Targeting the inflammatory pathways to enhance chemotherapy of cancer

Cancer Biology and Therapy

Volumn 12, Issue 2, 2011, Pages 95-105

  Zhu, Zhaowei ^a   Zhong, Shan ^a   Shen, Zhoujun ^a  

^a SHANGHAI JIAO TONG UNIVERSITY SCHOOL OF MEDICINE   (China)

Author keywords

Cancer; Chemokines; COX 2; Cytokines; HIF 1; Inflammation; NF B; STAT3; Therapy

Indexed keywords

2 METHOXYESTRADIOL; ACETYLSALICYLIC ACID; ANTINEOPLASTIC AGENT; BEVACIZUMAB; BORTEZOMIB; CARBOPLATIN; CURCUMIN; CYCLOPHOSPHAMIDE; CYTOKINE; DEGRASYN; DIHYDROARTEMISININ; DOCETAXEL; DOXORUBICIN; ETANERCEPT; GEMCITABINE; GINSENOSIDE RG 3; GLYCERYL TRINITRATE; INTERLEUKIN 6 ANTIBODY; IRINOTECAN; JP 1201; PACLITAXEL; PREDNISOLONE; RESVERATROL; RITUXIMAB; SD 1029; SILTUXIMAB; SORAFENIB; TAUROLIDINE; TIPIFARNIB; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ADJUVANT THERAPY; ANTINEOPLASTIC ACTIVITY; BREAST CANCER; CANCER CELL; CANCER CHEMOTHERAPY; CANCER INHIBITION; CANCER RESISTANCE; CANCER SURVIVAL; CARCINOGENESIS; CELL SURVIVAL; CHRONIC LYMPHATIC LEUKEMIA; COLON CARCINOGENESIS; COLORECTAL CANCER; CYTOTOXICITY; DRUG TARGETING; GENE ACTIVATION; GENE OVEREXPRESSION; HODGKIN DISEASE; HUMAN; INFLAMMATION; INFLAMMATORY CELL; KIDNEY CARCINOMA; LARGE CELL LYMPHOMA; LIVER METASTASIS; LUNG ADENOCARCINOMA; NONHODGKIN LYMPHOMA; NONHUMAN; PANCREAS CANCER; PROSTATE CANCER; REVIEW; TUMOR VASCULARIZATION;

ANTINEOPLASTIC AGENTS; CELL TRANSFORMATION, NEOPLASTIC; CHEMOKINES; CYCLOOXYGENASE 2; CYTOKINES; HUMANS; INFLAMMATION; NEOPLASMS; NF-KAPPA B; STAT3 TRANSCRIPTION FACTOR; TRANSCRIPTION FACTORS;

EID: 79960428358     PISSN: 15384047     EISSN: 15558576     Source Type: Journal    
DOI: 10.4161/cbt.12.2.15952     Document Type: Review

References (172)

1. Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet 2001; 357:539-45; PMID: 11229684; DOI: 10.1016/S0140-6736(00)04046-0.
2. Coussens LM, Werb Z. Inflammation and cancer. Nature 2002; 420:860-7; PMID: 12490959; DOI: 10.1038/nature01322.
3. Schottenfeld D, Beebe-Dimmer J. Chronic inflammation: a common and important factor in the pathogenesis of neoplasia. CA Cancer J Clin 2006; 56:69-83; PMID: 16514135.
4. Parkin DM. The global health burden of infection-associated cancers in the year 2002. Int J Cancer 2006; 118:3030-44; PMID: 16404738; DOI: 10.1002/ijc.21731.
5. Ferrero-Miliani L, Nielsen OH, Andersen PS, Girardin SE. Chronic inflammation: importance of NOD2 and NALP3 in interleukin-1beta generation. Clin Exp Immunol 2007; 147:227-35; PMID: 17223962; DOI: 10.1111/j.1365-2249.2006. 03261.x.
6. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation and cancer. Cell 2010; 140:883-99; PMID: 20303878; DOI: 10.1016/j.cell.2010.01.025.
7. Aggarwal BB, Gehlot P. Inflammation and cancer: how friendly is the relationship for cancer patients? Curr Opin Pharmacol 2009; 9:351-69; PMID: 19665429; DOI: 10.1016/j.coph.2009.06.020.
8. Porta C, Larghi P, Rimoldi M, Totaro MG, Allavena P, Mantovani A, et al. Cellular and molecular pathways linking inflammation and cancer. Immunobiology 2009; 214:761-77; PMID: 19616341; DOI: 10.1016/j.imbio.2009.06.014.
9. Borrello MG, Alberti L, Fischer A, Degl'innocenti D, Ferrario C, Gariboldi M, et al. Induction of a pro-inflammatory program in normal human thyrocytes by the RET/PTC1 oncogene. Proc Natl Acad Sci USA 2005; 102:14825-30; PMID: 16203990; DOI: 10.1073/pnas.0503039102.
10. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature 2008; 454:436-44; PMID: 18650914; DOI: 10.1038/nature07205.
11. Mantovani A. Cancer: Inflaming metastasis. Nature 2009; 457:36-7; PMID: 19122629; DOI: 10.1038/457036b.
12. Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis 2009; 30:1073-81; PMID: 19468060; DOI: 10.1093/carcin/bgp127.
13. Tan A, Yeh SH, Liu CJ, Cheung C, Chen PJ. Viral hepatocarcinogenesis: from infection to cancer. Liver Int 2008; 28:175-88; PMID: 18251977; DOI: 10.1111/j.1478-3231.2007.01652.x.
14. Koong AC, Chen EY, Giaccia AJ. Hypoxia causes the activation of nuclear factor kappaB through the phosphorylation of IkappaBalpha on tyrosine residues. Cancer Res 1994; 54:1425-30; PMID: 8137243.
15. Aggarwal BB, Vijayalekshmi RV, Sung B. Targeting inflammatory pathways for prevention and therapy of cancer: short-term friend, long-term foe. Clin Cancer Res 2009; 15:425-30; PMID: 19147746; DOI: 10.1158/1078-0432.CCR-08-0149.
16. Vilimas T, Mascarenhas J, Palomero T, Mandal M, Buonamici S, Meng F, et al. Targeting the NFkappaB signaling pathway in Notch1-induced T-cell leukemia. Nat Med 2007; 13:70-7; PMID: 17173050; DOI: 10.1038/nm1524.
17. Grivennikov S, Karin E, Terzic J, Mucida D, Yu GY, 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; 15:103-13; PMID: 19185845; DOI: 10.1016/j.ccr.2009.01.001.
18. Du Q, Zhang X, Cardinal J, Cao Z, Guo Z, Shao L, et al. Wnt/beta-catenin signaling regulates cytokine-induced human inducible nitric oxide synthase expression by inhibiting nuclear factor-kappaB activation in cancer cells. Cancer Res 2009; 69:3764-71; PMID: 19383900; DOI: 10.1158/0008-5472.CAN-09-0014.
19. Garlanda C, Riva F, Veliz T, Polentarutti N, Pasqualini F, Radaelli E, et al. Increased susceptibility to colitis-associated cancer of mice lacking TIR8, an inhibitory member of the interleukin-1 receptor family. Cancer Res 2007; 67:6017-21; PMID: 17616656; DOI: 10.1158/0008-5472.CAN-07-0560.
20. Xiao H, Gulen MF, Qin J, Yao J, Bulek K, Kish D, et al. The Toll-interleukin-1 receptor member SIGIRR regulates colonic epithelial homeostasis, inflammation and tumorigenesis. Immunity 2007; 26:461-75; PMID: 17398123; DOI: 10.1016/j.immuni.2007.02.012.
21. Kim DW, Sovak MA, Zanieski G, Nonet G, Romieu-Mourez R, Lau AW, et al. Activation of NFkappaB/Rel occurs early during neoplastic transformation of mammary cells. Carcinogenesis 2000; 21:871-9; PMID: 10783306.
22. Hewamana S, Lin TT, Rowntree C, Karunanithi K, Pratt G, Hills R, et al. Rel a is an independent biomarker of clinical outcome in chronic lympho-cytic leukemia. J Clin Oncol 2009; 27:763-9; PMID: 19124804; DOI: 10.1200/JCO.2008.19. 1114.
23. Keats JJ, Fonseca R, Chesi M, Schop R, Baker A, Chng WJ, et al. Promiscuous mutations activate the non-canonical NFkappaB pathway in multiple myeloma. Cancer Cell 2007; 12:131-44; PMID: 17692805; DOI: 10.1016/j.ccr.2007. 07.003.
24. Zhang PL, Pellitteri PK, Law A, Gilroy PA, Wood GC, Kennedy TL, et al. Overexpression of phosphorylated nuclear factor-kappaB in tonsillar squamous cell carcinoma and high-grade dysplasia is associated with poor prognosis. Mod Pathol 2005; 18:924-32; PMID: 15920558; DOI: 10.1038/modpathol.3800372.
25. Wu L, Pu Z, Feng J, Li G, Zheng Z, Shen W. The ubiquitin-proteasome pathway and enhanced activity of NFkappaB in gastric carcinoma. J Surg Oncol 2008; 97:439-44; PMID: 18163448; DOI: 10.1002/jso.20952.
26. Izzo JG, Malhotra U, Wu TT, Ensor J, Luthra R, Lee JH, et al. Association of activated transcription factor nuclear factor kappab with chemoradiation resistance and poor outcome in esophageal carcinoma. J Clin Oncol 2006; 24:748-54; PMID: 16401681; DOI: 10.1200/JCO.2005.03.8810.
27. Weichert W, Boehm M, Gekeler V, Bahra M, Langrehr J, Neuhaus P, et al. High expression of RelA/p65 is associated with activation of nuclear factor-kappaB-dependent signaling in pancreatic cancer and marks a patient population with poor prognosis. Br J Cancer 2007; 97:523-30; PMID: 17622249; DOI: 10.1038/sj.bjc.6603878.
28. O'Neil BH, Buzkova P, Farrah H, Kashatus D, Sanoff H, Goldberg RM, et al. Expression of nuclear factor-kappaB family proteins in hepatocellular carcinomas. Oncology 2007; 72:97-104; PMID: 18025803; DOI: 10.1159/111116.
29. Voboril R, Voborilova J, Rychterova V, Jirasek T, Dvorak J. Dissociated invasively growing cancer cells with NFkappaB/p65 positivity after radiotherapy: a new marker for worse clinical outcome in rectal cancer? Preliminary data. Clin Exp Metastasis 2008; 25:491-6; PMID: 18324356; DOI: 10.1007/s10585-008- 9155-5.
30. Biswas DK, Shi Q, Baily S, Strickland I, Ghosh S, Pardee AB, et al. NFkappaB activation in human breast cancer specimens and its role in cell proliferation and apoptosis. Proc Natl Acad Sci USA 2004; 101:10137-42; PMID: 15220474; DOI: 10.1073/pnas.0403621101.
31. Guo RX, Qiao YH, Zhou Y, Li LX, Shi HR, Chen KS. Increased staining for phosphorylated AKT and nuclear factor-kappaB p65 and their relationship with prognosis in epithelial ovarian cancer. Pathol Int 2008; 58:749-56; PMID: 19067848; DOI: 10.1111/j.1440-827.2008.02306.x.
32. Tang X, Liu D, Shishodia S, Ozburn N, Behrens C, Lee JJ, et al. Nuclear factor-kappaB (NFkappaB) is frequently expressed in lung cancer and preneoplastic lesions. Cancer 2006; 107:2637-46; PMID: 17078054; DOI: 10.1002/cncr.22315.
33. Kashani-Sabet M, Shaikh L, Miller JR, 3rd, Nosrati M, Ferreira CM, Debs RJ, et al. NFkappaB in the vascular progression of melanoma. J Clin Oncol 2004; 22:617-23; PMID: 14966085; DOI: 10.1200/JCO.2004.06.047.
34. Meteoglu I, Erdogdu IH, Meydan N, Erkus M, Barutca S. NFKappaB expression correlates with apoptosis and angiogenesis in clear cell renal cell carcinoma tissues. J Exp Clin Cancer Res 2008; 27:53; PMID: 18928570; DOI: 10.1186/1756-9966-27-53.
35. Lessard L, Begin LR, Gleave ME, Mes-Masson AM, Saad F. Nuclear localisation of nuclear factor-kappaB transcription factors in prostate cancer: an immunohistochemical study. Br J Cancer 2005; 93:1019-23; PMID: 16205698; DOI: 10.1038/sj.bjc.6602796.
36. Levidou G, Saetta AA, Korkolopoulou P, Papanastasiou P, Gioti K, Pavlopoulos P, et al. Clinical significance of nuclear factor (NF)kappaB levels in urothelial carcinoma of the urinary bladder. Virchows Arch 2008; 452:295-304; PMID: 18188593; DOI: 10.1007/s00428-007-0560-y.
37. Kopp E, Ghosh S. Inhibition of NFkappaB by sodium salicylate and aspirin. Science 1994; 265:956-9; PMID: 8052854.
38. Bharti AC, Donato N, Singh S, Aggarwal BB. Curcumin (diferuloylmethane) downregulates the constitutive activation of nuclear factor-kappaB and IkappaBalpha kinase in human multiple myeloma cells, leading to suppression of proliferation and induction of apoptosis. Blood 2003; 101:1053-62; PMID: 12393461; DOI: 10.1182/blood-2002-05-1320.
39. Holmes-McNary M, Baldwin AS Jr. Chemopreventive properties of trans-resveratrol are associated with inhibition of activation of the IkappaB kinase. Cancer Res 2000; 60:3477-83; PMID: 10910059.
40. Karin M. Nuclear factor-kappaB in cancer development and progression. Nature 2006; 441:431-6; PMID: 16724054; DOI: 10.1038/nature04870.
41. Karin M. The IkappaB kinase - a bridge between inflammation and cancer. Cell Res 2008; 18:334-42; PMID: 18301380; DOI: 10.1038/cr.2008.30.
42. Grivennikov SI, Karin M. Inflammation and oncogenesis: a vicious connection. Curr Opin Genet Dev 2010; 20:65-71; PMID: 20036794; DOI: 10.1016/j.gde.2009.11.004.
43. Grivennikov SI, Karin M. Dangerous liaisons: STAT3 and NFkappaB collaboration and crosstalk in cancer. Cytokine Growth Factor Rev 2010; 21:11-9; PMID: 20018552; DOI: 10.1016/j.cytogfr.2009.11.005.
44. Ismail HA, Lessard L, Mes-Masson AM, Saad F. Expression of NFkappaB in prostate cancer lymph node metastases. Prostate 2004; 58:308-13; PMID: 14743471; DOI: 10.1002/pros.10335.
45. Izzo JG, Malhotra U, Wu TT, Luthra R, Correa AM, Swisher SG, et al. Clinical biology of esophageal adenocarcinoma after surgery is influenced by nuclear factor-kappaB expression. Cancer Epidemiol Biomarkers Prev 2007; 16:1200-5; PMID: 17548685; DOI: 10.1158/1055-9965.EPI-06-1083.
46. Greten FR, Eckmann L, Greten TF, Park JM, Li ZW, Egan LJ, et al. IKKbeta links inflammation and tumori-genesis in a mouse model of colitis-associated cancer. Cell 2004; 118:285-96; PMID: 15294155; DOI: 10.1016/j.cell.2004.07.013.
47. Maeda S, Kamata H, Luo JL, Leffert H, Karin M. IKKbeta couples hepatocyte death to cytokine-driven compensatory proliferation that promotes chemical hepatocarcinogenesis. Cell 2005; 121:977-90; PMID: 15989949; DOI: 10.1016/j.cell.2005.04.014.
48. Pikarsky E, Porat RM, Stein I, Abramovitch R, Amit S, Kasem S, et al. NFkappaB functions as a tumour promoter in inflammation-associated cancer. Nature 2004; 431:461-6; PMID: 15329734; DOI: 10.1038/nature02924.
49. Garg AK, Hortobagyi GN, Aggarwal BB, Sahin AA, Buchholz TA. Nuclear factor-kappaB as a predictor of treatment response in breast cancer. Curr Opin Oncol 2003; 15:405-11; PMID: 14624221.
50. Azuma H, Tomita N, Sakamoto T, Kiyama S, Inamoto T, Takahara K, et al. Marked regression of liver metastasis by combined therapy of ultrasound-mediated NFkappaB-decoy transfer and transportal injection of paclitaxel, in mouse. Int J Cancer 2008; 122:1645-56; PMID: 18058816; DOI: 10.1002/ijc.23280.
51. Harikumar KB, Kunnumakkara AB, Sethi G, Diagaradjane P, Anand P, Pandey MK, et al. Resveratrol, a multitargeted agent, can enhance antitumor activity of gemcitabine in vitro and in orthotopic mouse model of human pancreatic cancer. Int J Cancer 2010; 127:257-68; PMID: 19908231; DOI: 10.1002/ijc.25041.
52. Kim SM, Lee SY, Cho JS, Son SM, Choi SS, Yun YP, et al. Combination of ginsenoside Rg3 with docetaxel enhances the susceptibility of prostate cancer cells via inhibition of NFkappaB. Eur J Pharmacol 2010; 631:1-9; PMID: 20056115; DOI: 10.1016/j.ejphar.2009.12.018.
53. Li Y, Xing D, Chen Q, Chen WR. Enhancement of chemotherapeutic agent-induced apoptosis by inhibition of NFkappaB using ursolic acid. Int J Cancer 2010; 127:462-73; PMID: 19908232; DOI: 10.1002/ijc.25044.
54. Wang SJ, Gao Y, Chen H, Kong R, Jiang HC, Pan SH, et al. Dihydroartemisinin inactivates NFkappaB and potentiates the anti-tumor effect of gemcitabine on pancreatic cancer both in vitro and in vivo. Cancer Lett 2010; 293:99-108; PMID: 20137856; DOI: 10.1016/j.canlet.2010.01.001.
55. 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; PMID: 17186030; DOI: 10.1038/nri1995.
56. Bromberg J, Wang TC. Inflammation and cancer: IL-6 and STAT3 complete the link. Cancer Cell 2009; 15:79-80; PMID: 19185839; DOI: 10.1016/j.ccr.2009.01. 009.
57. Wang L, Yi T, Kortylewski M, Pardoll DM, Zeng D, Yu H. IL-17 can promote tumor growth through an IL-6-Stat3 signaling pathway. J Exp Med 2009; 206:1457-64; PMID: 19564351; DOI: 10.1084/jem.20090207.
58. Pickert G, Neufert C, Leppkes M, Zheng Y, Wittkopf N, Warntjen M, et al. STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing. J Exp Med 2009; 206:1465-72; PMID: 19564350; DOI: 10.1084/jem.20082683.
59. Haura EB, Turkson J, Jove R. Mechanisms of disease: Insights into the emerging role of signal transducers and activators of transcription in cancer. Nat Clin Pract Oncol 2005; 2:315-24; PMID: 16264989; DOI: 10.1038/ncponc0195.
60. Aggarwal BB, Kunnumakkara AB, Harikumar KB, Gupta SR, Tharakan ST, Koca C, et al. Signal transducer and activator of transcription-3, inflammation and cancer: how intimate is the relationship? Ann NY Acad Sci 2009; 1171:59-76; PMID: 19723038; DOI: 10.1111/j.1749-6632.2009.04911.x.
61. Kortylewski M, Kujawski M, Wang T, Wei S, Zhang S, Pilon-Thomas S, et al. Inhibiting Stat3 signaling in the hematopoietic system elicits multicomponent anti-tumor immunity. Nat Med 2005; 11:1314-21; PMID: 16288283; DOI: 10.1038/nm1325.
62. Wang T, Niu G, Kortylewski M, Burdelya L, Shain K, Zhang S, et al. Regulation of the innate and adaptive immune responses by Stat-3 signaling in tumor cells. Nat Med 2004; 10:48-54; PMID: 14702634; DOI: 10.1038/nm976.
63. Lee H, Herrmann A, Deng JH, Kujawski M, Niu G, Li Z, et al. Persistently activated Stat3 maintains constitutive NFkappaB activity in tumors. Cancer Cell 2009; 15:283-93; PMID: 19345327; DOI: 10.1016/j.ccr.2009.02.015.
64. + cells derived from multiple myeloma patients and suppression of these transcription factors leads to apoptosis. Blood 2004; 103:3175-84; PMID: 15070700; DOI: 10.1182/blood-2003-06-2151.
65. Kanda N, Seno H, Konda Y, Marusawa H, Kanai M, Nakajima T, et al. STAT3 is constitutively activated and supports cell survival in association with survivin expression in gastric cancer cells. Oncogene 2004; 23:4921-9; PMID: 15077160; DOI: 10.1038/sj.onc.1207606.
66. Benekli M, Xia Z, Donohue KA, Ford LA, Pixley LA, Baer MR, et al. Constitutive activity of signal transducer and activator of transcription 3 protein in acute myeloid leukemia blasts is associated with short disease-free survival. Blood 2002; 99:252-7; PMID: 11756179.
67. Gao SP, Mark KG, Leslie K, Pao W, Motoi N, Gerald WL, et al. Mutations in the EGFR kinase domain mediate STAT3 activation via IL-6 production in human lung adenocarcinomas. J Clin Invest 2007; 117:3846-56; PMID: 18060032; DOI: 10.1172/JCI31871.
68. Grivennikov S, Karin M. Autocrine IL-6 signaling: a key event in tumorigenesis? Cancer Cell 2008; 13:7-9; PMID: 18167335; DOI: 10.1016/j.ccr.2007.12.020.
69. Bollrath J, Phesse TJ, von Burstin VA, 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; PMID: 19185844; DOI: 10.1016/j.ccr.2009.01.002.
70. Chan KS, Sano S, Kiguchi K, Anders J, Komazawa N, Takeda J, et al. Disruption of Stat3 reveals a critical role in both the initiation and the promotion stages of epithelial carcinogenesis. J Clin Invest 2004; 114:720-8; PMID: 15343391; DOI: 10.1172/JCI21032.
71. Haura EB, Zheng Z, Song L, Cantor A, Bepler G. Activated epidermal growth factor receptor-Stat-3 signaling promotes tumor survival in vivo in non-small cell lung cancer. Clin Cancer Res 2005; 11:8288-94; PMID: 16322287; DOI: 10.1158/1078-0432.CCR-05-0827.
72. Real PJ, Sierra A, De Juan A, Segovia JC, Lopez-Vega JM, Fernandez-Luna JL. Resistance to chemotherapy via Stat3-dependent overexpression of Bcl-2 in metastatic breast cancer cells. Oncogene 2002; 21:7611-8; PMID: 12400004; DOI: 10.1038/sj.onc.1206004.
73. Bhardwaj A, Sethi G, Vadhan-Raj S, Bueso-Ramos C, Takada Y, Gaur U, et al. Resveratrol inhibits proliferation, induces apoptosis and overcomes chemoresistance through downregulation of STAT3 and nuclear factor-kappaB- regulated antiapoptotic and cell survival gene products in human multiple myeloma cells. Blood 2007; 109:2293-302; PMID: 17164350; DOI: 10.1182/blood-2006-02-003988.
74. Costantino L, Barlocco D. STAT 3 as a target for cancer drug discovery. Curr Med Chem 2008; 15:834-43; PMID: 18473793.
75. Heimberger AB, Priebe W. Small molecular inhibitors of p-STAT3: novel agents for treatment of primary and metastatic CNS cancers. Recent Pat CNS Drug Discov 2008; 3:179-88; PMID: 18991807.
76. Alas S, Bonavida B. Inhibition of constitutive STAT3 activity sensitizes resistant non-Hodgkin's lymphoma and multiple myeloma to chemotherapeutic drug-mediated apoptosis. Clin Cancer Res 2003; 9:316-26; PMID: 12538484.
77. Chen KF, Tai WT, Liu TH, Huang HP, Lin YC, Shiau CW, et al. Sorafenib overcomes TRAIL resistance of hepatocellular carcinoma cells through the inhibition of STAT3. Clin Cancer Res 2010; 16:5189-99; PMID: 20884624; DOI: 10.1158/1078-0432.CCR-09-3389.
78. Sparano JA, Moulder S, Kazi A, Coppola D, Negassa A, Vahdat L, et al. Phase II trial of tipifarnib plus neo-adjuvant doxorubicin-cyclophosphamide in patients with clinical stage IIB-IIIC breast cancer. Clin Cancer Res 2009; 15:2942-8; PMID: 19351752; DOI: 10.1158/1078-0432.CCR-08-2658.
79. Pham LV, Tamayo AT, Li C, Bornmann W, Priebe W, Ford RJ. Degrasyn potentiates the antitumor effects of bortezomib in mantle cell lymphoma cells in vitro and in vivo: therapeutic implications. Mol Cancer Ther 2010; 9:2026-36; PMID: 20606045; DOI: 10.1158/1535-7163.MCT-10-0238.
80. Li J, Favata M, Kelley JA, Caulder E, Thomas B, Wen X, et al. INCB16562, a JAK1/2 selective inhibitor, is efficacious against multiple myeloma cells and reverses the protective effects of cytokine and stromal cell support. Neoplasia 2010; 12:28-38; PMID: 20072651.
81. Jing N, Zhu Q, Yuan P, Li Y, Mao L, Tweardy DJ. Targeting signal transducer and activator of transcription 3 with G-quartet oligonucleotides: a potential novel therapy for head and neck cancer. Mol Cancer Ther 2006; 5:279-86; PMID: 16505101; DOI: 10.1158/1535-7163.MCT-05-0302.
82. Yang C, Schwab JH, Schoenfeld AJ, Hornicek FJ, Wood KB, Nielsen GP, et al. A novel target for treatment of chordoma: signal transducers and activators of transcription 3. Mol Cancer Ther 2009; 8:2597-605; PMID: 19723879; DOI: 10.1158/1535-7163.MCT-09-0504.
83. Ramachandran C, Resek AP, Escalon E, Aviram A, Melnick SJ. Potentiation of gemcitabine by Turmeric Force in pancreatic cancer cell lines. Oncol Rep 2010; 23:1529-35; PMID: 20428806.
84. Kaufman B, Scharf O, Arbeit J, Ashcroft M, Brown JM, Bruick RK, et al. Proceedings of the Oxygen Homeostasis/Hypoxia Meeting. Cancer Res 2004; 64:3350-6; PMID: 15126380.
85. Rius J, Guma M, Schachtrup C, Akassoglou K, Zinkernagel AS, Nizet V, et al. NFkappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha. Nature 2008; 453:807-11; PMID: 18432192; DOI: 10.1038/nature06905.
86. Mariani F, Sena P, Marzona L, Riccio M, Fano R, Manni P, et al. Cyclooxygenase-2 and Hypoxia-Inducible Factor-1alpha protein expression is related to inflammation and upregulated since the early steps of colorectal carcinogenesis. Cancer Lett 2009; 279:221-9; PMID: 19268443; DOI: 10.1016/j.canlet. 2009.02.001.
87. Yeo EJ, Chun YS, Cho YS, Kim J, Lee JC, Kim MS, et al. YC-1: a potential anticancer drug targeting hypoxia-inducible factor 1. J Natl Cancer Inst 2003; 95:516-25; PMID: 12671019.
88. Stoeltzing O, McCarty MF, Wey JS, Fan F, Liu W, Belcheva A, et al. Role of hypoxia-inducible factor 1alpha in gastric cancer cell growth, angiogenesis and vessel maturation. J Natl Cancer Inst 2004; 96:946-56; PMID: 15199114.
89. Rohwer N, Lobitz S, Daskalow K, Jons T, Vieth M, Schlag PM, et al. HIF-1alpha determines the metastatic potential of gastric cancer cells. Br J Cancer 2009; 100:772-81; PMID: 19223895; DOI: 10.1038/sj.bjc.6604919.
90. Ravizza R, Molteni R, Gariboldi MB, Marras E, Perletti G, Monti E. Effect of HIF-1 modulation on the response of two- and three-dimensional cultures of human colon cancer cells to 5-fluorouracil. Eur J Cancer 2009; 45:890-8; PMID: 19171477; DOI: 10.1016/j.ejca.2008.12.021.
91. Huang L, Ao Q, Zhang Q, Yang X, Xing H, Li F, et al. Hypoxia induced paclitaxel resistance in human ovarian cancers via hypoxia-inducible factor 1alpha. J Cancer Res Clin Oncol 2010; 136:447-56; PMID: 19760195; DOI: 10.1007/s00432-009-0675-4.
92. Yasuda H, Nakayama K, Watanabe M, Suzuki S, Fuji H, Okinaga S, et al. Nitroglycerin treatment may enhance chemosensitivity to docetaxel and carboplatin in patients with lung adenocarcinoma. Clin Cancer Res 2006; 12:6748-57; PMID: 17121895; DOI: 10.1158/1078-0432.CCR-06-1124.
93. Nakai H, Watanabe Y, Ueda H, Hoshiai H. Hypoxia inducible factor-1alpha expression as a factor predictive of efficacy of taxane/platinum chemotherapy in advanced primary epithelial ovarian cancer. Cancer Lett 2007; 251:164-7; PMID: 17215078; DOI: 10.1016/j.canlet.2006.11.017.
94. Wang Y, Saad M, Pakunlu RI, Khandare JJ, Garbuzenko OB, Vetcher AA, et al. Nonviral nanoscale-based delivery of antisense oligonucleotides targeted to hypoxiainducible factor 1alpha enhances the efficacy of chemotherapy in drug-resistant tumor. Clin Cancer Res 2008; 14:3607-16; PMID: 18519795; DOI: 10.1158/1078-0432.CCR-07-2020.
95. Verheul HM, Salumbides B, Van Erp K, Hammers H, Qian DZ, Sanni T, et al. Combination strategy targeting the hypoxia inducible factor-1alpha with mammalian target of rapamycin and histone deacetylase inhibitors. Clin Cancer Res 2008; 14:3589-97; PMID: 18519793; DOI: 10.1158/1078-0432.CCR-07-4306.
96. Rapisarda A, Hollingshead M, Uranchimeg B, Bonomi CA, Borgel SD, Carter JP, et al. Increased antitumor activity of bevacizumab in combination with hypoxia inducible factor-1 inhibition. Mol Cancer Ther 2009; 8:1867-77; PMID: 19584228; DOI: 10.1158/1535-7163.MCT-09-0274.
97. Chintala S, Toth K, Cao S, Durrani FA, Vaughan MM, Jensen RL, et al. Se-methylselenocysteine sensitizes hypoxic tumor cells to irinotecan by targeting hypoxia-inducible factor 1alpha. Cancer Chemother Pharmacol 2010; 66:899-911; PMID: 20066420; DOI: 10.1007/s00280-009-1238-8.
98. Balkwill F, Osborne R, Burke F, Naylor S, Talbot D, Durbin H, et al. Evidence for tumour necrosis factor/ cachectin production in cancer. Lancet 1987; 2:1229-32; PMID: 2890853.
99. Moore RJ, Owens DM, Stamp G, Arnott C, Burke F, East N, et al. Mice deficient in tumor necrosis factor-alpha are resistant to skin carcinogenesis. Nat Med 1999; 5:828-31; PMID: 10395330; DOI: 10.1038/10552.
100. Ferrajoli A, Keating MJ, Manshouri T, Giles FJ, Dey A, Estrov Z, et al. The clinical significance of tumor necrosis factor-alpha plasma level in patients having chronic lymphocytic leukemia. Blood 2002; 100:1215- 9; PMID: 12149200.
101. Pollard JW. Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer 2004; 4:71-8; PMID: 14708027; DOI: 10.1038/nrc1256.
102. Kulbe H, Thompson R, Wilson JL, Robinson S, Hagemann T, Fatah R, et al. The inflammatory cytokine tumor necrosis factor-alpha generates an autocrine tumor-promoting network in epithelial ovarian cancer cells. Cancer Res 2007; 67:585-92; PMID: 17234767; DOI: 10.1158/0008-5472.CAN-06-2941.
103. Mocellin S, Nitti D. TNF and cancer: the two sides of the coin. Front Biosci 2008; 13:2774-83; PMID: 17981752.
104. Danforth KN, Rodriguez C, Hayes RB, Sakoda LC, Huang WY, Yu K, et al. TNF polymorphisms and prostate cancer risk. Prostate 2008; 68:400-7; PMID: 18196539; DOI: 10.1002/pros.20694.
105. Garrity-Park MM, Loftus EV Jr, Bryant SC, Sandborn WJ, Smyrk TC. Tumor necrosis factor-alpha polymorphisms in ulcerative colitis-associated colorectal cancer. Am J Gastroenterol 2008; 103:407-15; PMID: 18289203; DOI: 10.1111/j.1572-0241.2007.01572.x.
106. Zhang J, Dou C, Song Y, Ji C, Gu S, Xie Y, et al. Polymorphisms of tumor necrosis factor-alpha are associated with increased susceptibility to gastric cancer: a meta-analysis. J Hum Genet 2008; 53:479-89; PMID: 18350251; DOI: 10.1007/s10038-008-0273-3.
107. Szlosarek PW, Balkwill FR. Tumour necrosis factoralpha: a potential target for the therapy of solid tumours. Lancet Oncol 2003; 4:565-73; PMID: 12965278.
108. Popivanova BK, Kitamura K, Wu Y, Kondo T, Kagaya T, Kaneko S, et al. Blocking TNFalpha in mice reduces colorectal carcinogenesis associated with chronic colitis. J Clin Invest 2008; 118:560-70; PMID: 18219394; DOI: 10.1172/JCI32453.
109. Woyach JA, Lin TS, Lucas MS, Heerema N, Moran ME, Cheney C, et al. A phase I/II study of rituximab and etanercept in patients with chronic lymphocytic leukemia and small lymphocytic lymphoma. Leukemia 2009; 23:912-8; PMID: 19225537; DOI: 10.1038/leu.2008.385.
110. Dineen SP, Roland CL, Greer R, Carbon JG, Toombs JE, Gupta P, et al. Smac mimetic increases chemotherapy response and improves survival in mice with pancreatic cancer. Cancer Res 2010; 70:2852-61; PMID: 20332237; DOI: 10.1158/0008-5472.CAN-09-3892.
111. Williams GM. Antitumor necrosis factor-alpha therapy and potential cancer inhibition. Eur J Cancer Prev 2008; 17:169-77; PMID: 18287875; DOI: 10.1097/CEJ.0b013e3282b6fcff.
112. Giavazzi R, Garofalo A, Bani MR, Abbate M, Ghezzi P, Boraschi D, et al. Interleukin 1-induced augmentation of experimental metastases from a human melanoma in nude mice. Cancer Res 1990; 50:4771-5; PMID: 2196116.
113. Tu S, Bhagat G, Cui G, Takaishi S, Kurt-Jones EA, Rickman B, et al. Overexpression of interleukin-1beta induces gastric inflammation and cancer and mobilizes myeloid-derived suppressor cells in mice. Cancer Cell 2008; 14:408-19; PMID: 18977329; DOI: 10.1016/j.ccr.2008.10.011.
114. Deans DA, Wigmore SJ, Gilmour H, Paterson-Brown S, Ross JA, Fearon KC. Elevated tumour interleukin-1beta is associated with systemic inflammation: A marker of reduced survival in gastro-oesophageal cancer. Br J Cancer 2006; 95:1568-75; PMID: 17088911; DOI: 10.1038/sj.bjc.6603446.
115. Krelin Y, Voronov E, Dotan S, Elkabets M, Reich E, Fogel M, et al. Interleukin-1beta-driven inflammation promotes the development and invasiveness of chemical carcinogen-induced tumors. Cancer Res 2007; 67:1062-71; PMID: 17283139; DOI: 10.1158/0008-5472.CAN-06-2956.
116. Sakurai T, He G, Matsuzawa A, Yu GY, Maeda S, Hardiman G, et al. Hepatocyte necrosis induced by oxidative stress and IL-1alpha release mediate carcinogen-induced compensatory proliferation and liver tumorigenesis. Cancer Cell 2008; 14:156-65; PMID: 18691550; DOI: 10.1016/j.ccr.2008.06.016.
117. Villani F, Busia A, Villani M, Vismara C, Viviani S, Bonfante V. Serum cytokine in response to chemo-radiotherapy for Hodgkin's disease. Tumori 2008; 94:803-8; PMID: 19267096; DOI: (Unknown).
118. Ghiringhelli F, Apetoh L, Tesniere A, Aymeric L, Ma Y, Ortiz C, et al. Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors. Nat Med 2009; 15:1170-8; PMID: 19767732; DOI: 10.1038/nm.2028.
119. Braumann C, Gutt CN, Scheele J, Menenakos C, Willems W, Mueller JM, et al. Taurolidine reduces the tumor stimulating cytokine interleukin-1beta in patients with resectable gastrointestinal cancer: a multicentre prospective randomized trial. World J Surg Oncol 2009; 7:32; PMID: 19309495; DOI: 10.1186/1477-7819-7-32.
120. Voronov E, Shouval DS, Krelin Y, Cagnano E, Benharroch D, Iwakura Y, et al. IL-1 is required for tumor invasiveness and angiogenesis. Proc Natl Acad Sci USA 2003; 100:2645-50; PMID: 12598651; DOI: 10.1073/pnas.0437939100.
121. Triozzi PL, Aldrich W. Effects of interleukin-1 receptor antagonist and chemotherapy on host-tumor interactions in established melanoma. Anticancer Res 2010; 30:345-54; PMID: 20332438.
122. Dinarello CA. The paradox of pro-inflammatory cytokines in cancer. Cancer Metastasis Rev 2006; 25:307-13; PMID: 17029030; DOI: 10.1007/s10555-006-9000-8.
123. Hong DS, Angelo LS, Kurzrock R. Interleukin-6 and its receptor in cancer: implications for translational therapeutics. Cancer 2007; 110:1911-28; PMID: 17849470; DOI: 10.1002/cncr.22999.
124. Ancrile B, Lim KH, Counter CM. Oncogenic Ras-induced secretion of IL6 is required for tumorigenesis. Genes Dev 2007; 21:1714-9; PMID: 17639077; DOI: 10.1101/gad.1549407.
125. Sharma R, Zucknick M, London R, Kacevska M, Liddle C, Clarke SJ. Systemic inflammatory response predicts prognosis in patients with advanced-stage colorectal cancer. Clin Colorectal Cancer 2008; 7:331-7; PMID: 18794066; DOI: 10.3816/CCC.2008.n.044.
126. Smith PC, Keller ET. Anti-interleukin-6 monoclonal antibody induces regression of human prostate cancer xenografts in nude mice. Prostate 2001; 48:47-53; PMID: 11391686; DOI: 10.1002/pros.1080.
127. Dorff TB, Goldman B, Pinski JK, Mack PC, Lara PN Jr, Van Veldhuizen PJ Jr, 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. Clin Cancer Res 2010; 16:3028-34; PMID: 20484019; DOI: 10.1158/1078-0432.CCR-09- 3122.
128. Rossi JF, Negrier S, James ND, Kocak I, Hawkins R, Davis H, et al. A phase I/II study of siltuximab (CNTO 328), an anti-interleukin-6 monoclonal antibody, in metastatic renal cell cancer. Br J Cancer 2010; 103:1154-62; PMID: 20808314; DOI: 10.1038/sj.bjc.6605872.
129. Matsuda M, Salazar F, Petersson M, Masucci G, Hansson J, Pisa P, et al. Interleukin 10 pretreatment protects target cells from tumor- and allo-specific cytotoxic T cells and downregulates HLA class I expression. J Exp Med 1994; 180:2371-6; PMID: 7964510.
130. Dummer W, Bastian BC, Ernst N, Schanzle C, Schwaaf A, Brocker EB. Interleukin-10 production in malignant melanoma: preferential detection of IL-10- secreting tumor cells in metastatic lesions. Int J Cancer 1996; 66:607-10; PMID: 8647620; DOI: 10.1002/(SICI)1097-0215(19960529)66:5〈607:: AIDIJC4〉 3.0.CO;2-X.
131. Salazar-Onfray F, Lopez MN, Mendoza-Naranjo A. Paradoxical effects of cytokines in tumor immune surveillance and tumor immune escape. Cytokine Growth Factor Rev 2007; 18:171-82; PMID: 17329145; DOI: 10.1016/j.cytogfr.2007.01.015.
132. Vairaktaris E, Yapijakis C, Serefoglou Z, Derka S, Vassiliou S, Nkenke E, et al. The interleukin-10 (-1082A/G) polymorphism is strongly associated with increased risk for oral squamous cell carcinoma. Anticancer Res 2008; 28:309-14; PMID: 18383862.
133. Schauer MC, Holzmann B, Peiper M, Friess H, Knoefel WT, Theisen J. Interleukin-10 and -12 predict chemotherapy-associated toxicity in esophageal adeno-carcinoma. J Thorac Oncol 2010; 5:1849-54; PMID: 20881642; DOI: 10.1097/JTO.0b013e3181f19028.
134. Park YH, Sohn SK, Kim JG, Lee MH, Song HS, Kim MK, et al. Interaction between BCL2 and interleukin- 10 gene polymorphisms alter outcomes of diffuse large B-cell lymphoma following rituximab plus CHOP chemotherapy. Clin Cancer Res 2009; 15:2107-15; PMID: 19276283; DOI: 10.1158/1078-0432.CCR-08-1588.
135. Stearns ME, Rhim J, Wang M. 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. Clin Cancer Res 1999; 5:189-96; PMID: 9918218.
136. Lazennec G, Richmond A. Chemokines and chemokine receptors: new insights into cancer-related inflammation. Trends Mol Med 2010; 16:133-44; PMID: 20163989; DOI: 10.1016/j.molmed.2010.01.003.
137. Kubo F, Ueno S, Hiwatashi K, Sakoda M, Kawaida K, Nuruki K, et al. Interleukin 8 in human hepatocellular carcinoma correlates with cancer cell invasion of vessels but not with tumor angiogenesis. Ann Surg Oncol 2005; 12:800-7; PMID: 16132378; DOI: 10.1245/ASO.2005.07.015.
138. Murphy C, McGurk M, Pettigrew J, Santinelli A, Mazzucchelli R, Johnston PG, et al. Nonapical and cytoplasmic expression of interleukin-8, CXCR1 and CXCR2 correlates with cell proliferation and microvessel density in prostate cancer. Clin Cancer Res 2005; 11:4117-27; PMID: 15930347; DOI: 10.1158/1078-0432.CCR-04-1518.
139. Schioppa T, Uranchimeg B, Saccani A, Biswas SK, Doni A, Rapisarda A, et al. Regulation of the chemokine receptor CXCR4 by hypoxia. J Exp Med 2003; 198:1391-402; PMID: 14597738; DOI: 10.1084/jem.20030267.
140. Darash-Yahana M, Pikarsky E, Abramovitch R, Zeira E, Pal B, Karplus R, et al. Role of high expression levels of CXCR4 in tumor growth, vascularization and metastasis. Faseb J 2004; 18:1240-2; PMID: 15180966; DOI: 10.1096/fj.03-0935fje.
141. Kim J, Takeuchi H, Lam ST, Turner RR, Wang HJ, Kuo C, et al. Chemokine receptor CXCR4 expression in colorectal cancer patients increases the risk for recurrence and for poor survival. J Clin Oncol 2005; 23:2744-53; PMID: 15837989; DOI: 10.1200/JCO.2005.07.078.
142. Yoshitake N, Fukui H, Yamagishi H, Sekikawa A, Fujii S, Tomita S, et al. Expression of SDF-1 alpha and nuclear CXCR4 predicts lymph node metastasis in colorectal cancer. Br J Cancer 2008; 98:1682-9; PMID: 18443596; DOI: 10.1038/sj.bjc.6604363.
143. Salvucci O, Bouchard A, Baccarelli A, Deschenes J, Sauter G, Simon R, et al. The role of CXCR4 receptor expression in breast cancer: a large tissue microarray study. Breast Cancer Res Treat 2006; 97:275-83; PMID: 16344916; DOI: 10.1007/s10549-005-9121-8.
144. Woo SU, Bae JW, Kim CH, Lee JB, Koo BW. A significant correlation between nuclear CXCR4 expression and axillary lymph node metastasis in hormonal receptor negative breast cancer. Ann Surg Oncol 2008; 15:281-5; PMID: 17763975; DOI: 10.1245/s10434-007-9595-1.
145. Barbieri F, Bajetto A, Florio T. Role of chemokine network in the development and progression of ovarian cancer: a potential novel pharmacological target. J Oncol 2010; 2010:426956; PMID: 20049170; DOI: 10.1155/2010/426956.
146. Kucia M, Reca R, Miekus K, Wanzeck J, Wojakowski W, Janowska-Wieczorek A, et al. Trafficking of normal stem cells and metastasis of cancer stem cells involve similar mechanisms: pivotal role of the SDF-1-CXCR4 axis. Stem Cells 2005; 23:879-94; PMID: 15888687; DOI: 10.1634/stemcells.2004-0342.
147. Zlotnik A. Chemokines in neoplastic progression. Semin Cancer Biol 2004; 14:181-5; PMID: 15246053; DOI: 10.1016/j.semcancer.2003.10.004.
148. Marchesi F, Piemonti L, Fedele G, Destro A, Roncalli M, Albarello L, et al. The chemokine receptor CX3CR1 is involved in the neural tropism and malignant behavior of pancreatic ductal adenocarcinoma. Cancer Res 2008; 68:9060-9; PMID: 18974152; DOI: 10.1158/0008-5472.CAN-08-1810.
149. Kazemfar K, Chen R, Nicholson K, Coppola D, Zhou JM, Chen X, et al. Combined IL-8 and TGF-beta blockade efficiently prevents neutrophil infiltrates into an A549-cell tumor. Immunol Lett 2009; 122:26-9; PMID: 19056425; DOI: 10.1016/j.imlet.2008.10.010.
150. Niedermeier M, Hennessy BT, Knight ZA, Henneberg M, Hu J, Kurtova AV, et al. Isoform-selective phosphoinositide 3′-kinase inhibitors inhibit CXCR4 signaling and overcome stromal cell-mediated drug resistance in chronic lymphocytic leukemia: a novel therapeutic approach. Blood 2009; 113:5549-57; PMID: 19318683; DOI: 10.1182/blood-2008-06-165068.
151. Ruffini PA, Morandi P, Cabioglu N, Altundag K, Cristofanilli M. Manipulating the chemokine-chemokine receptor network to treat cancer. Cancer 2007; 109:2392-404; PMID: 17503430; DOI: 10.1002/cncr.22706.
152. Wong D, Korz W. Translating an antagonist of chemokine receptor CXCR4: from bench to bedside. Clin Cancer Res 2008; 14:7975-80; PMID: 19088012; DOI: 10.1158/1078-0432.CCR-07-4846.
153. Rozel S, Galban CJ, Nicolay K, Lee KC, Sud S, Neeley C, et al. Synergy between anti-CCL2 and docetaxel as determined by DW-MRI in a metastatic bone cancer model. J Cell Biochem 2009; 107:58-64; PMID: 19259948; DOI: 10.1002/jcb.22056.
154. Zhang J, Lu Y, Pienta KJ. Multiple roles of chemokine (C-C motif ) ligand 2 in promoting prostate cancer growth. J Natl Cancer Inst 2010; 102:522-8; PMID: 20233997; DOI: 10.1093/jnci/djq044.
155. Slettenaar VI, Wilson JL. The chemokine network: a target in cancer biology? Adv Drug Deliv Rev 2006; 58:962-74; PMID: 16996642; DOI: 10.1016/j.addr.2006.03.012.
156. Deutsch E, Maggiorella L, Eschwege P, Bourhis J, Soria JC, Abdulkarim B. Environmental, genetic and molecular features of prostate cancer. Lancet Oncol 2004; 5:303-13; PMID: 15120667; DOI: 10.1016/ S1470-2045(04)01468-8.
157. Khor LY, Bae K, Pollack A, Hammond ME, Grignon DJ, Venkatesan VM, et al. COX-2 expression predicts prostate-cancer outcome: analysis of data from the RTOG 92-02 trial. Lancet Oncol 2007; 8:912-20; PMID: 17881290; DOI: 10.1016/S1470-2045(07)70280-2.
158. Cetin M, Buyukberber S, Demir M, Sari I, Deniz K, Eser B, et al. Overexpression of cyclooxygenase-2 in multiple myeloma: association with reduced survival. Am J Hematol 2005; 80:169-73; PMID: 16247750; DOI: 10.1002/ajh.20460.
159. Zhang XH, Huang DP, Guo GL, Chen GR, Zhang HX, Wan L, et al. Coexpression of VEGF-C and COX-2 and its association with lymphangiogenesis in human breast cancer. BMC Cancer 2008; 8:4; PMID: 18190720; DOI: 10.1186/1471-2407-8-4.
160. Kim YB, Kim GE, Cho NH, Pyo HR, Shim SJ, Chang SK, et al. Overexpression of cyclooxygenase-2 is associated with a poor prognosis in patients with squamous cell carcinoma of the uterine cervix treated with radiation and concurrent chemotherapy. Cancer 2002; 95:531-9; PMID: 12209745; DOI: 10.1002/cncr.10684.
161. Muller-Decker K, Neufang G, Berger I, Neumann M, Marks F, Furstenberger G. Transgenic cyclooxygenase-2 overexpression sensitizes mouse skin for carcinogenesis. Proc Natl Acad Sci USA 2002; 99:12483-8; PMID: 12221288; DOI: 10.1073/pnas.192323799.
162. Tiano HF, Loftin CD, Akunda J, Lee CA, Spalding J, Sessoms A, et al. Deficiency of either cyclooxygenase (COX)-1 or COX-2 alters epidermal differentiation and reduces mouse skin tumorigenesis. Cancer Res 2002; 62:3395-401; PMID: 12067981.
163. Howe LR, Chang SH, Tolle KC, Dillon R, Young LJ, Cardiff RD, et al. HER2/neu-induced mammary tumorigenesis and angiogenesis are reduced in cyclooxygenase-2 knockout mice. Cancer Res 2005; 65:10113-9; PMID: 16267038; DOI: 10.1158/0008-5472.CAN-05-1524.
164. Koehne CH, Dubois RN. COX-2 inhibition and colorectal cancer. Semin Oncol 2004; 31:12-21; PMID: 15252926.
165. Flossmann E, Rothwell PM. Effect of aspirin on long-term risk of colorectal cancer: consistent evidence from randomised and observational studies. Lancet 2007; 369:1603-13; PMID: 17499602; DOI: 10.1016/S0140-6736(07) 60747-8.
166. Chan AT, Ogino S, Fuchs CS. Aspirin and the risk of colorectal cancer in relation to the expression of COX-2. N Engl J Med 2007; 356:2131-42; PMID: 17522398; DOI: 10.1056/NEJMoa067208.
167. Fosslien E. Review: molecular pathology of cyclooxy-genase-2 in cancer-induced angiogenesis. Ann Clin Lab Sci 2001; 31:325-48; PMID: 11688844.
168. Lucci A, Krishnamurthy S, Singh B, Bedrosian I, Meric-Bernstam F, Reuben J, et al. Cyclooxygenase-2 expression in primary breast cancers predicts dissemination of cancer cells to the bone marrow. Breast Cancer Res Treat 2009; 117:61-8; PMID: 18663571; DOI: 10.1007/s10549-008-0135-x.
169. Subbaramaiah K, Dannenberg AJ. Cyclooxygenase 2: a molecular target for cancer prevention and treatment. Trends Pharmacol Sci 2003; 24:96-102; PMID: 12559775.
170. Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, et al. Type, density and location of immune cells within human colorectal tumors predict clinical outcome. Science 2006; 313:1960-4; PMID: 17008531; DOI: 10.1126/science.1129139.
171. Haabeth OA, Lorvik KB, Hammarstrom C, Donaldson IM, Haraldsen G, Bogen B, et al. Inflammation driven by tumour-specific Th1 cells protects against B-cell cancer. Nat Commun 2011; 2:240; PMID: 21407206; DOI: 10.1038/ncomms1239.
172. Lavon I, Goldberg I, Amit S, Landsman L, Jung S, Tsuberi BZ, et al. High susceptibility to bacterial infection, but no liver dysfunction, in mice compromised for hepatocyte NFkappaB activation. Nat Med 2000; 6:573-7; PMID: 10802715; DOI: 10.1038/75057.