• 제목/요약/키워드: spheroids

검색결과 65건 처리시간 0.026초

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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    • 제63권4호
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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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    • 제17권1_2_3호
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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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    • 제50권2호
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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.

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

  • 배광준;김세은
    • 대한조선학회지
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    • 제24권3호
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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
    • 한국고분자학회:학술대회논문집
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    • 한국고분자학회 2006년도 IUPAC International Symposium on Advanced Polymers for Emerging Technologies
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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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은하계(銀河系)의 질량분포(質量分布) 모형(模型)-III (A Model of the Mass Distribution of the Galaxy-III)

  • 유경노;강용희
    • 천문학회지
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    • 제8권1호
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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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60Hz ELF 자계에 의한 인체내부 유도 전류밀도 해석 (Analysis on Induced Current Density Inside Human Body by 60 Hz ELF Magnetic Fields)

  • 민석원;송기현
    • 대한전기학회논문지:전기물성ㆍ응용부문C
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    • 제55권2호
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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.

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

  • 송기현;민석원
    • 대한전기학회논문지:전기물성ㆍ응용부문C
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    • 제55권5호
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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.

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

  • 이승준;김형갑;이향범;문유석
    • 생명과학회지
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    • 제26권11호
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    • pp.1313-1319
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    • 2016
  • 암은 비균질적으로 구성된 세포집합체로 간질세포 및 세포 외 기질로 구성된 미세환경과 상호작용에 의해 발병, 전이, 심화되는 복잡한 질병이다. 하지만, 기존의 2차원 배양 세포 기반 플랫폼이 3차원적 생체 환경과 암의 비균질성을 대표하기 힘든 한계를 극복하기 위해 스페로이드 배양 세포를 비롯한 다양한 플랫폼 개발이 활발해지고 있다. 본 연구에서는 특히 감염, 염증 및 식이적 환경성 영향력에 민감한 HCT-8 대장암 세포주를 기반으로 하여 3차원 스페로이드 배양법을 보다 효과적인 방법으로 개선하고, 대장암 스페로이드 세포를 기반으로 암의 비균질적인 특질과 항암내성 연구의 간단하고 개선된 플랫폼을 제시고자 하였다. 3차원 배양법 최적화를 위해 물리적 배양환경 조성과 배양배지 구성에 따른 스페로이드 형태형성을 비교 분석하고 암 줄기세포군의 증가 양상을 확인한 결과, 필수요소로 구성된 제한 배지와 균일한 형태의 비부착성 표면 배양접시에서 배양된 스페로이드가 균일한 형태의 구형을 형성하고 암 줄기세포군이 증가함을 확인하였다. 대장암 스페로이드 세포를 기반으로 대장암 치료제인 5-Fluorouracil (5-FU)에 대한 화학적 감응성 변화를 측정한 결과, 암 줄기세포가 5-FU에 대한 화학적 감수성 저해의 원인이 되며, 최적배양 조건에서 암 줄기세포의 약제 내성의 표현이 증대되었다. 이는 암줄기세포의 항암제 내성에 대한 잠재적 위험성을 내포하는 것으로, 이 방법론은 감염, 염증 및 식이적 요인과 연관된 대장암 스페로이드 세포 기반 항암제 약물반응을 검증하기 위해 효과적이면서 간소한 시험법으로 활용될 수 있을 것이다.

Novel Alternative Methods in Toxicity Testing

  • Satoh, Tetsuo
    • 한국응용약물학회:학술대회논문집
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    • 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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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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