Download Bortezomib in the Treatment of Multiple Myeloma (Milestones by Irene M. Ghobrial, Paul G. Richardson, Kenneth C. Anderson PDF

By Irene M. Ghobrial, Paul G. Richardson, Kenneth C. Anderson

A number of Myeloma (MM) is the second one commonest form of blood melanoma, as a result of an overproduction of cancerous infection-fighting white blood cells, referred to as plasma cells. Plasma cells are a vital a part of the immune procedure liable for the construction of antibodies. Bortezomib is a promising anticancer drug concentrating on the proteasome. This proteasome inhibitor induces phone tension and apoptosis within the melanoma cells. whereas a number of mechanisms usually are concerned, proteasome inhibition may well hinder the degradation of pro-apoptotic components, allowing activation of programmed phone demise in neoplastic cells based upon the suppression of proapoptotic pathways. This monograph on bortezomib is a priceless resource of knowledge for researchers and clinicians from the fields of oncology and pharmacology, operating both in academia or the pharmaceutical undefined.

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Extra info for Bortezomib in the Treatment of Multiple Myeloma (Milestones in Drug Therapy)

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Goldberg 3. Lecker SH et al (1999) Muscle protein breakdown and the critical role of the ubiquitin proteasome pathway in normal and disease states. J Nutr 129(1S Suppl):227S 237S 4. Goldberg AL, Dice JF (1974) Intracellular protein degradation in mammalian and bacterial cells. Annu Rev Biochem 43:835 869 5. Goldberg AL, St John AC (1976) Intracellular protein degradation in mammalian and bacterial cells: part 2. Annu Rev Biochem 45:747 803 6. Goldberg AL (1971) A role of aminoacyl tRNA in the regulation of protein breakdown in Escherichia coli.

Moreover, Bortezomib inhibits DNA repair by cleavage of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and ATM [17]. Importantly, treatment of MM cell lines resistant to DNA damaging agents (Mel, Dox) with those agents to which they are resistant, followed 12 24 h later with sublethal doses of Bortezomib, can inhibit repair of 32 T. Hideshima et al. Fig. 1 Possible mechanism whereby bortezomib triggers canonical NF kB activation. Bortezomib either directly or indirectly activates IKKb, which subsequently phosphorylates IkBa, an inhibitor of p50/p65.

Fenteany G et al (1995) Inhibition of proteasome activities and subunit specific amino terminal threonine modification by lactacystin. Science 268(5211):726 731 61. Bogyo M et al (1997) Covalent modification of the active site Thr of proteasome beta subunits and the E. coli homologue HslV by a new class of inhibitors. Proc Natl Acad Sci USA 94:6629 6634 62. Meng L et al (1999) Epoxomicin, a potent and selective proteasome inhibitor, exhibits in vivo antiinflammatory activity. Kaneko T, Hamazaki J, Iemura S, Sasaki K, Furuyama K, Natsume T, Tanaka K, Murata S (2009) Assembly pathway of the Mammalian proteasome base subcomplex is mediated by multiple specific chaperones.

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