• Title/Summary/Keyword: PD-L2

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Baseline Serum Interleukin-6 Levels Predict the Response of Patients with Advanced Non-small Cell Lung Cancer to PD-1/PD-L1 Inhibitors

  • Da Hyun Kang;Cheol-Kyu Park;Chaeuk Chung;In-Jae Oh;Young-Chul Kim;Dongil Park;Jinhyun Kim;Gye Cheol Kwon;Insun Kwon;Pureum Sun;Eui-Cheol Shin;Jeong Eun Lee
    • IMMUNE NETWORK
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    • v.20 no.3
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    • pp.27.1-27.11
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    • 2020
  • Although various studies on predictive markers in the use of PD-1/PD-L1 inhibitors are in progress, only PD-L1 expression levels in tumor tissues are currently used. In the present study, we investigated whether baseline serum levels of IL-6 can predict the treatment response of patients with advanced non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 inhibitors. In our cohort of 125 NSCLC patients, the objective response rate (ORR) and disease control rate (DCR) were significantly higher in those with low IL-6 (<13.1 pg/ml) than those with high IL-6 (ORR 33.9% vs. 11.1%, p=0.003; DCR 80.6% vs. 34.9%, p<0.001). The median progression-free survival was 6.3 months (95% confidence interval [CI], 3.9-8.7) in the low IL-6 group, significantly longer than in the high IL-6 group (1.9 months, 95% CI, 1.6-2.2, p<0.001). The median overall survival in the low IL-6 group was significantly longer than in the high IL-6 group (not reached vs. 7.4 months, 95% CI, 4.8-10.0). Thus, baseline serum IL-6 levels could be a potential biomarker for predicting the efficacy and survival benefit of PD-1/PD-L1 inhibitors in NSCLC.

Molecular Orbital Interpretation on Antitumor Activity of trans-Palladium(Ⅱ) Complexes by Geometrical Structure of Ligands (Ⅰ) (리간드의 기하학적 구조에 의한 trans-팔라듐(Ⅱ) 착물의 항암활성에 관한 분자궤도함수론적 해석 (Ⅰ))

  • Song, Young Dae;Park, Byung Kak
    • Journal of the Korean Chemical Society
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    • v.39 no.4
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    • pp.244-251
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    • 1995
  • The palladium(II) complexes(where, [Pd(L)2X2], L=isoxazole(isox), 3,5-dimethylisoxazole(3,5-diMeisox), 3-methyl, 5-phenylisoxazole(3-Me, 5-Phisox), and 4-amino, 3,5-dimethylisoxazole(4-ADI); X=Cl, Br] with isoxazole and its derivatives are investigated on antitumor activity by EHMO calculation. It is found that the net charge of the two halogen atoms in trans-isomers are greater than those in cis-ones, indicating that ionic character of Pd-X bond in trans-isomers is greater than that of cis-ones, and so dissociation of Cl- ion is easier than that of Br- ion in aqueous solution in body. Furthermore, it is found that the ${\sigma}MO$ energy of Pd(dx2-y2)-X(px) bond $(E{\sigma}(Pd-X))$ is higher than that of Pd(dx2-y2)-N(px) bond $(E{\sigma}(Pd-N))$ without exception, about all the complexes, and also the $E{\sigma}(Pd-X)$ of trans-isomers is higher than that of cis-isomers. From the above facts, the degree of dissociation in Pd-X bond would be related to antitumor activity. In fact, the linear equation of correlation coefficient 0.96 is fairly established between ${\Delta}E{\sigma}(N-X)(E\sigma(Pd-N)-E{\sigma}(Pd-X))$ and inhibitory activity coefficient, logIA.

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Enhanced Hydrogen Production from Methanol/Water Photo-Splitting in TiO2 Including Pd Component

  • Kwak, Byeong-Sub;Chae, Jin-Ho;Kim, Ji-Yeon;Kang, Mi-Sook
    • Bulletin of the Korean Chemical Society
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    • v.30 no.5
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    • pp.1047-1053
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    • 2009
  • The future use of hydrogen as an energy source is expected to increase on account of its environmentally friendliness. In order to enhance the production of hydrogen, Pd ions (0.01, 0.05, 0.1, and 0.5 mol%) were incorporated $TiO_2$ (Pd-$TiO_2$) and used as a photocatalyst. The UV-visible absorbance decreased with increasing level of palladium incorporation without a wavelength shift. Although all the absorption plots showed excitation characteristics, there was an asymmetric tail observed towards a higher wavelength caused by scattering. However, the intensity of the photoluminescence (PL) curves of Pd-$TiO_2$ was smaller, with the smallest case being observed at 0.1 and 0.5 mol% Pd-$TiO_2$, which was attributedto recombination between the excited electrons and holes. Based on these optical characteristics, the evolution of $H_2$ from methanol/water (1:1) photo-splitting over Pd-$TiO_2$ in the liquid system was enhanced, compared with that over pure $TiO_2$. In particular, 2.4 mL of $H_2$ gas was produced after 8 h when 0.5 g of a 1.0 mol% Pd-$TiO_2$ catalyst was used. $H_2$ was stably evolved even after 28 h without catalytic deactivation, and the amount of $H_2$ produced reached 14.5 mL after 28 h. This is in contrast to the case of the Pd 0.1 mol% impregnated $TiO_2$ of $H_2$ evolution of 17.5 mL due to the more decreasedelectron-hole recombination.

A Structure-Function Relationship Exists for Ginsenosides in Reducing Cell Proliferation and Inducing Apoptosis in THP-1 Cells

  • Popovich David G.;Kitts David D.
    • Proceedings of the Ginseng society Conference
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    • 2002.10a
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    • pp.545-555
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    • 2002
  • Ginsenosides of 20(S)-protopanaxadiol and 20(S)-protopanaxatriol classification including the aglycones, PD, PI and ginsenosides Rh2, Rhl were shown to posses characteristic effects on proliferation of THP-l human leukaemia cells. A similar result was not apparent for ginsenoside Rg3 or dexamathasone. The concentration to inhibit $50\%$ of cells $(LC_{50})$ for PD, Rh2, PI and Rhl were 13 ${\mu}g/mL,\;15{\mu}g/mL,\;19{\mu}g/mL\;and\;210\;{\mu}g/mL$ respectively. Cell cycle analysis showed apoptosis with PD and PI treatment of THP-1 cells resulting in a build up of sub-G1 cells after 24, 48 and 72 hours of treatment. Rh2, and dexamathasone treatments also increased apoptotic cells after 24 hours, where as Rhl did not. After 48 and 72 hours Rh2, Rhl and dexamathasone similarly increased apoptosis, but these effects were significantly (P<0.05) lower than observed for both PD and PI treatments. Furthermore, treatments that produced the largest build up of apoptotic cells were also found to have the largest release of lactate dehydrogenase (LDH). It can be concluded from these studies that the presence of sugars to PD and PI aglycone structure reduces the potency to induce apoptosis, and alternately alter membrane integrity. These cytotoxic effects to THP-l cells were different from dexamethasone.

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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.

Fabrication of Pd/NiCr gate MISFET sensor for detecting hydrogen dissolved in Oil. (유중 용존수소 감지를 위한 Pd/NiCr 게이트 MISFET 센서의 제작)

  • Kim, Gop-Sick;Lee, Jae-Gon;Hahm, Sung-Ho;Choi, Sie-Young
    • Journal of Sensor Science and Technology
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    • v.6 no.3
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    • pp.221-227
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    • 1997
  • The Pd/NiCr gate MISFET-type sensors were fabricated for detecting hydrogen dissolved in high-capacivity transformer oil. To improve stability and high concentration sensitivity of the sensor, Pd/NiCr double catalysis metal gate was used. To reduce the serious gate voltage drift of the sensor induced by hydrogen, the gate insulators of 2 FETs were constructed with double layer of silicon dioxide and silicon nitride. The hydrogen sensitivity of the Pd/NiCr gate MISFET is about a half of Pd/Pt gate MISFET's sensitivity but the Pd/NiCr gate MISFET has good stability and high concentration detectivity up to 1000 ppm.

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Catalytic Reactivity of Transition Metal (Pd, Ni) complexes with Aminophosphines; I. Carbon-Carbon coupling reactions (Aminophosphine류가 배위된 전이금속(Pd, Ni) 착물의 촉매반응; I. 탄소-탄소 짝지움 반응)

  • Jung, Maeng-Joon;Lee, Chul-Jae;Kim, Dong-Yeub
    • Journal of the Korean Society of Industry Convergence
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    • v.7 no.1
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    • pp.107-113
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    • 2004
  • Several transition metal complexes, [$M(L)X_2$](M=Pd(II), Ni(II); X=CI, Br) are prepared with aminophosphine ligands such as 1,2-bis{(diphenylphosphino)amino}ethane{$Ph_2PNHCH_2CH_2NHPPh_2$}($L_1$), 1,2-bis{(diphenylphosphino)amino}propane{$Ph_2PNHCH(CH_3)CH_2NHPPh_2$}($L_2$), trans-1,2-bis{(diphenylphosphino)amino}cyclohexane{$Ph_2PNHC_6H_{10}NHPPh_2$}($L_3$) and 1,2-bis{(diphenylphosphino)amino}benzene{$Ph_2PNHC_6H_4NHPPh_2$}($L_4$). The properties of these complexes are characterized by optical spectroscopic methods including UV/vis spectroscopy, CD, IR, $^1H$- and $^{31}P-NMR$ together with conductometer and elemental analysis. All complexes are stable under atmospheric environment. Catalytic reactivity for C-C coupling between [$M(L)X_2$] and Grignard reagents(RMgX; R=phenyl, propyl, buthyl) by thermolysis were investigated utilizing GC/mass, $^1H$- and $^{13}C-NMR$. When mol scale is 1:20 at [$Pd(L)Cl_2$] and Grignard reagents, the high catalytic activity for C-C coupling is apparent. The [$M(L)X_2$](X=Cl, Br) complexes which have strong bond at M-P exhibit high yields for C-C coupling reactions. When the central metal ion is Pd(II), the high catalytic activity for C-C coupling is apparent. The complex coordinated with Br shows higher catalytic activity for C-C coupling reactions compared to Cl.

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The Effect of Au Addition on the Hardening Mechanism in Ag-25wt% Pd-15wt% Cu (Ag-25wt% Pd-15wt% Cu 3원합금(元合金) 및 Au 첨가합금(添加合金)의 시효경화특성(時效京華特性))

  • Bea, B.J.;Lee, H.S.;Lee, K.D.
    • Journal of Technologic Dentistry
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    • v.20 no.1
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    • pp.37-49
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    • 1998
  • The specimens used were Ag-25 Pd-15 Cu ternary alloy and Au addition alloy. These alloys were melted and casted by induction electric furnace and centrifugal casting machine in Ar atmosphere. These specimens were solution treated for 2hr at $800^{\circ}C$ and were then quenched into iced water, and aged at $350{\sim}550^{\circ}C$ Age- hardening characteristics of the small Au-containing Ag-Pd-Cu dental alloys were investigated by means of hardness testing. X-ray diffraction and electron microscope observations, electrical resistance, ergy dispersed spectra and electron probe microanalysis. Principal results are as follows : Hardening occured in two stages, i.e., stage I in low temperature and stage II in high temperature regions, during continuous aging. The case of hardening in stage I was due to the formation of the $L1_0$ type face-centered tetragonal PdCu-ordered phase in the grain interior and hardening in stage I was affected by the Cu concentration. In stage II, decomposition of the ${\alpha}$ solid solution to a PdCu ordered phase($L1_0$ type) and an Ag-rich ${\alpha}2$ phase occurred and a discontinuous precipitation occurred at the grain boundary. From the electron microscope study, it was conclued that the cause of age-hardening in this alloy is the precipitation of the PdCu ordered phase, which has AuCu I type face-centered tetragonal structure. Precipetation procedure was ${\alpha}{\to}{\alpha}+{\alpha}_2+PdCu {\to}{\alpha}_1+{\alpha}_2+PdCu$ at Pd/Cu = 1.7 Ag-Pd-Cu alloy is more effective dental alloy as ageing treatment and is suitable to isothermal ageing at $450^{\circ}C$.

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Preparation of Electromagnetic Wave Shielding Fabrics by Electroless Silver Plating using PdCl2 and Dextrose (포도당 환원제와 PdCl2 촉매를 사용한 무전해 은도금 PET 직물의 제조)

  • Kim, Su-Mi;Song, Wha-Soon
    • Journal of the Korean Society of Clothing and Textiles
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    • v.32 no.2
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    • pp.319-327
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    • 2008
  • The purpose of this study is to propose the development of high quality electromagnetic wave shielding fabrics. Silver nitrate is used for polyester fabric as an electromagnetic wave shielding material. The effects of activators and electroless silver plating condition on the evenness and adhesion of silver to fabrics, are observed through the SEM micrographs. Surface morphology and wash-ability are measured using SEM. The results are as follows: The optimum weight loss by alkaline hydrolysis of polyester fabrics is about 20%. The optimum concentration of $SnCl_2$ and $PdCl_2$in catalyst reaction using $PdCl_2$ as an activator is 2.5g/L and 0.5g/L, respectively. The optimum concentration of dextrose to improve adhesion between the silver plating and fabrics is 45g/L. The optimum concentration of silver nitrate in the catalyst reaction, using $PdCl_2$ as an activator is 56g/L, respectively. The optimum plating temperature and time are $15^{\circ}C$ and 30minutes, respectively.

Synthesis and Characterization of Palladium (IV) Complexes with Guanine, Adenine, and Uracil Base (Guanine, Adenine 및 Uracil 염기를 갖는 팔라듐 (IV) 착물의 합성과 그 성질)

  • Oh Sang Oh;Chung Duck Young;Kim Hee Seon
    • Journal of the Korean Chemical Society
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    • v.36 no.5
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    • pp.679-684
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    • 1992
  • New Pd(IV) complexes have been prepared through the reactions of $trans-[Pd(en)_2Cl_2](ClO_4)_2 $(en = ethylenediamine) with Guanine, Adenine, or Uracil anion as purine and pyrimidine base. We identified the ratio of central metal versus ligands by $C{\cdot}H{\cdot}N$ elemental analysis and proposed the coordinating site of the base by infrared spectrum, $^1H-NMR,\; and\; ^{13}C$-NMR spectrum. Guanine or Adenine ligand coordinated at N7 site and an en ligand exchanged for $ClO_4^-$ counter ions of the starting material . As these results, the complexes showed the formula $[Pd(en)L_2(ClO_4)_2](ClO_4)_2{\cdot}(en)$, (L = Guanine, Adenine). But in the Uracil complex no exchange of the en ligand and $ClO_4^-$ occured and Uracil anion preferred the N1 to N3 as coordinating site, the complex $[Pd(en)_2(Urac)_2](ClO_4)_2(Urac = Uracil anion).$

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