Urinary Bladder Complications With Cyclophosphamide Therapy

Foad, Baher S. I.

doi:10.1001/archinte.1976.03630050090015

Cited by 35 publications

(5 citation statements)

References 13 publications

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“…They are thought to induce urothelial injury by multiple mechanisms that result from the accumulation of high urinary concentrations of these drugs and their highly reactive metabolites (Wagner, 1994). The incidence of CP-induced hemorrhagic cystitis varies from 2 to 40% depending on dose and duration of therapy (Foad and Hess, 1976). This study provided a clear demonstration that KGF could be of benefit in ameliorating the toxic effects associated with cancer treatment regimens, and as such foreshadowed the development of this application as the primary clinical indication for KGF.…”

Section: Bladdermentioning

confidence: 99%

Keratinocyte Growth Factor⧸Fibroblast Growth Factor 7, a Homeostatic Factor with Therapeutic Potential for Epithelial Protection and Repair

Finch¹,

Rubin

2004

Advances in Cancer Research

206

184

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Keratinocyte growth factor (KGF) is a paracrine-acting, epithelial mitogen produced by cells of mesenchymal origin. It is a member of the fibroblast growth factor (FGF) family, and acts exclusively through a subset of FGF receptor isoforms (FGFR2b) expressed predominantly by epithelial cells. The upregulation of KGF after epithelial injury suggested it had an important role in tissue repair. This hypothesis was reinforced by evidence that intestinal damage was worse and healing impaired in KGF null mice. Preclinical data from several animal models demonstrated that recombinant human KGF could enhance the regenerative capacity of epithelial tissues and protect them from a variety of toxic exposures. These beneficial effects are attributed to multiple mechanisms that collectively act to strengthen the integrity of the epithelial barrier, and include the stimulation of cell proliferation, migration, differentiation, survival, DNA repair, and induction of enzymes involved in the detoxification of reactive oxygen species. KGF is currently being evaluated in clinical trials to test its ability to ameliorate severe oral mucositis (OM) that results from cancer chemoradiotherapy. In a phase 3 trial involving patients who were treated with myeloablative chemoradiotherapy before autologous peripheral blood progenitor cell transplantation for hematologic malignancies, KGF significantly reduced both the incidence and duration of severe OM. Similar investigations are underway in patients being treated for solid tumors. On the basis of its success in ameliorating chemoradiotherapy-induced OM in humans and tissue damage in a variety of animal models, additional clinical applications of KGF are worthy of investigation.

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Section: Bladdermentioning

confidence: 99%

Keratinocyte Growth Factor⧸Fibroblast Growth Factor 7, a Homeostatic Factor with Therapeutic Potential for Epithelial Protection and Repair

Finch¹,

Rubin

2004

Advances in Cancer Research

206

184

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“…Cyclophosphamide is a kind of alkylating agent which is used for the treatment of solid tumours, Hodgkin's disease, and non-neoplastic conditions, such as rheumatic arthritis, and also as a combatant of transplant rejection. However, haemorrhagic cystitis is a major side effect of cyclophosphamide chemotherapy (Philips et al 1961;Bennett 1974;Foad & Hess 1976). The incidence of haemorrhagic cystitis is related to the dosage and varies from 2% to 40% in patients, while the mortality rate in patients with massive haemorrhage receiving a high intravenous dose has been reported to be as high as 75% (Droller et al 1982;Ehrlich et al 1984;Stillwell & Benson 1988;Kranc et al 1992).…”

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confidence: 99%

Protective Effect of Berberine on Cyclophosphamide‐Induced Haemorrhagic Cystitis in Rats

Malavé²

2001

Pharmacology & Toxicology

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The urotoxicity of cyclophosphamide and the protective effect of the herb berberine were investigated in this study. Administration of 150 mg/kg cyclophosphamide intraperitoneally caused a serious haemorrhagic cystitis in rats after 12 hr, including bladder oedema, haemorrhage, and dramatic elevation of nitric oxide metabolites (nitriteπnitrate) in urine and in plasma. To explore whether cyclophosphamide-induced cystitis could be prevented by berberine, rats were pretreated with a single dose or two doses of berberine at 50, 100, or 200 mg/kg intraperitoneally then challenged with cyclophosphamide (150 mg/kg, intraperitoneally). The results indicated that pretreatment of rats with berberine could reduce cyclophosphamide-induced cystitis in a dose-dependent manner. Furthermore, we found that two doses of berberine showed greater protection against cyclophosphamide urotoxicity than when given a single dose. In addition, our data shows that a single dose of 200 mg/kg berberine, or two doses of 100, and 200 mg/kg berberine could completely block cyclophosphamide-induced bladder oedema and haemorrhage, as well as nitric oxide metabolites increase in rat urine and plasma. In conclusion, our findings suggest that berberine could be a potential effective drug in the treatment of cyclophosphamide-induced cystitis, and provides us with the bright hope in the prevention and treatment of cyclophosphamide urotoxicity.

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“…In the present study, we found a marked expression of kinin B 1 receptors in the bladder wall of CYP-treated rats. One of the main metabolites of CYP is acrolein which is eliminated through the urine and therefore produces severe lesions in the bladder (Foad & Hess, 1976;Cox, 1979) characterized at an histological level by moderate to severe oedema, transmural hemorrhage, mucosal erosion and ulceration (Phillips et al, 1961). Whilst there was no functional evidence for the presence of B 1 receptors in the bladder of untreated normal rats, contractions to des-Arg 9 -BK were obtained at 14 h and onwards after treatment with CYP.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological and molecular evidence for kinin B₁ receptor expression in urinary bladder of cyclophosphamide‐treated rats

Bélichard

Luccarini

Defrêne

et al. 1999

British J Pharmacology

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1 In the present study, we developed an experimental model of cystitis induced by cyclophosphamide (CYP). In order to characterize des-Arg 9 -BK-induced contraction on the urinary bladder (UB) during the development of in¯ammation and to quantify kinin B 1 receptor gene expression using a quantitative RT ± PCR technique. 2 In the presence of peptidase inhibitors captopril (10 mM), DL-thiorphan (1 mM) and DL-2-mercaptomethyl-3-guanidino-ethylthiopropanoic acid (MERGEPTA 5 mM), bradykinin (BK) (0.3 ± 3,000 nM) evoked a concentration-dependent contraction of rat UB which was not dierent between the CYP-and vehicle-treated groups. Unlike BK, des-Arg 9 -BK (0.3 ± 100,000 nM) did not contract UB from vehicle-treated rats but contracted vigorously bladder strips from CYP-treated rats 14, 24 and 168 h after treatment. In UB of 24 h treated rat, the pD 2 value of des-Arg 9 -BK was 7.3+0.1. 3 The cyclo-oxygenase inhibitor indomethacin (3 mM) reduced by 30% the maximal response of des-Arg -BK yielding pK B values of 6.8+0.2 and 7.2+0.1, respectively, whilst the kinin B 2 receptor antagonist Hoe 140 (1 mM) had no eect. 4 After CYP treatment, mRNA coding for the kinin B 1 receptor appeared predominantly in UB. In this organ, the induction was progressive, reaching a maximum 48 h after CYP treatment. 5 In conclusion, the present study provides strong evidence for an induction of kinin B 1 receptors in UB of CYP-treated rats. This was associated at a molecular level with an increase in mRNA expression of the gene coding for the kinin B 1 receptor. This kinin receptor displayed the whole features of a classical rat kinin B 1 receptor.

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Urinary Bladder Complications With Cyclophosphamide Therapy

Cited by 35 publications

References 13 publications

Keratinocyte Growth Factor⧸Fibroblast Growth Factor 7, a Homeostatic Factor with Therapeutic Potential for Epithelial Protection and Repair

Keratinocyte Growth Factor⧸Fibroblast Growth Factor 7, a Homeostatic Factor with Therapeutic Potential for Epithelial Protection and Repair

Protective Effect of Berberine on Cyclophosphamide‐Induced Haemorrhagic Cystitis in Rats

Pharmacological and molecular evidence for kinin B₁ receptor expression in urinary bladder of cyclophosphamide‐treated rats

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Urinary Bladder Complications With Cyclophosphamide Therapy

Cited by 35 publications

References 13 publications

Keratinocyte Growth Factor⧸Fibroblast Growth Factor 7, a Homeostatic Factor with Therapeutic Potential for Epithelial Protection and Repair

Keratinocyte Growth Factor⧸Fibroblast Growth Factor 7, a Homeostatic Factor with Therapeutic Potential for Epithelial Protection and Repair

Protective Effect of Berberine on Cyclophosphamide‐Induced Haemorrhagic Cystitis in Rats

Pharmacological and molecular evidence for kinin B1 receptor expression in urinary bladder of cyclophosphamide‐treated rats

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Pharmacological and molecular evidence for kinin B₁ receptor expression in urinary bladder of cyclophosphamide‐treated rats