing effects, skin proliferation control effect, inflammatory control effect and improvement effects on the skin barrier function through UV ray damage. GPSE is a functional ingredient with a potential for skin protection effects, and has high utilization as an ingredient for functional food and functional cosmetics.

• Radiation Oncology Journal
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• v.12 no.2
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• pp.209-217
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• 1994

Between July 1987 and December 1992, we treated 22 patients with chronic myelogenous leukemia; 14 in the chronic phase and 8 with more advanced disease. All were received with allogeneic bone marrow transplantation from HLA-identical sibling donors after a total body irradiation(TBI) cyclophosphamide conditioning regimen. Patients were non-randomly assigned to either 1200 cGy/6fractions/3days (6 patients) or 1320 cGy/8 fractions/4days (16 patients) by dose of TBI. Of the 22 patients, 8 were prepared with cyclophosphamide alone, 14 were conditioned with additional adriamycin or daunorubicin. To prevent graft versus host disease, cyclosporine was given either alone or in conjunction with methotrexate. The actuarial survival and leukemic-free survival at four years were $58.5\%$ and $41.2\%$, respectively, and the relapse rate was $36\%$ among 22 patients. There was a statistically significant difference in survival between the patients in chronic phase and more advanced phase ($76\%\;vs\;33\%$, p=0.05). The relapse rate of patients receiving splenectomy was higher than that of patients receiving splenic irradiation ($50\%\;vs\;0\%$, p=0.04). We conclude that the probability of cure is highest if transplantation is performed while the patients remains in the chronic phase.

• Radiation Oncology Journal
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• v.13 no.2
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• pp.163-171
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• 1995

Purpose: Primary radiation therapy following breast-conserving surgery has been an accepted alternative to mastectomy during the past 2 decades. In this country, however, the practice of conservative therapy for early invasive breast cancer has not been generalized yet. The purpose of this report was to evaluate the results and complications of breast conservation therapy in Korean Cancer Center Hospital(KCCH). Materials and Methods: From January 1987 to December 1989. 45 Patients with early breast cancer treated with conservative treatment in KCCH were studied retrospectively Median follow up was 54 months(range, 4 to 82 months) . All patients received partial mastectomy (biopsy, tumorectomy. or quadrantectomy) and radiation therapy. Twenty eight patients received axillary dissection The breast was treated with two opposing tangential fields (total 50 Gy or 50.4 Gy in 5 weeks with daily target dose of 2 Gy or 1.8 Gy) Thirty patients received chemotherapy before and after radio-therapy Eleven patients received hormonal therapy. Results: Five-year survival rate, 5-rear disease free survival rate and 5-year local control rate were 87.2%, 86.5% and 97.6%,$ respectively. Administration of systemic Therapy (chemotherapy or hormonal therapy) correlated with good prognosis but statistically not significant (0.05 < p < 0.1). The severe late complication rate was 8.9% Conclusion: Primary radiation therapy following breast-conserving surgery for early breast cancer is an alternative treatment comparing to radical treatment. Long term follow-up and more patients collection is needed to evaluate the Prognostic factor and cosmetic outcome.

• Radiation Oncology Journal
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• v.14 no.3
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• pp.181-189
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• 1996

Purpose : To find the more effective treatment methods that improving the survival of patients with glioblastoma multiforme(GBM), we analyze the prognostic factors and the outcome of therapy in patients with GBM. Materials and Methods : One hundred twently-one patients with a diagnosis of GBM treated at Severance Hospital between 1973 and 1993 were analyzed for survival with respect to patients characteristics, that is, duration of symptom, age, and Karnofsky performance status, as well as treatment related variables such as extent of surgery and radiotherapy. Results : The median survival time(MST) and 2-year overall survival rate (OSR) of the patients with GBM were 13 months and $20.8\%$, respectively. Duration of symptom, age, Karnofsky performance status(KPS), radiotherapy, and extent of surgical resection were associated with improved survial in a univariate analysis. Patients whose duration of symptom was longer than 3 months, had the 2-year OSR of $47.2\%$(p=0.0082), who were younger than age 50, $32.9\%$(p=0.0003) In patients with a KPS of 80 or higher, the 2-rear OSR was $36.9\%$(p=0.0422). Patients undergoing radiotherapy had the 2-year OSR of $22.9\%$(p=0.0030), and surgical resection of $23.3\%$ (p<0.000). A Cox regression model confirmed a significant correlation of duration of symptom, age, radiotherapy, and extent of surgical resection with survival, excluding KPS(P=0.8823). The 2-year OSR were $22.3\%$ and $19.4\%$, combined with chemotherapy or without, respectively(p=0.6028). The duration of symptom of 3 months or shorter, 50 years of age or older, and undergoing stereotactic biopsy only were considered as risk factors, then patients without any risk factors had the MST of 29 months and 2-year OSR of $53.9\%$ compared to 4 months and $0\%$ for Patients who had all 3 risk factors. Most of all treatment failures occurred in the primary tumor site($80.4\%$). Conclusion : The duration of symptom, age, radiotherapy, and extent of surgical resection were a prognostically significant indeuendent variables. To get a better survival, it seems to be reasonable that the study design which improves the local control rates is warranted.

• Radiation Oncology Journal
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• v.18 no.4
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• pp.283-292
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• 2000

Purpose :A retrospective review of 72 patients with locally advanced gallbladder carcinoma, between January 1990 and December 1996, was peformed. Survival results and prognostic factors are analyzed for the patients treated with a various modalities. Materials and Methods :We patients were classified by treatment modality: group 1 included to 27 patients treated with palliative surgery alone, and group 2 for 11 patient treated with palliative surgery and radiotherapy; group 3 for 18 patients not treated by any treatment modality, and group 4 for 16 patients treated with radiotherapy alone. Age distribution ranged from 35 to 80 years with mean of 63 years. The stage was classified by TNM and Nevin's staging system; all patients had an advanced stage more than III. Palliative surgery was done in .: patients and adiuvant radiation therapy (RT) was followed in 11. For 34 patients, in whom no resection was tried, definitive RT was done in 16. Radiation delivered to tumor site and draining nodes up to 45~61.2 Gy using 10 MV linear accelerator. Chemotherapy was given to 25 patients with 5-FU based regimens. Results :Modian suwival time was 10.3 months and 3-year survival rates (3-YSR) were 13.0$\%$ in all patients. Survival rates according to the treatment modalities were as followed; in palliative surgery alone, 3-YSR was 2.5$\%$; in palliative surgery and adjuvant RT, 3-YSR was 45.5$\%$, in no treatment group, 3-VSR were 8.3$\%$; and definitive RT was 13.1$\%$. It was better survival in additional RT after palliative surgery group than palliative surgery alone (p=0.0009). It was better survival in definitive RT group than no treatment group (p=0.002). Significant prognostic factors by univariate analysis were treatment moonlities, the type of tumor and TNM stage. Significant prognostic factors by multivariate analysis were treatment modalities, the type of tumor and the presence of jaundice. Conclusion : It is suggested that RT could be potentially of effective as adjuvant treatment modalities after palliative surgery or primary treatment for locally advanced and unresectable gallbladder carcinoma.

• The Korean Journal of Food And Nutrition
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• v.28 no.4
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• pp.594-601
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• 2015

In the present study, the total content of polyphenols and flavonoids, the antioxidant activities, and cytotoxic effects of the ethanol extracts from different parts of Taraxacum coreanum Nakai were investigated for their use as functional foods. The extract yields of the flower, leaf, and root were $32.15{\pm}3.21%$, $31.63{\pm}0.63%$, and $27.48{\pm}2.47%$, respectively. Total polyphenol and flavonoid content of the flower extract were $61.29{\pm}2.11mg/g$ and $46.11{\pm}1.88mg/g$, respectively, which were much higher than those of any other plant parts. The antioxidant activities of the flower, leaf, and root extracts were $89.99{\pm}2.83%$, $85.29{\pm}2.22%$, and $37.88{\pm}2.34%$, respectively, at a concentration of 1.0 mg/mL. Cell cytotoxicity effects of AGS (human gastric carcinoma), HCT116 (human colon carcinoma), and A549 (human pulmonary carcinoma) cells were the highest in the flower extract, with values of $62.85{\pm}4.63%$, $69.89{\pm}3.44%$, and $85.72{\pm}4.17%$, respectively, at a concentration of 400 mg/kg. Both the antioxidant activities and cytotoxic effects of the ethanol extracts from all the parts of the T. coreanum Nakai increased dose-dependently. These results provide preliminary data for the development of T. coreanum Nakai as an edible functional food material.