메뉴 건너뛰기




Volumn 9, Issue 4, 2006, Pages 366-378

Oxygen-sensing in tumors

Author keywords

Crabtree effect; Dioxygenase; Electron transport; Energy homeostasis; Hemoprotein; Hypoxia; Hypoxia inducible factor 1; Oxidoreductase; Pasteur effect; Pyruvate; Warburg effect

Indexed keywords

2 (2 NITRO 1H IMIDAZOL 1 YL) N (2,2,3,3,3 PENTAFLUOROPROPYL)ACETAMIDE; 2 OXOGLUTARIC ACID; DIOXYGENASE; GLUCOSE; GROWTH FACTOR; HEME; HYPOXIA INDUCIBLE FACTOR 1; IRON; MESSENGER RNA; OXYGEN; PHOSPHOTRANSFERASE; PIMONIDAZOLE; REACTIVE OXYGEN METABOLITE;

EID: 33746253907     PISSN: 13631950     EISSN: 15353885     Source Type: Journal    
DOI: 10.1097/01.mco.0000232895.28674.79     Document Type: Review
Times cited : (25)

References (101)
  • 1
    • 10644270846 scopus 로고    scopus 로고
    • Tumor hypoxia: Causative factors, compensatory mechanisms, and cellular response
    • Vaupel P, Harrison L. Tumor hypoxia: causative factors, compensatory mechanisms, and cellular response. Oncologist 2004; 9 (Suppl 5):4-9.
    • (2004) Oncologist , vol.9 , Issue.5 SUPPL. , pp. 4-9
    • Vaupel, P.1    Harrison, L.2
  • 2
    • 0038293080 scopus 로고    scopus 로고
    • Prognostic significance of tumor oxygenation in humans
    • Evans SM, Koch CJ. Prognostic significance of tumor oxygenation in humans. Cancer Lett 2003; 195:1-16.
    • (2003) Cancer Lett , vol.195 , pp. 1-16
    • Evans, S.M.1    Koch, C.J.2
  • 3
    • 2342588221 scopus 로고    scopus 로고
    • Vaso-occlusive and prothrombotic mechanisms associated with tumor hypoxia, necrosis, and accelerated growth in glioblastoma
    • Brat DJ, Van Meir EG. Vaso-occlusive and prothrombotic mechanisms associated with tumor hypoxia, necrosis, and accelerated growth in glioblastoma. Lab Invest 2004; 84:397-405.
    • (2004) Lab Invest , vol.84 , pp. 397-405
    • Brat, D.J.1    Van Meir, E.G.2
  • 4
    • 27944473690 scopus 로고    scopus 로고
    • VEGF as a key mediator of angiogenesis in cancer
    • Carmeliet P. VEGF as a key mediator of angiogenesis in cancer. Oncology 2005; 69 (Suppl 3):4-10.
    • (2005) Oncology , vol.69 , Issue.3 SUPPL. , pp. 4-10
    • Carmeliet, P.1
  • 5
    • 0141988559 scopus 로고    scopus 로고
    • Molecular mechanisms of tumor invasion and metastasis: An integrated view
    • Cairns RA, Khokha R, Hill RP. Molecular mechanisms of tumor invasion and metastasis: an integrated view. Curr Mol Med 2003; 3:659-671.
    • (2003) Curr Mol Med , vol.3 , pp. 659-671
    • Cairns, R.A.1    Khokha, R.2    Hill, R.P.3
  • 6
    • 31444444162 scopus 로고    scopus 로고
    • Integration of oxygen signaling at the consensus HRE
    • Wenger RH, Stiehl DP, Camenisch G. Integration of oxygen signaling at the consensus HRE. Sci STKE 2005; 2005:re12. A comprehensive review of HIF-1 regulated genes and signaling pathways converging on the hypoxia-recognition element.
    • (2005) Sci STKE , vol.2005
    • Wenger, R.H.1    Stiehl, D.P.2    Camenisch, G.3
  • 7
    • 0031307796 scopus 로고    scopus 로고
    • Oxygen delivery: Implications for the biology and therapy of solid tumors
    • Rockwell S. Oxygen delivery: implications for the biology and therapy of solid tumors. Oncol Res 1997; 9:383-390.
    • (1997) Oncol Res , vol.9 , pp. 383-390
    • Rockwell, S.1
  • 8
    • 0142166332 scopus 로고    scopus 로고
    • Targeting HIF-1 for cancer therapy
    • Semenza GL. Targeting HIF-1 for cancer therapy. Nat Rev Cancer 2003; 3:721-732.
    • (2003) Nat Rev Cancer , vol.3 , pp. 721-732
    • Semenza, G.L.1
  • 9
    • 0027210562 scopus 로고
    • General involvement of hypoxia-inducible factor 1 in transcriptional response to hypoxia
    • U S A
    • Wang GL, Semenza GL. General involvement of hypoxia-inducible factor 1 in transcriptional response to hypoxia. Proc Natl Acad Sci U S A 1993; 90:4304-4308.
    • (1993) Proc Natl Acad Sci , vol.90 , pp. 4304-4308
    • Wang, G.L.1    Semenza, G.L.2
  • 10
    • 0033571682 scopus 로고    scopus 로고
    • Overexpression of hypoxia-inducible factor 1α in common human cancers and their metastases
    • Zhong H, De Marzo AM, Laughner E, et al. Overexpression of hypoxia-inducible factor 1α in common human cancers and their metastases. Cancer Res 1999; 59:5830-5835.
    • (1999) Cancer Res , vol.59 , pp. 5830-5835
    • Zhong, H.1    De Marzo, A.M.2    Laughner, E.3
  • 11
    • 0142154635 scopus 로고    scopus 로고
    • Oxygen-dependent and -independent regulation of HIF-1alpha
    • Chun YS, Kim MS, Park JW. Oxygen-dependent and -independent regulation of HIF-1alpha. J Korean Med Sci 2002; 17:581-588.
    • (2002) J Korean Med Sci , vol.17 , pp. 581-588
    • Chun, Y.S.1    Kim, M.S.2    Park, J.W.3
  • 12
    • 0033587146 scopus 로고    scopus 로고
    • The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
    • Maxwell PH, Wiesener MS, Chang GW, et al. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 1999; 399:271-275.
    • (1999) Nature , vol.399 , pp. 271-275
    • Maxwell, P.H.1    Wiesener, M.S.2    Chang, G.W.3
  • 13
    • 16644373473 scopus 로고    scopus 로고
    • Role of VHL gene mutation in human cancer
    • Kim WY, Kaelin WG. Role of VHL gene mutation in human cancer. J Clin Oncol 2004; 22:4991-5004.
    • (2004) J Clin Oncol , vol.22 , pp. 4991-5004
    • Kim, W.Y.1    Kaelin, W.G.2
  • 16
    • 0035834409 scopus 로고    scopus 로고
    • A conserved family of prolyl-4-hydroxylases that modify HIF
    • Bruick RK. McKnight SL A conserved family of prolyl-4-hydroxylases that modify HIF. Science 2001; 294:1337-1340.
    • (2001) Science , vol.294 , pp. 1337-1340
    • Bruick, R.K.1    McKnight, S.L.2
  • 17
    • 17944375360 scopus 로고    scopus 로고
    • C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation
    • Epstein AC, Gleadle JM, McNeill LA, et al. C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell 2001; 107:43-54.
    • (2001) Cell , vol.107 , pp. 43-54
    • Epstein, A.C.1    Gleadle, J.M.2    McNeill, L.A.3
  • 18
    • 0037097861 scopus 로고    scopus 로고
    • FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor
    • Lando D, Peet DJ, Gorman JJ, et al. FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. Genes Dev 2002; 16:1466-1471.
    • (2002) Genes Dev , vol.16 , pp. 1466-1471
    • Lando, D.1    Peet, D.J.2    Gorman, J.J.3
  • 19
    • 27844577728 scopus 로고    scopus 로고
    • Suppression of hypoxia-inducible factor 1alpha (HIF-1alpha) transcriptional activity by the HIF prolyl hydroxylase EGLN1
    • To KK, Huang LE. Suppression of hypoxia-inducible factor 1alpha (HIF-1alpha) transcriptional activity by the HIF prolyl hydroxylase EGLN1. J Biol Chem 2005; 280:38102-38107. An additional function of HPH-2 in blocking HIF-1-mediated transcription is shown.
    • (2005) J Biol Chem , vol.280 , pp. 38102-38107
    • To, K.K.1    Huang, L.E.2
  • 20
    • 0043234538 scopus 로고    scopus 로고
    • Characterization of the human prolyl 4-hydroxylases that modify the hypoxia-inducible factor
    • Hirsila M, Koivunen P, Gunzler V, et al. Characterization of the human prolyl 4-hydroxylases that modify the hypoxia-inducible factor. J Biol Chem 2003; 278:30772-30780.
    • (2003) J Biol Chem , vol.278 , pp. 30772-30780
    • Hirsila, M.1    Koivunen, P.2    Gunzler, V.3
  • 21
    • 0037131159 scopus 로고    scopus 로고
    • Sequence determinants in hypoxia-inducible factor-1α for hydroxylation by the prolyl hydroxylases PHD1, PHD2, and PHD3
    • Huang J, Zhao Q, Mooney SM, Lee FS. Sequence determinants in hypoxia-inducible factor-1α for hydroxylation by the prolyl hydroxylases PHD1, PHD2, and PHD3. J Biol Chem 2002; 277:39792-39800.
    • (2002) J Biol Chem , vol.277 , pp. 39792-39800
    • Huang, J.1    Zhao, Q.2    Mooney, S.M.3    Lee, F.S.4
  • 22
    • 22544464403 scopus 로고    scopus 로고
    • Coordinate regulation of the oxygen-dependent degradation domains of hypoxia-inducible factor 1 alpha
    • Chan DA, Sutphin PD, Yen SE, Giaccia AJ. Coordinate regulation of the oxygen-dependent degradation domains of hypoxia-inducible factor 1 alpha. Mol Cell Biol 2005; 25:6415-6426.
    • (2005) Mol Cell Biol , vol.25 , pp. 6415-6426
    • Chan, D.A.1    Sutphin, P.D.2    Yen, S.E.3    Giaccia, A.J.4
  • 23
    • 4644318828 scopus 로고    scopus 로고
    • Differential function of the prolyl hydroxylases PHD1, PHD2, and PHD3 in the regulation of hypoxia-inducible factor
    • Appelhoff RJ, Tian YM, Raval RR, et al. Differential function of the prolyl hydroxylases PHD1, PHD2, and PHD3 in the regulation of hypoxia-inducible factor. J Biol Chem 2004; 279:38458-38465.
    • (2004) J Biol Chem , vol.279 , pp. 38458-38465
    • Appelhoff, R.J.1    Tian, Y.M.2    Raval, R.R.3
  • 24
    • 13944276440 scopus 로고    scopus 로고
    • OS-9 interacts with hypoxia-inducible factor 1alpha and prolyl hydroxylases to promote oxygen-dependent degradation of HIF-1alpha
    • Baek JH, Mahon PC, Oh J, et al. OS-9 interacts with hypoxia-inducible factor 1alpha and prolyl hydroxylases to promote oxygen-dependent degradation of HIF-1alpha. Mol Cell 2005; 17:503-512.
    • (2005) Mol Cell , vol.17 , pp. 503-512
    • Baek, J.H.1    Mahon, P.C.2    Oh, J.3
  • 25
    • 3142646779 scopus 로고    scopus 로고
    • The HIF prolyl hydroxylase PHD3 is a potential substrate of the TRiC chaperonin
    • Masson N, Appelhoff RJ, Tuckerman JR, et al. The HIF prolyl hydroxylase PHD3 is a potential substrate of the TRiC chaperonin. FEBS Lett 2004; 570:166-170.
    • (2004) FEBS Lett , vol.570 , pp. 166-170
    • Masson, N.1    Appelhoff, R.J.2    Tuckerman, J.R.3
  • 26
    • 33646852807 scopus 로고    scopus 로고
    • The novel WD-repeat protein Morg1 acts as a molecular scaffold for hypoxia-inducible factor prolyl hydroxylase 3 (PHD3)
    • Hopfer U, Hopfer H, Jablonski K, et al. The novel WD-repeat protein Morg1 acts as a molecular scaffold for hypoxia-inducible factor prolyl hydroxylase 3 (PHD3). J Biol Chem 2006; 281:8645-8655.
    • (2006) J Biol Chem , vol.281 , pp. 8645-8655
    • Hopfer, U.1    Hopfer, H.2    Jablonski, K.3
  • 27
    • 0037386143 scopus 로고    scopus 로고
    • Intracellular localisation of human HIF-1α hydroxylases: Implications for oxygen sensing
    • Metzen E, Berchner-Pfannschmidt U, Stengel P, et al. Intracellular localisation of human HIF-1α hydroxylases: implications for oxygen sensing. J Cell Sci 2003; 116:1319-1326.
    • (2003) J Cell Sci , vol.116 , pp. 1319-1326
    • Metzen, E.1    Berchner-Pfannschmidt, U.2    Stengel, P.3
  • 28
    • 0041465022 scopus 로고    scopus 로고
    • HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1α in normoxia
    • Berra E, Benizri E, Ginouves A, et al. HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1α in normoxia. EMBO J 2003; 22:4082-4090.
    • (2003) EMBO J , vol.22 , pp. 4082-4090
    • Berra, E.1    Benizri, E.2    Ginouves, A.3
  • 29
    • 1542300383 scopus 로고    scopus 로고
    • The von Hippel Lindau/hypoxia-inducible factor (HIF) pathway regulates the transcription of the HIF-proline hydroxylase genes in response to low oxygen
    • del Peso L, Castellanos MC, Temes E, et al. The von Hippel Lindau/hypoxia-inducible factor (HIF) pathway regulates the transcription of the HIF-proline hydroxylase genes in response to low oxygen. J Biol Chem 2003; 278:48690-48695.
    • (2003) J Biol Chem , vol.278 , pp. 48690-48695
    • Del Peso, L.1    Castellanos, M.C.2    Temes, E.3
  • 30
    • 33644781737 scopus 로고    scopus 로고
    • Overexpression and nuclear translocation of hypoxia-inducible factor prolyl hydroxylase PHD2 in head and neck squamous cell carcinoma is associated with tumor aggressiveness
    • Jokilehto T, Rantanen K, Luukkaa M, et al. Overexpression and nuclear translocation of hypoxia-inducible factor prolyl hydroxylase PHD2 in head and neck squamous cell carcinoma is associated with tumor aggressiveness. Clin Cancer Res 2006; 12:1080-1087.
    • (2006) Clin Cancer Res , vol.12 , pp. 1080-1087
    • Jokilehto, T.1    Rantanen, K.2    Luukkaa, M.3
  • 31
    • 0038324399 scopus 로고    scopus 로고
    • The HAG mechanism: A molecular rationale for the therapeutic application of iron chelators in human diseases involving the 2-oxoacid utilizing dioxygenases
    • Hanauske-Abel HM, Popowicz AM. The HAG mechanism: a molecular rationale for the therapeutic application of iron chelators in human diseases involving the 2-oxoacid utilizing dioxygenases. Curr Med Chem 2003; 10:1005-1019.
    • (2003) Curr Med Chem , vol.10 , pp. 1005-1019
    • Hanauske-Abel, H.M.1    Popowicz, A.M.2
  • 33
    • 0037189542 scopus 로고    scopus 로고
    • Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis
    • Lu H, Forbes RA, Verma A. Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis. J Biol Chem 2002; 277:23111-23115.
    • (2002) J Biol Chem , vol.277 , pp. 23111-23115
    • Lu, H.1    Forbes, R.A.2    Verma, A.3
  • 34
    • 29644442625 scopus 로고    scopus 로고
    • Reversible inactivation of HIF-1 prolyl hydroxylases allows cell metabolism to control basal HIF-1
    • Lu H, Dalgard CL, Mohyeldin A, et al. Reversible inactivation of HIF-1 prolyl hydroxylases allows cell metabolism to control basal HIF-1. J Biol Chem 2005; 280:41928-41939. This paper provides evidence for reversible inactivation of HPHs as a regulatory mechanism used by metabolites and ROS for activating HIF-1.
    • (2005) J Biol Chem , vol.280 , pp. 41928-41939
    • Lu, H.1    Dalgard, C.L.2    Mohyeldin, A.3
  • 35
    • 2642542967 scopus 로고    scopus 로고
    • Endogenous 2-oxoacids differentially regulate expression of oxygen sensors
    • Dalgard CL, Lu H, Mohyeldin A, Verma A. Endogenous 2-oxoacids differentially regulate expression of oxygen sensors. Biochem J 2004; 380:419-424.
    • (2004) Biochem J , vol.380 , pp. 419-424
    • Dalgard, C.L.1    Lu, H.2    Mohyeldin, A.3    Verma, A.4
  • 36
    • 0037446983 scopus 로고    scopus 로고
    • Effect of ascorbate on the activity of hypoxia-inducible factor in cancer cells
    • Knowles HJ, Raval RR, Harris AL, Ratcliffe PJ. Effect of ascorbate on the activity of hypoxia-inducible factor in cancer cells. Cancer Res 2003; 63:1764-1768.
    • (2003) Cancer Res , vol.63 , pp. 1764-1768
    • Knowles, H.J.1    Raval, R.R.2    Harris, A.L.3    Ratcliffe, P.J.4
  • 37
    • 0023021512 scopus 로고
    • Partial identity of the 2-oxoglutarate and ascorbate binding sites of prolyl 4-hydroxylase
    • Majamaa K, Gunzler V, Hanauske-Abel HM, et al. Partial identity of the 2-oxoglutarate and ascorbate binding sites of prolyl 4-hydroxylase. J Biol Chem 1986; 261:7819-7823.
    • (1986) J Biol Chem , vol.261 , pp. 7819-7823
    • Majamaa, K.1    Gunzler, V.2    Hanauske-Abel, H.M.3
  • 38
    • 0021864525 scopus 로고
    • Differences between collagen hydroxylases and 2-oxoglutarate dehydrogenase in their inhibition by structural analogues of 2-oxoglutarate
    • Majamaa K, Turpeenniemi-Hujanen TM, Latipaa P, et al. Differences between collagen hydroxylases and 2-oxoglutarate dehydrogenase in their inhibition by structural analogues of 2-oxoglutarate. Biochem J 1985; 229:127-133.
    • (1985) Biochem J , vol.229 , pp. 127-133
    • Majamaa, K.1    Turpeenniemi-Hujanen, T.M.2    Latipaa, P.3
  • 39
    • 0031879608 scopus 로고    scopus 로고
    • Prolyl hydroxylase activity in tissue homogenates of annelids from deep sea hydrothermal vents
    • Kaule G, Timpl R, Gaill F, Gunzler V. Prolyl hydroxylase activity in tissue homogenates of annelids from deep sea hydrothermal vents. Matrix Biol 1998; 17:205-212.
    • (1998) Matrix Biol , vol.17 , pp. 205-212
    • Kaule, G.1    Timpl, R.2    Gaill, F.3    Gunzler, V.4
  • 41
    • 0035870271 scopus 로고    scopus 로고
    • Angiogenic activity of pyruvic acid in in vivo and in vitro angiogenesis models
    • Lee MS, Moon EJ, Lee SW, et al. Angiogenic activity of pyruvic acid in in vivo and in vitro angiogenesis models. Cancer Res 2001; 61:3290-3293.
    • (2001) Cancer Res , vol.61 , pp. 3290-3293
    • Lee, M.S.1    Moon, E.J.2    Lee, S.W.3
  • 42
  • 43
    • 0035501326 scopus 로고    scopus 로고
    • Tissue gradients of energy metabolites mirror oxygen tension gradients in a rat mammary carcinoma model
    • Walenta S, Snyder S, Haroon ZA, et al. Tissue gradients of energy metabolites mirror oxygen tension gradients in a rat mammary carcinoma model. Int J Radiat Oncol Biol Phys 2001; 51:840-848.
    • (2001) Int J Radiat Oncol Biol Phys , vol.51 , pp. 840-848
    • Walenta, S.1    Snyder, S.2    Haroon, Z.A.3
  • 44
    • 0034652620 scopus 로고    scopus 로고
    • High lactate levels predict likelihood of metastases, tumor recurrence, and restricted patient survival in human cervical cancers
    • Walenta S, Wetterling M, Lehrke M, et al. High lactate levels predict likelihood of metastases, tumor recurrence, and restricted patient survival in human cervical cancers. Cancer Res 2000; 60:916-921.
    • (2000) Cancer Res , vol.60 , pp. 916-921
    • Walenta, S.1    Wetterling, M.2    Lehrke, M.3
  • 45
    • 0035479076 scopus 로고    scopus 로고
    • Elevated tumor lactate concentrations predict for an increased risk of metastases in head-and-neck cancer
    • Brizel DM, Schroeder T, Scher RL, et al. Elevated tumor lactate concentrations predict for an increased risk of metastases in head-and-neck cancer. Int J Radiat Oncol Biol Phys 2001; 51:349-353.
    • (2001) Int J Radiat Oncol Biol Phys , vol.51 , pp. 349-353
    • Brizel, D.M.1    Schroeder, T.2    Scher, R.L.3
  • 46
    • 31544445490 scopus 로고    scopus 로고
    • Comparison of metabolic pathways between cancer cells and stromal cells in colorectal carcinomas: A metabolic survival role for tumor-associated stroma
    • Koukourakis MI, Giatromanolaki A, Harris AL, Sivridis E. Comparison of metabolic pathways between cancer cells and stromal cells in colorectal carcinomas: a metabolic survival role for tumor-associated stroma. Cancer Res 2006; 66:632-637.
    • (2006) Cancer Res , vol.66 , pp. 632-637
    • Koukourakis, M.I.1    Giatromanolaki, A.2    Harris, A.L.3    Sivridis, E.4
  • 47
    • 19944433653 scopus 로고    scopus 로고
    • Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase
    • Selak MA, Armour SM, MacKenzie ED, et al. Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase. Cancer Cell 2005; 7:77-85. A novel role is identified for the TCA cycle metabolites succinate and fumarate in regulating HIF-1.
    • (2005) Cancer Cell , vol.7 , pp. 77-85
    • Selak, M.A.1    Armour, S.M.2    MacKenzie, E.D.3
  • 48
    • 23644448721 scopus 로고    scopus 로고
    • HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: Novel role of fumarate in regulation of HIF stability
    • Isaacs JS, Jung YJ, Mole DR, et al. HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: novel role of fumarate in regulation of HIF stability. Cancer Cell 2005; 8:143-153. A novel role is identified for the TCA cycle metabolites succinate and fumarate in regulating HIF-1.
    • (2005) Cancer Cell , vol.8 , pp. 143-153
    • Isaacs, J.S.1    Jung, Y.J.2    Mole, D.R.3
  • 49
    • 26444570010 scopus 로고    scopus 로고
    • Accumulation of Krebs cycle intermediates and over-expression of HIF1alpha in tumours which result from germline FH and SDH mutations
    • Pollard PJ, Briere JJ, Alam NA, et al. Accumulation of Krebs cycle intermediates and over-expression of HIF1alpha in tumours which result from germline FH and SDH mutations. Hum Mol Genet 2005; 14:2231-2239. A novel role is identified for the TCA cycle metabolites succinate and fumarate in regulating HIF-1.
    • (2005) Hum Mol Genet , vol.14 , pp. 2231-2239
    • Pollard, P.J.1    Briere, J.J.2    Alam, N.A.3
  • 50
    • 28544446058 scopus 로고    scopus 로고
    • Mitochondrial tumour suppressors: A genetic and biochemical update
    • Gottlieb E, Tomlinson IP. Mitochondrial tumour suppressors: a genetic and biochemical update. Nat Rev Cancer 2005; 5:857-866. A timely review on the novel role of mitochondrial proteins playing tumor suppressor roles through metabolic signaling mechanisms.
    • (2005) Nat Rev Cancer , vol.5 , pp. 857-866
    • Gottlieb, E.1    Tomlinson, I.P.2
  • 52
    • 24344438196 scopus 로고    scopus 로고
    • Reactive oxygen species in the control of hypoxia-inducible factor-mediated gene expression
    • Kietzmann T, Gorlach A. Reactive oxygen species in the control of hypoxia-inducible factor-mediated gene expression. Semin Cell Dev Biol 2005; 16:474-486. Thorough coverage of the evidence and controversies regarding ROS signaling mechanisms in relation to HIF-1 activation.
    • (2005) Semin Cell Dev Biol , vol.16 , pp. 474-486
    • Kietzmann, T.1    Gorlach, A.2
  • 53
    • 4544346656 scopus 로고    scopus 로고
    • JunD reduces tumor angiogenesis by protecting cells from oxidative stress
    • Gerald D, Berra E, Frapart YM, et al. JunD reduces tumor angiogenesis by protecting cells from oxidative stress. Cell 2004; 118:781-794.
    • (2004) Cell , vol.118 , pp. 781-794
    • Gerald, D.1    Berra, E.2    Frapart, Y.M.3
  • 54
    • 0037262072 scopus 로고    scopus 로고
    • The role of nitric oxide (NO) in stability regulation of hypoxia inducible factor-1alpha (HIF-1alpha)
    • Brune B, Zhou J. The role of nitric oxide (NO) in stability regulation of hypoxia inducible factor-1alpha (HIF-1alpha). Curr Med Chem 2003; 10:845-855.
    • (2003) Curr Med Chem , vol.10 , pp. 845-855
    • Brune, B.1    Zhou, J.2
  • 55
    • 31544473721 scopus 로고    scopus 로고
    • Nitric oxide is a factor in the stabilization of hypoxia-inducible factor-1alpha in cancer: Role of free radical formation
    • Quintero M, Brennan PA, Thomas GJ, Moncada S. Nitric oxide is a factor in the stabilization of hypoxia-inducible factor-1alpha in cancer: role of free radical formation. Cancer Res 2006; 66:770-774.
    • (2006) Cancer Res , vol.66 , pp. 770-774
    • Quintero, M.1    Brennan, P.A.2    Thomas, G.J.3    Moncada, S.4
  • 56
    • 2342611976 scopus 로고    scopus 로고
    • Radiation activates HIF-1 to regulate vascular radiosensitivity in tumors: Role of reoxygenation, free radicals, and stress granules
    • Moeller BJ, Cao Y, Li CY, Dewhirst MW. Radiation activates HIF-1 to regulate vascular radiosensitivity in tumors: role of reoxygenation, free radicals, and stress granules. Cancer Cell 2004; 5:429-441.
    • (2004) Cancer Cell , vol.5 , pp. 429-441
    • Moeller, B.J.1    Cao, Y.2    Li, C.Y.3    Dewhirst, M.W.4
  • 57
    • 33644620740 scopus 로고    scopus 로고
    • NO restores HIF-1alpha hydroxylation during hypoxia: Role of reactive oxygen species
    • Callapina M, Zhou J, Schmid T, et al. NO restores HIF-1alpha hydroxylation during hypoxia: role of reactive oxygen species. Free Radic Biol Med 2005; 39:925-936.
    • (2005) Free Radic Biol Med , vol.39 , pp. 925-936
    • Callapina, M.1    Zhou, J.2    Schmid, T.3
  • 58
    • 26444439977 scopus 로고    scopus 로고
    • Mitochondrial regulation of oxygen sensing
    • Bell EL, Emerling BM, Chandel NS. Mitochondrial regulation of oxygen sensing. Mitochondrion 2005; 5:322-332. An excellent review of the evidence for and gaps in knowledge regarding a role for mitochondrial ROS in HIF-1 regulation.
    • (2005) Mitochondrion , vol.5 , pp. 322-332
    • Bell, E.L.1    Emerling, B.M.2    Chandel, N.S.3
  • 59
    • 24144444133 scopus 로고    scopus 로고
    • Oxygen sensing requires mitochondrial ROS but not oxidative phosphorylation
    • Brunelle JK, Bell EL, Quesada NM, et al. Oxygen sensing requires mitochondrial ROS but not oxidative phosphorylation. Cell Metab 2005; 1:409-414. Provides important evidence that mitochondrial ROS production is required for HIF-1 regulation during hypoxia, but not anoxia.
    • (2005) Cell Metab , vol.1 , pp. 409-414
    • Brunelle, J.K.1    Bell, E.L.2    Quesada, N.M.3
  • 60
    • 24144493814 scopus 로고    scopus 로고
    • Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing
    • Guzy RD, Hoyos B, Robin E, et al. Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing. Cell Metab 2005; 1:401-408. Provides important evidence that mitochondrial ROS production is required for HIF-1 regulation during hypoxia, but not anoxia.
    • (2005) Cell Metab , vol.1 , pp. 401-408
    • Guzy, R.D.1    Hoyos, B.2    Robin, E.3
  • 61
    • 24144447915 scopus 로고    scopus 로고
    • Mitochondrial dysfunction resulting from loss of cytochrome c impairs cellular oxygen sensing and hypoxic HIF-alpha activation
    • Mansfield KD, Guzy RD, Pan Y, et al. Mitochondrial dysfunction resulting from loss of cytochrome c impairs cellular oxygen sensing and hypoxic HIF-alpha activation. Cell Metab 2005; 1:393-399. Provides important evidence that mitochondrial ROS production is required for HIF-1 regulation during hypoxia, but not anoxia.
    • (2005) Cell Metab , vol.1 , pp. 393-399
    • Mansfield, K.D.1    Guzy, R.D.2    Pan, Y.3
  • 62
    • 33645958257 scopus 로고    scopus 로고
    • Regulation of the pyruvate dehydrogenase complex
    • Patel MS, Korotchkina LG. Regulation of the pyruvate dehydrogenase complex. Biochem Soc Trans 2006; 34:217-222. A thorough yet succinct review of the regulation of the pyruvate dehydrogenase complex.
    • (2006) Biochem Soc Trans , vol.34 , pp. 217-222
    • Patel, M.S.1    Korotchkina, L.G.2
  • 63
    • 27144439058 scopus 로고    scopus 로고
    • Glucose requirement for hypoxic accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha)
    • Vordermark D, Kraft P, Katzer A, et al. Glucose requirement for hypoxic accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha). Cancer Lett 2005; 230:122-133.
    • (2005) Cancer Lett , vol.230 , pp. 122-133
    • Vordermark, D.1    Kraft, P.2    Katzer, A.3
  • 64
    • 0348010307 scopus 로고    scopus 로고
    • A mechanism of oxygen sensing in yeast: Multiple oxygen-responsive steps in the heme biosynthetic pathway affect Hap1 activity
    • Hon T, Dodd A, Dirmeier R, et al. A mechanism of oxygen sensing in yeast: multiple oxygen-responsive steps in the heme biosynthetic pathway affect Hap1 activity. J Biol Chem 2003; 278:50771-50780.
    • (2003) J Biol Chem , vol.278 , pp. 50771-50780
    • Hon, T.1    Dodd, A.2    Dirmeier, R.3
  • 65
    • 33644643191 scopus 로고    scopus 로고
    • The heme-bach1 pathway in the regulation of oxidative stress response and erythroid differentiation
    • Igarashi K, Sun J. The heme-bach1 pathway in the regulation of oxidative stress response and erythroid differentiation. Antioxid Redox Signal 2006; 8:107-118.
    • (2006) Antioxid Redox Signal , vol.8 , pp. 107-118
    • Igarashi, K.1    Sun, J.2
  • 66
    • 0042074645 scopus 로고
    • Porphyrins are endogenous ligands for the mitochondrial (peripheral-type) benzodiazepine receptor
    • U S A
    • Verma A, Nye JS, Snyder SH. Porphyrins are endogenous ligands for the mitochondrial (peripheral-type) benzodiazepine receptor. Proc Natl Acad Sci U S A 1987; 84:2256-2260.
    • (1987) Proc Natl Acad Sci , vol.84 , pp. 2256-2260
    • Verma, A.1    Nye, J.S.2    Snyder, S.H.3
  • 67
    • 16344382359 scopus 로고    scopus 로고
    • Up-regulation of the peripheral benzodiazepine receptor during human colorectal carcinogenesis and tumor spread
    • Maaser K, Grabowski P, Oezdem Y, et al. Up-regulation of the peripheral benzodiazepine receptor during human colorectal carcinogenesis and tumor spread. Clin Cancer Res 2005; 11:1751-1756.
    • (2005) Clin Cancer Res , vol.11 , pp. 1751-1756
    • Maaser, K.1    Grabowski, P.2    Oezdem, Y.3
  • 68
    • 0031893337 scopus 로고    scopus 로고
    • Photodynamic tumor therapy: Mitochondrial benzodiazepine receptors as a therapeutic target
    • Verma A, Facchina SL, Hirsch DJ, et al. Photodynamic tumor therapy: mitochondrial benzodiazepine receptors as a therapeutic target. Mol Med 1998; 4:40-45.
    • (1998) Mol Med , vol.4 , pp. 40-45
    • Verma, A.1    Facchina, S.L.2    Hirsch, D.J.3
  • 69
    • 0030977125 scopus 로고    scopus 로고
    • A mammalian mitochondrial drug receptor functions as a bacterial 'oxygen' sensor
    • U S A
    • Yeliseev AA, Krueger KE, Kaplan S. A mammalian mitochondrial drug receptor functions as a bacterial 'oxygen' sensor. Proc Natl Acad Sci U S A 1997; 94:5101-5106.
    • (1997) Proc Natl Acad Sci , vol.94 , pp. 5101-5106
    • Yeliseev, A.A.1    Krueger, K.E.2    Kaplan, S.3
  • 70
    • 17144382480 scopus 로고    scopus 로고
    • Reversible hexa- to penta-coordination of the heme Fe atom modulates ligand binding properties of neuroglobin and cytoglobin
    • Pesce A, De Sanctis D, Nardini M, et al. Reversible hexa- to penta-coordination of the heme Fe atom modulates ligand binding properties of neuroglobin and cytoglobin. IUBMB Life 2004; 56:657-664.
    • (2004) IUBMB Life , vol.56 , pp. 657-664
    • Pesce, A.1    De Sanctis, D.2    Nardini, M.3
  • 71
    • 0141704224 scopus 로고    scopus 로고
    • Oxidized human neuroglobin acts as a heterotrimeric Galpha protein guanine nucleotide dissociation inhibitor
    • Wakasugi K, Nakano T, Morishima I. Oxidized human neuroglobin acts as a heterotrimeric Galpha protein guanine nucleotide dissociation inhibitor. J Biol Chem 2003; 278:36505-36512.
    • (2003) J Biol Chem , vol.278 , pp. 36505-36512
    • Wakasugi, K.1    Nakano, T.2    Morishima, I.3
  • 72
    • 33645823676 scopus 로고    scopus 로고
    • Downregulation of the cytoglobin gene, located on 17q25, in tylosis with oesophageal cancer (TOC): Evidence for trans-allele repression
    • McRonald FE, Liloglou T, Xinarianos G, et al. Downregulation of the cytoglobin gene, located on 17q25, in tylosis with oesophageal cancer (TOC): evidence for trans-allele repression. Hum Mol Genet 2006; 15:1271-1277. An intriguing paper suggesting a role for novel hemoproteins in cancer.
    • (2006) Hum Mol Genet , vol.15 , pp. 1271-1277
    • McRonald, F.E.1    Liloglou, T.2    Xinarianos, G.3
  • 73
    • 0027458551 scopus 로고
    • Carbon monoxide: A putative neural messenger
    • Verma A, Hirsch DJ, Glatt CE, et al. Carbon monoxide: a putative neural messenger. Science 1993; 259:381-384.
    • (1993) Science , vol.259 , pp. 381-384
    • Verma, A.1    Hirsch, D.J.2    Glatt, C.E.3
  • 75
    • 33746259583 scopus 로고    scopus 로고
    • CCAAT/enhancer-binding protein mediates carbon monoxide-induced suppression of cyclooxygenase-2
    • 16 March [Epub ahead of print]
    • Suh GY, Jin Y, Yi AK, et al. CCAAT/enhancer-binding protein mediates carbon monoxide-induced suppression of cyclooxygenase-2. Am J Respir Cell Mol Biol 2006; 16 March [Epub ahead of print]. A novel mechanism for carbon monoxide-mediated signaling is introduced.
    • (2006) Am J Respir Cell Mol Biol
    • Suh, G.Y.1    Jin, Y.2    Yi, A.K.3
  • 76
    • 0033605676 scopus 로고    scopus 로고
    • Inhibition of hypoxia-inducible factor 1 activation by carbon monoxide and nitric oxide: Implications for oxygen sensing and signaling
    • Huang LE, Willmore WG, Gu J, et al. Inhibition of hypoxia-inducible factor 1 activation by carbon monoxide and nitric oxide: implications for oxygen sensing and signaling. J Biol Chem 1999; 274:9038-9044.
    • (1999) J Biol Chem , vol.274 , pp. 9038-9044
    • Huang, L.E.1    Willmore, W.G.2    Gu, J.3
  • 77
    • 0031732387 scopus 로고    scopus 로고
    • Endogenous carbon monoxide in control of respiration
    • Prabhakar NR. Endogenous carbon monoxide in control of respiration. Respir Physiol 1998; 114:57-64.
    • (1998) Respir Physiol , vol.114 , pp. 57-64
    • Prabhakar, N.R.1
  • 78
    • 10844248490 scopus 로고    scopus 로고
    • Hemoxygenase-2 is an oxygen sensor for a calcium-sensitive potassium channel
    • Williams SE, Wootton P, Mason HS, et al. Hemoxygenase-2 is an oxygen sensor for a calcium-sensitive potassium channel. Science 2004; 306:2093-2097.
    • (2004) Science , vol.306 , pp. 2093-2097
    • Williams, S.E.1    Wootton, P.2    Mason, H.S.3
  • 79
    • 27944494427 scopus 로고    scopus 로고
    • Effect of p47phox gene deletion on ROS production and oxygen sensing in mouse carotid body chemoreceptor cells
    • He L, Dinger B, Sanders K, et al. Effect of p47phox gene deletion on ROS production and oxygen sensing in mouse carotid body chemoreceptor cells. Am J Physiol Lung Cell Mol Physiol 2005; 289:L916-L924.
    • (2005) Am J Physiol Lung Cell Mol Physiol , vol.289
    • He, L.1    Dinger, B.2    Sanders, K.3
  • 80
  • 81
    • 24344485624 scopus 로고    scopus 로고
    • Control of the hypoxic response through regulation of mRNA translation
    • Wouters BG, van den Beucken T, Magagnin MG, et al. Control of the hypoxic response through regulation of mRNA translation. Semin Cell Dev Biol 2005; 16:487-501. Excellent and insightful review of translational control by hypoxia.
    • (2005) Semin Cell Dev Biol , vol.16 , pp. 487-501
    • Wouters, B.G.1    Van Den Beucken, T.2    Magagnin, M.G.3
  • 82
    • 28844470269 scopus 로고    scopus 로고
    • The unfolded protein response: A novel component of the hypoxic stress response in tumors
    • Feldman DE, Chauhan V, Koong AC. The unfolded protein response: a novel component of the hypoxic stress response in tumors. Mol Cancer Res 2005; 3:597-605.
    • (2005) Mol Cancer Res , vol.3 , pp. 597-605
    • Feldman, D.E.1    Chauhan, V.2    Koong, A.C.3
  • 83
    • 27144458505 scopus 로고    scopus 로고
    • ER stress-regulated translation increases tolerance to extreme hypoxia and promotes tumor growth
    • Bi M, Naczki C, Koritzinsky M, et al. ER stress-regulated translation increases tolerance to extreme hypoxia and promotes tumor growth. EMBO J 2005; 24:3470-3481. Uses elegant approaches to demonstrate that the mRNA expression and protein expression responses are differentially regulated under hypoxia to produce a unique and restricted proteomic response.
    • (2005) EMBO J , vol.24 , pp. 3470-3481
    • Bi, M.1    Naczki, C.2    Koritzinsky, M.3
  • 84
    • 33644852277 scopus 로고    scopus 로고
    • Gene expression during acute and prolonged hypoxia is regulated by distinct mechanisms of translational control
    • Koritzinsky M, Magagnin MG, van den Beucken T, et al. Gene expression during acute and prolonged hypoxia is regulated by distinct mechanisms of translational control. EMBO J 2006; 25:1114-1125. Uses elegant approaches to demonstrate that the mRNA expression and protein expression responses are differentially regulated under hypoxia to produce a unique and restricted proteomic response.
    • (2006) EMBO J , vol.25 , pp. 1114-1125
    • Koritzinsky, M.1    Magagnin, M.G.2    Van Den Beucken, T.3
  • 85
    • 32444433450 scopus 로고    scopus 로고
    • Hypoxia-induced energy stress regulates mRNA translation and cell growth
    • Liu L, Cash TP, Jones RG, et al. Hypoxia-induced energy stress regulates mRNA translation and cell growth. Mol Cell 2006; 21:521-531.
    • (2006) Mol Cell , vol.21 , pp. 521-531
    • Liu, L.1    Cash, T.P.2    Jones, R.G.3
  • 86
    • 0026654524 scopus 로고
    • Pyruvate dehydrogenase E1 alpha deficiency
    • Brown GK. Pyruvate dehydrogenase E1 alpha deficiency. J Inherit Metab Dis 1992; 15:625-633.
    • (1992) J Inherit Metab Dis , vol.15 , pp. 625-633
    • Brown, G.K.1
  • 87
    • 0027991912 scopus 로고
    • Transformation linked decrease of pyruvate dehydrogenase complex in human epidermis
    • Eboli ML, Pasquini A. Transformation linked decrease of pyruvate dehydrogenase complex in human epidermis. Cancer Lett 1994; 85:239-243.
    • (1994) Cancer Lett , vol.85 , pp. 239-243
    • Eboli, M.L.1    Pasquini, A.2
  • 89
    • 0000766945 scopus 로고
    • Experiments and novel views on the nature of fermentation
    • Pasteur L. Experiments and novel views on the nature of fermentation. Comp Rend Acad Sci 1861; 52:1260-1264.
    • (1861) Comp Rend Acad Sci , vol.52 , pp. 1260-1264
    • Pasteur, L.1
  • 90
    • 0000089325 scopus 로고
    • Observations on the carbohydrate metabolism of tumours
    • Crabtree HG. Observations on the carbohydrate metabolism of tumours. Biochem J 1929; 23:536-545.
    • (1929) Biochem J , vol.23 , pp. 536-545
    • Crabtree, H.G.1
  • 92
    • 0034687243 scopus 로고    scopus 로고
    • Metabolic control: A new solution to an old problem
    • Hardie DG. Metabolic control: a new solution to an old problem. Curr Biol 2000; 10:R757-R759.
    • (2000) Curr Biol , vol.10
    • Hardie, D.G.1
  • 93
    • 0028068606 scopus 로고
    • Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1
    • Semenza GL, Roth PH, Fang HM, Wang GL. Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1. J Biol Chem 1994; 269:23757-23763.
    • (1994) J Biol Chem , vol.269 , pp. 23757-23763
    • Semenza, G.L.1    Roth, P.H.2    Fang, H.M.3    Wang, G.L.4
  • 94
    • 0035027828 scopus 로고    scopus 로고
    • Transcription factor HIF-1 is a necessary mediator of the Pasteur effect in mammalian cells
    • Seagroves TN, Ryan HE, Lu H, et al. Transcription factor HIF-1 is a necessary mediator of the Pasteur effect in mammalian cells. Mol Cell Biol 2001; 21:3436-3444.
    • (2001) Mol Cell Biol , vol.21 , pp. 3436-3444
    • Seagroves, T.N.1    Ryan, H.E.2    Lu, H.3
  • 95
    • 33644622570 scopus 로고    scopus 로고
    • HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption
    • Papandreou I, Cairns RA, Fontana L, et al. HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metab 2006; 3:187-197. Implicates an HIF-1-mediated mechanism for potentially regulating pyruvate dehydrogenase activity and therefore mitochondrial oxygen consumption.
    • (2006) Cell Metab , vol.3 , pp. 187-197
    • Papandreou, I.1    Cairns, R.A.2    Fontana, L.3
  • 96
    • 33644614520 scopus 로고    scopus 로고
    • HIF-1-mediated expression of pyruvate dehydrogenase kinase: A metabolic switch required for cellular adaptation to hypoxia
    • Kim JW, Tchernyshyov I, Semenza GL, Dang CV. HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab 2006; 3:177-185. Implicates an HIF-1-mediated mechanism for potentially regulating pyruvate dehydrogenase activity and therefore mitochondrial oxygen consumption.
    • (2006) Cell Metab , vol.3 , pp. 177-185
    • Kim, J.W.1    Tchernyshyov, I.2    Semenza, G.L.3    Dang, C.V.4
  • 97
    • 30044447187 scopus 로고    scopus 로고
    • Oxygen tension regulates mitochondrial DNA-encoded complex I gene expression
    • Piruat JI, Lopez-Barneo J. Oxygen tension regulates mitochondrial DNA-encoded complex I gene expression. J Biol Chem 2005; 280:42676-42684. A novel effect of hypoxia in reducing mitochondrial electron transport chain activity is shown to be mediated by a decrease in gene expression from mitochondrial DNA.
    • (2005) J Biol Chem , vol.280 , pp. 42676-42684
    • Piruat, J.I.1    Lopez-Barneo, J.2
  • 98
    • 77955594623 scopus 로고    scopus 로고
    • A HIF1alpha regulatory loop links hypoxia and mitochondrial signals in pheochromocytomas
    • Dahia PL, Ross KN, Wright ME, et al. A HIF1alpha regulatory loop links hypoxia and mitochondrial signals in pheochromocytomas. PLoS Genet 2005; 1:72-80.
    • (2005) PLoS Genet , vol.1 , pp. 72-80
    • Dahia, P.L.1    Ross, K.N.2    Wright, M.E.3
  • 99
    • 33644867986 scopus 로고    scopus 로고
    • Protein kinase A-mediated phosphorylation modulates cytochrome c oxidase function and augments hypoxia and myocardial ischemia-related injury
    • Prabu SK, Anandatheerthavarada HK, Raza H, et al. Protein kinase A-mediated phosphorylation modulates cytochrome c oxidase function and augments hypoxia and myocardial ischemia-related injury. J Biol Chem 2006; 281:2061-2070.
    • (2006) J Biol Chem , vol.281 , pp. 2061-2070
    • Prabu, S.K.1    Anandatheerthavarada, H.K.2    Raza, H.3
  • 100
    • 11144241609 scopus 로고    scopus 로고
    • Regulation of 2-oxoglutarate (alpha-ketoglutarate) dehydrogenase stability by the RING finger ubiquitin ligase Siah
    • Habelhah H, Laine A, Erdjument-Bromage H, et al. Regulation of 2-oxoglutarate (alpha-ketoglutarate) dehydrogenase stability by the RING finger ubiquitin ligase Siah. J Biol Chem 2004; 279:53782-53788.
    • (2004) J Biol Chem , vol.279 , pp. 53782-53788
    • Habelhah, H.1    Laine, A.2    Erdjument-Bromage, H.3
  • 101
    • 33646404099 scopus 로고    scopus 로고
    • Fasting blood glucose and cancer risk in a cohort of more than 140,000 adults in Austria
    • Rapp K, Schroeder J, Klenk J, et al. Fasting blood glucose and cancer risk in a cohort of more than 140,000 adults in Austria. Diabetologia 2006; 49:945-952.
    • (2006) Diabetologia , vol.49 , pp. 945-952
    • Rapp, K.1    Schroeder, J.2    Klenk, J.3


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.