Structure-activity relationships of (1'S)-1'-acetoxychavicol acetate, a major constituent of a southeast Asian condiment plant Languas galanga, on the inhibition of tumor-promoter-induced Epstein-Barr virus activation.

The structure-activity relationships of (1'S)-1'-acetoxychavicol acetate (ACA), a cancer chemopreventive agent of food origin, were investigated in an inhibitory test of tumor promoter teleocidin B-4-induced Epstein-Barr virus (EBV) activation in Raji cells. Through a test of 16 derivatives, the structural factors regulating activity were found to be as follows: (1) the absolute configuration at the 1'-position does not affect activity; (2) hydrogenation of the terminal methylene group abolishes activity; (3) both the phenolic and alcoholic hydroxyl groups are compulsorily acetylated, and it is necessary that the former is oriented only at the position para to the side chain; (4) an additional acetoxyl group is allowed to locate at the ortho or meta position; and (5) substitution of the hydrogen atom at the 1'-position by a methyl group reduces activity. Upon esterase blockade in Raji cells, (1'R,S)-ACA suppressed EBV activation, the extent of which was the same as tested in the control, suggesting that ACA bearing two acetoxyl groups is an intracellular structure prerequisite for activity exhibition. The present study suggests that nucleophilic attack to the 3'-position is important and involved in the interaction of ACA with an unidentified target molecule(s) participating in the process of EBV activation.

Minor triterpenoid saponins from Ardisia crenata.

Two minor triterpenoid saponins, ardisicrenoside G [3 beta-O-{alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->4)- [beta-D-glucopyranosyl-(1-->2)]-alpha-L-arabinopyranosyl}-16 alpha,28-dihydroxyolean-12-en-30-oic acid] and ardisicrenoside H [3 beta-O-{beta-D-xylopyranosyl-(1-->2)-beta-D- glucopyranosyl-(1-->4)-[beta-D-glucopyranosyl-(1-->2)]-alpha-L- arabinopyranosyl}-16 alpha,28-dihydroxyolean-12-en-30-oic acid] were isolated from the roots of Ardisia crenata. Structural assignments are based on NMR, MS and chemical reactions.

1'-Acetoxychavicol acetate, a superoxide anion generation inhibitor, potently inhibits tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in ICR mouse skin.

The anti-tumor-promoting activity of 1'-acetoxychavicol acetate (ACA) was examined in a two-stage carcinogenesis experiment in ICR mouse skin using 7,12-dimethylbenz[a]anthracene (0.19 mumol) and 12-O-tetradecanoylphorbol-13-acetate (TPA; 1.6 nmol). Topical application of ACA (160 nmol) markedly reduced the average number of tumors per mouse and the ratio of tumor-bearing mice: inhibition ratios 90% (p < 0.001) and 42% (p < 0.005), respectively. ACA even at a dose equimolar to TPA (1.6 nmol) significantly reduced the average number of tumors per mouse: inhibitory ratio 44% (p < 0.05). ACA potently inhibited TPA-induced superoxide (O2-) generation in differentiated HL-60 cells (IC50 = 4.3 microM) and suppressed the lipid hydroperoxide formation by 42% (p < 0.001) in the ethyl linoleate autoxidation test.

[Non-decompression surgery for esophagogastric varices--indication and postoperative result of esophageal transection with paraesophagogastric devascularization and Hassab procedure].

A total of 548 patients had an non-decompression surgery for esophagogastric varices in our hospital, from September 1979 to August 1995. Type of operation includes 402 cases of esophageal transection with paraesophagogastric devascularization (via thoracic approach). 40 cases via abdominal approach, and 106 cases of Hassab procedure. The origin was cirrhosis in 454 patients, IPH in 46, extrahepatic portal occlusion in 29, primary biliary cirrhosis in 6, Budd-Chiari syndrome in 4 and others in 9. Operative mortality rate was less than 1% in child A group, although overall mortality rate including child B, C was 5.0%. By thoracic approach, residual esophageal varices were observed only in 2.5%. Postoperative variceal recurrence were appeared high in cases with hepatocellular carcinoma (HCC). Cumulative recurrence rates at 15 years after surgery were 20.2%, unless HCC had occurred. Cumulative survival rates at 10, 15 years were 52.1%, 45.6% respectively in liver cirrhosis without HCC. Present study confirmed that our operation is effective in controlling esophagogastric varices in long term of periods. Esophagogastric varices of IPH, EHO, and liver cirrhosis of Child A group should be treated by non-decompression surgery.

[Results of non-decompression surgery for esophago-gastric varices--postoperative disappearance, recurrence, rebleeding rate of varices, and cumulative survival rate].

A total of 508 patients had an non-decompression surgery for esophago-gastric varices in our department, from September 1979 to December 1991. These patients consisted of 387 cases of transthoracic esophageal transection with para-esophagogastric devascularization, 40 cases of transabdominal esophageal transection, and 81 cases of Hassab procedure. The original diseases were cirrhosis in 432 patients, IPH in 35, extrahepatic-portal occlusion in 24, primary biliary cirrhosis in 6, Budd-Chiari syndrome in 4, and others in 7. Operative mortality rate was 5.3%. By thoracic approach, esophageal varices completely disappeared. Postoperative cumulative variceal recurrence and bleeding rates at 10 years were 12% and 7%, although recurrence occurred more often than not in cases with hepatocellular carcinoma (HCC). Cumulative survival rates at 5, 10 years were 69%, 46% in liver cirrhosis without HCC. Present study confirmed that our non-decompression surgery is effective in controlling esophagogastric varices in long term of periods.