• Title/Summary/Keyword: LAK cell

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Impact of IL-2 and IL-2R SNPs on Proliferation and Tumor-killing Activity of Lymphokine-Activated Killer Cells from Healthy Chinese Blood Donors

  • Li, Yan;Meng, Fan-Dong;Tian, Xin;Sui, Cheng-Guang;Liu, Yun-Peng;Jiang, You-Hong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.18
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    • pp.7965-7970
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    • 2014
  • One of the goals of tumor immunotherapy is to generate immune cells with potent anti-tumor activity through in vitro techniques using peripheral blood collected from patients. However, cancer patients generally have poor immunological function. Thus using patient T cells, which have reduced in vitro proliferative capabilities and less tumor cell killing activity to generate lymphokine-activated killer (LAK) cells, fails to achieve optimal clinical efficacy. Interleukin-2 (IL-2) is a potent activating cytokine for both T cells and natural killer cells. Thus, this study aimed to identify optimal donors for allogeneic LAK cell immunotherapy based on single nucleotide polymorphisms (SNP) in the IL-2 and IL-2R genes. IL-2 and IL-2R SNPs were analyzed using HRM-PCR. LAK cells were derived from peripheral blood mononuclear cells by culturing with IL-2. The frequency and tumor-killing activity of LAK cells in each group were analyzed by flow cytometry and tumor cell killing assays, respectively. Regarding polymorphisms at IL-2-330 (rs2069762) T/G, LAK cells from GG donors had significantly greater proliferation, tumor-killing activity, and IFN-${\gamma}$ production than LAK cells from TT donors (P<0.05). Regarding polymorphisms at IL-2R rs2104286 A/G, LAK cell proliferation and tumor cell killing were significantly greater in LAK cells from AA donors than GG donors (P<0.05). These data suggest that either IL-2-330(rs2069762)T/G GG donors or IL-2R rs2104286 A/G AA donors are excellent candidates for allogeneic LAK cell immunotherapy.

Effect of target cell nitric oxide synthesis on the sensitivity to lymphokine-activated killer cell cytotoxicity (표적세포의 Nitric oxide 합성이 LAK 세포의 세포독성에 대한 예민도에 미치는 영향)

  • Park, Sung Il;Park, Ju Hyung;Lee, Chi Kug;Kim, Shin Chae;Choi, Bo Geum;Kwak, Jae Yong;Yim, Chang Yeol
    • IMMUNE NETWORK
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    • v.1 no.2
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    • pp.162-169
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    • 2001
  • Background: Nitric oxide (NO), a cytotoxic molecule is produced in various tissues including tumor cells during interleukin-2 (IL-2) therapy . Lymphokine-activated killer (LAK) cells are induced during IL-2 therapy, and have cytotoxic activity against tumor cells. The current study investigated the effects of NO synthesized in target cells or exposure of target cells to NO on the sensitivity of target cells to LAK cell cytotoxicity. Methods: Cytotoxicity was measured using 4 h chromium release assays. LAK cells which were induced by a 4 day incubation of BALB/c mouse splenocytes with IL-2 (6,000 IU/mL) were employed as effector cells. RD-995 skin tumor cells originated from a C3H/HeN mouse were employed as target cells. NO synthesis in target cells was induced by a 24 h incubation of RD-995 cells with $IFN{\gamma}$ (25 U/mL), TNF (50 U/mL) and IL-1 (20 U/mL). S-nitrosyl acetylpenicillamine (SNAP), an NO donor, was used to expose target cells to NO. $N^G$-monomethyl-L-arginine (MLA) and carboxy-PTIO were added during cytotoxicity assays to inhibit NO synthesis, and to scavenge NO produced by target cells, respectively. Results: Sensitivity of NO-producing RD-995 cells to LAK cell cytotoxicity was decreased by addition of MLA and carboxy-PTIO during cytotoxicity assays. However, the two reagents had no effect on the sensitivity of non-NO-producing RD-995 cells. Pretreatment of RD-995 target cells with SNAP increased the sensitivity in comparison with untreated cells. Conclusions: Sensitivity of target cells to LAK cell cytotoxicity is increased by target cell NO synthesis or exposure to NO. Further studies are needed to evaluate whether these in vitro results have relevance to in vivo phenomena.

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Preclinlcal Evaluation of Polysaccharides Extracted from Korean Red-ginseng as an Antineoplastic Immunostimulator (홍삼다당체의 항암면역증강작용 연구)

  • 김기환;정인성
    • Journal of Ginseng Research
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    • v.21 no.2
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    • pp.78-84
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    • 1997
  • As a part of our ongoing effort to develop new antineoplastic immunostimulator from natural sources, bioassay-directed fractionationn of polysaccharides from Korean red ginseng was carried out by observing the proliferation of marine spleen cells and the generation of lymphoklne activated killer (LAK) cells. The acidic polysaccharide fractions proliferated spleen cells and generated LAK cells in proportion to their acidity in vitro. The LAK cell which was induced by ginseng showed tumoricidal activity against both NK celt sensitive and insensitive tumor target cells without major histocompatibility (MHC) restriction. Adherent macrophages and CD4+helper T cells were involved in the generation of the LAK cells. The acidic polysaccharide from Korean red ginseng synerglzed with recombinant IL-2 (rIff-2) at lower than 3 U/ml. The optimal doses of the acidic polysaccharide from Korean red ginseng for the proliferation of spleen cells and for the generation of LAK cells were 1 mg/ml and 100 $\mu\textrm{g}$/ml, respectively; this means that the mechanisms for the both activities may be different from each other.

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Ginsenoside Rh2 inhibiting HCT116 colon cancer cell proliferation through blocking PDZ-binding kinase/T-LAK cell-originated protein kinase

  • Yang, Jianjun;Yuan, Donghong;Xing, Tongchao;Su, Hongli;Zhang, Shengjun;Wen, Jiansheng;Bai, Qiqiang;Dang, Dongmei
    • Journal of Ginseng Research
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    • v.40 no.4
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    • pp.400-408
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    • 2016
  • Background: Ginsenoside Rh2 (GRh2) is the main bioactive component in American ginseng, a commonly used herb, and its antitumor activity had been studied in previous studies. PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK), a serine/threonine protein kinase, is highly expressed in HCT116 colorectal cancer cells. Methods: We examined the effect of GRh2 on HCT116 cells ex vivo. Next, we performed in vitro binding assay and in vitro kinase assay to search for the target of GRh2. Furthermore, we elucidated the underlying molecular mechanisms for the antitumor effect of GRh2 ex vivo and in vivo. Results: The results of our in vitro studies indicated that GRh2 can directly bind with PBK/TOPK and GRh2 also can directly inhibit PBK/TOPK activity. Ex vivo studies showed that GRh2 significantly induced cell death in HCT116 colorectal cancer cells. Further mechanistic study demonstrated that these compounds inhibited the phosphorylation levels of the extracellular regulated protein kinases 1/2 (ERK1/2) and (H3) in HCT116 colorectal cancer cells. In vivo studies showed GRh2 inhibited the growth of xenograft tumors of HCT116 cells and inhibited the phosphorylation levels of the extracellular regulated protein kinases 1/2 and histone H3. Conclusion: The results indicate that GRh2 exerts promising antitumor effect that is specific to human HCT116 colorectal cancer cells through inhibiting the activity of PBK/TOPK.

Platycodon grandiflorum enhanced macrophages function and NK and LAK cell mediated cell lysis.

  • Choi, Chul-Yung;Kim, Ji-Young;Jeong, Hye-Gwang
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.206.2-207
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    • 2003
  • The immunostimulatory and host resistance effects of the Platycodon grandiflorum A. DC, changkil (CK) and inulin (CKI) isolated from CK were investigated in rats. SD rat were exposed to CK or CKI by gavages for 7days and isolated peritoneal macrophages and splenocyte were used for these studies. CK and CKI significantly enhanced peritoneal macrophages activities such as ROS production and phargocytosis. (omitted)

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The in Vivo Distribution of $^{99m}Tc-Phytate$ IL-2 Complex on Selective Splenic Arterial Injection (비장동맥에 선택적으로 투여한 Interleukin-2와 $^{99m}Tc-Phytate$ 혼합물의 생체내 분포)

  • Zeon, Seok-Kil;Lee, Hee-Jung;Sohn, Soo-Sang
    • The Korean Journal of Nuclear Medicine
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    • v.26 no.1
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    • pp.124-126
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    • 1992
  • Interleukin-2 (IL-2)는 많은 immunoenhancing lymphokine의 한 종류로서 lymphokine activiated killer (LAK) cell의 생성을 자극시켜 흑종의 종양세포를 죽인다고 알려져 있다. 최근 간종양에서 비장동맥 또는 간동맥으로 투여한 IL-2가 비장의 임파계를 자극하여 LAK cell을 생성하여 어느정도효과가 있음이 밝혀지면서, 여러가지의 투여 방법이 시도되고 있다. 그러나 각종의 투여 방법에서 실제로 투여한 IL-2의 인체내 분포에 관한 연구는 없다. 저자들은 비정맥과 간문맥에 이상이 없는 증례의 비동맥에 IL-2와 $^{99m}Tc-phytate$ 혼합물을 투여하고, IL-2의 생체에서의 비장과 간에 어떻게 분포하는지 알아보기 위하여 $^{99m}Tc$의 radioactivity를 계측하여 보았다. 6예의 간세포암과 3예의 위암으로부터의 전이성간암에서 동맥조영술적방법을 이용하여 초선택적 비장동맥에 투여한 IL-2와 $^{99m}Tc-phytate$ 혼합물이 비장 27%, 간73%의 분포를 보여 비장을 거쳐온 $^{99m}Tc$의 방사능이 간에 많이 침착함을 확인하였고 간과 비장이외의 부위 즉 골수, 복수 또는 폐장이나 늑막에는 전혀 방사능 분포가 없음을 알 수 있었다. 따라서 비정맥이나 간문백에 이상이 없는 증례에서 IL-2의 비장동맥 투여는 목적하는 바 IL-2의 생체내 분포를 이룩할 수 있을 것으로 사료된다.

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Antitumor and Immunopotentiating Effects of Manda Enzyme

  • Hwang, Woo-Ik;Hwang, Yoon-Kyung;Lee, Ji-Young;Lee, Jae-Yeon;Okuda, Hiromichi
    • Natural Product Sciences
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    • v.2 no.1
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    • pp.29-36
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    • 1996
  • This study was to evaluate the antitumor and immunopotentiation effects of Manda Enzyme (ME). Oral administration of ME (0.2ml/mouse) to tumor bearing mice significantly prolonged survival rate compared to the control group with the prolongation ratio of 40%. The inhibition ratios for the first and the second experiments were 51.8% and 26.4%, respectively. Only the spleen index was significantly increased in the MEF-treated group, but not in the control group. Gamma globulin level of the MEF-treated group was elevated when mice were injected with sarcoma-180 cells on the left groin. Activities of natural killer (NK) and lymphokineactivated killer (LAK) cells were observed by $^{51}Cr-release$ method. Activities of NK cell against YAC-1 cells were significantly increased in the MEF treated group. And LAK cell activities against P815 cells were also significantly increased in the experimental group. These observations, therefore, suggest that ME may have an anticancer effect and immunopotentiating effect in vivo.

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Analysis of Solid Oxide Fuel Cell/Oxy-fuel Combustion Power Generation System Using Oxygen Separation Technology (산소분리기술을 사용한 연료전지/순산소연소 발전시스템 해석)

  • Park, Sung-Ku;Kim, Tong-Seop;Sohn, Jeong-Lak;Lee, Young-Duk
    • 한국신재생에너지학회:학술대회논문집
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    • 2008.10a
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    • pp.51-54
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    • 2008
  • This study aims to devise and analyze a power generation system combining the solid oxide fuel cell and oxy-fuel combustion technology. The fuel cell operates at an elevated pressure, a constituting a SOFC/gas turbine hybrid system. Oxygen is extracted from the high pressure cathode exit gas using ion transport membrane technology and supplied to the oxy-fuel power system. The entire system generates much more power than the fuel cell only system due to increased fuel cell voltage and power addition from oxy-fuel system. More than one third of the power comes out of the oxy-fuel system. The system efficiency is also higher than that of the fuel cell only system. Recovering most of the generated carbon dioxide is major advantage of the system.

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Ultraviolet Microscopic Study on Lignin Distribution in the Fiber Cell Wall of BCTMP

  • Yoon, Seung-Lak;Yasuo Kojina
    • Journal of Korea Technical Association of The Pulp and Paper Industry
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    • v.36 no.1
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    • pp.61-66
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    • 2004
  • Bleached chemithermomechanical pulp (BCTMP) was produced from CTMP of Betula maximowicziana Regel by two staged ozone-hydrogen peroxide bleaching in order to improve the optical properties of high yield pulp. This pulp was used for the evaluation of optical properties improvement, chemical characteristics of lignin in fiber and the relationship between lignin and optical properties in fiber cell wall. Hydrogen peroxide treatment improved the brightness, but the post color number (PC No.). There was little improvement on optical properties by ozone treatment, but this could be improved more by using two staged ozone-hydrogen peroxide bleaching. The hydrogen peroxide treatment did not make any change on chemical characteristics of lignin in cell wall, but by ozone treatment, it was found that the non-aromatic conjugated structure was existed in the surface of cell wall, but this could be removed by hydrogen peroxide treatment in two staged ozone-hydrogen peroxide treatment. Therefore, the optical properties was significantly improved, due to the removal of non-aromatic conjugated structure.

A Study on the Dynamic Performance Behavior of Solid Oxide Fuel Cells with Stepwise Load Changes (갑작스런 부하 변동에 따른 고체산화물 연료전지의 동적 성능 거동 특성에 관한 연구)

  • Sohn Jeong Lak;Ro Sung Tack;Yang Jin Sik
    • Transactions of the Korean Society of Mechanical Engineers B
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    • v.29 no.4 s.235
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    • pp.477-484
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    • 2005
  • Model fer the dynamic simulation of dynamic behaviors of a solid oxide fuel cell (SOFC) is provided. This model is based upon (1) coupled mass and heat transfer characteristics and (2) important chemical reactions such as electrochemical and reforming reactions in high temperature fuel cells such as SOFC. It is found that the thermal inertia of solid materials in SOFC plays an important role to the dynamic behavior of cell temperature. Dynamic characteristics of cell voltage, power, and chemical compositions with different levels of load change are investigated.