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Journal ArticleDOI

A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin

DavidA Gewirtz
- 01 Apr 1999 - 
- Vol. 57, Iss: 7, pp 727-741
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TLDR
The potential role of DNA synthesis inhibition, free radical formation and lipid peroxidation, DNA binding and alkylation, DNA cross-linking, interference with DNA strand separation and helicase activity, direct membrane effects, and the initiation of DNA damage via the inhibition of topoisomerase II in the interaction of these drugs with the tumor cell are addressed.
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This article is published in Biochemical Pharmacology.The article was published on 1999-04-01. It has received 2118 citations till now. The article focuses on the topics: Daunorubicin & Anthracycline.

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Journal ArticleDOI

Anthracyclines: Molecular Advances and Pharmacologic Developments in Antitumor Activity and Cardiotoxicity

TL;DR: An overview of issues confirms that anthracyclines remain “evergreen” drugs with broad clinical indications but have still an improvable therapeutic index.
Journal ArticleDOI

Roles of the raf/mek/erk pathway in cell growth, malignant transformation and drug resistance

TL;DR: The Raf/MEK/ERK pathway has different effects on growth, prevention of apoptosis, cell cycle arrest and induction of drug resistance in cells of various lineages which may be due to the presence of functional p53 and PTEN and the expression of lineage specific factors.
Journal ArticleDOI

Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems

TL;DR: The frontline drug doxorubicin has been used for treating cancer for over 30 years but causes toxicity to most major organs, especially life‐threatening cardiotoxicity, which forces the treatment to become dose‐limiting.
Journal ArticleDOI

Antioxidants in health and disease

TL;DR: The basic chemistry of freeradical formation in the body, the consequences of free radical induced tissue damage, and the function of antioxidant defence systems are reviewed, with particular reference to the development of atherosclerosis.
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Systems biology: Metabonomics

Jeremy K. Nicholson, +1 more
- 23 Oct 2008 - 
TL;DR: By measuring and mathematically modelling changes in the levels of products of metabolism found in biological fluids and tissues, metabonomics offers fresh insight into the effects of diet, drugs and disease.
References
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Journal Article

Participation of p53 Protein in the Cellular Response to DNA Damage

TL;DR: A role for the wild-type p53 protein in the inhibition of DNA synthesis that follows DNA damage is suggested and a new mechanism for how the loss of wild- type p53 might contribute to tumorigenesis is suggested.
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Adriamycin-induced DNA damage mediated by mammalian DNA topoisomerase II

TL;DR: In studies in vitro, mammalian DNA topoisomerase II mediates DNA damage by adriamycin and other related antitumor drugs, and has been shown to induce single- and double-strand breaks in DNA.
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Apoptotic death in epithelial cells: cleavage of DNA to 300 and/or 50 kb fragments prior to or in the absence of internucleosomal fragmentation.

TL;DR: Results suggest that changes in the integrity of DNA indicative of the release of chromatin loop domains occur before cleavage at internucleosomal sites is initiated and that the latter is not an essential step in the apoptotic process.
Journal ArticleDOI

Adriamycin: the role of lipid peroxidation in cardiac toxicity and tumor response

TL;DR: The results suggest that adriamycin has at least two mechanisms of tissue damage: one, which involves lipid peroxidation, is blocked by tocopherol and results in cardiac toxicity; the other, which consists of binding to DNA, is not antagonized by toCophero and is responsible for tumor response.
Journal ArticleDOI

Intercalative antitumor drugs interfere with the breakage-reunion reaction of mammalian DNA topoisomerase II.

TL;DR: The agreement between the in vivo and in vitro studies suggests that mammalian DNA topoisomerase II is a drug target in vivo, and the cytotoxic action of epipodophyllotoxins may be analogous to the bactericidal action of nalidixic acid.
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