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BioMed Research International
Volume 2014, Article ID 473536, 10 pages
http://dx.doi.org/10.1155/2014/473536
Review Article

Cystitis: From Urothelial Cell Biology to Clinical Applications

1Department of Urology, Dankook University College of Medicine, 359 Manghyang-ro, Cheonan 330-715, Republic of Korea
2Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, SI-1000 Ljubljana, Slovenia

Received 28 February 2014; Accepted 15 April 2014; Published 30 April 2014

Academic Editor: Michael Winder

Copyright © 2014 Gilho Lee et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. G. P. Paner, J. Y. Ro, E. M. Wojcik, G. Venkataraman, M. W. Datta, and M. B. Amin, “Further characterization of the muscle layers and lamina propria of the urinary bladder by systematic histologic mapping: implications for pathologic staging of invasive urothelial carcinoma,” The American Journal of Surgical Pathology, vol. 31, no. 9, pp. 1420–1429, 2007. View at Publisher · View at Google Scholar · View at Scopus
  2. R. Romih, P. Korošec, W. de Mello Jr., and K. Jezernik, “Differentiation of epithelial cells in the urinary tract,” Cell and Tissue Research, vol. 320, no. 2, pp. 259–268, 2005. View at Publisher · View at Google Scholar · View at Scopus
  3. R. M. Hicks, “The mammalian urinary bladder: an accommodating organ,” Biological Reviews of the Cambridge Philosophical Society, vol. 50, no. 2, pp. 215–246, 1975. View at Google Scholar · View at Scopus
  4. S. A. Lewis, “Everything you wanted to know about the bladder epithelium but were afraid to ask,” American Journal of Physiology—Renal Physiology, vol. 278, no. 6, pp. F867–F874, 2000. View at Google Scholar · View at Scopus
  5. P. Hu, S. Meyers, F.-X. Liang et al., “Role of membrane proteins in permeability barrier function: uroplakin ablation elevates urothelial permeability,” American Journal of Physiology—Renal Physiology, vol. 283, no. 6, pp. F1200–F1207, 2002. View at Google Scholar · View at Scopus
  6. M. E. Kreft, K. Jezernik, M. Kreft, and R. Romih, “Apical plasma membrane traffic in superficial cells of bladder urothelium,” Annals of the New York Academy of Sciences, vol. 1152, pp. 18–29, 2009. View at Publisher · View at Google Scholar · View at Scopus
  7. G. Apodaca, E. Balestreire, and L. A. Birder, “The Uroepithelial-associated sensory web,” Kidney International, vol. 72, no. 9, pp. 1057–1064, 2007. View at Publisher · View at Google Scholar · View at Scopus
  8. D. M. Daly, V. M. Collins, C. R. Chapple, and D. Grundy, “The afferent system and its role in lower urinary tract dysfunction,” Current Opinion in Urology, vol. 21, no. 4, pp. 268–274, 2011. View at Publisher · View at Google Scholar · View at Scopus
  9. J. Nishiguchi, Y. Hayashi, M. B. Chancellor et al., “Detrusor overactivity induced by intravesical application of adenosine 5′-triphosphate under different delivery conditions in rats,” Urology, vol. 66, no. 6, pp. 1332–1337, 2005. View at Publisher · View at Google Scholar · View at Scopus
  10. H. Zhang, G. Lin, X. Qiu et al., “Label retaining and stem cell marker expression in the developing rat urinary bladder,” Urology, vol. 79, no. 3, pp. 746.e1–746.e6, 2012. View at Publisher · View at Google Scholar · View at Scopus
  11. E. A. Kurzrock, D. K. Lieu, L. A. DeGraffenried, C. W. Chan, and R. R. Isseroff, “Label-retaining cells of the bladder: candidate urothelial stem cells,” American Journal of Physiology—Renal Physiology, vol. 294, no. 6, pp. F1415–F1421, 2008. View at Publisher · View at Google Scholar · View at Scopus
  12. R. Romih, K. Jezernik, and A. Mašera, “Uroplankins and cytokeratins in the regenerating rat urothelium after sodium saccharin treatment,” Histochemistry and Cell Biology, vol. 109, no. 3, pp. 263–269, 1998. View at Publisher · View at Google Scholar · View at Scopus
  13. S. Hudoklin, D. Zupancic, and R. Romih, “Maturation of the Golgi apparatus in urothelial cells,” Cell and Tissue Research, vol. 336, no. 3, pp. 453–463, 2009. View at Publisher · View at Google Scholar · View at Scopus
  14. X.-R. Wu, X.-P. Kong, A. Pellicer, G. Kreibich, and T.-T. Sun, “Uroplakins in urothelial biology, function, and disease,” Kidney International, vol. 75, no. 11, pp. 1153–1165, 2009. View at Publisher · View at Google Scholar · View at Scopus
  15. X.-R. Wu, M. Manabe, J. Yu, and T.-T. Sun, “Large scale purification and immunolocalization of bovine uroplakins I, II, and III. Molecular markers of urothelial differentiation,” The Journal of Biological Chemistry, vol. 265, no. 31, pp. 19170–19179, 1990. View at Google Scholar · View at Scopus
  16. X.-R. Wu, J.-H. Lin, T. Walz et al., “Mammalian uroplakins. A group of highly conserved urothelial differentiation-related membrane proteins,” The Journal of Biological Chemistry, vol. 269, no. 18, pp. 13716–13724, 1994. View at Google Scholar · View at Scopus
  17. K. R. Porter, K. Kenyon, and S. Badenhausen, “Specializations of the unit membrane,” Protoplasma, vol. 63, no. 1–3, pp. 262–274, 1967. View at Publisher · View at Google Scholar · View at Scopus
  18. T.-T. Sun, “Altered phenotype of cultured urothelial and other stratified epithelial cells: implications for wound healing,” American Journal of Physiology–Renal Physiology, vol. 291, no. 1, pp. F9–F21, 2006. View at Publisher · View at Google Scholar · View at Scopus
  19. B. Kachar, F. Liang, U. Lins et al., “Three-dimensional analysis of the 16 nm urothelial plaque particle: luminal surface exposure, preferential head-to-head interaction, and hinge formation,” Journal of Molecular Biology, vol. 285, no. 2, pp. 595–608, 1999. View at Publisher · View at Google Scholar · View at Scopus
  20. S. Hudoklin, K. Jezernik, J. Neumüller, M. Pavelka, and R. Romih, “Electron tomography of fusiform vesicles and their organization in urothelial cells,” PLoS ONE, vol. 7, no. 3, Article ID e32935, 2012. View at Publisher · View at Google Scholar · View at Scopus
  21. S. Hudoklin, K. Jezernik, J. Neumüller, M. Pavelka, and R. Romih, “Urothelial plaque formation in post-golgi compartments,” PLoS ONE, vol. 6, no. 8, Article ID e23636, 2011. View at Publisher · View at Google Scholar · View at Scopus
  22. P. Veranič and K. Jezernik, “Trajectorial organisation of cytokeratins within the subapical region of umbrella cells,” Cell Motility and the Cytoskeleton, vol. 53, no. 4, pp. 317–325, 2002. View at Publisher · View at Google Scholar · View at Scopus
  23. G. Zhou, F.-X. Liang, R. Romih et al., “MAL facilitates the incorporation of exocytic uroplakin-delivering vesicles into the apical membrane of urothelial umbrella cells,” Molecular Biology of the Cell, vol. 23, no. 7, pp. 1354–1366, 2012. View at Publisher · View at Google Scholar · View at Scopus
  24. P. Veranič, R. Romih, and K. Jezernik, “What determines differentiation of urothelial umbrella cells?” European Journal of Cell Biology, vol. 83, no. 1, pp. 27–34, 2004. View at Publisher · View at Google Scholar · View at Scopus
  25. R. Romih, P. Veranic, and K. Jezernik, “Appraisal of differentiation markers in urothelial cells,” Applied Immunohistochemistry and Molecular Morphology, vol. 10, no. 4, pp. 339–343, 2002. View at Publisher · View at Google Scholar · View at Scopus
  26. H.-Y. Huang, S. F. Shariat, T.-T. Sun et al., “Persistent uroplakin expression in advanced urothelial carcinomas: implications in urothelial tumor progression and clinical outcome,” Human Pathology, vol. 38, no. 11, pp. 1703–1713, 2007. View at Publisher · View at Google Scholar · View at Scopus
  27. A. J. Schaeffer and E. M. Schaeffer, “Infections of the urinary tract,” in Campbell-Walsh Urology, A. J. Wein, L. R. Kavoussi, A. C. Novick, A. W. Partin, and C. A. Peters, Eds., pp. 252–326, 2012. View at Google Scholar
  28. M. Sundqvist and G. Kahlmeter, “Uncomplicated and community acquired urinary tract infections: aetiology and resistence,” in Urogenital Infections, K. G. Naber, A. J. Schaeffer, C. F. Heyns, T. Matsumoto, D. A. Shoskes , and T. E. B. Johansen, Eds., pp. 72–81, European Association of Urology, Arnhem, The Netherlands, 2010. View at Google Scholar
  29. M. S. Bader, J. Hawboldt, and A. Brooks, “Management of complicated urinary tract infections in the era of antimicrobial resistance,” Postgraduate Medicine, vol. 122, no. 6, pp. 7–15, 2010. View at Publisher · View at Google Scholar · View at Scopus
  30. B. Foxman, “Epidemiology of urinary tract infections: incidence, morbidity, and economic costs,” The American Journal of Medicine, vol. 113, supplement 1, no. 1, pp. 5S–13S, 2002. View at Publisher · View at Google Scholar · View at Scopus
  31. R. Colgan and M. Williams, “Diagnosis and treatment of acute uncomplicated cystitis,” American Family Physician, vol. 84, no. 7, pp. 771–776, 2011. View at Google Scholar · View at Scopus
  32. A. E. Barber, J. P. Norton, A. M. Spivak, and M. A. Mulvey, “Urinary tract infections: current and emerging management strategies,” Clinical Infectious Diseases, vol. 57, no. 5, pp. 719–724, 2013. View at Publisher · View at Google Scholar
  33. E. J. Dielubanza and A. J. Schaeffer, “Urinary tract infections in women,” Medical Clinics of North America, vol. 95, no. 1, pp. 27–41, 2011. View at Publisher · View at Google Scholar · View at Scopus
  34. T. M. Hooton, S. F. Bradley, D. D. Cardenas et al., “Diagnosis, prevention, and treatment of catheter-aassociated urinary tract infection in adults: 2009 international clinical practice guidelines from the infectious diseases society of America,” Clinical Infectious Diseases, vol. 50, no. 5, pp. 625–663, 2010. View at Publisher · View at Google Scholar · View at Scopus
  35. U. Dobrindt and J. Hacker, “Uropathogenes and virulence factors,” in Urogenital Infections, K. G. Naber, A. J. Schaeffer, C. F. Heyns, T. Matsumoto, D. A. Shoskes , and T. E. B. Johansen, Eds., pp. 4–22, European Association of Urology, Arnhem, The Netherlands, 2010. View at Google Scholar
  36. G. Zhou, W.-J. Mo, P. Sebbel et al., “Uroplakin la is the urothelial receptor for uropathogenic Escherichia coli: evidence from in vitro FimH binding,” Journal of Cell Science, vol. 114, part 22, pp. 4095–4103, 2001. View at Google Scholar · View at Scopus
  37. C. S. Kim, M. E. Kim, Y.-H. Cho, I. R. Cho, and G. Lee, “Virulence characteristics and phylogenetic background of ciprofloxacin resistant Escherichia coli in the urine samples from Korean women with acute uncomplicated cystitis,” Journal of Korean Medical Science, vol. 25, no. 4, pp. 602–607, 2010. View at Publisher · View at Google Scholar · View at Scopus
  38. X.-R. Wu, T.-T. Sun, and J. J. Medina, “In vitro binding of type 1-fimbriated Escherichia coli to uroplakins Ia and Ib: relation to urinary tract infections,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 18, pp. 9630–9635, 1996. View at Publisher · View at Google Scholar · View at Scopus
  39. M. A. Mulvey, “Adhesion and entry of uropathogenic Escherichia coli,” Cellular Microbiology, vol. 4, no. 5, pp. 257–271, 2002. View at Publisher · View at Google Scholar · View at Scopus
  40. B. S. Norinder, P. Lüthje, M. Yadav et al., “Cellulose and PapG are important for Escherichia coli causing recurrent urinary tract infection in women,” Infection, vol. 39, no. 6, pp. 571–574, 2011. View at Publisher · View at Google Scholar · View at Scopus
  41. J. J. Martinez, M. A. Mulvey, J. D. Schilling, J. S. Pinkner, and S. J. Hultgren, “Type 1 pilus-mediated bacterial invasion of bladder epithelial cells,” The EMBO Journal, vol. 19, no. 12, pp. 2803–2812, 2000. View at Google Scholar · View at Scopus
  42. M. J. Duncan, G. Li, J.-S. Shin, J. L. Carson, and S. N. Abraham, “Bacterial penetration of bladder epithelium through lipid rafts,” The Journal of Biological Chemistry, vol. 279, no. 18, pp. 18944–18951, 2004. View at Publisher · View at Google Scholar · View at Scopus
  43. G. G. Anderson, K. W. Dodson, T. M. Hooton, and S. J. Hultgren, “Intracellular bacterial communities of uropathogenic Escherichia coli in urinary tract pathogenesis,” Trends in Microbiology, vol. 12, no. 9, pp. 424–430, 2004. View at Publisher · View at Google Scholar · View at Scopus
  44. J. J. Martinez and S. J. Hultgren, “Requirement of Rho-family GTPases in the invasion of type 1-piliated uropathogenic Escherichia coli,” Cellular Microbiology, vol. 4, no. 1, pp. 19–28, 2002. View at Publisher · View at Google Scholar · View at Scopus
  45. Z. Han, J. S. Pinkner, B. Ford et al., “Structure-based drug design and optimization of mannoside bacterial fimH antagonists,” Journal of Medicinal Chemistry, vol. 53, no. 12, pp. 4779–4792, 2010. View at Publisher · View at Google Scholar · View at Scopus
  46. Y. Kurimura, C. Nishitani, S. Ariki et al., “Surfactant protein D inhibits adherence of uropathogenic Escherichia coli to the bladder epithelial cells and the bacterium-induced cytotoxicity: a possible function in urinary tract,” The Journal of Biological Chemistry, vol. 287, no. 47, pp. 39578–39588, 2012. View at Google Scholar
  47. P. D. Cotter, C. Stanton, R. P. Ross, and C. Hill, “The impact of antibiotics on the gut microbiota as revealed by high throughput DNA sequencing,” Discovery Medicine, vol. 13, no. 70, pp. 193–199, 2012. View at Google Scholar
  48. S. S. Justice, C. Hung, J. A. Theriot et al., “Differentiation and developmental pathways of uropathogenic Escherichia coli in urinary tract pathogenesis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 5, pp. 1333–1338, 2004. View at Publisher · View at Google Scholar · View at Scopus
  49. M. G. Blango and M. A. Mulvey, “Persistence of uropathogenic Escherichia coli in the face of multiple antibiotics,” Antimicrobial Agents and Chemotherapy, vol. 54, no. 5, pp. 1855–1863, 2010. View at Publisher · View at Google Scholar · View at Scopus
  50. K. G. Campellone, “Cytoskeleton-modulating effectors of enteropathogenic and enterohaemorrhagic Escherichia coli: tir, EspFU and actin pedestal assembly,” The FEBS Journal, vol. 277, no. 11, pp. 2390–2402, 2010. View at Publisher · View at Google Scholar · View at Scopus
  51. J. M. Bower, D. S. Eto, and M. A. Mulvey, “Covert operations of uropathogenic Escherichia coli within the urinary tract,” Traffic, vol. 6, no. 1, pp. 18–31, 2005. View at Publisher · View at Google Scholar · View at Scopus
  52. B. Ragnarsdóttir, N. Lutay, J. Grönberg-Hernandez, B. Köves, and C. Svanborg, “Genetics of innate immunity and UTI susceptibility,” Nature Reviews Urology, vol. 8, no. 8, pp. 449–468, 2011. View at Publisher · View at Google Scholar · View at Scopus
  53. C. Svanborg, G. Bergsten, H. Fischer et al., “Uropathogenic Escherichia coli as a model of host-parasite interaction,” Current Opinion in Microbiology, vol. 9, no. 1, pp. 33–39, 2006. View at Publisher · View at Google Scholar · View at Scopus
  54. J. C. Nickel, “Practical management of recurrent urinary tract infections in premenopausal women,” Reviews in Urology, vol. 7, no. 1, pp. 11–17, 2005. View at Google Scholar
  55. T. M. Hooton and W. E. Stamm, “Management of acute uncomplicated urinary tract infection in adults,” Medical Clinics of North America, vol. 75, no. 2, pp. 339–357, 1991. View at Google Scholar · View at Scopus
  56. G. Reid, A. W. Bruce, J. A. McGroarty, K.-J. Cheng, and J. W. Costerton, “Is there a role for lactobacilli in prevention of urogenital and intestinal infections?” Clinical Microbiology Reviews, vol. 3, no. 4, pp. 335–344, 1990. View at Google Scholar · View at Scopus
  57. R. Raz and W. E. Stamm, “A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections,” The New England Journal of Medicine, vol. 329, no. 11, pp. 753–756, 1993. View at Publisher · View at Google Scholar · View at Scopus
  58. Y. S. Kyung, H. Park, and G. Lee, “Intravesical epinephrine preserves uroplakin II expression in urinary bladder from cyclophosphamide-induced rat cystitis,” Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 385, no. 8, pp. 769–776, 2012. View at Publisher · View at Google Scholar
  59. Ł. Dobrek and P. J. Thor, “Bladder urotoxicity pathophysiology induced by the oxazaphosphorine alkylating agents and its chemoprevention,” Postȩpy Higieny i Medycyny Doświadczalnej, vol. 66, pp. 592–602, 2012. View at Publisher · View at Google Scholar
  60. M. Siguier, P. Sellier, and J. F. Bergmann, “BK-virus infections: a literature review,” Médecine et Maladies Infectieuses, vol. 42, no. 5, pp. 181–187, 2012. View at Google Scholar
  61. E. Giné, M. Rovira, I. Real et al., “Successful treatment of severe hemorrhagic cystitis after hemopoietic cell transplantation by selective embolization of the vesical arteries,” Bone Marrow Transplantation, vol. 31, no. 10, pp. 923–925, 2003. View at Publisher · View at Google Scholar · View at Scopus
  62. P. Sèbe, L. Garderet, O. Traxer, M. Nouri, E. Gluckman, and B. Gattegno, “Subtotal cystectomy with ileocystoplasty for severe hemorrhagic cystitis after bone marrow transplantation,” Urology, vol. 57, no. 1, article 168, 2001. View at Google Scholar · View at Scopus
  63. L. A. Levine and J. P. Richie, “Urological complications of cyclophosphamide,” The Journal of Urology, vol. 141, no. 5, pp. 1063–1069, 1989. View at Google Scholar · View at Scopus
  64. H. Arnold, F. Bourseaux, and N. Brock, “Chemotherapeutic action of a cyclic nitrogen mustard phosphamide ester (B 518-ASTA) in experimental tumours of the rat,” Nature, vol. 181, no. 4613, article 931, 1958. View at Publisher · View at Google Scholar · View at Scopus
  65. R. Manikandan, S. Kumar, and L. N. Dorairajan, “Hemorrhagic cystitis: a challenge to the urologist,” Indian Journal of Urology, vol. 26, no. 2, pp. 159–166, 2010. View at Publisher · View at Google Scholar · View at Scopus
  66. S. Mukhtar and C. Woodhouse, “The management of cyclophosphamide-induced haematuria,” BJU International, vol. 105, no. 7, pp. 908–912, 2010. View at Publisher · View at Google Scholar · View at Scopus
  67. K. J. Gray, U. H. Engelmann, E. H. Johnson, and I. J. Fishman, “Evaluation of misoprostol cytoprotection of the bladder with cyclophosphamide (Cytoxan) therapy,” The Journal of Urology, vol. 136, no. 2, pp. 497–500, 1986. View at Google Scholar · View at Scopus
  68. T. Farsund, “Cell kinetics of mouse urinary bladder epithelium. II. Changes in proliferation and nuclear DNA content during necrosis, regeneration, and hyperplasia caused by a single dose of cyclophosphamide,” Virchows Archiv Abteilung B: Cell Pathology, vol. 21, no. 4, pp. 279–298, 1976. View at Google Scholar · View at Scopus
  69. L. G. Koss, “A light and electron microscopic study of the effects of a single dose of cyclophosphamide on various organs in the rat. I. The urinary bladder,” Laboratory Investigation, vol. 16, no. 1, pp. 44–65, 1967. View at Google Scholar · View at Scopus
  70. P. J. Cox, “Cyclophosphamide cystitis—identification of acrolein as the causative agent,” Biochemical Pharmacology, vol. 28, no. 13, pp. 2045–2049, 1979. View at Publisher · View at Google Scholar · View at Scopus
  71. D. E. Bjorling, J. E. Elkahwaji, W. Bushman et al., “Acute acrolein-induced cystitis in mice,” BJU International, vol. 99, no. 6, pp. 1523–1529, 2007. View at Publisher · View at Google Scholar · View at Scopus
  72. H. Payne, A. Adamson, A. Bahl et al., “Chemical- and radiation-induced haemorrhagic cystitis: current treatments and challenges,” BJU International, vol. 112, no. 7, pp. 885–897, 2013. View at Google Scholar
  73. T. Yoshida, A. Kawashima, T. Ujike, M. Uemura, K. Nishimura, and S. Miyoshi, “Hyperbaric oxygen therapy for radiation-induced hemorrhagic cystitis,” International Journal of Urology, vol. 15, no. 7, pp. 639–641, 2008. View at Publisher · View at Google Scholar · View at Scopus
  74. D. Zupančič, K. Jezernik, and G. Vidmar, “Effect of melatonin on apoptosis, proliferation and differentiation of urothelial cells after cyclophosphamide treatment,” Journal of Pineal Research, vol. 44, no. 3, pp. 299–306, 2008. View at Publisher · View at Google Scholar · View at Scopus
  75. Y.-C. Chow, S. Yang, C.-J. Huang et al., “Epinephrine promotes hemostasis in rats with cyclophosphamide-induced hemorrhagic cystitis,” Urology, vol. 67, no. 3, pp. 636–641, 2006. View at Publisher · View at Google Scholar · View at Scopus
  76. Y. S. Kyung, H. Y. Park, and G. Lee, “Preservation of uroplakins by 2-mercaptoethanesulfonate in cyclophosphamide-induced rat cystitis,” Archives of Toxicology, vol. 85, no. 1, pp. 51–57, 2011. View at Publisher · View at Google Scholar · View at Scopus
  77. S. D. Levine, H. Weber, and D. Schlondorff, “Inhibition of adenylate cyclase by general anesthetics in toad urinary bladder,” The American Journal of Physiology, vol. 237, no. 5, pp. F372–F378, 1979. View at Google Scholar · View at Scopus
  78. F. S. Philips, S. S. Sternberg, A. P. Cronin, and P. M. Vidal, “Cyclophosphamide and urinary bladder toxicity,” Cancer Research, vol. 21, pp. 1577–1589, 1961. View at Google Scholar · View at Scopus
  79. S. Fukushima, M. Arai, and S. M. Cohen, “Scanning electron microscopy of cyclophosphamide-induced hyperplasia of the rat urinary bladder,” Laboratory Investigation, vol. 44, no. 2, pp. 89–96, 1981. View at Google Scholar · View at Scopus
  80. R. Romih, D. Koprivec, D. S. Martincic, and K. Jezernik, “Restoration of the rat urothelium after cyclophosphamide treatment,” Cell Biology International, vol. 25, no. 6, pp. 531–537, 2001. View at Publisher · View at Google Scholar · View at Scopus
  81. D. Zupančič, M. Zakrajšek, G. Zhou, and R. Romih, “Expression and localization of four uroplakins in urothelial preneoplastic lesions,” Histochemistry and Cell Biology, vol. 136, no. 4, pp. 491–500, 2011. View at Publisher · View at Google Scholar · View at Scopus
  82. D. Schmähl and M. Habs, “Carcinogenic action of low-dose cyclophosphamide given orally to Sprague-Dawley rats in a lifetime experiment,” International Journal of Cancer, vol. 23, no. 5, pp. 706–712, 1979. View at Google Scholar · View at Scopus
  83. I. Jung and E. Messing, “Molecular mechanisms and pathways in bladder cancer development and progression,” Cancer Control, vol. 7, no. 4, pp. 325–334, 2000. View at Google Scholar · View at Scopus
  84. T. M. Tuttle, G. M. Williams, and F. F. Marshall, “Evidence for cyclophosphamide-induced transitional cell carcinoma in a renal transplant patient,” The Journal of Urology, vol. 140, no. 5, pp. 1009–1011, 1988. View at Google Scholar · View at Scopus
  85. C. Augé, G. Chene, M. Dubourdeau et al., “Relevance of the cyclophosphamide-induced cystitis model for pharmacological studies targeting inflammation and pain of the bladder,” European Journal of Pharmacology, vol. 707, no. 1–3, pp. 32–40, 2013. View at Publisher · View at Google Scholar
  86. K. Jezernik, R. Romih, H. G. Mannherz, and D. Koprivec, “Immunohistochemical detection of apoptosis, proliferation and inducible nitric oxide synthase in rat urothelium damaged by cyclophosphamide treatment,” Cell Biology International, vol. 27, no. 10, pp. 863–869, 2003. View at Publisher · View at Google Scholar · View at Scopus
  87. G. W. Locher and E. H. Cooper, “Repair of rat urinary bladder epithelium following injury by cyclophosphamide,” Investigative Urology, vol. 8, no. 1, pp. 116–123, 1970. View at Google Scholar · View at Scopus
  88. T. Višnjar, P. Kocbek, and M. E. Kreft, “Hyperplasia as a mechanism for rapid resealing urothelial injuries and maintaining high transepithelial resistance,” Histochemistry and Cell Biology, vol. 137, no. 2, pp. 177–186, 2012. View at Publisher · View at Google Scholar · View at Scopus
  89. R. Romih and K. Jezernik, “Reorganisation of the urothelial luminal plasma membrane in the cyclophosphamide treated rats,” Pflügers Archiv: European Journal of Physiology, vol. 431, no. 6, supplement 2, pp. R241–R242, 1996. View at Google Scholar · View at Scopus