메뉴 건너뛰기




Volumn 28, Issue 5 SUPPL. 61, 2010, Pages

How does methotrexate suppress inflammation?

Author keywords

Adenosine; Inflammation; Methotrexate; Purine metabolism

Indexed keywords

ADENOSINE; ADENOSINE PHOSPHATE; DIHYDROFOLATE REDUCTASE; FOLIC ACID; HOMOCYSTEINE; METHIONINE; METHOTREXATE; METHOTREXATE POLYGLUTAMATE; PEROXIDE; REACTIVE OXYGEN METABOLITE; TETRAHYDROFOLIC ACID; ADENOSINE A2A RECEPTOR; FOLINIC ACID;

EID: 78650528837     PISSN: 0392856X     EISSN: 1593098X     Source Type: Journal    
DOI: None     Document Type: Article
Times cited : (76)

References (44)
  • 1
    • 76549239323 scopus 로고
    • Therapeutic suppression of tissue reactivity. II. Effect of aminopterin in rheumatoid arthritis and psoriasis
    • GUBNER R, AUGUST S, GINSBERG V: Therapeutic suppression of tissue reactivity. II. Effect of aminopterin in rheumatoid arthritis and psoriasis. Am J Med Sci 1951;221:176-82.
    • (1951) Am. J. Med. Sci. , vol.221 , pp. 176-182
    • Gubner, R.1    August, S.2    Ginsberg, V.3
  • 2
    • 67549096874 scopus 로고    scopus 로고
    • Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis: Integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative
    • VISSER K, KATCHAMART W, LOZA E et al.: Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative. Ann Rheum Dis 2009;68:1086-93.
    • (2009) Ann. Rheum. Dis. , vol.68 , pp. 1086-1093
    • Visser, K.1    Katchamart, W.2    Loza, E.3
  • 3
    • 0041305877 scopus 로고    scopus 로고
    • Membrane transport of folates
    • MATHERLY LH, GOLDMAN DI: Membrane transport of folates. Vitam Horm 2003;66:403-56.
    • (2003) Vitam Horm , vol.66 , pp. 403-456
    • Matherly, L.H.1    Goldman, D.I.2
  • 4
    • 3142750489 scopus 로고    scopus 로고
    • Sulfasalazine is a potent inhibitor of the reduced folate carrier: Implications for combination therapies with methotrexate in rheumatoid arthritis
    • JANSEN G, VAN DER HEUDEN J, OERLEMANS R et al.: Sulfasalazine is a potent inhibitor of the reduced folate carrier: implications for combination therapies with methotrexate in rheumatoid arthritis. Arthritis Rheum 2004;50:2130-9.
    • (2004) Arthritis Rheum. , vol.50 , pp. 2130-2139
    • Jansen, G.1    Van Der Heuden, J.2    Oerlemans, R.3
  • 5
    • 0037331142 scopus 로고    scopus 로고
    • The anti-inflammatory actions of methotrexate are critically dependent upon the production of reactive oxygen species
    • PHILLIPS DC, WOOLLARD KJ, GRIFFITHS HR: The anti-inflammatory actions of methotrexate are critically dependent upon the production of reactive oxygen species. Br J Pharmacol 2003;138:501-11.
    • (2003) Br. J. Pharmacol. , vol.138 , pp. 501-511
    • Phillips, D.C.1    Woollard, K.J.2    Griffiths, H.R.3
  • 6
    • 0025868117 scopus 로고
    • In vitro effects of methotrexate on peripheral blood monocytes: Modulation by folinic acid and S-adenosylmethionine
    • NESHER G, MOORE TL, DORNER RW: In vitro effects of methotrexate on peripheral blood monocytes: modulation by folinic acid and S-adenosylmethionine. Ann Rheum Dis 1991;50:637-41.
    • (1991) Ann. Rheum. Dis. , vol.50 , pp. 637-641
    • Nesher, G.1    Moore, T.L.2    Dorner, R.W.3
  • 7
    • 0025352428 scopus 로고
    • The in vitro effects of methotrexate on peripheral blood mononuclear cells: Modulation by methyl donors and spermidine
    • NESHER G, MOORE TM: The in vitro effects of methotrexate on peripheral blood mononuclear cells: modulation by methyl donors and spermidine. Arthritis Rheum 1990;33:954-9.
    • (1990) Arthritis Rheum. , vol.33 , pp. 954-959
    • Nesher, G.1    Moore, T.M.2
  • 8
    • 0030017917 scopus 로고    scopus 로고
    • In vitro effects of methotrexate on polyamine levels in lymphocytes from rheumatoid arthritis patients
    • NESHER G, OSBORN TG, MOORE TL: In vitro effects of methotrexate on polyamine levels in lymphocytes from rheumatoid arthritis patients. Clin Exp Rheumatol 1996;14:395-9.
    • (1996) Clin. Exp. Rheumatol. , vol.14 , pp. 395-399
    • Nesher, G.1    Osborn, T.G.2    Moore, T.L.3
  • 9
    • 0025877441 scopus 로고
    • Biochemical perturbations of BW 91Y (3-deazaadenosine) on human neutrophil chemotactic potential and lipid metabolism
    • SMITH DM, JOHNSON JA, TURNER RA: Biochemical perturbations of BW 91Y (3-deazaadenosine) on human neutrophil chemotactic potential and lipid metabolism. Int J Tissue React 1991;13:1-18.
    • (1991) Int. J. Tissue React , vol.13 , pp. 1-18
    • Smith, D.M.1    Johnson, J.A.2    Turner, R.A.3
  • 10
    • 33645121428 scopus 로고    scopus 로고
    • Methotrexate modulates the kinetics of adenosine in humans in vivo
    • RIKSEN NP, BARRERA P, VAN DEN BROEK PH et al.: Methotrexate modulates the kinetics of adenosine in humans in vivo. Ann Rheum Dis 2006;65:465-70.
    • (2006) Ann. Rheum. Dis. , vol.65 , pp. 465-470
    • Riksen, N.P.1    Barrera, P.2    Van Den Broek, P.H.3
  • 12
    • 0025967399 scopus 로고
    • Methotrexate inhibits neutrophil function by stimulating adenosine release from connective tissue cells
    • CRONSTEIN BN, EBERLE MA, GRUBER HE, LEVIN RI: Methotrexate inhibits neutrophil function by stimulating adenosine release from connective tissue cells. Proc Nat Acad Sci USA 1991;88:2441-5.
    • (1991) Proc. Nat. Acad. Sci. USA , vol.88 , pp. 2441-2445
    • Cronstein, B.N.1    Eberle, M.A.2    Gruber, H.E.3    Levin, R.I.4
  • 13
    • 0027139914 scopus 로고
    • The antiinflammatory mechanism of methotrexate: Increased adenosine release at inflamed sites diminishes leukocyte accumulation in an in vivo model of inflammation
    • CRONSTEIN BN, NAIME D, OSTAD E: The antiinflammatory mechanism of methotrexate: increased adenosine release at inflamed sites diminishes leukocyte accumulation in an in vivo model of inflammation. J Clin Invest 1993;92:2675-82.
    • (1993) J. Clin. Invest. , vol.92 , pp. 2675-2682
    • Cronstein, B.N.1    Naime, D.2    Ostad, E.3
  • 14
    • 0028354309 scopus 로고
    • Differences in methotrexate and 7-hydroxymethotrexate inhibition of folate-dependent enzymes of purine nucleotide biosynthesis
    • BAGGOTT JE, MORGAN SL, VAUGHN WH: Differences in methotrexate and 7-hydroxymethotrexate inhibition of folate-dependent enzymes of purine nucleotide biosynthesis. Biochem J 1994;300(Pt 3):627-9.
    • (1994) Biochem. J. , vol.300 , Issue.3 PT. , pp. 627-629
    • Baggott, J.E.1    Morgan, S.L.2    Vaughn, W.H.3
  • 15
    • 34248524004 scopus 로고    scopus 로고
    • The antiinflammatory mechanism of methotrexate depends on extracellular conversion of adenine nucleotides to adenosine by ecto-5'-nucleotidase: Findings in a study of ecto-5'-nucleotidase gene-deficient mice
    • MONTESINOS MC, TAKEDACHI M, THOMPSON LF et al.: The antiinflammatory mechanism of methotrexate depends on extracellular conversion of adenine nucleotides to adenosine by ecto-5'-nucleotidase: Findings in a study of ecto-5'-nucleotidase gene-deficient mice. Arthritis Rheum 2007;56:1440-5.
    • (2007) Arthritis Rheum. , vol.56 , pp. 1440-1445
    • Montesinos, M.C.1    Takedachi, M.2    Thompson, L.F.3
  • 16
    • 0034096901 scopus 로고    scopus 로고
    • Reversal of the antiinflammatory effects of methotrexate by the nonselective adenosine receptor antagonists theophylline and caffeine. Evidence that the antiinflammatory effects of methotrexate are mediated via multiple adenosine receptors in rat adjuvant arthritis
    • MONTESINOS C, YAP JS, DESAI A et al.: Reversal of the antiinflammatory effects of methotrexate by the nonselective adenosine receptor antagonists theophylline and caffeine. Evidence that the antiinflammatory effects of methotrexate are mediated via multiple adenosine receptors in rat adjuvant arthritis. Arthritis Rheum 2000;43:656-63.
    • (2000) Arthritis Rheum. , vol.43 , pp. 656-663
    • Montesinos, C.1    Yap, J.S.2    Desai, A.3
  • 17
    • 70349260610 scopus 로고    scopus 로고
    • Suppression of inflammation by low-dose methotrexate is mediated by adenosine A2A receptor but not A3 receptor activation in thioglycollate-induced peritonitis
    • MONTESINOS MC, DESAI A, CRONSTEIN BN: Suppression of inflammation by low-dose methotrexate is mediated by adenosine A2A receptor but not A3 receptor activation in thioglycollate-induced peritonitis. Arthritis Res Ther 2006;8: R53.
    • (2006) Arthritis Res. Ther. , vol.8
    • Montesinos, M.C.1    Desai, A.2    Cronstein, B.N.3
  • 18
    • 0037207972 scopus 로고    scopus 로고
    • Adenosine A2A or A3 receptors are required for inhibition of inflammation by methotrexate and its analog MX-68
    • MONTESINOS MC, DESAI A, DELANO D et al.: Adenosine A2A or A3 receptors are required for inhibition of inflammation by methotrexate and its analog MX-68. Arthritis Rheum 2003;48:240-7.
    • (2003) Arthritis Rheum. , vol.48 , pp. 240-247
    • Montesinos, M.C.1    Desai, A.2    Delano, D.3
  • 19
    • 0032518281 scopus 로고    scopus 로고
    • Methotrexate and sulfasalazine promote adenosine release by a mechanism that requires Ecto-5'-nucleotidase-mediated conversion of adenine nucleotides
    • MORABITO L, MONTESINOS MC, SCHREIBMAN DM et al.: Methotrexate and Sulfasalazine Promote Adenosine Release by a Mechanism that Requires Ecto-5'-nucleotidase-mediated Conversion of Adenine Nucleotides. J Clin Invest 1998;101:295-300.
    • (1998) J. Clin. Invest. , vol.101 , pp. 295-300
    • Morabito, L.1    Montesinos, M.C.2    Schreibman, D.M.3
  • 20
    • 23644450093 scopus 로고    scopus 로고
    • Genetically based resistance to the antiinflammatory effects of methotrexate in the air-pouch model of acute inflammation
    • DELANO DL, MONTESINOS MC, DESAI A et al.: Genetically based resistance to the antiinflammatory effects of methotrexate in the air-pouch model of acute inflammation. Arthritis Rheum 2005;52:2567-75.
    • (2005) Arthritis Rheum. , vol.52 , pp. 2567-2575
    • Delano, D.L.1    Montesinos, M.C.2    Desai, A.3
  • 21
    • 0002719491 scopus 로고    scopus 로고
    • The effects of caffeine ingestion on the efficacy of methotrexate
    • SILKE C, MURPHY MS, BUCKLEY T et al.: The effects of caffeine ingestion on the efficacy of methotrexate. Rheumatology (Oxford) 2001;40(Suppl. 1):34.
    • (2001) Rheumatology (Oxford) , vol.40 , Issue.1 SUPPL. , pp. 34
    • Silke, C.1    Murphy, M.S.2    Buckley, T.3
  • 22
    • 0037332053 scopus 로고    scopus 로고
    • Effect of caffeine consumption on efficacy of methotrexate in rheumatoid arthritis
    • NESHER G, MATES M, ZEVIN S: Effect of caffeine consumption on efficacy of methotrexate in rheumatoid arthritis. Arthritis Rheum 2003;48:571-2.
    • (2003) Arthritis Rheum. , vol.48 , pp. 571-572
    • Nesher, G.1    Mates, M.2    Zevin, S.3
  • 23
    • 33745789404 scopus 로고    scopus 로고
    • Dietary caffeine intake does not affect methotrexate efficacy in patients with rheumatoid arthritis
    • BENITO-GARCIA E, HELLER JE, CHIBNIK LB et al.: Dietary caffeine intake does not affect methotrexate efficacy in patients with rheumatoid arthritis. J Rheumatol 2006;33:1275-1281.
    • (2006) J. Rheumatol. , vol.33 , pp. 1275-1281
    • Benito-Garcia, E.1    Heller, J.E.2    Chibnik, L.B.3
  • 24
    • 73949120791 scopus 로고    scopus 로고
    • Gene-gene interactions in folate and adenosine biosynthesis pathways affect methotrexate efficacy and tolerability in rheumatoid arthritis
    • Oct. 24. Epub ahead of prim
    • DERVIEUX T, WESSELS JA, VAN DER STRAATEN T et al.: Gene-gene interactions in folate and adenosine biosynthesis pathways affect methotrexate efficacy and tolerability in rheumatoid arthritis. Pharmacogenet Genomics 2009 Oct. 24. [Epub ahead of prim]
    • (2009) Pharmacogenet. Genomics
    • Dervieux, T.1    Wessels, J.A.2    Van Der Straaten, T.3
  • 25
    • 33646354882 scopus 로고    scopus 로고
    • Efficacy and toxicity of methotrexate in early rheumatoid arthritis are associated with single-nucleotide polymorphisms in genes coding for folate pathway enzymes
    • WESSELS JA, DE VRIES-BOUWSTRA JK, HEIJMANS BT et al.: Efficacy and toxicity of methotrexate in early rheumatoid arthritis are associated with single-nucleotide polymorphisms in genes coding for folate pathway enzymes. Arthritis Rheum 2006;54:1087-95.
    • (2006) Arthritis Rheum. , vol.54 , pp. 1087-1095
    • Wessels, J.A.1    De Vries-Bouwstra, J.K.2    Heijmans, B.T.3
  • 26
    • 33749370785 scopus 로고    scopus 로고
    • Relationship between genetic variants in the adenosine pathway and outcome of methotrexate treatment in patients with recent-onset rheumatoid arthritis
    • WESSELS JA, KOOLOOS WM, JONGE RD et al.: Relationship between genetic variants in the adenosine pathway and outcome of methotrexate treatment in patients with recent-onset rheumatoid arthritis. Arthritis Rheum 2006;54:28309.
    • (2006) Arthritis Rheum. , vol.54 , pp. 28309
    • Wessels, J.A.1    Kooloos, W.M.2    Jonge, R.D.3
  • 27
    • 65849260738 scopus 로고    scopus 로고
    • Methotrexate pharmacogenomics in rheumatoid arthritis: Introducing false-positive report probability
    • DERVIEUX T: Methotrexate pharmacogenomics in rheumatoid arthritis: introducing false-positive report probability. Rheumatology (Oxford) 2009;48:597-8.
    • (2009) Rheumatology (Oxford) , vol.48 , pp. 597-598
    • Dervieux, T.1
  • 28
    • 33845898754 scopus 로고    scopus 로고
    • Overview of the pharmacoeconomics of pharmacogenetics
    • DERVIEUX T, BALA MV: Overview of the pharmacoeconomics of pharmacogenetics. Pharmacogenomics 2006;7:1175-84.
    • (2006) Pharmacogenomics , vol.7 , pp. 1175-1184
    • Dervieux, T.1    Bala, M.V.2
  • 29
    • 23444443994 scopus 로고    scopus 로고
    • Pharmacogenetic and metabolite measurements are associated with clinical status in patients with rheumatoid arthritis treated with methotrexate: Results of a multicentred cross sectional observational study
    • DERVIEUX T, FURST D, LEIN DO et al.: Pharmacogenetic and metabolite measurements are associated with clinical status in patients with rheumatoid arthritis treated with methotrexate: results of a multicentred cross sectional observational study. Ann Rheum Dis 2005;64:1180-5.
    • (2005) Ann. Rheum. Dis. , vol.64 , pp. 1180-1185
    • Dervieux, T.1    Furst, D.2    Lein, D.O.3
  • 30
    • 4444376725 scopus 로고    scopus 로고
    • Polyglutamation of methotrexate with common polymorphisms in reduced folate carrier, aminoimidazole carboxamide ribonucleotide transformylase, and thymidylate synthase are associated with methotrexate effects in rheumatoid arthritis
    • DERVIEUX T, FURST D, LEIN DO et al.: Polyglutamation of methotrexate with common polymorphisms in reduced folate carrier, aminoimidazole carboxamide ribonucleotide transformylase, and thymidylate synthase are associated with methotrexate effects in rheumatoid arthritis. Arthritis Rheum 2004;50:2766-74.
    • (2004) Arthritis Rheum. , vol.50 , pp. 2766-2774
    • Dervieux, T.1    Furst, D.2    Lein, D.O.3
  • 31
    • 33750352061 scopus 로고    scopus 로고
    • Pharmacogenomic and metabolic biomarkers in the folate pathway and their association with methotrexate effects during dosage escalation in rheumatoid arthritis
    • DERVIEUX T, GREENSTEIN N, KREMER J: Pharmacogenomic and metabolic biomarkers in the folate pathway and their association with methotrexate effects during dosage escalation in rheumatoid arthritis. Arthritis Rheum 2006;54:3095-103.
    • (2006) Arthritis Rheum. , vol.54 , pp. 3095-3103
    • Dervieux, T.1    Greenstein, N.2    Kremer, J.3
  • 32
    • 32444436350 scopus 로고    scopus 로고
    • Risk genotypes in folate-dependent enzymes and their association with methotrexate-related side effects in rheumatoid arthritis
    • WEISMAN MH, FURST DE, PARK GS et al.: Risk genotypes in folate-dependent enzymes and their association with methotrexate-related side effects in rheumatoid arthritis. Arthritis Rheum 2006;54:607-12.
    • (2006) Arthritis Rheum. , vol.54 , pp. 607-612
    • Weisman, M.H.1    Furst, D.E.2    Park, G.S.3
  • 33
    • 65649129311 scopus 로고    scopus 로고
    • Adenosine signaling contributes to ethanol-induced fatty liver in mice
    • PENG Z, BOREA PA, WILDER T et al.: Adenosine signaling contributes to ethanol-induced fatty liver in mice. J Clin Invest 2009;119:582-94.
    • (2009) J. Clin. Invest. , vol.119 , pp. 582-594
    • Peng, Z.1    Borea, P.A.2    Wilder, T.3
  • 34
    • 33751095370 scopus 로고    scopus 로고
    • Effect of anti-TNFalpha treatment on circulating endothelial progenitor cells (EPCs) in rheumatoid arthritis
    • ABLIN JN, BOGUSLAVSKI V, ALOUSH V et al.: Effect of anti-TNFalpha treatment on circulating endothelial progenitor cells (EPCs) in rheumatoid arthritis. Life Sci 2006;79:2364-9.
    • (2006) Life Sci. , vol.79 , pp. 2364-2369
    • Ablin, J.N.1    Boguslavski, V.2    Aloush, V.3
  • 35
    • 46749091223 scopus 로고    scopus 로고
    • Ecto-5'-nucleotidase (CD73) -mediated extracellular adenosine production plays a critical role in hepatic fibrosis
    • DOI 10.1096/fj.07-100685
    • PENG Z, FERNANDEZ P, WILDER T et al.: Ecto-5'-nucleotidase (CD73)-mediated extracellular adenosine production plays a critical role in hepatic fibrosis. Faseb J 2008;22:2263-72. (Pubitemid 351948645)
    • (2008) FASEB Journal , vol.22 , Issue.7 , pp. 2263-2272
    • Peng, Z.1    Fernandez, P.2    Wilder, T.3    Yee, H.4    Chiriboga, L.5    Chan, E.S.L.6    Cronstein, B.N.7
  • 36
    • 0036092565 scopus 로고    scopus 로고
    • Molecular genetic studies on sleep-wake regulation, with special emphasis on the prostaglandin D (2) system
    • HAYAISHI O: Molecular genetic studies on sleep-wake regulation, with special emphasis on the prostaglandin D (2) system. J Appl Physiol 2002;92:863-868.
    • (2002) J. Appl. Physiol. , vol.92 , pp. 863-868
    • Hayaishi, O.1
  • 37
    • 0035980493 scopus 로고    scopus 로고
    • The sulphydryl reagent, N-ethylmaleimide, disrupts sleep and blocks A1 adenosine receptormediated inhibition of intracellular calcium signaling in the in vivo ventromedial preoptic nucleus
    • IKEDA M, SAGARA M, SEKINO Y et al.: The sulphydryl reagent, N-ethylmaleimide, disrupts sleep and blocks A1 adenosine receptormediated inhibition of intracellular calcium signaling in the in vivo ventromedial preoptic nucleus. Neuroscience 2001;106:733-43.
    • (2001) Neuroscience , vol.106 , pp. 733-743
    • Ikeda, M.1    Sagara, M.2    Sekino, Y.3
  • 39
    • 34249010847 scopus 로고    scopus 로고
    • Neuroanatomy and neurochemistry of sleep
    • STENBERG D: Neuroanatomy and neurochemistry of sleep. Cell Mol Life Sci 2007;64:1187-204.
    • (2007) Cell. Mol. Life Sci. , vol.64 , pp. 1187-1204
    • Stenberg, D.1
  • 40
    • 0347517768 scopus 로고    scopus 로고
    • Sleep and its homeostatic regulation in mice lacking the adenosine A1 receptor
    • STENBERG D, LITONIUS E, HALLDNER L et al.: Sleep and its homeostatic regulation in mice lacking the adenosine A1 receptor. J Sleep Res 2003;12:283-90.
    • (2003) J. Sleep Res. , vol.12 , pp. 283-290
    • Stenberg, D.1    Litonius, E.2    Halldner, L.3
  • 41
    • 43949099252 scopus 로고    scopus 로고
    • Adenosine and the homeostatic control of sleep: Effects of A1 receptor blockade in the perifornical lateral hypothalamus on sleep-wakefulness
    • THAKKAR MM, ENGEMANN SC, WALSH KM, SAHOTA PK: Adenosine and the homeostatic control of sleep: effects of A1 receptor blockade in the perifornical lateral hypothalamus on sleep-wakefulness. Neuroscience 2008;153:875-80.
    • (2008) Neuroscience , vol.153 , pp. 875-880
    • Thakkar, M.M.1    Engemann, S.C.2    Walsh, K.M.3    Sahota, P.K.4
  • 42
    • 0028919570 scopus 로고
    • Aminophylline for methotrexate-induced neurotoxicity
    • BERNINI JC, FORT DW, GRIENER JC et al.: Aminophylline for methotrexate-induced neurotoxicity. Lancet 1995;345:544-7.
    • (1995) Lancet , vol.345 , pp. 544-547
    • Bernini, J.C.1    Fort, D.W.2    Griener, J.C.3
  • 43
    • 0348222661 scopus 로고    scopus 로고
    • Adenosine: An endogenous regulator of innate immunity
    • HASKO G, CRONSTEIN BN: Adenosine: an endogenous regulator of innate immunity. Trends Immunol 2004;25:33-9.
    • (2004) Trends Immunol. , vol.25 , pp. 33-39
    • Hasko, G.1    Cronstein, B.N.2
  • 44
    • 51049101334 scopus 로고    scopus 로고
    • Adenosine receptors: Therapeutic aspects for inflammatory and immune diseases
    • HASKO G, LINDEN J, CRONSTEIN B, PACHER P: Adenosine receptors: therapeutic aspects for inflammatory and immune diseases. Nat Rev Drug Discov 2008;7:759-70.
    • (2008) Nat. Rev. Drug Discov. , vol.7 , pp. 759-770
    • Hasko, G.1    Linden, J.2    Cronstein, B.3    Pacher, P.4


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.