메뉴 건너뛰기




Volumn 45, Issue 3, 2012, Pages 367-378

Microarray analysis revealed dysregulation of multiple genes associated with chemoresistance to As 2O 3 and increased tumor aggressiveness in a newly established arsenic-resistant ovarian cancer cell line, OVCAR-3/AsR

Author keywords

Arsenic trioxide; Chemoresistance; Gene expression; Microarray; Ovarian cancer

Indexed keywords

ARSENIC; ARSENIC TRIOXIDE; CISPLATIN; COMPLEMENTARY DNA; INTERLEUKIN 1ALPHA; PACLITAXEL; TRANSCRIPTION FACTOR NRF2;

EID: 84855807757     PISSN: 09280987     EISSN: 18790720     Source Type: Journal    
DOI: 10.1016/j.ejps.2011.12.003     Document Type: Article
Times cited : (11)

References (87)
  • 1
    • 62749191287 scopus 로고    scopus 로고
    • The role of MMP7 and its cross-talk with the FAS/FASL system during the acquisition of chemoresistance to oxaliplatin
    • V. Almendro, E. Ametller, S. García-Recio, O. Collazo, I. Casas, J.M. Augé, J. Maurel, and P. Gascón The role of MMP7 and its cross-talk with the FAS/FASL system during the acquisition of chemoresistance to oxaliplatin PLoS One 4 2009 E4728
    • (2009) PLoS One , vol.4 , pp. 4728
    • Almendro, V.1    Ametller, E.2    García-Recio, S.3    Collazo, O.4    Casas, I.5    Augé, J.M.6    Maurel, J.7    Gascón, P.8
  • 2
    • 70449450646 scopus 로고    scopus 로고
    • Local expression of insulin-like growth factor-I, insulin-like growth factor-I receptor, and estrogen receptor alpha in ovarian cancer
    • Y. An, L. Cai, Y. Wang, D. Zhu, Y. Guan, and J. Zheng Local expression of insulin-like growth factor-I, insulin-like growth factor-I receptor, and estrogen receptor alpha in ovarian cancer Onkologie 32 2009 638 644
    • (2009) Onkologie , vol.32 , pp. 638-644
    • An, Y.1    Cai, L.2    Wang, Y.3    Zhu, D.4    Guan, Y.5    Zheng, J.6
  • 3
    • 21244460674 scopus 로고    scopus 로고
    • Reduced expression of chemokine (C-C motif) ligand-2 (CCL2) in ovarian adenocarcinoma
    • DOI 10.1038/sj.bjc.6602596
    • J.M. Arnold, P.R. Huggard, M. Cummings, G.A. Ramm, and G. Chenevix-Trench Reduced expression of chemokine (C-C motif) ligand-2 (CCL2) in ovarian adenocarcinoma Br. J. Cancer 92 2005 2024 2031 (Pubitemid 40897425)
    • (2005) British Journal of Cancer , vol.92 , Issue.11 , pp. 2024-2031
    • Arnold, J.M.1    Huggard, P.R.2    Cummings, M.3    Ramm, G.A.4    Chenevix-Trench, G.5
  • 4
    • 45849119823 scopus 로고    scopus 로고
    • S100A8 and S100A9 overexpression is associated with poor pathological parameters in invasive ductal carcinoma of the breast
    • DOI 10.2174/156800908784533445
    • K. Arai, S. Takano, T. Teratani, Y. Ito, T. Yamada, and R. Nozawa S100A8 and S100A9 overexpression is associated with poor pathological parameters in invasive ductal carcinoma of the breast Curr. Cancer Drug Targets 8 2008 243 252 (Pubitemid 351881350)
    • (2008) Current Cancer Drug Targets , vol.8 , Issue.4 , pp. 243-252
    • Arai, K.1    Takano, S.2    Teratani, T.3    Ito, Y.4    Yamada, T.5    Nozawa, R.6
  • 6
    • 0344196965 scopus 로고    scopus 로고
    • The interleukin 1 receptor: Ligand interactions and signal transduction
    • DOI 10.1016/S1359-6101(98)00018-5, PII S1359610198000185
    • P.E. Auron The interleukin 1 receptor: ligand interactions and signal transduction Cytokine Growth Factor Rev. 9 1998 221 237 (Pubitemid 29019708)
    • (1998) Cytokine and Growth Factor Reviews , vol.9 , Issue.3-4 , pp. 221-237
    • Auron, P.E.1
  • 7
    • 0028890744 scopus 로고
    • The insulin-like growth factor i receptor: A key to tumor growth?
    • R. Baserga The insulin-like growth factor I receptor: a key to tumor growth? Cancer Res. 55 1995 249 252
    • (1995) Cancer Res. , vol.55 , pp. 249-252
    • Baserga, R.1
  • 8
    • 0001677717 scopus 로고
    • Controlling the false discovery rate - A practical and powerful approach to multiple testing
    • Y. Benjamini, and Y. Hochberg Controlling the false discovery rate - a practical and powerful approach to multiple testing J. R. Statist. Soc. B 57 1995 289 300
    • (1995) J. R. Statist. Soc. B , vol.57 , pp. 289-300
    • Benjamini, Y.1    Hochberg, Y.2
  • 9
    • 0037316303 scopus 로고    scopus 로고
    • A comparison of normalization methods for high density oligonucleotide array data based on variance and bias
    • DOI 10.1093/bioinformatics/19.2.185
    • B.M. Bolstad, R.A. Irizarry, M. Astrand, and T.P. Speed A comparison of normalization methods for high density oligonucleotide array data based on bias and variance Bioinformatics 19 2003 185 193 (Pubitemid 36181903)
    • (2003) Bioinformatics , vol.19 , Issue.2 , pp. 185-193
    • Bolstad, B.M.1    Irizarry, R.A.2    Astrand, M.3    Speed, T.P.4
  • 10
    • 3543150203 scopus 로고    scopus 로고
    • Human tissue kallikreins: Physiologic roles and applications in cancer
    • C.A. Borgoño, I.P. Michael, and E.P. Diamandis Human tissue kallikreins: physiologic roles and applications in cancer Mol. Cancer Res. 2 2004 257 280 (Pubitemid 39031076)
    • (2004) Molecular Cancer Research , vol.2 , Issue.5 , pp. 257-280
    • Borgono, C.A.1    Michael, I.P.2    Diamandis, E.P.3
  • 13
    • 0032933610 scopus 로고    scopus 로고
    • Malignant cells can be sensitized to undergo growth inhibition and apoptosis by arsenic trioxide through modulation of the glutathione redox system
    • J. Dai, R.S. Weinberg, S. Waxman, and Y. Jing Malignant cells can be sensitized to undergo growth inhibition and apoptosis by arsenic trioxide through modulation of the glutathione redox system Blood 93 1999 268 277 (Pubitemid 29019412)
    • (1999) Blood , vol.93 , Issue.1 , pp. 268-277
    • Dai, J.1    Weinberg, R.S.2    Waxman, S.3    Jing, Y.4
  • 14
  • 16
    • 0031831906 scopus 로고    scopus 로고
    • Interleukin-1, interleukin-1 receptors, and interleukin-1 receptor antagonist
    • C.A. Dinarello Interleukin-1, interleukin-1 receptors, and interleukin-1 receptor antagonist Int. Rev. Immunol. 16 1998 457 499
    • (1998) Int. Rev. Immunol. , vol.16 , pp. 457-499
    • Dinarello, C.A.1
  • 17
    • 0036176560 scopus 로고    scopus 로고
    • Tissue plasminogen activator is required for the growth, invasion, and angiogenesis of pancreatic tumor cells
    • V.M. Díaz, J. Planaguma, T.M. Thomson, J. Reventós, and R. Paciucci Tissue plasminogen activator is required for the growth, invasion, and angiogenesis of pancreatic tumor cells Gastroenterology 122 2002 806 819 (Pubitemid 34173834)
    • (2002) Gastroenterology , vol.122 , Issue.3 , pp. 806-819
    • Diaz, V.M.1    Planaguma, J.2    Thomson, T.M.3    Reventos, J.4    Paciucci, R.5
  • 18
    • 77950818717 scopus 로고    scopus 로고
    • Kallikrein-related peptidase 7 promotes multicellular aggregation via the alpha(5)beta(1) integrin pathway and paclitaxel chemoresistance in serous epithelial ovarian carcinoma
    • Y. Dong, O.L. Tan, D. Loessner, C. Stephens, C. Walpole, G.M. Boyle, P.G. Parsons, and J.A. Clements Kallikrein-related peptidase 7 promotes multicellular aggregation via the alpha(5)beta(1) integrin pathway and paclitaxel chemoresistance in serous epithelial ovarian carcinoma Cancer Res. 70 2010 2624 2633
    • (2010) Cancer Res. , vol.70 , pp. 2624-2633
    • Dong, Y.1    Tan, O.L.2    Loessner, D.3    Stephens, C.4    Walpole, C.5    Boyle, G.M.6    Parsons, P.G.7    Clements, J.A.8
  • 19
    • 78649691794 scopus 로고    scopus 로고
    • Elevated AKR1C3 expression promotes prostate cancer cell survival and prostate cell-mediated endothelial cell tube formation: Implications for prostate cancer progression
    • M.G. Dozmorov, J.T. Azzarello, J.D. Wren, K.M. Fung, Q. Yang, J.S. Davis, R.E. Hurst, D.J. Culkin, T.M. Penning, and H.K. Lin Elevated AKR1C3 expression promotes prostate cancer cell survival and prostate cell-mediated endothelial cell tube formation: implications for prostate cancer progression BMC Cancer 10 2010 672
    • (2010) BMC Cancer , vol.10 , pp. 672
    • Dozmorov, M.G.1    Azzarello, J.T.2    Wren, J.D.3    Fung, K.M.4    Yang, Q.5    Davis, J.S.6    Hurst, R.E.7    Culkin, D.J.8    Penning, T.M.9    Lin, H.K.10
  • 20
    • 0035007008 scopus 로고    scopus 로고
    • Arsenic compounds induce cytotoxicity and apoptosis in cisplatin-sensitive and -resistant gynecological cancer cell lines
    • DOI 10.1007/s002800100278
    • Y.H. Du, and P.C. Ho Arsenic compounds induce cytotoxicity and apoptosis in cisplatin-sensitive and -resistant gynecological cancer cell lines Cancer Chemother. Pharmacol. 47 2001 481 490 (Pubitemid 32477294)
    • (2001) Cancer Chemotherapy and Pharmacology , vol.47 , Issue.6 , pp. 481-490
    • Yu-Hong, D.1    Ho, P.C.2
  • 21
    • 0347917028 scopus 로고    scopus 로고
    • The urokinase plasminogen activator system: Role in malignancy
    • DOI 10.2174/1381612043453559
    • M.J. Duffy The urokinase plasminogen activator system: role in malignancy Curr. Pharm. Des. 10 2004 39 49 (Pubitemid 38072742)
    • (2004) Current Pharmaceutical Design , vol.10 , Issue.1 , pp. 39-49
    • Duffy, M.J.1
  • 22
    • 67649460732 scopus 로고    scopus 로고
    • Elevated expressions of MMP7, TROP2, and survivin are associated with survival, disease recurrence, and liver metastasis of colon cancer
    • Y.J. Fang, Z.H. Lu, G.Q. Wang, Z.Z. Pan, Z.W. Zhou, J.P. Yun, M.F. Zhang, and D.S. Wan Elevated expressions of MMP7, TROP2, and survivin are associated with survival, disease recurrence, and liver metastasis of colon cancer Int. J. Colorectal Dis. 24 2009 875 884
    • (2009) Int. J. Colorectal Dis. , vol.24 , pp. 875-884
    • Fang, Y.J.1    Lu, Z.H.2    Wang, G.Q.3    Pan, Z.Z.4    Zhou, Z.W.5    Yun, J.P.6    Zhang, M.F.7    Wan, D.S.8
  • 25
    • 78650424066 scopus 로고    scopus 로고
    • Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting
    • C. Gialeli, A.D. Theocharis, and N.K. Karamanos Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting FEBS J. 278 2011 16 27
    • (2011) FEBS J. , vol.278 , pp. 16-27
    • Gialeli, C.1    Theocharis, A.D.2    Karamanos, N.K.3
  • 26
    • 77951553359 scopus 로고    scopus 로고
    • P57: A multifunctional protein in cancer
    • H. Guo, T. Tian, K. Nan, and W. Wang P57: a multifunctional protein in cancer Int. J. Oncol. 36 2010 1321 1329
    • (2010) Int. J. Oncol. , vol.36 , pp. 1321-1329
    • Guo, H.1    Tian, T.2    Nan, K.3    Wang, W.4
  • 27
    • 28344438623 scopus 로고    scopus 로고
    • S100A8 and S100A9 activate MAP kinase and NF-κB signaling pathways and trigger translocation of RAGE in human prostate cancer cells
    • DOI 10.1016/j.yexcr.2005.10.013, PII S0014482705004775
    • A. Hermani, B. De Servi, S. Medunjanin, P.A. Tessier, and D. Mayer S100A8 and S100A9 activate MAP kinase and NF-kappaB signaling pathways and trigger translocation of RAGE in human prostate cancer cells Exp. Cell Res. 312 2006 184 197 (Pubitemid 41721180)
    • (2006) Experimental Cell Research , vol.312 , Issue.2 , pp. 184-197
    • Hermani, A.1    De Servi, B.2    Medunjanin, S.3    Tessier, P.A.4    Mayer, D.5
  • 28
    • 33751504690 scopus 로고    scopus 로고
    • Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis
    • DOI 10.1038/ncb1507, PII NCB1507
    • S. Hiratsuka, A. Watanabe, H. Aburatani, and Y. Maru Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis Nat. Cell Biol. 8 2006 1369 1375 (Pubitemid 44835111)
    • (2006) Nature Cell Biology , vol.8 , Issue.12 , pp. 1369-1375
    • Hiratsuka, S.1    Watanabe, A.2    Aburatani, H.3    Maru, Y.4
  • 29
    • 34548128023 scopus 로고    scopus 로고
    • Activation of the epidermal growth factor signalling pathway by tissue plasminogen activator in pancreas cancer cells
    • DOI 10.1136/gut.2006.097188
    • M. Hurtado, J.J. Lozano, E. Castellanos, L.A. López- Fernández, K. Harshman, C. Martínez-A, A.R. Ortiz, T.M. Thomson, and R. Paciucci Activation of the epidermal growth factor signalling pathway by tissue plasminogen activator in pancreas cancer cells Gut 56 2007 1266 1274 (Pubitemid 47300429)
    • (2007) Gut , vol.56 , Issue.9 , pp. 1266-1274
    • Hurtado, M.1    Lozano, J.J.2    Castellanos, E.3    Lopez-Fernandez, L.A.4    Harshman, K.5    Martinez-A, C.6    Ortiz, A.R.7    Thomson, T.M.8    Paciucci, R.9
  • 30
    • 0032953192 scopus 로고    scopus 로고
    • Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain
    • K. Itoh, N. Wakabayashi, Y. Katoh, T. Ishii, K. Igarashi, J.D. Engel, and M. Yamamoto Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain Genes Dev. 13 1999 76 86 (Pubitemid 29045117)
    • (1999) Genes and Development , vol.13 , Issue.1 , pp. 76-86
    • Itoh, K.1    Wakabayashi, N.2    Katoh, Y.3    Ishii, T.4    Igarashi, K.5    Engel, J.D.6    Yamamoto, M.7
  • 31
    • 33845728020 scopus 로고    scopus 로고
    • 17β-hydroxysteroid dehydrogenase 14 affects estradiol levels in breast cancer cells and is a prognostic marker in estrogen receptor-positive breast cancer
    • DOI 10.1158/0008-5472.CAN-06-1448
    • A.K. Jansson, C. Gunnarsson, M. Cohen, T. Sivik, and O. Stl 17β-Hydroxysteroid dehydrogenase 14 affects estradiol levels in breast cancer cells and is a prognostic marker in estrogen receptor positive breast cancer Cancer Res. 66 2006 11471 11477 (Pubitemid 46009980)
    • (2006) Cancer Research , vol.66 , Issue.23 , pp. 11471-11477
    • Jansson, A.K.1    Gunnarsson, C.2    Cohen, M.3    Sivik, T.4    Stal, O.5
  • 34
    • 75649089728 scopus 로고    scopus 로고
    • Identification of genes with differential expression in chemoresistant epithelial ovarian cancer using high-density oligonucleotide microarrays
    • W. Ju, B.C. Yoo, I.J. Kim, J.W. Kim, S.C. Kim, and H.P. Lee Identification of genes with differential expression in chemoresistant epithelial ovarian cancer using high-density oligonucleotide microarrays Oncol. Res. 18 2009 47 56
    • (2009) Oncol. Res. , vol.18 , pp. 47-56
    • Ju, W.1    Yoo, B.C.2    Kim, I.J.3    Kim, J.W.4    Kim, S.C.5    Lee, H.P.6
  • 35
    • 1542464000 scopus 로고    scopus 로고
    • The insulin-like growth factor/insulin system in epithelial ovarian cancer
    • K.R. Kalli, and C.A. Conover The insulin-like growth factor/insulin system in epithelial ovarian cancer Front. Biosci. 8 2003 714 722
    • (2003) Front. Biosci. , vol.8 , pp. 714-722
    • Kalli, K.R.1    Conover, C.A.2
  • 36
    • 0030841751 scopus 로고    scopus 로고
    • Leukemia inhibitory factor induces apoptosis and proliferation of human carcinoma cells through different oncogene pathways
    • DOI 10.1002/(SICI)1097-0215(19970807)72:4<687::AID-IJC22>3.0.CO;2-7
    • H. Kamohara, K. Sakamoto, T. Ishiko, Y. Masuda, T. Abe, and M. Ogawa Leukemia inhibitory factor induces apoptosis and proliferation of human carcinoma cells through different oncogene pathways Int. J. Cancer 72 1997 687 695 (Pubitemid 27356173)
    • (1997) International Journal of Cancer , vol.72 , Issue.4 , pp. 687-695
    • Kamohara, H.1    Sakamoto, K.2    Ishiko, T.3    Masuda, Y.4    Abe, T.5    Ogawa, M.6
  • 37
    • 34247877760 scopus 로고    scopus 로고
    • Leukemia inhibitory factor functions as a growth factor in pancreas carcinoma cells: Involvement of regulation of LIF and its receptor expression
    • H. Kamohara, M. Ogawa, T. Ishiko, K. Sakamoto, and H. Baba Leukemia inhibitory factor functions as a growth factor in pancreas carcinoma cells: involvement of regulation of LIF and its receptor expression Int. J. Oncol. 30 2007 977 983
    • (2007) Int. J. Oncol. , vol.30 , pp. 977-983
    • Kamohara, H.1    Ogawa, M.2    Ishiko, T.3    Sakamoto, K.4    Baba, H.5
  • 38
    • 80052340202 scopus 로고    scopus 로고
    • Prognostic impact of S100A9 overexpression in non-small cell lung cancer
    • H. Kawai, Y. Minamiya, and N. Takahashi Prognostic impact of S100A9 overexpression in non-small cell lung cancer Tumour Biol. 32 2011 641 646
    • (2011) Tumour Biol. , vol.32 , pp. 641-646
    • Kawai, H.1    Minamiya, Y.2    Takahashi, N.3
  • 39
    • 0029888789 scopus 로고    scopus 로고
    • Leukemia-inhibitory factor stimulates breast, kidney and prostate cancer cell proliferation by paracrine and autocrine pathways
    • DOI 10.1002/(SICI)1097-0215(19960516)66:4<515::AID-IJC15>3.0.CO;2-6
    • P. Kellokumpu-Lehtinen, M. Talpaz, D. Harris, Q. Van, R. Kurzrock, and Z. Estrov Leukemia-inhibitory factor stimulates breast, kidney and prostate cancer cell proliferation by paracrine and autocrine pathways Int. J. Cancer 66 1996 515 519 (Pubitemid 26176769)
    • (1996) International Journal of Cancer , vol.66 , Issue.4 , pp. 515-519
    • Kellokumpu-Lehtinen, P.1    Talpaz, M.2    Harris, D.3    Van, Q.4    Kurzrock, R.5    Estrov, Z.6
  • 40
    • 14244267810 scopus 로고    scopus 로고
    • IFI16 is an essential mediator of growth inhibition, but not differentiation, induced by the leukemia inhibitory factor/JAK/STAT pathway in medullary thyroid carcinoma cells
    • DOI 10.1074/jbc.M410542200
    • E.J. Kim, J.I. Park, and B.D. Nelkin IFI16 is an essential mediator of growth inhibition, but not differentiation, induced by the leukemia inhibitory factor/JAK/STAT pathway in medullary thyroid carcinoma cells J. Biol. Chem. 280 2005 4913 4920 (Pubitemid 40288666)
    • (2005) Journal of Biological Chemistry , vol.280 , Issue.6 , pp. 4913-4920
    • Kim, E.-J.1    Park, J.-I.2    Nelkin, B.D.3
  • 42
    • 33847192750 scopus 로고    scopus 로고
    • Gene expression profiling of paired ovarian tumors obtained prior to and following adjuvant chemotherapy: Molecular signatures of chemoresistant tumors
    • S. L'Espérance, I. Popa, M. Bachvarova, M. Plante, N. Patten, L. Wu, B. Têtu, and D. Bachvarov Gene expression profiling of paired ovarian tumors obtained prior to and following adjuvant chemotherapy: molecular signatures of chemoresistant tumors Int. J. Oncol. 29 2006 5 24
    • (2006) Int. J. Oncol. , vol.29 , pp. 5-24
    • L'Espérance, S.1    Popa, I.2    Bachvarova, M.3    Plante, M.4    Patten, N.5    Wu, L.6    Têtu, B.7    Bachvarov, D.8
  • 43
    • 0038398622 scopus 로고    scopus 로고
    • The insulin-like growth factor system and cancer
    • DOI 10.1016/S0304-3835(03)00159-9
    • D. LeRoith, and C.T. Roberts Jr. The insulin-like growth factor system and cancer Cancer Lett. 195 2003 127 137 (Pubitemid 36588961)
    • (2003) Cancer Letters , vol.195 , Issue.2 , pp. 127-137
    • LeRoith, D.1    Roberts Jr., C.T.2
  • 44
    • 33845212729 scopus 로고    scopus 로고
    • Interleukin-1 and cancer progression: The emerging role of interleukin-1 receptor antagonist as a novel therapeutic agent in cancer treatment
    • A.M. Lewis, S. Varghese, H. Xu, and H.R. Alexander Interleukin-1 and cancer progression: the emerging role of interleukin-1 receptor antagonist as a novel therapeutic agent in cancer treatment J. Transl. Med. 4 2006 48
    • (2006) J. Transl. Med. , vol.4 , pp. 48
    • Lewis, A.M.1    Varghese, S.2    Xu, H.3    Alexander, H.R.4
  • 45
    • 0036765344 scopus 로고    scopus 로고
    • Arsenic trioxide produces polymerization of microtubules and mitotic arrest before apoptosis in human tumor cell lines
    • DOI 10.1124/mol.62.3.529
    • Y.H. Ling, J.D. Jiang, J.F. Holland, and R. Perez-Soler Arsenic trioxide produces polymerization of microtubules and mitotic arrest before apoptosis in human tumor cell lines Mol. Pharmacol. 62 2002 529 538 (Pubitemid 36329371)
    • (2002) Molecular Pharmacology , vol.62 , Issue.3 , pp. 529-538
    • Ling, Y.-H.1    Jiang, J.-D.2    Holland, J.F.3    Perez-Soler, R.4
  • 46
    • 77955484372 scopus 로고    scopus 로고
    • The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel
    • Q. Liu, H. Zhang, L. Smeester, F. Zou, M. Kesic, I. Jaspers, J. Pi, and R.C. Fry The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel BMC Med. Genomics 3 2010 37
    • (2010) BMC Med. Genomics , vol.3 , pp. 37
    • Liu, Q.1    Zhang, H.2    Smeester, L.3    Zou, F.4    Kesic, M.5    Jaspers, I.6    Pi, J.7    Fry, R.C.8
  • 47
    • 0035710746 scopus 로고    scopus 로고
    • -ΔΔCT method
    • DOI 10.1006/meth.2001.1262
    • K.J. Livak, and T.D. Schmittgen Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method Methods 25 2001 402 408 (Pubitemid 34164012)
    • (2001) Methods , vol.25 , Issue.4 , pp. 402-408
    • Livak, K.J.1    Schmittgen, T.D.2
  • 48
    • 0029561319 scopus 로고
    • Glutathione in health and disease: Pharmacotherapeutic issues
    • B.M. Lomaestro, and M. Malone Glutathione in health and disease: pharmacotherapeutic issues Ann. Pharmacother. 29 1995 1263 1273 (Pubitemid 26044866)
    • (1995) Annals of Pharmacotherapy , vol.29 , Issue.12 , pp. 1263-1273
    • Lomaestro, B.M.1    Malone, M.2
  • 49
    • 42249094731 scopus 로고    scopus 로고
    • Pharmaceutical management of ovarian cancer: Current status
    • DOI 10.2165/00003495-200868060-00004
    • M. Markman Pharmaceutical management of ovarian cancer: current status Drugs 68 2008 771 789 (Pubitemid 351550530)
    • (2008) Drugs , vol.68 , Issue.6 , pp. 771-789
    • Markman, M.1
  • 50
    • 0030891270 scopus 로고    scopus 로고
    • The interleukin-1 receptor complex and interleukin-1 signal transduction
    • M.U. Martin, and W. Falk The interleukin-1 receptor complex and interleukin-1 signal transduction Eur. Cytokine Netw. 8 1997 5 17 (Pubitemid 27189850)
    • (1997) European Cytokine Network , vol.8 , Issue.1 , pp. 5-17
    • Martin, M.U.1    Falk, W.2
  • 51
    • 34547941224 scopus 로고    scopus 로고
    • Expression and biological role of the prostaglandin D synthase/SOX9 pathway in human ovarian cancer cells
    • DOI 10.1016/j.canlet.2007.04.007, PII S0304383507001954
    • S. Malki, F. Bibeau, C. Notarnicola, S. Roques, P. Berta, F. Poulat, and B. Boizet-Bonhoure Expression and biological role of the prostaglandin D synthase/SOX9 pathway in human ovarian cancer cells Cancer Lett. 255 2007 182 193 (Pubitemid 47268638)
    • (2007) Cancer Letters , vol.255 , Issue.2 , pp. 182-193
    • Malki, S.1    Bibeau, F.2    Notarnicola, C.3    Roques, S.4    Berta, P.5    Poulat, F.6    Boizet-Bonhoure, B.7
  • 52
    • 73449148422 scopus 로고    scopus 로고
    • CIAP2 as a therapeutic target in colorectal cancer and other malignancies
    • K. Miura, H. Karasawa, and I. Sasaki CIAP2 as a therapeutic target in colorectal cancer and other malignancies Expert Opin. Ther. Targets 13 2009 1333 1345
    • (2009) Expert Opin. Ther. Targets , vol.13 , pp. 1333-1345
    • Miura, K.1    Karasawa, H.2    Sasaki, I.3
  • 53
    • 0034039215 scopus 로고    scopus 로고
    • Emergence of cisplatin-resistant cells from the OVCAR-3 ovarian carcinoma cell line with p53 mutations, altered tumorigenicity, and increased apoptotic sensitivity to p53 gene replacement
    • DOI 10.1046/j.1525-1438.2000.00018.x
    • K. Mujoo, L. Zhang, J. Klostergaard, and N.J. Donato Emergence of cisplatin-resistant cells from the OVCAR-3 ovarian carcinoma cell line with p53 mutations, altered tumorigenicity, and increased apoptotic sensitivity to p53 gene replacement Int. J. Gynecol. Cancer 10 2000 105 114 (Pubitemid 30351309)
    • (2000) International Journal of Gynecological Cancer , vol.10 , Issue.2 , pp. 105-114
    • Mujoo, K.1    Zhang, L.2    Klostergaard, J.3    Donato, N.J.4
  • 54
    • 33750589355 scopus 로고    scopus 로고
    • IAP family protein expression correlates with poor outcome of multiple myeloma patients in association with chemotherapy-induced overexpression of multidrug resistance genes
    • DOI 10.1002/ajh.20656
    • Y. Nakagawa, S. Abe, M. Kurata, M. Hasegawa, K. Yamamoto, M. Inoue, T. Takemura, K. Suzuki, and M. Kitagawa IAP family protein expression correlates with poor outcome of multiple myeloma patients in association with chemotherapy-induced overexpression of multidrug resistance genes Am. J. Hematol. 81 2006 824 831 (Pubitemid 44682183)
    • (2006) American Journal of Hematology , vol.81 , Issue.11 , pp. 824-831
    • Nakagawa, Y.1    Abe, S.2    Kurata, M.3    Hasegawa, M.4    Yamamoto, K.5    Inoue, M.6    Takemura, T.7    Suzuki, K.8    Kitagawa, M.9
  • 55
    • 0242559054 scopus 로고    scopus 로고
    • Pathway studio - The analysis and navigation of molecular networks
    • DOI 10.1093/bioinformatics/btg290
    • A. Nikitin, S. Egorov, N. Daraselia, and I. Mazo Pathway studio - the analysis and navigation of molecular networks Bioinformatics 19 2003 2155 2157 (Pubitemid 37408171)
    • (2003) Bioinformatics , vol.19 , Issue.16 , pp. 2155-2157
    • Nikitin, A.1    Egorov, S.2    Daraselia, N.3    Mazo, I.4
  • 56
    • 0037763721 scopus 로고    scopus 로고
    • Regulatory Mechanisms Controlling Gene Expression Mediated by the Antioxidant Response Element
    • DOI 10.1146/annurev.pharmtox.43.100901.140229
    • T. Nguyen, P.J. Sherratt, and C.B. Pickett Regulatory mechanisms controlling gene expression mediated by the antioxidant response element Annu. Rev. Pharmacol. Toxicol. 43 2003 233 260 (Pubitemid 37372641)
    • (2003) Annual Review of Pharmacology and Toxicology , vol.43 , pp. 233-260
    • Nguyen, T.1    Sherratt, P.J.2    Pickett, C.B.3
  • 57
    • 74949111637 scopus 로고    scopus 로고
    • Targeting CCL11 in the treatment of ovarian cancer
    • B.M. Nolen, and A.E. Lokshin Targeting CCL11 in the treatment of ovarian cancer Expert Opin. Ther. Targets 14 2010 157 167
    • (2010) Expert Opin. Ther. Targets , vol.14 , pp. 157-167
    • Nolen, B.M.1    Lokshin, A.E.2
  • 58
    • 5644246147 scopus 로고    scopus 로고
    • 17β-Hydroxysteroid dehydrogenase type 1 is an independent prognostic marker in breast cancer
    • DOI 10.1158/0008-5472.CAN-04-0446
    • O.O. Oduwole, Y. Li, V.V. Isomaa, A. Mäntyniemi, A.E. Pulkka, Y. Soini, and P.T. Vihko 17β-Hydroxysteroid dehydrogenase type 1 is an independent prognostic marker in breast cancer Cancer Res. 64 2004 7604 7609 (Pubitemid 39372106)
    • (2004) Cancer Research , vol.64 , Issue.20 , pp. 7604-7609
    • Oduwole, O.O.1    Li, Y.2    Isomaa, V.V.3    Mantyniemi, A.4    Pulkka, A.E.5    Soini, Y.6    Vihko, P.T.7
  • 59
    • 79955833044 scopus 로고    scopus 로고
    • 3-induced ovarian cancer cell death: Oxidative stress-independent and -dependent cytotoxic potentiation
    • 3-induced ovarian cancer cell death: oxidative stress-independent and -dependent cytotoxic potentiation Int. J. Oncol. 38 2011 1731 1739
    • (2011) Int. J. Oncol. , vol.38 , pp. 1731-1739
    • Ong, P.S.1    Chan, S.Y.2    Ho, P.C.3
  • 60
    • 34250885201 scopus 로고    scopus 로고
    • Tissue plasminogen activator induces pancreatic cancer cell proliferation by a non-catalytic mechanism that requires extracellular signal-regulated kinase 1/2 activation through epidermal growth factor receptor and annexin A2
    • DOI 10.2353/ajpath.2007.060850
    • E. Ortiz-Zapater, S. Peiró, O. Roda, J.M. Corominas, S. Aguilar, C. Ampurdanés, F.X. Real, and P. Navarro Tissue plasminogen activator induces pancreatic cancer cell proliferation by a non-catalytic mechanism that requires extracellular signal-regulated kinase 1/2 activation through epidermal growth factor receptor and annexin A2 Am. J. Pathol. 170 2007 1573 1584 (Pubitemid 47339302)
    • (2007) American Journal of Pathology , vol.170 , Issue.5 , pp. 1573-1584
    • Ortiz-Zapater, E.1    Peiro, S.2    Roda, O.3    Corominas, J.M.4    Aguilar, S.5    Ampurdanes, C.6    Real, F.X.7    Navarro, P.8
  • 61
    • 65249112671 scopus 로고    scopus 로고
    • Upregulation of SOX9 inhibits the growth of human and mouse melanomas and restores their sensitivity to retinoic acid
    • T. Passeron, J.C. Valencia, T. Namiki, W.D. Vieira, H. Passeron, Y. Miyamura, and V.J. Hearing Upregulation of SOX9 inhibits the growth of human and mouse melanomas and restores their sensitivity to retinoic acid J. Clin. Invest. 119 2009 954 963
    • (2009) J. Clin. Invest. , vol.119 , pp. 954-963
    • Passeron, T.1    Valencia, J.C.2    Namiki, T.3    Vieira, W.D.4    Passeron, H.5    Miyamura, Y.6    Hearing, V.J.7
  • 62
    • 61649103983 scopus 로고    scopus 로고
    • Steroid hormone transforming aldo-keto reductases and cancer
    • T.M. Penning, and M.C. Byrns Steroid hormone transforming aldo-keto reductases and cancer Ann. NY Acad. Sci. 1155 2009 33 42
    • (2009) Ann. NY Acad. Sci. , vol.1155 , pp. 33-42
    • Penning, T.M.1    Byrns, M.C.2
  • 63
    • 0035721955 scopus 로고    scopus 로고
    • Role of matrix metalloproteinase and plasminogen activator-plasmin systems in angiogenesis
    • M.S. Pepper Role of matrix metalloproteinase and plasminogen activator-plasmin systems in angiogenesis Arterioscler. Thromb. Vasc. Biol. 21 2001 1104 1107
    • (2001) Arterioscler. Thromb. Vasc. Biol. , vol.21 , pp. 1104-1107
    • Pepper, M.S.1
  • 64
    • 77957668367 scopus 로고    scopus 로고
    • SnoN/SkiL, a TGFβ signaling mediator: A participant in autophagy induced by arsenic trioxide
    • F. Raffoul, C. Campla, and M. Nanjundan SnoN/SkiL, a TGFβ signaling mediator: a participant in autophagy induced by arsenic trioxide Autophagy 6 2010 955 957
    • (2010) Autophagy , vol.6 , pp. 955-957
    • Raffoul, F.1    Campla, C.2    Nanjundan, M.3
  • 65
    • 33644909044 scopus 로고    scopus 로고
    • AKR1C1 and AKR1C3 may determine progesterone and estrogen ratios in endometrial cancer
    • T.L. Rizner, T. Smuc, R. Rupreht, J. Sinkovec, and T.M. Penning AKR1C1 and AKR1C3 may determine progesterone and estrogen ratios in endometrial cancer Mol. Cell. Endocrinol. 248 2006 126 135
    • (2006) Mol. Cell. Endocrinol. , vol.248 , pp. 126-135
    • Rizner, T.L.1    Smuc, T.2    Rupreht, R.3    Sinkovec, J.4    Penning, T.M.5
  • 66
    • 8144227602 scopus 로고    scopus 로고
    • Human kallikrein 8 (hK8/TADG-14) expression is associated with an early clinical stage and favorable prognosis in ovarian cancer
    • K. Shigemasa, X. Tian, L. Gu, H. Tanimoto, L.J. Underwood, T.J. O'Brien, and K. Ohama Human kallikrein 8 (hK8/TADG-14) expression is associated with an early clinical stage and favorable prognosis in ovarian cancer Oncol. Rep. 11 2004 1153 1159
    • (2004) Oncol. Rep. , vol.11 , pp. 1153-1159
    • Shigemasa, K.1    Tian, X.2    Gu, L.3    Tanimoto, H.4    Underwood, L.J.5    O'Brien, T.J.6    Ohama, K.7
  • 67
    • 27744571741 scopus 로고    scopus 로고
    • Downregulation of human kallikrein 10 (KLK10/NES1) by CpG island hypermethylation in breast, ovarian and prostate cancers
    • DOI 10.1159/000089290
    • M. Sidiropoulos, G. Pampalakis, G. Sotiropoulou, D. Katsaros, and E.P. Diamandis Downregulation of human kallikrein 10 (KLK10/NES1) by CpG island hypermethylation in breast, ovarian and prostate cancers Tumour Biol. 26 2005 324 336 (Pubitemid 41619463)
    • (2005) Tumor Biology , vol.26 , Issue.6 , pp. 324-336
    • Sidiropoulos, M.1    Pampalakis, G.2    Sotiropoulou, G.3    Katsaros, D.4    Diamandis, E.P.5
  • 69
    • 78349311964 scopus 로고    scopus 로고
    • Arsenic trioxide induces a beclin-1-independent autophagic pathway via modulation of SnoN/SkiL expression in ovarian carcinoma cells
    • D.M. Smith, S. Patel, F. Raffoul, E. Haller, G.B. Mills, and M. Nanjundan Arsenic trioxide induces a beclin-1-independent autophagic pathway via modulation of SnoN/SkiL expression in ovarian carcinoma cells Cell Death Differ. 17 2010 1867 1881
    • (2010) Cell Death Differ. , vol.17 , pp. 1867-1881
    • Smith, D.M.1    Patel, S.2    Raffoul, F.3    Haller, E.4    Mills, G.B.5    Nanjundan, M.6
  • 70
    • 0027251832 scopus 로고
    • Modulation of murine B16F10 melanoma plasminogen activator production by a synthetic peptide derived from the laminin A chain
    • M.S. Stack, R.D. Gray, and S.V. Pizzo Modulation of murine B16F10 melanoma plasminogen activator production by a synthetic peptide derived from the laminin A chain Cancer Res. 53 1993 1998 2004 (Pubitemid 23145717)
    • (1993) Cancer Research , vol.53 , Issue.9 , pp. 1998-2004
    • Stack, M.S.1    Gray, R.D.2    Pizzo, S.V.3
  • 72
    • 0032902356 scopus 로고    scopus 로고
    • The analysis of S100A9 and S100A8 expression in matched sets of macroscopically normal colon mucosa and colorectal carcinoma: The S100A9 and S100A8 positive cells underlie and invade tumor mass
    • DOI 10.1002/(SICI)1522-2683(19990101)20:4/5<1047::AID-ELPS1047>3.0. CO;2-E
    • J. Stulík, J. Osterreicher, K. Koupilová, J. Knízek, A. Macela, J. Bures, P. Jandík, F. Langr, K. Dedic, and P.R. Jungblut The analysis of S100A9 and S100A8 expression in matched sets of macroscopically normal colon mucosa and colorectal carcinoma: the S100A9 and S100A8 positive cells underlie and invade tumor mass Electrophoresis 20 1999 1047 1054 (Pubitemid 29222467)
    • (1999) Electrophoresis , vol.20 , Issue.4-5 , pp. 1047-1054
    • Stulik, J.1    Osterreicher, J.2    Koupilova, K.3    Knizek, J.4    Macela, A.5    Bures, J.6    Jandik, P.7    Langr, F.8    Dedic, K.9    Jungblut, P.R.10
  • 73
    • 0036827465 scopus 로고    scopus 로고
    • kip2 and its clinical relevance in epithelial ovarian tumors
    • L. Sui, Y. Dong, M. Ohno, Y. Watanabe, K. Sugimoto, and M. Tokuda Expression of p57kip2 and its clinical relevance in epithelial ovarian tumors Anticancer Res. 22 2002 3191 3196 (Pubitemid 36070092)
    • (2002) Anticancer Research , vol.22 , Issue.A6 , pp. 3191-3196
    • Sui, L.1    Dong, Y.2    Ohno, M.3    Watanabe, Y.4    Sugimoto, K.5    Tokuda, M.6
  • 74
    • 79952390935 scopus 로고    scopus 로고
    • Identification and validation of SAA as a potential lung cancer biomarker and its involvement in metastatic pathogenesis of lung cancer
    • H.J. Sung, J.M. Ahn, Y.H. Yoon, T.Y. Rhim, C.S. Park, J.Y. Park, S.Y. Lee, J.W. Kim, and J.Y. Cho Identification and validation of SAA as a potential lung cancer biomarker and its involvement in metastatic pathogenesis of lung cancer J. Proteome Res. 10 2011 1383 1395
    • (2011) J. Proteome Res. , vol.10 , pp. 1383-1395
    • Sung, H.J.1    Ahn, J.M.2    Yoon, Y.H.3    Rhim, T.Y.4    Park, C.S.5    Park, J.Y.6    Lee, S.Y.7    Kim, J.W.8    Cho, J.Y.9
  • 76
    • 0037049878 scopus 로고    scopus 로고
    • Induced transcriptional expression of calcium-binding protein S100A1 and S100A10 genes in human renal cell carcinoma
    • DOI 10.1016/S0304-3835(01)00724-8, PII S0304383501007248
    • T. Teratani, T. Watanabe, F. Kuwahara, H. Kumagai, S. Kobayashi, U. Aoki, A. Ishikawa, K. Arai, and R. Nozawa Induced transcriptional expression of calcium-binding protein S100A1 and S100A10 genes in human renal cell carcinoma Cancer Lett. 175 2002 71 77 (Pubitemid 33153046)
    • (2002) Cancer Letters , vol.175 , Issue.1 , pp. 71-77
    • Teratani, T.1    Watanabe, T.2    Kuwahara, F.3    Kumagai, H.4    Kobayashi, S.5    Aoki, U.6    Ishikawa, A.7    Arai, K.8    Nozawa, R.9
  • 77
    • 0034490080 scopus 로고    scopus 로고
    • Arsenic trioxide-mediated cytotoxicity and apoptosis inprostate and ovarian carcinoma cell lines
    • R. Uslu, U.A. Sanli, C. Sezgin, B. Karabulut, E. Terzioglu, S.B. Omay, and E. Goker Arsenic trioxide-mediated cytotoxicity and apoptosis in prostate and ovarian carcinoma cell lines Clin. Cancer Res. 6 2000 4957 4964 (Pubitemid 32110442)
    • (2000) Clinical Cancer Research , vol.6 , Issue.12 , pp. 4957-4964
    • Uslu, R.1    Sanli, U.A.2    Sezgin, C.3    Karabulut, B.4    Terzioglu, E.5    Omay, S.B.6    Goker, E.7
  • 78
    • 0036348616 scopus 로고    scopus 로고
    • Insulin-like growth factor receptor-1 as an anti-cancer target: Blocking transformation and inducing apoptosis
    • Y. Wang, and Y. Sun Insulin-like growth factor receptor-1 as an anti-cancer target: blocking transformation and inducing apoptosis Curr. Cancer Drug Targets 2 2002 191 207
    • (2002) Curr. Cancer Drug Targets , vol.2 , pp. 191-207
    • Wang, Y.1    Sun, Y.2
  • 79
    • 0034742512 scopus 로고    scopus 로고
    • IL (interleukin)-1α promotes nuclear factor-κB and AP-1-induced IL-8 expression, cell survival, and proliferation in head and neck squamous cell carcinomas
    • J.S. Wolf, Z. Chen, G. Dong, J.B. Sunwoo, C.C. Bancroft, D.E. Capo, N.T. Yeh, N. Mukaida, and C. Van Waes IL (Interleukin)-1a promotes nuclear factor-kB and AP-1-induced IL-8 expression, cell survival, and proliferation in head and neck squamous cell carcinomas Clin. Cancer Res. 7 2001 1812 1820 (Pubitemid 32708653)
    • (2001) Clinical Cancer Research , vol.7 , Issue.6 , pp. 1812-1820
    • Wolf, J.S.1    Chen, Z.2    Dong, G.3    Sunwoo, J.B.4    Bancroft, C.C.5    Capo, D.E.6    Yeh, N.T.7    Mukaida, N.8    Van Waes, C.9
  • 82
    • 0037147240 scopus 로고    scopus 로고
    • Initial characterization of the glutamate-cysteine ligase modifier subunit Gclm(-/-) knockout mouse: Novel model system for a severely compromised oxidative stress response
    • DOI 10.1074/jbc.M209372200
    • Y. Yang, M.Z. Dieter, Y. Chen, H.G. Shertzer, D.W. Nebert, and T.P. Dalton Initial characterization of the glutamate-cysteine ligase modifier subunit Gclm(-/-) knockout mouse. Novel model system for a severely compromised oxidative stress response J. Biol. Chem. 277 2002 49446 49452 (Pubitemid 36014379)
    • (2002) Journal of Biological Chemistry , vol.277 , Issue.51 , pp. 49446-49452
    • Yang, Y.1    Dieter, M.Z.2    Chen, Y.3    Shertzer, H.G.4    Nebert, D.W.5    Dalton, T.P.6
  • 83
    • 47749094679 scopus 로고    scopus 로고
    • Expression of leukaemia inhibitory factor in epithelial ovarian carcinoma: Correlation with clinical characteristics
    • DOI 10.1111/j.1365-2559.2008.03068.x
    • F. Ye, Y. Hu, W. Lu, C. Zhou, and X. Xie Expression of leukaemia inhibitory factor in epithelial ovarian carcinoma: correlation with clinical characteristics Histopathology 53 2008 224 228 (Pubitemid 352032768)
    • (2008) Histopathology , vol.53 , Issue.2 , pp. 224-228
    • Ye, F.1    Hu, Y.2    Lu, W.3    Zhou, C.4    Xie, X.5
  • 84
    • 77954424331 scopus 로고    scopus 로고
    • Elevated serum matrix metalloproteinase-3 and -7 in H. Pylori-related gastric cancer can be biomarkers correlating with a poor survival
    • Y.C. Yeh, B.S. Sheu, H.C. Cheng, Y.L. Wang, H.B. Yang, and J.J. Wu Elevated serum matrix metalloproteinase-3 and -7 in H. Pylori-related gastric cancer can be biomarkers correlating with a poor survival Dig. Dis. Sci. 55 2010 1649 1657
    • (2010) Dig. Dis. Sci. , vol.55 , pp. 1649-1657
    • Yeh, Y.C.1    Sheu, B.S.2    Cheng, H.C.3    Wang, Y.L.4    Yang, H.B.5    Wu, J.J.6
  • 85
    • 33846847550 scopus 로고    scopus 로고
    • Roles of calcium-binding proteins, S100A8 and S100A9, in invasive phenotype of human gastric cancer cells
    • H.Y. Yong, and A. Moon Roles of calcium-binding proteins, S100A8 and S100A9, in invasive phenotype of human gastric cancer cells Arch. Pharm. Res. 30 2007 75 81
    • (2007) Arch. Pharm. Res. , vol.30 , pp. 75-81
    • Yong, H.Y.1    Moon, A.2
  • 86
    • 33748537775 scopus 로고    scopus 로고
    • 3) inhibits peritoneal invasion of ovarian carcinoma cells in vitro and in vivo
    • DOI 10.1016/j.ygyno.2006.02.037, PII S0090825806002034
    • J. Zhang, and B. Wang Arsenic trioxide (As(2)O(3)) inhibits peritoneal invasion of ovarian carcinoma cells in vitro and in vivo Gynecol. Oncol. 103 2006 199 206 (Pubitemid 44374690)
    • (2006) Gynecologic Oncology , vol.103 , Issue.1 , pp. 199-206
    • Zhang, J.1    Wang, B.2
  • 87
    • 70649107674 scopus 로고    scopus 로고
    • Arsenic trioxide and cisplatin synergism increase cytotoxicity in human ovarian cancer cells: Therapeutic potential for ovarian cancer
    • N. Zhang, Z.M. Wu, E. McGowan, J. Shi, Z.B. Hong, C.W. Ding, P. Xia, and W. Di Arsenic trioxide and cisplatin synergism increase cytotoxicity in human ovarian cancer cells: therapeutic potential for ovarian cancer Cancer Sci. 100 2009 2459 2464
    • (2009) Cancer Sci. , vol.100 , pp. 2459-2464
    • Zhang, N.1    Wu, Z.M.2    McGowan, E.3    Shi, J.4    Hong, Z.B.5    Ding, C.W.6    Xia, P.7    Di, W.8


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.