Biomarkers of apoptosis and necrosis in patients with hepatocellular carcinoma treated with sorafenib.
OBJECTIVE
Sorafenib is the medical reference for treatment of hepatocellular carcinoma (HCC). Multiple forms of cytotoxicity are induced by sorafenib in HCC cells in vitro but it is unclear what extent of apoptosis and necrosis is induced in HCC patients receiving sorafenib.


METHODS
The M30 and M65 biomarkers, which reflect the release of cytokeratin-18 and its apoptotic cleavage fragments, were measured in patients with HCC (n=36) and matched patients with cirrhosis (n=47). A serum sample was collected from 20 patients with HCC four weeks after the onset of treatment with sorafenib.


RESULTS
Basal serum levels of M30 and M65 were increased in patients with HCC compared to those with uncomplicated cirrhosis. No statistically significant increase in the level of M30 or M65 was found in the sera of patients with HCC after sorafenib.


CONCLUSIONS
The findings indicate that sorafenib is not a potent inducer of HCC cell death in most patients.
Laboratory of Biochemistry, CHU Sud, Amiens, France EA4666, Université de Picardie Jules Verne, Amiens, France.
Corinne
C
Godin
Laboratory of Biochemistry, CHU Sud, Amiens, France EA4666, Université de Picardie Jules Verne, Amiens, France.
Christophe
C
Louandre
Laboratory of Pharmacology, CHU Sud, Amiens, France.
Sandra
S
Bodeau
EA4666, Université de Picardie Jules Verne, Amiens, France.
Momar
M
Diouf
Laboratory of Biochemistry, CHU Sud, Amiens, France.
Zuzana
Z
Saidak
Laboratory of Biochemistry, CHU Sud, Amiens, France.
Marie-Alix
MA
Conte
EA4666, Université de Picardie Jules Verne, Amiens, France.
Bruno
B
Chauffert
EA4666, Université de Picardie Jules Verne, Amiens, France.
Jean-Claude
JC
Barbare
Centre de Ressources Biologiques, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris Seine-Saint-Denis, Bondy, France.
Nathalie
N
Barget
Centre de Ressources Biologiques, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris Seine-Saint-Denis, Bondy, France Department of Hepatology, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris Seine-Saint-Denis, Site Jean Verdier, Pôle d'Activités Cancérologiques Spécialisées, Bondy, France Université Paris 13, Sorbonne Paris Cité, UFR Santé Médecine Biologie Humaine, Bobigny, France Inserm UMR-1162, Génomique Fonctionnelle des Tumeurs solides, Paris, France.
Jean-Claude
JC
Trinchet
Department of Hepatology, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris Seine-Saint-Denis, Site Jean Verdier, Pôle d'Activités Cancérologiques Spécialisées, Bondy, France Université Paris 13, Sorbonne Paris Cité, UFR Santé Médecine Biologie Humaine, Bobigny, France Inserm UMR-1162, Génomique Fonctionnelle des Tumeurs solides, Paris, France.
Nathalie
N
Ganne
Laboratory of Biochemistry, CHU Sud, Amiens, France EA4666, Université de Picardie Jules Verne, Amiens, France Galmiche.Antoine@chu-amiens.fr.
Antoine
A
Galmiche
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D015415:Biomarkers; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D053538:Keratin-18 / Q000097:blood; D008113:Liver Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009336:Necrosis; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000097:blood / Q000627:therapeutic use*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D000077157:Sorafenib
D000970:Antineoplastic Agents; D015415:Biomarkers; D053538:Keratin-18; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib; D040262:Receptors, Vascular Endothelial Growth Factor
Hepatocellular carcinoma; M30; M65; programmed cell death; sorafenib