• 대한의사협회지
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• 제61권11호
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• pp.662-669
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• 2018

The cutaneous melanoma has been regarded as rare disease entity in Korea for long time but it shows a silent growth recently. Furthermore the management of cutaneous melanoma including staging system, surgical principle, sentinel lymph node biopsy and subsequent complete node dissection and, most importantly, immunotherapy and target therapy against cutaneous melanoma recently. The incidence of cutaneous melanoma is steadily increasing in Korea but its increase is rapid recent 2 decades to 4.3 times and should be greater soon according to the steeper increase of life expectancy. New staging system proposed by American Joint Committee on Cancer (2017) includes changes in individual TNM category and stage groups, particularly from a prognostic viewpoint. Dermoscopy has been successfully introduced in the differential diagnosis of pigmented skin lesion focusing on cutaneous melanoma by non-invasive simple diagnostic tool. Sentinel lymph node biopsy was a issue of long debate whether survival benefit is real or not. Temporary conclusion about this question is reached after two large scale studies and immediate complete node dissection should be performed in a certain situations. Most important change is drug therapy focusing on immunotherapy and target therapy. Braf- and MEK-inhibitor, immune checkpoint inhibitor and PD-1 blocker has been proved to be effective as a sole or combination regimen against advanced and/or high-risk adjuvant setting of cutaneous melanoma. In conclusion, these remarkable changes will be reviewed shortly here.

• KSBB Journal
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• 제29권1호
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• pp.50-57
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• 2014

NF-${\kappa}B$ is a transcriptional factor which is involved in many biological processes including immunity, inflammation, and cell survival. Many investigators studied on the mechanism involved in activation of NF-${\kappa}B$ signalling pathway via ubiquitination and degradation of $I{\kappa}B$ regarding skin disease. Some specific molecules including Akt, MEK, p38 MAP Kinase, Stat3, et al. represent convergence points and key regulatory proteins in signaling pathways controlling cellular events such as growth and differentiation, energy homeostasis, and the response to stress and inflammation. Ultraviolet (UV) irradiation has many adverse effects on skin, including inflammation, alteration in the extracellular matrix, cellular senescence, apoptosis and skin cancer. Prunus mume, a naturally derived plant extract, has beneficial biological activities as blood fluidity improvement, anti-fatigue action, antioxidative and free radical scavenging activities, inhibiting the motility of Helicobacter pyolri. Previous reports on various beneficial function prompted us to investigate UVB-induced or other immunostimulated biological marker regarding P. mume extract. P. mume extract suppresses UVB-induced cyclooxygenase-2 (COX-2) expression in mouse skin epidermal JB6 P+ cells. The activation of activator protein-1 and nuclear factor-${\kappa}B$ induced by UVB was dose-dependently inhibited by P. mume extract treatment. This results suggest that P. mume extracts might be used as a potential agents for protection of inflammation or UVB induced skin damage.

• Molecules and Cells
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• 제42권5호
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• pp.397-405
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• 2019

The regulatory role of long noncoding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) in both cancerous and noncancerous cells have been widely reported. This study aimed to evaluate the role of lncRNA GAS5 in heart failure caused by myocardial infarction. We reported that silence of lncRNA GAS5 attenuated hypoxia-triggered cell death, as cell viability was increased and apoptosis rate was decreased. This phenomenon was coupled with the down-regulated expression of p53, Bax and cleaved caspase-3, as well as the up-regulated expression of CyclinD1, CDK4 and Bcl-2. At the meantime, the expression of four heart failure-related miR-NAs was altered when lncRNA GAS5 was silenced (miR-21 and miR-142-5p were up-regulated; miR-30b and miR-93 were down-regulated). RNA immunoprecipitation assay results showed that lncRNA GAS5 worked as a molecular sponge for miR-142-5p. More interestingly, the protective actions of lncRNA GAS5 silence on hypoxia-stimulated cells were attenuated by miR-142-5p suppression. Besides, TP53INP1 was a target gene for miR-142-5p. Silence of lncRNA GAS5 promoted the activation of PI3K/AKT and MEK/ERK signaling pathways in a miR-142-5p-dependent manner. Collectively, this study demonstrated that silence of lncRNA GAS5 protected H9c2 cells against hypoxia-induced injury possibly via sponging miR-142-5p, functionally releasing TP53INP1 mRNA transcripts that are normally targeted by miR-142-5p.

• 한국도시환경학회지
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• 제18권4호
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• pp.503-509
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• 2018

본 연구에서는 양자전이 비행시간질량분석기(PTR-ToF-MS)를 이용하여 반도체 공정의 작업환경(PHOTO, FPD, OLED, WET 공정)에서 VOCs를 실시간으로 모니터링하였다. 작업환경에서 평균 VOCs 농도는 PHOTO 6.5 ppm, FPH 6.4 ppm, WET 2.0 ppm, OLED 1.3 ppm이었다. VOCs 중 methyl ethyl ketone이 2.8 ppm (69%), acetaldehyde가 0.5 ppm (13.2%)로 나타났다. 반도체 공정 특성에 따라 다양한 VOCs 가 작업환경에서 관측되었다. 관측된 VOCs 농도는 작업환경기준보다 낮지만, 이러한 VOCs를 지속적으로 모니터링하여 효과적으로 관리해 나갈 필요가 있다.

• 한국발생생물학회지:발생과생식
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• 제6권1호
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• pp.1-6
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• 2002

세포외기질(exrtracellular matrix, ECM)에 의한 생쥐 초기 배아의 발생 조절 현상의 기작 규명을 위한 연구의 일환으로 Engelbreth-Holm-Swarm(EHS) mouse sarcoma의 세포외기질로부터 추출한 ECM 복합체인 Matrigel의 성장인자 제거형(GFR-Matrigel)을 생쥐 포배에 처리한 후 mitogen activated protein kinase (MAPK, ERK1/2) 활성 의 변화를 조사하였다. Matrigel 처리 후 10분 이내에 배아의 MAPK 활성이 유의하게 증가하였고, 60분 후에도 유의하게 높은 활성을 유지하였다. 한편 MAPK cascade의 저해제인 PD098059를 전처리한 경우 Matrigel에 의한 MAPK 활성의 증가가 관찰되지 않았다. Matrigel 배양액 내에서 12시간 동안 배양한 포배의 MAPK 활성은 대조군과는 현격한 차이를 보였다. 이러한 결과로부터 ECM에 의한 생쥐초기 배아의 발생 촉진효과 발현기작에는 하위 신호전달 과정의 MAPK 활성화 과정이 관여하는 것으로 사료된다.

• The Korean Journal of Physiology and Pharmacology
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• 제17권2호
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• pp.139-147
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• 2013

Lysolipids such as LPA, S1P and SPC have diverse biological activities including cell proliferation, differentiation, and migration. We investigated signaling pathways of LPA-induced contraction in feline esophageal smooth muscle cells. We used freshly isolated smooth muscle cells and permeabilized cells from cat esophagus to measure the length of cells. Maximal contraction occurred at $10^{-6}M$ and the response peaked at 30s. To identify LPA receptor subtypes in cells, western blot analysis was performed with antibodies to LPA receptor subtypes. LPA1 and LPA3 receptor were detected at 50 kDa and 44 kDa. LPA-induced contraction was almost completely blocked by LPA receptor (1/3) antagonist KI16425. Pertussis toxin (PTX) inhibited the contraction induced by LPA, suggesting that the contraction is mediated by a PTX-sensitive G protein. Phospholipase C (PLC) inhibitors U73122 and neomycin, and protein kinase C (PKC) inhibitor GF109203X also reduced the contraction. The PKC-mediated contraction may be isozyme-specific since only $PKC{\varepsilon}$ antibody inhibited the contraction. MEK inhibitor PD98059 and JNK inhibitor SP600125 blocked the contraction. However, there is no synergistic effect of PKC and MAPK on the LPA-induced contraction. In addition, RhoA inhibitor C3 exoenzyme and ROCK inhibitor Y27632 significantly, but not completely, reduced the contraction. The present study demonstrated that LPA-induced contraction seems to be mediated by LPA receptors (1/3), coupled to PTX-sensitive G protein, resulting in activation of PLC, PKC-${\varepsilon}$ pathway, which subsequently mediates activation of ERK and JNK. The data also suggest that RhoA/ROCK are involved in the LPA-induced contraction.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2001년도 추계학술대회 및 정기총회
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• pp.107-107
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• 2001

During the last decade, enormous progress has been made on the biological significance of apoptosis. Since ras is among the most central molecule in signaling, we asked if ras regulates apoptotic pathway. We have previously shown that H-ras, but not N-ras, induces an invasiveness and motility in human breast epithelial cells (MCF10A), while both H-ras and N-ras induce transformed phenotype. In this study, we wished to seek a chemopreventive agent that effectively induces apoptosis in H-ras-activated cells. Here we show that capsaicin, the major pungent phytochemical in red pepper, induces caspase 3-involved apoptosis selectively in H-ras activated MCF10A cells while the parental MCF10A cells are not effected. In order to study the molecular mechanisms for the increased sensitivity of H-ras MCF10A cells to capsaicin-induced apoptosis, activation of ras downstream signaling molecules, mitogen-activated protein kinases (MAPKinases), upon capsaicin treatment was investigated. Phosphorylated forms of JNK1 and p38 MAPKinase were prominently increased whereas activated ERK-1/2 was decreased by capsaicin in ras-activated cells. The parental cells did not respond to capsaicin, suggesting that capsaicin selectively induces apoptosis through modulating activities of ras downstream signaling molecules in H-ras-activated cells. Studies using chemical inhibitors (CPT-cAMP, SB203580 and PD98059) and dominant negative constructs of JNKl, p38 and MEK show that activation of JNK1 and p38 MAPKinase, but not ERK-1/2, is critical for ras-mediated apoptosis by capsaicin.

• 한국연초학회지
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• 제27권1호
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• pp.51-58
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• 2005

The objective of this study was to evaluate the effect of cigarette filter on in vitro cytotoxicity of cigarette mainstream smoke from the cigarette. In this work, we used 3 types of cigarettes included non-filtered 2R4F cigarette, cellulose acetate-filtered 2R4F cigarette, and carbon dual-filtered 2R4F cigarette which was made from original 2R4F by replacing with an acetate filter containing carbon. The cytotoxicity of both the cigarette smoke condensate (CSC), which was collected in Cambridge filter pad, and the gas/vapor phase (GVP), which was bubbled through in phosphate-buffered saline in a gas-washing bottle, was determined using a neutral red uptake assay with CHO-K1 cells. With regard to cytotoxicity when calculated on an equal puff basis, the cytotoxicity of CSC from the filtered cigarettes was lower than that of the non filtered cigarette. Also, $EC_{50}$ vlaue of GVP from carbon filter cigarette was 40.9 puff/L, indicating the cytotoxicity to be $20\%$ lower than that of the CA filter cigarette. The cytotoxicity of the GVP was correlated to the several vapor phase components (formaldehyde, acetaldehyde, acetone, acrolein, crotonaldehyde and MEK). In conclusion, carbon filter, which significantly reduced the amount of carbonyl compounds in mainstream cigarette smoke, results in significant reductions in the cytotoxicity potential of the smoke.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2001년도 추계학술대회 및 정기총회
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• pp.104-104
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• 2001

Ras는 세포의 성장과 분화 등 여러 필수적인 세포기능에 없어서는 안될 중요한 역할을 담당하며 Ras가 mutation되면 암 등의 치명적인 결과를 초래한다. Ras 발현은 유방암에서 tumor aggressiveness의 지표로 간주되고 있으며 유방세포의 침습성과 연관이 있다고 알려져 있으므로 ras가 전이과정에 미치는 영향에 관한 연구는 중요한 의미를 갖는다. 본 연구의 선행연구결과, H-ras와 N-ras 모두 transformed phenotype을 나타내지만 H-ras 만이 암전이에 있어서 중요한 침윤성을 유도하는 것을 밝혔다. 이 결과는 MCF10A 세포에서 H-ras와 N-ras에 의한 신호전달경로가 각각 다른 생물학적 전이활성을 나타냄을 시사한다. 세포의 이동성은 침습성에 있어서 결정적인 역할을 하므로, 본 연구에서 H-ras와 N-ras로 형질전환된 MCF10A세포에서 이동성을 시험한 결과, 세포의 이동성이 N-ras가 아닌 H-ras MCF10A 세포에서만 크게 증가된다는 것을 보았다. 이는 침습성을 나타내는 H-ras가 세포의 이동성을 증가시키는데 작용한다는 것을 말한다. H-ras에 의해 유도된 침습성과 이동성에 대한 분자적 기전에 관하여 연구하기 위하여 H-ras MCF10A와 N-ras MCF10A 세포에서 Ras의 downstream effector들, 특히 mitogen-activated protein kinases(MAPKinases)들인 JNK1, ERK, p38의 활성화를 살펴본 결과 p38 MAPKinase가 H-ras MCF10A 세포에서 현저하게 활성화됨을 보았다. p38 MAPKinase 저해제인 SB203580를 처리하던지 dominant negative p38 (DN p38) transfectant로 p38을 불활성화시켰을 때 세포침습성 및 이동성이 저해되는 결과를 얻었다. SB203580 처리한 H-ras MCF10A 세포에서 전이에 관여하는 효소인 MMP-2 분비가 감소되었다. H-ras에 의해 유도된 침습성과 이동성은 DN JNK1 transfectant에서는 변화가 없었으나 DN MEK transfectants에서는 유의성있게 감소되었다. 이상의 결과를 종합하면, MCF10A 세포의 침윤성과 이동성에는 p38 MAPKinase 활성이 중심적인 역할을 하며, JNK 활성은 영향을 미치지 않고, ERK-1/2 활성은 충분하지는 않으나 필요하다는 것을 알 수 있었다.

• Molecules and Cells
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• 제39권10호
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• pp.742-749
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• 2016

The cancer chemo-preventive effects of equol have been demonstrated for a wide variety of experimental tumours. In a previous study, we found that equol inhibited proliferation and induced apoptotic death of human gastric cancer MGC-803 cells. However, the mechanisms underlying equol-mediated apoptosis have not been well understood. In the present study, the dual AO (acridine orange)/EB (ethidium bromide) fluorescent assay, the comet assay, MTS, western blotting and flow cytometric assays were performed to further investigate the pro-apoptotic effect of equol and its associated mechanisms in MGC-803 cells. The results demonstrated that equol induced an apoptotic nuclear morphology revealed by AO/EB staining, the presence of a comet tail, the cleavage of caspase-3 and PARP and the depletion of cIAP1, indicating its pro-apoptotic effect. In addition, equol-induced apoptosis involves the mitochondria-dependent cell-death pathway, evidenced by the depolarization of the mitochondrial membrane potential, the cleavage of caspase-9 and the depletion of Bcl-xL and full-length Bid. Moreover, treating MGC-803 cells with equol induced the sustained activation of extracellular signal-regulated kinase (ERK), and inhibiting ERK by U0126, a MEK/ERK pathway inhibitor, significantly attenuated the equol-induced cell apoptosis. These results suggest that equol induces mitochondria-dependent apoptosis in human gastric cancer MGC-803 cells via the sustained activation of the ERK1/2 pathway. Therefore, equol may be a novel candidate for the chemoprevention and therapy of gastric cancer.