title: Cell death after high-LET irradiation in orthotopic human hepatocellular carcinoma in vivo.
abstract: Hepatocellular carcinoma (HCC) represents the sixth most common cancer worldwide and a major health problem since the choice of treatment is limited due to chemo- and radio-resistance. It was previously reported that high linear energy transfer (LET) radiation induced massive autophagic cell death in the human HCC SK-Hep1 cell line in vitro. This study analyzed the effects of high-LET radiation on the same HCC tumor model, orthotopically transplanted into nude mice. For this purpose, after surgical xenograft in the liver, animals were irradiated with fast neutrons and cell death occurring in the tumors was assessed with various techniques, including electron microscopy and probe-based confocal laser endomicroscopy. Results indicate that considerable autophagy and only limited apoptosis took place in the tumor xenografts after high-LET irradiation. These data confirm the previous in vitro results, suggesting that autophagy may act as a predominant mode of cell death in the efficacy of high-LET radiation.
authors.affiliation: EA-3430, Université de Strasbourg, Centre Régional de Lutte contre le Cancer Paul Strauss, 3 rue de la porte de l'Hôpital, 67065 Strasbourg, France.
authors.forename: Anaïs
authors.initials: A
authors.lastname: Altmeyer
authors.forename: Mihaela
authors.initials: M
authors.lastname: Ignat
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Denis
authors.forename: Nadia
authors.initials: N
authors.lastname: Messaddeq
authors.forename: John
authors.initials: J
authors.lastname: Gueulette
authors.forename: Didier
authors.initials: D
authors.lastname: Mutter
authors.forename: Pierre
authors.initials: P
authors.lastname: Bischoff
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D001343:Autophagy / Q000528:radiation effects*; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D005214:Fast Neutrons; D006801:Humans; D018499:Linear Energy Transfer; D008113:Liver Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D023041:Xenograft Model Antitumor Assays