Tetsuya Higami

BRAF and K-ras gene mutations in human pancreatic cancers

We investigated the frequency of BRAF mutations in human pancreatic cancer specimens to determine its role in the development of pancreatic cancer. Nine pancreatic cancer samples without a K-ras codon 12 mutation and 19 with a K-ras mutation were included in the study. Analyses of the BRAF sequence revealed mutations in exon 15 (V599E) in two cases, both of which also exhibited a K-ras codon 12 mutation. No BRAF mutation was found in cases without a K-ras mutation. The BRAF V599E mutation was not found to be a major mutation in pancreatic cancers that had no K-ras codon 12 mutation.

EFFECTS OF ORAL BERAPROST SODIUM, A PROSTAGLANDIN I2 ANALOGUE, ON ENDOTHELIUM DEPENDENT VASODILATATION IN THE FOREARM OF PATIENTS WITH CORONARY ARTERY DISEASE

1 Previous clinical studies with prostaglandin I2 (PGI2) analogue beraprost sodium suggested the potential effects on protection of cardiovascular events in patients with peripheral artery disease. Although the mechanism is not well known, experimental studies have shown protective effects of endothelial cells. This study was designed to examine the effects of beraprost sodium on vascular endothelial function in the forearm of patients with coronary artery disease. 2 Beraprost sodium (120 mg/day) was orally administered to 14 coronary artery disease patients for 4 weeks and then stopped for 4 weeks. Eleven control patients did not receive beraprost sodium treatment. Reactive hyperemia was induced in the forearm, endothelium‐dependent vasodilatation was assessed by plethysmography, and urinary 8‐iso‐prostaglandin F2a (8‐iso‐PGF2a) was measured at baseline, 4 weeks and 8 weeks. 3 Both groups had similar reactive hyperemic responses at baseline. In the control group, reactive hyperemic response and urinary 8‐iso‐PGF2a remained unchanged for 8 weeks. In the beraprost group, maximum forearm blood flow increased significantly (P = 0.01) after 4 weeks of treatment and returned to baseline at 8 weeks. Duration of hyperemia increased significantly (P = 0.003) after 4 weeks, and remained greater than baseline at 8 weeks (P = 0.02). Urinary 8‐iso‐PGF2a decreased significantly (P = 0.03) after 4 weeks, and tended to be lower at 8 weeks (P = 0.07). Changes in reactive hyperemia correlated weakly but significantly with changes in 8‐iso‐PGF2a (P < 0.001). 4 Beraprost sodium decreased oxidative stress and improved forearm endothelium‐dependent vasodilatation in coronary artery disease patients. The favorable effects on vascular endothelium could potentially lead to a decrease in vascular events.