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Cytokines, NF-κB, Microenvironment, Intestinal Inflammation and Cancer

  • Chapter
The Link Between Inflammation and Cancer

Part of the book series: Cancer Treatment and Research ((CTAR,volume 130))

Abstract

Inflammation and cancer have been viewed as closely linked for many years. This link is not merely a loose association but causative. In colorectal cancer (CRC), chronic inflammation as observed in inflammatory bowel (IBD) disease is a key predisposing factor and IBD-associated CRC comprises five percent of all CRCs. Although the molecular mechanisms linking IBD with CRC are not well understood, recent results obtained in preclinical models point to the transcription factor NF-κB as a central player. On the one hand, NF-κB regulates the expression of various cytokines and modulates the inflammatory processes in IBD. On the other, NF-κB stimulates the proliferation of tumor cells and enhances their survival through the regulation of anti-apoptotic genes. Furthermore, it has been clearly established that most carcinogens and tumor promoters activate NF-κB, while chemopreventive agents generally suppress this transcription factor. Actually, several lines of evidence suggest that activation of NF-κB may cause cancer. These include the finding that NF-κB genes can be oncogenes, and that this transcription factor controls apoptosis, cell-cycle progression and proliferation, and possibly also cell differentiation.

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6. References

  • Akagi, Y. et al. (1999). Regulation of vascular endothelial growth factor expression in human colon cancer by interleukin-lbeta. Br. J. Cancer 80: 1506–1511.

    PubMed  CAS  Google Scholar 

  • Ames, B.N. et al. (1995). The causes and prevention of cancer. Proc. Natl Acad. Sci. USA 92: 5258–5265.

    PubMed  CAS  Google Scholar 

  • Arii, S. et al. (1999). Implication of vascular endothelial growth factor in the development and metastasis of human cancers. Hum. Cell 12: 25–30.

    PubMed  CAS  Google Scholar 

  • Ashikawa, K. et al. (2004). Evidence that activation of nuclear factor-kappaB is essential for the cytotoxic effects of doxorubicin and its analogues. Biochem. Pharmacol. 67: 353–364.

    PubMed  CAS  Google Scholar 

  • Baldwin, A.S., Jr. (1996). The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu. Rev. Immunol. 14: 649–683.

    PubMed  CAS  Google Scholar 

  • Baldwin, A.S., Jr. (2001). Control of oncogenesis and cancer therapy resistance by the transcription factor NF-kappaB. J. Clin. Invest. 107: 241–246.

    PubMed  CAS  Google Scholar 

  • Baldwin, A.S., Jr. (2001). Series Introduction: The transcription factor NF-kappaB and human disease. J. Clin. Invest. 107: 3–6.

    PubMed  CAS  Google Scholar 

  • Balkwill, F. and Mantovani, A. (2001). Inflammation and cancer: back to Virchow? Lancet 357: 539–545.

    PubMed  CAS  Google Scholar 

  • Balmain, A. and Pragnell, I.B. (1983). Mouse skin carcinomas induced in vivo by chemical carcinogens have a transforming Harvey-ras oncogene. Nature 303: 72–74.

    PubMed  CAS  Google Scholar 

  • Bargou, R.C. et al. (1997). Constitutive Nuclear Factor-kappa B-RelA Activation Is Required for Proliferation and Survival of Hodgkin’s Disease Tumor Cells. J. Clin. Invest. 100: 2961–2969.

    PubMed  CAS  Google Scholar 

  • Baron, F. et al. (2002). Leukemic target susceptibility to natural killer cytotoxicity: relationship with BCR-ABL expression. Blood 99: 2107–2113.

    PubMed  CAS  Google Scholar 

  • Beg, A.A. and Baltimore D. (1996). An essential role for NF-kappaB in preventing TNF-alpha-induced cell death. Science 274: 782–784.

    PubMed  CAS  Google Scholar 

  • Bentires-Alj, M. et al. (2003). NF-kappaB transcription factor induces drug resistance through MDRl expression in cancer cells. Oncogene 22: 90–97.

    PubMed  CAS  Google Scholar 

  • Berrebi, D. et al. Card15 gene overexpression in mononuclear and epithelial cells of the inflamed Crohn’s disease colon. Gut 52: 840–846.

    Google Scholar 

  • Beutler, B. (2004). Inferences, questions and possibilities in Toll-like receptor signaling. Nature 430: 257–263.

    PubMed  CAS  Google Scholar 

  • Bhat-Nakshatri, P. et al. (2002). Identification of signal transduction pathways involved in constitutive NF-kappaB activation in breast cancer cells. Oncogene 21: 2066–2078.

    PubMed  CAS  Google Scholar 

  • Bingle, L. et al. (2002). The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. J. Pathol. 196: 254–265.

    PubMed  CAS  Google Scholar 

  • Biswas, D.K. et al. Epidermal growth factor-induced nuclear factor kappa B activation: A major pathway of cell-cycle progression in estrogen-receptor negative breast cancer cells. Proc. Natl Acad. Sci. U.S.A. 97: 8542–8547.

    Google Scholar 

  • Bottomley et al. (1999) Peripheral blood mononuclear cells from patients with rheumatoid arthritis spontaneously secrete vascular endothelial growth factor (VEGF): specific upregulation by tumour necrosis factor-alpha in synovial fluid. Clin. Exp. Immunol. 117: 171–176.

    PubMed  CAS  Google Scholar 

  • Bouma, G. and Strober W. (2003). The immunological and genetic basis of inflammatory bowel disease. Nat. Rev. Immunol. 3: 521–533.

    PubMed  CAS  Google Scholar 

  • Burke, F. et al. (1996). A cytokine profile of normal and malignant ovary. Cytokine 8: 578–585.

    PubMed  CAS  Google Scholar 

  • Cabannes, E. et al. (1999). Mutations in the IkappaBalpha gene in Hodgkin’s disease suggest a tumour suppressor role for IkappaBalpha. Oncogene 18: 3063–3070.

    PubMed  CAS  Google Scholar 

  • Chan, T.A. (2003). Cyclooxygenase inhibition and mechanisms of colorectal cancer prevention. Curr. Cancer Drug Targets 3: 455–463.

    PubMed  CAS  Google Scholar 

  • Charalambous, M.P. et al. (2003). Upregulation of cyclooxygenase-2 is accompanied by increased expression of nuclear factor-kappa B and IkappaBkinase-alpha in human colorectal cancer epithelial cells. Br. J. Cancer 88: 1598–1604.

    PubMed  CAS  Google Scholar 

  • Chen, L.W. et al. (2003). The two faces of IKK and NF-kappaB inhibition: prevention of systemic inflammation but incrcascd local injury following intcstinal ischcmiareperfusion. Nat. Med. 9: 575–581.

    PubMed  CAS  Google Scholar 

  • Cogswell, P.C. et al. (2000). Selective activation of NF-kappa B subunits in human breast cancer: potential roles for NF-kappa B2/p52 and for Bcl-3. Oncogene 19: 1123–1131.

    PubMed  CAS  Google Scholar 

  • Cohen, T. et al. (1996). Interleukin 6 induces the expression of vascular endothelial growth factor. J. Biol. Chem. 271: 736–741.

    PubMed  CAS  Google Scholar 

  • Collet, J.P. et al. (1999). Colorectal cancer prevention by non-steroidal anti-inflammatory drugs: effects of dosage and timing. Br. J. Cancer 81: 62–68.

    PubMed  CAS  Google Scholar 

  • Cusack, J.C., Jr. et al. (2000). Inducible chemoresistance to 7-ethyl-10-[4-(1-piperidino)-l-piperidino]carbonyloxycamptothecin (CPT-11) in colorectal cancer cells and a xenograft model is overcome by inhibition of nuclear factor-kappaB activation. Cancer Res. 60: 2323–2330.

    PubMed  CAS  Google Scholar 

  • Cusack, J.C., Jr. et al. (2001). Enhanced chemosensitivity to CPT-11 with protcasome inhibitor PS-341: implications for systemic nuclear factor-kappaB inhibition. Cancer Res. 61: 3535–3540.

    PubMed  CAS  Google Scholar 

  • Dajee, M. et al. (2003). NF-kappaB blockade and oncogenic Ras trigger invasive human epidermal neoplasia. Nature 421: 639–643.

    PubMed  CAS  Google Scholar 

  • Din, F.V. et al. (2004). Evidence for colorectal cancer cell specificity of aspirin effects on NF-kappa B signaling and apoptosis. Br. J. Cancer 91: 381–388.

    PubMed  CAS  Google Scholar 

  • Eaden, J. et al. (2000). Colorectal cancer prevention in ulcerative colitis: a case-control study. Aliment. Pharmacol. Ther. 14: 145–153.

    PubMed  CAS  Google Scholar 

  • Feinman, R. et al. (1999). Role of NF-kappaB in the rescue of multiple myeloma cells from glucocorticoid-induced apoptosis by Bcl-2. Blood 93: 3044–3052.

    PubMed  CAS  Google Scholar 

  • Fox, C.J. et al. (2003). The serine/threonine kinase Pim-2 is a transcriptionally regulated apoptotic inhibitor. Genes Dev. 17: 1841–1854.

    PubMed  CAS  Google Scholar 

  • Garg, A. and Aggarwal B.B. (2002). Nuclear transcription factor-kappaB as a target for cancer drug development. Leukemia 16: 1053–1068.

    PubMed  CAS  Google Scholar 

  • Gilmore, T.D. et al. (2004). RELevant gene amplification in B-cell lymphomas? Blood 103: 3243–3244.

    PubMed  CAS  Google Scholar 

  • Giovannucci, E. et al. (1994). Aspirin use and the risk for colorectal cancer and adenoma in male health professionals. Ann. Intern. Med. 121: 241–246.

    PubMed  CAS  Google Scholar 

  • Girardin, S.E. et al. (2003). Lessons from Nod2 studies: towards a link between Crohn’s disease and bacterial sensing. Trends Immunol. 24: 652–658.

    PubMed  CAS  Google Scholar 

  • Greten, F.R. et al. (2004). IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 118: 285–296.

    PubMed  CAS  Google Scholar 

  • Griffin, J.D. (2001). Leukemia stem cells and constitutive activation of NF-kappaB. Blood 98: 2291.

    PubMed  CAS  Google Scholar 

  • Gupta, R.A. and Dubois R.N. (2001). Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2. Nat. Rev. Cancer 1: 11–21.

    PubMed  CAS  Google Scholar 

  • Haefner, B. (2002). NF-kappaB: arresting a major culprit in cancer. Drug Discov. Today 7: 653–663.

    PubMed  CAS  Google Scholar 

  • Haghnegahdar, H. et al. (2000). The tumorigenic and angiogenic effects of MGSA/GRO proteins in melanoma. J. Leukoc. Biol. 67: 53–62.

    PubMed  CAS  Google Scholar 

  • Hah, N. and Lee S.T. (2003). An absolute role of the PKC-dependent NF-kappaB activation for induction of MMP-9 in hepatocellular carcinoma cells. Biochem. Biophys. Res. Commun. 30: 428–433.

    Google Scholar 

  • Helbig, G. et al. (2003). NF-kappaB promotes breast cancer cell migration and metastasis by inducing the expression of the chemokine receptor CXCR4. J. Biol Chem. 278: 21631–21638.

    PubMed  CAS  Google Scholar 

  • Hershberg, R.M. (2002). The epithelial cell cytoskeleton and intracellular trafficking: V. Polarized compartmentalization of antigen processing and Toll-like receptor signaling in intestinal epithelial cells. Am. J. Physiol. Gastrointest. Liver Physiol. 283: G833–G839.

    PubMed  CAS  Google Scholar 

  • Hideshima, T. et al. (2001). The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells. Cancer Res. 61: 3071–3076.

    PubMed  CAS  Google Scholar 

  • Hinz, M. et al. (1999). NF-kappaB function in growth control: regulation of cyclin D1 expression and GO/G1-to-S-Phase transition. Mol Cell. Biol. 19: 2690–2698.

    PubMed  CAS  Google Scholar 

  • Huber, M.A. et al. (2004). NF-kappaB is essential for epithelial-mesenchymal transition and metastasis in a model of breast cancer progression. J. Clin. Invest. 114: 569–581.

    PubMed  CAS  Google Scholar 

  • Iademarco, M.F. et al. (1992). Characterization of the promoter for vascular cell adhesion molecule-1 (VCAM-1). J. Biol. Chem. 267: 16323–16329.

    PubMed  CAS  Google Scholar 

  • Itzkowitz, S.H. and Yio, X. (2004). Inflammation and cancer IV. Colorectal cancer in inflammatory bowel disease: the role of inflammation. Am. J. Physiol. Gastrointest. Liver Physiol. 287: G7–G17.

    PubMed  CAS  Google Scholar 

  • Jolly, K. et al. (1999). NSAIDs and gastrointestinal cancer prevention. Drugs 62: 945–956.

    Google Scholar 

  • Kaiser, G.C. et al. (1999). Mesalamine blocks tumor necrosis factor growth inhibition and nuclear factor kappaB activation in mouse colonocytes. Gastroenterology 116: 602–609.

    PubMed  CAS  Google Scholar 

  • Kim, B.Y. et al. (2002). Constitutive activation of NF-kappaB in Ki-ras-transformed prostate epithelial cells. Oncogene 21: 4490–4497.

    PubMed  CAS  Google Scholar 

  • Kim, D.W. et al. (2000). The RelA NF-kappaB subunit and the aryl hydrocarbon receptor (AhR) cooperate to transactivate the c-myc promoter in mammary cells. Oncogene 19: 5498–5506.

    PubMed  CAS  Google Scholar 

  • Koehne, C.H. and Dubois, R.N. (2004). COX-2 inhibition and colorectal cancer. Semin. Oncol. 31(Suppl. 7): 12–21.

    PubMed  CAS  Google Scholar 

  • Kojima, M. et al. (2004). Increased nuclear factor-kappaB activation in human colorectal carcinoma and its correlation with tumor progression. Anticancer Res. 24: 675–681.

    PubMed  CAS  Google Scholar 

  • Kollias, G. et al. (1999). On the role of tumor necrosis factor and receptors in models of multiorgan failure, rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease. Immunol. Rev. 169: 175–194.

    PubMed  CAS  Google Scholar 

  • Konno, H. et al. (2002). Cyclooxygenase-2 expression correlates with uPAR levels and is responsible for poor prognosis of colorectal cancer. Clin. Exp. Metastasis 19: 527–534.

    PubMed  CAS  Google Scholar 

  • Koong, A.C. et al. (1994). Hypoxic activation of nuclear factor-kappa B is mediated by a Ras and Raf signaling pathway and does not involve MAP kinase (ERK1 or ERK2). Cancer Res. 54: 5273–5279.

    PubMed  CAS  Google Scholar 

  • Koong, A.C. et al. (2000). Candidate genes for the hypoxic tumor phenotype. Cancer Res. 60: 883–887.

    PubMed  CAS  Google Scholar 

  • Kopp, E. and Ghosh S. (1994), Inhibition of NF-kappa B by sodium salicylate and aspirin. Science 265: 956–959.

    PubMed  CAS  Google Scholar 

  • Kordes, U. et al. (2000). Transcription factor NF-kappaB is constitutively activated in acute lymphoblastic leukemia cells. Leukemia 14: 399–402.

    PubMed  CAS  Google Scholar 

  • LaCasse, E.C. et al. (1998). The inhibitors of apoptosis (IAPs) and their emerging role in cancer. Oncogene 17: 3247–3259.

    PubMed  Google Scholar 

  • Lackner, C. et al. (2004). Prognostic relevance of tumour-associated macrophages and von Willebrand factor-positive microvessels in colorectal cancer. Virchows Arch. 445: 160–167.

    PubMed  CAS  Google Scholar 

  • Langman, M.J. et al. (2001). Effect of anti-inflammatory drugs on overall risk of common cancer: case-control study in general practice research database. Br Med. J. 320: 1642–1646.

    Google Scholar 

  • Lcck, R. D. and Harris A.L. (2002). Tumor-associatcd macrophages in breast cancer. J Mammary Gland Biol Neoplasia 7: 177–189.

    Google Scholar 

  • Lesage, S. et al. (2002) CARD15/NOD2 mutational analysis and genotype-phenotype correlation in 612 patients with inflammatory bowel disease. Am. J. Hum. Genet. 70: 845–857.

    PubMed  CAS  Google Scholar 

  • Lin, E. Y. and Pollard J.W. (2004). Macrophages: modulators of breast cancer progression. Novartis Found Symp. 256: 158–168.

    PubMed  CAS  Google Scholar 

  • Liu, W. et al. (2003). Cyclooxygenase-2 is up-regulated by interleukin-lbeta in human colorectal cancer cells via multiple signaling pathways. Cancer Res. 63: 3632–3636.

    PubMed  CAS  Google Scholar 

  • Lodes, M.J. et al. (2004). Bacterial flagellin is a dominant antigen in Crohn disease. J. Clin. Invest. 113: 1296–1306.

    PubMed  CAS  Google Scholar 

  • Lorenzo, E. et al. (2002). Doxorubicin induces apoptosis and CD95 gene expression in human primary endothelial cells through a p53-dependent mechanism. J. Biol. Chem. 277: 10883–10892.

    PubMed  CAS  Google Scholar 

  • Loukinova, E. et al. (2001). Expression of proangiogenic chemokine Gro 1 in low and high metastatic variants of Pam murine squamous cell carcinoma is differentially regulated by IL-1alpha, EGF and TGF-betal through NF-kappaB dependent and independent mechanisms. Int. J. Cancer: 637–644.

    Google Scholar 

  • Luo, J.L. et al. (2004). Inhibition of NF-kappaB in cancer cells converts inflammation-induced tumor growth mediated by TNFalpha to TRAIL-mediated tumor regression. Cancer Cell 6: 297–305.

    PubMed  CAS  Google Scholar 

  • Maeda, S. et al. (2003) IKKbeta is required for prevention of apoptosis mediated by cell-bound but not by circulating TNFalpha. Immunity 19: 725–737.

    PubMed  CAS  Google Scholar 

  • Mantovani, A. et al. (1992). The origin and function of tumor-associated macrophages. Immunol. Today 13: 265–270.

    PubMed  CAS  Google Scholar 

  • Mantovani, A. et al. (1992). Cytokine regulation of endothelial cell function. FASEB J. 6: 2591–2599.

    PubMed  CAS  Google Scholar 

  • Maruo, Y. et al. (2002). ICAM-1 expression and the soluble ICAM-1 level for evaluating the metastatic potential of gastric cancer. Int. J. Cancer 100: 486–490.

    PubMed  CAS  Google Scholar 

  • Mayo, M.W. et al. (2001). Ras regulation of NF-kappa B and apoptosis. Methods Enzymol. 333: 73–87.

    PubMed  CAS  Google Scholar 

  • Mayo, M.W. et al. (1997). Requirement of NF-kappaB activation to suppress p53-independent apoptosis induced by oncogenic Ras. Science 278: 1812–1815.

    PubMed  CAS  Google Scholar 

  • Mettouchi, A. et al. (1997). The c-Jun-induced transformation process involves complex regulation of tenascin-C expression. Mol. Cell Biol. 17: 3202–3209.

    PubMed  CAS  Google Scholar 

  • Miyagawa, S. et al. (2002). Morphometric analysis of liver macrophages in patients with colorectal liver metastasis. Clin. Exp. Metastasis 19: 119–125.

    PubMed  Google Scholar 

  • Monteleone, G. (1997). Interleukin 12 is expressed and actively released by Crohn’s disease intestinal lamina propria mononuclear cells. Gastroenterology 112: 1169–1178.

    PubMed  CAS  Google Scholar 

  • Mukogawa, T. et al. (2003). Adenovirus-mediated gene transduction of truncated IkappaBalpha enhances radiosensitivity in human colon cancer cells. Cancer Sci. 94: 745–750.

    PubMed  CAS  Google Scholar 

  • Mulder, W.M. et al. (1997). Low intercellular adhesion molecule 1 and high 5T4 expression on tumor cells correlate with reduced disease-free survival in colorectal carcinoma patients. Clin. Cancer Res. 3: 1923–1930.

    PubMed  CAS  Google Scholar 

  • Munkholm, P. (2003). Review article: the incidence and prevalence of colorectal cancer in inflammatory bowel disease. Aliment. Pharmacol. Ther. 18(Suppl. 2): 1–5.

    PubMed  Google Scholar 

  • Munzert, G. et al. (2004). Constitutive NF-kappab/Rel activation in Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL). Leuk. Lymphoma 45: 1181–1184.

    PubMed  CAS  Google Scholar 

  • Myers, R.B. et al. (1996). Elevated serum levels of p105(erbB-2) in patients with advanced-stage prostatic adenocarcinoma. Int. J. Cancer 69: 398–402.

    PubMed  CAS  Google Scholar 

  • Nakshatri, H. et al. (1997). Constitutive activation of NF-kappaB during progression of breast cancer to hormone-independent growth. Mol. Cell. Biol. 17: 3629–3639.

    PubMed  CAS  Google Scholar 

  • Naylor, M.S. et al. (1990). Investigation of cytokine gene expression in human colorectal cancer. Cancer Res. 50: 4436–4440.

    PubMed  CAS  Google Scholar 

  • Neurath, M.F. et al. (1998) Cytokine gene transcription by NF-kappaB family members in patients with inflammatory bowel disease. Ann. N. Y. Acad. Sci. 859: 149–159.

    PubMed  CAS  Google Scholar 

  • Neurath, M.F. et al. (1996). Local administration of antisense phosphorothioate oligonucleotides to the p65 subunit of NF-kappaB abrogates established experimental colitis in mice. Nat. Med. 2: 998–1004.

    PubMed  CAS  Google Scholar 

  • O’Hanlon, D.M. et al. (2002). Soluble adhesion molecules (E-selectin, ICAM-1 and VCAM-1) in breast carcinoma. Eur. J. Cancer 38: 2252–2257.

    PubMed  Google Scholar 

  • Ogura, Y. et al. (2001). A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature 411: 603–606.

    PubMed  CAS  Google Scholar 

  • Orlowski, R.Z. and Baldwin, A.S., Jr. (2002) NF-kappaB as a therapeutic target in cancer. Trends Mol. Med. 8: 385–389.

    PubMed  CAS  Google Scholar 

  • Osborn, L.S. et al. (1989). Tumor necrosis factor alpha and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kappa B. Proc. Natl Acad. Sci. U.S.A. 86: 2336–2340.

    PubMed  CAS  Google Scholar 

  • Oshima, M. and Taketo, M.M. (2002). COX selectivity and animal models for colon cancer. Curr. Pharm. Des. 8: 1021–1034.

    PubMed  CAS  Google Scholar 

  • Pahl, H.L. (1999). Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene 18: 6853–6866.

    PubMed  CAS  Google Scholar 

  • Palayoor, S.T. et al. (1999). Constitutive activation of IkappaB kinase alpha and NF-kappaB in prostate cancer cells is inhibited by ibuprofen. Oncogene 18: 7389–7394.

    PubMed  CAS  Google Scholar 

  • Philip, S. et al. (2001). Osteopontin stimulates tumor growth and activation of promatrix metalloproteinase-2 through nuclear factor-kappaB-mediated induction of membrane type 1 matrix metalloproteinase in murine melanoma cells. J. Biol. Chem. 276: 44926–44935.

    PubMed  CAS  Google Scholar 

  • Pierce, J.W. et al. (1996). Salicylates inhibit IkappaB-alpha phosphorylation, endothelialleukocyte adhesion molecule expression, and neutrophil transmigration. J. Immunol. 156: 3961–3969.

    PubMed  CAS  Google Scholar 

  • Pikarsky, E. et al. (2004). NF-kappaB functions as a tumour promoter in inflammation-associated cancer. Nature 431: 461–466.

    PubMed  CAS  Google Scholar 

  • Podolsky, D.K. (2002). Inflammatory bowel disease. New Engl. J. Med. 347: 417–429.

    PubMed  CAS  Google Scholar 

  • Potoka, D.A. et al. (2002). NF-kappaB inhibition enhances peroxynitrite-induced enterocyte apoptosis. J. Surg. Res. 106: 7–14.

    PubMed  CAS  Google Scholar 

  • Rakoff-Nahoum, S. et al. (2004). Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 118: 671–674.

    Google Scholar 

  • Rayet, B. and Gelinas C. (1999). Aberrant rel/nfkb genes and activity in human cancer. Oncogene 18: 6938–47.

    PubMed  CAS  Google Scholar 

  • Reuter, B.K. and Pizarro, T.T. (2004). Commentary: the role of the IL-18 system and other members of the IL-lR/TLR superfamily in innate mucosal immunity and the pathogenesis of inflammatory bowel disease: friend or foe? Eur. J. Immunol 34: 2347–2355.

    PubMed  CAS  Google Scholar 

  • Roebuck, K.A. and Finnegan, A. (1999). Regulation of intercellular adhesion molecule-1 (CD54) gene expression. J. Leukoc. Biol. 66: 876–888.

    PubMed  CAS  Google Scholar 

  • Rogler, G. et al. (1998). Nuclear factor kappaB is activated in macrophages and epithelial cells of inflamed intestinal mucosa. Gastroenterology 115: 357–369.

    PubMed  CAS  Google Scholar 

  • Russo, S.M. et al. (2001). Enhancement of radiosensitivity by proteasome inhibition: implications for a role of NF-kappaB. Int. J. Radiat. Oncol Biol Phys. 50: 183–193.

    PubMed  CAS  Google Scholar 

  • Ryan, K.M. et al. (2000). Role of NF-kappaB in p53-mediated programmed cell death. Nature 404: 892–897.

    PubMed  CAS  Google Scholar 

  • Sartor, R.B. (2003). Innate immunity in the pathogenesis and therapy of IBD. J. Gastroenterol. 38(Suppl. 15): 43–47.

    PubMed  CAS  Google Scholar 

  • Schottclius, A.J. and Baldwin, A.S., Jr. (1999). A rolc for transcription factor NF-kappa B in intestinal inflammation. Int. J. Colorectal. Dis. 14: 18–28.

    Google Scholar 

  • Schottelius, A.J. et al. (2004). Biology of tumor necrosis factor-alpha-implications for psoriasis. Exp. Dermatol 13: 193–222.

    PubMed  CAS  Google Scholar 

  • Schreiber, S. et al. (1998). Activation of nuclear factor kappa B inflammatory bowel disease. Gut: 477–484.

    Google Scholar 

  • Schwenger, P. et al. (1998). Activation of p38 mitogen-activated protein kinase by sodium salicylate leads to inhibition of tumor necrosis factor-induced IkappaB alpha phosphorylation and degradation. Mol. Cell. Biol. 18: 78–84.

    PubMed  CAS  Google Scholar 

  • Sevilla, L. et al. (2001). Transcriptional regulation of the bcl-x gene encoding the antiapoptotic Bcl-xL protein by Ets, Rel/NFkappaB, STAT and AP1 transcription factor families. Histol Histopathol. 16: 595–601.

    PubMed  CAS  Google Scholar 

  • Shin, H.S. et al. (2004). The relationship between the serum intercellular adhesion molecule-1 level and the prognosis of the disease in lung cancer. Korean J. Intern. Med. 19: 48–52.

    PubMed  CAS  Google Scholar 

  • Sovak, M.A. et al. (1997). Aberrant Nuclear Factor-kappa B/Rel Expression and the Pathogenesis of Breast Cancer. J. Clin. Invest. 100: 2952–2960.

    PubMed  CAS  Google Scholar 

  • Spiik, A.K. et al. (2002). Abrogated lymphocyte infiltration and lowered CD14 in dextran sulfate induced colitis in mice treated with p65 antisense oligonucleotides. Int. J. Colorectal Dis. 17: 223–232.

    PubMed  Google Scholar 

  • Stark, L.A. et al. (2001) Aspirin-induced activation of the NF-kappaB signaling pathway: a novel mechanism for aspirin-mediated apoptosis in colon cancer cells. FASEB J. 15: 1273–1275.

    PubMed  CAS  Google Scholar 

  • Strober, W. et al. (2002). The immunology of mucosal models of inflammation. Annu. Rev. Immunol 20: 495–549.

    PubMed  CAS  Google Scholar 

  • Thornburg, N. et al. (2003). Activation of nuclear factor-kappaB p50 homodimer/Bcl-3 complexes in nasopharyngeal carcinoma. Cancer Res. 63: 8293–8301.

    PubMed  CAS  Google Scholar 

  • Thun, M.J. et al. (1999). Aspirin use and risk of fatal cancer. Cancer Res. 53: 1322–1327.

    Google Scholar 

  • Toomey, D. et al. (1999). Phenotyping of immune cell infiltrates in breast and colorectal tumours. Immunol Invest. 28: 29–41.

    PubMed  CAS  Google Scholar 

  • Tsujii, M. et al. (1998). Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 93: 705–716.

    PubMed  CAS  Google Scholar 

  • Vane, J. (1994). Towards a better aspirin. Nature 367: 215–216.

    PubMed  CAS  Google Scholar 

  • Wang, C.Y. et al. (1999). Control of inducible chemoresistance: enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-kappaB. Nat. Med. 5: 412–417.

    PubMed  Google Scholar 

  • Wang, C.Y. et al. (1996). TNF-and cancer therapy-induced apoptosis: potentiation by inhibition of NF-kappaB. Science 274: 784–787.

    PubMed  CAS  Google Scholar 

  • Wang, C.Y. et al. (1998). NF-kappaB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science 281: 1680–1683.

    PubMed  CAS  Google Scholar 

  • Wang, L. et al. (2003). IL-6 induces NF-kappaB activation in the intestinal epithelia. J. Immunol. 171: 3194–3201.

    PubMed  CAS  Google Scholar 

  • Weber, C.K. et al. (2000). Suppression of NF-kappaB activity by sulfasalazine is mediated by direct inhibition of IkappaB kinases alpha and beta. Gastroenterology 119: 1209–1218.

    PubMed  CAS  Google Scholar 

  • Webster, G.A. and Perkins, N.D. (1999). Transcriptional cross talk between NF-kappaB and p53. Mol. Cell. Biol. 19: 3485–3495.

    PubMed  CAS  Google Scholar 

  • Whelan, J. et al. (1991). An NF-kappa B-like factor is essential but not sufficient for cytokine induction of endothelial leukocyte adhesion molecule 1 (ELAM-1) gene transcription. Nucleic Acids Res. 19: 2645–2653.

    PubMed  CAS  Google Scholar 

  • Wu, G.S. and Ding, Z. (2002). Caspase 9 is required for p53-dependent apoptosis and chemosensitivity in a human ovarian cancer cell line. Oncogene 21: 1–8.

    PubMed  CAS  Google Scholar 

  • Yamamoto, Y. and Gaynor, R.B. (2001). Therapeutic potential of inhibition of the NF-kappaB pathway in the treatment of inflammation and cancer. J. Clin. Invest. 107: 135–42.

    PubMed  CAS  Google Scholar 

  • Yamamoto, Y. et al. (1999). Sulindac inhibits activation of the NF-kappaB pathway. J. Biol. Chem. 274: 27307–27314.

    PubMed  CAS  Google Scholar 

  • Yamanaka, N. et al. (2004). Interleukin-lbeta enhances invasive ability of gastric carcinoma through nuclear factor-kappaB activation. Clin. Cancer Res. 10: 1853–1859.

    PubMed  CAS  Google Scholar 

  • Yin, M.J. et al. (1998). The anti-inflammatory agents aspirin and salicylate inhibit the activity of IkappaB kinase-beta. Nature 396: 77–80.

    PubMed  CAS  Google Scholar 

  • Yu, H.G. et al. (2003). Increased expression of RelA/nuclear factor-kappa B protein correlates with colorectal tumorigenesis. Oncology 65: 37–45.

    PubMed  CAS  Google Scholar 

  • Zhan, J. et al. (2004). Relationship between COX-2 expression and clinicopathological features of colorectal cancers. Chin. Med. J. (Engl.) 117: 1151–54

    CAS  Google Scholar 

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Authors and Affiliations

  1. Development Sciences, Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080

    Arndt J. Schottelius

  2. Berlex Biosciences, Research Business Area Dermatology USA and Research Business Area Oncology USA, 2600 Hilltop Drive, Richmond, CA, 94806

    Harald Dinter

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  1. Arndt J. Schottelius
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  2. Harald Dinter
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Editors and Affiliations

  1. Division of Oncology, St. George’s Hospital Medical School, Cranmer Terrace, London, SW17 0RE, UK

    Angus G. Dalgleish MD

  2. Department of Oncology Johnson and Johnson Pharmaceutical, Research and Development, Turnhoutseweg 30, Box 6423, 2340, Beerse, Belgium

    Burkhard Haefner PhD

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© 2006 Springer Science+Business Media, Inc.

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Schottelius, A.J., Dinter, H. (2006). Cytokines, NF-κB, Microenvironment, Intestinal Inflammation and Cancer. In: Dalgleish, A.G., Haefner, B. (eds) The Link Between Inflammation and Cancer. Cancer Treatment and Research, vol 130. Springer, Boston, MA. https://doi.org/10.1007/0-387-26283-0_3

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  • DOI: https://doi.org/10.1007/0-387-26283-0_3

  • Publisher Name: Springer, Boston, MA

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  • Online ISBN: 978-0-387-26283-3

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