Download DNA Topoisomerases in Cancer Therapy: Present and Future by James C. Wang (auth.), Toshiwo Andoh (eds.) PDF

By James C. Wang (auth.), Toshiwo Andoh (eds.)

In the mid 80's sort I and II enzymes have been came upon to be the intracellular objectives of a couple of efficacious anticancer medications resembling doxorubicin, mitoxantrone, etoposide and camptothecin because of a persevered efforts of many investigators, specifically Leroy Liu and his collaborators at Johns Hopkins college. Readers will discover a sequence of chapters written by way of researchers actively engaged within the increasing box of topoisomerase and their inhibitors. The sequence of chapters conceal overview articles on pharmacology and the molecular mechanism of topoisomerase I- and II-targeting anticancer medications in mammals and within the yeast Saccharomyces cerevisiae, which has proved to be an outstanding version organism for reviews of anticancer medicines. This quantity compiles up to date info at the topoisomerase-targeting compounds in medical and preclinical improvement as an invaluable and demanding reference ebook for college kids and researchers within the box of pharmacology, toxicology, oncology and molecular biology.

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In the case of the replication-mediated suicide complexes on the leading strand for DNA synthesis (Fig. 4). In the case of top! 24 Yves Pommier et al. suicide complexes resulting from cleavage complexes in nicked DNA (Fig. 2C and D) or from neighboring cleavage complexes on opposite strands of the DNA duplex (Fig. 2F), a staggered DNA double-strand break is formed. The repair/removal of the topl-DNA adduct at the 3'-end of the suicide complex is effected by a specific pathway centered around a recently discovered enzyme, tyrosyl DNA phosphodiesterase (Tdpl).

By contrast to ionizing radiation, p53 elevation is preserved in AT cells treated with camptothecin or the top2 inhibitor, etoposide (192), indicating that p53 elevation in response to camptothecin is independent of ATM. Because of 40 Yves Pommier et aZ. the diversity of the p53 responses, which can either induce apoptosis or cell cycle arrest or enhance DNA repair, the outcome of p53 deficiencies is probably dependent upon the cellular context. The sensitivity of Fanconi anemia (FA) cells to camptothecin is controversial.

Hofmann, G. , McCabe, F. , and Johnson, R. K. Synergic cell killing by ionizing radiation and topoisomerase I inhibitor topotecan (SK&F 10864), Cancer Research. 51: 5813-5816, 1991. , Lihou, M. , and Liu, L. F. Arrest ofDNA replication by drugstabilized topoisomerase I-DNA cleavable complexes as a mechanism of cell killing by camptothecin, Cancer Res. 49: 5077-5082, 1989. , O'Connor, P. , Kohn, K. , and Pommier, Y. Correlations between S- and G2-phase arrest and cytotoxicity of camptothecin in human colon carcinoma cells, Cancer Res.

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