Studies on bleomycin

Umezawa, Hamao; Ishizuka, Masaaki; Maeda, Kenji; Takeuchi, Tomio

doi:10.1002/1097-0142(1967)20:5<891::aid-cncr2820200550>3.0.co;2-v

Cited by 160 publications

(49 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Bleomycin is a chemotherapeutic antibiotic, produced by the bacterium "Streptomyces verticillus" (Adamson, 1976;Umezawa, 1967). Its use in animal models of pulmonary fibrosis is based on the fact that fibrosis is one of the major adverse drug effects of bleomycin in human cancer therapy.…”

Section: Bleomycinmentioning

confidence: 99%

The bleomycin animal model: A useful tool to investigate treatment options for idiopathic pulmonary fibrosis?

Moeller

Ask

Warburton

et al. 2008

The International Journal of Biochemistry & Cell Biology

821

724

View full text Add to dashboard Cite

Different animal models of pulmonary fibrosis have been developed to investigate potential therapies for idiopathic pulmonary fibrosis (IPF). The most common is the bleomycin model in rodents (mouse, rat and hamster). Over the years, numerous agents have been shown to inhibit fibrosis in this model. However, to date none of these compounds are used in the clinical management of IPF and none has shown a comparable antifibrotic effect in humans. We performed a systematic review of publications on drug efficacy studies in the bleomycin model to evaluate the value of this model regarding transferability to clinical use. Between 1980 and 2006 we identified 246 experimental studies describing beneficial antifibrotic compounds in the bleomycin model. In 221 of the studies we found enough details about the timing of drug application to allow inter-study comparison. 211 of those used a preventive regimen (drug given ≤ day 7 after last bleomycin application), only 10 were therapeutic trials (> 7 days after last bleomycin application). It is critical to distinguish between drugs interfering with the inflammatory and early fibrogenic response from those preventing progression of fibrosis, the latter likely much more meaningful for clinical application. All potential antifibrotic compounds should be evaluated in the phase of established fibrosis rather than in the early period of bleomycin-induced inflammation for assessment of its antifibrotic properties. Further care should be taken in extrapolation of drugs successfully tested in the bleomycin model due to partial reversibility of bleomycin induced fibrosis over time. The use of alternative and more robust animal models, which better reflect human IPF, is warranted.

show abstract

Section: Bleomycinmentioning

confidence: 99%

The bleomycin animal model: A useful tool to investigate treatment options for idiopathic pulmonary fibrosis?

Moeller

Ask

Warburton

et al. 2008

The International Journal of Biochemistry & Cell Biology

821

724

View full text Add to dashboard Cite

show abstract

“…The drug was first isolated from Streptomyces verticillatus by a Japanese group headed by Umezawa (1,2), who showed bleomycin to be a mixture of watersoluble peptides with differences in their terminal amine groups. Separation of these compounds was achieved and clinical trials were carried out on several of them.…”

mentioning

confidence: 66%

“…Liver, intestine, spleen, plasma, kidney all contained more inactivation enzyme than skin and lung. This is the inverse of drug retention from in vivo studies of Umezawa (1), where bleomycin content was highest in lung and skin, the organs of lowest inactivation enzyme content.…”

Section: Mechanismmentioning

confidence: 99%

See 1 more Smart Citation

Pulmonary Toxicity of Bleomycin

1978

Inpharma

View full text Add to dashboard Cite

show abstract

“…These were prepared by extracting neutral salt soluble and acid soluble fractions of dorsal skin tissue collagen from guinea pigs given 14C-glycine and by diluting the fractions so that they contained 1,200^1,400cpm of radioactivity per mg, in accordance with the method of Nagai et al* (6) Collagenase assay. To 0.2ml of 0.4^14C-glycine collagen solution, 0.2ml of0.1 m Tris buffer containing 10mM CaCl2 and 0.4m NaCl, pH 7.5, was added and the mixture agitated at 2^4°C.…”

mentioning

confidence: 97%

Analysis of the Mechanism of Bleomycin-Induced Cutaneous Fibrosis in Mice

et al. 1973

View full text Add to dashboard Cite

Mouseskin assays for collagen, determined as hydroxyproline, were carried out on a bleomycin-treated group and on untreated controls. Animals receiving bleomycin showed cutaneous collagen levels approximately 1.75 time higher than those exhibited by the untreated controls. With respect to the ratios of hydroxyproline in soluble collagen fraction to cutaneous total hydroxyproline content, the bleomycin-treated group displayed a roughly 50 per cent decrease in neutral salt soluble fraction and a slight diminution of the acid soluble fraction, as compared with the untreated controls. The findings indicate a significant increase in insoluble collagen content in the skin of mice receiving bleomycin.In an attempt to clarify the mechanismof collagenolysis by the anticancer antibiotic, cutaneous tissue specimens taken from animals treated with the antibiotic were grown in vitro, and crude collagenase preparations isolated from tissue cultures assayed radiologically, using *4C-glycine labelled collagen as the substrate.Lower cutaneous collagenolytic activity was observed in mice treated with bleomycin.Developedrecently as a unique anticancer drug virtually devoid of adverse side effects on the hematopoietic system, bleomycin1.2) is used at present primarily in the treatment of squamous cell carcinoma. Clinical as well as laboratory studies3.4) , however, have demonstrated the development of pulmonary fibrosis5) and changes in nail tissue65 as an occasional consequence of bleomycin administration, thus presenting some intricate problems in this anticancer chemotherapy. Meanwhile, there is as yet a dearth of information of particular note as to the mechanismof fibrotic response to bleomycin, with the exception of a report by Tezuka7) that bleomycin is capable of enhancing the activity of protocollagen proline hydroxylase which is involved in the biosynthesis ofcollagen.In view of this, the present study was undertaken to attempt an analysis of the fibrotic response of the skin of mice treated with bleomycin and, at the same time, to determine the course of biotransformation of the drug in cutaneous fibrosis in order to clarify the underlying mechanism. Materials and Methods(1) Bl eomyci n.Solutions of sterile bleomycin powder, supplied in vials containing the equivalents of 15 mg pure bleomycin base (Nippon-Kayaku Co., Ltd.), were used.(2) Laboratory animals.Animals used were 14-week-old male mice of the ICR strain with an average body weight of 25g.(3) Mouse skin assay for hydroxyproline following administration of bleomycin. 1) Drug administration: Bleomycin solution was administered to mice intraperitoneally in doses of lOmg/kg daily for 10 days and, on the 20th day after the conclusion of the 10-day dosing,

show abstract

Studies on bleomycin

Cited by 160 publications

References 0 publications

The bleomycin animal model: A useful tool to investigate treatment options for idiopathic pulmonary fibrosis?

The bleomycin animal model: A useful tool to investigate treatment options for idiopathic pulmonary fibrosis?

Pulmonary Toxicity of Bleomycin

Analysis of the Mechanism of Bleomycin-Induced Cutaneous Fibrosis in Mice

Contact Info

Product

Resources

About