REFERENCES
2. Warburg O. On respiratory impairment in cancer cells. Science 1956;124:269-70.
3. Jones RG, Plas DR, Kubek S, Buzzai M, Mu J, Xu Y, Birnbaum MJ, Thompson CB. AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Mol Cell 2005;18:283-93.
4. Elstrom RL, Bauer DE, Buzzai M, Karnauskas R, Harris MH, Plas DR, Zhuang H, Cinalli RM, Alavi A, Rudin CM, Thompson CB. Akt stimulates aerobic glycolysis in cancer cells. Cancer Res 2004;64:3892-9.
6. Stambolic V, MacPherson D, Sas D, Lin Y, Snow B, Jang Y, Benchimol S, Mak TW. Regulation of PTEN transcription by p53. Mol Cell 2001;8:317-25.
7. Ward GR, Wainwright PE. Prenatal ethanol and stress in mice: 1. Pup behavioral development and maternal physiology. Physiol Behav 1989;45:533-40.
8. Galluzzi L, Kroemer G. Necroptosis: a specialized pathway of programmed necrosis. Cell 2008;135:1161-3.
9. Gogvadze V, Orrenius S, Zhivotovsky B. Mitochondria in cancer cells: what is so special about them? Trends Cell Biol 2008;18:165-73.
10. Fukuda R, Zhang H, Kim JW, Shimoda L, Dang CV, Semenza GL. HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells. Cell 2007;129:111-22.
12. Rabilloud T, Heller M, Rigobello MP, Bindoli A, Aebersold R, Lunardi J. The mitochondrial antioxidant defence system and its response to oxidative stress. Proteomics 2001;1:1105-10.
13. Banmeyer I, Marchand C, Clippe A, Knoops B. Human mitochondrial peroxiredoxin 5 protects from mitochondrial DNA damages induced by hydrogen peroxide. FEBS Lett 2005;579:2327-33.
14. Huh JY, Kim Y, Jeong J, Park J, Kim I, Huh KH, Kim YS, Woo HA, Rhee SG, Lee KJ, Ha H. Peroxiredoxin 3 is a key molecule regulating adipocyte oxidative stress, mitochondrial biogenesis, and adipokine expression. Antioxid Redox Signal 2012;16:229-43.
15. Nonn L, Williams RR, Erickson RP, Powis G. The absence of mitochondrial thioredoxin 2 causes massive apoptosis, exencephaly, and early embryonic lethality in homozygous mice. Mol Cell Biol 2003;23:916-22.
16. Lebovitz RM, Zhang H, Vogel H, Cartwright J, Jr, Dionne L, Lu N, Huang S, Matzuk MM. Neurodegeneration, myocardial injury, and perinatal death in mitochondrial superoxide dismutase-deficient mice. Proc Natl Acad Sci U S A 1996;93:9782-7.
17. Hinerfeld D, Traini MD, Weinberger RP, Cochran B, Doctrow SR, Harry J, Melov S. Endogenous mitochondrial oxidative stress: neurodegeneration, proteomic analysis, specific respiratory chain defects, and efficacious antioxidant therapy in superoxide dismutase 2 null mice. J Neurochem 2004;88:657-67.
18. Canter JA, Kallianpur AR, Parl FF, Millikan RC. Mitochondrial DNA G10398A polymorphism and invasive breast cancer in African-American women. Cancer Res 2005;65:8028-33.
19. Darvishi K, Sharma S, Bhat AK, Rai E, Bamezai RN. Mitochondrial DNA G10398A polymorphism imparts maternal Haplogroup N a risk for breast and esophageal cancer. Cancer Lett 2007;249:249-55.
20. Liu VW, Wang Y, Yang HJ, Tsang PC, Ng TY, Wong LC, Nagley P, Ngan HY. Mitochondrial DNA variant 16189T>C is associated with susceptibility to endometrial cancer. Hum Mutat 2003;22:173-4.
21. Ishikawa K, Takenaga K, Akimoto M, Koshikawa N, Yamaguchi A, Imanishi H, Nakada K, Honma Y, Hayashi J. ROS-generating mitochondrial DNA mutations can regulate tumor cell metastasis. Science 2008;320:661-4.
23. Matoba S, Kang JG, Patino WD, Wragg A, Boehm M, Gavrilova O, Hurley PJ, Bunz F, Hwang PM. p53 regulates mitochondrial respiration. Science 2006;312:1650-3.
24. Buchwald P, Krummeck G, Rodel G. Immunological identification of yeast SCO1 protein as a component of the inner mitochondrial membrane. Mol Gen Genet 1991;229:413-20.
25. Bensaad K, Tsuruta A, Selak MA, Vidal MN, Nakano K, Bartrons R, Gottlieb E, Vousden KH. TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell 2006;126:107-20.
26. Zhou X, Xie W, Li Q, Zhang Y, Zhang J, Zhao X, Liu J, Huang G. TIGAR is correlated with maximal standardized uptake value on FDG-PET and survival in non-small cell lung cancer. PLoS One 2013;8:e80576.
27. 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;3:177-85.
28. Papandreou I, Cairns RA, Fontana L, Lim AL, Denko NC. HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell Metab 2006;3:187-97.
29. Abel F, Sjoberg RM, Nilsson S, Kogner P, Martinsson T. Imbalance of the mitochondrial pro- and anti-apoptotic mediators in neuroblastoma tumours with unfavourable biology. Eur J Cancer 2005;41:635-46.
30. Shimizu S, Shinohara Y, Tsujimoto Y. Bax and Bcl-xL independently regulate apoptotic changes of yeast mitochondria that require VDAC but not adenine nucleotide translocator. Oncogene 2000;19:4309-18.
31. Mathupala SP, Ko YH, Pedersen PL. Hexokinase II: cancer's double-edged sword acting as both facilitator and gatekeeper of malignancy when bound to mitochondria. Oncogene 2006;25:4777-86.
32. Pastorino JG, Shulga N, Hoek JB. Mitochondrial binding of hexokinase II inhibits Bax-induced cytochrome c release and apoptosis. J Biol Chem 2002;277:7610-8.
33. Kennedy SG, Kandel ES, Cross TK, Hay N. Akt/Protein kinase B inhibits cell death by preventing the release of cytochrome c from mitochondria. Mol Cell Biol 1999;19:5800-10.
34. Bijur GN, Jope RS. Rapid accumulation of Akt in mitochondria following phosphatidylinositol 3-kinase activation. J Neurochem 2003;87:1427-35.
35. Nakano K, Vousden KH. PUMA, a novel proapoptotic gene, is induced by p53. Mol Cell 2001;7:683-94.
36. Oda E, Ohki R, Murasawa H, Nemoto J, Shibue T, Yamashita T, Tokino T, Taniguchi T, Tanaka N. Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science 2000;288:1053-8.
37. Zhong H, De Marzo AM, Laughner E, Lim M, Hilton DA, Zagzag D, Buechler P, Isaacs WB, Semenza GL, Simons JW. Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Res 1999;59:5830-5.
38. Zhang ZG, Zhang QN, Wang XH, Tian JH. Hypoxia-inducible factor 1 alpha (HIF-1alpha) as a prognostic indicator in patients with gastric tumors: a meta-analysis. Asian Pac J Cancer Prev 2013;14:4195-8.
39. Matsuyama T, Nakanishi K, Hayashi T, Yoshizumi Y, Aiko S, Sugiura Y, Tanimoto T, Uenoyama M, Ozeki Y, Maehara T. Expression of hypoxia-inducible factor-1alpha in esophageal squamous cell carcinoma. Cancer Sci 2005;96:176-82.
40. Ogane N, Yasuda M, Shimizu M, Miyazawa M, Kamoshida S, Ueda A, Takata K, Sakuma Y, Miyagi Y, Kameda Y. Clinicopathological implications of expressions of hypoxia-related molecules in esophageal superficial squamous cell carcinoma. Ann Diagn Pathol 2010;14:23-9.
41. Lin S, Ma R, Zheng XY, Yu H, Liang X, Lin H, Cai XJ. Meta-analysis of immunohistochemical expression of hypoxia inducible factor-1alpha as a prognostic role in gastric cancer. World J Gastroenterol 2014;20:1107-13.
42. Baba Y, Nosho K, Shima K, Irahara N, Chan AT, Meyerhardt JA, Chung DC, Giovannucci EL, Fuchs CS, Ogino S. HIF1A overexpression is associated with poor prognosis in a cohort of 731 colorectal cancers. Am J Pathol 2010;176:2292-301.
43. Zheng SS, Chen XH, Yin X, Zhang BH. Prognostic significance of HIF-1alpha expression in hepatocellular carcinoma: a meta-analysis. PLoS One 2013;8:e65753.
44. Nakamura J, Kitajima Y, Kai K, Mitsuno M, Ide T, Hashiguchi K, Hiraki M, Miyazaki K. Hypoxia-inducible factor-1alpha expression predicts the response to 5-fluorouracil-based adjuvant chemotherapy in advanced gastric cancer. Oncol Rep 2009;22:693-9.
45. Nakamura J, Kitajima Y, Kai K, Hashiguchi K, Hiraki M, Noshiro H, Miyazaki K. HIF-1alpha is an unfavorable determinant of relapse in gastric cancer patients who underwent curative surgery followed by adjuvant 5-FU chemotherapy. Int J Cancer 2010;127:1158-71.
46. Griffiths EA, Pritchard SA, McGrath SM, Valentine HR, Price PM, Welch IM, West CM. Hypoxia-associated markers in gastric carcinogenesis and HIF-2alpha in gastric and gastro-oesophageal cancer prognosis. Br J Cancer 2008;98:965-73.
47. Rasheed S, Harris AL, Tekkis PP, Turley H, Silver A, McDonald PJ, Talbot IC, Glynne-Jones R, Northover JM, Guenther T. Hypoxia-inducible factor-1alpha and -2alpha are expressed in most rectal cancers but only hypoxia-inducible factor-1alpha is associated with prognosis. Br J Cancer 2009;100:1666-73.
48. Fernandez PC, Frank SR, Wang L, Schroeder M, Liu S, Greene J, Cocito A, Amati B. Genomic targets of the human c-Myc protein. Genes Dev 2003;17:1115-29.
49. Lutz W, Leon J, Eilers M. Contributions of Myc to tumorigenesis. Biochim Biophys Acta 2002;1602:61-71.
50. de Souza CR, Leal MF, Calcagno DQ, Costa Sozinho EK, Borges Bdo N, Montenegro RC, Dos Santos AK, Dos Santos SE, Ribeiro HF, Assumpcao PP, de Arruda Cardoso Smith M, Burbano RR. MYC deregulation in gastric cancer and its clinicopathological implications. PLoS One 2013;8:e64420.
51. Joost HG, Thorens B. The extended GLUT-family of sugar/polyol transport facilitators: nomenclature, sequence characteristics, and potential function of its novel members (review). Mol Membr Biol 2001;18:247-56.
52. Younes M, Lechago LV, Somoano JR, Mosharaf M, Lechago J. Immunohistochemical detection of 3 in human tumors and normal tissues. Anticancer Res 1997;17:2747-50.
53. Ayala FR, Rocha RM, Carvalho KC, Carvalho AL, da Cunha IW, Lourenco SV, Soares FA. GLUT1 and GLUT3 as potential prognostic markers for Oral Squamous Cell Carcinoma. Molecules 2010;15:2374-87.
54. Fonteyne P, Casneuf V, Pauwels P, Van Damme N, Peeters M, Dierckx R, Van de Wiele C. Expression of hexokinases and glucose transporters in treated and untreated oesophageal adenocarcinoma. Histol Histopathol 2009;24:971-7.
55. Sawayama H, Ishimoto T, Watanabe M, Yoshida N, Baba Y, Sugihara H, Izumi D, Kurashige J, Baba H. High expression of glucose transporter 1 on primary lesions of esophageal squamous cell carcinoma is associated with hematogenous recurrence. Ann Surg Oncol 2014;21:1756-62.
56. Kawamura T, Kusakabe T, Sugino T, Watanabe K, Fukuda T, Nashimoto A, Honma K, Suzuki T. Expression of glucose transporter-1 in human gastric carcinoma: association with tumor aggressiveness, metastasis, and patient survival. Cancer 2001;92:634-41.
57. Haber RS, Rathan A, Weiser KR, Pritsker A, Itzkowitz SH, Bodian C, Slater G, Weiss A, Burstein DE. GLUT1 glucose transporter expression in colorectal carcinoma: a marker for poor prognosis. Cancer 1998;83:34-40.
58. Mueckler M, Caruso C, Baldwin SA, Panico M, Blench I, Morris HR, Allard WJ, Lienhard GE, Lodish HF. Sequence and structure of a human glucose transporter. Science 1985;229:941-5.
59. Deng D, Xu C, Sun P, Wu J, Yan C, Hu M, Yan N. Crystal structure of the human glucose transporter GLUT1. Nature 2014;510:121-5.
60. Griffiths EA, Pritchard SA, Welch IM, Price PM, West CM. Is the hypoxia-inducible factor pathway important in gastric cancer? Eur J Cancer 2005;41:2792-805.
61. Dang CV, Le A, Gao P. MYC-induced cancer cell energy metabolism and therapeutic opportunities. Clin Cancer Res 2009;15:6479-83.
62. Yun J, Rago C, Cheong I, Pagliarini R, Angenendt P, Rajagopalan H, Schmidt K, Willson JK, Markowitz S, Zhou S, Diaz LA Jr, Velculescu VE, Lengauer C, Kinzler KW, Vogelstein B, Papadopoulos N. Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells. Science 2009;325:1555-9.
63. Kawada K, Nakamoto Y, Kawada M, Hida K, Matsumoto T, Murakami T, Hasegawa S, Togashi K, Sakai Y. Relationship between 18F-fluorodeoxyglucose accumulation and KRAS/BRAF mutations in colorectal cancer. Clin Cancer Res 2012;18:1696-703.
64. Yang W, Zheng Y, Xia Y, Ji H, Chen X, Guo F, Lyssiotis CA, Aldape K, Cantley LC, Lu Z. ERK1/2-dependent phosphorylation and nuclear translocation of PKM2 promotes the Warburg effect. Nat Cell Biol 2012;14:1295-304.
65. Young CD, Lewis AS, Rudolph MC, Ruehle MD, Jackman MR, Yun UJ, Ilkun O, Pereira R, Abel ED, Anderson SM. Modulation of glucose transporter 1 (GLUT1) expression levels alters mouse mammary tumor cell growth in vitro and in vivo. PLoS One 2011;6:e23205.
66. Kwee SA, Hernandez B, Chan O, Wong L. Choline kinase alpha and hexokinase-2 protein expression in hepatocellular carcinoma: association with survival. PLoS One 2012;7:e46591.
67. Paudyal B, Paudyal P, Oriuchi N, Tsushima Y, Nakajima T, Endo K. Clinical implication of glucose transport and metabolism evaluated by 18F-FDG PET in hepatocellular carcinoma. Int J Oncol 2008;33:1047-54.
68. Gong L, Cui Z, Chen P, Han H, Peng J, Leng X. Reduced survival of patients with hepatocellular carcinoma expressing hexokinase II. Med Oncol 2012;29:909-14.
69. Mathupala SP, Ko YH, Pedersen PL. Hexokinase-2 bound to mitochondria: cancer's stygian link to the "Warburg Effect" and a pivotal target for effective therapy. Semin Cancer Biol 2009;19:17-24.
70. David CJ, Chen M, Assanah M, Canoll P, Manley JL. HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer. Nature 2010;463:364-8.
71. Clower CV, Chatterjee D, Wang Z, Cantley LC, Vander Heiden MG, Krainer AR. The alternative splicing repressors hnRNP A1/A2 and PTB influence pyruvate kinase isoform expression and cell metabolism. Proc Natl Acad Sci U S A 2010;107:1894-9.
72. Christofk HR, Vander Heiden MG, Harris MH, Ramanathan A, Gerszten RE, Wei R, Fleming MD, Schreiber SL, Cantley LC. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature 2008;452:230-3.
73. Yang W, Lu Z. Regulation and function of pyruvate kinase M2 in cancer. Cancer Lett 2013;339:153-8.
74. Tamada M, Suematsu M, Saya H. Pyruvate kinase M2: multiple faces for conferring benefits on cancer cells. Clin Cancer Res 2012;18:5554-61.
75. Kaplon J, Zheng L, Meissl K, Chaneton B, Selivanov VA, Mackay G, van der Burg SH, Verdegaal EM, Cascante M, Shlomi T, Gottlieb E, Peeper DS. A key role for mitochondrial gatekeeper pyruvate dehydrogenase in oncogene-induced senescence. Nature 2013;498:109-12.
76. Hur H, Xuan Y, Kim YB, Lee G, Shim W, Yun J, Ham IH, Han SU. Expression of pyruvate dehydrogenase kinase-1 in gastric cancer as a potential therapeutic target. Int J Oncol 2013;42:44-54.
77. Lu CW, Lin SC, Chien CW, Lin SC, Lee CT, Lin BW, Lee JC, Tsai SJ. Overexpression of pyruvate dehydrogenase kinase 3 increases drug resistance and early recurrence in colon cancer. Am J Pathol 2011;179:1405-14.
78. Fantin VR, St-Pierre J, Leder P. Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer Cell 2006;9:425-34.
79. Goldman RD, Kaplan NO, Hall TC. Lactic Dehydrogenase in Human Neoplastic Tissues. Cancer Res 1964;24:389-99.
80. Zhang Y, Zhang X, Wang X, Gan L, Yu G, Chen Y, Liu K, Li P, Pan J, Wang J, Qin S. Inhibition of LDH-A by lentivirus-mediated small interfering RNA suppresses intestinal-type gastric cancer tumorigenicity through the downregulation of Oct4. Cancer Lett 2012;321:45-54.
81. Koukourakis MI, Giatromanolaki A, Sivridis E, Gatter KC, Harris AL, Tumour Angiogenesis Research G. Lactate dehydrogenase 5 expression in operable colorectal cancer: strong association with survival and activated vascular endothelial growth factor pathway--a report of the Tumour Angiogenesis Research Group. J Clin Oncol 2006;24:4301-8.
82. Fan J, Hitosugi T, Chung TW, Xie J, Ge Q, Gu TL, Polakiewicz RD, Chen GZ, Boggon TJ, Lonial S, Khuri FR, Kang S, Chen J. Tyrosine phosphorylation of lactate dehydrogenase A is important for NADH/NAD(+) redox homeostasis in cancer cells. Mol Cell Biol 2011;31:4938-50.
83. Sheng SL, Liu JJ, Dai YH, Sun XG, Xiong XP, Huang G. Knockdown of lactate dehydrogenase A suppresses tumor growth and metastasis of human hepatocellular carcinoma. FEBS J 2012;279:3898-910.
84. Jiang P, Du W, Wu M. Regulation of the pentose phosphate pathway in cancer. Protein Cell 2014;5:592-602.
85. Kletzien RF, Harris PK, Foellmi LA. Glucose-6-phosphate dehydrogenase: a "housekeeping" enzyme subject to tissue-specific regulation by hormones, nutrients, and oxidant stress. FASEB J 1994;8:174-81.
86. Tsouko E, Khan AS, White MA, Han JJ, Shi Y, Merchant FA, Sharpe MA, Xin L, Frigo DE. Regulation of the pentose phosphate pathway by an androgen receptor-mTOR-mediated mechanism and its role in prostate cancer cell growth. Oncogenesis 2014;3:e103.
87. Wang J, Yuan W, Chen Z, Wu S, Chen J, Ge J, Hou F, Chen Z. Overexpression of G6PD is associated with poor clinical outcome in gastric cancer. Tumour Biol 2012;33:95-101.
88. Lucarelli G, Galleggiante V, Rutigliano M, Sanguedolce F, Cagiano S, Bufo P, Lastilla G, Maiorano E, Ribatti D, Giglio A, Serino G, Vavallo A, Bettocchi C, Selvaggi FP, Battaglia M, Ditonno P. Metabolomic profile of glycolysis and the pentose phosphate pathway identifies the central role of glucose-6-phosphate dehydrogenase in clear cell-renal cell carcinoma. Oncotarget 2015;6:13371-86.
89. Zhang C, Zhang Z, Zhu Y, Qin S. Glucose-6-phosphate dehydrogenase: a biomarker and potential therapeutic target for cancer. Anticancer Agents Med Chem 2014;14:280-9.
90. Wang Z, Liang S, Lian X, Liu L, Zhao S, Xuan Q, Guo L, Liu H, Yang Y, Dong T, Liu Y, Liu Z, Zhang Q. Identification of proteins responsible for adriamycin resistance in breast cancer cells using proteomics analysis. Sci Rep 2015;5:9301.
91. Ying H, Kimmelman AC, Lyssiotis CA, Hua S, Chu GC, Fletcher-Sananikone E, Locasale JW, Son J, Zhang H, Coloff JL, Yan H, Wang W, Chen S, Viale A, Zheng H, Paik JH, Lim C, Guimaraes AR, Martin ES, Chang J, Hezel AF, Perry SR, Hu J, Gan B, Xiao Y, Asara JM, Weissleder R, Wang YA, Chin L, Cantley LC, DePinho RA. Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism. Cell 2012;149:656-70.
92. Duvel K, Yecies JL, Menon S, Raman P, Lipovsky AI, Souza AL, Triantafellow E, Ma Q, Gorski R, Cleaver S, Vander Heiden MG, MacKeigan JP, Finan PM, Clish CB, Murphy LO, Manning BD. Activation of a metabolic gene regulatory network downstream of mTOR complex 1. Mol Cell 2010;39:171-83.
93. Jiang P, Du W, Yang X. A critical role of glucose-6-phosphate dehydrogenase in TAp73-mediated cell proliferation. Cell Cycle 2013;12:3720-6.
94. Du W, Jiang P, Mancuso A, Stonestrom A, Brewer MD, Minn AJ, Mak TW, Wu M, Yang X. TAp73 enhances the pentose phosphate pathway and supports cell proliferation. Nat Cell Biol 2013;15:991-1000.
95. Cosentino C, Grieco D, Costanzo V. ATM activates the pentose phosphate pathway promoting anti-oxidant defence and DNA repair. EMBO J 2011;30:546-55.
96. Hong X, Song R, Song H, Zheng T, Wang J, Liang Y, Qi S, Lu Z, Song X, Jiang H, Liu L, Zhang Z. PTEN antagonises Tcl1/hnRNPK-mediated G6PD pre-mRNA splicing which contributes to hepatocarcinogenesis. Gut 2014;63:1635-47.
97. Leopold JA, Dam A, Maron BA, Scribner AW, Liao R, Handy DE, Stanton RC, Pitt B, Loscalzo J. Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity. Nat Med 2007;13:189-97.
98. Mitsuishi Y, Taguchi K, Kawatani Y, Shibata T, Nukiwa T, Aburatani H, Yamamoto M, Motohashi H. Nrf2 redirects glucose and glutamine into anabolic pathways in metabolic reprogramming. Cancer Cell 2012;22:66-79.
99. Wu KC, Cui JY, Klaassen CD. Beneficial role of Nrf2 in regulating NADPH generation and consumption. Toxicol Sci 2011;123:590-600.
100. Kobayashi A, Kang MI, Okawa H, Ohtsuji M, Zenke Y, Chiba T, Igarashi K, Yamamoto M. Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2. Mol Cell Biol 2004;24:7130-9.
101. Jaramillo MC, Zhang DD. The emerging role of the Nrf2-Keap1 signaling pathway in cancer. Genes Dev 2013;27:2179-91.
102. Solis LM, Behrens C, Dong W, Suraokar M, Ozburn NC, Moran CA, Corvalan AH, Biswal S, Swisher SG, Bekele BN, Minna JD, Stewart DJ, Wistuba, II. Nrf2 and Keap1 abnormalities in non-small cell lung carcinoma and association with clinicopathologic features. Clin Cancer Res 2010;16:3743-53.
103. Fer ND, Shoemaker RH, Monks A. Adaphostin toxicity in a sensitive non-small cell lung cancer model is mediated through Nrf2 signaling and heme oxygenase 1. J Exp Clin Cancer Res 2010;29:91.
104. Martinez VD, Vucic EA, Thu KL, Pikor LA, Lam S, Lam WL. Disruption of KEAP1/CUL3/RBX1 E3-ubiquitin ligase complex components by multiple genetic mechanisms: Association with poor prognosis in head and neck cancer. Head Neck 2015;37:727-34.
105. Onodera Y, Motohashi H, Takagi K, Miki Y, Shibahara Y, Watanabe M, Ishida T, Hirakawa H, Sasano H, Yamamoto M, Suzuki T. NRF2 immunolocalization in human breast cancer patients as a prognostic factor. Endocr Relat Cancer 2014;21:241-52.
106. Soini Y, Eskelinen M, Juvonen P, Karja V, Haapasaari KM, Saarela A, Karihtala P. Nuclear Nrf2 expression is related to a poor survival in pancreatic adenocarcinoma. Pathol Res Pract 2014;210:35-9.
107. Kawasaki Y, Ishigami S, Arigami T, Uenosono Y, Yanagita S, Uchikado Y, Kita Y, Nishizono Y, Okumura H, Nakajo A, Kijima Y, Maemura K, Natsugoe S. Clinicopathological significance of nuclear factor (erythroid-2)-related factor 2 (Nrf2) expression in gastric cancer. BMC Cancer 2015;15:5.
108. Yang Y, Cai X, Yang J, Sun X, Hu C, Yan Z, Xu X, Lu W, Wang X, Cao P. Chemoprevention of dietary digitoflavone on colitis-associated colon tumorigenesis through inducing Nrf2 signaling pathway and inhibition of inflammation. Mol Cancer 2014;13:48.
109. Kawasaki Y, Okumura H, Uchikado Y, Kita Y, Sasaki K, Owaki T, Ishigami S, Natsugoe S. Nrf2 is useful for predicting the effect of chemoradiation therapy on esophageal squamous cell carcinoma. Ann Surg Oncol 2014;21:2347-52.
110. Andreyev AY, Kushnareva YE, Starkov AA. Mitochondrial metabolism of reactive oxygen species. Biochemistry (Mosc) 2005;70:200-14.
111. Trachootham D, Alexandre J, Huang P. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov 2009;8:579-91.
112. Klaunig JE, Kamendulis LM. The role of oxidative stress in carcinogenesis. Annu Rev Pharmacol Toxicol 2004;44:239-67.
113. Sullivan R, Graham CH. Chemosensitization of cancer by nitric oxide. Curr Pharm Des 2008;14:1113-23.
114. Chen EI, Hewel J, Krueger JS, Tiraby C, Weber MR, Kralli A, Becker K, Yates JR, 3rd, Felding-Habermann B. Adaptation of energy metabolism in breast cancer brain metastases. Cancer Res 2007;67:1472-86.
115. Young TW, Mei FC, Yang G, Thompson-Lanza JA, Liu J, Cheng X. Activation of antioxidant pathways in ras-mediated oncogenic transformation of human surface ovarian epithelial cells revealed by functional proteomics and mass spectrometry. Cancer Res 2004;64:4577-84.
116. Xia C, Meng Q, Liu LZ, Rojanasakul Y, Wang XR, Jiang BH. Reactive oxygen species regulate angiogenesis and tumor growth through vascular endothelial growth factor. Cancer Res 2007;67:10823-30.
117. Kondoh H, Lleonart ME, Bernard D, Gil J. Protection from oxidative stress by enhanced glycolysis; a possible mechanism of cellular immortalization. Histol Histopathol 2007;22:85-90.
118. Pervaiz S, Clement MV. Tumor intracellular redox status and drug resistance--serendipity or a causal relationship? Curr Pharm Des 2004;10:1969-77.
119. Tiligada E. Chemotherapy: induction of stress responses. Endocr Relat Cancer 2006;13 Suppl 1:S115-24.
120. Hwang PM, Bunz F, Yu J, Rago C, Chan TA, Murphy MP, Kelso GF, Smith RA, Kinzler KW, Vogelstein B. Ferredoxin reductase affects p53-dependent, 5-fluorouracil-induced apoptosis in colorectal cancer cells. Nat Med 2001;7:1111-7.
121. Hwang IT, Chung YM, Kim JJ, Chung JS, Kim BS, Kim HJ, Kim JS, Yoo YD. Drug resistance to 5-FU linked to reactive oxygen species modulator 1. Biochem Biophys Res Commun 2007;359:304-10.
122. Conklin KA. Chemotherapy-associated oxidative stress: impact on chemotherapeutic effectiveness. Integr Cancer Ther 2004;3:294-300.
123. Sullivan LB, Chandel NS. Mitochondrial reactive oxygen species and cancer. Cancer Metab 2014;2:17.
124. Raj L, Ide T, Gurkar AU, Foley M, Schenone M, Li X, Tolliday NJ, Golub TR, Carr SA, Shamji AF, Stern AM, Mandinova A, Schreiber SL, Lee SW. Selective killing of cancer cells by a small molecule targeting the stress response to ROS. Nature 2011;475:231-4.
125. Trachootham D, Zhou Y, Zhang H, Demizu Y, Chen Z, Pelicano H, Chiao PJ, Achanta G, Arlinghaus RB, Liu J, Huang P. Selective killing of oncogenically transformed cells through a ROS-mediated mechanism by beta-phenylethyl isothiocyanate. Cancer Cell 2006;10:241-52.
126. Sawayama H, Ishimoto T, Watanabe M, Yoshida N, Sugihara H, Kurashige J, Hirashima K, Iwatsuki M, Baba Y, Oki E, Morita M, Shiose Y, Baba H. Small molecule agonists of PPAR-gamma exert therapeutic effects in esophageal cancer. Cancer Res 2014;74:575-85.
127. Cao X, Fang L, Gibbs S, Huang Y, Dai Z, Wen P, Zheng X, Sadee W, Sun D. Glucose uptake inhibitor sensitizes cancer cells to daunorubicin and overcomes drug resistance in hypoxia. Cancer Chemother Pharmacol 2007;59:495-505.
128. Wu CH, Ho YS, Tsai CY, Wang YJ, Tseng H, Wei PL, Lee CH, Liu RS, Lin SY. In vitro and in vivo study of phloretin-induced apoptosis in human liver cancer cells involving inhibition of type II glucose transporter. Int J Cancer 2009;124:2210-9.
129. Liu Y, Cao Y, Zhang W, Bergmeier S, Qian Y, Akbar H, Colvin R, Ding J, Tong L, Wu S, Hines J, Chen X. A small-molecule inhibitor of glucose transporter 1 downregulates glycolysis, induces cell-cycle arrest, and inhibits cancer cell growth in vitro and in vivo. Mol Cancer Ther 2012;11:1672-82.
130. Ganapathy-Kanniappan S, Vali M, Kunjithapatham R, Buijs M, Syed LH, Rao PP, Ota S, Kwak BK, Loffroy R, Geschwind JF. 3-bromopyruvate: a new targeted antiglycolytic agent and a promise for cancer therapy. Curr Pharm Biotechnol 2010;11:510-7.
131. Zhou Y, Tozzi F, Chen J, Fan F, Xia L, Wang J, Gao G, Zhang A, Xia X, Brasher H, Widger W, Ellis LM, Weihua Z. Intracellular ATP levels are a pivotal determinant of chemoresistance in colon cancer cells. Cancer Res 2012;72:304-14.
132. Yu SJ, Yoon JH, Yang JI, Cho EJ, Kwak MS, Jang ES, Lee JH, Kim YJ, Lee HS, Kim CY. Enhancement of hexokinase II inhibitor-induced apoptosis in hepatocellular carcinoma cells via augmenting ER stress and anti-angiogenesis by protein disulfide isomerase inhibition. J Bioenerg Biomembr 2012;44:101-15.
133. Tong J, Xie G, He J, Li J, Pan F, Liang H. Synergistic antitumor effect of dichloroacetate in combination with 5-fluorouracil in colorectal cancer. J Biomed Biotechnol 2011;2011:740564.
134. Shen YC, Ou DL, Hsu C, Lin KL, Chang CY, Lin CY, Liu SH, Cheng AL. Activating oxidative phosphorylation by a pyruvate dehydrogenase kinase inhibitor overcomes sorafenib resistance of hepatocellular carcinoma. Br J Cancer 2013;108:72-81.
135. Miskimins WK, Ahn HJ, Kim JY, Ryu S, Jung YS, Choi JY. Synergistic anti-cancer effect of phenformin and oxamate. PLoS One 2014;9:e85576.
136. Kim TH, Hur EG, Kang SJ, Kim JA, Thapa D, Lee YM, Ku SK, Jung Y, Kwak MK. NRF2 blockade suppresses colon tumor angiogenesis by inhibiting hypoxia-induced activation of HIF-1alpha. Cancer Res 2011;71:2260-75.
138. Hockel M, Vaupel P. Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. J Natl Cancer Inst 2001;93:266-76.
139. Brown JM, Wilson WR. Exploiting tumour hypoxia in cancer treatment. Nat Rev Cancer 2004;4:437-47.
141. Brown JM, Lemmon MJ. Potentiation by the hypoxic cytotoxin SR 4233 of cell killing produced by fractionated irradiation of mouse tumors. Cancer Res 1990;50:7745-9.
142. DiSilvestro PA, Ali S, Craighead PS, Lucci JA, Lee YC, Cohn DE, Spirtos NM, Tewari KS, Muller C, Gajewski WH, Steinhoff MM, Monk BJ. Phase III randomized trial of weekly cisplatin and irradiation versus cisplatin and tirapazamine and irradiation in stages IB2, IIA, IIB, IIIB, and IVA cervical carcinoma limited to the pelvis: a Gynecologic Oncology Group study. J Clin Oncol 2014;32:458-64.
143. Duan JX, Jiao H, Kaizerman J, Stanton T, Evans JW, Lan L, Lorente G, Banica M, Jung D, Wang J, Ma H, Li X, Yang Z, Hoffman RM, Ammons WS, Hart CP, Matteucci M. Potent and highly selective hypoxia-activated achiral phosphoramidate mustards as anticancer drugs. J Med Chem 2008;51:2412-20.
144. Borad MJ, Reddy SG, Bahary N, Uronis HE, Sigal D, Cohn AL, Schelman WR, Stephenson J Jr, Chiorean EG, Rosen PJ, Ulrich B, Dragovich T, Del Prete SA, Rarick M, Eng C, Kroll S, Ryan DP. Randomized Phase II Trial of Gemcitabine Plus TH-302 Versus Gemcitabine in Patients With Advanced Pancreatic Cancer. J Clin Oncol 2015;33:1475-81.
145. Townsend DM, He L, Hutchens S, Garrett TE, Pazoles CJ, Tew KD. NOV-002, a glutathione disulfide mimetic, as a modulator of cellular redox balance. Cancer Res 2008;68:2870-7.
146. Montero AJ, Diaz-Montero CM, Deutsch YE, Hurley J, Koniaris LG, Rumboldt T, Yasir S, Jorda M, Garret-Mayer E, Avisar E, Slingerland J, Silva O, Welsh C, Schuhwerk K, Seo P, Pegram MD, Gluck S. Phase 2 study of neoadjuvant treatment with NOV-002 in combination with doxorubicin and cyclophosphamide followed by docetaxel in patients with HER-2 negative clinical stage II-IIIc breast cancer. Breast Cancer Res Treat 2012;132:215-23.
147. Ishimoto T, Nagano O, Yae T, Tamada M, Motohara T, Oshima H, Oshima M, Ikeda T, Asaba R, Yagi H, Masuko T, Shimizu T, Ishikawa T, Kai K, Takahashi E, Imamura Y, Baba Y, Ohmura M, Suematsu M, Baba H, Saya H. CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc(-) and thereby promotes tumor growth. Cancer Cell 2011;19:387-400.
148. Lo M, Ling V, Low C, Wang YZ, Gout PW. Potential use of the anti-inflammatory drug, sulfasalazine, for targeted therapy of pancreatic cancer. Curr Oncol 2010;17:9-16.
149. Guan J, Lo M, Dockery P, Mahon S, Karp CM, Buckley AR, Lam S, Gout PW, Wang YZ. The xc- cystine/glutamate antiporter as a potential therapeutic target for small-cell lung cancer: use of sulfasalazine. Cancer Chemother Pharmacol 2009;64:463-72.
