These sites are predicted to be the most appropriate drug targets since they are structurally and/or functionally essential, and are the least likely to undergo viable mutations, thereby limiting resistance and increasing the lifespan of a drug.
Although imatinib has been shown to promote apoptosis, there are in vitro data indicating that primitive Ph+ stem cells not undergoing mitosis remain viable following exposure to the drug (Graham et al, 2002).
Cells lacking CNM67 display defects in cytoplasmic microtubule organization but remain viable, undergoing a normal SPB duplication cycle (Brachat et al., 1998; Hoepfner et al., 2000; Schaerer et al., 2001).
In contrast to CD19highIgD+ B cells, CD19lowIgD+ B cells are small, in the G0/G1 phase with very few cells in the S/G2/M phase or undergoing apoptosis, remain viable in the G0/G1 phase in short-term culture without additional stimulation, and are positive for the anti-apoptotic gene A20.
The phenomena of insertion and deletion probably also play an important role in the evolution of complexity, given the high probability of a viable individual to remain viable after undergoing an insertion or a deletion.
The proliferation marker Ki67 was used to estimate the fraction of viable cells undergoing active proliferation within the tumor (positive Ki67 staining divided by total viable tissue, expressed as Ki67 positive fraction).
DNA synthesis (measured by BrdU uptake) was maintained, showing that the cells were still viable and undergoing cell division.
Hence, we examined the effect of TZDs on Ovcar3 cells and determined whether cells were either viable or undergoing apoptosis and were dead at 4, 8 or 12 hours after treatment using FACS analysis.
Subsequently, it could be demonstrated that cells undergoing apoptosis, but not viable cells, carry the same OSEs in their membranes, which is consistent with the fact that oxidative processes are known to be triggered during apoptosis [6,7].
The International Mouse Phenotyping Consortium (IMPC; www.mousephenotype.org) aims to create 20,000 knockout (KO) mouse strains over the next 10 years, with viable strains undergoing comprehensive phenotyping as adult mice in order to identify the consequences of gene disruption.
