• Title/Summary/Keyword: PD-1

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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.

PD-L1 expression correlated with p53 expression in oral squamous cell carcinoma

  • Tojyo, Itaru;Shintani, Yukari;Nakanishi, Takashi;Okamoto, Kenjiro;Hiraishi, Yukihiro;Fujita, Shigeyuki;Enaka, Mayu;Sato, Fuyuki;Muragaki, Yasuteru
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.41
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    • pp.56.1-56.6
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    • 2019
  • Background: Programmed cell death ligand 1 (PD-L1) is an immune checkpoint molecule that attenuates the immune response. PD-L1 contributes to failed antitumor immunity; thereby, blockade of PD-L1 with monoclonal antibody enhances the immune response. Recently, it was reported that PD-L1 was regulated by protein 53 (p53). Besides, cytokeratin 17 (CK17) is thought to be a diagnostic marker of oral squamous cell carcinoma (OSCC). Our aim was to evaluate the correlation between the immunohistochemical expression of PD-L1, p53 and CK17 with clinicopathological characteristics and disease-specific survival in patients with OSCC. Methods: A total of 48 patients with OSCC were included in this study. Immunohistochemical staining was performed to evaluate the correlation among the expressions of PD-L1, p53 and CK17, and furthermore the correlation among various clinicopathological factors, PD-L1, p53 and CK17. Results: The positive rate of p53, CK17, PD-L1 (tumor cells) and PD-L1 (tumor-infiltrating lymphocytes) was 63.2%, 91.7%, 48.9% and 57.1%. A statistically significant correlation between p53 expression and T stage and TNM stage (p = 0.049, p = 0.03, respectively) was observed. Also, a statistically significant correlation between p53 and PD-L1 (TCs) expression (p = 0.0009) was observed. Five-year disease-specific survival rate was not significantly correlated with gender, TNM stage, p53 expression, PD-L1 expression and CK17 expression. Conclusion: The expression of p53 and PD-L1 shows significantly positive correlation in oral squamous cell carcinoma in tumor cells. Also, a significant correlation between p53 expression and T stage and TNM stage was observed. No other significant correlation between PD-L1 staining or CK17 and clinical or pathologic characteristics was identified.

A Study on the Ohmi Ccontact Characteristics of Au-Pd-Ge System to (n)GaAs by Hot Plate Sintering (핫플래이트 소결에 의한 (n)GaAs에 Au-Pd-Ge계의 음성접촉 특성에 관한 연구)

  • 박창엽;남춘우;소지영
    • Electrical & Electronic Materials
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    • v.1 no.3
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    • pp.251-260
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    • 1988
  • n형 GaAs에 음성접촉을 형성함에 있어서 Au-Ge 공융합금을 용해시키는 alloying 보다는 sintering을 필요로 하는 Su-Pd-Ge계의 새로운 융성접촉을 도입하였다. Au-Pd-Ge계의 최적의 음성조건을 조사하기 위하여 Au/Pd/Ge, Au/Ge/Pd, Au/Pd/Ge/Pd 그리고 Au/Pd/Au/Ge 음성접촉을 제조하였다. 비접촉저항을 조사하는데 있어서 sintering 온도는 390-450.deg.C사이였고 시간은 30초에서 6분 사이였다. Au-Pd-Ge계의 비접촉저항은 alloying된 Au/Pd/Ge 접촉의 그것에 필적할 만큼 낮았으며 특히 Au/Ge/Pd 접촉은 430.deg.C, 3분의 sintering 조건에서 가장 낮은 1.2*$10^{-6}$.OMEGA..$cm^{2}$의 비접촉저항을 나타냈다. Au/Ge/Pd 접촉의 표면형상 및 접촉패턴 가장자리는 450.deg.C에서 2분 이상 sintering된 접촉을 제외하고는 sintering 후에 as-deposited 상태와 다를 바가 없었다. 430.deg.C, 3분 sintering에서 가장 낮은 비접촉저항을 나타낸 Au/Ge/Pd 접촉의 비접촉저항은 430.deg.C에서 Ge/Pd 두께 변화에 비교적 변화가 적었다.

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Geometrical Characteristics and Atomic Charge Variations of Pd(II) Complexes [Pd(L)Cl2] with an Axial (Pd·O) Interaction

  • Park, Jong-Keun;Cho, Yong-Guk;Lee, Shim-Sung;Kim, Bong-Gon
    • Bulletin of the Korean Chemical Society
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    • v.25 no.1
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    • pp.85-89
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    • 2004
  • Geometrical structures of [Pd(L)$Cl_2$] with oxathia macrocycles have been calculated using ab initio secondorder Moller-Plesset (MP2) and Density Functional Theory (DFT) methods with triple zeta plus polarization (TZP) basis set level. In optimized Pd(L)$Cl_2$ complexes, Pd(II) locates at the center surrounded by a square planar array of two sulfurs on an oxathia macrocycle and two chlorides. The endo-Pd(II) complexes with an axial (Pd${\cdots}$O) interaction are more stable than the exo-Pd(II) complexes without the interaction. In the endo-Pd(II) complexes, the atomic charge of the oxygen atom moves to Pd(II) via the axial ($Pd{\cdots}$O) interaction and then, the charge transfer from Pd(II) to the S-atoms occurs stepwise via ${\pi}$-acceptors of the empty d-orbitals.

Phase Equilibria of the System Pd-Sb-Te and Its Geological Implications (팔라듐-안티몬-테루르 계(系)의 상평형(相平衡)과 지질학적(地質學的) 의의(意義))

  • Kim, Won-Sa;Chao, George Y.
    • Economic and Environmental Geology
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    • v.26 no.3
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    • pp.327-335
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    • 1993
  • Phase relations in the system Pd-Sb-Te were investigated at $1000^{\circ}$, $800^{\circ}$, and $600^{\circ}C$, using the sealed-capsule technique; the quenched products were studied by reflected light microscopy, X-ray diffraction, and electron microprobe analysis. At $1000^{\circ}C$, the solid phases Pd, $Pd_{20}Sb_7$, $Pd_8Sb_3$, $Pd_{31}Sb_{12}$, and $Pd_5Sb_2$ are stable with a liquid phase that occupies most of the isothermal diagram. Additional solid phases at $800^{\circ}C$ are $Pd_5Sb_3$, PdSb, $Pd_8Te_3$, $Pd_7Te_3$, and a continuous $Pd_{20}Te_7-Pd_{20}Sb_7$ solid solution becomes stable. At $600^{\circ}$, $PdSb_2$, $Pd_{17}Te_4$, $Pd_9Te_4$, PdTe, $PdTe_2$, $Sb_2Te_3$, and Sb and continuous PdSb-PdTe and $PdTe-PdTe_2$ solid solutions are stable. All the solid phases exhibit solid solution, mainly by substitution between Sb and Te to an extent that varies with temperature of formation. The maximum substitution (at.%) of Te for Sb in the Pd-Sb phases is: 44.3 in $Pd_8Sb_3$, 52.0 in $Pd_{31}Sb_{12}$, 46.2 in $Pd_5Sb_2$ at $800^{\circ}C$; 15.3 in $Pd_5Sb_3$, 68.3 in $PdSb_2$ at $600^{\circ}C$. The maximum substitution (at.%) of Sb for Te in the Pd-Te phases is 34.5 in $Pd_5Sb_3$ at $800^{\circ}C$, and 41.6 in $Pd_7Te_3$, 5.2 in $Pd_{17}T_4$, 12.4 in $Pd_9Te_4$, and 19.1 in $PdTe_2$ at $600^{\circ}C$. Physical properties and X-ray data of the synthetic $Pd_9Te_4$, PdTe, $PdTe_2$, $Pd_8Sb_3$, PdSb, and $Sb_2Te_3$ correspond very well with those of telluropalladinite, kotulskite, merenskyite, mertieite II, sudburyite, and tellurantimony, respectively. Because X-ray powder diffraction data consistently reveal a 310 peak ($2.035{\AA}$), the $PdSb_2$ phase is most probably of cubic structure with space group $P2_13$. The X-ray powder pattern of a phase with PdSbTe composition, synthesized at $600^{\circ}C$, compares well with that of testibipalladite. Therefore, testibiopalladite may be a member of the $PdSb_2-Pd(Sb_{0.32}Te_{0.68})$ solid solution series which is cubic and $P2_13$ in symmetry. Thus the ideal fonnula for testibiopalladite, presently PdSbTe, must be revised to PdTe(Sb, Te). Borovskite($pd_3SbTe_4$) has not been found in the synthetic system in the temperature range $1000^{\circ}-600^{\circ}C$.

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Reconstructed Adeno-Associated Virus with the Extracellular Domain of Murine PD-1 Induces Antitumor Immunity

  • Elhag, Osama A.O.;Hu, Xiao-Jing;Wen-Ying, Zhang;Li, Xiong;Yuan, Yong-Ze;Deng, Ling-Feng;Liu, De-Li;Liu, Ying-Le;Hui, Geng
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.8
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    • pp.4031-4036
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    • 2012
  • Background: The negative signaling provided by interactions of the co-inhibitory molecule, programmed death-1 (PD-1), and its ligands, B7-H1 (PD-L1) and B7-DC (PD-L2), is a critical mechanism contributing to tumor evasion; blockade of this pathway has been proven to enhance cytotoxic activity and mediate antitumor therapy. Here we evaluated the anti-tumor efficacy of AAV-mediated delivery of the extracellular domain of murine PD-1 (sPD-1) to a tumor site. Material and Methods: An rAAV vector was constructed in which the expression of sPD-1, a known negative regulator of TCR signals, is driven by human cytomegalovirus immediate early promoter (CMV-P), using a triple plasmid transfection system. Tumor-bearing mice were then treated with the AAV/sPD1 construct and expression of sPD-1 in tumor tissues was determined by semi quantitative RT-PCR, and tumor weights and cytotoxic activity of splenocytes were measured. Results: Analysis of tumor homogenates revealed sPD-1 mRNA to be significantly overexpressed in rAAV/sPD-1 treated mice as compared with control levels. Its use for local gene therapy at the inoculation site of H22 hepatoma cells could inhibit tumor growth, also enhancing lysis of tumor cells by lymphocytes stimulated specifically with an antigen. In addition, PD-1 was also found expressed on the surfaces of activated CD8+ T cells. Conclusion: This study confirmed that expression of the soluble extracellular domain of PD-1 molecule could reduce tumor microenvironment inhibitory effects on T cells and enhance cytotoxicity. This suggests that it might be a potential target for development of therapies to augment T-cell responses in patients with malignancies.

Phase Constitution of the Palladium and Tellurium System (팰래듐과 테루리움계의 상평형 연구)

  • ;G.Y.Chao, L.J.Cabri
    • Korean Journal of Crystallography
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    • v.1 no.2
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    • pp.66-75
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    • 1990
  • The Pd-Te system has been investigated by differential thermal analysis, X-ray diffration, electron probe microanalysis and reflected light microscopy. New phase relations in 0-50at% Te portion of the binary system are proposed. Eight binary phases exist in the system:Pd17Te4, Pd20Te7.PdsTe3, P477e3, P497e4, P637e2, PeTe and PaTe2. Of these, P677e3 is a newly reported phase. P4177e4 is cubic, space group Fd3c, with a=12.678(5)A. The X-ray powder data of PdsTe3, indexed on an orthorhombic cell, give a= 12.843(3), b=15.126(3), c: 11.304(2)A and those of PdTTe.1, indexed on a monoclinic cell, give a=7.444(1), b= 13.918(2) , c=8.873(2)A. p =92.46(2). Some physical and optical properties of synthetic phases in the system are also reported.

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Effects of Aging on Electrocatalytic Activities of Pt and Pd Nanoparticles

  • Dutta, Gorachand;Yang, Haesik
    • Journal of Electrochemical Science and Technology
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    • v.7 no.1
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    • pp.27-32
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    • 2016
  • Although the time dependences of the electrocatalytic activities of Pt and Pd nanoparticles during electrochemical operations have been widely studied, the time dependences under nonpolarized conditions have never been investigated in depth. This study reports the changes in the electrocatalytic activities of Pt and Pd nanoparticles with aging in air and in solution. Pt (or Pd) nanoparticle-modified electrodes are obtained by adsorbing citrate-stabilized Pt (or Pd) nanoparticles on amine-modified indium-tin oxide (ITO) electrodes, or by electrodeposition of Pt (or Pd) nanoparticles on ITO electrodes. The electrocatalytic activities of freshly prepared Pt and Pd nanoparticles in the oxygen reduction reaction slowly decrease with aging. The electrocatalytic activities decrease more slowly in solution than in air. An increase in surface contamination may cause electrocatalytic deactivation during aging. The electrocatalytic activities of long-aged Pt (or Pd) nanoparticles are significantly enhanced and recovered by NaBH4 treatment.

Usage Patterns and Incidence of Thyroid-related Adverse Events in Patients Treated with PD-1 Inhibitors (PD-1 억제제의 사용패턴 및 갑상선 관련 유해사례 발현 양상 분석)

  • Hwang, Seoyoung;Kim, Heuijae;Chung, Seonyoung;Min, Myungsook;Suh, Dong-Churl
    • Korean Journal of Clinical Pharmacy
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    • v.31 no.3
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    • pp.188-197
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    • 2021
  • Objective: PD-1 inhibitors have demonstrated improved health outcomes in cancer patients. PD-1 inhibitors are well-tolerated and associated with immune-related adverse events. The objectives of this study are to analyze use patterns of PD-1 inhibitors in patients with cancer and to investigate the incidence of thyroid-related adverse reactions in patients treated with PD-1 inhibitors. Methods: The study included patients who had been administered PD-1 inhibitors (either nivolumab or pembrolizumab) at the Samsung Medical Center between October 1, 2016 and June 30, 2017. Data was collected from electronic medical records and tested using Mann-Whitney tests and Chi-Square tests for statistical significance. Associations between PD-1 inhibitors and incidence of adverse events were tested using Cox regression for age, gender, BMI, ECOG PS and medication. Results: Two hundred fifteen patients were identified as eligible for analyses. Thyroid-related adverse events occurred in 20% of patients (n=43). Thyroid function tests (TFTs) was performed in 109 patients (50.7%). Positive results of PD-L1 testing were found in 53.2% of the 94 patients who had the test. Approved doses of nivolumab (3 m/kg) and pembrolizumab (200 mg) were administered in 70.4% and 53% of patients, respectively. The analysis of risk factor of thyroid-related adverse reaction did not show statistically significant differences (Cox regression). Conclusion: Thyroid-related adverse events are common in patients treated with PD-1 inhibitors and hypothyroidism is the most frequent adverse reaction. Routine TFTs monitoring is strongly recommended to evaluate thyroid function in real-world clinical practice.

Optimization of Culture Conditions for 1,3-propanediol Production from Glycerol Using Klebsiella pneumoniae (글리세롤로부터 1,3-propanediol 생산을 위한 Klebsiella pneumoniae 배양 조건 최적화)

  • Jun, Sun-Ae;Kong, Sean W;Sang, Byoung-In;Um, Youngsoon
    • Korean Chemical Engineering Research
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    • v.47 no.6
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    • pp.768-774
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    • 2009
  • To improve the productivity of 1,3-propanediol(1,3-PD) with K. pneumoniae DSM4799 using pure glycerol and crude glycerol derived from the biodiesel process, optimizing fermentation conditions was performed by changing environmental factors such as anaerobic/aerobic condition, temperature, glycerol concentration, and pH. When anaerobic conditions were maintained, there was an improved 1,3-PD production compared with that from aerobic/anaerobic 2-stage fermentation. From the results with temperature $26{\sim}37^{\circ}C$, the higher 1,3-PD production yield was observed at $30{\sim}33^{\circ}C$. For an initial glycerol concentration higher than 60 g/L, cell growth and 1,3-PD production were inhibited. When crude glycerol was used, the initial 1,3-PD production appeared to be inhibited. After 48 hr of incubation, however, 1,3-PD production with crude glycerol was even higher than that with pure glycerol, demonstrating the feasibility of 1,3-PD production using crude glycerol as a substrate. Fed-batch fermentation was applied for the high concentration of 1,3-PD without substrate inhibition. By regulating pH at 7 during the fed-batch with glycerol lower than 40 g/L, the yield of 1,3-PD was 25% higher than that without pH regulation(0.56 g/g vs. 0.45 g/g). In conclusion, based on our results, anaerobic conditions, temperature at $30^{\circ}C$, pure or crude glycerol lower than 40 g/L, and pH regulation at 7 were the optimized conditions for 1,3-PD production using K. pneumoniae DSM4799, making it more feasible to produce 1,3-PD at higher concentration and a lower price.