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Archives of Toxicology 1991Bleomycins are a family of compounds produced by Streptomyces verticillis. They have potent tumour killing properties which have given them an important place in cancer... (Review)
Review
Bleomycins are a family of compounds produced by Streptomyces verticillis. They have potent tumour killing properties which have given them an important place in cancer chemotherapy. They cause little marrow suppression, but pulmonary toxicity is a major adverse effect. The mechanisms of cell toxicity are well described based on in vitro experiments on DNA. The bleomycin molecule has two main structural components: a bithiazole component which partially intercalates into the DNA helix, parting the strands, as well as pyrimidine and imidazole structures, which bind iron and oxygen forming an activated complex capable of releasing damaging oxidants in close proximity to the polynucleotide chains of DNA. This may lead to chain scission or structural modifications leading to release of free bases or their propenal derivatives. The mechanisms are well described based on in vitro experiments on DNA, but how they relate to intact cells in whole animals is more tenuous. Bleomycin is able to cause cell damage independent from its effect on DNA by induction lipid peroxidation. This may be particularly important in the lung and in part account for its ability to cause alveolar cell damage and subsequent pulmonary inflammation. The lung injury seen following bleomycin comprises an interstitial oedema with an influx of inflammatory and immune cells. This may lead to the development of pulmonary fibrosis, characterized by enhanced production and deposition of collagen and other matrix components. Several polypeptide mediators capable of stimulating fibroblasts replication or excessive collagen deposition have been implicated in this, but the precise role of these in bleomycin-induced fibrosis is yet to be demonstrated. Current therapy for bleomycin-induced lung damage is inadequate, with corticosteroids most often used. Given the mechanism of action described above, antioxidants and iron chelators might be beneficial. Although, studies to date are equivocal and there is insufficient evidence to promote their use clinically. Novel drugs are currently being developed and it is hoped these may be more useful.
Topics: Animals; Bleomycin; Cell Division; Collagen; DNA Damage; Humans; Iron Chelating Agents; Lung
PubMed: 1711838
DOI: 10.1007/BF02034932 -
Cancer Chemotherapy and Biological... 1999
Review
Topics: Animals; Antibiotics, Antineoplastic; Bleomycin; Cysteine Endopeptidases; Drug Resistance, Neoplasm; Humans; Pulmonary Fibrosis
PubMed: 10800476
DOI: No ID Found -
Cancer Chemotherapy and Biological... 1997
Review
Topics: Animals; Antibiotics, Antineoplastic; Bleomycin; Drug Resistance, Neoplasm; Humans; Pulmonary Fibrosis
PubMed: 9551207
DOI: No ID Found -
Mutation Research Mar 1991
Review
Topics: Animals; Bleomycin; Carcinogens; Chromosomes; DNA Damage; Humans; Mutagenesis; Mutagens
PubMed: 1706477
DOI: 10.1016/0165-1110(91)90022-n -
Seminars in Oncology Apr 1992Bleomycin is a cell-cycle--specific chemotherapeutic agent, with several interesting properties, that lends itself to use in combination chemotherapeutic protocols,... (Review)
Review
Bleomycin is a cell-cycle--specific chemotherapeutic agent, with several interesting properties, that lends itself to use in combination chemotherapeutic protocols, especially those for malignant lymphomas. In the following article, bleomycin's use as a single agent and subsequently in three generations of combination chemotherapeutic regimens is reviewed. Bleomycin's lack of myelosuppression and its tendency to concentrate in lymphoid tissue while maintaining tolerable toxicities has been the rationale for its incorporation into more aggressive treatment regimens.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Clinical Protocols; Humans; Lymphoma, Non-Hodgkin
PubMed: 1384144
DOI: No ID Found -
Otolaryngology and Head and Neck Surgery 1979
Topics: Bleomycin; Drug Therapy, Combination
PubMed: 92001
DOI: 10.1177/019459987908700401 -
Dermatologic Surgery : Official... Oct 2008Intralesional bleomycin has been favorably used off-label to treat various skin conditions. These include warts, hemangiomas, vascular malformations, telangiectasias,... (Review)
Review
Intralesional bleomycin has been favorably used off-label to treat various skin conditions. These include warts, hemangiomas, vascular malformations, telangiectasias, several types of cutaneous malignancies, condyloma acuminata, and the lesions of leishmaniasis cutis. Currently, there is a limited amount of evidence from randomized placebo-controlled trials comparing intralesional bleomycin with other local treatments for these disorders. In this article, we review the pharmacodynamics, mechanism of action, safety profile, and clinical applications of intralesional bleomycin. Dosages, techniques for administration, and efficacy of intralesional bleomycin for each aforementioned clinical entity are also provided. Given its ease and safety in administration, efficacy, and availability, off-label use of intralesional bleomycin can be considered another primary and/or adjunctive therapy for various common cutaneous conditions by practitioners in dermatology today.
Topics: Antibiotics, Antineoplastic; Bleomycin; Humans; Injections, Intralesional; Skin Diseases
PubMed: 18616538
DOI: 10.1111/j.1524-4725.2008.34281.x -
Cancer Chemotherapy and Biological... 1994
Review
Topics: Animals; Bleomycin; DNA Damage; Drug Resistance; Humans; Pulmonary Fibrosis
PubMed: 7540032
DOI: No ID Found -
Journal of Natural Products Jan 2000The bleomycin group antitumor antibiotics have long been of interest as a consequence of their efficacy in the treatment of certain tumors, not to mention their unique... (Review)
Review
The bleomycin group antitumor antibiotics have long been of interest as a consequence of their efficacy in the treatment of certain tumors, not to mention their unique structures and properties in mediating dioxygen activation and sequence selective degradation of DNA. At a chemical level, the structure originally assigned to bleomycin was subsequently reassigned and the new structure has been confirmed by total synthesis. Through the elaboration of structurally modified bleomycin congeners and fragments, synthetic efforts have also facilitated an understanding of the contribution of individual structural domains in bleomycin to sequence selective DNA binding and cleavage, and have also provided insights into the nature of the chemical processes by which DNA degradation takes place. Within the last several years, it has also become apparent that bleomycin can mediate the oxidative degradation of all major classes of cellular RNAs; it seems entirely plausible that RNA may also represent an important locus of action for this class of antitumor agent. In parallel with ongoing synthetic and mechanistic efforts using classical methods, the study of bleomycins attached to solid supports has been shown to provide important mechanistic insights, and the actual elaboration of modified bleomycins by solid phase synthesis constitutes a logical extension of such efforts.
Topics: Antibiotics, Antineoplastic; Base Sequence; Bleomycin; Molecular Sequence Data; Molecular Structure; Nucleic Acid Conformation; Oxidation-Reduction; RNA; Structure-Activity Relationship
PubMed: 10650103
DOI: 10.1021/np990549f -
Applied Microbiology and Biotechnology Aug 2018The bleomycins (BLMs) belong to a subfamily of glycopeptide antibiotics and are clinically applied in combination chemotherapy regimens to treat various malignancies.... (Review)
Review
The bleomycins (BLMs) belong to a subfamily of glycopeptide antibiotics and are clinically applied in combination chemotherapy regimens to treat various malignancies. But the therapeutic applications of BLMs are restricted by the accompanied dose-dependent lung toxicity and potential incidence of lung fibrosis. Many efforts have been devoted to develop novel BLM analogues, for seeking of drug leads with improved antitumor activity and/or reduced lung toxicity. The progresses in the biosynthetic studies of BLMs have greatly expedited the process to achieve such goals. This review highlights the discovery and development of microbial BLM analogues in the past two decades, especially those derived from engineered biosynthesis. Moreover, the summarized structure-activity relationship, which is specifically focusing on the sugar moiety, shall shed new insights into the prospective development of BLM analogues.
Topics: Bleomycin; Fermentation; Glycopeptides; Humans; Neoplasms; Prospective Studies; Protein Engineering; Structure-Activity Relationship
PubMed: 29876605
DOI: 10.1007/s00253-018-9129-8