• 제목/요약/키워드: PD-1/PD-L1

검색결과 306건 처리시간 0.028초

Analysis of Mutant Isocitrate Dehydrogenase 1 Immunoexpression, Ki-67 and Programmed Death Ligand 1 in Diffuse Astrocytic Tumours : Study of Single Center in Bandung, Indonesia

  • Bolly, Hendrikus Masang Ban;Faried, Ahmad;Hermanto, Yulius;Lubis, Billy Parulian;Tjahjono, Firman Priguna;Hernowo, Bethy Suryawathy;Arifin, Muhammad Zafrullah
    • Journal of Korean Neurosurgical Society
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    • 제64권1호
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    • pp.100-109
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    • 2021
  • Objective : Diffuse astrocytic tumour (DAT) is a diffuse infiltrative astrocytoma tumour accompanied by molecular parameters such as the presence or absence of isocitrate dehydrogenase (IDH) gene mutations. Ki-67 is a marker for DAT proliferation, while programmed death ligand 1 (PD-L1) indicates an immune evasion mechanism. This study aimed to analyze the correlation among mutant IDH1 R132H, Ki-67, and PD-L1 immunoexpression in the DAT. Methods : A cross-sectional study was carried out on 30 paraffin blocks of DAT cases. Paraffin block samples consist of grade II (n=14), grade III (n=8), and grade IV (n=8). In this study, the immunohistochemistry-staining of mutant IDH1 R132H, Ki-67, and PD-L1 were carried out to determine the frequency of DAT with IDH1 mutations. Results : Our study shown the frequency of IDH1 mutations in grade II 50.0% (7/14), grade III 37.5% (3/8), and grade IV 12.5% (1/8). Our study also showed a difference in Ki-67 and PD-L1 expression between each the degree of DAT histopathology (p=0.0001 and p=0.002, respectively). There was an association between both mutant IDH1 R132H, and Ki-67 with PD-L1 expression in DAT (p=0.0087 and p=0.0049, respectively). Conclusion : DAT with the mutant IDH1 is frequently observed in grade II and small number of grade III. The expression of wild type IDH1, Ki-67, and PD-L1 were found to be higher in high grade DAT (grade III and grade IV). There is a correlation between each of mutant IDH1 status and Ki-67 with PD-L1 expression in DAT.

Effects of Ni Addition on the Microstructures and Magnetic Properties of Fe70-xPd30Nix High-Temperature Ferromagnetic Shape Memory Alloys

  • Lin, Chien-Feng;Yang, Jin-Bin
    • Journal of Magnetics
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    • 제17권2호
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    • pp.86-95
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    • 2012
  • This study investigated the effects of adding a third alloying element, Ni, to create $Fe_{70-x}Pd_{30}Ni_x$ (x = 2, 4, 6, 8 at.% Ni) ferromagnetic shape memory alloys (FSMAs). The Ni replaced a portion of the Fe. The $Fe_{70-x}Pd_{30}Ni_x$ alloys were homogenized through hot and cold forging to gain a ~38% reduction in thickness, next they were solution-treated (ST) with annealing recrystallization at $1100^{\circ}C$ for 8 h and quenched in ice brine, and then aged at $500^{\circ}C$ for 100 h. Investigation of the microstructures and magnetostriction indicated that the greater Ni amount in the $Fe_{70-x}Pd_{30}Ni_x$ alloys reduced saturation magnetostriction at room temperature (RT). It was also observed that it was more difficult to generate annealed recrystallization. However, with greater Ni addition into the $Fe_{70-x}Pd_{30}Ni_x$ (x = 6, 8 at.% Ni) alloys, the $L1_0+L1_m$ twin phase decomposition into stoichiometric $L1_0+L1_m+{\alpha}_{bct}$ structures was suppressed after the $500^{\circ}C$/100 h aging treatment. The result was that the $Fe_{70-x}Pd_{30}Ni_x$ (x = 6, 8 at.% Ni) alloys maintained a high magnetostriction and magnetostrictive susceptibility (${\Delta}{\lambda}{_\parallel}{^s}/{\Delta}H$) after the alloys were aged at $500^{\circ}C$ for 100 h. This magnetic property of the $Fe_{70-x}Pd_{30}Ni_x$ (x = 6, 8 at.% Ni) alloys make it suitable for application in a high temperature (T > $500^{\circ}C$) and high frequency environments.

T-Cell Immunoglobulin Mucin 3 Expression on Tumor Infiltrating Lymphocytes as a Positive Prognosticator in Triple-Negative Breast Cancer

  • Byun, Kyung Do;Hwang, Hyo Jun;Park, Ki Jae;Kim, Min Chan;Cho, Se Heon;Ju, Mi Ha;Lee, Jin Hwa;Jeong, Jin Sook
    • Journal of Breast Cancer
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    • 제21권4호
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    • pp.406-414
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    • 2018
  • Purpose: T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) is an emerging immune response molecule related to T-cell anergy. There has been tremendous interest in breast cancer targeting immune checkpoint molecules, especially in the triple-negative breast cancer (TNBC). This study was designed to investigate TIM-3 expression on tumor infiltrating lymphocytes (TILs), its relationships with clinicopathological parameters and expression of programmed death receptor 1 (PD-1)/programmed death receptor ligand 1 (PD-L1), and its prognostic role. Methods: Immunohistochemistry on tissue microarray blocks produced from 109 samples of invasive ductal carcinoma type TNBC was performed with antibodies toward TIM-3, PD-1, PD-L1 and breast cancer-related molecular markers. Associations between their expression and clinicopathological parameters as well as survival analyses were performed. Results: TIM-3 was expressed in TILs from all 109 TNBCs, consisting of 17 cases (<5%), 31 cases (6%-25%), 48 cases (26%-50%), and 13 cases (>51%). High TIM-3 was significantly correlated with younger patients (p=0.0101), high TILs (p=0.0029), high tumor stage (p=0.0018), high PD-1 (p=0.0001) and high PD-L1 (p=0.0019), and tended to be associated with higher histologic grade, absence of extensive in situ components and microcalcification. High TIM-3 expression was significantly associated with a combinational immunophenotype group of high PD-L1 and high PD-1 (p<0.0001). High TIM-3 demonstrated a significantly better disease-free survival (DFS) (p<0.0001) and longer overall survival (OS) (p=0.0001), together with high TILs and high PD-1. In univariate survival analysis, high TIM-3 showed reduced relapse risk (p<0.0001) and longer OS (p=0.0003), together with high PD-1 expression. In multivariate analysis, high TIM-3 was statistically significant in predicting prognosis, showing better DFS (hazard ratio [HR], 0.0994; 95% confidence interval [CI], 0.0296-0.3337; p=0.0002) and longer OS (HR, 0.1109; 95% CI, 0.0314-0.3912; p=0.0006). Conclusion: In this study, we demonstrate that TIM-3 expression is an independent positive prognostic factor in TNBC, despite its association with poor clinical and pathologic features.

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

  • Popovich David G.;Kitts David D.
    • 고려인삼학회:학술대회논문집
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    • 고려인삼학회 2002년도 학술대회지
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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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Immune checkpoint inhibitors: recent progress and potential biomarkers

  • Darvin, Pramod;Toor, Salman M.;Nair, Varun Sasidharan;Elkord, Eyad
    • Experimental and Molecular Medicine
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    • 제50권12호
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    • pp.10.1-10.11
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    • 2018
  • Cancer growth and progression are associated with immune suppression. Cancer cells have the ability to activate different immune checkpoint pathways that harbor immunosuppressive functions. Monoclonal antibodies that target immune checkpoints provided an immense breakthrough in cancer therapeutics. Among the immune checkpoint inhibitors, PD-1/PD-L1 and CTLA-4 inhibitors showed promising therapeutic outcomes, and some have been approved for certain cancer treatments, while others are under clinical trials. Recent reports have shown that patients with various malignancies benefit from immune checkpoint inhibitor treatment. However, mainstream initiation of immune checkpoint therapy to treat cancers is obstructed by the low response rate and immune-related adverse events in some cancer patients. This has given rise to the need for developing sets of biomarkers that predict the response to immune checkpoint blockade and immune-related adverse events. In this review, we discuss different predictive biomarkers for anti-PD-1/PD-L1 and anti-CTLA-4 inhibitors, including immune cells, PD-L1 overexpression, neoantigens, and genetic and epigenetic signatures. Potential approaches for further developing highly reliable predictive biomarkers should facilitate patient selection for and decision-making related to immune checkpoint inhibitor-based therapies.

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

  • 김원사
    • 한국결정학회지
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    • 제1권2호
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    • pp.66-75
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    • 1990
  • Pd-Te계의 상평형도를 시차열분석, X선회절분석, 전자현미분석, 반사현미경을 사용해 연구하였다. 본 계의 0-50 at.%Te 부분의 새로운 상관계가 정립되었다. 본 계에는 Pd17Te4, Pd20Te7, Pd8Te3, Pd7Te3, PdgTe4, Pd3Te2, PdTe, PdTe2 등 8개의 화합물이 존재하며 이중 Pd17Te4와 Pd7Te3는 처음 보고되는 신종 화합물이다. Pd17Te4는 등축정계이며 공간군 Fd3r에 속하며 단위포 크기 (a)는 12. 678(5)차이다. PdaTe.4와Pd7Te3의 X선회절분말자료는 사방정계의 단위포 a=12.843(3), b=15.126(3), c=11.304(2)A와 단사 정계의 단위포 a=7.444(1), b=13.918(2), c=8.873 (2)il, β=92.46(2)에 의해 각각 격자지수화가 가능하였다. 본계에 존재하는 합성 화합물의 일부 물리적, 광학적 자료를 새로 보고하였다.

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

  • 황서영;김희재;정선영;민명숙;서동철
    • 한국임상약학회지
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    • 제31권3호
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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.

Pd/Al2O3, Pd/Ag/Al2O3 분리막의 제조와 수소 투과 성능 평가 (Preparation of Pd/Al2O3, Pd/Ag/Al2O3 Membranes and Evaluation of Hydrogen Permeation Performance)

  • 이정인;신민창;장학룡;황재연;김억용;정창훈;박정훈
    • 멤브레인
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    • 제32권2호
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    • pp.116-125
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    • 2022
  • 본 실험에서는 α-Al2O3 세라믹 중공사를 지지체로 사용하였고, 무전해 도금을 통해 Pd 및 Pd-Ag가 도금된 수소 분리막을 제조하였다. Pd-Ag 분리막은 Pd와 Ag 합금 형태로 만들기 위하여 500℃, 10 h 동안의 annealing 과정을 거쳤으며, EDS (Energy Dispersive X-ray Spectroscopy) 분석을 통해 Pd-Ag 합금이 되었다는 것을 확인하였다. 또한, SEM (Scanning Electron Microscope) 분석을 통해 제조된 Pd 및 Pd-Ag 도금층의 두께는 약 8.98, 9.29 ㎛으로 측정되었다. 제조된 수소 분리막은 350~450℃, 1-4 bar의 범위에서 수소 단일 가스, 혼합가스(H2, N2)를 이용하여 수소 투과 실험을 진행하였다. 수소 단일 가스에서 Pd와 Pd-Ag 분리막은 최대 각각 21.85, 13.76 mL/cm2·min의 flux를 가지며, 혼합가스에서는 450℃, 4 bar의 조건일 때, 1216, 361의 separation factor가 각각 나오는 것을 확인하였다.

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

  • 오상오;정덕영;김희선
    • 대한화학회지
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    • 제36권5호
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    • pp.679-684
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    • 1992
  • $trans-[Pd(en)_2Cl_2](ClO_4)-2$ (en = ethylenediamine)와 purine 염기인 Guanine, Adenine 또는 pyrimidine 염기인 Uracil anion을 반응시켜 새로운 팔라듐(IV) 착물을 얻었다. 착물의 중심금속과 각 리간드의 조성비는 $C{\cdot}H{\cdot}N$ 원소 분석으로써 확인하였으며 리간드의 배위자리 등 착물의 구조는 적외선 흡수 스펙트럼 및 $^1H-NMR,\; ^{13}C-NMR$로써 조사하였다. Guanine 또는 Adenine 착물을 purine계 염기가 N7 자리에 배위되었고 출발물질로부터 하나의 en 리간드가 이탈하고 두 $ClO_4^-$가 배위된 $[Pd(en)L_2(ClO_4)_2](ClO_4)_2{\cdot}(en)$ (L = Guanine, Adenine) 구조이다. Uracil 착물은 en과 $ClO_4^-$의 이동없이 Uracil anion의 N1 자리가 배위된 $[Pd(en)_2(Urac)_2](ClO_4)_2$ (Urac = Uracil anion) 구조의 착물로 추정되었다.

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

  • 정맹준;이철재;김동엽
    • 한국산업융합학회 논문집
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    • 제7권1호
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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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