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Review

Inflammation and CYP3A4-mediated drug metabolism in advanced cancer: impact and implications for chemotherapeutic drug dosing

, BMedSci (Hons), , BSc (Hons) PhD, , MBBS PhD FRACP & , BSc (Med) MBBS PhD FRACP
Pages 137-149 | Published online: 05 Feb 2008

Bibliography

  • Shimada T, Yamazaki H, Mimura M, Inui Y, Guengerich FP. Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther 1994;270(1):414-23
  • Kolars JC, Lown KS, Schmiedlin-Ren P, et al. CYP3A gene expression in human gut epithelium. Pharmacogenetics 1994;4(5):247-59
  • Brian WR, Sari MA, Iwasaki M, et al. Catalytic activities of human liver cytochrome P-450 IIIA4 expressed in Saccharomyces cerevisiae. Biochemistry 1990;29(51):11280-92
  • Araya Z, Wikvall K. 6alpha-hydroxylation of taurochenodeoxycholic acid and lithocholic acid by CYP3A4 in human liver microsomes. Biochim Biophys Acta 1999;1438(1):47-54
  • Stedman C, Robertson G, Coulter S, Liddle C. Feed-forward regulation of bile acid detoxification by CYP3A4: studies in humanized transgenic mice. J Biol Chem 2004;279(12):11336-43
  • Guengerich FP. Cytochrome P-450 3A4: regulation and role in drug metabolism. Ann Rev Pharmacol Toxicol 1999;39:1-17
  • Michalets EL. Update: clinically significant cytochrome P-450 drug interactions. Pharmacotherapy 1998;18(1):84-112
  • Liddle C, Robertson GR. Predicting inductive drug-drug interactions. Pharmacogenomics 2003;4(2):141-52
  • Gurney H. Dose calculation of anticancer drugs: a review of the current practice and introduction of an alternative. J Clin Oncol 1996;14(9):2590-611
  • Felici A, Verweij J, Sparreboom A. Dosing strategies for anticancer drugs: the good, the bad and body-surface area. Eur J Cancer 2002;38(13):1677-84
  • Calvert AH, Newell DR, Gumbrell LA, et al. Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol 1989;7(11):1748-56
  • Jodrell DI, Egorin MJ, Canetta RM, et al. Relationships between carboplatin exposure and tumor response and toxicity in patients with ovarian cancer. J Clin Oncol 1992;10(4):520-8
  • Fujita K. Cytochrome P450 and anticancer drugs. Curr Drug Metab 2006;7(1):23-37
  • Smith NF, Figg WD, Sparreboom A. Pharmacogenetics of irinotecan metabolism and transport: an update. Toxicol In Vitro 2006;20(2):163-75
  • Weinshilboum R. Inheritance and drug response. N Engl J Med 2003;348(6):529-37
  • Meyer UA. Pharmacogenetics – five decades of therapeutic lessons from genetic diversity. Nat Rev 2004;5(9):669-76
  • Wilkinson GR. Drug metabolism and variability among patients in drug response. N Engl J Med 2005;352(21):2211-21
  • Goh BC, Lee SC, Wang LZ, et al. Explaining interindividual variability of docetaxel pharmacokinetics and pharmacodynamics in Asians through phenotyping and genotyping strategies. J Clin Oncol 2002;20(17):3683-90
  • Rodriguez-Antona C, Ingelman-Sundberg M. Cytochrome P450 pharmacogenetics and cancer. Oncogene 2006;25(11):1679-91
  • Homepage of the Human Cytochrome P450 (CYP) Allele Nomenclature Committee (2001). Available at: URL: www.cypalleles.ki.se/ [Accessed January 2008]
  • Jin Y, Desta Z, Stearns V, et al. CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. J Natl Cancer Inst 2005;97(1):30-9
  • Gandara DR, Ohe Y, Kubota K, et al. Japan-SWOG common arm analysis of paclitaxel/carboplatin in advanced stage non-small cell lung cancer (NSCLC): a model for prospective comparison of cooperative group trials. J Clin Oncol (Meeting Abstracts) 2004;22:7007
  • Gandara DR, Kawaguchi T, Crowley JJ, et al. Pharmacogenomic (PG) analysis of Japan-SWOG common arm study in advanced stage non-small cell lung cancer (NSCLC): a model for testing population-related pharmacogenomics. J Clin Oncol (Meeting Abstracts) 2007;25:7500
  • Baker SD, Van Schaik RH, Rivory LP, et al. Factors affecting cytochrome P-450 3A activity in cancer patients. Clin Cancer Res 2004;10(24):8341-50
  • Lepper ER, Baker SD, Permenter M, et al. Effect of common CYP3A4 and CYP3A5 variants on the pharmacokinetics of the cytochrome P450 3A phenotyping probe midazolam in cancer patients. Clin Cancer Res 2005;11(20):7398-404
  • Tran A, Jullien V, Alexandre J, et al. Pharmacokinetics and toxicity of docetaxel: role of CYP3A, MDR1, and GST polymorphisms. Clin Pharmacol Ther 2006;79(6):570-80
  • Henningsson A, Marsh S, Loos WJ, et al. Association of CYP2C8, CYP3A4, CYP3A5, and ABCB1 polymorphisms with the pharmacokinetics of paclitaxel. Clin Cancer Res 2005;11(22):8097-104
  • Marsh S, Somlo G, Li X, et al. Pharmacogenetic analysis of paclitaxel transport and metabolism genes in breast cancer. Pharmacogenomics J 2007;7(5):362-5
  • Eap CB, Buclin T, Hustert E, et al. Pharmacokinetics of midazolam in CYP3A4- and CYP3A5-genotyped subjects. Eur J Clin Pharmacol 2004;60(4):231-6
  • Floyd MD, Gervasini G, Masica AL, et al. Genotype-phenotype associations for common CYP3A4 and CYP3A5 variants in the basal and induced metabolism of midazolam in European- and African-American men and women. Pharmacogenetics 2003;13(10):595-606
  • Shih PS, Huang JD. Pharmacokinetics of midazolam and 1′-hydroxymidazolam in Chinese with different CYP3A5 genotypes. Drug Metab Dispos 2002;30(12):1491-6
  • Yu KS, Cho JY, Jang IJ, et al. Effect of the CYP3A5 genotype on the pharmacokinetics of intravenous midazolam during inhibited and induced metabolic states. Clin Pharmacol Ther 2004;76(2):104-12
  • Fukuda T, Onishi S, Fukuen S, et al. CYP3A5 genotype did not impact on nifedipine disposition in healthy volunteers. Pharmacogenomics J 2004;4(1):34-9
  • Lown K, Kolars J, Turgeon K, et al. The erythromycin breath test selectively measures P450IIIA in patients with severe liver disease. Clin Pharmacol Ther 1992;51(3):229-38
  • Rivory LP, Slaviero K, Seale JP, et al. Optimizing the erythromycin breath test for use in cancer patients. Clin Cancer Res 2000;6(9):3480-5
  • Thummel KE, Shen DD, Podoll TD, et al. Use of midazolam as a human cytochrome P450 3A probe: I. In vitro-in vivo correlations in liver transplant patients. J Pharmacol Exp Ther 1994;271(1):549-56
  • Thummel KE, O'Shea D, Paine MF, et al. Oral first-pass elimination of midazolam involves both gastrointestinal and hepatic CYP3A-mediated metabolism. Clin Pharmacol Ther 1996;59(5):491-502
  • Kurnik D, Wood AJ, Wilkinson GR. The erythromycin breath test reflects P-glycoprotein function independently of cytochrome P450 3A activity. Clin Pharmacol Ther 2006;80(3):228-34
  • Rivory LP, Slaviero KA, Hoskins JM, Clarke SJ. The erythromycin breath test for the prediction of drug clearance. Clin Pharmacokinet 2001;40(3):151-8
  • Rivory LP, Slaviero KA, Clarke SJ. Hepatic cytochrome P450 3A drug metabolism is reduced in cancer patients who have an acute-phase response. Br J Cancer 2002;87(3):277-80
  • Mathijssen RH, De Jong FA, Van Schaik RH, et al. Prediction of irinotecan pharmacokinetics by use of cytochrome P450 3A4 phenotyping probes. J Natl Cancer Inst 2004;96(21):1585-92
  • Gurney H, Wong M, Balleine RL, et al. Imatinib disposition and ABCB1 (MDR1, P-glycoprotein) genotype. Clin Pharmacol Ther 2007;82(1):33-40
  • Wong M, Balleine RL, Blair EY, et al. Predictors of vinorelbine pharmacokinetics and pharmacodynamics in patients with cancer. J Clin Oncol 2006;24(16):2448-55
  • Swaisland HC, Cantarini MV, Fuhr R, Holt A. Exploring the relationship between expression of cytochrome P450 enzymes and gefitinib pharmacokinetics. Clin Pharmacokinet 2006;45(6):633-44
  • Eap CB, Buclin T, Cucchia G, et al. Oral administration of a low dose of midazolam (75 microg) as an in vivo probe for CYP3A activity. Eur J Clin Pharmacol 2004;60(4):237-46
  • Yamamoto N, Tamura T, Kamiya Y, et al. Correlation between docetaxel clearance and estimated cytochrome P450 activity by urinary metabolite of exogenous cortisol. J Clin Oncol 2000;18(11):2301-8
  • Yamamoto N, Tamura T, Murakami H, et al. Randomized pharmacokinetic and pharmacodynamic study of docetaxel: dosing based on body-surface area compared with individualized dosing based on cytochrome P450 activity estimated using a urinary metabolite of exogenous cortisol. J Clin Oncol 2005;23(6):1061-9
  • George J, Byth K, Farrell GC. Influence of clinicopathological variables on CYP protein expression in human liver. J Gastroenterol Hepatol 1996;11(1):33-9
  • Liddle C, Goodwin BJ, George J, Tapner M, Farrell GC. Separate and interactive regulation of cytochrome P450 3A4 by triiodothyronine, dexamethasone, and growth hormone in cultured hepatocytes. J Clin Endocrinol Metab 1998;83(7):2411-6
  • Villeneuve JP, Pichette V. Cytochrome P450 and liver diseases. Curr Drug Metab 2004;5(3):273-82
  • Kraemer MJ, Furukawa CT, Koup JR, et al. Altered theophylline clearance during an influenza B outbreak. Pediatrics 1982;69(4):476-80
  • Morgan ET. Regulation of cytochrome p450 by inflammatory mediators: why and how? Drug Metab Dispos 2001;29(3):207-12
  • Aitken AE, Richardson TA, Morgan ET. Regulation of drug-metabolizing enzymes and transporters in inflammation. Ann Rev Pharmacol Toxicol 2006;46:123-49
  • Petrovic V, Teng S, Piquette-Miller M. Regulation of drug transporters during infection and inflammation. Mol Interv 2007;7(2):99-111
  • Slaviero KA, Read JA, Clarke SJ, Rivory LP. Baseline nutritional assessment in advanced cancer patients receiving palliative chemotherapy. Nutr Cancer 2003;46(2):148-57
  • Alexandre J, Rey E, Girre V, et al. Relationship between cytochrome 3A activity, inflammatory status and the risk of docetaxel-induced febrile neutropenia: a prospective study. Ann Oncol 2007;18(1):168-72
  • Balkwill F, Charles KA, Mantovani A. Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell 2005;7(3):211-7
  • Karin M. Inflammation and cancer: the long reach of Ras. Nat Med 2005;11(1):20-1
  • Lin WW, Karin M. A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest 2007;117(5):1175-83
  • Galon J, Costes A, Sanchez-Cabo F, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 2006;313(5795):1960-4
  • Galon J, Fridman WH, Pages F. The adaptive immunologic microenvironment in colorectal cancer: a novel perspective. Cancer Res 2007;67(5):1883-6
  • Canna K, Mcardle PA, Mcmillan DC, et al. The relationship between tumour T-lymphocyte infiltration, the systemic inflammatory response and survival in patients undergoing curative resection for colorectal cancer. Br J Cancer 2005;92(4):651-4
  • Crozier JE, Mckee RF, Mcardle CS, et al. The presence of a systemic inflammatory response predicts poorer survival in patients receiving adjuvant 5-FU chemotherapy following potentially curative resection for colorectal cancer. Br J Cancer 2006;94(12):1833-6
  • Crozier JE, Mckee RF, Mcardle CS, et al. Preoperative but not postoperative systemic inflammatory response correlates with survival in colorectal cancer. Br J Surg 2007;94(8):1028-32
  • Elahi MM, Mcmillan DC, Mcardle CS, et al. The systemic inflammatory response predicts overall and cancer specific survival in patients with malignant lymphoma. Med Sci Monit 2005;11(2):CR75-8
  • Guillem P, Triboulet JP. Elevated serum levels of C-reactive protein are indicative of a poor prognosis in patients with esophageal cancer. Dis Esophagus 2005;18(3):146-50
  • Hilmy M, Campbell R, Bartlett JM, et al. The relationship between the systemic inflammatory response, tumour proliferative activity, T-lymphocytic infiltration and COX-2 expression and survival in patients with transitional cell carcinoma of the urinary bladder. Br J Cancer 2006;95(9):1234-8
  • Jamieson NB, Glen P, Mcmillan DC, et al. Systemic inflammatory response predicts outcome in patients undergoing resection for ductal adenocarcinoma head of pancreas. Br J Cancer 2005;92(1):21-3
  • Miki C, Konishi N, Ojima E, et al. C-reactive protein as a prognostic variable that reflects uncontrolled up-regulation of the IL-1-IL-6 network system in colorectal carcinoma. Dig Dis Sci 2004;49(6):970-6
  • Al Murri AM, Bartlett JM, Canney PA, et al. Evaluation of an inflammation-based prognostic score (GPS) in patients with metastatic breast cancer. Br J Cancer 2006;94(2):227-30
  • Crumley AB, Stuart RC, Mckernan M, Mcdonald AC, Mcmillan DC. Comparison of an inflammation-based prognostic score (GPS) with performance status (ECOG-ps) in patients receiving palliative chemotherapy for gastroesophageal cancer. J Gastroenterol Hepatol 2007;In Press
  • Glen P, Jamieson NB, Mcmillan DC, et al. Evaluation of an inflammation-based prognostic score in patients with inoperable pancreatic cancer. Pancreatology 2006;6(5):450-3
  • Mcmillan DC, Crozier JE, Canna K, Angerson WJ, Mcardle CS. Evaluation of an inflammation-based prognostic score (GPS) in patients undergoing resection for colon and rectal cancer. Int J Colorectal Dis 2007;22(8):881-6
  • Ramsey S, Lamb GW, Aitchison M, Graham J, Mcmillan DC. Evaluation of an inflammation-based prognostic score in patients with metastatic renal cancer. Cancer 2007;109(2):205-12
  • Read JA, Choy ST, Beale PJ, Clarke SJ. Evaluation of nutritional and inflammatory status of advanced colorectal cancer patients and its correlation with survival. Nutr Cancer 2006;55(1):78-85
  • Tirona RG, Kim RB. Nuclear receptors and drug disposition gene regulation. J Pharm Sci 2005;94(6):1169-86
  • Goodwin B, Hodgson E, Liddle C. The orphan human pregnane X receptor mediates the transcriptional activation of CYP3A4 by rifampicin through a distal enhancer module. Mol Pharmacol 1999;56(6):1329-39
  • Goodwin B, Hodgson E, D'Costa DJ, Robertson GR, Liddle C. Transcriptional regulation of the human CYP3A4 gene by the constitutive androstane receptor. Mol Pharmacol 2002;62(2):359-65
  • Gnerre C, Blattler S, Kaufmann MR, Looser R, Meyer UA. Regulation of CYP3A4 by the bile acid receptor FXR: evidence for functional binding sites in the CYP3A4 gene. Pharmacogenetics 2004;14(10):635-45
  • Thummel KE, Brimer C, Yasuda K, et al. Transcriptional control of intestinal cytochrome P-4503A by 1alpha,25-dihydroxy vitamin D3. Mol Pharmacol 2001;60(6):1399-406
  • Eloranta JJ, Kullak-Ublick GA. Coordinate transcriptional regulation of bile acid homeostasis and drug metabolism. Arch Biochem Biophys 2005;433(2):397-412
  • Goodwin B, Moore JT. CAR: detailing new models. Trends Pharmacol Sci 2004;25(8):437-41
  • Martinez-Jimenez CP, Jover R, Donato MT, Castell JV, Gomez-Lechon MJ. Transcriptional regulation and expression of CYP3A4 in hepatocytes. Curr Drug Metab 2007;8(2):185-94
  • Martinez-Jimenez CP, Gomez-Lechon MJ, Castell JV, Jover R. Transcriptional regulation of the human hepatic CYP3A4: identification of a new distal enhancer region responsive to CCAAT/enhancer-binding protein beta isoforms (liver activating protein and liver inhibitory protein). Mol Pharmacol 2005;67(6):2088-101
  • Aitken AE, Morgan ET. Gene-specific effects of inflammatory cytokines on cytochrome P450 2C, 2B6 and 3A4 mRNA levels in human hepatocytes. Drug Metab Dispos 2007;35(9):1687-93
  • Beigneux AP, Moser AH, Shigenaga JK, Grunfeld C, Feingold KR. Reduction in cytochrome P-450 enzyme expression is associated with repression of CAR (constitutive androstane receptor) and PXR (pregnane X receptor) in mouse liver during the acute phase response. Biochem Biophys Res Commun 2002;293(1):145-9
  • Pascussi JM, Gerbal-Chaloin S, Pichard-Garcia L, et al. Interleukin-6 negatively regulates the expression of pregnane X receptor and constitutively activated receptor in primary human hepatocytes. Biochem Biophys Res Commun 2000;274(3):707-13
  • Ruminy P, Gangneux C, Claeyssens S, et al. Gene transcription in hepatocytes during the acute phase of a systemic inflammation: from transcription factors to target genes. Inflamm Res 2001;50(8):383-90
  • Xie W, Barwick JL, Downes M, et al. Humanized xenobiotic response in mice expressing nuclear receptor SXR. Nature 2000;406(6794):435-9
  • Teng S, Piquette-Miller M. The involvement of the pregnane X receptor in hepatic gene regulation during inflammation in mice. J Pharmacol Exp Ther 2005;312(2):841-8
  • Richardson TA, Morgan ET. Hepatic cytochrome P450 gene regulation during endotoxin-induced inflammation in nuclear receptor knockout mice. J Pharmacol Exp Ther 2005;314(2):703-9
  • Jover R, Bort R, Gomez-Lechon MJ, Castell JV. Down-regulation of human CYP3A4 by the inflammatory signal interleukin-6: molecular mechanism and transcription factors involved. FASEB J 2002;16(13):1799-801
  • Sayeed MM. Alterations in calcium signaling and cellular responses in septic injury. New Horiz 1996;4(1):72-86
  • Ding X, Staudinger JL. Repression of PXR-mediated induction of hepatic CYP3A gene expression by protein kinase C. Biochem Pharmacol 2005;69(5):867-73
  • Hong YH, Varanasi US, Yang W, Leff T. AMP-activated protein kinase regulates HNF4alpha transcriptional activity by inhibiting dimer formation and decreasing protein stability. J Biol Chem 2003;278(30):27495-501
  • Viollet B, Kahn A, Raymondjean M. Protein kinase A-dependent phosphorylation modulates DNA-binding activity of hepatocyte nuclear factor 4. Mol Cell Biol 1997;17(8):4208-19
  • Lee HY, Suh YA, Robinson MJ, et al. Stress pathway activation induces phosphorylation of retinoid X receptor. J Biol Chem 2000;275(41):32193-9
  • Zimmerman TL, Thevananther S, Ghose R, Burns AR, Karpen SJ. Nuclear export of retinoid X receptor alpha in response to interleukin-1beta-mediated cell signaling: roles for JNK and SER260. J Biol Chem 2006;281(22):15434-40
  • Ghose R, Zimmerman TL, Thevananther S, Karpen SJ. Endotoxin leads to rapid subcellular re-localization of hepatic RXRalpha: a novel mechanism for reduced hepatic gene expression in inflammation. Nucl Recept 2004;2(1):4
  • Charles KA, Rivory LP, Brown SL, et al. Transcriptional repression of hepatic cytochrome P450 3A4 gene in the presence of cancer. Clin Cancer Res 2006;12(24):7492-7
  • Morgan ET, Norman CA. Pretranslational suppression of cytochrome P-450h (IIC11) gene expression in rat liver after administration of interferon inducers. Drug Metab Dispos 1990;18(5):649-53
  • Renton KW, Knickle LC. Regulation of hepatic cytochrome P-450 during infectious disease. Can J Physiol Pharmacol 1990;68(6):777-81
  • Cribb AE, Delaporte E, Kim SG, Novak RF, Renton KW. Regulation of cytochrome P-4501A and cytochrome P-4502E induction in the rat during the production of interferon alpha/beta. J Pharmacol Exp Ther 1994;268(1):487-94
  • Iber H, Li-Masters T, Chen Q, Yu S, Morgan ET. Regulation of hepatic cytochrome P450 2C11 via cAMP: implications for down-regulation in diabetes, fasting, and inflammation. J Pharmacol Exp Ther 2001;297(1):174-80
  • Morgan ET. Suppression of constitutive cytochrome P-450 gene expression in livers of rats undergoing an acute phase response to endotoxin. Mol Pharmacol 1989;36(5):699-707
  • Sewer MB, Koop DR, Morgan ET. Endotoxemia in rats is associated with induction of the P4504A subfamily and suppression of several other forms of cytochrome P450. Drug Metab Dispos 1996;24(4):401-7
  • Chung YC, Chaen YL, Hsu CP. Clinical significance of tissue expression of interleukin-6 in colorectal carcinoma. Anticancer Res 2006;26:3905-11
  • Knupfer H, Preiss R. Significance of interleukin-6 (IL-6) in breast cancer. Breast Cancer Res Treat 2007;102:129-35
  • Nicolini A, Capri A, Rossi G. Cytokines in breast cancer. Cytokine Growth Factor Rev 2006;17:325-37
  • Steuber T, Helo P, Lilja H. Circulating biomarkers for prostate cancer. World J Urol 2007;25:111-9
  • Cardillo MR, Ippoliti F. IL-6, IL-10 and HSP-90 expression in tissue microarrays from human prostate cancer assessed by computer-assisted image analysis. Anticancer Res 2006;26(5A):3409-16
  • Tan D, Wu X, Hou M, et al. Interleukin-6 polymorphism is associated with more aggressive prostate cancer. J Urol 2005;174(2):753-6
  • Legouffe E, Rodriguez C, Picot MC, et al. C-reactive protein serum level is a valuable and simple prognostic marker in non Hodgkin's lymphoma. Leuk Lymphoma 1998;31(3-4):351-7
  • Preti HA, Cabanillas F, Talpaz M, et al. Prognostic value of serum interleukin-6 in diffuse large-cell lymphoma. Ann Intern Med 1997;127(3):186-94
  • Seymour JF, Talpaz M, Cabanillas F, Wetzler M, Kurzrock R. Serum interleukin-6 levels correlate with prognosis in diffuse large-cell lymphoma. J Clin Oncol 1995;13(3):575-82
  • Niitsu N, Okamato M, Nakamine H, et al. Simultaneous elevation of the serum concentrations of vascular endothelial growth factor and interleukin-6 as independent predictors of prognosis in aggressive non-Hodgkin's lymphoma. Eur J Haematol 2002;68(2):91-100
  • Pedersen LM, Klausen TW, Davidsen UH, Johnsen HE. Early changes in serum IL-6 and VEGF levels predict clinical outcome following first-line therapy in aggressive non-Hodgkin's lymphoma. Ann Hematol 2005;84(8):510-6
  • Cheon YK, Cho YD, Moon JH, et al. Diagnostic utility of interleukin-6 (IL-6) for primary bile duct cancer and changes in serum IL-6 levels following photodynamic therapy. Am J Gastroenterol 2007;102(10):2164-70
  • Ramsey S, Lamb GW, Aitchison M, Mcmillan DC. The longitudinal relationship between circulating concentrations of C-reactive protein, interleukin-6 and interleukin-10 in patients undergoing resection for renal cancer. Br J Cancer 2006;95:1076-80
  • Mckeown DJ, Brown DJ, Kelly A, Wallace AM, Mcmillan DC. The relationship between circulating concentrations of C-reactive protein, inflammatory cytokines and cytokine receptors in patients with non-small-cell lung cancer. Br J Cancer 2004;91:1993-5

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