Cancer cells metabolically "fertilize" the tumor microenvironment with hydrogen peroxide, driving the Warburg effect: Implications for PET imaging of human tumors

Cell Cycle

Volumn 10, Issue 15, 2011, Pages 2504-2520

  Martinez Outschoorn, Ubaldo E ^a,b   Lin, Zhao ^a   Trimmer, Casey ^a   Flomenberg, Neal ^a,b   Wang, Chenguang ^a   Pavlides, Stephanos ^a   Pestell, Richard G ^a   Howell, Anthony ^c   Sotgia, Federica ^a,c   Lisanti, Michael P ^a,b,c  

^a THOMAS JEFFERSON UNIVERSITY   (United States)

^b THOMAS JEFFERSON UNIVERSITY   (United States)

^c UNIVERSITY OF MANCHESTER   (United Kingdom)

Author keywords

Aerobic glycolysis; Cancer associated fibroblasts; Caveolin 1; Glucose uptake; Hydrogen peroxide; Microenvironment; Mitochondrial oxidative phosphorylation; Oxidative stress; PET imaging; Reactive oxygen species (ROS); The field effect; Tumor stroma

Indexed keywords

CATALASE; GLUCOSE TRANSPORTER 1; HYDROGEN PEROXIDE; REACTIVE OXYGEN METABOLITE;

ARTICLE; AUTOPHAGY; CANCER CELL CULTURE; CELL METABOLISM; CELL STRAIN MCF 7; COCULTURE; CONTROLLED STUDY; FIBROBLAST CULTURE; FLUORESCENCE ACTIVATED CELL SORTING; GLUCOSE TRANSPORT; GLYCOLYSIS; HUMAN; HUMAN CELL; NEOPLASM; OXIDATIVE STRESS; POSITRON EMISSION TOMOGRAPHY;

EID: 79961101955     PISSN: 15384101     EISSN: 15514005     Source Type: Journal    
DOI: 10.4161/cc.10.15.16585     Document Type: Article

References (103)

1. Pavlides S, Whitaker-Menezes D, Castello-Cros R, Flomenberg N, Witkiewicz AK, Frank PG, et al. The reverse Warburg effect: Aerobic glycolysis in cancer associated fibroblasts and the tumor stroma. Cell Cycle 2009; 8:3984-4001; PMID: 19923890; DOI: 10.4161/cc.8.23.10238.
2. Pavlides S, Tsirigos A, Vera I, Flomenberg N, Frank PG, Casimiro MC, et al. Loss of stromal caveolin-1 leads to oxidative stress, mimics hypoxia and drives inflammation in the tumor microenvironment, conferring the "reverse Warburg effect": A transcriptional informatics analysis with validation. Cell Cycle 2010; 9:2201-19; PMID: 20519932; DOI: 10.4161/cc.9.11.11848.
3. Pavlides S, Tsirigos A, Vera I, Flomenberg N, Frank PG, Casimiro MC, et al. Transcriptional evidence for the "Reverse Warburg Effect" in human breast cancer tumor stroma and metastasis: similarities with oxidative stress, inflammation, Alzheimer's disease and "Neuron- Glia Metabolic Coupling". Aging (Albany NY) 2010; 2:185-99; PMID: 20442453.
4. Pavlides S, Tsirigos A, Migneco G, Whitaker-Menezes D, Chiavarina B, Flomenberg N, et al. The autophagic tumor stroma model of cancer: Role of oxidative stress and ketone production in fueling tumor cell metabolism. Cell Cycle 2010; 9:3485-505; PMID: 20861672; DOI: 10.4161/cc.9.17.12721.
5. Martinez-Outschoorn UE, Balliet RM, Rivadeneira DB, Chiavarina B, Pavlides S, Wang C, et al. Oxidative stress in cancer associated fibroblasts drives tumor-stroma co-evolution: A new paradigm for understanding tumor metabolism, the field effect and genomic instability in cancer cells. Cell Cycle 2010; 9:3256-76; PMID: 20814239; DOI: 10.4161/cc.9.16.12553.
6. Martinez-Outschoorn UE, Trimmer C, Lin Z, Whitaker-Menezes D, Chiavarina B, Zhou J, et al. Autophagy in cancer associated fibroblasts promotes tumor cell survival: Role of hypoxia, HIF1 induction and NFkappaB activation in the tumor stromal microenvironment. Cell Cycle 2010; 9:3515-33; PMID: 20855962; DOI: 10.4161/cc.9.17.12928.
7. Martinez-Outschoorn UE, Whitaker-Menezes D, Lin Z, Flomenberg N, Howell A, Pestell RG, et al. Cytokine production and inflammation drive autophagy in the tumor microenvironment: Role of stromal caveolin-1 as a key regulator. Cell Cycle 2011; 10:1784-93; PMID: 21566463.
8. Martinez-Outschoorn UE, Prisco M, Ertel A, Tsirigos A, Lin Z, Pavlides S, et al. Ketones and lactate increase cancer cell "stemness," driving recurrence, metastasis and poor clinical outcome in breast cancer: Achieving personalized medicine via Metabolo-Genomics. Cell Cycle 2011; 10:1271-86; PMID: 21512313; DOI: 10.4161/cc.10.8.15330.
9. Lisanti MP, Martinez-Outschoorn UE, Chiavarina B, Pavlides S, Whitaker-Menezes D, Tsirigos A, et al. Understanding the "lethal" drivers of tumor-stroma co-evolution: emerging role(s) for hypoxia, oxidative stress and autophagy/mitophagy in the tumor microenvironment. Cancer Biol Ther 2010; 10:537-42; PMID: 20861671; DOI: 10.4161/cbt.10.6.13370.
10. Martinez-Outschoorn UE, Pavlides S, Whitaker- Menezes D, Daumer KM, Milliman JN, Chiavarina B, et al. Tumor cells induce the cancer associated fibroblast phenotype via caveolin-1 degradation: Implications for breast cancer and DCIS therapy with autophagy inhibitors. Cell Cycle 2010; 9:2423-33; PMID: 20562526; DOI: 10.4161/cc.9.12.12048.
11. Martinez-Outschoorn UE, Pavlides S, Howell A, Pestell RG, Tanowitz HB, Sotgia F, Lisanti MP. Stromal-epithelial metabolic coupling in cancer: Integrating autophagy and metabolism in the tumor microenvironment. Int J Biochem Cell Biol 2011; 43:1045-51.
12. Gargini R, Garcia-Escudero V, Izquierdo M. Therapy mediated by mitophagy abrogates tumor progression. Autophagy 2011; 7; In press; PMID: 21270513; DOI: 10.4161/auto.7.5.14731.
13. Niethammer P, Grabher C, Look AT, Mitchison TJ. A tissue-scale gradient of hydrogen peroxide mediates rapid wound detection in zebrafish. Nature 2009; 459:996-9; PMID: 19494811; DOI: 10.1038/nature08119.
14. Cheng YM, Ho CL, Chiu NT, Hsu KF. Cesarean section scar mimicking uterine malignant neoplasm at positron emission tomography/computed tomography. J Minim Invasive Gynecol 2009; 16:372-4; PMID: 19423072; DOI: 10.1016/j.jmig.2009.02. 005.
15. Gorenberg M, Bar-Shalom R, Israel O. Patterns of FDG uptake in post-thoracotomy surgical scars in patients with lung cancer. Br J Radiol 2008; 81:821-5; PMID: 18796557; DOI: 10.1259/bjr/26210052.
16. Ozawa T, Okamura T, Harada T, Muraoka M, Ozawa N, Koyama K, et al. Accumulation of glucose in keloids with FDG-PET. Ann Nucl Med 2006; 20:41-4; PMID: 16485573; DOI: 10.1007/BF02985589.
17. 18F- fluorodeoxyglucose positron emission tomography. Clin Exp Rheumatol 2005; 23:231-4; PMID: 15895895.
18. Hofer C, Laubenbacher C, Block T, Breul J, Hartung R, Schwaiger M. Fluorine-18-fluorodeoxyglucose positron emission tomography is useless for the detection of local recurrence after radical prostatectomy. Eur Urol 1999; 36:31-5; PMID: 10364652; DOI: 10.1159/000019923.
19. Groves AM, Win T, Screaton NJ, Berovic M, Endozo R, Booth H, et al. Idiopathic pulmonary fibrosis and diffuse parenchymal lung disease: implications from initial experience with 18F-FDG PET/CT. J Nucl Med 2009; 50:538-45; PMID: 19289428; DOI: 10.2967/jnumed.108.057901.
20. Nishiyama Y, Yamamoto Y, Dobashi H, Kameda T. Clinical value of 18F-fluorodeoxyglucose positron emission tomography in patients with connective tissue disease. Jpn J Radiol 2010; 28:405-13; PMID: 20661690; DOI: 10.1007/s11604-010-0445-x.
21. Okabe T, Shibata H, Shizukuishi K, Yoneyama T, Inoue T, Tateishi U. F-18 FDG Uptake Patterns and Disease Activity of Collagen Vascular Diseases-Associated Arthritis. Clin Nucl Med 2011; 36:350-4; PMID: 21467850; DOI: 10.1097/RLU.0b013e318212c858.
22. Witkiewicz AK, Casimiro MC, Dasgupta A, Mercier I, Wang C, Bonuccelli G, et al. Towards a new "stromal-based"classification system for human breast cancer prognosis and therapy. Cell Cycle 2009; 8:1654-8; PMID: 19448435; DOI: 10.4161/cc.8.11.8544.
23. Witkiewicz AK, Dasgupta A, Nguyen KH, Liu C, Kovatich AJ, Schwartz GF, et al. Stromal caveolin-1 levels predict early DCIS progression to invasive breast cancer. Cancer Biol Ther 2009; 8:1071-9; PMID: 19502809; DOI: 10.4161/cbt.8.11.8874.
24. Witkiewicz AK, Dasgupta A, Sammons S, Er O, Potoczek MB, Guiles F, et al. Loss of stromal caveolin-1 expression predicts poor clinical outcome in triple negative and basal-like breast cancers. Cancer Biol Ther 2010; 10:135-43; PMID: 20431349; DOI: 10.4161/cbt.10.2.11983.
25. Witkiewicz AK, Dasgupta A, Sotgia F, Mercier I, Pestell RG, Sabel M, et al. An absence of stromal caveolin-1 expression predicts early tumor recurrence and poor clinical outcome in human breast cancers. Am J Pathol 2009; 174:2023-34; PMID: 19411448; DOI: 10.2353/ajpath.2009.080873.
26. Witkiewicz AK, Kline J, Queenan M, Brody JR, Tsirigos A, Bilal E, et al. Molecular profiling of a lethal tumor microenvironment, as defined by stromal caveolin-1 status in breast cancers. Cell Cycle 2011; 10:1794-809; PMID: 21521946.
27. Sloan EK, Ciocca DR, Pouliot N, Natoli A, Restall C, Henderson MA, et al. Stromal cell expression of caveolin-1 predicts outcome in breast cancer. Am J Pathol 2009; 174:2035-43; PMID: 19411449; DOI: 10.2353/ajpath.2009.080924.
28. Koo JS, Park S, Kim SI, Lee S, Park BW. The impact of caveolin protein expression in tumor stroma on prognosis of breast cancer. Tumour Biol 2011; 32:787-99; PMID: 21584795; DOI: 10.1007/s13277-011-0181-6.
29. Qian N, Ueno T, Kawaguchi-Sakita N, Kawashima M, Yoshida N, Mikami Y, et al. Prognostic significance of tumor/stromal caveolin-1 expression in breast cancer patients. Cancer Sci 2011; In press; PMID: 21585620; DOI: 10.1111/j.1349-7006.2011.01985.x.
30. Ghajar CM, Meier R, Bissell MJ. Quis custodiet ipsos custodies: who watches the watchmen? Am J Pathol 2009; 174:1996-9; PMID: 19465642; DOI: 10.2353/ajpath.2009.090363.
31. Volonte D, Galbiati F. Caveolin-1, cellular senescence and pulmonary emphysema. Aging (Albany NY) 2009; 1:831-5; PMID: 20157570.
32. Sáinz-Jaspeado M, Martin-Liberal J, Lagares-Tena L, Mateo-Lozano S, Garcia Del Muro X, Tirado OM. Caveolin-1 in sarcomas: friend or foe? Oncotarget 2011; 2:305-12; PMID: 21471610.
33. Darnell JE Jr. STAT3, HIF-1, glucose addiction and Warburg effect. Aging (Albany NY) 2010; 2:890-1; PMID: 21149895.
34. Whitaker-Menezes D, Martinez-Outschoorn UE, Lin Z, Ertel A, Flomenberg N, Witkiewicz AK, et al. Evidence for a stromal-epithelial "lactate shuttle"in human tumors: MCT4 is a marker of oxidative stress in cancer-associated fibroblasts. Cell Cycle 2011; 10:1772-83; PMID: 21558814.
35. Szatrowski TP, Nathan CF. Production of large amounts of hydrogen peroxide by human tumor cells. Cancer Res 1991; 51:794-8; PMID: 1846317.
36. Burdon RH. Superoxide and hydrogen peroxide in relation to mammalian cell proliferation. Free Radic Biol Med 1995; 18:775-94; PMID: 7750801; DOI: 10.1016/0891-5849(94)00198-S.
37. Feng Y, Santoriello C, Mione M, Hurlstone A, Martin P. Live imaging of innate immune cell sensing of transformed cells in zebrafish larvae: parallels between tumor initiation and wound inflammation. PLoS Biol 2010; 8:1000562; PMID: 21179501; DOI: 10.1371/journal.pbio.1000562.
38. Ubezio P, Civoli F. Flow cytometric detection of hydrogen peroxide production induced by doxorubicin in cancer cells. Free Radic Biol Med 1994; 16:509-16; PMID: 8005536; DOI: 10.1016/0891-5849(94)90129-5.
39. Trimmer C, Sotgia F, Whitaker-Menezes D, Balliet RM, Eaton G, Martinez-Outschoorn UE, et al. Caveolin-1 and mitochondrial SOD2 (MnSOD) function as tumor suppressors in the stromal microenvironment: a new genetically tractable model for human cancer associated fibroblasts. Cancer Biol Ther 2011; 11:383-94; PMID: 21150282; DOI: 10.4161/cbt.11.4.14101.
40. Martinez-Outschoorn UE, Whitaker-Menezes D, Pavlides S, Chiavarina B, Bonuccelli G, Casey T, et al. The Autophagic Tumor Stroma Model of Cancer or "Battery-Operated Tumor Growth": A Simple Solution to the Autophagy Paradox. Cell Cycle 2010; 9:4297-306; PMID: 21051947; DOI: 10.4161/cc.9.21. 13817.
41. Martin OA, Redon CE, Dickey JS, Nakamura AJ, Bonner WM. Para-inflammation mediates systemic DNA damage in response to tumor growth. Commun Integr Biol 2011; 4:78-81; PMID: 21509186.
42. Redon CE, Dickey JS, Nakamura AJ, Kareva IG, Naf D, Nowsheen S, et al. Tumors induce complex DNA damage in distant proliferative tissues in vivo. Proc Natl Acad Sci USA 2010; 107:17992-7; PMID: 20855610; DOI: 10.1073/pnas. 1008260107.
43. Hyoudou K, Nishikawa M, Ikemura M, Kobayashi Y, Mendelsohn A, Miyazaki N, et al. Prevention of pulmonary metastasis from subcutaneous tumors by binary system-based sustained delivery of catalase. J Control Release 2009; 137:110-5; PMID: 19361547; DOI: 10.1016/j.jconrel.2009.04.005.
44. Hyoudou K, Nishikawa M, Kobayashi Y, Umeyama Y, Yamashita F, Hashida M. PEGylated catalase prevents metastatic tumor growth aggravated by tumor removal. Free Radic Biol Med 2006; 41:1449-58; PMID: 17023272; DOI: 10.1016/j. freeradbiomed.2006.08.004.
45. Nishikawa M. Reactive oxygen species in tumor metastasis. Cancer Lett 2008; 266:53-9; PMID: 18362051; DOI: 10.1016/j.canlet.2008.02.031.
46. Nishikawa M, Hashida M. Inhibition of tumour metastasis by targeted delivery of antioxidant enzymes. Expert Opin Drug Deliv 2006; 3:355-69; PMID: 16640496; DOI: 10.1517/17425247.3.3.355.
47. Nishikawa M, Hashida M, Takakura Y. Catalase delivery for inhibiting ROS-mediated tissue injury and tumor metastasis. Adv Drug Deliv Rev 2009; 61:319-26; PMID: 19385054; DOI: 10.1016/j.addr.2009.01.001.
48. Nishikawa M, Tamada A, Hyoudou K, Umeyama Y, Takahashi Y, Kobayashi Y, et al. Inhibition of experimental hepatic metastasis by targeted delivery of catalase in mice. Clin Exp Metastasis 2004; 21:213-21; PMID: 15387371; DOI: 10.1023/B:CLIN.0000037706.13747.5e.
49. Nishikawa M, Tamada A, Kumai H, Yamashita F, Hashida M. Inhibition of experimental pulmonary metastasis by controlling biodistribution of catalase in mice. Int J Cancer 2002; 99:474-9; PMID: 11992420; DOI: 10.1002/ijc.10387.
50. Goh J, Enns L, Fatemie S, Hopkins H, Morton J, Pettan-Brewer C, et al. Mitochondrial targeted catalase suppresses invasive breast cancer in mice. BMC Cancer 2011; 11:191; PMID: 21605372; DOI: 10.1186/1471-2407-11-191.
51. Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M, et al. Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 2005; 308:1909-11; PMID: 15879174; DOI: 10.1126/science.1106653.
52. Sotgia F, Martinez-Outschoorn UE, Lisanti MP. Mitochondrial Oxidative Stress Drives Tumor Progression and Metastasis: Should We Use Antioxidants As A Key Component of Cancer Treatment and Prevention? BMC Med 2011; 9:62; PMID: 21605374; DOI: 10.1186/1741-7015-9-62.
53. Ahn J, Gammon MD, Santella RM, Gaudet MM, Britton JA, Teitelbaum SL, et al. Associations between breast cancer risk and the catalase genotype, fruit and vegetable consumption and supplement use. Am J Epidemiol 2005; 162:943-52; PMID: 16192345; DOI: 10.1093/aje/kwi306.
54. Nechuta S, Lu W, Chen Z, Zheng Y, Gu K, Cai H, et al. Vitamin supplement use during breast cancer treatment and survival: a prospective cohort study. Cancer Epidemiol Biomarkers Prev 2011; 20:262-71; PMID: 21177425; DOI: 10.1158/1055-9965.EPI-10-1072.
55. Trimmer C, Sotgia F, Whitaker-Menezes D, Balliet R, Eaton G, Martinez-Outschoorn UE, et al. Caveolin-1 and mitochondrial SOD2 (MnSOD) function as tumor suppressors in the stromal microenvironment: A new genetically tractable model for human cancer associated fibroblasts. Cancer Biol Ther 2011; 11:383-94; PMID: 21150282; DOI: 10.4161/cbt.11.4.14101.
56. Ishii K, Zhen LX, Wang DH, Funamori Y, Ogawa K, Taketa K. Prevention of mammary tumorigenesis in acatalasemic mice by vitamin E supplementation. Jpn J Cancer Res 1996; 87:680-4; PMID: 8698615.
57. Kobayashi M, Sugiyama H, Wang DH, Toda N, Maeshima Y, Yamasaki Y, et al. Catalase deficiency renders remnant kidneys more susceptible to oxidant tissue injury and renal fibrosis in mice. Kidney Int 2005; 68:1018-31; PMID: 16105032; DOI: 10.1111/j.1523-755.2005.00494.x.
58. Sunami R, Sugiyama H, Wang DH, Kobayashi M, Maeshima Y, Yamasaki Y, et al. Acatalasemia sensitizes renal tubular epithelial cells to apoptosis and exacerbates renal fibrosis after unilateral ureteral obstruction. Am J Physiol Renal Physiol 2004; 286:1030-8; PMID: 14722014; DOI: 10.1152/ajprenal.00266. 2003.
59. Fukuoka N, Sugiyama H, Inoue T, Kikumoto Y, Takiue K, Morinaga H, et al. Increased susceptibility to oxidant-mediated tissue injury and peritoneal fibrosis in acatalasemic mice. Am J Nephrol 2008; 28:661-8; PMID: 18337633; DOI: 10.1159/000121357.
60. Odajima N, Betsuyaku T, Nagai K, Moriyama C, Wang DH, Takigawa T, et al. The role of catalase in pulmonary fibrosis. Respir Res 2010; 11:183; PMID: 21190578; DOI: 10.1186/1465-9921-11-183.
61. Murthy S, Adamcakova-Dodd A, Perry SS, Tephly LA, Keller RM, Metwali N, et al. Modulation of reactive oxygen species by Rac1 or catalase prevents asbestos-induced pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 2009; 297:846-55; PMID: 19684199; DOI: 10.1152/ajplung.90590.2008.
62. Brezniceanu ML, Liu F, Wei CC, Chenier I, Godin N, Zhang SL, et al. Attenuation of interstitial fibrosis and tubular apoptosis in db/db transgenic mice overexpressing catalase in renal proximal tubular cells. Diabetes 2008; 57:451-9; PMID: 17977949; DOI: 10.2337/db07-0013.
63. Maksimenko AV, Bezrukavnikova LM, Grigor'eva EL, Tishchenko EG, Arkhipova OG, Iaglov VV, et al. [Antifibrosis effect of modified forms of catalase and superoxide dismutase in experimental silicosis]. Vopr Med Khim 1992; 38:4-8; PMID: 1384235.
64. Cantin AM, Larivee P, Begin RO. Extracellular glutathione suppresses human lung fibroblast proliferation. Am J Respir Cell Mol Biol 1990; 3:79-85; PMID: 2363938.
65. Fang HL, Lai JT, Lin WC. Inhibitory effect of olive oil on fibrosis induced by carbon tetrachloride in rat liver. Clin Nutr 2008; 27:900-7; PMID: 18824281; DOI: 10.1016/j.clnu.2008.08.004.
66. Yildiz H, Durmus AS, Simsek H, Yaman I. The comparison of methylene blue and vitamin E in prevention of abdominal postoperative adhesion formation in rat uterine horn models: Biochemical and histopathologic evaluation. Acta Cir Bras 2011; 26:51-7; PMID: 21271204.
67. Waghray M, Cui Z, Horowitz JC, Subramanian IM, Martinez FJ, Toews GB, et al. Hydrogen peroxide is a diffusible paracrine signal for the induction of epithelial cell death by activated myofibroblasts. FASEB J 2005; 19:854-6; PMID: 15857893.
68. Kasapovic J, Pejic S, Todorovic A, Stojiljkovic V, Pajovic SB. Antioxidant status and lipid peroxidation in the blood of breast cancer patients of different ages. Cell Biochem Funct 2008; 26:723-30; PMID: 18636415; DOI: 10.1002/cbf.1499.
69. Kasapovic J, Pejic S, Stojiljkovic V, Todorovic A, Radosevic-Jelic L, Saicic ZS, et al. Antioxidant status and lipid peroxidation in the blood of breast cancer patients of different ages after chemotherapy with 5-fluorouracil, doxorubicin and cyclophosphamide. Clin Biochem 2010; 43:1287-93; PMID: 20713039; DOI: 10.1016/j.clinbiochem.2010.08.009.
70. Kumaraguruparan R, Subapriya R, Kabalimoorthy J, Nagini S. Antioxidant profile in the circulation of patients with fibroadenoma and adenocarcinoma of the breast. Clin Biochem 2002; 35:275-9; PMID: 12135688; DOI: 10.1016/S0009-9120(02)00310-7.
71. Dilley TK, Bowden GT, Chen QM. Novel mechanisms of sublethal oxidant toxicity: induction of premature senescence in human fibroblasts confers tumor promoter activity. Exp Cell Res 2003; 290:38-48; PMID: 14516786; DOI: 10.1016/S0014-4827(03)00308-2.
72. Fukino K, Shen L, Patocs A, Mutter GL, Eng C. Genomic instability within tumor stroma and clinicopathological characteristics of sporadic primary invasive breast carcinoma. JAMA 2007; 297:2103-11; PMID: 17507346; DOI: 10.1001/jama.297.19.2103.
73. Weber F, Shen L, Fukino K, Patocs A, Mutter GL, Caldes T, et al. Total-genome analysis of BRCA1/2-related invasive carcinomas of the breast identifies tumor stroma as potential landscaper for neoplastic initiation. Am J Hum Genet 2006; 78:961-72; PMID: 16685647; DOI: 10.1086/504090.
74. Weber F, Xu Y, Zhang L, Patocs A, Shen L, Platzer P, et al. Microenvironmental genomic alterations and clinicopathological behavior in head and neck squamous cell carcinoma. JAMA 2007; 297:187-95; PMID: 17213402; DOI: 10.1001/jama.297.2.187.
75. Magistretti PJ. Neuron-glia metabolic coupling and plasticity. J Exp Biol 2006; 209:2304-11; PMID: 16731806; DOI: 10.1242/jeb.02208.
76. Magistretti PJ. Role of glutamate in neuronglia metabolic coupling. Am J Clin Nutr 2009; 90:875-80; PMID: 19571222; DOI: 10.3945/ajcn.2009.27462CC.
77. 18F-2-deoxyglucose signal in PET activation studies. Mol Psychiatry 1996; 1:445-52; PMID: 9154245.
78. Gotthardt M, Bleeker-Rovers CP, Boerman OC, Oyen WJ. Imaging of inflammation by PET, conventional scintigraphy, and other imaging techniques. J Nucl Med 2010; 51:1937-49; PMID: 21078798; DOI: 10.2967/jnumed.110.076232.
79. Kubota K, Nakamoto Y, Tamaki N, Kanegae K, Fukuda H, Kaneda T, et al. FDG-PET for the diagnosis of fever of unknown origin: a Japanese multi-center study. Ann Nucl Med 2011; 25:355-64.
80. Vos FJ, Bleeker-Rovers CP, Sturm PD, Krabbe PF, van Dijk AP, Cuijpers ML, et al. 18F-FDG PET/CT for detection of metastatic infection in gram-positive bacteremia. J Nucl Med 2010; 51:1234-40; PMID: 20660384; DOI: 10.2967/jnumed.109.072371.
81. Glaudemans AW, Signore A. FDG-PET/CT in infections: the imaging method of choice? Eur J Nucl Med Mol Imaging 2010; 37:1986-91; PMID: 20700737; DOI: 10.1007/s00259-010-1587-x.
82. Tsuji AB, Morita M, Li XK, Sogawa C, Sudo H, Sugyo A, et al. 18F-FDG PET for semiquantitative evaluation of acute allograft rejection and immunosuppressive therapy efficacy in rat models of liver transplantation. J Nucl Med 2009; 50:827-30; PMID: 19372488; DOI: 10.2967/jnumed.108.058925.
83. Reuter S, Schnockel U, Edemir B, Schroter R, Kentrup D, Pavenstadt H, et al. Potential of noninvasive serial assessment of acute renal allograft rejection by 18F-FDG PET to monitor treatment efficiency. J Nucl Med 2010; 51:1644-52; PMID: 20847180; DOI: 10.2967/jnumed.110.078550.
84. Reuter S, Schnockel U, Schroter R, Schober O, Pavenstadt H, Schafers M, et al. Non-invasive imaging of acute renal allograft rejection in rats using small animal F-FDG-PET. PLoS ONE 2009; 4:5296; PMID: 19390685; DOI: 10.1371/journal.pone.0005296.
85. 18F-fluoride small animal PET to noninvasively assess renal function in rats. Eur J Nucl Med Mol Imaging 2008; 35:2267-74; PMID: 18622612; DOI: 10.1007/s00259-008-0878-y.
86. Pierce BL, Ballard-Barbash R, Bernstein L, Baumgartner RN, Neuhouser ML, Wener MH, et al. Elevated biomarkers of inflammation are associated with reduced survival among breast cancer patients. J Clin Oncol 2009; 27:3437-44; PMID: 19470939; DOI: 10.1200/JCO.2008.18.9068.
87. Mankoff DA, Dunnwald LK, Gralow JR, Ellis GK, Charlop A, Lawton TJ, et al. Blood flow and metabolism in locally advanced breast cancer: relationship to response to therapy. J Nucl Med 2002; 43:500-9; PMID: 11937594.
88. Specht JM, Kurland BF, Montgomery SK, Dunnwald LK, Doot RK, Gralow JR, et al. Tumor metabolism and blood flow as assessed by positron emission tomography varies by tumor subtype in locally advanced breast cancer. Clin Cancer Res 2010; 16:2803-10; PMID: 20460489; DOI: 10.1158/1078-0432.CCR-10-0026.
89. Dunnwald LK, Gralow JR, Ellis GK, Livingston RB, Linden HM, Specht JM, et al. Tumor metabolism and blood flow changes by positron emission tomography: relation to survival in patients treated with neoadjuvant chemotherapy for locally advanced breast cancer. J Clin Oncol 2008; 26:4449-57; PMID: 18626006; DOI: 10.1200/JCO.2007.15.4385.
90. Mankoff DA, Eary JF, Link JM, Muzi M, Rajendran JG, Spence AM, et al. Tumor-specific positron emission tomography imaging in patients: [18F] fluorodeoxyglucose and beyond. Clin Cancer Res 2007; 13:3460-9; PMID: 17575208; DOI: 10.1158/1078-0432.CCR-07-0074.
91. Juweid ME, Stroobants S, Hoekstra OS, Mottaghy FM, Dietlein M, Guermazi A, et al. Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma. J Clin Oncol 2007; 25:571-8; PMID: 17242397; DOI: 10.1200/JCO.2006.08.2305.
92. Ambrosone CB, Abrams SM, Gorlewska-Roberts K, Kadlubar FF. Hair dye use, meat intake and tobacco exposure and presence of carcinogen-DNA adducts in exfoliated breast ductal epithelial cells. Arch Biochem Biophys 2007; 464:169-75; PMID: 17601487; DOI: 10.1016/j.abb.2007.05.018.
93. Kinae N, Masuda H, Shin IS, Furugori M, Shimoi K. Functional properties of wasabi and horseradish. Biofactors 2000; 13:265-9; PMID: 11237192; DOI: 10.1002/biof.5520130140.
94. Merliss RR. Talc-treated rice and Japanese stomach cancer. Science 1971; 173:1141-2; PMID: 5098957; DOI: 10.1126/science.173.4002.1141.
95. Khan N, Afaq F, Mukhtar H. Cancer chemoprevention through dietary antioxidants: progress and promise. Antioxid Redox Signal 2008; 10:475-510; PMID: 18154485; DOI: 10.1089/ars.2007.1740.
96. López-Lázaro M. Dual role of hydrogen peroxide in cancer: possible relevance to cancer chemoprevention and therapy. Cancer Lett 2007; 252:1-8; PMID: 17150302; DOI: 10.1016/j.canlet.2006.10.029.
97. 2from living cancer cells based on ZnO nanosheets. Anal Chim Acta 2010; 670:57-62; PMID: 20685417; DOI: 10.1016/j.aca.2010.04.065.
98. Van de Bittner GC, Dubikovskaya EA, Bertozzi CR, Chang CJ. In vivo imaging of hydrogen peroxide production in a murine tumor model with a chemoselective bioluminescent reporter. Proc Natl Acad Sci USA 2010; 107:21316-21; PMID: 21115844; DOI: 10.1073/pnas.1012864107.
99. 2level in exhaled breath condensate in primary breast cancer patients. J Cancer Res Clin Oncol 2010; 136:923-30; PMID: 19967414; DOI: 10.1007/s00432-009-0734-x.
100. Chan HP, Tran V, Lewis C, Thomas PS. Elevated levels of oxidative stress markers in exhaled breath condensate. J Thorac Oncol 2009; 4:172-8; PMID: 19179892; DOI: 10.1097/JTO.0b013e3181949eb9.
101. Chan HP, Lewis C, Thomas PS. Exhaled breath analysis: novel approach for early detection of lung cancer. Lung Cancer 2009; 63:164-8; PMID: 18599152; DOI: 10.1016/j.lungcan.2008.05.020.
102. Psathakis K, Mermigkis D, Papatheodorou G, Loukides S, Panagou P, Polychronopoulos V, et al. Exhaled markers of oxidative stress in idiopathic pulmonary fibrosis. Eur J Clin Invest 2006; 36:362-7; PMID: 16634841; DOI: 10.1111/j.1365-2362.2006.01636.x.
103. Kobayashi Y, Nishikawa M, Hyoudou K, Yamashita F, Hashida M. Hydrogen peroxide-mediated nuclear factor kappaB activation in both liver and tumor cells during initial stages of hepatic metastasis. Cancer Sci 2008; 99:1546-52; PMID: 18754865; DOI: 10.1111/j.1349-7006.2008.00856.x.