HUMAN TUMOR BLOOD-FLOW IS ENHANCED BY NICOTINAMIDE AND CARBOGEN BREATHING

Perfusion insufficiency and the resultant hypoxia are recognized as im portant mechanisms of resistance to anticancer therapy, Modification o f the tumor microenvironment to increase perfusion and oxygenation of tumors may improve on the efficacy of these treatments, Using laser Do ppler probes to measure microregional RBC flux, this study examines th e influence of nicotinamide and carbogen on human tumor perfusion, Ten patients with advanced cancers were studied, Nicotinamide (80 mg/kg) was given p.o., and 60 min Later, up to six probes were inserted into the tumor, Readings were taken for 1 h, followed by 10 min of carbogen breathing and 10 additional min of breathing room air, Results were c ompared with those from a similar group of eight control patients who were not given nicotinamide, but who breathed carbogen, In 44 microreg ions analyzed, 33 (73%) shelved perfusion fluctuations of 50% or more, and 20 (44%) by 100% or more, This compared with the control group in whom 62% and 27% of microregions varied by 50% or more and 100% or mo re, respectively, Perfusion increases outweighed decreases by 30% with nicotinamide and 20% in the controls, On breathing carbogen, patients pretreated with nicotinamide showed an increase in tumor perfusion of 17% at 5 min and 22% at 10 min, compared with only 0% and 1% in the c ontrol group, Pretreatment with nicotinamide made little difference to the random blood flow fluctuations seen in controls, However, when ca rbogen was introduced, tumor perfusion increased compared with the con trol group, This may have important therapeutic implications by improv ing response to treatment and allowing better delivery of systemically administered agents.