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)
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 . 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.