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Anti-tumor Effects of Penfluridol through Dysregulation of Cholesterol Homeostasis

  • Wu, Lu;Liu, Yan-Yang;Li, Zhi-Xi;Zhao, Qian;Wang, Xia;Yu, Yang;Wang, Yu-Yi;Wang, Yi-Qin;Luo, Feng
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.1
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    • pp.489-494
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    • 2014
  • Background: Psychiatric patients appear to be at lower risk of cancer. Some antipsychotic drugs might have inhibitory effects on tumor growth, including penfluridol, a strong agent. To test this, we conducted a study to determine whether penfluridol exerts cytotoxic effects on tumor cells and, if so, to explore its anti-tumor mechanisms. Methods: Growth inhibition of mouse cancer cell lines by penfluridol was determined using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Cytotoxic activity was determined by clonogenic cell survival and trypan blue assays. Animal tumor models of these cancer cells were established and to evaluate penfluridol for its anti-tumor efficacy in vivo. Unesterified cholesterol in cancer cells was examined by filipin staining. Serum total cholesterol and tumor total cholesterol were detected using the cholesterol oxidase/p-aminophenazone (CHOD-PAP) method. Results: Penfluridol inhibited the proliferation of B16 melanoma (B16/F10), LL/2 lung carcinoma (LL/2), CT26 colon carcinoma (CT26) and 4T1 breast cancer (4T1) cells in vitro. In vivo penfluridol was particularly effective at inhibiting LL/2 lung tumor growth, and obviously prolonged the survival time of mice bearing LL/2 lung tumors implanted subcutaneously. Accumulated unesterified cholesterol was found in all of the cancer cells treated with penfluridol, and this effect was most evident in LL/2, 4T1 and CT26 cells. No significant difference in serum cholesterol levels was found between the normal saline-treated mice and the penfluridol-treated mice. However, a dose-dependent decrease of total cholesterol in tumor tissues was observed in penfluridol-treated mice, which was most evident in B16/F10-, LL/2-, and 4T1-tumor-bearing mice. Conclusion: Our results suggested that penfluridol is not only cytotoxic to cancer cells in vitro but can also inhibit tumor growth in vivo. Dysregulation of cholesterol homeostasis by penfluridol may be involved in its anti-tumor mechanisms.

PKA-Mediated Regulation of B/K Gene Transcription in PC12 Cells

  • Choi, Mi-Hyun;Kim, Ho-Shik;Choi, Sung-Ho;Kim, Mi-Young;Jang, Yoon-Seong;Jang, Young-Min;Lee, Jeong-Hwa;Jeong, Seong-Whan;Kim, In-Kyung;Kwon, Oh-Joo
    • The Korean Journal of Physiology and Pharmacology
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    • v.9 no.6
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    • pp.333-339
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    • 2005
  • B/K protein is a novel protein containing double C2-like domains. We examined the specific signaling pathway that regulates the transcription of B/K in PC12 cells. When the cells were treated with forskolin ($50{\mu}M$), B/K mRNA and protein levels were time-dependently decreased, reaching the lowest level at 3 or 4 hr, and thereafter returning to the control level. Chemicals such as dibutyryl-cAMP, cellpermeable cyclic AMP (cAMP) analogue and CGS21680, adenosine receptor $A_{2A}$ agonist, also repressed the B/K transcription. However, 1,9-dideoxyforskolin did not show inhibitory effect on B/K transcription, suggesting direct involvement of cAMP in the forskolin-induced inhibition of B/K transcription. Effect of forskolin, dibutyryl cAMP and CGS21680 was significantly reduced in PKA-deficient PC12 cell line (PC12-123.7). One cAMP-response element (CRE)-like sequence (B/K CLS) was found in the promoter region of B/K DNA, and electrophoretic mobility shift assay indicated its binding to CREM and CREB. Forskolin significantly suppressed the promoter activity in CHO-K1 cells transfected with the constructs containing B/K CLS, but not with the construct in which B/K CLS was mutated (AC:TG). Taken together, we suggest that the transcription of B/K gene in PC12 cells may be regulated by PKA-dependent mechanism.

Estimating the Determinants of Households' Monthly Average Income : A Panel Data Model Approach (패널 데이터모형을 적용한 가구당 월평균 가계소득 결정요인 추정에 관한 연구)

  • Yi, Hyun-Joo;Cheul, Hee-Cheul
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.11 no.6
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    • pp.2038-2045
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    • 2010
  • Households' monthly average income is composed of various factors. This study paper studies focuses on estimating the determinants of a households' monthly average income. The region for analysis consist of three groups, that is, the whole country, a metropolitan city(such as Busan, Daegu, Incheon, Gwangiu, Daejeon, Ulsan.) and Seoul. Analyzing period be formed over a 57 time points(2005. 01~2009. 09). In this paper the dependent variable setting up the households' monthly average income, explanatory (independent) variables are composed of the consumer price index, employment to population ratio, Index of housing sale price, the preceding composite index, loans of housing mortgage, spending rate for care medical expense and the composite stock price index. In looking at the factors which determine the monthly average income, evidence was produced supporting the hypothesis that there is a significant positive relationship between the composite index and housing loans. The study also produced evidence supporting the view that there is a significant negative relationship between employment ratios, the house sale pricing index and spending rates for care or medical needs. The study found that the consumer price index and composite stock price index were not significant variables. The implications of these findings are discussed for further research.

Combined Skin Moisturization of Liposomal Serine Incorporated in Hydrogels Prepared with Carbopol ETD 2020, Rhesperse RM 100 and Hyaluronic Acid

  • Kim, Hyeongmin;Ro, Jieun;Barua, Sonia;Hwang, Deuk Sun;Na, Seon-Jeong;Lee, Ho Sung;Jeong, Ji Hoon;Woo, Seulki;Kim, Hyewon;Hong, Bomi;Yun, Gyiae;Kim, Joong-Hark;Yoon, Young-Ho;Park, Myung-Gyu;Kim, Jia;Sohn, Uy Dong;Lee, Jaehwi
    • The Korean Journal of Physiology and Pharmacology
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    • v.19 no.6
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    • pp.543-547
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    • 2015
  • We investigated the combined moisturizing effect of liposomal serine and a cosmeceutical base selected in this study. Serine is a major amino acid consisting of natural moisturizing factors and keratin, and the hydroxyl group of serine can actively interact with water molecules. Therefore, we hypothesized that serine efficiently delivered to the stratum corneum (SC) of the skin would enhance the moisturizing capability of the skin. We prepared four different cosmeceutical bases (hydrogel, oil-in-water (O/W) essence, O/W cream, and water-in-oil (W/O) cream); their moisturizing abilities were then assessed using a $Corneometer^{(R)}$. The hydrogel was selected as the optimum base for skin moisturization based on the area under the moisture content change-time curves (AUMCC) values used as a parameter for the water hold capacity of the skin. Liposomal serine prepared by a reverse-phase evaporation method was then incorporated in the hydrogel. The liposomal serine-incorporated hydrogel (serine level=1%) showed an approximately 1.62~1.77 times greater moisturizing effect on the skin than those of hydrogel, hydrogel with serine (1%), and hydrogel with blank liposome. However, the AUMCC values were not dependent on the level of serine in liposomal serine-loaded hydrogels. Together, the delivery of serine to the SC of the skin is a promising strategy for moisturizing the skin. This study is expected to be an important step in developing highly effective moisturizing cosmeceutical products.

The Effect of Tissue Plasminogen Activator on TGF-${\beta}1$ Pre-Treated Human Mesothelial Cell Line (TGF-${\beta}1$으로 자극한 사람중피세포주에서 조직플라스미노겐 활성제가 미치는 영향)

  • Lee, Jung-Lim;Jeon, Soo-Jin;Yoo, Young-Choon;Kim, Ji-Hye;Lee, Yu-Mi;Kwon, Sun-Jung;Son, Ji-Woong;Choi, Eu-Gene;Na, Moon-Jun
    • Tuberculosis and Respiratory Diseases
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    • v.70 no.5
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    • pp.405-415
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    • 2011
  • Background: In an effort to find alternative therapeutic agents to prevent excessive fibrosis as a sequela to complicated parapneumonic effusion or empyema, we examined the effect of tissue plasminogen activator (tPA) as a fibrinolytic agent combined with talc or transforming growth factor (TGF)-${\beta}1$ in a human pleural mesothelial cell line, MeT-5A. Methods: MeT-5A cells were stimulated with various doses of talc, doxycycline or TGF-${\beta}1$ for 24 h and then were treated with tPA for an additional 24 h. Cell viability was measured by MTT assay. The production of interleukin (IL)-8 and vascular endothelial growth factor (VEGF) in the culture supernatants was measured by ELISA. Real-time PCR was carried out for measurement of type I collagen mRNA. Results: MeT-5A cells treated with talc showed a dose-dependent increase in production of IL-8. Talc also increased production of type I collagen mRNA at low doses, but talc did not influence the induction of VEGF. Addition of tPA to talc-stimulated cells showed further increases in the production of IL-8, but tPA did not influence the production of VEGF or type I collagen mRNA. TGF-${\beta}1$ increased the production of both VEGF and collagen type I mRNA, both of which were effectively inhibited by additional tPA treatment in MeT-5A cells. Conclusion: TGF-${\beta}1$ is a potent inducer of collagen synthesis without induction of IL-8 in MeT-5A cells. Addition of tPA after TGF-${\beta}1$ stimulation inhibited further fibrosis by direct inhibition of collagen mRNA synthesis as well as by inhibition of VEGF production.

The Effect of CEO Characteristics and Knowledge Management on Business Performance - Focusing on Small Manufacturing Business - (소공인 CEO의 개인적 자질과 지식경영 실천이 경영성과에 미치는 영향)

  • Lee, Ru-Ri;Lee, So-Young
    • Journal of Venture Innovation
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    • v.3 no.1
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    • pp.143-163
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    • 2020
  • When we assume the transition to a knowledge management society, what factors should be differentially added to the characteristics of CEOs of small enterprises to enhance management performance? This can be done by measuring the core competence of the CEO who is an importance asset of the small firms. This study focuses on the following four inquiries to clarify the relationship among the core competence of the CEO, the knowledge management and the performance of the firms. First, we test the influence of the core competence of CEO on business performance. Second, we explore the effects of CEO characteristics on the knowledge management and the performance of the firm. Third, we test whether knowledge management has a mediating effect in the relationship between the characteristics of CEO which is a parameter, and the business performance of the firm which is a dependent variable. Fourth, for the sake of a deeper understanding of the CEO of the small firms, we conduct t-test or multiple comparison to find out the statistically significant differences among means of the main variables such as demographic characteristics, work experience, and entrepreneurship. The academic contribution of this study is to verify the characteristics of the CEO, which influence the business performance:the global competence, challenge spirit, interpersonal flexibility and stress tolerance, in connection with the knowledge management of small firms. The practical contribution of this study is to test whether CEOs can demonstrate successful business performance through knowledge management rather than measuring business performance after a certain period of time through profit and loss statements in this era of uncertainty.

Pronephros Induction by Combined-dose of Activin A and IGF-1, and High-dose Effect of IGF-1 in Xenopus Animal Cap Assay (Xenopus 동물극의 분리배양에서 Activin A와 IGF-1의 복합처리에 의한 전신의 분화와 IGF-I 고농도의 효과)

  • 정선우;진정효;윤춘식
    • Journal of Life Science
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    • v.8 no.5
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    • pp.479-485
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    • 1998
  • The induction of nephric duct from Xenopus presumptive ectoderm(animal cap) was studied and the high-dose ef-fect of IGF-1 was investigated. Activin A induce various organs from cultured animal cap explants and the effects are time and dose-dependent. On the induction of nephric duct, the combined-dose of activin A and retinoic acid was very efficient method in reference study. In present study, we used IGF-1 as well as activin A as a combined growth factor. The concentration ranges of growth factors were activin A l00ng/ml an IGF-1 0-500ng/m1. Explants were cultured in combined solution for 3days to the normal embryo arrives at st. 43. In general, when the explant was cultured in high concentration(l00ng/ml) of activin A, it was destroyed, however, nephric duct and other tis-sues were differentiated by adding IGF-1. In addition, eye induction by adding IGF-1 500ng/ml to activin A 1- 100 ng/ml solution was studied. The low concentration of activin A(1ng/ml) have blood-like cell inducing effect and the explant was balloon-shaped, however, the high dose combination with IGF-1 extended the range of eye inductive concentration of activin A.

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NDRG2-mediated Modulation of SOCS3 and STAT3 Activity Inhibits IL-10 Production

  • Lee, Eun-Byul;Kim, Ae-Yung;Kang, Kyeong-Ah;Kim, Hye-Ree;Lim, Jong-Seok
    • IMMUNE NETWORK
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    • v.10 no.6
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    • pp.219-229
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    • 2010
  • Background: N-myc downstream regulated gene 2 (NDRG2) is a member of the NDRG gene family. Our previous report indicated a possible role for NDRG2 in regulating the cytokine, interleukin-10 (IL-10), which is an important immunosuppressive cytokine. Several pathways, including p38-MAPK, NF-${\kappa}B$, and JAK/STAT, are used for IL-10 production, and the JAK/STAT pathway can be inhibited in a negative feedback loop by the inducible protein, SOCS3. In the present study, we investigated the effect of NDRG2 gene expression on IL-10 signaling pathway that is modulated via SOCS3 and STAT3. Methods: We generated NDRG2-overexpressing U937 cell line (U937-NDRG2) and treated the cells with PMA to investigate the role of NDRG2 in IL-10 production. U937 cells were also transfected with SOCS3- or NDRG2-specific siRNAs to examine whether the knockdown of SOCS3 or NDRG2 influenced IL-10 expression. Lastly, STAT3 and SOCS3 induction was measured to identify the signaling pathway that was associated with IL-10 production. Results: RT-PCR and ELISA assays showed that IL-10 was increased in U937-mock cells upon stimulation with PMA, but IL-10 was inhibited by overexpression NDRG2. After PMA treatment, STAT3 phosphorylation was decreased in a time-dependent manner in U937-mock cells, whereas it was maintained in U937-NDRG2 cells. SOCS3 was markedly reduced in U937-NDRG2 cells compared with U937-mock cells. IL-10 production after PMA stimulation was reduced in U937 cells when SOCS3 was inhibited, but this effect was less severe when NDRG2 was inhibited. Conclusion: NDRG2 expression modulates SOCS3 and STAT3 activity, eventually leading to the inhibition of IL-10 production.

The Anticancer Effects and Drug Metabolic Enzyme Change by Intraperitoneal Injection of Agrimonia Pilosa Ledeb (선학초 (짚신나물) 복강주사의 항암효과 탐색 및 약물 대사효소의 변화)

  • Choi, Jung-Won;Jang, Bo-Hyung;Lee, Ju-Ah;Ko, Ho-Yeon;Jung, Hee;Jun, Chan-Yong;Park, Jong-Hyung;Kim, Ji-Hye;Ko, Seong-Gyu;Choi, You-Kyung
    • The Journal of Korean Medicine
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    • v.30 no.4
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    • pp.129-141
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    • 2009
  • Objective: This study was to investigate the anti-tumor effect, safety, safety, mechanism and metabolizing enzyme of Agrimonia pilosa LEDEB (APL) in female C57B/L mouse tumor (in vivo). Method: First, to evaluate the antitumor activity of APL, we divided the mice into four groups: normal, control, APL50 (50mg/kg), and APL100 (100mg/kg). LLC-obtained American Type Culture Collection was used. LLC had been inoculated to induce tumors. To measure the anti-tumor effect of APL, we calibrated tumor size and weight. To analyze the mechanism of anti-tumor in APL, we used western blotting and to observe metabolizing enzyme in APL we used to real-time PCR. Result: APL50 and APL100 significantly inhibited tumor growth from 12 days after medicine injected. APL did not induce caspase-dependent apoptosis in LLC-bearing mouse tumor. In APL100, it decreased 41% and 71% in CYP2D22 and CYP3A11, respectively. Conclusion: These results suggest that APL has some anti-tumor effects in female C57B/L mouse tumor. APL should be used carefully with other drugs related with CYP2D22 and CYP3A11.

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The Effect of Business Relationships on Conflict and Satisfaction in the Cosmetics Industry's Distribution Channel (코스메틱 산업에서의 유통경로상 거래관계가 갈등과 관계만족에 미치는 영향)

  • Park, Soo-Hong;Yang, Hoe-Chang;Sun, Il-Suck
    • Journal of Distribution Science
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    • v.13 no.6
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    • pp.79-86
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    • 2015
  • Purpose - The cosmetics industry is a traditional high value-added industry in terms of the domestic demand, small batch production systems, exclusive competition, and raw materials highly dependent on overseas countries as well as an oligopolistic market structure. However, new foreign brands and growing consumer awareness of inexpensive products, has triggered a shift. In line with changing lifestyles and the polarization of consumption, the industry faces a new market structure. Among its key characteristics is the cosmetics industry's numerous distribution channels (i.e., department stores, door-to-door sales, online shopping malls, brand shops, and discount stores). Therefore, the study of its distribution channels is essential. Research design, data, and methodology - The study analyzed channel distribution power divided into coercive and non-coercive power. The factors of coercive power included: unilateral request of an increase in commissions, interference in sales by taking advantage of a superior status, unilateral buck-passing at the time of a problem, unilateral request to stop sales activities, and a unilateral business contract; the factors of non-coercive power included favorable payment conditions, offers of various kinds of information, policy on commission reduction, pride in market entrance, and promotion support. In addition, the mediating variable "interdependence" was applied to the execution of department store (or mart) power and their shop conflicts and satisfaction to examine direct and indirect influential power. The methodology was a survey of managers of cosmetics shops in department stores (or marts). The questionnaire, based on a five-point Likert scale, included questions about basic personal information, execution of power, interdependence, conflict, and satisfaction. The study distributed 198 questionnaires and collected 131. Ten questionnaires with missing or hard to analyze data were excluded. Thus, 121 copies were analyzed. Results - According to the analysis, the execution of coercive power by department stores (or marts) did not affect interdependence, but the execution of non-coercive power did. Interdependence did not influence conflict, but did affect satisfaction. Additionally, the analysis revealed direct influential power: the execution of coercive power positively affected conflict and negatively influenced satisfaction; the execution of non-coercive power positively affected satisfaction. Conclusions - To offer suggestions for distribution business relations in the cosmetics industry, this study investigated how the execution of power by department stores (or marts) affected their shops. More specifically, it examined how much the execution of both coercive power and non-coercive power influenced conflict and satisfaction, and analyzed the mediating role of interdependence. In line with previous study results in various areas, coercive power was shown to be the source of conflict, leading to a decrease in satisfaction, whereas non-coercive power significantly positively influenced satisfaction. Moreover, non-coercive power increased interdependence, which led to greater satisfaction. As a result, interdependence had a mediating effect on non-coercive power and satisfaction. Based on the results, department stores (or marts) should look for improvements plans that increase interdependence. Such plans could alleviate conflict with the shops, increasing their satisfaction.