Abstract

The long-term objectives are to improve our understanding of the pharmacology and toxicology of antitumor agents. A host of environmental substances and therapeutic agents cause pulmonary toxicity. A serious untoward effect of therapy with some antitumor agents is pulmonary toxicity. This project will examine the biochemical and cellular mechanisms responsible for anticancer drug-induced lung toxicity. Particular emphasis will be placed upon evaluating the damage caused by antitumor agents to pulmonary endothelial cell plasma membranes.
The aim of this project is to (a) characterize the biophysical and biochemical damage caused by bleomycin and other antitumor agents to the plasma membrane of pulmonary endothelium, (b) quantify the metabolism of bleomycin in various pulmonary cells and the biologic activity of novel metabolites, (c) determine if specific pulmonary cell types localize bleomycin in vivo, (d) evaluate the influence of other antitumor agents on bleomycin-induced lung toxicity and bleomycin pulmonary content and, (e) study the actions of pharmacologic agents that might reduce drug-induced lung toxicity.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Modified Research Career Development Award (K04)
Project #
5K04CA001012-02
Application #
3071585
Study Section
Experimental Therapeutics Subcommittee 2 (ET)
Project Start
1985-05-01
Project End
1990-04-30
Budget Start
1986-05-01
Budget End
1987-04-30
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520

  Publications

Naismith, Robert T; Shepherd, James B; Weihl, Conrad C et al. (2009) Acute and bilateral blindness due to optic neuropathy associated with copper deficiency. Arch Neurol 66:1025-7
Klawiter, E C; Alvarez 3rd, E; Xu, J et al. (2009) NMO-IgG detected in CSF in seronegative neuromyelitis optica. Neurology 72:1101-3
Naismith, R T; Tutlam, N T; Xu, J et al. (2009) Optical coherence tomography is less sensitive than visual evoked potentials in optic neuritis. Neurology 73:46-52
Naismith, R T; Tutlam, N T; Xu, J et al. (2009) Optical coherence tomography differs in neuromyelitis optica compared with multiple sclerosis. Neurology 72:1077-82
Klawiter, Eric C; Cross, Anne H; Naismith, Robert T (2009) The present efficacy of multiple sclerosis therapeutics: Is the new 66% just the old 33%? Neurology 73:984-90
Ou, Xiawei; Sun, Shu-Wei; Liang, Hsiao-Fang et al. (2009) Quantitative magnetization transfer measured pool-size ratio reflects optic nerve myelin content in ex vivo mice. Magn Reson Med 61:364-71
Sun, Shu-Wei; Liang, Hsiao-Fang; Xie, Mingqiang et al. (2009) Fixation, not death, reduces sensitivity of DTI in detecting optic nerve damage. Neuroimage 44:611-9
Xu, Junqian; Sun, Shu-Wei; Naismith, Robert T et al. (2008) Assessing optic nerve pathology with diffusion MRI: from mouse to human. NMR Biomed 21:928-40
Sun, Shu-Wei; Liang, Hsiao-Fang; Schmidt, Robert E et al. (2007) Selective vulnerability of cerebral white matter in a murine model of multiple sclerosis detected using diffusion tensor imaging. Neurobiol Dis 28:30-8
Mistry, J S; Jani, J P; Morris, G et al. (1992) Synthesis and evaluation of fluoromycin: a novel fluorescence-labeled derivative of talisomycin S10b. Cancer Res 52:709-18

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