The enhancement of interstitial transport of a doxorubicin-lactosaminated  albumin conjugate by imatinib: in rat hepatocellular carcinoma it is not  preferentially higher than that in liver and bone marrow.
The finding that imatinib enhances the drug transport from bloodstream to neoplastic cells suggested a possible role of this drug as an adjuvant to the chemotherapeutics given in the treatment of solid malignancies.The present experiments aimed to verify whether imatinib can selectively increase the penetration of a doxorubicin-lactosaminated human albumin conjugate (L-HSA-DOXO) in chemically induced rat hepatocellular carcinomas (HCCs). We observed that imatinib increased the uptake of L-HSA-DOXOby HCCs but at the same time caused a similar enhanced penetration of the conjugate in liver and bone marrow. To our knowledge, this is the first demonstration that the enhancing effect of imatinib on interstitial drug transport is not restricted to the tumors, but can be also displayed in normal tissues. This observation casts some doubts about the possibility that the value of anticancer agents with toxic side effects on liver and bone marrow can be improved by imatinib.
Fiume
L
L
Department of Experimental Pathology, University of Bologna, Italy. luigi.fiume@unibo.it
Baglioni
M
M
Busi
C
C
Manerba
M
M
Di Stefano
G
G
D000818:Animals; D001549:Benzamides; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D004317:Doxorubicin / Q000737:chemistry / Q000493:pharmacokinetics*; D004357:Drug Synergism; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D000068877:Imatinib Mesylate; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D008297:Male; D010879:Piperazines / Q000737:chemistry / Q000493:pharmacokinetics*; D011743:Pyrimidines / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000737:chemistry / Q000493:pharmacokinetics*
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D012709:Serum Albumin; C046912:lactosaminated serum albumin; D004317:Doxorubicin; D000068877:Imatinib Mesylate