[A patient with congenital antithrombin III deficiency who underwent laparoscopic renal resection].

A 66-year-old man with congenital antithrombin III (ATIII) deficiency was scheduled to undergo laparoscopic renal resection. On admission the plasma ATIII activity was as low as 56%. After giving ATIII intravenously, the plasma ATIII activity increased to 103% on the day of surgery. It is usually difficult to monitor ATIII during surgery. Instead, we measured activated clotting times (ACTs). The ACT before operation was 178 seconds. During the operation, the ACT dropped to 81 seconds. We administered 3,000 units of heparin, and the ACT increased to 182 seconds. After surgery, the plasma ATIII activity was 68%. We managed the ACT activity to a target value of 100% postoperatively, until the patient was switched from heparin to oral warfarin. He was discharged without complications 10 days after surgery. In this patient, the ACT decreased during the operation, as did the ATIII activity. Although the half-life of the ATIII preparation was 3 days, it appeared that the ATIII activity, which was high preoperatively, decreased during the operation. Coagulation abnormalities could be managed quickly by measuring ACT. Our results suggest that the measurement of ACT is an effective technique for the intraoperative monitoring of patients with congenital ATIII deficiency.

Growth inhibition of human pancreatic cancer cells by human interferon-beta gene combined with gemcitabine.

We examined the anti-tumor effect of cationic multilamellar liposome containing human IFN-beta (huIFN-beta) gene against cultured human pancreatic cancer cells. We also evaluated the combined effect of huIFN-beta gene entrapped in liposomes and gemcitabine. Furthermore, we examined the anti-tumor mechanisms of the therapy, with emphasis on the Ras-related signal pathway. Three human pancreatic cancer cell lines (AsPc-1, MIAPaCa-2, and PANC-1) were used in this study. The growth inhibition together with the therapy were evaluated by WST-1 assay; the production of huIFN-beta protein was measured by ELISA; the cell cycle and apoptosis were analyzed using a FACScan flow cytometer; the protein levels of Son of sevenless (SOS-1) and Ras-GAP were measured by Western blotting; and the activation of Ras-GTP was evaluated by the immunoprecipitation method. As a result, we found that huIFN-beta gene entrapped in liposomes demonstrated a strong anti-tumor effect against human pancreatic cancer cells. The treatment that combined huIFN-beta gene entrapped in liposomes and gemcitabine was more effective than each treatment alone. Although gemcitabine remarkably reduced the level of SOS-1, the above combined therapy reduced the level of SOS-1 even more significantly. Both huIFN-beta gene entrapped in liposomes and the com-bination of huIFN-beta gene entrapped in liposomes and gemcitabine increased the level of Ras-GAP, and decreased the activity of Ras-GTP. These results suggest that this combination therapy can induce strong anti-tumor activity against human pancreatic cancer cells through the regulation of the Ras-related signal pathway.