Download Camptothecins in Cancer Therapy by Val R. Adams PDF

Download Camptothecins in Cancer Therapy by Val R. Adams PDF

By Val R. Adams

A severe evaluate our present knowing of camptothecins, their shortcomings, and of the chances for making improvements to their medical functionality. The authors speak about new camptothecin analog improvement, drug supply concerns for optimizing their anticancer task, and their power use in various diverse cancers. extra chapters describe what's identified in regards to the biochemistry, the pharmacology, and the chemistry of the camptothecins, together with the mechanism of topoisomerase and the way camptothecins poison this enzyme, using animal types in defining the anticancer power of camptothecins, and the query of camptothecin resistance.

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Example text

Because TOP-I is an essential enzyme in humans, it is also not possible to avoid inhibition by CPT via dramatic lowering of intracellular TOP-I levels. Accordingly, resistance to CPT is often characterized by alteration of TOP-I structure (22,23). 2. Other Nitrogen Heterocycles In addition to the camptothecins, several other classes of nitrogen heterocycles have been found to promote the cleavage of DNA by TOP-I, with concomitant stabilization of the formed enzyme-DNA covalent binary complex. These have included the benzophenanthridine alkaloids nitidine (12) and fagaronine (13) (24), protoberberine-type alkaloids such as coralyne (14) and dihydrocoralyne (15), and a number of indolocarbazole derivatives, exemplified by 16 and 17 (25) (Fig.

Cancer Res 56:4430–4437. 98. Tsao YP, D’Arpa P, Liu LF. 1992 The involvement of active DNA synthesis in camptothecin-induced G2 arrest: altered regulation of p34cdc2/cyclin B. Cancer Res 52:1823–1829. 99. D’Arpa P, Beardmore C, Liu LF. 1990 Involvement of nucleic acid synthesis in cell killing mechanisms of topoisomerase poisons. Cancer Res 50:6919–6924. 100. Zhang H, D’Arpa P, Liu LF. 1990 A model for tumor cell killing by topoisomerase poisons. Cancer Cells 2:23–27. 101. Hsiang YH, Lihou MG, Liu LF.

1999 Plasmid linking umber change induced by topoisomerase I-mediated DNA damage. Nucleic Acids Res 27:2905–2911. 114. Desai SD, Liu LF, Vazquez-Abad D, D’Arpa P. 1997 Ubiquitin-dependent destruction of topoisomerase I is stimulated by the antitumor drug camptothecin. J Biol Chem 272: 24159–24164. 115. Mao Y, Desai SD, Ting CY, Hwang J, Liu LF. 2001 26 S proteasome-mediated degradation of topoisomerase II cleavable complexes. J Biol Chem 276:40652–40658. 116. Hochstrasser M. 2000 Biochemistry. All in the ubiquitin family.

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