Molecular mechanisms in urinary bladder carcinogenesis

Journal of B.U.ON.

Volumn 16, Issue 4, 2011, Pages 589-601

  Volanis, D ^a   Papadopoulos, Georgios I ^b   Doumas, K ^b   Gkialas, I ^b   Delakas, D ^a  

^a IASO GENERAL HOSPITAL   (Greece)

^b G GENNIMATAS GENERAL HOSPITAL   (Greece)

Author keywords

Bladder cancer; Carcinogenesis; DNA; Markers; Oncogenes; Risk factors

Indexed keywords

CYCLIN DEPENDENT KINASE INHIBITOR 2A; DEATH ASSOCIATED PROTEIN KINASE;

BLADDER CANCER; BLADDER CARCINOGENESIS; CHROMOSOME 3P; CHROMOSOME 9; CHROMOSOME ABERRATION; DIETARY INTAKE; DNA METHYLATION; DNA REPAIR; EARLY DIAGNOSIS; ENVIRONMENTAL FACTOR; EPITHELIUM DYSPLASIA; GENE SILENCING; GENETIC SUSCEPTIBILITY; HETEROZYGOSITY LOSS; HUMAN; MICROSATELLITE INSTABILITY; OCCUPATIONAL EXPOSURE; PROMOTER REGION; PROTO ONCOGENE; REVIEW; RISK FACTOR; SMOKING; TRANSITIONAL CELL CARCINOMA; TUMOR SUPPRESSOR GENE;

CELL TRANSFORMATION, NEOPLASTIC; FEMALE; HUMANS; MALE; RISK FACTORS; URINARY BLADDER NEOPLASMS;

EID: 84855425712     PISSN: 11070625     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (129)

1. Jemal A, Siegel R, Xu J et al. Cancer statistics, 2010. CA Cancer J Clin 2010; 6: 277-300.
2. Scosyrev E, Trivedi D, Messing E. Female bladder cancer: incidence, treatment, and outcome. Curr Opin Urol 2010; 20: 404-408.
3. Edwards BK, Ward E, Kohler BA et al. Annual report to the nation on the status of cancer, 1975-2006, featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates. Cancer 2010; 116: 544-573.
4. Pectasides D, Iacovidou I, Psyrri A et al. Primary non-Hodgkin's lymphoma of the bladder: report of two cases and review of literature. J BUON 2008; 13: 277-279. (Pubitemid 351836714)
5. Kaya AO, Coskun U, Yildiz R et al. Primary pure small cell carcinoma of the urinary bladder that responded to carboplatin plus etoposide: a case report and review of the literature. J BUON 2009; 14: 703-706.
6. van Rhijn BW, Burger M, Lotan Y et al. Recurrence and progression of disease in non-muscle-invasive bladder cancer from epidemiology to treatment strategy. Eur Urol 2009; 56: 430-442.
7. Zieger K, Marcussen N, Borre M et al. Consistent genomic alterations in carcinoma in situ of the urinary bladder confirm the presence of two major pathways in bladder cancer development. Int J Cancer 2009; 125: 2095-2103.
8. Schulz WA. Understanding urothelial carcinoma through cancer pathways. Int J Cancer 2006; 119: 1513-1518. (Pubitemid 44258755)
9. Castillo-Martin M, Domingo-Domenech J, Kami-Schmidt O et al. Molecular pathways of urothelial development and bladder tumorigenesis. Urol Oncol 2010; 28: 401-418.
10. Gkialas I, Papadopoulos G, Iordanidou L et al. Evaluation of urine tumor-associated trypsin inhibitor, CYFRA21-1, and urinary bladder cancer antigen for detection of high-grade bladder carcinoma. Urology 2008; 72: 1159-1163.
11. Skagias L, Politi E, Karameris A et al. Prognostic impact of HER2/neu protein in urothelial bladder cancer. Survival analysis of 80 cases and an overview of almost 20 years' research. J BUON 2009; 14: 457-462.
12. Zaravinos A, Lambou GI, Volanis D et al. Spotlight on differentially expressed genes in urinary bladder cancer. PLOS One 2011; 5: 6: e18255.
13. Ioachim E, Stavropoulos NE, Charalabopoulos K et al. Immunohistochemical prognostic markers in bladder cancer. J BUON 2002; 7: 207-216. (Pubitemid 35345202)
14. Volanis D, Kadiyska T, Galanis A et al. Environmental factors and genetic susceptibility promote urinary bladder cancer. Toxicol Lett 2010; 193: 131-137.
15. Boffetta P. Tobacco smoking and risk of bladder cancer. Scand J Urol Nephrol Suppl 2008; 218: 45-54.
16. Wiencke JK. DNA adduct burden and tobacco carcinogenesis. Oncogene 2002; 21: 7376-7391. (Pubitemid 35305595)
17. Pfeifer GP, Denissenko MF, Olivier M et al. Tobacco smoke carcinogens, DNA damage and p53 mutations in smoking-associated cancers. Oncogene 2002; 21: 7435-7451. (Pubitemid 35305599)
18. Wallerand H, Bakkar AA, de Medina SG et al. Mutations in TP53, but not FGFR3, in urothelial cell carcinoma of the bladder are influenced by smoking: contribution of exogenous versus endogenous carcinogens. Carcinogenesis 2005; 26: 177-184. (Pubitemid 40207713)
19. van Rhijn BW, Vis AN, van der Kwast TH et al. Molecular grading of urothelial cell carcinoma with fibroblast growth factor receptor 3 and MIB-1 is superior to pathologic grade for the prediction of clinical outcome. J Clin Oncol 2003; 21: 1912-1921. (Pubitemid 46606378)
20. Dietrich H, Dietrich B. Ludwig Rehn (1849-1930)-pioneering findings on the aetiology of bladder tumours. World J Urol 2001; 19: 151-153. (Pubitemid 33777047)
21. Delclos GL, Lerner SP. Occupational risk factors. Scand J Urol Nephrol Suppl 2008; 218: 58-63.
22. Leppert JT, Shvarts O, Kawaoka K et al. Prevention of bladder cancer: a review. Eur Urol 2006; 49: 226-234. (Pubitemid 43197858)
23. Neumann HG. Aromatic amines: mechanisms of carcinogenesis and implications for risk assessment. Front Biosci 2010; 15: 1119-1130.
24. Mink PJ, Alexander DD, Barraj LM et al. Low-level arsenic exposure in drinking water and bladder cancer: a review and meta-analysis. Regul Toxicol Pharmacol 2008; 52: 299-310.
25. Huang C, Ke Q, Costa M et al. Molecular mechanisms of arsenic carcinogenesis. Mol Cell Biochem 2004; 255: 57-66. (Pubitemid 38159765)
26. Klein CB, Leszczynska J, Hickey C et al. Further evidence against a direct genotoxic mode of action for arsenic-induced cancer. Toxicol Appl Pharmacol 2007; 222: 289-297. (Pubitemid 47198279)
27. Wilhelm-Benartzi CS, Koestler DC, Houseman EA et al. DNA methylation profiles delineate etiologic heterogeneity and clinically important subgroups of bladder cancer. Carcinogenesis 2010; 31: 1972-1976.
28. Hasegawa R, Futakuchi M, Mizoguchi Y et al. Studies of initiation and promotion of carcinogenesis by N-nitroso compounds. Cancer Lett 1998; 123: 185-191. (Pubitemid 28064098)
29. Chiu HF, Tsai SS, Yang CY. Nitrate in drinking water and risk of death from bladder cancer: an ecological case-control study in Taiwan. J Toxicol Environ Health A 2007; 70: 1000-1004.
30. Ferrucci LM, Sinha R, Ward MH et al. Meat and components of meat and the risk of bladder cancer in the NIH-AARP Diet and Health Study. Cancer 2010; 116: 4345-4353.
31. Zeegers MP, Selen RF, Kleinjans JC et al. Nitrate intake does not influence bladder cancer risk: the Netherlands cohort study. Environ Health Perspect 2006; 114: 1527-1531. (Pubitemid 44509649)
32. Boorjian S, Cowan JE, Konety BR et al. Cancer of the Prostate Strategic Urologic Research Endeavor Investigators. Bladder cancer incidence and risk factors in men with prostate cancer: results from Cancer of the Prostate Strategic Urologic Research Endeavor. J Urol 2007; 177: 883-887.
33. Franco R, Schoneveld O, Georgakilas AG et al. Oxidative stress, DNA methylation and carcinogenesis. Cancer Lett 2008; 266: 6-11.
34. Romanenko A, Morimura K, Wanibuchi H et al. Increased oxidative stress with gene alteration in urinary bladder urothelium after the Chernobyl accident. Int J Cancer 2000; 86: 790-798.
35. Romanenko A, Kakehashi A, Morimura K et al. Urinary bladder carcinogenesis induced by chronic exposure to persistent low-dose ionizing radiation after Chernobyl accident Carcinogenesis 2009; 30: 1821-1831.
36. Vennervald BJ, Polman K. Helminths and malignancy. Parasite Immunol 2009; 31: 686-696.
37. Botelho M, Ferreira AC, Oliveira MJ et al. Schistosoma haematobium total antigen induces increased proliferation, migration and invasion, and decreases apoptosis of normal epithelial cells. Int J Parasitol 2009; 39: 1083-1091.
38. El Nouby KA, Abd El Hameed AH, Negm OE et al. Genetic polymorphism of glutathione-S-transferase (GST-M1 and GST-T1) in schistosomiasis-associated bladder cancer in Egyptian patients. J Egypt Soc Parasitai 2008; 38: 991-1006.
39. Conklin DJ, Haberzettl P, Prough RA et al. Glutathione-S-transferase P protects against endothelial dysfunction induced by exposure to tobacco smoke. Am J Physiol Heart Circ Physiol 2009; 296: H1586-1597.
40. Reszka E, Wasowicz W, Gromadzinska J. Antioxidant defense markers modulated by glutathione S-transferase genetic polymorphism: results of lung cancer case-control study. Genes Nutr 2007; 2: 287-294.
41. Zeng FF, Liu SY, Wei W et al. Genetic polymorphisms of glutathione S-transferase T1 and bladder cancer risk: a meta-analysis. Clin Exp Med 2010; 10: 59-68.
42. Zhang R, Xu G, Chen W et al. Genetic polymorphisms of glutathione S-transferase M1 and bladder cancer risk: a meta-analysis of 26 studies. Mol Biol Rep 2010 Nov 17 [Epub ahead of print].
43. García-Closas M, Malats N, Silverman D et al. NAT2 slow acetylation, GSTM1 null genotype, and risk of bladder cancer: results from the Spanish Bladder Cancer Study and meta-analyses. Lancet 2005; 366: 649-659. (Pubitemid 41176017)
44. Moore L, Baris D, Figueroa J et al. GSTM1 Null and NAT2 Slow Acetylation Genotypes, Smoking Intensity, and Bladder Cancer Risk: Results from the New England Bladder Cancer Case-Control Study and NAT2 Meta-Analysis. Carcinogenesis 2011; 32: 182-189.
45. Arizono K, Osada Y, Kuroda Y. DNA repair gene hOGG1 codon 326 and XRCC1 codon 399 polymorphisms and bladder cancer risk in a Japanese population. Jpn J Clin Oncol 2008; 38: 186-191. (Pubitemid 351419742)
46. Duggan BJ, Gray SB, McKnight JJ et al. Oligoclonality in bladder cancer: the implication for molecular therapies. J Urol 2004; 171: 419-425. (Pubitemid 37549202)
47. Höglund M. On the origin of syn- and metachronous urothelial carcinomas. Eur Urol 2007; 51: 1185-1193. (Pubitemid 46436302)
48. Borhan A, Reeder JE, O'Connel MJ et al. Grade progression and regression in recurrent urothelial cancer. J Urol 2003; 169: 2106-2109.
49. Blanes A, Rubio J, Sanchez-Carrillo JJ et al. Coexistent intraurothelial carcinoma and muscle-invasive urothelial carcinoma of the bladder: clonality and somatic down-regulation of DNA mismatch repair. Hum Pathol 2009; 40: 988-997.
50. Jones TD, Wang M, Eble JN, McLennan GT et al. Molecular Evidence Supporting Field Effect in Urothelial Carcinogenesis. Clin Cancer Res 2005; 11: 6512-6519. (Pubitemid 41338989)
51. Denzinger S, Mohren K, Knuechel R et al. Improved clonality analysis of multifocal bladder tumors by combination of histopathologic organ mapping, loss of heterozygosity, fluorescence in situ hybridization, and p53 analyses. Hum Pathol 2006; 37: 143-151. (Pubitemid 43099833)
52. Qin SL, Chen XJ, Xu X et al. Detection of chromosomal alterations in bladder transitional cell carcinomas from Northern China by comparative genomic hybridization. Cancer Lett 2006; 238: 230-239. (Pubitemid 43867913)
53. Richter J, Wagner U, Schraml P et al. Chromosomal imbalances are associated with a high risk of progression in early invasive (pT1) urinary bladder cancer. Cancer Res 1999; 59: 5687-5691.
54. Hirao S, Hirao T, Marsit C et al. Loss of heterozygosity on chromosome 9q and p53 alterations in human bladder cancer. Cancer 2005; 104: 1918-1923. (Pubitemid 41513175)
55. Abraham R, Pagano F, Gomella LG et al. Chromosomal deletions in bladder cancer: shutting down pathways. Front Biosci 2007; 12: 826-838. (Pubitemid 46846859)
56. Hartman A Schlake G, Zaak D et al. Occurrence of Chromosome 9 and p53 Alterations in Multifocal Dysplasia and Carcinoma in Situ of Human Urinary Bladder. Cancer Res 2002; 62: 809-818. (Pubitemid 34126958)
57. Dinney CP, McConkey DJ, Millikan RE et al. Focus on bladder cancer. Cancer Cell 2004; 6: 111-116. (Pubitemid 39485683)
58. Chapman EJ, Hamden P, Chambers P et al. Comprehensive analysis of CDKN2A status in microdissected urothelial cell carcinoma reveals potential haploinsufficiency, a high frequency of homozygous co-deletion and associations with clinical phenotype. Clin Cancer Res 2005; 11: 5740-5747. (Pubitemid 41170298)
59. Simon R, Bürger H, Brinkschmidt C et al. Chromosomal aberrations associated with invasion in papillary superficial bladder cancer. J Pathol 1998; 185: 345-351. (Pubitemid 28355966)
60. Stoer R, Wissmann C, Suzuki H et al. Deletions of chromosome 8p and loss of sFRP1 expression are progression markers of papillary bladder cancer. Lab Invest 2004; 84: 465-478. (Pubitemid 41656474)
61. Gallucci M, Guadagni F, Marzano R et al. Status of the p53, p16, RB1, and HER-2 genes and chromosomes 3, 7, 9, and 17 in advanced bladder cancer: correlation with adjacent mucosa and pathological parameters. J Clin Pathol 2005; 58: 367-371.
62. Mhawech-Fauceglia P, Cheney RT, Schwaller J. Genetic alterations in urothelial bladder carcinoma: an updated review. Cancer 2006; 106: 1205-1216. (Pubitemid 43363896)
63. Roupret M, Fromont G, Azzouzi AR et al. Microsatellite instability as predictor of survival in patients with invasive upper urinary tract transitional cell carcinoma. Urology 2005; 65: 1233-1237. (Pubitemid 40824937)
64. Vaish M, Mandhani A, Mittal RD et al. Microsatellite instability as prognostic marker in bladder tumors: a clinical significance. BMC Urol 2005; 5: 2-9
65. Bartoletti R, Cai T, Dal Canto M et al. Multiplex polymerase chain reaction for microsatellite analysis of urine sediment cells: a rapid and inexpensive method for diagnosing and monitoring superficial transitional cell carcinoma. J Urol 2006; 175: 2032-2037. (Pubitemid 43668529)
66. Enokida H, Nakagawa M. Epigenetics in bladder cancer. Int J Clin Oncol 2008; 13: 298-307.
67. Brait M, Begum S, Carvalho AL et al. Aberrant promoter methylation of multiple genes during pathogenesis of bladder cancer. Cancer Epidemiol Biomarkers Prev 2008; 17: 2786-2794.
68. Hoque MO, Begum S, Topaloglu O et al. Quantitation of promoter methylation of multiple genes in urine DNA and bladder cancer detection. J Natl Cancer Inst 2006; 98: 996-1004. (Pubitemid 44288164)
69. Lin HH, Ke HL, Wu WJ et al. Hypermethylation of E-cadherin, p16, p14, and RASSF1A genes in pathologically normal urothelium predict bladder recurrence of bladder cancer after transurethral resection. Urol Oncol 2010, Aug 25 [Epub ahead of print].
70. Negraes PD, Favaro FP, Camargo JL et al. DNA methylation patterns in bladder cancer and washing cell sediments: a perspective for tumor recurrence detection. BMC Cancer 2008; 8: 238-250
71. Toki K, Enokida H, Kawakami K et al. CpG hypermethylation of cellular retinol-binding protein 1 contributes to cell proliferation and migration in bladder cancer. Int J Oncol 2010; 37: 1379-1388.
72. Moore LE, Pfeiffer RM, Poscablo C et al. Genomic DNA hypomethylation as a biomarker for bladder cancer susceptibility in the Spanish Bladder Cancer Study: a case-control study. Lancet Oncol 2008; 9: 359-366.
73. Jarmalaite S, Jankevicius F, Kurgonaite K et al. Promoter hypermethylation in tumour suppressor genes shows association with stage, grade and invasiveness of bladder cancer. Oncology 2008; 75: 145-151.
74. Dhawan D, Hamdy FC, Rehman I et al. Evidence for the early onset of aberrant promoter methylation in urothelial carcinoma. J Pathol 2006; 209: 336-343. (Pubitemid 43997742)
75. Phé V, Cussenot O, Rouprêt M. Interest of methylated genes as biomarkers in urothelial cell carcinomas of the urinary tract BJU Int 2009; 104: 896-901.
76. Dudziec E, Miah S, Choudhry H et al. Hypermethylation of CpG islands and shores around specific microRNAs and mirtrons is associated with the phenotype and presence of bladder cancer. Clin Cancer Res 2010, Dec 7 [Epub ahead of print].
77. Esteller M. DNA methylation and cancer therapy: new developments and expectations. Curr Opin Oncol 2005; 17: 55-60. (Pubitemid 40179913)
78. Cheng JC, Weisenberger DJ, Gonzales FA et al. Continuous zebularine treatment effectively sustains demethylation in human bladder cancer cells. Mol Cell Biol 2004; 24: 1270-1278. (Pubitemid 38112188)
79. Pandith AA, Shah ZA, Siddiqi MA. Oncogenic role of fibroblast growth factor receptor 3 in tumorigenesis of urinary bladder cancer. Urol Oncol 2010, Sep 3 [Epub ahead of print].
80. Wolff EM, Liang G, Jones PA. Mechanisms of disease: genetic and epigenetic alterations that drive bladder cancer. Nat Clin Pract Urol 2005; 2: 502-510. (Pubitemid 41594404)
81. van Rhijn BW, Montironi R, Zwarthoff EC et al. Frequent FGFR3 mutations in urothelial papilloma. J Pathol 2002; 198: 245-251. (Pubitemid 35243883)
82. Wennerberg K, Rossman KL, Der CJ. The Ras superfamily at a glance. J Cell Sci 2005; 118: 843-846.
83. Donovan S, Shannon KM, Bollag G. GTPase activating proteins: critical regulators of intracellular signalling. Biochim Biophys Acta 2002; 1602: 23-45 (Pubitemid 34311898)
84. Przybojewska B, Jagiello A, Jalmuzna P. H-RAS, K-RAS, and N-RAS gene activation in human bladder cancers. Cancer Genet Cytogenet 2000; 121: 73-77. (Pubitemid 30665745)
85. Knowles MA, Williamson M. Mutation of H-ras is infrequent in bladder cancer: confirmation by single-strand conformation polymorphism analysis, designed restriction fragment length polymorphism and direct sequencing. Cancer Res 1993; 53: 133-139. (Pubitemid 23019388)
86. Boulalas I, Zaravinos A Karyotis I et al. Activation of RAS family genes in urothelial carcinoma. J Urol 2009; 181: 2312-2319.
87. Cantley LC. The phosphoinositide 3-kinase pathway. Science 2002; 296: 1655-1657. (Pubitemid 34579158)
88. Yuan TL, Cantley LC. PDK pathway alterations in cancer variations on a theme. Oncogene 2008; 27: 5497-5510.
89. Chen M, Cassidy A, Gu J et al. Genetic variations in PI3K-AKT-mTOR pathway and bladder cancer risk. Carcinogenesis 2009; 30: 2047-2052.
90. Knowles MA, Platt FM, Ross RL et al. Phosphatidylinositol 3-kinase (PI3K) pathway activation in bladder cancer. Cancer Metastasis Rev 2009; 28: 305-316.
91. Platt FM, Hurst CD, Taylor CF et al. Spectrum of phosphatidylinositol 3-kinase pathway gene alterations in bladder cancer. Clin Cancer Res 2009; 15: 6008-6017.
92. Ramjaun AR, Downward J. Ras and phosphoinositide 3-kinase: partners in development and tumorigenesis. Cell Cycle 2007; 6: 2902-2905.
93. López-Knowles E, Hernández S, Malats N et al. PDGCA mutations are an early genetic alteration associated with FGFR3 mutations in superficial papillary bladder tumors. Cancer Res 2006; 66: 7401-7404. (Pubitemid 44289191)
94. Garcia-Espana A, Salazar E, Sun TT et al. Differential expression of cell cycle regulators in phenotypic variants of transgenically induced bladder tumors: implications for tumor behavior. Cancer Res 2005; 65: 1150-1157. (Pubitemid 40270138)
95. Arima Y, Inoue Y, Shibata T et al. Rb depletion results in deregulation of E-cadherin and induction of cellular phenotypic changes that are characteristic of the epithelial-to-mesenchymal transition. Cancer Res 2008; 68: 5104-5112.
96. Gallucci M, Guadagni F, Marzano R et al. Status of the p53, p16, RB1, and HER-2 genes and chromosomes 3, 7, 9, and 17 in advanced bladder cancer: correlation with adjacent mucosa and pathological parameters. J Clin Pathol 2005; 58: 367-371.
97. Cordon-Cardo C. Molecular alterations associated with bladder cancer initiation and progression. Scand J Urol Nephrol Suppl 2008; 218: 154-165.
98. Olsson AY, Feber A, Edwards S et al. Role of E2F3 expression in modulating cellular proliferation rate in human bladder and prostate cancer cells. Oncogene 2007; 26: 1028-1037.
99. Hurst CD, Tomlinson DC, Williams SV et al. Inactivation of the Rb pathway and overexpression of both isoforms of E2F3 are obligate events in bladder tumours with 6p22 amplification. Oncogene 2008; 27: 2716-2727. (Pubitemid 351581468)
100. Hollstein M, Sidransky D, Vogelstein B et al. P53 mutations in human cancers. Science 1991 5; 253(5015): 4953.
101. Olivier M, Hussain SP, Caron de Fromentel C et al. TP53 mutation spectra and load: a tool for generating hypotheses on the etiology of cancer. IARC SCI Publ 2004; 157: 247-270.
102. Brosh R, Rotter V. When mutants gain new powers: news from the mutant p53 field. Nat Rev Cancer 2009; 9: 701-713.
103. Ecke TH, Sachs MD, Lenk SV et al. TP53 gene mutations as an independent marker for urinary bladder cancer progression. Int J Mol Med 2008; 21: 655-661.
104. Eymin B, Karayan L, Séité P et al. Human ARF binds E2F1 and inhibits its transcriptional activity. Oncogene 2001; 20: 1033-1041. (Pubitemid 32238852)
105. Simon R, Struckmann K, Schraml P et al. Amplification pattern of 12q13-q15 genes (MDM2, CDK4, GLI) in urinary bladder cancer. Oncogene 2002; 21: 2476-2483. (Pubitemid 34438100)
106. Voss MJ, Niggemann B, Zänker KS et al. Tumour reactions to hypoxia. Curr Mol Med 2010; 10: 381-386.
107. Conway EM, Collen D, Carmeliet P. Molecular mechanisms of blood vessel growth. Cardiovasc Res 2001; 16: 507-521. (Pubitemid 32146414)
108. Wu W, Shu X, Hoysepyan H et al. VEGF receptor expression and signalling in human bladder tumors. Oncogene 2003; 22: 3361-3370. (Pubitemid 36713733)
109. Xia G, Kumar SR, Hawes D et al. Expression and significance of vascular endothelial growth factor receptor 2 in bladder cancer. J Urol 2006; 175: 1245-1252.
110. Yang CC, Chu KC, Yah WM. The expression of vascular endothelial growth factor in transitional cell carcinoma of urinary bladder is correlated with cancer progression. Urol Oncol 2004; 22: 1-6.
111. Bernardini S, Fauconnet S, Chabannes E et al. Serum levels of vascular endothelial growth factor as a prognostic factor in bladder cancer. J Urol 2001; 166: 1275-1279. (Pubitemid 32862155)
112. Mohamedali KA, Kedar D, Sweeney P et al. The vascular-targeting fusion toxin VEGF121/rGel inhibits the growth of orthotopic human bladder carcinoma tumors. Neoplasia 2005; 7: 912-920.
113. Elfiky AA, Rosenberg JE. Targeting angiogenesis in bladder cancer. Curr Oncol Rep 2009; 11: 244-249.
114. Beecken WD, Engl T, Hofman J et al. Clinical relevance of serum angiogenic activity in patients with transitional cell carcinoma of the bladder. J Cell Mol Med 2005; 9: 655-661. (Pubitemid 44151952)
115. Gravas S, Bosinakou I, Kehayas P et al. Urinary basic fibroblast growth factor in bladder cancer patients. Histopathological correlation and clinical potential. Urol Int 2004; 73: 173-177. (Pubitemid 39482731)
116. Gee J, Lee IL, Grossman HB et al. Forced COX-2 expression induces PGE(2) and invasion in immortalized urothelial cells. Urol Oncol 2008; 26: 641-645.
117. Wang D, Dubois RN. Prostaglandins and cancer. Gut 2006; 55: 115-122. (Pubitemid 41820645)
118. Shirahama T, Arima J, Akiba S et al. Relation between cyclooxygenase-2 expression and tumor invasiveness and patient survival in transitional cell carcinoma of the urinary bladder. Cancer 2001; 92: 188-193. (Pubitemid 32623056)
119. Ji RC. Lymphatic endothelial cells, tumor lymphangiogenesis and metastasis: New insights into intratumoral and peritumoral lymphatics. Cancer Metastasis Rev 2006; 25: 677-694.
120. Tammela T, Alitalo K. Lymphangiogenesis: Molecular medianisms and future promise. Cell 2010; 140: 460-476.
121. Saban MR, Towner R, Smith N et al. Lymphatic vessel density in experimental bladder cancer. BMC Cancer 2007; 7: 219-239
122. Schledzewski K, Falkowski M, Moldenhauer G et al. Lymphatic endothelium-specific hyaluronan receptor LYVE-1 is expressed by stabilin-1+, F4/80+, CD1 1b+ macrophages in malignant tumours and wound healing tissue in vivo and in bone marrow cultures in vitro: implications for the assessment of lymphangiogenesis. J Pathol 2006; 209: 67-77.
123. Kerjaschki D. The crucial role of macrophages in lymphangiogenesis. J Clin Invest 2005; 115: 2316-2319. (Pubitemid 41266190)
124. Halotera H, Alitalo K. The VEGF family: the inside story. Cell 2007; 130: 591-592.
125. Afonso J, Santos LL, Amaro T et al. The aggressiveness of urothelial carcinoma depends to a large extent on lymphovascular invasion-the prognostic contribution of related molecular markers. Histopathology 2009; 55: 514-524.
126. Miyata Y, Kanda S, Ohba K et al. Lymphangiogenesis and angiogenesis in bladder cancer Prognostic implications and regulation by vascular endothelial growth factors-A, -C, and -D. Clin Cancer Res 2006; 12: 800-806. (Pubitemid 43259860)
127. Fernandez MI, Bolenz C, Trojan L et al. Prognostic implications of lymphangiogenesis in muscle-invasive transitional cell carcinoma of the bladder. Eur Urol 2008; 53: 571-578.
128. Zhou M, He L, Zu X et al. Lymphatic vessel density as a predictor of lymph node metastasis and its relationship with prognosis in urothelial carcinoma of the bladder. BJU Int 2010 Sep 30. doi: 10.1111/j.1464-410X.2010. 09725.x. [Epub ahead of print].
129. Ischenko I, Seeliger H, Camaj P et al. Src tyrosine kinase inhibition suppresses lymphangiogenesis in vitro and in vivo. Curr Cancer Drug Targets 2010; 10: 546-553.