• 제목/요약/키워드: PLA2

검색결과 496건 처리시간 0.034초

Efficacy and Safety of Sorafenib for Advanced Non-Small Cell Lung Cancer: a Meta-analysis of Randomized Controlled Trials

  • Wang, Wei-Lan;Tang, Zhi-Hui;Xie, Ting-Ting;Xiao, Bing-Kun;Zhang, Xin-Yu;Guo, Dai-Hong;Wang, Dong-Xiao;Pei, Fei;Si, Hai-Yan;Zhu, Man
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권14호
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    • pp.5691-5696
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    • 2014
  • Background: Many clinical trials have been conducted to evaluate sorafenib for the treatment of advanced NSCLC, but the results for efficacy have been inconsistent. The aim of this study was to evaluate the efficacy and safety of sorafenib in patients with advanced NSCLC in more detail by meta-analysis. Methods: This meta-analysis of randomized controlled trials (RCTs) was performed after searching PubMed, EMBASE, ASCO Abstracts, ESMO Abstracts, and the proceedings of major conferences for relevant clinical trials. Two reviewers independently assessed the quality of the trials. Outcomes analysis were disease control rate (DCR), progression- free survival (PFS), overall survival (OS) with 95% confidence intervals (CI) and major toxicity. Subgroup analysis was conducted according to sorafenib monotherapy, in combination with chemotherapy or EGFR-TKI to investigate the preferred therapy strategy. Results: Results reported from 6 RCTs involving 2, 748 patients were included in the analysis. Compared to sorafenib-free group, SBT was not associated with higher DCR (RR 1.31 (0.96- 1.79), p=0.09), PFS (HR 0.82 (0.66-1.02), p=0.07) and OS (HR 1.01 (0.92-1.12), p=0.77). In terms of subgroup results, sorafenib monotherapy was associated with significant superior DCR and longer PFS, but failed to show advantage with regard to OS. Grade 3 or greater sorafenib-related adverse events included fatigue, hypertension, diarrhea, oral mucositis, rash and HFSR. Conclusions: SBT was revealed to yield no improvement in DCR, PFS and OS. However, sorafenib as monotherapy showed some activity in NSCLC. Further evaluation may be considered in subsets of patients who may benefit from this treatment. Sorafenib combined inhibition therapy should be limited unless the choice of platinum-doublet regimen, administration sequence or identification of predictive biomarkers are considered to receive better anti-tumor activity and prevention of resistance mechanisms.

가죽나무 에타놀 추출물 및 luteolin-7-O-glucoside의 phospholipase $A_2$ 저해활성 (Inhibitory Activity of Ethanol Extracts of Ailanthus altissima and Luteolin-7-glucoside on Phospholipase $A_2$ activity)

  • 김미화;황남경;홍태균;김윤경;정환기;양주혜;전철구;배기환;;손건호;김현표;강삼식;장현욱
    • 생약학회지
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    • 제38권3호통권150호
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    • pp.277-280
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    • 2007
  • In our continuing effort to investigate compounds having anti-inflammatory activity from natural products, Ailanthus altissima was examined. Among six compounds isolated from Ailanthus altissima, Luteolin-7-O-glucoside (L7G) along with ethanol extract of Ailnathus altissima (EAa) were chosen to determine their inhibitory activity on secretory recombinant phospholipase $A_2s$ enzyme activity in vitro. As a results, EAa inhibited human recombinant $sPLA_2-V$ ($IC_{50}$ of about 100 ${\mu}g/ml$) and $cPLA_2$, ($IC_{50}$ of about 59 ${\mu}g/ml$), while L7G showed strong inhibitory effect on $sPLA_2-A$, V and $cPLA_2$ with an $IC_{50}$ value of approximately 40 ${\mu}M$, respectively.

Expression of Phospholipase A2 Receptor in Pediatric Hepatitis B Virus-Related Membranous Nephropathy

  • Choi, Sung-Eun;Bae, Yoon Sung;Lee, Keum Hwa;Shin, Jae Il;Jeong, Hyeon Joo;Lim, Beom Jin
    • Childhood Kidney Diseases
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    • 제24권1호
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    • pp.36-41
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    • 2020
  • Purpose: Hepatitis B virus (HBV) infection is among etiologies of secondary membranous nephropathy (MN) in pediatric patients. We evaluated expression of phospholipase A2 receptor (PLA2R), a specific target antigen of primary MN, in pediatric HBV-related MN. Methods: We retrospectively reviewed patients with biopsy-proven HBV-related MN from the renal biopsy registry and electronic medical records of Severance Hospital, Seoul, Korea, from 1993 to 2004. Paraffin-embedded human kidney tissues were retrieved and immunohistochemically stained for PLA2R. Results: Ten pediatric patients with 13 biopsied specimens were reviewed. The predominant pathological stage was stage II-III, and second was stage II. The intensity of staining for IgG was greatest, with less intense staining for IgM, IgA, C3, C4, and C1q. All the patients had angiotensin-converting enzyme inhibitor combined with glucocorticoid, and four patients converted to cyclosporine treatment from glucocorticoid monotherapy. Urinalysis of all the patients normalized after variable period. PLA2R staining was demonstrated in the outer glomerulus in 3 out of 13 biopsies, 2 of which were obtained from the same patient over a 5-year interval. Conclusions: PLA2R was expressed in a small number of cases diagnosed as pediatric HBV-related MN, indicating that some HBV-related MN cases may be primary MN concurrent with HBV infection.

UV조사에 의한 Poly(lactic acid)-g-Acrylic Acid 이온교환체의 합성 및 흡착특성 (Synthesis of Poly(lactic acid)-g-Acrylic Acid Ion Exchanger by UV Radiation Method and Metal Adsorption Properties)

  • 최은미;손복기;이창수;황택성
    • 폴리머
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    • 제33권1호
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    • pp.52-57
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    • 2009
  • 본 연구는 UV 조사법으로 poly(lactic acid)-g-acrylic acid(PLA-g-AAc) 이온교환체를 합성하고 이들의 금속흡착 특성을 ICP-AES 분석을 통해 확인하였다. PLA-g-AAC의 UV 조사량과 AAc의 농도변화에 따른 함수율, 그래프트율 및 이온교환용량을 측정하였다. 그래프트율은 AAc 및 benzophenone(BP) 농도가 각각 1.0, 0.1 mol/L일때 최대 28%이었으며, 이온교환용량과 함수율은 각각 1.13 meq/g와 38%로 UV 조사량 및 AAc의 농도가 증가함에 따라 증가하였다. 한편, PLA-g-AAc의 흡착시간에 따른 $Cu^{2+}$, $Co^{2+}$, $Ni^{2+}$에 대한 선택 흡착성은 모두 높게 나타났으며 $Cu^{2+}$가 가장 우수한 선택흡착성을 나타내었다.

고분자 사슬연장제를 이용한 폴리유산 / 폴리부틸렌 아디페이트테레프탈레이트 복합필름의 제조 및 특성 분석 (Study on Characteristics of PLA/PBAT Composite Film with Various Chain Extenders)

  • 김선종;조현승;이재환;유명제;엄유준;박수일
    • 한국포장학회지
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    • 제23권2호
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    • pp.61-66
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    • 2017
  • 고분자 사슬연장제(Chain extender)를 적정 함량별로 넣어 PLA와 PBAT 생분해성 복합 필름을 제조하였으며 제조된 필름의 기계적 특성 및 열적 특성을 분석하였다. 고분자 사슬연장제인 $Joncryl^{(R)}$과 헥사메틸렌 디이시소시아네이트(HDI, Hexamethylene Diisocyanate)를 각각 단일로 넣었을 경우, 고분자 사슬연장제의 함량 증가에 따라 인장강도(Tensile strength)가 함량에 비례하여 소폭 증가하는 영향을 주는 것으로 나타났으나, 연신율에 있어서는 비례적인 차이를 나타내지 않았다. 하지만 두 종류의 사슬연장제를 적정비율로 같이 넣어 압출한 결과 인장강도가 40 MPa에 이르는 것으로 나타나 대조구의 인장강도 25 MPa보다 약 15 MPa 정도 증가하여 강도개선의 효과가 있는것으로 나타났으며 연신율의 경우 대조구보다 개선된 것으로 나타났다.

Moxifloxacin의 Cytosolic Phospholipase $A_2$ 억제효과가 흰 쥐 호중구의 Respiratory Burst에 미치는 영향 (Moxifloxacin Alleviates Oleic Acid-provoked Neutrophilic Respiratory Burst in the Rat Lung through the Inhibition of Cytosolic Phospholipase $A_2$)

  • 이영만
    • Tuberculosis and Respiratory Diseases
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    • 제69권4호
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    • pp.256-264
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    • 2010
  • Background: According to the notion of the immunoregulatory functions of moxifloxacin (MFX), the effect of MFX on the neutrophilic respiratory burst in conjunction with the expression of cytosolic phospholipase $A_2$ ($cPLA_2$) was investigated. Methods: The effects and possible mechanisms of MFX on neutrophilic respiratory burst in oleic acid (OA)-induced acutely injured rats lung and OA-stimulated, isolated murine neutrophils were probed, associated with the expression of cytosolic phospholipase $A_2$ in vivo and in vitro. Results: In the OA-induced acutely-injured lungs, neutrophils were accumulated, which was attenuated by MFX. The parameters denoting a neutrophilic respiratory burst, such as nitro blue tetrazolium reaction, cytochrome-c reduction, neutrophil aggregation, $H_2O_2$ production in neutrophils revealed increased neutrophilic respiratory burst by OA, and MFX decreased all of these parameters. In addition, the enhanced expression of $cPLA_2$ in the lung and isolated murine neutrophils by OA were decreased by MFX. Conclusion: MFX suppresses the OA-induced neutrophilic respiratory burst by the suppression of $cPLA_2$ in neutrophils.

사람 위 상피세포의 염증반응에 대한 무의 효과 (Effect of Radish on Inflammatory Reaction in Human Epithelial Gastric Cell)

  • 손윤희;정유선;서정일;박인경;남경수
    • 생명과학회지
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    • 제16권1호
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    • pp.17-21
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    • 2006
  • The effects of Korean and Japanese radishes on inflammatory reaction that involves arachidonic acid cascades were investigated in human epithelial gastric cell. The activities of type I (porcine pancreas) and type II (Crotalus atrox) phospholipase $A_2(PLA_2$) were inhibited by radish. Cyclooxygenase-2 (COX-2) activity was significantly suppressed by radish (p<0.05, p<0.01 and p<0.005). The nitric oxide production was also inhibited by radish. The Korean radish was more effective in inhibition of $PLA_2$ and COX-2 activities and nitric oxide production than Japanease radish. These results indicate that radish has a protective effect on gastric epithelial cell inflammation by suppressing the activities of $PLA_2$ and COX-2 activities and nitric oxide production from gastric epithelial cell.

Role of Phospholipase $A_2$ in Oxidant-induced Alteration in Phosphate Transport in Primary Cultured Rabbit Renal Proximal Tubule Cells

  • Park, Kwon-Moo;Ko, Sun-Hee;Woo, Jae-Suk;Jung, Jin-Sup;Lee, Sang-Ho;Kim, Yong-Keun
    • The Korean Journal of Physiology and Pharmacology
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    • 제2권5호
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    • pp.601-609
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    • 1998
  • The present study was undertaken to examine the role of phospholipase $A_2\;(PLA_2)$ in oxidant-induced inhibition of phosphate transport in primary cultured rabbit renal proximal tubule cells. Uptakes of phosphate and glucose were dose-dependently inhibited by an oxidant t-butylhydroperoxide (tBHP), and the significant inhibition appeared at 0.025 mM of tBHP, whereas tBHP-induced alterations in lipid peroxidation and cell viability were seen at 0.5 mM. tBHP stimulated arachidonic acid (AA) release in a dose-dependent fashion. A $PLA_2$ inhibitor mepacrine prevented tBHP-induced AA release, but it did not alter the inhibition of phosphate uptake and the decrease in cell viability induced by tBHP. tBHP-induced inhibition of phosphate transport was not affected by a PKC inhibitor, staurosporine. tBHP at 0.1 mM did not produce the inhibition of $Na^+-K^+-ATPase$ activity in microsomal fraction, although it significantly inhibited at 1.0 mM. These results suggest that tBHP can inhibit phosphate uptake through a mechanism independent of $PLA_2$ activation, irreversible cell injury, and lipid peroxidation in primary cultured rabbit renal proximal tubular cells.

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Alterations in Membrane Transport Function and Cell Viability Induced by ATP Depletion in Primary Cultured Rabbit Renal Proximal Tubular Cells

  • Lee, Sung-Ju;Kwon, Chae-Hwa;Kim, Yong-Keun
    • The Korean Journal of Physiology and Pharmacology
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    • 제13권1호
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    • pp.15-22
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    • 2009
  • This study was undertaken to elucidate the underlying mechanisms of ATP depletion-induced membrane transport dysfunction and cell death in renal proximal tubular cells. ATP depletion was induced by incubating cells with 2.5 mM potassium cyanide(KCN)/0.1 mM iodoacetic acid(IAA), and membrane transport function and cell viability were evaluated by measuring $Na^+$-dependent phosphate uptake and trypan blue exclusion, respectively. ATP depletion resulted in a decrease in $Na^+$-dependent phosphate uptake and cell viability in a time-dependent manner. ATP depletion inhibited $Na^+$-dependent phosphate uptake in cells, when treated with 2 mM ouabain, a $Na^+$ pump-specific inhibitor, suggesting that ATP depletion impairs membrane transport functional integrity. Alterations in $Na^+$-dependent phosphate uptake and cell viability induced by ATP depletion were prevented by the hydrogen peroxide scavenger such as catalase and the hydroxyl radical scavengers(dimethylthiourea and thiourea), and amino acids(glycine and alanine). ATP depletion caused arachidonic acid release and increased mRNA levels of cytosolic phospholipase $A_2(cPLA_2)$. The ATP depletion-dependent arachidonic acid release was inhibited by $cPLA_2$ specific inhibitor $AACOCF_3$. ATP depletion-induced alterations in $Na^+$-dependent phosphate uptake and cell viability were prevented by $AACOCF_3$. Inhibition of $Na^+$-dependent phosphate uptake by ATP depletion was prevented by antipain and leupetin, serine/cysteine protease inhibitors, whereas ATP depletion-induced cell death was not altered by these agents. These results indicate that ATP depletion-induced alterations in membrane transport function and cell viability are due to reactive oxygen species generation and $cPLA_2$ activation in renal proximal tubular cells. In addition, the present data suggest that serine/cysteine proteases play an important role in membrane transport dysfunction, but not cell death, induced by ATP depletion.

흰쥐에서 내독소로 유도된 급성 폐손상에서 moxofloxacin의 개선효과 (Ameliorating Effects of Moxifloxacin on Endotoxin-Induced Acute Lung Injury in Rats)

  • 이영만;최휘건
    • 생명과학회지
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    • 제21권8호
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    • pp.1100-1108
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    • 2011
  • 흰쥐에서 내독소로 유도된 급성 폐손상에서 moxifloxacin의 효과를 형태학적으로 호중구의 폐장 내 침윤 및 세포질형 포스포리파아제(cytosolic phospholipase A2) 발현과 관련하여 알아보았다. 내독소는 잘 알려진대로 흰쥐에서 급성 폐손상을 유발하였고 이때 폐장 내의 호중구의 침윤 및 폐장 및 호중구에서의 세포질형 포스포리파아제의 발현이 증가하였고, 또한 염증성 사이토카인의 일종인 종양괴사성인자(tumor necrosis factor)의 발현도 증가하였다. 전자현미경을 이용한 산소기 생성의 검사에서도 내독소에 의하여 산소기의 생성이 폐장 내에 증가한 사실을 확인하였고, 산화성 스트레스에 유발되는 제2형 폐포세포에서의 층상체의 변화도 관찰하였다. 면역변환효과가 있다고 알려진 moxifloxacin은 이러한 변화들을 억제하고 형태학적으로 내독소에 의한 급성 폐손상을 현저히 감소시켰다.