DETERMINANTS OF PACLITAXEL PENETRATION AND ACCUMULATION IN HUMAN SOLID TUMOR

摘要: The present study examined the determinants of penetration and accumulation [ 3 H]paclitaxel (12–12,000 nM) in three-dimensional histocultures patient tumors a human xenograft tumor mice. results showed 1) significant saturable drug tumors, 2) extensive retention 3) slower but more compared with tumors. Drug was not rate-limited by diffusion from medium through matrix supporting histocultures. difference expression mdr1 P-glycoprotein did fully account for Autoradiography imaging were used to evaluate spatial relationship between architecture, cell distribution, distribution as function time initial concentration culture medium. density kinetics drug-induced apoptosis also evaluated. indicate that high is barrier paclitaxel apoptotic effect enhances its solid tumor. These factors are responsible time- concentration-dependent rate, confined periphery until reduction epithelial occurred at 24 h, after which penetrated inner parts