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        息賁湯이 抗癌 및 免疫調節作用에 미치는 影響

        尹星默,河智容 대한동의병리학회 1996 동의생리병리학회지 Vol.10 No.2

        세계적으로 암환자의 증가는 물론이거와 사망자수도 증가하고 있는 추세이다. 우리나라의경우도 암이 주된 사망원인으로 보고되어있다. 종양의 발생기전이나 생물학적인 성장은 매우 복잡하고, 암을 치료하는 기전도 매우 복잡하다. 최근의 한의학적 접근이 시도되면서 많은 경우에서 그 효능이 실험적으로 연구되고 있다. 한의학에서의 腫瘍의 治療方法은 舒肝理氣, 降逆止嘔, 活血化瘀, 理氣化結, 健脾燥濕, 化鬱散結, 良陰淸熱, 生津化痰,을 이용하는데, 息賁湯은‘治肺之積, 在右脇下, 大如覆杯, 久不愈, 酒酒寒熱, 氣逆喘咳, 發爲肺癰’의 효과가 있고, 구성약재들도 한의학적인 치료법에 합당하여 암 치료에 응용할 수 있는 처방을 생각된다. 따라서 息賁湯을 이용하여 항암력과 면역능의 증진 및 폐전이 흑색종의 증식억제에 대하여 연구하고자 하였다. 본 연구에서는 식분탕의 폐암 및 복강암에 대한 효과를 알아보기 위하여 암을 유발시킨 웅성 생쥐에 식분탕 엑기스를 투여하여 항암효과 및 면역능을 측정하였다. 측정항목은 시험관내 세포독성능을 위하여 MTT 법을 실시하였으며, Sarcoma-180세포를 ICR생쥐에 이식한 후 복강암 생쥐의 생존기간 및 고형종양의 저지율, IL-2(interleukin-2) 생산능, NK(Natural Killer cell)- Activity을 측정하였고, B16세포를 C57BL/6생쥐에 정맥주사한 후 폐에 전이된 악성 흑색종의 집락수를 측정하였다. 시험관내 세포독성을 MTT법에 의한 측정하였던 바 식분탕의 용량이 10㎍/㎖, 100㎍/㎖의 경우에 대조군에 비하여 유의성있는 효과를 보였다(P〈0.05). 발암 생쥐의 생존기간 연장효과에 있어서 息賁湯투여군에서 대조군에 비하여 증가하는 경향이 있었으나 유의성은 없었다. 종양의 중량을 측정하였던 바 息賁湯투여군에서 대조군에 비하여 감소하는 경향이 있었으나 유의성은 없었다. 폐전이 흑생종의 군집수 측정에서는 息賁湯투여군이 대조군에 비하여 유의성있는 감소를 보였다(P〈0.05). IL-2의 생산능은 식분탕 엑기스 투여군에서는 대조군에 비하여 7일과 14일째에 유의성있는 증가를 보였고(P〈0.05), 21일째는 증가하는 경향만 보였다. NK-Acitivty에서는 작동세포와 표적세포의 비가 50:1일 때 대조군에 비하여 유의성있게 증가하였고(P〈0.05), 나머지의 경우는 증가하는 경향을 보였다. In order to study the effect of Sikbuntang on the in vitro Cell-cytotoxicity, This study had put through MTT Assay, And to investigate the effect of Sikbuntang on the ICR mice which had Abdominal tumor induced by Sarcoma-180 cell line, C57Bl/6 mice which had pulmonary melanoma induced by B16 cell line. After Sarcoma-180 cell line and B16 cell line were transplanted, the extract of Sikbuntang was orally adminstered to the mice to observe th extension of survival time of the mice, inhibition of solid tumor, inhibition of pulmonary melanoma metastasis, productivity of Interleukin-2, NK-Activity. The results were summarized as follows: 1. On the MTT assay, in case of 100μg/ml and 10 μg/ml of Sikbuntang concentration were inhibited cell viability significantly. But 1 μg/ml of Sikbuntang concentration just had tend to inhibit cell viability. 2. In the effect of life extension, Sikbuntang treated group appeared to survive longer than the control group, but which were not significant. 3. In the effect of inhibition solid tumor, Sikbuntang treated group appeared to decrease than the control group, but which were not significant. 4. In the effect of inhibition melanoma pulmonary metastasis, Sikbuntang treated group appeared to inhibit than the control group significantly 5. In the productivity of interleukin-2 on 7 and 14 day, Sikbuntang treated group increased than control group significantly. But on 21 day, Sikbuntang treated group had tend to increase with no significance. 6, In the NK-Activity, the ratio of effector cell and target cell. In case which the ratio was 50:1, Sikbuntang treated group showed increase than control group significantly. But in another cases, they showed increase with no significance.

      • A Study on the Malicious Process Detection System Model based on Security Agent

        Seong-Muk Choi,Yeol-Joo Ryou,Hoo-Ki Lee,Hee-Hoon Cho,Jong-Bae Kim 한국정보통신학회 2015 2016 INTERNATIONAL CONFERENCE Vol.7 No.1

        As recently use of Internet gets increased rapidly, infection path through the network becomes diverse. In particular, attacks by Bot mainly work at C&C (command-andcontrol) server but it can be secured just by blocking IP because C&C server runs in form of IP. However, these attackers too get gradually intelligent as they try to connect periphrastically in order to avoid server blocking. Once these malicious codes infiltrate user’s system, it is not easy to detect it through general detection method while it is running. In this paper, so, we propose malicious process detection system based on security agent in order to prevent damage caused by malicious code infection from being spread.

      • A Study of Effective Defense-In-Depth Strategy of Cyber Security on ICS

        Seong-Muk Choi,Rae-Hyung Kim,Ga-Ye Kim,Hyeon-Kyung Lee,GwangYong Gim,Jong-Bae Kim 보안공학연구지원센터 2016 International Journal of Security and Its Applicat Vol.10 No.5

        The system of SCADA(Supervisory Control and Data Acquisition Security) used in electricity, water, petroleum and gas, transportation as well as manufacturing, is to collect scattered data and to monitor assets related as a centralized suppression system. ICS system, including current SCADA, is not isolated from outside, being connected with IT solution, and can operate equipment through broadband network, instead of accessing physically. Accordingly, the security accident of suppressing system can occur in the fields of antagonistic nations, terrorists, foundational facility invaders, natural disasters and ill-will or accidental actions. The security control examined in this study provides a defense-in-depth strategy which is applicable to the effective cyber security strategy regarding ICS to protect the confidentiality of information, zero defect, availability through the classification of control, operational control and technological control.

      • Malicious Processor Detection based on the Security Agent

        Seong-Muk Choi,Yeol-Joo Ryou,Hoo-Ki Lee,Hee-Hoon Cho,Jong-Bae Kim 보안공학연구지원센터 2015 International Journal of Security and Its Applicat Vol.9 No.11

        Recently, as Internet is widely used due to the increased spread of the internet network, the software with malicious intent is distributed via the internet and its infection path gets various too. In particular, attacks by Bot mainly work at C&C (command-and-control) server but it can be secured just by blocking IP because C&C server runs in form of IP. However, this attacker too gets gradually intelligent as they try to connect periphrastically in order to avoid server blocking. Once these malicious codes infiltrate user’s system, it is not easy to detect it through general detection method while it is running. In this paper, we propose malicious process detection system based on security agent in order to prevent damage caused by malicious code infection from spreading.

      • In vivo near-infrared imaging for the tracking of systemically delivered mesenchymal stem cells: tropism for brain tumors and biodistribution

        Kim, Seong Muk,Jeong, Chang Hyun,Woo, Ji Sun,Ryu, Chung Heon,Lee, Jeong-Hwa,Jeun, Sin-Soo Dove Medical Press 2016 INTERNATIONAL JOURNAL OF NANOMEDICINE Vol.11 No.-

        <P>Mesenchymal stem cell (MSC)-based gene therapy is a promising tool for the treatment of various neurological diseases, including brain tumors. However, the tracking of in vivo stem cell migration, distribution, and survival need to be defined for their clinical application. The systemic routes of stem cell delivery must be determined because direct intracerebral injection as a cure for brain tumors is an invasive method. In this study, we show for the first time that near-infrared (NIR) imaging can reveal the distribution and tumor tropism of intravenously injected MSCs in an intracranial xenograft glioma model. MSCs were labeled with NIR fluorescent nanoparticles, and the effects of the NIR dye on cell proliferation and migratory capacity were evaluated in vitro. We investigated the tumor-targeting properties and tissue distribution of labeled MSCs introduced by intravenous injection and followed by in vivo imaging analysis, histological analysis, and real-time quantitative polymerase chain reaction. We observed no cytotoxicity or change in the overall growth rate and characteristics of labeled MSCs compared with control MSCs. NIR fluorescent imaging showed the organ distribution and targeted tumor tropism of systemically injected human MSCs. A significant number of MSCs accumulated specifically at the tumor site in the mouse brain. These results suggest that NIR-based cell tracking is a potentially useful imaging technique to visualize cell survival, migration, and distribution for the application of MSC-mediated therapies in the treatment of malignant gliomas.</P>

      • SCISCIESCOPUS

        Irradiation Enhances the Tumor Tropism and Therapeutic Potential of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand-Secreting Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Glioma Therapy

        Kim, Seong Muk,Oh, Ji Hyeon,Park, Soon A,Ryu, Chung Heon,Lim, Jung Yeon,Kim, Dal-Soo,Chang, Jong Wook,Oh, Wonil,Jeun, Sin-Soo Wiley (John WileySons) 2010 Stem Cells Vol.28 No.12

        <P>Irradiation is a standard therapy for gliomas and many other cancers. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is one of the most promising candidates for cancer gene therapy. Here, we show that tumor irradiation enhances the tumor tropism of human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) and the therapeutic effect of TRAIL delivered by UCB-MSCs. The sequential treatment with irradiation followed by TRAIL-secreting UCB-MSCs (MSC-TRAIL) synergistically enhanced apoptosis in either TRAIL-sensitive or TRAIL-resistant glioma cells by upregulating the death receptor 5 and by inducing caspase activation. Migration assays showed greater MSC migration toward irradiated glioma cells and the tumor site in glioma-bearing mice compared with unirradiated tumors. Irradiated glioma cells had increased expression of interleukin-8 (IL-8), which leads to the upregulation of the IL-8 receptor on MSCs. This upregulation, which is involved in the migratory capacity of UCB-MSCs, was confirmed by siRNA inhibition and an antibody-neutralizing assay. In vivo survival experiments in orthotopic xenografted mice showed that MSC-based TRAIL gene delivery to irradiated tumors had greater therapeutic efficacy than a single treatment. These results suggest that clinically relevant tumor irradiation increases the therapeutic efficacy of MSC-TRAIL by increasing tropism of MSCs and TRAIL-induced apoptosis, which may be a more useful strategy for cancer gene therapy.</P>

      • Potential application of temozolomide in mesenchymal stem cell-based TRAIL gene therapy against malignant glioma.

        Kim, Seong Muk,Woo, Ji Sun,Jeong, Chang Hyun,Ryu, Chung Heon,Jang, Jae-Deog,Jeun, Sin-Soo The AlphaMed Press 2014 Stem cells translational medicine Vol.3 No.2

        <P>Because the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively kills tumor cells, it is one of the most promising candidates for cancer treatment. TRAIL-secreting human mesenchymal stem cells (MSC-TRAIL) provide targeted and prolonged delivery of TRAIL in glioma therapy. However, acquired resistance to TRAIL of glioma cells is a major problem to be overcome. We showed a potential therapy that used MSC-TRAIL combined with the chemotherapeutic agent temozolomide (TMZ). The antitumor effects of the combination with MSC-TRAIL and TMZ on human glioma cells were determined by using an in vitro coculture system and an in vivo experimental xenografted mouse model. Intracellular signaling events that are responsible for the TMZ-mediated sensitization to TRAIL-induced apoptosis were also evaluated. Treatment of either TRAIL-sensitive or -resistant human glioma cells with TMZ and MSC-TRAIL resulted in a significant enhancement of apoptosis compared with the administration of each agent alone. We demonstrated that TMZ effectively increased the sensitivity to TRAIL-induced apoptosis via extracellular signal-regulated kinase-mediated upregulation of the death receptor 5 and downregulation of antiapoptotic proteins, such as X-linked inhibitor of apoptosis protein and cellular FLICE-inhibitory protein. Subsequently, this combined treatment resulted in a substantial increase in caspase activation. Furthermore, in vivo survival experiments and bioluminescence imaging analyses showed that treatment using MSC-TRAIL combined with TMZ had greater therapeutic efficacy than did single-agent treatments. These results suggest that the combination of clinically relevant TMZ and MSC-TRAIL is a potential therapeutic strategy for improving the treatment of malignant gliomas.</P>

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