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ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS—ABSTRACTS introducing wild type or a constitutively active form (TTAA) of 4EBP1 (the negative regulator of eIF4E). Cells were assayed for changes in proliferation (MTT assay), clonogenic growth, and cell cycle (FACS). Changes in the level of cap-dependent mRNA translation were measured using a bicistronic luciferase reporter plasmid where Renilla luciferase is translated in a cap-dependent and firefly luciferase in a cap-independent (IRES) manner. Results: Rapamycin was a potent inhibitor of proliferation in all cell lines tested with IC50s in the nanomolar range. Treatment was associated with a reduction in cap-dependent mRNA translation in all cases (data not shown). Introduction into cells of 4EBP1, a downstream target of mTOR, inhibited proliferation and clonogenic growth of OE19 and OE33 but not of Bic-1 nor Seg-1. The effect was associated with cell cycle arrest, the induction of apoptosis, and with a reduction in the fraction of cap-dependent protein synthesis (See Figure for OE33). Conclusions: Targeting the activity of the cap-dependent mRNA translational machinery at the level of mTOR is an effective strategy for altering the malignant phenotype of EAC cell lines in vitro. In at least some cell lines the anti-neoplastic effect is likely to be mediated by effects on targets of Mtor other than 4EBP1.

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tial infarct (41.9 ⫾ 4.3% vs 9.4 ⫾ 4.9%, *p ⬍.004). IKK␤ inhibition significantly reduced infarct size (21.9 ⫾ 5.9%, **p⬍0.02). There was no difference between sham and IKK␤ groups. After 2 hours of reperfusion, hearts were procured for biomolecular analysis. Interestingly, there was no difference in the p65 NF-␬B nuclear/ cytoplasmic ratios between all groups. Furthermore, IKK␤ inhibition appeared to increase cytoplasmic content of p65. Similarly, compared to control ligation mice, IKK␤ inhibition also increased the relative expression of the myocardial early response genes BNP and cfos, as well as p65. Conclusion: In this murine infarct model, IKK␤ inhibition significantly reduced the size of myocardial infarction. This potent upstream inhibitor of NF-␬B also resulted in increased expression of cytoplasmic p65 and early response genes. This paradox could be explained, in part, by NF-␬B-I␬B autoregulation, timing of our molecular analysis, or alternative pathways. Although its exact mechanism remains to be determined, proximal blockade of the NF-␬B signaling pathway with IKK inhibition may prove useful to limit myocardial ischemia-reperfusion.

148. WITHDRAWN 147. INHIBITORY KAPPA B KINASE (IKK) INHIBITION ATTENUATES INFARCT SIZE IN A MURINE MODEL OF MYOCARDIAL ISCHEMIA-REPERFUSION. N. C. Moss, W. E. Stansfield, M. Rojas, M. Willis, R. Tang, C. H. Selzman; University of North Carolina, Chapel Hill, NC Introduction: Despite improvements in protection, myocardial ischemia/reperfusion remains an important cause of cardiac dysfunction. Multiple strategies exist experimentally; few are clinically accessible. Nuclear factor kappa-B (NF-␬B) is a transcription factor central to the inflammatory response and is implicated in reperfusion injury. Its activation relies on the phosphorylation of its inhibitor, I␬B, through its upstream kinase complex (IKK). IKK consist of two catalytic subunits, IKK␣ and IKK␤, and a regulatory subunit, IKK␥. IKK␤ is essential for regulating the inflammatory effects of NF-␬B. To date, no studies have examined the influence of IKK inhibition of NF-␬B on myocardial ischemia and reperfusion. Methods: Under ketamine/xylazine anesthesia, 15 C57BL6 mice had thorocotomy and exposure of the left anterior descending artery (LAD). Sham animals had a suture placed under the LAD; control mice had temporary ligation for 30 minutes followed by either 2 or 24 hours of reperfusion; IKK␤ mice were treated with the inhibitor (i.p) 30 minutes prior to similar ligation and release. After 24 hours, hearts were excised and examined for viability by staining with TTC. Areas of infarct were quantified using an NIH image analysis program. Western blot was performed to measure the NF-␬B nuclear translocation of its key subunit, p65. Early myocardial response gene expression was measured by realtime PCR. Results: Compared to sham animals, LAD occlusion in control mice resulted in a substan-

149. WITHDRAWN 150. WITHDRAWN

CLINICAL TRIALS/OUTCOMES II: CLINICAL CONSIDERATIONS 151. SURVIVAL FOLLOWING LIVER RESECTION FOR METASTATIC COLORECTAL CARCINOMA IN A LARGE POPULATION. S. A. Shah 1, R. Bromberg 2, A. Coates 3, M. Simunovic 3, S. Gallinger 2; 1University of Massachusetts, Worcester, MA, 2University of Toronto, Toronto, ON, Canada, 3Hamilton Health Sciences, Hamilton, ON, Canada Previous reports of liver resection for metastatic colon cancer (CRC) are typically from single-centers and thus may not account for selection or referral bias. We measured long-term survival following liver resection for CRC in the province of Ontario, Canada (population 12 million). Methods: The Ontario Cancer Registry is an administrative database that links all hospital records, pathology reports, and vital statistics for patients with a diagnosis of cancer. We used the Registry to identify patients who underwent liver resection for metastatic CRC in calendar years 19962004. Pathology reports were directly reviewed to obtain variables including type of resection, number and size of lesions, tumor grade and margin status. Other variables available included patient (age, gender, original CRC TNM stage, and timing of liver