PubMed Health⌕ Search

PubMed · 1704153

Malignant pleural effusion.

Abstract

Malignancy is the most common cause of exudative pleural effusion in patients over the age of 60 years. Control of the effusion significantly reduces morbidity and improves quality of life. Tube thoracostomy with subsequent chemical pleurodesis is the treatment of choice for patients with tumors that are relatively insensitive to systemic chemotherapy. The agents most commonly used for chemical pleurodesis are tetracycline and bleomycin. A 13-center randomized trial compared tetracycline 1 g and bleomycin 60 U. Median time to recurrence or progression of the malignant effusion was 32 days for tetracycline and more than 46 days for bleomycin (P = .037). The recurrence rate within 30 days of instillation was 36% for bleomycin (10 of 28 patients) and 67% (18 of 27 patients) for tetracycline (P = .023). At 90 days, the recurrence rate was 30% (11 of 37) for bleomycin, and 53% (19 of 36) for tetracycline (P = .047). From this study, the authors concluded that intrapleural bleomycin appears superior to tetracycline for controlling malignant pleural effusions. Selected patients who fail tube thoracostomy and chemical pleurodesis should be considered for pleuroperitoneal shunting or pleurectomy.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

D W Moores. 1991. Malignant pleural effusion.. https://pubmed.ncbi.nlm.nih.gov/1704153/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Selective inhibition of bleomycin-induced G2 cell cycle checkpoint by simaomicin alpha.

Human T-cell leukemia-derived Jurkat cells are known to be defective in the G1 checkpoint. DNA-damaging agent bleomycin arrests the cell cycle at G2 phase of Jurkat cells, and microtubule-acting colchicine arrests it at the M phase. Simaomicin alpha, an actinomycete metabolite, itself showed no effect on the cell cycle status of Jurkat cells at least up to 6.0 nM. However, the compound (0.6-6.0 nM) was found to abrogate the bleomycin-induced G2 arrest, yielding a drastic decrease in cells at the G2 phase and increase in cells at the subG1 and G1 phases. On the other hand, the compound did not show any effect on the colchicine-induced M phase arrest in Jurkat cells. Furthermore, the compound showed almost no effect on the cell cycle status of the bleomycin-treated or -untreated normal cell line HUVEC. These data suggested that simaomicin alpha disrupts the cell cycle G2 checkpoint of cancer cells selectively, leading to sensitization of cancer cells to anti-cancer reagents.

Bleomycin↗

Axial ligation of Fe(II)-bleomycin probed by XANES spectroscopy.

Full multiple scattering calculations of the Fe K-edge X-ray absorption near edge structure of bleomycin have been performed. Structural insight is based on the comparison between experimental and theoretical data calculated for different active site models coming from NMR-informed molecular dynamic simulations. In all models considered, the equatorial ligands (secondary amine in beta-aminoalanine, pyrimidine and imidazole rings and the beta-hydroxyhistidine) were left unchanged. Seven models with two axial ligands (the primary amine in beta-aminoalanine and the carbomoyl group of the mannose or a solvent molecule) were tested. The best agreement between theoretical and experimental spectra is achieved for the model of bleomycin with the primary amine and the oxygen of the mannose sugar occupying the axial positions. The coordination environment is characterized by serious distortions of the Fe octahedron, including the presence of one ligand with a very short bond length and significant angular distortions.

Bleomycin↗

Structural study of copper(I)-bleomycin.

Previous NMR studies on Cu(I)-bleomycin have suggested that this adduct has a geometry distinct from Fe(II)BLM. The coordination chemistry of this bleomycin derivative has been investigated through the extension of the NMR data reported previously, and the use of molecular dynamics calculations. The data collected from the NMR experiments support the coordination to the metal center of the primary and secondary amines in beta-aminoalanine and the pyrimidine ring. The detection in the NMR spectra of the signal derived from the amide hydrogen in beta-hydroxyhistidine indicates that this amide is protonated in Cu(I)-bleomycin, precluding participation of the pyrimidinyl carboxamide nitrogen in the coordination of Cu(I), as previously reported. Three-dimensional solution structures compatible with the NMR data have been assayed for Cu(I)-bleomycin for the first time by way of molecular dynamics calculations, and two models showing four and five coordination have been found to be those that better fit the experimental data. In both models the primary amine in beta-aminoalanine is coordinated such that it is located on the same side, with respect to the coordination cage, as the peptide linker fragment. This result seems important for the favored models to be compatible with either their possible oxidation to become one of the reported structures for Cu(II)BLM, or their transformation into Fe(II) adducts able to cause DNA damage.

Bleomycin↗