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Inflammation and Colorectal Cancer

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Intestinal Tumorigenesis

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Abstract

Chronic intestinal Inflammation occurs in response to environmental factors, infection and genetics; and plays a critical role in initiation, promotion, progression and metastasis of colon cancer. Colitis associated colon cancer (CAC) is a classic example of multifactorial, multi-step colorectal cancer associated with inflammatory bowel diseases. In recent years, the generation of animal models of CAC and recognition of the importance of the gut microbiota, altered immune system, and other environmental factors in CAC, has expanded the basic understanding of inflammation associated colon cancer. In this chapter, we discuss the cellular alterations and mechanisms by which inflammation contributes towards the development of colon cancer using CAC as a model system. We have also explored some of the promising strategies for preventing progression of inflammation to colon cancer. The emerging role of dietary factors, obesity and gut microbiota in colon cancer is also reviewed.

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References

  1. Haggar FA, Boushey RP (2009) Colorectal cancer epidemiology: incidence, mortality, survival, and risk factors. Clin Colon Rectal Surg 22(4):191–197. doi:10.1055/s-0029-1242458

    Article  PubMed Central  PubMed  Google Scholar 

  2. Jiao S, Peters U, Berndt S, Brenner H, Butterbach K, Caan BJ, Carlson CS, Chan AT, Chang-Claude J, Chanock S, Curtis KR, Duggan D, Gong J, Harrison TA, Hayes RB, Henderson BE, Hoffmeister M, Kolonel LN, Marchand LL, Potter JD, Rudolph A, Schoen RE, Seminara D, Slattery ML, White E, Hsu L (2014) Estimating the heritability of colorectal cancer. Hum Mol Genet. doi:10.1093/hmg/ddu087

    Google Scholar 

  3. Terzic J, Grivennikov S, Karin E, Karin M (2010) Inflammation and colon cancer. Gastroenterology 138(6):2101–2114, e2105. doi:10.1053/j.gastro.2010.01.058

    Article  CAS  PubMed  Google Scholar 

  4. Canavan C, Abrams KR, Mayberry J (2006) Meta-analysis: colorectal and small bowel cancer risk in patients with Crohn’s disease. Aliment Pharmacol Ther 23(8):1097–1104. doi:10.1111/j.1365-2036.2006.02854.x

    Article  CAS  PubMed  Google Scholar 

  5. Eaden JA, Abrams KR, Mayberry JF (2001) The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut 48(4):526–535

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Kappelman MD, Rifas-Shiman SL, Kleinman K, Ollendorf D, Bousvaros A, Grand RJ, Finkelstein JA (2007) The prevalence and geographic distribution of Crohn’s disease and ulcerative colitis in the United States. Clin Gastroenterol Hepatol 5(12):1424–1429. doi:10.1016/j.cgh.2007.07.012

    Article  PubMed  Google Scholar 

  7. Andersen NN, Jess T (2013) Has the risk of colorectal cancer in inflammatory bowel disease decreased? World J Gastroenterol 19(43):7561–7568. doi:10.3748/wjg.v19.i43.7561

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Lutgens MW, van Oijen MG, van der Heijden GJ, Vleggaar FP, Siersema PD, Oldenburg B (2013) Declining risk of colorectal cancer in inflammatory bowel disease: an updated meta-analysis of population-based cohort studies. Inflamm Bowel Dis 19(4):789–799. doi:10.1097/MIB.0b013e31828029c0

    Article  PubMed  Google Scholar 

  9. Yen EF, Pokhrel B, Bianchi LK, Roy HK, Du H, Patel A, Hall CR, Witt BL (2012) Decreased colorectal cancer and adenoma risk in patients with microscopic colitis. Dig Dis Sci 57(1):161–169. doi:10.1007/s10620-011-1852-2

    Article  PubMed  Google Scholar 

  10. Neufert C, Becker C, Neurath MF (2007) An inducible mouse model of colon carcinogenesis for the analysis of sporadic and inflammation-driven tumor progression. Nat Protoc 2(8):1998–2004. doi:10.1038/nprot.2007.279

    Article  CAS  PubMed  Google Scholar 

  11. Ullman TA, Itzkowitz SH (2011) Intestinal inflammation and cancer. Gastroenterology 140(6):1807–1816. doi:10.1053/j.gastro.2011.01.057

    Article  CAS  PubMed  Google Scholar 

  12. Fearon ER (2011) Molecular genetics of colorectal cancer. Annu Rev Pathol 6:479–507. doi:10.1146/annurev-pathol-011110-130235

    Article  CAS  PubMed  Google Scholar 

  13. Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA Jr, Kinzler KW (2013) Cancer genome landscapes. Science 339(6127):1546–1558. doi:10.1126/science.1235122

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Vogelstein B, Kinzler KW (1993) The multistep nature of cancer. Trends Genet 9(4):138–141

    Article  CAS  PubMed  Google Scholar 

  15. Atreya I, Neurath MF (2008) Immune cells in colorectal cancer: prognostic relevance and therapeutic strategies. Expert Rev Anticancer Ther 8(4):561–572. doi:10.1586/14737140.8.4.561

    Article  CAS  PubMed  Google Scholar 

  16. Waldner MJ, Neurath MF (2008) Cytokines in colitis associated cancer: potential drug targets? Inflamm Allergy Drug Targets 7(3):187–194

    Article  CAS  PubMed  Google Scholar 

  17. Nosho K, Baba Y, Tanaka N, Shima K, Hayashi M, Meyerhardt JA, Giovannucci E, Dranoff G, Fuchs CS, Ogino S (2010) Tumour-infiltrating T-cell subsets, molecular changes in colorectal cancer, and prognosis: cohort study and literature review. J Pathol 222(4):350–366. doi:10.1002/path.2774

    Article  PubMed Central  PubMed  Google Scholar 

  18. Sears CL, Garrett WS (2014) Microbes, microbiota, and colon cancer. Cell Host Microbe 15(3):317–328. doi:10.1016/j.chom.2014.02.007

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Abreu MT, Peek RM Jr (2014) Gastrointestinal malignancy and the microbiome. Gastroenterology 146(6):1534–1546, e1533. doi:10.1053/j.gastro.2014.01.001

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Greer JB, O’Keefe SJ (2011) Microbial induction of immunity, inflammation, and cancer. Front Physiol 1:168. doi:10.3389/fphys.2010.00168

    Article  PubMed Central  PubMed  Google Scholar 

  21. Kato I, Majumdar AP, L and SJ, Barnholtz-Sloan JS, Severson RK (2010) Dietary fatty acids, luminal modifiers, and risk of colorectal cancer. Int J Cancer 127(4):942–951. doi:10.1002/ijc.25103

    PubMed Central  CAS  PubMed  Google Scholar 

  22. Sussman DA, Santaolalla R, Strobel S, Dheer R, Abreu MT (2012) Cancer in inflammatory bowel disease: lessons from animal models. Curr Opin Gastroenterol 28(4):327–333. doi:10.1097/MOG.0b013e328354cc36

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Kanneganti M, Mino-Kenudson M, Mizoguchi E (2011) Animal models of colitis-associated carcinogenesis. J Biomed Biotechnol 2011:342637. doi:10.1155/2011/342637

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  24. Westbrook AM, Szakmary A, Schiestl RH (2010) Mechanisms of intestinal inflammation and development of associated cancers: lessons learned from mouse models. Mutat Res 705(1):40–59. doi:10.1016/j.mrrev.2010.03.001

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Wirtz S, Neufert C, Weigmann B, Neurath MF (2007) Chemically induced mouse models of intestinal inflammation. Nat Protoc 2(3):541–546. doi:10.1038/nprot.2007.41

    Article  CAS  PubMed  Google Scholar 

  26. Cooper HS, Murthy S, Kido K, Yoshitake H, Flanigan A (2000) Dysplasia and cancer in the dextran sulfate sodium mouse colitis model. Relevance to colitis-associated neoplasia in the human: a study of histopathology, B-catenin and p53 expression and the role of inflammation. Carcinogenesis 21(4):757–768

    Article  CAS  PubMed  Google Scholar 

  27. Fukata M, Shang L, Santaolalla R, Sotolongo J, Pastorini C, Espana C, Ungaro R, Harpaz N, Cooper HS, Elson G, Kosco-Vilbois M, Zaias J, Perez MT, Mayer L, Vamadevan AS, Lira SA, Abreu MT (2011) Constitutive activation of epithelial TLR4 augments inflammatory responses to mucosal injury and drives colitis-associated tumorigenesis. Inflamm Bowel Dis 17(7):1464–1473. doi:10.1002/ibd.21527

    Article  PubMed Central  PubMed  Google Scholar 

  28. Aust DE, Terdiman JP, Willenbucher RF, Chew K, Ferrell L, Florendo C, Molinaro-Clark A, Baretton GB, Lohrs U, Waldman FM (2001) Altered distribution of beta-catenin, and its binding proteins E-cadherin and APC, in ulcerative colitis-related colorectal cancers. Modern Pathol 14(1):29–39. doi:10.1038/modpathol.3880253

    Article  CAS  Google Scholar 

  29. Suzuki R, Kohno H, Sugie S, Nakagama H, Tanaka T (2006) Strain differences in the susceptibility to azoxymethane and dextran sodium sulfate-induced colon carcinogenesis in mice. Carcinogenesis 27(1):162–169

    Article  CAS  PubMed  Google Scholar 

  30. Suzuki R, Kohno H, Sugie S, Tanaka T (2005) Dose-dependent promoting effect of dextran sodium sulfate on mouse colon carcinogenesis initiated with azoxymethane. Histol Histopathol 20(2):483–492

    CAS  PubMed  Google Scholar 

  31. Bhan AK, Mizoguchi E, Smith RN, Mizoguchi A (1999) Colitis in transgenic and knockout animals as models of human inflammatory bowel disease. Immunol Rev 169:195–207

    Article  CAS  PubMed  Google Scholar 

  32. Moser AR, Pitot HC, Dove WF (1990) A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse. Science 247(4940):322–324

    Article  CAS  PubMed  Google Scholar 

  33. Tanaka T, Kohno H, Suzuki R, Hata K, Sugie S, Niho N, Sakano K, Takahashi M, Wakabayashi K (2006) Dextran sodium sulfate strongly promotes colorectal carcinogenesis in Apc(Min/+) mice: inflammatory stimuli by dextran sodium sulfate results in development of multiple colonic neoplasms. Int J Cancer 118(1):25–34

    Article  CAS  PubMed  Google Scholar 

  34. Housseau F, Sears CL (2010) Enterotoxigenic Bacteroides fragilis (ETBF)-mediated colitis in Min (Apc+/–) mice: a human commensal-based murine model of colon carcinogenesis. Cell Cycle 9(1):3–5

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Erdman SE, Poutahidis T, Tomczak M, Rogers AB, Cormier K, Plank B, Horwitz BH, Fox JG (2003) CD4+ CD25+ regulatory T lymphocytes inhibit microbially induced colon cancer in Rag2-deficient mice. Am J Pathol 162(2):691–702

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Erdman SE, Sohn JJ, Rao VP, Nambiar PR, Ge Z, Fox JG, Schauer DB (2005) CD4+ CD25+ regulatory lymphocytes induce regression of intestinal tumors in ApcMin/+ mice. Cancer Res 65(10):3998–4004. doi:10.1158/0008-5472.CAN-04-3104

    Article  CAS  PubMed  Google Scholar 

  37. Blat D, Zigmond E, Alteber Z, Waks T, Eshhar Z (2014) Suppression of murine colitis and its associated cancer by carcinoembryonic antigen-specific regulatory T cells. Mol Ther 22(5):1018–1028. doi:10.1038/mt.2014.41

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Erdman SE, Poutahidis T (2010) Roles for inflammation and regulatory T cells in colon cancer. Toxicol Pathol 38(1):76–87. doi:10.1177/0192623309354110

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Grivennikov SI (2013) Inflammation and colorectal cancer: colitis-associated neoplasia. Semin Immunopathol 35(2):229–244. doi:10.1007/s00281-012-0352-6

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Schulz O, Jaensson E, Persson EK, Liu X, Worbs T, Agace WW, Pabst O (2009) Intestinal CD103+, but not CX3CR1+, antigen sampling cells migrate in lymph and serve classical dendritic cell functions. J Exp Med 206(13):3101–3114. doi:10.1084/jem.20091925

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Platt AM, Bain CC, Bordon Y, Sester DP, Mowat AM (2010) An independent subset of TLR expressing CCR2-dependent macrophages promotes colonic inflammation. J Immunol 184(12):6843–6854. doi:10.4049/jimmunol.0903987

    Article  CAS  PubMed  Google Scholar 

  42. Smythies LE, Shen R, Bimczok D, Novak L, Clements RH, Eckhoff DE, Bouchard P, George MD, Hu WK, Dandekar S, Smith PD (2010) Inflammation anergy in human intestinal macrophages is due to Smad-induced IkappaBalpha expression and NF-kappaB inactivation. J Biol Chem 285(25):19593–19604. doi:10.1074/jbc.M109.069955

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Kamada N, Hisamatsu T, Okamoto S, Chinen H, Kobayashi T, Sato T, Sakuraba A, Kitazume MT, Sugita A, Koganei K, Akagawa KS, Hibi T (2008) Unique CD14 intestinal macrophages contribute to the pathogenesis of Crohn disease via IL-23/IFN-gamma axis. J Clin Invest 118(6):2269–2280. doi:10.1172/JCI34610

    PubMed Central  CAS  PubMed  Google Scholar 

  44. Cader MZ, Kaser A (2013) Recent advances in inflammatory bowel disease: mucosal immune cells in intestinal inflammation. Gut 62(11):1653–1664. doi:10.1136/gutjnl-2012-303955

    Article  CAS  PubMed  Google Scholar 

  45. Watanabe N, Ikuta K, Okazaki K, Nakase H, Tabata Y, Matsuura M, Tamaki H, Kawanami C, Honjo T, Chiba T (2003) Elimination of local macrophages in intestine prevents chronic colitis in interleukin-10-deficient mice. Dig Dis Sci 48(2):408–414

    Article  PubMed  Google Scholar 

  46. Zigmond E, Varol C, Farache J, Elmaliah E, Satpathy AT, Friedlander G, Mack M, Shpigel N, Boneca IG, Murphy KM, Shakhar G, Halpern Z, Jung S (2012) Ly6C hi monocytes in the inflamed colon give rise to proinflammatory effector cells and migratory antigen-presenting cells. Immunity 37(6):1076–1090. doi:10.1016/j.immuni.2012.08.026

    Article  CAS  PubMed  Google Scholar 

  47. Pollard JW (2004) Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer 4(1):71–78. doi:10.1038/nrc1256

    Article  CAS  PubMed  Google Scholar 

  48. Zhou Q, Peng RQ, Wu XJ, Xia Q, Hou JH, Ding Y, Zhou QM, Zhang X, Pang ZZ, Wan DS, Zeng YX, Zhang XS (2010) The density of macrophages in the invasive front is inversely correlated to liver metastasis in colon cancer. J Transl Med 8:13. doi:10.1186/1479-5876-8-13

    Article  PubMed Central  PubMed  Google Scholar 

  49. Forssell J, Oberg A, Henriksson ML, Stenling R, Jung A, Palmqvist R (2007) High macrophage infiltration along the tumor front correlates with improved survival in colon cancer. Clin Cancer Res 13(5):1472–1479. doi:10.1158/1078-0432.CCR-06-2073

    Article  CAS  PubMed  Google Scholar 

  50. Chaput N, Svrcek M, Auperin A, Locher C, Drusch F, Malka D, Taieb J, Goere D, Ducreux M, Boige V (2013) Tumour-infiltrating CD68+ and CD57+ cells predict patient outcome in stage II-III colorectal cancer. Br J Cancer 109(4):1013–1022. doi:10.1038/bjc.2013.362

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  51. Gulubova M, Ananiev J, Yovchev Y, Julianov A, Karashmalakov A, Vlaykova T (2013) The density of macrophages in colorectal cancer is inversely correlated to TGF-beta1 expression and patients’ survival. J Mol Histol 44(6):679–692. doi:10.1007/s10735-013-9520-9

    Article  CAS  PubMed  Google Scholar 

  52. Funada Y, Noguchi T, Kikuchi R, Takeno S, Uchida Y, Gabbert HE (2003) Prognostic significance of CD8+ T cell and macrophage peritumoral infiltration in colorectal cancer. Oncol Rep 10(2):309–313

    PubMed  Google Scholar 

  53. Ohno S, Inagawa H, Dhar DK, Fujii T, Ueda S, Tachibana M, Suzuki N, Inoue M, Soma G, Nagasue N (2003) The degree of macrophage infiltration into the cancer cell nest is a significant predictor of survival in gastric cancer patients. Anticancer Res 23(6D):5015–5022

    PubMed  Google Scholar 

  54. Kinouchi M, Miura K, Mizoi T, Ishida K, Fujibuchi W, Ando T, Yazaki N, Saito K, Shiiba K, Sasaki I (2011) Infiltration of CD14-positive macrophages at the invasive front indicates a favorable prognosis in colorectal cancer patients with lymph node metastasis. Hepatogastroenterology 58(106):352–358

    PubMed  Google Scholar 

  55. Edin S, Wikberg ML, Dahlin AM, Rutegard J, Oberg A, Oldenborg PA, Palmqvist R (2012) The distribution of macrophages with a M1 or M2 phenotype in relation to prognosis and the molecular characteristics of colorectal cancer. PLoS One 7(10):e47045. doi:10.1371/journal.pone.0047045

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  56. Algars A, Irjala H, Vaittinen S, Huhtinen H, Sundstrom J, Salmi M, Ristamaki R, Jalkanen S (2012) Type and location of tumor-infiltrating macrophages and lymphatic vessels predict survival of colorectal cancer patients. Int J Cancer 131(4):864–873. doi:10.1002/ijc.26457

    Article  PubMed  CAS  Google Scholar 

  57. Sugita J, Ohtani H, Mizoi T, Saito K, Shiiba K, Sasaki I, Matsuno S, Yagita H, Miyazawa M, Nagura H (2002) Close association between Fas ligand (FasL; CD95 L)-positive tumor-associated macrophages and apoptotic cancer cells along invasive margin of colorectal carcinoma: a proposal on tumor-host interactions. Jpn J Cancer Res 93(3):320–328

    Article  CAS  PubMed  Google Scholar 

  58. Gulubova MV, Ananiev JR, Vlaykova TI, Yovchev Y, Tsoneva V, Manolova IM (2012) Role of dendritic cells in progression and clinical outcome of colon cancer. Int J Colorectal Dis 27(2):159–169. doi:10.1007/s00384-011-1334-1

    Article  PubMed  Google Scholar 

  59. Garrett WS, Punit S, Gallini CA, Michaud M, Zhang D, Sigrist KS, Lord GM, Glickman JN, Glimcher LH (2009) Colitis-associated colorectal cancer driven by T-bet deficiency in dendritic cells. Cancer Cell 16(3):208–219. doi:10.1016/j.ccr.2009.07.015

    Google Scholar 

  60. Garrett WS, Lord GM, Punit S, Lugo-Villarino G, Mazmanian SK, Ito S, Glickman JN, Glimcher LH (2007) Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system. Cell 131(1):33–45. doi:10.1016/j.cell.2007.08.017

    Google Scholar 

  61. Powell N, Walker AW, Stolarczyk E, Canavan JB, Gokmen MR, Marks E, Jackson I, Hashim A, Curtis MA, Jenner RG, Howard JK, Parkhill J, MacDonald TT, Lord GM (2012) The transcription factor T-bet regulates intestinal inflammation mediated by interleukin-7 receptor + innate lymphoid cells. Immunity 37(4):674–684. doi:10.1016/j.immuni.2012.09.008

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  62. Fridlender ZG, Albelda SM (2012) Tumor-associated neutrophils: friend or foe? Carcinogenesis 33(5):949–955. doi:10.1093/carcin/bgs123

    Article  CAS  PubMed  Google Scholar 

  63. Houghton AM (2010) The paradox of tumor-associated neutrophils: fueling tumor growth with cytotoxic substances. Cell Cycle 9(9):1732–1737

    Article  CAS  PubMed  Google Scholar 

  64. Houghton AM, Rzymkiewicz DM, Ji H, Gregory AD, Egea EE, Metz HE, Stolz DB, L and SR, Marconcini LA, Kliment CR, Jenkins KM, Beaulieu KA, Mouded M, Frank SJ, Wong KK, Shapiro SD (2010) Neutrophil elastase-mediated degradation of IRS-1 accelerates lung tumor growth. Nat Med 16(2):219–223. doi:10.1038/nm.2084

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  65. Nozawa H, Chiu C, Hanahan D (2006) Infiltrating neutrophils mediate the initial angiogenic switch in a mouse model of multistage carcinogenesis. Proc Natl Acad Sci U S A 103(33):12493–12498. doi:10.1073/pnas.0601807103

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  66. Rao HL, Chen JW, Li M, Xiao YB, Fu J, Zeng YX, Cai MY, Xie D (2012) Increased intratumoral neutrophil in colorectal carcinomas correlates closely with malignant phenotype and predicts patients’ adverse prognosis. PLoS One 7(1):e30806. doi:10.1371/journal.pone.0030806

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  67. Shang K, Bai YP, Wang C, Wang Z, Gu HY, Du X, Zhou XY, Zheng CL, Chi YY, Mukaida N, Li YY (2012) Crucial involvement of tumor-associated neutrophils in the regulation of chronic colitis-associated carcinogenesis in mice. PLoS One 7(12):e51848. doi:10.1371/journal.pone.0051848

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  68. Gounaris E, Erdman SE, Restaino C, Gurish MF, Friend DS, Gounari F, Lee DM, Zhang G, Glickman JN, Shin K, Rao VP, Poutahidis T, Weissleder R, McNagny KM, Khazaie K (2007) Mast cells are an essential hematopoietic component for polyp development. Proc Natl Acad Sci U S A 104(50):19977–19982. doi:10.1073/pnas.0704620104

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  69. Gounaris E, Blatner NR, Dennis K, Magnusson F, Gurish MF, Strom TB, Beckhove P, Gounari F, Khazaie K (2009) T-regulatory cells shift from a protective anti-inflammatory to a cancer-promoting proinflammatory phenotype in polyposis. Cancer Res 69(13):5490–5497. doi:10.1158/0008-5472.CAN-09-0304

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  70. Egelston C, Kurko J, Besenyei T, Tryniszewska B, Rauch TA, Glant TT, Mikecz K (2012) Suppression of dendritic cell maturation and T cell proliferation by synovial fluid myeloid cells from mice with autoimmune arthritis. Arthritis Rheum 64(10):3179–3188. doi:10.1002/art.34494

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  71. Zhu B, Bando Y, Xiao S, Yang K, Anderson AC, Kuchroo VK, Khoury SJ (2007) CD11b+ Ly-6C(hi) suppressive monocytes in experimental autoimmune encephalomyelitis. J Immunol 179(8):5228–5237

    Article  CAS  PubMed  Google Scholar 

  72. Dilek N, Vuillefroy de Silly R, Blancho G, Vanhove B (2012) Myeloid-derived suppressor cells: mechanisms of action and recent advances in their role in transplant tolerance. Front Immunol 3:208. doi:10.3389/fimmu.2012.00208

    Article  PubMed Central  PubMed  Google Scholar 

  73. Saiwai H, Kumamaru H, Ohkawa Y, Kubota K, Kobayakawa K, Yamada H, Yokomizo T, Iwamoto Y, Okada S (2013) Ly6C+ Ly6G– Myeloid-derived suppressor cells play a critical role in the resolution of acute inflammation and the subsequent tissue repair process after spinal cord injury. J Neurochem 125(1):74–88. doi:10.1111/jnc.12135

    Article  CAS  PubMed  Google Scholar 

  74. Nagaraj S, Schrum AG, Cho HI, Celis E, Gabrilovich DI (2010) Mechanism of T cell tolerance induced by myeloid-derived suppressor cells. J Immunol 184(6):3106–3116. doi:10.4049/jimmunol.0902661

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  75. Cheng P, Corzo CA, Luetteke N, Yu B, Nagaraj S, Bui MM, Ortiz M, Nacken W, Sorg C, Vogl T, Roth J, Gabrilovich DI (2008) Inhibition of dendritic cell differentiation and accumulation of myeloid-derived suppressor cells in cancer is regulated by S100A9 protein. J Exp Med 205(10):2235–2249. doi:10.1084/jem.20080132

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  76. Vogl T, Tenbrock K, Ludwig S, Leukert N, Ehrhardt C, van Zoelen MA, Nacken W, Foell D, van der Poll T, Sorg C, Roth J (2007) Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock. Nat Med 13(9):1042–1049. doi:10.1038/nm1638

    Article  CAS  PubMed  Google Scholar 

  77. Bunt SK, Clements VK, Hanson EM, Sinha P, Ostrand-Rosenberg S (2009) Inflammation enhances myeloid-derived suppressor cell cross-talk by signaling through Toll-like receptor 4. J Leukoc Biol 85(6):996–1004. doi:10.1189/jlb.0708446

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  78. Kallberg E, Vogl T, Liberg D, Olsson A, Bjork P, Wikstrom P, Bergh A, Roth J, Ivars F, Leanderson T (2012) S100A9 interaction with TLR4 promotes tumor growth. PLoS One 7(3):e34207. doi:10.1371/journal.pone.0034207

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  79. Hong EH, Chang SY, Lee BR, Kim YS, Lee JM, Kang CY, Kweon MN, Ko HJ (2013) Blockade of Myd88 signaling induces antitumor effects by skewing the immunosuppressive function of myeloid-derived suppressor cells. Int J Cancer 132(12):2839–2848. doi:10.1002/ijc.27974

    Article  CAS  PubMed  Google Scholar 

  80. Tartour E, Pere H, Maillere B, Terme M, Merillon N, Taieb J, Sandoval F, Quintin-Colonna F, Lacerda K, Karadimou A, Badoual C, Tedgui A, Fridman WH, Oudard S (2011) Angiogenesis and immunity: a bidirectional link potentially relevant for the monitoring of antiangiogenic therapy and the development of novel therapeutic combination with immunotherapy. Cancer Metastasis Rev 30(1):83–95. doi:10.1007/s10555-011-9281-4

    Article  CAS  PubMed  Google Scholar 

  81. Haile LA, von Wasielewski R, Gamrekelashvili J, Kruger C, Bachmann O, Westendorf AM, Buer J, Liblau R, Manns MP, Korangy F, Greten TF (2008) Myeloid-derived suppressor cells in inflammatory bowel disease: a new immunoregulatory pathway. Gastroenterology 135(3):871–881, 881, e871–e875. doi:10.1053/j.gastro.2008.06.032

    Article  CAS  PubMed  Google Scholar 

  82. Singh UP, Singh NP, Singh B, Hofseth LJ, Taub DD, Price RL, Nagarkatti M, Nagarkatti PS (2012) Role of resveratrol-induced CD11b(+) Gr-1(+) myeloid derived suppressor cells (MDSCs) in the reduction of CXCR3(+) T cells and amelioration of chronic colitis in IL-10(–/–) mice. Brain Behav Immun 26(1):72–82. doi:10.1016/j.bbi.2011.07.236

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  83. Zhang R, Ito S, Nishio N, Cheng Z, Suzuki H, Isobe KI (2011) Dextran sulphate sodium increases splenic Gr1(+)CD11b(+) cells which accelerate recovery from colitis following intravenous transplantation. Clin Exp Immunol 164(3):417–427. doi:10.1111/j.1365-2249.2011.04374.x

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  84. Turovskaya O, Foell D, Sinha P, Vogl T, Newlin R, Nayak J, Nguyen M, Olsson A, Nawroth PP, Bierhaus A, Varki N, Kronenberg M, Freeze HH, Srikrishna G (2008) RAGE, carboxylated glycans and S100A8/A9 play essential roles in colitis-associated carcinogenesis. Carcinogenesis 29(10):2035–2043. doi:10.1093/carcin/bgn188

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  85. Ichikawa M, Williams R, Wang L, Vogl T, Srikrishna G (2011) S100A8/A9 activate key genes and pathways in colon tumor progression. Mol Cancer Res 9(2):133–148. doi:10.1158/1541-7786.MCR-10-0394

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  86. Santaolalla R, Sussman DA, Ruiz JR, Davies JM, Pastorini C, Espana CL, Sotolongo J, Burlingame O, Bejarano PA, Philip S, Ahmed MM, Ko J, Dirisina R, Barrett TA, Shang L, Lira SA, Fukata M, Abreu MT (2013) TLR4 activates the beta-catenin pathway to cause intestinal neoplasia. PLoS One 8(5):e63298. doi:10.1371/journal.pone.0063298

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  87. Sade-Feldman M, Kanterman J, Ish-Shalom E, Elnekave M, Horwitz E, Baniyash M (2013) Tumor necrosis factor-alpha blocks differentiation and enhances suppressive activity of immature myeloid cells during chronic inflammation. Immunity 38(3):541–554. doi:10.1016/j.immuni.2013.02.007

    Article  CAS  PubMed  Google Scholar 

  88. Zhang B, Wang Z, Wu L, Zhang M, Li W, Ding J, Zhu J, Wei H, Zhao K (2013) Circulating and tumor-infiltrating myeloid-derived suppressor cells in patients with colorectal carcinoma. PLoS One 8(2):e57114. doi:10.1371/journal.pone.0057114

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  89. Collart MA, Baeuerle P, Vassalli P (1990) Regulation of tumor necrosis factor alpha transcription in macrophages: involvement of four kappa B-like motifs and of constitutive and inducible forms of NF-kappa B. Mol Cell Biol 10(4):1498–1506

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  90. Shakhov AN, Collart MA, Vassalli P, Nedospasov SA, Jongeneel CV (1990) Kappa B-type enhancers are involved in lipopolysaccharide-mediated transcriptional activation of the tumor necrosis factor alpha gene in primary macrophages. J Exp Med 171(1):35–47

    Article  CAS  PubMed  Google Scholar 

  91. Woo CH, Eom YW, Yoo MH, You HJ, Han HJ, Song WK, Yoo YJ, Chun JS, Kim JH (2000) Tumor necrosis factor-alpha generates reactive oxygen species via a cytosolic phospholipase A2-linked cascade. J Biol Chem 275(41):32357–32362. doi:10.1074/jbc.M005638200

    Article  CAS  PubMed  Google Scholar 

  92. Waris G, Ahsan H (2006) Reactive oxygen species: role in the development of cancer and various chronic conditions. J Carcinog 5:14. doi:10.1186/1477-3163-5-14

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  93. Kim S, Keku TO, Martin C, Galanko J, Woosley JT, Schroeder JC, Satia JA, Halabi S, Sandler RS (2008) Circulating levels of inflammatory cytokines and risk of colorectal adenomas. Cancer Res 68(1):323–328. doi:10.1158/0008-5472.CAN-07-2924

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  94. Garrity-Park MM, Loftus EV Jr, Bryant SC, Sandborn WJ, Smyrk TC (2008) Tumor necrosis factor-alpha polymorphisms in ulcerative colitis-associated colorectal cancer. Am J Gastroenterol 103(2):407–415. doi:10.1111/j.1572-0241.2007.01572.x

    Article  CAS  PubMed  Google Scholar 

  95. Wang K, Han G, Dou Y, Wang Y, Liu G, Wang R, Xiao H, Li X, Hou C, Shen B, Guo R, Li Y, Shi Y, Chen G (2012) Opposite role of tumor necrosis factor receptors in dextran sulfate sodium-induced colitis in mice. PLoS One 7(12):e52924. doi:10.1371/journal.pone.0052924

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  96. Popivanova BK, Kitamura K, Wu Y, Kondo T, Kagaya T, Kaneko S, Oshima M, Fujii C, Mukaida N (2008) Blocking TNF-alpha in mice reduces colorectal carcinogenesis associated with chronic colitis. J Clin Invest. doi:10.1172/JCI32453

    Google Scholar 

  97. Roulis M, Armaka M, Manoloukos M, Apostolaki M, Kollias G (2011) Intestinal epithelial cells as producers but not targets of chronic TNF suffice to cause murine Crohn-like pathology. Proc Natl Acad Sci U S A 108(13):5396–5401. doi:10.1073/pnas.1007811108

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  98. Wang H, Wang HS, Zhou BH, Li CL, Zhang F, Wang XF, Zhang G, Bu XZ, Cai SH, Du J (2013) Epithelial-mesenchymal transition (EMT) induced by TNF-alpha requires AKT/GSK-3beta-mediated stabilization of snail in colorectal cancer. PLoS One 8(2):e56664. doi:10.1371/journal.pone.0056664

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  99. Asadullah K, Sterry W, Volk HD (2003) Interleukin-10 therapy—review of a new approach. Pharmacol Rev 55(2):241–269. doi:10.1124/pr.55.2.4

    Article  CAS  PubMed  Google Scholar 

  100. Berg DJ, Davidson N, Kuhn R, Muller W, Menon S, Holland G, Thompson-Snipes L, Leach MW, Rennick D (1996) Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4(+) TH1-like responses. J Clin Invest 98(4):1010–1020

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  101. Sellon RK, Tonkonogy S, Schultz M, Dieleman LA, Grenther W, Balish E, Rennick DM, Sartor RB (1998) Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice. Infect Immun 66(11):5224–5231

    PubMed Central  CAS  PubMed  Google Scholar 

  102. Narushima S, Spitz DR, Oberley LW, Toyokuni S, Miyata T, Gunnett CA, Buettner GR, Zhang J, Ismail H, Lynch RG, Berg DJ (2003) Evidence for oxidative stress in NSAID-induced colitis in IL10–/– mice. Free Radic Biol Med 34(9):1153–1166

    Article  CAS  PubMed  Google Scholar 

  103. Zigmond E, Bernshtein B, Friedlander G, Walker CR, Yona S, Kim KW, Brenner O, Krauthgamer R, Varol C, Muller W, Jung S (2014) Macrophage-restricted interleukin-10 receptor deficiency, but not IL-10 deficiency, causes severe spontaneous colitis. Immunity 40(5):720–733. doi:10.1016/j.immuni.2014.03.012

    Article  CAS  PubMed  Google Scholar 

  104. Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, Hui KY, Lee JC, Schumm LP, Sharma Y, Anderson CA, Essers J, Mitrovic M, Ning K, Cleynen I, Theatre E, Spain SL, Raychaudhuri S, Goyette P, Wei Z, Abraham C, Achkar JP, Ahmad T, Amininejad L, Ananthakrishnan AN, Andersen V, Andrews JM, Baidoo L, Balschun T, Bampton PA, Bitton A, Boucher G, Brand S, Buning C, Cohain A, Cichon S, D’Amato M, De Jong D, Devaney KL, Dubinsky M, Edwards C, Ellinghaus D, Ferguson LR, Franchimont D, Fransen K, Gearry R, Georges M, Gieger C, Glas J, Haritunians T, Hart A, Hawkey C, Hedl M, Hu X, Karlsen TH, Kupcinskas L, Kugathasan S, Latiano A, Laukens D, Lawrance IC, Lees CW, Louis E, Mahy G, Mansfield J, Morgan AR, Mowat C, Newman W, Palmieri O, Ponsioen CY, Potocnik U, Prescott NJ, Regueiro M, Rotter JI, Russell RK, Sanderson JD, Sans M, Satsangi J, Schreiber S, Simms LA, Sventoraityte J, Targan SR, Taylor KD, Tremelling M, Verspaget HW, De Vos M, Wijmenga C, Wilson DC, Winkelmann J, Xavier RJ, Zeissig S, Zhang B, Zhang CK, Zhao H, Silverberg MS, Annese V, Hakonarson H, Brant SR, Radford-Smith G, Mathew CG, Rioux JD, Schadt EE, Daly MJ, Franke A, Parkes M, Vermeire S, Barrett JC, Cho JH (2012) Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491(7422):119–124. doi:10.1038/nature11582

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  105. Moran CJ, Walters TD, Guo CH, Kugathasan S, Klein C, Turner D, Wolters VM, Bandsma RH, Mouzaki M, Zachos M, Langer JC, Cutz E, Benseler SM, Roifman CM, Silverberg MS, Griffiths AM, Snapper SB, Muise AM (2013) IL-10R polymorphisms are associated with very-early-onset ulcerative colitis. Inflamm Bowel Dis 19(1):115–123. doi:10.1002/ibd.22974

    Article  PubMed Central  PubMed  Google Scholar 

  106. Naugler WE, Karin M (2008) The wolf in sheep’s clothing: the role of interleukin-6 in immunity, inflammation and cancer. Trends Mol Med 14(3):109–119. doi:10.1016/j.molmed.2007.12.007

    Article  CAS  PubMed  Google Scholar 

  107. Matsumoto S, Hara T, Mitsuyama K, Yamamoto M, Tsuruta O, Sata M, Scheller J, Rose-John S, Kado S, Takada T (2010) Essential roles of IL-6 trans-signaling in colonic epithelial cells, induced by the IL-6/soluble-IL-6 receptor derived from lamina propria macrophages, on the development of colitis-associated premalignant cancer in a murine model. J Immunol 184(3):1543–1551. doi:10.4049/jimmunol.0801217

    Article  CAS  PubMed  Google Scholar 

  108. Waldner MJ, Foersch S, Neurath MF (2012) Interleukin-6—a key regulator of colorectal cancer development. Int J Biol Sci 8(9):1248–1253. doi:10.7150/ijbs.4614

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  109. Knupfer H, Preiss R (2010) Serum interleukin-6 levels in colorectal cancer patients—a summary of published results. Int J Colorectal Dis 25(2):135–140. doi:10.1007/s00384-009-0818-8

    Article  PubMed  Google Scholar 

  110. Louis E, Belaiche J, van Kemseke C, Franchimont D, de Groote D, Gueenen V, Mary JY (1997) A high serum concentration of interleukin-6 is predictive of relapse in quiescent Crohn’s disease. Eur J Gastroenterol Hepatol 9(10):939–944

    Article  CAS  PubMed  Google Scholar 

  111. Van Kemseke C, Belaiche J, Louis E (2000) Frequently relapsing Crohn’s disease is characterized by persistent elevation in interleukin-6 and soluble interleukin-2 receptor serum levels during remission. Int J Colorectal Dis 15(4):206–210

    Article  CAS  PubMed  Google Scholar 

  112. Atreya R, Neurath MF (2008) New therapeutic strategies for treatment of inflammatory bowel disease. Mucosal Immunol 1(3):175–182. doi:10.1038/mi.2008.7

    Article  CAS  PubMed  Google Scholar 

  113. Dinarello CA (2009) Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol 27:519–550. doi:10.1146/annurev.immunol.021908.132612

    Article  CAS  PubMed  Google Scholar 

  114. Dupaul-Chicoine J, Yeretssian G, Doiron K, Bergstrom KS, McIntire CR, LeBlanc PM, Meunier C, Turbide C, Gros P, Beauchemin N, Vallance BA, Saleh M (2010) Control of intestinal homeostasis, colitis, and colitis-associated colorectal cancer by the inflammatory caspases. Immunity 32(3):367–378. doi:10.1016/j.immuni.2010.02.012

    Article  CAS  PubMed  Google Scholar 

  115. Kaler P, Godasi BN, Augenlicht L, Klampfer L (2009) The NF-kappaB/AKT-dependent Induction of Wnt signaling in colon cancer cells by macrophages and IL-1beta. Cancer Microenviron. doi:10.1007/s12307-009-0030-y

    Google Scholar 

  116. Li Y, Wang L, Pappan L, Galliher-Beckley A, Shi J (2012) IL-1beta promotes stemness and invasiveness of colon cancer cells through Zeb1 activation. Mol Cancer 11:87. doi:10.1186/1476-4598-11-87

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  117. Kaler P, Galea V, Augenlicht L, Klampfer L (2010) Tumor associated macrophages protect colon cancer cells from TRAIL-induced apoptosis through IL-1beta-dependent stabilization of Snail in tumor cells. PLoS One 5(7):e11700. doi:10.1371/journal.pone.0011700

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  118. Kobayashi T, Okamoto S, Hisamatsu T, Kamada N, Chinen H, Saito R, Kitazume MT, Nakazawa A, Sugita A, Koganei K, Isobe K, Hibi T (2008) IL23 differentially regulates the Th1/Th17 balance in ulcerative colitis and Crohn’s disease. Gut 57 (12):1682–1689. doi:10.1136/gut.2007.135053

    Article  CAS  PubMed  Google Scholar 

  119. Sugihara T, Kobori A, Imaeda H, Tsujikawa T, Amagase K, Takeuchi K, Fujiyama Y, Andoh A (2010) The increased mucosal mRNA expressions of complement C3 and interleukin-17 in inflammatory bowel disease. Clin Exp Immunol 160(3):386–393. doi:10.1111/j.1365-2249.2010.04093.x

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  120. Fujino S, Andoh A, Bamba S, Ogawa A, Hata K, Araki Y, Bamba T, Fujiyama Y (2003) Increased expression of interleukin 17 in inflammatory bowel disease. Gut 52(1):65–70

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  121. Wang Y, Liu XP, Zhao ZB, Chen JH, Yu CG (2011) Expression of CD4+ forkhead box P3 (FOXP3)+ regulatory T cells in inflammatory bowel disease. J Dig Dis 12(4):286–294. doi:10.1111/j.1751-2980.2011.00505.x

    Article  CAS  PubMed  Google Scholar 

  122. Maul J, Loddenkemper C, Mundt P, Berg E, Giese T, Stallmach A, Zeitz M, Duchmann R (2005) Peripheral and intestinal regulatory CD4+ CD25(high) T cells in inflammatory bowel disease. Gastroenterology 128(7):1868–1878

    Article  CAS  PubMed  Google Scholar 

  123. Hovhannisyan Z, Treatman J, Littman DR, Mayer L (2011) Characterization of interleukin-17-producing regulatory T cells in inflamed intestinal mucosa from patients with inflammatory bowel diseases. Gastroenterology 140(3):957–965. doi:10.1053/j.gastro.2010.12.002

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  124. Kryczek I, Wu K, Zhao E, Wei S, Vatan L, Szeliga W, Huang E, Greenson J, Chang A, Rolinski J, Radwan P, Fang J, Wang G, Zou W (2011) IL-17+ regulatory T cells in the microenvironments of chronic inflammation and cancer. J Immunol 186(7):4388–4395. doi:10.4049/jimmunol.1003251

    Article  CAS  PubMed  Google Scholar 

  125. Salama P, Phillips M, Grieu F, Morris M, Zeps N, Joseph D, Platell C, Iacopetta B (2009) Tumor-infiltrating FOXP3+ T regulatory cells show strong prognostic significance in colorectal cancer. J Clin Oncol 27(2):186–192. doi:10.1200/JCO.2008.18.7229

    Article  PubMed  Google Scholar 

  126. Frey DM, Droeser RA, Viehl CT, Zlobec I, Lugli A, Zingg U, Oertli D, Kettelhack C, Terracciano L, Tornillo L (2010) High frequency of tumor-infiltrating FOXP3(+) regulatory T cells predicts improved survival in mismatch repair-proficient colorectal cancer patients. Int J Cancer 126(11):2635–2643. doi:10.1002/ijc.24989

    CAS  PubMed  Google Scholar 

  127. Erdman SE, Poutahidis T (2010) Cancer inflammation and regulatory T cells. Int J Cancer 127(4):768–779. doi:10.1002/ijc.25430

    PubMed Central  CAS  PubMed  Google Scholar 

  128. Erdman SE, Rao VP, Poutahidis T, Ihrig MM, Ge Z, Feng Y, Tomczak M, Rogers AB, Horwitz BH, Fox JG (2003) CD4(+)CD25(+) regulatory lymphocytes require interleukin 10 to interrupt colon carcinogenesis in mice. Cancer Res 63(18):6042–6050

    CAS  PubMed  Google Scholar 

  129. Mei Z, Liu Y, Liu C, Cui A, Liang Z, Wang G, Peng H, Cui L, Li C (2014) Tumour-infiltrating inflammation and prognosis in colorectal cancer: systematic review and meta-analysis. Br J Cancer 110(6):1595–1605. doi:10.1038/bjc.2014.46

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  130. Maseda D, Candando KM, Smith SH, Kalampokis I, Weaver CT, Plevy SE, Poe JC, Tedder TF (2013) Peritoneal cavity regulatory B cells (B10 cells) modulate IFN-gamma+CD4+ T cell numbers during colitis development in mice. J Immunol 191(5):2780–2795. doi:10.4049/jimmunol.1300649

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  131. Mizoguchi A, Mizoguchi E, Smith RN, Preffer FI, Bhan AK (1997) Suppressive role of B cells in chronic colitis of T cell receptor alpha mutant mice. J Exp Med 186(10):1749–1756

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  132. Mizoguchi A, Mizoguchi E, Takedatsu H, Blumberg RS, Bhan AK (2002) Chronic intestinal inflammatory condition generates IL-10-producing regulatory B cell subset characterized by CD1d upregulation. Immunity 16(2):219–230

    Article  CAS  PubMed  Google Scholar 

  133. Goetz M, Atreya R, Ghalibafian M, Galle PR, Neurath MF (2007) Exacerbation of ulcerative colitis after rituximab salvage therapy. Inflamm Bowel Dis 13(11):1365–1368. doi:10.1002/ibd.20215

    Article  PubMed  Google Scholar 

  134. Ardelean DS, Gonska T, Wires S, Cutz E, Griffiths A, Harvey E, Tse SM, Benseler SM (2010) Severe ulcerative colitis after rituximab therapy. Pediatrics 126(1):e243–e246. doi:10.1542/peds.2009-3395

    Article  PubMed  Google Scholar 

  135. El Fassi D, Nielsen CH, Kjeldsen J, Clemmensen O, Hegedus L (2008) Ulcerative colitis following B lymphocyte depletion with rituximab in a patient with Graves’ disease. Gut 57(5):714–715. doi:10.1136/gut.2007.138305

    Article  PubMed  Google Scholar 

  136. Leiper K, Martin K, Ellis A, Subramanian S, Watson AJ, Christmas SE, Howarth D, Campbell F, Rhodes JM (2011) Randomised placebo-controlled trial of rituximab (anti-CD20) in active ulcerative colitis. Gut 60(11):1520–1526. doi:10.1136/gut.2010.225482

    Article  PubMed  Google Scholar 

  137. Erdag G, Schaefer JT, Smolkin ME, Deacon DH, Shea SM, Dengel LT, Patterson JW, Slingluff CL Jr (2012) Immunotype and immunohistologic characteristics of tumor-infiltrating immune cells are associated with clinical outcome in metastatic melanoma. Cancer Res 72(5):1070–1080. doi:10.1158/0008-5472.CAN-11-3218

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  138. Schmidt M, Bohm D, von Torne C, Steiner E, Puhl A, Pilch H, Lehr HA, Hengstler JG, Kolbl H, Gehrmann M (2008) The humoral immune system has a key prognostic impact in node-negative breast cancer. Cancer Res 68(13):5405–5413. doi:10.1158/0008-5472.CAN-07-5206

    Article  CAS  PubMed  Google Scholar 

  139. Milne K, Kobel M, Kalloger SE, Barnes RO, Gao D, Gilks CB, Watson PH, Nelson BH (2009) Systematic analysis of immune infiltrates in high-grade serous ovarian cancer reveals CD20, FoxP3 and TIA-1 as positive prognostic factors. PLoS One 4(7):e6412. doi:10.1371/journal.pone.0006412

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  140. Linnebacher M (2013) Tumor-infiltrating B cells come into vogue. World J Gastroenterol 19(1):8–11. doi:10.3748/wjg.v19.i1.8

    Article  PubMed Central  PubMed  Google Scholar 

  141. Maletzki C, Jahnke A, Ostwald C, Klar E, Prall F, Linnebacher M (2012) Ex-vivo clonally expanded B lymphocytes infiltrating colorectal carcinoma are of mature immunophenotype and produce functional IgG. PLoS One 7(2):e32639. doi:10.1371/journal.pone.0032639

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  142. Barbera-Guillem E, Nelson MB, Barr B, Nyhus JK, May KF Jr, Feng L, Sampsel JW (2000) B lymphocyte pathology in human colorectal cancer. Experimental and clinical therapeutic effects of partial B cell depletion. Cancer Immunol Immunother 48(10):541–549

    Article  CAS  PubMed  Google Scholar 

  143. Erdman SE, Rao VP, Poutahidis T, Rogers AB, Taylor CL, Jackson EA, Ge Z, Lee CW, Schauer DB, Wogan GN, Tannenbaum SR, Fox JG (2009) Nitric oxide and TNF-alpha trigger colonic inflammation and carcinogenesis in Helicobacter hepaticus-infected, Rag2-deficient mice. Proc Natl Acad Sci U S A 106(4):1027–1032. pii:0812347106. doi:10.1073/pnas.0812347106

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  144. Meira LB, Bugni JM, Green SL, Lee CW, Pang B, Borenshtein D, Rickman BH, Rogers AB, Moroski-Erkul CA, McFaline JL, Schauer DB, Dedon PC, Fox JG, Samson LD (2008) DNA damage induced by chronic inflammation contributes to colon carcinogenesis in mice. J Clin Investig 118(7):2516–2525. doi:10.1172/JCI35073

    PubMed Central  CAS  PubMed  Google Scholar 

  145. Halliwell B (1999) Oxygen and nitrogen are pro-carcinogens. Damage to DNA by reactive oxygen, chlorine and nitrogen species: measurement, mechanism and the effects of nutrition. Mutat Res 443(1–2):37–52

    Article  CAS  PubMed  Google Scholar 

  146. Westbrook AM, Schiestl RH (2010) Atm-deficient mice exhibit increased sensitivity to dextran sulfate sodium-induced colitis characterized by elevated DNA damage and persistent immune activation. Cancer Res 70(5):1875–1884. doi:10.1158/0008-5472.CAN-09-2584

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  147. Takai A, Marusawa H, Minaki Y, Watanabe T, Nakase H, Kinoshita K, Tsujimoto G, Chiba T (2012) Targeting activation-induced cytidine deaminase prevents colon cancer development despite persistent colonic inflammation. Oncogene 31(13):1733–1742. doi:10.1038/onc.2011.352

    Article  CAS  PubMed  Google Scholar 

  148. Edwards RA, Witherspoon M, Wang K, Afrasiabi K, Pham T, Birnbaumer L, Lipkin SM (2009) Epigenetic repression of DNA mismatch repair by inflammation and hypoxia in inflammatory bowel disease-associated colorectal cancer. Cancer Res 69(16):6423–6429. doi:10.1158/0008-5472.CAN-09-1285

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  149. Endo Y, Marusawa H, Kou T, Nakase H, Fujii S, Fujimori T, Kinoshita K, Honjo T, Chiba T (2008) Activation-induced cytidine deaminase links between inflammation and the development of colitis-associated colorectal cancers. Gastroenterology 135(3):889–898, 898, e881–e883. doi:10.1053/j.gastro.2008.06.091

    Article  CAS  PubMed  Google Scholar 

  150. Hammoud SS, Cairns BR, Jones DA (2013) Epigenetic regulation of colon cancer and intestinal stem cells. Curr Opin Cell Biol 25(2):177–183. doi:10.1016/j.ceb.2013.01.007

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  151. Saito S, Kato J, Hiraoka S, Horii J, Suzuki H, Higashi R, Kaji E, Kondo Y, Yamamoto K (2011) DNA methylation of colon mucosa in ulcerative colitis patients: correlation with inflammatory status. Inflamm Bowel Dis 17(9):1955–1965. doi:10.1002/ibd.21573

    Article  PubMed  Google Scholar 

  152. Wang FY, Arisawa T, Tahara T, Takahama K, Watanabe M, Hirata I, Nakano H (2008) Aberrant DNA methylation in ulcerative colitis without neoplasia. Hepatogastroenterology 55(81):62–65

    CAS  PubMed  Google Scholar 

  153. Issa JP, Ahuja N, Toyota M, Bronner MP, Brentnall TA (2001) Accelerated age-related CpG island methylation in ulcerative colitis. Cancer Res 61(9):3573–3577

    CAS  PubMed  Google Scholar 

  154. Li Y, Deuring J, Peppelenbosch MP, Kuipers EJ, de Haar C, van der Woude CJ (2012) IL-6-induced DNMT1 activity mediates SOCS3 promoter hypermethylation in ulcerative colitis-related colorectal cancer. Carcinogenesis 33(10):1889–1896. doi:10.1093/carcin/bgs214

    Article  CAS  PubMed  Google Scholar 

  155. Eads CA, Nickel AE, Laird PW (2002) Complete genetic suppression of polyp formation and reduction of CpG-island hypermethylation in Apc(Min/+) Dnmt1-hypomorphic Mice. Cancer Res 62(5):1296–1299

    CAS  PubMed  Google Scholar 

  156. Dhir M, Montgomery EA, Glockner SC, Schuebel KE, Hooker CM, Herman JG, Baylin SB, Gearhart SL, Ahuja N (2008) Epigenetic regulation of WNT signaling pathway genes in inflammatory bowel disease (IBD) associated neoplasia. J Gastrointest Surg 12(10):1745–1753. doi:10.1007/s11605-008-0633-5

    Article  PubMed Central  PubMed  Google Scholar 

  157. Fleisher AS, Esteller M, Harpaz N, Leytin A, Rashid A, Xu Y, Liang J, Stine OC, Yin J, Zou TT, Abraham JM, Kong D, Wilson KT, James SP, Herman JG, Meltzer SJ (2000) Microsatellite instability in inflammatory bowel disease-associated neoplastic lesions is associated with hypermethylation and diminished expression of the DNA mismatch repair gene, hMLH1. Cancer Res 60(17):4864–4868

    CAS  PubMed  Google Scholar 

  158. Glauben R, Batra A, Stroh T, Erben U, Fedke I, Lehr HA, Leoni F, Mascagni P, Dinarello CA, Zeitz M, Siegmund B (2008) Histone deacetylases: novel targets for prevention of colitis-associated cancer in mice. Gut. pii:gut.2007.134650. doi:10.1136/gut.2007.134650

    Google Scholar 

  159. Motoyama K, Inoue H, Takatsuno Y, Tanaka F, Mimori K, Uetake H, Sugihara K, Mori M (2009) Over- and under-expressed microRNAs in human colorectal cancer. Int J Oncol 34(4):1069–1075

    CAS  PubMed  Google Scholar 

  160. Kanaan Z, Rai SN, Eichenberger MR, Barnes C, Dworkin AM, Weller C, Cohen E, Roberts H, Keskey B, Petras RE, Crawford NP, Galandiuk S (2012) Differential microRNA expression tracks neoplastic progression in inflammatory bowel disease-associated colorectal cancer. Hum Mutat 33(3):551–560. doi:10.1002/humu.22021

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  161. Josse C, Bouznad N, Geurts P, Irrthum A, Huynh-Thu VA, Servais L, Hego A, Delvenne P, Bours V, Oury C (2014) Identification of a microRNA landscape targeting the PI3K/Akt signaling pathway in inflammation-induced colorectal carcinogenesis. Am J Physiol Gastrointest Liver Physiol 306(3):G229–G243. doi:10.1152/ajpgi.00484.2012

    Article  CAS  PubMed  Google Scholar 

  162. Iliopoulos D, Jaeger SA, Hirsch HA, Bulyk ML, Struhl K (2010) STAT3 activation of miR-21 and miR-181b-1 via PTEN and CYLD are part of the epigenetic switch linking inflammation to cancer. Mol Cell 39(4):493–506. doi:10.1016/j.molcel.2010.07.023

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  163. Okayama H, Schetter AJ, Harris CC (2012) MicroRNAs and inflammation in the pathogenesis and progression of colon cancer. Dig Dis 30(2):9–15. doi:10.1159/000341882

    Article  PubMed  Google Scholar 

  164. Sturm A, Dignass AU (2008) Epithelial restitution and wound healing in inflammatory bowel disease. World J Gastroenterol 14(3):348–353

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  165. Nenci A, Becker C, Wullaert A, Gareus R, van Loo G, Danese S, Huth M, Nikolaev A, Neufert C, Madison B, Gumucio D, Neurath MF, Pasparakis M (2007) Epithelial NEMO links innate immunity to chronic intestinal inflammation. Nature 446(7135):557–561. doi:10.1038/nature05698

    Article  CAS  PubMed  Google Scholar 

  166. Hayden MS, West AP, Ghosh S (2006) NF-kappaB and the immune response. Oncogene 25(51):6758–6780. doi:10.1038/sj.onc.1209943

    Article  CAS  PubMed  Google Scholar 

  167. Kawai T, Akira S (2007) Signaling to NF-kappaB by Toll-like receptors. Trends Mol Med 13(11):460–469. doi:10.1016/j.molmed.2007.09.002

    Article  CAS  PubMed  Google Scholar 

  168. Vallabhapurapu S, Karin M (2009) Regulation and function of NF-kappaB transcription factors in the immune system. Annu Rev Immunol 27:693–733. doi:10.1146/annurev.immunol.021908.132641

    Article  CAS  PubMed  Google Scholar 

  169. Rogler G, Brand K, Vogl D, Page S, Hofmeister R, Andus T, Knuechel R, Baeuerle PA, Scholmerich J, Gross V (1998) Nuclear factor kappaB is activated in macrophages and epithelial cells of inflamed intestinal mucosa. Gastroenterology 115(2):357–369

    Article  CAS  PubMed  Google Scholar 

  170. Sakamoto K, Maeda S, Hikiba Y, Nakagawa H, Hayakawa Y, Shibata W, Yanai A, Ogura K, Omata M (2009) Constitutive NF-kappaB activation in colorectal carcinoma plays a key role in angiogenesis, promoting tumor growth. Clin Cancer Res 15(7):2248–2258. doi:10.1158/1078-0432.CCR-08-1383

    Article  CAS  PubMed  Google Scholar 

  171. Greten FR, Eckmann L, Greten TF, Park JM, Li ZW, Egan LJ, Kagnoff MF, Karin M (2004) IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 118(3):285–296

    Article  CAS  PubMed  Google Scholar 

  172. Lauscher JC, Grone J, Dullat S, Hotz B, Ritz JP, Steinhoff U, Buhr HJ, Visekruna A (2010) Association between activation of atypical NF-kappaB1 p105 signaling pathway and nuclear beta-catenin accumulation in colorectal carcinoma. Mol Carcinog 49(2):121–129. doi:10.1002/mc.20606

    CAS  PubMed  Google Scholar 

  173. Bollrath J, Phesse TJ, von Burstin VA, Putoczki T, Bennecke M, Bateman T, Nebelsiek T, Lundgren-May T, Canli O, Schwitalla S, Matthews V, Schmid RM, Kirchner T, Arkan MC, Ernst M, Greten FR (2009) gp130-mediated Stat3 activation in enterocytes regulates cell survival and cell-cycle progression during colitis-associated tumorigenesis. Cancer Cell 15(2):91–102. doi:10.1016/j.ccr.2009.01.002

    Article  CAS  PubMed  Google Scholar 

  174. Grivennikov S, Karin E, Terzic J, Mucida D, Yu GY, Vallabhapurapu S, Scheller J, Rose-John S, Cheroutre H, Eckmann L, Karin M (2009) IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer. Cancer Cell 15(2):103–113. doi:10.1016/j.ccr.2009.01.001

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  175. Takeda K, Clausen BE, Kaisho T, Tsujimura T, Terada N, Forster I, Akira S (1999) Enhanced Th1 activity and development of chronic enterocolitis in mice devoid of Stat3 in macrophages and neutrophils. Immunity 10(1):39–49

    Article  CAS  PubMed  Google Scholar 

  176. Welte T, Zhang SS, Wang T, Zhang Z, Hesslein DG, Yin Z, Kano A, Iwamoto Y, Li E, Craft JE, Bothwell AL, Fikrig E, Koni PA, Flavell RA, Fu XY (2003) STAT3 deletion during hematopoiesis causes Crohn’s disease-like pathogenesis and lethality: a critical role of STAT3 in innate immunity. Proc Natl Acad Sci U S A 100(4):1879–1884. doi:10.1073/pnas.0237137100

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  177. Kobayashi M, Kweon MN, Kuwata H, Schreiber RD, Kiyono H, Takeda K, Akira S (2003) Toll-like receptor-dependent production of IL-12p40 causes chronic enterocolitis in myeloid cell-specific Stat3-deficient mice. J Clin Invest 111(9):1297–1308. doi:10.1172/JCI17085

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  178. Waldner MJ, Wirtz S, Jefremow A, Warntjen M, Neufert C, Atreya R, Becker C, Weigmann B, Vieth M, Rose-John S, Neurath MF (2010) VEGF receptor signaling links inflammation and tumorigenesis in colitis-associated cancer. J Exp Med 207(13):2855–2868. doi:10.1084/jem.20100438

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  179. Musteanu M, Blaas L, Mair M, Schlederer M, Bilban M, Tauber S, Esterbauer H, Mueller M, Casanova E, Kenner L, Poli V, Eferl R (2010) Stat3 is a negative regulator of intestinal tumor progression in Apc(Min) mice. Gastroenterology 138(3):1003–1011, e1001–e1005. doi:10.1053/j.gastro.2009.11.049

    Article  CAS  PubMed  Google Scholar 

  180. Bollrath J, Greten FR (2009) IKK/NF-kappaB and STAT3 pathways: central signalling hubs in inflammation-mediated tumour promotion and metastasis. EMBO Rep 10(12):1314–1319. doi:10.1038/embor.2009.243

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  181. de Lau W, Barker N, Clevers H (2007) WNT signaling in the normal intestine and colorectal cancer. Front Biosci 12:471–491

    Article  CAS  PubMed  Google Scholar 

  182. Kanwar SS, Yu Y, Nautiyal J, Patel BB, Majumdar AP (2010) The Wnt/beta-catenin pathway regulates growth and maintenance of colonospheres. Mol Cancer 9:212. doi:10.1186/1476-4598-9-212

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  183. Claessen MM, Schipper ME, Oldenburg B, Siersema PD, Offerhaus GJ, Vleggaar FP (2010) WNT-pathway activation in IBD-associated colorectal carcinogenesis: potential biomarkers for colonic surveillance. Cell Oncol 32(4):303–310. pii:F4784644K33268J1. doi:10.3233/CLO-2009-0503

    CAS  PubMed  PubMed Central  Google Scholar 

  184. van Dekken H, Wink JC, Vissers KJ, Franken PF, Ruud Schouten W, WC JH, Kuipers EJ, Fodde R, Janneke van der Woude C (2007) Wnt pathway-related gene expression during malignant progression in ulcerative colitis. Acta Histochem 109(4):266–272. doi:10.1016/j.acthis.2007.02.007

    Article  CAS  PubMed  Google Scholar 

  185. Castellone MD, Teramoto H, Williams BO, Druey KM, Gutkind JS (2005) Prostaglandin E2 promotes colon cancer cell growth through a Gs-axin-beta-catenin signaling axis. Science 310(5753):1504–1510

    Article  CAS  PubMed  Google Scholar 

  186. Duan Y, Liao AP, Kuppireddi S, Ye Z, Ciancio MJ, Sun J (2007) Beta-catenin activity negatively regulates bacteria-induced inflammation. Lab Invest 87(6):613–624. doi:10.1038/labinvest.3700545

    CAS  PubMed  Google Scholar 

  187. Deng J, Xia W, Miller SA, Wen Y, Wang HY, Hung MC (2004) Crossregulation of NF-kappaB by the APC/GSK-3beta/beta-catenin pathway. Mol Carcinog 39(3):139–146. doi:10.1002/mc.10169

    Article  CAS  PubMed  Google Scholar 

  188. Du Q, Zhang X, Cardinal J, Cao Z, Guo Z, Shao L, Geller DA (2009) Wnt/beta-catenin signaling regulates cytokine-induced human inducible nitric oxide synthase expression by inhibiting nuclear factor-kappaB activation in cancer cells. Cancer Res 69(9):3764–3771. doi:10.1158/0008-5472.CAN-09-0014

    Article  CAS  PubMed  Google Scholar 

  189. Schon S, Flierman I, Ofner A, Stahringer A, Holdt LM, Kolligs FT, Herbst A (2014) Beta-catenin regulates NF-kappaB activity via TNFRSF19 in colorectal cancer cells. Int J Cancer. doi:10.1002/ijc.28839

    Google Scholar 

  190. Chandrakesan P, Jakkula LU, Ahmed I, Roy B, Anant S, Umar S (2013) Differential effects of beta-catenin and NF-kappaB interplay in the regulation of cell proliferation, inflammation and tumorigenesis in response to bacterial infection. PLoS One 8(11):e79432. doi:10.1371/journal.pone.0079432

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  191. Chen W, Liu F, Ling Z, Tong X, Xiang C (2012) Human intestinal lumen and mucosa-associated microbiota in patients with colorectal cancer. PLoS One 7(6):e39743. doi:10.1371/journal.pone.0039743

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  192. Frank DN, Robertson CE, Hamm CM, Kpadeh Z, Zhang T, Chen H, Zhu W, Sartor RB, Boedeker EC, Harpaz N, Pace NR, Li E (2011) Disease phenotype and genotype are associated with shifts in intestinal-associated microbiota in inflammatory bowel diseases. Inflamm Bowel Dis 17(1):179–184. doi:10.1002/ibd.21339

    Article  PubMed  Google Scholar 

  193. Shen XJ, Rawls JF, Randall T, Burcal L, Mpande CN, Jenkins N, Jovov B, Abdo Z, Sandler RS, Keku TO (2010) Molecular characterization of mucosal adherent bacteria and associations with colorectal adenomas. Gut Microbes 1(3):138–147. doi:10.4161/gmic.1.3.12360

    Article  PubMed Central  PubMed  Google Scholar 

  194. Sobhani I, Tap J, Roudot-Thoraval F, Roperch JP, Letulle S, Langella P, Corthier G, Tran Van Nhieu J, Furet JP (2011) Microbial dysbiosis in colorectal cancer (CRC) patients. PLoS One 6(1):e16393. doi:10.1371/journal.pone.0016393

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  195. Wang Y, Devkota S, Musch MW, Jabri B, Nagler C, Antonopoulos DA, Chervonsky A, Chang EB (2010) Regional mucosa-associated microbiota determine physiological expression of TLR2 and TLR4 in murine colon. PLoS One 5(10):e13607. doi:10.1371/journal.pone.0013607

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  196. Willing BP, Dicksved J, Halfvarson J, Andersson AF, Lucio M, Zheng Z, Jarnerot G, Tysk C, Jansson JK, Engstrand L (2010) A pyrosequencing study in twins shows that gastrointestinal microbial profiles vary with inflammatory bowel disease phenotypes. Gastroenterology 139(6):1844–1854, e1841. doi:10.1053/j.gastro.2010.08.049

    Article  PubMed  Google Scholar 

  197. Uronis JM, Muhlbauer M, Herfarth HH, Rubinas TC, Jones GS, Jobin C (2009) Modulation of the intestinal microbiota alters colitis-associated colorectal cancer susceptibility. PLoS One 4(6):e6026. doi:10.1371/journal.pone.0006026

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  198. Nagamine CM, Rogers AB, Fox JG, Schauer DB (2008) Helicobacter hepaticus promotes azoxymethane-initiated colon tumorigenesis in BALB/c-IL10-deficient mice. Int J Cancer 122(4):832–838. doi:10.1002/ijc.23175

    Article  CAS  PubMed  Google Scholar 

  199. Arthur JC, Perez-Chanona E, Muhlbauer M, Tomkovich S, Uronis JM, Fan TJ, Campbell BJ, Abujamel T, Dogan B, Rogers AB, Rhodes JM, Stintzi A, Simpson KW, Hansen JJ, Keku TO, Fodor AA, Jobin C (2012) Intestinal inflammation targets cancer-inducing activity of the microbiota. Science 338(6103):120–123. doi:10.1126/science.1224820

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  200. Wu S, Rhee KJ, Albesiano E, Rabizadeh S, Wu X, Yen HR, Huso DL, Brancati FL, Wick E, McAllister F, Housseau F, Pardoll DM, Sears CL (2009) A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat Med 15(9):1016–1022. doi:10.1038/nm.2015

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  201. Sears CL, Pardoll DM (2011) Perspective: alpha-bugs, their microbial partners, and the link to colon cancer. J Infect Dis 203(3):306–311. doi:10.1093/jinfdis/jiq061

    Article  PubMed Central  PubMed  Google Scholar 

  202. Backhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI (2005) Host-bacterial mutualism in the human intestine. Science 307(5717):1915–1920

    Article  PubMed  CAS  Google Scholar 

  203. Couturier-Maillard A, Secher T, Rehman A, Normand S, De Arcangelis A, Haesler R, Huot L, Grandjean T, Bressenot A, Delanoye-Crespin A, Gaillot O, Schreiber S, Lemoine Y, Ryffel B, Hot D, Nunez G, Chen G, Rosenstiel P, Chamaillard M (2013) NOD2-mediated dysbiosis predisposes mice to transmissible colitis and colorectal cancer. J Clin Invest 123(2):700–711. doi:10.1172/JCI62236

    PubMed Central  CAS  PubMed  Google Scholar 

  204. Liang X, Li H, Tian G, Li S (2014) Dynamic microbe and molecule networks in a mouse model of colitis-associated colorectal cancer. Sci Rep 4:4985. doi:10.1038/srep04985

    PubMed Central  CAS  PubMed  Google Scholar 

  205. Tjalsma H, Boleij A, Marchesi JR, Dutilh BE (2012) A bacterial driver-passenger model for colorectal cancer: beyond the usual suspects. Nat Rev Microbiol 10(8):575–582. doi:10.1038/nrmicro2819

    Article  CAS  PubMed  Google Scholar 

  206. Moossavi S, Rezaei N (2013) Toll-like receptor signalling and their therapeutic targeting in colorectal cancer. Int Immunopharmacol 16(2):199–209. doi:10.1016/j.intimp.2013.03.017

    Article  CAS  PubMed  Google Scholar 

  207. Cario E, Podolsky DK (2000) Differential alteration in intestinal epithelial cell expression of toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease. Infect Immun 68(12):7010–7017

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  208. Hausmann M, Kiessling S, Mestermann S, Webb G, Spottl T, Andus T, Scholmerich J, Herfarth H, Ray K, Falk W, Rogler G (2002) Toll-like receptors 2 and 4 are up-regulated during intestinal inflammation. Gastroenterology 122(7):1987–2000

    Article  CAS  PubMed  Google Scholar 

  209. Fukata M, Chen A, Vamadevan AS, Cohen J, Breglio K, Krishnareddy S, Hsu D, Xu R, Harpaz N, Dannenberg AJ, Subbaramaiah K, Cooper HS, Itzkowitz SH, Abreu MT (2007) Toll-like receptor-4 promotes the development of colitis-associated colorectal tumors. Gastroenterology 133(6):1869–1881. doi:10.1053/j.gastro.2007.09.008

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  210. Lowe EL, Crother TR, Rabizadeh S, Hu B, Wang H, Chen S, Shimada K, Wong MH, Michelsen KS, Arditi M (2010) Toll-like receptor 2 signaling protects mice from tumor development in a mouse model of colitis-induced cancer. PLoS One 5(9):e13027. doi:10.1371/journal.pone.0013027

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  211. Salcedo R, Worschech A, Cardone M, Jones Y, Gyulai Z, Dai RM, Wang E, Ma W, Haines D, O’HUigin C, Marincola FM, Trinchieri G (2010) MyD88-mediated signaling prevents development of adenocarcinomas of the colon: role of interleukin 18. J Exp Med 207(8):1625–1636. doi:10.1084/jem.20100199

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  212. Rakoff-Nahoum S, Medzhitov R (2007) Regulation of spontaneous intestinal tumorigenesis through the adaptor protein MyD88. Science 317(5834):124–127. doi:10.1126/science.1140488

    Article  CAS  PubMed  Google Scholar 

  213. Kim YS, Milner JA (2007) Dietary modulation of colon cancer risk. J Nutr 137(11 Suppl):2576S–2579S

    PubMed  Google Scholar 

  214. Pericleous M, Mandair D, Caplin ME (2013) Diet and supplements and their impact on colorectal cancer. J Gastrointest Oncol 4(4):409–423. doi:10.3978/j.issn.2078-6891.2013.003

    PubMed Central  CAS  PubMed  Google Scholar 

  215. Magalhaes B, Peleteiro B, Lunet N (2012) Dietary patterns and colorectal cancer: systematic review and meta-analysis. Eur J Cancer Prevent 21(1):15–23. doi:10.1097/CEJ.0b013e3283472241

    Article  CAS  Google Scholar 

  216. Ou J, Carbonero F, Zoetendal EG, DeLany JP, Wang M, Newton K, Gaskins HR, O’Keefe SJ (2013) Diet, microbiota, and microbial metabolites in colon cancer risk in rural Africans and African Americans. Am J Clin Nutr 98(1):111–120. doi:10.3945/ajcn.112.056689

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  217. Hofmanova J, Strakova N, Vaculova AH, Tylichova Z, Safarikova B, Skender B, Kozubik A (2014) Interaction of dietary fatty acids with tumour necrosis factor family cytokines during colon inflammation and cancer. Mediators Inflamm 2014:848632. doi:10.1155/2014/848632

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  218. Bernstein C, Holubec H, Bhattacharyya AK, Nguyen H, Payne CM, Zaitlin B, Bernstein H (2011) Carcinogenicity of deoxycholate, a secondary bile acid. Arch Toxicol 85 (8):863–871. doi:10.1007/s00204-011-0648-7

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  219. Yasui Y, Hosokawa M, Mikami N, Miyashita K, Tanaka T (2011) Dietary astaxanthin inhibits colitis and colitis-associated colon carcinogenesis in mice via modulation of the inflammatory cytokines. Chem Biol Interact 193(1):79–87. doi:10.1016/j.cbi.2011.05.006

    Article  CAS  PubMed  Google Scholar 

  220. Chung MY, Lim TG, Lee KW (2013) Molecular mechanisms of chemopreventive phytochemicals against gastroenterological cancer development. World J Gastroenterol 19(7):984–993. doi:10.3748/wjg.v19.i7.984

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  221. Piazzi G, D’Argenio G, Prossomariti A, Lembo V, Mazzone G, Candela M, Biagi E, Brigidi P, Vitaglione P, Fogliano V, D’Angelo L, Fazio C, Munarini A, Belluzzi A, Ceccarelli C, Chieco P, Balbi T, Loadman PM, Hull MA, Romano M, Bazzoli F, Ricciardiello L (2014) Eicosapentaenoic acid free fatty acid prevents and suppresses colonic neoplasia in colitis-associated colorectal cancer acting on Notch signaling and gut microbiota. Int J Cancer. doi:10.1002/ijc.28853

    Google Scholar 

  222. Meeker S, Seamons A, Paik J, Treuting PM, Brabb T, Grady WM, Maggio-Price L (2014) Increased dietary vitamin D suppresses MAPK signaling, colitis and colon cancer. Cancer Res. doi:10.1158/0008-5472.CAN-13-2820

    Google Scholar 

  223. Murillo G, Nagpal V, Tiwari N, Benya RV, Mehta RG (2010) Actions of vitamin D are mediated by the TLR4 pathway in inflammation-induced colon cancer. J Steroid Biochem Mol Biol 121(1–2):403–407. doi:10.1016/j.jsbmb.2010.03.009

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  224. Chapkin RS, Kamen BA, Callaway ES, Davidson LA, George NI, Wang N, Lupton JR, Finnell RH (2009) Use of a novel genetic mouse model to investigate the role of folate in colitis-associated colon cancer. J Nutr Biochem 20(8):649–655. doi:10.1016/j.jnutbio.2008.07.001

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  225. Ning Y, Wang L, Giovannucci EL (2010) A quantitative analysis of body mass index and colorectal cancer: findings from 56 observational studies. Obes Rev 11(1):19–30. doi:10.1111/j.1467-789X.2009.00613.x

    Article  CAS  PubMed  Google Scholar 

  226. Aleksandrova K, Nimptsch K, Pischon T (2013) Obesity and colorectal cancer. Front Biosci 5:61–77

    Google Scholar 

  227. Chen J, Huang XF (2009) Adiponectin in obesity-associated colon cancer and its preventive implications: comment on ‟Association of visceral fat accumulation and adiponectin levels with colorectal neoplasia”. Dig Dis Sci 54(8):1810–1811. doi:10.1007/s10620-009-0857-6

    Article  PubMed  Google Scholar 

  228. Yehuda-Shnaidman E, Schwartz B (2012) Mechanisms linking obesity, inflammation and altered metabolism to colon carcinogenesis. Obes Rev 13(12):1083–1095. doi:10.1111/j.1467-789X.2012.01024.x

    Article  CAS  PubMed  Google Scholar 

  229. Arkan MC, Hevener AL, Greten FR, Maeda S, Li ZW, Long JM, Wynshaw-Boris A, Poli G, Olefsky J, Karin M (2005) IKK-beta links inflammation to obesity-induced insulin resistance. Nat Med 11(2):191–198. pii:nm1185. doi:10.1038/nm1185

    Article  CAS  PubMed  Google Scholar 

  230. Suganami T, Tanimoto-Koyama K, Nishida J, Itoh M, Yuan X, Mizuarai S, Kotani H, Yamaoka S, Miyake K, Aoe S, Kamei Y, Ogawa Y (2007) Role of the Toll-like receptor 4/NF-kappaB pathway in saturated fatty acid-induced inflammatory changes in the interaction between adipocytes and macrophages. Arterioscler Thromb Vasc Biol 27(1):84–91. doi:10.1161/01.ATV.0000251608.09329.9a

    Article  CAS  PubMed  Google Scholar 

  231. de La Serre CB, Ellis CL, Lee J, Hartman AL, Rutledge JC, Raybould HE (2010) Propensity to high-fat diet-induced obesity in rats is associated with changes in the gut microbiota and gut inflammation. Am J Physiol Gastrointest Liver Physiol 299(2):G440–G448. doi:10.1152/ajpgi.00098.2010

    Article  CAS  Google Scholar 

  232. Fenton JI, Nunez NP, Yakar S, Perkins SN, Hord NG, Hursting SD (2009) Diet-induced adiposity alters the serum profile of inflammation in C57BL/6N mice as measured by antibody array. Diabetes Obes Metab 11(4):343–354. doi:10.1111/j.1463-1326.2008.00974.x

    Article  CAS  PubMed  Google Scholar 

  233. Siegmund B, Lehr HA, Fantuzzi G (2002) Leptin: a pivotal mediator of intestinal inflammation in mice. Gastroenterology 122(7):2011–2025

    Article  CAS  PubMed  Google Scholar 

  234. Tuominen I, Al-Rabadi L, Stavrakis D, Karagiannides I, Pothoulakis C, Bugni JM (2013) Diet-induced obesity promotes colon tumor development in azoxymethane-treated mice. PLoS One 8(4):e60939. doi:10.1371/journal.pone.0060939

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  235. Park SY, Kim JS, Seo YR, Sung MK (2012) Effects of diet-induced obesity on colitis-associated colon tumor formation in A/J mice. Int J Obes (Lond) 36(2):273–280. doi:10.1038/ijo.2011.83

    Article  CAS  Google Scholar 

  236. Jain SS, Bird RP (2010) Elevated expression of tumor necrosis factor-alpha signaling molecules in colonic tumors of Zucker obese (fa/fa) rats. Int J Cancer 127(9):2042–2050. doi:10.1002/ijc.25232

    Article  CAS  PubMed  Google Scholar 

  237. Teraoka N, Mutoh M, Takasu S, Ueno T, Nakano K, Takahashi M, Imai T, Masuda S, Sugimura T, Wakabayashi K (2011) High susceptibility to azoxymethane-induced colorectal carcinogenesis in obese KK-Ay mice. Int J Cancer 129(3):528–535. doi:10.1002/ijc.25711

    Article  CAS  PubMed  Google Scholar 

  238. Ealey KN, Lu S, Archer MC (2008) Development of aberrant crypt foci in the colons of ob/ob and db/db mice: evidence that leptin is not a promoter. Mol Carcinog 47(9):667–677. doi:10.1002/mc.20419

    Article  CAS  PubMed  Google Scholar 

  239. Hirose Y, Hata K, Kuno T, Yoshida K, Sakata K, Yamada Y, Tanaka T, Reddy BS, Mori H (2004) Enhancement of development of azoxymethane-induced colonic premalignant lesions in C57BL/KsJ-db/db mice. Carcinogenesis 25(5):821–825. doi:10.1093/carcin/bgh059

    Article  CAS  PubMed  Google Scholar 

  240. Flores MB, Rocha GZ, Damas-Souza DM, Osorio-Costa F, Dias MM, Ropelle ER, Camargo JA, de Carvalho RB, Carvalho HF, Saad MJ, Carvalheira JB (2012) Obesity-induced increase in tumor necrosis factor-alpha leads to development of colon cancer in mice. Gastroenterology 143(3):741–753, e741–e744. doi:10.1053/j.gastro.2012.05.045

    Article  CAS  PubMed  Google Scholar 

  241. Backhed F, Manchester JK, Semenkovich CF, Gordon JI (2007) Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci U S A 104(3):979–984. doi:10.1073/pnas.0605374104

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  242. Ley RE, Backhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI (2005) Obesity alters gut microbial ecology. Proc Natl Acad S U S A 102(31):11070–11075. doi:10.1073/pnas.0504978102

    Article  CAS  Google Scholar 

  243. Ley RE, Turnbaugh PJ, Klein S, Gordon JI (2006) Microbial ecology: human gut microbes associated with obesity. Nature 444(7122):1022–1023. doi:10.1038/4441022a

    Article  CAS  PubMed  Google Scholar 

  244. Turnbaugh PJ, Backhed F, Fulton L, Gordon JI (2008) Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe 3(4):213–223. doi:10.1016/j.chom.2008.02.015

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  245. Brun P, Castagliuolo I, Di Leo V, Buda A, Pinzani M, Palu G, Martines D (2007) Increased intestinal permeability in obese mice: new evidence in the pathogenesis of nonalcoholic steatohepatitis. Am J Physiol Gastrointest Liver Physiol 292(2):G518–G525. doi:10.1152/ajpgi.00024.2006

    Article  CAS  PubMed  Google Scholar 

  246. Erridge C, Attina T, Spickett CM, Webb DJ (2007) A high-fat meal induces low-grade endotoxemia: evidence of a novel mechanism of postprandial inflammation. Am J Clinical Nutr 86(5):1286–1292

    CAS  Google Scholar 

  247. Lassenius MI, Pietilainen KH, Kaartinen K, Pussinen PJ, Syrjanen J, Forsblom C, Porsti I, Rissanen A, Kaprio J, Mustonen J, Groop PH, Lehto M (2011) Bacterial endotoxin activity in human serum is associated with dyslipidemia, insulin resistance, obesity, and chronic inflammation. Diabetes Care 34(8):1809–1815. doi:10.2337/dc10-2197

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  248. Kim SJ, Choi Y, Choi YH, Park T (2011) Obesity activates toll-like receptor-mediated proinflammatory signaling cascades in the adipose tissue of mice. J Nutr Biochem. doi:10.1016/j.jnutbio.2010.10.012

    Google Scholar 

  249. Nakarai H, Yamashita A, Nagayasu S, Iwashita M, Kumamoto S, Ohyama H, Hata M, Soga Y, Kushiyama A, Asano T, Abiko Y, Nishimura F (2011) Adipocyte-macrophage interaction may mediate LPS-induced low-grade inflammation: potential link with metabolic complications. Innate Immun. doi:10.1177/1753425910393370

    Google Scholar 

  250. Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin H, Flier JS (2006) TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clinical Invest 116(11):3015–3025. doi:10.1172/JCI28898

    Article  CAS  Google Scholar 

  251. Batra A, Heimesaat MM, Bereswill S, Fischer A, Glauben R, Kunkel D, Scheffold A, Erben U, Kuhl A, Loddenkemper C, Lehr HA, Schumann M, Schulzke JD, Zeitz M, Siegmund B (2012) Mesenteric fat—control site for bacterial translocation in colitis? Mucosal Immunol 5(5):580–591. doi:10.1038/mi.2012.33

    CAS  PubMed  Google Scholar 

  252. Pinczowski D, Ekbom A, Baron J, Yuen J, Adami HO (1994) Risk factors for colorectal cancer in patients with ulcerative colitis: a case-control study. Gastroenterology 107(1):117–120

    CAS  PubMed  Google Scholar 

  253. Stolfi C, De Simone V, Pallone F, Monteleone G (2013) Mechanisms of action of non-steroidal anti-inflammatory drugs (NSAIDs) and mesalazine in the chemoprevention of colorectal cancer. Int J Mol Sci 14(9):17972–17985. doi:10.3390/ijms140917972

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  254. Bernstein CN, Nugent Z, Blanchard JF (2011) 5-aminosalicylate is not chemoprophylactic for colorectal cancer in IBD: a population based study. A J Gastroenterol 106(4):731–736. doi:10.1038/ajg.2011.50

    Article  CAS  Google Scholar 

  255. Tang J, Sharif O, Pai C, Silverman AL (2010) Mesalamine protects against colorectal cancer in inflammatory bowel disease. Dig Dis Sci 55(6):1696–1703. doi:10.1007/s10620-009-0942-x

    Article  CAS  PubMed  Google Scholar 

  256. Terdiman JP, Steinbuch M, Blumentals WA, Ullman TA, Rubin DT (2007) 5-Aminosalicylic acid therapy and the risk of colorectal cancer among patients with inflammatory bowel disease. Inflamm Bowel Dis 13(4):367–371. doi:10.1002/ibd.20074

    Article  PubMed  Google Scholar 

  257. van Staa TP, Card T, Logan RF, Leufkens HG (2005) 5-Aminosalicylate use and colorectal cancer risk in inflammatory bowel disease: a large epidemiological study. Gut 54(11):1573–1578. doi:10.1136/gut.2005.070896

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  258. Gasche C, Goel A, Natarajan L, Boland CR (2005) Mesalazine improves replication fidelity in cultured colorectal cells. Cancer Res 65(10):3993–3997

    Article  CAS  PubMed  Google Scholar 

  259. Koelink PJ, Robanus-Maandag EC, Devilee P, Hommes DW, Lamers CB, Verspaget HW (2009) 5-Aminosalicylic acid inhibits colitis-associated but not sporadic colorectal neoplasia in a novel conditional Apc mouse model. Carcinogenesis 30(7):1217–1224. pii:bgp113. doi:10.1093/carcin/bgp113

    Article  CAS  PubMed  Google Scholar 

  260. Lu D, Cottam HB, Corr M, Carson DA (2005) Repression of beta-catenin function in malignant cells by nonsteroidal antiinflammatory drugs. Proc Natl Acad Sci U S A 102(51):18567–18571. doi:10.1073/pnas.0509316102

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  261. Stolfi C, Pellegrini R, Franze E, Pallone F, Monteleone G (2008) Molecular basis of the potential of mesalazine to prevent colorectal cancer. World J Gastroenterol 14(28):4434–4439

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  262. Konidari A, Matary WE (2014) Use of thiopurines in inflammatory bowel disease: Safety issues. World J Gastrointest Pharmacol Ther 5(2):63–76. doi:10.4292/wjgpt.v5.i2.63

    PubMed Central  PubMed  Google Scholar 

  263. Matula S, Croog V, Itzkowitz S, Harpaz N, Bodian C, Hossain S, Ullman T (2005) Chemoprevention of colorectal neoplasia in ulcerative colitis: the effect of 6-mercaptopurine. Clin Gastroenterol Hepatol 3(10):1015–1021

    Article  CAS  PubMed  Google Scholar 

  264. van Schaik FD, van Oijen MG, Smeets HM, van der Heijden GJ, Siersema PD, Oldenburg B (2012) Thiopurines prevent advanced colorectal neoplasia in patients with inflammatory bowel disease. Gut 61(2):235–240. doi:10.1136/gut.2011.237412

    Article  CAS  PubMed  Google Scholar 

  265. Subramanian V, Logan RF (2011) Chemoprevention of colorectal cancer in inflammatory bowel disease. Best Pract Res Clin Gastroenterol 25(4–5):593–606. doi:10.1016/j.bpg.2011.09.003

    Article  CAS  PubMed  Google Scholar 

  266. Beaugerie L, Svrcek M, Seksik P, Bouvier AM, Simon T, Allez M, Brixi H, Gornet JM, Altwegg R, Beau P, Duclos B, Bourreille A, Faivre J, Peyrin-Biroulet L, Flejou JF, Carrat F, Group CS (2013) Risk of colorectal high-grade dysplasia and cancer in a prospective observational cohort of patients with inflammatory bowel disease. Gastroenterology 145(1):166–175, e168. doi:10.1053/j.gastro.2013.03.044

    Article  PubMed  Google Scholar 

  267. Lopez A, Mounier M, Bouvier AM, Carrat F, Maynadie M, Beaugerie L, Peyrin-Biroulet L, Group CS (2014) Increased risk of acute myeloid leukemias and myelodysplastic syndromes in patients who received thiopurine treatment for inflammatory bowel disease. Clin Gastroenterol Hepatol. doi:10.1016/j.cgh.2014.02.026

    Google Scholar 

  268. Sokol H, Beaugerie L, Maynadie M, Laharie D, Dupas JL, Flourie B, Lerebours E, Peyrin-Biroulet L, Allez M, Simon T, Carrat F, Brousse N, Group CS (2012) Excess primary intestinal lymphoproliferative disorders in patients with inflammatory bowel disease. Inflamm Bowel Dis 18(11):2063–2071. doi:10.1002/ibd.22889

    Article  PubMed  Google Scholar 

  269. Kim YJ, Hong KS, Chung JW, Kim JH, Hahm KB (2010) Prevention of colitis-associated carcinogenesis with infliximab. Cancer Prev Res 3(10):1314–1333. doi:10.1158/1940-6207.CAPR-09-0272

    Article  CAS  Google Scholar 

  270. Csillag C, Borup R, Olsen J, Nielsen FC, Nielsen OH (2007) Treatment response and colonic gene expression in patients with Crohn’s disease. Scand J Gastroenterol 42(7):834–840. doi:10.1080/00365520601127166

    Article  CAS  PubMed  Google Scholar 

  271. Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, Travers S, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJ, Present D, Sands BE, Colombel JF (2005) Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 353(23):2462–2476. pii:353/23/2462. doi:10.1056/NEJMoa050516

    Article  CAS  PubMed  Google Scholar 

  272. Yao X, Huang J, Zhong H, Shen N, Faggioni R, Fung M, Yao Y (2014) Targeting interleukin-6 in inflammatory autoimmune diseases and cancers. Pharmacol Ther 141(2):125–139. doi:10.1016/j.pharmthera.2013.09.004

    Article  CAS  PubMed  Google Scholar 

  273. Abraham C, Medzhitov R (2011) Interactions between the host innate immune system and microbes in inflammatory bowel disease. Gastroenterology 140(6):1729–1737. doi:10.1053/j.gastro.2011.02.012

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  274. Isaacs K, Herfarth H (2008) Role of probiotic therapy in IBD. Inflamm Bowel Dis 14(11):1597–1605. doi:10.1002/ibd.20465

    Article  PubMed  Google Scholar 

  275. Appleyard CB, Cruz ML, Isidro AA, Arthur JC, Jobin C, De Simone C (2011) Pretreatment with the probiotic VSL#3 delays transition from inflammation to dysplasia in a rat model of colitis-associated cancer. Am J Physiol Gastrointest Liver Physiol 301(6):G1004–G1013. doi:10.1152/ajpgi.00167.2011

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  276. Arthur JC, Gharaibeh RZ, Uronis JM, Perez-Chanona E, Sha W, Tomkovich S, Muhlbauer M, Fodor AA, Jobin C (2013) VSL#3 probiotic modifies mucosal microbial composition but does not reduce colitis-associated colorectal cancer. Sci Rep 3:2868. doi:10.1038/srep02868

    Article  PubMed Central  PubMed  Google Scholar 

  277. Bassaganya-Riera J, Viladomiu M, Pedragosa M, De Simone C, Hontecillas R (2012) Immunoregulatory mechanisms underlying prevention of colitis-associated colorectal cancer by probiotic bacteria. PLoS One 7(4):e34676. doi:10.1371/journal.pone.0034676

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  278. Ley RE, Hamady M, Lozupone C, Turnbaugh PJ, Ramey RR, Bircher JS, Schlegel ML, Tucker TA, Schrenzel MD, Knight R, Gordon JI (2008) Evolution of mammals and their gut microbes. Science 320(5883):1647–1651. pii:1155725. doi:10.1126/science.1155725

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  279. Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R (2012) Diversity, stability and resilience of the human gut microbiota. Nature 489(7415):220–230. doi:10.1038/nature11550

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  280. Mueller MM, Fusenig NE (2004) Friends or foes—bipolar effects of the tumour stroma in cancer. Nat Rev Cancer 4(11):839–849. doi:10.1038/nrc1477

    Article  CAS  PubMed  Google Scholar 

  281. Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420(6917):860–867

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  282. Oohashi Y, Ishioka T, Wakabayashi K, Kuwabara N (1981) A study on carcinogenesis induced by degraded carrageenan arising from squamous metaplasia of the rat colorectum. Cancer Lett 14(3):267–272

    Article  CAS  PubMed  Google Scholar 

  283. Wang JG, Wang DF, Lv BJ, Si JM (2004) A novel mouse model for colitis-associated colon carcinogenesis induced by 1,2-dimethylhydrazine and dextran sulfate sodium. World J Gastroenterol 10(20):2958–2962

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  284. Shattuck-Brandt RL, Varilek GW, Radhika A, Yang F, Washington MK, DuBois RN (2000) Cyclooxygenase 2 expression is increased in the stroma of colon carcinomas from IL-10(–/–) mice. Gastroenterology 118(2):337–345

    Article  CAS  PubMed  Google Scholar 

  285. Rudolph U, Finegold MJ, Rich SS, Harriman GR, Srinivasan Y, Brabet P, Boulay G, Bradley A, Birnbaumer L (1995) Ulcerative colitis and adenocarcinoma of the colon in G alpha i2-deficient mice. Nat Genet 10(2):143–150. doi:10.1038/ng0695-143

    Article  CAS  PubMed  Google Scholar 

  286. Chu FF, Esworthy RS, Chu PG, Longmate JA, Huycke MM, Wilczynski S, Doroshow JH (2004) Bacteria-induced intestinal cancer in mice with disrupted Gpx1 and Gpx2 genes. Cancer Res 64(3):962–968

    Article  CAS  PubMed  Google Scholar 

  287. Kado S, Uchida K, Funabashi H, Iwata S, Nagata Y, Ando M, Onoue M, Matsuoka Y, Ohwaki M, Morotomi M (2001) Intestinal microflora are necessary for development of spontaneous adenocarcinoma of the large intestine in T-cell receptor beta chain and p53 double-knockout mice. Cancer Res 61(6):2395–2398

    CAS  PubMed  Google Scholar 

  288. Sohn KJ, Shah SA, Reid S, Choi M, Carrier J, Comiskey M, Terhorst C, Kim YI (2001) Molecular genetics of ulcerative colitis-associated colon cancer in the interleukin 2- and beta(2)-microglobulin-deficient mouse. Cancer Res 61(18):6912–6917

    CAS  PubMed  Google Scholar 

  289. Ben-Neriah Y, Karin M (2011) Inflammation meets cancer, with NF-[kappa]B as the matchmake. Nat Immunol 12(8):715–723

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Division of Gastroenterology, University of Miami Miller School of Medicine, Miami, FL, USA

    Rishu Dheer PhD, Julie M. Davies PhD & Maria T. Abreu MD

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  1. Rishu Dheer PhD
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  2. Julie M. Davies PhD
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Correspondence to Maria T. Abreu MD .

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  1. Department of Medicine, Stony Brook University, Stony Brook, USA

    Vincent W. Yang

  2. Department of Medicine, Stony Brook University, Stony Brook, New York, USA

    Agnieszka B. Bialkowska

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Dheer, R., Davies, J., Abreu, M. (2015). Inflammation and Colorectal Cancer. In: Yang, V., Bialkowska, A. (eds) Intestinal Tumorigenesis. Springer, Cham. https://doi.org/10.1007/978-3-319-19986-3_8

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