• The Korean Journal of Physiology and Pharmacology
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• 제18권2호
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• pp.109-120
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• 2014

The epothilones are a class of microtubule inhibitors that exhibit a strong antitumor activity. UTD2 is a novel epothilone analog generated by genetic manipulation of the polyketide biosynthetic gene cluster. This study investigated the effects of UTD2 on the actin cytoskeleton and its critical regulators, and the signaling pathways which are essential for cell motility, growth and survival in MCF-7 breast cancer cells. Results showed that UTD2 inhibited the cellular functions of actin cytoskeleton, such as wound-closure, migration and invasion, as well as adhesion. Our study further demonstrated that UTD2 suppressed Rac1 GTPase activation and reduced the activity of PAK1, which is a downstream effector of Rac1, while the activity of Cdc42 was not affected. Additionally, the phosphorylation of p38 and ERK were significantly inhibited, but the phosphorylation of JNK remained the same after UTD2 treatment. Moreover, UTD2 inhibited the activity and mRNA expression of MMP-2, which plays a key role in cell motility. UTD2 also reduced the phosphorylation of Akt, which is an important signaling kinase regulating the cell survival through Rac1. Furthermore, UTD2 interrupted the synergy between Rac1 and Raf in focus formation assays. Taken together, these results indicated that UTD2 exerted multiple effects on the actin cytoskeleton and signaling pathways associated with Rac1. This study provided novel insights into the molecular mechanism of the antineoplastic and antimetastatic activities of epothilones. Our findings also suggest that the signaling pathways regulated by Rac1 may be evaluated as biomarkers for the response to therapy in clinical trials of epothilones.

• Journal of Chest Surgery
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• 제25권12호
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• pp.1530-1536
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• 1992

From January 1984 to December 1991, One hundred sixty five patients with carcinomoa of the esophagus were treated surgically at the department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital. Among them, hospital records were available in 121 patients and were included in this study. There were 115 men and 6 women, with ages ranging from 40 years to 79 years[mean age of 59.2 years]. The most frequent preoperative symptoms included dysphagia[72.7%], weight loss[60.3%], chest pain or discomfort[14.9%], general malaise[13.2%]. All were treated surgically: 100 patients were managed by curative or palliative resection with reconstruction, and 6 by palliative bypass surgery. In 15 patients, explorative thoracotomy or laparotomy was only done due to unresectability. [operability: 87.6%, resectability: 82.6%] All specimens[those from resectable 100 cases] were sent to pathology, and histopathologic examinations were done; squamous cell carcinomas were found in 95 cases, adenocarcinoma in l. Adenosquamous carcinomas were found in 3, and malignant melanoma in l. Postoperative complications occurred in 34 cases; anastomotic site leakage[10], which was followed by empyema in 9 of them, wound problem[7], hepatic failure[6], pneumonia [3], post-operative bleeding[3], chylothorax[2], post-operative stricture[2], sepsis[1], and tracheobronchial fistula[1]. Hospital deaths were in 6 cases[Hospital mortality: 5.0%]. During the follow up period, 26 patients were proven to be recurrence of cancer locally or distantly. The one, two, and five-year actuarial survival raf.es were 71.3$\pm$4.5%, 57.4$\pm$5.6%, 34.7$\pm$8.9%, respectively. The data from this study suggested that esophagectomy with reconstruction of gastrointestinal tract could be performed with a low operative mortality and a few serious postoperative complications and achieved reasonable long term palliation for carcinoma of the esophagus.

• 생명과학회지
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• 제26권12호
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• pp.1466-1469
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• 2016

운향과(Rutaceae) 식물의 과실을 소재로 하는 일군의 한약재들은 위장관 운동 기능 항진을 목적으로 우리나라와 중국 등지에서 오래 전부터 널리 사용되어 왔으며, 대표적인 약재로 각각 탱자나무 및 광귤나무의 미성숙 과실인 지실 및 지각, 각각 광귤나무 및 귤나무의 성숙 과피인 등피 및 진피 등이 있다. 본 연구에서는, 이러한 운향과 과실 유래 한약재들이 위장관 운동 기능에 미치는 영향을 검정하고 이 약재들 간의 효능을 비교하기 위해, 이들 한약재의 열수 및 에탄올 추출물을 제조하여 마우스에 경구 투여한 후 위 배출 속도 및 장 이송률을 측정하는 실험을 수행하였다. 본 연구는, 공통 성분을 다수 함유하는 운향과 과실 유래 한약재들 간의 위장관 운동 기능개선 효과를 in vivo 동물 실험을 통해 직접 비교한 최초의 연구 자료로서 의미를 가진다. 특히, 등피 에탄올 추출물 투여 시 위 배출 속도에는 유의적인 변화 없이 장 이송률의 유의적 및 용량 의존적 증가 양상을 보였으며, 이전 연구들을 통해 장 이송률 증가 효능이 보고된 바 있는 지실, 지각, 진피 열수 추출물 투여군들과 비교했을 때에도 수치 상으로 등피 에탄올 추출물의 장 이송률이 가장 높았다.

• 대한임상검사과학회지
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• 제45권2호
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• pp.66-72
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• 2013

Fine Needle Aspiration Biopsy Cytology (FNABC), which is known as the most accurate and cost-effective method for diagnosis of the thyroid nodule, may still result in indeterminate cases that are cellular paucity and show minor nuclear atypia. However, most cases are associated with suspicion of papillary thyroid carcinoma (PTC). A B-type Raf kinase (BRAF) mutation was found in about half of PTCs which is currently helping us to differentiate malignancies from benign lesions. Cases studied included 46 histological, confirmed PTC cases. FNABC 102 cell paucity and 74 atypia benign cases were previously diagnosed as suspicious of PTC using cytologic examination. These cases were analyzed for BRAF mutation by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) with a new restriction enzyme. In this study, the sensitivity and specificity were calculated and, BRAF mutation was detected by means of a histological method in 23 of 46 cases of PTC and no mutation was found in 22 cases. However, one case was not detected. In using FNABC, BRAF mutation was detected in 6 of 102 cases in cell paucity and in 11 of 74 cases in the atypia. Two cases were not detected in the atypia. The sensitivity and specificity of PCR-RFLP in FNABC were 60% and 97.4% respectively. Assessment of Formalin Fixed Paraffin Embedding (FFPE) block demonstrated similarly a 51.1% positive and 48.9% negative in PTC. Evaluation of BRAF mutation revealed high specificity and low sensitivity in using FNABC method. This study suggests that BRAF mutation analysis should be useful for the clinical diagnosis of PTC in FNABC with cytological findings suspicious for PTC.

• Archives of Pharmacal Research
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• 제25권5호
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• pp.561-571
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• 2002

The action mechanisms of several chemopreventive agents derived from herbal medicine and edible plants have become attractive issues in cancer research. Tea is the most widely consumed beverage worldwide. Recently, the cancer chemopreventive actions of tea have been intensively investigated. It have been demonstrated that the active principles of tea were attributed to their tea polyphenols. Recently, tremendous progress has been made in elucidating the molecular mechanisms of cancer chemoprevention by tea and tea polyphenols. The suppression of various tumor biomarkers including growth factor receptor tyrosine kinases, cytokine receptor kinases, P13K, phosphatases, ras, raf, MAPK cascades, NㆍFB, IㆍB kinase, PKA, PKB, PKC, c-jun, c-fos, c-myc, cdks, cyclins, and related transducing proteins by tea polyphenols has been studied in our laboratory and others. The IㆍB kinase (IKK) activity in LPS-activated murine macrophages (RAW 264.7 cells) was found to be inhibited by various tea polyphenols including (-) epigallocatechin-3-gallate (EGCG), theaflavin (TF-1), theaflavin-3-gal-late (TF-2) and theaflavin-3,3'-digallate (TF-3). TF-3 inhibited IKK activity in activated macrophages more strongly than did the other tea polyphenols. TF-3 inhibited both IKK1 and IKK2 activity and prevented the degradation of IㆍBㆍand IㆍBㆍin activated macrophage cells. The results suggested that the inhibition of IKK activity by TF-3 and other tea polyphenols could occur by a direct effect on IKKs or on upstream events in the signal transduction pathway. TF-3 and other tea polyphenols blocked phosphorylation of IB from the cytosolic fraction, inhibited NFB activity and inhibited increases in inducible nitric oxide synthase levels in activated macrophage. TF-3 and other tea polyphenols also inhibited strongly the activities of xanthine oxidase, cyclooxygenase, EGF-receptor tyrosine kinase and protein kinase C. These results suggest that TF-3 and other tea polyphenols may exert their cancer chemoprevention through suppressing tumor promotion and inflammation by blocking signal transduction. The mechanisms of this inhibition may be due to the blockade of the mitogenic and differentiating signals through modulating EGFR function, MAPK cascades, NFkB activation as wll as c-myc, c-jun and c-fos expression.

• Environmental Analysis Health and Toxicology
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• 제11권1_2호
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• pp.1-10
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• 1996

A decrease in stratospheric ozone probably caused by chloroflurocarbons (CFCs) emissions, has been observed large parts of-the globe. It is generally accepted that if ozone levels in the stratosphere are depleted, greater amounts of shortwave ultraviolet radiationB (UVB) will reach the earth's surface, resulting in increased incidence of nonmelanoma skin cancer. In this study, we evaluated several mathematical models, such as a power and an exponential model, and a geometric model considering the surface area of a human body part and ages for the prediction of Skin cancer incidence caused by exposure to the UVB radiation. These models basically estimated the risk of skin cancer based on those measurements of the local ozone in stratosphere and UVB. Both were measured at a part of Seoul with a Dobson ozone spectrometer and Robertson-Berger UV Biometer for 1995. As a result, we calculated the point estimation applying a biological amplification factor (BAF), UVB radiation and other factors. We used a Monte-Carlo simulation technique with assumption on the distribution of each considered factor. The sensitivity analysis of model by there components conducted using Gaussian sensitivity method. The annual integral of UVB radiation was 2275 MED (minimal erythema dose)/yr. Also, an estimate of the annual amount of UVB reaching the earth's surface at a korea's latitude and altitude was 3328 MED/yr. The values of the radiation amplification factor (RAF) were ranged from 0.9 to 1.5 in Seoul. To give the effective factors required to model the prediction of skin cancer incidence caused by exposure to the UVB radiation in Korea, we studied the pros and cons of above mentioned models with the application of those parameters measured in Seoul, Korea.

• 복식
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• 제67권2호
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• pp.68-87
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• 2017

The New Look, which Christian Dior presented in 1947, has been a source of inspiration for contemporary fashion designers, as well as designers for the House of Dior, and has a great influence on them. The purpose of this study is to compare and analyze the aesthetic characteristics of Christian Dior's New Look and the New Look that Christian Dior House designers reinterpreted. The subject and the scope of this study were limited to Christian Dior and the New Look designed by Gianfranco $Ferr\acute{e}$, John Galliano, and Raf Simons who are regarded as worthy successors. The research method was a literature review on previous studies on Christian Dior and related literatures to examine the history of the House of Dior and the aesthetic characteristics of the New Look presented by Christian Dior. Then, an empirical study was conducted through the analysis of collection photographs from 1989 to 2016 that were gathered from the Mode et Mode and Hi Fashion, and websites (British Vogue, Firstview). The results of the study were as follows. First, the aesthetic characteristics of Christian Dior's New Look in 1947 used femininity to express an elegant and beautiful woman, structural property to render the contours of a woman's body, and innovation that changed the formal and gloomy social atmosphere in the post-war years. Second, the aesthetic characteristics of the New Look by Christian Dior were compared with those of the New Look made by designers for the House of Dior. The elegant femininity of Dior can be seen as gorgeous femininity, and sensual femininity, minimalistic femininity, structurality is represented by the spatial structurality of Dior and $Ferr\acute{e}$, the organic structure of Galliano, and the orthodox structure of Simons. Moreover, Dior's retro innovativeness appeared to be $Ferr\acute{e}^{\prime}s$ androgyny innovation, Galliano's deconstructive innovation, and Simons' romantic futuristic innovation.

• 한국환경성돌연변이발암원학회지
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• 제25권1호
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• pp.40-46
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• 2005

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) displays high toxicity in animals and has been implicated in human carcinogenesis. Although the mechanism of carcinogenesis by TCDD is unclear, it is considered to be a non-genotoxic compound and tumor promoter. In our experiment, we investigated the effects of TCDD on gene expression in mouse skin carcinogenesis. We used cDNA microarray to detect the differential gene expression in tumors induced in hairless mouse skin by MNNG plus TCDD protocol. We found that erb-2, c-ets2 and p27$^{kip1}$ were significantly up-regulated, but TNFR2, AKT-l, integrin $\beta$l, maspin, IGF-l, c-raf-l, Rb were significantly down-regulated, in tumor region, respectively. We also found that the expression of 53 genes involved in cen cycle, signal transduction, apoptosis, adhesion molecule, angiogenesis, and invasion, were changed two fold more, in tumor surrounding region. These data suggest that TCDD alters the expression of a large array of genes involved in apoptosis, cytokine production and angiogenesis in mouse skin carcinogenesis.

• 한국자원식물학회지
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• 제31권6호
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• pp.684-694
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• 2018

This study describes the successful establishment of a cryopreservation protocol for Citrus limon cultivars: 'Frost Eureka limon' and 'Cook Eureka limon', using a droplet-vitrification method. The shoot tips that were excised from in vitro grown seedlings of the two cultivars were preserved in liquid nitrogen (LN) and successfully regenerated into whole plants. Excised shoot tips were pre-cultured for 1 or 2 days in 0.3 M and 0.5 M sucrose solutions at $25^{\circ}C$ and incubated in a loading solution (LS) composed of 17.5% glycerol + 17.5% sucrose in Murashige and Skoog (MS) medium for 40 min at $25^{\circ}C$. Prior to direct immersion in LN for 1 h, the shoot tips were dehydrated with plant vitrification solution 2 (PVS2) at $0^{\circ}C$ or PVS3 at $25^{\circ}C$. The frozen shoot tips were re-warmed and unloaded with 1.2 M sucrose in $\text\tiny{^1/_2}$ MS for 30 min at $25^{\circ}C$. Shoot tips were post-cultured overnight on survival medium and then micrografted onto 'trifoliate orange' (Poncirus trifoliate (L.) Raf. seedling rootstocks for recovery and to produce whole plants. The highest regrowth rates were 53.5% and 50.3% for cryopreserved shoot tips of 'Frost Eureka limon' and 'Cook Eureka limon', respectively, when pre-cultured in 0.3 M and 0.5 M sucrose concentrations in a sequencing manner, with LS and treated with PVS2 for 60 min at $0^{\circ}C$. We also investigated whether the ammonium ion concentration on post-culture medium affected the viability of the cryopreserved Citrus shoot tips. The viability of cooled samples, following culturing on woody plant media (WPM) containing $\text\tiny{^1/_4}$ ammonium nitrate overnight before micrografting, was the highest (70.3%) in 'Frost Eureka limon'. The study described here is a cost-effective and safe method to conserve Citrus fruit cultivars, for the improvement and large-scale multiplication of fruit plants and for breeding disease resistance.

• Journal of Microbiology and Biotechnology
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• 제32권3호
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• pp.387-395
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• 2022

Deciphering the metabolites of human diseases is an important objective of biomedical research. Here, we aimed to capture the core metabolites of Fanconi anemia (FA) using the bioinformatics method of a multi-omics composite network. Based on the assumption that metabolite levels can directly mirror the physiological state of the human body, we used a multi-omics composite network that integrates six types of interactions in humans (gene-gene, disease phenotype-phenotype, disease-related metabolite-metabolite, gene-phenotype, gene-metabolite, and metabolite-phenotype) to procure the core metabolites of FA. This method is applicable in predicting and prioritizing disease candidate metabolites and is effective in a network without known disease metabolites. In this report, we first singled out the differentially expressed genes upon different groups that were related with FA and then constructed the multi-omics composite network of FA by integrating the aforementioned six networks. Ultimately, we utilized random walk with restart (RWR) to screen the prioritized candidate metabolites of FA, and meanwhile the co-expression gene network of FA was also obtained. As a result, the top 5 metabolites of FA were tenormin (TN), guanosine 5'-triphosphate, guanosine 5'-diphosphate, triphosadenine (DCF) and adenosine 5'-diphosphate, all of which were reported to have a direct or indirect relationship with FA. Furthermore, the top 5 co-expressed genes were CASP3, BCL2, HSPD1, RAF1 and MMP9. By prioritizing the metabolites, the multi-omics composite network may provide us with additional indicators closely linked to FA.