The Disrupted Steady-State: Tipping the Balance in Favour of Cancer

Chapter

Abstract

Genetic changes, such as the activation of oncogenes or the repression of tumour suppressors, contribute to the development of cancer, imparting malignant cells with the potential for self-promoting growth and survival in the presence of anti-growth or pro-apoptotic signals. However, while these changes may initiate the process of cancer development, they are not necessarily sufficient for disease progression, given the body’s intrinsic ability to regain homeostasis. Cancer initiation, promotion, and eventual progression depend on disruptions in normal homeostasis, as well as subsidiary processes imparted by cells of the tumour microenvironment. Recurring players that have been linked with disrupted homeostasis include inflammation and oxidative stress, which have both been strongly associated with the development of cancer. This chapter discusses the intricate relationship between the body and cancer, and how disruptions in normal physiological processes impact the maintenance of homeostasis and tissue repair, providing a framework for understanding the connection between dysregulated homeostatis and a complex disease such as cancer.

Keywords

Homeostasis Allostasis Cancer initiation Hallmarks of cancer Inflammation Oxidative stress 

References

  1. 1.
    Le Moal M. Historical approach and evolution of the stress concept: a personal account. Psychoneuroendocrinology. 2007;32(Suppl 1):S3–9 (Epub 2007/07/31).PubMedCrossRefGoogle Scholar
  2. 2.
    Clendening L. Sourcebook of medical history. New York: Dover Publications; 1942.Google Scholar
  3. 3.
    Goldstein DS, Kopin IJ. Evolution of concepts of stress. Stress. 2007;10(2):109–20 (Epub 2007/05/22).PubMedCrossRefGoogle Scholar
  4. 4.
    Buchman TG. The community of the self. Nature. 2002;420(6912):246–51 (Epub 2002/11/15).PubMedCrossRefGoogle Scholar
  5. 5.
    Dickmeis T, Weger BD, Weger M. The circadian clock and glucocorticoids–interactions across many time scales. Mol Cell Endocrinol. 2013;380(1–2):2–15 (Epub 2013/05/28).PubMedCrossRefGoogle Scholar
  6. 6.
    Streat SJ, Plank LD, Hill GL. Overview of modern management of patients with critical injury and severe sepsis. World J Surg. 2000;24(6):655–63 (Epub 2000/04/25).PubMedCrossRefGoogle Scholar
  7. 7.
    Foex BA. Systemic responses to trauma. Br Med Bull. 1999;55(4):726–43 (Epub 2000/04/04).PubMedCrossRefGoogle Scholar
  8. 8.
    Jaffer U, Wade RG, Gourlay T. Cytokines in the systemic inflammatory response syndrome: a review. HSR Proc Intensive Care Cardiovasc Anesth. 2010;2(3):161–75 (Epub 2010/01/01).PubMedCentralPubMedGoogle Scholar
  9. 9.
    Sterling P, Eyer J. Handbook of life stress, cognition, and health. In: Fisher S, Reason JT, editors. Chichester, New York: Wiley; 1988. p. xxxiii, 750 p.Google Scholar
  10. 10.
    McEwen BS, Wingfield JC. The concept of allostasis in biology and biomedicine. Horm Behav. 2003;43(1):2–15 (Epub 2003/03/05).PubMedCrossRefGoogle Scholar
  11. 11.
    Vannucci L, Stepankova R, Kozakova H, Fiserova A, Rossmann P, Tlaskalova-Hogenova H. Colorectal carcinogenesis in germ-free and conventionally reared rats: different intestinal environments affect the systemic immunity. Int J Oncol. 2008;32(3):609–17 (Epub 2008/02/23).PubMedGoogle Scholar
  12. 12.
    Yoshimoto S, Loo TM, Atarashi K, Kanda H, Sato S, Oyadomari S, et al. Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature. 2013;499(7456):97–101 (Epub 2013/06/28).PubMedCrossRefGoogle Scholar
  13. 13.
    Welsh JS. Contagious cancer. Oncologist. 2011;16(1):1–4 (Epub 2011/01/08).PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100(1):57–70 (Epub 2000/01/27).PubMedCrossRefGoogle Scholar
  15. 15.
    Lazebnik Y. What are the hallmarks of cancer? Nat Rev Cancer. 2010;10(4):232–3 (Epub 2010/04/01).PubMedCrossRefGoogle Scholar
  16. 16.
    Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74 (Epub 2011/03/08).PubMedCrossRefGoogle Scholar
  17. 17.
    Warburg O, Wind F, Negelein E. The metabolism of tumors in the body. J Gen Physiol. 1927;8(6):519–30 (Epub 1927/03/07).PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Targeting Tumour Metabolism. Nature reviews. Drug Discov. 2010;9(7):503–4 (Epub 2010/07/02).CrossRefGoogle Scholar
  19. 19.
    Polyak K, Haviv I, Campbell IG. Co-evolution of tumor cells and their microenvironment. Trends Genet TIG. 2009;25(1):30–8 (Epub 2008/12/05).PubMedCrossRefGoogle Scholar
  20. 20.
    Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet. 2001;357(9255):539–45 (Epub 2001/03/07).PubMedCrossRefGoogle Scholar
  21. 21.
    Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420(6917):860–7 (Epub 2002/12/20).PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Meylan E, Tschopp J, Karin M. Intracellular pattern recognition receptors in the host response. Nature. 2006;442(7098):39–44 (Epub 2006/07/11).PubMedCrossRefGoogle Scholar
  23. 23.
    de Visser KE, Eichten A, Coussens LM. Paradoxical roles of the immune system during cancer development. Nat Rev Cancer. 2006;6(1):24–37 (Epub 2006/01/07).PubMedCrossRefGoogle Scholar
  24. 24.
    Balkwill F, Charles KA, Mantovani A. Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell. 2005;7(3):211–7 (Epub 2005/03/16).PubMedCrossRefGoogle Scholar
  25. 25.
    de Visser KE, Coussens LM. The inflammatory tumor microenvironment and its impact on cancer development. Contrib Microbiol. 2006;13:118–37 (Epub 2006/04/22).PubMedCrossRefGoogle Scholar
  26. 26.
    Coussens LM, Werb Z. Inflammatory cells and cancer: think different! J Exp Med. 2001;193(6):F23–6 (Epub 2001/03/21).PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Osada T, Clay TM, Woo CY, Morse MA, Lyerly HK. Dendritic cell-based immunotherapy. Int Rev Immunol. 2006;25(5–6):377–413 (Epub 2006/12/16).PubMedCrossRefGoogle Scholar
  28. 28.
    Ghiringhelli F, Apetoh L, Housseau F, Kroemer G, Zitvogel L. Links between innate and cognate tumor immunity. Curr Opin Immunol. 2007;19(2):224–31 (Epub 2007/02/17).PubMedCrossRefGoogle Scholar
  29. 29.
    David H. Rudolf Virchow and modern aspects of tumor pathology. Pathol Res Pract. 1988;183(3):356–64 (Epub 1988/06/01).PubMedCrossRefGoogle Scholar
  30. 30.
    Krtolica A, Campisi J. Cancer and aging: a model for the cancer promoting effects of the aging stroma. Int J Biochem Cell Biol. 2002;34(11):1401–14 (Epub 2002/08/30).PubMedCrossRefGoogle Scholar
  31. 31.
    Parrinello S, Coppe JP, Krtolica A, Campisi J. Stromal-epithelial interactions in aging and cancer: senescent fibroblasts alter epithelial cell differentiation. J Cell Sci. 2005;118(Pt 3):485–96 (Epub 2005/01/20).PubMedCrossRefGoogle Scholar
  32. 32.
    Hu M, Yao J, Carroll DK, Weremowicz S, Chen H, Carrasco D, et al. Regulation of in situ to invasive breast carcinoma transition. Cancer Cell. 2008;13(5):394–406 (Epub 2008/05/06).PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Yoshimura A, Naka T, Kubo M. SOCS proteins, cytokine signalling and immune regulation. Nat Rev Immunol. 2007;7(6):454–65 (Epub 2007/05/26).PubMedCrossRefGoogle Scholar
  34. 34.
    Rakoff-Nahoum S. Why cancer and inflammation? Yale J Biol Med. 2006;79(3–4):123–30 (Epub 2007/10/18).PubMedCentralPubMedGoogle Scholar
  35. 35.
    Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB. Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal. 2014;20(7):1126–67 (Epub 2013/09/03).PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Federico A, Morgillo F, Tuccillo C, Ciardiello F, Loguercio C. Chronic inflammation and oxidative stress in human carcinogenesis. Int J Cancer J Int Du cancer. 2007;121(11):2381–6 (Epub 2007/09/26).CrossRefGoogle Scholar
  37. 37.
    O’Connell RM, Rao DS, Chaudhuri AA, Baltimore D. Physiological and pathological roles for microRNAs in the immune system. Nat Rev Immunol. 2010;10(2):111–22 (Epub 2010/01/26).PubMedCrossRefGoogle Scholar
  38. 38.
    Tili E, Croce CM, Michaille JJ. miR-155: on the crosstalk between inflammation and cancer. Int Rev Immunol. 2009;28(5):264–84 (Epub 2009/10/09).PubMedCrossRefGoogle Scholar
  39. 39.
    Tili E, Michaille JJ, Wernicke D, Alder H, Costinean S, Volinia S, et al. Mutator activity induced by microRNA-155 (miR-155) links inflammation and cancer. Proc Natl Acad Sci USA. 2011;108(12):4908–13 (Epub 2011/03/09).PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Veglia F, Cighetti G, De Franceschi M, Zingaro L, Boccotti L, Tremoli E, et al. Age- and gender-related oxidative status determined in healthy subjects by means of OXY-SCORE, a potential new comprehensive index. Biomarkers Biochem Ind Expo Response Susceptibility Chem. 2006;11(6):562–73 (Epub 2006/10/24).Google Scholar
  41. 41.
    Roth E, Manhart N, Wessner B. Assessing the antioxidative status in critically ill patients. Curr Opin Clin Nutr Metab Care. 2004;7(2):161–8 (Epub 2004/04/13).PubMedCrossRefGoogle Scholar
  42. 42.
    Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 2007;39(1):44–84 (Epub 2006/09/19).PubMedCrossRefGoogle Scholar
  43. 43.
    Eferl R, Wagner EF. AP-1: a double-edged sword in tumorigenesis. Nat Rev Cancer. 2003;3(11):859–68 (Epub 2003/12/12).PubMedCrossRefGoogle Scholar
  44. 44.
    Grivennikov SI, Karin M. Dangerous liaisons: STAT3 and NF-kappaB collaboration and crosstalk in cancer. Cytokine Growth Fact Rev. 2010;21(1):11–9 (Epub 2009/12/19).CrossRefGoogle Scholar
  45. 45.
    Klaus A, Birchmeier W. Wnt signalling and its impact on development and cancer. Nat Rev Cancer. 2008;8(5):387–98 (Epub 2008/04/25).PubMedCrossRefGoogle Scholar
  46. 46.
    Koh MY, Spivak-Kroizman TR, Powis G. HIF-1alpha and cancer therapy. Recent results in cancer research. Fortschritte der Krebsforschung Progres dans les recherches sur le cancer. 2010;180:15–34 (Epub 2009/12/25).PubMedGoogle Scholar
  47. 47.
    Gudkov AV, Gurova KV, Komarova EA. Inflammation and p53: a tale of two stresses. Genes Cancer. 2011;2(4):503–16 (Epub 2011/07/23).PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med. 2010;49(11):1603–16 (Epub 2010/09/16).PubMedCentralPubMedCrossRefGoogle Scholar
  49. 49.
    Vincent HK, Innes KE, Vincent KR. Oxidative stress and potential interventions to reduce oxidative stress in overweight and obesity. Diab Obes Metab. 2007;9(6):813–39 (Epub 2007/10/11).CrossRefGoogle Scholar
  50. 50.
    Dunn GP, Old LJ, Schreiber RD. The immunobiology of cancer immunosurveillance and immunoediting. Immunity. 2004;21(2):137–48 (Epub 2004/08/17).PubMedCrossRefGoogle Scholar
  51. 51.
    Boshoff C, Weiss R. AIDS-related malignancies. Nat Rev Cancer. 2002;2(5):373–82 (Epub 2002/06/05).PubMedCrossRefGoogle Scholar
  52. 52.
    Penn I. Posttransplant malignancies. Transpl Proc. 1999;31(1–2):1260–2 (Epub 1999/03/20).CrossRefGoogle Scholar
  53. 53.
    Euvrard S, Kanitakis J, Claudy A. Skin cancers after organ transplantation. N Engl J Med. 2003;348(17):1681–91 (Epub 2003/04/25).PubMedCrossRefGoogle Scholar
  54. 54.
    Pham SM, Kormos RL, Landreneau RJ, Kawai A, Gonzalez-Cancel I, Hardesty RL, et al. Solid tumors after heart transplantation: lethality of lung cancer. Ann Thoracic Surg. 1995;60(6):1623–6 (Epub 1995/12/01).CrossRefGoogle Scholar
  55. 55.
    Oluwole SF, Ali AO, Shafaee Z, DePaz HA. Breast cancer in women with HIV/AIDS: report of five cases with a review of the literature. J Surg Oncol. 2005;89(1):23–7 (Epub 2004/12/22).PubMedCrossRefGoogle Scholar
  56. 56.
    Stewart T, Tsai SC, Grayson H, Henderson R, Opelz G. Incidence of de-novo breast cancer in women chronically immuno suppressed after organ transplantation. Lancet. 1995;346(8978):796–8 (Epub 1995/09/23).PubMedCrossRefGoogle Scholar
  57. 57.
    Bishop JM. Viral oncogenes. Cell. 1985;42(1):23–38 (Epub 1985/08/01).PubMedCrossRefGoogle Scholar
  58. 58.
    Woolhouse M, Scott F, Hudson Z, Howey R, Chase-Topping M. Human viruses: discovery and emergence. Philos Trans R Soc Lond B Biol Sci. 2012;367(1604):2864–71 (Epub 2012/09/12).PubMedCentralPubMedCrossRefGoogle Scholar
  59. 59.
    Fontana JM, Alexander E, Salvatore M. Translational research in infectious disease: current paradigms and challenges ahead. Transl Res J Lab Clin Med. 2012;159(6):430–53 (Epub 2012/05/29).CrossRefGoogle Scholar
  60. 60.
    Williams SC. The other microbiome. Proc Natl Acad Sci USA. 2013;110(8):2682–4 (Epub 2013/02/08).PubMedCentralPubMedCrossRefGoogle Scholar
  61. 61.
    Wylie KM, Weinstock GM, Storch GA. Emerging view of the human virome. Trans Res J Lab Clin Med. 2012;160(4):283–90 (Epub 2012/06/12).CrossRefGoogle Scholar
  62. 62.
    Delwart E. A roadmap to the human virome. PLoS Pathog. 2013;9(2):e1003146 (Epub 2013/03/05).Google Scholar
  63. 63.
    Foxman EF, Iwasaki A. Genome-virome interactions: examining the role of common viral infections in complex disease. Nat Rev Microbiol. 2011;9(4):254–64 (Epub 2011/03/17).PubMedCentralPubMedCrossRefGoogle Scholar
  64. 64.
    Ault KA. Epidemiology and natural history of human papillomavirus infections in the female genital tract. Infect Dis Obstet Gynecol. 2006; Suppl:40470 (Epub 2006/09/14).Google Scholar
  65. 65.
    Mork J, Lie AK, Glattre E, Hallmans G, Jellum E, Koskela P, et al. Human papillomavirus infection as a risk factor for squamous-cell carcinoma of the head and neck. N Engl J Med. 2001;344(15):1125–31 (Epub 2001/04/12).PubMedCrossRefGoogle Scholar
  66. 66.
    Verteramo R, Pierangeli A, Mancini E, Calzolari E, Bucci M, Osborn J, et al. Human Papillomaviruses and genital co-infections in gynaecological outpatients. BMC Infect Dis. 2009;9:16 (Epub 2009/02/17).PubMedCentralPubMedCrossRefGoogle Scholar
  67. 67.
    Amon W, Farrell PJ. Reactivation of Epstein-Barr virus from latency. Rev Med Virol. 2005;15(3):149–56 (Epub 2004/11/17).PubMedCrossRefGoogle Scholar
  68. 68.
    Henle W, Henle G. Epidemiologic aspects of Epstein-Barr virus (EBV)-associated diseases. Ann NY Acad Sci. 1980;354:326–31 (Epub 1980/01/01).PubMedCrossRefGoogle Scholar
  69. 69.
    Gratama JW, Oosterveer MA, Zwaan FE, Lepoutre J, Klein G, Ernberg I. Eradication of Epstein-Barr virus by allogeneic bone marrow transplantation: implications for sites of viral latency. Proc Natl Acad Sci USA. 1988;85(22):8693–6 (Epub 1988/11/01).PubMedCentralPubMedCrossRefGoogle Scholar
  70. 70.
    Weiss LM, O’Malley D. Benign lymphadenopathies. Mod Pathol Off J US Can Acad Pathol Inc. 2013;26(Suppl 1):S88–96 (Epub 2013/01/04).Google Scholar
  71. 71.
    Toussirot E, Roudier J. Epstein-Barr virus in autoimmune diseases. Best Pract Res Clin Rheumatol. 2008;22(5):883–96 (Epub 2008/11/26).PubMedCrossRefGoogle Scholar
  72. 72.
    Thompson MP, Kurzrock R. Epstein-Barr virus and cancer. Clin Cancer Res Off J Am Assoc Cancer Res. 2004;10(3):803–21 (Epub 2004/02/12).CrossRefGoogle Scholar
  73. 73.
    Maeda E, Akahane M, Kiryu S, Kato N, Yoshikawa T, Hayashi N, et al. Spectrum of Epstein-Barr virus-related diseases: a pictorial review. Japan J Radiol. 2009;27(1):4–19 (Epub 2009/04/18).CrossRefGoogle Scholar
  74. 74.
    Epstein MA, Achong BG, Barr YM. Virus particles in cultured lymphoblasts from Burkitt’s lymphoma. Lancet. 1964;1(7335):702–3 (Epub 1964/03/28).PubMedCrossRefGoogle Scholar
  75. 75.
    Arvey A, Tempera I, Tsai K, Chen HS, Tikhmyanova N, Klichinsky M, et al. An atlas of the Epstein-Barr virus transcriptome and epigenome reveals host-virus regulatory interactions. Cell Host Microbe. 2012;12(2):233–45 (Epub 2012/08/21).PubMedCentralPubMedCrossRefGoogle Scholar
  76. 76.
    El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365(12):1118–27 (Epub 2011/10/14).PubMedCrossRefGoogle Scholar
  77. 77.
    El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132(7):2557–76 (Epub 2007/06/16).PubMedCrossRefGoogle Scholar
  78. 78.
    Schillie S, Murphy TV, Sawyer M, Ly K, Hughes E, Jiles R, et al. CDC guidance for evaluating health-care personnel for hepatitis B virus protection and for administering postexposure management. MMWR recommendations and reports: morbidity and mortality weekly report recommendations and reports/centers for disease control. 2013;62(RR-10):1–19 (Epub 2013/12/20).Google Scholar
  79. 79.
    Bonnet F, Lewden C, May T, Heripret L, Jougla E, Bevilacqua S, et al. Malignancy-related causes of death in human immunodeficiency virus-infected patients in the era of highly active antiretroviral therapy. Cancer. 2004;101(2):317–24 (Epub 2004/07/09).PubMedCrossRefGoogle Scholar
  80. 80.
    Cote TR, Biggar RJ, Rosenberg PS, Devesa SS, Percy C, Yellin FJ, et al. Non-Hodgkin’s lymphoma among people with AIDS: incidence, presentation and public health burden. AIDS/Cancer Study Group. Int J Cancer J Int Du Cancer. 1997;73(5):645–50 (Epub 1997/12/16).Google Scholar
  81. 81.
    Lanoy E, Dores GM, Madeleine MM, Toro JR, Fraumeni JF Jr, Engels EA. Epidemiology of nonkeratinocytic skin cancers among persons with AIDS in the United States. AIDS. 2009;23(3):385–93 (Epub 2008/12/31).PubMedCentralPubMedCrossRefGoogle Scholar
  82. 82.
    Sahasrabuddhe VV, Shiels MS, McGlynn KA, Engels EA. The risk of hepatocellular carcinoma among individuals with acquired immunodeficiency syndrome in the United States. Cancer. 2012;118(24):6226–33 (Epub 2012/06/28).PubMedCentralPubMedCrossRefGoogle Scholar
  83. 83.
    Engels EA, Atkinson JO, Graubard BI, McQuillan GM, Gamache C, Mbisa G, et al. Risk factors for human herpesvirus 8 infection among adults in the United States and evidence for sexual transmission. J Infect Dis. 2007;196(2):199–207 (Epub 2007/06/16).PubMedCrossRefGoogle Scholar
  84. 84.
    Qu L, Jenkins F, Triulzi DJ. Human herpesvirus 8 genomes and seroprevalence in United States blood donors. Transfusion. 2010;50(5):1050–6 (Epub 2010/01/22).PubMedCrossRefGoogle Scholar
  85. 85.
    Caskey MF, Morgan DJ, Porto AF, Giozza SP, Muniz AL, Orge GO, et al. Clinical manifestations associated with HTLV type I infection: a cross-sectional study. AIDS Res Hum Retroviruses. 2007;23(3):365–71 (Epub 2007/04/07).PubMedCentralPubMedCrossRefGoogle Scholar
  86. 86.
    Poiesz BJ, Papsidero LD, Ehrlich G, Sherman M, Dube S, Poiesz M, et al. Prevalence of HTLV-I-associated T-cell lymphoma. Am J Hematol. 2001;66(1):32–8 (Epub 2001/06/28).PubMedCrossRefGoogle Scholar
  87. 87.
    Feng H, Shuda M, Chang Y, Moore PS. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science. 2008;319(5866):1096–100 (Epub 2008/01/19).PubMedCentralPubMedCrossRefGoogle Scholar
  88. 88.
    Chen T, Hedman L, Mattila PS, Jartti T, Ruuskanen O, Soderlund-Venermo M, et al. Serological evidence of Merkel cell polyomavirus primary infections in childhood. J Clin Virol Off Publ Pan Am Soc Clin Virol. 2011;50(2):125–9 (Epub 2010/11/26).CrossRefGoogle Scholar
  89. 89.
    Bialasiewicz S, Lambert SB, Whiley DM, Nissen MD, Sloots TP. Merkel cell polyomavirus DNA in respiratory specimens from children and adults. Emerg Infect Dis. 2009;15(3):492–4 (Epub 2009/02/26).PubMedCentralPubMedCrossRefGoogle Scholar
  90. 90.
    Bichakjian CK, Lowe L, Lao CD, Sandler HM, Bradford CR, Johnson TM, et al. Merkel cell carcinoma: critical review with guidelines for multidisciplinary management. Cancer. 2007;110(1):1–12 (Epub 2007/05/24).PubMedCrossRefGoogle Scholar
  91. 91.
    Shuda M, Feng H, Kwun HJ, Rosen ST, Gjoerup O, Moore PS, et al. T antigen mutations are a human tumor-specific signature for Merkel cell polyomavirus. Proc Natl Acad Sci USA. 2008;105(42):16272–7 (Epub 2008/09/25).PubMedCentralPubMedCrossRefGoogle Scholar
  92. 92.
    Armstrong BK, Kricker A. The epidemiology of UV induced skin cancer. J Photochem Photobiol, B. 2001;63(1–3):8–18 (Epub 2001/10/31).CrossRefGoogle Scholar
  93. 93.
    Zur Hausen A. Merkel cell polyomavirus in the pathogenesis of non-melanoma skin cancer. Der Pathologe. 2009;30(Suppl 2):217–20. (Epub 2009/11/19). Das Merkel-Zell-Polyomavirus in der Pathogenese nichtmelanozytarer Hauttumoren.Google Scholar
  94. 94.
    Imajoh M, Hashida Y, Nemoto Y, Oguri H, Maeda N, Furihata M, et al. Detection of Merkel cell polyomavirus in cervical squamous cell carcinomas and adenocarcinomas from Japanese patients. Virol J. 2012;9:154 (Epub 2012/08/11).PubMedCentralPubMedCrossRefGoogle Scholar
  95. 95.
    Hourdequin KC, Lefferts JA, Brennick JB, Ernstoff MS, Tsongalis GJ, Pipas JM. Merkel cell polyomavirus and extrapulmonary small cell carcinoma. Oncol Lett. 2013;6(4):1049–52 (Epub 2013/10/19).PubMedCentralPubMedGoogle Scholar
  96. 96.
    Xu S, Jiang J, Yu X, Sheng D, Zhu T, Jin M. Association of Merkel cell polyomavirus infection with EGFR mutation status in Chinese non-small cell lung cancer patients. Lung Cancer. 2014;83(3):341–6 (Epub 2014/02/04).PubMedCrossRefGoogle Scholar
  97. 97.
    Butel JS. Simian virus 40, poliovirus vaccines, and human cancer: research progress versus media and public interests. Bull World Health Organ. 2000;78(2):195–8 (Epub 2000/04/01).PubMedCentralPubMedGoogle Scholar
  98. 98.
    Manfredi JJ, Dong J, Liu WJ, Resnick-Silverman L, Qiao R, Chahinian P, et al. Evidence against a role for SV40 in human mesothelioma. Cancer Res. 2005;65(7):2602–9 (Epub 2005/04/05).PubMedCrossRefGoogle Scholar
  99. 99.
    Eddy BE, Borman GS, Berkeley WH, Young RD. Tumors induced in hamsters by injection of rhesus monkey kidney cell extracts. Proc Soc Exp Biol Med. 1961;107:191–7 (Epub 1961/05/01).PubMedCrossRefGoogle Scholar
  100. 100.
    Eibl RH, Kleihues P, Jat PS, Wiestler OD. A model for primitive neuroectodermal tumors in transgenic neural transplants harboring the SV40 large T antigen. Am J Pathol. 1994;144(3):556–64 (Epub 1994/03/01).PubMedCentralPubMedGoogle Scholar
  101. 101.
    Sithithaworn P, Yongvanit P, Duenngai K, Kiatsopit N, Pairojkul C. Roles of liver fluke infection as risk factor for cholangiocarcinoma. J Hepato-Biliary-Pancreat Sci. 2014;21(5):301–8 (Epub 2014/01/11).CrossRefGoogle Scholar
  102. 102.
    Jenkins-Holick DS, Kaul TL. Schistosomiasis. Urol Nurs. 2013;33(4):163–70 (Epub 2013/10/02).PubMedGoogle Scholar
  103. 103.
    Porter SB, Sande MA. Toxoplasmosis of the central nervous system in the acquired immunodeficiency syndrome. N Engl J Med. 1992;327(23):1643–8 (Epub 1992/12/03).PubMedCrossRefGoogle Scholar
  104. 104.
    Thomas F, Lafferty KD, Brodeur J, Elguero E, Gauthier-Clerc M, Misse D. Incidence of adult brain cancers is higher in countries where the protozoan parasite Toxoplasma gondii is common. Biol Lett. 2012;8(1):101–3 (Epub 2011/07/29).PubMedCentralPubMedCrossRefGoogle Scholar
  105. 105.
    Vittecoq M, Elguero E, Lafferty KD, Roche B, Brodeur J, Gauthier-Clerc M, et al. Brain cancer mortality rates increase with Toxoplasma gondii seroprevalence in France. Inf Genet Evol J Mol Epidemiol Evol Genet Inf Dis. 2012;12(2):496–8 (Epub 2012/01/31).Google Scholar
  106. 106.
    Russell W. An address on a characteristic organism of cancer. Br Med J. 1890;2(1563):1356–60 (Epub 1890/12/13).PubMedCentralPubMedCrossRefGoogle Scholar
  107. 107.
    Marshall BJ, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet. 1984;1(8390):1311–5 (Epub 1984/06/16).PubMedCrossRefGoogle Scholar
  108. 108.
    Dumrese C, Slomianka L, Ziegler U, Choi SS, Kalia A, Fulurija A, et al. The secreted Helicobacter cysteine-rich protein A causes adherence of human monocytes and differentiation into a macrophage-like phenotype. FEBS Lett. 2009;583(10):1637–43 (Epub 2009/04/28).PubMedCentralPubMedCrossRefGoogle Scholar
  109. 109.
    Brown LM. Helicobacter pylori: epidemiology and routes of transmission. Epidemiol Rev. 2000;22(2):283–97 (Epub 2001/02/24).PubMedCrossRefGoogle Scholar
  110. 110.
    Talley NJ, Fock KM, Moayyedi P. Gastric cancer consensus conference recommends Helicobacter pylori screening and treatment in asymptomatic persons from high-risk populations to prevent gastric cancer. Am J Gastroenterol. 2008;103(3):510–4 (Epub 2008/03/18).PubMedCrossRefGoogle Scholar
  111. 111.
    Wu Q, Yang ZP, Xu P, Gao LC, Fan DM. Association between helicobacter pylori infection and the risk of colorectal neoplasia: a systematic review and meta-analysis. Colorectal Dis Off J Assoc Coloproctol Great Br Irel. 2013;15(7):e352–64 (Epub 2013/05/16).CrossRefGoogle Scholar
  112. 112.
    Anttila T, Saikku P, Koskela P, Bloigu A, Dillner J, Ikaheimo I, et al. Serotypes of Chlamydia trachomatis and risk for development of cervical squamous cell carcinoma. JAMA, J Am Med Assoc. 2001;285(1):47–51 (Epub 2001/01/10).CrossRefGoogle Scholar
  113. 113.
    Samoff E, Koumans EH, Markowitz LE, Sternberg M, Sawyer MK, Swan D, et al. Association of Chlamydia trachomatis with persistence of high-risk types of human papillomavirus in a cohort of female adolescents. Am J Epidemiol. 2005;162(7):668–75 (Epub 2005/08/27).PubMedCrossRefGoogle Scholar
  114. 114.
    Kostic AD, Chun E, Robertson L, Glickman JN, Gallini CA, Michaud M, et al. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe. 2013;14(2):207–15 (Epub 2013/08/21).PubMedCentralPubMedCrossRefGoogle Scholar
  115. 115.
    Rubinstein MR, Wang X, Liu W, Hao Y, Cai G, Han YW. Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/beta-catenin signaling via its FadA adhesin. Cell Host Microbe. 2013;14(2):195–206 (Epub 2013/08/21).PubMedCentralPubMedCrossRefGoogle Scholar
  116. 116.
    Anand PK, Kanneganti TD. NLRP6 in infection and inflammation. Microbe Inf Inst Pasteur. 2013;15(10–11):661–8 (Epub 2013/07/03).CrossRefGoogle Scholar
  117. 117.
    Liu XX, Li XJ, Zhang B, Liang YJ, Zhou CX, Cao DX, et al. MicroRNA-26b is underexpressed in human breast cancer and induces cell apoptosis by targeting SLC7A11. FEBS Lett. 2011;585(9):1363–7 (Epub 2011/04/23).PubMedCrossRefGoogle Scholar
  118. 118.
    Couturier-Maillard A, Secher T, Rehman A, Normand S, De Arcangelis A, Haesler R, et al. NOD2-mediated dysbiosis predisposes mice to transmissible colitis and colorectal cancer. J Clin Investig. 2013;123(2):700–11 (Epub 2013/01/03).PubMedCentralPubMedGoogle Scholar
  119. 119.
    Jin C, Flavell RA. Innate sensors of pathogen and stress: linking inflammation to obesity. J Allergy Clin Immunol. 2013;132(2):287–94 (Epub 2013/08/03).PubMedCrossRefGoogle Scholar
  120. 120.
    Minot S, Sinha R, Chen J, Li H, Keilbaugh SA, Wu GD, et al. The human gut virome: inter-individual variation and dynamic response to diet. Genome Res. 2011;21(10):1616–25 (Epub 2011/09/02).PubMedCentralPubMedCrossRefGoogle Scholar
  121. 121.
    Haslam DW, James WP. Obesity. Lancet. 2005;366(9492):1197–209 (Epub 2005/10/04).PubMedCrossRefGoogle Scholar
  122. 122.
    Pedersen BK. Muscle as a secretory organ. Comprehensive Physiology. 2013;3(3):1337–62 (Epub 2013/07/31).PubMedGoogle Scholar
  123. 123.
    Rogowski O, Shapira I, Bassat OK, Chundadze T, Finn T, Berliner S, et al. Waist circumference as the predominant contributor to the micro-inflammatory response in the metabolic syndrome: a cross sectional study. J Inflamm (Lond). 2010;7:35 (Epub 2010/07/28).CrossRefGoogle Scholar
  124. 124.
    Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab. 2004;89(6):2548–56 (Epub 2004/06/08).PubMedCrossRefGoogle Scholar
  125. 125.
    Bastard JP, Jardel C, Bruckert E, Blondy P, Capeau J, Laville M, et al. Elevated levels of interleukin 6 are reduced in serum and subcutaneous adipose tissue of obese women after weight loss. J Clin Endocrinol Metab. 2000;85(9):3338–42 (Epub 2000/09/22).PubMedGoogle Scholar
  126. 126.
    Esposito K, Nappo F, Marfella R, Giugliano G, Giugliano F, Ciotola M, et al. Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation. 2002;106(16):2067–72 (Epub 2002/10/16).PubMedCrossRefGoogle Scholar
  127. 127.
    Loffreda S, Yang SQ, Lin HZ, Karp CL, Brengman ML, Wang DJ, et al. Leptin regulates proinflammatory immune responses. FASEB J Off Pub Fed Am Soc Exp Biol. 1998;12(1):57–65 (Epub 1998/01/23).Google Scholar
  128. 128.
    Mohamed-Ali V, Flower L, Sethi J, Hotamisligil G, Gray R, Humphries SE, et al. beta-Adrenergic regulation of IL-6 release from adipose tissue: in vivo and in vitro studies. J Clin Endocrinol Metab. 2001;86(12):5864–9 (Epub 2001/12/12).PubMedGoogle Scholar
  129. 129.
    Mantzoros CS. The role of leptin in human obesity and disease: a review of current evidence. Ann Intern Med. 1999;130(8):671–80 (Epub 1999/04/24).PubMedCrossRefGoogle Scholar
  130. 130.
    Kao PC, Shiesh SC, Wu TJ. Serum C-reactive protein as a marker for wellness assessment. Ann Clin Lab Sci. 2006;36(2):163–9 (Epub 2006/05/10).PubMedGoogle Scholar
  131. 131.
    Emanuela F, Grazia M, de Marco R, Maria Paola L, Giorgio F, Marco B. Inflammation as a Link between obesity and metabolic syndrome. J Nutr Metab. 2012;2012:476380 (Epub 2012/04/24).PubMedCentralPubMedCrossRefGoogle Scholar
  132. 132.
    Mohamed-Ali V, Goodrick S, Rawesh A, Katz DR, Miles JM, Yudkin JS, et al. Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo. J Clin Endocrinol Metab. 1997;82(12):4196–200 (Epub 1997/12/17).PubMedGoogle Scholar
  133. 133.
    Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Investig. 2006;116(7):1793–801 (Epub 2006/07/11).PubMedCentralPubMedCrossRefGoogle Scholar
  134. 134.
    Blackburn P, Cote M, Lamarche B, Couillard C, Pascot A, Tremblay A, et al. Impact of postprandial variation in triglyceridemia on low-density lipoprotein particle size. Metab, Clin Exp. 2003;52(11):1379–86 (Epub 2003/11/19).CrossRefGoogle Scholar
  135. 135.
    van Dijk SJ, Feskens EJ, Bos MB, Hoelen DW, Heijligenberg R, Bromhaar MG, et al. A saturated fatty acid-rich diet induces an obesity-linked proinflammatory gene expression profile in adipose tissue of subjects at risk of metabolic syndrome. Am J Clin Nutr. 2009;90(6):1656–64 (Epub 2009/10/16).PubMedCrossRefGoogle Scholar
  136. 136.
    Clement K, Viguerie N, Poitou C, Carette C, Pelloux V, Curat CA, et al. Weight loss regulates inflammation-related genes in white adipose tissue of obese subjects. FASEB J Off Pub Fed Am Soc Exp Biol. 2004;18(14):1657–69 (Epub 2004/11/04).Google Scholar
  137. 137.
    Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Investig. 2003;112(12):1821–30 (Epub 2003/12/18).PubMedCentralPubMedCrossRefGoogle Scholar
  138. 138.
    Tabata M, Kadomatsu T, Fukuhara S, Miyata K, Ito Y, Endo M, et al. Angiopoietin-like protein 2 promotes chronic adipose tissue inflammation and obesity-related systemic insulin resistance. Cell Metab. 2009;10(3):178–88 (Epub 2009/09/03).PubMedCrossRefGoogle Scholar
  139. 139.
    Aoi J, Endo M, Kadomatsu T, Miyata K, Nakano M, Horiguchi H, et al. Angiopoietin-like protein 2 is an important facilitator of inflammatory carcinogenesis and metastasis. Cancer Res. 2011;71(24):7502–12 (Epub 2011/11/02).PubMedCrossRefGoogle Scholar
  140. 140.
    Aoi J, Endo M, Kadomatsu T, Miyata K, Ogata A, Horiguchi H, et al. Angiopoietin-like protein 2 accelerates carcinogenesis by activating chronic inflammation and oxidative stress. Mol Cancer Res Mcr. 2014;12(2):239–49 (Epub 2013/11/22).PubMedCrossRefGoogle Scholar
  141. 141.
    Glass AG, Lacey JV Jr, Carreon JD, Hoover RN. Breast cancer incidence, 1980–2006: combined roles of menopausal hormone therapy, screening mammography, and estrogen receptor status. J Natl Cancer Inst. 2007;99(15):1152–61 (Epub 2007/07/27).PubMedCrossRefGoogle Scholar
  142. 142.
    Cleary MP, Grossmann ME. Minireview: Obesity and breast cancer: the estrogen connection. Endocrinology. 2009;150(6):2537–42 (Epub 2009/04/18).PubMedCentralPubMedCrossRefGoogle Scholar
  143. 143.
    Reed MJ, Purohit A. Aromatase regulation and breast cancer. Clin Endocrinol. 2001;54(5):563–71 (Epub 2001/05/31).CrossRefGoogle Scholar
  144. 144.
    Jerry DJ. Roles for estrogen and progesterone in breast cancer prevention. Breast Cancer Res BCR. 2007;9(2):102 (Epub 2007/03/27).Google Scholar
  145. 145.
    Bhat HK, Calaf G, Hei TK, Loya T, Vadgama JV. Critical role of oxidative stress in estrogen-induced carcinogenesis. Proc Natl Acad Sci USA. 2003;100(7):3913–8 (Epub 2003/03/26).PubMedCentralPubMedCrossRefGoogle Scholar
  146. 146.
    Vegeto E, Ciana P, Maggi A. Estrogen and inflammation: hormone generous action spreads to the brain. Mol Psychiatry. 2002;7(3):236–8 (Epub 2002/03/29).PubMedCrossRefGoogle Scholar
  147. 147.
    Sifferlin A. Hormone-replacement therapy: could estrogen have saved 50,000 lives? Time [Internet] (2013).Google Scholar
  148. 148.
    Bath PM, Gray LJ. Association between hormone replacement therapy and subsequent stroke: a meta-analysis. BMJ. 2005;330(7487):342 (Epub 2005/01/11).Google Scholar
  149. 149.
    Carr MC. The emergence of the metabolic syndrome with menopause. J Clin Endocrinol Metab. 2003;88(6):2404–11 (Epub 2003/06/06).PubMedCrossRefGoogle Scholar
  150. 150.
    Rogers NH, Perfield JW 2nd, Strissel KJ, Obin MS, Greenberg AS. Reduced energy expenditure and increased inflammation are early events in the development of ovariectomy-induced obesity. Endocrinology. 2009;150(5):2161–8 (Epub 2009/01/31).PubMedCentralPubMedCrossRefGoogle Scholar
  151. 151.
    Wren BG. The benefits of oestrogen following menopause: why hormone replacement therapy should be offered to postmenopausal women. Med J Aust. 2009;190(6):321–5 (Epub 2009/03/20).PubMedGoogle Scholar
  152. 152.
    Heine PA, Taylor JA, Iwamoto GA, Lubahn DB, Cooke PS. Increased adipose tissue in male and female estrogen receptor-alpha knockout mice. Proc Natl Acad Sci USA. 2000;97(23):12729–34 (Epub 2000/11/09).PubMedCentralPubMedCrossRefGoogle Scholar
  153. 153.
    Okura T, Koda M, Ando F, Niino N, Ohta S, Shimokata H. Association of polymorphisms in the estrogen receptor alpha gene with body fat distribution. Int J Obes Relat Metab Disord J Int Assoc Study Obes. 2003;27(9):1020–7 (Epub 2003/08/15).CrossRefGoogle Scholar
  154. 154.
    Saha S, Sadhukhan P, Sil PC. Genistein: a phytoestrogen with multifaceted therapeutic properties. Mini Rev Med Chem. 2014 (Epub 2014/10/31).Google Scholar
  155. 155.
    Xu Y, Nedungadi TP, Zhu L, Sobhani N, Irani BG, Davis KE, et al. Distinct hypothalamic neurons mediate estrogenic effects on energy homeostasis and reproduction. Cell Metab. 2011;14(4):453–65 (Epub 2011/10/11).PubMedCentralPubMedCrossRefGoogle Scholar
  156. 156.
    Lee YS, Kim JW, Osborne O, da Oh Y, Sasik R, Schenk S, et al. Increased adipocyte O2 consumption triggers HIF-1alpha, causing inflammation and insulin resistance in obesity. Cell. 2014;157(6):1339–52 (Epub 2014/06/07).PubMedCentralPubMedCrossRefGoogle Scholar
  157. 157.
    Wood IS, de Heredia FP, Wang B, Trayhurn P. Cellular hypoxia and adipose tissue dysfunction in obesity. Proc Nutr Soc. 2009;68(4):370–7 (Epub 2009/08/25).PubMedCrossRefGoogle Scholar
  158. 158.
    Gillies RJ, Gatenby RA. Hypoxia and adaptive landscapes in the evolution of carcinogenesis. Cancer Metastasis Rev. 2007;26(2):311–7 (Epub 2007/04/04).PubMedCrossRefGoogle Scholar
  159. 159.
    Semenza GL. HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations. J Clin Investig. 2013;123(9):3664–71 (Epub 2013/09/04).PubMedCentralPubMedCrossRefGoogle Scholar
  160. 160.
    Olsen RH, Krogh-Madsen R, Thomsen C, Booth FW, Pedersen BK. Metabolic responses to reduced daily steps in healthy nonexercising men. JAMA, J Am Med Assoc. 2008;299(11):1261–3 (Epub 2008/03/20).CrossRefGoogle Scholar
  161. 161.
    Petersen AM, Pedersen BK. The anti-inflammatory effect of exercise. J Appl Physiol (1985). 2005;98(4):1154–62 (Epub 2005/03/18).Google Scholar
  162. 162.
    Handschin C, Spiegelman BM. The role of exercise and PGC1alpha in inflammation and chronic disease. Nature. 2008;454(7203):463–9 (Epub 2008/07/25).PubMedCentralPubMedCrossRefGoogle Scholar
  163. 163.
    Pedersen BK. The diseasome of physical inactivity—and the role of myokines in muscle–fat cross talk. J Physiol. 2009;587(Pt 23):5559–68 (Epub 2009/09/16).PubMedCentralPubMedCrossRefGoogle Scholar
  164. 164.
    Pedersen BK, Febbraio MA. Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol. 2012;8(8):457–65 (Epub 2012/04/05).PubMedCrossRefGoogle Scholar
  165. 165.
    Fischer CP. Interleukin-6 in acute exercise and training: what is the biological relevance? Exerc Immunol Rev. 2006;12:6–33 (Epub 2007/01/05).PubMedGoogle Scholar
  166. 166.
    Pedersen BK, Steensberg A, Fischer C, Keller C, Keller P, Plomgaard P, et al. Searching for the exercise factor: is IL-6 a candidate? J Muscle Res Cell Motil. 2003;24(2–3):113–9 (Epub 2003/11/12).PubMedCrossRefGoogle Scholar
  167. 167.
    Steensberg A, Fischer CP, Keller C, Moller K, Pedersen BK. IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans. Am J Physiol Endocrinol Metab. 2003;285(2):E433–7 (Epub 2003/07/15).PubMedCrossRefGoogle Scholar
  168. 168.
    Steinberg GR, Watt MJ, Febbraio MA. Cytokine regulation of AMPK signalling. Front Biosci (Landmark Ed). 2009;14:1902–16 (Epub 2009/03/11).CrossRefGoogle Scholar
  169. 169.
    Kelly M, Gauthier MS, Saha AK, Ruderman NB. Activation of AMP-activated protein kinase by interleukin-6 in rat skeletal muscle: association with changes in cAMP, energy state, and endogenous fuel mobilization. Diabetes. 2009;58(9):1953–60 (Epub 2009/06/09).PubMedCentralPubMedCrossRefGoogle Scholar
  170. 170.
    Carey AL, Steinberg GR, Macaulay SL, Thomas WG, Holmes AG, Ramm G, et al. Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase. Diabetes. 2006;55(10):2688–97 (Epub 2006/09/28).PubMedCrossRefGoogle Scholar
  171. 171.
    Bruce CR, Dyck DJ. Cytokine regulation of skeletal muscle fatty acid metabolism: effect of interleukin-6 and tumor necrosis factor-alpha. Am J Phys Endocrinol Metab. 2004;287(4):E616–21 (Epub 2004/05/20).CrossRefGoogle Scholar
  172. 172.
    van Hall G, Steensberg A, Sacchetti M, Fischer C, Keller C, Schjerling P, et al. Interleukin-6 stimulates lipolysis and fat oxidation in humans. J Clin Endocrinol Metab. 2003;88(7):3005–10 (Epub 2003/07/05).PubMedCrossRefGoogle Scholar
  173. 173.
    Wallenius V, Wallenius K, Ahren B, Rudling M, Carlsten H, Dickson SL, et al. Interleukin-6-deficient mice develop mature-onset obesity. Nat Med. 2002;8(1):75–9 (Epub 2002/01/12).PubMedCrossRefGoogle Scholar
  174. 174.
    Mizuhara H, O’Neill E, Seki N, Ogawa T, Kusunoki C, Otsuka K, et al. T cell activation-associated hepatic injury: mediation by tumor necrosis factors and protection by interleukin 6. J Exp Med. 1994;179(5):1529–37 (Epub 1994/05/01).PubMedCrossRefGoogle Scholar
  175. 175.
    Vigneri P, Frasca F, Sciacca L, Pandini G, Vigneri R. Diabetes and cancer. Endocr Relat Cancer. 2009;16(4):1103–23 (Epub 2009/07/22).PubMedCrossRefGoogle Scholar
  176. 176.
    Chen HF, Li CY, Chen P, See TT, Lee HY. Seroprevalence of hepatitis B and C in type 2 diabetic patients. J Chin Med Assoc JCMA. 2006;69(4):146–52 (Epub 2006/05/13).PubMedCrossRefGoogle Scholar
  177. 177.
    Davila JA, Morgan RO, Shaib Y, McGlynn KA, El-Serag HB. Diabetes increases the risk of hepatocellular carcinoma in the United States: a population based case control study. Gut. 2005;54(4):533–9 (Epub 2005/03/09).PubMedCentralPubMedCrossRefGoogle Scholar
  178. 178.
    Kaaks R. Nutrition, hormones, and breast cancer: is insulin the missing link? Cancer Causes Control CCC. 1996;7(6):605–25 (Epub 1996/11/01).PubMedCrossRefGoogle Scholar
  179. 179.
    Kaaks R, Lukanova A. Energy balance and cancer: the role of insulin and insulin-like growth factor-I. Proc Nutr Soc. 2001;60(1):91–106 (Epub 2001/04/20).PubMedCrossRefGoogle Scholar
  180. 180.
    Frasca F, Pandini G, Scalia P, Sciacca L, Mineo R, Costantino A, et al. Insulin receptor isoform A, a newly recognized, high-affinity insulin-like growth factor II receptor in fetal and cancer cells. Mol Cell Biol. 1999;19(5):3278–88 (Epub 1999/04/17).PubMedCentralPubMedCrossRefGoogle Scholar
  181. 181.
    Frasca F, Pandini G, Malaguarnera R, Mandarino A, Messina RL, Sciacca L, et al. Role of c-Abl in directing metabolic versus mitogenic effects in insulin receptor signaling. J Biol Chem. 2007;282(36):26077–88 (Epub 2007/07/11).PubMedCrossRefGoogle Scholar
  182. 182.
    Corbould A, Zhao H, Mirzoeva S, Aird F, Dunaif A. Enhanced mitogenic signaling in skeletal muscle of women with polycystic ovary syndrome. Diabetes. 2006;55(3):751–9 (Epub 2006/03/01).PubMedCrossRefGoogle Scholar
  183. 183.
    Evans JM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD. Metformin and reduced risk of cancer in diabetic patients. BMJ. 2005;330(7503):1304–5 (Epub 2005/04/26).PubMedCentralPubMedCrossRefGoogle Scholar
  184. 184.
    Luo Z, Saha AK, Xiang X, Ruderman NB. AMPK, the metabolic syndrome and cancer. Trends Pharmacol Sci. 2005;26(2):69–76 (Epub 2005/02/01).PubMedCrossRefGoogle Scholar
  185. 185.
    Alimova IN, Liu B, Fan Z, Edgerton SM, Dillon T, Lind SE, et al. Metformin inhibits breast cancer cell growth, colony formation and induces cell cycle arrest in vitro. Cell Cycle. 2009;8(6):909–15 (Epub 2009/02/18).PubMedCrossRefGoogle Scholar
  186. 186.
    Ruderman N, Prentki M. AMP kinase and malonyl-CoA: targets for therapy of the metabolic syndrome. Nat Rev Drug Discov. 2004;3(4):340–51 (Epub 2004/04/03).PubMedCrossRefGoogle Scholar
  187. 187.
    Stocks T, Van Hemelrijck M, Manjer J, Bjorge T, Ulmer H, Hallmans G, et al. Blood pressure and risk of cancer incidence and mortality in the metabolic syndrome and cancer project. Hypertension. 2012;59(4):802–10 (Epub 2012/02/23).PubMedCrossRefGoogle Scholar
  188. 188.
    Bonomini F, Tengattini S, Fabiano A, Bianchi R, Rezzani R. Atherosclerosis and oxidative stress. Histol Histopathol. 2008;23(3):381–90 (Epub 2007/12/12).PubMedGoogle Scholar
  189. 189.
    Baynes JW, Thorpe SR. Role of oxidative stress in diabetic complications: a new perspective on an old paradigm. Diabetes. 1999;48(1):1–9 (Epub 1999/01/19).PubMedCrossRefGoogle Scholar
  190. 190.
    Nashed MG, Balenko MD, Singh G. Cancer-induced oxidative stress and pain. Current Pain Headache Rep. 2014;18(1):384 (Epub 2013/12/03).Google Scholar
  191. 191.
    Yasunari K, Maeda K, Nakamura M, Yoshikawa J. Oxidative stress in leukocytes is a possible link between blood pressure, blood glucose, and C-reacting protein. Hypertension. 2002;39(3):777–80 (Epub 2002/03/19).PubMedCrossRefGoogle Scholar
  192. 192.
    Wang H, Li H, Hou Z, Pan L, Shen X, Li G. Role of oxidative stress in elevated blood pressure induced by high free fatty acids. Hypertens Res Off J Japan Soc Hypertens. 2009;32(2):152–8 (Epub 2009/03/06).CrossRefGoogle Scholar
  193. 193.
    Menendez JA, Vazquez-Martin A, Ortega FJ, Fernandez-Real JM. Fatty acid synthase: association with insulin resistance, type 2 diabetes, and cancer. Clin Chem. 2009;55(3):425–38 (Epub 2009/02/03).PubMedCrossRefGoogle Scholar
  194. 194.
    Claycombe KJ, Jones BH, Standridge MK, Guo Y, Chun JT, Taylor JW, et al. Insulin increases fatty acid synthase gene transcription in human adipocytes. Am J Physiol. 1998;274(5 Pt 2):R1253–9 (Epub 1998/06/27).PubMedGoogle Scholar
  195. 195.
    Caldwell S, Lazo M. Is exercise an effective treatment for NASH? Knowns and unknowns. Annals of hepatology. 2009;8(Suppl 1):S60–6 (Epub 2009/06/25).PubMedGoogle Scholar
  196. 196.
    Yudkin JS, Eringa E, Stehouwer CD. “Vasocrine” signalling from perivascular fat: a mechanism linking insulin resistance to vascular disease. Lancet. 2005;365(9473):1817–20 (Epub 2005/05/25).PubMedCrossRefGoogle Scholar
  197. 197.
    Matter CM, Handschin C. RANTES (regulated on activation, normal T cell expressed and secreted), inflammation, obesity, and the metabolic syndrome. Circulation. 2007;115(8):946–8 (Epub 2007/02/28).PubMedCrossRefGoogle Scholar
  198. 198.
    DePinho RA. The age of cancer. Nature. 2000;408(6809):248–54 (Epub 2000/11/23).PubMedCrossRefGoogle Scholar
  199. 199.
    Marusyk A, DeGregori J. Declining cellular fitness with age promotes cancer initiation by selecting for adaptive oncogenic mutations. Biochim Biophys Acta. 2008;1785(1):1–11 (Epub 2007/11/06).PubMedCentralPubMedGoogle Scholar
  200. 200.
    Collado M, Blasco MA, Serrano M. Cellular senescence in cancer and aging. Cell. 2007;130(2):223–33 (Epub 2007/07/31).PubMedCrossRefGoogle Scholar
  201. 201.
    Ishikawa F. Cellular senescence as a stress response. Cornea. 2006;25(10 Suppl 1):S3–6 (Epub 2006/09/27).PubMedCrossRefGoogle Scholar
  202. 202.
    Blagosklonny MV. Cell cycle arrest is not senescence. Aging. 2011;3(2):94–101 (Epub 2011/02/08).PubMedCentralPubMedGoogle Scholar
  203. 203.
    Campisi J, Andersen JK, Kapahi P, Melov S. Cellular senescence: a link between cancer and age-related degenerative disease? Semin Cancer Biol. 2011;21(6):354–9 (Epub 2011/09/20).PubMedCentralPubMedGoogle Scholar
  204. 204.
    Tsai KK, Chuang EY, Little JB, Yuan ZM. Cellular mechanisms for low-dose ionizing radiation-induced perturbation of the breast tissue microenvironment. Cancer Res. 2005;65(15):6734–44 (Epub 2005/08/03).PubMedCrossRefGoogle Scholar
  205. 205.
    Hasty P, Campisi J, Hoeijmakers J, van Steeg H, Vijg J. Aging and genome maintenance: lessons from the mouse? Science. 2003;299(5611):1355–9 (Epub 2003/03/01).PubMedCrossRefGoogle Scholar
  206. 206.
    Testa R, Ceriello A. Pathogenetic loop between diabetes and cell senescence. Diab Care. 2007;30(11):2974–5 (Epub 2007/10/30).CrossRefGoogle Scholar
  207. 207.
    Brodsky SV, Gealekman O, Chen J, Zhang F, Togashi N, Crabtree M, et al. Prevention and reversal of premature endothelial cell senescence and vasculopathy in obesity-induced diabetes by ebselen. Circ Res. 2004;94(3):377–84 (Epub 2003/12/13).PubMedCrossRefGoogle Scholar
  208. 208.
    Tez M. Cancer is an adaptation mechanism of the aged stem cell against stress. Rejuvenation Res. 2008;11(6):1059–60 (Epub 2008/12/17).PubMedCrossRefGoogle Scholar
  209. 209.
    Pekovic V, Hutchison CJ. Adult stem cell maintenance and tissue regeneration in the ageing context: the role for A-type lamins as intrinsic modulators of ageing in adult stem cells and their niches. J Anat. 2008;213(1):5–25 (Epub 2008/07/22).PubMedCentralPubMedCrossRefGoogle Scholar
  210. 210.
    Lagasse E. Cancer stem cells with genetic instability: the best vehicle with the best engine for cancer. Gene Ther. 2008;15(2):136–42 (Epub 2007/11/09).PubMedCrossRefGoogle Scholar
  211. 211.
    Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414(6859):105–11 (Epub 2001/11/02).PubMedCrossRefGoogle Scholar
  212. 212.
    Galhardo RS, Hastings PJ, Rosenberg SM. Mutation as a stress response and the regulation of evolvability. Crit Rev Biochem Mol Biol. 2007;42(5):399–435 (Epub 2007/10/06).PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of Pathology and Molecular MedicineMcMaster UniversityHamiltonCanada
  2. 2.Department of Pathology and Molecular MedicineMcMaster UniversityHamiltonCanada

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