• Title/Summary/Keyword: PD-1/PD-L1

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The Effect of Electron-withdrawing Group Functionalization on Antibacterial and Catalytic Activity of Palladium(II) Complexes

  • Feng, Zhi-Qiang;Yang, Xiao-Li;Ye, Yuan-Feng;Hao, Lin-Yun
    • Bulletin of the Korean Chemical Society
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    • v.35 no.4
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    • pp.1121-1127
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    • 2014
  • The design, synthesis, and structural characterization of two new palladium complexes based on Schiff base ligands is reported; $[Pd(L1)_2]$ (1) and $[Pd(L2)_2]$ (2), [HL1 = 2-((E)-(2,6-diethylphenylimino)methyl)-4,6-dibromophenol, L2 = (E)-N-benzylidene-2,6-diethylbenzenamine], which are obtained by functionalizing Schiff base ligands with or without electron-withdrawing groups. Both compounds are mononuclear structures. Comparisons are made to the compounds 1 and 2 to analyze and understand the effect of electron-withdrawing groups. Antibacterial activity studies indicate the electron-withdrawing groups on Schiff base ligands enhance antibacterial activity. Catalytic activity, however, is reduced due to the enhanced steric-hindrance of the electron-withdrawing groups. Electronic absorption and emission properties of HL1, L2, 1 and 2 are also reported.

Syntheses and Theoretical Study of Palladium(II) Complexes with Aminophosphines as 7-Membered Chelate Rings

  • 김봉곤;양기열;정맹준;이배욱;도명기
    • Bulletin of the Korean Chemical Society
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    • v.18 no.11
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    • pp.1162-1166
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    • 1997
  • Nature of palladium(Ⅱ) complexes with 7-membered chelates was studied by experimental and theoretical methods on a Pd(L)Cl2 system, where L is Ph2PNHCH2CH2NHPPh2(L1), Ph2PNHC6H4NHPPh2(L2). The palladium(Ⅱ) complexes were prepared and characterized by elemental analysis, IR, UV, 1H, and 31P NMR spectroscopy. Ab initio calculations with geometry optimizations were also performed for related model systems, Pd(L)Cl2; L=R2PNH(CH2)2NHPR2(L3), R2PNHC6H4NHPR2(L4), R2P(CH2)4PR2(L5), R2PCH2(C6H4)CH2PR2(L6); R=H, CH3.

Emerging Targets for Systemic Treatment of Gastric Cancer: HER2 and Beyond

  • In-Ho Kim
    • Journal of Gastric Cancer
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    • v.24 no.1
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    • pp.29-56
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    • 2024
  • In recent years, remarkable progress has been made in the molecular profiling of gastric cancer. This progress has led to the development of various molecular classifications to uncover subtype-specific dependencies that can be targeted for therapeutic interventions. Human epidermal growth factor receptor 2 (HER2) is a crucial biomarker for advanced gastric cancer. The recent promising results of novel approaches, including combination therapies or newer potent agents such as antibody-drug conjugates, have once again brought attention to anti-HER2 targeted treatments. In HER2-negative diseases, the combination of cytotoxic chemotherapy and programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors has become the established standard of care in first-line settings. In the context of gastric cancer, potential biomarkers such as PD-L1 expression, Epstein-Barr virus, microsatellite instability, and tumor mutational burden are being considered for immunotherapy. Recently, promising results have been reported in studies on anti-Claudin18.2 and fibroblast growth factor receptor 2 treatments. Currently, many ongoing trials are aimed at identifying potential targets using novel approaches. Further investigations will be conducted to enhance the progress of these therapies, addressing challenges such as primary and acquired resistance, tumor heterogeneity, and clonal evolution. We believe that these efforts will improve patient prognoses. Herein, we discuss the current evidence of potential targets for systemic treatment, clinical considerations, and future perspectives.

The Optimal Tumor Mutational Burden Cutoff Value as a Novel Marker for Predicting the Efficacy of Programmed Cell Death-1 Checkpoint Inhibitors in Advanced Gastric Cancer

  • Jae Yeon Jang;Youngkyung Jeon ;Sun Young Jeong ;Sung Hee Lim ;Won Ki Kang;Jeeyun Lee ;Seung Tae Kim
    • Journal of Gastric Cancer
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    • v.23 no.3
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    • pp.476-486
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    • 2023
  • Purpose: The optimal tumor mutational burden (TMB) value for predicting treatment response to programmed cell death-1 (PD-1) checkpoint inhibitors in advanced gastric cancer (AGC) remains unclear. We aimed to investigate the optimal TMB cutoff value that could predict the efficacy of PD-1 checkpoint inhibitors in AGC. Materials and Methods: Patients with AGC who received pembrolizumab or nivolumab between October 1, 2020, and July 27, 2021, at Samsung Medical Center in Korea were retrospectively analyzed. The TMB levels were measured using a next-generation sequencing assay. Based on receiver operating characteristic curve analysis, the TMB cutoff value was determined. Results: A total 53 patients were analyzed. The TMB cutoff value for predicting the overall response rate (ORR) to PD-1 checkpoint inhibitors was defined as 13.31 mutations per megabase (mt/Mb) with 56% sensitivity and 95% specificity. Based on this definition, 7 (13.2%) patients were TMB-high (TMB-H). The ORR differed between the TMB-low (TMB-L) and TMB-H (8.7% vs. 71.4%, P=0.001). The progression-free survival and overall survival (OS) for 53 patients were 1.93 (95% confidence interval [CI], 1.600-2.268) and 4.26 months (95% CI, 2.992-5.532). The median OS was longer in the TMB-H (20.8 months; 95% CI, 2.292-39.281) than in the TMB-L (3.31 months; 95% CI, 1.604-5.019; P=0.049). Conclusions: The TMB cutoff value for predicting treatment response in AGC patients who received PD-1 checkpoint inhibitor monotherapy as salvage treatment was 13.31 mt/Mb. When applying the programmed death ligand-1 status to TMB-H, patients who would benefit from PD-1 checkpoint inhibitors can be selected.

Construction of a Genetic System for Streptomyces albulus PD-1 and Improving Poly(ε-ʟ-lysine) Production Through Expression of Vitreoscilla Hemoglobin

  • Xu, Zhaoxian;Cao, Changhong;Sun, Zhuzhen;Li, Sha;Xu, Zheng;Feng, Xiaohai;Xu, Hong
    • Journal of Microbiology and Biotechnology
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    • v.25 no.11
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    • pp.1819-1826
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    • 2015
  • Poly(ε-ʟ-lysine) (ε-PL) is a novel bioactive polymer secreted by filamentous bacteria. Owing to lack of a genetic system for most ε-PL-producing strains, very little research on enhancing ε-PL biosynthesis by genetic manipulation has been reported. In this study, an effective genetic system was established via intergeneric conjugal transfer for Streptomyces albulus PD-1, a famous ε-PL-producing strain. Using the established genetic system, the Vitreoscilla hemoglobin (VHb) gene was integrated into the chromosome of S. albulus PD-1 to alleviate oxygen limitation and to enhance the biosynthesis of ε-PL in submerged fermentation. Ultimately, the production of ε-PL increased from 22.7 g/l to 34.2 g/l after fed-batch culture in a 5 L bioreactor. Determination of the oxygen uptake rate, transcriptional level of ε-PL synthetase gene, and ATP level unveiled that the expression of VHb in S. albulus PD-1 enhanced ε-PL biosynthesis by improving respiration and ATP supply. To the best of our knowledge, this is the first report on enhancing ε-PL production by chromosomal integration of the VHb gene in an ε-PL-producing strain, and it will open a new avenue for ε-PL production.

Oxidative Modification of Neurofilament-L by the Cytochrome c and Hydrogen Peroxide System

  • Kang, Jung-Hoon
    • Bulletin of the Korean Chemical Society
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    • v.28 no.1
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    • pp.77-80
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    • 2007
  • As neurofilament proteins are major cytoskeletal components of neuron, abnormality of neurofilament is proposed in brain with neurodegenerative disorders such as Parkinson's disease (PD). Since oxidative stress might play a critical role in altering normal brain proteins, we investigated the oxidative modification of neurofilament-L (NF-L) induced by the reaction of cytochrome c with H2O2. When NF-L was incubated with cytochrome c and H2O2, the protein aggregation was increased in cytochrome c and H2O2 concentrationsdependent manner. Radical scavengers, azide, formate and N-acetyl cysteine, prevented the aggregation of NFL induced by the cytochrome c/H2O2 system. The formations of carbonyl group and dityrosine were obtained in cytochrome c/H2O2-mediated NF-L aggregates. Iron specific chelator, desferoxamine, prevented the cytochrome c/H2O2 system-mediated NF-L aggregation. These results suggest that the cytochrome c/H2O2 system may be related to abnormal aggregation of NF-L which may be involved in the pathogenesis of PD and related disorders.

Characteristics of Pd-MIS devices on hydrogen gas sensing (Pd-MIS 소자의 수소가스 검지 특성)

  • Yi, Cheal W.;Cha, Won I.;Shin, Chee B.;Yun, Kyung S.;Ju, Jeh B.
    • Transactions of the Korean hydrogen and new energy society
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    • v.3 no.2
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    • pp.17-24
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    • 1992
  • Hydrogen gas sensors were fabricated after the form of metal/insulator/semiconductor(MIS) structure on a p-type silicon wafer and a insulating layer (silicon dioxide) thickness was changed from $500{\AA}$ to $5000{\AA}$. Their electrical properties were investigated with the variation of the hydrogen gas concentration at room temperature. At the applied forward bias of lV to both ends of Pd-MIS sensors the current was decreased logarithmically with the increase of hydrogen concentration in air. In the case of a thin $SiO_2$ layered ($500{\AA}$) sensor the current ratio was decreased to 25 % at 1 % of hydrogen concentration in air and 50% for a thick $SiO_2$ layered ($5000{\AA}$) sensor. And the response time of the thick insulating layered sensor to 1% hydrogen containing air was about 50 seconds and regeneration time was 2.5 minutes. When a 0.5mA current was appied to the thick insulating layered sensor the maximun voltage shift was calculated to 0.8V in the case of ${\theta}$ = 1 and the Pd surface coverage of hydrogen was increased logarithmically with hydrogen partial pressure.

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SOME RESULTS RELATED WITH POISSON-SZEGÖKERNEL AND BEREZIN TRANSFORM

  • Yang, Gye Tak;Choi, Ki Seong
    • Journal of the Chungcheong Mathematical Society
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    • v.24 no.3
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    • pp.417-426
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    • 2011
  • Let ${\mu}$ be a finite positive Borel measure on the unit ball $B{\subset}{\mathbb{C}}^n$ and ${\nu}$ be the Euclidean volume measure such that ${\nu}(B)=1$. For the unit sphere $S=\{z:{\mid}z{\mid}=1\}$, ${\sigma}$ is the rotation-invariant measure on S such that ${\sigma}(S) =1$. Let ${\mathcal{P}}[f]$ be the Poisson-$Szeg{\ddot{o}}$ integral of f and $\tilde{\mu}$ be the Berezin transform of ${\mu}$. In this paper, we show that if there is a constant M > 0 such that ${\int_B}{\mid}{\mathcal{P}}[f](z){\mid}^pd{\mu}(z){\leq}M{\int_B}{\mid}{\mathcal{P}}[f](z){\mid}^pd{\nu}(z)$ for all $f{\in}L^p(\sigma)$, then ${\parallel}{\tilde{\mu}}{\parallel}_{\infty}{\equiv}{\sup}_{z{\in}B}{\mid}{\tilde{\mu}}(z){\mid}<{\infty}$, and we show that if ${\parallel}{\tilde{\mu}{\parallel}_{\infty}<{\infty}$, then ${\int_B}{\mid}{\mathcal{P}}[f](z){\mid}^pd{\mu}(z){\leq}C{\mid}{\mid}{\tilde{\mu}}{\mid}{\mid}_{\infty}{\int_S}{\mid}f(\zeta){\mid}^pd{\sigma}(\zeta)$ for some constant C.

Estimation of Rumen Microbial Protein Supply Using Urinary Purine Derivatives Excretion in Crossbred Calves Fed at Different Levels of Feed Intake

  • Singh, M.;Sharma, K.;Dutta, N.;Singh, P.;Verma, A.K.;Mehra, U.R.
    • Asian-Australasian Journal of Animal Sciences
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    • v.20 no.10
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    • pp.1567-1574
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    • 2007
  • A study was carried out to study the response of total purine derivatives (PD) excretion in urine to determine microbial N (MN) supply at four fixed levels of feed intake (namely 95, 80, 60 and 40% of voluntary intake). The crossbred (CB) calves were allocated according to a $4{\times}4$ Latin Square Design and fed wheat straw and concentrate (1:1). The rate of PD excretion (mmol/d) as a linear function of feed intake was 15.85/kg DMI and 20.12/kg DOMI. Based on the endogenous and PD excretion rates obtained in this study, a relationship between daily urinary PD excretion (Y, mmol) and daily microbial protein supply (X, mmol) was developed for crossbred calves as Y = 0.83X+0.296 kg $W^{0.75}$. The derived microbial N values using this equation differed (p<0.001) among the 4 groups and was the highest in L-95 followed by L-80, L-60 and L-40. The relationship between urinary nitrogen loss (Y, g/d) and DOMI (X, kg/d) was established as: Y = 6.038X+21.753 ($r^2$ = 0.663, p<0.01). When urinary excretion of PD (Y, mmol/d) was plotted against intake of DM and DOM (X, kg/d), the equations obtained were: Y = 7.1711X+8.674 ($r^2$ = 0.889, p<0.01) and Y = 12.434X+7.683 ($r^2$ = 0.896, p<0.01), respectively. The proportional contribution of allantoin and uric acid to total PD remained stable irrespective of level of feed intake. Similarly, urinary excretion of creatinine did not differ (p>0.05) between animals fed at different levels. The MN supply was the highest to animals at intake levels L-95, and decreased linearly with corresponding decrease in feed intake. However, the MN supply when expressed per kg DOMI remained statistically (p>0.05) similar irrespective of level of intake. The results revealed that the excretion of urinary purine derivatives were positively correlated with the level of feed intake as well as rumen microbial supply and thus it could be a good indicator for measuring the microbial protein supply and nutritional status of animals.

NOTES ON CARLESON TYPE MEASURES ON BOUNDED SYMMETRIC DOMAIN

  • Choi, Ki-Seong
    • Communications of the Korean Mathematical Society
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    • v.22 no.1
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    • pp.65-74
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    • 2007
  • Suppose that $\mu$ is a finite positive Borel measure on bounded symmetric domain $\Omega{\subset}\mathbb{C}^n\;and\;\nu$ is the Euclidean volume measure such that $\nu(\Omega)=1$. Suppose 1 < p < $\infty$ and r > 0. In this paper, we will show that the norms $sup\{\int_\Omega{\mid}k_z(w)\mid^2d\mu(w)\;:\;z\in\Omega\}$, $sup\{\int_\Omega{\mid}h(w)\mid^pd\mu(w)/\int_\Omega{\mid}h(w)^pd\nu(w)\;:\;h{\in}L_a^p(\Omega,d\nu),\;h\neq0\}$ and $$sup\{\frac{\mu(E(z,r))}{\nu(E(z,r))}\;:\;z\in\Omega\}$$ are are all equivalent. We will also show that the inclusion mapping $ip\;:\;L_a^p(\Omega,d\nu){\rightarrow}L^p(\Omega,d\mu)$ is compact if and only if lim $w\rightarrow\partial\Omega\frac{\mu(E(w,r))}{\nu(E(w,r))}=0$.