Abstract:
:Notwithstanding ongoing progress in anticancer therapeutics development, the persistent problem remains to selectively target tumors while sparing normal tissues. This is confounding largely because the differences between normal and tumor cells are often subtle and part of a gradient, where a gene product may be more or less expressed in tumor compared with the host normal tissue, but seldom expressed (or turned off) in tumors. The role of glutathione (GSH) and related enzymes in cellular resistance to xenobiotics, including chemotherapy is well established. This study is among those attempting to modulate GSH to therapeutic advantage. The authors briefly describe the experience with the gamma-glutamylcysteine synthetase inhibitor buthionine sulfoximine, and then in greater detail outline recent evidence for a potentially more selective approach using the cysteine prodrug L-2-oxothiazolidine-4-carboxylate. This has led to a detailed study of the activating enzyme 5-oxo-L-prolinase, including enzymatic and immunocharacterization, as well as in vitro study of the effect of its modulators on anticancer drug toxicity. Using high affinity antibodies the authors have generated interesting information on the distribution of this enzyme in tumor versus normal human tissues. Finally, the authors have been studying the potential for modulating gap junctions as a part of anti-cancer therapeutics, since they transport GSH between cells and are generally deficient in tumor cells. Preliminary studies suggest that gap junction induction may dramatically deplete GSH concentration in tumor cells and sensitize them to a variety of treatments.
journal_name
Chem Biol Interactjournal_title
Chemico-biological interactionsauthors
Chen X,Carystinos GD,Batist Gdoi
10.1016/s0009-2797(97)00166-xsubject
Has Abstractpub_date
1998-04-24 00:00:00pages
263-75eissn
0009-2797issn
1872-7786pii
S0009-2797(97)00166-Xjournal_volume
111-112pub_type
杂志文章,评审abstract::This study assessed the effect of the combination of anethole and ibuprofen in comparison with monotherapy by either drug alone, using two in vivo inflammatory models, namely the pleurisy and paw edema in rats. We also measured the levels of the TNF protein in plasma, and the ability of anethole to inhibit, in vitro, ...
journal_title:Chemico-biological interactions
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journal_title:Chemico-biological interactions
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journal_title:Chemico-biological interactions
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journal_title:Chemico-biological interactions
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journal_title:Chemico-biological interactions
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abstract::At pH 7.35, N-(2-oxopropyl)-N-nitrosourea (OPNU) reacted with calf thymus DNA to yield O6-methylguanine, 7-methylguanine and 3-methyladenine. Kinetic measurements of the base catalyzed decomposition of OPNU and the extent of methylation of DNA by OPNU suggested that methylnitrosourea is not formed as an intermediate p...
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journal_title:Chemico-biological interactions
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journal_title:Chemico-biological interactions
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journal_title:Chemico-biological interactions
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journal_title:Chemico-biological interactions
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journal_title:Chemico-biological interactions
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journal_title:Chemico-biological interactions
pub_type: 杂志文章
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journal_title:Chemico-biological interactions
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journal_title:Chemico-biological interactions
pub_type: 杂志文章
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journal_title:Chemico-biological interactions
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journal_title:Chemico-biological interactions
pub_type: 杂志文章
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pub_type: 杂志文章,评审
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journal_title:Chemico-biological interactions
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journal_title:Chemico-biological interactions
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journal_title:Chemico-biological interactions
pub_type: 杂志文章,评审
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journal_title:Chemico-biological interactions
pub_type: 杂志文章
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journal_title:Chemico-biological interactions
pub_type: 杂志文章
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journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2014.07.007
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journal_title:Chemico-biological interactions
pub_type: 杂志文章
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journal_title:Chemico-biological interactions
pub_type: 杂志文章
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journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2010.04.003
更新日期:2010-06-07 00:00:00
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journal_title:Chemico-biological interactions
pub_type: 杂志文章
doi:10.1016/j.cbi.2015.06.027
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