Phosphoproteomic change resulting from nocodazole treatment varied among cell lines in terms of the numbers of total phosphopeptides identified, motif groups, and functional annotation groups; however,
the cell lines were equally sensitive to nocodazole. The identified phosphoproteome subset contained major signaling proteins and proteins known to be involved in mitosis, but did not always exhibit the same changes in the tumor cells from nocodazole treatment. In spite of the complex changes observed in the phosphorylation of many of the proteins, possible common features induced by nocodazole were found, including click here phosphorylation of nucleophosmin (NPM) S254 and coatomer protein complex, subunit alpha (COPA) S173, suggesting that
the events are not cell-type specific but events generally occurring in mitosis or induced by a microtubule-interfering agent. Further, temporal analysis of phosphoproteome change revealed that phosphorylation of NPM S254 and COPA S173 was observed from the early (6 h) and late (24 h) time point after nocodazole treatment, respectively, suggesting that NPM S254 may be involved in the induction of M-phase arrest by nocodazole, whereas COPA S173 may be caused as a result of M-phase arrest.”
“In the age of genomic medicine we can often now do the genetic testing that will permit more accurate personal tailoring of medications to obtain the best therapeutic results. This is certainly a medically and morally desirable result. However, in other areas of medicine pharmacogenomics is generating
Necrostatin-1 consequences that are much less ethically benign and much less amenable to a satisfactory ethical resolution. More specifically, we will often find ourselves left with ‘wicked problems,’ ‘ragged edges,’ and well-disguised Epothilone B (EPO906, Patupilone) ethical precipices. This will be especially true with regard to these extraordinarily expensive cancer drugs that generally yield only extra weeks or extra months of life. Our key ethical question is this: Does every individual faced with cancer have a just claim to receive treatment with one of more of these targeted cancer therapies at social expense? If any of these drugs literally made the difference between an unlimited life expectancy (a cure) and a premature death, that would be a powerful moral consideration in favor of saying that such individuals had a strong just claim to that drug. However, what we are beginning to discover is that different individuals with different genotypes respond more or less positively to these targeted drugs with some in a cohort gaining a couple extra years of life while others gain only extra weeks or months. Should only the strongest responders have a just claim to these drugs at social expense when there is no bright line that separates strong responders from modest responders from marginal responders? This is the key ethical issue we address.