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Liver Int. 2006 Aug;26(6):726-33.

A conjugate of doxorubicin with lactosaminated albumin enhances the drug concentrations in all the forms of rat hepatocellular carcinomas independently of their differentiation grade.

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  • 1Department of Experimental Pathology, University of Bologna, Bologna, Italy.

Abstract

BACKGROUND/AIMS:

Doxorubicin (DOXO) was coupled to lactosaminated human serum albumin (L-HSA) in order to enhance the drug concentration in the well differentiated hepatocellular carcinomas (HCCs), which can accumulate L-HSA through the asialoglycoprotein receptor. In the present experiments we compared the DOXO concentrations produced by this conjugate (L-HSA-DOXO) and by the uncoupled drug in the well, moderately, and poorly differentiated rat HCCs.

METHODS:

The same dose (1 microg/g) of free or L-HSA coupled-DOXO was injected in rats with HCCs induced by diethylnitrosamine. At different times, the animals were killed and the neoplastic nodules of liver were isolated. Their differentiation grade was determined histologically and their DOXO content was measured.

RESULTS:

Unexpectedly, we found that also in the poorly differentiated forms of HCCs, which display no or only a poor capacity of accumulating L-HSA, the conjugate raised DOXO levels that were approximately twofold higher than those produced by the free drug.

CONCLUSIONS:

The conjugate L-HSA-DOXO could improve the potential of DOXO in the treatment of all HCCs, including the poorly differentiated tumors that are the common forms in the advanced disease for which an effective chemotherapy is particularly needed.

PMID:
16842330
[PubMed - indexed for MEDLINE]
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