title: A conjugate of doxorubicin with lactosaminated albumin enhances the drug concentrations in all the forms of rat hepatocellular carcinomas independently of their differentiation grade.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Experimental Pathology, University of Bologna, Bologna, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Di Stefano
authors.forename: Luigi
authors.initials: L
authors.lastname: Fiume
authors.forename: Michele
authors.initials: M
authors.lastname: Baglioni
authors.forename: Luigi
authors.initials: L
authors.lastname: Bolondi
authors.forename: Corrado
authors.initials: C
authors.lastname: Busi
authors.forename: Pasquale
authors.initials: P
authors.lastname: Chieco
authors.forename: Felix
authors.initials: F
authors.lastname: Kratz
authors.forename: Francesca
authors.initials: F
authors.lastname: Manaresi
authors.forename: Milena
authors.initials: M
authors.lastname: Pariali
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002454:Cell Differentiation; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006801:Humans; D007958:Leukocyte Count; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D000903:Antibiotics, Antineoplastic; D012709:Serum Albumin; D004317:Doxorubicin