• 제목/요약/키워드: PD-1/PD-L1

검색결과 312건 처리시간 0.024초

Syntheses and Spectroscopic properties of Palladium(II) Complexes with Bidentate Aminophosphine of N,N-Dialkyl-N'-diphenylphosphinodiaminoethane

  • Doh, Myung-Ki;Kim, Bong-Gon
    • Bulletin of the Korean Chemical Society
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    • 제9권4호
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    • pp.198-202
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    • 1988
  • Several new palladium(II) complexes of aminophosphines, $(Pd(L)X_2)$, (L = $Ph_2PNH$ ++ $NR_2$; R = $CH_3(L_1)$, $C_2H_5(L_2)$ : X = Cl, Br, I, and NCS) that contain two different donor atoms of nitrogen and phosphorus as ${\pi}$-electron acceptor, were synthesized and characterized by conductivity measurement, ir, and UV/Vis-spectra. For the dithiocyanatopalladium(II) complexes with aminophosphines, it was confirmed that the thiocyanate group trans to phosphorus is coordinated as Pd-NCS mode and the one trans to nitrogen as Pd-SCN mode, and the aminophosphines form six-membered chelate ring. The spectra of dihalogenopalladium(II) complexes with aminophosphines show that the band maxima are shifted to the short wavelengths as the concentration is decreased.

Immune Regulatory Function of Cancer-Associated Fibroblasts in Non-small Cell Lung Cancer

  • Hyewon Lee;Mina Hwang;Seonae Jang;Sang-Won Um
    • Tuberculosis and Respiratory Diseases
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    • 제86권4호
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    • pp.304-318
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    • 2023
  • Background: Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment and significantly contribute to immune evasion. We investigated the effects of CAFs on the immune function of CD4+ and CD8+ T cells in non-small cell lung cancer (NSCLC). Methods: We isolated CAFs and normal fibroblasts (NFs) from tumors and normal lung tissues of NSCLC patients, respectively. CAFs were co-cultured with activated T cells to evaluate their immune regulatory function. We investigated the effect of CAF conditioned medium (CAF-CM) on the cytotoxicity of T cells. CAFs were also co-cultured with activated peripheral blood mononuclear cells and further incubated with cyclooxygenase-2 (COX2) inhibitors to investigate the potential role of COX2 in immune evasion. Results: CAFs and NFs were isolated from the lung tissues (n=8) and lymph nodes (n=3) of NSCLC patients. Immune suppressive markers, such as COX2 and programmed death-ligand 1 (PD-L1), were increased in CAFs after co-culture with activated T cells. Interestingly, CAFs promoted the expression of programmed death-1 in CD4+ and CD8+ T cells, and strongly inhibited T cell proliferation in allogenic and autologous pairs of CAFs and T cells. CAF-CM decreased the cytotoxicity of T cells. COX2 inhibitors partially restored the proliferation of CD4+ and CD8+ T cells, and downregulated the expression of COX2, prostaglandin E synthase, prostaglandin E2, and PD-L1 in CAFs. Conclusion: CAFs promote immune evasion by suppressing the function of CD4+ and CD8+ T cells via their effects on COX2 and PD-L1 in NSCLC. The immunosuppressive function of CAFs could be alleviated by COX2 inhibitors.

C3H/HeJ 마우스 간암에서 MEK 억제제에 의한 방사선 감수성 향상 효과 (Enhancement of Tumor Response by MEK Inhibitor in Murine HCa-I Tumors)

  • 김성희;성진실
    • Radiation Oncology Journal
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    • 제21권3호
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    • pp.207-215
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    • 2003
  • 목적: Extracellular signal-regulated kinase (ERK)는 mitogen-activated protein kinase cascade의 일원으로 다양한 세포독성 자극에 의해 유도되는 apoptosis에 반대되는 역할을 한다. 따라서 ERK의 억제는 항암제로서 유용하게 사용될 것으로 생각되어진다. 대상 및 방법: 마우스 간암인 HCa-I는 TCD50가 80 Gy 이상으로 강한 방사선 내성종양으로 알려져 있으며, 방사선 민감성의 증진을 위해 다양한 항암제가 실험되었으나 뚜렷한 효과를 나타내지 못했다. 이 실험을 통해 in vivo,, 특히 방사선 내성종양에서 ERK의 억제가 방사선에 의한 항암 작용을 증진시키는지 알아보고자 하였다. C3H/HeJ 마우스에 종양의 크기가 $7.5\~8\;mm$가 되었을 때 PD98059 ($0.16\;\mug/50\;\mul$로 종양에 직접 주사)를 처리하였다. 결과: 처리 1시간째에 p-ERK가 0.5배로 억제되었다. 종양 성장 지연 분석에서 증강 지수가 전 처리군과 후 처리군에서 각각 1.6과 1.87로 PD98059가 종양의 방사선 감수성을 증가시키는 것으로 관찰되었다. 25 Gy 방사선과 PD98059 복합처리 시 apoptosis가 크게 증가되었다. 각 실험군의 apoptosis 최대치는 방사선 조사군에서 $1.4\%$, PD98059 처리군에서 $0.9\%$ 복합처리군의 전 처리군과 후 처리군에서 각각 $4.9\%\;5.3\%$를 나타냈다. Apoptosis 조절 물질의 변화는, p53의 발현이 복합 처리군에서 PD98059 전 처리군과 후 처리군 모두에서 24시간까지 대조군에 비해 2.7배, 3.2배의 높은 발현 수준을 유지하여 처리 1시간째부터 발현 증가를 하여 24시간까지 지속되는 것이 관찰되었다. $p21^{WAF1/CIP1}$의 발현은 p53 발현 변화와 유사한 양상으로 특히 PD98059 후 처리군에서 방사선 조사군이나 PD98059 전 처리군과 비교하여 높은 발현수준을 보였으며, 24시간까지 3.2배의 높은 발현 수준을 유지하는 것으로 나타났다. Bcl-Xs는 25 Gy 방사선 조사군이나 PD98059 처리군에서는 뚜렷한 변화를 보이지 않았으나 복합 처리군중 전 처리군에서 4시간 째 대조군에 비해 1.93배 증가를 보였으며, 후 처리군에서는 1시간 후에 1.83배의 증가를 보였다. 모든 실험군에서 Bcl-2, $Bcl-X_L$, BaX는 뚜렷한 발현 변화를 보이지 않았다. 결론: 방사선 내성 종양인 간암에 MEK 억제제를 방사선 조사와 복합 처리하여 방사선 감수성을 향상시켜 치료 효율의 상승을 유도 할 수 있을 것으로 생각된다.

암줄기세포의 특성 및 면역관문억제 (Characteristics of Cancer Stem Cells and Immune Checkpoint Inhibition)

  • 최상훈;김형기
    • 생명과학회지
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    • 제29권4호
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    • pp.499-508
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    • 2019
  • 암줄기세포는 전이와 재발의 주요한 요인이 되는 자가재생능력, 분화할 수 있는 능력, 치료에 대한 저항성 및 암 형성 능력의 특성을 가진다. WNT/${\beta}$-catenin, Hedgehog, Notch, BMI1, BMP 및 TGF-${\beta}$와 같은 암줄기세포의 특성을 획득 및 유지할 수 있는 신호기전의 연구 결과가 존재하지만, 현재까지 선택적으로 암줄기세포를 표적할 수 있는 치료 전략은 미미하다. 최근, 면역관문억제제인 CTLA-4, PD-1/PD-L1 단일클론항체는 흑색종, 폐암, 췌장암 및 혈액암에 괄목할만한 임상 시험 결과를 나타냈으며, 긴 항암지속효과와 적은 부작용은 기존 항암제보다 개선 된 모습을 보였다. 또한 두경부편평상피암, 흑색종, 유방암 줄기세포를 선택적으로 제거 하였다. 위의 결과를 종합하면, 면역관문억제제는 이전 항암제에 비해 효과적인 항암전략이며, 동시에 암줄기세포를 선택적으로 제거할 수 있는 가능성을 시사한다. 따라서 본 리뷰에서는 암줄기세포와 면역관문억제제의 이해를 통해, 면역관문억제제의 암줄기세포 표적 가능성에 대해 고찰하고자 한다.

Measurement of Microbial Protein Supply in Murrah Buffaloes (Bubalus bubalis) Using Urinary Purine Derivatives Excretion and PDC Index

  • Dipu, M.T.;George, S.K.;Singh, P.;Verma, A.K.;Mehra, U.R.
    • Asian-Australasian Journal of Animal Sciences
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    • 제19권3호
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    • pp.347-355
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    • 2006
  • A study was conducted to predict the rumen microbial protein production based on urinary excretion of purine derivatives in buffaloes fed a diet of wheat straw and concentrate (40:60) at four fixed levels of feed intake. (95, 80, 60 and 40% of preliminary voluntary feed intake) following experimental protocol of IAEA (Phase I). The buffaloes were allocated according to a $4{\times}4$ latin square design. The urinary allantoin, uric acid, total PD excretion (mmol/d) in treatments L-95, L-80, L-60 and L-40 was 20.13, 16.00, 12.96 and 9.17; 1.88, 2.12, 2.11 and 2.15; 22.01, 18.12, 15.07 and 11.32, respectively and were significantly (p<0.05) different among treatments except for uric acid. The rate of PD excretion (mmol/d) was positively correlated with the digestible organic matter intake. Variations were observed in PD and creatinine concentration in spot samples collected at 6-hour interval. However, daily PD:Creatinine ratio (PDC index) appears to be a reasonably good predictor of microbial-N supply. The contribution of basal purine excretion to total excretion of purine derivatives (PD) was determined in pre-fasting period followed by a fasting period of 6 d (Phase II). Daily PD and creatinine excretion (mmol/kg $W^{0.75}$) during fasting averaged 0.117 and 0.456 respectively for buffaloes. The excretion rates of PD decreased significantly (p<0.01) during fasting compare to pre-fasting period, the urinary creatinine excretion remained almost similar. Except for creatinine, plasma concentration of target parameters significantly (p<0.01) declined during fasting. Likewise, glomerular filtration rate (GFR) and renal clearance of allantoin and uric acid also decreased. Based on the PD excretion rates during fasting and at different levels of feed intake obtained in this study, a relationship between daily urinary PD excretion (Y-mmol) and microbial purine absorption (X-mmol) was developed for buffaloes as Y = 0.74X+0.117 kg $W^{0.75}$. The microbial N supply (g/kg DOMI) remained statistically similar irrespective of dietary treatment. The results showed that excretion of urinary purine derivatives is positively correlated with the levels of feed intake in Murrah buffaloes and thus, estimation of urinary purine derivatives and PDC index could be used to determine microbial nitrogen supply when there is large variation in level of feed intake.

자생식물 Essential Oil 5 종의 항 아토피피부염 활성 연구 (A Study on the Activities of Five Natural Plant Essential Oils on Atopic Dermatitis)

  • 정정화;;최민진;응웬리;신흥묵;이병욱;양인준
    • 대한화장품학회지
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    • 제47권1호
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    • pp.23-30
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    • 2021
  • 본 연구는 개똥쑥(Artemisia annua L., AA), 유자(Citrus junos Sieb. ex TANAKA, CJ), 산국화(Chrysanthemum boreale Makino, CB), 잣나무(Pinus koraiensis, PK), 금강송(Pinus densiflora for. erecta, PD) 총 5 종의 자생식물 essential oil의 항 아토피 효능을 확인하기 위한 실험이다. 항균 효과를 확인하기 위해 자생식물 essential oil 5 종을 Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Candida albicans 총 4 종류의 균에 처리했다. 항염증 효과를 확인하기 위해 TNF-α와 IFN-γ (TI)를 처리한 HaCaT 세포에 5 종의 자생식물 essential oil을 처리했다. AA, CJ, CB, PK, PD은 10 mg/mL 농도에서 Candida albicans에 대한 항균 효과를 나타냈다. AA (1 ㎍/mL), CB (1 ㎍/mL), PK (0.1, 1 ㎍/mL)에서 thymus and activation-regulated chemokine (TARC) 생성량이 억제되었고, AA 및 PK (1 ㎍/mL)에서 macrophage-derived chemokine (MDC) 생성량이 억제되었으며, AA (0.1, 1 ㎍/mL), PK (0.1, 1 ㎍/mL)에서 IL-6 생성량이 억제되었다. AA, CB, PK essential oil의 항균 및 항염증 효과가 확인되었으며, 이에 아토피 피부염 완화에 기여할 수 있음을 기대한다.

해양심층수 및 Protease 고생산성 Bacillus subtilis DH3으로 제조한 된장(Doenjang)의 품질특성 (Quality Characteristics of Soybean Paste (Doenjang) Prepared with Bacillus subtilis DH3 Expressing High Protease Levels, and Deep-Sea Water)

  • 정희경;정유석;윤광섭;김대익;홍주헌
    • 한국식품저장유통학회지
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    • 제16권3호
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    • pp.348-354
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    • 2009
  • 된장의 영양성과 기능성을 향상시키기 위해 해양심층수와 protease 고 생산성 미생물을 이용하여 개량식 된장을 제조하여 다양한 기능적 특성을 조사하였다. Protease 활성은 재래식 된장에서 분리한 DH3을 접종시킨 된장이 $278.83{\pm}1.68$(unit/mL/min)로 가장 우수하였다. Protease 활성과 ACE저해 활성은 발효기간이 길어질수록 증가되었으며 발효 30일 후 된장M과 된장 PD의 동결건조 분말(10mg/mL)의 ACE 저해활성은 각각 $14.11{\pm}0.13%$, $88.43{\pm}0.61%$로 조사되었다. 발효 기간이 30일 경과한 후, 항산화 활성은 된장 PD가 $61.27{\pm}0.42%$로 된장 M의 $14.47{\pm}0.41%$ 보다 약 5배정도 활성을 나타내었으며 무기질함량은 된장 PD가 K, Ca 및 Mg의 함량이 각각 1.347 g/100 g, 0.749 g/100 g 및 1.187 g/100 g로 된장 M의 함량보다 높게 나타났다. 관능평가 결과 맛, 향, 전체적 기호도에서 된장 PD의 평가 점수가 된장 M에 비해 더 높게 측정되어 관능적으로 양호함을 확인하였다.

Rotenone- 및 MPTP-유도 파킨슨병 동물 모델에서 돌외 에탄올 추출물의 Dopamine 신경세포 보호작용 (Neuroprotective Effects of Herbal Ethanol Extract from Gynostemma pentaphyllum on Dopamine Neurons in Rotenone- and MPTP-induced Animal Model of Parkinson's Disease)

  • 서광훈;최현숙;신건성;조정정;김승환;황방연;이종길;이명구
    • 약학회지
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    • 제57권2호
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    • pp.77-86
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    • 2013
  • The neuroprotective effects of herbal ethanol extract (GP-EX) from Gynostemma pentaphyllum on dopamine neurons in animal model of Parkinson's disease (PD) were investigated. Rats and mice were administered with rotenone (2.5 mg/kg) for 28 days and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg) for 5 days for the PD models, respectively and the animals were simultaneously treated with GP-EX (30 mg/kg, daily). After preparing the PD models, the animals were also administered with L-DOPA (10 mg/kg) for 14 days with or without GP-EX treatment. Treatment with GP-EX (30 mg/kg) inhibited the rotenone- and MPTP-induced neurotoxic effects in dopamine neurons of rats or mice, which was determined by the numbers of tyrosine hydroxylase-immunohistochemical staining survival cells, as well as the levels of dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid. GP-EX (30 mg/kg) also showed the protective effects on neurotoxicity which was induced by long-term administration of L-DOPA (10 mg/kg) in rotenone- and MPTP-induced animal model of PD. The used doses of GP-EX (30 mg/kg) did not produce any signs of toxicity, such as weight loss, diarrhea, or vomiting, in rats and mice during the treatment periods. These results suggest that GP-EX has the protective functions against chronic L-DOPA-induced neurotoxic reactions in dopamine neurons of rotenone- and MPTP-induced animal model of PD. Therefore, the natural GP-EX may be beneficial in the prevention of PD progress and L-DOPA-induced neurotoxicity in PD patients.

큰느타리버섯의 MA저장중 품질변화 (Changes in Quality of King Oyster Mushroom (Pleurotus eryngii) during Modified Atmosphere Storage)

  • 조숙현;이상대;류재산;김낙구;이동선
    • 한국식품저장유통학회지
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    • 제8권4호
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    • pp.367-373
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    • 2001
  • 큰느타리버섯의 신선도 연장을 위해 PVC wrap과 20$\mu\textrm{m}$ Polyolefin계열의 PD941 필름을 이용하여 밀봉한 후 저장온도 $0^{\circ}C$, 5$^{\circ}C$, 1$0^{\circ}C$에서 저장하면서 품질변화를 조사하였다. 큰느타리버섯은 저장온도가 높을수록 호흡속도가 빠르며, 중량감소율은 저장온도 $0^{\circ}C$, 5$^{\circ}C$, 1$0^{\circ}C$에서 Polyolefin계열의 PD941 밀봉포장이 PVC wrap 포장보다 중량감소가 훨씬 적었다. 포장내 가스농도중 $O_2$농도는 PVC wrap포장과 Polyolefin계열의 PD941 밀봉포장이 $0^{\circ}C$, 5$^{\circ}C$, 1$0^{\circ}C$에서 1%이하로, $CO_2$농도는 6~10%를 나타내었다. Hardness, Hunter L값, Hunter b값, 관능평가 결과를 고려할 때 Polyolefin계열의PD941 밀봉포장이 PVC wrap 포장에 비해서 우수하였고, 큰느타리버섯의 저장가능기간은 PVC wrap 포장의 경우 $0^{\circ}C$에서 50일, 5$^{\circ}C$에서 28일, 1$0^{\circ}C$ 12일이 가능하고, Polyoefin계열의 PD941 밀봉포장은 $0^{\circ}C$에서 50일, 5$^{\circ}C$에서 32일, 1$0^{\circ}C$에서 21일이 가능하였다.

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복막투석 환자의 빈혈 관리에 있어 에리스로포이에틴 자극제의 사용현황 및 비교평가 (A Comparative Study on Trends and Efficacy of Erythropoietin Stimulating Agents in Patient Receiving Peritoneal Dialysis)

  • 임수연;진혜경;김선아;이은경;이정연
    • 한국임상약학회지
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    • 제24권3호
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    • pp.206-212
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    • 2014
  • Objectives: This was to evaluate the current usage of three erythropoietin stimulating agents (ESA) and their efficacy for management of anemia in peritoneal dialysis (PD) patients with chronic kidney disease. Methods: It was a retrospective comparative study through review of electronic medical records of chronic kidney disease patients undergoing PD at a tertiary teaching hospital from January 1998 to June 2013. Results: Average administration frequency was 1.66 times/week in EPO group, 0.75 times/week in DA group, and 0.19 times/week in MPG-EPO group. At the first 4 weeks, there were significant differences in mean hemoglobin levels between EPO and DA groups ($9.25{\pm}1.28g/dL$, $10.02{\pm}0.95g/dL$ each, p = 0.018) and also in hemoglobin response rates (10.0%, 45.2% each, p = 0.008), but since after 4 week, there had been no significant differences. There also showed no significant differences in achievement of hemoglobin target between the two groups. When converted to MPG-EPO in EPO/DA groups, there showed a slight increase in hemoglobin levels of both groups. MPG-EPO was the highest compared with two other drugs by the average cost based on the average weekly dose. Conclusion: EPO, DA, and MPG-EPO showed similar effects in treatment of anemia of PD patients based on hemoglobin target range (11.0~12.0 g/dL) which NFK-K/DOQI guidelines suggest. Though the average cost of MPG-EPO was higher than the other two drugs, the number of PD patients using MPG-EPO has increased and it is thought that long half-life and low administration frequency of MPG-EPO have improved the compliance of PD patients who have to self-administrate.