• Journal of Life Science
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• v.20 no.4
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• pp.519-527
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• 2010

Paclitaxel is known as a potent inhibitor of microtubule depolymerization. It leads to mitotic arrest and cell death by stabilizing the spindle in various cell types. Here, we investigated the effects of paclitaxel on the proliferation and cell death of rabbit articular chondrocytes. Paclitaxel inhibited proliferation in a dose- and time- dependent manner, determined by MTT assay in rabbit articular chondrocytes. We also established paclitaxel-induced G2/M arrest by fluorescent activated cell sorter (FACS) analysis. Paclitaxel increased expression of cyclin B, p53 and p21, while reducing expression of cdc2 and cdc25C in chondrocytes, as detected by Western blot analysis. Interestingly, paclitaxel showed the mitotic catastrophe that leads to abnormal nucleus division and cell death without DNA fragmentation through activation of caspase. Cell death by mitotic catastrophe in cells treated with paclitaxel was suppressed by inhibiting G1/S arrest with 2 mM thymidine. These results demonstrate that paclitaxel induces cell death via mitotic catastrophe without activation of casepase in rabbit articular chondrocytes.

• Journal of Life Science
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• v.16 no.4
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• pp.589-597
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• 2006

Genistein, a natural isoflavonoid phytoestrogen, is a strong inhibitor of protein tyrosine kinase and DNA topoisomerase activities. There are several studies documenting molecular alterations leading to cell cycle arrest and induction of apoptosis by genistein as a chemopreventive agent in a variety of cancer cell lines; however, its mechanism of action and its molecular targets on human bladder carcinoma and leukemic cells remain unclear. In the present study, we have addressed the mechanism of action by which genistein suppressed the proliferation of T24 bladder carcinoma and U937 leukemic cells. Genistein significantly inhibited the cell growth and induced morphological changes, and induced the G2/M arrest of the cell cycle in both T24 and U937 cells with a relatively stronger cytotoxicity in U937. The G2/M arrest in T24 cells was associated with the inhibition of cyclin A, cyclin B1 and Cdc25C protein expression without alteration of tumor suppressor p53 and cyclin-dependent kinase (Cdk) inhibitor p21(WAF1/CIP1). However, the inhibitory effects of genistein on the cell growth of U937 cells were connected with a marked inhibition of cyclin B1 and an induction of Cdk inhibitor p21 proteins by p53-independent manner. These data suggest that genistein may exert a strong anticancer effect and additional studies will be needed to evaluate the different mechanisms between T24 and U937 cells.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8623-8629
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• 2014

Background: As an important component of the NDC80 kinetochore complex, NUF2 is essential for kinetochore-microtubule attachment and chromosome segregation. Previous studies also suggested its involvement in development of various kinds of human cancers, however, its expression and functions in human hepatocellular carcinoma (HCC) are still unclear. Materials and Methods: In the present study, we aimed to test the hypothesis that NUF2 is aberrant in human HCCs and associated with cell growth. Results: Our results showed significantly elevated expression of NUF2 in human HCC tissues compared to adjacent normal tissues, and high expression of NUF2 in HCC cell lines. Using lentivirus-mediated silencing of NUF2 in HepG2 human HCC cells, we found that NUF2 depletion markedly suppressed proliferation and colony formation capacity in vitro, and dramatically hampered tumor growth of xenografts in vivo. Moreover, NUF2 silencing could induce cell cycle arrest and trigger cell apoptosis. Additionally, altered levels of cell cycle and apoptosis related proteins including cyclin B1, Cdc25A, Cdc2, Bad and Bax were also observed. Conclusions: In conclusion, these results demonstrate that NUF2 plays a critical role in the regulation of HCC cell proliferation and apoptosis, indicating that NUF2 may serve as a potential molecular target for therapeutic approaches.

• Tribology and Lubricants
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• v.25 no.1
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• pp.20-24
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• 2009

TiC-derived carbon coatings have been synthesized at $600^{\circ}C$ temperature treatment with $H_2/Cl_2$ mixture gases. From Raman spectroscopy measurements, the modified layer was covered with carbon and the thick-ness of the layer was increased with increasing reaction time. And $I_D/I_G$ ratio was decreased with increasing reaction time. The superior tribological property was obtained from TiC reacted with $Cl_2$ gas for 2 hrs. And the tribological property measurements indicate that TiC-derived carbon layer has $0.9{\times}10_{-6}mm^3/Nm$ in wear coefficient and 0.13 in friction coefficient.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.05a
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• pp.81-81
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• 2002

The recent development of cDNA microarray or cDNA chip technology has made it possible to analyze the expression of thousands of genes at once. In present study, we made radioresistant clones (#1 and #4) from NIH3T3 cells which are not tumorigenic and we identified 4 genes using microarray system, cdk6, cdc25B, mdm-2 and nidogene, which were altered in radiaiton resistanct NIH3T3 cells.(omitted)

• BMB Reports
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• v.48 no.1
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• pp.25-29
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• 2015

Ubiquitination is a post translational modification which mostly links with proteasome dependent protein degradation. This process has been known to play pivotal roles in the number of biological events including apoptosis, cell signaling, transcription and translation. Although the process of ubiquitination has been studied extensively, the mechanism of polyubiquitination by multi protein E3 ubiquitin ligase, SCF complex remains elusive. In the present study, we identified UbcH5a as a novel stimulating factor for poly-ubiquitination catalyzed by $SCF^{hFBH1}$ using biochemical fractionations and MALDI-TOF. Moreover, we showed that recombinant UbcH5a and Cdc34 synergistically stimulate $SCF^{hFBH1}$ catalyzed polyubiquitination in vitro. These data may provide an important cue to understand the mechanism how the SCF complex efficiently polyubiquitinates target substrates.

• The Microorganisms and Industry
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• v.19 no.4
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• pp.32-35
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• 1993

ras는 활성화 형태인 GTP bound form과 비활성화 형태인 GDP bound form의 두 형태로 존재하며 두 형태를 매개하는 regulatory protein들에 의해 그 activity가 조절된다. 또한 ras는 GTP와 GDP에 강한 친화성이 있으며 세포내에는 GTP보다 GDP가 더 많이 있어서 평소에는 ras가 GDP와 결합하고 있다가 활성화될때만 GTP와 결합하는 것으로 추정된다. GDP bound ras는 guanine nucloetide exchange protein(GEP)에 의해 활성화된 GTP bound form으로 전환되며 ras의 기능이 발휘된 후에는 GTPase activating protein(GAP)에 의해 비활성화된다. Yeast의 경우 IRA1과 2의 product가 GAP의 역할을 하는 것으로 알려져 있고 CDC25 gene의 product가 GEP의 기능을 담당하는 것으로 알려져 있다. NF1 gene은 Von Recklinghausen Neurofibromatosis Type I 질병을 가진 환자에게서 발견되었는데 부분적으로 sequencing한 결과에 따르면 yeast의 IRA1/2, mammalian GAP gene product와 protein homology가 높은 것으로 나타났다. Yeast의 경우 IRA1/2 gene의 손실이나 mammalian ras gene의 transformation으로 인한 heat shock sensitivity가 NF1 gene(2,3) 혹은 GAP(4)의 expression으로 suppression된 것으로 보아 NF1이 GAP protein으로서 ras를 불활성화 시킨다는 것이 판명되었다. 결론적으로 ras의 활성은 GTP bound 혹은 GDP bound의 양쪽형태를 이동하면서 조절되는데 이 기능은 GAP과 GEP 또는 그의 유사 protein들에 의해 수행되며 이러한 regulatory protein들은 growth factor, cytokine 그리고 protein kinase 같은 signal에 의해 활성화된다고 생각된다. 본 총설에서는 ras protein의 여러가지 성질보다는 ras의 modification과 관련하여 항암제로 사용할 수 있는 ras에 specific한 약품개발의 가능성과 현재 알려진 ras의 inhibitor를 중심으로 논하고자 한다.

• Clinical and Experimental Pediatrics
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• v.51 no.1
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• pp.1-25
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• 2008

Purpose : Since 1967, The Korean Pediatric Society and Korean Government have developed Korean Growth Standards every 10 years. Last version was published in 1998. During past 40 years, Korean Growth Standards were mainly descriptive charts without any systematic nor statistical standardization. With the global epidemic of obesity, many authorities such as World Health Organization (WHO) and United States' Centers for Disease Control (CDC) have been changed their principles of growth charts to cope with the situations like ours. This article summarizes and reviews the whole developmental process of new 2007 Korean Growth Charts with discussion. Methods : With the initiative of Division of Chronic Disease Surveillance in Korea Centers for Disease Control and Prevention, we have performed new national survey for the development of new Standards in 2005 and identified marked increase of childhood obesity and plateau of secular increment of final height in late adolescents. We have developed new Growth Standards via adapting several innovative methods, including standardization of all available raw data, which were acquired in 1997 and 2005 national survey and full application of LMS method. Results : We could get new standardized charts; weight-for-age, length/height-for-age, weight-for-height, head circumference-for-age and BMI-for-age. Other non-standardized charts based on 2005 survey data were also published; waist circumference-for-age, mid-arm circumference-for-age, chest circumference-for-age and skinfold-for-age. Clinical guideline was also developed. Conclusion : Developmental process and results of new Korean Growth Charts are comparable with other internationally well-known Growth Standards, WHO 2006 Growth Standards and CDC Growth Charts. 2007 Korean Growth Charts are relevant especially in Korea and Korean ethnic groups.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1343-1348
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• 2015

Human UHRF1 (ubiquitin-like PHD and RING finger domain-containing 1) has been reported to be over-expressed in many cancers, but its role in ovarian cancer remains elusive. Here, we determined whether knockdown of UHRF1 by lentivirus-mediated shRNA could inhibit ovarian cancer cell growth. Lentivirus-mediated short hairpin RNAs (lv-shRNAs-UHRF1) were designed to trigger the gene silencing RNA interference (RNAi) pathway. The efficiency of lentivirus-mediated shRNA infection into HO-8910 and HO-8910 PM cells was determined using fluorescence microscopy to observe lentivirus-mediated GFP expression and was confirmed to be over 80 percent. UHRF1 expression in infected HO-8910 and HO-8910 PM was evaluated by real-time PCR and Western blot analysis. The Cell Counting Kit-8 (CCK-8) assay was used to measure cell viability; flow cytometry and Hoechst 33342 assay was applied to measure cell cycle arrest and apoptosis. Cell invasion was assessed using transwell chambers. Our results demonstrated that the loss of UHRF1 promoted HO-8910 and HO-8910 PM cell apoptosis, while inhibiting cell proliferation. In addition, UHRF1 knockdown significantly inhibited the invasion of human ovarian cancer cells. In the present study, we also showed that depleting HO-8910 cells of UHRF1 caused activation of the DNA damage response pathway, with the cell cycle arrested in G2/M-phase. The DNA damage response in cells depleted of UHRF1 was illustrated by phosphorylation of CHK (checkpoint kinase) 2 on Thr68, phosphorylation of CDC25 (cell division control 25) on Ser 216 and phosphorylation of CDK1 (cyclin-dependent kinase 1) on Tyr 15.

• Molecular & Cellular Toxicology
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• v.2 no.3
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• pp.159-165
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• 2006

To determine the anticancer effect of D-amygdalin (D-mandelinitrole-${\beta}$-D-gentiobioside) in human chronic myeloid leukemia cells K562, we profiled the gene expression between amygdalin treatment and control groups. Through 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, the cytotoxicity of D-amygdalin was $57.79{\pm}1.83%$ at the concentration of 5 mg/mL for 24 h. We performed cDNA microarray analysis and compared the gene expression profiles between D-amygdalin (5 mg/mL, 24 h) treatment and control groups. Among the genes changed by D-amygdalin, we paid attention to cell cycle-related genes, and particularly cell cycle regulator genes; because arrest of cell cycle processing was ideal tactic in remedy for cancer. In our data, expressions of cyclin-dependent kinase inhibitor 1B (p27, Kip1) (CDKN1B), ataxia telangiectasia mutated (includes complementation groups A, C, and D) (ATM), cyclin-dependent kinase inhibitor 1C (p57, Kip2) (CDKN1C), and CHK1 checkpoint homolog (CHEK1, formally known as CHK1) were increased, while expressions of cyclin-dependent kinase 2 (CDK2), cell division cycle 25A (CDC25A), and cyclin E1 (CCNE1) were decreased. The pattern of these gene expressions were confirmed through RT-PCR. Our results showed that D-amygdalin might control cell cycle regulator genes and arrest S phase of cell cycle in K562 cells as the useful anticancer drug.