Supercritical Fluid Extraction of <i>Citrus iyo</i> Hort. ex Tanaka Pericarp Inhibits Growth and Induces Apoptosis Through Abrogation of STAT3 Regulated Gene Products in Human Prostate Cancer Xenograft Mouse Model

Kim, Chulwon,Lee, Il Ho,Hyun, Ho Bong,Kim, Jong-Chan,Gyawali, Rajendra,Lee, Seok-Geun,Lee, Junhee,Kim, Sung-Hoon,Shim, Bum Sang,Cho, Somi K.,Ahn, Kwang Seok SAGE Publications 2017 Integrative cancer therapies Vol.16 No.2

<P>Activation of signal transducer and activator of transcription 3 (STAT3) is well known to play a major role in the cell growth, survival, proliferation, metastasis, and angiogenesis of various cancer cells. Most of the citrus species offer large quantities of phytochemicals that have beneficial effects attributed to their chemical components. Our study was carried out to evaluate the anticancer effects of the pericarp of Iyokan (<I>Citrus iyo</I> Hort. ex Tanaka), locally known as yeagam in Korea, through modulation of the STAT3 signaling pathway in both tumor cells and a nude mice model. The effect of supercritical extracts of yeagam peel (SEYG) on STAT3 activation, associated protein kinases, STAT3-regulated gene products, cellular proliferation, and apoptosis was examined. The in vivo effect of SEYG on the growth of DU145 human prostate xenograft tumors in athymic <I>nu/nu</I> male mice was also investigated. We found SEYG exerted substantial inhibitory effect on STAT3 activation in human prostate cancer DU145 cells as compared to other tumor cells analyzed. SEYG inhibited proliferation and downregulated the expression of various STAT3-regulated gene products such as bcl-2, bcl-xL, survivin, IAP-1/2, cyclin D1, cyclin E, COX-2, VEGF, and MMP-9. This correlated with an increase in apoptosis as indicated by an increase in the expression of p53 and p21 proteins, the sub-G1 arrest, and caspase-3-induced PARP cleavage. When administered intraperitoneally, SEYG reduced the growth of DU145 human prostate xenograft tumors through downmodulation of STAT3 activation in athymic <I>nu/nu</I> male mice. Overall, these results suggest that SEYG extract has the potential source of STAT3 inhibitors that may have a potential in chemoprevention of human prostate cancer cells.</P>

Does knowledge matter to seniors’ usage of mobile devices? Focusing on motivation and attachment

Kim, Myung Ja,Kim, Woo Gon,Kim, Joung Man,Kim, Chulwon Emerald (MCB UP ) 2016 INTERNATIONAL JOURNAL OF CONTEMPORARY HOSPITALITY Vol.28 No.8

비소세포성폐암의 수술후 MVP복합화학요법과 방사선병용치료 결과

김종훈(Jong Hoon Kim),최은경(Eun Kyung Choi),장혜숙(Hyesook Chang),김상위(Sang Wee Kim),서철원(Chulwon Suh),이규형(Kyoo Hyung Lee),이정신(Jung Shin Lee),김상희(Sang Hee Kim),김우성(Woo Sung Kim),김동순(Dong Soon Kim),김원동(Won Dong 대한방사선종양학회 1995 Radiation Oncology Journal Vol.13 No.2

목적 : 비소세포성폐암은 조기에 진단되어 근치적 수술을 시행하고 필요한 경우 술후 방사선 치료를 시행하는 것이 원칙으로 되어왔으나 약 50%의 환자에서는 원격전이가 치료실패의 원인으로 알려져있다. 이에 임파절전이가 있거나 절세면에서 종양세포의 미세침윤이 의심되는 비소세포성 폐암에서 근치적 수술후 MVP복합항암요법과 방사선치료를 시행하여 치료실패양상, 부작용과 생존기간에 미치는 효과를 알기 위하여 1991년 2월부터 전향적 연구를 시행하였다. 방법 : 수술가능한 비소세포성 폐암환자를 대상으로 근치적 수술 시행후 술후 치료의 적응증이 되는 경우 MVP(Mitomycin C 6mg/m², Vinblastin 6mg/m², Cisplatin 60mg/m²) 복합함암요법을 2회 시행하고 방사선치료를 시행하였다. 1993년 9월까지 등록된 29명의 병기분포는 Ⅱ기 12명, Ⅲa기 15명, Ⅲb기는 2명이었고 ⅢB기 2명은 상이한 폐엽에 각각 종양이 존재하였거나 수술시 소량의 흉막삼출액이 발견된 경우였다. 등록된 29명의 환자중 계획된 치료를 모두 마친 26명의 환자를 대상으로 분석을 시행하였고 최소 추적관찰기간은 12개월이었다. 결과 : 전체 26명중 치료실패는 총 13명(50%)에서 관찰되었고 이중 국소임파절재발은 4명(15.4%), 원격전이는 7명(26.9%), 국소임파절재발과 원격전이가 함께 발견된 환자는 2명(7.7%)이었다. 전체 환자의 1년 생존율은 76.5%, 2년 생존율은 58.6%이고 무병생존율은 각각 59.7%와 46.6%이었다. 치료실패의 예후인자로는 전이된 임파절의 갯수가 많을수록 원격전이율이 높게 나타났으며 국소 재발율은 임파절의 갯수와 절제면 종양침윤여부에 따라 차이가 있음을 관찰하였으나 통계적 유의성에는 도달하지 못하였다. 한편 수술후 항암제 치료까지의 기간이 15일 이하인 경우 16일 이상에 비하여 원격전이율이 낮게 관찰되었고(23.1%와 53.8%), 수술후 방사선치료까지의 기간이 70일 이상인 경우 원격전이율이 높게 관찰되었으나(30.8%와 46.2%) 통계적 유의성에는 도달하지 못하였고 국소재발율에는 차이가 없었다. SWOG기준의 Grade 1 방사선폐렴은 8명(30.8%), Grade 2는 2명(7.7%)의 환자에서 관찰되었으나 Grade 3이상의 합병증은 발견되지 않았다. 결론 : 술후 방사선치료에 MVP복합항암요법을 병행함으로써 국소재발율이 차이는 없었으나 원격전이율이 기존의 문헌보고에 비해 다소 낮아진 것으로 관찰되었으며 복합항암요법과 방사선치료 병행에 따른 부작용도 크지 않았다. 수술후 항암제개시 까지의 기간은 15일이하, 방사선치료까지의 기간은 70일 이하인 경우가 더 효과적인 경향을 나타냈으나 추적관찰기간이 짧고 환자수가 적어 명확한 결론을 도출할 수는 없었으며 복합항암요법이 원격전이를 줄임으로써 큰 합병증없이 치료결과의 향상을 가져올 수 있다는 가능성을 엿볼수 있어 향후 수술후 항암요법에 대한 전향적 임의선택연구가 필요할 것으로 생각된다. Purpose : Since February 1991. a prospective study for non-small cell lung cancer patients who underwent radical resection and had a risk factor of positive resection margin or regional lymph node metastasis has been conducted to evaluate the effect of MVP chemotherapy and radiotherapy on the pattern of failure, disease free and overall survival, and tolerance of combined treatment. Materials and Methods : Twenty nine patients were registered to this study until Sep. 1993: of these 26 received planned therapy. Within 3weeks after radical resection, two cycles of MVP(Mitomycin C 6mg/m², Vinblastin 6mg/m², Cisplatin 60mg/m²) chemotherapy was given with 4 weeks intervals. Radiotherapy (5040cGy tumor bed dose and 900cGy boost to high risk area) was started 3 to 4 weeks after chemotherapy. Results : One and two year overall survival rates were 76.5% and 58.6% respectively. Locoregional failure developed in 6 patients(23.1%) and distant failure in 9 patients (34.6%). Number of involved lymph nodes, resection margin positivity showed some correlation with failure pattern but T-stage and N-stage showed no statistical significance. The group of patients who received chemotherapy within 2 weeks postoperatively and radiotherapy within 70 days showed lower incidence of distant metastasis. Postoperative combined therapy were well tolerated without definite increase of complication rate, and compliance rate in this study was 90%. Comclusion : 1) MVP chemotheapy showed no effect on locoregional recurrencel, but appeared to decrease the distant metastasis rate and 2) combined treatments were well tolerated in all patients. 3) The group of patients who received chemotherapy within 2 weeks postoperatively and radiotherapy with-in 70days showed lower incidence of distant metastasis. 4) Addition of chemotherapy to radiotherapy failed to increase the overall or disease free survival.

Formononetin-induced oxidative stress abrogates the activation of STAT3/5 signaling axis and suppresses the tumor growth in multiple myeloma preclinical model

Kim, Chulwon,Lee, Seok-Geun,Yang, Woong Mo,Arfuso, Frank,Um, Jae-Young,Kumar, Alan Prem,Bian, Jinsong,Sethi, Gautam,Ahn, Kwang Seok Elsevier 2018 Cancer letters Vol.431 No.-

<P><B>Abstract</B></P> <P>Aberrant reactions of signal transducer and transcriptional activator (STAT) are frequently detected in multiple myeloma (MM) cancers and can upregulate the expression of multiple genes related to cell proliferation, survival, metastasis, and angiogenesis. Therefore, agents capable of inhibiting STAT activation can form the basis of novel therapies for MM patients. In the present study, we investigated whether the potential anti-cancer effects of Formononetin (FT), a naturally occurring isoflavone derived from <I>Astragalus membranaceus</I>, <I>Trifolium pratense</I>, <I>Glycyrrhiza glabra</I>, and <I>Pueraria lobata</I>, against MM cell lines and human multiple myeloma xenograft tumors in athymic nu/nu mice model are mediated through the negative regulation of STAT3 and STAT5 pathways. Data from the <I>in vitro</I> studies indicated that FT could significantly inhibit cell viability, and induce apoptosis. Interestingly, FT also suppressed constitutive STAT3 (tyrosine residue 705 and serine residue 727) and STAT5 (tyrosine residue 694/699) activation, which correlated with the suppression of the upstream kinases (JAK1, JAK2, and c-Src) in MM cells, and this effect was found to be mediated <I>via</I> an increased production of reactive oxygen species (ROS) due to GSH/GSSG imbalance. Also, FT abrogated STAT3 and STAT5 DNA binding capacity and nuclear translocation. FT induced cell cycle arrest, downregulated the expression of STAT3-regulated anti-apoptotic, angiogenetic, and proliferative gene products; and this correlated with induction of caspase-3 activation and cleavage of PARP. Intraperitoneal administration of FT significantly suppressed the tumor growth in the multiple myeloma xenograft mouse model without exhibiting any significant adverse effects. Overall, our findings indicate that FT exhibits significant anti-cancer effects in MM that may be primarily mediated through the ROS-regulated inhibition of the STAT3 and STAT5 signaling cascade.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Formononetin (FT) attenuated constitutive STAT3 and STAT5 activation in MM cells <I>via</I> an increased production of reactive oxygen species (ROS) due to GSH/GSSG imbalance. </LI> <LI> FT significantly attenuated the tumor growth in the multiple myeloma xenograft mouse model without exhibiting any significant adverse effects. </LI> <LI> FT treatment also substantially downregulated the expression of STAT3 regulated gene products in tumor tissues obtained from xenograft mouse model. </LI> </UL> </P>

A Creative Leadership: Enhancing Competitiveness of Convention Destination

Chulwon Kim 한국무역전시학회 2009 무역전시연구 Vol.4 No.1

본 연구는 컨벤션 개최지의 경쟁력을 제고하기 위하여 창의적 리더십의 역할 을 심층 분석하고, 경쟁력의 원천을 체계적으로 분석하여 지표 및 모형을 제시 하였고, 또한 경쟁력을 바탕으로 고부가가치를 창출할 수 있는 가치사슬체계를 도출하여 컨벤션 산업의 기반을 조성하는 토대를 도출하였다. 특히, 본 연구는 컨벤션 경쟁력 모형의 개발을 통하여 컨벤션 개최지가 경쟁적 우위를 확보하기 위해서는 4가지의 경쟁력의 원천을 파악하여, 타국가의 컨벤션 개최지와 비교 측정하여 자국의 컨벤션 개최지의 약점과 강점을 도출하는 기반을 개발하였다. 창의적 사고와 실천력만이 도출된 경쟁력의 원천을 수익 창출의 핵심적 역할을 수행하도록 할 것이며, 창의성을 바탕으로 한 컨벤션 정책은 이러한 경쟁력의 원천에 기반을 두어야 한다.

A Study on the Efficiency of Salesforce for B2B Organizations in Foodservice : Implementation of Six Sigma Methodologies 6시그마 분석기법의 적용을 중심으로

Kim, Chulwon 우송대학교 2004 우송대학교 논문집 Vol.9 No.-

본 연구는 외식산업을 대상으로 6시그마에서 사용하는 프로세스 개선의 접근방식과 그 통계적 기법을 활용하여, 단체급식 부문의 수주영업 효율 향상 방안을 제시하고자 하였다. 6시그마 접근방식을 외식산업에 적용하여 특정 프로세스의 효율향상을 도모하는 데에 연구의 의의와 중요성을 두었다. 연구의 범위는 현재 6시그마의 종합적인 시스템 적용이 되고 있음을 전제로 하여, 단체급식 운영상에서 발생하는 특정 문제개선에 국한하여 진행하였다. 연구방법으로는, 프로세스 개선을 위한 6시그마 로드맵 DMAIC(Define, Measure, Analyze, Improve, Control) 방식을 사용하였고, 연구대상은 단체급식 사업의 수주영업 프로세스를 중심으로 조사, 분석하였다. 관련 데이터는 해당 기업의 수주영업 담당관리자와 직원 78명을 대상으로 설문과 인터뷰를 통해 수집하였으며, 내부 전문가 집단을 대상으로 한 Brainstorming, Matrix 분석기법, 그리고 상관분석과 t-test 등을 이용하여 제반 문제점과 해결방안을 도출하였다. 기업과 기업간의 수주영업에 있어서 효율을 저하시키는 요인으로는 내부 운영시스템의 비효율성과 조직 내부구조의 비합리성으로 인한 업무 중복, 조직 내부의 의사소통이 원활하지 못한 점 등이 도출되었고, 이에 대한 세부적인 개선방안으로 내부 커뮤니케이션 활성화와 관련 시스템의 재정립에 관한 방법이 제시되었다.

Exploring Four Dimensional Sources of Destination Competitiveness

Chulwon Kim,Taesuk Lee 한국관광학회 2005 International Journal of Tourism Sciences Vol.5 No.1

This study developed the evaluation model of competitiveness, and suggested "four dimensional sources of competitiveness". The primary sources of competitiveness include the subject, environment, and tourism resources. The secondary sources of competitiveness are comprised of tourism policy, tourism planning, tourism investment, tourism tax and prices, and tourism management. The tertiary sources of competitiveness include tourism infrastructure, tourism reception system, tourism attractiveness, tourism publicity system, and tourism manpower. The fourth sources of competitiveness are comprised of tourism demand, tourism employment, overall tourism performance, and tourism export. These four sources of competitiveness are determinants which dominate competitiveness in the tourism sector. The constantly growing number of travel destinations, and the enhanced quality of existing ones, is putting great pressure on those responsible for a given destination to find better ways to compete in the tourism marketplace and to do so in a sustainable manner. The first step in achieving this goal is to better understand those forces and factors that determine the competitiveness of major tourism destinations.

β-Caryophyllene oxide potentiates TNFα-induced apoptosis and inhibits invasion through down-modulation of NF-κB-regulated gene products.

Kim, Chulwon,Cho, Somi K,Kim, Ki-Dong,Nam, Dongwoo,Chung, Won-Seok,Jang, Hyeung-Jin,Lee, Seok-Geun,Shim, Bum Sang,Sethi, Gautam,Ahn, Kwang Seok Rapid Science Publishers ; Kluwer Academic Publish 2014 Apoptosis Vol.19 No.4

<P>We have recently reported that β-caryophyllene oxide (CPO) can induce apoptosis, suppress tumor growth, and inhibit metastasis through the suppression of signal transducer and activator of transcription 3, PI3K/AKT/mTOR/S6K1 signaling cascades and ROS-mediated MAPKs activation. In the present study, we found that CPO potentiated the apoptosis induced by tumor necrosis factor α (TNFα) and chemotherapeutic agents, suppressed TNFα-induced tumor cell invasion, all of which are known to require NF-κB activation. We found that TNFα stimulated the expression of gene products involved in anti-apoptosis (IAP1, IAP2, Bcl-2, Bcl-xL, and survivin), proliferation (COX-2, cyclin D1, and c-Myc), invasion (MMP 9 and ICAM-1), and angiogenesis (VEGF) and that CPO treatment suppressed their expression. Because these gene products are also regulated by proinflammatory transcription factor NF-κB, we postulated that CPO may mediate its effects by modulating the NF-κB pathway. We found that CPO blocked both inducible and constitutive NF-κB activation in a wide variety of tumor cells. CPO was also found to inhibit the TNFα-induced degradation of IκBα through the inhibition of activation of IκBα kinase and p65 nuclear translocation and phosphorylation. Interestingly, CPO failed to potentiate the apoptotic effect induced by TNFα in p65 (-/-) cells as compared to the wild-type. Thus, overall, our results indicate that the inhibition of NF-κB is one of major mechanisms by which CPO enhances TNFα-induced apoptosis and suppresses invasion.</P>

The Social Organization of Leisure in Human Society. Cheek, N.H. & Burch, W.R. New York, Harper Row Publishers, 1976

Chulwon Kim (서평자) 한국관광학회 2006 International Journal of Tourism Sciences Vol.6 No.1

Understanding Cross-cultural Differences in Leisure Motivation : Testing Structural Equation Modeling

Chulwon Kim 한국관광학회 2006 International Journal of Tourism Sciences Vol.6 No.1

The study is to examine a fundamental dimension of cultural identity. Specifically, the paper conceptualized an exploratory theoretical model concerning how a set of observed and latent constructs might explain the relationships between American and Korean students in terms of cultural dimension and leisure motivation. In addition, this paper applied the LISREL method of structural modeling to estimate and test the validity of the conceptualized model. It seems that structural equation modeling can make a significant contribution to research questions. However, since this model has been problematic in terms of theoretical ground, this study did not find a satisfactory result. As researchers suggest, structural models are optimally used when they are guided by strong substantive theory and when psychometrically sound data and collection procedures are utilized to test the theory. In addition, methodologically, this study should have set up at least two latent exogenous variables and this study should have done a confirmatory factor analysis to verify an exploratory factor analysis.