Table of Contents Author Guidelines Submit a Manuscript
Journal of Immunology Research
Volume 2014, Article ID 149185, 19 pages
http://dx.doi.org/10.1155/2014/149185
Review Article

Chronic Inflammation and Cytokines in the Tumor Microenvironment

1Disciplinary Program, Institute of Biomedical Sciences, School of Medicine, University of Chile, Independencia 1027, 8380453 Santiago, Chile
2Department of Immunology, School of Medicine, Siriraj Hospital, Mahidol University, 2 Prannok Road, Bangkok Noi, Bangkok 10700, Thailand

Received 10 February 2014; Accepted 15 April 2014; Published 13 May 2014

Academic Editor: Evelin Grage-Griebenow

Copyright © 2014 Glauben Landskron et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. R. Virchow, Die Krankhaften Geschwülste, Berlin, Germany, 1863.
  2. F. Balkwill and A. Mantovani, “Inflammation and cancer: back to Virchow?” The Lancet, vol. 357, no. 9255, pp. 539–545, 2001. View at Publisher · View at Google Scholar · View at Scopus
  3. S. P. Hussain and C. C. Harris, “Inflammation and cancer: an ancient link with novel potentials,” International Journal of Cancer, vol. 121, no. 11, pp. 2373–2380, 2007. View at Publisher · View at Google Scholar · View at Scopus
  4. L. Yan, G. M. Anderson, M. DeWitte, and M. T. Nakada, “Therapeutic potential of cytokine and chemokine antagonists in cancer therapy,” European Journal of Cancer, vol. 42, no. 6, pp. 793–802, 2006. View at Publisher · View at Google Scholar · View at Scopus
  5. R. Medzhitov, “Origin and physiological roles of inflammation,” Nature, vol. 454, no. 7203, pp. 428–435, 2008. View at Publisher · View at Google Scholar · View at Scopus
  6. L. V. Norling and C. N. Serhan, “Profiling in resolving inflammatory exudates identifies novel anti-inflammatory and pro-resolving mediators and signals for termination,” Journal of Internal Medicine, vol. 268, no. 1, pp. 15–24, 2010. View at Publisher · View at Google Scholar · View at Scopus
  7. D. Hanahan and R. A. Weinberg, “Hallmarks of cancer: the next generation,” Cell, vol. 144, no. 5, pp. 646–674, 2011. View at Publisher · View at Google Scholar · View at Scopus
  8. T. Jess, E. V. Loftus Jr., F. S. Velayos et al., “Risk of intestinal cancer in inflammatory bowel disease: a population-based study from olmsted county, Minnesota,” Gastroenterology, vol. 130, no. 4, pp. 1039–1046, 2006. View at Publisher · View at Google Scholar · View at Scopus
  9. A. Zabron, R. J. Edwards, and S. Khan, “The challenge of cholangiocarcinoma: dissecting the molecular mechanisms of an insidious cancer,” Disease Models & Mechanisms, vol. 6, no. 2, pp. 281–292, 2013. View at Google Scholar
  10. T. Yoshida, J. Kato, I. Inoue et al., “Cancer development based on chronic active gastritis and resulting gastric atrophy as assessed by serum levels of pepsinogen and Helicobacter pylori antibody titer,” International Journal of Cancer, vol. 134, no. 6, pp. 1445–1457, 2014. View at Google Scholar
  11. H. Vainio and P. Boffetta, “Mechanisms of the combined effect of asbestos and smoking in the etiology of lung cancer,” Scandinavian Journal of Work, Environment and Health, vol. 20, no. 4, pp. 235–242, 1994. View at Google Scholar · View at Scopus
  12. J. N. Krieger, D. E. Riley, R. L. Vesella, D. C. Miner, S. O. Ross, and P. H. Lange, “Bacterial DNA sequences in prostate tissue from patients with prostate cancer and chronic prostatitis,” Journal of Urology, vol. 164, no. 4, pp. 1221–1228, 2000. View at Google Scholar · View at Scopus
  13. H. B. El-Serag, “Epidemiology of viral hepatitis and hepatocellular carcinoma,” Gastroenterology, vol. 142, no. 6, pp. 1264–1273, 2012. View at Publisher · View at Google Scholar · View at Scopus
  14. R. K. Singh, M. Gutman, R. Reich, and M. Bar-Eli, “Ultraviolet B irradiation promotes tumorigenic and metastatic properties in primary cutaneous melanoma via induction of interleukin 8,” Cancer Research, vol. 55, no. 16, pp. 3669–3674, 1995. View at Google Scholar · View at Scopus
  15. A. S. Bats, Y. Zafrani, P. Pautier, P. Duvillard, and P. Morice, “Malignant transformation of abdominal wall endometriosis to clear cell carcinoma: case report and review of the literature,” Fertility and Sterility, vol. 90, no. 4, pp. 1197.e13–1197.e16, 2008. View at Publisher · View at Google Scholar · View at Scopus
  16. J. G. Fox, F. E. Dewhirst, Z. Shen et al., “Hepatic Helicobacter species identified in bile and gallbladder tissue from Chileans with chronic cholecystitis,” Gastroenterology, vol. 114, no. 4 I, pp. 755–763, 1998. View at Publisher · View at Google Scholar · View at Scopus
  17. B. Levin, “Gallbladder carcinoma,” Annals of Oncology, vol. 10, no. 4, pp. S129–S130, 1999. View at Google Scholar · View at Scopus
  18. A. J. Cameron and H. A. Carpenter, “Barrett's esophagus, high-grade dysplasia, and early adenocarcinoma: a pathological study,” American Journal of Gastroenterology, vol. 92, no. 4, pp. 586–591, 1997. View at Google Scholar · View at Scopus
  19. M. Murata, R. Thanan, N. Ma, and S. Kawanishi, “Role of nitrative and oxidative DNA damage in inflammation-related carcinogenesis,” Journal of Biomedicine and Biotechnology, vol. 2012, Article ID 623019, 11 pages, 2012. View at Publisher · View at Google Scholar · View at Scopus
  20. J.-L. Luo, S. Maeda, L.-C. Hsu, H. Yagita, and M. Karin, “Inhibition of NF-κB in cancer cells converts inflammation- induced tumor growth mediated by TNFα to TRAIL-mediated tumor regression,” Cancer Cell, vol. 6, no. 3, pp. 297–305, 2004. View at Publisher · View at Google Scholar · View at Scopus
  21. R. C. Bates and A. M. Mercurio, “Tumor necrosis factor-α stimulates the epithelial-tomesenchymal transition of human colonic organoids,” Molecular Biology of the Cell, vol. 14, no. 5, pp. 1790–1800, 2003. View at Publisher · View at Google Scholar · View at Scopus
  22. S. Danese, M. Sans, C. de la Motte et al., “Angiogenesis as a novel component of inflammatory bowel disease pathogenesis,” Gastroenterology, vol. 130, no. 7, pp. 2060–2073, 2006. View at Publisher · View at Google Scholar · View at Scopus
  23. R. Al-Bahrani, Y. Abuetabh, N. Zeitouni, and C. Sergi, “Cholangiocarcinoma: risk factors, environmental influences and oncogenesis,” Annals of Clinical & Laboratory Science, vol. 43, no. 2, pp. 195–210, 2013. View at Google Scholar
  24. S. Hanada, M. Harada, H. Koga et al., “Tumor necrosis factor-α and interferon-γ directly impair epithelial barrier function in cultured moused cholangiocytes,” Liver International, vol. 23, no. 1, pp. 3–11, 2003. View at Google Scholar · View at Scopus
  25. J. Komori, H. Marusawa, T. Machimoto et al., “Activation-induced cytidine deaminase links bile duct inflammation to human cholangiocarcinoma,” Hepatology, vol. 47, no. 3, pp. 888–896, 2008. View at Publisher · View at Google Scholar · View at Scopus
  26. A. Techasen, N. Namwat, W. Loilome et al., “Tumor necrosis factor-α (TNF-α) stimulates the epithelial-mesenchymal transition regulator Snail in cholangiocarcinoma,” Medical Oncology, vol. 29, no. 5, pp. 3083–3091, 2012. View at Google Scholar
  27. L. Camoglio, A. A. Te Velde, A. J. Tigges, P. K. Das, and S. J. H. Van Deventer, “Altered expression of interferon-γ and interleukin-4 in inflammatory bowel disease,” Inflammatory Bowel Diseases, vol. 4, no. 4, pp. 285–290, 1998. View at Google Scholar · View at Scopus
  28. R. Ito, M. Shin-Ya, T. Kishida et al., “Interferon-gamma is causatively involved in experimental inflammatory bowel disease in mice,” Clinical and Experimental Immunology, vol. 146, no. 2, pp. 330–338, 2006. View at Publisher · View at Google Scholar · View at Scopus
  29. M. Bruewer, A. Luegering, T. Kucharzik et al., “Proinflammatory cytokines disrupt epithelial barrier function by apoptosis-independent mechanisms,” Journal of Immunology, vol. 171, no. 11, pp. 6164–6172, 2003. View at Google Scholar · View at Scopus
  30. E. Osawa, A. Nakajima, T. Fujisawa et al., “Predominant T helper type 2-inflammatory responses promote murine colon cancers,” International Journal of Cancer, vol. 118, no. 9, pp. 2232–2236, 2006. View at Publisher · View at Google Scholar · View at Scopus
  31. T. Hisamatsu, M. Watanabe, H. Ogata et al., “Interferon-inducible gene family 1-8U expression in colitis-associated colon cancer and severely inflamed mucosa in ulcerative colitis,” Cancer Research, vol. 59, no. 23, pp. 5927–5931, 1999. View at Google Scholar · View at Scopus
  32. J. Paulukat, M. Bosmann, M. Nold et al., “Expression and release of IL-18 binding protein in response to IFN-γ,” Journal of Immunology, vol. 167, no. 12, pp. 7038–7043, 2001. View at Google Scholar · View at Scopus
  33. S. Matsumoto, T. Hara, K. Mitsuyama et al., “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,” Journal of Immunology, vol. 184, no. 3, pp. 1543–1551, 2010. View at Publisher · View at Google Scholar · View at Scopus
  34. S. Grivennikov, E. Karin, J. Terzic et al., “IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer,” Cancer Cell, vol. 15, no. 2, pp. 103–113, 2009. View at Publisher · View at Google Scholar · View at Scopus
  35. K. Middleton, J. Jones, Z. Lwin, and J. I. G. Coward, “Interleukin-6: an angiogenic target in solid tumours,” Critical Reviews in Oncology/Hematology, vol. 89, no. 1, pp. 129–139, 2014. View at Google Scholar
  36. A. M. Elsharkawy and D. A. Mann, “Nuclear factor-κB and the hepatic inflammation-fibrosis-cancer axis,” Hepatology, vol. 46, no. 2, pp. 590–597, 2007. View at Publisher · View at Google Scholar · View at Scopus
  37. F. Meng, H. Wehbe-Janek, R. Henson, H. Smith, and T. Patel, “Epigenetic regulation of microRNA-370 by interleukin-6 in malignant human cholangiocytes,” Oncogene, vol. 27, no. 3, pp. 378–386, 2008. View at Publisher · View at Google Scholar · View at Scopus
  38. R. C. Bates and A. M. Mercurio, “The epithelial-mesenchymal transition (EMT) and colorectal cancer progression,” Cancer Biology and Therapy, vol. 4, no. 4, pp. 365–370, 2005. View at Google Scholar · View at Scopus
  39. L. A. Feagins, “Role of transforming growth factor-β in inflammatory bowel disease and colitis-associated colon cancer,” Inflammatory Bowel Diseases, vol. 16, no. 11, pp. 1963–1968, 2010. View at Publisher · View at Google Scholar · View at Scopus
  40. Y. Sato, K. Harada, K. Itatsu et al., “Epithelial-mesenchymal transition induced by transforming growth factor-β1/snail activation aggravates invasive growth of cholangiocarcinoma,” American Journal of Pathology, vol. 177, no. 1, pp. 141–152, 2010. View at Publisher · View at Google Scholar · View at Scopus
  41. Y. Ning, P. C. Manegold, Y. K. Hong et al., “Interleukin-8 is associated with proliferation, migration, angiogenesis and chemosensitivity in vitro and in vivo in colon cancer cell line models,” International Journal of Cancer, vol. 128, no. 9, pp. 2038–2049, 2011. View at Publisher · View at Google Scholar · View at Scopus
  42. C. Spirlì, L. Fabris, E. Duner et al., “Cytokine-stimulated nitric oxide production inhibits adenylyl cyclase and cAMP-dependent secretion in cholangiocytes,” Gastroenterology, vol. 124, no. 3, pp. 737–753, 2003. View at Publisher · View at Google Scholar · View at Scopus
  43. C. Spiral, M. H. Nathanson, R. Fiorotto et al., “Proinflammatory cytokines inhibit secretion in rat bile duct epithelium,” Gastroenterology, vol. 121, no. 1, pp. 156–169, 2001. View at Google Scholar · View at Scopus
  44. S. Sturlan, G. Oberhuber, B. G. Beinhauer et al., “Interleukin-10-deficient mice and inflammatory bowel disease associated cancer development,” Carcinogenesis, vol. 22, no. 4, pp. 665–671, 2001. View at Google Scholar · View at Scopus
  45. H. Hasita, Y. Komohara, H. Okabe et al., “Significance of alternatively activated macrophages in patients with intrahepatic cholangiocarcinoma,” Cancer Science, vol. 101, no. 8, pp. 1913–1919, 2010. View at Publisher · View at Google Scholar · View at Scopus
  46. J. Liu, Y. Duan, X. Cheng et al., “IL-17 is associated with poor prognosis and promotes angiogenesis via stimulating VEGF production of cancer cells in colorectal carcinoma,” Biochemical and Biophysical Research Communications, vol. 407, no. 2, pp. 348–354, 2011. View at Publisher · View at Google Scholar · View at Scopus
  47. E. Gounaris, N. R. Blatner, K. Dennis et al., “T-regulatory cells shift from a protective anti-inflammatory to a cancer-promoting proinflammatory phenotype in polyposis,” Cancer Research, vol. 69, no. 13, pp. 5490–5497, 2009. View at Publisher · View at Google Scholar · View at Scopus
  48. F.-M. Gu, Q. Gao, G.-M. Shi et al., “Intratumoral IL-17+ cells and neutrophils show strong prognostic significance in intrahepatic cholangiocarcinoma,” Annals of Surgical Oncology, vol. 19, no. 8, pp. 2506–2514, 2012. View at Google Scholar
  49. C. Stolfi, A. Rizzo, E. Franzè et al., “Involvement of interleukin-21 in the regulation of colitis-associated colon cancer,” Journal of Experimental Medicine, vol. 208, no. 11, pp. 2279–2290, 2011. View at Publisher · View at Google Scholar · View at Scopus
  50. B. F. Zamarron and W. Chen, “Dual roles of immune cells and their factors in cancer development and progression,” International Journal of Biological Sciences, vol. 7, no. 5, pp. 651–658, 2011. View at Google Scholar · View at Scopus
  51. C. Popa, M. G. Netea, P. L. C. M. Van Riel, J. W. M. Van Der Meer, and A. F. H. Stalenhoef, “The role of TNF-α in chronic inflammatory conditions, intermediary metabolism, and cardiovascular risk,” Journal of Lipid Research, vol. 48, no. 4, pp. 751–762, 2007. View at Publisher · View at Google Scholar · View at Scopus
  52. R. J. Moore, D. M. Owens, G. Stamp et al., “Mice deficient in tumor necrosis factor-alpha are resistant to skin carcinogenesis,” Nature Medicine, vol. 5, no. 7, pp. 828–831, 1999. View at Google Scholar
  53. P. Szlosarek, K. A. Charles, and F. R. Balkwill, “Tumour necrosis factor-α as a tumour promoter,” European Journal of Cancer, vol. 42, no. 6, pp. 745–750, 2006. View at Publisher · View at Google Scholar · View at Scopus
  54. G. Chen and D. V. Goeddel, “TNF-R1 signaling: a beautiful pathway,” Science, vol. 296, no. 5573, pp. 1634–1635, 2002. View at Publisher · View at Google Scholar · View at Scopus
  55. E. A. Havell, W. Fiers, and R. J. North, “The antitumor function of tumor necrosis factor (TNF)—I. Therapeutic action of TNF against an established murine sarcoma is indirect, immunologically dependent, and limited by severe toxicity,” Journal of Experimental Medicine, vol. 167, no. 3, pp. 1067–1085, 1988. View at Google Scholar · View at Scopus
  56. B. Wiemann and C. O. Starnes, “Coley's toxins, tumor necrosis factor and cancer research: a historical perspective,” Pharmacology and Therapeutics, vol. 64, no. 3, pp. 529–564, 1994. View at Publisher · View at Google Scholar · View at Scopus
  57. F. J. Lejeune, C. Rüegg, and D. Liénard, “Clinical applications of TNF-alpha in cancer,” Current Opinion in Immunology, vol. 10, no. 5, pp. 573–580, 1998. View at Google Scholar
  58. J. M. Herman, A. T. Wild, H. Wang et al., “Randomized phase III multi-institutional study of TNFerade biologic with fluorouracil and radiotherapy for locally advanced pancreatic cancer: final results,” Journal of Clinical Oncology, vol. 31, no. 7, pp. 886–894, 2013. View at Google Scholar
  59. K. J. Chang, T. Reid, N. Senzer et al., “Phase I evaluation of TNFerade Biologic plus chemoradiotherapy before esophagectomy for locally advanced resectable esophageal cancer,” Gastrointestinal Endoscopy, vol. 75, pp. 1139–1146, 2012. View at Publisher · View at Google Scholar · View at Scopus
  60. G. M. Anderson, M. T. Nakada, and M. DeWitte, “Tumor necrosis factor-α in the pathogenesis and treatment of cancer,” Current Opinion in Pharmacology, vol. 4, no. 4, pp. 314–320, 2004. View at Publisher · View at Google Scholar · View at Scopus
  61. F. Balkwill, “TNF-α in promotion and progression of cancer,” Cancer and Metastasis Reviews, vol. 25, no. 3, pp. 409–416, 2006. View at Publisher · View at Google Scholar · View at Scopus
  62. C.-H. Woo, Y.-W. Eom, M.-H. Yoo et al., “Tumor necrosis factor-α generates reactive oxygen species via a cytosolic phospholipase A2-linked cascade,” Journal of Biological Chemistry, vol. 275, no. 41, pp. 32357–32362, 2000. View at Google Scholar · View at Scopus
  63. S. P. Hussain, L. J. Hofseth, and C. C. Harris, “Radical causes of cancer,” Nature Reviews Cancer, vol. 3, no. 4, pp. 276–285, 2003. View at Google Scholar · View at Scopus
  64. L. A. Noach, N. B. Bosma, J. Jansen, F. J. Hoek, S. J. H. Van Deventer, and G. N. J. Tytgat, “Mucosal tumor necrosis factor-α interleukin-1β, and interleukin-8 production in patients with helicobacter pylori infection,” Scandinavian Journal of Gastroenterology, vol. 29, no. 5, pp. 425–429, 1994. View at Google Scholar · View at Scopus
  65. M. Suganuma, T. Watanabe, K. Yamaguchi, A. Takahashi, and H. Fujiki, “Human gastric cancer development with TNF-α-inducing protein secreted from Helicobacter pylori,” Cancer Letters, vol. 322, no. 2, pp. 133–138, 2012. View at Publisher · View at Google Scholar · View at Scopus
  66. J. Kwong, L. C. Franky, K.-K. Wong et al., “Inflammatory cytokine tumor necrosis factor α confers precancerous phenotype in an organoid model of normal human ovarian surface epithelial cells,” Neoplasia, vol. 11, no. 6, pp. 529–541, 2009. View at Publisher · View at Google Scholar · View at Scopus
  67. C. M. Ohri, A. Shikotra, R. H. Green, D. A. Waller, and P. Bradding, “Tumour necrosis factor-alpha expression in tumour islets confers a survival advantage in non-small cell lung cancer,” BMC Cancer, vol. 10, article 323, 2010. View at Publisher · View at Google Scholar · View at Scopus
  68. S. H. Lee, H. S. Hong, Z. X. Liu et al., “TNFα enhances cancer stem cell-like phenotype via Notch-Hes1 activation in oral squamous cell carcinoma cells,” Biochemical and Biophysical Research Communications, vol. 424, no. 1, pp. 58–64, 2012. View at Google Scholar
  69. K. Heikkilä, S. Ebrahim, and D. A. Lawlor, “Systematic review of the association between circulating interleukin-6 (IL-6) and cancer,” European Journal of Cancer, vol. 44, no. 7, pp. 937–945, 2008. View at Publisher · View at Google Scholar · View at Scopus
  70. D. R. Hodge, E. M. Hurt, and W. L. Farrar, “The role of IL-6 and STAT3 in inflammation and cancer,” European Journal of Cancer, vol. 41, no. 16, pp. 2502–2512, 2005. View at Publisher · View at Google Scholar · View at Scopus
  71. J. A. Gasche, J. Hoffmann, C. R. Boland, and A. Goel, “Interleukin-6 promotes tumorigenesis by altering DNA methylation in oral cancer cells,” International Journal of Cancer, vol. 129, no. 5, pp. 1053–1063, 2011. View at Publisher · View at Google Scholar · View at Scopus
  72. H. Kinoshita, Y. Hirata, H. Nakagawa et al., “Interleukin-6 mediates epithelial-stromal interactions and promotes gastric tumorigenesis,” PLoS ONE, vol. 8, no. 4, Article ID e60914, 2013. View at Google Scholar
  73. M. Chatterjee, T. Stühmer, P. Herrmann, K. Bommert, B. Dörken, and R. C. Bargou, “Combined disruption of both the MEK/ERK and the IL-6R/STAT3 pathways is required to induce apoptosis of multiple myeloma cells in the presence of bone marrow stromal cells,” Blood, vol. 104, no. 12, pp. 3712–3721, 2004. View at Publisher · View at Google Scholar · View at Scopus
  74. D. M. Hilbert, M. Kopf, B. A. Mock, G. Köhler, and S. Rudikoff, “Interleukin 6 is essential for in vivo development of B lineage neoplasms,” Journal of Experimental Medicine, vol. 182, no. 1, pp. 243–248, 1995. View at Publisher · View at Google Scholar · View at Scopus
  75. S.-Y. Kim, J. W. Kang, X. Song et al., “Role of the IL-6-JAK1-STAT3-Oct-4 pathway in the conversion of non-stem cancer cells into cancer stem-like cells,” Cell Signaling, vol. 25, no. 4, pp. 961–969, 2013. View at Google Scholar
  76. L. Song, B. Rawal, J. A. Nemeth, and E. B. Haura, “JAK1 activates STAT3 activity in non-small-cell lung cancer cells and IL-6 neutralizing antibodies can suppress JAK1-STAT3 signaling,” Molecular Cancer Therapeutics, vol. 10, no. 3, pp. 481–494, 2011. View at Publisher · View at Google Scholar · View at Scopus
  77. J. Coward, H. Kulbe, P. Chakravarty et al., “Interleukin-6 as a therapeutic target in human ovarian cancer,” Clinical Cancer Research, vol. 17, no. 18, pp. 6083–6096, 2011. View at Publisher · View at Google Scholar · View at Scopus
  78. R. Kurzrock, P. M. Voorhees, C. Casper et al., “A phase I, open-label study of siltuximab, an anti-IL-6 monoclonal antibody, in patients with B-cell non-Hodgkin lymphoma, multiple myeloma, or Castleman disease,” Clinical Cancer Research, vol. 19, no. 13, pp. 3659–3670, 2013. View at Google Scholar
  79. J.-F. Rossi, S. Négrier, N. D. James et al., “A phase I/II study of siltuximab (CNTO 328), an anti-interleukin-6 monoclonal antibody, in metastatic renal cell cancer,” British Journal of Cancer, vol. 103, no. 8, pp. 1154–1162, 2010. View at Publisher · View at Google Scholar · View at Scopus
  80. T. B. Dorff, B. Goldman, J. K. Pinski et al., “Clinical and correlative results of SWOG S0354: a phase II trial of CNTO328 (siltuximab), a monoclonal antibody against interleukin-6, in chemotherapy-pretreated patients with castration-resistant prostate cancer,” Clinical Cancer Research, vol. 16, no. 11, pp. 3028–3034, 2010. View at Publisher · View at Google Scholar · View at Scopus
  81. J. F. Santibañez, M. Quintanilla, and C. Bernabeu, “TGF-β/TGF-β receptor system and its role in physiological and pathological conditions,” Clinical Science, vol. 121, no. 6, pp. 233–251, 2011. View at Google Scholar
  82. J. Massagué, “TGFbeta in cancer,” Cell, vol. 134, no. 2, pp. 215–230, 2008. View at Google Scholar
  83. K. Matsuzaki, “Smad phospho-isoforms direct context-dependent TGF-β signaling,” Cytokine & Growth Factor Reviews, vol. 24, no. 4, pp. 385–399, 2013. View at Google Scholar
  84. C. D. Morrison, J. G. Parvani, and W. P. Schiemann, “The relevance of the TGF-β Paradox to EMT-MET programs,” Cancer Letters, vol. 341, no. 1, pp. 30–40, 2013. View at Google Scholar
  85. A. Malliri, W. Andrew Yeudall, M. Nikolic, D. H. Crouch, E. Kenneth Parkinson, and B. Ozanne, “Sensitivity to transforming growth factor β1-induced growth arrest is common in human squamous cell carcinoma cell lines: c-MYC down-regulation and p21(waf1) induction are important early events,” Cell Growth and Differentiation, vol. 7, no. 10, pp. 1291–1304, 1996. View at Google Scholar · View at Scopus
  86. G. Guasch, M. Schober, H. A. Pasolli, E. B. Conn, L. Polak, and E. Fuchs, “Loss of TGF& signaling destabilizes homeostasis and promotes squamous cell carcinomas in stratified epithelia,” Cancer Cell, vol. 12, no. 4, pp. 313–327, 2007. View at Publisher · View at Google Scholar · View at Scopus
  87. B. Bierie and H. L. Moses, “TGF-β and cancer,” Cytokine and Growth Factor Reviews, vol. 17, no. 1-2, pp. 29–40, 2006. View at Publisher · View at Google Scholar · View at Scopus
  88. L. Levy and C. S. Hill, “Alterations in components of the TGF-β superfamily signaling pathways in human cancer,” Cytokine and Growth Factor Reviews, vol. 17, no. 1-2, pp. 41–58, 2006. View at Publisher · View at Google Scholar · View at Scopus
  89. E. C. Connolly, J. Freimuth, and R. J. Akhurst, “Complexities of TGF-β targeted cancer therapy,” International Journal of Biological Sciences, vol. 8, no. 7, pp. 964–978, 2012. View at Google Scholar
  90. R. Sabat, G. Grütz, K. Warszawska et al., “Biology of interleukin-10,” Cytokine and Growth Factor Reviews, vol. 21, no. 5, pp. 331–344, 2010. View at Publisher · View at Google Scholar · View at Scopus
  91. N. L. Costa, M. C. Valadares, P. P. C. Souza et al., “Tumor-associated macrophages and the profile of inflammatory cytokines in oral squamous cell carcinoma,” Oral Oncology, vol. 49, no. 3, pp. 216–223, 2013. View at Google Scholar
  92. G. A. Gastl, J. S. Abrams, D. M. Nanus et al., “Interleukin-10 production by human carcinoma cell lines and its relationship to interleukin-6 expression,” International Journal of Cancer, vol. 55, no. 1, pp. 96–101, 1993. View at Google Scholar · View at Scopus
  93. D. S. Finbloom and K. D. Winestock, “IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 and the differential assembly of STAT1α and STAT3 complexes in human T cells and monocytes,” Journal of Immunology, vol. 155, no. 3, pp. 1079–1090, 1995. View at Google Scholar · View at Scopus
  94. A. J. G. Schottelius, M. W. Mayo, R. Balfour Sartor, and A. S. Baldwin Jr., “Interleukin-10 signaling blocks inhibitor of κB kinase activity and nuclear factor κB DNA binding,” Journal of Biological Chemistry, vol. 274, no. 45, pp. 31868–31874, 1999. View at Publisher · View at Google Scholar · View at Scopus
  95. D. J. Berg, N. Davidson, R. Kühn et al., “Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4+ Th1-like responses,” Journal of Clinical Investigation, vol. 98, no. 4, pp. 1010–1020, 1996. View at Google Scholar · View at Scopus
  96. S. E. Erdman, T. Poutahidis, M. Tomczak et al., “CD4+ CD25+ regulatory T lymphocytes inhibit microbially induced colon cancer in Rag2-deficient mice,” American Journal of Pathology, vol. 162, no. 2, pp. 691–702, 2003. View at Google Scholar · View at Scopus
  97. S. E. Erdman, V. P. Rao, T. Poutahidis et al., “CD4+CD25+ regulatory lymphocytes require interleukin 10 to interrupt colon carcinogenesis in mice,” Cancer Research, vol. 63, no. 18, pp. 6042–6050, 2003. View at Google Scholar · View at Scopus
  98. W.-W. Lin and M. Karin, “A cytokine-mediated link between innate immunity, inflammation, and cancer,” Journal of Clinical Investigation, vol. 117, no. 5, pp. 1175–1183, 2007. View at Publisher · View at Google Scholar · View at Scopus
  99. N. Kundu and A. M. Fulton, “Interleukin-10 inhibits tumor metastasis, downregulates MHC class I, and enhances NK lysis,” Cellular Immunology, vol. 180, no. 1, pp. 55–61, 1997. View at Publisher · View at Google Scholar · View at Scopus
  100. H. Hamidullah, B. Changkija, and R. Konwar, “Role of interleukin-10 in breast cancer,” Breast Cancer Research and Treatment, vol. 133, no. 1, pp. 11–21, 2012. View at Publisher · View at Google Scholar · View at Scopus
  101. D. A. Braun, M. Fribourg, and S. C. Sealfon, “Cytokine response is determined by duration of receptor and signal transducers and activators of transcription 3 (STAT3) activation,” Journal of Biological Chemistry, vol. 288, no. 5, pp. 2986–2993, 2013. View at Google Scholar
  102. B. Sredni, M. Weil, G. Khomenok et al., “Ammonium trichloro(dioxoethylene-o,o’)tellurate (AS101) sensitizes tumors to chemotherapy by inhibiting the tumor interleukin 10 autocrine loop,” Cancer Research, vol. 64, no. 5, pp. 1843–1852, 2004. View at Publisher · View at Google Scholar · View at Scopus
  103. S. Alas, C. Emmanouilides, and B. Bonavida, “Inhibition of interleukin 10 by Rituximab results in down-regulation of Bcl-2 and sensitization of B-cell non-Hodgkin's lymphoma to apoptosis,” Clinical Cancer Research, vol. 7, no. 3, pp. 709–723, 2001. View at Google Scholar · View at Scopus
  104. L. Zeng, C. O'Connor, J. Zhang, A. M. Kaplan, and D. A. Cohen, “IL-10 promotes resistance to apoptosis and metastatic potential in lung tumor cell lines,” Cytokine, vol. 49, no. 3, pp. 294–302, 2010. View at Publisher · View at Google Scholar · View at Scopus
  105. E. Lech-Maranda, J. Bienvenu, A.-S. Michallet et al., “Elevated IL-10 plasma levels correlate with poor prognosis in diffuse large B-cell lymphoma,” European Cytokine Network, vol. 17, no. 1, pp. 60–66, 2006. View at Google Scholar · View at Scopus
  106. C. A. Ogden, J. D. Pound, B. K. Batth et al., “Enhanced apoptotic cell clearance capacity and B cell survival factor production by IL-10-activated macrophages: implications for Burkitt's lymphoma,” Journal of Immunology, vol. 174, no. 5, pp. 3015–3023, 2005. View at Google Scholar · View at Scopus
  107. K. Bedard and K.-H. Krause, “The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology,” Physiological Reviews, vol. 87, no. 1, pp. 245–313, 2007. View at Publisher · View at Google Scholar · View at Scopus
  108. U. Förstermann and W. C. Sessa, “Nitric oxide synthases: regulation and function,” European Heart Journal, vol. 33, no. 7, pp. 829–837, 2012. View at Publisher · View at Google Scholar · View at Scopus
  109. R. S. Flannagan, G. Cosío, and S. Grinstein, “Antimicrobial mechanisms of phagocytes and bacterial evasion strategies,” Nature Reviews Microbiology, vol. 7, no. 5, pp. 355–366, 2009. View at Publisher · View at Google Scholar · View at Scopus
  110. T. Finkel, “Reactive oxygen species and signal transduction,” IUBMB Life, vol. 52, no. 1-2, pp. 3–6, 2001. View at Publisher · View at Google Scholar · View at Scopus
  111. D. Yang, S. G. Elner, Z.-M. Bian, G. O. Till, H. R. Petty, and V. M. Elner, “Pro-inflammatory cytokines increase reactive oxygen species through mitochondria and NADPH oxidase in cultured RPE cells,” Experimental Eye Research, vol. 85, no. 4, pp. 462–472, 2007. View at Publisher · View at Google Scholar · View at Scopus
  112. A. Sturrock, B. Cahill, K. Norman et al., “Transforming growth factor-β1 induces Nox4 NAD(P)H oxidase and reactive oxygen species-dependent proliferation in human pulmonary artery smooth muscle cells,” American Journal of Physiology. Lung Cellular and Molecular Physiology, vol. 290, no. 4, pp. L661–L673, 2006. View at Publisher · View at Google Scholar · View at Scopus
  113. M. da Silva Krause, A. Bittencourt, P. I. Homem de Bittencourt et al., “Physiological concentrations of interleukin-6 directly promote insulin secretion, signal transduction, nitric oxide release, and redox status in a clonal pancreatic β-cell line and mouse islets,” Journal of Endocrinology, vol. 214, no. 3, pp. 301–311, 2012. View at Google Scholar
  114. G. Rieder, J. A. Hofmann, R. A. Hatz, M. Stolte, and G. A. Enders, “Up-regulation of inducible nitric oxide synthase in Helicobacter pylori-associated gastritis may represent an increased risk factor to develop gastric carcinoma of the intestinal type,” International Journal of Medical Microbiology, vol. 293, no. 6, pp. 403–412, 2003. View at Publisher · View at Google Scholar · View at Scopus
  115. D. Rachmilewitz, J. S. Stamler, D. Bachwich, F. Karmeli, Z. Ackerman, and D. K. Podolsky, “Enhanced colonic nitric oxide generation and nitric oxide synthase activity in ulcerative colitis and Crohn's disease,” Gut, vol. 36, no. 5, pp. 718–723, 1995. View at Google Scholar · View at Scopus
  116. L. J. Hofseth, S. Saito, S. Perwez Hussain et al., “Nitric oxide-induced cellular stress and p53 activation in chronic inflammation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 1, pp. 143–148, 2003. View at Publisher · View at Google Scholar · View at Scopus
  117. N. Ma, Y. Adachi, Y. Hiraku et al., “Accumulation of 8-nitroguanine in human gastric epithelium induced by Helicobacter pylori infection,” Biochemical and Biophysical Research Communications, vol. 319, no. 2, pp. 506–510, 2004. View at Publisher · View at Google Scholar · View at Scopus
  118. S. Horiike, S. Kawanishi, M. Kaito et al., “Accumulation of 8-nitroguanine in the liver of patients with chronic hepatitis C,” Journal of Hepatology, vol. 43, no. 3, pp. 403–410, 2005. View at Publisher · View at Google Scholar · View at Scopus
  119. M. Jaiswal, N. F. LaRusso, R. A. Shapiro, T. R. Billiar, and G. J. Gores, “Nitric oxide-mediated inhibition of DNA repair potentiates oxidative DNA damage in cholangiocytes,” Gastroenterology, vol. 120, no. 1, pp. 190–199, 2001. View at Google Scholar · View at Scopus
  120. C.-H. Tang, W. Wei, and L. Liu, “Regulation of DNA repair by S-nitrosylation,” Biochimica et Biophysica Acta, vol. 1820, no. 6, pp. 730–735, 2012. View at Publisher · View at Google Scholar · View at Scopus
  121. Q. Li, G.-B. Fu, J.-T. Zheng et al., “NADPH oxidase subunit p22(phox)-mediated reactive oxygen species contribute to angiogenesis and tumor growth through AKT and ERK1/2 signaling pathways in prostate cancer,” Biochimica et Biophysica Acta, vol. 1833, no. 12, pp. 3375–3385, 2013. View at Google Scholar
  122. S.-N. Jung, W. K. Yang, J. Kim et al., “Reactive oxygen species stabilize hypoxia-inducible factor-1 alpha protein and stimulate transcriptional activity via AMP-activated protein kinase in DU145 human prostate cancer cells,” Carcinogenesis, vol. 29, no. 4, pp. 713–721, 2008. View at Publisher · View at Google Scholar · View at Scopus
  123. C. V. Rao, C. Indranie, B. Simi, P. T. Manning, J. R. Connor, and B. S. Reddy, “Chemopreventive properties of a selective inducible nitric oxide synthase inhibitor in colon carcinogenesis, administered alone or in combination with celecoxib, a selective cyclooxygenase-2 inhibitor,” Cancer Research, vol. 62, no. 1, pp. 165–170, 2002. View at Google Scholar · View at Scopus
  124. M. Takahashi, T. Kitahashi, R. Ishigamori et al., “Increased expression of inducible nitric oxide synthase (iNOS) in N-nitrosobis(2-oxopropyl)amine-induced hamster pancreatic carcinogenesis and prevention of cancer development by ONO-1714, an iNOS inhibitor,” Carcinogenesis, vol. 29, no. 8, pp. 1608–1613, 2008. View at Publisher · View at Google Scholar · View at Scopus
  125. B. Li, R. Alli, P. Vogel, and T. L. Geiger, “IL-10 modulates DSS-induced colitis through a macrophage-ROS-NO axis,” Mucosal Immunology, 2013. View at Google Scholar
  126. G. Zhu, Q. Du, X. Wang et al., “TNF-α promotes gallbladder cancer cell growth and invasion through autocrine mechanisms,” International Journal of Molecular Medicine, 2014. View at Google Scholar
  127. K. A. Charles, H. Kulbe, R. Soper et al., “The tumor-promoting actions of TNF-α involve TNFR1 and IL-17 in ovarian cancer in mice and humans,” Journal of Clinical Investigation, vol. 119, no. 10, pp. 3011–3023, 2009. View at Publisher · View at Google Scholar · View at Scopus
  128. D. He, H. Li, N. Yusuf et al., “IL-17 mediated inflammation promotes tumor growth and progression in the skin,” PLoS ONE, vol. 7, no. 2, Article ID e32126, 2012. View at Publisher · View at Google Scholar · View at Scopus
  129. T. Shouda, K. Hiraoka, S. Komiya et al., “Suppression of IL-6 production and proliferation by blocking STAT3 activation in malignant soft tissue tumor cells,” Cancer Letters, vol. 231, no. 2, pp. 176–184, 2006. View at Publisher · View at Google Scholar · View at Scopus
  130. Q. Tang, J. Li, H. Zhu et al., “Hmgb1-IL-23-IL-17-IL-6-Stat3 axis promotes tumor growth in murine models of melanoma,” Mediators of Inflammation, vol. 2013, Article ID 713859, 13 pages, 2013. View at Publisher · View at Google Scholar
  131. T. Zheng, X. Hong, and J. Wang, “Gankyrin promotes tumor growth and metastasis through activation of IL-6/STAT3 signaling in human cholangiocarcinoma,” Hepatology, vol. 59, no. 3, pp. 935–946, 2014. View at Google Scholar
  132. Y. Dai, H. Jiao, G. Teng et al., “Embelin reduces colitis-associated tumorigenesis through limiting IL-6/STAT3 signaling,” Molecular Cancer Therapeutics, 2014. View at Google Scholar
  133. M. L. García-Hernández, R. Hernández-Pando, P. Gariglio, and J. Berumen, “Interleukin-10 promotes B16-melanoma growth by inhibition of macrophage functions and induction of tumour and vascular cell proliferation,” Immunology, vol. 105, no. 2, pp. 231–243, 2002. View at Publisher · View at Google Scholar · View at Scopus
  134. B. Baum, J. Settleman, and M. P. Quinlan, “Transitions between epithelial and mesenchymal states in development and disease,” Seminars in Cell and Developmental Biology, vol. 19, no. 3, pp. 294–308, 2008. View at Publisher · View at Google Scholar · View at Scopus
  135. R. Kalluri and R. A. Weinberg, “The basics of epithelial-mesenchymal transition,” Journal of Clinical Investigation, vol. 119, no. 6, pp. 1420–1428, 2009. View at Publisher · View at Google Scholar · View at Scopus
  136. J. P. Thiery and J. P. Sleeman, “Complex networks orchestrate epithelial-mesenchymal transitions,” Nature Reviews Molecular Cell Biology, vol. 7, no. 2, pp. 131–142, 2006. View at Publisher · View at Google Scholar · View at Scopus
  137. J. Xu, S. Lamouille, and R. Derynck, “TGF-Β-induced epithelial to mesenchymal transition,” Cell Research, vol. 19, no. 2, pp. 156–172, 2009. View at Publisher · View at Google Scholar · View at Scopus
  138. J. P. Thiery, “Epithelial-mesenchymal transitions in tumour progression,” Nature Reviews Cancer, vol. 2, no. 6, pp. 442–454, 2002. View at Google Scholar
  139. V. Tirino, R. Camerlingo, K. Bifulco et al., “TGF-β1 exposure induces epithelial to mesenchymal transition both in CSCs and non-CSCs of the A549 cell line, leading to an increase of migration ability in the CD133+ A549 cell fraction,” Cell Death & Disease, vol. 4, no. 5, article e620, 2013. View at Google Scholar
  140. V. Ellenrieder, S. F. Hendler, W. Boeck et al., “Transforming growth factor β1 treatment leads to an epithelial-mesenchymal transdifferentiation of pancreatic cancer cells requiring extracellular signal-regulated kinase 2 activation,” Cancer Research, vol. 61, no. 10, pp. 4222–4228, 2001. View at Google Scholar · View at Scopus
  141. B. C. Willis, J. M. Liebler, K. Luby-Phelps et al., “Induction of epithelial-mesenchymal transition in alveolar epithelial cells by transforming growth factor-β1: potential role in idiopathic pulmonary fibrosis,” American Journal of Pathology, vol. 166, no. 5, pp. 1321–1332, 2005. View at Google Scholar · View at Scopus
  142. T. Yamagishi, K. Ando, H. Nakamura, and Y. Nakajima, “Expression of the Tgfβ2 gene during chick embryogenesis,” Anatomical Record, vol. 295, no. 2, pp. 257–267, 2012. View at Publisher · View at Google Scholar · View at Scopus
  143. M. Sato, Y. Muragaki, S. Saika, A. B. Roberts, and A. Ooshima, “Targeted disruption of TGF-β1/Smad3 signaling protects against renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction,” Journal of Clinical Investigation, vol. 112, no. 10, pp. 1486–1494, 2003. View at Publisher · View at Google Scholar · View at Scopus
  144. U. Valcourt, M. Kowanetz, H. Niimi, C.-H. Heldin, and A. Moustakas, “TGF-β and the Smad signaling pathway support transcriptomic reprogramming during epithelial-mesenchymal cell transition,” Molecular Biology of the Cell, vol. 16, no. 4, pp. 1987–2002, 2005. View at Publisher · View at Google Scholar · View at Scopus
  145. A. Abulaiti, Y. Shintani, S. Funaki et al., “Interaction between non-small-cell lung cancer cells and fibroblasts via enhancement of TGF-β signaling by IL-6,” Lung Cancer, vol. 82, no. 2, pp. 204–213, 2013. View at Google Scholar
  146. H. J. Maier, U. Schmidt-Straßburger, M. A. Huber, E. M. Wiedemann, H. Beug, and T. Wirth, “NF-κB promotes epithelial-mesenchymal transition, migration and invasion of pancreatic carcinoma cells,” Cancer Letters, vol. 295, no. 2, pp. 214–228, 2010. View at Publisher · View at Google Scholar · View at Scopus
  147. M. Kumar, D. F. Allison, N. N. Baranova et al., “NF-κB regulates mesenchymal transition for the induction of non-small cell lung cancer initiating cells,” PLoS ONE, vol. 8, no. 7, Article ID e68597, 2013. View at Google Scholar
  148. A. Yadav, B. Kumar, J. Datta, T. N. Teknos, and P. Kumar, “IL-6 promotes head and neck tumor metastasis by inducing epithelial-mesenchymal transition via the JAK-STAT3-SNAIL signaling pathway,” Molecular Cancer Research, vol. 9, no. 12, pp. 1658–1667, 2011. View at Publisher · View at Google Scholar · View at Scopus
  149. Z. Wang, Y. Li, and F. H. Sarkar, “Signaling mechanism(S) of reactive oxygen species in epithelial-mesenchymal transition reminiscent of cancer stem cells in tumor progression,” Current Stem Cell Research and Therapy, vol. 5, no. 1, pp. 74–80, 2010. View at Publisher · View at Google Scholar · View at Scopus
  150. D. Y. Rhyu, Y. Yang, H. Ha et al., “Role of reactive oxygen species in TGF-β1-induced mitogen-activated protein kinase activation and epithelial-mesenchymal transition in renal tubular epithelial cells,” Journal of the American Society of Nephrology, vol. 16, no. 3, pp. 667–675, 2005. View at Publisher · View at Google Scholar · View at Scopus
  151. Y. Cao, “Tumor angiogenesis and therapy,” Biomedicine and Pharmacotherapy, vol. 59, no. 2, pp. S340–S343, 2005. View at Publisher · View at Google Scholar · View at Scopus
  152. O.-H. Kim, G.-H. Kang, H. Noh et al., “Proangiogenic TIE2+/CD31+) macrophages are the predominant population of tumor-associated macrophages infiltrating metastatic lymph nodes,” Molecules and Cells, vol. 36, no. 5, pp. 432–438, 2013. View at Google Scholar
  153. L. F. Fajardo, H. H. Kwan, J. Kowalski, S. D. Prionas, and A. C. Allison, “Dual role of tumor necrosis factor-α in angiogenesis,” American Journal of Pathology, vol. 140, no. 3, pp. 539–544, 1992. View at Google Scholar · View at Scopus
  154. R. R. Weichselbaum, D. W. Kufe, S. Hellman et al., “Radiation-induced tumour necrosis factor-α expression: clinical application of transcriptional and physical targeting of gene therapy,” The Lancet Oncology, vol. 3, no. 11, pp. 665–671, 2002. View at Publisher · View at Google Scholar · View at Scopus
  155. S. Yoshida, M. Ono, T. Shono et al., “Involvement of interleukin-8, vascular endothelial growth factor, and basic fibroblast growth factor in tumor necrosis factor alpha-dependent angiogenesis,” Molecular and Cellular Biology, vol. 17, no. 7, pp. 4015–4023, 1997. View at Google Scholar · View at Scopus
  156. B. Li, A. Vincent, J. Cates, D. M. Brantley-Sieders, D. B. Polk, and P. P. Young, “Low levels of tumor necrosis factor α increase tumor growth by inducing an endothelial phenotype of monocytes recruited to the tumor site,” Cancer Research, vol. 69, no. 1, pp. 338–348, 2009. View at Publisher · View at Google Scholar · View at Scopus
  157. H. Kulbe, R. Thompson, J. L. Wilson et al., “The inflammatory cytokine tumor necrosis factor-α generates an autocrine tumor-promoting network in epithelial ovarian cancer cells,” Cancer Research, vol. 67, no. 2, pp. 585–592, 2007. View at Publisher · View at Google Scholar · View at Scopus
  158. A. Eldesoky, A. Shouma, Y. Mosaad, and A. Elhawary, “Clinical relevance of serum vascular endothelial growth factor and interleukin-6 in patients with colorectal cancer,” Saudi Journal of Gastroenterology, vol. 17, no. 3, pp. 170–173, 2011. View at Google Scholar · View at Scopus
  159. H. K. Kim, K. S. Song, Y. S. Park et al., “Elevated levels of circulating platelet microparticles, VEGF, IL-6 and RANTES in patients with gastric cancer: possible role of a metastasis predictor,” European Journal of Cancer, vol. 39, no. 2, pp. 184–191, 2003. View at Publisher · View at Google Scholar · View at Scopus
  160. S.-P. Huang, M.-S. Wu, C.-T. Shun et al., “Interleukin-6 increases vascular endothelial growth factor and angiogenesis in gastric carcinoma,” Journal of Biomedical Science, vol. 11, no. 4, pp. 517–527, 2004. View at Publisher · View at Google Scholar · View at Scopus
  161. L.-H. Wei, M.-L. Kuo, C.-A. Chen et al., “Interleukin-6 promotes cervical tumor growth by VEGF-dependent angiogenesis via a STAT3 pathway,” Oncogene, vol. 22, no. 10, pp. 1517–1527, 2003. View at Publisher · View at Google Scholar · View at Scopus
  162. L. W. Feurino, Y. Zhang, U. Bharadwaj et al., “IL-6 stimulates Th2 type cytokine secretion and upregulates VEGF and NRP-1 expression in pancreatic cancer cells,” Cancer Biology and Therapy, vol. 6, no. 7, pp. 1096–1100, 2007. View at Google Scholar · View at Scopus
  163. S. R. Boreddy, R. P. Sahu, and S. K. Srivastava, “Benzyl isothiocyanate suppresses pancreatic tumor angiogenesis and invasion by inhibiting HIF-α/VEGF/Rho-GTPases: pivotal role of STAT-3,” PLoS ONE, vol. 6, no. 10, Article ID e25799, 2011. View at Publisher · View at Google Scholar · View at Scopus
  164. P. Wikström, P. Stattin, I. Franck-Lissbrant et al., “Transforming growth factor beta1 is associated with angiogenesis, metastasis, and poor clinical outcome in prostate cancer,” Prostate, vol. 37, no. 1, pp. 19–29, 1998. View at Google Scholar
  165. H. Saito, S. Tsujitani, S. Oka et al., “The expression of transforming growth factor-beta1 is significantly correlated with the expression of vascular endothelial growth factor and poor prognosis of patients with advanced gastric carcinoma,” Cancer, vol. 86, no. 8, pp. 1455–1462, 1999. View at Google Scholar
  166. M. C. Dickson, J. S. Martin, F. M. Cousins, A. B. Kulkarni, S. Karlsson, and R. J. Akhurst, “Defective haematopoiesis and vasculogenesis in transforming growth factor-β1 knock out mice,” Development, vol. 121, no. 6, pp. 1845–1854, 1995. View at Google Scholar · View at Scopus
  167. S. Huang, K. Xie, C. D. Bucana, S. E. Ullrich, and M. Bar-Eli, “Interleukin 10 suppresses tumor growth and metastasis of human melanoma cells: potential inhibition of angiogenesis,” Clinical Cancer Research, vol. 2, no. 12, pp. 1969–1979, 1996. View at Google Scholar · View at Scopus
  168. M. E. Stearns, J. Rhim, and M. Wang, “Interleukin 10 (IL-10) inhibition of primary human prostate cell- induced angiogenesis: IL-10 stimulation of tissue inhibitor of metalloproteinase-1 and inhibition of matrix metalloproteinase (MMP)-2/MMP-9 secretion,” Clinical Cancer Research, vol. 5, no. 1, pp. 189–196, 1999. View at Google Scholar · View at Scopus
  169. T. Kohno, H. Mizukami, M. Suzuki et al., “Interleukin-10-mediated inhibition of angiogenesis and tumor growth in mice bearing VEGF-producing ovarian cancer,” Cancer Research, vol. 63, no. 16, pp. 5091–5094, 2003. View at Google Scholar · View at Scopus
  170. P. Orosz, B. Echtenacher, W. Falk, J. Ruschoff, D. Weber, and D. N. Mannel, “Enhancement of experimental metastasis by tumor necrosis factor,” Journal of Experimental Medicine, vol. 177, no. 5, pp. 1391–1398, 1993. View at Google Scholar · View at Scopus
  171. P. Orosz, A. Kruger, M. Hubbe, J. Ruschoff, P. Von Hoegen, and D. N. Mannel, “Promotion of experimental liver metastasis by tumor necrosis factor,” International Journal of Cancer, vol. 60, no. 6, pp. 867–871, 1995. View at Publisher · View at Google Scholar · View at Scopus
  172. S. Kim, H. Takahashi, W.-W. Lin et al., “Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis,” Nature, vol. 457, no. 7225, pp. 102–106, 2009. View at Publisher · View at Google Scholar · View at Scopus
  173. J.-H. Egberts, V. Cloosters, A. Noack et al., “Anti-tumor necrosis factor therapy inhibits pancreatic tumor growth and metastasis,” Cancer Research, vol. 68, no. 5, pp. 1443–1450, 2008. View at Publisher · View at Google Scholar · View at Scopus
  174. G. D. Roodman, “Role of stromal-derived cytokines and growth factors in bone metastasis,” Cancer, vol. 97, no. 3, pp. 733–738, 2003. View at Google Scholar · View at Scopus
  175. K. Tawara, J. T. Oxford, and C. L. Jorcyk, “Clinical significance of interleukin (IL)-6 in cancer metastasis to bone:Potential of anti-IL-6 therapies,” Cancer Management and Research, vol. 3, no. 1, pp. 177–189, 2011. View at Publisher · View at Google Scholar · View at Scopus
  176. T. R. Samatov, A. G. Tonevitsky, and U. Schumacher, “Epithelial-mesenchymal transition: focus on metastatic cascade, alternative splicing, non-coding RNAs and modulating compounds,” Molecular Cancer, vol. 12, no. 1, article 107, 2013. View at Google Scholar
  177. J. Ferlay, H.-R. Shin, F. Bray, D. Forman, C. Mathers, and D. M. Parkin, “Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008,” International Journal of Cancer, vol. 127, no. 12, pp. 2893–2917, 2010. View at Publisher · View at Google Scholar · View at Scopus
  178. R. Siegel, D. Naishadham, and A. Jemal, “Cancer statistics, 2013,” CA Cancer Journal for Clinicians, vol. 63, pp. 11–30, 2013. View at Google Scholar
  179. C. J. Ooi, K. M. Fock, G. K. Makharia et al., “The Asia-Pacific consensus on ulcerative colitis,” Journal of Gastroenterology and Hepatology, vol. 25, no. 3, pp. 453–468, 2010. View at Publisher · View at Google Scholar · View at Scopus
  180. T. Watanabe, T. Konishi, J. Kishimoto, K. Kotake, T. Muto, and K. Sugihara, “Ulcerative colitis-associated colorectal cancer shows a poorer survival than sporadic colorectal cancer: a nationwide Japanese study,” Inflammatory Bowel Diseases, vol. 17, no. 3, pp. 802–808, 2011. View at Publisher · View at Google Scholar · View at Scopus
  181. T. A. Ullman and S. H. Itzkowitz, “Intestinal inflammation and cancer,” Gastroenterology, vol. 140, no. 6, pp. 1807–1816, 2011. View at Publisher · View at Google Scholar · View at Scopus
  182. R. M. Soetikno, O. S. Lin, P. A. Heidenreich, H. S. Young, and M. O. Blackstone, “Increased risk of colorectal neoplasia in patiets with primary sclerosing cholangitis and ulcerative colitis: a meta-analysis,” Gastrointestinal Endoscopy, vol. 56, no. 1, pp. 48–54, 2002. View at Publisher · View at Google Scholar · View at Scopus
  183. B. Chassaing and A. Darfeuillemichaud, “The commensal microbiota and enteropathogens in the pathogenesis of inflammatory bowel diseases,” Gastroenterology, vol. 140, no. 6, pp. 1720–1728, 2011. View at Publisher · View at Google Scholar · View at Scopus
  184. M. de la Fuente, L. Franchi, and D. Araya, “Escherichia coli isolates from inflammatory bowel diseases patients survive in macrophages and activate NLRP3 inflammasome,” International Journal of Medical Microbiology, 2014. View at Google Scholar
  185. M. Sasaki, S. V. Sitaraman, B. A. Babbin et al., “Invasive Escherichia coli are a feature of Crohn's disease,” Laboratory Investigation, vol. 87, no. 10, pp. 1042–1054, 2007. View at Publisher · View at Google Scholar · View at Scopus
  186. H. Nakase, H. Tamaki, M. Matsuura, T. Chiba, and K. Okazaki, “Involvement of Mycobacterium avium subspecies paratuberculosis in TNF-α production from macrophage: possible link between MAP and immune response in Crohn's disease,” Inflammatory Bowel Diseases, vol. 17, no. 11, pp. e140–e142, 2011. View at Publisher · View at Google Scholar · View at Scopus
  187. E. Mizoguchi, M. Kanneganti, and M. Mino-Kenudson, “Animal models of colitis-associated carcinogenesis,” Journal of Biomedicine and Biotechnology, vol. 2011, Article ID 342637, 23 pages, 2011. View at Publisher · View at Google Scholar · View at Scopus
  188. I. Okayasu, M. Yamada, T. Mikami, T. Yoshida, J. Kanno, and T. Ohkusa, “Dysplasia and carcinoma development in a repeated dextran sulfate sodium-induced colitis model,” Journal of Gastroenterology and Hepatology, vol. 17, no. 10, pp. 1078–1083, 2002. View at Publisher · View at Google Scholar · View at Scopus
  189. H. S. Cooper, S. Murthy, K. Kido, H. Yoshitake, and A. Flanigan, “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, vol. 21, no. 4, pp. 757–768, 2000. View at Google Scholar · View at Scopus
  190. T. Tanaka, H. Kohno, R. Suzuki, Y. Yamada, S. Sugie, and H. Mori, “A novel inflammation-related mouse colon carcinogenesis model induced by azoxymethane and dextran sodium sulfate,” Cancer Science, vol. 94, no. 11, pp. 965–973, 2003. View at Publisher · View at Google Scholar · View at Scopus
  191. M. Takahashi, M. Mutoh, T. Kawamori, T. Sugimura, and K. Wakabayashi, “Altered expression of β-catenin, inducible nitric oxide synthase and cyclooxygenase-2 in azoxymethane-induced rat colon carcinogenesis,” Carcinogenesis, vol. 21, no. 7, pp. 1319–1327, 2000. View at Google Scholar · View at Scopus
  192. T. Olsen, R. Goll, G. Cui et al., “Tissue levels of tumor necrosis factor-alpha correlates with grade of inflammation in untreated ulcerative colitis,” Scandinavian Journal of Gastroenterology, vol. 42, no. 11, pp. 1312–1320, 2007. View at Publisher · View at Google Scholar · View at Scopus
  193. K. Kusugami, A. Fukatsu, M. Tanimoto et al., “Elevation of interleukin-6 in inflammatory bowel disease is macrophage- and epithelial cell-dependent,” Digestive Diseases and Sciences, vol. 40, no. 5, pp. 949–959, 1995. View at Google Scholar · View at Scopus
  194. B. K. Popivanova, K. Kitamura, Y. Wu et al., “Blocking TNF-α in mice reduces colorectal carcinogenesis associated with chronic colitis,” Journal of Clinical Investigation, vol. 118, no. 2, pp. 560–570, 2008. View at Publisher · View at Google Scholar · View at Scopus
  195. D. N. Seril, J. Liao, G.-Y. Yang, and C. S. Yang, “Oxidative stress and ulcerative colitis-associated carcinogenesis: studies in humans and animal models,” Carcinogenesis, vol. 24, no. 3, pp. 353–362, 2003. View at Publisher · View at Google Scholar · View at Scopus
  196. S. P. Hussain, P. Amstad, K. Raja et al., “Increased p53 mutation load in noncancerous colon tissue from ulcerative colitis: a cancer-prone chronic inflammatory disease,” Cancer Research, vol. 60, no. 13, pp. 3333–3337, 2000. View at Google Scholar · View at Scopus
  197. H. Tsushima, S. Kawata, S. Tamura et al., “High levels of transforming growth factor in patients with colorectal cancer: association with disease progression,” Gastroenterology, vol. 110, no. 2, pp. 375–382, 1996. View at Publisher · View at Google Scholar · View at Scopus
  198. I. C. Lawrance, L. Maxwell, and W. Doe, “Inflammation location, but not type, determines the increase in TGF-β1 and IGF-1 expression and collagen deposition in IBD intestine,” Inflammatory Bowel Diseases, vol. 7, no. 1, pp. 16–26, 2001. View at Google Scholar
  199. F. Scaldaferri, S. Vetrano, M. Sans et al., “VEGF-A links angiogenesis and inflammation in inflammatory bowel disease pathogenesis,” Gastroenterology, vol. 136, no. 2, pp. 585–595, 2009. View at Publisher · View at Google Scholar · View at Scopus
  200. M. J. Waldner, S. Wirtz, A. Jefremow et al., “VEGF receptor signaling links inflammation and tumorigenesis in colitis-associated cancer,” Journal of Experimental Medicine, vol. 207, no. 13, pp. 2855–2868, 2010. View at Publisher · View at Google Scholar · View at Scopus
  201. Y. Kikuchi, T. G. Kashima, T. Nishiyama et al., “Periostin is expressed in pericryptal fibroblasts and cancer-associated fibroblasts in the colon,” Journal of Histochemistry and Cytochemistry, vol. 56, no. 8, pp. 753–764, 2008. View at Publisher · View at Google Scholar · View at Scopus
  202. S. Bao, G. Ouyang, X. Bai et al., “Periostin potently promotes metastatic growth of colon cancer by augmenting cell survival via the Akt/PKB pathway,” Cancer Cell, vol. 5, no. 4, pp. 329–339, 2004. View at Publisher · View at Google Scholar · View at Scopus
  203. S. Fujino, A. Andoh, S. Bamba et al., “Increased expression of interleukin 17 in inflammatory bowel disease,” Gut, vol. 52, no. 1, pp. 65–70, 2003. View at Publisher · View at Google Scholar · View at Scopus
  204. Y. S. Hyun, D. S. Han, A. R. Lee, C. S. Eun, J. Youn, and H.-Y. Kim, “Role of IL-17A in the development of colitis-associated cancer,” Carcinogenesis, vol. 33, no. 4, pp. 931–936, 2012. View at Publisher · View at Google Scholar · View at Scopus
  205. M. A. Farrar and R. D. Schreiber, “The molecular cell biology of interferon-γ and its receptor,” Annual Review of Immunology, vol. 11, pp. 571–611, 1993. View at Google Scholar · View at Scopus
  206. A. Harada, N. Sekido, T. Akahoshi, T. Wada, N. Mukaida, and K. Matsushima, “Essential involvement of interleukin-8 (IL-8) in acute inflammation,” Journal of Leukocyte Biology, vol. 56, no. 5, pp. 559–564, 1994. View at Google Scholar · View at Scopus
  207. R. Daig, T. Andus, E. Aschenbrenner, W. Falk, J. Schölmerich, and V. Gross, “Increased interleukin 8 expression in the colon mucosa of patients with inflammatory bowel disease,” Gut, vol. 38, no. 2, pp. 216–222, 1996. View at Google Scholar · View at Scopus
  208. L. Mazzucchelli, C. Hauser, K. Zgraggen et al., “Expression of interleukin-8 gene in inflammatory bowel disease is related to the histological grade of active inflammation,” American Journal of Pathology, vol. 144, no. 5, pp. 997–1007, 1994. View at Google Scholar · View at Scopus
  209. M. C. Grimm, S. K. O. Elsbury, P. Pavli, and W. F. Doe, “Interleukin 8: cells of origin in inflammatory bowel disease,” Gut, vol. 38, no. 1, pp. 90–98, 1996. View at Google Scholar · View at Scopus
  210. A. Li, M. L. Varney, and R. K. Singh, “Expression of interleukin 8 and its receptors in human colon carcinoma cells with different metastatic potentials,” Clinical Cancer Research, vol. 7, no. 10, pp. 3298–3304, 2001. View at Google Scholar · View at Scopus
  211. T. Cacev, S. Radosević, S. Krizanac, and S. Kapitanović, “Influence of interleukin-8 and interleukin-10 on sporadic colon cancer development and progression,” Carcinogenesis, vol. 29, no. 8, pp. 1572–1580, 2008. View at Google Scholar
  212. J. Heidemann, H. Ogawa, M. B. Dwinell et al., “Angiogenic effects of interleukin 8 (CXCL8) in human intestinal microvascular endothelial cells are mediated by CXCR2,” Journal of Biological Chemistry, vol. 278, no. 10, pp. 8508–8515, 2003. View at Publisher · View at Google Scholar · View at Scopus
  213. J. E. Everhart and C. E. Ruhl, “Burden of digestive diseases in the United States—part III: liver, biliary tract, and pancreas,” Gastroenterology, vol. 136, no. 4, pp. 1134–1144, 2009. View at Publisher · View at Google Scholar · View at Scopus
  214. Y. Shaib and H. B. El-Serag, “The epidemiology of cholangiocarcinoma,” Seminars in Liver Disease, vol. 24, no. 2, pp. 115–125, 2004. View at Publisher · View at Google Scholar · View at Scopus
  215. B. Sripa and C. Pairojkul, “Cholangiocarcinoma: lessons from Thailand,” Current Opinion in Gastroenterology, vol. 24, no. 3, pp. 349–356, 2008. View at Publisher · View at Google Scholar · View at Scopus
  216. G. L. Tyson and H. B. El-Serag, “Risk factors for cholangiocarcinoma,” Hepatology, vol. 54, no. 1, pp. 173–184, 2011. View at Publisher · View at Google Scholar · View at Scopus
  217. J. Fevery, C. Verslype, G. Lai, R. Aerts, and W. van Steenbergen, “Incidence, diagnosis, and therapy of cholangiocarcinoma in patients with primary sclerosing cholangitis,” Digestive Diseases and Sciences, vol. 52, no. 11, pp. 3123–3135, 2007. View at Publisher · View at Google Scholar · View at Scopus
  218. P. Charatcharoenwitthaya, F. B. Enders, K. C. Halling, and K. D. Lindor, “Utility of serum tumor markers, imaging, and biliary cytology for detecting cholangiocarcinoma in primary sclerosing cholangitis,” Hepatology, vol. 48, no. 4, pp. 1106–1117, 2008. View at Publisher · View at Google Scholar · View at Scopus
  219. K. Burak, P. Angulo, T. M. Pasha, K. Egan, J. Petz, and K. D. Lindor, “Incidence and risk factors for cholangiocarcinoma in primary sclerosing cholangitis,” American Journal of Gastroenterology, vol. 99, no. 3, pp. 523–526, 2004. View at Publisher · View at Google Scholar · View at Scopus
  220. V. Bouvard, R. Baan, K. Straif et al., “A review of human carcinogens—part B: biological agents,” The Lancet Oncology, vol. 10, no. 4, pp. 321–322, 2009. View at Google Scholar · View at Scopus
  221. B. Sripa, J. M. Bethony, P. Sithithaworn et al., “Opisthorchiasis and Opisthorchis-associated cholangiocarcinoma in Thailand and Laos,” Acta Tropica, vol. 120, no. 1, pp. S158–S168, 2011. View at Publisher · View at Google Scholar · View at Scopus
  222. K. L. Min, Y.-H. Ju, S. Franceschi et al., “Clonorchis sinensis infection and increasing risk of cholangiocarcinoma in the republic of korea,” American Journal of Tropical Medicine and Hygiene, vol. 75, no. 1, pp. 93–96, 2006. View at Google Scholar · View at Scopus
  223. X. Zhou, W. Peng, D. W. T. Crompton, and J. Xiong, “Treatment of biliary ascariasis in China,” Transactions of the Royal Society of Tropical Medicine and Hygiene, vol. 93, no. 6, pp. 561–564, 1999. View at Google Scholar · View at Scopus
  224. M. Mukhopadhyay, “Biliary ascariasis in the Indian subcontinent: a study of 42 cases,” Saudi Journal of Gastroenterology, vol. 15, no. 2, pp. 121–124, 2009. View at Publisher · View at Google Scholar · View at Scopus
  225. A. M. Di Bisceglie, “Hepatitis B and hepatocellular carcinoma,” Hepatology, vol. 49, no. 5, pp. S56–S60, 2009. View at Publisher · View at Google Scholar · View at Scopus
  226. T. Y. Lee, S. S. Lee, S. W. Jung et al., “Hepatitis B virus infection and intrahepatic cholangiocarcinoma in Korea: a case-control study,” American Journal of Gastroenterology, vol. 103, no. 7, pp. 1716–1720, 2008. View at Publisher · View at Google Scholar · View at Scopus
  227. T. Isa, S. Tomita, A. Nakachi et al., “Analysis of microsatellite instability, K-ras gene mutation and p53 protein overexpression in intrahepatic cholangiocarcinoma,” Hepato-Gastroenterology, vol. 49, no. 45, pp. 604–608, 2002. View at Google Scholar · View at Scopus
  228. Y. Wang, Y. Yamaguchi, H. Watanabe, K. Ohtsubo, T. Wakabayashi, and N. Sawabu, “Usefulness of p53 gene mutations in the supernatant of bile for diagnosis of biliary tract carcinoma: comparison with K-ras mutation,” Journal of Gastroenterology, vol. 37, no. 10, pp. 831–839, 2002. View at Publisher · View at Google Scholar · View at Scopus
  229. T. Itoi, K. Takei, Y. Shinohara et al., “K-ras codon 12 and p53 mutations in biopsy specimens and bile from biliary tract cancers,” Pathology International, vol. 49, no. 1, pp. 30–37, 1999. View at Publisher · View at Google Scholar · View at Scopus
  230. S.-I. Aishima, K.-I. Taguchi, K. Sugimachi, M. Shimada, K. Sugimachi, and M. Tsuneyoshi, “c-erbB-2 and c-Met expression relates to cholangiocarcinogenesis and progression of intrahepatic cholangiocarcinoma,” Histopathology, vol. 40, no. 3, pp. 269–278, 2002. View at Publisher · View at Google Scholar · View at Scopus
  231. A. C. Okaro, A. R. Deery, R. R. Hutchins, and B. R. Davidson, “The expression of antiapoptotic proteins Bcl-2, Bcl-xL, and Mcl-1 in benign, dysplastic, and malignant biliary epithelium,” Journal of Clinical Pathology, vol. 54, no. 12, pp. 927–932, 2001. View at Google Scholar · View at Scopus
  232. M. Taniai, H. Higuchi, L. J. Burgart, and G. J. Gores, “p16INK4a promoter mutations are frequent in primary sclerosing cholangitis (PSC) and PSC-associated cholangiocarcinoma,” Gastroenterology, vol. 123, no. 4, pp. 1090–1098, 2002. View at Publisher · View at Google Scholar · View at Scopus
  233. S. Boonjaraspinyo, Z. Wu, T. Boonmars et al., “Overexpression of PDGFA and its receptor during carcinogenesis of Opisthorchis viverrini-associated cholangiocarcinoma,” Parasitology International, vol. 61, no. 1, pp. 145–150, 2012. View at Publisher · View at Google Scholar · View at Scopus
  234. S. Boonjaraspinyo, T. Boonmars, Z. Wu et al., “Platelet-derived growth factor may be a potential diagnostic and prognostic marker for cholangiocarcinoma,” Tumor Biology, vol. 33, no. 5, pp. 1785–1802, 2012. View at Google Scholar
  235. D. J. Drucker, “Biological actions and therapeutic potential of the glucagon-like peptides,” Gastroenterology, vol. 122, no. 2, pp. 531–544, 2002. View at Google Scholar · View at Scopus
  236. M. Marzioni, G. Alpini, S. Saccomanno et al., “Glucagon-like peptide-1 and its receptor agonist exendin-4 modulate cholangiocyte adaptive response to cholestasis,” Gastroenterology, vol. 133, no. 1, pp. 244–255, 2007. View at Publisher · View at Google Scholar · View at Scopus
  237. E. Gaudio, B. Barbaro, D. Alvaro et al., “Vascular endothelial growth factor stimulates rat cholangiocyte proliferation via an autocrine mechanism,” Gastroenterology, vol. 130, no. 4, pp. 1270–1282, 2006. View at Publisher · View at Google Scholar · View at Scopus
  238. E. Gaudio, B. Barbaro, D. Alvaro et al., “Administration of r-VEGF-A prevents hepatic artery ligation-induced bile duct damage in bile duct ligated rats,” American Journal of Physiology. Gastrointestinal and Liver Physiology, vol. 291, no. 2, pp. G307–G317, 2006. View at Publisher · View at Google Scholar · View at Scopus
  239. A. E. Sirica, M. H. Nathanson, G. J. Gores, and N. F. LaRusso, “Pathobiology of biliary epithelia and cholangiocarcinoma: proceedings of the Henry M. and Lillian Stratton Basic Research Single-Topic Conference,” Hepatology, vol. 48, no. 6, pp. 2040–2046, 2008. View at Publisher · View at Google Scholar · View at Scopus
  240. D. Hanahan and L. M. Coussens, “Accessories to the crime: functions of cells recruited to the tumor microenvironment,” Cancer Cell, vol. 21, no. 3, pp. 309–322, 2012. View at Publisher · View at Google Scholar · View at Scopus
  241. C. Chuaysri, P. Thuwajit, A. Paupairoj, S. Chau-In, T. Suthiphongchai, and C. Thuwajit, “Alpha-smooth muscle actin-positive fibroblasts promote biliary cell proliferation and correlate with poor survival in cholangiocarcinoma,” Oncology Reports, vol. 21, no. 4, pp. 957–969, 2009. View at Publisher · View at Google Scholar · View at Scopus
  242. K. Utispan, P. Thuwajit, Y. Abiko et al., “Gene expression profiling of cholangiocarcinoma-derived fibroblast reveals alterations related to tumor progression and indicates periostin as a poor prognostic marker,” Molecular Cancer, vol. 9, article 13, 2010. View at Publisher · View at Google Scholar · View at Scopus
  243. A. E. Sirica, “The role of cancer-associated myofibroblasts in intrahepatic cholangiocarcinoma,” Nature Reviews Gastroenterology and Hepatology, vol. 9, no. 1, pp. 44–54, 2012. View at Publisher · View at Google Scholar · View at Scopus
  244. S. Rizvi and G. J. Gores, “Pathogenesis, diagnosis, and management of cholangiocarcinoma,” Gastroenterology, vol. 145, no. 6, pp. 1215–1229, 2013. View at Google Scholar
  245. A. E. Sirica, D. J. Campbell, and C. I. Dumur, “Cancer-associated fibroblasts in intrahepatic cholangiocarcinoma,” Current Opinion in Gastroenterology, vol. 27, no. 3, pp. 276–284, 2011. View at Publisher · View at Google Scholar · View at Scopus