In order to block peritoneal metastasis of pancreatic cancer cells, we have attempted to block the signal transduction pathway involving hyaluronan (HA), Src, phosphoinositide 3-kinase (PI3K) and Akt. We examined the effects of Src, PI3K and Akt inhibitors on pancreatic cancer cell motility, invasion and metastasis. The pancreatic cancer cell line SW1990, known to cause peritoneal metastasis efficiently in nude mice, was used in this study. SW1990 cells were stimulated by HA to induce Akt phosphorylation. Then, the inhibitory effects of PI3K and Src kinase inhibitors were examined. Cell motility and cell migration assays were adopted to assess the cancer cell motility and its migration capability. We also examined the therapeutic efficacies of PI3K inhibitor wortmannin on peritoneal metastasis of SW1990 cells in the nude mouse model.

The transcription factor NF-kB is a positive transcription factor for a number of genes and has been recognized as an anti-apoptotic regulator. However, the mechanism by which NF-kB blocks apoptosis is still controversial. Here, we demonstrate the evidence that NF-kB could attenuate the TNF-a-induced apoptosis without de novo protein synthesis using human pancreatic cancer cell lines, MIA PaCa-2 and Capan-2. The TNF-a-induced apoptosis was blocked by IL-1b, a potent inducer of NF-kB activation. This inhibitory eect of IL-1b was evident when cells were treated with protein synthesis inhibitors such as cycloheximide (CHX). Moreover, NF-kB decoy oligonucleotides could not block the anti-apoptotic eect of IL-1b at doses sucient to block the NF-kB-dependent transcription induced by IL-1b. To con®rm the role of NF-kB in blocking apoptosis, we generated stable cell lines expressing IkBDN, a highly stable form of IkBa, a cytoplasmic inhibitor of NF-kB. In these stable transfectants, the antiapoptotic eect of IL-1b was totally abolished, indicating that the anti-apoptotic action of IL-1b could be ascribed to the NF-kB action. These ®ndings show that de novo protein synthesis is dispensable for anti-apoptotic eects of NF-kB and support the possibility that NF-kB could exert its anti-apoptotic action through protein-protein interaction.

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A solitary recurrence of gastric carcinoma in the peritoneal cavity is extremely rare. We herein present a case of solitary intraperitoneal recurrence in a patient with alpha-fetoprotein (AFP)-producing gastric carcinoma. As far as we can determine, this is the first report of such a form of recurrence in a patient with gastric carcinoma who underwent a successful resection. A review of our eight patients who had AFP-producing gastric carcinoma showed a frequent association with hepatic metastasis and a poor prognosis as has been reported previously. Our patient received intra-arterial chemotherapy with low-dose cisplatin and 5-fluorouracil to prevent hepatic recurrence, but eventually developed multiple hepatic metastases after ceasing this therapy. Therefore, adjuvant intra-arterial chemotherapy may have altered the site of first recurrence in this patient.