• Title/Summary/Keyword: bound form

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Tumor Therapy Applying Membrane-bound Form of Cytokines

  • Kim, Young-Sang
    • IMMUNE NETWORK
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    • v.9 no.5
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    • pp.158-168
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    • 2009
  • Tumor therapy using cytokines has been developed for last two decades. Several recombinant cytokines and tumor cell vaccines produced by cytokine gene transfer have been in clinical trials, but several side effects hamper routine clinical applications. Many cytokines are originally expressed as membrane-bound form and then processed to secretory form exerting paracrine effects. Though functional differences of these two types of cytokines are elusive yet, the membrane-bound form of cytokine may exert its effects on restricted target cells as a juxtacrine, which are in physical contacts. With the efforts to improve antitumor activities of cytokines in cancer patients, developing new strategies to alleviate life-threatening side effects became an inevitable goal of tumor immunologists. Among these, tumor cell vaccines expressing cytokines as membrane-bound form on tumor cell surface have been developed by genetic engineering techniques with the hope of selective stimulation of the target cells that are in cell-to-cell contacts. In this review, recent progress of tumor cell vaccines expressing membrane-bound form of cytokines will be discussed.

The Membrane-Bound Form of IL-17A Promotes the Growth and Tumorigenicity of Colon Cancer Cells

  • Thi, Van Anh Do;Park, Sang Min;Lee, Hayyoung;Kim, Young Sang
    • Molecules and Cells
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    • v.39 no.7
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    • pp.536-542
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    • 2016
  • Interleukin-17A is a member of the IL-17 family, and is known as CTLA8 in the mouse. It is produced by T lymphocytes and NK cells and has proinflammatory roles, inducing cytokine and chemokine production. However, its role in tumor biology remains controversial. We investigated the effects of locally produced IL-17A by transferring the gene encoding it into CT26 colon cancer cells, either in a secretory or a membrane-bound form. Expression of the membrane-bound form on CT26 cells dramatically enhanced their proliferation in vitro. The enhanced growth was shown to be due to an increased rate of cell cycle progression: after synchronizing cells by adding and withdrawing colcemid, the rate of cell cycle progression in the cells expressing the membrane-bound form of IL-17A was much faster than that of the control cells. Both secretory and membrane-bound IL-17A induced the expression of Sca-1 in the cancer cells. When tumor clones were grafted into syngeneic BALB/c mice, the tumor clones expressing the membrane-bound form IL-17A grew rapidly; those expressing the secretory form also grew faster than the wild type CT26 cells, but slower than the clones expressing the membrane-bound form. These results indicate that IL-17A promotes tumorigenicity by enhancing cell cycle progression. This finding should be considered in treating tumors and immune-related diseases.

Relationship between Fraction of Cd in Paddy Soils near Closed Mine and Cd in Polished Rice Cultivated on the same Fields (광산인근 논토양의 카드뮴 존재형태와 쌀의 카드뮴의 함량과의 관계)

  • Kim, Won-Il;Park, Byung-Jun;Park, Sang-Won;Kim, Jin-Kyoung;Kwon, Oh-Kyung;Jung, Goo-Bok;Lee, Jong-Keun;Kim, Jeong-Gyu
    • Korean Journal of Soil Science and Fertilizer
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    • v.41 no.3
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    • pp.184-189
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    • 2008
  • To assess the relationship between Cd fraction in paddy soils and Cd in polished rice, soils and rice were analyzed at the 3 Cd contaminated paddy fields near closed mines. Major Cd fractions of A field were organically bound (62.6%) and Fe-Mn oxide bound (25.3%) forms. In case of B field, major Cd fractions of B1 field were carbonate bound (46.3%) and Fe-Mn oxide bound (31.6%) form whereas B2 field were residual (54.3%) and carbonate bound (21.8%) form, respectively. It showed a huge difference of Cd fraction each other. 0.1M HCl extractable Cd in soil was positively correlated with Cd in rice. Specially, the ratios of 0.1M HCl extractable Cd against total Cd content in soils were 13.7%, 2.6%, and 0.45% in A, B1, and B2 fields, respectively. These ratio were largely affected with Cd uptake to rice grain. Also, exchangable, Fe-Mn oxide bound, and carbonate bound form, which are partially bioavailable Cd fraction to the plant, were positively correlated with Cd in rice while organically bound and residual form was not correlated. Multiple regression equation was developed with Rice Cd = -0.02861 + 0.07456 FR 1(exchangeable) + 0.00252 FR 2(carbonate bound) + 0.001075 FR 3(Fe Mn oxide bound) - 0.00095 FR 4(organically bound) - 0.00348 FR 5(residual) ($R^2=0.7893^{***}$) considering Cd fraction in soils.

RAS inhibitor를 이용한 항암제의 개발에 관하여

  • 어미숙
    • The Microorganisms and Industry
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    • v.19 no.4
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    • pp.32-35
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    • 1993
  • ras는 활성화 형태인 GTP bound form과 비활성화 형태인 GDP bound form의 두 형태로 존재하며 두 형태를 매개하는 regulatory protein들에 의해 그 activity가 조절된다. 또한 ras는 GTP와 GDP에 강한 친화성이 있으며 세포내에는 GTP보다 GDP가 더 많이 있어서 평소에는 ras가 GDP와 결합하고 있다가 활성화될때만 GTP와 결합하는 것으로 추정된다. GDP bound ras는 guanine nucloetide exchange protein(GEP)에 의해 활성화된 GTP bound form으로 전환되며 ras의 기능이 발휘된 후에는 GTPase activating protein(GAP)에 의해 비활성화된다. Yeast의 경우 IRA1과 2의 product가 GAP의 역할을 하는 것으로 알려져 있고 CDC25 gene의 product가 GEP의 기능을 담당하는 것으로 알려져 있다. NF1 gene은 Von Recklinghausen Neurofibromatosis Type I 질병을 가진 환자에게서 발견되었는데 부분적으로 sequencing한 결과에 따르면 yeast의 IRA1/2, mammalian GAP gene product와 protein homology가 높은 것으로 나타났다. Yeast의 경우 IRA1/2 gene의 손실이나 mammalian ras gene의 transformation으로 인한 heat shock sensitivity가 NF1 gene(2,3) 혹은 GAP(4)의 expression으로 suppression된 것으로 보아 NF1이 GAP protein으로서 ras를 불활성화 시킨다는 것이 판명되었다. 결론적으로 ras의 활성은 GTP bound 혹은 GDP bound의 양쪽형태를 이동하면서 조절되는데 이 기능은 GAP과 GEP 또는 그의 유사 protein들에 의해 수행되며 이러한 regulatory protein들은 growth factor, cytokine 그리고 protein kinase 같은 signal에 의해 활성화된다고 생각된다. 본 총설에서는 ras protein의 여러가지 성질보다는 ras의 modification과 관련하여 항암제로 사용할 수 있는 ras에 specific한 약품개발의 가능성과 현재 알려진 ras의 inhibitor를 중심으로 논하고자 한다.

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THE EIGENVALUE ESTIMATE ON A COMPACT RIEMANNIAN MANIFOLD

  • Kim, Bang-Ok;Kim, Kwon-Wook
    • Bulletin of the Korean Mathematical Society
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    • v.32 no.1
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    • pp.19-23
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    • 1995
  • We will estimate the lower bound of the first nonzero Neumann and Dirichlet eigenvalue of Laplacian equation on compact Riemannian manifold M with boundary. In case that the boundary of M has positive second fundamental form elements, Ly-Yau[3] gave the lower bound of the first nonzero neumann eigenvalue $\eta_1$. In case that the second fundamental form elements of $\partial$M is bounded below by negative constant, Roger Chen[4] investigated the lower bound of $\eta_1$. In [1], [2], we obtained the lower bound of the first nonzero Neumann eigenvalue is estimated under the condtion that the second fundamental form elements of boundary is bounded below by zero. Moreover, I realize that "the interior rolling $\varepsilon$ - ball condition" is not necessary when the first Dirichlet eigenvalue was estimated in [1].ed in [1].

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Tumor Cell Clone Expressing the Membrane-bound Form of IL-12p35 Subunit Stimulates Antitumor Immune Responses Dominated by $CD8^+$ T Cells

  • Lim, Hoyong;Do, Seon Ah;Park, Sang Min;Kim, Young Sang
    • IMMUNE NETWORK
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    • v.13 no.2
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    • pp.63-69
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    • 2013
  • IL-12 is a secretory heterodimeric cytokine composed of p35 and p40 subunits. IL-12 p35 and p40 subunits are sometimes produced as monomers or homodimers. IL-12 is also produced as a membrane-bound form in some cases. In this study, we hypothesized that the membrane-bound form of IL-12 subunits may function as a costimulatory signal for selective activation of TAA-specific CTL through direct priming without involving antigen presenting cells and helper T cells. MethA fibrosarcoma cells were transfected with expression vectors of membrane-bound form of IL-12p35 (mbIL-12p35) or IL-12p40 subunit (mbIL-12p40) and were selected under G418-containing medium. The tumor cell clones were analyzed for the expression of mbIL-12p35 or p40 subunit and for their stimulatory effects on macrophages. The responsible T-cell subpopulation for antitumor activity of mbIL-12p35 expressing tumor clone was also analyzed in T cell subset-depleted mice. Expression of transfected membranebound form of IL-12 subunits was stable during more than 3 months of in vitro culture, and the chimeric molecules were not released into culture supernatants. Neither the mbIL-12p35-expressing tumor clones nor mbIL-12p40-expressing tumor clones activated macrophages to secrete TNF-${\alpha}$. Growth of mbIL-12p35-expressing tumor clones was more accelerated in the $CD8^+$ T cell-depleted mice than in $CD4^+$ T cell-depleted or normal mice. These results suggest that $CD8^+$ T cells could be responsible for the rejection of mbIL-12p35-expressing tumor clone, which may bypass activation of antigen presenting cells and $CD4^+$ helper T cells.

Phenolic acid composition and antioxidative activity of white ginseng (Panax ginseng, C. A. Meyer) (백삼의 페놀산 조성과 항산화 활성)

  • Choi, Chang-Suk;Kim, Kyung-Im;Hong, Hee-Do;Choi, Sang-Yoon;Lee, Young-Chul;Kim, Kyung-Tack;Rho, Jeong-Hae;Kim, Sung-Soo;Kim, Young-Chan
    • Journal of Ginseng Research
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    • v.30 no.1
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    • pp.22-30
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    • 2006
  • Phenolic acids of white ginseng were extracted and fractionated into free, esterified, and insoluble-bound forms. The contents of individual phenolic acids in different forms were quantified by gas liquid chromatography. Nine different phenolic acids as free, esterified, and insoluble-bound forms were identified in white ginseng. Total phenolic compounds in different forms of extracts was 0.309% (free form), 0.230% (esterified form) and 0.138% (insoluble-bound form), respectively. Total phenolic acid contents in free, esterified and insoluble-bound form were 889.3, 356.8, 1,176.9 mg/100g fraction, respectively. Ferulic acid was the predominant phenolic acid, representing 63.7% and 50.9% of total phenolic acids in esterified fom and insoluble-bound form, respectively. While caffeic acid was only detected in esterified form. At 10 mg/ml insoluble-bound form quenched 95.9% ABTS free radicals generated from 2,2-azobis(2-amidinopropane) dihydrochloride (AAPH). Also, electron donating ability and lipid peroxidation inhibitory activity of insoluble-bound fom were higher than other fraction. All phenolic acid fractions scavenged over 80% of hydroxyl radical at 10 mg/ml.

Enhanced Upper Bound for Erasure Recovery in SPC Product Codes

  • Muqaibel, Ali
    • ETRI Journal
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    • v.31 no.5
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    • pp.518-524
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    • 2009
  • Single parity check (SPC) product codes are simple yet powerful codes that are used to correct errors and/or recover erasures. The focus of this paper is to evaluate the performance of such codes under erasure scenarios and to develop a closed-form tight upper bound for the post-decoding erasure rate. Closed-form exact expressions are derived for up to seven erasures. Previously published closed-form bounds assumed that all unrecoverable patterns should contain four erasures in a square. Additional non-square patterns are accounted for in the proposed expressions. The derived expressions are verified using exhaustive search. Eight or more erasures are accounted for by using a bound. The developed expressions improve the evaluation of the recoverability of SPC product codes without the need for simulation or search algorithms, whether exhaustive or novel.

Membrane-bound p35 Subunit of IL-12 on Tumor Cells is Functionally Equivalent to Membrane-bound Heterodimeric Single Chain IL-12 for Induction of Anti-tumor Immunity

  • Hyun-Jin Kim;Sang Min Park;Hayyoung Lee;Young Sang Kim
    • IMMUNE NETWORK
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    • v.16 no.5
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    • pp.305-310
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    • 2016
  • In this study, we compared two different tumor cell vaccines for their induction of anti-tumor immunity; one was a tumor cell clone expressing a membrane-bound form of IL-12 p35 subunit (mbIL-12 p35 tumor clone), and the other was a tumor clone expressing heterodimeric IL-12 as a single chain (mb-scIL-12 tumor clone). The stimulatory effect of mb-scIL-12 on the proliferation of ConA-activated splenocytes was higher than that of mbIL-12 p35 in vitro. However, the stimulatory effect of mbIL-12 p35 was equivalent to that of recombinant soluble IL-12 (3 ng/ml). Interestingly, both tumor clones (mbIL-12 p35 and mb-scIL-12) showed similar tumorigenicity and induction of systemic anti-tumor immunity in vivo, suggesting that tumor cell expression of the membrane-bound p35 subunit is sufficient to induce anti-tumor immunity in our tumor vaccine model.

Closed-form Expressions for Capacity Bounds of MRT/MRC MIMO with Multiuser Diversity (다중사용자 다이버시티가 적용된 MRT/MRC MIMO의 Capacity Bound의 Closed-form 표현)

  • Lee, Myougn-Won;Mun, Cheol;Yook, Jong-Gwan
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.31 no.12A
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    • pp.1223-1228
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    • 2006
  • Closed-form expressions for capacity bounds of multiuser diversity combined with maximum ratio transmission (MRT) and maximum ratio combining (MRC) at each link are presented under the assumption of independent and quasi-static flat multiple-input multiple-output (MIMO) Rayleigh fading channels. The analysis results precisely agree with the numerical verification results and clearly show the impact of MRT/MRC on multiuser diversity.