Up-regulation of peripheral benzodiazepine receptor system in hepatocellular carcinoma.
Increased number of peripheral benzodiazepine receptors (PBRs) have been found in some tumors outside the liver. The present study was to verify whether the PBR system is altered in hepatocellular carcinoma (HCC). The levels of endogenous benzodiazepine-like compounds (BZDs), measured by radioreceptor binding technique after HPLC purification and the endogenous ligand for PBRs, termed diazepam binding inhibitor (DBI), measured by radioimmunoassay utilizing a specific antibody for human DBI, were studied in the blood of 15 normal subjects, 12 liver cirrhosis and 10 patients with HCC. The levels of BZDs in serum were increased hundred fold in liver cirrhosis patients and slightly elevated in HCC patients. DBI was found to be increased in HCC patients. The binding recognition sites for PBRs (Bmax) were increased 4 to 7 fold in HCC tissue in comparison with that found in non-tumoral liver tissue (NTLT). On the contrary the concentrations of DBI were found to be significantly decreased in HCC tissue in comparison with the respective NTLT. These results seem to suggest an implication of PBRs and of their putative endogenous ligands in the metabolism of these neoplastic cells and possibly in their proliferation. The up-regulation of PBRs found in HCC tissue seems to indicate an increased functional activity of these receptors and opens up the possibility of new pharmacological and diagnostic approaches while the changes in the circulating endogenous ligands for the above receptors might be envisaged as early markers of tumorigenesis in liver cirrhosis.
Venturini
I
I
Cattedra di Semeiotica e Metodologia Medica, Università di Modena, Italy.
Zeneroli
M L
ML
Corsi
L
L
Avallone
R
R
Farina
F
F
Alho
H
H
Baraldi
C
C
Ferrarese
C
C
Pecora
N
N
Frigo
M
M
Ardizzone
G
G
Arrigo
A
A
Pellicci
R
R
Baraldi
M
M
D000328:Adult; D000368:Aged; D001569:Benzodiazepines / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000737:chemistry*; D002352:Carrier Proteins / Q000097:blood; D026261:Diazepam Binding Inhibitor; D005260:Female; D006801:Humans; D008099:Liver / Q000737:chemistry; D008113:Liver Neoplasms / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D011963:Receptors, GABA-A / Q000032:analysis*; D015854:Up-Regulation
D002352:Carrier Proteins; D026261:Diazepam Binding Inhibitor; D011963:Receptors, GABA-A; D001569:Benzodiazepines