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Kang, Seokmin,Lee, Jung Moo,Jeon, Borami,Elkamhawy, Ahmed,Paik, Sora,Hong, Jinpyo,Oh, Soo-Jin,Paek, Sun Ha,Lee, C. Justin,Hassan, Ahmed H.E.,Kang, Sang Soo,Roh, Eun Joo Elsevier 2018 European journal of medicinal chemistry Vol.151 No.-
<P><B>Abstract</B></P> <P>Repositioning of the antipsychotic drug trifluoperazine for treatment of glioblastoma, an aggressive brain tumor, has been previously suggested. However, trifluoperazine did not increase the survival time in mice models of glioblastoma. In attempt to identify an effective trifluoperazine analog, fourteen compounds have been synthesized and biologically <I>in vitro</I> and <I>in vivo</I> assessed. Using MTT assay, compounds <B>3dc</B> and <B>3dd</B> elicited 4–5 times more potent inhibitory activity than trifluoperazine with IC<SUB>50</SUB> = 2.3 and 2.2 μM against U87MG glioblastoma cells, as well as, IC<SUB>50</SUB> = 2.2 and 2.1 μM against GBL28 human glioblastoma patient derived primary cells, respectively. Furthermore, they have shown a reasonable selectivity for glioblastoma cells over NSC normal neural cell. <I>In vivo</I> evaluation of analog <B>3dc</B> confirmed its advantageous effect on reduction of tumor size and increasing the survival time in brain xenograft mouse model of glioblastoma. Molecular modeling simulation provided a reasonable explanation for the observed variation in the capability of the synthesized analogs to increase the intracellular Ca<SUP>2+</SUP> levels. In summary, this study presents compound <B>3dc</B> as a proposed new tool for the adjuvant chemotherapy of glioblastoma.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Fourteen TFP derivatives were synthesized and biologically assessed. </LI> <LI> <B>3dc</B> and <B>3dd</B> elicited promising inhibitory activities against U87MG and GBL28 cells. </LI> <LI> <B>3dc</B> was assessed in brain xenograft mouse model of glioblastoma. </LI> <LI> Molecular modeling provided explanation for observed activity variations. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Kang, Seokmin,Hong, Jinpyo,Lee, Jung Moo,Moon, Hyo Eun,Jeon, Borami,Choi, Jungil,Yoon, Nal Ae,Paek, Sun Ha,Roh, Eun Joo,Lee, C. Justin,Kang, Sang Soo American Association for Cancer Research 2017 Molecular cancer therapeutics Vol.16 No.1
<P>Calcium (Ca2+) signaling is an important signaling process, implicated in cancer cell proliferation and motility of the deadly glioblastomas that aggressively invade neighboring brain tissue. We have previously demonstrated that caffeine blocks glioblastoma invasion and extends survival by inhibiting Ca2+ release channel inositol 1,4,5-trisphosphate receptor (IP3R) subtype 3. Trifluoperazine (TFP) is an FDA-approved antipsychotic drug for schizophrenia. Interestingly, TFP has been recently reported to show a strong anticancer effect on lung cancer, hepatocellular carcinoma, and T-cell lymphoma. However, the possible anticancer effect of TFP on glioblastoma has not been tested. Here, we report that TFP potently suppresses proliferation, motility, and invasion of glioblas-toma cells in vitro, and tumor growth in in vivo xenograft mouse model. Unlike caffeine, TFP triggers massive and irreversible release of Ca2+ from intracellular stores by IP3R subtype 1 and 2 by directly interacting at the TFP-binding site of a Ca2+-binding protein, calmodulin subtype 2 (CaM2). TFP binding to CaM2 causes a dissociation of CaM2 from IP3R and subsequent opening of IP3R. Compared with the control neural stem cells, various glioblastoma cell lines showed enhanced expression of CaM2 and thus enhanced sensitivity to TFP. On the basis of these findings, we propose TFP as a potential therapeutic drug for glioblastoma by aberrantly and irreversibly increasing Ca2+ in glioblastoma cells. (C) 2016 AACR.</P>
Seokmin Kang 한국국제경영관리학회 2010 국제경영리뷰 Vol.14 No.1
최근에 해외직접투자를 유치하는데 진출대상이 되는 각국의 지배기관의 질(quality)적 중요성은 증대되고 있다. 지배기관이 해외직접투자에 미치는 영향을 조사한 이전의 연구들은 동일한 결론을 도출하지 못하고 있으나, 여전히 진출대상이 되는 각국의 지배기관의 질은 해외직접투자를 유치함에 있어서 중요한 역할을 한다. 이 연구는 진출대상이 되는 각국의 지배기관의 질이 미국 다국적기업 특히 제조업 분야의 직접투자를 유치하는데 미치는 영향을 조사한다. 이 연구에서 1999년부터 2007년 기간 동안 미국 제조분야의 직접투자를 유치한 50개국을 대상으로 한 2차 자료는 이용되었다. 이 연구에서는 누락된 자료의 문제를 해결하기 위해서 해외직접투자의 자료는 3년 평균(당해 연도와 이전 2개 년도의 평균)으로 계산된다. 연구결과는 경제적․지역적 요인들을 고려하면서, 진출대상이 되는 각국의 지배기관의 질은 미국 제조산업 분야의 직접투자를 유치하는데 있어서 정(+)의 영향을 미치고 있음을 보여준다. In recent, importance of quality of governance institutions of the host country has been increased in attracting FDI. Previous studies evaluating the impact of governance institutions on FDI have been inconclusive, yet quality of governance institution still plays in attracting FDI. This study examines the effect of quality of governance institutions of the host country on U.S. manufacturing foreign direct investment(FDI). Secondary data for the 50 host countries of U.S. manufacturing FDI over the period 1999-2007 were used in this study. In this study, FDI data are computed within a three- years moving average framework(the average of the present year and the two preceding years) to solve the missing data problem. Research findings show that quality of governance institutions has the positive effect on U.S. manufacturing FDI, when controlling for economic and demographic factors
글로벌 강소기업 육성을 위한 지역 중소기업의 지원방안에 관한 연구
강석민(Kang, SeokMin) 계명대학교 국제학연구소 2018 국제학논총 Vol.28 No.-
Using 74 small and medium sized firms located in Taegu region, this study found that there is the positive effect of product innovation on firm performance and that there is the mediating effect of knowledge management system between product innovation and firm performance. In order for the regional small and medium sized firms to be the global hidden champion, the government should support the small and medium sized firms that make product innovation, and the government should support the knowledge management system of the firms.
협력 네트워크에 관한 내부 및 외부 선행요인과 기업성과에 미치는 협력 네트워크의 영향
강석민(Kang, Seokmin) 조선대학교 지식경영연구원 2016 기업과 혁신연구 Vol.9 No.1
협력 네트워크는 빠르게 변화되는 사업 환경하에서 기업에게 요구되는 필수조건으로 인식되고 있는 실정이다. 특히, 기술 협력을 통한 네트워크의 구축을 통하여 기업은 생존과 발전을 도모할 수 있으며, 성장을 향한 밑거름이 될 수도 있다. 이러한 이유로 본 연구는 먼저 기업의 협력 네트워크를 구축하는 선행요인을 규명하고, 협력 네트워크가 기업성과에 미치는 영향을 실증분석하였다. 협력 네트워크의 선행요인으로 기업 내부적 요인(기술능력, 기업문화)과 외부적 요인(환경적 변화, 산업환경)으로 나누어 협력 네트워크에 미치는 영향을 분석하였다. 실증분석 결과는 기업 내부적 요인과 산업환경은 기업의 협력 네트워크를 형성하는 요인으로 작용하고 있는 것으로 나타났으나, 환경적 변화는 어떠한 유의적인 영향이 발견되지 않았다. 다음으로 기업성과에 대한 기업의 협력 네트워크의 영향을 분석한 결과에서는 기업의 협력 네트워크가 국내영업 및 판로구축과 해외시장개척으로 대변되는 기업성과에 유의적으로 긍정적인 영향을 미치고 있는 것으로 나타났다. 이러한 결과로부터, 협력 네트워크를 형성하기 위해서는 기업 내부의 영향과 산업환경이 중요한 영향을 제공하고 있으며, 기업의 성장과 발전을 도모하기 위해서는 협력 네트워크가 필요하다는 사실을 제시하고 있다. Under rapidly changing business environment, collaboration network is known as a necessary factor. In particular, firms can be survived and developed by technological collaboration network, and it can be an engine for growing. In this reason, this study investigates the determinants for promoting collaboration network and empirically examines the effect of collaboration network on firm performance. In investigating the determinants of collaboration network, internal factors(technology capability and firm culture) and external factors(environment change and industrial infra) are used. Internal factors and industrial infra are reported to be positively significant for increasing collaboration network, but significance of environment change are not found. In empirical result for the effect of collaboration network on firm performance, collaboration network are reported to be positively significant for domestic sales & market building and foreign market entry. These results suggest that internal factors and industrial infra are factors to increase collaboration network and that in order for firms to be survived and developed collaboration network of technology is important