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PMID: 17541600 Published · ppublish English Journal Article Review

The NF-kappaB/IL-6 pathway in metastatic androgen-independent prostate cancer: new therapeutic approaches?

World journal of urology ·Vol. 25 ·No. 5 ·2007-10-00 ·Pages 477-89

Paule B, Terry S, Kheuang L, Soyeux P, Vacherot F, de la Taille A

Abstract

The nuclear factor of kappa beta (NF-kappaB) transcription factor regulates the transcription of numerous genes including that of interleukin 6 (IL-6). The IL-6 acts as an autocrine and paracrine growth factor of androgen-independent prostate cancer. An aberrant expression of the IL-6 gene and an increase in IL-6 expression are detected in bone metastatic and hormone-refractory prostate cancer. IL-6 has been suggested to have a crucial role in the resistance to chemotherapy or hormonal therapy involving apoptotic cell death. The NF-kappaB/IL-6 dependent pathways promote tumour-cell survival and in most situations protect cells against apoptotic stimuli. These data provide a rational framework for targeting NF-kappaB and IL-6 activity in novel biologically based therapies for aggressive and androgen independent prostate cancers.

MeSH Terms
Bone Neoplasms/drug therapy,physiopathology,secondary Cell Communication/drug effects,physiology Gene Expression Regulation, Neoplastic/drug effects Humans Interleukin-6/metabolism Male NF-kappa B/drug effects,metabolism Neoplasm Metastasis/drug therapy,physiopathology Osteoblasts/drug effects,pathology Prostatic Neoplasms/drug therapy,metabolism,physiopathology
Chemicals
Interleukin-6 NF-kappa B
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Paule Bernard
AP-HP, Groupe Hospitalier Henri Mondor, Service d'Urologie, 94000 Créteil, France.
Terry Stéphane
Kheuang Laurence
Soyeux Pascale
Vacherot Francis
de la Taille Alexandre
References (112)
112 references, click to expand
  1. Akt in prostate cancer: possible role in androgen-independence.
    Curr Drug Metab. 2003 Dec;4(6):487-96 PMID: 14683476
  2. NE-10 neuroendocrine cancer promotes the LNCaP xenograft growth in castrated mice.
    Cancer Res. 2004 Aug 1;64(15):5489-95 PMID: 15289359
  3. EGFR and Her-2 regulate the constitutive activation of NF-kappaB in PC-3 prostate cancer cells.
    Prostate. 2005 Oct 1;65(2):130-40 PMID: 15880609
  4. Stat3 activation in prostatic carcinomas.
    Prostate. 2002 Jun 1;51(4):241-6 PMID: 11987152
  5. Interleukin-6 is an autocrine growth factor in human prostate cancer.
    Am J Pathol. 2001 Dec;159(6):2159-65 PMID: 11733366
  6. The role of IKK in constitutive activation of NF-kappaB transcription factor in prostate carcinoma cells.
    J Cell Sci. 2002 Jan 1;115(Pt 1):141-51 PMID: 11801732
  7. The nuclear factor-kappa B RelA transcription factor is constitutively activated in human pancreatic adenocarcinoma cells.
    Clin Cancer Res. 1999 Jan;5(1):119-27 PMID: 9918209
  8. Transforming growth factor-beta1 activates interleukin-6 expression in prostate cancer cells through the synergistic collaboration of the Smad2, p38-NF-kappaB, JNK, and Ras signaling pathways.
    Oncogene. 2003 Jul 10;22(28):4314-32 PMID: 12853969
  9. Interleukin-6 regulates prostate-specific protein expression in prostate carcinoma cells by activation of the androgen receptor.
    Cancer Res. 1998 Oct 15;58(20):4640-5 PMID: 9788616
  10. In vivo antitumor efficacy of STAT3 blockade using a transcription factor decoy approach: implications for cancer therapy.
    Oncogene. 2005 Feb 3;24(6):970-9 PMID: 15592503
  11. Plasma levels of interleukin-6 and its soluble receptor are associated with prostate cancer progression and metastasis.
    Urology. 2001 Dec;58(6):1008-15 PMID: 11744478
  12. Control of apoptosis by Rel/NF-kappaB transcription factors.
    Oncogene. 1999 Nov 22;18(49):6910-24 PMID: 10602466
  13. Propapoptotic effects of NF-kappaB in LNCaP prostate cancer cells lead to serine protease activation.
    Cell Death Differ. 2002 Sep;9(9):972-80 PMID: 12181748
  14. Interleukin 6 receptor mRNA in prostate carcinomas and benign prostate hyperplasia.
    J Urol. 1994 May;151(5):1396-9 PMID: 7512667
  15. Phase I trial of the proteasome inhibitor bortezomib in patients with advanced solid tumors with observations in androgen-independent prostate cancer.
    J Clin Oncol. 2004 Jun 1;22(11):2108-21 PMID: 15169797
  16. Thalidomide and its analogues as cyclooxygenase inhibitors.
    Bioorg Med Chem Lett. 2002 Apr 8;12(7):1043-6 PMID: 11909713
  17. Id-1 expression promotes cell survival through activation of NF-kappaB signalling pathway in prostate cancer cells.
    Oncogene. 2003 Jul 17;22(29):4498-508 PMID: 12881706
  18. Interleukin-6 induces prostate cancer cell growth accompanied by activation of stat3 signaling pathway .
    Prostate. 2000 Feb 15;42(3):239-42 PMID: 10639195
  19. STAT3 mediates IL-6-induced neuroendocrine differentiation in prostate cancer cells .
    Prostate. 2000 Feb 15;42(3):186-95 PMID: 10639189
  20. Enhanced GBX2 expression stimulates growth of human prostate cancer cells via transcriptional up-regulation of the interleukin 6 gene.
    Clin Cancer Res. 2000 Feb;6(2):493-7 PMID: 10690529
  21. Role of NF-kappaB in p53-mediated programmed cell death.
    Nature. 2000 Apr 20;404(6780):892-7 PMID: 10786798
  22. Inhibition of nuclear factor kappaB activation in PC3 cells by genistein is mediated via Akt signaling pathway.
    Clin Cancer Res. 2002 Jul;8(7):2369-77 PMID: 12114442
  23. Control of oncogenesis and cancer therapy resistance by the transcription factor NF-kappaB.
    J Clin Invest. 2001 Feb;107(3):241-6 PMID: 11160144
  24. Elevated levels of circulating interleukin-6 and transforming growth factor-beta1 in patients with metastatic prostatic carcinoma.
    J Urol. 1999 Jan;161(1):182-7 PMID: 10037394
  25. Androgen receptor represses the neuroendocrine transdifferentiation process in prostate cancer cells.
    Mol Endocrinol. 2003 Sep;17(9):1726-37 PMID: 12775765
  26. Expression of the interleukin 6 receptor and interleukin 6 in prostate carcinoma cells.
    Cancer Res. 1990 Dec 15;50(24):7786-8 PMID: 2253221
  27. Synergistic roles for Pim-1 and c-Myc in STAT3-mediated cell cycle progression and antiapoptosis.
    Immunity. 1999 Dec;11(6):709-19 PMID: 10626893
  28. Bisphosphonates in the management of prostate carcinoma metastatic to the skeleton.
    Cancer. 2000 Jun 15;88(12 Suppl):3047-53 PMID: 10898350
  29. The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells.
    Cancer Res. 2001 Apr 1;61(7):3071-6 PMID: 11306489
  30. NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses.
    Annu Rev Immunol. 1998;16:225-60 PMID: 9597130
  31. Small molecule inhibitors of IkappaB kinase are selectively toxic for subgroups of diffuse large B-cell lymphoma defined by gene expression profiling.
    Clin Cancer Res. 2005 Jan 1;11(1):28-40 PMID: 15671525
  32. Interleukin-6 as a paracrine and autocrine growth factor in human prostatic carcinoma cells in vitro.
    Cancer Res. 1997 Jan 1;57(1):141-6 PMID: 8988055
  33. Constitutive activation of gp130 leads to neuroendocrine differentiation in vitro and in vivo.
    Prostate. 2005 Feb 15;62(3):282-9 PMID: 15389784
  34. Accelerated in vivo growth of prostate tumors that up-regulate interleukin-6 is associated with reduced retinoblastoma protein expression and activation of the mitogen-activated protein kinase pathway.
    Am J Pathol. 2003 Feb;162(2):655-63 PMID: 12547723
  35. Osteoprotegerin inhibits prostate cancer-induced osteoclastogenesis and prevents prostate tumor growth in the bone.
    J Clin Invest. 2001 May;107(10):1235-44 PMID: 11375413
  36. The addition of interleukin-6 soluble receptor and transforming growth factor beta1 improves a preoperative nomogram for predicting biochemical progression in patients with clinically localized prostate cancer.
    J Clin Oncol. 2003 Oct 1;21(19):3573-9 PMID: 12913106
  37. TGF-beta suppresses tumor progression in colon cancer by inhibition of IL-6 trans-signaling.
    Immunity. 2004 Oct;21(4):491-501 PMID: 15485627
  38. APPL suppresses androgen receptor transactivation via potentiating Akt activity.
    J Biol Chem. 2003 May 9;278(19):16820-7 PMID: 12621049
  39. Transcriptional regulation of bcl-2 by nuclear factor kappa B and its significance in prostate cancer.
    Oncogene. 2001 Nov 1;20(50):7342-51 PMID: 11704864
  40. Expression of nuclear factor-kappa B and I kappa B alpha proteins in prostatic adenocarcinomas: correlation of nuclear factor-kappa B immunoreactivity with disease recurrence.
    Clin Cancer Res. 2004 Apr 1;10 (7):2466-72 PMID: 15073126
  41. Endogenous interleukin 6 is a resistance factor for cis-diamminedichloroplatinum and etoposide-mediated cytotoxicity of human prostate carcinoma cell lines.
    Cancer Res. 1995 Oct 15;55(20):4633-9 PMID: 7553641
  42. Interleukin-6 differentially regulates androgen receptor transactivation via PI3K-Akt, STAT3, and MAPK, three distinct signal pathways in prostate cancer cells.
    Biochem Biophys Res Commun. 2003 Jun 6;305(3):462-9 PMID: 12763015
  43. Mitogen-activated protein kinase/ERK kinase kinases 2 and 3 activate nuclear factor-kappaB through IkappaB kinase-alpha and IkappaB kinase-beta.
    J Biol Chem. 1999 Mar 26;274(13):8355-8 PMID: 10085062
  44. Antitumor and antimetastatic activities of docetaxel are enhanced by genistein through regulation of osteoprotegerin/receptor activator of nuclear factor-kappaB (RANK)/RANK ligand/MMP-9 signaling in prostate cancer.
    Cancer Res. 2006 May 1;66(9):4816-25 PMID: 16651437
  45. Nuclear factor-kappaB is constitutively active in C-cell carcinoma and required for RET-induced transformation.
    Cancer Res. 2001 Jun 1;61(11):4526-35 PMID: 11389085
  46. p300 mediates androgen-independent transactivation of the androgen receptor by interleukin 6.
    Cancer Res. 2002 Oct 15;62(20):5632-6 PMID: 12384515
  47. From HER2/Neu signal cascade to androgen receptor and its coactivators: a novel pathway by induction of androgen target genes through MAP kinase in prostate cancer cells.
    Proc Natl Acad Sci U S A. 1999 May 11;96(10):5458-63 PMID: 10318905
  48. Interleukin 6, a nuclear factor-kappaB target, predicts resistance to docetaxel in hormone-independent prostate cancer and nuclear factor-kappaB inhibition by PS-1145 enhances docetaxel antitumor activity.
    Clin Cancer Res. 2006 Sep 15;12(18):5578-86 PMID: 17000695
  49. The PTEN tumor suppressor protein inhibits tumor necrosis factor-induced nuclear factor kappa B activity.
    J Biol Chem. 2001 Jul 20;276(29):27740-4 PMID: 11356844
  50. Genistein inhibits radiation-induced activation of NF-kappaB in prostate cancer cells promoting apoptosis and G2/M cell cycle arrest.
    BMC Cancer. 2006 Apr 26;6:107 PMID: 16640785
  51. IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer.
    Cell. 2004 Aug 6;118(3):285-96 PMID: 15294155
  52. Constitutive activation of IkappaB kinase alpha and NF-kappaB in prostate cancer cells is inhibited by ibuprofen.
    Oncogene. 1999 Dec 2;18(51):7389-94 PMID: 10602496
  53. Androgen deprivation increases p300 expression in prostate cancer cells.
    Cancer Res. 2007 Apr 1;67(7):3422-30 PMID: 17409453
  54. Interleukin-6 induces G1 arrest through induction of p27(Kip1), a cyclin-dependent kinase inhibitor, and neuron-like morphology in LNCaP prostate tumor cells.
    Biochem Biophys Res Commun. 1999 Apr 13;257(2):609-14 PMID: 10198259
  55. Akt suppresses androgen-induced apoptosis by phosphorylating and inhibiting androgen receptor.
    Proc Natl Acad Sci U S A. 2001 Jun 19;98 (13):7200-5 PMID: 11404460
  56. Genetic analysis of neuroendocrine tumor cells in prostatic carcinoma.
    Prostate. 2006 Feb 15;66(3):227-34 PMID: 16173029
  57. NF-kappaB activation in human prostate cancer: important mediator or epiphenomenon?
    J Cell Biochem. 2004 Jan 1;91(1):100-17 PMID: 14689584
  58. Suppression versus induction of androgen receptor functions by the phosphatidylinositol 3-kinase/Akt pathway in prostate cancer LNCaP cells with different passage numbers.
    J Biol Chem. 2003 Dec 19;278(51):50902-7 PMID: 14555644
  59. Activation of the androgen receptor N-terminal domain by interleukin-6 via MAPK and STAT3 signal transduction pathways.
    J Biol Chem. 2002 Mar 1;277(9):7076-85 PMID: 11751884
  60. Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points.
    J Clin Oncol. 1996 Jun;14(6):1756-64 PMID: 8656243
  61. Prostate carcinoma cell death resulting from inhibition of proteasome activity is independent of functional Bcl-2 and p53.
    Oncogene. 1998 Dec 3;17 (22):2889-99 PMID: 9879995
  62. Thalidomid: current role in the treatment of non-plasma cell malignancies.
    J Clin Oncol. 2004 Jun 15;22(12):2477-88 PMID: 15197211
  63. Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases.
    N Engl J Med. 1997 Apr 10;336(15):1066-71 PMID: 9091804
  64. Contributions of mitogen-activated protein kinase and nuclear factor kappa B to N-(4-hydroxyphenyl)retinamide-induced apoptosis in prostate cancer cells.
    Mol Carcinog. 2002 Nov;35(3):127-37 PMID: 12410564
  65. Enhanced chemosensitivity to CPT-11 with proteasome inhibitor PS-341: implications for systemic nuclear factor-kappaB inhibition.
    Cancer Res. 2001 May 1;61(9):3535-40 PMID: 11325813
  66. Selective inhibition of NF-kappa B blocks osteoclastogenesis and prevents inflammatory bone destruction in vivo.
    Nat Med. 2004 Jun;10(6):617-24 PMID: 15156202
  67. STAT3 orchestrates contradictory signals in cytokine-induced G1 to S cell-cycle transition.
    EMBO J. 1998 Nov 16;17(22):6670-7 PMID: 9822610
  68. NF-kappaB function in growth control: regulation of cyclin D1 expression and G0/G1-to-S-phase transition.
    Mol Cell Biol. 1999 Apr;19(4):2690-8 PMID: 10082535
  69. Androgen receptor signaling: mechanism of interleukin-6 inhibition.
    Cancer Res. 2004 Apr 1;64(7):2619-26 PMID: 15059919
  70. Constitutive activation of NF-kappaB during progression of breast cancer to hormone-independent growth.
    Mol Cell Biol. 1997 Jul;17(7):3629-39 PMID: 9199297
  71. Mutations in the IkBa gene in Hodgkin's disease suggest a tumour suppressor role for IkappaBalpha.
    Oncogene. 1999 May 20;18(20):3063-70 PMID: 10340377
  72. Inhibition of NFkappaB activity through maintenance of IkappaBalpha levels contributes to dihydrotestosterone-mediated repression of the interleukin-6 promoter.
    J Biol Chem. 1996 Oct 18;271(42):26267-75 PMID: 8824277
  73. NFkappaB: a pivotal transcription factor in prostate cancer metastasis to bone.
    Clin Orthop Relat Res. 2003 Oct;(415 Suppl):S75-85 PMID: 14600595
  74. Constitutive activation of the Ras/mitogen-activated protein kinase signaling pathway promotes androgen hypersensitivity in LNCaP prostate cancer cells.
    Cancer Res. 2003 Apr 15;63(8):1981-9 PMID: 12702592
  75. The ubiquitin-proteasome pathway is required for processing the NF-kappa B1 precursor protein and the activation of NF-kappa B.
    Cell. 1994 Sep 9;78(5):773-85 PMID: 8087845
  76. Blockade of NF-kappaB activity in human prostate cancer cells is associated with suppression of angiogenesis, invasion, and metastasis.
    Oncogene. 2001 Jul 12;20(31):4188-97 PMID: 11464285
  77. Transcriptional activation of the p21(WAF1,CIP1,SDI1) gene by interleukin-6 type cytokines. A prerequisite for their pro-differentiating and anti-apoptotic effects on human osteoblastic cells.
    J Biol Chem. 1998 Aug 14;273(33):21137-44 PMID: 9694869
  78. Bombesin stimulates nuclear factor kappa B activation and expression of proangiogenic factors in prostate cancer cells.
    Cancer Res. 2003 Jul 1;63(13):3495-502 PMID: 12839933
  79. Secreted transforming growth factor beta2 activates NF-kappaB, blocks apoptosis, and is essential for the survival of some tumor cells.
    Proc Natl Acad Sci U S A. 2004 May 4;101(18):7112-7 PMID: 15118089
  80. Requirement of ErbB2 for signalling by interleukin-6 in prostate carcinoma cells.
    Nature. 1998 May 7;393(6680):83-5 PMID: 9590694
  81. Proteasome inhibitors: a novel class of potent and effective antitumor agents.
    Cancer Res. 1999 Jun 1;59(11):2615-22 PMID: 10363983
  82. Interleukin-6 and prostate cancer progression.
    Cytokine Growth Factor Rev. 2001 Mar;12(1):33-40 PMID: 11312117
  83. Cytokine traps: multi-component, high-affinity blockers of cytokine action.
    Nat Med. 2003 Jan;9(1):47-52 PMID: 12483208
  84. Interleukin-6 activates phosphatidylinositol-3 kinase, which inhibits apoptosis in human prostate cancer cell lines.
    Prostate. 2000 Jan;42(1):1-7 PMID: 10579793
  85. Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors.
    Oncogene. 2000 May 15;19(21):2548-56 PMID: 10851053
  86. Endogenous inhibitors of nuclear factor-kappaB, an opportunity for cancer control.
    Cancer Res. 2004 Nov 15;64(22):8135-8 PMID: 15548674
  87. Aberrant nuclear factor-kappaB/Rel expression and the pathogenesis of breast cancer.
    J Clin Invest. 1997 Dec 15;100(12):2952-60 PMID: 9399940
  88. NF-kappaB in cancer: from innocent bystander to major culprit.
    Nat Rev Cancer. 2002 Apr;2(4):301-10 PMID: 12001991
  89. A mechanism for hormone-independent prostate cancer through modulation of androgen receptor signaling by the HER-2/neu tyrosine kinase.
    Nat Med. 1999 Mar;5(3):280-5 PMID: 10086382
  90. An essential role for NF-kappaB in preventing TNF-alpha-induced cell death.
    Science. 1996 Nov 1;274(5288):782-4 PMID: 8864118
  91. Regulation of interleukin-6-mediated PI3K activation and neuroendocrine differentiation by androgen signaling in prostate cancer LNCaP cells.
    Prostate. 2004 Jun 15;60(1):61-7 PMID: 15129430
  92. C/EBPdelta is a downstream mediator of IL-6 induced growth inhibition of prostate cancer cells.
    Prostate. 2005 May 1;63(2):143-54 PMID: 15486993
  93. Mechanisms of constitutive NF-kappaB activation in human prostate cancer cells.
    Prostate. 2002 Aug 1;52(3):183-200 PMID: 12111695
  94. Constitutive activation of nuclear factor kappaB p50/p65 and Fra-1 and JunD is essential for deregulated interleukin 6 expression in prostate cancer.
    Cancer Res. 2003 May 1;63(9):2206-15 PMID: 12727841
  95. Prostate cancer cells (LNCaP) generated after long-term interleukin 6 (IL-6) treatment express IL-6 and acquire an IL-6 partially resistant phenotype.
    Clin Cancer Res. 2001 Sep;7(9):2941-8 PMID: 11555613
  96. PAR1-mediated NFkappaB activation promotes survival of prostate cancer cells through a Bcl-xL-dependent mechanism.
    J Cell Biochem. 2005 Oct 15;96(3):641-52 PMID: 16052512
  97. Circulating levels of interleukin-6 in patients with hormone refractory prostate cancer.
    Prostate. 1999 Oct 1;41(2):127-33 PMID: 10477909
  98. Inhibition of constitutively activated Stat3 signaling pathway suppresses growth of prostate cancer cells.
    Cancer Res. 2000 Mar 1;60(5):1225-8 PMID: 10728680
  99. Expression of epidermal growth factor receptor correlates with disease relapse and progression to androgen-independence in human prostate cancer.
    Clin Cancer Res. 2002 Nov;8(11):3438-44 PMID: 12429632
  100. Antiangiogenic activity of N-substituted and tetrafluorinated thalidomide analogues.
    Cancer Res. 2003 Jun 15;63(12):3189-94 PMID: 12810647
  101. Inhibition of NF-kappa B activity by thalidomide through suppression of IkappaB kinase activity.
    J Biol Chem. 2001 Jun 22;276(25):22382-7 PMID: 11297551
  102. Constitutive activation of nuclear factor kappaB in hepatocellular carcinoma.
    Cancer. 2000 Dec 1;89(11):2274-81 PMID: 11147598
  103. p300 regulates androgen receptor-independent expression of prostate-specific antigen in prostate cancer cells treated chronically with interleukin-6.
    Cancer Res. 2005 Jul 1;65(13):5965-73 PMID: 15994976
  104. Interleukin 6 activates androgen receptor-mediated gene expression through a signal transducer and activator of transcription 3-dependent pathway in LNCaP prostate cancer cells.
    Cancer Res. 2000 Apr 15;60(8):2132-5 PMID: 10786674
  105. Constitutive activation of P I3 K-Akt and NF-kappaB during prostate cancer progression in autochthonous transgenic mouse model.
    Prostate. 2005 Aug 1;64(3):224-39 PMID: 15712212
  106. Alteration of the hormonal bioactivity of parathyroid hormone-related protein (PTHrP) as a result of limited proteolysis by prostate-specific antigen.
    Urology. 1996 Aug;48(2):317-25 PMID: 8753751
  107. Interleukin-6 promotes androgen-independent growth in LNCaP human prostate cancer cells.
    Clin Cancer Res. 2003 Jan;9(1):370-6 PMID: 12538490
  108. Activation-dependent transcriptional regulation of the human Fas promoter requires NF-kappaB p50-p65 recruitment.
    Mol Cell Biol. 1999 Mar;19(3):2098-108 PMID: 10022897
  109. Protease inhibitor-induced apoptosis: accumulation of wt p53, p21WAF1/CIP1, and induction of apoptosis are independent markers of proteasome inhibition.
    Leukemia. 2000 Jul;14(7):1276-83 PMID: 10914553
  110. A Stat3-interacting protein (StIP1) regulates cytokine signal transduction.
    Proc Natl Acad Sci U S A. 2000 Aug 29;97(18):10120-5 PMID: 10954736
  111. Interleukin-6 induces androgen responsiveness in prostate cancer cells through up-regulation of androgen receptor expression.
    Clin Cancer Res. 2001 Jun;7(6):1773-81 PMID: 11410519
  112. NF-kappa B activates prostate-specific antigen expression and is upregulated in androgen-independent prostate cancer.
    Mol Cell Biol. 2002 Apr;22(8):2862-70 PMID: 11909978
Article Info
Journal
World journal of urology
Abbr.
World J Urol
ISSN
0724-4983
DOI
10.1007/s00345-007-0175-6
Published
2007-10-00
Epub
2007-00-31
Pages
477-89
Language
English
Region
Germany
NLM ID
8307716
Subset
IM
External Links
PubMed source DOI: 10.1007/s00345-007-0175-6 View journal details
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