with AHA, ACOG has alerted OB/GYN specialists and subspecialists to pay attention to one of the most important threats to women's health. The risk assessment and counseling steps being advocated are straightforward. The AHA's Life's Simple 7 tool can be completed by patients before their visits (even privately in the waiting room). The results can identify patients' specific risks to enable efficient use of the face-to-face visit. Fortunately, even brief messages from physicians repeated over time can be effective. Universal implementation of the advisory recommendations by the OB/GYN community is an important step toward reducing cardiovascular morbidity and premature death in women.-LAL)

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Poster Session -Cellular TherapiesBurkitt's lymphoma cell line BJAB-LexR that has been made naturally resistant to TRAIL through long-term culture in the presence of increasing concentrations of the drug Lexatumumab, an anti-DR5 antibody, as well as BJAB cells with Six1 overexpression. Performing experiments in both these contexts would allow us to distinguish between resistance genes that arise spontaneously versus resistance genes that are a direct effect of Six1 expression. We performed a genome-wide loss of function screen using the GeneNet lentiviral shRNA library containing 200 000 shRNAs with sequencing tags, allowing for high throughput deep sequencing. After selection for a particular phenotype, in this case TRAIL resistance, the shRNAs that promote or prevent this phenotype can be deduced from the frequency in which the shRNA is present in the selected population versus the unselected population. A library was constructed using sequence tag specific primers and deep sequencing was performed using Illumina sequencing technology. Bioinformatic analysis yielded a list of putative resistance genes that are currently being validated in the BJAB system and also in MDAMB231 breast cancer cells that have been made resistant to TRAIL in a similar fashion. With this unbiased approach, we aim to identify not only known components of the TRAIL pathway that may be deregulated but also completely novel pathways of TRAIL resistance that could be targeted for improved cancer therapy. Background: Acquired therapeutic resistance due to tumor cell adaptation to persistent therapeutic stress is an unmet challenge in inflammatory breast cancer (IBC), designated as an orphan cancer with the worst survival rates amongst all breast cancers. IBC tumor cells behave differently from other breast cancer by reprogramming the protein synthesis machinery enabling constitutive translation of key survival proteins. We have identified overexpression of X-linked Inhibitor of Apoptosis Protein (XIAP), the most potent mammalian caspase inhibitor via post-transcriptional mechanisms as a dominant feature of anti-apoptotic dysregulation involved in acquired therapeutic resistance to epidermal growth factor receptor (EGFR, and/or ErbB2/HER2)-targeting drugs like trastuzumab and lapatinib as well as apoptosis inducing agents such as TRAIL (TNF-related apoptosis inducing ligand). The second mitochondria-derived activator of caspases (Smac) protein is a potent antagonist of IAP proteins including XIAP and the basis for the development of Smac mimetic drugs. Methods: In the present study, we have characterized bivalent Smac mimetics as single agents and in combination with TRAIL to determine the ability of these agents to induce cell death in basal type (SUM149) and ErbB2-overexpressing (SUM190) IBC cell lines, as well as in an isogenic SUM149 derivative with stable XIAP overexpression (SUM149 wtXIAP) and an isogenic SUM190 derivative with stable XIAP knockdown (SUM190 shXIAP). Results: Here, we report that Smac mimetic induces cell death as a si...