Urothelial Hyperplasia and Neoplasia: A Response to Chronic Urinary Tract Infections in Rats

Davis, Charles P.; Cohen, Marc; Gruber, Michael B.; Warren, Michael M.

doi:10.1016/s0022-5347(17)49992-7

Cited by 55 publications

(9 citation statements)

References 12 publications

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“…The dysplasia is characterized by cell atypia with nuclear asymmetry and it can be considered a true precancerous lesion. The potential causes of bladder pre-neoplastic lesions are chronic urinary infection [20], chronic inflammation [21,22], reaction to suture material [23], and a high Na concentration in the presence of basic urine [24][25][26]. In our study, urinary infection and foreign body reaction were absent in the presence of sterile urine and normal histological results in controls, while phlogosis was frequent, especially in group A.…”

Section: Discussionsupporting

confidence: 44%

Histological Changes following Two-Step Flap Gastrocystoplasty in Rats

et al. 2002

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Introduction: A gastric segment used to increase bladder capacity can undergo considerable changes over time, as can all intestinal segments implanted in the urinary tract and in contact with urine. This experimental study reports the differences between the histological alterations observed in the gastric patch transposed in the bladder both with its own pedicle and after deafferentation from the stomach. Materials and Methods: A group of 30 young male Sprague-Dawley rats underwent gastrocystoplasty. Survivors were divided into 3 groups: gastrocystoplasty alone (8 rats); gastrocystoplasty with vascular deafferentation at 15 days (7 rats), and at 2 months (8 rats). 5 rats were used as controls. Urinary pH was evaluated during a 6-month follow-up. Results: Histology showed that early devascularization hindered the fusion of the two mucosae in the junctional area but reduced papillary hyperplasia (p = 0.013) of the gastric mucosa. No changes were observed in urinary pH after patch devascularization. Conclusions: Vascular deafferentation creates a gastric flap on the bladder which, even if it does not prevent urinary acidification, reduces the frequency of histologically detected changes susceptible for transformation into neoplasms.

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Section: Discussionsupporting

confidence: 44%

Histological Changes following Two-Step Flap Gastrocystoplasty in Rats

et al. 2002

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“…The development of carcinomas in these cases has to be attributed to the chronic mechanical irritation of the urothelium, possibly in combination with infec tion. This has been described for rats by Davis et al [1984] using steel wire implants and by Oyashu et al [1984] injecting saline solution repeatedly into rat blad ders.…”

Section: Discussionmentioning

confidence: 99%

Bladder Carcinogenesis in Portacaval Shunt Rats

et al. 1987

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The induction of transitional cell bladder tumors following portacaval shunt (PCA) in rats was investigated. Thirty-five (29 males; 6 females) out of 86 animals developed a carcinoma. The highest incidence of tumors (73%) was seen in control animals without a PCA but with implantation of a bladder stone. PCA rats had an induction rate of 34% and a spontaneous bladder tumor was seen in 2/13 sham-operated controls. All rats with a bladder tumor also had urolithiasis; 34 rats had bladder stones in 1 rat had kidney stones. The induction rate in males was 29/52, 55.7% compared to 6/34, 17.6% in females. All tumors were transitional cell carcinomas and were graded G0-GIII [1(G0); 24 (GI); 1 (GI-II); 9 (GII)] accompanied in 20 cases by squamous cell metaplasia. Chronic irritation by stones and infection are the most likely causes of tumor development; however, other mechanisms such as excretion of carcinogens or tumor promoters cannot be completely excluded. The sex difference in stone formation – and tumor induction – are subject to further investigations.

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“…The bladder and ureteral urothelium consist of five to six cell layers, comprising a basal cell layer, three or four intermediate cell layers, and a superficial cell layer composed of highly differentiated umbrella cells (Jost et al, 1989). Urothelial cell turnover is extremely low under normal conditions (Martin, 1972) but is increased after exposure to cytotoxic agents (Simeonova et al, 2000) and bacteria (Uchida et al, 1989) and also during tumorigenesis (Davis et al, 1984) and wound healing (Edlich and London, 1996). Bladder catheterization, cystoscopy fulguration, laser traumatisms, and irradiation, procedures commonly used in the management of patients with bladder cancer, initiate a complex sequence of events that culminates in wound repair (Cooper and See, 1992).…”

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confidence: 99%

Epidermal Growth Factor Receptor Regulates Normal Urothelial Regeneration

Daher

Boer

Elmarjou

et al. 2003

Laboratory Investigation

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SUMMARY:Members of the epidermal growth factor (EGF) family and their receptors are involved in many cellular processes, including proliferation, migration, and differentiation. We have previously reported that these growth factors are expressed and have specific regulatory functions in an organ-like culture model of normal human urothelial cells. Here, we used this model to investigate the involvement of EGF receptor (EGFR) in human urothelial regeneration. Three 4-mm-diameter damaged areas were made in confluent normal human urothelial cell cultures with a biopsy punch. Regeneration was measured, on fixed stained cultures, with an image analyzer, at 4, 24, and 48 hours after injury. Cell proliferation was assessed by 5-bromo-2-deoxyuridine incorporation. To identify EGF family factors potentially involved in the healing process, we studied the effect of these factors on damaged confluent cultures and the level of expression of mRNAs extracted from these cultures. EGFR inhibition of the proliferation and migration of urothelial cells was tested with (1) a specific tyrosine kinase inhibitor (AG1478) and (2) a blocking anti-EGFR antibody (LA22). Exogenously added amphiregulin, EGF, transforming growth factor-␣ and heparin-binding EGF (HB-EGF) stimulated urothelial regeneration. The damaged areas were repaired by regrowth within 48 hours. Both AG1478 and LA22 inhibited the repair (by 50% and 30%, respectively), as well as proliferation and migration. This regeneration was accompanied by increased HB-EGF mRNA expression in cultures of cells from four of six subjects, but no corresponding change in EGFR protein level was observed. These results indicate that the EGFR signaling pathway is involved in urothelial regeneration. Our data support an autocrine role of HB-EGF in this process and suggest that the EGFR pathway is a potential therapeutic target for modulating urothelial cell proliferation. (Lab Invest 2003, 83:1333-1341.

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Urothelial Hyperplasia and Neoplasia: A Response to Chronic Urinary Tract Infections in Rats

Cited by 55 publications

References 12 publications

Histological Changes following Two-Step Flap Gastrocystoplasty in Rats

Histological Changes following Two-Step Flap Gastrocystoplasty in Rats

Bladder Carcinogenesis in Portacaval Shunt Rats

Epidermal Growth Factor Receptor Regulates Normal Urothelial Regeneration

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