• Title, Summary, Keyword: PD-1

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Synthesis and Characterization of Tetrathiafulvalene (TTF) and 7,7,8,8-Tetracyanoquinodimethane (TCNQ) Compounds with PdX2(X=CI, NO3and Hexafluoroacetylacetonate)

  • Kim, Young-Inn;Jeong, Chan-Kyou;Lee, Yong-Min;Choi, Sung-Nak
    • Bulletin of the Korean Chemical Society
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    • v.23 no.12
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    • pp.1754-1758
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    • 2002
  • Tetrathiafulvalene(TTF) reacts with $PdCl_2,Pd(NO_3)_2$ and $Pd(hfacac)_2$(hexafluoroacetylacetonate) in ethanol to give $(TTF)_{1.5}PdCl_2$ (1a), $(TTF)_3Pd(NO_3)_2$ (1b) and $(TTF)_4Pd(hfacas)_2$ nd (1c), respectively. $PdCl(TCNQ)_{2.5}{\cdot}CH_3OH(2a)$was obtained from the reaction of $PdCl_2$ with LiTCNQ in methanol via the partial replacement of $Cl^-$ in $PdCl_2$ by $TCNQ^-$anion, whereas the total substitution of the labile $NO_3^-$ in $Pd(NO_3)_2$ yielded pd(TCNQ)·$CH_3OH$ (2b). $Pd(hfacac)_2(TCNQ)_2\cdot3CH_3OH$ (2c) was obtained from $Pd(hfacac)_2$ and LiTCNQ in methanol. The prepared compounds were characterized by spectroscopic (IR, UV, XPS) methods and magnetic (EPR, magnetic susceptibility) studies. The powdered electrical conductivities (${\sigma}_{rt}$) of the prepared compounds at room temperature were about~$10^{-7}S{\cdot}cm^{-1}$. The effective magnetic moments were lass than the spin-only value of one unpaired electron and no EPR signals from Pd metal ions were observed in any of the compounds, indicating that the Pd ions were diamagnetic and the magnetic moments arose from$(TTF)_n$ or $(TCNQ)_n$ moieties. The experimental evidences revealed that the charge transfer had occurred form $(TTF)_n$ moiety to the central Pd metal ion in 1a, 1b and 1c. Thus the TTF donors were ions in 2a and 2b were diamagnetic Pd(II) oxidation state. In contrast, the Pd metal ion was oxidized to Pd(IV) state in 2c as a result of an addition of $TCNQ^-$anion to $Pd(hfacac)_2$ in methanol. The oxidation states of the Pd metal ions were confirmed using the x-ray photoelectron spectroscopy.

PD-1 Expression in LPS-Induced Raw264.7 Cells Is Regulated via Co-activation of Transcription Factor NF-κB and IRF-1 (Lipopolysaccharide 유도된 Raw264.7 세포주에서 전사조절인자 NF-κB와 IRF-1의 공동작용에 의해 조절되는 PD-1 발현연구)

  • Choi, Eun-Kyoung;Lee, Soo-Woon;Lee, Soo-Woong
    • Korean Journal of Microbiology
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    • v.49 no.4
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    • pp.301-308
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    • 2013
  • Programmed Death-1 (PD-1) is one of the important immune-inhibitory molecules which was expressed in T cells, B cells, NKT cells, and macrophages activated by various immune activating factors. Lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, is one of the crucial immunogens for PD-1 expression. However, there are only a few reports on the expression mechanisms of PD-1 in innate immune cells. In this study, we investigate the expression mechanisms of PD-1 in LPS-stimulated Raw264.7 cell lines by RT-PCR, Western Blot, flow cytometry as well as ChIP assay and co-immunoprecipitation. When Raw264.7 cells were stimulated with LPS, PD-1 expression was greatly up-regulated via PI3K and p38 signaling. Primary macrophages isolated from LPS-injected mice were also shown the increased expression of PD-1. In promoter assay, NF-${\kappa}B$ and IRF-1 binding regions in mouse PD-1 promoter are important for PD-1 expression. We also found that the co-activation of NF-${\kappa}B$ and IRF-1 is indispensable for the maximum PD-1 expression. These results indicate that the modulation of PD-1 expressed in innate immune cells could be a crucial for the disease therapy such as LPS-induced mouse sepsis model.

Synthesis and Characterization of PtPd and PtRuPd Anode Catalysts for Direct Methanol Fuel Cells

  • Horvath G.;Park K. W.;Sung Y. E.
    • 한국전기화학회:학술대회논문집
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    • pp.211-218
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    • 2002
  • In this study, Pt/Pd (1.1), PtPd (2:1) and PtPd (3:1) binary catalysts and Pt/Ru/Pd (5:4:1) ternary catalyst were designed. The catalysts were synthesized by impregnation method using $NaBH_4$ as a reducing agent. A good catalyst for methanol oxidation requires low on-set potential, stable durability and low activation energy. In order to investigate the catalytic activity for the methanol oxidation, electrochemical measurements such as cyclic voltammetry and chronoamperometry were peformed in sulfuric acid with/without methanol solution. In order to calculate the activation energy of the reaction, electrochemical measurements were also tested at different temperatures. For investigation of the structural analysis such as particle size and alloying, X-ray diffraction and transmission electron microscopy analysis were used. In order to identify the role of the Pd and to determine the composition of the surface of the Pt/Pd nanoparticles, X-ray photoelectron spectroscopy (XPS) analysis was investigated. The XPS spectra of Pd showed that Pd appears only as a metallic state in the binary catalysts. The chemical states of Pt in PtPd catalysts are both metallic and oxidative. Polarization curves and power density data were obtained by testing the DMFC unit cell performance of PtPd and PtRuPd catalysts. These data showed that Pt/Pd (2:1) and Pt/Ru/Pd (5:4:1) have better performance than Pt and Pt/Ru, respectively.

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Induction Mechanism of PD-L1 (Programmed Cell Death-ligand 1) in Sepsis (패혈증에서 PD-L1 (Programmed Cell Death-ligand 1)의 발현 증가 기전)

  • Lee, Sang-Min
    • Tuberculosis and Respiratory Diseases
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    • v.65 no.4
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    • pp.343-350
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    • 2008
  • PD-L1 is expressed in a variety of antigen-presenting cells and provides T cell tolerance via ligation with its receptor PD-1 and B7-1 on T cells. Stimulation with lipopolysaccharide (LPS) can increase the level of PD-L1 expression in B cells and macrophages, which suggests that this molecule plays a role in the immunosuppression observed in severe sepsis. The aim of this study was to identify which of the downstream pathways of TLR4 are involved in the up-regulation of PD-L1 by LPS in macrophages. Flow cytometry was used to examine the expression of PD-L1 in RAW 264.7 macrophages stimulated with LPS. The following chemical inhibitors were used to evaluate the role of each pathway: LY294002 for PI3K/Akt, SB202190 for p38 MAPK, and U0126 for MEK. LPS induced the expression of PD-L1 in a time- and dose-dependent manner. Transfection of siRNA for TLR4 suppressed the induction of PD-L1. Pretreatment with LY294002 and SB202190 decreased the level of PD-L1 expression but U0126 did not. Overall, the PI3K/Akt and p38 MAPK pathways are involved in the up-regulation of PD-L1 expression in RAW 264.7 macrophages stimulated with LPS.

Study of the formation of Pd-silicide with x-ray photoelectron spectroscopy (광전자분광법을 이용한 Pd-실리사이드의 형성 연구)

  • 조은진;최일상;이한길;황찬용
    • Journal of the Korean Vacuum Society
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    • v.6 no.2
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    • pp.165-171
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    • 1997
  • If the thickness of Pd deposited is larger than 9$\AA$, its phase is $Pd_3Si$. This phase is followed by pure Pd phase with further deposition of Pd. Also, when the thickness of Pd deposited on top of Si(111) is larger than 1$\AA$, the phase of Pd-silicide formed is found to be Pd2Si. The full width at half maximum of Pd 3d core-levels increases with decreasing of Pd film thickness at low coverages ($\leq0.5\AA$). This is due to the formation of additional phase of Pd silicide, i.e. PdSi, in addition to $Pd_2Si$.

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Analysis of the Expression and Regulation of PD-1 Protein on the Surface of Myeloid-Derived Suppressor Cells (MDSCs)

  • Nam, Sorim;Lee, Aram;Lim, Jihyun;Lim, Jong-Seok
    • Biomolecules & Therapeutics
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    • v.27 no.1
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    • pp.63-70
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    • 2019
  • Myeloid-derived suppressor cells (MDSCs) that are able to suppress T cell function are a heterogeneous cell population frequently observed in cancer, infection, and autoimmune disease. Immune checkpoint molecules, such as programmed death 1 (PD-1) expressed on T cells and its ligand (PD-L1) expressed on tumor cells or antigen-presenting cells, have received extensive attention in the past decade due to the dramatic effects of their inhibitors in patients with various types of cancer. In the present study, we investigated the expression of PD-1 on MDSCs in bone marrow, spleen, and tumor tissue derived from breast tumor-bearing mice. Our studies demonstrate that PD-1 expression is markedly increased in tumor-infiltrating MDSCs compared to expression in bone marrow and spleens and that it can be induced by LPS that is able to mediate $NF-{\kappa}B$ signaling. Moreover, expression of PD-L1 and CD80 on $PD-1^+$ MDSCs was higher than on $PD-1^-$ MDSCs and proliferation of MDSCs in a tumor microenvironment was more strongly induced in $PD-1^+$ MDSCs than in $PD-1^-$ MDSCs. Although we could not characterize the inducer of PD-1 expression derived from cancer cells, our findings indicate that the study on the mechanism of PD-1 induction in MDSCs is important and necessary for the control of MDSC activity; our results suggest that $PD-1^+$ MDSCs in a tumor microenvironment may induce tumor development and relapse through the modulation of their proliferation and suppressive molecules.

Influence of Pd Contents and Substrate Temperature on the Magnetic Property in Co1-xPdx Films (Co1-xPdx 합금의 Pd함량과 스퍼터 기판온도에 따른 자기적 특성 변화)

  • 이기영;송오성
    • Journal of the Korean Institute of Electrical and Electronic Material Engineers
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    • v.16 no.8
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    • pp.744-751
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    • 2003
  • Co-Pd alloy thin films prepared by a DC-sputter that have self-organized nano structure(SONS), are promising for high-density information storage media in information era. We prepared the samples by varying Pd contents of 0~8.1 wt% at the substrate temperatures of room temperature (RT) and 200 $^{\circ}C$, respectively Microstructure and Pd contents of the Co$_{1-x}$ Pd$_{x}$ films are probed by a scanning electron microscope (SEM), a transmission electron microscope (TEM) and an energy dispersive spectrometer (EDS). We also investigated the saturation magnetization (Ms), remanence and coercivity of the Co$_{1-x}$ Pd$_{x}$ films. Surface roughness are measured by an atomic force microscope (AFM). We revealed that self-organized nano size Co-enriched phase and Pd-enriched phase existed with Pd contents at the substrate temperatures of RT and 20$0^{\circ}C$ through microstructure characterization. SONS helped to keep the saturation magnetization and enhance the perpendicular anisotropy with Pd contents. Out result implies that we may tune the perpendicular magnetic properties with keeping the saturation magnetization by varying substrate temperatures and Pd contents for high density magnetic recording.rding.

Overexpression of PD-L1 and PD-L2 Is Associated with Poor Prognosis in Patients with Hepatocellular Carcinoma

  • Jung, Hae Il;Jeong, Dongjun;Ji, Sanghee;Ahn, Tae Sung;Bae, Sang Ho;Chin, Susie;Chung, Jun Chul;Kim, Hyung Chul;Lee, Moon Soo;Baek, Moo-Jun
    • Cancer Research and Treatment
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    • v.49 no.1
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    • pp.246-254
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    • 2017
  • Purpose Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies. Recently, the overexpression of programmed cell death 1 (PD-1) and PD-1 ligand 1 (PD-L1) has been shown to correlate with poor prognosis in many cancers. However, the expression of PD-L1 or PD-1 ligand 2 (PD-L2) and clinical outcomes have not been fully investigated in HCC. Materials and Methods Formalin-fixed paraffin-embedded samples were obtained from 85 patients with HCC who underwent surgery. The expression of PD-Ls (PD-L1, PD-L2) was evaluated by immunohistochemical analysis. Results The proportion of high expression groups of PD-L1 and PD-L2 was 27.1% and 23.5%, respectively. Univariate analysis revealed that tumor size (p < 0.001), histological differentiation (p=0.010), PD-L1 expression (p < 0.001), and PD-L2 expression (p=0.039) were significant prognostic factors of overall survival in patients with HCC. Multivariate analysis revealed that overall tumor size (hazard ratio [HR], 4.131; 95% confidence interval [CI], 2.233 to 7.643; p < 0.001 and HR, 3.455; 95% CI, 1.967 to 6.067; p < 0.001) and PD-L1 expression (HR, 5.172; 95% CI, 2.661 to 10.054; p < 0.001 and HR, 3.730; 95% CI, 1.453 to 9.574; p=0.006) were independent prognostic values for overall and disease-free survival. Patients with high expression of PD-Ls had a significantly poorer survival than those with low expression (p < 0.001, p=0.034). Conclusion The overexpression of PD-Ls in HCC patients is correlated with survival and tumor recurrence. Further evaluation of PD-1 and PD-Ls as therapeutic targets and predictive biomarkers for HCC is warranted.

An engineered PD-1-based and MMP-2/9-oriented fusion protein exerts potent antitumor effects against melanoma

  • Wei, Mulan;Liu, Xujie;Cao, Chunyu;Yang, Jianlin;Lv, Yafeng;Huang, Jiaojiao;Wang, Yanlin;Qin, Ye
    • BMB Reports
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    • v.51 no.11
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    • pp.572-577
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    • 2018
  • Recent studies showed that the PD-1/PD-L1 checkpoint blockade is a dramatic therapy for melanoma by enhancing antitumor immune activity. Currently, major strategies for the PD-1/PD-L1 blockade have mainly focused on the use of antibodies and compounds. Seeking an alternative approach, others employ endogenous proteins as blocking agents. The extracellular domain of PD-1 (ePD1) includes the binding site with PD-L1. Accordingly, we constructed a PD-1-based recombinantly tailored fusion protein (dFv-ePD1) that consists of bivalent variable fragments (dFv) of an MMP-2/9-targeted antibody and ePD1. The melanoma-binding intensity and antitumor activity were also investigated. We found the intense and selective binding capability of the protein dFv-ePD1 to human melanoma specimens was confirmed by a tissue microarray. In addition, dFv-ePD1 significantly suppressed the migration and invasion of mouse melanoma B16-F1 cells, and displayed cytotoxicity to cancer cells in vitro. Notably, dFv-ePD1 significantly inhibited the growth of mouse melanoma B16-F1 tumor cells in mice and in vivo fluorescence imaging showed that dFv-ePD was gradually accumulated into the B16-F1 tumor. Also the B16-F1 tumor fluorescence intensity at the tumor site was stronger than that of dFv. This study indicates that the recombinant protein dFv-ePD1 has an intensive melanoma-binding capability and exerts potent therapeutic efficacy against melanoma. The novel format of the PD-L1-blocked agent may play an active role in antitumor immunotherapy.

PD-1 deficiency protects experimental colitis via alteration of gut microbiota

  • Park, Seong Jeong;Kim, Ji-Hae;Song, Mi-Young;Sung, Young Chul;Lee, Seung-Woo;Park, Yunji
    • BMB Reports
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    • v.50 no.11
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    • pp.578-583
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    • 2017
  • Programmed cell death-1 (PD-1) is a coinhibitory molecule and plays a pivotal role in immune regulation. Here, we demonstrate a role for PD-1 in pathogenesis of inflammatory bowel disease (IBD). Wild-type (WT) mice had severe wasting disease during experimentally induced colitis, while mice deficient for PD-1 ($PD-1^{-/-}$) did not develop colon inflammation. Interestingly, $PD-1^{-/-}$ mice cohoused with WT mice became susceptible to colitis, suggesting that resistance of $PD-1^{-/-}$ mice to colitis is dependent on their gut microbiota. 16S rRNA gene-pyrosequencing analysis showed that $PD-1^{-/-}$ mice had altered composition of gut microbiota with significant reduction in Rikenellaceae family. These altered colon bacteria of $PD-1^{-/-}$ mice induced less amount of inflammatory mediators from colon epithelial cells, including interleukin (IL)-6, and inflammatory chemokines. Taken together, our study indicates that PD-1 expression is involved in the resistance to experimental colitis through altered bacterial communities of colon.