INTRODUCTIONMyeloid cell leukemia 1 (Mcl-1) was first identified as a gene induced during myeloid cell differentiation (Kozopas et al., 1993) and is a prosurvival member of the Bcl-2 family. The activity of Bcl-2 family proteins involves several Bcl-2 homology (BH) domains (Danial and Korsmeyer, 2004) that control protein-protein interactions. These proteins play an important role in cancer by regulating cell death and survival. Compared with other prosurvival members such as Bcl-2 or Bcl-xL, Mcl-1 has been shown to have more transient survival effects (Zhou et al., 1997). Unlike other members of the family, the half-life of Mcl-1 is very short and its expression is highly regulated by growth factors and a variety of other agents. Moreover, Mcl-1 has an extended N-terminus that is not conserved in any other Bcl-2 family protein. The N-terminus contains two PEST domains, which are found in proteins that are rapidly turned over, but deletion of the PEST domains does not extend the short half-life of Mcl-1 (Akgul et al., 2000;Clohessy et al., 2004). When the Mcl-1 gene was knocked out in a mouse model, it resulted in peri-implantation lethality (Rinkenberger et al., 2000), but Mcl-1Ϫ/Ϫ embryos showed no alterations in the extent of apoptosis, indicating that Mcl-1 plays a role early in development distinct from its prosurvival functions. We and others reported that Mcl-1 expression can lead to suppression of cell proliferation and may have effects on cell cycle machinery (Fujise et al., 2000;Jamil et al., 2005). We showed that a short nuclear form of Mcl-1 (snMcl-1) was associated primarily with the inactive form of Cdk-1 in the nucleus, most prominently during the G2 phase of the cell cycle, which suggested a potential means by which Mcl-1 mediates its anti-proliferative effects (Jamil et al., 2005).It is now well established that genome surveillance mechanisms function to cause a delay, or arrest, in progression of the cell cycle at the boundary of G1/S or G2/M in response to DNA damage (Zhou and Elledge, 2000;Abraham, 2001;Kastan, 2001;Nyberg et al., 2002;Sancar et al., 2004). These surveillance mechanisms are known to involve a network of interacting proteins that recognize damage and elicit responses including cell cycle delay, DNA repair, and apoptosis (Elledge, 1996;Zhou and Elledge, 2000). Cdk's, which play a central role in cell cycle progression, are key targets of these checkpoints (Iliakis et al., 2003 MATERIALS AND METHODS Cell LinesHeLa, HL-60, and FDC-P1 cells were obtained from ATCC (Manassas, VA). ATM-deficient HT-144 cells were a kind gift from Dr. P. Olive (BC Cancer Agency). ATR-defective fibroblasts, F02-98, were a kind gift from Dr. P. Jeggo. Hs68, which are primary human foreskin fibroblasts (Wheaton and Riabowol, 2004), maintained within 30 -60 mean population doublings, were kindly provided by Dr. K. Riabowol (University of Calgary). HL-60 cells were cultured in RPMI1640 supplemented with 10% fetal bovine serum (FBS), 1 mM sodium pyruvate, 2 mM l-glutamine. FDC-P1 cells were grown in RPMI...

Each year funding agencies and academic institutions spend millions of dollars and euros on biobanking. All funding providers assume that after initial investments biobanks should be able to operate sustainably. However the topic of sustainability is challenging for the discipline of biobanking for several major reasons: the diversity in the biobanking landscape, the different purposes of biobanks, the fact that biobanks are dissimilar to other research infrastructures and the absence of universally understood or applicable value metrics for funders and other stakeholders. In this article our aim is to delineate a framework to allow more effective discussion and action around approaches for improving biobank sustainability. The term sustainability is often used to mean fiscally self-sustaining, but this restricted definition is not sufficient for biobanking. Instead we propose that biobank sustainability should be considered within a framework of three dimensions - financial, operational, and social. In each dimension, areas of focus or elements are identified that may allow different types of biobanks to distinguish and evaluate the relevance, likelihood, and impact of each element, as well as the risks to the biobank of failure to address them. Examples of practical solutions, tools and strategies to address biobank sustainability are also discussed.

A PTC platform is a feasible mechanism to engage patients in research programs such as biobanking. It is well supported by clinic staff and receives high engagement and acceptance from patients. Patient-approach rates vary in different clinics, likely due to both clinic and PTC process factors, but this strategy provides an efficient means of engaging patients in research and sets the stage for enhanced enrollment into translational research programs.