Bleomycin-induced Pulmonary Toxicity: Origins and Mechanisms of Pro-fibrotic Activities in the Lung Bleomycin-induced Pulmonary Toxicity: Origins and Mechanisms of Pro-fibrotic Activities in the Lung Bleomycins are a family of glycopeptides that are clinically relevant anti-cancer drugs, with demonstrated efficacy and history of use in the treatment of testicular cancer, lymphomas, and squamous cell carcinomas. Unfortunately, Bleomycin-induced pulmonary toxicity, which affects nearly 50% of treated cancer patients, severely limits the use of these drugs. This proposal represents a collaborative effort to identify structural motifs in Bleomycins that are linked with the pro-fibrotic activities of these molecules. Specifically, we hypothesize that it is possible to synthesize structural analogues of Bleomycin that remain efficacious anti-tumor drugs that do not elicit the confounding issue of induced pulmonary fibrosis. Indeed, the long term goal of this proposal is the development of safer next generationBleomycin-based drugs that do not induce pulmonary fibrosis yet still display the anti-tumor abilities of currently available drugs (e.g., Blenoxane). The immediate objectives of this application will be achieved by completing the following Specific Aim: To define and quantify the extent of induced pulmonary fibrosis in mice following the intratracheal administration of Bleomycin structural analogues.-ex
|Effective start/end date||1/1/09 → 12/31/09|
- Mayo Clinic Arizona: $15,000.00
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