Development of Urinary Bladder Cancer in the Rat

Kunze, Ekkehard

doi:10.1007/978-3-642-67292-7_3

Cited by 53 publications

(18 citation statements)

References 183 publications

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“…Sodium 2-mercaptoethane sulfonate (Mesna) leads to regional detoxification limited to the kidneys and the lower uri nary tract without impairing the systemic antitumoral efficacy of the cytostatics [10. 11, 13, 15-18], Previous proliferation-kinetic studies of the urotoxicity of the oxa zaphosphorines in rats had shown that a single intraperi toneal administration of CP induces an intensive repara tive regeneration [36] of the normally slowly renewing [35] bladder urothelium. The aim of the autoradiographic study presented here was to obtain information on whether the morphologically and clinically demonstrable protective action of Mesna against damage by CP is also reflected in the proliferative behavior of the bladder uro thelium.…”

Section: Introductionmentioning

confidence: 99%

Effect of the Uroprotector Sodium 2-Mercaptoethane Sulfonate (Mesna) on the Proliferation of the Bladder Urothelium in the Rat after Administration of Cyclophosphamide

et al. 1984

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The chemotherapy of malignant tumors with oxazaphosphorine cytostatics, e.g., cyclophosphamide (CP) and ifosfamide, is limited by their severe urotoxic side effects. As a result of cytotoxic damage, the proliferation of the urinary bladder urothelium is considerably stimulated during an intensive reparative regeneration. The recently developed uroprotector sodium 2-mercaptoethane sulfonate (Mesna) allows regional detoxification limited to the kidneys and lower urinary tract and thus protects against damage by aggressive oxazaphosphorine metabolites. The object of the present quantitative autoradiographic investigation was to study urothelial proliferation in the bladder of rats after administration of CP alone and in combination with Mesna. 20 h after intraperitoneal injection of a single dose of CP alone (100 mg/kg), the urothelium showed a steep rise of the ³H-thymidine (³H-TdR) labeling index which reached a peak of 17.6% at 30 h. Thereafter, the ³H-TdR index rapidly dropped. A second peak of 4.4% was observed after 7 days. With supplementary intravenous administration of a single dose of Mesna (100 mg/kg) 15 min before treatment with CP, the labeling index was substantially lower than after administration of CP alone. Thus, maximal values of only 1.6 and 1.9% were observed at 35 h and 7 days, respectively. Histopathological examination of the bladders showed severe necrotizing and ulcerative cystitis, 10, 20 and 25 h after administration of CP alone whereas with additional treatment with Mesna only slight edema of the lamina propria developed. The results obtained clearly demonstrate the protective action of Mesna on the urothelium of the lower urinary tract against the urotoxic effects of CP.

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Section: Introductionmentioning

confidence: 99%

Effect of the Uroprotector Sodium 2-Mercaptoethane Sulfonate (Mesna) on the Proliferation of the Bladder Urothelium in the Rat after Administration of Cyclophosphamide

et al. 1984

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“…Although there is no proven "cause and effect" between RPN and upper urothelial carcinoma, the development of bladder carcinoma has been well described in the experimental situation, where hyperplasia may be a prelude to malignancy (10). Hyperplastic bladder cells also show changes in histochemical profiles which include an increased loss of Alk Phos and an increased staining for GGT (16,29). The absence of these 2 features from the hyperplastic urothelia reported in these investigations suggests that the proliferative changes that follow the BEA-induced lesion probably represents a repair of injured tissue (1,28), rather than a premalignant change per se.…”

Section: Discussionmentioning

confidence: 71%

Enzyme Histochemical Changes in an Acutely Induced Renal Papillary Necrosis

1990

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Enzyme histochemistry was assessed in semi-thin glycolmethacrylate sections after 100 mg/kg 2-bromoethanamine (BEA) hydrobromide had been given ip to male Wistar rats to induce renal papillary necrosis. Changes in the proximal tubular marker enzymes alkaline phosphatase (A1k Phos), gamma-glutamyltranspeptidase (GGT) and adenosine triphosphatase (ATPase) were not apparent before 8 hr, but there was a progressive loss up to 144 hr. The proteinaceous PAS-positive casts in the loops of Henle and the collecting ducts stained for A1k Phos and GGT (from 12 hr) and for ATPase (from 18 hr). Acid phosphatase (Acid Phos) staining was increased in the proximal tubule lysosomes from 18 hr. There was a marked increase in Alk Phos in all hyperplastic upper urothelial cells from 8 to 24 hr, and a mosaic of staining remained in the pelvis adjacent to the necrosed papilla at 144 hr. At 12 hr, there was an increase in the staining of the pelvic, ureter and bladder vascular endothelial ATPase, the intensity and area of which increased progressively from 18 hr and almost occluded the capillary lumens in the worst affected areas by 144 hr. These data show several distinct series of pathological changes after the administration of BEA. The subtle degenerative changes in the proximal tubule followed the papillary lesion, but exfoliated brush border and proximal tubular cells were important components of the protein casts in the distal nephron. Similarly, the intense Alk Phos staining in the hyperplastic regions of the upper urothelium and the increased pelvic, ureteric and bladder endothelial ATPase staining suggested they develop as a consequence of the papillary lesion.

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“…Various experimental models using rodents have been established to study the various stages of chemical carcinogenesis [1,2,4,12]. In some animal models, use of putative preneoplastic lesions have been established to predict the subsequent development of neoplastic changes: for example, immunohistochemically demonstrated glutathione S-transferase placental form (GST-P)-posirive foci and pepsinogen isozyme 1 (Pgl)-altered pyloric glands (PAPG) are applied for rat hepatocarcinogenesis [2] and stomach carcinogenesis [12] respectively.…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemically demonstrated variation in expression of cathepsin E between uracil-induced papillomatosis and N-butyl-N-(4-hydroxybutyl)nitrosamine-induced preneoplastic and neoplastic changes in rat urinary bladder

Yamamoto

Yonezawa

Ichinose

et al. 1996

Vichows Archiv A Pathol Anat

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Expression of rat urinary bladder cathepsin E in benign papillomatosis induced by uracil and various stages of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced carcinogenesis was investigated immunohistochemically. Seven-week-old, male F344/DuCrj rats were used. In the normal urothelium of control rats, cathepsin E stained in all layers of cells, although in umbrella cells and some basal cells the reaction was relatively weak. In rats given a diet containing 3% uracil for 5 weeks immunoreactivity of cathepsin E in uracil-induced papillomatosis was consistently homogeneous in all layers, but weaker than in normal urothelium. In rats given 0.05% BBN in drinking water for 12 weeks and subsequently maintained without treatment for 48 weeks cells with little cathepsin E, never observed in normal urothelium, appeared at 5 weeks above the basement membrane in the earliest stage of BBN-induced urinary bladder cancer (simple hyperplasia). Throughout the neoplastic process, groups of cells with a little cathepsin E were randomly distributed, with expression in the urothelium being markedly unstable. Almost all areas of squamous cell proliferation in TCC were negative for cathepsin E. Instability of cathepsin E expression in rat urothelium therefore appears characteristic for carcinogenesis and offers the possibility of using this feature as an early biomarker for urinary bladder carcinogenesis.

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Development of Urinary Bladder Cancer in the Rat

Cited by 53 publications

References 183 publications

Effect of the Uroprotector Sodium 2-Mercaptoethane Sulfonate (Mesna) on the Proliferation of the Bladder Urothelium in the Rat after Administration of Cyclophosphamide

Effect of the Uroprotector Sodium 2-Mercaptoethane Sulfonate (Mesna) on the Proliferation of the Bladder Urothelium in the Rat after Administration of Cyclophosphamide

Enzyme Histochemical Changes in an Acutely Induced Renal Papillary Necrosis

Immunohistochemically demonstrated variation in expression of cathepsin E between uracil-induced papillomatosis and N-butyl-N-(4-hydroxybutyl)nitrosamine-induced preneoplastic and neoplastic changes in rat urinary bladder

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