IL-6 and related cytokines as the critical lynchpins between inflammation and cancer

Seminars in Immunology

Volumn 26, Issue 1, 2014, Pages 54-74

  Taniguchi, Koji ^a,c,d   Karin, Michael ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

^c KYUSHU UNIVERSITY   (Japan)

^d KEIO UNIVERSITY SCHOOL OF MEDICINE   (Japan)

Author keywords

Colorectal cancer; Gastric cancer; Gp130; Hepatocellular carcinoma; IL 11; IL 6; STAT3

Indexed keywords

1 CYCLOPROPYL 3 [3 (5 MORPHOLINOMETHYL 1H BENZIMIDAZOL 2 YL) 1H PYRAZOL 4 YL]UREA; 5 CHLORO N2 [1 (5 FLUORO 2 PYRIMIDINYL)ETHYL] N4 (5 METHYL 1H PYRAZOL 3 YL) 2,4 PYRIMIDINEDIAMINE; BARICITINIB; CLAZAKIZUMAB; CYTOKINE; ELSILIMOMAB; ENZYME INHIBITOR; FEDRATINIB; GANDOTINIB; GLYCOPROTEIN GP 130; INTERLEUKIN 11; INTERLEUKIN 6; JANUS KINASE INHIBITOR; LESTAURTINIB; MICRORNA; MOMELOTINIB; OLOKIZUMAB; PACRITINIB; RUXOLITINIB; SARILUMAB; SILTUXIMAB; SIRUKUMAB; TOCILIZUMAB; TOFACITINIB;

ANGIOGENESIS; BLADDER CANCER; BREAST CANCER; CACHEXIA; CANCER COMBINATION CHEMOTHERAPY; CANCER GROWTH; CANCER THERAPY; CARCINOGENESIS; CELL DIFFERENTIATION; CELL PROLIFERATION; CELL SURVIVAL; COLORECTAL CANCER; ESOPHAGUS CANCER; GYNECOLOGIC CANCER; IMMUNITY; INFLAMMATION; KIDNEY CANCER; LIVER CANCER; LUNG CANCER; METABOLISM; METASTASIS; MOLECULAR MECHANICS; NEOPLASM; OBESITY; PANCREAS CANCER; PROSTATE CANCER; REVIEW; SIGNAL TRANSDUCTION; STEM CELL; STOMACH CANCER; TUMOR INVASION; UPREGULATION;

COLORECTAL CANCER; GASTRIC CANCER; GP130; HEPATOCELLULAR CARCINOMA; IL-11; IL-6; STAT3;

ANIMALS; ANTINEOPLASTIC AGENTS; CYTOKINES; HUMANS; INFLAMMATION; INTERLEUKIN-6; MOLECULAR TARGETED THERAPY; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC; PROTEIN KINASE INHIBITORS; RECEPTORS, INTERLEUKIN-6; SIGNAL TRANSDUCTION;

EID: 84896494013     PISSN: 10445323     EISSN: 10963618     Source Type: Journal    
DOI: 10.1016/j.smim.2014.01.001     Document Type: Review

References (419)

1. Grivennikov S.I., Greten F.R., Karin M. Immunity, inflammation, and cancer. Cell 2010, 140:883-899.
2. Hanahan D., Weinberg R.A. Hallmarks of cancer: the next generation. Cell 2011, 144:646-674.
3. Grivennikov S.I., Karin M. Inflammatory cytokines in cancer: tumour necrosis factor and interleukin 6 take the stage. Ann Rheum Dis 2011, 70(Suppl. 1):i104-i108.
4. Elinav E., Nowarski R., Thaiss C.A., Hu B., Jin C., Flavell R.A. Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms. Nat Rev Cancer 2013, 13:759-771.
5. Garbers C., Hermanns H.M., Schaper F., Muller-Newen G., Grotzinger J., Rose-John S., et al. Plasticity and cross-talk of interleukin 6-type cytokines. Cytokine Growth Factor Rev 2012, 23:85-97.
6. Kishimoto T. IL-6: from its discovery to clinical applications. Int Immunol 2010, 22:347-352.
7. Bromberg J.F., Wrzeszczynska M.H., Devgan G., Zhao Y., Pestell R.G., Albanese C., et al. Stat3 as an oncogene. Cell 1999, 98:295-303.
8. Yu H., Pardoll D., Jove R. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer 2009, 9:798-809.
9. Boccaccio C., Ando M., Tamagnone L., Bardelli A., Michieli P., Battistini C., et al. Induction of epithelial tubules by growth factor HGF depends on the STAT pathway. Nature 1998, 391:285-288.
10. Quesnelle K.M., Boehm A.L., Grandis J.R. STAT-mediated EGFR signaling in cancer. J Cell Biochem 2007, 102:311-319.
11. Bowman T., Garcia R., Turkson J., Jove R. STATs in oncogenesis. Oncogene 2000, 19:2474-2488.
12. Grivennikov S.I. IL-11: a prominent pro-tumorigenic member of the IL-6 family. Cancer Cell 2013, 24:145-147.
13. Garbers C., Scheller J. Interleukin-6 and interleukin-11: same same but different. Biol Chem 2013, 394:1145-1161.
14. Guo Y., Xu F., Lu T., Duan Z., Zhang Z. Interleukin-6 signaling pathway in targeted therapy for cancer. Cancer Treat Rev 2012, 38:904-910.
15. Putoczki T., Ernst M. More than a sidekick: the IL-6 family cytokine IL-11 links inflammation to cancer. J Leukocyte Biol 2010, 88:1109-1117.
16. Howlett M., Menheniott T.R., Judd L.M., Giraud A.S. Cytokine signalling via gp130 in gastric cancer. Biochim Biophys Acta 2009, 1793:1623-1633.
17. Chalaris A., Schmidt-Arras D., Yamamoto K., Rose-John S. Interleukin-6 trans-signaling and colonic cancer associated with inflammatory bowel disease. Dig Dis 2012, 30:492-499.
18. Scheller J., Chalaris A., Schmidt-Arras D., Rose-John S. The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta 2011, 1813:878-888.
19. Nandurkar H.H., Robb L., Tarlinton D., Barnett L., Kontgen F., Begley C.G. Adult mice with targeted mutation of the interleukin-11 receptor (IL11Ra) display normal hematopoiesis. Blood 1997, 90:2148-2159.
20. Mansell A., Jenkins B.J. Dangerous liaisons between interleukin-6 cytokine and toll-like receptor families: a potent combination in inflammation and cancer. Cytokine Growth Factor Rev 2013, 24:249-256.
21. Yoshida H., Miyazaki Y. Regulation of immune responses by interleukin-27. Immunol Rev 2008, 226:234-247.
22. Pratt S.L., Ogle C.K., Mao J.X., Zhao W., Lovell G., Horseman N.D. Interleukin-6 signal transduction in human intestinal epithelial cells. Shock 2000, 13:435-440.
23. Tormo A.J., Letellier M.C., Sharma M., Elson G., Crabe S., Gauchat J.F. IL-6 activates STAT5 in T cells. Cytokine 2012, 60:575-582.
24. Yoshimura A., Naka T., Kubo M. SOCS proteins, cytokine signalling and immune regulation. Nat Rev Immunol 2007, 7:454-465.
25. Yoshimura A., Yasukawa H. J.A.K's SOCS: a mechanism of inhibition. Immunity 2012, 36:157-159.
26. White C.A., Nicola N.A. SOCS3: an essential physiological inhibitor of signaling by interleukin-6 and G-CSF family cytokines. JAK-STAT 2013, 2:e25045.
27. Greenhalgh C.J., Hilton D.J. Negative regulation of cytokine signaling. J Leukocyte Biol 2001, 70:348-356.
28. Wang Y., van Boxel-Dezaire A.H., Cheon H., Yang J., Stark G.R. STAT3 activation in response to IL-6 is prolonged by the binding of IL-6 receptor to EGF receptor. Proc Natl Acad Sci USA 2013, 110:16975-16980.
29. Takahashi-Tezuka M., Yoshida Y., Fukada T., Ohtani T., Yamanaka Y., Nishida K., et al. Gab1 acts as an adapter molecule linking the cytokine receptor gp130 to ERK mitogen-activated protein kinase. Mol Cell Biol 1998, 18:4109-4117.
30. Hideshima T., Nakamura N., Chauhan D., Anderson K.C. Biologic sequelae of interleukin-6 induced PI3-K/Akt signaling in multiple myeloma. Oncogene 2001, 20:5991-6000.
31. Ara T., Declerck Y.A. Interleukin-6 in bone metastasis and cancer progression. Eur J Cancer 2010, 46:1223-1231.
32. Poncet N., Guillaume J., Mouchiroud G. Epidermal growth factor receptor transactivation is implicated in IL-6-induced proliferation and ERK1/2 activation in non-transformed prostate epithelial cells. Cell Signal 2011, 23:572-578.
33. Hov H., Tian E., Holien T., Holt R.U., Vatsveen T.K., Fagerli U.M., et al. c-Met signaling promotes IL-6-induced myeloma cell proliferation. Eur J Haematol 2009, 82:277-287.
34. Yao X., Huang J., Zhong H., Shen N., Faggioni R., Fung M., et al. Targeting interleukin-6 in inflammatory autoimmune diseases and cancers. Pharmacol Ther 2014, 141:125-139.
35. Yamagiwa Y., Meng F., Patel T. Interleukin-6 decreases senescence and increases telomerase activity in malignant human cholangiocytes. Life Sci 2006, 78:2494-2502.
36. Walter M., Liang S., Ghosh S., Hornsby P.J., Li R. Interleukin 6 secreted from adipose stromal cells promotes migration and invasion of breast cancer cells. Oncogene 2009, 28:2745-2755.
37. Foran E., Garrity-Park M.M., Mureau C., Newell J., Smyrk T.C., Limburg P.J., et al. Upregulation of DNA methyltransferase-mediated gene silencing, anchorage-independent growth, and migration of colon cancer cells by interleukin-6. Mol Cancer Res 2010, 8:471-481.
38. Mano Y., Aishima S., Fujita N., Tanaka Y., Kubo Y., Motomura T., et al. Tumor-associated macrophage promotes tumor progression via STAT3 signaling in hepatocellular carcinoma. Pathobiology 2013, 80:146-154.
39. Zhang Z., Zhang J., Miao L., Liu K., Yang S., Pan C., et al. Interleukin-11 promotes the progress of gastric carcinoma via abnormally expressed versican. Int J Biol Sci 2012, 8:383-393.
40. Lay V., Yap J., Sonderegger S., Dimitriadis E. Interleukin 11 regulates endometrial cancer cell adhesion and migration via STAT3. Int J Oncol 2012, 41:759-764.
41. Nakayama T., Yoshizaki A., Izumida S., Suehiro T., Miura S., Uemura T., et al. Expression of interleukin-11 (IL-11) and IL-11 receptor alpha in human gastric carcinoma and IL-11 upregulates the invasive activity of human gastric carcinoma cells. Int J Oncol 2007, 30:825-833.
42. Yoshizaki A., Nakayama T., Yamazumi K., Yakata Y., Taba M., Sekine I. Expression of interleukin (IL)-11 and IL-11 receptor in human colorectal adenocarcinoma: IL-11 up-regulation of the invasive and proliferative activity of human colorectal carcinoma cells. Int J Oncol 2006, 29:869-876.
43. Lin M.T., Lin B.R., Chang C.C., Chu C.Y., Su H.J., Chen S.T., et al. IL-6 induces AGS gastric cancer cell invasion via activation of the c-Src/RhoA/ROCK signaling pathway. Int J Cancer 2007, 120:2600-2608.
44. Nieto M.A. Epithelial plasticity: a common theme in embryonic and cancer cells. Science 2013, 342:1234850.
45. De Craene B., Berx G. Regulatory networks defining EMT during cancer initiation and progression. Nat Rev Cancer 2013, 13:97-110.
46. Tsai J.H., Yang J. Epithelial-mesenchymal plasticity in carcinoma metastasis. Genes Dev 2013, 27:2192-2206.
47. Tam W.L., Weinberg R.A. The epigenetics of epithelial-mesenchymal plasticity in cancer. Nat Med 2013, 19:1438-1449.
48. Creighton C.J., Gibbons D.L., Kurie J.M. The role of epithelial-mesenchymal transition programming in invasion and metastasis: a clinical perspective. Cancer Manage Res 2013, 5:187-195.
49. Sullivan N.J., Sasser A.K., Axel A.E., Vesuna F., Raman V., Ramirez N., et al. Interleukin-6 induces an epithelial-mesenchymal transition phenotype in human breast cancer cells. Oncogene 2009, 28:2940-2947.
50. Huang C., Yang G., Jiang T., Zhu G., Li H., Qiu Z. The effects and mechanisms of blockage of STAT3 signaling pathway on IL-6 inducing EMT in human pancreatic cancer cells in vitro. Neoplasma 2011, 58:396-405.
51. Yadav A., Kumar B., Datta J., Teknos T.N., Kumar P. IL-6 promotes head and neck tumor metastasis by inducing epithelial-mesenchymal transition via the JAK-STAT3-SNAIL signaling pathway. Mol Cancer Res 2011, 9:1658-1667.
52. Guo L., Chen C., Shi M., Wang F., Chen X., Diao D., et al. Stat3-coordinated Lin-28-let-7-HMGA2 and miR-200-ZEB1 circuits initiate and maintain oncostatin M-driven epithelial-mesenchymal transition. Oncogene 2013, 32:5272-5282.
53. West N.R., Murray J.I., Watson P.H. Oncostatin-M promotes phenotypic changes associated with mesenchymal and stem cell-like differentiation in breast cancer. Oncogene 2013, in press.
54. Middleton K., Jones J., Lwin Z., Coward J.I. Interleukin-6. An angiogenic target in solid tumours. Crit Rev Oncol Hematol 2014, 89:129-139.
55. Xu Q., Briggs J., Park S., Niu G., Kortylewski M., Zhang S., et al. Targeting Stat3 blocks both HIF-1 and VEGF expression induced by multiple oncogenic growth signaling pathways. Oncogene 2005, 24:5552-5560.
56. Jung J.E., Lee H.G., Cho I.H., Chung D.H., Yoon S.H., Yang Y.M., et al. STAT3 is a potential modulator of HIF-1-mediated VEGF expression in human renal carcinoma cells. FASEB J 2005, 19:1296-1298.
57. Dang E.V., Barbi J., Yang H.Y., Jinasena D., Yu H., Zheng Y., et al. Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1. Cell 2011, 146:772-784.
58. Coward J., Kulbe H., Chakravarty P., Leader D., Vassileva V., Leinster D.A., et al. Interleukin-6 as a therapeutic target in human ovarian cancer. Clin Cancer Res 2011, 17:6083-6096.
59. Eldesoky A., Shouma A., Mosaad Y., Elhawary A. Clinical relevance of serum vascular endothelial growth factor and interleukin-6 in patients with colorectal cancer. Scand J Gastroenterol 2011, 17:170-173.
60. Huang Y.H., Yang H.Y., Hsu Y.F., Chiu P.T., Ou G., Hsu M.J. Src contributes to IL6-induced vascular endothelial growth factor-C expression in lymphatic endothelial cells. Angiogenesis 2013, in press.
61. Shinriki S., Jono H., Ueda M., Ota K., Ota T., Sueyoshi T., et al. Interleukin-6 signalling regulates vascular endothelial growth factor-C synthesis and lymphangiogenesis in human oral squamous cell carcinoma. J Pathol 2011, 225:142-150.
62. Maeda S., Hikiba Y., Sakamoto K., Nakagawa H., Hirata Y., Hayakawa Y., et al. Ikappa B kinasebeta/nuclear factor-kappaB activation controls the development of liver metastasis by way of interleukin-6 expression. Hepatology 2009, 50:1851-1860.
63. Xie T.X., Huang F.J., Aldape K.D., Kang S.H., Liu M., Gershenwald J.E., et al. Activation of stat3 in human melanoma promotes brain metastasis. Cancer Res 2006, 66:3188-3196.
64. Chung Y.C., Chang Y.F. Serum interleukin-6 levels reflect the disease status of colorectal cancer. J Surg Oncol 2003, 83:222-226.
65. Ren L., Wang X., Dong Z., Liu J., Zhang S. Bone metastasis from breast cancer involves elevated IL-11 expression and the gp130/STAT3 pathway. Med Oncol 2013, 30:634.
66. Gao Y.B., Xiang Z.L., Zhou L.Y., Wu Z.F., Fan J., Zeng H.Y., et al. Enhanced production of CTGF and IL-11 from highly metastatic hepatoma cells under hypoxic conditions: an implication of hepatocellular carcinoma metastasis to bone. J Cancer Res Clin Oncol 2013, 139:669-679.
67. Mathieu M.E., Saucourt C., Mournetas V., Gauthereau X., Theze N., Praloran V., et al. LIF-dependent signaling: new pieces in the Lego. Stem Cell Rev 2012, 8:1-15.
68. Kuphal S., Wallner S., Bosserhoff A.K. Impact of LIF (leukemia inhibitory factor) expression in malignant melanoma. Exp Mol Pathol 2013, 95:156-165.
69. Kamohara H., Sakamoto K., Ishiko T., Mita S., Masuda Y., Abe T., et al. Human carcinoma cell lines produce biologically active leukemia inhibitory factor (LIF). Res Commun Mol Pathol Pharmacol 1994, 85:131-140.
70. Bourillot P.Y., Aksoy I., Schreiber V., Wianny F., Schulz H., Hummel O., et al. Novel STAT3 target genes exert distinct roles in the inhibition of mesoderm and endoderm differentiation in cooperation with Nanog. Stem Cells 2009, 27:1760-1771.
71. Brady J.J., Li M., Suthram S., Jiang H., Wong W.H., Blau H.M. Early role for IL-6 signalling during generation of induced pluripotent stem cells revealed by heterokaryon RNA-Seq. Nat Cell Biol 2013, 15:1244-1252.
72. Peterson H., Abu Dawud R., Garg A., Wang Y., Vilo J., Xenarios I., et al. Qualitative modeling identifies IL-11 as a novel regulator in maintaining self-renewal in human pluripotent stem cells. Front Physiol 2013, 4:303.
73. Chin A.R., Wang S.E. Cytokines driving breast cancer stemness. Mol Cell Endocrinol 2014, 382:598-602.
74. Sansone P., Storci G., Tavolari S., Guarnieri T., Giovannini C., Taffurelli M., et al. IL-6 triggers malignant features in mammospheres from human ductal breast carcinoma and normal mammary gland. J Clin Invest 2007, 117:3988-4002.
75. Kim S.Y., Kang J.W., Song X., Kim B.K., Yoo Y.D., Kwon Y.T., 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 Signal 2013, 25:961-969.
76. Yi H., Cho H.J., Cho S.M., Jo K., Park J.A., Kim N.H., et al. Blockade of interleukin-6 receptor suppresses the proliferation of H460 lung cancer stem cells. Int J Oncol 2012, 41:310-316.
77. Lin L., Liu A., Peng Z., Lin H.J., Li P.K., Li C., et al. STAT3 is necessary for proliferation and survival in colon cancer-initiating cells. Cancer Res 2011, 71:7226-7237.
78. Lin L., Fuchs J., Li C., Olson V., Bekaii-Saab T., Lin J. STAT3 signaling pathway is necessary for cell survival and tumorsphere forming capacity in ALDH(+)/CD133(+) stem cell-like human colon cancer cells. Biochem Biophys Res Commun 2011, 416:246-251.
79. Matthews J.R., Sansom O.J., Clarke A.R. Absolute requirement for STAT3 function in small-intestine crypt stem cell survival. Cell Death Differ 2011, 18:1934-1943.
80. Garner J.M., Fan M., Yang C.H., Du Z., Sims M., Davidoff A.M., et al. Constitutive activation of signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappaB signaling in glioblastoma cancer stem cells regulates the notch pathway. J Biol Chem 2013, 288:26167-26176.
81. Myung S.J., Yoon J.H., Yu S.J. STAT3 & cytochrome P450 2C9: a novel signaling pathway in liver cancer stem cells. Biomed Pharmacother 2012, 66:612-616.
82. Bird T.G., Lorenzini S., Forbes S.J. Activation of stem cells in hepatic diseases. Cell Tissue Res 2008, 331:283-300.
83. Lee K.P., Lee J.H., Kim T.S., Kim T.H., Park H.D., Byun J.S., et al. The Hippo-Salvador pathway restrains hepatic oval cell proliferation, liver size, and liver tumorigenesis. Proc Natl Acad Sci USA 2010, 107:8248-8253.
84. Yeoh G.C., Ernst M., Rose-John S., Akhurst B., Payne C., Long S., et al. Opposing roles of gp130-mediated STAT-3 and ERK-1/2 signaling in liver progenitor cell migration and proliferation. Hepatology 2007, 45:486-494.
85. Omori N., Evarts R.P., Omori M., Hu Z., Marsden E.R., Thorgeirsson S.S. Expression of leukemia inhibitory factor and its receptor during liver regeneration in the adult rat. Lab Invest 1996, 75:15-24.
86. Okaya A., Kitanaka J., Kitanaka N., Satake M., Kim Y., Terada K., et al. Oncostatin M inhibits proliferation of rat oval cells, OC15-5, inducing differentiation into hepatocytes. Am J Pathol 2005, 166:709-719.
87. McCoy C.E. The role of miRNAs in cytokine signaling. Front Biosci (Landmark Ed) 2011, 16:2161-2171.
88. Cao Q., Li Y.Y., He W.F., Zhang Z.Z., Zhou Q., Liu X., et al. Interplay between microRNAs and the STAT3 signaling pathway in human cancers. Physiol Genomics 2013, 45:1206-1214.
89. Soriano A., Jubierre L., Almazan-Moga A., Molist C., Roma J., de Toledo J.S., et al. microRNAs as pharmacological targets in cancer. Pharmacol Res 2013, 75:3-14.
90. Loffler D., Brocke-Heidrich K., Pfeifer G., Stocsits C., Hackermuller J., Kretzschmar A.K., et al. Interleukin-6 dependent survival of multiple myeloma cells involves the Stat3-mediated induction of microRNA-21 through a highly conserved enhancer. Blood 2007, 110:1330-1333.
91. Meng F., Henson R., Wehbe-Janek H., Smith H., Ueno Y., Patel T. The microRNA let-7a modulates interleukin-6-dependent STAT-3 survival signaling in malignant human cholangiocytes. J Biol Chem 2007, 282:8256-8264.
92. Haider K.H., Idris N.M., Kim H.W., Ahmed R.P., Shujia J., Ashraf M. MicroRNA-21 is a key determinant in IL-11/Stat3 anti-apoptotic signalling pathway in preconditioning of skeletal myoblasts. Cardiovasc Res 2010, 88:168-178.
93. Iliopoulos D., Hirsch H.A., Struhl K. An epigenetic switch involving NF-kappaB, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation. Cell 2009, 139:693-706.
94. He G., Dhar D., Nakagawa H., Font-Burgada J., Ogata H., Jiang Y., et al. Identification of liver cancer progenitors whose malignant progression depends on autocrine IL-6 signaling. Cell 2013, 155:384-396.
95. Pichiorri F., Suh S.S., Ladetto M., Kuehl M., Palumbo T., Drandi D., et al. MicroRNAs regulate critical genes associated with multiple myeloma pathogenesis. Proc Natl Acad Sci USA 2008, 105:12885-12890.
96. Yang X., Liang L., Zhang X.F., Jia H.L., Qin Y., Zhu X.C., et al. MicroRNA-26a suppresses tumor growth and metastasis of human hepatocellular carcinoma by targeting interleukin-6-Stat3 pathway. Hepatology 2013, 58:158-170.
97. He Y., Sun X., Huang C., Long X.R., Lin X., Zhang L., et al. MiR-146a regulates IL-6 production in lipopolysaccharide-induced RAW264.7 macrophage cells by inhibiting Notch1. Inflammation 2014, 37:71-82.
98. Bockhorn J., Dalton R., Nwachukwu C., Huang S., Prat A., Yee K., et al. MicroRNA-30c inhibits human breast tumour chemotherapy resistance by regulating TWF1 and IL-11. Nat Commun 2013, 4:1393.
99. Pollari S., Leivonen S.K., Perala M., Fey V., Kakonen S.M., Kallioniemi O. Identification of microRNAs inhibiting TGF-beta-induced IL-11 production in bone metastatic breast cancer cells. PLoS ONE 2012, 7:e37361.
100. Collins A.S., McCoy C.E., Lloyd A.T., O'Farrelly C., Stevenson N.J. miR-19a: an effective regulator of SOCS3 and enhancer of JAK-STAT signalling. PLoS ONE 2013, 8:e69090.
101. Dong C. TH17 cells in development: an updated view of their molecular identity and genetic programming. Nat Rev Immunol 2008, 8:337-348.
102. Grivennikov S.I., Wang K., Mucida D., Stewart C.A., Schnabl B., Jauch D., et al. Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature 2012, 491:254-258.
103. Tosolini M., Kirilovsky A., Mlecnik B., Fredriksen T., Mauger S., Bindea G., et al. Clinical impact of different classes of infiltrating T cytotoxic and helper cells (Th1, th2, treg, th17) in patients with colorectal cancer. Cancer Res 2011, 71:1263-1271.
104. Tan W., Zhang W., Strasner A., Grivennikov S., Cheng J.Q., Hoffman R.M., et al. Tumour-infiltrating regulatory T cells stimulate mammary cancer metastasis through RANKL-RANK signalling. Nature 2011, 470:548-553.
105. Martin-Orozco N., Muranski P., Chung Y., Yang X.O., Yamazaki T., Lu S., et al. T helper 17 cells promote cytotoxic T cell activation in tumor immunity. Immunity 2009, 31:787-798.
106. Atreya R., Mudter J., Finotto S., Mullberg J., Jostock T., Wirtz S., et al. Blockade of interleukin 6 trans signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation: evidence in Crohn disease and experimental colitis in vivo. Nat Med 2000, 6:583-588.
107. Romano M., Sironi M., Toniatti C., Polentarutti N., Fruscella P., Ghezzi P., et al. Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment. Immunity 1997, 6:315-325.
108. Park S.J., Nakagawa T., Kitamura H., Atsumi T., Kamon H., Sawa S., et al. IL-6 regulates in vivo dendritic cell differentiation through STAT3 activation. J Immunol 2004, 173:3844-3854.
109. Stumhofer J.S., Laurence A., Wilson E.H., Huang E., Tato C.M., Johnson L.M., et al. Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system. Nat Immunol 2006, 7:937-945.
110. Diveu C., McGeachy M.J., Boniface K., Stumhofer J.S., Sathe M., Joyce-Shaikh B., et al. IL-27 blocks RORc expression to inhibit lineage commitment of Th17 cells. J Immunol 2009, 182:5748-5756.
111. Visperas A., Do J.S., Bulek K., Li X., Min B. IL-27, targeting antigen-presenting cells, promotes Th17 differentiation and colitis in mice. Mucosal Immunol 2013, in press.
112. Mascanfroni I.D., Yeste A., Vieira S.M., Burns E.J., Patel B., Sloma I., et al. IL-27 acts on DCs to suppress the T cell response and autoimmunity by inducing expression of the immunoregulatory molecule CD39. Nat Immunol 2013, 14:1054-1063.
113. Calle E.E., Kaaks R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 2004, 4:579-591.
114. Calle E.E., Rodriguez C., Walker-Thurmond K., Thun M.J. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 2003, 348:1625-1638.
115. Gallagher E.J., LeRoith D. Epidemiology and molecular mechanisms tying obesity, diabetes, and the metabolic syndrome with cancer. Diabetes Care 2013, 36(Suppl. 2):S233-S239.
116. El-Kadre L.J., Tinoco A.C. Interleukin-6 and obesity: the crosstalk between intestine, pancreas and liver. Curr Opin Clin Nutr Metab Care 2013, 16:564-568.
117. Wallenius V., Wallenius K., Ahren B., Rudling M., Carlsten H., Dickson S.L., et al. Interleukin-6-deficient mice develop mature-onset obesity. Nat Med 2002, 8:75-79.
118. Matthews V.B., Allen T.L., Risis S., Chan M.H., Henstridge D.C., Watson N., et al. Interleukin-6-deficient mice develop hepatic inflammation and systemic insulin resistance. Diabetologia 2010, 53:2431-2441.
119. Di Gregorio G.B., Hensley L., Lu T., Ranganathan G., Kern P.A. Lipid and carbohydrate metabolism in mice with a targeted mutation in the IL-6 gene: absence of development of age-related obesity. Am J Physiol Endocrinol Metab 2004, 287:E182-E187.
120. Park E.J., Lee J.H., Yu G.Y., He G., Ali S.R., Holzer R.G., et al. Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression. Cell 2010, 140:197-208.
121. Ellingsgaard H., Ehses J.A., Hammar E.B., Van Lommel L., Quintens R., Martens G., et al. Interleukin-6 regulates pancreatic alpha-cell mass expansion. Proc Natl Acad Sci USA 2008, 105:13163-13168.
122. Pini M., Rhodes D.H., Fantuzzi G. Hematological and acute-phase responses to diet-induced obesity in IL-6 KO mice. Cytokine 2011, 56:708-716.
123. Wunderlich F.T., Strohle P., Konner A.C., Gruber S., Tovar S., Bronneke H.S., et al. Interleukin-6 signaling in liver-parenchymal cells suppresses hepatic inflammation and improves systemic insulin action. Cell Metab 2010, 12:237-249.
124. Yamamoto K., Rose-John S. Therapeutic blockade of interleukin-6 in chronic inflammatory disease. Clin Pharmacol Ther 2012, 91:574-576.
125. Weidle U.H., Klostermann S., Eggle D., Kruger A. Interleukin 6/interleukin 6 receptor interaction and its role as a therapeutic target for treatment of cachexia and cancer. Cancer Genomics Proteomics 2010, 7:287-302.
126. Molotkov A., Satoh M., Tohyama C. Tumor growth and food intake in interleukin-6 gene knock-out mice. Cancer Lett 1998, 132:187-192.
127. Okada S., Okusaka T., Ishii H., Kyogoku A., Yoshimori M., Kajimura N., et al. Elevated serum interleukin-6 levels in patients with pancreatic cancer. Jpn J Clin Oncol 1998, 28:12-15.
128. Martignoni M.E., Dimitriu C., Bachmann J., Krakowski-Rosen H., Ketterer K., Kinscherf R., et al. Liver macrophages contribute to pancreatic cancer-related cachexia. Oncol Rep 2009, 21:363-369.
129. Ohe Y., Podack E.R., Olsen K.J., Miyahara Y., Miura K., Saito H., et al. Interleukin-6 cDNA transfected Lewis lung carcinoma cells show unaltered net tumour growth rate but cause weight loss and shortened survival in syngeneic mice. Br J Cancer 1993, 67:939-944.
130. Bonetto A., Aydogdu T., Kunzevitzky N., Guttridge D.C., Khuri S., Koniaris L.G., et al. STAT3 activation in skeletal muscle links muscle wasting and the acute phase response in cancer cachexia. PLoS ONE 2011, 6:e22538.
131. Sultani M., Stringer A.M., Bowen J.M., Gibson R.J. Anti-inflammatory cytokines: important immunoregulatory factors contributing to chemotherapy-induced gastrointestinal mucositis. Chemother Res Pract 2012, 2012:490804.
132. Herrlinger K.R., Witthoeft T., Raedler A., Bokemeyer B., Krummenerl T., Schulzke J.D., et al. Randomized, double blind controlled trial of subcutaneous recombinant human interleukin-11 versus prednisolone in active Crohn's disease. Am J Gastroenterol 2006, 101:793-797.
133. Bhatia M., Davenport V., Cairo M.S. The role of interleukin-11 to prevent chemotherapy-induced thrombocytopenia in patients with solid tumors, lymphoma, acute myeloid leukemia and bone marrow failure syndromes. Leukemia Lymphoma 2007, 48:9-15.
134. Becker C., Fantini M.C., Schramm C., Lehr H.A., Wirtz S., Nikolaev A., et al. TGF-beta suppresses tumor progression in colon cancer by inhibition of IL-6 trans-signaling. Immunity 2004, 21:491-501.
135. Grivennikov S., Karin E., Terzic J., Mucida D., Yu G.Y., Vallabhapurapu S., et al. IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer. Cancer Cell 2009, 15:103-113.
136. Calon A., Espinet E., Palomo-Ponce S., Tauriello D.V., Iglesias M., Cespedes M.V., et al. Dependency of colorectal cancer on a TGF-beta-driven program in stromal cells for metastasis initiation. Cancer Cell 2012, 22:571-584.
137. Putoczki T.L., Thiem S., Loving A., Busuttil R.A., Wilson N.J., Ziegler P.K., et al. Interleukin-11 is the dominant IL-6 family cytokine during gastrointestinal tumorigenesis and can be targeted therapeutically. Cancer Cell 2013, 24:257-271.
138. Knupfer H., Preiss R. Significance of interleukin-6 (IL-6) in breast cancer (review). Breast Cancer Res Treat 2007, 102:129-135.
139. Huang W.L., Yeh H.H., Lin C.C., Lai W.W., Chang J.Y., Chang W.T., et al. Signal transducer and activator of transcription 3 activation up-regulates interleukin-6 autocrine production: a biochemical and genetic study of established cancer cell lines and clinical isolated human cancer cells. Mol Cancer 2010, 9:309.
140. Tawara K., Oxford J.T., Jorcyk C.L. Clinical significance of interleukin (IL)-6 in cancer metastasis to bone: potential of anti-IL-6 therapies. Cancer Manage Res 2011, 3:177-189.
141. Aziz M., Ishihara S., Ansary M.U., Sonoyama H., Tada Y., Oka A., et al. Crosstalk between TLR5 and Notch1 signaling in epithelial cells during intestinal inflammation. Int J Mol Med 2013, 32:1051-1062.
142. Ernst M., Najdovska M., Grail D., Lundgren-May T., Buchert M., Tye H., et al. STAT3 and STAT1 mediate IL-11-dependent and inflammation-associated gastric tumorigenesis in gp130 receptor mutant mice. J Clin Invest 2008, 118:1727-1738.
143. Tang W., Yang L., Yang Y.C., Leng S.X., Elias J.A. Transforming growth factor-beta stimulates interleukin-11 transcription via complex activating protein-1-dependent pathways. J Biol Chem 1998, 273:5506-5513.
144. Shin S.Y., Choi C., Lee H.G., Lim Y., Lee Y.H. Transcriptional regulation of the interleukin-11 gene by oncogenic Ras. Carcinogenesis 2012, 33:2467-2476.
145. Onnis B., Fer N., Rapisarda A., Perez V.S., Melillo G. Autocrine production of IL-11 mediates tumorigenicity in hypoxic cancer cells. J Clin Invest 2013, 123:1615-1629.
146. Nishina T., Komazawa-Sakon S., Yanaka S., Piao X., Zheng D.M., Piao J.H., et al. Interleukin-11 links oxidative stress and compensatory proliferation. Sci Signal 2012, 5:ra5.
147. Chalaris A., Garbers C., Rabe B., Rose-John S., Scheller J. The soluble interleukin 6 receptor: generation and role in inflammation and cancer. Eur J Cell Biol 2011, 90:484-494.
148. Geisterfer M., Richards C., Baumann M., Fey G., Gywnne D., Gauldie J. Regulation of IL-6 and the hepatic IL-6 receptor in acute inflammation in vivo. Cytokine 1993, 5:1-7.
149. Geisterfer M., Richards C.D., Gauldie J. Cytokines oncostatin M and interleukin 1 regulate the expression of the IL-6 receptor (gp80, gp130). Cytokine 1995, 7:503-509.
150. O'Brien C.A., Manolagas S.C. Isolation and characterization of the human gp130 promoter. Regulation by STATS. J Biol Chem 1997, 272:15003-15010.
151. Heinrich P.C., Behrmann I., Haan S., Hermanns H.M., Muller-Newen G., Schaper F. Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J 2003, 374:1-20.
152. Bonito N.A., Drechsler J., Stoecker S., Carmo C.R., Seckl M.J., Hermanns H.M., et al. Control of gp130 expression by the mitogen-activated protein kinase ERK2. Oncogene 2013, in press.
153. Rose-John S., Mitsuyama K., Matsumoto S., Thaiss W.M., Scheller J. Interleukin-6 trans-signaling and colonic cancer associated with inflammatory bowel disease. Curr Pharm Des 2009, 15:2095-2103.
154. Kim S., Keku T.O., Martin C., Galanko J., Woosley J.T., Schroeder J.C., et al. Circulating levels of inflammatory cytokines and risk of colorectal adenomas. Cancer Res 2008, 68:323-328.
155. Ognjanovic S., Yamamoto J., Saltzman B., Franke A., Ognjanovic M., Yokochi L., et al. Serum CRP and IL-6, genetic variants and risk of colorectal adenoma in a multiethnic population. Cancer Causes Control 2010, 21:1131-1138.
156. Belluco C., Nitti D., Frantz M., Toppan P., Basso D., Plebani M., et al. Interleukin-6 blood level is associated with circulating carcinoembryonic antigen and prognosis in patients with colorectal cancer. Ann Surg Oncol 2000, 7:133-138.
157. Yamazumi K., Nakayama T., Kusaba T., Wen C.Y., Yoshizaki A., Yakata Y., et al. Expression of interleukin-11 and interleukin-11 receptor alpha in human colorectal adenocarcinoma; immunohistochemical analyses and correlation with clinicopathological factors. World J Gastroenterol 2006, 12:317-321.
158. Kusaba T., Nakayama T., Yamazumi K., Yakata Y., Yoshizaki A., Inoue K., et al. Activation of STAT3 is a marker of poor prognosis in human colorectal cancer. Oncol Rep 2006, 15:1445-1451.
159. Morikawa T., Baba Y., Yamauchi M., Kuchiba A., Nosho K., Shima K., et al. STAT3 expression, molecular features, inflammation patterns, and prognosis in a database of 724 colorectal cancers. Clin Cancer Res 2011, 17:1452-1462.
160. Jin C., Wang A., Chen J., Liu X., Wang G. Relationship between expression and prognostic ability of PTEN, STAT3 and VEGF-C in colorectal cancer. Exp Ther Med 2012, 4:633-639.
161. Matsumoto S., Hara T., Mitsuyama K., Yamamoto M., Tsuruta O., Sata M., 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. J Immunol 2010, 184:1543-1551.
162. Greten F.R., Eckmann L., Greten T.F., Park J.M., Li Z.W., Egan L.J., et al. IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 2004, 118:285-296.
163. Grivennikov S., Karin M. Autocrine IL-6 signaling: a key event in tumorigenesis. Cancer Cell 2008, 13:7-9.
164. Bromberg J., Wang T.C. Inflammation and cancer: IL-6 and STAT3 complete the link. Cancer Cell 2009, 15:79-80.
165. Terzic J., Grivennikov S., Karin E., Karin M. Inflammation and colon cancer. Gastroenterology 2010, 138:2101-2114. e2105.
166. Lin J.T., Wang J.Y., Chen M.K., Chen H.C., Chang T.H., Su B.W., et al. Colon cancer mesenchymal stem cells modulate the tumorigenicity of colon cancer through interleukin 6. Exp Cell Res 2013, 319:2216-2229.
167. Nagasaki T., Hara M., Nakanishi H., Takahashi H., Sato M., Takeyama H. Interleukin-6 released by colon cancer-associated fibroblasts is critical for tumour angiogenesis: anti-interleukin-6 receptor antibody suppressed angiogenesis and inhibited tumour-stroma interaction. Br J Cancer 2014, 110:469-478.
168. Rose-John S. IL-6 trans-signaling via the soluble IL-6 receptor: importance for the pro-inflammatory activities of IL-6. Int J Biol Sci 2012, 8:1237-1247.
169. Hu B., Elinav E., Huber S., Strowig T., Hao L., Hafemann A., et al. Microbiota-induced activation of epithelial IL-6 signaling links inflammasome-driven inflammation with transmissible cancer. Proc Natl Acad Sci USA 2013, 110:9862-9867.
170. Becker C., Fantini M.C., Wirtz S., Nikolaev A., Lehr H.A., Galle P.R., et al. IL-6 signaling promotes tumor growth in colorectal cancer. Cell Cycle 2005, 4:217-220.
171. Bollrath J., Phesse T.J., von Burstin V.A., Putoczki T., Bennecke M., Bateman T., et al. gp130-mediated Stat3 activation in enterocytes regulates cell survival and cell-cycle progression during colitis-associated tumorigenesis. Cancer Cell 2009, 15:91-102.
172. Huber S., Gagliani N., Zenewicz L.A., Huber F.J., Bosurgi L., Hu B., et al. IL-22BP is regulated by the inflammasome and modulates tumorigenesis in the intestine. Nature 2012, 491:259-263.
173. Kirchberger S., Royston D.J., Boulard O., Thornton E., Franchini F., Szabady R.L., et al. Innate lymphoid cells sustain colon cancer through production of interleukin-22 in a mouse model. J Exp Med 2013, 210:917-931.
174. Jarnicki A., Putoczki T., Ernst M. Stat3: linking inflammation to epithelial cancer - more than a gut feeling?. Cell Div 2010, 5:14.
175. Thiem S., Pierce T.P., Palmieri M., Putoczki T.L., Buchert M., Preaudet A., et al. mTORC1 inhibition restricts inflammation-associated gastrointestinal tumorigenesis in mice. J Clin Invest 2013, 123:767-781.
176. Xiao H., Yin W., Khan M.A., Gulen M.F., Zhou H., Sham H.P., et al. Loss of single immunoglobulin interlukin-1 receptor-related molecule leads to enhanced colonic polyposis in Apc(min) mice. Gastroenterology 2010, 139:574-585.
177. Lee S.H., Hu L.L., Gonzalez-Navajas J., Seo G.S., Shen C., Brick J., et al. ERK activation drives intestinal tumorigenesis in Apc(min/+) mice. Nat Med 2010, 16:665-670.
178. Seavey M.M., Lu L.D., Stump K.L., Wallace N.H., Hockeimer W., O'Kane T.M., et al. Therapeutic efficacy of CEP-33779, a novel selective JAK2 inhibitor, in a mouse model of colitis-induced colorectal cancer. Mol Cancer Ther 2012, 11:984-993.
179. Nguyen A.V., Wu Y.Y., Liu Q., Wang D., Nguyen S., Loh R., et al. STAT3 in epithelial cells regulates inflammation and tumor progression to malignant state in colon. Neoplasia 2013, 15:998-1008.
180. Deng L., Zhou J.F., Sellers R.S., Li J.F., Nguyen A.V., Wang Y., et al. A novel mouse model of inflammatory bowel disease links mammalian target of rapamycin-dependent hyperproliferation of colonic epithelium to inflammation-associated tumorigenesis. Am J Pathol 2010, 176:952-967.
181. Liang J., Nagahashi M., Kim E.Y., Harikumar K.B., Yamada A., Huang W.C., et al. Sphingosine-1-phosphate links persistent STAT3 activation, chronic intestinal inflammation, and development of colitis-associated cancer. Cancer Cell 2013, 23:107-120.
182. Kawamori T., Kaneshiro T., Okumura M., Maalouf S., Uflacker A., Bielawski J., et al. Role for sphingosine kinase 1 in colon carcinogenesis. FASEB J 2009, 23:405-414.
183. Waldner M.J., Wirtz S., Jefremow A., Warntjen M., Neufert C., Atreya R., et al. VEGF receptor signaling links inflammation and tumorigenesis in colitis-associated cancer. J Exp Med 2010, 207:2855-2868.
184. Rigby R.J., Simmons J.G., Greenhalgh C.J., Alexander W.S., Lund P.K. Suppressor of cytokine signaling 3 (SOCS3) limits damage-induced crypt hyper-proliferation and inflammation-associated tumorigenesis in the colon. Oncogene 2007, 26:4833-4841.
185. Fenton J.I., Hursting S.D., Perkins S.N., Hord N.G. Interleukin-6 production induced by leptin treatment promotes cell proliferation in an Apc (Min/+) colon epithelial cell line. Carcinogenesis 2006, 27:1507-1515.
186. Musteanu M., Blaas L., Mair M., Schlederer M., Bilban M., Tauber S., et al. Stat3 is a negative regulator of intestinal tumor progression in Apc(Min) mice. Gastroenterology 2010, 138:1003-1011. e1001-1005.
187. Lee J., Kim J.C., Lee S.E., Quinley C., Kim H., Herdman S., et al. Signal transducer and activator of transcription 3 (STAT3) protein suppresses adenoma-to-carcinoma transition in Apcmin/+ mice via regulation of Snail-1 (SNAI) protein stability. J Biol Chem 2012, 287:18182-18189.
188. Ernst M., Putoczki T.L. Targeting IL-11 signaling in colon cancer. Oncotarget 2013, 4:1860-1861.
189. Wu S., Rhee K.J., Albesiano E., Rabizadeh S., Wu X., Yen H.R., et al. A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17T cell responses. Nat Med 2009, 15:1016-1022.
190. Chae W.J., Gibson T.F., Zelterman D., Hao L., Henegariu O., Bothwell A.L. Ablation of IL-17A abrogates progression of spontaneous intestinal tumorigenesis. Proc Natl Acad Sci USA 2010, 107:5540-5544.
191. Chung A.S., Wu X., Zhuang G., Ngu H., Kasman I., Zhang J., et al. An interleukin-17-mediated paracrine network promotes tumor resistance to anti-angiogenic therapy. Nat Med 2013, 19:1114-1123.
192. Hinoi T., Akyol A., Theisen B.K., Ferguson D.O., Greenson J.K., Williams B.O., et al. Mouse model of colonic adenoma-carcinoma progression based on somatic Apc inactivation. Cancer Res 2007, 67:9721-9730.
193. Kaiser S., Park Y.K., Franklin J.L., Halberg R.B., Yu M., Jessen W.J., et al. Transcriptional recapitulation and subversion of embryonic colon development by mouse colon tumor models and human colon cancer. Genome Biol 2007, 8:R131.
194. Guimbaud R., Abitbol V., Bertrand V., Quartier G., Chauvelot-Moachon L., Giroud J., et al. Leukemia inhibitory factor involvement in human ulcerative colitis and its potential role in malignant course. Eur Cytokine Netw 1998, 9:607-612.
195. Kim M.S., Louwagie J., Carvalho B., Terhaar Sive Droste J.S., Park H.L., Chae Y.K., et al. Promoter DNA methylation of oncostatin m receptor-beta as a novel diagnostic and therapeutic marker in colon cancer. PLoS ONE 2009, 4:e6555.
196. Hibi K., Goto T., Sakuraba K., Shirahata A., Saito M., Ishibashi K., et al. Methylation of OSMR gene is frequently observed in non-invasive colorectal cancer. Anticancer Res 2011, 31:1293-1295.
197. Huang S.P., Wu M.S., Shun C.T., Wang H.P., Lin M.T., Kuo M.L., et al. Interleukin-6 increases vascular endothelial growth factor and angiogenesis in gastric carcinoma. J Biomed Sci 2004, 11:517-527.
198. Lee S.A., Choi S.R., Jang J.S., Lee J.H., Roh M.H., Kim S.O., et al. Expression of VEGF, EGFR, and IL-6 in gastric adenomas and adenocarcinomas by endoscopic submucosal dissection. Dig Dis Sci 2010, 55:1955-1963.
199. Ashizawa T., Okada R., Suzuki Y., Takagi M., Yamazaki T., Sumi T., et al. Clinical significance of interleukin-6 (IL-6) in the spread of gastric cancer: role of IL-6 as a prognostic factor. Gastric Cancer 2005, 8:124-131.
200. Liao W.C., Lin J.T., Wu C.Y., Huang S.P., Lin M.T., Wu A.S., et al. Serum interleukin-6 level but not genotype predicts survival after resection in stages II and III gastric carcinoma. Clin Cancer Res 2008, 14:428-434.
201. Wang Z., Si X., Xu A., Meng X., Gao S., Qi Y., et al. Activation of STAT3 in human gastric cancer cells via interleukin (IL)-6-type cytokine signaling correlates with clinical implications. PLoS ONE 2013, 8:e75788.
202. Ikeguchi M., Hatada T., Yamamoto M., Miyake T., Matsunaga T., Fukumoto Y., et al. Serum interleukin-6 and -10 levels in patients with gastric cancer. Gastric Cancer 2009, 12:95-100.
203. Necula L.G., Chivu-Economescu M., Stanciulescu E.L., Bleotu C., Dima S.O., Alexiu I., et al. IL-6 and IL-11 as markers for tumor aggressiveness and prognosis in gastric adenocarcinoma patients without mutations in Gp130 subunits. J Gastrointestin Liver Dis 2012, 21:23-29.
204. Jackson C.B., Judd L.M., Menheniott T.R., Kronborg I., Dow C., Yeomans N.D., et al. Augmented gp130-mediated cytokine signalling accompanies human gastric cancer progression. J Pathol 2007, 213:140-151.
205. Jackson C.B., Giraud A.S. STAT3 as a prognostic marker in human gastric cancer. J Gastroenterol Hepatol 2009, 24:505-507.
206. Yakata Y., Nakayama T., Yoshizaki A., Kusaba T., Inoue K., Sekine I. Expression of p-STAT3 in human gastric carcinoma: significant correlation in tumour invasion and prognosis. Int J Oncol 2007, 30:437-442.
207. Gong W., Wang L., Yao J.C., Ajani J.A., Wei D., Aldape K.D., et al. Expression of activated signal transducer and activator of transcription 3 predicts expression of vascular endothelial growth factor in and angiogenic phenotype of human gastric cancer. Clin Cancer Res 2005, 11:1386-1393.
208. Tebbutt N.C., Giraud A.S., Inglese M., Jenkins B., Waring P., Clay F.J., et al. Reciprocal regulation of gastrointestinal homeostasis by SHP2 and STAT-mediated trefoil gene activation in gp130 mutant mice. Nat Med 2002, 8:1089-1097.
209. Jenkins B.J., Grail D., Nheu T., Najdovska M., Wang B., Waring P., et al. Hyperactivation of Stat3 in gp130 mutant mice promotes gastric hyperproliferation and desensitizes TGF-beta signaling. Nat Med 2005, 11:845-852.
210. Howlett M., Giraud A.S., Lescesen H., Jackson C.B., Kalantzis A., Van Driel I.R., et al. The interleukin-6 family cytokine interleukin-11 regulates homeostatic epithelial cell turnover and promotes gastric tumor development. Gastroenterology 2009, 136:967-977.
211. Howlett M., Judd L.M., Jenkins B., La Gruta N.L., Grail D., Ernst M., et al. Differential regulation of gastric tumor growth by cytokines that signal exclusively through the coreceptor gp130. Gastroenterology 2005, 129:1005-1018.
212. Kinoshita H., Hirata Y., Nakagawa H., Sakamoto K., Hayakawa Y., Takahashi R., et al. Interleukin-6 mediates epithelial-stromal interactions and promotes gastric tumorigenesis. PLoS ONE 2013, 8:e60914.
213. Inagaki-Ohara K., Mayuzumi H., Kato S., Minokoshi Y., Otsubo T., Kawamura Y.I., et al. Enhancement of leptin receptor signaling by SOCS3 deficiency induces development of gastric tumors in mice. Oncogene 2014, 33:74-84.
214. El-Serag H.B., Rudolph K.L. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 2007, 132:2557-2576.
215. Ghosh S., Ashcraft K. An IL-6 link between obesity and cancer. Front Biosci (Elite Ed) 2013, 5:461-478.
216. Giannitrapani L., Cervello M., Soresi M., Notarbartolo M., La Rosa M., Virruso L., et al. Circulating IL-6 and sIL-6R in patients with hepatocellular carcinoma. Ann NY Acad Sci 2002, 963:46-52.
217. Porta C., De Amici M., Quaglini S., Paglino C., Tagliani F., Boncimino A., et al. Circulating interleukin-6 as a tumor marker for hepatocellular carcinoma. Ann Oncol 2008, 19:353-358.
218. Soresi M., Giannitrapani L., D'Antona F., Florena A.M., La Spada E., Terranova A., et al. Interleukin-6 and its soluble receptor in patients with liver cirrhosis and hepatocellular carcinoma. World J Gastroenterol 2006, 12:2563-2568.
219. Ohishi W., Cologne J.B., Fujiwara S., Suzuki G., Hayashi T., Niwa Y., et al. Serum interleukin-6 associated with hepatocellular carcinoma risk: a nested case-control study. Int J Cancer 2014, 134:154-163.
220. Jang J.W., Oh B.S., Kwon J.H., You C.R., Chung K.W., Kay C.S., et al. Serum interleukin-6 and C-reactive protein as a prognostic indicator in hepatocellular carcinoma. Cytokine 2012, 60:686-693.
221. Nakagawa H., Maeda S., Yoshida H., Tateishi R., Masuzaki R., Ohki T., et al. Serum IL-6 levels and the risk for hepatocarcinogenesis in chronic hepatitis C patients: an analysis based on gender differences. Int J Cancer 2009, 125:2264-2269.
222. Yu G.Y., He G., Li C.Y., Tang M., Grivennikov S., Tsai W.T., et al. Hepatic expression of HCV RNA-dependent RNA polymerase triggers innate immune signaling and cytokine production. Mol Cell 2012, 48:313-321.
223. Cheon Y.K., Cho Y.D., Moon J.H., Jang J.Y., Kim Y.S., Kim Y.S., et al. Diagnostic utility of interleukin-6 (IL-6) for primary bile duct cancer and changes in serum IL-6 levels following photodynamic therapy. Am J Gastroenterol 2007, 102:2164-2170.
224. Goydos J.S., Brumfield A.M., Frezza E., Booth A., Lotze M.T., Carty S.E. Marked elevation of serum interleukin-6 in patients with cholangiocarcinoma: validation of utility as a clinical marker. Ann Surg 1998, 227:398-404.
225. Xiang Z.L., Zeng Z.C., Fan J., Tang Z.Y., Zeng H.Y. Expression of connective tissue growth factor and interleukin-11 in intratumoral tissue is associated with poor survival after curative resection of hepatocellular carcinoma. Mol Biol Rep 2012, 39:6001-6006.
226. Naugler W.E., Karin M. The wolf in sheep's clothing: the role of interleukin-6 in immunity, inflammation and cancer. Trends Mol Med 2008, 14:109-119.
227. Maeda S., Kamata H., Luo J.L., Leffert H., Karin M. IKKbeta couples hepatocyte death to cytokine-driven compensatory proliferation that promotes chemical hepatocarcinogenesis. Cell 2005, 121:977-990.
228. Naugler W.E., Sakurai T., Kim S., Maeda S., Kim K., Elsharkawy A.M., et al. Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science 2007, 317:121-124.
229. Gao B. Cytokines, STATs and liver disease. Cell Mol Immunol 2005, 2:92-100.
230. He G., Yu G.Y., Temkin V., Ogata H., Kuntzen C., Sakurai T., et al. Hepatocyte IKKbeta/NF-kappaB inhibits tumor promotion and progression by preventing oxidative stress-driven STAT3 activation. Cancer Cell 2010, 17:286-297.
231. Ogata H., Kobayashi T., Chinen T., Takaki H., Sanada T., Minoda Y., et al. Deletion of the SOCS3 gene in liver parenchymal cells promotes hepatitis-induced hepatocarcinogenesis. Gastroenterology 2006, 131:179-193.
232. Yang S.F., Wang S.N., Wu C.F., Yeh Y.T., Chai C.Y., Chunag S.C., et al. Altered p-STAT3 (tyr705) expression is associated with histological grading and intratumour microvessel density in hepatocellular carcinoma. J Clin Pathol 2007, 60:642-648.
233. Wu W.Y., Li J., Wu Z.S., Zhang C.L., Meng X.L., Lobie P.E. Prognostic significance of phosphorylated signal transducer and activator of transcription 3 and suppressor of cytokine signaling 3 expression in hepatocellular carcinoma. Exp Ther Med 2011, 2:647-653.
234. Maione D., Di Carlo E., Li W., Musiani P., Modesti A., Peters M., et al. Coexpression of IL-6 and soluble IL-6R causes nodular regenerative hyperplasia and adenomas of the liver. EMBO J 1998, 17:5588-5597.
235. Sakurai T., He G., Matsuzawa A., Yu G.Y., Maeda S., Hardiman G., et al. Hepatocyte necrosis induced by oxidative stress and IL-1 alpha release mediate carcinogen-induced compensatory proliferation and liver tumorigenesis. Cancer Cell 2008, 14:156-165.
236. Riehle K.J., Campbell J.S., McMahan R.S., Johnson M.M., Beyer R.P., Bammler T.K., et al. Regulation of liver regeneration and hepatocarcinogenesis by suppressor of cytokine signaling 3. J Exp Med 2008, 205:91-103.
237. Ershler W.B., Keller E.T. Age-associated increased interleukin-6 gene expression, late-life diseases, and frailty. Annu Rev Med 2000, 51:245-270.
238. Bosch F.X., Ribes J., Diaz M., Cleries R. Primary liver cancer: worldwide incidence and trends. Gastroenterology 2004, 127:S5-S16.
239. Gruber S., Straub B.K., Ackermann P.J., Wunderlich C.M., Mauer J., Seeger J.M., et al. Obesity promotes liver carcinogenesis via Mcl-1 stabilization independent of IL-6Ralpha signaling. Cell Rep 2013, 4:669-680.
240. Yoshimoto S., Loo T.M., Atarashi K., Kanda H., Sato S., Oyadomari S., et al. Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature 2013, 499:97-101.
241. Davalos A.R., Coppe J.P., Campisi J., Desprez P.Y. Senescent cells as a source of inflammatory factors for tumor progression. Cancer Metastasis Rev 2010, 29:273-283.
242. Wang H., Lafdil F., Wang L., Park O., Yin S., Niu J., et al. Hepatoprotective versus oncogenic functions of STAT3 in liver tumorigenesis. Am J Pathol 2011, 179:714-724.
243. Hatziapostolou M., Polytarchou C., Aggelidou E., Drakaki A., Poultsides G.A., Jaeger S.A., et al. An HNF4alpha-miRNA inflammatory feedback circuit regulates hepatocellular oncogenesis. Cell 2011, 147:1233-1247.
244. Xu W.P., Yi M., Li Q.Q., Zhou W.P., Cong W.M., Yang Y., et al. Perturbation of miR-370-LIN28A-NF-kappaB regulatory circuit contributes to the development of hepatocellular carcinoma. Hepatology 2013, 58:1977-1991.
245. Pilati C., Amessou M., Bihl M.P., Balabaud C., Nhieu J.T., Paradis V., et al. Somatic mutations activating STAT3 in human inflammatory hepatocellular adenomas. J Exp Med 2011, 208:1359-1366.
246. Rebouissou S., Amessou M., Couchy G., Poussin K., Imbeaud S., Pilati C., et al. Frequent in-frame somatic deletions activate gp130 in inflammatory hepatocellular tumours. Nature 2009, 457:200-204.
247. Lee T.K., Cheung V.C., Ng I.O. Liver tumor-initiating cells as a therapeutic target for hepatocellular carcinoma. Cancer Lett 2013, 338:101-109.
248. Yoon S.M., Gerasimidou D., Kuwahara R., Hytiroglou P., Yoo J.E., Park Y.N., et al. Epithelial cell adhesion molecule (EpCAM) marks hepatocytes newly derived from stem/progenitor cells in humans. Hepatology 2011, 53:964-973.
249. Yamashita T., Honda M., Nio K., Nakamoto Y., Yamashita T., Takamura H., et al. Oncostatin m renders epithelial cell adhesion molecule-positive liver cancer stem cells sensitive to 5-Fluorouracil by inducing hepatocytic differentiation. Cancer Res 2010, 70:4687-4697.
250. Vollmer S., Haan C., Behrmann I. Oncostatin M up-regulates the ER chaperone Grp78/BiP in liver cells. Biochem Pharmacol 2010, 80:2066-2073.
251. Kanda J., Uchiyama T., Tomosugi N., Higuchi M., Uchiyama T., Kawabata H. Oncostatin M and leukemia inhibitory factor increase hepcidin expression in hepatoma cell lines. Int J Hematol 2009, 90:545-552.
252. Guillen M.I., Donato M.T., Jover R., Castell J.V., Fabra R., Trullenque R., et al. Oncostatin M down-regulates basal and induced cytochromes P450 in human hepatocytes. J Pharmacol Exp Ther 1998, 285:127-134.
253. Le Vee M., Jouan E., Stieger B., Lecureur V., Fardel O. Regulation of drug transporter expression by oncostatin M in human hepatocytes. Biochem Pharmacol 2011, 82:304-311.
254. Liang H., Block T.M., Wang M., Nefsky B., Long R., Hafner J., et al. Interleukin-6 and oncostatin M are elevated in liver disease in conjunction with candidate hepatocellular carcinoma biomarker GP73. Cancer Biomark 2012, 11:161-171.
255. Talar-Wojnarowska R., Gasiorowska A., Smolarz B., Romanowicz-Makowska H., Kulig A., Malecka-Panas E. Clinical significance of interleukin-6 (IL-6) gene polymorphism and IL-6 serum level in pancreatic adenocarcinoma and chronic pancreatitis. Dig Dis Sci 2009, 54:683-689.
256. Mitsunaga S., Ikeda M., Shimizu S., Ohno I., Furuse J., Inagaki M., et al. Serum levels of IL-6 and IL-1beta can predict the efficacy of gemcitabine in patients with advanced pancreatic cancer. Br J Cancer 2013, 108:2063-2069.
257. Denley S.M., Jamieson N.B., McCall P., Oien K.A., Morton J.P., Carter C.R., et al. Activation of the IL-6R/Jak/stat pathway is associated with a poor outcome in resected pancreatic ductal adenocarcinoma. J Gastrointestin Surg 2013, 17:887-898.
258. Bellone G., Smirne C., Mauri F.A., Tonel E., Carbone A., Buffolino A., et al. Cytokine expression profile in human pancreatic carcinoma cells and in surgical specimens: implications for survival. Cancer Immunol Immunother 2006, 55:684-698.
259. Scholz A., Heinze S., Detjen K.M., Peters M., Welzel M., Hauff P., et al. Activated signal transducer and activator of transcription 3 (STAT3) supports the malignant phenotype of human pancreatic cancer. Gastroenterology 2003, 125:891-905.
260. Huang C., Huang R., Chang W., Jiang T., Huang K., Cao J., et al. The expression and clinical significance of pSTAT3, VEGF and VEGF-C in pancreatic adenocarcinoma. Neoplasma 2012, 59:52-61.
261. Miyatsuka T., Kaneto H., Shiraiwa T., Matsuoka T.A., Yamamoto K., Kato K., et al. Persistent expression of PDX-1 in the pancreas causes acinar-to-ductal metaplasia through Stat3 activation. Genes Dev 2006, 20:1435-1440.
262. Lesina M., Kurkowski M.U., Ludes K., Rose-John S., Treiber M., Kloppel G., et al. Stat3/Socs3 activation by IL-6 transsignaling promotes progression of pancreatic intraepithelial neoplasia and development of pancreatic cancer. Cancer Cell 2011, 19:456-469.
263. Fukuda A., Wang S.C., Morris J.P., Folias A.E., Liou A., Kim G.E., et al. Stat3 and MMP7 contribute to pancreatic ductal adenocarcinoma initiation and progression. Cancer Cell 2011, 19:441-455.
264. Corcoran R.B., Contino G., Deshpande V., Tzatsos A., Conrad C., Benes C.H., et al. STAT3 plays a critical role in KRAS-induced pancreatic tumorigenesis. Cancer Res 2011, 71:5020-5029.
265. Kang R., Loux T., Tang D., Schapiro N.E., Vernon P., Livesey K.M., et al. The expression of the receptor for advanced glycation endproducts (RAGE) is permissive for early pancreatic neoplasia. Proc Natl Acad Sci USA 2012, 109:7031-7036.
266. Kamohara H., Ogawa M., Ishiko T., Sakamoto K., Baba H. Leukemia inhibitory factor functions as a growth factor in pancreas carcinoma cells: involvement of regulation of LIF and its receptor expression. Int J Oncol 2007, 30:977-983.
267. Benson D.D., Meng X., Fullerton D.A., Moore E.E., Lee J.H., Ao L., et al. Activation state of stromal inflammatory cells in murine metastatic pancreatic adenocarcinoma. Am J Physiol Regul Integr Comp Physiol 2012, 302:R1067-R1075.
268. Songur N., Kuru B., Kalkan F., Ozdilekcan C., Cakmak H., Hizel N. Serum interleukin-6 levels correlate with malnutrition and survival in patients with advanced non-small cell lung cancer. Tumori 2004, 90:196-200.
269. Chang K.T., Tsai C.M., Chiou Y.C., Chiu C.H., Jeng K.S., Huang C.Y. IL-6 induces neuroendocrine dedifferentiation and cell proliferation in non-small cell lung cancer cells. Am J Physiol Lung Cell Mol Physiol 2005, 289:L446-L453.
270. Li Q., Han Y., Fei G., Guo Z., Ren T., Liu Z. IL-17 promoted metastasis of non-small-cell lung cancer cells. Immunol Lett 2012, 148:144-150.
271. Jiang R., Jin Z., Liu Z., Sun L., Wang L., Li K. Correlation of activated STAT3 expression with clinicopathologic features in lung adenocarcinoma and squamous cell carcinoma. Mol Diagn Ther 2011, 15:347-352.
272. Ai T., Wang Z., Zhang M., Zhang L., Wang N., Li W., et al. Expression and prognostic relevance of STAT3 and cyclin D1 in non-small cell lung cancer. Int J Biol Markers 2012, 27:e132-e138.
273. Zhao X., Sun X., Li X.L. Expression and clinical significance of STAT3, P-STAT3, and VEGF-C in small cell lung cancer. Asian Pac J Cancer Prev 2012, 13:2873-2877.
274. Yin Z.J., Jin F.G., Liu T.G., Fu E.Q., Xie Y.H., Sun R.L. Overexpression of STAT3 potentiates growth, survival, and radioresistance of non-small-cell lung cancer (NSCLC) cells. J Surg Res 2011, 171:675-683.
275. Xu G., Zhang C., Zhang J. Dominant negative STAT3 suppresses the growth and invasion capability of human lung cancer cells. Mol Med Rep 2009, 2:819-824.
276. Yeh H.H., Lai W.W., Chen H.H., Liu H.S., Su W.C. Autocrine IL-6-induced Stat3 activation contributes to the pathogenesis of lung adenocarcinoma and malignant pleural effusion. Oncogene 2006, 25:4300-4309.
277. Gao S.P., Mark K.G., Leslie K., Pao W., Motoi N., Gerald W.L., et al. Mutations in the EGFR kinase domain mediate STAT3 activation via IL-6 production in human lung adenocarcinomas. J Clin Invest 2007, 117:3846-3856.
278. Takahashi H., Ogata H., Nishigaki R., Broide D.H., Karin M. Tobacco smoke promotes lung tumorigenesis by triggering IKKbeta- and JNK1-dependent inflammation. Cancer Cell 2010, 17:89-97.
279. Dougan M., Li D., Neuberg D., Mihm M., Googe P., Wong K.K., et al. A dual role for the immune response in a mouse model of inflammation-associated lung cancer. J Clin Invest 2011, 121:2436-2446.
280. Oka M., Yamamoto K., Takahashi M., Hakozaki M., Abe T., Iizuka N., et al. Relationship between serum levels of interleukin 6, various disease parameters and malnutrition in patients with esophageal squamous cell carcinoma. Cancer Res 1996, 56:2776-2780.
281. Wang L.S., Chow K.C., Wu C.W. Expression and up-regulation of interleukin-6 in oesophageal carcinoma cells by n-sodium butyrate. Br J Cancer 1999, 80:1617-1622.
282. Lukaszewicz-Zajac M., Mroczko B., Kozlowski M., Niklinski J., Laudanski J., Szmitkowski M. Higher importance of interleukin 6 than classic tumor markers (carcinoembryonic antigen and squamous cell cancer antigen) in the diagnosis of esophageal cancer patients. Dis Esophagus 2012, 25:242-249.
283. Chen M.F., Chen P.T., Lu M.S., Lin P.Y., Chen W.C., Lee K.D. IL-6 expression predicts treatment response and outcome in squamous cell carcinoma of the esophagus. Mol Cancer 2013, 12:26.
284. Yoneda M., Fujiwara H., Furutani A., Ikai A., Tada H., Shiozaki A., et al. Prognostic impact of tumor IL-6 expression after preoperative chemoradiotherapy in patients with advanced esophageal squamous cell carcinoma. Anticancer Res 2013, 33:2699-2705.
285. Makuuchi Y., Honda K., Osaka Y., Kato K., Kojima T., Daiko H., et al. Soluble interleukin-6 receptor is a serum biomarker for the response of esophageal carcinoma to neoadjuvant chemoradiotherapy. Cancer Sci 2013, 104:1045-1051.
286. Leu C.M., Wong F.H., Chang C., Huang S.F., Hu C.P. Interleukin-6 acts as an antiapoptotic factor in human esophageal carcinoma cells through the activation of both STAT3 and mitogen-activated protein kinase pathways. Oncogene 2003, 22:7809-7818.
287. Okamura S., Fujiwara H., Yoneda M., Furutani A., Todo M., Ikai A., et al. Overexpression of IL-6 by gene transfer stimulates IL-8-mediated invasiveness of KYSE170 esophageal carcinoma cells. Anticancer Res 2013, 33:1483-1489.
288. Sugimura K., Miyata H., Tanaka K., Hamano R., Takahashi T., Kurokawa Y., et al. Let-7 expression is a significant determinant of response to chemotherapy through the regulation of IL-6/STAT3 pathway in esophageal squamous cell carcinoma. Clin Cancer Res 2012, 18:5144-5153.
289. Zhang Y., Du X.L., Wang C.J., Lin D.C., Ruan X., Feng Y.B., et al. Reciprocal activation between PLK1 and Stat3 contributes to survival and proliferation of esophageal cancer cells. Gastroenterology 2012, 142:521-530. e523.
290. Timme S., Ihde S., Fichter C.D., Waehle V., Bogatyreva L., Atanasov K., et al. STAT3 expression, activity and functional consequences of STAT3 inhibition in esophageal squamous cell carcinomas and Barrett's adenocarcinomas. Oncogene 2013, in press.
291. Schoppmann S.F., Jesch B., Friedrich J., Jomrich G., Maroske F., Birner P. Phosphorylation of signal transducer and activator of transcription 3 (STAT3) correlates with Her-2 status, carbonic anhydrase 9 expression and prognosis in esophageal cancer. Clin Exp Metastasis 2012, 29:615-624.
292. You Z., Xu D., Ji J., Guo W., Zhu W., He J. JAK/STAT signal pathway activation promotes progression and survival of human oesophageal squamous cell carcinoma. Clin Transl Oncol 2012, 14:143-149.
293. Wang Z., Zhu S., Shen M., Liu J., Wang M., Li C., et al. STAT3 is involved in esophageal carcinogenesis through regulation of Oct-1. Carcinogenesis 2013, 34:678-688.
294. Yan S., Zhou C., Zhang W., Zhang G., Zhao X., Yang S., et al. beta-Catenin/TCF pathway upregulates STAT3 expression in human esophageal squamous cell carcinoma. Cancer Lett 2008, 271:85-97.
295. Kausar T., Sharma R., Hasan M.R., Saraya A., Chattopadhyay T.K., Gupta S.D., et al. Overexpression of a splice variant of oncostatin M receptor beta in human esophageal squamous carcinoma. Cell Oncol 2011, 34:177-187.
296. Zhang G.J., Adachi I. Serum interleukin-6 levels correlate to tumor progression and prognosis in metastatic breast carcinoma. Anticancer Res 1999, 19:1427-1432.
297. Salgado R., Junius S., Benoy I., Van Dam P., Vermeulen P., Van Marck E., et al. Circulating interleukin-6 predicts survival in patients with metastatic breast cancer. Int J Cancer 2003, 103:642-646.
298. Dethlefsen C., Hojfeldt G., Hojman P. The role of intratumoral and systemic IL-6 in breast cancer. Breast Cancer Res Treat 2013, 138:657-664.
299. Erez N., Glanz S., Raz Y., Avivi C., Barshack I. Cancer associated fibroblasts express pro-inflammatory factors in human breast and ovarian tumors. Biochem Biophys Res Commun 2013, 437:397-402.
300. Korkaya H., Kim G.I., Davis A., Malik F., Henry N.L., Ithimakin S., et al. Activation of an IL6 inflammatory loop mediates trastuzumab resistance in HER2+ breast cancer by expanding the cancer stem cell population. Mol Cell 2012, 47:570-584.
301. Garcia-Tunon I., Ricote M., Ruiz A., Fraile B., Paniagua R., Royuela M. IL-6, its receptors and its relationship with bcl-2 and bax proteins in infiltrating and in situ human breast carcinoma. Histopathology 2005, 47:82-89.
302. Rincon M., Broadwater G., Harris L., Crocker A., Weaver D., Dressler L., et al. Interleukin-6, multidrug resistance protein-1 expression and response to paclitaxel in women with metastatic breast cancer: results of cancer and leukemia group B trial 159806. Breast Cancer Res Treat 2006, 100:301-308.
303. Widschwendter A., Tonko-Geymayer S., Welte T., Daxenbichler G., Marth C., Doppler W. Prognostic significance of signal transducer and activator of transcription 1 activation in breast cancer. Clin Cancer Res 2002, 8:3065-3074.
304. Sato T., Neilson L.M., Peck A.R., Liu C., Tran T.H., Witkiewicz A., et al. Signal transducer and activator of transcription-3 and breast cancer prognosis. Am J Cancer Res 2011, 1:347-355.
305. Meng L., Zhou J., Sasano H., Suzuki T., Zeitoun K.M., Bulun S.E. Tumor necrosis factor alpha and interleukin 11 secreted by malignant breast epithelial cells inhibit adipocyte differentiation by selectively down-regulating CCAAT/enhancer binding protein alpha and peroxisome proliferator-activated receptor gamma: mechanism of desmoplastic reaction. Cancer Res 2001, 61:2250-2255.
306. Grant S.L., Douglas A.M., Goss G.A., Begley C.G. Oncostatin M and leukemia inhibitory factor regulate the growth of normal human breast epithelial cells. Growth Factors 2001, 19:153-162.
307. Garcia-Tunon I., Ricote M., Ruiz A., Fraile B., Paniagua R., Royuela M. OSM, LIF, its receptors, and its relationship with the malignance in human breast carcinoma (in situ and in infiltrative). Cancer Invest 2008, 26:222-229.
308. Estrov Z., Samal B., Lapushin R., Kellokumpu-Lehtinen P., Sahin A.A., Kurzrock R., et al. Leukemia inhibitory factor binds to human breast cancer cells and stimulates their proliferation. J Interferon Cytokine Res 1995, 15:905-913.
309. Dhingra K., Sahin A., Emami K., Hortobagyi G.N., Estrov Z. Expression of leukemia inhibitory factor and its receptor in breast cancer: a potential autocrine and paracrine growth regulatory mechanism. Breast Cancer Res Treat 1998, 48:165-174.
310. Shin J.E., Park S.H., Jang Y.K. Epigenetic up-regulation of leukemia inhibitory factor (LIF) gene during the progression to breast cancer. Mol Cells 2011, 31:181-189.
311. Quaglino A., Schere-Levy C., Romorini L., Meiss R.P., Kordon E.C. Mouse mammary tumors display Stat3 activation dependent on leukemia inhibitory factor signaling. Breast Cancer Res 2007, 9:R69.
312. Chen D., Sun Y., Wei Y., Zhang P., Rezaeian A.H., Teruya-Feldstein J., et al. LIFR is a breast cancer metastasis suppressor upstream of the Hippo-YAP pathway and a prognostic marker. Nat Med 2012, 18:1511-1517.
313. Bolin C., Tawara K., Sutherland C., Redshaw J., Aranda P., Moselhy J., et al. Oncostatin m promotes mammary tumor metastasis to bone and osteolytic bone degradation. Genes Cancer 2012, 3:117-130.
314. Liu J., Spence M.J., Wallace P.M., Forcier K., Hellstrom I., Vestal R.E. Oncostatin M-specific receptor mediates inhibition of breast cancer cell growth and down-regulation of the c-myc proto-oncogene. Cell Growth Differ 1997, 8:667-676.
315. Spence M.J., Vestal R.E., Liu J. Oncostatin M-mediated transcriptional suppression of the c-myc gene in breast cancer cells. Cancer Res 1997, 57:2223-2228.
316. Douglas A.M., Grant S.L., Goss G.A., Clouston D.R., Sutherland R.L., Begley C.G. Oncostatin M induces the differentiation of breast cancer cells. Int J Cancer 1998, 75:64-73.
317. Underhill-Day N., Heath J.K. Oncostatin M (OSM) cytostasis of breast tumor cells: characterization of an OSM receptor beta-specific kernel. Cancer Res 2006, 66:10891-10901.
318. Coward J.I., Kulbe H. The role of interleukin-6 in gynaecological malignancies. Cytokine Growth Factor Rev 2012, 23:333-342.
319. Takano H., Harigaya K., Ishii G., Sugaya Y., Soeta S., Nunoyama T., et al. Interleukin-6 (IL-6) production in carcinoma of the cervix. Arch Gynecol Obstet 1996, 258:25-33.
320. Chopra V., Dinh T.V., Hannigan E.V. Circulating serum levels of cytokines and angiogenic factors in patients with cervical cancer. Cancer Invest 1998, 16:152-159.
321. Tartour E., Gey A., Sastre-Garau X., Pannetier C., Mosseri V., Kourilsky P., et al. Analysis of interleukin 6 gene expression in cervical neoplasia using a quantitative polymerase chain reaction assay: evidence for enhanced interleukin 6 gene expression in invasive carcinoma. Cancer Res 1994, 54:6243-6248.
322. Castrilli G., Tatone D., Diodoro M.G., Rosini S., Piantelli M., Musiani P. Interleukin 1alpha and interleukin 6 promote the in vitro growth of both normal and neoplastic human cervical epithelial cells. Br J Cancer 1997, 75:855-859.
323. Eustace D., Han X., Gooding R., Rowbottom A., Riches P., Heyderman E. Interleukin-6 (IL-6) functions as an autocrine growth factor in cervical carcinomas in vitro. Gynecol Oncol 1993, 50:15-19.
324. Chen C.L., Hsieh F.C., Lieblein J.C., Brown J., Chan C., Wallace J.A., et al. Stat3 activation in human endometrial and cervical cancers. Br J Cancer 2007, 96:591-599.
325. Takemoto S., Ushijima K., Kawano K., Yamaguchi T., Terada A., Fujiyoshi N., et al. Expression of activated signal transducer and activator of transcription-3 predicts poor prognosis in cervical squamous-cell carcinoma. Br J Cancer 2009, 101:967-972.
326. Liu Y., Zhang Y., Fu J., Tan W. Inflammation-related gene expression profiles of endocervical polyps. J Interferon Cytokine Res 2012, 32:191-197.
327. Bay J.M., Patterson B.K., Teng N.N. Leukemia inhibitory factor downregulates human papillomavirus-16 oncogene expression and inhibits the proliferation of cervical carcinoma cells. Infect Dis Obstet Gynecol 2011, 2011:463081.
328. Ng G., Winder D., Muralidhar B., Gooding E., Roberts I., Pett M., et al. Gain and overexpression of the oncostatin M receptor occur frequently in cervical squamous cell carcinoma and are associated with adverse clinical outcome. J Pathol 2007, 212:325-334.
329. Bellone S., Watts K., Cane S., Palmieri M., Cannon M.J., Burnett A., et al. High serum levels of interleukin-6 in endometrial carcinoma are associated with uterine serous papillary histology, a highly aggressive and chemotherapy-resistant variant of endometrial cancer. Gynecol Oncol 2005, 98:92-98.
330. Chopra V., Dinh T.V., Hannigan E.V. Serum levels of interleukins, growth factors and angiogenin in patients with endometrial cancer. J Cancer Res Clin Oncol 1997, 123:167-172.
331. Sales K.J., Grant V., Cook I.H., Maldonado-Perez D., Anderson R.A., Williams A.R., et al. Interleukin-11 in endometrial adenocarcinoma is regulated by prostaglandin F2alpha-F-prostanoid receptor interaction via the calcium-calcineurin-nuclear factor of activated T cells pathway and negatively regulated by the regulator of calcineurin-1. Am J Pathol 2010, 176:435-445.
332. Yap J., Salamonsen L.A., Jobling T., Nicholls P.K., Dimitriadis E. Interleukin 11 is upregulated in uterine lavage and endometrial cancer cells in women with endometrial carcinoma. Reprod Biol Endocrinol 2010, 8:63.
333. Mylonas I., Makovitzky J., Shabani N., Richter D.U., Kuhn C., Jeschke U., et al. Leukaemia inhibitory factor (LIF) is immunohistochemically expressed in normal, hyperplastic and malignant endometrial tissue. Eur J Obstet Gynecol Reprod Biol 2005, 118:101-108.
334. Dijkgraaf E.M., Welters M.J., Nortier J.W., van der Burg S.H., Kroep J.R. Interleukin-6/interleukin-6 receptor pathway as a new therapy target in epithelial ovarian cancer. Curr Pharm Des 2012, 18:3816-3827.
335. Maccio A., Madeddu C. Inflammation and ovarian cancer. Cytokine 2012, 58:133-147.
336. Punnonen R., Teisala K., Kuoppala T., Bennett B., Punnonen J. Cytokine production profiles in the peritoneal fluids of patients with malignant or benign gynecologic tumors. Cancer 1998, 83:788-796.
337. Lo C.W., Chen M.W., Hsiao M., Wang S., Chen C.A., Hsiao S.M., et al. IL-6 trans-signaling in formation and progression of malignant ascites in ovarian cancer. Cancer Res 2011, 71:424-434.
338. Watson J.M., Sensintaffar J.L., Berek J.S., Martinez-Maza O. Constitutive production of interleukin 6 by ovarian cancer cell lines and by primary ovarian tumor cultures. Cancer Res 1990, 50:6959-6965.
339. Anglesio M.S., George J., Kulbe H., Friedlander M., Rischin D., Lemech C., et al. IL6-STAT3-HIF signaling and therapeutic response to the angiogenesis inhibitor sunitinib in ovarian clear cell cancer. Clin Cancer Res 2011, 17:2538-2548.
340. Wang Y., Niu X.L., Qu Y., Wu J., Zhu Y.Q., Sun W.J., et al. Autocrine production of interleukin-6 confers cisplatin and paclitaxel resistance in ovarian cancer cells. Cancer Lett 2010, 295:110-123.
341. Asschert J.G., Vellenga E., Hollema H., van der Zee A.G., de Vries E.G. Expression of macrophage colony-stimulating factor (M-CSF), interleukin-6, (IL-6), interleukin-1 beta (IL-1 beta), interleukin-11 (IL-11) and tumour necrosis factor-alpha (TNF-alpha) in p53-characterised human ovarian carcinomas. Eur J Cancer 1997, 33:2246-2251.
342. Campbell C.L., Guardiani R., Ollari C., Nelson B.E., Quesenberry P.J., Savarese T.M. Interleukin-11 receptor expression in primary ovarian carcinomas. Gynecol Oncol 2001, 80:121-127.
343. Huang M., Page C., Reynolds R.K., Lin J. Constitutive activation of stat 3 oncogene product in human ovarian carcinoma cells. Gynecol Oncol 2000, 79:67-73.
344. Rosen D.G., Mercado-Uribe I., Yang G., Bast R.C., Amin H.M., Lai R., et al. The role of constitutively active signal transducer and activator of transcription 3 in ovarian tumorigenesis and prognosis. Cancer 2006, 107:2730-2740.
345. Savarese T.M., Campbell C.L., McQuain C., Mitchell K., Guardiani R., Quesenberry P.J., et al. Coexpression of oncostatin M and its receptors and evidence for STAT3 activation in human ovarian carcinomas. Cytokine 2002, 17:324-334.
346. Li Q., Zhu J., Sun F., Liu L., Liu X., Yue Y. Oncostatin M promotes proliferation of ovarian cancer cells through signal transducer and activator of transcription 3. Int J Mol Med 2011, 28:101-108.
347. Nguyen D.P., Li J., Tewari A.K. Inflammation and prostate cancer: the role of interleukin-6. BJU Int 2013, in press.
348. Furuya Y., Nishio R., Junicho A., Nagakawa O., Fuse H. Serum interleukin-11 in patients with benign prostatic hyperplasia and prostate cancer. Int Urol Nephrol 2005, 37:69-71.
349. Campbell C.L., Jiang Z., Savarese D.M., Savarese T.M. Increased expression of the interleukin-11 receptor and evidence of STAT3 activation in prostate carcinoma. Am J Pathol 2001, 158:25-32.
350. Zurita A.J., Troncoso P., Cardo-Vila M., Logothetis C.J., Pasqualini R., Arap W. Combinatorial screenings in patients: the interleukin-11 receptor alpha as a candidate target in the progression of human prostate cancer. Cancer Res 2004, 64:435-439.
351. Torres-Roca J.F., DeSilvio M., Mora L.B., Khor L.Y., Hammond E., Ahmad N., et al. Activated STAT3 as a correlate of distant metastasis in prostate cancer: a secondary analysis of Radiation Therapy Oncology Group 86-10. Urology 2007, 69:505-509.
352. Liu X., He Z., Li C.H., Huang G., Ding C., Liu H. Correlation analysis of JAK-STAT pathway components on prognosis of patients with prostate cancer. Pathol Oncol Res 2012, 18:17-23.
353. Smith P.C., Hobisch A., Lin D.L., Culig Z., Keller E.T. Interleukin-6 and prostate cancer progression. Cytokine Growth Factor Rev 2001, 12:33-40.
354. Culig Z., Puhr M. Interleukin-6: a multifunctional targetable cytokine in human prostate cancer. Mol Cell Endocrinol 2012, 360:52-58.
355. Tam L., McGlynn L.M., Traynor P., Mukherjee R., Bartlett J.M., Edwards J. Expression levels of the JAK/STAT pathway in the transition from hormone-sensitive to hormone-refractory prostate cancer. Br J Cancer 2007, 97:378-383.
356. Wu C.T., Hsieh C.C., Lin C.C., Chen W.C., Hong J.H., Chen M.F. Significance of IL-6 in the transition of hormone-resistant prostate cancer and the induction of myeloid-derived suppressor cells. J Mol Med (Berl) 2012, 90:1343-1355.
357. Ammirante M., Luo J.L., Grivennikov S., Nedospasov S., Karin M. B-cell-derived lymphotoxin promotes castration-resistant prostate cancer. Nature 2010, 464:302-305.
358. Chung T.D., Yu J.J., Kong T.A., Spiotto M.T., Lin J.M. Interleukin-6 activates phosphatidylinositol-3 kinase, which inhibits apoptosis in human prostate cancer cell lines. Prostate 2000, 42:1-7.
359. Smith D.A., Kiba A., Zong Y., Witte O.N. Interleukin-6 and oncostatin-M synergize with the PI3K/AKT pathway to promote aggressive prostate malignancy in mouse and human tissues. Mol Cancer Res 2013, 11:1159-1165.
360. Wu C.T., Chen M.F., Chen W.C., Hsieh C.C. The role of IL-6 in the radiation response of prostate cancer. Radiat Oncol 2013, 8:159.
361. Borsellino N., Belldegrun A., Bonavida B. Endogenous interleukin 6 is a resistance factor for cis-diamminedichloroplatinum and etoposide-mediated cytotoxicity of human prostate carcinoma cell lines. Cancer Res 1995, 55:4633-4639.
362. Domingo-Domenech J., Oliva C., Rovira A., Codony-Servat J., Bosch M., Filella X., et al. Interleukin 6, a nuclear factor-kappaB target, predicts resistance to docetaxel in hormone-independent prostate cancer and nuclear factor-kappaB inhibition by PS-1145 enhances docetaxel antitumor activity. Clin Cancer Res 2006, 12:5578-5586.
363. Matsuda T., Junicho A., Yamamoto T., Kishi H., Korkmaz K., Saatcioglu F., et al. Cross-talk between signal transducer and activator of transcription 3 and androgen receptor signaling in prostate carcinoma cells. Biochem Biophys Res Commun 2001, 283:179-187.
364. Schroeder A., Herrmann A., Cherryholmes G., Kowolik C., Buettner R., Pal S., et al. Loss of androgen receptor expression promotes a stem-like cell phenotype in prostate cancer through STAT3 signaling. Cancer Res 2013, in press.
365. Kroon P., Berry P.A., Stower M.J., Rodrigues G., Mann V.M., Simms M., et al. JAK-STAT blockade inhibits tumor initiation and clonogenic recovery of prostate cancer stem-like cells. Cancer Res 2013, 73:5288-5298.
366. Thiounn N., Pages F., Flam T., Tartour E., Mosseri V., Zerbib M., et al. IL-6 is a survival prognostic factor in renal cell carcinoma. Immunol Lett 1997, 58:121-124.
367. Ljungberg B., Grankvist K., Rasmuson T. Serum interleukin-6 in relation to acute-phase reactants and survival in patients with renal cell carcinoma. Eur J Cancer 1997, 33:1794-1798.
368. Yoshida N., Ikemoto S., Narita K., Sugimura K., Wada S., Yasumoto R., et al. Interleukin-6, tumour necrosis factor alpha and interleukin-1beta in patients with renal cell carcinoma. Br J Cancer 2002, 86:1396-1400.
369. Costes V., Liautard J., Picot M.C., Robert M., Lequeux N., Brochier J., et al. Expression of the interleukin 6 receptor in primary renal cell carcinoma. J Clin Pathol 1997, 50:835-840.
370. Blay J.Y., Negrier S., Combaret V., Attali S., Goillot E., Merrouche Y., et al. Serum level of interleukin 6 as a prognosis factor in metastatic renal cell carcinoma. Cancer Res 1992, 52:3317-3322.
371. Knoefel B., Nuske K., Steiner T., Junker K., Kosmehl H., Rebstock K., et al. Renal cell carcinomas produce IL-6, IL-10, IL-11, and TGF-beta 1 in primary cultures and modulate T lymphocyte blast transformation. J Interferon Cytokine Res 1997, 17:95-102.
372. Miki S., Iwano M., Miki Y., Yamamoto M., Tang B., Yokokawa K., et al. Interleukin-6 (IL-6) functions as an in vitro autocrine growth factor in renal cell carcinomas. FEBS Lett 1989, 250:607-610.
373. Takenawa J., Kaneko Y., Fukumoto M., Fukatsu A., Hirano T., Fukuyama H., et al. Enhanced expression of interleukin-6 in primary human renal cell carcinomas. J Natl Cancer Inst 1991, 83:1668-1672.
374. Alberti L., Thomachot M.C., Bachelot T., Menetrier-Caux C., Puisieux I., Blay J.Y. IL-6 as an intracrine growth factor for renal carcinoma cell lines. Int J Cancer 2004, 111:653-661.
375. Mizutani Y., Bonavida B., Koishihara Y., Akamatsu K., Ohsugi Y., Yoshida O. Sensitization of human renal cell carcinoma cells to cis-diamminedichloroplatinum(II) by anti-interleukin 6 monoclonal antibody or anti-interleukin 6 receptor monoclonal antibody. Cancer Res 1995, 55:590-596.
376. Horiguchi A., Oya M., Shimada T., Uchida A., Marumo K., Murai M. Activation of signal transducer and activator of transcription 3 in renal cell carcinoma: a study of incidence and its association with pathological features and clinical outcome. J Urol 2002, 168:762-765.
377. Chen M.F., Lin P.Y., Wu C.F., Chen W.C., Wu C.T. IL-6 expression regulates tumorigenicity and correlates with prognosis in bladder cancer. PLoS ONE 2013, 8:e61901.
378. Okamoto M., Hattori K., Oyasu R. Interleukin-6 functions as an autocrine growth factor in human bladder carcinoma cell lines in vitro. Int J Cancer 1997, 72:149-154.
379. Wu D., Tao J., Ding J., Qu P., Lu Q., Zhang W. Interleukin-11: an interleukin-6-like cytokine, is a promising predictor for bladder cancer prognosis. Mol Med Rep 2013, 7:684-688.
380. Wang L., Yi T., Kortylewski M., Pardoll D.M., Zeng D., Yu H. IL-17 can promote tumor growth through an IL-6-Stat3 signaling pathway. J Exp Med 2009, 206:1457-1464.
381. Xu S., Neamati N. gp130: a promising drug target for cancer therapy. Expert Opin Ther Targets 2013, 17:1303-1328.
382. Bournazou E., Bromberg J. Targeting the tumor microenvironment: JAK-STAT3 signaling. JAK-STAT 2013, 2:e23828.
383. Tanaka T., Narazaki M., Kishimoto T. Therapeutic targeting of the interleukin-6 receptor. Annu Rev Pharmacol Toxicol 2012, 52:199-219.
384. Lee C.G., Hartl D., Matsuura H., Dunlop F.M., Scotney P.D., Fabri L.J., et al. Endogenous IL-11 signaling is essential in Th2- and IL-13-induced inflammation and mucus production. Am J Respir Cell Mol Biol 2008, 39:739-746.
385. Xu S., Grande F., Garofalo A., Neamati N. Discovery of a novel orally active small-molecule gp130 inhibitor for the treatment of ovarian cancer. Mol Cancer Ther 2013, 12:937-949.
386. Constantinescu S.N., Girardot M., Pecquet C. Mining for JAK-STAT mutations in cancer. Trends Biochem Sci 2008, 33:122-131.
387. Hedvat M., Huszar D., Herrmann A., Gozgit J.M., Schroeder A., Sheehy A., et al. The JAK2 inhibitor AZD1480 potently blocks Stat3 signaling and oncogenesis in solid tumors. Cancer Cell 2009, 16:487-497.
388. McFarland B.C., Ma J.Y., Langford C.P., Gillespie G.Y., Yu H., Zheng Y., et al. Therapeutic potential of AZD1480 for the treatment of human glioblastoma. Mol Cancer Ther 2011, 10:2384-2393.
389. Yan S., Li Z., Thiele C.J. Inhibition of STAT3 with orally active JAK inhibitor, AZD1480, decreases tumor growth in neuroblastoma and pediatric sarcomas in vitro and in vivo. Oncotarget 2013, 4:433-445.
390. Lee J.H., Park K.S., Alberobello A.T., Kallakury B., Weng M.T., Wang Y., et al. The Janus kinases inhibitor AZD1480 attenuates growth of small cell lung cancers in vitro and in vivo. Clin Cancer Res 2013, 19:6777-6786.
391. Murakami T., Takigawa N., Ninomiya T., Ochi N., Yasugi M., Honda Y., et al. Effect of AZD1480 in an epidermal growth factor receptor-driven lung cancer model. Lung Cancer 2014, 83:30-36.
392. Xin H., Herrmann A., Reckamp K., Zhang W., Pal S., Hedvat M., et al. Antiangiogenic and antimetastatic activity of JAK inhibitor AZD1480. Cancer Res 2011, 71:6601-6610.
393. Bhagwat N., Levine R.L., Koppikar P. Sensitivity and resistance of JAK2 inhibitors to myeloproliferative neoplasms. Int J Hematol 2013, 97:695-702.
394. Yang L.P., Keating G.M. Ruxolitinib: in the treatment of myelofibrosis. Drugs 2012, 72:2117-2127.
395. Mankan A.K., Greten F.R. Inhibiting signal transducer and activator of transcription 3: rationality and rationale design of inhibitors. Expert Opin Investig Drugs 2011, 20:1263-1275.
396. Wang X., Crowe P.J., Goldstein D., Yang J.L. STAT3 inhibition, a novel approach to enhancing targeted therapy in human cancers (review). Int J Oncol 2012, 41:1181-1191.
397. Page B.D., Ball D.P., Gunning P.T. Signal transducer and activator of transcription 3 inhibitors: a patent review. Expert Opin Ther Patients 2011, 21:65-83.
398. Haftchenary S., Avadisian M., Gunning P.T. Inhibiting aberrant Stat3 function with molecular therapeutics: a progress report. Anti-cancer Drugs 2011, 22:115-127.
399. Sen M., Thomas S.M., Kim S., Yeh J.I., Ferris R.L., Johnson J.T., et al. First-in-human trial of a STAT3 decoy oligonucleotide in head and neck tumors: implications for cancer therapy. Cancer Discov 2012, 2:694-705.
400. Hayakawa F., Sugimoto K., Harada Y., Hashimoto N., Ohi N., Kurahashi S., et al. A novel STAT inhibitor, OPB-31121, has a significant antitumor effect on leukemia with STAT-addictive oncokinases. Blood Cancer J 2013, 3:e166.
401. Kim M.J., Nam H.J., Kim H.P., Han S.W., Im S.A., Kim T.Y., et al. OPB-31121, a novel small molecular inhibitor, disrupts the JAK2/STAT3 pathway and exhibits an antitumor activity in gastric cancer cells. Cancer Lett 2013, 335:145-152.
402. Takakura A., Nelson E.A., Haque N., Humphreys B.D., Zandi-Nejad K., Frank D.A., et al. Pyrimethamine inhibits adult polycystic kidney disease by modulating STAT signaling pathways. Hum Mol Genet 2011, 20:4143-4154.
403. Gupta S.C., Patchva S., Aggarwal B.B. Therapeutic roles of curcumin: lessons learned from clinical trials. AAPS J 2013, 15:195-218.
404. Huang T., Karsy M., Zhuge J., Zhong M., Liu D. B-Raf and the inhibitors: from bench to bedside. J Hematol Oncol 2013, 6:30.
405. Britten C.D. PI3K and MEK inhibitor combinations: examining the evidence in selected tumor types. Cancer Chemother Pharmacol 2013, 71:1395-1409.
406. Gatti L., Zunino F. Overview of tumor cell chemoresistance mechanisms. Methods Mol Med 2005, 111:127-148.
407. Zhou S., Ye W., Shao Q., Zhang M., Liang J. Nrf2 is a potential therapeutic target in radioresistance in human cancer. Crit Rev Oncol Hematol 2013, 88:706-715.
408. Ganan-Gomez I., Wei Y., Yang H., Boyano-Adanez M.C., Garcia-Manero G. Oncogenic functions of the transcription factor Nrf2. Free Rad Biol Med 2013, 65:750-764.
409. Wruck C.J., Streetz K., Pavic G., Gotz M.E., Tohidnezhad M., Brandenburg L.O., et al. Nrf2 induces interleukin-6 (IL-6) expression via an antioxidant response element within the IL-6 promoter. J Biol Chem 2011, 286:4493-4499.
410. Lo H.W., Cao X., Zhu H., Ali-Osman F. Constitutively activated STAT3 frequently coexpresses with epidermal growth factor receptor in high-grade gliomas and targeting STAT3 sensitizes them to Iressa and alkylators. Clin Cancer Res 2008, 14:6042-6054.
411. Real P.J., Sierra A., De Juan A., Segovia J.C., Lopez-Vega J.M., Fernandez-Luna J.L. Resistance to chemotherapy via Stat3-dependent overexpression of Bcl-2 in metastatic breast cancer cells. Oncogene 2002, 21:7611-7618.
412. Fox B.A., Schendel D.J., Butterfield L.H., Aamdal S., Allison J.P., Ascierto P.A., et al. Defining the critical hurdles in cancer immunotherapy. J Transl Med 2011, 9:214.
413. Wang T.H., Chan Y.H., Chen C.W., Kung W.H., Lee Y.S., Wang S.T., et al. Paclitaxel (Taxol) upregulates expression of functional interleukin-6 in human ovarian cancer cells through multiple signaling pathways. Oncogene 2006, 25:4857-4866.
414. Yu H., Kortylewski M., Pardoll D. Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nat Rev Immunol 2007, 7:41-51.
415. Greten F.R., Karin M. Peering into the aftermath: JAKi rips STAT3 in cancer. Nat Med 2010, 16:1085-1087.
416. Seavey M.M., Dobrzanski P. The many faces of Janus kinase. Biochem Pharmacol 2012, 83:1136-1145.
417. de Groot J., Liang J., Kong L.Y., Wei J., Piao Y., Fuller G., et al. Modulating antiangiogenic resistance by inhibiting the signal transducer and activator of transcription 3 pathway in glioblastoma. Oncotarget 2012, 3:1036-1048.
418. Bogani C., Bartalucci N., Martinelli S., Tozzi L., Guglielmelli P., Bosi A., et al. mTOR inhibitors alone and in combination with JAK2 inhibitors effectively inhibit cells of myeloproliferative neoplasms. PLoS ONE 2013, 8:e54826.
419. Grivennikov S.I., Karin M. Dangerous liaisons: STAT3 and NF-kappaB collaboration and crosstalk in cancer. Cytokine Growth Factor Rev 2010, 21:11-19.