• Title/Summary/Keyword: survival model

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Studies on the antimetastasis & antiangiogenesis effects of Gamisoamsan (가미소암산(加味消癌散)의 혈관신생(血管新生) 억제에 관한 항암효과 연구)

  • Yoon Sung-Chan;Ahn Seong-Hun;Kim Jin-Kyeoung;Mun Yeon-Ja;Chu Yeong-Guk;Jeong Gyu-Yong;Whoo Won-Hong
    • Herbal Formula Science
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    • v.10 no.2
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    • pp.113-126
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    • 2002
  • Soamsan is known as an anti-cancer remedy in the traditional Korean Medicine. To enhance the synergic effects of anti-cancer activity of Soamsan, this study reconstituted the original components of Soamsan with a slight modification and produced a novel herbal remedy, namely Gamisoamsan. Extracts of Gamisoamsan inhibited the growth of cultured CT-26 cells, mouse colon adenocarcinoma, in a dose-dependent manner $(1\;to\;50{\mu}g/ml)$, and $ID_{50}$ was estimated approximately $16.7{\mu}g/ml$. Using tumor-bearing mouse model, in which was produced by subcutaneous injection of CT-26 cells ($1{\times}10^5$cells). the effects of Gamisoamsan on tumor growth and host survival were examined by evaluating tumor volume and increase in life span. When Gamisoamsan extracts in variable doses of 100, 200 and 500mg/kg body weight per day were orally administered to tumor-bearing mice, following results were obtained: Improvement in the hematological parameters following Gamisoamsan treatment such as hemoglobin contents, red blood cells and white blood cells of the tumor-bearing mice have been observed. Gamisoamsan treatment also showed a prolongation of life span and a reduction of tumor volume in the CT-26 tumor hosts. The results of the present study suggest that Gamisoamsan extracts has a potential anti-tumor activity and may be an useful remedy to prevent and/or treat cancer.

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A Study on the Establishment of Basic Design Concept for Semi-Submersibles (해저자원(海底資源) 개발용(開發用) Semi-Submersible 설계기준(設計基準)의 정립(定立)을 위한 연구(硏究))

  • J.E.,Park;Z.G.,Kim;J.H.,Hwang;S.J.,Yim;H.S.,Choi
    • Bulletin of the Society of Naval Architects of Korea
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    • v.20 no.2
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    • pp.1-20
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    • 1983
  • In this paper design criteria for semi-submersibles, effective at the stage of basic design, are reviewed first generally. Thereafter an extensive study is focussed on essential problematic areas such as design load, heaving motion, overall structural analysis and welding technique. The necessity for this kind of research is apparent in the light of the fact that ocean exploration and exploitation becomes extended to deeper ocean and that semi-submersibles are the most favorite unit for operation under this environment. In some sense principles in naval architecture are indeed applicable to the design of semi-submersible. However, because of the difference in geometry between ships and semi-submersibles, there are significant deviations in design method. A thorough discussion is made on particular behaviours of a semi-submersible in stability, wave load, motion characteristics and structural responses. Then some calculation-procedures and design guidelines are tentatively proposed. A numerical calculation for a semi-submersible Sedco 708 is exemplified for better understanding of the concept. The structure has 4 main and another 4 secondary stabilizing columns with catamaran-type lower hull. In this example design condition is supposed to be 28m wave height, 90 knots wind speed for survival condition and seastate 6 for operational condition in water of 100m depth. The numerical result implies that the actual design of this model can be assessed close to optimum. Further intensive research is strongly required in the subject fields of dynamic stability, rational evaluation of wave load statistical basis for fatigue life judgement.

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Study of Computer Aided Diagnosis for the Improvement of Survival Rate of Lung Cancer based on Adaboost Learning (폐암 생존율 향상을 위한 아다부스트 학습 기반의 컴퓨터보조 진단방법에 관한 연구)

  • Won, Chulho
    • Journal of rehabilitation welfare engineering & assistive technology
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    • v.10 no.1
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    • pp.87-92
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    • 2016
  • In this paper, we improved classification performance of benign and malignant lung nodules by including the parenchyma features. For small pulmonary nodules (4-10mm) nodules, there are a limited number of CT data voxels within the solid tumor, making them difficult to process through traditional CAD(computer aided diagnosis) tools. Increasing feature extraction to include the surrounding parenchyma will increase the CT voxel set for analysis in these very small pulmonary nodule cases and likely improve diagnostic performance while keeping the CAD tool flexible to scanner model and parameters. In AdaBoost learning using naive Bayes and SVM weak classifier, a number of significant features were selected from 304 features. The results from the COPDGene test yielded an accuracy, sensitivity and specificity of 100%. Therefore proposed method can be used for the computer aided diagnosis effectively.

Korean Red Ginseng water extract arrests growth of xenografted lymphoma cells

  • Park, Jae Gwang;Son, Young-Jin;Aravinthan, Adithan;Kim, Jong-Hoon;Cho, Jae Youl
    • Journal of Ginseng Research
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    • v.40 no.4
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    • pp.431-436
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    • 2016
  • Background: Although numerous studies of the anticancer activities of Korean Red Ginseng (KRG) have been performed, the therapeutic effect of KRG on leukemia has not been fully elucidated. In this study, we investigated the antileukemia activities of KRG and its cellular and molecular mechanisms. Methods: An established leukemia tumor model induced by xenografted T cell lymphoma (RMA cells) was used to test the therapeutic activity of KRG water extract (KRG-WE). Direct cytotoxic activity of KRG-WE was confirmed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The immunomodulatory activities of KRG-WE were verified by immunohistochemistry, nitric oxide production assay. The inhibitory effect of KRG-WE on cell survival signaling was also examined. Results: Orally administered KRG-WE reduced the sizes of tumor masses. Levels of apoptosis regulatory enzymes and cleaved forms of caspases-3 and -8 were increased by this extract. In addition, expression of matrix metalloproteinase-9, a metastasis regulatory enzyme, was decreased by KRG-WE treatment. The proportion of CD11c+ cells was remarkably increased in the KRG-treated group compared to the control group. However, KRG-WE did not show significant direct cytotoxicity against RMA cells. Conclusion: Our results strongly suggest that the KRG might have antileukemia activity through CD11c+ cell-mediated antitumor immunity.

PARP1 Impedes SIRT1-Mediated Autophagy during Degeneration of the Retinal Pigment Epithelium under Oxidative Stress

  • Jang, Ki-Hong;Hwang, Yeseong;Kim, Eunhee
    • Molecules and Cells
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    • v.43 no.7
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    • pp.632-644
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    • 2020
  • The molecular mechanism underlying autophagy impairment in the retinal pigment epithelium (RPE) in dry age-related macular degeneration (AMD) is not yet clear. Based on the causative role of poly(ADP-ribose) polymerase 1 (PARP1) in RPE necrosis, this study examined whether PARP1 is involved in the autophagy impairment observed during dry AMD pathogenesis. We found that autophagy was downregulated following H2O2-induced PARP1 activation in ARPE-19 cells and olaparib, PARP1 inhibitor, preserved the autophagy process upon H2O2 exposure in ARPE-19 cells. These findings imply that PARP1 participates in the autophagy impairment upon oxidative stress in ARPE-19 cells. Furthermore, PARP1 inhibited autolysosome formation but did not affect autophagosome formation in H2O2-exposed ARPE-19 cells, demonstrating that PARP1 is responsible for impairment of late-stage autophagy in particular. Because PARP1 consumes NAD+ while exerting its catalytic activity, we investigated whether PARP1 impedes autophagy mediated by sirtuin1 (SIRT1), which uses NAD+ as its cofactor. A NAD+ precursor restored autophagy and protected mitochondria in ARPE-19 cells by preserving SIRT1 activity upon H2O2. Moreover, olaparib failed to restore autophagy in SIRT1-depleted ARPE-19 cells, indicating that PARP1 inhibits autophagy through SIRT1 inhibition. Next, we further examined whether PARP1-induced autophagy impairment occurs in the retinas of dry AMD model mice. Histological analyses revealed that olaparib treatment protected mouse retinas against sodium iodate (SI) insult, but not in retinas cotreated with SI and wortmannin, an autophagy inhibitor. Collectively, our data demonstrate that PARP1-dependent inhibition of SIRT1 activity impedes autophagic survival of RPE cells, leading to retinal degeneration during dry AMD pathogenesis.

PRP4 Kinase Domain Loss Nullifies Drug Resistance and Epithelial-Mesenchymal Transition in Human Colorectal Carcinoma Cells

  • Ahmed, Muhammad Bilal;Islam, Salman Ul;Sonn, Jong Kyung;Lee, Young Sup
    • Molecules and Cells
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    • v.43 no.7
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    • pp.662-670
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    • 2020
  • We have investigated the involvement of the pre-mRNA processing factor 4B (PRP4) kinase domain in mediating drug resistance. HCT116 cells were treated with curcumin, and apoptosis was assessed based on flow cytometry and the generation of reactive oxygen species (ROS). Cells were then transfected with PRP4 or pre-mRNA-processing-splicing factor 8 (PRP8), and drug resistance was analyzed both in vitro and in vivo. Furthermore, we deleted the kinase domain in PRP4 using Gateway™ technology. Curcumin induced cell death through the production of ROS and decreased the activation of survival signals, but PRP4 overexpression reversed the curcumin-induced oxidative stress and apoptosis. PRP8 failed to reverse the curcumin-induced apoptosis in the HCT116 colon cancer cell line. In xenograft mouse model experiments, curcumin effectively reduced tumour size whereas PRP4 conferred resistance to curcumin, which was evident from increasing tumour size, while PRP8 failed to regulate the curcumin action. PRP4 overexpression altered the morphology, rearranged the actin cytoskeleton, triggered epithelial-mesenchymal transition (EMT), and decreased the invasiveness of HCT116 cells. The loss of E-cadherin, a hallmark of EMT, was observed in HCT116 cells overexpressing PRP4. Moreover, we observed that the EMT-inducing potential of PRP4 was aborted after the deletion of its kinase domain. Collectively, our investigations suggest that the PRP4 kinase domain is responsible for promoting drug resistance to curcumin by inducing EMT. Further evaluation of PRP4-induced inhibition of cell death and PRP4 kinase domain interactions with various other proteins might lead to the development of novel approaches for overcoming drug resistance in patients with colon cancer.

Protective effects of red ginseng extract against vaginal herpes simplex virus infection

  • Cho, Ara;Roh, Yoon Seok;Uyangaa, Erdenebileg;Park, Surim;Kim, Jong Won;Lim, Kyu Hee;Kwon, Jungkee;Eo, Seong Kug;Lim, Chae Woong;Kim, Bumseok
    • Journal of Ginseng Research
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    • v.37 no.2
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    • pp.210-218
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    • 2013
  • Numerous studies have suggested that Korean red ginseng (KRG) extract has various immune modulatory activities both in vivo and in vitro. In this study, we used a mouse model to examine the effects of orally administered KRG extract on immunity against herpes simplex virus (HSV). Balb/c mice were administered with 100, 200, and 400 mg/kg oral doses of KRG extract for 10 d and then vaginally infected with HSV. We found that KRG extract rendered recipients more resistant against HSV vaginal infection and further systemic infection, including decreased clinical severity, increased survival rate, and accelerated viral clearance. Such results appeared to be mediated by increased vaginal IFN-${\gamma}$ secretion. Moreover, increased mRNA expression of IFN-${\gamma}$, granzyme B, and Fas-ligand was identified in the iliac lymph node and vaginal tracts of KRG extract treated groups (200 and 400 mg/kg). These results suggest that the activities of local natural killer cells were promoted by KRG extract consumption and that KRG may be an attractive immune stimulator for helping hosts overcome HSV infection.

Fibula Free Flap for Mandibular Reconstruction using Simulation Surgery in Bisphosphonate related Osteonecrosis of the Jaw

  • Kim, Hong-Joon;Hwang, Jong-Hyun;Ahn, Kang-Min
    • Journal of International Society for Simulation Surgery
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    • v.2 no.1
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    • pp.1-6
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    • 2015
  • Purpose Bisphophonate-related osteonecrosis of the jaw (BRONJ) is an emerging problem. Extensive osteonecrosis of the jaw needs free flap reconstruction. Free fibular flap is the most useful flap for maxilla-mandibular hard and soft tissue reconstruction. The advantages of fibular free flap are simultaneous soft and hard tissue reconstruction and placing implant in reconstructed mandible and maxilla. In this study, four consecutive BRONJ patients who underwent fibula free flap reconstruction using simulation surgery were reviewed. Materials and Methods Four BRONJ patients who underwent free fibula reconstruction between May 2006 and September 2014 were included in this study. Male to female ratio was 1:3 and average age was 67.3 years old (62-70). All patients need mandibular bone reconstruction. Three patients suffered from osteoporosis and one male patient had multiple myeloma. Postoperative flap survival, functional reconstruction, esthetic results, food taking were evaluated. Results Three osseous flaps and one osteocutaneous flap were used. All the fibular flaps were survived and patients were recovered without complications. Oro-cutaneous fistula was resolved after operation. All patients were satisfied with the esthetic results. Patients reported improved solid food intake after operation with partial denture. One fully edentulous patient had semi-fluid diet after operation. Conclusion Treatment of the BRONJ is difficult due to lack of standard protocol. Fibular free flap using simulation surgery is the workhorse flap for mandibular hard and soft tissue reconstruction, especially in stage III BRONJ patient. In this study, functional and esthetic results were successful in all patients. Normal diet was possible with partial dentures.

Effects of Pre-conditioning dose on the Immune Kinetics and Cytokine Production in the Leukocytes Infiltrating GVHD Tissues after MHC-matched Transplantation

  • Choi, Jung-Hwa;Yoon, Hye-Won;Min, Chang-Ki;Choi, Eun-Young
    • IMMUNE NETWORK
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    • v.11 no.1
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    • pp.68-78
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    • 2011
  • Background: Graft-versus-host disease (GVHD) is a huddle for success of hematopoietic stem cell transplantation. In this study, effects of irradiation dose on immune kinetics of GVHD were investigated using B6 ${\rightarrow}$ BALB.B system, a mouse model for GVHD after MHC-matched allogeneic transplantation. Methods: BALB.B mice were transplanted with bone marrow and spleen cells from C57BL/6 mice after irradiation with different doses. Leukocytes residing in the peripheral blood and target organs were collected periodically from the GVHD hosts for analysis of chimerism formation and immune kinetics along the GVHD development via flow cytometry. Myeloid cells were tested for production of IL-17 via flow cytometry. Results: Pre-conditioning of BALB.B hosts with 900 cGy and 400 cGy resulted in different chimerism of leukocytes from the blood and affected survival of GVHD hosts. Profiles of leukocytes infiltrating GVHD target organs, rather than profiles of peripheral blood leukocytes (PBLs), were significantly influenced by irradiation dose. Proportions of IL-17 producing cells in the infiltrating $Gr-1^+$ or $Mac-1^+$ cells were higher in the GVHD hosts with high does irradiation than those with low dose irradiation. Conclusion: Pre-conditioning dose affected tissue infiltration of leukocytes and cytokine production by myeloid cells in the target organs.

The Challenge of the Third Generation Port and Port Competition (제 3 세대 항만의 도래와 항만경쟁)

  • 문성혁
    • Journal of the Korean Institute of Navigation
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    • v.18 no.2
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    • pp.91-109
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    • 1994
  • Technological and organisational changes in transport system have introduced new dimension into port system development and inter-port competition. The quality of service now required by the customer is costly and not easily provided by small shipping companies and small ports. It has been suggested that in the future container shipping may be concentrated by space-sharing arrangements or actual mergers into the hands of a few mega-operators with the investment potential to provide total logistics networks. In order to compete effectively, high load factors will be essential and port concentration inevitable. A fa-voured few ports will become the load centres and other ports will assume a secondary feeder role. In this study, three questions are raised and attempts are made to answer them : (a) what is the new role of ports today ; (b) why should ports be engaged in this new role ; and (c) how can ports play this new role. In short, a modern port should be a service centre and a logistic platform for international trade and transport-a third generation port. Ports, in particular, have to make every effort to be competitive in the cost and quality of services and to make the port a transport and distribution service centre. For most ports, this is not an option but a must ; an essential requirement for survival in this win or lose situation. The best way to win is to maintain a close contact with port users, listen to them, discuss with them, help them and satisfy them. That is port marketing. Starting from the findings of port marketing, it is es-sential to work out appropriate development plans and marketing targets and to improve port competitive-ness. As an alternative method, a port competitiveness model is suggested, which may help port managers to make appropriate improvements.

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