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Evolution on experimental animal model for upper urothelium carcinogenesis

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Abstract

Purpose

No optimal, well designed and reproducible animal model for upper urothelial carcinogenesis exists. This study characterized the histopathological features on top of immunolocalization of alpha-dystroglycans (α-DG) and matrix metalloproteinase (MMP-9) and cell turn-over in the upper urinary tract using a novel experimental model.

Methods

Seventy-five female Fischer 344 rats were divided into three groups: the control group received a 0.30-ml dose of 0.9% physiological saline; the MNU group (chemical carcinogen N-methyl-N-nitrosourea) received 0.30 ml of MNU; and the MNU-citrate group received 0.30 ml of MNU plus sodium citrate, every one intravesically every other week for a total of 4 doses. After 15 weeks, bladder, ureters and renal pelvis were collected for morphological and molecular analysis.

Results

Associated management with MNU and sodium citrate was able to lead to 100% of both urinary bladder and upper urinary tract tumors, being the high-grade noninvasive papillary urothelial carcinoma the most frequent lesion. The upper urothelium showed reduced α-DG and increased MMP-9 and Ki-67 immunoreactivities in the MNU-citrate group in relation to the other groups. MNU group presented no upper urothelium tumor and 100% bladder tumor.

Conclusions

This is a relevant evolution on experimental animal model for upper urinary tract carcinogenesis field. MMP-dependent disruption of the DG complex plays an important role in urothelial tumor carcinogenesis and showed the model applicability and significance. MNU-citrate model could contribute to a better understanding of human upper urothelial cancer development as well as to its local treatment strategies in a near future.

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Authors and Affiliations

  1. Department of Urology, Division of Urologic Oncology, School of Medicine, University of Campinas (UNICAMP), R. Votorantim, 51, ap. 43, Campinas, SP, 13073-090, Brazil

    Leonardo O. Reis & Ubirajara Ferreira

  2. Department of Anatomy, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil

    Wagner J. Fávaro & Valéria H. A. Cagnon

  3. Department of Pathology, School of Medicine, University of Campinas (UNICAMP), Campinas, SP, Brazil

    Athanase Billis & Mariana G. Fazuoli

Authors
  1. Leonardo O. Reis
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  2. Wagner J. Fávaro
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  3. Ubirajara Ferreira
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  4. Athanase Billis
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  5. Mariana G. Fazuoli
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  6. Valéria H. A. Cagnon
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Correspondence to Leonardo O. Reis.

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Reis, L.O., Fávaro, W.J., Ferreira, U. et al. Evolution on experimental animal model for upper urothelium carcinogenesis. World J Urol 28, 499–505 (2010). https://doi.org/10.1007/s00345-010-0545-3

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  • DOI: https://doi.org/10.1007/s00345-010-0545-3

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