{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T23:11:33Z","timestamp":1772320293633,"version":"3.50.1"},"reference-count":182,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2013,8,6]],"date-time":"2013-08-06T00:00:00Z","timestamp":1375747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>It is well established that chronic inflammation underpins the development of  a number of human cancers, with pro-inflammatory signaling within the tumor microenvironment contributing to tumor progression and metastasis. CXCL8 is an ELR+ pro-inflammatory CXC-chemokine which mediates its effects via signaling through two G protein-coupled receptors, CXCR1 and CXCR2. Elevated CXCL8-CXCR1\/2 signaling within the tumor microenvironment of numerous cancers is known to enhance tumor progression via activation of signaling pathways promoting proliferation, angiogenesis, migration, invasion and cell survival. This review provides an overview of established roles of CXCL8-CXCR1\/2 signaling in cancer and subsequently, discusses the possible strategies of targeting CXCL8-CXCR1\/2 signaling in cancer, covering indirect strategies (e.g., anti-inflammatories, NF\u03baB inhibitors) and direct CXCL8 or CXCR1\/2 inhibition (e.g., neutralizing antibodies, small molecule receptor antagonists, pepducin inhibitors  and siRNA strategies). Reports of pre-clinical cancer studies and clinical trials using CXCL8-CXCR1\/2-targeting strategies for the treatment of inflammatory diseases will be discussed. The future translational opportunities for use of such agents in oncology will be discussed, with emphasis on exploitation in stratified populations.<\/jats:p>","DOI":"10.3390\/ph6080929","type":"journal-article","created":{"date-parts":[[2013,8,6]],"date-time":"2013-08-06T12:33:17Z","timestamp":1375792397000},"page":"929-959","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":118,"title":["Rationale and Means to Target Pro-Inflammatory Interleukin-8 (CXCL8) Signaling in Cancer"],"prefix":"10.3390","volume":"6","author":[{"given":"Laura","family":"Campbell","sequence":"first","affiliation":[{"name":"Centre for Cancer Research and Cell Biology, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland, BT9 7BL, UK"}]},{"given":"Pamela","family":"Maxwell","sequence":"additional","affiliation":[{"name":"Centre for Cancer Research and Cell Biology, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland, BT9 7BL, UK"}]},{"given":"David","family":"Waugh","sequence":"additional","affiliation":[{"name":"Centre for Cancer Research and Cell Biology, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland, BT9 7BL, UK"}]}],"member":"1968","published-online":{"date-parts":[[2013,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1002\/jcb.10747","article-title":"Pathological and molecular mechanisms of prostate carcinogenesis: Implications for diagnosis, detection, prevention, and treatment","volume":"91","author":"DeWeese","year":"2004","journal-title":"J. Cell. Biochem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1053\/j.gastro.2007.08.001","article-title":"Histologic inflammation is a risk factor for progression to colorectal neoplasia in ulcerative colitis: A cohort study","volume":"133","author":"Gupta","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_4","first-page":"2727","article-title":"Colorectal cancer and inflammatory bowel disease: Epidemiology, risk factors, mechanisms of carcinogenesis and prevention strategies","volume":"29","author":"Triantafillidis","year":"2009","journal-title":"Anticancer Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S6","DOI":"10.1097\/01.ju.0000142058.99614.ff","article-title":"The role of inflammation in the pathogenesis of prostate cancer","volume":"172","author":"Nelson","year":"2004","journal-title":"J. Urol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1097\/01.ju.0000158161.15277.78","article-title":"Propionibacterium acnes associated with inflammation in radical prostatectomy specimens: A possible link to cancer evolution?","volume":"173","author":"Cohen","year":"2005","journal-title":"J. Urol."},{"key":"ref_7","first-page":"71","article-title":"Prospective study of nonsteroidal anti-inflammatory drugs and breast cancer","volume":"6","author":"Harris","year":"1999","journal-title":"Oncol. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1016\/S0140-6736(07)60747-8","article-title":"Effect of aspirin on long-term risk of colorectal cancer: Consistent evidence from randomised and observational studies","volume":"369","author":"Flossmann","year":"2007","journal-title":"Lancet"},{"key":"ref_9","first-page":"854","article-title":"Nitric oxide and oxygen radicals in infection, inflammation, and cancer","volume":"63","author":"Maeda","year":"1998","journal-title":"Biochemistry Mosc."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/nature07205","article-title":"Cancer-related inflammation","volume":"454","author":"Mantovani","year":"2008","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.ccr.2004.09.028","article-title":"Ras-induced interleukin-8 expression plays a critical role in tumor growth and angiogenesis","volume":"6","author":"Sparmann","year":"2004","journal-title":"Cancer Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4198","DOI":"10.1158\/0008-5472.CAN-05-3842","article-title":"High expression of ligands for chemokine receptor CXCR2 in alveolar epithelial neoplasia induced by oncogenic kras","volume":"66","author":"Wislez","year":"2006","journal-title":"Cancer Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1124\/mi.8.1.6","article-title":"Oncogenic Ras-nduced Expression of Cytokines: A New Target of Anti-Cancer Therapeutics","volume":"8","author":"Ancrile","year":"2008","journal-title":"Mol. Interventions"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.eururo.2012.08.032","article-title":"Potentiation of Inflammatory CXCL8 Signalling Sustains Cell Survival in PTEN-deficient Prostate Carcinoma","volume":"64","author":"Maxwell","year":"2013","journal-title":"Eur. Urol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.molmed.2010.01.003","article-title":"Chemokines and chemokine receptors: New insights into cancer-related inflammation","volume":"16","author":"Lazennec","year":"2010","journal-title":"Trends Mol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1093\/carcin\/bgp127","article-title":"Cancer-related inflammation, the seventh hallmark of cancer: Links to genetic instability","volume":"30","author":"Colotta","year":"2009","journal-title":"Carcinogenesis"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/nature08782","article-title":"B-cell-derived lymphotoxin promotes castration-resistant prostate cancer","volume":"464","author":"Ammirante","year":"2010","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.2174\/138161209788453239","article-title":"Towards understanding the role of cancer-associated inflammation in chemoresistance","volume":"15","author":"Jonkers","year":"2009","journal-title":"Curr. Pharm. Des."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1084\/jem.167.6.1883","article-title":"Molecular cloning of a human monocyte-derived neutrophil chemotactic factor (MDNCF) and the induction of MDNCF mRNA by interleukin 1 and tumor necrosis factor","volume":"167","author":"Matsushima","year":"1988","journal-title":"J. Exp. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1097\/00062752-200005000-00009","article-title":"Role of interleukin-8 in neutrophil signaling","volume":"7","author":"Zeilhofer","year":"2000","journal-title":"Curr. Opin. Hematol."},{"key":"ref_21","first-page":"997","article-title":"Expression of interleukin-8 gene in inflammatory bowel disease is related to the histological grade of active inflammation","volume":"144","author":"Mazzucchelli","year":"1994","journal-title":"Am. J. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1136\/gut.38.1.90","article-title":"Interleukin 8: Cells of origin in inflammatory bowel disease","volume":"38","author":"Grimm","year":"1996","journal-title":"Gut"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1002\/eji.1830200938","article-title":"Detection of interleukin 8 biological activity in synovial fluids from patients with rheumatoid arthritis and production of interleukin 8 mRNA by isolated synovial cells","volume":"20","author":"Brennan","year":"1990","journal-title":"Eur. J. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"743","DOI":"10.3109\/07357909309046949","article-title":"Interleukin-8: A review","volume":"11","author":"Baker","year":"1993","journal-title":"Cancer Invest."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1128\/iai.61.4.1307-1314.1993","article-title":"Elevated interleukin-8 levels in the urine of patients with urinary tract infections","volume":"61","author":"Ko","year":"1993","journal-title":"Infect. Immun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3425","DOI":"10.4049\/jimmunol.0900305","article-title":"Differential activation and regulation of CXCR1 and CXCR2 by CXCL8 monomer and dimer","volume":"183","author":"Nasser","year":"2009","journal-title":"J. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1146\/annurev.iy.12.040194.003113","article-title":"The molecular biology of leukocyte chemoattractant receptors","volume":"12","author":"Murphy","year":"1994","journal-title":"Annu. Rev. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/nrc1388","article-title":"Cancer and the chemokine network","volume":"4","author":"Balkwill","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/nm1567","article-title":"MIF is a noncognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment","volume":"13","author":"Bernhagen","year":"2007","journal-title":"Nat. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1016\/j.bbamem.2006.10.021","article-title":"G protein coupled receptor structure and activation","volume":"1768","author":"Kobilka","year":"2007","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/84219","article-title":"Lymphocyte traffic control by chemokines","volume":"2","author":"Moser","year":"2001","journal-title":"Nat. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/84224","article-title":"Dancing to the tune of chemokines","volume":"2","author":"Thelen","year":"2001","journal-title":"Nat. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"L1094","DOI":"10.1152\/ajplung.2001.280.6.L1094","article-title":"IL-8 activates endothelial cell CXCR1 and CXCR2 through Rho and Rac signaling pathways","volume":"280","author":"Schraufstatter","year":"2001","journal-title":"Am. J. Physiol. Lung. C"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.4049\/jimmunol.166.2.1272","article-title":"Actin filaments are involved in the regulation of trafficking of two closely related chemokine receptors, CXCR1 and CXCR2","volume":"166","author":"Zaslaver","year":"2001","journal-title":"J. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6735","DOI":"10.1158\/1078-0432.CCR-07-4843","article-title":"The interleukin-8 pathway in cancer","volume":"14","author":"Waugh","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1189\/jlb.72.5.847","article-title":"Multiple control of interleukin-8 gene expression","volume":"72","author":"Hoffmann","year":"2002","journal-title":"J. Leukocyte Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1089\/10799900152547812","article-title":"Regulation of interleukin-8 expression by tumor-associated stress factors","volume":"21","author":"Shi","year":"2001","journal-title":"J. Interf. Cytok. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"46415","DOI":"10.1074\/jbc.M403226200","article-title":"Fas ligand induces cell-autonomous NF-kappaB activation and interleukin-8 production by a mechanism distinct from that of tumor necrosis factor-alpha","volume":"279","author":"Imamura","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s10456-005-5612-9","article-title":"Wnt\/beta-catenin signaling induces proliferation, survival and interleukin-8 in human endothelial cells","volume":"8","author":"Shawber","year":"2005","journal-title":"Angiogenesis"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"7211","DOI":"10.4049\/jimmunol.177.10.7211","article-title":"A novel role of hypoxia-inducible factor in cobalt chloride-and hypoxia-mediated expression of IL-8 chemokine in human endothelial cells","volume":"177","author":"Kim","year":"2006","journal-title":"J. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1002\/jlb.56.5.554","article-title":"Molecular mechanism of interleukin-8 gene expression","volume":"56","author":"Mukaida","year":"1994","journal-title":"J. Leukocyte Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1089\/107999099313866","article-title":"Regulation of interleukin-8 gene expression","volume":"19","author":"Roebuck","year":"1999","journal-title":"J. Interf. Cytok. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.4049\/jimmunol.162.2.1077","article-title":"Chemotactic migration triggers IL-8 generation in neutrophilic leukocytes","volume":"162","author":"Siddiqui","year":"1999","journal-title":"J. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"G282","DOI":"10.1152\/ajpgi.00503.2002","article-title":"TLR5-mediated activation of p38 MAPK regulates epithelial IL-8 expression via posttranscriptional mechanism","volume":"285","author":"Yu","year":"2003","journal-title":"Am. J. Physiol. Gastr. L"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"6556","DOI":"10.4049\/jimmunol.154.12.6556","article-title":"Increased cell-associated IL-8 in human exudative and A23187-treated peripheral blood neutrophils","volume":"154","author":"Kuhns","year":"1995","journal-title":"J. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4117","DOI":"10.1158\/1078-0432.CCR-04-1518","article-title":"Nonapical and cytoplasmic expression of interleukin-8, CXCR1, and CXCR2 correlates with cell proliferation and microvessel density in prostate cancer","volume":"11","author":"Murphy","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"ref_47","unstructured":"Li, A., Varney, M.L., and Singh, R.K. (2001). Expression of Interleukin 8 and Its Receptors in Human Colon Carcinoma Cells with Different Metastatic Potentials Expression of Interleukin 8 and Its Receptors in Human Colon Carcinoma Cells with Different Metastatic Potentials 1. Clin. Cancer Res., 3298\u20133304."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1164\/ajrccm.162.5.2002108","article-title":"Interleukin-8 messenger ribonucleic acid expression correlates with tumor progression, tumor angiogenesis, patient survival, and timing of relapse in non-small-cell lung cancer","volume":"162","author":"Yuan","year":"2000","journal-title":"Am. J. Res. Crit. Care"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Veltri, R.W., Miller, M.C., Zhao, G., Ng, A., Marley, G.M., Wright, G.L., Vessella, R.L., and Ralph, D. (4295). Interleukin-8 serum levels in patients with benign prostatic hyperplasia and prostate cancer. Urology, 139\u2013147.","DOI":"10.1016\/S0090-4295(98)00455-5"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1093\/carcin\/bgn109","article-title":"Interleukin-8 signaling promotes androgen-independent proliferation of prostate cancer cells via induction of androgen receptor expression and activation","volume":"29","author":"Seaton","year":"2008","journal-title":"Carcinogenesis"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"6854","DOI":"10.1158\/0008-5472.CAN-07-1162","article-title":"Interleukin-8 is a molecular determinant of androgen independence and progression in prostate cancer","volume":"67","author":"Araki","year":"2007","journal-title":"Cancer Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1038\/sj.onc.1207344","article-title":"Interleukin-8 confers androgen-independent growth and migration of LNCaP: Differential effects of tyrosine kinases Src and FAK","volume":"23","author":"Lee","year":"2004","journal-title":"Oncogene"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1158\/1541-7786.MCR-07-0032","article-title":"Interleukin-8 signaling promotes translational regulation of cyclin D in androgen-independent prostate cancer cells","volume":"5","author":"MacManus","year":"2007","journal-title":"Mol. Cancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1002\/ijc.25562","article-title":"Interleukin-8 is associated with proliferation, migration, angiogenesis and chemosensitivity in vitro and in vivo in colon cancer cell line models","volume":"128","author":"Ning","year":"2011","journal-title":"Int. J. Cancer"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.lungcan.2006.11.014","article-title":"Interleukin-8 stimulates cell proliferation in non-small cell lung cancer through epidermal growth factor receptor transactivation","volume":"56","author":"Luppi","year":"2007","journal-title":"Lung Cancer"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2618","DOI":"10.1016\/j.ejca.2009.07.007","article-title":"Functional activity of CXCL8 receptors, CXCR1 and CXCR2, on human malignant melanoma progression","volume":"45","author":"Gabellini","year":"2009","journal-title":"Eur. J. Cancer"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.semcancer.2003.10.006","article-title":"CXC chemokines in angiogenesis of cancer","volume":"14","author":"Strieter","year":"2004","journal-title":"Semin. Cancer Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/sj.neo.7900124","article-title":"Expression of interleukin-8 correlates with angiogenesis, tumorigenicity, and metastasis of human prostate cancer cells implanted orthotopically in nude mice","volume":"3","author":"Kim","year":"2001","journal-title":"Neoplasia"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1016\/S0002-9440(10)65404-1","article-title":"Distinct CXC chemokines mediate tumorigenicity of prostate cancer cells","volume":"154","author":"Moore","year":"1999","journal-title":"Am. J. Pathol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1158\/0008-5472.CAN-08-3378","article-title":"Host CXCR2-dependent regulation of melanoma growth, angiogenesis, and experimental lung metastasis","volume":"69","author":"Singh","year":"2009","journal-title":"Cancer Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1002\/ijc.24383","article-title":"CXC-chemokine\/CXCR2 biological axis promotes angiogenesis in vitro and in vivo in pancreatic cancer","volume":"125","author":"Matsuo","year":"2009","journal-title":"Int. J. Cancer"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2792","DOI":"10.1172\/JCI118734","article-title":"Inhibition of interleukin-8 reduces tumorigenesis of human non-small cell lung cancer in SCID mice","volume":"97","author":"Arenberg","year":"1996","journal-title":"J. Clin. Invest."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1002\/(SICI)1097-0045(19991001)41:2<78::AID-PROS2>3.0.CO;2-P","article-title":"CXC-chemokines stimulate invasion and chemotaxis in prostate carcinoma cells through the CXCR2 receptor","volume":"41","author":"Reiland","year":"1999","journal-title":"Prostate"},{"key":"ref_64","unstructured":"McFarlane, S., and Waugh, D. Personal communication."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/0006-291X(90)91449-3","article-title":"Induction of haptotactic migration of melanoma cells by neutrophil activating protein\/interleukin-8","volume":"169","author":"Wang","year":"1990","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1042\/cs0970385","article-title":"Interleukin-8 stimulates the migration of human colonic epithelial cells in vitro","volume":"97","author":"Wilson","year":"1999","journal-title":"Clin. Sci. (London)"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"979","DOI":"10.3748\/wjg.v18.i9.979","article-title":"Interleukin-8 associates with adhesion, migration, invasion and chemosensitivity of human gastric cancer cells","volume":"18","author":"Kuai","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.4161\/cc.9.9.11297","article-title":"The paradox of tumor-associated neutrophils: Fueling tumor growth with cytotoxic substances","volume":"9","author":"Houghton","year":"2010","journal-title":"Cell Cycle"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1111\/j.1365-2613.2009.00641.x","article-title":"Neutrophils: Key mediators of tumour angiogenesis","volume":"90","author":"Tazzyman","year":"2009","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2476","DOI":"10.1002\/cncr.26511","article-title":"Intratumoral neutrophils and plasmacytoid dendritic cells indicate poor prognosis and are associated with pSTAT3 expression in AJCC stage I\/II melanoma","volume":"118","author":"Jensen","year":"2012","journal-title":"Cancer"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e30806","DOI":"10.1371\/journal.pone.0030806","article-title":"Increased intratumoral neutrophil in colorectal carcinomas correlates closely with malignant phenotype and predicts patients\u2019 adverse prognosis","volume":"7","author":"Rao","year":"2012","journal-title":"PLoS One"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4709","DOI":"10.1200\/JCO.2008.18.9498","article-title":"Presence of intratumoral neutrophils is an independent prognostic factor in localized renal cell carcinoma","volume":"27","author":"Jensen","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"8896","DOI":"10.1158\/0008-5472.CAN-05-1734","article-title":"Breast cancer cells stimulate neutrophils to produce oncostatin M: Potential implications for tumor progression","volume":"65","author":"Queen","year":"2005","journal-title":"Cancer Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e51848","DOI":"10.1371\/journal.pone.0051848","article-title":"Crucial involvement of tumor-associated neutrophils in the regulation of chronic colitis-associated carcinogenesis in mice","volume":"7","author":"Shang","year":"2012","journal-title":"PLoS One"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1002\/ijc.25987","article-title":"Inhibition of neutrophil infiltration into A549 lung tumors in vitro and in vivo using a CXCR2-specific antagonist is associated with reduced tumor growth","volume":"129","author":"Tazzyman","year":"2011","journal-title":"Int. J. Cancer"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1124\/jpet.108.145862","article-title":"Therapeutic effect of blocking CXCR2 on neutrophil recruitment and dextran sodium sulfate-induced colitis","volume":"329","author":"Farooq","year":"2009","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3127","DOI":"10.1172\/JCI61067","article-title":"Inhibition of CXCR2 profoundly suppresses inflammation-driven and spontaneous tumorigenesis","volume":"122","author":"Jamieson","year":"2012","journal-title":"J. Clin. Invest."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"7333","DOI":"10.1038\/sj.onc.1210536","article-title":"HIF-1 and NF-kappaB-mediated upregulation of CXCR1 and CXCR2 expression promotes cell survival in hypoxic prostate cancer cells","volume":"26","author":"Maxwell","year":"2007","journal-title":"Oncogene"},{"key":"ref_79","first-page":"746","article-title":"Chemotherapy-induced CXC-chemokine\/CXC-chemokine receptor signaling in metastatic prostate cancer cells confers resistance to oxaliplatin through potentiation of nuclear factor-kappaB transcription and evasion of apoptosis","volume":"327","author":"Wilson","year":"2008","journal-title":"Pharmacology"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2649","DOI":"10.1158\/1535-7163.MCT-08-0148","article-title":"Interleukin-8 signaling attenuates TRAIL- and chemotherapy-induced apoptosis through transcriptional regulation of c-FLIP in prostate cancer cells","volume":"7","author":"Wilson","year":"2008","journal-title":"Mol. Cancer Ther."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e36545","DOI":"10.1371\/journal.pone.0036545","article-title":"Constitutive and treatment-induced CXCL8-signalling selectively modulates the efficacy of anti-metabolite therapeutics in metastatic prostate cancer","volume":"7","author":"Wilson","year":"2012","journal-title":"PloS One"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1158\/1535-7163.MCT-11-0915","article-title":"The CXCR2 antagonist, SCH-527123, shows antitumor activity and sensitizes cells to oxaliplatin in preclinical colon cancer models","volume":"11","author":"Ning","year":"2012","journal-title":"Mol Cancer Ther."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.cyto.2011.06.005","article-title":"Autocrine production of interleukin-8 confers cisplatin and paclitaxel resistance in ovarian cancer cells","volume":"56","author":"Wang","year":"2011","journal-title":"Cytokine"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1089\/107999099312821","article-title":"Cooperation between transcription factor AP-1 and NF-kappaB in the induction of interleukin-8 in human pancreatic adenocarcinoma cells by hypoxia","volume":"19","author":"Shi","year":"1999","journal-title":"J. Interf. Cytok. Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/S1359-6101(01)00016-8","article-title":"Interleukin-8 and human cancer biology","volume":"12","author":"Xie","year":"2001","journal-title":"Cytokine Growth F. R."},{"key":"ref_86","first-page":"1357","article-title":"p38 Mitogen-activated protein kinase regulates IL-8 expression in human pulmonary vascular endothelial cells","volume":"13","author":"Hashimoto","year":"1999","journal-title":"Eur. Respir. J."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"F1020","DOI":"10.1152\/ajprenal.00291.2001","article-title":"CD40 ligation stimulates MCP-1 and IL-8 production, TRAF6 recruitment, and MAPK activation in proximal tubule cells","volume":"282","author":"Li","year":"2002","journal-title":"Am. J. Physiol. Renal."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3165","DOI":"10.4049\/jimmunol.158.7.3165","article-title":"Actions of IL-1 are selectively controlled by p38 mitogen-activated protein kinase: Regulation of prostaglandin H synthase-2, metalloproteinases, and IL-6 at different levels","volume":"158","author":"Ridley","year":"1997","journal-title":"J. Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"C1229","DOI":"10.1152\/ajpcell.00620.2004","article-title":"Differential effects of NF-{kappa}B and p38 MAPK inhibitors and combinations thereof on TNF-{alpha}- and IL-1{beta}-induced proinflammatory status of endothelial cells in vitro","volume":"289","author":"Kuldo","year":"2005","journal-title":"Am. J. Physiol. Cell Ph."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"4054","DOI":"10.1038\/onc.2011.563","article-title":"EGFRvIII promotes glioma angiogenesis and growth through the NF-kappaB, interleukin-8 pathway","volume":"31","author":"Bonavia","year":"2012","journal-title":"Oncogene"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1177\/0091270010397050","article-title":"An oral inhibitor of p38 MAP kinase reduces plasma fibrinogen in patients with chronic obstructive pulmonary disease","volume":"52","author":"Lomas","year":"2012","journal-title":"J. Clin. Pharmacol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S0092-8674(00)00114-8","article-title":"Cell signaling by receptor tyrosine kinases","volume":"103","author":"Schlessinger","year":"2000","journal-title":"Cell"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1038\/nrd1902","article-title":"Exploiting the PI3K\/AKT pathway for cancer drug discovery","volume":"4","author":"Hennessy","year":"2005","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1111\/j.1582-4934.2011.01337.x","article-title":"Regulatory mechanisms of interleukin-8 production induced by tumour necrosis factor-alpha in human hepatocellular carcinoma cells","volume":"16","author":"Wang","year":"2012","journal-title":"J. Cell Mol. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"3690","DOI":"10.1091\/mbc.e08-10-1068","article-title":"Proteasome inactivation promotes p38 mitogen-activated protein kinase-dependent phosphatidylinositol 3-kinase activation and increases interleukin-8 production in retinal pigment epithelial cells","volume":"20","author":"Fernandes","year":"2009","journal-title":"Mol. Biol. Cell"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"6294","DOI":"10.1128\/IAI.70.11.6294-6301.2002","article-title":"Tumor necrosis factor alpha-induced interleukin-8 production via NF-kappaB and phosphatidylinositol 3-kinase\/Akt pathways inhibits cell apoptosis in human hepatocytes","volume":"70","author":"Osawa","year":"2002","journal-title":"Infect. Immun."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/jcp.22722","article-title":"Potential mechanism of interleukin-8 production from lung cancer cells: An involvement of EGF-EGFR-PI3K-Akt-Erk pathway","volume":"227","author":"Zhang","year":"2012","journal-title":"J. Cell Physiol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1111\/pcmr.12007","article-title":"Mechanisms of intrinsic and acquired resistance to kinase-targeted therapies","volume":"25","author":"Bagrodia","year":"2012","journal-title":"Pigm. Cell Melanoma R"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/j.ccr.2012.10.023","article-title":"JAK2\/STAT5 inhibition circumvents resistance to PI3K\/mTOR blockade: A rationale for cotargeting these pathways in metastatic breast cancer","volume":"22","author":"Britschgi","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.bbagrm.2010.05.004","article-title":"Inhibiting NF-kappaB activation by small molecules as a therapeutic strategy","volume":"1799","author":"Gupta","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/cmi.2009.43","article-title":"NF-kappaB signaling pathway, inflammation and colorectal cancer","volume":"6","author":"Wang","year":"2009","journal-title":"Cell Mol. Immunol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"7389","DOI":"10.1038\/sj.onc.1203160","article-title":"Constitutive activation of IkappaB kinase alpha and NF-kappaB in prostate cancer cells is inhibited by ibuprofen","volume":"18","author":"Palayoor","year":"1999","journal-title":"Oncogene"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1242\/jcs.115.1.141","article-title":"The role of IKK in constitutive activation of NF-kappaB transcription factor in prostate carcinoma cells","volume":"115","author":"Gasparian","year":"2002","journal-title":"J. Cell Sci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1002\/pros.10082","article-title":"Mechanisms of constitutive NF-kappaB activation in human prostate cancer cells","volume":"52","author":"Suh","year":"2002","journal-title":"Prostate"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3389\/fphar.2013.00013","article-title":"Modulators of HIF1alpha and NFkB in Cancer Treatment: Is it a Rational Approach for Controlling Malignant Progression?","volume":"4","author":"Tafani","year":"2013","journal-title":"Front. Pharmacol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"5656","DOI":"10.1158\/1078-0432.CCR-08-0123","article-title":"Advances in targeting IKK and IKK-related kinases for cancer therapy","volume":"14","author":"Lee","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/1475-2867-5-18","article-title":"Preclinical evaluation of the proteasome inhibitor bortezomib in cancer therapy","volume":"5","author":"Boccadoro","year":"2005","journal-title":"Cancer Cell"},{"key":"ref_108","first-page":"7338","article-title":"The proteasome inhibitor bortezomib stabilizes a novel active form of p53 in human LNCaP-Pro5 prostate cancer cells","volume":"63","author":"Williams","year":"2003","journal-title":"Cancer Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1158\/1535-7163.279.3.3","article-title":"The proteasome inhibitor bortezomib synergizes with gemcitabine to block the growth of human 253JB-V bladder tumors in vivo","volume":"3","author":"Kamat","year":"2004","journal-title":"Mol. Cancer Ther."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1111\/j.1442-2042.2012.02967.x","article-title":"Bortezomib reverses the proliferative and antiapoptotic effect of neuropeptides on prostate cancer cells","volume":"19","author":"Tsapakidis","year":"2012","journal-title":"Int. J. Urol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"6013","DOI":"10.1038\/sj.onc.1202980","article-title":"Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopreventive agent curcumin involves inhibition of NF-kappaB activation via the NIK\/IKK signalling complex","volume":"18","author":"Plummer","year":"1999","journal-title":"Oncogene"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/sj.onc.1201941","article-title":"Inhibition of the c-Jun N-terminal kinase (JNK) signaling pathway by curcumin","volume":"17","author":"Chen","year":"1998","journal-title":"Oncogene"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1055\/s-0038-1656049","article-title":"The dietary pigment curcumin reduces endothelial tissue factor gene expression by inhibiting binding of AP-1 to the DNA and activation of NF-kappa B","volume":"77","author":"Bierhaus","year":"1997","journal-title":"Thromb. Haemostasis"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/978-0-387-46401-5_4","article-title":"Modulation of transcription factors by curcumin","volume":"595","author":"Shishodia","year":"2007","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"332","DOI":"10.2174\/138945011794815356","article-title":"The targets of curcumin","volume":"12","author":"Zhou","year":"2011","journal-title":"Curr. Drug Targets"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1089\/ars.2007.1769","article-title":"Curcumin: Preventive and therapeutic properties in laboratory studies and clinical trials","volume":"10","author":"Strimpakos","year":"2008","journal-title":"Antioxid. Redox Sign."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1002\/cncr.10812","article-title":"Curcumin inhibits interleukin 8 production and enhances interleukin 8 receptor expression on the cell surface: Impact on human pancreatic carcinoma cell growth by autocrine regulation","volume":"95","author":"Hidaka","year":"2002","journal-title":"Cancer"},{"key":"ref_118","first-page":"389","article-title":"Inhibition of interleukin-8 expression by dexamethasone in human cultured airway epithelial cells","volume":"81","author":"Kwon","year":"1994","journal-title":"Immunology"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"L107","DOI":"10.1152\/ajplung.2001.280.1.L107","article-title":"Mechanism of dexamethasone-mediated interleukin-8 gene suppression in cultured airway epithelial cells","volume":"280","author":"Chang","year":"2001","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.jaci.2006.08.027","article-title":"The anti-inflammatory effect of glucocorticoids is mediated by glucocorticoid-induced leucine zipper in epithelial cells","volume":"119","author":"Eddleston","year":"2007","journal-title":"J. Allergy Clin. Immun."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1128\/MCB.15.2.943","article-title":"Characterization of mechanisms involved in transrepression of NF-kappa B by activated glucocorticoid receptors","volume":"15","author":"Scheinman","year":"1995","journal-title":"Mol. Cell. Biol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"15998","DOI":"10.1074\/jbc.M110.205724","article-title":"Down-regulation of cytokine-induced interleukin-8 requires inhibition of p38 mitogen-activated protein kinase (MAPK) via MAPK phosphatase 1-dependent and -independent mechanisms","volume":"286","author":"Dauletbaev","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_123","first-page":"729","article-title":"Up-regulation of tumor interleukin-8 expression by infiltrating macrophages: Its correlation with tumor angiogenesis and patient survival in non-small cell lung cancer","volume":"9","author":"Chen","year":"2003","journal-title":"Clin. Cancer Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1111\/j.1464-410X.2007.07261.x","article-title":"Efficacy of low-dose dexamethasone in castration-refractory prostate cancer","volume":"101","author":"Venkitaraman","year":"2008","journal-title":"BJU Int."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"3003","DOI":"10.1158\/1078-0432.CCR-05-2085","article-title":"Glucocorticoids suppress tumor angiogenesis and in vivo growth of prostate cancer cells","volume":"12","author":"Yano","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"2054","DOI":"10.1038\/sj.bjc.6604804","article-title":"Dexamethasone potentiates the antiangiogenic activity of docetaxel in castration-resistant prostate cancer","volume":"99","author":"Wilson","year":"2008","journal-title":"Br. J. Cancer"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1136\/ard.61.11.1027","article-title":"Modulation of cell recruitment by anti-inflammatory agents in antigen-induced arthritis","volume":"61","author":"Largo","year":"2002","journal-title":"Ann. Rheum. Dis."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"247","DOI":"10.3109\/07853899708999342","article-title":"Cyclo-oxygenase and colon cancer: Clues to the aspirin effect?","volume":"29","author":"Lilja","year":"1997","journal-title":"Ann. Med."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1093\/annonc\/mds113","article-title":"Aspirin and cancer risk: A quantitative review to 2011","volume":"23","author":"Bosetti","year":"2012","journal-title":"Ann. Oncol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"643","DOI":"10.3892\/ijo.2012.1756","article-title":"A novel NSAID derivative, phospho-ibuprofen, prevents AOM-induced colon cancer in rats","volume":"42","author":"Ouyang","year":"2013","journal-title":"Int. J. Oncol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1002\/prca.200800077","article-title":"Secretome-based proteomics reveals sulindac-modulated proteins released from colon cancer cells","volume":"3","author":"Ji","year":"2009","journal-title":"Proteom. Clin. Appl."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1006\/cyto.1998.0437","article-title":"Non-steroidal anti-inflammatory drugs inhibit the expression of cytokines and induce HSP70 in human monocytes","volume":"11","author":"Housby","year":"1999","journal-title":"Cytokine"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1016\/j.ajpath.2011.05.031","article-title":"Tumor-recruited neutrophils and neutrophil TIMP-free MMP-9 regulate coordinately the levels of tumor angiogenesis and efficiency of malignant cell intravasation","volume":"179","author":"Bekes","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.pharmthera.2006.04.002","article-title":"ELR+ CXC chemokines and their receptors (CXC chemokine receptor 1 and CXC chemokine receptor 2) as new therapeutic targets","volume":"112","author":"Bizzarri","year":"2006","journal-title":"Pharmacol. Therapeut."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1378\/chest.126.3.926","article-title":"Efficacy and safety of a monoclonal antibody recognizing interleukin-8 in COPD: A pilot study","volume":"126","author":"Mahler","year":"2004","journal-title":"Chest"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0002-9440(10)64164-8","article-title":"Fully humanized neutralizing antibodies to interleukin-8 (ABX-IL8) inhibit angiogenesis, tumor growth, and metastasis of human melanoma","volume":"161","author":"Huang","year":"2002","journal-title":"Am. J. Pathol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"669","DOI":"10.4049\/jimmunol.181.1.669","article-title":"IL-8 as antibody therapeutic target in inflammatory diseases: Reduction of clinical activity in palmoplantar pustulosis","volume":"181","author":"Skov","year":"2008","journal-title":"J. Immunol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.cell.2012.04.042","article-title":"A CXCL1 paracrine network links cancer chemoresistance and metastasis","volume":"150","author":"Acharyya","year":"2012","journal-title":"Cell"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1158\/0008-5472.CAN-12-0263","article-title":"CXCR2 expression in tumor cells is a poor prognostic factor and promotes invasion and metastasis in lung adenocarcinoma","volume":"73","author":"Saintigny","year":"2013","journal-title":"Cancer Res."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1936","DOI":"10.1038\/sj.bjc.6603177","article-title":"Production and upregulation of granulocyte chemotactic protein-2\/CXCL6 by IL-1beta and hypoxia in small cell lung cancer","volume":"94","author":"Zhu","year":"2006","journal-title":"Br. J. Cancer"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1158\/1535-7163.MCT-12-0988","article-title":"Human Anti-Macrophage Migration Inhibitory Factor (MIF) Antibodies Inhibit Growth of Human Prostate Cancer Cells In Vitro and In Vivo","volume":"12","author":"Hussain","year":"2013","journal-title":"Mol. Cancer Ther."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1970","DOI":"10.1038\/sj.bjc.6602227","article-title":"Interleukin-8\/CXCL8 is a growth factor for human lung cancer cells","volume":"91","author":"Zhu","year":"2004","journal-title":"Br. J. Cancer"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1152\/japplphysiol.00037.2007","article-title":"The role of CXCR2 in systemic neovascularization of the mouse lung","volume":"103","author":"Moldobaeva","year":"2007","journal-title":"J. Appl. Physiol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"4312","DOI":"10.1021\/jm049082i","article-title":"2-Arylpropionic CXC chemokine receptor 1 (CXCR1) ligands as novel noncompetitive CXCL8 inhibitors","volume":"48","author":"Allegretti","year":"2005","journal-title":"J. Med. Chem."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"3984","DOI":"10.1021\/jm061469t","article-title":"Design of noncompetitive interleukin-8 inhibitors acting on CXCR1 and CXCR2","volume":"50","author":"Moriconi","year":"2007","journal-title":"J. Med. Chem."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1172\/JCI39397","article-title":"CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts","volume":"120","author":"Ginestier","year":"2010","journal-title":"J. Clin. Invest."},{"key":"ref_147","unstructured":"Hitting Cancer at Its Core: At San Antonio Breast Cancer Symposium Eyes Focused on Reparixin, a Drug Fruit of Domp\u00e9\u2019s Research, with Action Aimed at Breast Cancer Stem Cells. Available online:www.pharmaceutical-tech.com\/press\/pressrelease_archives.asp?PID=1242\/."},{"key":"ref_148","unstructured":"Dompe Signs Up First Patient for Reparixin Phase III Trial. Available online:www.clinicalprofessionals.co.uk\/blog\/dompe-signs-up-first-patient-for-reparixin-phase-iii-trial\/."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"3647","DOI":"10.1172\/JCI63089","article-title":"CXCR1\/2 inhibition enhances pancreatic islet survival after transplantation","volume":"122","author":"Citro","year":"2012","journal-title":"J. Clin. Invest."},{"key":"ref_150","unstructured":"Study number NCT00248040."},{"key":"ref_151","unstructured":"Study number NCT00224406."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1038\/sj.bjp.0707462","article-title":"Blockade of the chemokine receptor CXCR2 ameliorates adjuvant-induced arthritis in rats","volume":"153","author":"Barsante","year":"2008","journal-title":"Br. J. Pharmacol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1165\/rcmb.2007-0364OC","article-title":"Role of the chemokine receptor CXCR2 in bleomycin-induced pulmonary inflammation and fibrosis","volume":"40","author":"Russo","year":"2009","journal-title":"Am. J. Resp. Cell Mol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1111\/j.1476-5381.2009.00623.x","article-title":"A common intracellular allosteric binding site for antagonists of the CXCR2 receptor","volume":"159","author":"Salchow","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1124\/jpet.106.118927","article-title":"Pharmacological characterization of Sch527123, a potent allosteric CXCR1\/CXCR2 antagonist","volume":"322","author":"Gonsiorek","year":"2007","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.canlet.2010.10.004","article-title":"Small molecule antagonists for CXCR2 and CXCR1 inhibit human colon cancer liver metastases","volume":"300","author":"Varney","year":"2011","journal-title":"Cancer Lett."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1183\/09031936.00048509","article-title":"SCH527123, a novel CXCR2 antagonist, inhibits ozone-induced neutrophilia in healthy subjects","volume":"35","author":"Holz","year":"2010","journal-title":"Eur. Respir. J."},{"key":"ref_158","unstructured":"Available online:https:\/\/www.ersnetsecure.org\/public\/prg_congres.abstract?ww_i_presentation=46823."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1111\/j.1365-2222.2012.04014.x","article-title":"Safety and efficacy of a CXCR2 antagonist in patients with severe asthma and sputum neutrophils: A randomized, placebo-controlled clinical trial","volume":"42","author":"Nair","year":"2012","journal-title":"Clin. Exp. Allergy"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"10095","DOI":"10.1074\/jbc.273.17.10095","article-title":"Identification of a potent, selective non-peptide CXCR2 antagonist that inhibits interleukin-8-induced neutrophil migration","volume":"273","author":"White","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"9363","DOI":"10.1021\/jm300682j","article-title":"Chemokine receptor antagonists","volume":"55","author":"Pease","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1189\/jlb.0408231","article-title":"The selective nonpeptide CXCR2 antagonist SB225002 ameliorates acute experimental colitis in mice","volume":"84","author":"Bento","year":"2008","journal-title":"J. Leukocyte Biol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"4375","DOI":"10.1016\/j.bmcl.2004.06.097","article-title":"Discovery of potent and orally bioavailable N,N\u2032-diarylurea antagonists for the CXCR2 chemokine receptor","volume":"14","author":"Jin","year":"2004","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1111\/j.1365-2125.2011.03968.x","article-title":"SB-656933, a novel CXCR2 selective antagonist, inhibits ex vivo neutrophil activation and ozone-induced airway inflammation in humans","volume":"72","author":"Lazaar","year":"2011","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.jcf.2012.08.016","article-title":"CF2110399 Investigators. Safety and early treatment effects of the CXCR2 antagonist SB-656933 in patients with cystic fibrosis","volume":"12","author":"Moss","year":"2013","journal-title":"J. Cyst. Fibros."},{"key":"ref_166","unstructured":"Study number NCT00748410."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.pharmthera.2008.10.005","article-title":"CXCR2 antagonists for the treatment of pulmonary disease","volume":"121","author":"Chapman","year":"2009","journal-title":"Pharmacol. Therapeut."},{"key":"ref_168","first-page":"205","article-title":"Future therapeutic treatment of COPD: Struggle between oxidants and cytokines","volume":"2","author":"Yao","year":"2007","journal-title":"Int. J. Chron. Obstruct. Pulmon. Dis."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1111\/j.1365-2222.2011.03921.x","article-title":"Airway inflammation evaluated in a human nasal lipopolysaccharide challenge model by investigating the effect of a CXCR2 inhibitor","volume":"42","author":"Virtala","year":"2012","journal-title":"Clin. Exp. Allergy."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"2731","DOI":"10.1016\/j.bmcl.2007.02.080","article-title":"SAR studies on thiazolo[4,5-d]pyrimidine based CXCR2 antagonists involving a novel tandem displacement reaction","volume":"17","author":"Hunt","year":"2007","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_171","unstructured":"The safety, tolerability and pharmacokinetics of AZD5069, a novel CXCR2 antagonist, in healthy Japanese volunteers. Available online:www.richmondpharmacology.com\/downloads\/Publications\/ERS JSAD-JMAD poster_57.pdf."},{"key":"ref_172","unstructured":"Study number NCT01233232."},{"key":"ref_173","unstructured":"Study number NCT01255592."},{"key":"ref_174","unstructured":"Study number NCT01704495."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"12787","DOI":"10.1074\/jbc.R112.355461","article-title":"Turning receptors on and off with intracellular pepducins: New insights into G-protein-coupled receptor drug development","volume":"287","author":"Kuliopulos","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/nm1245","article-title":"Reversing systemic inflammatory response syndrome with chemokine receptor pepducins","volume":"11","author":"Kaneider","year":"2005","journal-title":"Nat. Med."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/j.1749-6632.2011.06039.x","article-title":"G protein-coupled receptor modulation with pepducins: Moving closer to the clinic","volume":"1226","author":"Dimond","year":"2011","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1038\/nature08956","article-title":"Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles","volume":"464","author":"Davis","year":"2010","journal-title":"Nature"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1002\/bit.22858","article-title":"Co-encapsulation of anti-BCR-ABL siRNA and imatinib mesylate in transferrin receptor-targeted sterically stabilized liposomes for chronic myeloid leukemia treatment","volume":"107","author":"Moreira","year":"2010","journal-title":"Biotechnol. Bioeng."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1038\/mt.2011.54","article-title":"Neuroblastoma-targeted nanoparticles entrapping siRNA specifically knockdown ALK","volume":"19","author":"Brignole","year":"2011","journal-title":"Mol. Ther."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1093\/jnci\/djn024","article-title":"Effect of interleukin-8 gene silencing with liposome-encapsulated small interfering RNA on ovarian cancer cell growth","volume":"100","author":"Merritt","year":"2008","journal-title":"J. Natl. Cancer I."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"E59","DOI":"10.1371\/journal.pbio.0000059","article-title":"Pten dose dictates cancer progression in the prostate","volume":"1","author":"Trotman","year":"2003","journal-title":"PLoS Biol."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/6\/8\/929\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:48:28Z","timestamp":1760219308000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/6\/8\/929"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,8,6]]},"references-count":182,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2013,8]]}},"alternative-id":["ph6080929"],"URL":"https:\/\/doi.org\/10.3390\/ph6080929","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,8,6]]}}}