• Proceedings of the Korean Society of Applied Pharmacology
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• 2007.11a
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• pp.79-92
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• 2007

Oxidative stress have known to be a risk factor for the degenerative processes and closely related to a lot of diseases. It is well established that antioxidants are good in protection and therapeutic means against oxidative damage. There is increasing interest in natural antioxidants and many natural antioxidants have been found and utilized as the possible protection for various diseases and skin aging. We have screened natural antioxidant agents for cosmeceuticals, nutraceuticals, and drugs as therapeutic and preventive means against oxidative stress, and have developed a number of novel antioxidants from various natural sources. A novel melanin synthesis inhibitor, Melanocin A, isolated from the metabolite of a fungal strain Eupenicillium shearii F80695 inhibited mushroom tyrosinase and melanin biosynthesis of B16 melanoma cells with $IC_{50}$ value of 9.0 nM and MIC value of $0.9\;{\mu}M$, respectively. Melanocin A also exhibited potent antioxidant activity by scavenging of DPPH and superoxide anion radicals. UV was found to increase the level of hydrogen peroxides and other reactive oxygen species (ROS) in skin tissues. This increase in ROS may not only alter the structure and function of many genes and proteins directly but may also modulate their expressions through signal transduction pathways and, ultimately, lead to skin damage. We investigated the effect of Melanocin A on UV-induced premature skin aging. Firstly, the effect of Melanocin A on UV-induced matrix metalloproteinase (MMP)-9 expression in an immortalized human keratinocyte cell line, HaCaT in vitro was investigated. Acute UV irradiation induced MMP-9 expression at both the mRNA and protein levels and Melanocin A suppressed this expression in a dose-dependent manner. We then investigated UV-induced skin changes in hairless mice in vivo by Melanocin A. Chronic exposure of hairless mouse dorsal skin to UV increased skin thickness and induced wrinkle formation and the gelatinase activities of MMP-2 and MMP-9. Moreover, Melanocin A significantly suppressed UV-induced morphologic skin changes and MMP-2 and MMP-9 expression. These results show that Melanocin A can prevent the harmful effects of UV that lead to skin aging. Therefore, we suggest that Melanocin A should be viewed as a potential therapeutic agent for preventing and/or treating premature skin aging. Terrein is a bioactive fungal metabolite isolated from Penicillium species. Terrein has a relatively simple structure and can be easily synthesized. However, the biologic effects of terrein are comparatively unknown. We found for the first time that terrein potently inhibit melanin production in melanocytes and has a strong hypopigmentary effect in a spontaneously immortalized mouse melanocyte cell line, Mel-Ab. Treatment of Mel-Ab cells with terrein (10-100 mM) for 4 days significantly reduced melanin levels in a dose-dependent manner. In addition, terrein at the same concentration also reduced tyrosinase activity. We then investigated whether terrein influences the extracellular signal-regulated protein kinase (ERK) pathway and the expression of microphthalmia-associated transcription factor (MITF), which is required for tyrosinase expression. Terrein was found to induce sustained ERK activation and MITF down-regulation, and luciferase assays showed that terrein inhibits MITF promoter activity in a dose-dependent manner. To elucidate the correlation between ERK pathway activation and a decreased MITF transcriptional level, PD98059, a specific inhibitor of the ERK pathway, was applied before terrain treatment and found to abrogate the terrein-induced MITF attenuation. Terrein also reduced the tyrosinase protein level for at least 72 h. These results suggest that terrain reduces melanin synthesis by reducing tyrosinase production via ERK activation, and that this is followed by MITF down-regulation.

• Journal of Food Hygiene and Safety
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• v.36 no.5
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• pp.447-453
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• 2021

In this study, the effectiveness of physical control technology, a combined light sterilization (LED, UV) and hot water treatment in reducing Aspergillus ochraceus for food production environment was investigated. In brief, 1 mL aliquot of A. ochraceus spore suspension (10^7-8 spore/mL) was inoculated onto stainless steel chips, which was then dried at 37℃, and each was subjected to different physical treatment. Treatments were performed for 0.5, 1, 2, 5, 8, and 11 hours to reduce the strains using a light-emitting diode, but no significant difference was confirmed among the treatments. However, a significant reduction was observed on the chips treated with UV-C exposure and hot water immersion. After being treated solely with 360 kJ/m² of UV-C on stainless steel chip, the fungi were significantly reduced to 1.27 log CFU/cm². Concerning the hot water treatment, the initial inoculum amount of 6.49 log CFU/cm² was entirely killed by immersion in 83℃ water for 5 minutes. Maintaining a high temperature for 5 minutes at the site is difficult. Thus, considering economic feasibility and usability, we attempted to confirm the appropriate A. ochraceus reduction conditions by combining a relatively low temperature of 60℃ and UV rays. With the combined treatments, even in lukewarm water, A. ochraceus decreased significantly through the increases in the immersion time and the amount of UV-C irradiation, and the yield was below the detection limit. Based on these results, if work tools are immersed in 60℃ lukewarm water for 3 minutes and then placed in a UV sterilization device for more than 10 minutes, the possibility of A. ochraceus cross-contamination during work is expected to be reduced.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.47 no.3
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• pp.205-212
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• 2021

The skin fibroblasts of different origins showed different expression levels of MMP-1 in response to TNF-α treatment or UV irradiation. We hypothesized that this is caused by polymorphism in the MMP-1 promoter region. To elucidate it, first of all, we analyzed and classified the genotype of the -1607 site of the MMP-1 promoter in 23 commercially available primary fibroblasts, and then we examined the expression of MMP-1 by TNF-α or UVB stimulation for each classified genotype. As a result of the analysis, fibroblasts with 6 1G/1G genotypes, 10 1G/2G genotypes, and 7 2G/2G genotypes were identified. Hs68 and Detroit 551 cell lines were confirmed to have 1G/2G genotypes. In the 1G/1G genotype, MMP-1 was expressed twice as high as that of the control group by TNF-α treatment, and was hardly expressed by UV light. In the case of the 1G/2G genotype, MMP-1 was expressed 2.45 fold higher by TNF-α treatment, and 1.4 fold by UV light than the control. In the case of the 2G/2G genotype, MMP-1 was expressed 1.35 fold by TNF-α treatment, and was highly expressed by 2.5 fold by ultraviolet rays compared to control. It can be estimated that MMP-1 expression is better induced in the 1G genotype by TNF-α and in the 2G genotype by UV light. In addition, it can be presumed that MMP-1 expression is increased by creating a site where the Ets transcription factor can bind by another G inserted at the -1607 position. These studies have not been conducted at all in fibroblasts in relation to skin aging, so it is an area that needs to be further studied in the future. In conclusion, since the skin is an organ that is affected by both intrinsic aging and photoaging at the same time, when analyzing the expression of MMP-1 as a target for improving skin aging, it is necessary to select cells with a genotype suitable for the experimental conditions of the study.

• The Journal of Korean Society for Radiation Therapy
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• v.30 no.1_2
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• pp.153-160
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• 2018

Purpose : We retrospectively analyzed doses of each radiation therapy technique used in the treatment for left breast cancer patients after partial mastectomy through dose results for normalorgans and tumor volume to use this as a clinical reference for radiation therapy of domestic left breast cancer patients. Materials and Methods : 40 patients who underwent partial mastectomy on left breast cancer were classified in 3 treatment methods. The treatment plan was evaluated by HI(homogeneity index), $D_{95%}$, and CI(conformity index), and the $V_{hot}$ for gross tumor volume and clinical target volume of each treatment method. In Cyberknife treatment, tumor volume was the same as high dose volume in the other techniques, so no consideration was given to clinical target volume. Treatment plan evaluation for normal organs were evaluated by mean dose on ipsilateral lung, heart, left anterior descending artery, opposite breast and lung, and non-target tissue. Result : Treatment with volumetric arc radiotherapy(VMAT) showed $95.84{\pm}0.75%$ of $D_{95%}$ on the clinical target volume, significantly higher than that of 3D-CRT. The $D_{95%}$ value of the total tumor volume was slightly higher than the other treatments. In Cyberknife treatment, the dose to the normal organs was significantly lower than other treatments. Overall, the maximum dose and mean dose to the heart were $26.2{\pm}6.12Gy$ and $1.88{\pm}0.2Gy$ in VMAT treatment and $20.25{\pm}9.35Gy$ and $1.04{\pm}0.19Gy$ in 3D-CRT therapy, respectively. Conclusion : In comparison on 3D-CRT and VMAT, most of the dosimetric parameters for the evaluation of the treatment plan showed similar values, so that there is no significant difference in treatment plan evaluation. It is possible to select the treatment method according to the patient's anatomical structure or possibility of breath control. Cyberknife treatment is very useful treatment for normal organs because of its accurate dose exposure to the tumor volume However, it has restrictions to treat the local area, to have relatively long treatment time and to involve invasive procedure.

• Journal of Environmental Impact Assessment
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• v.32 no.1
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• pp.1-14
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• 2023

When carrying out development projects around Ardeidae breeding habitats, we intend to devise a plan for sustainable coexistence by presenting measures to select and reduce key evaluation items so that conflicts can be prevented in advance at the environmental impact assessment stage. The results of the study are as follows. The main evaluation items are animal and plant items for preservation of Ardeidae breeding habitats and odor and noise items that can evaluate the effects of odors and noise in Ardeidae breeding habitats. First, the scope of the survey in animals and plants categories is not limited to legal guardian species, but includes egrets breeding and feeding grounds corresponding to major species breeding grounds and migratory birds, and preservation measures are established according to the reduction of the area of breeding and feeding grounds. Second, in the odor category, the irradiation period includes the period when the odor generation is the highest from the end of June to the end of July. The odor evaluation standard is based on the complex odor discharge standard, which is a concentration regulation, and the odor concentration felt by humans shall be 2 to 5OU/m³ and the frequency shall be 2% or less. Third, in the noise category, the timing of the survey is measured every month from May to August, including when the sound of egrets and young birds is combined to maximize noise generation. Since the noise of Ardeidae, a bird in summer, occurs only for a certain period of time, measures are taken to reduce noise by securing separation distances, securing buffer green areas, and installing construction rather than installing artificial structures such as soundproof walls. In order for existing Ardeidae breeding sites to maintain an appropriate density of populations and not move populations elsewhere, it is necessary to manage nesting tree and maintain stable habitat quantity and quality.

• Radiation Oncology Journal
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• v.20 no.3
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• pp.237-245
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• 2002

Purpose : This study was conducted to evaluate the treatment results, prognostic factors, and complication rates after high dose rate (HDR) brachytherapy in patients with uterine cervix cancer who were treated with curative aim. Materials and Methods : Of 269 cervix cancer patients treated at the department of radiation oncology, Samsung Medical Center from September 1994 to July 1998, the 106 who were treated with radical radio-therapy were analyzed. The median age was 61 years (range 22 to 89). All patients except 4 with carcinoma in situ (CIS) were given external beam radiotherapy (range $30.6\~50.4\;Gy$ to whole pelvis) and HDR brachytherapy. The common regimens of HDR brachytherapy were a total dose of $24\~28\;Gy$ with $6\~7$ fractions to point A at two fractions per week. The median overall treatment time was 55 days (range 44 to 104) in patients given both external beam radiotherapy and HDR brachytherapy. Results : Early responses of radiotherapy were evaluated by gynecologic examination and follow-up MRI 1 month after radiotherapy. Treatment responses were complete remission in 72 patients, partial response in 33 and no response in 1. The overall survival (OS) rate of all patients was $82\%,\;and\;73\%$, and the disease free survival (DFS) rate was $72\%,\;and\;69\%$, at 3, and 5 years, respectively. The pelvic control rate (PCR) was $79\%$ at both 3 and 5 years. According to the FIGO stage,3 and 5 year OS were $100\%\;and\;50\%$ in CIS/IA, $100\%\;and\;100%$ in IB, $83\%\;and\;69\%$ in IIA, $87\%\;and\;80\%$ in IIB, and $62\%\;and\;62\%$ in III, respectively. The 3 year OS in 4 patients with stage IVA was $100\%$. Three-year DFS were $80\%$ in CIS/IA, $88\%$ in IB, $100\%$ in IIA, $64\%$ in IIB, $58\%$ in III, and $75\%$ in IVA. Three-year PCR were $100\%$ in CIS/IA, $94\%$ in IB, $100\%$ in IIA, $84\%$ in IIB, $69\%$ in III, and $50\%$ in IVA. By univariate analysis, FIGO stage and treatment response were significant factors for OS. The significant factors for DFS were age, FIGO stage, treatment response and overall treatment time (OTT). For pelvic control rate, treatment response and OTT were significant factors. By multivariate analysis, FIGO stage had a borderline significance for OS (p=0.0825) and treatment response had a borderline significance for DFS (0=0.0872). A total of 14 patients $(13\%)$ experienced rectal bleeding, which occurred from 3 to 44 months (median, 13 months) after the completion of radiotherapy. Conclusion : HDR brachytherapy protocol of Samsung Medical Center combined with properly optimal external beam pelvic irradiation is a safe and effective treatment for patients with uterine cervix cancer. The authors found that OTT of less than 55 days had a positive impact on pelvic control and survival rate.

• Radiation Oncology Journal
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• v.17 no.1
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• pp.23-29
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• 1999

Purpose : To evaluate the efficacy of radiation therapy and extrafascial hysterectomy in bulky stage IB, IIA-B uterine cervix cancers. Methods and Materials : Twenty four patients with bulky stage IB and IIA-B carcinoma of the uterine cervix were treated with extrafascial hysterectomy following radiation therapy due to doubts of residual disease at Department of therapeutic radiology, Keimyung University, Dongsan Hospital, from April 1986 to December 1997 According to FIGO staging system, there were 7 patients with stage IB, 9 patients with IIA and 8 patients with IIB stage whose median age was 45. Pathologic distribution showed 16 patients with squamous cell carcinoma and 8 patients with adenocarcinoma. Seven patients had tumors that are less than 5cm in size and 17 patients had tumors with larger than 5cm. The mean interval between radiation therapy and extrafascial hysterectomy was 57 days. The radiation therapy consisted of external irradition to the whole pelvis (180 cGy/fraction, mean 4100 cGy) and parametrial boost (for a mean total dose of 5000 cGy) with midline shield (4H 10 cm), followed by intracavitary irradiation up to 7500 cGy to point A (maximum 8500 cGy). The maximum follow up duration was 107 months and mean follow up duration was 42 months. Results :Ten out of 24 patients (41.7%) had residual disease found at the time of extrafascial hysterectomies. Five year overall survival rate (5Y OSR) and five year disease free survival rate (5Y DFSR) were 63.6% and 62.5% respectively. Five year overall survival rate for stage IB and IIA was 71.4% and 50% for stage IIB. There was a significant difference in 5Y OSR and 5Y DFSR between patients with and those without residual disease (negative vs positive, 83.3% vs. 40% (P=0.01), 83.3% vs 36% (P=0.01) respectively). There was a notable tendency of better survival with adenocarcinoma than with squamous cell carcinoma (adenocarcinoma vs squamous cell carcinoma, 85.7% vs. 53.3% (P=0.1), 85.7% vs. 50.9% (P=0.1) of 5Y OSR and 5Y DFS respectivey). Total dose to A point did not make a significant difference in survival rate or the existence of residual lesion (< 7500 cGy, ${\geq}$ 7500 cOy). It was also noted that significantly more frequent local failures have occurred in patients with positive residual disease compared with negative residual disease (5/10 vs. 0/14, p=0.003), There was no death related to the treatment. Conclusion : There was no improvement of residual disease and to the overall survival rate in spite of increased total dose to point A. We conclude that there is a possible beneficial effect of radiation therapy followed by extrafaseial hysterectomy in survival for adenocarcinoma of bulky stage IB and IIA-B uterine cervix. We need to confirm this with longer follow up and with large number of patients.

• Radiation Oncology Journal
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• v.26 no.2
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• pp.77-82
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• 2008

Purpose: We evaluated the failure pattern of the celiac axis, gastric lymph node, and treatment outcome in the upper and mid-esophageal region of cancer patients treated by definitive radiotherapy, except when treating the celiac axis and gastric lymph node for treatment volume, retrospectively. Materials and Methods: The study constituted the evaluation 108 patients with locally advanced esophageal cancer receiving radiotherapy or a combination of radiotherapy and chemotherapy at Chonbuk National University Hospital from January 1986 to December 2006. In total, 82 patients treated by planned radiotherapy, except when treating the celiac axis and gastric lymph node for treatment volume, were analysed retrospectively. The study population consisted of 78 men and 2 women(mean age of 63.2 years). In addition, 51 patients received radiotherapy alone, whereas 31 patients received a combination of radiation therapy and chemotherapy. The primary cancer sites were located in the upper portion(17 patients), and mid portion(65 patients), respectively. Further, the patients were in various clinical stages including T1N0-1M0(7 patients), T2N0-1M0(18 patients), T3N0-1M0(44 patients) and T4N0-1M0(13 patients). The mean follow up period was 15 months. Results: The various treatment outcomes included complete response(48 patients), partial response(31 patients) and no response(3 patients). The failure patterns of the lymph node were comprised of the regional lymph node(23 patients) and the distance lymph node which included celiac axis and gastric lymph node(13 patients). However, metastasis was not observed in the regional and distant lymph node in 10 patients, whereas 36 patients were not evaluated. Furthermore, of the 13 patients who developed celiac axis and gastric lymph node metastases, 3 were in stage T1N0-1M0 and 10 were in stage T2-4N0-1M0. A complete response appeared in 12 patients, whereas a partial response appeared in 1 patient. The mean survival time of the patients who appeared for regional and distant lymph node metastasis was 14.4 and 7.0 months, respectively. Conclusion: In locally advanced esophageal cancer patients, who were treated by definitive radiotherapy without celiac axis and gastric lymph node irradiation, the distant lymph node metastasis rate was high and the overall survival rate was lower compared to the regional lymph node metastasis. The incidence of regional and distant lymph node metastasis was high in patients who appeared beyond clinical stage T2 and received radiotherapy alone.

• Radiation Oncology Journal
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• v.24 no.3
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• pp.171-178
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• 2006

[ $\underline{Purpose}$ ]: To determine the efficacy and safety of concurrent chemotherapy and radiation therapy with high-dose-rate brachytherapy for cervical cancer. $\underline{Materials\;and\;Methods}$: From January 2001 to December 2002, 30 patients with cervical cancer were treated with concurrent chemotherapy (cisplatin and 5-FU) and definitive radiation therapy. The median age was 58 (range $34{\sim}74$) year old. The pathology of the biopsy sections was squamous cell carcinoma in 29 patients and one was adenocarcinoma. The distribution to FIGO staging system was as follows: stage IB, 7 (23%); IIA, 3 (10%); IIB, 12 (40%); IIIA, 3 (10%); IIIB, 5 (17%). All patients received pelvic external beam irradiation (EBRT) to a total dose of $45{\sim}50.4\;Gy$ (median: 50.4 Gy) over $5{\sim}5.5$ weeks. Ir-192 HDR intracavitary brachytherapy (ICBT) was given after a total dose of 41.4 Gy. HDR-ICBT was performed twice a week, with a fraction point A dose of 4 Gy and median dose to point A was 28 Gy (range: $16{\sim}32\;Gy$) in 7 fractions. The median cumulative biologic effective dose (BED) at point A (EBRT+ICBT) was $88\;Gy_{10}$ (range: $77{\sim}94\;Gy_{10}$). The median cumulative BED at ICRU 38 reference point (EBRT+ICBT) was $131\;Gy_3$ (range: $122{\sim}140\;Gy_3$) at point A, $109\;Gy_3$ (range: $88{\sim}125\;Gy_3$) at the rectum and $111\;Gy_3$ (range: $91{\sim}123\;Gy_3$) at the urinary bladder. Cisplatin ($60\;mg/m^2$) and 5-FU ($1,000\;mg/m^2$) was administered intravenously at 3 weeks interval from the first day of radiation for median 5 (range: $2{\sim}6$) cycles. The assessment was performed at 1 month after completion of radiation therapy by clinical examination and CT scan. The median follow-up time was 36 months (range: $8{\sim}50$ months). $\underline{: The complete response rate after concurrent chemoradiation therapy was 93.3%. The 3-yr actuarial pelvic control rate was 87% and 3-yr actuarial overall survival and disease-free survival rate was 93% and 87%, respectively. The local failure rate was 13% and distant metastatic rate was 3.3%. The crude rate of minor hematologic complications (RTOG grade 1-2) occurred in 3 patients (10%) and one patient had suffered from severe leukopenia (RTOG grade 4) during concurrent treatment. Acute minor enterocolitis (RTOG grade 1-2) occurred in 11 patients (37%) and one patient (3%) was suffered from colon perforation during radiation therapy. Late colitis of RTOG grade 1 occurred in 5 patients (15%). Acute cystitis of RTOG grade 1 occurred in 12 patients (40%) and late cystitis of RTOG grade 2 occurred in one patient (3%). No treatment related death was seen. $\underline{Conclusion}$: The results of this study suggest that the concurrent chemoradiation therapy with HDR brachytherapy could be accepted as an effective and safe treatment for cervical cancer.

• Radiation Oncology Journal
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• v.16 no.4
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• pp.485-495
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• 1998

Purpose : The major goal of the therapy in the soft tissue sarcoma is to control both local and distant tumor. However, the technique of obtaining local control has changed significantly over the past few decades from more aggressive surgery to combined therapy including conservative surgery and radiation and/or chemotherapy. We retrospectively analyzed the treatment results of the postoperative radiation therapy of soft tissue sarcoma and its prognostic factor. Materials and Methods : Between March 1983 and June 1994, 50 patients with soft tissue sarcoma were treated with surgery and postoperative radiation therapy at Kang-Nam St. Mary's hospital. Complete follow up was possible for all patients with median follow up duration 50 months (range 6-162 months). There were 28 male and 32 female patients. Their age ranged from 6 to 83 with a median of 44 years. Extremity (58$\%$) was the most frequent site of occurrence followed by trunk (20$\%$) and head and neck (12$\%$). Histologically malignant fibrous histiocytoma (23$\%$), liposarcoma (17$\%$), malignant schwannoma (12$\%$) constitute 52$\%$ of the patients. Daily radiation therapy designed to treat all areas at a risk for tumor spread upto dose of 4500-5000 cGy. A shrinking field technique was then used and total 55-65 Gy was delivered to tumor bed. Twenty-five patients (42$\%$) received chemotherapy with various regimen in the postoperative period. Results : Total 41 patients failed either with local recurrence or with distant metastasis. There were 29 patients (48$\%$) of local recurrence. Four patients (7$\%$) developed simultaneous local recurrence and distant metastasis and 8 patients (13$\%$) developed only distant metastasis. Local recurrence rate was rather higher than of other reported series. This study included patients of gross residual, recurrent cases after previous operation, trunk and head and neck Primary This feature is likely explanation for the decreased local control rate. Five of 29 Patients who failed only locally were salvaged by re-excision and/or re-irradiation and remained free of disease. Factors affecting local control include histologic type, grade, stage, extent of operation and surgical margin involvement, lymph node metastasis (p<0.05). All 21 patients who failed distantly are dead with progressive disease at the time of this report. Our overall survival results are similar to those of larger series. Actuarial 5 year overall survival and disease free survival were 60.4 $\%$, 30.6$\%$ respectively. Grade, stage (being close association with grade), residual disease (negative margin, microscopic, gross) were significant as a predictor of survival in our series (p<0.05). Conclusion : Combined surgery and postoperative radiation therapy obtained 5 year survival rate comparable to that of radical surgery.