Inhibitor of apoptosis proteins (IAPs) interact with and inhibit caspases-3, -7, and -9. This interaction can be inhibited by Smac/DIABLO, a polypeptide released from mitochondria upon initiation of the apoptotic signaling process. Here we demonstrate that the first 4 -8 N-terminal amino acids of Smac/DIABLO fused to the Drosophila antennapaedia penetratin sequence, a carrier peptide, enhance the induction of apoptosis and long term antiproliferative effects of diverse antineoplastic agents including paclitaxel, etoposide, 7-ethyl-10-hydroxycamptothecin (SN-38), and doxorubicin in MCF-7 breast cancer cells. Similar effects were observed in additional breast cancer and immortalized cholangiocyte cell lines. Further analysis demonstrated that the Smacpenetratin fusion peptide crossed the cellular membrane, bound XIAP and cIAP1, displaced caspase-3 from cytoplasmic aggregates, and enhanced drug-induced caspase action in situ. These studies demonstrate that inhibition of IAP proteins can modulate the efficacy of antineoplastic agents.

These results indicate that STI-571 induces caspase-dependent apoptosis in a human cholangiocarcinoma cell line and suggest that STI-571 might warrant further investigation as a possible agent for treatment of human cholangiocarcinoma.

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Arteriovenous fistula presents rarely with liver involvement. A 73-year-old man had new-onset ascites, hepatomegaly, and abnormal liver and renal function test results. An abdominal computed tomogram revealed a 7.6-cm internal iliac aneurysm but no other abnormality to account for his ascites. An aortogram demonstrated a 1.5-cm internal iliac arteriovenous fistula that subsequently was repaired, leading to resolution of his symptoms and laboratory abnormalities. High-output cardiac failure should be considered in the differential diagnosis of patients with new-onset massive ascites, hepatomegaly, and liver test abnormalities.

Physicians' practice of testing and treating for H. pylori in patients with confirmed peptic ulcer disease has steadily increased over the past 14 yr. However, in our study, only 36% of these patients were infected with H. pylori, whereas the majority used nonsteroidal anti-inflammatory drugs (NSAIDs). Therefore, testing seems to be more appropriate than empiric treatment in patients with peptic ulcer disease.