The 26S proteasome degrades proteins that regulate transcription factor activation, cell cycle progression, and apoptosis. In cancer, this may allow for uncontrolled cell division, promoting tumor growth, and spread. We examined whether selective inhibition of the 26S proteasome with PS-341, a dipeptide boronic acid analogue, would block proliferation and induce apoptosis in human pancreatic cancer. Proteasome inhibition significantly blocked mitogen (FCS) induced proliferation of BxPC3 human pancreatic cancer cells in vitro, while arresting cell cycle progression and inducing apoptosis by 24 h. Accumulation of p21(Cip1-Waf-1), a cyclin dependent kinase (CDK) inhibitor normally degraded by the 26S proteasome, occurred by 3 h and correlated with cell cycle arrest. When BxPC3 pancreatic cancer xenografts were established in athymic nu/nu mice, weekly administration of 1 mg/kg PS-341 significantly inhibited tumor growth. Both cellular apoptosis and p21(Cip1-Waf-1) protein levels were increased in PS-341 treated xenografts. Inhibition of tumor xenograft growth was greatest (89%) when PS-341 was combined with the tumoricidal agent CPT-11. Combined CPT-11/PS-341 therapy, but not single agent therapy, yielded highly apoptotic tumors, significantly inhibited tumor cell proliferation, and blocked NF-kappaB activation indicating this systemic therapy was effective at the cancer cell level. 26S proteasome inhibition may represent a new therapeutic approach against this highly resistant and lethal malignancy.

Adrenalectomy is increasingly performed nationwide for both benign and malignant indications. In this study, whereas perioperative mortality remained low, major postoperative complications increased significantly.

Racial disparities exist in pancreatic cancer specialist consultation and subsequent therapy use. Because receipt of care is fundamental to reducing outcome discrepancies, these barriers serve as discrete intervention points to ensure all locoregional pancreatic adenocarcinoma patients receive appropriate specialist referral and subsequent therapy.

BACKGROUND: Although surgical resection is generally recommended for patients with localized pancreatic neuroendocrine tumors (PNETs), the impact of resection on overall survival is unknown. The authors investigated the survival advantage of pancreatic resection using a national database. METHODS: This is a retrospective survival analysis of patients with PNETs from the Surveillance, Epidemiology, and End Results database (1988‐2002). RESULTS: A total of 728 patients with PNETs were identified with a median survival of 43 months using Kaplan‐Meier survival methods. Resection of tumor was associated with significantly improved survival compared with those patients who were recommended for but did not undergo resection (114 months vs 35 months; P < .0001). This survival benefit was demonstrated for patients with localized, regional, and metastatic disease. A multivariable Cox proportional hazards model was constructed to assess the overall effect of surgical resection on survival, and demonstrated an adjusted odds ratio of 0.48 (95% confidence interval, 0.35‐0.66) compared with those who were recommended for surgery but did not proceed to surgery. CONCLUSIONS: The authors have demonstrated in a large national study that resection of primary tumor in patients with PNETs is associated with improved survival across all disease stages. Patients with localized, regional, and metastatic PNETs who are reasonable operative candidates should be considered for resection of their primary tumors. Cancer 2009. © 2009 American Cancer Society.

An integer-based risk score can be used to accurately predict in-hospital mortality after pancreatectomy and may be useful for preoperative risk stratification and patient counseling.