Cancer research
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Brequinar sodium is a 4-quinolinecarboxylic acid analogue that inhibits dihydroorotate dehydrogenase and subsequent de novo pyrimidine biosynthesis. It has shown dose-dependent antineoplastic activity against several mouse and human tumor models. This trial evaluated Brequinar given as a single daily i.v. bolus over a 5-day period repeated every 28 days. ⋯ Renal excretion was a minor route of elimination for Brequinar. The maximally tolerated dose of Brequinar on a daily x 5 i.v. schedule was 250 mg/m2 for good risk patients. For the daily x 5 i.v. schedule, the recommended dose of Brequinar for phase II evaluation is 250 mg/m2 for good risk patients and 135 mg/m2 for poor risk patients.
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Several epidemiological studies suggest an inverse relationship between fiber intake and colon cancer risk. Animal model studies indicate that this inhibitory effect depends on the source of dietary fiber. Because of the potential significance of certain colonic mutagens and secondary bile acids in the pathogenesis of colon cancer, the effect of types of supplemental fiber on fecal mutagens and bile acids was studied in human volunteers. ⋯ The concentrations of fecal secondary bile acids (deoxycholic acid, lithocholic acid, and 12-ketolithocholic acid) and of fecal mutagenic activity in TA98 and TA100 with and without S9 activation were significantly lower during the wheat bran and cellulose supplementation periods. Oat fiber supplementation had no such effect on these fecal constituents. Thus, the increased fiber intake in the form of wheat bran or cellulose may reduce the production and/or excretion of mutagens in the stools and decrease the concentration of fecal secondary bile acids in humans.