• Title/Summary/Keyword: spheroids

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The Dose Dependent Effects of Ruxolitinib on the Invasion and Tumorigenesis in Gliomas Cells via Inhibition of Interferon Gamma-Depended JAK/STAT Signaling Pathway

  • Delen, Emre;Doganlar, Oguzhan
    • Journal of Korean Neurosurgical Society
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    • v.63 no.4
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    • pp.444-454
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    • 2020
  • Objective : Glioblastoma multiforme (GBM) is the most aggressive for of brain tumor and treatment often fails due to the invasion of tumor cells into neighboring healthy brain tissues. Activation of the Janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling pathway is essential for normal cellular function including angiogenesis, and has been proposed to have a pivotal role in glioma invasion. This study aimed to determine the dose-dependent effects of ruxolitinib, an inhibitor of JAK, on the interferon (IFN)-I/IFN-α/IFN-β receptor/STAT and IFN-γ/IFN-γ receptor/STAT1 axes of the IFN-receptor-dependent JAK/STAT signaling pathway in glioblastoma invasion and tumorigenesis in U87 glioblastoma tumor spheroids. Methods : We administered three different doses of ruxolitinib (50, 100, and 200 nM) to human U87 glioblastoma spheroids and analyzed the gene expression profiles of IFNs receptors from the JAK/STAT pathway. To evaluate activation of this pathway, we quantified the phosphorylation of JAK and STAT proteins using Western blotting. Results : Quantitative real-time polymerase chain reaction analysis demonstrated that ruxolitinib led to upregulated of the IFN-α and IFN-γ while no change on the hypoxia-inducible factor-1α and vascular endothelial growth factor expression levels. Additionally, we showed that ruxolitinib inhibited phosphorylation of JAK/STAT proteins. The inhibition of IFNs dependent JAK/STAT signaling by ruxolitinib leads to decreases of the U87 cells invasiveness and tumorigenesis. We demonstrate that ruxolitinib may inhibit glioma invasion and tumorigenesis through inhibition of the IFN-induced JAK/STAT signaling pathway. Conclusion : Collectively, our results revealed that ruxolitinib may have therapeutic potential in glioblastomas, possibly by JAK/STAT signaling triggered by IFN-α and IFN-γ.

NUMERICAL METHOD IN WAVE-BODY INTERACTIONS

  • MOUSAVIZADEGAN S. H.;RAHMAN M.
    • Journal of applied mathematics & informatics
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    • v.17 no.1_2_3
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    • pp.73-91
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    • 2005
  • The application of Green's function in calculation of flow characteristics around submerged and floating bodies due to a regular wave is presented. It is assumed that the fluid is homogeneous, inviscid and incompressible, the flow is irrotational and all body motions are small. Two methods based on the boundary integral equation method (BIEM) are applied to solve associated problems. The first is a low order panel method with triangular flat patches and uniform distribution of velocity potential on each panel. The second method is a high order panel method in which the kernels of the integral equations are modified to make it nonsingular and amenable to solution by the Gaussian quadrature formula. The calculations are performed on a submerged sphere and some floating spheroids of different aspect ratios. The excellent level of agreement with the analytical solutions shows that the second method is more accurate and reliable.

Human adipose-derived mesenchymal stem cell spheroids improve recovery in a mouse model of elastase-induced emphysema

  • Cho, Ryeon Jin;Kim, You-Sun;Kim, Ji-Young;Oh, Yeon-Mok
    • BMB Reports
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    • v.50 no.2
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    • pp.79-84
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    • 2017
  • Emphysema, a pathologic component of the chronic obstructive pulmonary disease, causes irreversible destruction of lung. Many researchers have reported that mesenchymal stem cells can regenerate lung tissue after emphysema. We evaluated if spheroid human adipose-derived mesenchymal stem cells (ASCs) showed greater regenerative effects than dissociated ASCs in mice with elastase-induced emphysema. ASCs were administered via an intrapleural route. Mice injected with spheroid ASCs showed improved regeneration of lung tissues, increased expression of growth factors such as fibroblast growth factor-2 (FGF2) and hepatocyte growth factor (HGF), and a reduction in proteases with an induction of protease inhibitors when compared with mice injected with dissociated ASCs. Our findings indicate that spheroid ASCs show better regeneration of lung tissues than dissociated ACSs in mice with elastase-induced emphysema.

An Application of the Localized Finite Element Method to 3-dimensional Free Surface Wave Problems (3차원 자유표면파 문제에서의 국소유한요소법의 응용)

  • K.J.,Bai;Se-Eun,Kim
    • Bulletin of the Society of Naval Architects of Korea
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    • v.24 no.3
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    • pp.1-8
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    • 1987
  • In this paper, the localized finite element method(LFEM) is applied to 3-dimensional ship motion problems in water of infinite depth. The LFEM used here is based on the functional constructed by Bai & Yeung(1974). To test the present numerical scheme, a few vertical axisymmetric bodies are treated by general 3-dimensional formulation. The computed results of hydrodynamic coefficients for a few vertical spheroids and vertical circular cylinders show good agreement with results obtained by others. The advantages of the present numerical method compared with the method of integral equation are as follows; (i) The cumbersome existence of irregular frequencies in the method of conventional integral equation is removed. (ii) The final matrix is banded and symmetric and the computation of the matrix elements is comparatively easier, whereas the size of the matrix in the present scheme is much larger. (iii) In the future research, it is possible to accommodate with the nonlinear exact free surface boundary condition in the localized finite element subdomain, whereas the linear solution is assumed in the truncated(far field) subdomain.

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Synthesis and Evaluation of Polymer for Crosslinking Cells

  • Ito, Michiko;Taguchi, Tetsushi;Kobayashi, Hisatoshi;Tateishi, Tetsuya
    • Proceedings of the Polymer Society of Korea Conference
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    • 2006.10a
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    • pp.266-266
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    • 2006
  • The cell spheroid (multicellular mass) is enhanced cell functions because of the cell-cell interaction compared with the individual cell. The objective of this study is synthesis, characterization and evaluation of novel crosslinkers to form spheroid in a short time. Our approach to bridge cells is based on the crosslinking of the cell membrane via the hydrophobic interaction. The crosslinker was prepared by the reaction between ethylenediamine and poly(ethylene glycol) (PEG) derivative with oleyl group as hydrophobic group at the terminal group. The product was characterized with gel permeation chromatography (GPC) and FT-IR. Furthermore, cell culture experiment was also performed to confirm spheroid formation. The function of prepared spheroids was evaluated.

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A Model of the Mass Distribution of the Galaxy-III (은하계(銀河系)의 질량분포(質量分布) 모형(模型)-III)

  • Yu, Kyung-Loh;Kang, Yong-Hee
    • Journal of The Korean Astronomical Society
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    • v.8 no.1
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    • pp.3-9
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    • 1975
  • Densities of the three constituent spheroids of the same eccentricity as our earlier model of the Galaxy are assumed to be given by an analytical form of $_{{\rho}i}$(r)=$k_ie^{-m_ir^u{_i}}$, where $k_i,\;m_i$, and ${\alpha}i$ are obtained by comparing with the results of the previous model. Using three values of $_{{\rho}i}$(r) the galactic rotation curve, mass of each spheroid and the whole Galaxy are calculated, and the three dimensional density distribution in the Galaxy is also obtained. The calculated rotation curve of the model Galaxy is in good agreement with the observed curve, and the shape of the cross section of the model Galaxy given by the computed density is very similar to the inferred shape of the spiral galaxies.

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Analysis on Induced Current Density Inside Human Body by 60 Hz ELF Magnetic Fields (60Hz ELF 자계에 의한 인체내부 유도 전류밀도 해석)

  • Min Suk-Won;Song Ki-Hyun
    • The Transactions of the Korean Institute of Electrical Engineers C
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    • v.55 no.2
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    • pp.76-81
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    • 2006
  • This paper analysed the characteristics of current density induced inside human body by 60 Hz extremely low frequency magnetic fields according to varying conductivities of human model. Human model was composed of several organs and other parts, whose shapes were expressed by spheroids or cylinders. Organs such as the brain, heart, lungs, liver and intestines were taken into account. Applying the boundary element method to the human model, we estimated effects on the induced current distribution due to differences of the organ conductivity and shape. We find organ conductivity influences most and a cross section area and a position of organ also gives effects.

Analysis on Current Density Induced Inside Body of Hot-Line Worker for 765kV Double Circuit Transmission Line (765 kV 2회선 송전선 활선 작업자 인체내부 유도전류 밀도 해석)

  • Song, Ki-Hyun;Min, Suk-Won
    • The Transactions of the Korean Institute of Electrical Engineers C
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    • v.55 no.5
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    • pp.231-238
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    • 2006
  • This paper analysed the induced current density inside human body of hot-line worker for 765kV double circuit transmission line according to locations of human body. Human model was composed of several organs and other parts, whose shapes were expressed by spheroids or cylinders. Organs such as the brain, heart, lungs, liver and intestines were taken into account. Applying the 3 dimensional boundary element method, we calculated induced current density in case a worker was located inside and outside a lowest phase of 765 kV transmission line in which a 60% current of maximum load flowed. As results of study, we found a maximum induced current density in all organs was less than $10mA/m^2$ when a wonder was outside. As one in brain and heart was higher than $10mA/m^2$ when a worker was inside, we propose a method for lowering current density.

Comparative Evaluation of Colon Cancer Stemness and Chemoresistance in Optimally Constituted HCT-8 cell-based Spheroids (적정 구성 배양 HCT-8 기반 대장암 스페로이드의 암 줄기세포능 및 항암제 내성 평가의 비교 평가 연구)

  • Lee, Seung Joon;Kim, Hyoung-Kab;Lee, Hyang Burm;Moon, Yuseok
    • Journal of Life Science
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    • v.26 no.11
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    • pp.1313-1319
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    • 2016
  • Cancer is a complex disease heterogeneously composed of various types of cells including cancer stem-like cells responsible for relapse and chemoresistance in the tumor microenvironment. The conventional two-dimensional cell culture-based platform has critical limitations for representing the heterogeneity of cancer cells in the three-dimensional tumor niche in vivo. To overcome this insufficiency, three-dimensional cell culture methods in a scaffold-dependent or -free physical environment have been developed. In this study, we improved and simplified the HCT-8 colon cancer cell-based spheroid culture protocol and evaluated the relationship between cancer stemness and responses of chemosensitivity to 5- Fluorouracil (5-FU), a representative anticancer agent against colon cancer. Supplementation with defined growth factors in the medium and the culture dish of the regular surface with low attachment were required for the formation of constant-sized spheroids containing $CD44^+$ and $CD133^+$ colon cancer stem cells. The chemo-sensitivities of $CD44^+$ cancer stem cells in the spheroids were much lower than those of $CD44^-$ non-stem-like cancer cells, indicating that the chemoresistance to 5-FU is due to the stemness of colon cancer cells. Taken together, the inflammation and oncogenic gut environment-sensitive HCT-8 cell-based colon cancer spheroid culture and comparative evaluation using the simplified model would be an efficient and applicable way to estimate colon cancer stemness and pharmaceutical response to anticancer drugs in the realistic tumor niche.

Novel Alternative Methods in Toxicity Testing

  • Satoh, Tetsuo
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1994.04a
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    • pp.129-130
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    • 1994
  • The science of toxicology is the understanding of the mechanisms by which exogenous agents produce deleterious effects in biological systems. The actions of chemicals such as drugs are ultimately exerted at the cellular and gene levels. Over the past decade. several in vitro alternative methods such as cultured cells for assessing the toxicity of various xenobiotics have been proposed to reduce the use of animals. In this workshop three advanced methods will be presented. These methods are novel important models for toxicologic studies. Dr. Tabuchis group has establishcd two immortalized gastric surface mucosa cell lines from the pminary cultore of gastric fundic mucosal cells of adult transgenic mice harboring a temperature sensitive simian virus 40 large T-anugen gene. As the immortalized cell lines of various tissues possess unique characteristics to maintain their normal functions for several months, these cell lines are extremely useful for not only toxicity testing but also pharmacological screening in new drug development. Professor Funatsu have studied the formation of spherical multicelluar aggregates of adult rat hepatocytes(spheroid) having tissue like structure. The sphcroid shown thre is a prototype module of an artificial liver support system. Thus, the urea synthesis activity of the artificial liver was maintained at least to days in 100% rat blood plasma. Dr. Takezawa and his coworkers have developed a novel culture system of multicellular spheroids considered 〃organoids〃 by utilizing a thermo-responsive polymer as a substratum of anchorage dependent cells. His final goal is to reconstitute the organoids of various normal organs, e.g., liver, skin etc. and also abnormal deseased organs such as tumor.

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