• Title/Summary/Keyword: Suppressor

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Analysis of p53 Somatic Mutation in Head and Neck Cancer Using Denaturing High Performance Liquid Chromatography(DHPLC) (두경부 종양에서 DHPLC를 이용한 p53체세포 돌연변이 검출 연구)

  • Kim, Kwang-Youl;Park, Sang-Bum;Han, Sang-Man;Nam, Youn-Hyoung;Jang, Won-Cheoul
    • Journal of the Korean Chemical Society
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    • v.48 no.1
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    • pp.33-38
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    • 2004
  • Mutation of p53 tumor suppressor gene in HNSCC (head and neck squamous cell carcinoma) has been proposed high rate. We extracted genomic DNA from 50 head and neck cancer. The DNA was amplified by PCR at exon 5-8 in p53 tumor suppressor gene. We have compared single strand conformation polymorphism (SSCP) and denaturing high performance liquid chromatography (DHPLC) method for analysis of p53 somatic mutation. As a result, 16 deleted mutations (32%) were detected by SSCP analysis and 17 deleted mutations (34%) were detected by DHPLC analysis at exon 8. All of 17 mutations were proved by sequencing. We conclude that DHPLC is a fast and simple screening method rather than SSCP analysis.

Influence of carrier suppressors on electrical properties of solution-derived InZnO-based thin-film transistors

  • Sim, Jae-Jun;Park, Sang-Hui;Jo, Won-Ju
    • Proceedings of the Korean Vacuum Society Conference
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    • 2016.02a
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    • pp.262-262
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    • 2016
  • 최근 고해상도 디스플레이가 주목받으면서 기존 비정질 실리콘(a-Si)을 대체할 수 있는 재료에 관한 연구가 활발히 진행되고 있다. a-Si의 경우 간단한 공정 과정, 적은 생산비용, 대면적화가 가능하다는 장점이 있지만 전자 이동도가 매우 낮은 단점이 있다. 반면, 산화물 반도체는 비정질 상태에서 전자 이동도가 높으며 큰 밴드갭을 가지고 있어 투명한 특성을 나타낼 뿐만 아니라, 저온공정이 가능하여 기판의 제한이 없는 장점을 가지고 있다. 대표적으로 가장 널리 연구되고 있는 산화물 반도체는 a-IGZO(amorphous indium-gallium-zinc oxide)이다. 그러나 InZnO(IZO) 기반의 산화물 반도체에서 carrier suppressor 역할을 하는 Ga(gallium)은 수요에 대한 공급이 원활하지 못하여 비싸다는 단점이 있다. 그러므로 경제적이면서 a-IGZO와 유사한 전기적 특성을 나타낼 수 있는 suppressor 물질이 필요하다. 따라서 본 연구에서는 IZO 기반의 산화물 반도체에서 Ga을 Hf(hafnium), Zr(zirconium), Si(silicon)으로 대체하여 용액증착(solution-deposition) 공정으로 각각의 채널층을 형성한 back-gate type의 박막 트랜지스터(thin-film transistor, TFT) 소자를 제작하였다. 용액증착 공정은 물질의 비율을 자유롭게 조절할 수 있고, 대기압의 조건에서도 공정이 가능하기 때문에 짧은 공정시간과 저비용의 장점이 있다. 제작된 소자는 p-type Si 위에 게이트 절연막으로 100 nm의 열산화막이 성장된 기판을 사용하였다. 표준 RCA 클리닝 후에 각 solution 물질을 spin coating 방식으로 증착하였다. 이후, photolithography, develop, wet etching의 과정을 거쳐 채널층 패턴을 형성하였다. 또한, 산화물 반도체의 전기적 특성을 향상시키기 위해서 후속 열처리 과정(post deposition annealing, PDA)은 필수적이다. CTA 방식은 높은 열처리 온도와 긴 열처리 시간의 단점이 있다. 따라서, 본 연구에서는 $100^{\circ}C$ 이하의 낮은 온도와 짧은 열처리 시간의 장점을 가지는 MWI (microwave irradiation)를 후속 열처리로 진행하였다. 그 결과, 각 물질로 구현된 소자들은 기존 a-IGZO와 비교하여 적은 양의 carrier suppressor로도 우수한 전기적 특성 및 안정성을 얻을 수 있었다. 따라서, Si, Hf, Zr 기반의 산화물 반도체는 기존의 Ga을 대체하여 저비용으로 디스플레이를 구현할 수 있는 IZO 기반 재료로 기대된다.

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Effect of Corynebacterium parvum on Immune Response to Sheep Red Blood Cells (Corynebacterium Parvum이 면양적혈구(緬羊赤血球)에 대(對)한 면역반응(免疫反應)에 미치는 영향(影響))

  • Oh, Jong-Hyun;Lee, Hern-Ku;Ha, Tai-You
    • The Journal of the Korean Society for Microbiology
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    • v.15 no.1
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    • pp.63-69
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    • 1980
  • The effects of intravenous administration of of C. parvum on immune cells in mice were investigated. Significant delayed type hypersensitivity parvum was given intravenously before antigen sensitization. The depressed effect of C. parvum was completely abolished by treatment of cyclophosphamide. However, delayed type hypersensitivity was not depressed when C. parvum given after antigen. This depression is considered to be attributable to the generation of suppressor cells which were either suppressor T cell or C. parvum activated macrophage, because C. parvum inhibited the proliferation of S. typhimurium in vivo and also induced splenomegaly and hepatomegaly, known as manifestation of macrophage activation. Serum antibody titers were not significantly affected by C. parvum regardless of time of C. parvum administration.

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Effect of Rice stripe virus NS3 on Transient Gene Expression and Transgene Co-Silencing

  • Sohn, Seong-Han;Huh, Sun-Mi;Kim, Kook-Hyung;Park, Jin-Woo;Lomonossoff, George
    • The Plant Pathology Journal
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    • v.27 no.4
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    • pp.310-314
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    • 2011
  • Nonstructural protein 3 (NS3) encoded by RNA3 of Rice stripe virus (RSV), known to be a suppressor of gene silencing, was cloned and sequenced. The cloned NS3 gene is composed of 636 nucleotides encoding 211 deduced amino acids, and showed a high degree of similarity with the equivalent genes isolated from Korea, Japan and China. The NS3 gene promoted the enhancement of transient gene expression and suppressed transgene co-silencing. In the transient GFP expression via agroinfiltration, GFP expression was dramatically enhanced in terms of both protein yield and expression period in the presence of NS3. The highest accumulation of GFP protein reached to 6.8% of total soluble proteins, which corresponded to a two-fold increase compared to that obtained in the absence of NS3. In addition, NS3 significantly suppressed the initiation of GFP co-silencing induced by the additive GFP infiltration in GFP-transgenic Nicotiana benthamiana. The NS3 gene was also found to be a stronger suppressor than Cucumber mosaic virus 2b. These observations are believed to be derived from the strong suppressive effect of NS3 on gene silencing, and indicate that NS3 could be used as an effective enhancer for the rapid production of foreign proteins in plants.

Apoptosis Suppressor에 관련된 유전자 스크린 방법과 동정된 유전자 특성 규명

  • 황규찬;옥도원;권득남;신혜경;김진회
    • Proceedings of the KSAR Conference
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    • 2001.03a
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    • pp.16-16
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    • 2001
  • Apoptosis로 일컬어지는 예정된 세포사멸(programmed cell death)은 개별 세포의 입장에서는 곧바로 사멸을 의미하지만, 정상적인 고등 생물의 입장에서는 개체의 발생과 분화하는데 프로그램된 과정이다. 자발적 세포사멸은 다른 조직에 비해 생식 조직인 난소나 정소에서 복잡한 apoptosis 기작들을 가지리라 사료된다. 본 연구는 Bcl-2 family중 apoptotic protein인 Bax에 대해 suppression하는 유전자를 yeast system을 활용하여 돼지 정소와 난소로부터 각각 cDNA library를 구축한 후 탐색하였다. 탐색에 활용된 cDNA library는 돼지의 정소와 난소로부터 mRNA를 분리하여 yeast vector인 pAD-GAL4-2.1에 구축하였고, 마우스 bax 유전자는 gal 1 promoter의 조절 하에 glucose 배지에서는 유도되지 않고, galactose 배지에서만 선택적으로 Bax를 발현할 수 있는 효모 vector(pL19-bax)를 구축하였다. Bax에 의한 apoptosis suppressor를 탐색하기 위해 우선 효모 W303에 pL19-bax를 transform하여 glucose 배지에서 Bax의 발현을 억제하였다. pL19-bax를 가진 효모에 정소와 난소로부터 구축된 cDNA library를 transform 시키고, transform된 효모는 각각 Bax에 의한 toxicity를 저해하는 유전자를 찾기 위해 스크린되었다. 이러한 방법으로 정소 cDNA library 탐색에서는 5 $\times$ $10^{6}$ transformant중 39개, 난소cDNA library 탐색에서는 2 $\times$ $10^{6}$ transformant중 26개의 콜로니가 생존하였다. 이들 콜로니로부터 유전자를 분리하여 분석해 본 결과 여러 그룹으로 분류할 수 있었다. 각 그룹의 관련 유전자는 protein synthesis/degradation 12종, oxidation/reductation 5종, detoxin/ cell cycle promoter 3종, signal transduction/growth factor 5종, 그리고 알려지지 않은 유전자 9종이었다. 그 중, bax-toxicity inhibition에 강력한 survival phenotype을 가지는 유전자(pSEDL)를 동정하였다. 이것은 T3-4-1 콜로니로부터 분리하였는데 140개 아미노산으로 이루어진 인간 SEDL(GenBank, XM_013096) 유전자와 매우 유사한 homology를 가지며, bax와 관련된 기능은 밝혀져 있지 않다. 이외에도 분리된 유전자에는 NADH, thioreduction, 그리고 cytochrome oxidase와 같은 positive 유전자 군이 크로닝되어, Bax를 이용한 효모에서 apoptosis suppressor에 관련된 유전자를 손쉽게 스크린하는 것이 가능하고, 분리된 유전자의 기능을 예측할 수 있어 지금까지 보고된 유전자 크로닝법 보다는 강력한 수단으로 활용될 수 있다는 사실을 시사하였다. 그러나, ORF에 관계없이 Bax 발현에 저항하는 유전자군이 선발된다든지 하는 문제점은 금후 검토가 필요하리라 사료된다.

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The Influence of Alpha-fetoprotein on Natural Suppressor Cell Activity and Ehrlich Carcinoma Growth

  • Belyaev, Nikolai Nikolaevich;Bogdanov, Andrei-Yurievich;Savvulidi, PhiIipp-Gorgievich;Krasnoshtanov, Vladimir-Konstantinovich;Tleulieva, Raikhan-Tleulievna;Alipov, Gabit-Kaimovich;Sekine, Ichiro;Bae, Jun-Sang;Lee, Jeong-Beom;Min, Young-Ki;Yang, Hun-Mo
    • The Korean Journal of Physiology and Pharmacology
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    • v.12 no.4
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    • pp.193-197
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    • 2008
  • The influence of alpha-fetoprotein (AFP) on the bone marrow (BM) natural suppressor (NS) cells of intact Ehrlich carcinoma -bearing CBA mice was studied. Bone marrow NS cells were fractionated into three fractions by isopycnic centrifugation on percoll gradients: NS1 (${\rho}$=1.080 g/ml), NS2 (${\rho}$=1.090 g/ml) and NS3 (1.100> ${\rho}$ > 1.090 g/ml). These fractions were highly different in their sensitivity to known NS cell inductors (interleukin (IL)-2, IL-3 or histamine). None of the NS fractions isolated from the intact mice spontaneously produced antiproliferative activity, however, they showed a high level of NS (antiproliferative and natural killer cell inhibitory) activity under the influence of AFP. A single injection of AFP to intact mice led to an increase of spontaneous NS activity and the inhibition of natural killer cell activity. NS activity, especially NS2, was increased in when tumor cells were subcutaneously inoculated three days after AFP injection. In the AFP-treated mice, the tumor mass at 14 days was 60% larger than that in the untreated mice. Our data confirmed that AFP is a tumor marker that can inhibit cancer immunity and plays a role in cancer pathogenesis.

Expression and Clinical Significance of Myeloid Derived Suppressor Cells in Chronic Hepatitis B Patients

  • Lu, Li-Rong;Liu, Jing;Xu, Zhen;Zhang, Geng-Lin;Li, De-Chang;Lin, Chao-Shuang
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.10
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    • pp.4367-4372
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    • 2014
  • We here document discovery of expression profile of myeloid derived suppressor cells (MDSCs) in chronic hepatitis B (CHB) patients and changes in the course of disease. The study population was composed of 75 outpatient HBV cases and 15 healthy control cases. Peripheral blood samples were collected for separation of mononuclear cells. Levels of MDSCs labeled with Lin-DR-CD11b+CD33+ obtained from peripheral blood mononuclear cells (PBMC), were revealed to have significant differences between the CHB and other groups. They were 0.414% for health control cases and 0.226% for CHB cases (Z=-2.356, p=0.0189). It also observed that the group of HBeAg positive cases had significant difference in MDSCs/PBMC median ($X^2=11.877$, p=0.003), compared with group of HBeAg negative cases and the healthy control group. It suggested considerable MDSCs might be involved in HBeAg immune tolerance. In addition, negative correlations between MDSCs/PBMC and parameters of ALT, AST and TBil, while positive correlation between MDSCs/PBMC and ALB parameter were found. Multiple comparisons between the four phases and health control phase again, there was a statistically sifnificant difference ($X^2=17.198$, p=0.002). Taken together, these findings may provide a new immunotherapy strategy for reduced the expression levels of MDSCs in CHB patients, through induction of an autoimmune response to virus removal.

The Role of Gastrokine 1 in Gastric Cancer

  • Yoon, Jung Hwan;Choi, Won Suk;Kim, Olga;Park, Won Sang
    • Journal of Gastric Cancer
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    • v.14 no.3
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    • pp.147-155
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    • 2014
  • Homeostatic imbalance between cell proliferation and death in gastric mucosal epithelia may lead to gastritis and gastric cancer. Despite abundant gastrokine 1 (GKN1) expression in the normal stomach, the loss of GKN1 expression is frequently detected in gastric mucosa infected with Helicobacter pylori, as well as in intestinal metaplasia and gastric cancer tissues, suggesting that GKN1 plays an important role in gastric mucosal defense, and the gene functions as a gastric tumor suppressor. In the stomach, GKN1 is involved in gastric mucosal inflammation by regulating cytokine production, the nuclear factor-${\kappa}B$ signaling pathway, and cyclooxygenase-2 expression. GKN1 also inhibits the carcinogenic potential of H. pylori protein CagA by binding to it, and up-regulates antioxidant enzymes. In addition, GKN1 reduces cell viability, proliferation, and colony formation by inhibiting cell cycle progression and epigenetic modification by down-regulating the expression levels of DNMT1 and EZH2, and DNMT1 activity, and inducing apoptosis through the death receptor-dependent pathway. Furthermore, GKN1 also inhibits gastric cancer cell invasion and metastasis via coordinated regulation of epithelial mesenchymal transition-related protein expression, reactive oxygen species production, and PI3K/Akt signaling pathway activation. Although the modes of action of GKN1 have not been clearly described, recent limited evidence suggests that GKN1 acts as a gastricspecific tumor suppressor. This review aims to discuss, comment, and summarize the recent progress in the understanding of the role of GKN1 in gastric cancer development and progression.

Agonistic Anti-CD137 Monoclonal Antibody Treatment Induces CD11b+Gr-1+ Myeloid-derived Suppressor Cells

  • Lee, Jung-Mi;Seo, Jeong-Hwan;Kim, Yeon-Jeong;Kim, Yun-Sun;Ko, Hyun-Jeong;Kang, Chang-Yuil
    • IMMUNE NETWORK
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    • v.10 no.3
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    • pp.104-108
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    • 2010
  • CD137 (4-1BB/tnfrsf9) has been shown to co-stimulate T cells. However, agonistic anti-CD137 monoclonal antibody (mAb) treatment can suppress $CD4^+$ T cells, ameliorating autoimmune diseases, whereas it induces activation of $CD8^+$ T cells, resulting in diverse therapeutic activity in cancer, viral infection. To investigate the CD137-mediated T cell suppression mechanism, we examined whether anti-CD137 mAb treatment could affect $CD11b^+Gr-1^+$ myeloid-derived suppressor cells (MDSCs). Intriguingly, anti-CD137 mAb injection significantly increased $CD11b^+Gr-1^+$ cells, peaking at days 5 to 10 and continuing for at least 25 days. Furthermore, this cell population could suppress both $CD8^+$ T cells and $CD4^+$ T cells. Thus, this study demonstrated that, for the first time, anti-CD137 mAb treatment could induce $CD11b^+Gr-1^+$ MDSCs under normal conditions, suggesting a possible relationship between myeloid cell induction and CD137-mediated immune suppression.